PATHOLOGY

NOTES

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 RGUHS SYLLABUS

UNIT CONTENTS
I INTRODUCTION
Importance of the study of pathology
Definition of terms
Methods and techniques
Cellular and tissue changes
Infiltration and regeneration
Inflammations
Infections
Wound healing
Vascular changes
Cellular growth (Neoplasms)
Normal and cancer cell
Benign and malignant growths
In situ carcinoma
Disturbances of fluid and electrolyte balance
II SPECIAL PATHOLOGY
Respiratory System
Tuberculosis
Bronchitis
Pleural effusion
Pneumonia
Lung abscess
Emphysema
Bronchiectasis
Bronchial asthma
Chronic Obstructive Pulmonary Disease (COPD)
Lung tumours
Cardio-vascular System
Pericardial effusion
Rheumatic Heart Disease
Infective endocarditis
Atherosclerosis
Ischemia
Infarction
Aneurysm
Gastro Intestinal Tract/GI System
Peptic ulcer
Typhoid
Carcinoma of GI tract (Buccal, Esophageal, Gastric and Intestinal)
Hepatitis
Chronic liver abscess
Cirrhosis of liver
Tumours of liver
Tumours of gall bladder
Tumours of pancreas
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 Cholecystitis
Kidneys and Urinary Tract
Glomerulonephritis
Pyelonephritis
Renal calculi
Renal failure
Renal carcinoma
Cystitis
Male Genital System
Cryptorchidism
Testicular atrophy
Prostatic hyperplasia (BPH)
Carcinoma of penis
Carcinoma of prostate
Female Genital System
Fibroids
Carcinoma of Cervix
Carcinoma of Endometrium
Vesicular mole
Choriocarcinoma
Ectopic gestation
Ovarian cyst
Ovarian tumours
Breast cancer
Central Nervous System
Hydrocephalus
Meningitis
Encephalitis
Vascular disorders-Thrombosis and Embolism
Stroke
Paraplegia
Quadriplegia
Brain tumours (Meningiomas, Gliomas and Metastatic tumour)
Skeletal System
Bone healing
Osteoporosis
Osteomyelitis
Osteoarthritis
Rheumatoid arthritis
Bone tumours
III CLINICAL PATHOLOGY
Methods of collection of blood
Hemoglobin estimation
Blood cell counts (RBC, WBC and Platelets)
Bleeding time
Clotting time
Prothrombin time
Blood grouping

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 Cross matching
Blood chemistry
Blood culture
Serological and Immunological tests
Bone marrow examination
IV EXAMINATION OF BODY CAVITY FLUIDS
Transudates and Exudates
CSF analysis
Sputum examination
Examination of wound discharge
Analysis of gastric and duodenal contents
Semen analysis
V URINE AND FAECES
Physical characteristics of urine
Urine analysis
Urine culture and sensitivity
Characteristics of faeces
Stool examination
(Occult blood, Ova, Parasites and Cyst, reducing substance)

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 GENERAL
PATHOLOGY

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 PATHOLOGY
Pathology is the medical specialty that focuses on the study and understanding of
diseases. It deals with the examination and analysis of the causes, nature, development,
and effects of diseases on the human body, including tissues, organs, cells, and body
fluids. Pathologists are healthcare professionals who use various techniques and
laboratory tests to diagnose and characterize diseases, helping guide treatment
decisions, prognosis, and medical research. Pathology plays a central role in healthcare
by providing essential insights into the understanding and management of diseases.

Pathology is a broad field that deals with several components or sub disciplines, each of
which focuses on specific aspects of the study of diseases. The key components of
pathology include:
ANATOMIC PATHOLOGY
Surgical Pathology: This involves the examination of tissue samples obtained through
biopsies or surgical procedures to diagnose and characterize diseases, including cancer
and non-cancerous conditions.
Cytopathology: Cytopathologists examine individual cells, often from smears or fine-
needle aspirations, to diagnose diseases, particularly in cases of suspected cancer.
CLINICAL PATHOLOGY (LABORATORY MEDICINE)
Clinical Chemistry: This component focuses on the analysis of blood, urine, and other
body fluids to assess the levels of various chemicals and metabolites. It plays a crucial
role in diagnosing and monitoring various medical conditions.
Hematology: Hematopathologists study blood and blood-forming tissues, including red
and white blood cells and platelets, to diagnose disorders such as anemia, leukemia, and
bleeding disorders.
Microbiology: Microbiologists investigate infectious agents, such as bacteria, viruses,
fungi, and parasites, to diagnose infections and guide appropriate treatment.
Transfusion Medicine: This component manages blood banks and ensures the safe
collection, storage, and transfusion of blood and blood products.
Immunology and Serology: Immunopathologists study the immune system's response
to diseases and infections, as well as perform tests to detect antibodies and antigens in
the blood.

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MOLECULAR PATHOLOGY: Molecular pathology involves the analysis of genes,
proteins, and other molecules to identify genetic mutations, molecular markers, and
biomarkers associated with diseases. It is crucial for personalized medicine and targeted
therapies.
FORENSIC PATHOLOGY: Forensic pathologists investigate the cause of death in cases
of unnatural or suspicious deaths, contributing to legal and criminal investigations. They
perform autopsies and collect evidence.
NEUROPATHOLOGY: Neuropathologists specialize in the study of diseases of the
nervous system, including the brain and spinal cord. They diagnose conditions like
neurodegenerative diseases and brain tumors.
PEDIATRIC PATHOLOGY: Pediatric pathologists focus on diseases that affect infants,
children, and adolescents. They diagnose and study diseases specific to this age group.
DERMATOPATHOLOGY: Dermatopathologists specialize in the study of skin diseases.
They diagnose skin conditions, including skin cancers and inflammatory skin disorders.
RENAL PATHOLOGY: Renal pathologists study diseases of the kidneys, such as
glomerulonephritis and renal tumors, by examining kidney tissue samples.
GASTROINTESTINAL PATHOLOGY: Gastrointestinal pathologists concentrate on
diseases of the gastrointestinal tract, including the esophagus, stomach, small and large
intestines. They diagnose conditions like inflammatory bowel disease and
gastrointestinal cancers.

IMPORTANCE OF PATHOLOGY
The study of pathology is critically important in various fields of medicine and healthcare
for several reasons:
 Disease Diagnosis: Pathologists play a crucial role in diagnosing diseases and medical
conditions. They examine tissues, cells, and body fluids to identify abnormalities,
which helps in determining the underlying cause of a patient's illness. Accurate
diagnosis is essential for effective treatment and patient care.
 Treatment Planning: Pathological findings are often integral to developing treatment
plans. Oncologists, for example, rely on pathology to determine the type and stage of
cancer, which informs decisions about surgery, chemotherapy, radiation therapy, and
targeted therapies.

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 Prognosis: Pathological assessments can help predict the likely course of a disease
and the patient's outcome. This information is vital for both patients and healthcare
providers to make informed decisions about treatment and to prepare for potential
complications.
 Research and Drug Development: Pathology is central to medical research.
Pathologists investigate the mechanisms of disease, contributing to our understanding
of how diseases develop and progress. This knowledge is essential for developing new
drugs, therapies, and preventive measures.
 Public Health: Pathology is key to monitoring and managing public health issues. It
helps in tracking the spread of infectious diseases, studying disease patterns, and
identifying potential outbreaks or epidemics, which is crucial for disease control and
prevention.
 Quality Control and Assurance: Pathology ensures the quality and safety of various
medical procedures. Pathologists oversee blood bank operations, assess the quality of
laboratory tests, and ensure that organs and tissues used in transplantation are safe
and compatible.
 Autopsies: Post-mortem examinations (autopsies) conducted by forensic pathologists
can help determine the cause of death in cases of unexplained or suspicious deaths.
This information is critical for legal investigations, insurance claims, and
understanding trends in mortality.
 Precision Medicine: With advancements in molecular pathology and genetics,
personalized or precision medicine has become possible. Pathologists can identify
specific genetic mutations and molecular markers that guide targeted treatments for
individual patients, optimizing therapeutic outcomes.
 Education and Training: Pathology is an integral part of medical education, as it
helps medical students and healthcare professionals understand disease processes,
diagnostic techniques, and treatment options. Pathology is also a separate specialty
that requires rigorous training.
 Continuous Learning and Quality Improvement: Pathologists continuously update
their knowledge and skills to keep pace with advancements in medical science and
technology. This commitment to ongoing education ensures the highest quality of
patient care.

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 IMPORTANCE OF PATHOLOGY FOR NURSES
Pathology is important for nurses because it:
 Enhances disease understanding and accurate patient assessment.
 Facilitates effective treatment planning and monitoring.
 Empowers nurses to educate patients and their families.
 Improves communication with physicians and interdisciplinary collaboration.
 Supports infection control and safe medication administration.
 Aids in providing palliative care and critical thinking.
 Strengthens nurses' role as patient advocates.

DEFINITION OF TERMS/TERMINOLOGY

 Histopathology: The microscopic examination of tissues to study their structure and

identify abnormalities.

 Cytopathology: The study of individual cells to diagnose diseases, particularly cancer.

 Biopsy: The removal of a small sample of tissue for examination, often used for
diagnosis.

 Autopsy: A post-mortem examination to determine the cause of death.

 Inflammation: The body's response to injury or infection, often characterized by

redness, swelling, pain, and heat.

 Neoplasm: An abnormal mass of tissue, which can be benign (non-cancerous) or

malignant (cancerous).

 Metastasis: The spread of cancer from its original site to other parts of the body.

 Pathogen: A microorganism or agent that causes disease, such as bacteria, viruses,

and fungi.

 Antigen: A foreign substance that triggers an immune response in the body.

 Antibody: A protein produced by the immune system in response to an antigen.

 Hematology: The study of blood and blood disorders.

 Clinical Chemistry: The analysis of chemicals and metabolites in blood and other
body fluids.

 Serology: The study of antibodies and antigens in the blood, often used for infectious
disease diagnosis.

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 Molecular Pathology: The study of genetic and molecular alterations in diseases.

 Immunohistochemistry: The use of antibodies to identify specific proteins in tissues.

 Gross Examination: The visual inspection of organs and tissues, often during
surgery.

 Cytogenetics: The study of chromosomal abnormalities related to genetic diseases

and cancer.

 Immunology: The study of the immune system and its response to diseases and
infections.

 Necrosis: The death of cells or tissues caused by injury or disease.

 Granuloma: A type of inflammation characterized by the formation of nodules in

response to chronic infection or irritation.

 Etiology: The study of the cause or origin of a disease.

 Pathognomonic: A sign or symptom that is so characteristic of a particular disease

that it is virtually diagnostic.

 Staging: The process of determining the extent of cancer's spread in the body.

 Grading: The assessment of the aggressiveness of a tumor, often in terms of its

differentiation and cell characteristics.

 Fibrin: A protein involved in blood clot formation.

 Thrombosis: The formation of a blood clot within a blood vessel.

 Atherosclerosis: The buildup of fatty deposits in arteries, leading to narrowed or

blocked blood flow.

 Dysplasia: Abnormal development or growth of tissues, often a precursor to cancer.

 Biological Marker (Biomarker): A measurable substance that indicates the presence

of a biological process, condition, or disease.

 Hemorrhage: Excessive bleeding, often due to injury or disease.

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 METHODS AND TECHNIQUES

 HISTOPATHOLOGY: Examination of tissues under a microscope. Techniques include:

 Hematoxylin and Eosin (H&E) staining to visualize cellular structures.
 Special stains to highlight specific features, such as connective tissue or
microorganisms.
 Immunohistochemistry (IHC) to identify specific proteins within tissue sections.

 CYTOPATHOLOGY: Analysis of individual cells, often obtained through techniques

like fine needle aspirations, smears, or brushings.

 MOLECULAR PATHOLOGY: Analysis of genes, proteins, and other molecules at the

molecular level. Techniques include:
 Polymerase Chain Reaction (PCR) to amplify and detect DNA or RNA sequences.
 Fluorescence In Situ Hybridization (FISH) to identify chromosomal abnormalities.
 Next-Generation Sequencing (NGS) to analyze DNA or RNA sequences at high
throughput.

 CLINICAL CHEMISTRY: Laboratory tests to analyze blood, urine, and other body
fluids, measuring various substances such as glucose, cholesterol, and enzymes.

 MICROBIOLOGY: Identification and characterization of microorganisms, including

bacteria, viruses, fungi, and parasites. Techniques include:
 Culture to grow and identify microorganisms.
 Gram staining and acid-fast staining to classify bacteria.
 Polymerase Chain Reaction (PCR) for detecting specific microorganism DNA.

 CYTOGENETICS: Study of chromosomes and chromosomal abnormalities. Techniques

include:
 Karyotyping to analyze the number and structure of chromosomes.
 Fluorescence In Situ Hybridization (FISH) to detect specific chromosomal
abnormalities.

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 FLOW CYTOMETRY: Analysis of cells in suspension to determine characteristics such
as size, complexity, and the presence of specific markers or proteins on the cell
surface.

 ELECTRON MICROSCOPY: Provides high-resolution images of tissues and cells at the

ultrastructural level, allowing for detailed analysis of cellular structures and
abnormalities.

 AUTOPSY AND POST-MORTEM EXAMINATION: Examination of a body after death to

determine the cause of death and understand disease processes. This includes gross
examination, histological analysis, and toxicology tests.

 SURGICAL PATHOLOGY: Examination of tissues removed during surgery, which

includes macroscopic examination, tissue processing, and microscopic examination to
aid in disease diagnosis.

 BLOOD BANKING AND TRANSFUSION MEDICINE: Ensures the safety and

compatibility of blood products for transfusions. Techniques include blood typing,
cross-matching, and screening for infectious diseases.

 FORENSIC PATHOLOGY: Application of pathology to legal investigations. Techniques

include autopsy, toxicology, and analysis of physical evidence to determine causes of
injury or death.

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 CELLULAR RESPONSE TO INJURY
A cell is in homeostasis when equilibrium is maintained between the cell and its
environment. This equilibrium may be altered by external stimuli or stress. The cell
responds to this external stimulus is severe, cellular injury occurs.

When a normal cell which is in homeostasis is exposed to stress or increased demand,

the cell tries to adapt to the new environment. If the stress or demand further increases,
the cell progresses to cell injury and cell death.

The adaptive response may occur in the form of hyperplasia, hypertrophy and atrophy.
Cell injury is reversible up to a certain extent. If the stimulus persists or increases, the
cell reaches a point of no return resulting in irreversible injury and cell death.

CAUSES OF CELL INJURY

Hypoxia and anoxia: Hypoxia is reduced availability of oxygen. Anoxia is the complete
lack of oxygen supply. These are the commonest causes of cellular injury. Ischemia is
loss of blood supply from either impeded arterial flow or reduced venous drainage.
Ischemic tissues are more rapidly and severely injured as ischemia compromises both
oxygen supply as well as supply of metabolic substrates like glucose to the tissues.

Physical agents: Mechanical trauma, extremes of temperature, radiation, electric shock

and sudden pressure changes are some of the physical agents which cause cell injury.

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Chemical agents: Mercury, arsenic, cyanide are some chemicals which are toxic.
Glucose, salt and oxygen in high concentration are also chemical agents which cause cell
injury. Other chemicals include alcohol, organophosphorus compounds such as
insecticides and pesticides and drugs.

Microbial pathogens: Bacteria, viruses, parasites and fungi are microbial pathogens
causing injury.

Inflammatory mediators and immune reactions: Chemical mediators of inflammation

like lymphokines and complement proteins are produced by the body in response to
infection.

Genetic and metabolic disturbances: Genetic inborn errors of metabolism lead to

accumulation of toxic metabolites in the cells and therefore cell injury.

Nutritional imbalances: Vitamin deficiencies and protein energy malnutrition are major
causes of cell injury.

CELLULAR ADAPTATIONS

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Persistent exposure of a cell to exaggerated stimuli leads to cell adaptation. This occurs
at the level of individual cell, tissues or organs. Once the excessive stimulus is removed,
the cell reverts to normalcy.

Hypertrophy: Hypertrophy is the increase in the size of the tissue or organ resulting
from enlargement of individual cells. In hypertrophy the cells become larger in size.
There is no increase in the number of cells. Pure hypertrophy occurs in the heart and
the striated muscles. This is because the cells of these organs do not have the capacity
to divide.

Hyperplasia: Hyperplasia is an increase in the size of a tissue or organ resulting from an

increase in the number of cells. Hyperplasia is seen in cells which have the capacity to
divide. Hyperplasia and hypertrophy frequently occur together though they are two
distinct processes.

Atrophy: Atrophy is a decrease in cell size, leading to a reduction in the size of the
affected tissue or organ. It can result from disuse (lack of stimulation or workload),
denervation (loss of nerve supply), inadequate blood supply, hormonal changes, or aging.

Metaplasia: Metaplasia is a reversible change in which one differentiated cell type is

replaced by another. It often occurs in response to chronic irritation or inflammation,
allowing cells to better withstand adverse conditions. In smokers, the normal ciliated
epithelium of the respiratory tract may be replaced by stratified squamous epithelium,
better able to resist the effects of smoke.

Dysplasia: Dysplasia refers to abnormal changes in cell size, shape, and organization,
indicating atypical hyperplasia. It is often associated with chronic irritation or
inflammation and can be a precursor to cancer.

Intracellular accumulations: Intracellular accumulations of various substances (water,

lipid, proteins and carbohydrates) occurs as a result of the metabolic derangements in
the cells or alternatively by accumulation of an exogenous material.

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There are 3 mechanisms by which substances accumulate.
 Increased production of a normal endogenous substance in the cells.
 Defective metabolism or secretion of a normal endogenous substance.
 Abnormal accumulation of an exogenous substance.
These substances accumulate in the cytoplasm or the nucleus. They may accumulate
transiently or permanently. They may be harmless or on occasion may be severely toxic,
resulting in cell death.

Fatty change: Fatty change is an abnormal accumulation of lipids within cells. The
commonest site where fatty change is seen is in the liver. It is also seen in the heart and
the skeletal muscles. Liver is an important site for fat metabolism. Fatty change may
occur due to a defect anywhere in the sequence of fatty acid entry into the hepatocytes to
lipoprotein exit from the hepatocytes.

Hyaline change: Hyaline change refers to a homogenous, glassy pink alteration seen
either intra-cellularly or extra cellularly. This change is appreciated in routine
hematoxylin and eosin stained tissue sections.

Pathologic calcification: Pathologic calcification is the abnormal deposition of calcium

salts and minerals in the tissues.

CELL DEATH: Death is the final and irreversible change of cells. Cells have a finite life
span. Cell death occurs in 2 forms: Necrosis and Apoptosis
Necrosis: Necrosis is an exogenously induced cell death. It is characterized by a series of
morphologic changes that follow cell death in living tissue. This occurs from progressive
enzymatic degradation of lethally injured cells. Necrosis elicits inflammation in the
surrounding tissue. This is because necrotic cells lack their membrane integrity and the
contents from the necrotic cells leak into the surroundings. Enzymatic degradation
occurs in 2 ways.
 From the lysosomes of the dead cells when it is called autolysis.
 From the lysosomes of the immigrant leukocytes.

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Types of necrosis

 Coagulative necrosis
 Liquefactive necrosis
 Caseation necrosis
 Fat necrosis
 Gangrene necrosis
 Fibrinoid necrosis

Apoptosis: Programmed cell death. It is a pathway of cell death that requires activation
of a specific set of genes and enzymes from the cell destined to die. The enzymes degrade
cells own nuclear DNA and cytoplasmic proteins. The plasma membrane of the cell
remains intact.

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 INFLAMMATION

Inflammation is defined as the reaction of vascularised tissue to a sublethal injury. It is

fundamentally a protective response to get rid of the offensive injury.

Inflammation is a response of vascularized living tissue to injury. The injury may be

caused by physical forces, chemical agents, microbes and exogenous or endogenous
stimuli.

SIGNS OF INFLAMMATION

 Rubor: Redness
 Calor: Heat
 Dolor: Pain
 Tumor: Swelling
 Loss of function

ACUTE INFLAMMATION
Acute inflammation is rapid in onset and short in duration. It is characterized by
exudation of fluid and plasma proteins and emigration of neutrophils.
The most important events in acute inflammation includes
 Alteration in caliber of blood vessels
 Structural changes in the blood vessels
 Emigration of lecucocytes and their accumulation

VASCULAR EVENTS
The following are the vascular events that occur in acute inflammation. It includes
 Transient vasoconstriction-occurs immediately after the injury.
 Vasodilatation of the arterioles with increased blood flow (this is the factor which
produces heat and redness in the site of inflammation).
 Increased vascular permeability: It is the important sign of acute inflammation. The
endothelial lining becomes leaky and protein rich plasma escapes into the
interstitium. This fluid is called Exudate. The exudate is rich in protein, has a specific
gravity more than 1.020 and rich in cellular debris. This can be distinguished from
transudate-which is an ultrafiltrate of plasma, comes out of the vessel due to
imbalances in the hydrostatic pressure. It has a very low protein content and specific

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 gravity. The increase in vascular permeability is due to the formation of endothelial
gaps, Contration and retraction of endothelial cells, endothelial injury and increased
transcytosis.
 Slowing of circulation (stasis): As the protein rich plasma escapes out of the vessels,
there will be accumulation of red cells, white cells and platelets within the vessel.

CELLULAR EVENTS
They play a critical role in inflammation and delivers the appropriate leucocytes to the
site of injury. This can be grouped as intravascular and extravascular events.
Intravascular events: It includes margination, rolling and adhesion.
Extravascular events: It includes diapedesis, chemotaxis and phagocytosis.
Margination: During normal blood flow the leucocytes occupy the central column of flow
rimmed by the red cells and platelets in the periphery. This is called the axial flow.
During acute inflammation as a result of stasis, the leucocytes from the central column
move to the periphery and this is referred to as margination.
Rolling and Pavementing: The leucocytes on reaching the periphery roll on the
endothelium and arrange themselves on the endothelium which appears like the stones
placed on the pavement. This event is called as pavementing.
Adhesion:The leucocytes are tightly bound to the endothelial cells by a group of proteins
called the adhesion molecules. They act as cellular glue and bridges leucocytes and
endothelium.
Transmigration: Once the cell is adhered well to the endothelium it slowly put forth long
foot processes called the pseudopods which extend to the endothelial cell junctions and
insert themselves into the gaps and slowly escape out of the vessel. This process is
termed as transmigration. A similar movement of the red blood cells is termed as
diapedesis.
Chemotaxis: It is defined as locomotion oriented along a chemical gradient. It is a
process in which the leucocytes are attracted by certain chemicals to reach the site of
injury.
PHAGOCYTOSIS: It is an important and critical cellular event in acute inflammation in
which the offending pathogen is recognized and killed by the leukocytes.
It comprises of three stages:

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 Stage of recognition and attachment
 Stage of engulfment
 Stage of killing and degradation.
Stage of recognition and attachment: The leucocytes will be able to recognize the
offending pathogen only when they are coated with protein substance called opsonin.
This process is called as opsonisation. The common opsonins include Fc fragment of
immunoglobulin, complement fraction C3 and collectins.
Stage of engulfment: The leucocytes have cell surface receptors for the opsonins. They
include FCR-receptor for Fc fragment of immunoglobulin and CR 1, 2, 3 for complement
fraction C3, CR3 for collectins. Once the receptor is occupied by the opsonin, the
contractile proteins of the cell gets activated and it put forth cytoplasmic extensions
called the peudopods which slowly engulfs the organism and completely surrounds it.
This is called Phagosome. By this process the organism gets internalized within the
cytoplasm of the leucocyte. Within the cytoplasm the phagosome is slowly moved close to
the lysosome of the leukocyte and they both fuse to form the phagolysosome. After the
fusion the contents of the lysosome are released into the phagosome which activates the
killing process.
Stage of killing and degradation: Killing is usually done by two processes called the
oxygen dependent mechanism and oxygen independent mechanisms.

TRANUDATE AND EXUDATE

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TRANSUDATE

Transudate is a fluid that passes through a membrane, such as the walls of blood
vessels, due to imbalances in hydrostatic and oncotic pressures. It is typically an
ultrafiltrate of blood plasma that has a low protein content.

Composition: Transudate has a low protein concentration (less than 3 g/dL) and is
characterized by a high fluid-to-protein ratio.

Causes: Conditions that lead to increased hydrostatic pressure or decreased oncotic

pressure, such as congestive heart failure, cirrhosis, or nephrotic syndrome, can result
in the formation of transudate.

Appearance: The fluid is usually clear and pale yellow.

EXUDATE

Exudate is a fluid that escapes from blood vessels into the surrounding tissue. It is
characterized by higher protein content than transudate and is associated with
inflammation.

Composition: Exudate has a high protein concentration (greater than 3 g/dL) and
contains inflammatory cells, such as white blood cells, as well as cellular debris.

Causes: Inflammatory conditions, infections, malignancies, and trauma can lead to the
formation of exudate.

Appearance: The fluid may appear cloudy and can vary in color depending on the
underlying cause.

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 WOUND HEALING

There are several important stages of wound healing, following four

processes: hemostasis, inflammation, proliferation and maturation.

Hemostasis (blood clotting)

Stage one of wound healing starts at the onset of injury and is designed to stop any
bleeding. Blood vessels constrict, restricting the blood flow to allow blood clotting.
Platelets then stick together, essentially forming a dam to block the drainage of blood.

Inflammation (preventing infection)

The next stage of wound healing occurs once the bleeding has stopped and involves the
body's key defence mechanism – inflammation. Localised swelling is caused by the
injured blood vessels leaking transudate (made up of water, protein and salt).
Inflammation enables the wound to be cleaned and ready for new tissue growth. In this
phase, white blood cells enter the wound to destroy bacteria and remove debris. This
stage can be painful as blood rushes to the wound to clean it.

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Proliferation (rebuilding)
Once the wound is clean, the next phase involves closing the wound. Proliferation can be
broken down into three mini-phases:
 Filling the wound: The woundbed is filled with connective tissue to help form new
blood vessels.
 Contraction: The edges of the wound contract and pull toward the centre, causing a
tightening feeling.
 Covering the wound: Cells that created a protective barrier, called epithelial cells, flood
the wound and multiply until the wound is covered with epithelium.

Maturation (strengthening)
The new tissue that was built in the proliferation stage needs to build strength and
flexibility. Water is reabsorbed so collagen fibres can lie closer together. Maturation can
take the longest of the four stages of wound healing.

HEALING BY FIRST INTENTION

This refers to healing of sterile surgical wounds. The incision site initially contains
coagulated blood that forms the scab. The scab is invaded by the neutrophils which act
as scavengers. These are replaced by macrophages in 2-4 days time which secrete
mediators. The mediators promote the activities of myofibroblasts, angioblasts and
fibroblasts. The resultant vascularised connective tissue rich in macrophages,
myofibroblasts, angioblasts and fibroblasts is called granulation tissue. The amount of
granulation tissue formed depends on the amount of tissue defect as well as the
intensity of the inflammatory reaction. In the dermis, the epithelial cells proliferate from
the margins of the wound. These cells cover the defect in 3-7 days. The granulation
tissue filling the skin defect in the wound is transformed into a scar in 3-6 weeks. The
scar is then remodeled to resemble the normal skin.

HEALING BY SECONDARY INTENTION

This refers to healing of large wounds and all infected wounds. In these types of injuries,
the myofibroblasts cannot juxtapose the tissue margins. Therefore the granulation tissue
remains exposed to the external world and healing is prolonged or there is a failure of
the wound to heal completely.

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FACTORS AFFECTING WOUND HEALING

Local factors

 Site of wound: skin wounds heal better than wounds occurring in the internal organs.
 Mechanical factors: wounds at joint heal slowly if the area is not kept immobile.
 Small wounds heal faster than the large wounds.
 Sterile wounds heal faster than the infected wounds.
Systemic factors
 Diabetes mellitus delays wound healing secondary to diabetic microangiopathy.
 Malnutrition and vitamin C deficiency delays wound healing.
 Inadequate blood supply
 Glucocorticoids they are anti- inflammatory and inhibit collagen synthesis.

COMPLICATIONS OF WOUND HEALING

 Deficient scar formation may result in wound dehiscence. This is especially seen in
diabetics and patients on corticosteroid treatment.
 Excessive scar formation results in the formation of keloids and hypertrophic scars.
They result from excessive scarring and defective remodeling.
 Large scars result in the formation of contractures. Contractures over the joint results
in immobility.
 Exuberant granulation tissue formation above the level of skin blocks re
epithelialization.

24 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 NEOPLASMS
The proliferation of neoplastic cells leads to the formation of a mass called tumor or
neoplasm. Tumor is defined as an abnormal mass of tissue, the growth of which exceeds
and is uncoordinated with that of the normal tissues and persists in the same excessive
manner after cessation of the stimuli which inducing the change.

ETIOLOGICAL FACTORS

 Genetic factors: genetic damage is the core etiology of tumor. Four main types of
genes responsible
1. Proto-oncotic gene: It produces growth factors. When activated to oncogene it
produces cancer.
2. Cancer suppressor gene: It prevents cancer formation. Its absence leads to tumor
formation.
3. Apoptic gene: It is responsible for apoptosis. Its absence leads to tumor formation.
4. DNA repair gene: It is responsible for repairing errors in DNA synthesis. Their
absence leads to tumor formation.
 Oncogenic viruses: Viruses containing oncogens which are transported to the human
genome during viral infection. Examples are Epstein Barr Virus and Hepatitis B virus.
 Hereditary factors: familial history of ovarian cancer, breast cancer and colon cancer.
 Cultural and environmental factors: alcohol abuse, cigarette smoking and
occupations
 Chemical carcinogens: stains, paints, cosmetics, drugs, insecticides and pesticides.
 Radiation carcinogens: Exposure to UV rays and X-rays.

PATHOGENESIS

Due to etiological factors WARNING SIGNS OF CANCER

(carcinogen/oncogen)

Hyperplasia

Metaplasia

Dysplasia

Neoplasia

Benign/malignant tumor

25 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

DIFFERENCES BETWEEN NORMAL CELL AND CANCER CELL

 Normal cells divide only when they receive a set of appropriate signals whereas cancer
cells divide themselves despite the absence of those signals, and they are resistant to
the signals telling them to self-destruct, known as apoptosis or programmed cell
death.

 Cancer cells fuel their growth with different nutrients than normal cells and some
utilize different pathway to transform those nutrients into energy, allowing them to
proliferate faster than normal cells. For instance, tumor can induce new blood vessels
formation (Angiogenesis), bringing in more nutrients supply.

 Normal cells stop dividing when touching other cells. They usually do not migrate to
other areas. Cancer cells, on the contrary, invade into surrounding tissues and spread
to other organs.

 Cancer cells can evade our immune system elements which normally eliminate
abnormal or invading cells. They can co-opt our immune system to help them
proliferate. For instance, cancer cells can disguise as normal cells via antigen
expression on the cell membrane.

 Cancer cell genes can be amplified, deleted, or altered. Their chromosomes can be
reshuffled.

26 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

DIFFERENCES BETWEEN BENIGN AND MALIGNANT TUMOR

Benign Tumors Malignant Tumors

Cells in benign tumors are Cells in malignant tumors
usually well-differentiated, can be poorly differentiated
meaning they resemble or undifferentiated,
normal cells. appearing different from
The growth is slow and normal cells.
Cell Growth and Behavior localized to a specific area. Malignant tumors grow
Benign tumors do not more rapidly and have the
invade nearby tissues or potential to invade nearby
spread to other parts of the tissues and spread to other
body. parts of the body
(metastasis
Benign tumors are typically Malignant tumors often lack
encapsulated, meaning they a well-defined capsule,
Encapsulation are surrounded by a fibrous which allows them to invade
capsule that separates them nearby tissues.
from surrounding tissues
Benign tumors do not Malignant tumors have the
metastasize. They remain ability to metastasize,
localized to the site of origin. meaning cancer cells can
break away from the
Metastasis
primary tumor, enter the
bloodstream or lymphatic
system, and form secondary
tumors in distant organs.
Benign tumor cells resemble Malignant tumor cells may
normal cells in terms of size, exhibit atypical features,
shape, and nuclear features including variations in size,
Cellular Characteristics
shape, and nuclear
characteristics.

27 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 The main concern with Malignant tumors can
benign tumors is their invade and destroy
localized growth and the surrounding tissues, leading
Local Effects potential for compressing to a range of local symptoms
adjacent structures, causing depending on the affected
symptoms related to organ.
pressure.
Benign tumors are generally Malignant tumors can be
non-life-threatening, and life-threatening, especially if
surgical removal is often they metastasize. The
Prognosis curative prognosis for malignancies
depends on factors such as
stage, grade, and the
success of treatment.

28 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

IN SITU CARCINOMA

"In situ carcinoma" refers to a type of cancer that is confined to its site of origin and has
not invaded neighboring tissues. The term "in situ" is Latin for "in place" or "in its
original place." In situ carcinomas are considered non-invasive at this stage, as the
cancer cells have not breached the basement membrane or invaded surrounding tissues.
These lesions are often identified through diagnostic tests such as biopsies or imaging
studies.

 Localized Growth: In situ carcinoma cells proliferate and form a tumor at the site of
origin, but they do not spread beyond the confines of that specific location.

 Cellular Characteristics: The cells in In situ carcinoma typically display abnormal

features when examined under a microscope, but they have not acquired the ability to
invade surrounding tissues.

 Early Stage: In situ carcinomas are often considered an early stage of cancer.
Detecting and treating cancer at this stage can be highly favorable for prognosis, as
the disease has not yet become invasive or metastatic.

 Precursor Lesions: In some cases, in situ carcinoma is considered a precursor lesion

to invasive cancer. If left untreated, there is a risk that the cancer may progress to a
more advanced and invasive stage.

 Treatment: The primary treatment for in situ carcinoma often involves the removal of
the abnormal tissue. This may be achieved through surgical excision, and in some
cases, additional therapies such as radiation or hormonal therapy may be
recommended.

Examples of in situ carcinomas include:

 Ductal Carcinoma In Situ (DCIS): A non-invasive form of breast cancer where

abnormal cells are found in the lining of a breast duct but have not spread outside the
duct.

 Cervical Intraepithelial Neoplasia (CIN): Abnormal changes in the cells on the cervix
that may progress to cervical cancer if not treated.

29 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 FLUID AND ELECTROLYTE BALANCE

Fluid and electrolyte balance is a critical aspect of maintaining homeostasis in the

human body. The balance is regulated by various physiological mechanisms to ensure
that the composition and volume of bodily fluids remain within a narrow range.

FLUID BALANCE

Water Distribution: The human body is about 60% water, and this water is distributed
between various compartments, including intracellular fluid (inside cells) and
extracellular fluid (outside cells). The extracellular fluid is further divided into interstitial
fluid (between cells) and plasma (the liquid component of blood).

Regulation of Water Balance: The hypothalamus, a region of the brain, plays a crucial
role in sensing changes in blood osmolality (concentration of solutes) and regulating
thirst and the release of antidiuretic hormone (ADH or vasopressin). ADH acts on the
kidneys to control water reabsorption, helping to concentrate or dilute urine.

Kidney Function: The kidneys play a key role in regulating fluid balance by adjusting
the excretion of water and electrolytes in response to hormonal signals. The renin-
angiotensin-aldosterone system (RAAS) is involved in regulating blood pressure and fluid
balance.

Fluid Intake and Output: Fluid intake is obtained through drinking fluids and
consuming food, while output occurs through urine, sweating, breathing, and feces.
Maintaining a balance between intake and output is essential for overall fluid balance.

ELECTROLYTE BALANCE

Sodium (Na+): Sodium is the primary extracellular cation and plays a crucial role in
maintaining osmotic balance. It is regulated by the kidneys and influences water
balance.

30 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

Potassium (K+): Potassium is the major intracellular cation and is vital for nerve and
muscle function. Its balance is tightly regulated to prevent disturbances in cardiac
rhythm.

Chloride (Cl-): Chloride is the major extracellular anion and often follows sodium to
maintain electrical neutrality. It plays a role in acid-base balance.

Calcium (Ca2+): Calcium is essential for muscle contraction, blood clotting, and bone
health. Parathyroid hormone (PTH) and calcitonin help regulate calcium levels.

Magnesium (Mg2+): Magnesium is involved in various enzymatic reactions and is crucial

for muscle and nerve function. It is regulated by the kidneys.

Phosphate (HPO4^2-): Phosphate is important for bone health, energy transfer, and
acid-base balance. It is regulated by parathyroid hormone and calcitonin.

FLUID AND ELECTROLYTES DISORDERS AND IMBALANCES

 Dehydration: Insufficient fluid intake or excessive fluid loss.

 Overhydration (Water Intoxication): Excessive water intake without proper
electrolyte balance.
 Electrolyte Imbalances: Disruptions in the levels of sodium, potassium, calcium,
magnesium, or phosphate, which can lead to various health issues.
 Edema: Accumulation of excess fluid in tissues, often due to heart failure, kidney
dysfunction, or liver disease.

31 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 EDEMA

DEFINITION: It is defined as an abnormal and excessive accumulation of fluid in the

interstitial space. The term is derived from a Greek word oidema which means swelling.

 Edema can be further categorized into local and general.

 The generalised edema is called as anasarca.
 Edema of the serous cavities are examples for localized edema and they are referred
according the space involved-
 Pleura-Hydrothorax (Pleural Effussion)
 Pericardium-Hydropericardium (Pericardial effusion)
 Peri toneum-Hydroperitoneum (Ascites)
 Clinically edema can be grouped as pitting and non-pitting edema.
 If the edema fluid could be displaced by applying pressure then it is called pitting
edema, e.g. cardiac and renal edema and if the fluid could not be displaced it is non-
pitting edema- myxoedema, elephantiasis.

PATHOGENESIS: Edema is caused by mechanism that interferes with the normal

balance of the intravascular and extravascular fluid transfer. The two main driving forces
for the transfer of fluid in and out of the vessels are the intravascular hydrostatic
pressure and the colloid osmotic pressure (plasma oncotic pressure). Normally at the
arteriolar end of vessel fluid escapes into the extravascular space due to increased
hydrostatic pressure. This fluid enters the vessel back at the venular end due to the
plasma oncotic pressure. A minor propotion of the fluid enters the lymphatics of the
interstitium. So normally there is a perfect balance of the fluid transfer in and out of the
vessel. This is referred to as the Starling's forces.

CAUSES FOR EDEMA

 Increased capillary hydrostatic pressure
 Congestive cardiac failure
 Constrictive pericarditis
 Reduced colloid Oncotic pressure
 Nephrotic syndrome (increased loss)
 Cirrhosis of liver (reduced synthesis)
32 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
  Malnurtition (reduced synthesis)
 Protein losing enteropathy
 Lymphatic obstruction
 Inflammatory-filarial infestation
 Neoplastic-tumor emboli
 Post-surgical-after axillary dissection
 Post-irradiation
 External pressure
 Sodium and Water Retention
 Renal insufficiency
 Abnormal secretion of aldosterone
 Inflammatory: Acute and chronic inflammation

PATHOGENESIS OF CARDIAC EDEMA

Heart failure

Reduced cardiac output

Decrease in the effective arterial circulation

Renal blood flow reduced

Increased secretion of rennin

Activation of renin angiotensin aldosterone axis

Increased renal reabsorption of Na and water

Increase in plasma volume

Increased transudation

EDEMA

33 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS OF RENAL EDEMA

Nephrotic syndrome, acute glomerulonephritis, cirrhosis, malnutrition

Reduced plasma oncotic pressure

Decrease in the effective arterial circulation

Renal blood flow reduced

Increased secretion of renin

Activation of renin angiotensin aldosterone axis

Increased renal reabsorption of Na and water

Increase in plasma volume

Increased transudation

EDEMA

CLINICAL PROFILE OF EDEMA

Cardiac edema: Usually develops in congestive cardiac failure. It is a dependent pitting
edema mostly seen in the lower extremities in ambulatory patients and in the sacral area
(back) in bed ridden patients. Accumulation of fluid also occurs in serous cavities.

Renal edema: Seen in patients with nephrotic syndrome, acute glomerulonephritis and
acute tubular injury. More severe and marked in the periorbital tissue since it is the
tissue of least resistance. Edema also occurs in the ankle area and over the genitalia.

Pulmonary edema: Most important form of localized edema. It occurs due to elevation of
pulmonary hydrostatic pressure and increased vascular permeability of the alveolar

34 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

capillaries. The common predisposing conditions include left sided cardiac failure, mitral
stenosis, after cardiac surgeries, fulminant infection damaging the alveolar capillaries,
Acute Respiratory Distress Syndrome (ARDS) and in high altitudes.

Cerebral edema: It is life threatening condition as the brain is encased in a bony skull
cage. There are three types of cerebral edema -Vasogenic, Cytotoxic and Interstitial
edema. Vasogenic edema is the most common form and it seen in conditions like
contusion and infarction of brain, brain abscess and tumors of brain.

SHOCK
Shock is a medical emergency characterized by a severe decrease in blood flow
throughout the body. This reduction in blood flow can lead to inadequate delivery of
oxygen and nutrients to the body's tissues and organs, potentially causing widespread
organ failure. Shock is a critical condition that requires immediate medical attention.

HYPOVOLEMIC SHOCK
Cause: Severe blood or fluid loss, such as from trauma, hemorrhage, severe dehydration,
or major burns.
Characteristics: Reduced blood volume leading to decreased cardiac output and
inadequate tissue perfusion.

CARDIOGENIC SHOCK
Cause: Heart failure or severe heart attack (myocardial infarction) that impairs the
heart's ability to pump blood effectively.
Characteristics: Inadequate cardiac output, leading to reduced blood flow to the body's
tissues.

DISTRIBUTIVE (VASOGENIC) SHOCK

Characteristics: Abnormal distribution of blood within the circulatory system, leading to
inadequate tissue perfusion
Septic Shock: Caused by severe infection leading to systemic inflammation.
Anaphylactic Shock: Caused by a severe allergic reaction.

35 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

Neurogenic Shock: Caused by spinal cord injury or severe damage to the nervous
system.

OBSTRUCTIVE SHOCK
Cause: Physical obstruction of blood flow, often due to conditions such as pulmonary
embolism, cardiac tamponade (compression of the heart by fluid or blood), or tension
pneumothorax.
Characteristics: Impaired blood flow due to mechanical obstruction.

COMMON SIGNS AND SYMPTOMS OF SHOCK

 Hypotension (Low Blood Pressure): Blood pressure drops significantly below normal
levels.
 Tachycardia (Rapid Heart Rate): The heart beats faster to compensate for reduced
blood flow.
 Cool and Clammy Skin: The body tries to conserve blood for vital organs, diverting it
away from the skin.
 Weak or Rapid Pulse: An attempt to maintain cardiac output.
 Altered Mental Status: Confusion, restlessness, or unconsciousness.
 Shallow or Rapid Breathing: The body tries to increase oxygen intake.

DEHYDRATION
Dehydration occurs when the body loses more fluids than it takes in, leading to an
insufficient amount of water to maintain normal bodily functions. Water is essential for
various physiological processes, and when the body doesn't have enough water, it can
result in dehydration. Causes of dehydration include inadequate fluid intake, excessive
fluid loss, or a combination of both.

CAUSES OF DEHYDRATION
Inadequate Fluid Intake
 Not drinking enough water, especially in hot weather or during physical activity.

 Inability to drink water due to illness, nausea, or difficulty swallowing.

Excessive Fluid Loss

 Vomiting and Diarrhea: Common causes of rapid fluid loss.

36 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Excessive Sweating: Especially in hot and humid conditions or during intense physical

activity.
 Fever: Elevated body temperature can increase fluid requirements.

Medical Conditions:
 Certain medical conditions, such as diabetes or kidney disorders, can contribute to

increased fluid loss.

SIGNS AND SYMPTOMS OF DEHYDRATION

 Thirst: An early sign that the body needs more fluids.
 Dark Urine: Concentrated urine with a darker color than usual.
 Reduced Urination: Decreased frequency of urination.
 Dry Mouth and Dry Skin: Insufficient moisture in the mouth and on the skin.
 Fatigue and Weakness: Lack of fluids can lead to decreased energy levels.
 Dizziness or Lightheadedness: Due to a drop in blood pressure.
 Sunken Eyes: A visible sign of dehydration, especially in children.
 Rapid Heartbeat and Breathing: The body tries to compensate for reduced blood
volume.
Mild Dehydration:
 Thirst and dry mouth.

 Dark yellow urine.

 Fatigue.

Moderate Dehydration:
 Increased heart rate.

 Sunken eyes.

 Dry, cool skin.

 Decreased urine output.

Severe Dehydration:
 Very dark urine or absence of urine.

 Rapid breathing and heart rate.

 Confusion or irritability.

 Fainting.

37 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 ELECTROLYTE IMBALANCES

Electrolyte balance is crucial for maintaining the proper functioning of cells, tissues, and
organs in the human body. Electrolytes are electrically charged minerals, including
sodium (Na+), potassium (K+), chloride (Cl-), calcium (Ca2+), magnesium (Mg2+),
phosphate (HPO4^2-), and bicarbonate (HCO3-). These electrolytes play key roles in
various physiological processes, such as nerve impulse transmission, muscle
contraction, and maintaining fluid balance.

SODIUM IMBALANCES
Normal Range: 135 to 145 milliequivalents per liter (mEq/L)
Hyponatremia (Low Sodium)
Causes: Excessive sweating, vomiting, diarrhea, kidney disorders, certain medications,
or excessive water intake without adequate electrolyte intake.
Effects: Nausea, headache, confusion, seizures, and in severe cases, it can lead to coma
or death.
Hypernatremia (High Sodium)
Causes: Dehydration, inadequate water intake, excessive sodium intake, certain medical
conditions.
Effects: Thirst, altered mental status, seizures, and, in severe cases, it can lead to coma
or death.

POTASSIUM IMBALANCES
Normal Range: 3.5 to 5.0 milliequivalents per liter (mEq/L)
Hypokalemia (Low Potassium)
Causes: Diarrhea, vomiting, excessive use of diuretics, certain kidney disorders, and
certain medications.
Effects: Weakness, muscle cramps, irregular heartbeat (arrhythmias), and, in severe
cases, paralysis.
Hyperkalemia (High Potassium)
Causes: Kidney dysfunction, certain medications, excessive potassium intake, severe
tissue injury.
Effects: Muscle weakness, numbness, tingling, and, in severe cases, it can lead to
cardiac arrest.

38 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CALCIUM IMBALANCES
Normal Range: 8.5 to 10.5 milligrams per deciliter (mg/dL)
Hypocalcemia (Low Calcium)
Causes: Vitamin D deficiency, certain medications, kidney disorders,
hypoparathyroidism.
Effects: Muscle spasms, numbness, tingling, and, in severe cases, it can lead to seizures.
Hypercalcemia (High Calcium)
Causes: Hyperparathyroidism, certain cancers, excessive calcium supplements.
Effects: Constipation, excessive thirst, confusion, and, in severe cases, it can lead to
kidney stones or cardiac arrhythmias.

MAGNESIUM IMBALANCES
Normal Range: 1.7 to 2.2 milligrams per deciliter (mg/dL)
Hypomagnesemia (Low Magnesium)
Causes: Malnutrition, alcoholism, certain medications, gastrointestinal disorders.
Effects: Muscle weakness, tremors, seizures, and, in severe cases, it can lead to cardiac
arrhythmias.
Hypermagnesemia (High Magnesium)
Causes: Kidney dysfunction, excessive magnesium intake.
Effects: Nausea, weakness, confusion, and, in severe cases, it can lead to respiratory and
cardiac arrest.

PHOSPHATE IMBALANCES
Normal Range: 2.5 to 4.5 milligrams per deciliter (mg/dL)
Hypophosphatemia (Low Phosphate)
Causes: Malnutrition, alcoholism, certain medications, respiratory alkalosis.
Effects: Muscle weakness, respiratory failure, and, in severe cases, it can lead to heart
failure.
Hyperphosphatemia (High Phosphate)
Causes: Kidney dysfunction, certain medications.
Effects: Muscle cramps, itching, and, in severe cases, it can lead to calcification of soft
tissues.

39 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 SPECIAL
PATHOLOGY

40 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PULMONARY TUBERCULOSIS

Granulomatous inflammation of the respiratory tract caused by Mycobacterium

tuberculosis is called Pulmonary tuberculosis.
Causative organism: Mycobacterium tuberculosis/ Tubercle bacilli/ Koch’s bacillus.
Mycobacterium bacilli are slender, straight/curved rods, non-motile, non-capsulated,
non-sporing, acid fast and Gram positive. Presence of wax/mycolic acid around the
bacterial cell gives integrity to the cell.

RISK FACTORS
 Living or residing in overcrowded areas.
 Malnutrition
 Substance abuse
 Consumption of alcohol
 Cigarette smoking
 HIV infection
 Diabetes mellitus
 Kidney diseases
 Organ transplant individuals
 Immuno suppression therapy
 Steroid therapy

Mode of transmission: Inhalation and Spread by aerosol droplets (cough, sneeze, speak,
sing and spit)

PATHOGENESIS

Due to etiological/risk factors

Inhalation of airborne droplets containing Mycobacterium tuberculosis

Mycobacterium tuberculi enters the respiratory tract

Travels through the respiratory tract and reach to the alveoli and distant airways

41 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

On reaching the lung the antigen from tubercle bacillus reaches draining lymph nodes
and is presented to T cells which produce cytokines

Cytokines cause development of activated macrophages

Engulfment of Mycobacterium tuberculosis by activated macrophages

Tubercle bacilli resist intracellular killing

Replication of Mycobacterium tuberculosis inside the macrophages

Bursting of cells and release of bacilli

Initial lesion or primary original site of infection is called Ghon focus

Bacilli may spread or migrate to other tissues by lymphatogenous dissemination

T-cell activation and initiation of cell mediated immunity

Migration of activated T-cell

Macrophages, T-lymphocytes, B-lymphocytes and fibroblasts aggregate to form hard

tubercle or Granuloma.

Granuloma

Peripheral development of fibrous tissue Containment of Mycobacterium

and the central area undergoes caseation tuberculosis
necrosis
Bacteria are not eliminated from
Liquefaction of granuloma granuloma and become dormant

Primary tuberculosis Latent tuberculosis

42 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Presentation of clinical symptoms Reactivation of primary lesion(Endogenous)

Chronic tissue lesions

Caseous necrosis
Formation of cavities
Rupture of blood vessels
Tubercle bacilli enter into the blood and
spread to many organs

Extrapulmonary tuberculosis

CLINICAL FEATURES

 Coughing
 Productive cough with mucus and blood
 Chest pain
 Weight loss
 Fatigue
 Fever
 Night sweat
 Chills
 Anorexia
 Hemoptysis
 Malaise

Miliary tuberculosis is a severe form of tuberculosis (TB) caused by the bacterium

Mycobacterium tuberculosis. Miliary TB is characterized by the widespread
dissemination of the bacteria throughout the body, leading to the formation of tiny
granulomas (small, round nodules) in various organs and tissues, resembling millet
seeds in appearance. These granulomas can affect multiple organs, including the lungs,
liver, spleen, kidneys, bone marrow, and lymph nodes.

43 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 BRONCHITIS

Inflammation and excessive mucus production in the bronchi and bronchioles called
bronchitis and bronchiolitis.

CAUSES AND RISK FACTORS

 Air pollution
 Viral Infections: Rhinoviruses and adenoviruses
 Bacterial infections: Bordetella pertussis and Mycoplasma pneumoniae.
 Irritants: Tobacco smoke, air pollution, dust and chemical fumes.
 Environmental factors: Changes in weather-cold and damp conditions.
 Occupational exposure to chemicals( cotton mills, mines and cracker industries)
 Long-term exposure to lung irritants: Industrial dust.
 Respiratory Infections: Frequent respiratory infections, especially during childhood,
can increase the risk of chronic bronchitis in adulthood.
 Genetics: Genetic deficiency in a protein called alpha-1 antitrypsin.
 Age: Young children and the elderly are more susceptible.
 Weakened immune system: HIV/AIDS, chemotherapy and chronic illnesses.
 Gastroesophageal reflux disease (GERD): Stomach acid entering the airways.
 Cold and flu season

PATHOGENESIS

Due to etiological and risk factors

Over production and hyper secretion of mucus by goblet cells

Epithelial lining releases inflammatory chemical mediators

Mucus membrane become hyperemic and edematous

44 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Luminal obstruction of small airway and obstruction to air flow

Severe cough with secretion of mucus and wheezing

CLINICAL FEATURES

 Productive cough
 Gray/yellow colored sputum
 Dyspnea
 Use of accessory muscles for breathing
 Tachypnea
 Wheezing
 Pulmonary hypertension
 Pedal edema
 Weight gain

45 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PLEURAL EFFUSION

An abnormal excessive accumulation of fluid in pleural space or pleural cavity is called

Pleural effusion.

Excessive fluid accumulation between the two pleural layers(parietal and visceral ) is
called pleural effusion.

CAUSES

 Increased hydrostatic pressure

 Decreased oncotic pressure
 Decresed lymphatic drainage
 Increased capillary permeability
 Increased production of pleural fluid
 Decreased reabsorption of fluid
 Infection and inflammation of the pleural membranes
 Atelectasis

PATHOGENESIS

 Pleura is a thin membrane that lines the surface of the lungs and inside of the chest
wall.
 Pleura fluid is a clear fluid in the pleural cavity which lubricates and prevents friction.
 Pleural fluid is secreted by the parietal layer of the pleura.
 Pleural cavity contains 15ml of pleural fluid.
 Normal level is maintained by balance between its production and removal from the
pleural cavity.
 Hydrothorax : Collection of clear Serous fluid.
 Hemothorax : Collection of Blood.
 Chylothorax : Collection of Chyle.
 Pyothorax : Collection of Pus.

46 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Due to etiological factors

Imbalance between fluid production and fluid removal in the pleural space

Excessive accumulation of fluid in the pleural cavity

Narrowed space for lung expansion

Altered level of oxygenation

Exertion on physical activities (activity intolerance)

MECHANISM

Transudative pleural effusion: Pleural effusion is caused by systemic factors that alter
the pleural equilibrium. Filtrate of blood plasma in the pleural cavity without the
changes of endothelial permeability.
Systemic factors: Increased hydrostatic pressure and decreased oncotic pressure.
Examples : Heart failure
Renal failure
Hepatic failure

Exudative pleural effusion: Pleural effusion caused by local factors that influence the
formation and absorption of pleural fluid. Collection of fluid with cells and other
components of blood associated with increased vascular permeability.
Local factors: Bacterial and viral infections

47 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CLINICAL FEATURES
 Dullness on percussion
 Tachypnea (Increased respiration rate)
 Dyspnea (Difficulty in respiration)
 Chest pain on breathing
 Sweating
 Non-productive cough
 Shortness of breath
 Stiffness of lungs

48 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PNEUMONIA

Acute inflammation of lung parenchyma distal to the terminal bronchioles, comprising of

respiratory bronchioles, alveolar ducts and alveoli is called Pneumonia.

ETIOLOGY AND RISK FACTORS

 Immunodeficiency status
 Impaired alveolar macrophage function
 Unconsciousness
 Depressed cough reflex
 Impaired mucociliary clearance
 Viral infections (cytomegalo virus)
 Hospital acquired or nosocomial infections
 Bacterial infections
 Cigarette smoking
 Cystic fibrosis
 Air pollutants
 Endotracheal intubation
 Malnutrition
 Prolonged bed rest and immobility
 Aspiration of liquids and foreign bodies
 Gastroesophageal reflux disease

PATHOGENESIS
Due to etiological/ risk factors

Inhalation of pathogens in air droplets/

Aspiration of infected secretions/
Aspiration of gastric contents/
Hematogenous spread

Inflammation of the parenchyma of the lungs distal to terminal bronchioles

49 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Alveoli fills with exudates Mucosal edema and airway obstruction

Interferes with diffusion of Lack of ventilation to alveolar sacs

oxygen(O2) & carbon dioxide(CO2)

Hypoxia and retention of carbon dioxide

Respiratory acidosis

CLASSIFICATION OF PNEUMONIA
Histopathologically pneumonia is classified based of the lung area involved.
Bronchopneumonia
 Descending infection of the respiratory tract involves bronchial tree.
 It starts around the bronchi and spreads into lower respiratory regions.
 Bronchial tree of the lower lobes are usually involved.
 Patchy areas of consolidation (neutrophils collection) found.
 Patchy infiltrates and multiple small, discrete areas of consolidation throughout the
lungs.
 One or both sides are involved(unilateral or bilateral)

Lobar pneumonia
 Primarily affects one or more entire lobes of a lung.
 The infection is usually confined to a specific lobe or lobes.
 Lobar pneumonia is typically caused by a single microorganism.
 More abrupt onset of symptoms, including high fever andpleuritic chest pain
 It results in a more consolidated and localized appearance on imaging
 Acute exudative type of secretions
 It is limited by anatomic boundaries.

STAGES OF LOBAR PNEUMONIA

 Congestion: The affected lobe is heavy and characterized by vascular engorgement,
intra alveolar edema and collection of neutrophils.

50 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Red hepatisation: The lung develops a liver like consistency characterized by alveolar
spaces is packed with RBCs, neutrophils and fibrin. Affected lung is red-pink,
granular, dry and airless.
 Grey hepatisation: The RBCs are lysed but the exudates persist in the alveoli. This
results in grey lung
 Resolution or restoration: exudates are enzymatically digested to produce a granular
semifluid material that is ingested by the macrophages. It may be coughed up and
restores aeration.

CLINICAL FEATURES
 Fever
 Chills
 Sweating
 Productive cough
 Chest pain
 Fatigue
 Tachypnea
 Dyspnea
 Hemoptysis
 Headache
 Cracking sounds
 Unequal chest movements

51 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 LUNG ABSCESS
A lung abscess is a localized collection of pus within the lung tissue that leads to the
formation of a cavity or necrotic area. It is typically caused by an infection, and it can
result in a loss of lung tissue function.

ETIOLOGY AND RISK FACTORS

 Bacterial Infection: Common pathogens include Streptococcus pneumoniae,
Staphylococcus aureus, and anaerobic bacteria.
 Aspiration: Aspiration of foreign material, such as food or vomit, into the lungs.
 Immunosuppression: HIV/AIDS or receiving immunosuppressive medications.
 Smoking: Smoking damages the respiratory tract and impairs the body's ability to
clear infections.
 Alcohol Abuse: Excessive alcohol consumption can weaken the immune system.
 Chronic Lung Disease: Chronic obstructive pulmonary disease (COPD).

ETIOPATHOGENESIS
Infection and Inflammation: Lung abscesses usually start as an infection within the
lung tissue. Bacteria multiply and trigger an inflammatory response, leading to tissue
destruction.
Cavity Formation: Over time, as the immune system attempts to contain the infection,
an area of necrosis forms, and a cavity filled with pus develops.
Drainage and Resolution: With appropriate treatment (antibiotics and sometimes
drainage procedures), the abscess can resolve by eliminating the infection and promoting
healing.

CLINICAL FEATURES:
 Fever

 Cough

 Chest

 Shortness of breath

 Weight loss

 Bad breath (Halitosis)

 Fatigue

52 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 EMPHYSEMA

Emphysema is a chronic lung disease characterized by the gradual destruction of the air
sacs (alveoli) in the lungs. This damage results in the enlargement of the air spaces and
a loss of lung elasticity, leading to difficulty in exhaling air and impaired lung function.

CAUSES

 Smoking: Cigarette smoking is the leading cause of emphysema. The harmful

chemicals in tobacco smoke irritate and inflame the airways and alveoli, leading to
tissue damage over time.
 Occupational exposures: Some jobs involve exposure to dust, chemicals, or fumes
that can contribute to the development of emphysema. Examples include coal mining,
construction, and textile work.
 Alpha-1 antitrypsin deficiency: This is a rare genetic condition in which the body
does not produce enough of a protein (alpha-1 antitrypsin) that protects the lungs.
 Aging: The risk of emphysema increases with age.
 Air Pollution: Long-term exposure to high levels of air pollution, both indoors and
outdoors, can contribute to lung damage and emphysema.

PATHOLOGY (MECHANISM)

The pathological changes in emphysema include:

 Alveolar Destruction: In emphysema, the alveoli, which are tiny air sacs responsible
for gas exchange in the lungs, become damaged and lose their elasticity.

 Enlarged Air Spaces: As the alveolar walls break down, adjacent air spaces merge to
form larger, less efficient air sacs.

 Loss of Elasticity: The destruction of elastin fibers in the lung tissue results in
decreased lung elasticity, making it difficult for the lungs to recoil during exhalation.

 Air Trapping: Emphysematous lungs have difficulty expelling air, leading to trapped
air in the lungs after exhalation, which reduces the efficiency of fresh air intake.

CLINICAL FEATURES (SIGNS AND SYMPTOMS)

 Dyspnea (Shortness of Breath): Progressive breathlessness is a hallmark symptom,

particularly during physical exertion. As the disease advances, it may also occur at
rest.

 Chronic cough: A persistent cough is common in emphysema, often accompanied by

the production of small amounts of mucus.
53 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Wheezing: Wheezing, or high-pitched whistling sounds during breathing, can occur
due to narrowed airways.

 Chest Tightness: Some individuals with emphysema may experience a sensation of

chest tightness or discomfort.

 Reduced exercise tolerance: As lung function declines, people with emphysema may
become less able to engage in physical activities.

 Barrel chest: Over time, the chest may become barrel-shaped due to the increased air
trapped in the lungs.

 Pursed-lip breathing: Some individuals adopt a pursed-lip breathing pattern, where

they exhale slowly through pursed lips to reduce airway resistance.

 Weight loss and fatigue: Severe emphysema can lead to weight loss and fatigue due
to the increased energy expenditure required for breathing.

54 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 BRONCHIECTASIS

Permanent dilatation of bronchi and bronchioles secondary to destruction of smooth

muscles and elastic tissues is called Bronchiectasis.

Bronchiectasis is the permanent and abnormal dilatation of one or more large bronchi of
the bronchial tree.

CAUSES AND RISK FACTORS

 Cystic fibrosis
 Immunodeficiency disorder (HIV & AIDS)
 Allergic bronchopulmonary aspergillosis
 Primary ciliary dyskinesia
 Chronic pulmonary aspiration (inhalation of foreign body)
 Connective tissue diseases
 Pneumonia
 Tuberculosis
 Air pollution

PATHOGENESIS
Due to etiological/risk factors
Etiological factors
Infection and inflammation Inflammation

Loss of supporting
Recruitment of inflammatory cells structures

Thick
Release of inflammatory cytokines sputum/obstruction

Bronchial wall
Destruction of mucociliary and permanently dilated
Cartilaginous supporting structures and distorted &
twisted

Loss of ventilator function

Impairment of mucociliary clearance

55 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Retention of sputum

Colonization and recurrent infections

Pneumonia

TYPES OF BRONCHIECTASIS

Cylindrical/tubular: Luminal
dilatation is uniform and the wall
thickening is smooth and failure of
normal tapering of the bronchi.

Saccular: Severely dilated and the

bronchi end blindly in a dilated
thick walled cyst.

Varicose: Altering areas of

luminal dilatation and constriction
creating a beaded appearance and
wall thickening is irregular

CLINICAL FEATURES
 Large quantities of foul smelling sputum
 Chronic cough
 Hemoptysis
 Recurrent pneumonia
 Systemic manifestations (fever, chills, weight loss)
 Dyspnea/wheezing

56 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 BRONCHIAL ASTHMA

Chronic inflammatory disease of the airways that causes airway hyper-responsiveness,

mucosal edema and excessive mucus production is called Bronchial asthma.
It is an episodic airway obstruction with reversible bronchial constriction manifested by
coughing, dyspnea and wheezing.
Increased responsiveness of the trachea and bronchi to variety of stimuli resulting in
narrowing of airway passages is called Asthma.

ETIOLOGY AND RISK FACTORS

 Genetic factors: Familial history

 Allergies: Common allergens include pollen, dust mites, pet dander, mold, and certain
foods.
 Environmental allergens: Air pollution, smoke, perfumes and strong odors.
 Airway irritants: Cold, heat and weather changes.
 Respiratory infections: Viral respiratory infections(Respiratory syncytial virus)
 Childhood respiratory infections: Early-life exposure to infections and certain
microbes may influence the development of asthma.
 Exposure to tobacco smoke: Both maternal smoking during pregnancy and exposure
to secondhand smoke in early childhood.
 Premature Birth: Babies born prematurely are at a higher risk of developing asthma
because their lungs may not have fully developed.
 Low Birth Weight
 Obesity
 Occupational Exposures: Exposure to workplace irritants or allergens, such as
chemicals, dust, or fumes, can contribute to the development of occupational asthma.
 Physical Activity: Some individuals experience exercise-induced bronchoconstriction,
also known as exercise-induced asthma, during or after physical activity.
 Gastroesophageal Reflux Disease (GERD): Chronic acid reflux
 Stress and Emotional Factors: Stress and strong emotions
 Hormonal changes: Hormonal fluctuations-during pregnancy or menstruation

57 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Medications: Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-blockers.
Allergen sensitization: Developing sensitivity to specific allergens over time can
increase the risk of asthma.
 Inhalation of Irritants: Strong odors, air pollution, or chemical fumes.

PATHOGENESIS

ALLERGIC ASTHMA (EXTRINSIC ASTHMA)

Due to etiological/risk factors

(Pollen, Animal dander, House dust, Food additives, Drugs and medications)

Sensitization and production of IgE antibodies

IgE antibodies attach on the mast cells

Re-exposure to similar allergens or antigens

Trigger mast cell degranulation in the lungs releasing histamine and prostaglandins

Histamine attaches to receptor sites in the larger bronchi, causing irritation,

inflammation and edema

Airway inflammation

Hyper secretion of mucus Airway muscle constriction Swelling of bronchial

membranes

Narrowing of breathing or airway passages

Wheezing, cough, shortness of breath and tightness in the chest

58 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Reduced airflow and gas exchange

Hypoxemia

Respiratory acidosis

NON ALLERGIC ASTHMA (INTRINSIC ASTHMA)

Due to etiological/risk factors

(Stress/emotional upset, physical exercises, inflammation, viral infections and weather

changes)

Narrowed airway passages

Decreased oxygenation

Hypoxemia

Respiratory acidosis

CLINICAL FEATURES

 Shortness of breath
 Recurrent wheezing: High-pitched whistling sound during breathing, especially
during exhalation. Wheezing is caused by the narrowing of the airways.
 Cough: Chronic cough, particularly at night or early in the morning.
 Dyspnea
 Chest pain
 Chest Tightness
 Exacerbations (Asthma Attacks): The airways become significantly narrowed, leading
to severe breathing difficulties.
 Nocturnal symptoms: Trouble sleeping
59 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Allergic symptoms: Sneezing, runny nose, and itchy or watery eyes.
 Respiratory rate increase: To compensate for the reduced airflow by breathing more
rapidly and shallowly.
 Use of accessory muscles: Use their neck and chest muscles to help with breathing.

STATUS ASTHMATICUS: Asthmatic attack occurs quickly and frequently without

recovery and does not respond to regular treatment. It represents the most severe form
of an asthma exacerbation and is associated with a high risk of respiratory failure.

60 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung disease characterized
by persistent airflow limitation that is not fully reversible.

ETIOLOGY (CAUSES)
Smoking: It irritates and damages the airways and air sacs in the lungs over time.
Environmental Factors: Exposure to indoor and outdoor air pollution, workplace dust
and chemicals, and secondhand smoke.
Genetics: Alpha-1 antitrypsin deficiency.
Recurrent lung infections: Frequent respiratory infections during childhood.
Aging: The risk of COPD increases with age.
Occupational exposures: Mining, construction, and agriculture, involve exposure to
respiratory irritants and can increase COPD risk.

PATHOGENESIS (DEVELOPMENT)
 Inflammatory Response: The initial insult, often from cigarette smoke or other
irritants, triggers an inflammatory response in the airways and lung tissue.
 Chronic Inflammation: Over time, chronic inflammation leads to structural changes
in the lungs, including thickening and narrowing of airways, increased mucus
production, and destruction of lung tissue.
 Airway Obstruction: These changes result in reduced airflow, leading to airflow
limitation that is characteristic of COPD.
 Emphysema development: In emphysema, the walls of the air sacs (alveoli) in the
lungs become damaged and lose their elasticity, making it difficult for the lungs to
empty air properly.
 Chronic Bronchitis: In chronic bronchitis, the airways become inflamed and
narrowed, leading to chronic cough and increased mucus production.

CLINICAL FEATURES (SIGNS AND SYMPTOMS)

 Chronic cough
 Excessive mucus production
 Shortness of breath (Dyspnea)
 Wheezing: Wheezing or high-pitched whistling sounds when breathing.
61 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Chest tightness
 Frequent respiratory infections
 Reduced exercise tolerance
 Fatigue
 Weight loss
 Cyanosis

62 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 LUNG TUMORS
Lung tumors refer to abnormal growths of cells in the lungs. These growths can be
benign (non-cancerous) or malignant (cancerous). Malignant lung tumors are commonly
referred to as lung cancer.

CAUSES AND RISK FACTORS

The exact causes of lung tumors, especially lung cancer, are complex and often involve a
combination of genetic and environmental factors. Key risk factors include:
 Tobacco Smoke: Cigarette smoking is the leading cause of lung cancer. The harmful
chemicals in tobacco smoke can damage lung cells and DNA, leading to the
development of cancerous tumors.
 Secondhand Smoke: Exposure to secondhand smoke (passive smoking) is a
significant risk factor, especially for non-smokers who live or work with smokers.
 Radon Gas: Radon is a naturally occurring radioactive gas that can seep into homes
and buildings. Prolonged exposure to high levels of radon is a known risk factor for
lung cancer.
 Occupational Exposures: Some occupations involve exposure to carcinogens such as
asbestos, arsenic, and certain chemicals, which can increase the risk of lung cancer.
 Family History: Individuals with a family history of lung cancer may have a genetic
predisposition to the disease.
 Air Pollution: Long-term exposure to high levels of outdoor air pollution, including
fine particulate matter and carcinogens, is associated with an increased risk of lung
cancer.
 Radiation Exposure: Previous radiation therapy to the chest, such as for the
treatment of other cancers, can increase the risk of developing lung cancer.

TYPES OF LUNG TUMORS

There are two primary types of lung tumors:
1. Benign Lung Tumors: These are non-cancerous growths that do not spread to other
parts of the body. Common benign lung tumors include hamartomas and adenomas.
They are typically surgically removed if they cause symptoms or complications.
2. Malignant Lung Tumors (Lung Cancer): Lung cancer is the most common malignant
lung tumor. It can be further categorized into two main types:
63 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
  Non-Small Cell Lung Cancer (NSCLC): NSCLC includes several subtypes,
such as adenocarcinoma, squamous cell carcinoma, and large cell
carcinoma. These cancers tend to grow more slowly and are often diagnosed
at a later stage.
 Small Cell Lung Cancer (SCLC): SCLC is a highly aggressive type of lung
cancer that tends to grow and spread rapidly.

PATHOLOGY (MECHANISM)
In lung cancer, the pathological process involves uncontrolled cell growth and the
formation of malignant tumors. This typically occurs in the bronchial epithelial cells
lining the airways or in the lung parenchyma. The sequence of events is as follows:
1. Metaplasia of the bronchial epithelium: Pseudostratified columnar epithelium to
squamous epithelium.
2. Mild, moderate and severe dysplasia
3. Carcinoma in situ
4. Invasive squamous cell carcinoma (irreversible stage)

CLINICAL FEATURES (SIGNS AND SYMPTOMS)

The clinical presentation of lung tumors, especially lung cancer, can vary widely but may
include:
 Persistent Cough: A chronic cough that may produce blood or sputum.
 Dyspnea (Shortness of Breath): Breathlessness, especially with physical activity.
 Chest Pain: Discomfort or pain in the chest, particularly with deep breathing or
coughing.
 Hoarseness: Changes in the voice.
 Weight Loss: Unexplained weight loss.
 Fatigue: Generalized weakness and fatigue.
 Wheezing: High-pitched whistling sounds when breathing.
 Recurrent Respiratory Infections: Frequent infections or pneumonia.
 Bone Pain: In advanced stages, lung cancer may spread to the bones, leading to bone
pain.
 Neurological Symptoms: If cancer metastasizes to the brain, it can cause symptoms
like headaches, seizures, or neurological deficits.

64 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PERICARDIAL EFFUSION
Accumulation of excess fluid in the pericardial sac surrounding the heart is called
pericardial effusion.

ETIOLOGY AND RISK FACTORS

 Autoimmune disorders
 Cancer of the pericardium
 Spread of cancer (metastasis)
 Chest trauma: blunt or penetrating
 Inflammation: inflammatory conditions like rheumatoid arthritis & systemic lupus
erythematosus
 Hypothyroidism
 Exposure to toxins
 Infections: Viral, bacterial infections and fungal infections.
 Kidney diseases: Kidney failure can cause fluid retention
 Medications: hydralazine and isoniazid
 Radiation therapy: Damages the pericardium

65 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
Due to etiological factors

Blood or fluid fills the pericardial space

Extreme pressure on the heart

Prevention of expansion of ventricles of the heart ( contraction and relaxation)

Decreased stroke volume and cardiac output

Increased venous pressure (causes pulmonary congestion and inturn leads to rales)
Increase arterial pressure

Decreased oxygen supply

Organ failure, shock and death

Pericardial effusion occurs when excess fluid accumulates in the pericardial sac. This
can happen due to increased fluid production, decreased fluid absorption, or a
combination of both. The excess fluid compresses the heart, limiting its ability to fill
and pump blood effectively. This can lead to a life-threatening condition known as
cardiac tamponade, where the pressure on the heart impairs its function.
Cardiac tampanode: compression of the heart by fluid collecting in the sac
surrounding the heart.

CLINICAL FEATURES

 Dyspnea  Hiccups  Palpitations

 Chest discomfort  Tachycardia  Fainting/syncope
 Cough  Hypotension  unconsciousness
 Fatigue  Muffled heart sounds  Anxiety and
 Hoarseness  Elevated jugular venous pressure confusion

66 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 RHEUMATIC HEART DISEASE
An acute immunologically mediated multisystem inflammatory disease that occurs
following pharyngitis caused by Group A beta hemolytic streptococci is called rheumatic
heart disease.

CAUSES AND RISK FACTORS

 Age: RHD is more common in children and young adults.
 Upper respiratory tract infection
 Streptococcal infection
 Excessive use of antibiotics
 Poor nutrition
 Low socioeconomic status
 Poor hygiene practices
 Overcrowded living conditions
 lack of access to healthcare

PATHOPHYSIOLOGY
Due to etiological factors

Exposure to Group A beta hemolytic streptococci

Infection
Pharyngitis (Throat infection)

Lymphadenopathy

Spread to blood stream (Hematogenous)

Rheumatic fever

Infectious materials in the endocardium and valves of the heart

67 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

Antibodies produced in the body act against the normal tissues of the endocardium and
valves of the heart

Damage of the endocardium and valves

Inflammatory process

Endocarditis and then Pancarditis

CLINICAL FEATURES
Major Criteria/Symptoms
 Carditis: Inflammation of the heart, which may involve different parts of the heart,
including the endocardium, myocardium, and pericardium.
 Polyarthritis: Acute, migratory arthritis involving multiple joints.
 Chorea: Also known as Sydenham chorea, this is a movement disorder characterized
by sudden, purposeless, and involuntary movements.
 Erythema Marginatum: This is a skin rash that appears as pink rings with clear
centers.
 Subcutaneous Nodules: Painful, small lumps or nodules under the skin are another
less common major criterion.

Minor Criteria/Symptoms
 Fever: Presence of a fever.
 Arthralgia: Joint pain without swelling.
 Elevated Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
 Prolonged PR interval: Prolonged PR interval on an electrocardiogram (ECG).

68 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 INFECTIVE ENDOCARDITIS
Infective endocarditis is a serious infection that affects the inner lining of the heart
chambers and heart valves. It is typically caused by the colonization and growth of
bacteria or other microorganisms on the heart valves or the endocardium (the inner
lining of the heart).

CAUSES AND RISK FACTORS

 Bacterial infections: Enterococcus, streptococci and staphylococci bacteria.
 Fungal infections: Fungal infections from Candida and Aspergillus species.
 Dental procedures: Dental procedures that cause bacteremia.
 IV drug use: Intravenous drug users.
 Heart valve abnormalities: People with pre-existing heart valve abnormalities,
congenital heart defects, or prosthetic heart valves.
 Immune system disorders: HIV/AIDS or immunosuppressive therapy.
 Indwelling catheters: Hemodialysis.

ETIOPATHOGENESIS
Endothelial Damage: Initially, there is damage to the endocardium or heart valves,
which can result from factors like turbulent blood flow, congenital heart defects, or prior
heart surgery.
Bacterial Entry: Bacteria from various sources, such as the bloodstream or oral cavity,
can enter the bloodstream during activities like dental procedures or intravenous drug
use.
Adherence and Colonization: Bacteria adhere to the damaged heart valves or
endocardium and form colonies, known as vegetations. These vegetations can grow in
size and may contain fibrin, platelets, and bacteria.
Infection and Inflammation: The presence of bacteria triggers an immune response,
leading to inflammation and damage to the heart tissue. This can result in valve
dysfunction, embolization (the release of infected material into the bloodstream), and
other complications.

69 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CLINICAL FEATURES
 Fever: A persistent fever is a hallmark symptom.
 Heart murmur: Abnormal heart sounds, or heart murmurs.
 Fatigue and weakness
 Joint Pain: Joint pain and muscle pain can occur.
 Embolic complications: Small pieces of infected material can break off and travel to
other parts of the body, causing symptoms like stroke, lung infections, or organ
damage.
 Janeway Lesions and Osler's Nodes: These are skin manifestations of IE and are
painful red spots on the palms and soles (Osler's nodes) or painless hemorrhagic spots
on the skin (Janeway lesions).
 Petechiae: Tiny red or purple spots on the skin or mucous membranes may appear
due to small blood vessel hemorrhages.
 Nailbed Hemorrhages: Splinter hemorrhages under the fingernails may be visible.

70 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 ATHEROSCLEROSIS
Disease of large and medium sized muscular arteries characterized by endothelial
dysfunction, vascular inflammation and build up of lipids, cholesterol and cellular debris
within the intima (inner layer) of the vessel wall is called Atherosclerosis.

Process of formation of intimal lesions that protrude into vascular lumen

Formation of atheromatous plaque consists of a raised lesion with a soft, yellow core of
lipid covered by a firm, white fibrous cap is called atherosclerosis.

CAUSES AND RISK FACTORS

 Age: It is more commonly seen in middle-aged and older individuals.
 Gender: Men tend to be at a higher risk of atherosclerosis than women.
 Family history: genetic predisposition.
 High blood pressure (Hypertension): High blood pressure can damage arterial walls,
making them more susceptible to plaque formation.
 High cholesterol levels: Elevated levels of LDL cholesterol and low levels of high-
density lipoprotein (HDL) cholesterol are associated with a higher risk of
atherosclerosis.
 Smoking: Smoking is a major risk factor for atherosclerosis. It damages the
endothelium, promotes inflammation, and increases oxidative stress.
 Diabetes: Individuals with diabetes are at increased risk because high blood sugar
levels can damage blood vessels and accelerate atherosclerosis.
 Obesity: Excess body weight.
 Physical Inactivity: A sedentary lifestyle.
 Diet: A diet high in saturated and trans fats, as well as excessive salt intake.
 Stress: Chronic stress.
 Inflammatory Conditions: Rheumatoid arthritis.
 Substance Abuse: Cocaine and methamphetamine.
 Post menopausal state
 High carbohydrate intake
 Infections

71 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
Due to etiological/risk factors
Mechanical trauma (injury)
Hemodynamic forces (hypertension)
Chemical mechanisms (toxins, lipids and tobacco products)
Infections (viruses)

Endothelial injury

Adherence and aggregation of platelets

Platelets release mitogens at the site of expose subendothelial tissues

Proliferation of smooth muscle cells

Recruitment of blood cells and plasma LDL

Fatty streak formation

Intimal thickening and lipid accumulation

Plaque formation (fibrofatty tissue)

Impinge on the lumen

Pathological changes
Rupture, ulceration, erosion and obstruction
Hemorrhage
Atheroembolism and Aneurysm formation

Ischemia and hypoxia

Infarction and necrosis

72 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CLINICAL FEATURES
 Asymptomatic Stage: it often begins silently without any noticeable symptoms.
 Angina (Chest pain): atherosclerotic plaques partially block the coronary arteries that
supply blood to the heart muscle; it can result in chest pain or discomfort known as
angina.
 Myocardial infarction (Heart Attack): If an atherosclerotic plaque ruptures or a blood
clot forms at the site of a plaque, it can completely block a coronary artery, leading to
a heart attack. Symptoms include severe chest pain, shortness of breath, and other
signs of cardiac distress.
 Stroke: Atherosclerosis can affect the arteries in the brain, leading to a reduction in
blood flow or the formation of blood clots. This can result in a stroke, which may
cause sudden weakness, numbness, difficulty speaking, or loss of consciousness.
 Peripheral artery disease (PAD): Atherosclerosis can narrow or block arteries in the
legs and other peripheral regions, causing symptoms such as leg pain, cramping, and
poor wound healing. Severe cases can lead to tissue damage and even gangrene.
 Carotid artery disease: Atherosclerotic plaques in the carotid arteries, which supply
blood to the brain, can lead to transient ischemic attacks (TIAs) or strokes when blood
flow to the brain is compromised.
 Renal artery disease: Atherosclerosis in the renal arteries can cause high blood
pressure (hypertension) and impaired kidney function.
 Abdominal aortic aneurysm: Weakened areas in the abdominal aorta due to
atherosclerosis can lead to the development of an aneurysm.
 Claudication: This term refers to pain, cramping, or weakness in the legs during
physical activity due to reduced blood flow caused by atherosclerosis.
 Erectile dysfunction (ED): Atherosclerosis can affect the arteries in the pelvis,
contributing to erectile dysfunction in men.
 Chronic kidney disease (CKD): Long-term atherosclerotic changes in the renal arteries
can lead to progressive kidney damage and the development of chronic kidney disease.

73 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 ISCHEMIA AND INFARCTION
Ischemic Heart Disease (IHD) is the imbalance between myocardial oxygen supply and
demand, resulting in myocardial hypoxia and accumulation of waste metabolities.
Ischemia is an insufficient supply of blood to an organ due to a blocked artery.

TYPES OF ISCHEMIC HEART DISEASE

ISCHEMIC HEART DISEASE

Infarct effect Non infarct effect

Myocardial infarction Chronic ischemic heart disease
Angina pectoris

CAUSES AND RISK FACTORS

 Atherosclerosis: The primary cause of IHD is atherosclerosis, a condition where fatty

deposits, cholesterol, and other substances build up in the walls of the coronary
arteries, forming plaques that narrow and can eventually block the arteries.
 Age: The risk of IHD increases with age.

 Gender: Men are at higher risk than women, but the risk for women increases after

menopause.
 Family History: A family history of IHD increases the risk.

 Smoking: Smoking is a major risk factor for IHD.

 High Blood Pressure: Hypertension can damage the coronary arteries.

 High Cholesterol: Elevated levels of LDL (low-density lipoprotein) cholesterol can lead

to plaque formation.
 Diabetes: People with diabetes are at increased risk due to elevated blood sugar levels.

 Obesity: Excess body weight can contribute to the development of IHD.

 Physical Inactivity: A sedentary lifestyle is a risk factor.

 Stress: Chronic stress can contribute to IHD.

 Diet: A diet high in saturated fats and low in fruits and vegetables can increase the
risk.

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 PATHOGENESIS

 Atherosclerosis: The process begins with the accumulation of fatty deposits on the
inner walls of the coronary arteries.
 Plaque Formation: Over time, these deposits can become plaques, which can narrow
the arteries and reduce blood flow.
 Plaque Rupture: Plaques can rupture or develop blood clots (thrombosis) on their
surface.
 Obstruction: When a plaque ruptures or a blood clot forms, it can completely block
an artery, leading to an acute myocardial infarction (heart attack).

CLINICAL FEATURES
 Angina Pectoris: Chest pain or discomfort is the hallmark symptom of IHD. It
typically occurs during physical activity or emotional stress and is relieved by rest or
nitroglycerin.
 Acute Myocardial Infarction (Heart Attack): This occurs when a coronary artery is
completely blocked, causing the heart muscle to be deprived of oxygen and nutrients.
Symptoms include severe chest pain, shortness of breath, nausea, and cold sweats.
 Chronic Stable Angina: This is characterized by recurring episodes of chest pain with
a predictable pattern, often triggered by exertion and relieved by rest or medication.
 Silent Ischemia: Some individuals with IHD may not experience any symptoms, a
condition known as silent ischemia. It is often detected during medical tests or
monitoring.
 Heart Failure: Chronic IHD can weaken the heart muscle, leading to heart failure,
which results in symptoms like fatigue, swelling of the legs, and shortness of breath.
 Arrhythmias: IHD can disrupt the heart's electrical system, leading to abnormal heart
rhythms (arrhythmias).

75 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 MYOCARDIAL INFARCTION

Myocardial infarction is defined as a condition caused by reduced blood supply in a

coronary artery due to atherosclerosis and occlusion of an artery by an embolus and
thrombus.
Irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia is
called myocardial infarction.
Death of the part of the heart due to complete loss of blood supply is called heart
attack/myocardial infarction.

CAUSES AND RISK FACTORS:

Coronary Artery Blockage: The primary cause of a heart attack is the sudden and
complete blockage of a coronary artery, usually due to the rupture of an atherosclerotic
plaque and the formation of a blood clot at the site.
 Atherosclerosis: The buildup of fatty deposits in the coronary arteries.

 Age: The risk increases with age.

 Gender: Men are at higher risk than women.

 Family History: A family history of heart disease increases the risk.

 Smoking: Smoking is a major risk factor.

 High Blood Pressure: Hypertension contributes to arterial damage.

 High Cholesterol: Elevated LDL cholesterol levels increase the risk.

 Diabetes: Diabetes is a significant risk factor due to elevated blood sugar levels.

 Obesity: Excess body weight can contribute to heart disease.

 Physical Inactivity: A sedentary lifestyle increases the risk.

 Stress: Chronic stress can be a contributing factor.

 Drug abuse

 Alocohol consumption

PATHOGENESIS
Due to etiological/risk factors

Atherosclerosis (obstruction)
Arterial spasm (reversible obstruction)
Thrombus formation (occlusion)
76 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Ischemia (lack of blood supply)

Hypoxia (lack of oxygen supply)

Infarction (death of tissue cells)

Anaerobic glycolysis

Accumulation of lactic acid

Irritation of myocardial nerve fibres

Transmission of pain to entire myocardium

Pressurized heavy chest pain and radiation of pain towards shoulder and arm

Impaired left ventricular pumping function

Cardiac failure

CLINICAL FEATURES
 Chest Pain or Discomfort: This is the hallmark symptom of MI and is often described
as:
 Severe, crushing, or squeezing pain in the center of the chest.
 A sensation of pressure, fullness, or tightness in the chest.
 The pain may last for several minutes or more.
 Radiation of Pain: The chest pain may radiate to other parts of the upper body,
including:
 The left arm
 The shoulder
 The neck
 The jaw

77 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

  The back
 The stomach or epigastric area
 Shortness of Breath: Many people with MI experience difficulty breathing or
shortness of breath, often as a result of the heart's decreased ability to pump
effectively.
 Sweating: Profuse sweating, often described as "breaking out in a cold sweat," is
common during a heart attack.
 Nausea and Vomiting: Some individuals may feel nauseous or may vomit during a
heart attack.
 Weakness and Fatigue: A feeling of weakness or extreme fatigue can occur.
 Anxiety and Restlessness: People experiencing a heart attack may feel anxious,
restless, or agitated.
 Dizziness or Lightheadedness: Some individuals may become dizzy or lightheaded.
 Hypertension/hypotension
 Sleeplessness
 Arrhythmias
 ECG changes-ST segment elevation, T wave inversion and appearance of wide deep Q
waves
 Loss of Consciousness: In severe cases, loss of consciousness or fainting may occur.
 Atypical Symptoms: Some individuals, particularly women and older adults, may
have atypical symptoms such as:
 Unexplained fatigue
 Shortness of breath without chest pain
 Upper abdominal discomfort or indigestion-like symptoms
 Pain in the lower jaw or upper back

78 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 ANEURYSM
 An aneurysm is a condition characterized by an abnormal, localized dilation or
bulging of a blood vessel wall. This weakening and ballooning of the blood vessel can
occur in arteries or veins and may be caused by various factors.

 CAUSES
 Atherosclerosis: The buildup of plaque in arteries can weaken and damage the vessel
walls, increasing the risk of an aneurysm.
 Hypertension (High Blood Pressure): Prolonged high blood pressure can weaken
blood vessel walls and contribute to the development of an aneurysm.
 Infections: Infections, such as syphilis or mycotic infections, can weaken blood
vessel walls.
 Trauma: Physical injury or trauma, including blunt force or penetrating wounds, can
damage blood vessels and lead to aneurysms.
 Genetic Factors: Some individuals may have a genetic predisposition to developing
aneurysms, particularly conditions like Marfan syndrome and Ehlers-Danlos
syndrome.
 Congenital Factors: Aneurysms can also be present at birth (congenital).

 RISK FACTORS:
 Age: The risk of aneurysms increases with age.
 Family History: A family history of aneurysms may elevate the risk.
 Smoking: Smoking is a significant risk factor for the development and growth of
aneurysms.
 High Blood Pressure: Hypertension is a risk factor for aneurysm formation and
rupture.
 Atherosclerosis: The presence of atherosclerosis increases the risk of aneurysms.
 Gender: Some types of aneurysms are more common in men, while others are more
common in women.

79 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PATHOLOGY:
 The pathology of an aneurysm involves the weakening and stretching of the blood
vessel wall. This weakening may occur gradually over time or suddenly due to injury.
The key processes involved include:
 Weakening of the vessel wall: Factors like atherosclerosis, hypertension, or genetic
conditions can lead to the degradation of the structural integrity of the blood vessel
wall.
 Dilation and bulging: As the vessel wall weakens, it begins to dilate and bulge at the
affected site. This results in the formation of the aneurysm.
 Risk of rupture: Aneurysms can rupture, causing severe bleeding, which can be life-
threatening. The risk of rupture depends on the size, location, and type of aneurysm.

 CLINICAL FEATURES:
 The clinical features of an aneurysm can vary depending on its size, location, and
whether it has ruptured or not. Common clinical features may include:
 Asymptomatic: Small aneurysms may be asymptomatic and go unnoticed until they
are detected incidentally during imaging tests for other medical conditions.
 Pain: Some aneurysms, particularly larger ones or those near the surface, can cause
pain or discomfort.
 Palpable mass: In some cases, a pulsatile mass may be felt in the affected area.
 Symptoms of rupture: If an aneurysm ruptures, it can lead to severe symptoms,
such as:
1. Sudden, intense, and excruciating pain
2. Rapid drop in blood pressure
3. Rapid heart rate
4. Loss of consciousness
5. Signs of shock, including cold and clammy skin, confusion, and dizziness
 Neurological Symptoms: In the case of cerebral aneurysms, symptoms may include
severe headaches, vision problems, and neurological deficits if they press on nearby
brain structures.
 Other Specific Symptoms: Depending on the location of the aneurysm (e.g., aortic
aneurysm), it may cause specific symptoms related to the affected organ or vessel.
80 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 PEPTIC ULCER
Erosion of superficial layer of inner wall of stomach and other parts of GI tract due to
excessive secretion of HCL acid and pepsin activity is called peptic ulcer.
Break in the continuity of the mucous membrane of the alimentary tract due to acid-
pepsin release.
Peptic ulcers are the areas of degeneration and necrosis of gastrointestinal mucosa
exposed to acid peptic secretions.

CAUSES AND RISK FACTORS

 Psychological stress
 Helicobacter pylori (H. pylori) infection: This bacterium is a common cause of peptic
ulcers. It can weaken the protective mucous layer in the stomach and duodenum,
allowing stomach acid to damage the underlying tissue.
 Nonsteroidal anti-inflammatory drugs (NSAIDs): Regular use of NSAIDs, such as
aspirin, ibuprofen, or naproxen, can irritate the stomach lining and increase the risk
of developing ulcers.
 Excessive stomach acid production
 Smoking
 Alcohol consumption
 Physiological stress
 Shock
 Trauma
 Septicemia
 Burns
 Intracranial lesions
 Local irritants
 Beverages: Coffee and tea
 Irregular food habits
 Sleeplessness
 Hot and spicy food
 Food poisoning
 Poisoning

81 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
 Histologically the wall of the stomach has four layers: serosa, muscularis, submucosa
& mucosa. Serosa is the outermost layer made up of fibroconnective tissue.
Muscularis has three layers from outer to inner are longitudinal, circular and oblique.
Submucosa has a network of blood vessels, lymph vessels and nerves. Mucosa
consists of two layers. Superficial layer of the mucosa is composed of regular mucin
secreting tall columnar cells. Deep layer of the mucosa consists of four types of
glandular cells.
o Parietal cells/oxyntic cells secrete HCL acid
o Chief cells /peptic cells secrete Pepsin
o Mucin producing neck cells secrete mucous
o Endocrine G cells produce gastrin
 Secretory products of the gastric mucosa are the gastric juice and intrinsic factor
which is required for the absorption of vitamin B 12.
 Gastric secretion is regulated by following mechanisms
Cephalic phase: this stage is initiated by sight, smell, taste or thought of food. A
neural reflex is initiated by vagus nerve that promotes the release of HCL, pepsinogen
and mucus.
Gastric phase: this stage is triggered by two mechanisms.
Mechanical stimulation: by stretching of the wall of the stomach by food causes
meullary stimulation and leads to secretion of gastric juice.
Chemical stimulation: presence of amino acids and alcohol induces the production of
HCL.
Intestinal phase: entry of protein rich food into the small intestine releases intestinal
hormone and in turn induces further production of HCL.

Due to etiological/risk factors

(Psychological stress, NSAIDS, alcohol, Helicobacter pylori)

Hyper secretion of HCL acid and pepsin

Injury to the mucin producing cells

82 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Depletion of mucosal barrier which protects mucosa

Erosion of mucosa and injury to the underlying structures (ulceration)

Inflammatory response

Gastritis

Damage to the sphincters

Esophageal ulcer
Duodenal ulcer

Gastric perforation

CLINICAL FEATURES
 Burning or gnawing pain: This is the most typical symptom and is usually felt in the
upper abdomen, between the breastbone and navel.
 Nausea and vomiting
 Bloating and fullness: Patients may feel bloated or overly full after eating, even with
small meals.
 Loss of appetite/anorexia
 Hemetemesis: blood in the vomitus
 Dark, tarry stools (melena) or bloody stools: Severe ulcers can lead to bleeding, which
can result in black, tarry stools or bloody stools.
 Heartburn or acid reflux/epigastric pain
 Deep tenderness
 Complications: perforation, obstruction, hemorrhage, anaemia and malignancy.

83 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 TYPHOID
Typhoid fever is an enteric fever characterized by systemic illness along with abdominal
pain and fever in a “step-ladder” pattern.

Causative agent: Salmonella typhi and Salmonella paratyphi

They are aerobes and facultative anaerobes.
They are Gram negative and non-sporing
They are non-acid fast
They are non-capsulated
They are rod shaped bacteria
They are motile and have peritrichous flagella.

Risk factors
Unhygienic practices
Eating sea food from a contaminated water source
Eating raw vegetables
Contaminated milk products

Mode of transmission: Faeco-oral route (it spreads through food, drinks and drinking
water that are contaminated with faecal matter.

PATHOGENESIS
Due to risk factors
(Ingestion of contaminated food and water)

Bacteria enters the GI tract

On reaching the gut, the bacteria attach themselves to the microvilli of the terminal
ileum (Peyer’s patches)

Penetrate the lamina propria of the lining of the GI tract and reaches the submucosa

Phagocytosis by neutrophils and macrophages

84 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Resist intracellular killing

Bacteria enter the mesenteric lymph nodes

Invade the blood stream via thoracic duct

Primary bacteremia

Bacteria will be accumulated in the liver, gall bladder, spleen, lungs and kidneys

Further multiplication of bacteria will pass into the blood

Secondary bacteremia
(Clinical symptoms of diarrhea and abdominal pain)

Secretion of bacteria in bile juice into the GI tract

Excreted in feces

CLINICAL FEATURES
Diarrhea
Abdominal cramps
Fever (step-ladder)
Nausea
Bloating
Anorexia
Vomiting
Blood in the stool
Malaise
Hepatomegaly and splenomegaly
Rash of rose spots
Coated tongue

85 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 CARCINOMA OF GASTROINTESTINAL TRACT
Carcinomas of the gastrointestinal tract can occur in various parts of the digestive
system, including the buccal cavity (oral cavity), esophagus, stomach, and intestines.

Buccal (Oral) Carcinoma: Buccal carcinoma refers to cancer that develops in the buccal
cavity, which includes the inner lining of the cheeks, lips, gums, and the front part of the
tongue.
Risk factors for buccal carcinoma include tobacco and alcohol use, as well as exposure
to the human papillomavirus (HPV).
Symptoms may include persistent mouth ulcers, white or red patches in the mouth,
difficulty swallowing, and pain or discomfort.

Esophageal Carcinoma: Esophageal carcinoma occurs in the esophagus, the muscular

tube that connects the throat to the stomach. There are two primary types of esophageal
cancer: squamous cell carcinoma and adenocarcinoma.
Symptoms may include difficulty swallowing (dysphagia), chest pain or discomfort,
unexplained weight loss, and coughing or hoarseness.

Gastric (Stomach) Carcinoma: Gastric carcinoma, also known as stomach cancer,

develops in the lining of the stomach.
Risk factors include infection with Helicobacter pylori bacteria, a family history of gastric
cancer, smoking, and certain dietary factors.
Symptoms may include abdominal pain, indigestion, and loss of appetite, unexplained
weight loss, and vomiting.

Intestinal Carcinoma: Intestinal carcinomas refer to cancers that occur in the

intestines, which can include the small intestine or the large intestine (colon and
rectum).
Risk factors for intestinal carcinomas often include a history of colorectal polyps, a
family history of colorectal cancer, a diet high in red or processed meats, and certain
genetic factors.
Symptoms may vary depending on the location but can include changes in bowel habits,
rectal bleeding, abdominal pain, and unexplained weight loss.

86 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS OF CARCINOMA OF GI TRACT
The pathogenesis of carcinoma (cancer) in the gastrointestinal (GI) tract involves a
complex series of events that ultimately result in the uncontrolled growth and spread of
malignant cells within the digestive system. Gastrointestinal tract carcinomas can occur
in various regions, including the esophagus, stomach, small intestine, and colon. Here is
a generalized overview of the pathogenesis of GI tract carcinoma:
1. Initiation: Carcinogenesis often begins with the initiation of genetic mutations or
alterations in the DNA of normal cells within the GI tract. These mutations can be
caused by various factors, including exposure to carcinogens (such as tobacco smoke,
certain chemicals, or radiation), genetic predisposition, chronic inflammation, or
infection with certain pathogens (e.g., Helicobacter pylori in the stomach).
2. Promotion: After initiation, the mutated cells may undergo further changes that
promote their growth and survival. These changes can be influenced by factors like
chronic irritation or inflammation in the GI tract. For instance, chronic
gastroesophageal reflux disease (GERD) can promote esophageal cancer, and chronic
gastritis can contribute to stomach cancer.
3. Progression: Over time, the genetically altered cells may accumulate additional
mutations, leading to the formation of a precancerous lesion or tumor. These early-
stage tumors are often referred to as adenomas in the case of colorectal cancer.
4. Invasion: As the tumor continues to grow, it can invade and infiltrate nearby tissues
and layers of the GI tract. This is a critical step in the pathogenesis, as it marks the
cancer's ability to spread locally.
5. Metastasis: Advanced GI tract carcinomas can metastasize, meaning that cancer cells
can break away from the primary tumor and travel through the bloodstream or
lymphatic system to establish secondary tumors (metastases) in distant organs or
lymph nodes. The specific pattern of metastasis depends on the location of the
primary tumor.
6. Angiogenesis: To sustain their growth, tumors need a blood supply. Cancer cells
release signals that promote the formation of new blood vessels (angiogenesis) to
supply oxygen and nutrients to the tumor.
7. Immune Evasion: Cancer cells can develop mechanisms to evade the body's immune
system, allowing them to escape immune surveillance and continue to grow
unchecked.

87 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

8. Clinical Presentation: As the tumor grows and invades surrounding tissues, it may
lead to clinical symptoms, such as difficulty swallowing (in esophageal cancer),
abdominal pain and indigestion (in stomach cancer), changes in bowel habits (in
colorectal cancer), or other GI-related symptoms.

Due to etiological factors

(Dietary factors-low in vitamin C & E and high salt diet
H.pylori infection)

Chronic superficial gastritis

Atrophic gastritis

Intestinal metaplasia

Dysplasia

Cancer of the stomach

88 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 HEPATITIS
Hepatitis is a medical condition characterized by inflammation of the liver. This
inflammation can be caused by various factors, including viruses, alcohol, certain
medications, autoimmune diseases, and metabolic disorders. Hepatitis can be acute,
lasting for a short period, or chronic, lasting for months or even years.

There are several types of hepatitis, with the most common ones being viral hepatitis:
Hepatitis A (HAV): Hepatitis A is caused by the hepatitis A virus, typically transmitted
through contaminated food or water or by close contact with an infected person. It is
usually an acute infection and rarely becomes chronic. Symptoms may include fever,
fatigue, jaundice (yellowing of the skin and eyes), abdominal pain, and nausea.

Hepatitis B (HBV): Hepatitis B is caused by the hepatitis B virus and can be transmitted
through contact with infected blood, unprotected sex, or from an infected mother to her
newborn during childbirth. It can result in both acute and chronic infections. Symptoms
are similar to hepatitis A but can lead to long-term liver problems, including cirrhosis
and liver cancer.

Hepatitis C (HCV): Hepatitis C is caused by the hepatitis C virus, which is primarily

transmitted through contact with infected blood, often through sharing needles or
equipment for drug use. Most people with acute hepatitis C do not have symptoms, but if
left untreated, it can become chronic and cause liver damage over time.

Hepatitis D (HDV): Hepatitis D is caused by the hepatitis D virus and only occurs in
individuals who are already infected with hepatitis B. It can make an existing hepatitis B
infection more severe.

Hepatitis E (HEV): Hepatitis E is caused by the hepatitis E virus and is usually

transmitted through contaminated water or food. It is similar to hepatitis A in its
symptoms and duration.

Autoimmune Hepatitis: This form of hepatitis occurs when the body's immune system
mistakenly attacks the liver, leading to inflammation and damage.

89 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

Alcoholic Hepatitis: Excessive and prolonged alcohol consumption can lead to alcoholic
hepatitis, which is inflammation of the liver due to alcohol-induced damage.

CAUSES AND RISK FACTORS

 Viral hepatitis is caused by specific viruses (HAV, HBV, HCV, HDV, HEV).
 Autoimmune hepatitis is triggered by an abnormal immune response.
 Alcoholic hepatitis results from excessive alcohol consumption.

ETIOPATHOGENESIS
The etiology of hepatitis varies depending on the type. Viral hepatitis is caused by
specific viruses, while other forms of hepatitis result from autoimmune reactions, alcohol
abuse, or metabolic factors.
Due to etiological factors
(Viruses, intravenous drug use, contaminated food and water, alcohol and blood borne
infections)

Inflammation of the liver

Liver cell destruction

Enlargement of liver

Necrosis of acinar cells of liver

Mononuclear infiltrates

Autolysis toxins
Scarring of liver

Hepatic failure

Coma and death

90 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CLINICAL FEATURES:
 Jaundice (yellowing of the skin and eyes)

 Fatigue

 Abdominal pain or discomfort

 Dark urine

 Pale stools

 Nausea and vomiting

 Loss of appetite

 Joint pain

 Fever

 Enlarged liver and spleen

91 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 CHRONIC LIVER ABSCESS
Liver abscess is the pus filled mass in the liver that can develop from injury to the liver
or an intra abdominal infection or disseminated from the portal circulation.

A chronic liver abscess is a long-standing accumulation of pus within the liver tissue,
characterized by the presence of a thick fibrous capsule that separates the abscess from
the surrounding liver parenchyma.

Liver abscess is the collection of pus (dead cells and neutrophils) that has accumulated
within a tissue because of an inflammatory process caused by bacteria/parasites and
foreign materials.

CAUSES AND RISK FACTORS

 Previous acute abscess
 Biliary tract infections
 Gall bladder infections
 Hematogenous spread: spread through the bloodstream and lodge in the liver.
 Direct extension: Infections from neighboring structures, such as the gastrointestinal
tract.
 Colonic diseases
 Pancreatitis
 Intra abdominal sepsis
 Traumatic injuries
 Infections: Streptococcus, pseudomonas, E.coli, klebsiella pneumonia and
opportunistic pathogens (staphylococcus)
 Diabetes
 Gallstones
 Liver Disease: Cirrhosis
 Immunosuppression: Conditions or medications that weaken the immune system can
make individuals more susceptible to infections, including liver abscesses.
Types: Pyogenic abscess (pyogenic pathogens), amoebic abscess (entamoeba histolytica)
and fungal abscee (candida species).

92 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
 Liver receives blood from both systemic and portal circulation
 Inflammatory conditions such as appendicitis, diverticulitis and perforated bowel
leads to bacteremia and in turn the infection spreads to the liver via portal vein results
in liver abscess.
 Infections of distant structures and systemic bacteremia enter the liver via hepatic
artery and leads to liver abscess.
 Gall stones and malignant conditions partially/completely obstruct and cause
ascending cholangitis and results in liver abscess.
 Direct extension of infection outside of the biliary tract to the parenchyma of the liver
cause liver abscess.
 Penetrating injury or trauma to the liver is the cause for direct introduction of
pathogens to the liver and lead to liver abscess.

Due to etiological factors

Infections and inflammation

Degeneration of liver cells

Formation of cavities

Collection of dead hepatocytes, leukocytes and connective tissue debris

Liver abscess

Chronic liver abscesses are characterized by the presence of a thick fibrous capsule that
separates the pus-filled cavity from the surrounding liver tissue. Over time, the abscess
may become walled off by this fibrous tissue. The abscess contains necrotic tissue,
bacteria, and inflammatory cells.

93 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

CLINICAL FEATURES
 Fever: A persistent low-grade fever may be present.
 Right Upper Quadrant Abdominal Pain: Patients may experience dull or mild
discomfort in the right upper abdomen.
 Weight Loss: Unexplained weight loss can occur over time.
 Jaundice: In some cases, jaundice (yellowing of the skin and eyes) may develop if the
abscess compresses the bile ducts.
 Fatigue: Generalized weakness and fatigue may be present.
 Mild Hepatomegaly: Enlargement of the liver may be detectable on physical
examination.
 Systemic Symptoms: Some patients may experience general malaise, night sweats,
and loss of appetite.
 Anorexia
 Anemia
 Nausea and vomiting

94 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 CIRRHOSIS OF LIVER
Irreversible end stage liver disease characterized by a loss of normal liver architecture
and function.

Diffuse disorder of liver characterized by complete loss of normal architecture replaced

by extensive fibrosis with regenerating parenchymal nodules is called cirrhosis of liver.

CAUSES AND RISK FACTORS

 Chronic alcohol abuse
 Viral hepatitis (B,C & D)
 Biliary obstruction
 Metabolic diseases: Wilson’s disease and Harmochromatosis
 Venous outflow obstruction
 Drug induced liver damage
 Autoimmune diseases
 Inherited diseases: Alpha-1 antitrypsin dificiency

PATHOGENESIS
Due to etiological factors
(Alcohol ingestion, viral hepatitis, exposure to toxins)

Hepatocytes damage
Activation of Kuffer cells (Phagocytic cells)

Activation of Hepatic stellate cells

(Fibroblasts reside in the sinusoidal walls)

Transformation of cells of the liver (Multifunctional cells)

Production of collagen and cytokines synthesis

Alteration in blood and lymph flow

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 Liver ischemia and necrosis
Fibrosis and scarring of liver

Nodule formation

Structural and functional alteration of liver (Cirrhosis)

Decreased metabolism (carbohydrates, proteins and fats, ADH and aldosterone, Estrogen
and androgen)
Decreased metabolism of bilirubin (jaundice)
Decreased absorption of vitamin K
Decreased synthesis of plasma proteins
Portal hypertension
Ascites, splenomegaly, hepatomegaly and thrombocytopenia

Hepatic encephalopathy

Coma and death

PATHOLOGICAL CHANGES
 Alcohol is metabolized by liver enzymes and produces NADH and increased
concentration of NADH fatty acid synthesis and decreased fatty acid oxidation
subsequently the higher levels of fatty acids resulting in fatty liver.
 Obstruction to flow of blood flow and portal hypertension causes transudation of fluid
into the abdominal cavity. hypoalbuminemia causes decreased oncotic pressure and
lead to passage of fluids from into the abdominal cavity (Ascites).
 Shunting of portal blood into the systemic circulation causes vasodilation, varices and
bleeding lead to hemetemesis and melena.
 Sequestration of blood in the spleen causes pancytopenia.
 Toxic substances bypass the liver and act on the neurons cause hepatic
encephalopathy.

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CLINICAL FEATURES
 Anorexia
 Nausea and vomiting
 Diarrhea
 Dull abdominal pain
 Jaundice
 Splenomegaly
 Anemia
 Thrombocytopenia
 Leucopenia
 Gynecomastia
 Loss of axillary and pubic hairs
 Impotence coagulation problem (Epistaxis, purpura, heavy menstrual flow and
petechiae)
 Abdominal distension

97 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 TUMORS OF LIVER

Liver tumors refer to abnormal growths or masses of cells in the liver. They can be
benign (non-cancerous) or malignant (cancerous). Malignant liver tumors are often
referred to as liver cancer or hepatocellular carcinoma.

CAUSES
The causes of liver tumors can vary, and the development of liver cancer is often a
complex process involving genetic and environmental factors. Some common causes
include:
 Chronic Viral Hepatitis: Chronic infections with hepatitis B or C viruses increase the
risk.
 Alcohol Abuse: Chronic alcohol consumption can contribute to liver damage and
increase the risk of liver cancer.
 Non-Alcoholic Fatty Liver Disease (NAFLD): Obesity and metabolic syndrome can
lead to NAFLD, which may progress to liver cancer.
 Cirrhosis: Liver cirrhosis, usually resulting from chronic liver diseases like hepatitis
or alcoholism, is a significant risk factor.
 Inherited Liver Diseases: Certain genetic conditions, such as hemochromatosis and
Wilson's disease, can elevate the risk.

RISK FACTORS

 Age: Liver cancer is more common in individuals over the age of 50.

 Gender: Men are more likely to develop liver cancer than women.

 Race/Ethnicity: Some populations, such as Asians and Pacific Islanders, have a

higher incidence.

 Tobacco Use: Smoking may increase the risk of liver cancer.

 Diabetes: Individuals with diabetes are at a higher risk.

 Exposure to Aflatoxins: Consuming food contaminated with aflatoxins, produced by

certain molds, is a risk factor.

98 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

TYPES

 Hepatocellular Carcinoma (HCC): The most common type, arising from hepatocytes.

 Cholangiocarcinoma: Arises in the bile ducts within the liver.

 Hepatoblastoma: Mostly occurs in young children.

 Angiosarcoma and Hemangiosarcoma: Rare types that involve blood vessels in the
liver.

PATHOGENESIS

The pathogenesis of liver tumors, particularly hepatocellular carcinoma, involves a

multi-step process. Chronic inflammation, often due to viral hepatitis or other liver
diseases, can lead to the development of cirrhosis. Cirrhosis, in turn, increases the risk
of liver cancer. Genetic mutations, environmental factors, and the presence of risk
factors contribute to the progression of liver tumors.

CLINICAL FEATURES

The clinical presentation of liver tumors can vary, and symptoms may not manifest until
the disease is advanced. Common clinical features include:
 Abdominal Pain: Pain or discomfort in the upper abdomen.

 Unexplained Weight Loss: Rapid and unexplained weight loss.

 Jaundice: Yellowing of the skin and eyes.

 Enlarged Liver: Palpable enlargement of the liver.

 Fatigue: Generalized weakness and fatigue.

 Loss of Appetite: A reduced desire to eat.

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 TUMOURS OF GALL BLADDER

Tumors of the gallbladder refer to abnormal growths or masses that develop in the
gallbladder, a small organ located beneath the liver. These tumors can be benign or
malignant, with malignant tumors often referred to as gallbladder cancer.

CAUSES
The exact cause of gallbladder tumors is often unclear, but certain factors and
conditions are associated with an increased risk:
 Gallstones: The presence of gallstones is a significant risk factor for gallbladder
cancer.
 Chronic Inflammation: Chronic inflammation of the gallbladder, often due to
conditions like chronic cholecystitis, can contribute to tumor development.
 Polyps: Gallbladder polyps, especially large ones, may pose an increased risk.
 Genetic Factors: Inherited conditions, such as familial adenomatous polyposis (FAP),
can elevate the risk.
 Age and Gender: Gallbladder cancer is more common in older adults and is more
prevalent in women.

RISK FACTORS
 Age: Gallbladder cancer is more common in people over the age of 65.

 Gender: Women are more prone to gallbladder cancer than men.

 Ethnicity: Native American populations, particularly Pima Indians, have a higher

incidence.
 Obesity: Being overweight or obese is associated with an increased risk.

 Gallstones: Persistent gallstones increase the risk of gallbladder cancer.

 Chronic Infections: Chronic infection with certain parasites, such as Salmonella

typhi, may be a risk factor.

TYPES
 Adenocarcinoma: The most common type, accounting for the majority of gallbladder
cancers.
 Papillary Adenocarcinoma: A subtype of adenocarcinoma with a better prognosis.
100 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Squamous Cell Carcinoma: A less common type.
 Adenosquamous Carcinoma: A mixed type containing both adenocarcinoma and
squamous cell carcinoma components.

PATHOGENESIS
The development of gallbladder tumors, particularly adenocarcinoma, is associated with
a progression from chronic inflammation to dysplasia and eventually invasive cancer.
Gallstones, chronic cholecystitis, and other inflammatory conditions contribute to this
process. Genetic mutations may also play a role in the transformation of normal cells
into cancerous ones.

CLINICAL FEATURES
Gallbladder tumors may not produce symptoms in the early stages. However, as the
disease progresses, clinical features may include:
 Abdominal Pain: Typically in the upper right side of the abdomen.

 Jaundice: Yellowing of the skin and eyes.

 Unexplained Weight Loss: Rapid and unintentional weight loss.

 Nausea and Vomiting: Especially after meals.

 Enlarged Gallbladder: Palpable mass in the abdomen.

 Fever: Sometimes associated with infection.

101 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 TUMOURS OF PANCREAS
Pancreatic tumors refer to abnormal growths or masses that develop in the pancreas, an organ
located behind the stomach. These tumors can be benign or malignant, with malignant tumors
often associated with pancreatic cancer.

CAUSES
The exact causes of pancreatic tumors are not always clear, but several factors and
conditions are associated with an increased risk:
 Age: The risk of pancreatic cancer increases with age, and it is more common in older
adults.
 Smoking: Cigarette smoking is a major risk factor for pancreatic cancer.
 Chronic Pancreatitis: Persistent inflammation of the pancreas can elevate the risk.
 Family History: Individuals with a family history of pancreatic cancer may have a
higher risk.
 Inherited Genetic Syndromes: Certain genetic conditions, such as Lynch syndrome
and hereditary breast and ovarian cancer syndrome, may increase the risk.

RISK FACTORS
 Smoking: Tobacco use is a significant risk factor for pancreatic cancer.

 Obesity: Being overweight or obese increases the risk.

 Diabetes: Chronic diabetes may be associated with an elevated risk.

 Chronic Pancreatitis: Long-term inflammation of the pancreas is a risk factor.

 Family History: Having close relatives with pancreatic cancer increases the risk.

 Inherited Genetic Mutations: Some genetic mutations are associated with a higher

likelihood of developing pancreatic cancer.

TYPES
 Exocrine Pancreatic Tumors
o Pancreatic Adenocarcinoma: The most common type, arising in the ducts of the

pancreas.
o Pancreatic Neuroendocrine Tumors (PNETs): A less common type that forms from

hormone-producing cells.
 Endocrine Pancreatic Tumors (Islet Cell Tumors)

102 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 o Insulinomas: Tumors that produce too much insulin.

o Glucagonomas: Tumors that produce too much glucagon.

o Somatostatinomas: Tumors that produce too much somatostatin.

o Gastrinomas: Tumors that produce too much gastrin (associated with Zollinger-

Ellison syndrome).

PATHOGENESIS
The pathogenesis of pancreatic tumors, especially pancreatic adenocarcinoma, is
complex and involves genetic mutations, environmental factors, and chronic
inflammation. Most pancreatic cancers arise in the exocrine cells of the pancreas and
often present at an advanced stage due to the lack of early symptoms.

CLINICAL FEATURES
Clinical features of pancreatic tumors, particularly adenocarcinoma, may include:
 Abdominal Pain: Often in the upper abdomen or radiating to the back.

 Weight Loss: Unintentional weight loss.

 Jaundice: Yellowing of the skin and eyes.

 Loss of Appetite: Reduced desire to eat.

 Digestive Problems: Nausea, vomiting, and changes in bowel habits.

 Diabetes: In some cases, new-onset diabetes may be a symptom.

103 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 CHOLECYSTITIS
Inflammatory condition of the gall bladder is called cholecystitis.

CAUSES AND RISK FACTORS

 Gall stones
 Tumors
 Biliary obstruction (bile duct blockage)
 Infections
 Female gender
 Old age or elderly
 Obesity
 Multiparity
 Physical inactivity
 Consumption of oral contraceptives (hormonal therapy)
 Pregnancy
 Losing or gaining weight rapidly
 Diabetes

PATHOGENESIS
Due to etiological and risk factors

Change in the composition of bile/

Hypomotility of the gall bladder/
Decreased bile flow/
Decreased bile acid synthesis

Cholestasis

Increased cholesterol synthesis in liver

Super saturation of bile with cholesterol

104 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Formation of precipitates

Sudge and then stone formation (Gall stones)

Obstruction to the flow of bile

Impaired hepatic uptake of Collection of soluble Cystic obstruction

bilirubin bilirubin in urine
Distension of gall bladder
Jaundice Right upper quadrant pain

Presence of bile in urine Decreased bile in the

duodenum
Dark yellow urine
Decreased stercobilirubin

Clay colored stools

CLINICAL FEATURES
 Colicky pain
 Nausea and vomiting
 Low grade fever
 Anorexia
 Leukocytosis
 Jaundice
 Abdominal distension

105 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 GLOMERULONEPHRITIS

Bilateral inflammation of the glomeruli of the kidney associated with autoimmune

disease is called glomerulonephritis.

Immune mediated glomerular disease due to post streptococcal upper respiratory tract
infection.

ETIOLOGY

 Group A beta hemolytic streptococcal infection

 Systemic diseases
 Hepatitis B
 Systemic lupus erythematosis/Autoimmune disease of the connective tissue
 Malignant tumors of the kidney

PATHOGENESIS
Due to etiological factor
(Group A beta hemolytic streptococcal infection)

Upper respiratory tract infection

Stimulation of production of antibodies

Formation of antigen-antibody complexes

Antigen-antibody complexes trapped in the glomerular basement membrane

Complement activation and attract the inflammatory cells into the kidney

Proliferation of mesangial cells and inflammatory cells (neutrophils and monocytes)

Hypercellular glomeruli Damage of the cells of filtering membrane

Occlusion of the capillaries and prevent the Leakage of proteins and RBCs in urine

106 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 blood flow Proteinuria and hematuria

Necrosis and renal failure Sclerosis and fibrosis

Renal failure

CLINICAL FEATURES
 Generalized edema (anasarca)
 Hypertension
 Hematuria
 Coca cola colored urine
 Decreased urination (oliguria)
 Smoky coffee colored urine
 Dyspnea
 Periorbital edema

107 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 PYELONEPHRITIS

Pyelonephritis is an upper urinary tract infection that specifically affects the kidneys and
is characterized by inflammation of the renal parenchyma.

CAUSES AND RISK FACTORS

 E. coli
 Urinary obstructions
 Kidney stones
 Vesicoureteral reflux
 Gender: Women are more susceptible to pyelonephritis due to their shorter urethra.
 Urinary tract abnormalities
 Weakened immune system
 Catheter use: Catheterization increases the risk of bacterial entry into the urinary
tract.
 Pregnancy

ETIOPATHOGENESIS

Bacterial entry: Bacteria, often from the lower urinary tract, enter the kidneys.

Infection and inflammation: The bacteria multiply and cause infection in the renal
parenchyma and pelvis, leading to inflammation.

Local tissue damage: The inflammatory response can damage kidney tissue and impair
function.

Systemic symptoms: The infection can lead to systemic symptoms like fever and chills.

CLINICAL FEATURES

 High fever and chills

 Flank pain or lower back pain, typically on one side

 Dysuria (painful urination)

 Increased frequency and urgency of urination

 Hematuria (blood in the urine)

 Nausea and vomiting

 Fatigue and malaise

108 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 RENAL CALCULI/RENAL STONES/KIDNEY STONES

Urolithiasis is the formation of urinary stones in the urinary tract. Small, hard deposit
that forms in the kidneys is considered to be as kidney stones.

Hard deposits of minerals and acid salts that stick together in concentrated urine are
called kidney stones.

Renal calculi, or kidney stones, are solid masses that develop in the kidneys or other
parts of the urinary tract when certain minerals and salts in the urine crystallize and
aggregate.

CAUSES AND RISK FACTORS

 Chemical Imbalance: An imbalance in the concentration of minerals and salts in the

urine can lead to the formation of kidney stones. Calcium, oxalate, and uric acid are
common components of kidney stones.
 Dehydration: Insufficient fluid intake.
 Excessive sweating
 Digestive diseases: chronic diarrhea and inflammatory bowel syndrome
 Diet: A diet high in certain foods, like oxalate-rich foods (e.g., spinach, beets, nuts).
Others are processed meat, cola beverages, fast foods, chocolates and sweet potatoes.
 Family History: A family history of kidney stones can increase one's risk.
 Medical Conditions: Certain medical conditions, such as hyperparathyroidism, gout,
and urinary tract infections, can increase the risk of kidney stones.
 Age and gender: People aged 30 to 60 and men are more likely to develop kidney
stones.
 Obesity: Excess body weight can increase the risk of stone formation.
 Previous history: A prior episode of kidney stones increases the risk of recurrence.
 Family or personal history: A family history or personal history of kidney stones
increases susceptibility.
 Lack of physical activities
 Medications: vitamin C dietary supplements, excessive use of laxatives and calcium
based antacids.
 Chemotherapeutic agents

109 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS

Due to modifiable and non-modifiable risk factors

More waste materials dissolved in small quantities of liquid plasma

Deposition of uric acid, ammonia phosphate and calcium oxalate on PCT of nephrons

Super saturation of urine by stone forming constituents

Precipitation of urine/crystallization

Nidation of crystals/foreign bodies from the supersaturated urine

Calculi formation

Urinary obstruction

Urinary tract infection

Dysuria

Etiopathogenesis: The formation of kidney stones typically involves the following

processes:

 Supersaturation: Urine becomes oversaturated with certain minerals and salts.

 Nucleation: Crystals form and grow from these oversaturated substances.

 Aggregation: Crystals combine and grow into stones.

 Obstruction: Stones may move within the urinary tract, causing blockages and pain.

110 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

TYPES OF KIDNEY STONES

 Calcium Stones: The most common type, primarily composed of calcium oxalate or
calcium phosphate.

 Uric Acid Stones: Formed when there's an excess of uric acid in the urine.

 Struvite Stones: Associated with urinary tract infections and can grow quite large.

 Cystine Stones: Rare and related to a hereditary disorder (cystinuria).

CLINICAL FEATURES

 Severe, colicky flank or lower back pain that radiates to the groin.

 Hematuria (blood in the urine).

 Frequent urination.

 Painful urination (dysuria).

 Nausea and vomiting.

 Chills and fever if there's an associated infection.

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 RENAL FAILURE

Sudden interruption of renal function is called renal failure.

Interruption of renal function characterized by reduced glomerular filtration rate and

sudden retention of endogenous and exogenous metabolites is considered to be as renal
failure. Metabolites are urea, potassium, phosphate, sulphate, creatinine and
administered drugs.

CAUSES AND RISK FACTORS

Pre renal causes Renal causes Post renal causes

Arrhythmias Nephrotoxins Bladder obstruction
Cardiogenic shock Crush injuries Urethral obstruction
Heart failure Transfusion reactions Urethral stricture
Myocardial infarction Glomerulonephritis Ureteral obstruction
Burns Pyelonephritis Calculi formation
Dehydration Infections
Diuretic overdoses Trauma
Hemorrhage
Hypovolemic shock
Trauma
Antihypertensive drugs

PATHOGENESIS

Due to pre renal causes

Decreased blood flow to the kidney

Hypoperfusion Interruption of renal blood Decreased glomerular

flow filtration rate
Ischemia
Accumulation of excessive Electrolyte imbalances
Hypoxia nitrogen waste products in
the blood Metabolic acidosis
Death of renal parenchyma
Azotemia

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 Due to intra renal causes

Nephrotoxins Infections and Injuries

inflammations
Delicate layer of filtering Rupture of blood vessels
membrane has irrepairable Disruption of filtering and urinary tubules
damage membrane
Damage of renal
Necrosis Fluid loss in the urine parenchyma

Dehydration and Extreme nitrogenous waste

hypotension in the blood

Increased azotemia

Due to post renal causes

Obstruction to the flow of urine

Reflux of urine into the kidney tissues

Decreased glomerular filtration rate

Excessive nitrogenous waste in the blood

Phases of renal failure: oliguric phase, diuretic phase and recovery phase

CLINICAL FEATURES

 Tachypnea
 Tenacious sputum
 Pain with coughing
 Pulmonary edema
 Anorexia
113 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Abdominal distension
 Gastrointestinal bleeding
 Nausea and vomiting
 Diarrhea and constipation
 Lethargy
 Confusion
 Unusual behavior
 Sleep disturbances
 Pigmentation
 Ecchymosis
 Pruritus
 Decreased urine output
 Proteinuria
 Infertility
 Decreased libido
 Erectile dysfunction
 Amenorrhoea

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 RENAL CARCINOMA
Renal carcinoma, also known as kidney cancer, refers to the abnormal growth of cells in the
kidneys. The most common type of renal carcinoma in adults is renal cell carcinoma (RCC).

CAUSES
The exact cause of renal carcinoma is often unclear, but several factors may contribute
to its development:
 Genetic factors: Inherited conditions such as Von Hippel-Lindau (VHL) syndrome and
hereditary papillary renal cell carcinoma can increase the risk.
 Smoking: Cigarette smoking is a significant risk factor for renal carcinoma.
 Obesity: Being overweight or obese increases the risk.
 Hypertension: Chronic high blood pressure may be associated with an elevated risk.
 Gender: Men are more commonly affected than women.

RISK FACTORS
 Age: The risk of renal carcinoma increases with age.
 Occupational exposures: Exposure to certain chemicals and substances in the
workplace may elevate the risk.
 Kidney disease: Individuals with certain kidney diseases, such as end-stage renal
disease, may have an increased risk.
 Family history: Having a family history of kidney cancer may increase the risk.
 Von Hippel-Lindau (VHL) syndrome: An inherited condition associated with an
increased risk of kidney cancer.

TYPES
 Renal Cell Carcinoma (RCC): The most common type, comprising several subtypes
such as clear cell, papillary, and chromophobe RCC.
 Transitional Cell Carcinoma: A type of kidney cancer that starts in the renal pelvis.
 Wilms Tumor: Primarily occurs in children and is a type of kidney cancer that affects
the cells of the developing kidney.

115 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
The pathogenesis of renal cell carcinoma involves the development of genetic mutations,
often leading to uncontrolled cell growth and the formation of tumors. The clear cell
subtype of RCC, in particular, is associated with mutations in the VHL gene.

CLINICAL FEATURES
Clinical features of renal carcinoma may include:
 Hematuria: Blood in the urine.

 Abdominal pain: Pain or discomfort in the side or back.

 Palpable mass: A lump or mass in the abdomen.

 Fatigue: Generalized weakness and tiredness.

 Unexplained weight loss: Rapid and unintentional weight loss.

 Fever: Occasionally associated with advanced disease.

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 URINARY TRACT INFECTION

An infection in any part of the urinary system (kidneys, ureters, bladder an d urethra) is
called urinary tract infection.

ETIOLOGY /CAUSES AND RISK FACTORS

 Bacterial Infection: Escherichia coli (E. coli), Klebsiella, Enterococcus, and

Staphylococcus.
 Anatomical Abnormalities: Congenital or acquired abnormalities in the urinary tract
 Catheterization: It introduces bacteria into the urinary tract, leading to infection.
 Sexual Activity: Sexual intercourse can introduce bacteria into the urethra.
 Gender: Women are more susceptible to UTIs than men. This is mainly because the
urethra in women is shorter and closer to the anus, making it easier for bacteria to
enter the urinary tract.
 Age: Infants and the elderly are at a higher risk of UTIs. Infants may have structural
abnormalities, and older individuals often have weakened immune systems or other
medical conditions that increase susceptibility.
 Use of spermicidal agents
 Urinary tract obstructions: Any blockage or obstruction in the urinary tract, such as
kidney stones or an enlarged prostate.
 Pregnancy: Pregnant women are more prone to UTIs due to changes in the urinary
tract and pressure on the bladder.
 Diabetes
 Weakened immune system: Conditions that compromise the immune system, such as
HIV/AIDS, cancer, or autoimmune diseases.
 Previous UTIs
 Menopause: Changes in the urinary tract during menopause, such as reduced
estrogen levels.
 Hygiene and Habits: Poor personal hygiene, wiping from back to front after a bowel
movement and infrequent or incomplete voiding can increase the risk of UTIs.

117 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS

Due to etiological/risk factors

Colonization of the periurethral area with pathogen

Uroepithelium penetration and entry into the bladder (cystitis)

Ascending infection into the ureters

Infection into the renal pelvis and then into the renal parenchyma

Continuation of inflammatory cascade

Acute kidney injury

CLINICAL FEATURES

 Dysuria: Pain or a burning sensation during urination.

 Increased frequency of urination

 Urgency: A sudden, strong urge to urinate, even if the bladder is not full.

 Lower abdominal pain or discomfort

 Hematuria: Blood in the urine.

 Pink, red, or brown-colored urine.

 Cloudy or foul-smelling urine

 Back pain or flank pain: due to infection of the kidneys (pyelonephritis.

 Fever and chills: Systemic symptoms like fever, chills, and fatigue.

 Nausea and vomiting.

 Pelvic pain
118 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 CYSTITIS
Cystitis refers to inflammation of the bladder, particularly the lining of the bladder wall. It is a
common urinary tract infection (UTI) that can be either acute or chronic.

CAUSES
Cystitis is most commonly caused by bacterial infection, often stemming from the
gastrointestinal tract. Escherichia coli (E. coli) bacteria are a frequent culprit, but other
bacteria can also be responsible. In some cases, cystitis may result from non-infectious
causes such as irritation or chemical exposure.

RISK FACTORS
Several factors can increase the risk of developing cystitis:
 Female gender: Women are more prone to cystitis due to their shorter urethra,
making it easier for bacteria to reach the bladder.
 Sexual activity: Sexual intercourse can introduce bacteria into the urethra and
subsequently the bladder.
 Menopause: Changes in hormone levels during menopause can increase the risk of
cystitis.
 Urinary tract abnormalities: Conditions that affect the structure or function of the
urinary tract may elevate the risk.
 Urinary catheter use: The use of urinary catheters can introduce bacteria into the
bladder.
 Blockages: Any obstruction in the urinary tract, such as kidney stones, may increase
the risk.

TYPES
 Bacterial Cystitis: Caused by bacterial infection, typically E. coli.
 Interstitial Cystitis: A chronic condition involving inflammation of the bladder wall,
often without evidence of infection.
 Chemical Cystitis: Resulting from exposure to irritants, such as certain medications
or hygiene products.

119 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOGENESIS
The pathogenesis of cystitis involves the introduction of bacteria into the bladder, leading
to infection and inflammation. Bacteria typically enter the urethra and travel up into the
bladder, where they multiply and cause irritation. Non-bacterial cystitis may result from
irritants that directly affect the bladder lining.

CLINICAL FEATURES
Clinical features of cystitis may include:
 Dysuria: Pain or discomfort during urination.

 Frequency: Increased urgency and frequency of urination.

 Urgency: A strong and sudden urge to urinate.

 Lower abdominal pain: Discomfort or pressure in the lower abdomen.

 Hematuria: Blood in the urine.

 Cloudy or foul-smelling urine: Changes in urine appearance or odor.

 Low-grade fever: In some cases, there may be a mild fever.

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 CRYPTORCHIDISM
Cryptorchidism, also known as undescended testicle, is a condition in which one or both of the
testicles fail to descend into the scrotum before birth. Normally, the testicles develop in the
abdominal area and descend into the scrotum by the time of birth or shortly thereafter. When
one or both testicles do not descend, it is referred to as cryptorchidism.

CAUSES
The exact cause of cryptorchidism is not always clear, but it is thought to involve a
combination of genetic and hormonal factors. Factors that may contribute include:
 Hormonal imbalances: Insufficient production of hormones that stimulate testicular
descent.
 Abnormalities in testicular development: Issues in the development of the
structures responsible for the descent of the testicles.
 Genetic factors: A family history of cryptorchidism may increase the risk.
 Premature birth: Premature infants are more likely to have undescended testicles.
 Narrowing of the inguinal canal
 Short spermatic cord

RISK FACTORS
Several factors may increase the risk of cryptorchidism:
 Prematurity: Infants born prematurely are at a higher risk.
 Low Birth weight: Low birth weight is associated with an increased risk.
 Family history: Having a family history of undescended testicles may elevate the risk.
 Maternal factors: Certain maternal conditions or exposures during pregnancy may
play a role.

TYPES
Cryptorchidism is typically classified based on the location of the undescended testicle:
 Unilateral Cryptorchidism: Only one testicle is undescended.
 Bilateral Cryptorchidism: Both testicles are undescended.
 Retractile/Pseudo Cryptorchidism: Testicle descends into thr scrotum but pull back
into the inguinal canal because of a hyperactive cremasteric reflex.

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 Palpable/Prepubic/Inguinal: Testicle is located between internal inguinal ring and
external inguinal ring in the groin region.
 Non-palpable: Testicle is in the abdomen and not present and not felt in the scrotum.
 Ectopic: Testicle has taken the wrong path and located in an unusual region.

PATHOGENESIS
The descent of the testicles is a complex process regulated by hormones and genetic
factors. Cryptorchidism occurs when this process is disrupted, leading to one or both
testicles remaining in the abdomen or other locations along the descent route. Hormonal
imbalances or abnormalities in the development of structures involved in testicular
descent may contribute to the condition.
Due to etiological factors
(Hormonal, Structural, Genetic and Congenital)

Failure of one/both testes descend into the scrotum

Cryptorchidism

Infertility

CLINICAL FEATURES
 Absence of testicle in the scrotum: One or both testicles may not be palpable in the

scrotum.
 Palpable testicle in the inguinal canal or abdomen: The undescended testicle can often

be felt in the inguinal canal or abdominal area.

 Infertility: Cryptorchidism is associated with an increased risk of infertility if not

treated.
 Increased risk of testicular cancer: There is a slightly higher risk of testicular cancer

in individuals with a history of cryptorchidism.

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 TESTICULAR ATROPHY
Testicular atrophy refers to the shrinking or reduction in size of one or both testicles. It is a
condition characterized by a decrease in the mass and volume of the testes, leading to potential
impairment of testicular function.

CAUSES
 Hormonal imbalance: Disruption in the hormonal regulation of testicular function,
such as low levels of testosterone.
 Vascular disorders: Conditions affecting blood flow to the testicles, like testicular
torsion or varicocele.
 Infections: Infections affecting the testicles, such as orchitis or epididymitis.
 Trauma: Physical injuries to the testicles, including blunt trauma or surgical trauma.
 Radiation therapy: Exposure to radiation, particularly in the pelvic area, can affect
testicular function.
 Chemotherapy: Certain chemotherapy drugs may have adverse effects on the testes.
 Undescended testicles (Cryptorchidism): If the testicles do not properly descend into
the scrotum, it can lead to impaired development and function.
 Genetic conditions: Some genetic disorders may contribute to testicular atrophy.
 Autoimmune disorders: Conditions where the immune system mistakenly attacks the
testicular tissue.

RISK FACTORS
 Age: Aging is associated with a natural decline in testosterone levels and can
contribute to testicular atrophy.
 Hormonal disorders: Conditions such as hypogonadism or other hormonal
imbalances.
 Infections: Sexually transmitted infections or other infections affecting the
reproductive system.
 History of trauma: Individuals with a history of trauma to the testicles may be at a
higher risk.
 Genetic predisposition: Family history of conditions affecting the testicles.

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TYPES
Testicular atrophy can be classified based on the underlying cause, such as:
 Primary testicular atrophy: Caused by intrinsic issues within the testicles, such as
hormonal imbalances or genetic conditions.
 Secondary testicular atrophy: Resulting from external factors, such as vascular
disorders, infections, or trauma.

PATHOGENESIS
The pathogenesis of testicular atrophy depends on the underlying cause. It often involves
damage to the testicular tissue, disruption of blood flow, or interference with hormonal
regulation. Over time, these factors can lead to a reduction in testicular size and
function.

CLINICAL FEATURES
 Reduced Testicular Size: One or both testicles may be noticeably smaller.

 Impaired Fertility: Testicular atrophy can lead to reduced sperm production and

fertility issues.
 Hormonal Changes: Low testosterone levels may result in symptoms such as fatigue,

reduced libido, and mood changes.

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 BENIGN PROSTATIC HYPERTROPHY/HYPERPLASIA (BPH)
Prostate gland lies just below the neck of the bladder. Prostate gland surrounds the
urethra and it is traversed by the ejaculatory duct (continuation of vas deferens). It
produces a secretion and contributes to the white component of the semen.

Enlargement of the prostate gland into the bladder obstructing the outflow of urine is
called benign prostatic hypertrophy.

CAUSES AND RISK FACTORS

 Age above 50years

 Family history of benign tumors of the prostate
 Obesity
 Heart and circulatory diseases
 Lack of physical exercises
 Type2 diabetes mellitus
 Races: native Americans and Hispanic
 Consumption of high saturated fats and red meat
 High cholesterol
 High blood pressure
 Smoking
 Increased Dihydrotestosterone

PATHOGENESIS

Due to etiological or risk factors

(Aging, changes in sex hormones, familial history and urinary tract infections)

Decreased testosterone conversion by 5-alpha reductase enzyme

Increased serum dihydrotestosterone (DHT)

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 Hyperplasia/hypertrophy of stromal and epithelial cells of prostate gland

Continuous growth of non-cancerous tumor (hypertrophy) of the smooth muscle

Formation of large discrete nodular structure

Nodules migrate or extend towards the transitional zone

Increased tissue constricting the lumen

Increased muscle tone at bladder neck, urethra and prostate

Urinary obstruction

Imcomplete emptying of bladder

Irritation and dribbling of urine

Bladder distension and infection (cystitis)

Ascending infection (pyelonephritis) and Hydronephrosis

Kidney damage

CLINICAL FEATURES

 Hesitance in starting urination

 Increased frequency of urination
 Dribbling of urine
 Symptoms of UTIs
 Nocturia
 Urgency of urination

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 CARCINOMA OF PENIS
Carcinoma of the penis, also known as penile cancer, is a rare malignancy that occurs in
the tissues of the penis. It usually originates in the squamous cells lining the penis and
can manifest as different types of penile carcinomas.

CAUSES
The primary cause of penile cancer is not always clear, but several factors may
contribute:
 Human Papillomavirus (HPV): Certain strains of HPV, particularly HPV-16 and HPV-
18, are associated with an increased risk of penile cancer.
 Poor Hygiene: Lack of proper hygiene, leading to the accumulation of smegma (a
substance that can build up under the foreskin), may be a risk factor.
 Phimosis: The inability to retract the foreskin may increase the risk.
 Smoking: Tobacco use is a potential risk factor for penile cancer.
 Age: The risk increases with age, with most cases diagnosed in older men.

RISK FACTORS
 HPV Infection: Infection with certain high-risk strains of HPV is a significant risk
factor.
 Lack of Circumcision: Uncircumcised men may have a slightly higher risk.
 Smoking: Tobacco use is associated with an increased risk.
 Phimosis: Inability to retract the foreskin can contribute to the development of
cancer.
 Poor Hygiene: Lack of proper hygiene increases the risk of penile cancer.
 Multiple Sexual Partners: Having multiple sexual partners may increase the risk of
HPV infection.

TYPES
Several types of penile carcinoma exist, with squamous cell carcinoma being the most
common. Other types include verrucous carcinoma, basaloid carcinoma, and
adenocarcinoma.

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PATHOGENESIS
The pathogenesis of penile carcinoma often involves the progression of precancerous
lesions to invasive cancer. Persistent infection with high-risk HPV strains, particularly
HPV-16 and HPV-18, is a key factor in the development of penile cancer. Other risk
factors, such as phimosis and poor hygiene, can contribute to the progression of
precancerous changes.

CLINICAL FEATURES
 Visible Lesions: Ulcers, lumps, or discolored areas on the penis.

 Changes in Skin Texture: Thickening or changes in skin texture on the penis.

 Bleeding: Unexplained bleeding from the penis.

 Foul Odor: Foul-smelling discharge associated with advanced disease.

 Swelling: Swelling of the penis or surrounding lymph nodes.

 Pain: Pain or discomfort in the penis.

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 CARCINOMA OF PROSTATE
Carcinoma of the prostate, commonly known as prostate cancer, is a malignancy that develops
in the prostate gland. The prostate is a small gland located below the bladder and in front of the
rectum, and it plays a role in the production of seminal fluid. Prostate cancer is one of the most
common cancers in men.

CAUSES
The precise cause of prostate cancer is not fully understood, but it is believed to involve
a combination of genetic, hormonal, and environmental factors. Mutations in certain
genes and changes in hormone levels, particularly testosterone, may contribute to the
development of prostate cancer.

RISK FACTORS
 Age: The risk of prostate cancer increases with age, with most cases diagnosed in
older men.
 Family History: Having a family history of prostate cancer, especially in a close
relative, increases the risk.
 Race/Ethnicity: African American men have a higher incidence of prostate cancer,
and it may be more aggressive in this population.
 Genetic Factors: Inherited gene mutations, such as those associated with hereditary
prostate cancer syndromes, may elevate the risk.
 Diet: High intake of red meat and high-fat dairy products, and low intake of fruits and
vegetables, may be associated with an increased risk.
 Geography: Prostate cancer rates vary geographically, with higher incidence in North
America, Europe, and Australia.

TYPES
Prostate cancer is primarily adenocarcinoma, which originates from glandular cells.
Other rare types include small cell carcinomas, sarcomas, and transitional cell
carcinomas.

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PATHOGENESIS
The development of prostate cancer involves the transformation of normal prostate cells
into cancerous cells. Genetic mutations, hormonal changes (particularly in androgen
levels), and environmental factors contribute to the initiation and progression of prostate
cancer. Most prostate cancers are androgen-dependent, meaning that they are
influenced by the male hormone testosterone.

CLINICAL FEATURES

 Asymptomatic in early stages: Prostate cancer in its early stages may not produce
noticeable symptoms.

 Urinary symptoms: As the cancer progresses, it may cause urinary symptoms such
as increased frequency, urgency, difficulty starting or stopping urine flow, and pain or
discomfort during urination.

 Blood in urine or semen: Hematuria (blood in urine) or hematospermia (blood in

semen) may occur.

 Erectile dysfunction: Difficulty achieving or maintaining an erection.

 Pelvic pain: Pain or discomfort in the pelvic area or lower back.

 Bone pain: Advanced prostate cancer may spread to the bones, causing bone pain.

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 FIBROIDS
Uterine fibroids, also known as leiomyomas or myomas, are noncancerous growths of the
uterus. They are composed of muscle cells and other tissues that grow within the wall of
the uterus.

CAUSES RISK FACTORS

 Genetic factors: There may be a genetic predisposition, as fibroids tend to run in
families.
 Hormonal factors: Estrogen and progesterone, hormones that stimulate the
development of the uterine lining during each menstrual cycle, may promote the
growth of fibroids. Pregnancy-related hormonal changes can also influence fibroid
development.
 Other growth factors: Other substances, such as insulin-like growth factor, may
affect fibroid growth.
 Age: Uterine fibroids are most common in women aged 30-40.
 Family history: Having a family member with fibroids increases the risk.
 Race: African-American women are more likely to develop fibroids.
 Obesity: Being overweight increases the risk of fibroids.

PATHOLOGY
 Uterine fibroids develop from the smooth muscular tissue of the uterus (myometrium).

They can vary in size, number, and location within the uterus.
 There are three main types of fibroids: subserosal (on the outer surface of the uterus),

intramural (within the muscular walls of the uterus), and submucosal (just below the
lining of the uterus).

CLINICAL FEATURES
 Symptoms: Many women with uterine fibroids do not experience symptoms.
Symptoms, when present, may include pelvic pain or pressure, heavy menstrual
bleeding, prolonged menstrual periods, and frequent urination.
 Complications: Fibroids can cause complications such as anemia due to heavy
bleeding.

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 Pelvic pain and discomfort: Large fibroids or those pressing on surrounding organs
may cause pelvic pain and discomfort.
 Menstrual changes: Heavy menstrual bleeding (menorrhagia) and prolonged periods
are common. Some women may experience irregular menstrual cycles.
 Urinary and bowel symptoms: Fibroids pressing on the bladder can cause frequent
urination. Pressure on the rectum may lead to constipation.

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 CARCINOMA OF CERVIX
Cervical carcinoma, also known as cervical cancer, is a type of cancer that originates in
the cells lining the cervix, which is the lower part of the uterus that connects to the
vagina.

CAUSES
The primary cause of cervical carcinoma is persistent infection with high-risk types of
human papillomavirus (HPV). HPV is a sexually transmitted virus, and certain strains,
such as HPV 16 and 18, are strongly associated with the development of cervical cancer.
Other factors that may contribute to the development of cervical cancer include:
 Weakened immune system: Conditions or medications that suppress the immune

system can increase the risk of HPV persistence and cervical cancer.
 Smoking: Tobacco use is linked to an increased risk of cervical cancer.

 Long-term use of oral contraceptives: Prolonged use of certain birth control pills

may be associated with a slightly increased risk.

 Multiple sexual partners: Increased exposure to HPV raises the risk.

 Early sexual activity: Beginning sexual activity at an early age increases the risk of

HPV exposure.
 High number of full-term pregnancies: Multiple pregnancies and childbirths may be

associated with an increased risk.

RISK FACTORS
 HPV infection: Particularly with high-risk types.

 Smoking: Increases the risk of cervical cancer and may reduce the effectiveness of the

immune system.
 Weakened immune system: Conditions such as HIV/AIDS or medications that

suppress the immune system.

 Long-term use of oral contraceptives: Especially for more than five years.

 Multiple sexual partners: Increases the likelihood of HPV exposure.

 Early sexual activity: Starting sexual activity at an early age.

 Family history: A family history of cervical cancer may contribute to the risk.

133 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOLOGY
Cervical cancer is primarily squamous cell carcinoma or adenocarcinoma. Most cases are
squamous cell carcinomas, and they typically begin in the flat, thin cells lining the
cervix. Adenocarcinomas originate in the glandular cells of the cervix. The progression
from normal cervical cells to precancerous changes (dysplasia) and eventually to invasive
cancer is a multistep process typically associated with persistent HPV infection.

CLINICAL FEATURES

 Abnormal vaginal bleeding, especially between menstrual periods or after menopause.

 Increased vaginal discharge.

 Pelvic pain or pain during intercourse.

 Pain during urination.

 Advanced cases may present with weight loss, fatigue, and bone pain if the cancer has
spread.

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 CARCINOMA OF ENDOMETRIUM

Carcinoma of the endometrium is a type of cancer that develops in the cells of the
endometrial lining, which is the innermost layer of the uterus. It is the most common
form of uterine cancer.

CAUSES
The exact cause of endometrial carcinoma is not fully understood, but certain risk
factors have been identified. The primary cause is believed to be an imbalance in the
levels of female hormones, particularly estrogen and progesterone. Other factors that
may contribute to the development of endometrial carcinoma include:
 Hormonal factors: Increased exposure to estrogen without sufficient levels of
progesterone can lead to an increased risk.
 Obesity: Adipose tissue (fat) can produce estrogen, leading to hormonal imbalance.

 Age: The risk increases with age, with most cases occurring after menopause.

 Diabetes: There is an association between diabetes and an increased risk of

endometrial cancer.
 Hereditary factors: A family history of certain genetic conditions, such as Lynch

syndrome, can predispose individuals to endometrial cancer.

RISK FACTORS
 Age (most commonly diagnosed after menopause)

 Obesity

 Estrogen replacement therapy without progesterone

 Tamoxifen use (a drug used for breast cancer treatment)

 Diabetes

 Hypertension

 Lynch syndrome or other hereditary nonpolyposis colorectal cancer (HNPCC)

syndromes
 Personal or family history of certain cancers, including colorectal cancer

PATHOLOGY
Endometrial carcinomas are typically classified into two main types based on their
histology:

135 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 Type I: This is the more common form and is typically associated with estrogen

excess. It often presents as well-differentiated endometrioid adenocarcinoma.

 Type II: This type is less common and is more aggressive. It includes poorly

differentiated endometrioid adenocarcinomas, serous carcinomas, and clear cell

carcinomas.
Pathologically, cancer cells invade the endometrial tissue, and the extent of invasion is
graded based on how deeply the cancer has penetrated the tissue layers.

CLINICAL FEATURES

 Abnormal vaginal bleeding or spotting, especially after menopause

 Pelvic pain or discomfort

 Painful urination

 Pain during intercourse

 Unintentional weight loss

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 VESICULAR MOLE
A vesicular mole, also known as a complete hydatidiform mole or simply a molar
pregnancy, is a type of gestational trophoblastic disease characterized by the abnormal
development of placental tissue.

Definition: A vesicular mole is a noncancerous tumor that forms in the uterus as a

result of an abnormal fertilization of an egg. In this condition, the cells that would
normally develop into the placenta (trophoblasts) grow into clusters of fluid-filled sacs
(vesicles) resembling grapes.

CAUSES
The primary cause of a vesicular mole is an abnormal fertilization event. This can occur
when an egg is fertilized by either an empty sperm (without genetic material) or by one
sperm that duplicates its genetic material, resulting in an abnormal number of
chromosomes.

RISK FACTORS
 Age: Women under 20 or over 35 years old are at a slightly higher risk.

 Previous molar pregnancy: Having had a vesicular mole in the past increases the

risk of having another.

 History of miscarriage: Women with a history of miscarriage may be at a slightly

increased risk.
 Dietary factors: Certain dietary deficiencies may contribute to the risk.

PATHOLOGY
In vesicular mole, the placental tissue develops abnormally, forming fluid-filled vesicles.
The trophoblastic tissue proliferates rapidly, and the characteristic appearance
resembles clusters of grapes. The molar tissue can invade the uterine wall, and if left
untreated, it can potentially develop into a more aggressive form known as gestational
trophoblastic neoplasia.

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CLINICAL FEATURES
 Vaginal bleeding: Often in the first trimester and may be darker or brighter than

typical menstrual bleeding.

 Abdominal swelling or rapid uterine growth: Due to the rapid proliferation of

abnormal tissue.
 Hyperemesis gravidarum: Severe nausea and vomiting during pregnancy.

 Hypertension and proteinuria: In some cases, symptoms similar to preeclampsia

may occur.

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 CHORIOCARCINOMA
Choriocarcinoma is a highly malignant and rare cancer that originates from
trophoblastic cells, which are cells that would normally develop into the placenta during
pregnancy. It can occur as a gestational trophoblastic neoplasia, either following a molar
pregnancy, a normal pregnancy, or rarely as a primary tumor.

CAUSES
Choriocarcinoma is primarily associated with abnormal fertilization events. The following
situations can lead to the development of choriocarcinoma:
 Molar pregnancy: Choriocarcinoma can arise from persistent trophoblastic tissue

after a molar pregnancy (complete or partial).

 Normal pregnancy: Although extremely rare, choriocarcinoma can develop after a

full-term pregnancy.
 Ectopic pregnancy: Choriocarcinoma can occur following an ectopic pregnancy,

where the fertilized egg implants outside the uterus.

RISK FACTORS
 Previous molar pregnancy: Women who have had a molar pregnancy are at an

increased risk.
 Age: Choriocarcinoma is more common in women of reproductive age, with a higher

incidence in teenagers and women over 35.

 History of miscarriage or abortion: In some cases, choriocarcinoma can develop

after a spontaneous abortion or induced abortion.

 Asian ethnicity: Choriocarcinoma has a higher incidence in women of Asian descent.

PATHOLOGY
Choriocarcinoma is characterized by the presence of abnormal trophoblastic cells,
including syncytiotrophoblasts and cytotrophoblasts, which are part of the tissue that
normally forms the placenta. These cells grow rapidly and can invade local tissues and
metastasize to distant organs, particularly the lungs, brain, and liver.

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CLINICAL FEATURES
 Vaginal bleeding: Irregular bleeding or heavy vaginal bleeding is a common symptom.

 Enlarged uterus: Due to the rapid growth of trophoblastic tissue.

 Hyperemesis gravidarum: Severe nausea and vomiting may occur.

 Pulmonary symptoms: If there is metastasis to the lungs, symptoms such as cough,

chest pain, or difficulty breathing may be present.

 Neurological symptoms: In cases of brain metastasis, symptoms like headaches,

seizures, or neurological deficits may occur.

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 ECTOPIC GESTATION
Ectopic gestation, also known as an ectopic pregnancy, is a condition in which a
fertilized egg implants and grows outside the uterus, most commonly in one of the
fallopian tubes. However, ectopic pregnancies can also occur in other locations such as
the cervix, ovary, or abdominal cavity.

CAUSES
The primary cause of an ectopic pregnancy is an issue with the normal transport of the
fertilized egg through the fallopian tube to the uterus. This may be due to:
 Structural abnormalities: Scar tissue from previous pelvic surgeries, inflammation,

or infections can block or narrow the fallopian tubes.

 Abnormalities in the fallopian tubes: Conditions that affect the structure or function

of the fallopian tubes, such as tubal scarring or congenital anomalies.

 Hormonal factors: Imbalances in hormones that regulate the reproductive system can

affect the movement of the fertilized egg.

 Previous ectopic pregnancy: Having had an ectopic pregnancy in the past increases

the risk.

RISK FACTORS
 Pelvic inflammatory disease (PID): Infections, often sexually transmitted, can cause

inflammation and scarring of the fallopian tubes.

 Previous surgery in the pelvic area: Surgeries such as tubal ligation or pelvic

surgeries can increase the risk of scarring.

 Endometriosis: The presence of endometrial tissue outside the uterus can affect the

function of the fallopian tubes.

 Pelvic surgeries or procedures: Previous surgeries in the pelvic area, including tubal

ligation or fertility treatments, can increase the risk.

 Maternal age: Ectopic pregnancy is more common in women over 35.

 Contraceptive methods: The use of intrauterine devices (IUDs) for birth control

slightly increases the risk.

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PATHOLOGY
In an ectopic pregnancy, the fertilized egg implants and begins to grow in a location
other than the uterus. The most common site is the fallopian tube. As the embryo grows,
it can cause the tube to rupture, leading to internal bleeding and a medical emergency.

CLINICAL FEATURES
 Abdominal pain: Often one-sided and may be sharp or stabbing.

 Vaginal bleeding: Light to heavy bleeding may occur, often different from typical

menstrual bleeding.
 Shoulder pain: In cases of a ruptured ectopic pregnancy, blood may irritate the

diaphragm, causing referred pain to the shoulder.

 Weakness, dizziness, or fainting: Indicating internal bleeding and shock.

 Gastrointestinal symptoms: Nausea, vomiting, or diarrhea may occur.

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 OVARIAN CYST

An ovarian cyst is a fluid-filled sac that forms on or within an ovary. Most ovarian cysts
are benign (non-cancerous) and do not cause noticeable symptoms. They are a common
occurrence in women of reproductive age.

CAUSES
Ovarian cysts can have various causes, and different types of cysts may result from
different mechanisms:
 Functional cysts: The most common type, these cysts form as a normal part of the

menstrual cycle. They include follicular cysts (developing from a follicle that doesn't
release an egg) and corpus luteum cysts (when the follicle ruptures but seals off and
accumulates fluid).
 Dermoid cysts: These cysts develop from cells present in the egg, and they can

contain tissues like hair, skin, or teeth.

 Cystadenomas: These cysts form on the surface of the ovary and are filled with a

watery or mucous-like material.

 Endometriomas: Resulting from endometriosis, these cysts involve the abnormal

growth of endometrial tissue outside the uterus.

 Polycystic ovary syndrome (PCOS): Women with PCOS may develop multiple small

cysts on their ovaries due to hormonal imbalances.

RISK FACTORS
 Age: Ovarian cysts are more common during the childbearing years.

 Irregular menstrual cycles: Conditions causing irregular ovulation may contribute.

 Hormonal imbalances: Conditions such as PCOS or hormonal therapies.

 Pregnancy: Cysts can form as a normal part of pregnancy.

 Endometriosis: A condition where endometrial tissue grows outside the uterus.

 Pelvic infections: Infections can lead to the development of cysts.

143 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PATHOLOGY
The pathology of ovarian cysts varies based on the type of cyst. Functional cysts are
usually a result of normal physiological processes during the menstrual cycle, while
other types, such as dermoid cysts or cystadenomas, involve specific cellular origins and
growth patterns.

CLINICAL FEATURES
Many ovarian cysts are asymptomatic and are often discovered incidentally during
routine pelvic examinations or imaging studies. However, some cysts may cause
symptoms, including:
 Pelvic pain: Dull aching or sharp pain in the lower abdomen, often on the side of the

affected ovary.
 Bloating or heaviness: Some women may experience a feeling of fullness or pressure.

 Changes in menstrual patterns: Irregular periods or changes in the menstrual cycle.

 Pain during intercourse: Cysts may cause discomfort during sexual activity.

 Frequent urination: Large cysts can press on the bladder.

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 OVARIAN TUMOURS

Ovarian tumors are abnormal growths that can occur in one or both ovaries. They can be
classified based on their behavior into benign tumors, which do not invade nearby
tissues or spread to other parts of the body, and malignant tumors, which have the
potential to invade surrounding tissues and metastasize to other organs.

CAUSES
 Genetic factors: Inherited gene mutations, such as those associated with the BRCA1

and BRCA2 genes, can increase the risk of ovarian cancer.

 Hormonal factors: Hormonal imbalances, such as those seen in polycystic ovary

syndrome (PCOS), may contribute to the development of certain ovarian tumors.

 Age: The risk of ovarian tumors, particularly ovarian cancer, increases with age.

 Family history: A family history of ovarian, breast, or colorectal cancer may increase

the risk.
 Reproductive factors: Factors such as early onset of menstruation, late onset of

menopause, and never having been pregnant may affect ovarian cancer risk.
 Endometriosis: Women with endometriosis may have an increased risk of certain

types of ovarian tumors.

RISK FACTORS
 Age: Ovarian cancer is more common in older women.

 Inherited gene mutations: BRCA1 and BRCA2 mutations are associated with an

increased risk of ovarian cancer.

 Personal or family history: A personal history of breast, ovarian, or colorectal cancer,

or a family history of these cancers, increases the risk.

 Never having been pregnant: Women who have never been pregnant may have a

higher risk.
 Hormone replacement therapy (HRT): Long-term use of estrogen without
progesterone may increase the risk.
 Endometriosis: Women with endometriosis have a slightly higher risk.

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PATHOLOGY
Ovarian tumors can have various histological types, including epithelial tumors (arising
from the surface layer of the ovary), germ cell tumors (arising from cells that produce
eggs), and stromal tumors (arising from the connective tissue). Malignant tumors may be
further classified into different stages based on the extent of spread.

CLINICAL FEATURES
 Abdominal or pelvic pain: Dull aching or persistent pain.

 Bloating or abdominal distension: Feeling of fullness or swelling in the abdomen.

 Changes in bowel habits: Such as constipation or diarrhea.

 Urinary symptoms: Increased frequency or urgency.

 Unexplained weight loss: Especially in cases of malignant tumors.

 Fatigue: Generalized tiredness or weakness.

 Irregular menstrual cycles: In cases of hormonal imbalance.

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 BREAST CANCER
 Breasts are modified sweat glands.
 They are conical in shape.
 They lie on superficial fascia of the front of the chest.
 Breast extends vertically from 2nd to 6th ribs and horizontally from lateral margin of
the sternum to the midaxillary line.
 Mammary gland is formed of 15-20lobes. Each lobe contains a number of glandular
structures called lobules. Each lobule is formed by several alveoli. Each alveolus is the
unit of milk production.
 Breasts lie on three muscles: pectoralis major, serratus anterior and oblique muscle.

MAJOR DISEASES OF THE BREASTS

 Inflammatory diseases: Mastitis
 Hormonally induced changes: Fibrocystic changes
 Tumors: Fibroadenoma & Carcinoma of the breast
Fibroadenoma
It is a benign tumor of the breast.
It is the solitary, hard mobile mass in the breast tissue.
It is encapsulated and round in appearance.
They are rubbery and grayish white nodules.
It is due to hormonal influence (estrogen).

CARCINOMA OF THE BREAST

It is a malignant tumor of the breast that originates in the cells of the breast. It is a type
of cancer that can occur in both men and women. Breast carcinoma is typically begins in
the milk ducts or lobules and potentially invade the surrounding tissues

RISK FACTORS
 Hereditary factors: deficiency or defective errors in the tumor suppressor genes
(BRCA1 & BRCA2)
 Post menopausal period
 Familial history

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 Age after 35 years
 Elderly primi mothers
 Nulliparous women
 Exogenous estrogen administration
 Oral contraceptives
 Obesity
 Lack of physical exercises
 Presence of other cancers
 Exposure to radiation
 Early stoppage of breast feeding

PATHOGENESIS
Due to etiological/ risk factors

Mutation of the epithelial cells of the ducts/lobules

Malignant tumors of the epithelial cells of the ducts or lobules of the mammary gland

Carcinoma in situ (Stage 0)

Continuous growth of tumor up to 2cms (Stage1)

Growth of the tumor up to 5cms (Stage2)

With or without local lymph node metastasis

Tumor growth more than 5cms with regional spread without distant metastasis (Stage3)

Growth of the tumor to large size associated with distant metastasis (Stage4)

CLINICAL FEATURES
 Lump in the breast
 Well defined or ill defined mass
 Single or multiple nodules
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 Nodules are soft/firm
 Nodules are mobile or attached to skin or underlying muscle
 Axillary lymphadenopathy (enlargement of lymph nodes)
 Dimpling of the skin
 Retraction of the nipple
 Changes in the shape and size of the breast on the affected side

COMPLICATIONS
 Breast cancer metastasizes via lymphatics to the axillary group of lymph nodes.
 Distant metastasis into the lungs, liver, bones, brain and the adrenal glands occur via
hematogenous spread.

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 HYDROCEPHALUS

Hydrocephalus is a medical condition characterized by the accumulation of

cerebrospinal fluid (CSF) in the brain's ventricles, leading to increased intracranial
pressure.

Hydrocephalus is a condition in which there is an abnormal buildup of cerebrospinal

fluid (CSF) within the brain, which can lead to increased intracranial pressure and
potentially damage brain tissue.

CAUSES AND RISK FACTORS

 Increased production of CSF

 Obstruction to the flow of CSF
 Faulty absorption of CSF

 Intrauterine infections
 Intracranial infections from birth trauma
 Infections such as meningitis or encephalitis
 Mastoiditis
 Otitis media
 Congenital malformation
 Tumors blocking the flow of CSF
 Head injuries or bleeding within the brain
 Bleeding into the CSF spaces (intraventricular hemorrhage)
 Obstruction in the normal flow of CSF (e.g., due to a tumor or cyst)
 Certain medical conditions, such as aqueductal stenosis, which narrows the aqueduct
of Sylvius, a passage for CSF in the brain

TYPES
Congenital hydrocephalus: Hydrocephalus is present at birth and can result from
genetic factors, developmental abnormalities, or maternal infections during pregnancy.
Acquired hydrocephalus: This type develops after birth and can be caused by various
factors, including infections, trauma and tumors.

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Non-communicating (obstructive) hydrocephalus: This occurs when there is an
obstruction that prevents the normal flow of CSF, such as a tumor blocking a ventricle
or the narrow aqueduct of Sylvius.

Communicating hydrocephalus: This type involves impaired reabsorption of CSF or

overproduction of CSF, leading to increased pressure throughout the ventricular system.

PATHOGENESIS

Due to etiological/risk factors

Accumulation of CSF in the ventricular spaces of the brain

Increased intracranial pressure

Dilatation of the ventricles

Disruption of ventricular lining and compression of white matter of the brain due to
expansion

Brain damage

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CLINICAL FEATURES

 Headache

 Nausea and vomiting

 Blurred or double vision

 Changes in mental function, such as confusion or irritability

 Difficulty walking or balance problems

 Cognitive impairment

 Seizures

 Enlargement of the head (common in infants with congenital hydrocephalus)

 In infants: bulging fontanelles (soft spots on the skull), poor feeding, irritability, and a

rapid increase in head size

 In children and adults: changes in personality, memory problems, and incontinence

 Eyes fixed downward (sun setting)

 Lethargy/sluggishness/sleepiness

 Loss of balance

 Poor co-ordination

 Loss of bladder control

 Decline in memory

 Difficulty walking

 Speech problems

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 MENINGITIS
 Inflammation of the meninges is called meningitis.
 Inflammation of the duramater is called pachymeningitis
 Inflammation of the arachnoid and piamater is called leptomeningitis
 Pachymeningitis is an extension of the inflammation from otitis media or fracture of
the skull
 Leptomeningitis is the result of infection by infiltration of subarachnoid space by
infectious agents.

ETIOLOGY
E. coli
Haemophilus influenza
Streptococcus pneumonia
Viral meningitis (entero viruses)

MODE OF TRANSMISSION
Blood stream (Bacteremia)
From an adjacent focus of infection (sinusitis and otitis media)
Traumatic (Skull fracture and penetrating head wound)
Iatrogenic (lumbar puncture and ventricular shunting)

PATHOGENESIS
Due to etiological factors (Blood stream/local focus/trauma)

Infection cross the blood brain barrier

Pathogens enter the mucosal surface or cavity or between the layers of meninges

Proliferates in the CSF

Inflammation of the meninges

Transendothelial migration of granulocytes and monocytes

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 Increased intracranial pressure
Cerebral edema
Impaired circulation
Encephaliltis

CLINICAL FEATURES
 Fever
 Chills
 Malaise
 Nuchal rigidity
 Headache
 Vomiting
 Papilledema (optic nerve inflammation)
 Photophobia
 Irritability
 Brudzinski’s and Kernig’s sign
 Opisthotonos (back and extremities of the body arch backwards and body rests on the
head and heels)

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 ENCEPHALITIS

Encephalitis is an inflammation of the brain parenchyma, which includes the brain

tissue itself. It can be caused by infectious agents, immune system responses, or other
factors leading to inflammation within the brain.

CAUSES AND RISK FACTORS

 Infections: Viral infections are the most common cause of encephalitis. Herpes
simplex virus (HSV), enteroviruses, and arboviruses (like West Nile virus) are
examples. Bacterial and fungal infections can also lead to encephalitis, although they
are less common.
 Immune system dysfunction: Autoimmune encephalitis occurs when the immune
system mistakenly targets and attacks the brain tissue.
 Non-infectious causes: Certain drugs, chemicals, and toxins can lead to encephalitis.
Inflammatory conditions elsewhere in the body may sometimes affect the brain.

PATHOLOGY
Viral Encephalitis:
 Viruses invade the brain, causing inflammation and tissue damage.

 The immune response may contribute to further damage.

 In severe cases, the blood-brain barrier can be compromised.

Autoimmune Encephalitis:
 The immune system produces antibodies that mistakenly target proteins in the brain.

 This immune response leads to inflammation and damage to neural tissues.

Non-infectious Encephalitis:
 Exposure to certain drugs or toxins can trigger inflammation in the brain.

 Autoimmune reactions may also play a role in some non-infectious cases.

Due to etiological factors (Primary/Secondary)

Infection in the brain

Inflammation of the brain tissue and surrounding membranes

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 Dysfunction of the neuronal cells

Cerebral edema, vascular congestion and intracranial hemorrhage

Degenerative changes in the nerve cells of the brain

Brain damage

Neurological deficit
CLINICAL FEATURES
 Fever
 Headache
 Vomiting
 Stiff neck
 Lethargy
 Confusion
 Drowsiness
 Hallucination
 Slower movements
 Seizures
 Irritability
 Sensitivity to light (photophobia)
 Unconsciousness

156 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 THROMBOSIS

Thrombosis is a vascular disorder characterized by the formation of blood clots, known

as thrombi, within blood vessels. This condition can occur in arteries or veins and may
have serious consequences if the clot obstructs blood flow. The pathology of thrombosis
involves a complex interplay of factors related to the coagulation system, blood vessels,
and blood flow.

Endothelial injury or dysfunction: Thrombosis often begins with damage to the

endothelium, the inner lining of blood vessels. Endothelial injury can be caused by
factors such as inflammation, trauma, or turbulent blood flow.

Alteration in blood flow: Disturbed or slow blood flow can contribute to the formation
of blood clots. Turbulent flow in areas of vascular stenosis (narrowing) or bifurcations
may promote clot formation.

Hypercoagulability: Conditions that increase the tendency of blood to clot, known as

hypercoagulability, play a significant role. Genetic factors, acquired disorders, and
certain medical conditions can contribute to an imbalance in the coagulation system.

Platelet Activation: Platelets, which are involved in blood clotting, can be activated by
exposed collagen or tissue factor due to endothelial injury. Activated platelets release
substances that further enhance the coagulation process.

Coagulation Cascade: The coagulation cascade involves a series of sequential steps that
ultimately lead to the formation of fibrin, a protein that stabilizes the blood clot. Factors
in the coagulation system are activated in response to vessel injury, initiating the
cascade.

Thrombus Formation: Fibrin and platelets accumulate at the site of injury, forming a
thrombus. Thrombi can partially or completely obstruct blood vessels, leading to reduced
blood flow.

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Embolization: In some cases, parts of the thrombus can break off and travel through
the bloodstream as emboli. Emboli can lodge in smaller blood vessels, causing ischemia
(lack of blood supply) in distant tissues.

Clinical consequences

 Thrombosis can lead to various clinical conditions, depending on the location and size
of the thrombus.

 Examples include deep vein thrombosis (DVT), pulmonary embolism, stroke, and
myocardial infarction.

EMBOLISM
An embolism is a vascular disorder characterized by the obstruction of blood vessels by
an embolus, which is a detached, moving mass within the bloodstream. Emboli can be
solid, liquid, or gas, and their presence can lead to the blockage of blood vessels, causing
tissue ischemia (lack of blood supply) and damage.

FORMATION OF EMBOLI
 Thromboembolism: Blood clots (thrombi) are the most common type of emboli. They

can form in veins (e.g., deep vein thrombosis) or the heart (e.g., atrial fibrillation) and
then break loose, traveling through the bloodstream.
 Fat Embolism: Fat globules, often released from fractured bones, can enter the

bloodstream and cause embolism.

 Air Embolism: Introduction of air into the bloodstream, often through medical

procedures or trauma, can result in air embolism.

EMBOLUS TRANSPORT
 The embolus is carried through the bloodstream, and its destination depends on its

size and shape.

 Larger emboli may lodge in major arteries, causing more immediate and severe

blockages, while smaller emboli may travel to smaller vessels.

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VASCULAR OBSTRUCTION
 When the embolus reaches a blood vessel that is too small for it to pass through, it

becomes lodged, causing an obstruction.

 The obstruction disrupts normal blood flow, leading to ischemia in the downstream

tissues.

TISSUE ISCHEMIA AND INFARCTION

 Ischemia occurs when blood flow is insufficient to meet the metabolic demands of

tissues.
 Prolonged ischemia can lead to tissue damage and necrosis (cell death).

 The severity and consequences depend on the size and location of the blood vessel

affected and the tissues it supplies.

CLINICAL MANIFESTATIONS
 Symptoms of embolism vary depending on the affected organ or tissue.

 Examples of conditions resulting from embolism include pulmonary embolism

(blockage of pulmonary arteries), cerebral embolism (stroke), and peripheral arterial
embolism.

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 CEREBROVASCULAR ACCIDENT (CVA)/STROKE

An abrupt neurological outburst/dysfunction caused by impaired perfusion through the

blood vessels to the brain is called cerebrovascular accident/stroke.
Acute onset of neurological deficit is called stroke.

RISK FACTORS

Non- modifiable Modifiable

Age: elderly Hypertension
Sex: men/male Smoking
Race/ethnicity: black and latino community Alcohol and drug abuse
Genetics Physical inactivity
Transient Ischemic Attack (it is also known Hyperlipidemia
as mini stroke and it is due to temporary Diabetes mellitus
blockage of blood supply to the brain. It is Atrial fibrillation
the warning sign before the actual stroke Medications (anticoagulants & thrombolytics
event) Heady injury
High cholesterol levels
obesity

PATHOGENESIS

The blood flow to the brain is managed by two internal arteries and two vertebral arteries
posteriorly (circle of Willis).

Ischemic stroke is caused by deficient blood and oxygen supply.

Hemorrhagic stroke is caused by bleeding or leaky blood vessels.

ISCHEMIC STROKE

Due to etiological or risk factors (cholesterol and obesity)

Atherosclerosis (thickening of the blood vessels due to deposition)

Plaque constrict the vascular lumen or chamber of the heart

Thrombi (stationary blood clot) /Emboli (circulating blood clot)

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 Decreased blood flow to the brain region

Ischemic cascade begins (blood flow less than 250ml/100gm/min)

Neurons no longer maintain aerobic respiration

Large amount of lactic acid generation due to anaerobic respiration

Change in the pH level and production of energy/ATP failure

Membrane pumps that maintain electrolyte balances begin to fail and the cells cease to
function

An area of low cerebral blood flow exists around the area of infarction called Penumbra

Ischemic cascade threatens cells in the penumbra

(Increase in intracellular calcium
Depolarization of cell membrane
Release of glutamate)

Enlarge the area of infarction into the penumbra and extending the stroke

HEMORRHAGIC STROKE

Due to etiological or risk factors

(Physical trauma/injury, aneurysm and hypertension)

Stress in the brain tissue and internal injury cause blood vessels to rupture

Bleeding in and around the brain region

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 Intracranial hemorrhage cause abnormal accumulation of blood within the brain

Compression of tissue from an expanding hematoma

Distort and injure tissue and pressure lead to a loss of blood supply to the brain tissue

Infarction of brain parenchyma

Neurological dysfunction

CLINICAL FEATURES

 Muscle weakness
 Numbness
 Reduction in sensory or vibratory sensation
 Altered smell, taste, hearing and vision
 Drooping of eye lid
 Weakness of ocular muscles
 Decreased reflexes (gag, swallow, pupil reactivity to light)
 Aphasia (inability to speak/understand the language)
 Memory deficits
 Dysphasia
 Dysarthria
 Apraxia (inability to perform learnt actions)
 Loss of visual field
 Hemiplegia (paralysis of one side of the body)
 Hemiparesis (weakness of one side of the body)
 Cognitive impairment
 Depression
 Paraplegia (impairment in motor and sensory function of the lower extremities)
 Quadriplegia (also known as tetraplegia, paralysis affecting all four limbs due to
damage to the brain and spinal cord )
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 HEMIPLEGIA

Hemiplegia is a medical term used to describe a condition in which one side of the body
is partially or completely paralyzed. It typically results from damage to the brain or
spinal cord, and it can affect various functions and body parts on the affected side.

CAUSES

 Stroke
 Traumatic brain injury
 Cerebral palsy
 Brain tumors
 Multiple Sclerosis

CLINICAL FEATURES

 Weakness or Paralysis
 Muscle spasticity.
 Sensory changes: changes in sensation on the affected side, such as numbness or
tingling.
 Impaired coordination: Coordination and fine motor skills may be compromised,
making it difficult to perform everyday tasks.
 Speech and language deficits: If the brain regions responsible for speech and language
are affected, individuals may experience difficulty with speech and language, such as
aphasia.
 Cognitive impairments: Depending on the extent of brain damage, cognitive functions
like memory, attention, and problem-solving may be affected.
 Visual disturbances: Hemiplegia can sometimes be associated with visual deficits,
especially if the damage involves the visual cortex in the brain.
 Difficulty with activities of daily living: People with hemiplegia may struggle with
activities such as dressing, bathing, and eating independently.
 Pain: Hemiplegia can be associated with pain in the affected limbs due to muscle
stiffness, spasms, or joint problems.

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 PARAPLEGIA

Paraplegia is a condition characterized by paralysis or loss of function in the lower half of

the body, typically affecting both legs and sometimes part of the trunk.

CAUSES

Spinal cord injury: The most common cause of paraplegia is a spinal cord injury, often
resulting from trauma such as accidents or falls.

Medical conditions: Some medical conditions like spina bifida or tumors in the spinal
cord can also lead to paraplegia.

CLINICAL FEATURES

 Paralysis: Experience paralysis in the lower limbs, affecting movement, sensation, and

bowel and bladder control.

 Muscle spasticity: Muscles in the lower limbs may become spastic and stiff, making it

difficult to move or control the legs.

 Sensory changes: Loss of sensation below the level of the spinal cord injury is

common.

 Bowel and bladder issues: Control over bowel and bladder function may be

compromised, leading to incontinence.

 Mobility aids: Individuals with paraplegia often rely on mobility aids like wheelchairs

or braces to move around.

164 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 QUADRIPLEGIA

Quadriplegia, also known as tetraplegia, is a condition characterized by paralysis or loss

of function in all four limbs (both arms and both legs) and sometimes the trunk. It is
often more severe than paraplegia.

CAUSES

 Spinal cord injury: Traumatic spinal cord injuries, often higher up on the spinal cord,

are the primary cause of quadriplegia.

 Medical conditions: Certain medical conditions, such as amyotrophic lateral sclerosis

(ALS) or severe forms of spina bifida, can lead to quadriplegia.

CLINICAL FEATURES:

 Paralysis: Individuals with quadriplegia experience complete or partial paralysis in all

four limbs, which can be accompanied by limited or no sensation.

 Respiratory impairment: Quadriplegia may affect respiratory muscles, making it

necessary to use assisted ventilation.

 Limited fine motor skills: Fine motor skills are often severely compromised, affecting

the ability to perform detailed tasks.

 Bowel and bladder dysfunction: Control over bowel and bladder function is often

impaired.

165 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 BRAIN TUMORS

A cancerous or non-cancerous mass/growth of abnormal cells in the brain is called

brain tumor. A tumor is localized in the intracranial space within the skull is considered
to be as brain tumor.

CAUSES AND RISK FACTORS

 Genetic factors: Neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni

syndrome, and tuberous sclerosis, can increase the risk of brain tumors.
 Ionizing radiation: Radiation therapy, or environmental sources, such as nuclear
fallout.
 Age: The risk of brain tumors increases with age. Certain types, like
medulloblastomas, are more common in children and young adults.
 Gender: Men being more susceptible to certain types (e.g., glioblastomas) and women
to others (e.g., meningiomas).
 Chemical Exposures: Occupational exposure to certain chemicals or toxins, such as
formaldehyde, may be associated with an increased risk of developing brain tumors.
 Family history
 Immune system disorders: HIV and AIDS.
 Chemical exposures: solvents, pesticides, oil products, rubber and plastic
 Electromagnetic fields: Power lines
 Use of cell phones
 N-nitroso compounds
 Exposure to cosmetics, dyes and sprays
 Psychological stress
 Viral infections: Epstein barr virus and cytomegalo virus
 Head injuries

ETIOPATHOLOGY

Primary brain tumors: These tumors originate within the brain or its surrounding
tissues. The exact cause of primary brain tumors remains largely unknown, but genetic
mutations and alterations in cell growth regulation are believed to play a significant role.

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Common types include gliomas (e.g., glioblastoma), meningiomas, pituitary adenomas,
and medulloblastomas.

Secondary brain tumors (Metastatic Brain Tumors): These tumors originate elsewhere
in the body and spread to the brain through the bloodstream or the lymphatic system.
Common primary cancer sites that can metastasize to the brain include the lung, breast,
kidney, and skin (melanoma).

Due to etiological/risk factors

Changes in the pattern of cell division and formation of tumors

Tumors are space-occupied lesions and displace normal tissue or occupy normal tissue
spaces

When normal brain tissue is compressed, blood flow is altered and ischemia leading to
necrosis may occurs disrupting major functions

Cerebral edema

The skull is rigid, box like structure containing little room for expansion of any of the
intracranial contents

Brain tumors cause progressive intracranial pressure

Displacement of brain structure with herniation of brain

Altered functions of the brain

CLINICAL FEATURES

 Increased cranial pressure

 Headache: morning headache, coughing, straining and sudden movement
 Projectile vomiting

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 Papilledema
 Visual disturbances (diplopia, visual acuity and visual field deficits)
 Seizures
 Hemiparesis
 Mental confusion
 Sensory and motor abnormalities
 Alteration in cognition
 Language disturbances (Aphasia)

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 FRACTURE

“Break in the continuity or intactness of bone”

“Disruption in the continuity of the bone or normal architecture of the bone resulting
from mechanical forces like trauma”
A fracture is a medical term used to describe a broken bone. It occurs when there is a
disruption in the continuity of the bone, resulting in a crack or complete break.

CAUSES
Trauma: The most common cause of fractures is physical trauma, such as a fall, motor
vehicle accident, or sports injury.
Overuse or Repetitive Stress: Continuous stress on a bone, especially in weight-
bearing activities, can lead to stress fractures.
Medical Conditions: Certain medical conditions, such as osteoporosis (weakening of
bones), can make bones more susceptible to fractures.
Pathological Conditions: Tumors or infections in bones can weaken them and
contribute to fractures.
RISK FACTORS
Age: Bones become more brittle with age, making older individuals more prone to
fractures.
Osteoporosis: Decreased bone density increases the risk of fractures.
Gender: Women, especially after menopause, have a higher risk of fractures due to
decreased estrogen levels.
Sports Participation: Athletes involved in high-impact or contact sports are at an
increased risk.
Genetics: Family history of fractures or bone disorders can be a risk factor.

TYPES OF FRACTURES
Fractures can be classified into various types based on their characteristics.
 Closed Fracture: The bone breaks, but the skin remains intact.
 Open Fracture: The broken bone protrudes through the skin.
 Greenstick Fracture: The bone bends and cracks but doesn't break completely.
 Comminuted Fracture: The bone shatters into multiple pieces.
 Hairline Fracture: A small crack in the bone without significant separation.
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PATHOGENESIS
The pathogenesis of a fracture involves the disruption of the bone's integrity, often due to
mechanical force exceeding the bone's strength. This can lead to the formation of a
fracture line, affecting the bone's blood supply and initiating the healing process.
Fractures occur when the force applied to a bone exceeds its strength. The sequence of
events includes:
 Force Application: External force, such as trauma or excessive stress, is applied to
the bone.
 Bone Reaction: The bone responds by bending, cracking, or breaking based on the
applied force.
 Fracture Formation: A fracture line develops, disrupting the bone's continuity.
 Vascular and Cellular Response: Blood vessels within and around the fracture site
are damaged, leading to bleeding and inflammation.
 Initiation of Healing: The body's natural healing response begins with the formation
of a blood clot and the migration of cells to the fracture site.
 Callus Formation: A callus (a mass of tissue) forms around the fracture, providing
stability.
 Remodeling: Over time, the bone undergoes remodeling, where excess callus is
resorbed, and the bone is reshaped to its original form.

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 Due to etiological/risk factors

Break in the continuity of bone

Disruption of muscles attached to bone

Muscles undergo spasms and pull the fracture fragments out of position

Fracture fragments may be displaced

Periosteum and blood vessels in the cortex and bone marrow of the fractured bone
disrupted

Bleeding from soft tissues and damaged end of the bone

Hematoma formation

Healing of fractured bone begins

CLINICAL FEATURES

 Pain: Immediate and localized at the site of the fracture.

 Swelling and Bruising: Due to bleeding and inflammation.
 Deformity: The affected limb may appear misshapen or out of alignment.
 Limited Range of Motion: Difficulty moving the injured part.
 Tenderness: The area around the fracture is sensitive to touch.
 Inability to Bear Weight: Depending on the location and severity of the fracture.

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 BONE HEALING

The process of bone healing involves a series of stages, generally classified into three
main phases: the inflammatory phase, the reparative phase, and the remodeling phase.
These stages represent the body's natural response to a bone fracture, and each phase
plays a crucial role in the overall healing process.

INFLAMMATORY PHASE
Duration of this stage is the first few days after the fracture.
Hematoma formation: Blood vessels around the fracture site break, leading to the
formation of a blood clot (hematoma).
Inflammation: Inflammatory cells, such as white blood cells, infiltrate the area to clean
up debris and bacteria.
Release of growth factors: Growth factors are released, signaling the beginning of the
repair process. Proliferation of capillaries and fibroblasts resulting in the formation of
granulation tissue occurs in this stage.

REPARATIVE PHASE/CALLUS FORMATION

Fibrocartilaginous callus formation: Fibroblasts and chondroblasts produce a soft
callus composed of collagen and cartilage, stabilizing the fractured ends of the bone.
Bony callus formation: Osteoblasts then replace the fibrocartilaginous callus with a
stronger, bony callus made of spongy bone.
Mineralization: The bony callus undergoes mineralization, becoming harder and more
stable.

REMODELING PHASE
Bone remodeling: Osteoclasts resorb excess bone tissue, while osteoblasts deposit new
bone tissue, leading to the restructuring of the bone to its original shape and strength.
Corticalization: The spongy bone is replaced by compact bone, restoring the original
structure.
Regaining strength:The bone gradually regains its full strength and functionality.

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 OSTEOPOROSIS

A bone disease characterized by low bone mass and microarchitectural deterioration of

bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk.

A condition in which the bones become weak and brittle or fragile is called osteoporosis.

It is characterized by decreased bone mineral density which is affected by low calcium

and phosphate salts and bones become porous and brittle which are susceptible to
fracture.

Osteoporosis is a medical condition characterized by the weakening of bones, making

them fragile and more prone to fractures

CAUSES AND RISK FACTORS

 Aging: As people get older, bone density naturally decreases.

 Gender: Women are at a higher risk of osteoporosis, especially after menopause.
 Family history
 Hormonal changes: Conditions or treatments that disrupt hormonal balance, such as
hyperthyroidism, hypogonadism, and long-term use of corticosteroids.
 Low body weight: Having a low body weight or a small frame.
 Dietary factors: Inadequate intake of calcium and vitamin D.
 Lack of physical activity: A sedentary lifestyle can weaken bones over time.
 Smoking: Smoking is associated with reduced bone density.
 Excessive alcohol: Chronic heavy alcohol consumption can weaken bones.
 Medications: corticosteroids, certain anticonvulsants, and some cancer treatments.
 Microgravity: astronauts
 Protein deficiency

ETIOPATHOLOGY

Osteoporosis is primarily characterized by a reduction in bone density and quality due to

an imbalance in the processes of bone formation and bone resorption (breakdown). The
key factors in its etiopathology include:

Imbalance in bone remodeling: Bone is continuously being remodeled through a

process called bone remodeling. Osteoclasts break down old bone tissue, and osteoblasts

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build new bone. In osteoporosis, there is an excess of bone resorption compared to bone
formation.

Loss of bone mineral density: Osteoporosis results in a decrease in bone mineral

density, which makes bones more fragile and susceptible to fractures.

Microstructural changes: Changes in the microstructure of bones, such as a loss of

trabecular bone (the spongy part of bone) and thinning of cortical bone, contribute to
bone fragility.

Due to etiological factors

Decreased bone mineral density

Imbalance of bone remodelling

Increased bone resorption than construction

Bones become weak, fragile and porous

Osteoporosis

Exposure to physical stress

Risk of fracture

CLINICAL FEATURES

 Fractures: Complications of osteoporosis are fractures, often occurring in the hip,

spine, and wrist. These fractures can result from minor trauma or even occur
spontaneously.
 Back pain: Vertebral fractures can cause severe back pain and may lead to a stooped
posture or loss of height.
 Gradual loss of height: Osteoporosis can result in a gradual loss of height over time as
vertebral fractures cause a reduction in spine height.
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 Bone pain: Osteoporosis can cause bone pain, typically in the hips, wrists, or spine.
 Reduced mobility: Fractures, especially hip fractures, can limit an individual's mobility
and independence.
 Deformities: Severe spinal fractures can lead to kyphosis (hunched back), leading to a
visible deformity.

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 OSTEOMYELITIS
It is an inflammatory process of bone and bone marrow caused by an infectious
organism which results in local bone destruction, necrosis and apposition of new bone.

Osteomyelitis is an infection of the bone, which can be a serious and potentially

life-threatening condition.

CAUSES AND RISK FACTORS

 Bacterial Infection: Staphylococcus aureus, Streptococcus and Escherichia coli.
 Direct entry: Bacteria can enter the bone through several routes, including open
fractures, surgical procedures, or bloodstream dissemination (hematogenous spread).
 Trauma
 Open wounds: Open wounds, such as those resulting from trauma, surgery, or
diabetic ulcers, can provide a direct path for bacteria to enter the bone.
 Bloodstream Infections: In some cases, bacteria from infections in other parts of the
body can travel through the bloodstream and infect the bone.
 Compromised immune system: diabetes, HIV/AIDS, or cancer.
 Iatrogenic/Prosthetic joints: joint replacements or other implanted hardwareare.
 Intravenous (IV) Drug Use: Injection drug use can introduce bacteria.
 Chronic illness: sickle cell disease, which can lead to reduced blood flow to the bones.

ETIOPATHOLOGY

Infection entry: Bacteria enter the bone through a breach in the protective barrier, such
as an open wound, surgery, or via the bloodstream.

Local inflammation: The immune system responds by triggering inflammation at the

site of infection, leading to redness, swelling, and heat.

Bone infection: Bacteria multiply within the bone, causing destruction of bone tissue.

Formation of abscess: The body may form an abscess or a pocket of pus within the
bone, which further contributes to bone damage.

Osteonecrosis: Bone tissue may become necrotic (die) due to lack of blood supply in the
infected area.

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Sequestrum formation: Dead bone fragments (sequestrum) may form, which can be
walled off by the body's defenses.

Chronic infection: Osteomyelitis can become chronic, with recurrent infections and
persistent inflammation if not treated adequately.

Due to etiological factors

Organisms grow and form pus within the bone

Tension builds within rigid medullary cavity

Pus is forced through the Haversian canals forming a subperiosteal abscess

Bone is deprived of its blood supply

Ischemic bone becomes necrotic

Periosteum is stimulated

Formation of new bone

Dead bone detaches and forms sinuses

Bone destruction

CLINICAL FEATURES

 Severe bone pain: Intense pain in the infected bone or joint, often worsening with
movement.
 Fever: Elevated body temperature due to the systemic infection.
 Swelling and redness: Localized swelling and redness over the affected bone.

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 Limited Range of Motion: Reduced ability to move the adjacent joint.
 Localized tenderness: Tenderness or pain upon touching the infected area.
 Pus drainage: In some cases, the infection may lead to the formation of a sinus tract
with pus draining through the skin.
 Fatigue and malaise: General feelings of weakness, fatigue, and overall unwellness.
 Draining from the affected bone
 Sinus tracts
 Bony destruction
 leukocytosis

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 OSTEOARTHRITIS

It is a degenerative condition of joints characterized by degeneration of articular

cartilage and formation of new bone in the joint.

A degenerative joint disease characterized by the breakdown of cartilage and the

underlying bone.

Osteoarthritis, degenerative disease is the clinical and pathological outcome of a

range of disorders that results in structural and functional failure of synovial joints.

It is primarily a disease of the cartilage that ultimately leads to a tissue respon se

and consequently to mechanical changes that result in the failure of these structures to
function.

ETIOLOGY AND RISK FACTORS

 Idiopathic
 Age: more common in older individuals because the wear and tear on joints
accumulate over time.
 Obesity: Excess body weight can put additional stress on weight-bearing joints, such
as the knees and hips.
 Defective lubrication
 Joint Injuries: Previous joint injuries, such as fractures or ligament damage.
 Joint Overuse: Repetitive motions or activities that place stress on a joint.
 Gender: OA is more common in women, especially after menopause.
 Occupation: Jobs that involve repetitive joint stress or heavy lifting.
 Muscle Weakness: Weak muscles around a joint can lead to instability.
 Medical Conditions: Conditions like rheumatoid arthritis, gout, or diabetes.

ETIOPATHOLOGY
Osteoarthritis typically involves a combination of factors, including:
Cartilage Degeneration: The protective cartilage that covers the ends of bones gradually
breaks down, leading to pain, swelling, and joint deformities.

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Bone Changes: The underlying bone may thicken and develop bone spurs (osteophytes)
in an attempt to repair itself.
Inflammation: Low-level inflammation within the joint can contribute to cartilage
breakdown and pain.
Synovitis: The synovial membrane, which lines the joint, may become inflamed and
produce excess synovial fluid, further contributing to joint swelling.
Mechanical Stress: Overuse, misalignment, or joint instability can contribute to
cartilage wear and tear.

Pathogenesis: cartilage is made of water and collagen framework with proteoglycans and
glycosaminoglycans produced by chondrocytes. Chondrocytes receive nutrition from the
synovium by diffusion and the synovial fluid is circulated by joint movement. If the joint
stops moving and chondrocytes lose their source of nutrition, they go into shock and
cartilage repair ceases. Enzymes are produced which catalyse collagen and proteoglycan
degradation.

Due to etiological factors

Restricted movements of joints

Progressive destruction and loss of articular cartilage

Exposure of subchondral bone and particular bone response

Increased vascularity and cyst formation

Bone surfaces become hard and polished because of friction

Bone is brittle and microfractures

Osteophytes form at the margin of the articular surface which may projected into the
joint

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 Alteration in the shape of the bone (flat and mushroom shaped)

Synovial membrane undergoes edematous

Reduction of synovial fluid secretion

Ligaments attached to the joint undergo fibrous degeneration

Muscles undergo atrophy

Pain, limitation of movements and stiffness of joints

CLINICAL FEATURES
 Arthralgia/Joint Pain: Persistent, aching pain in the affected joint, especially after
activity or in the evening.
 Stiffness: Joint stiffness, particularly in the morning or after inactivity.
 Reduced Range of Motion: Decreased ability to move the joint through its full range of
motion.
 Crepitus: A grating or crackling sensation when moving the joint.
 Swelling: Joint swelling and tenderness may occur due to inflammation.
 Bony enlargements: Osteophytes or bone spurs can develop, causing joint deformities.
 Muscle Weakness: Weakness in the muscles around the affected joint due to pain and
disuse.
 Altered gait and posture
 Functional limitations: Osteoarthritis can impact an individual's ability to perform
daily activities.

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 RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that primarily affects the
joints. It leads to inflammation, pain, swelling, and potential deformity of joints. Unlike
osteoarthritis, which is primarily a result of wear and tear on the joints, rheumatoid
arthritis involves the immune system mistakenly attacking the synovium—the lining of
the membranes that surround the joints.

CAUSES
The exact cause of rheumatoid arthritis is not known, but it is considered to be a
complex interplay of genetic, environmental, and hormonal factors. Genetic
predisposition is a significant risk factor, with certain genes (like HLA-DR4) being
associated with an increased susceptibility to RA. Environmental factors, such as
smoking, may also contribute to the development of the disease.

RISK FACTORS
 Genetics: Individuals with a family history of rheumatoid arthritis are at a higher risk.
 Gender: Women are more commonly affected than men.
 Age: Although RA can occur at any age, it often begins between the ages of 30 and 60.
 Environmental Factors: Smoking has been identified as a significant environmental
risk factor.
 Hormones: Hormonal changes, especially in women, may influence the development
of RA.

PATHOLOGY
RA is characterized by chronic inflammation of the synovium, leading to the formation of
a thickened layer of inflamed tissue called the pannus. This pannus can erode cartilage
and bone within the joint. The inflammatory process involves the activation of immune
cells, particularly T cells and B cells, and the release of various inflammatory mediators,
including cytokines like tumor necrosis factor (TNF) and interleukins.

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CLINICAL FEATURES
 Joint Symptoms: Pain, swelling, stiffness, and warmth in affected joints, typically
affecting smaller joints first (e.g., hands and feet).
 Symmetrical Involvement: RA often affects joints on both sides of the body
symmetrically.
 Morning Stiffness: Prolonged stiffness in the morning or after periods of inactivity.
 Fatigue: Many individuals with RA experience significant fatigue.
 Systemic Involvement: RA can affect organs and systems beyond the joints, leading
to complications such as rheumatoid nodules, lung involvement, and cardiovascular
issues.
 Deformities: In advanced stages, RA can cause joint deformities and functional
impairments.

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 BONE TUMOURS
Bone tumors are abnormal growths or masses of tissue within bones. They can be
benign (non-cancerous) or malignant (cancerous). Primary bone tumors originate in the
bone tissue, while secondary or metastatic bone tumors spread to the bones from other
parts of the body.

CAUSES
The exact causes of most bone tumors are unknown. However, certain factors and
conditions may contribute, including genetic mutations, hereditary syndromes, exposure
to radiation, and some inherited conditions like Li-Fraumeni syndrome.

RISK FACTORS
 Genetic Factors: Some bone tumors have a hereditary component.
 Radiation Exposure: Previous exposure to ionizing radiation increases the risk.
 Paget's Disease: People with Paget's disease of bone have an elevated risk of bone
tumors.
 Certain Inherited Conditions: Syndromes like hereditary retinoblastoma and Li-
Fraumeni syndrome increase the risk of bone tumors.

TYPES
 Benign Bone Tumors:
 Osteochondroma: Most common benign bone tumor, often seen in young
individuals.
 Enchondroma: Develops in the cartilage inside the bone.
 Giant Cell Tumor: Typically occurs near the ends of long bones.
 Malignant Bone Tumors:
 Osteosarcoma: The most common primary malignant bone tumor, often occurring
in adolescents.
 Chondrosarcoma: Arises in the cartilage; more common in older adults.
 Ewing Sarcoma: Affects primarily children and young adults.
 Multiple Myeloma: A cancer of plasma cells that can affect multiple bones.

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PATHOLOGY
The pathology of bone tumors varies based on the type. Benign tumors are characterized
by slow growth and a lack of invasion into surrounding tissues. Malignant tumors, on
the other hand, may invade nearby tissues and have the potential to spread
(metastasize) to other parts of the body.

CLINICAL FEATURES
 Pain: Persistent pain, often increasing over time, is a common symptom.
 Swelling or Mass: A noticeable lump or swelling may be present.
 Fractures: Weakened bones may be more prone to fractures.
 Limited Range of Motion: Depending on the location and size of the tumor, there
may be restricted movement.
 Systemic Symptoms: In advanced cases, general symptoms like weight loss and
fatigue may occur.
 Pathological Fractures: Malignant tumors can weaken bones, leading to fractures
even with minimal trauma.

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 CLINICAL
PATHOLOGY

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 COLLECTION OF BLOOD FOR DIFFERENT PURPOSES

Collection of blood from a subject is necessary for –

 Haematological study
 Biochemical Analysis
 Bacteriological culture
 Immunological study
 Blood Transfusion Services.
Haematological study indicates TLC, DLC, HB%, ESR, PCV, Blood Viscosity, Coagulation
profile study, Study of Haemolytic disorder etc. Biochemical study includes all sorts of
biochemical profiles. Bacteriological culture indicates culture for septicaemia and
Bacteraemia producing organisms.
Immunological studies include detection of antibodies and antigens in the blood,
different factors involved in immunological reactions.
Blood Transfusion services include detection of Blood Groups, Cross matching of the
blood, immunological study for detection of infecting viruses and organisms. Culture
study is done for detection of infecting bacteria, detection of protozoa etc.

SITES SELECTED FOR COLLECTION OF BLOOD

Blood is usually collected from veins, capillaries and arteries. Venous blood is collected
from Anti-cubital vein most commonly. Besides this vein, blood is also collected from the
veins of arm, dorsum of the hands, Long Saphenous vein is also used in situations of
non – availability of the former veins. In infants, femoral vein is the commonest site of
puncture. In new born child, Umbilical vein and scalp vein are commonly used.
Capillary blood is used where small quantity of blood is required, e.g in micro methods
and in preparation of blood films on the slides. This is collected from the finger tips or
ball of finger or lobule of ear. In infants, the heal and thumb is used for collection of
capillary blood.

COLLECTION OF BLOOD FROM VEINS

A blood pressure calf is applied in the arm and pressure is raised up to 40 mm of Hg. In
this situation of non – availability of blood calf, a tourniquet is sufficient to make the

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vein prominent. The skin is prepared aseptically before putting in the needl e in the vein.
The needle of 1’, 21 to 23 G is suitable.

COLLECTION OF BLOOD FROM CAPILLARY

The part is cleaned with alcohol or betadine or any other Antiseptic available. A bold
puncture is made with a cutting needle or gun after the part is dried. Help of gravity is
taken if possible to drain freely from the punctured site. Initial one or two drops are
discarded, then the free flowing blood is collected. The finger should not be squeezed to
prevent dilution of blood from the tissue fluid and plasma.

PRECAUTIONS ADOPTED DURING COLLECTION OF BLOOD

The following precautions should be adopted.
 Blood should be drawn with all aseptic precautions with sterile dry syringe and
needle.
 The needle should not be too fine or too thick. Usually 21G – 23G, 1’ to 1½’ needle is
used for adults. For children and infants same type of needle can be used. Yet a short
needle with shaft of about 15 mm long is the most suitable for infants and children.
 The technicians drawing the blood should use gloves and gown during the blood
collection and should be careful to avoid needle prick.

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 HAEMOGLOBIN ESTIMATION

Hemoglobin estimation is a common clinical test used to measure the concentration of

hemoglobin in a person's blood. Hemoglobin is a protein found in red blood cells and is
responsible for transporting oxygen from the lungs to the body's tissues .

PRINCIPLE

Sahli's method is based on the principle of colorimetry. It involves comparing the color of
a diluted blood sample with that of a standardized hemoglobin solution. The more
hemoglobin present in the blood, the darker the color will be.

MATERIALS AND EQUIPMENT NEEDED

 Sahli's hemoglobinometer (a specially designed apparatus for this method)

 Drabkin's solution (a reagent containing potassium ferricyanide, potassium cyanide,

and potassium dihydrogen phosphate)

 Graduated pipettes

 Test tubes or cuvettes

 A spectrophotometer or colorimeter (for modern adaptations)

 A light source with a specific wavelength (for colorimetric measurements)

PROCEDURE

Preparation: Calibrate the Sahli's hemoglobinometer as per the standard instructions.

Ensure that the Drabkin's solution and all equipment are ready and properly prepared.

Sample Collection: Collect a blood sample from the patient, typically from a finger or
earlobe, and mix it gently to prevent clotting.

Dilution: Using a graduated pipette, transfer a known volume of the patient's blood
(usually a few milliliters) into a test tube or cuvette. Add a measured volume of Drabkin's
solution to the blood sample, and mix thoroughly. The Drabkin's solution lyses the red
blood cells and forms a stable colored compound with hemoglobin.

Comparison: Place the test tube or cuvette containing the diluted blood sample next to
the Sahli's hemoglobinometer. Look through the hemoglobinometer and adjust the color
189 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
density by rotating the eyepiece. The device has a comparison scale that allows you to
visually match the color of the diluted blood sample with that of a standardized
hemoglobin solution in the hemoglobinometer.

Reading: Once the colors match, note the hemoglobin concentration from the scale on
the hemoglobinometer. This reading is in g/dL or the appropriate units.

Safety and Disposal: Properly dispose of bio-hazardous materials, including used test
tubes and any contaminated materials. Decontaminate and clean equipment and work
surfaces as per laboratory safety protocols.

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 BLOOD CELL COUNTS
Hemocytometer is an instrument used for counting blood cells. It consists of a counting
chamber and 2 pipettes.
RBC COUNT: This is defined as determination of the number of RBCs per μl of blood.

VISUAL HAEMACYTOMETER METHOD

PRINCIPLE: This is counting of RBCs in a calibrated chamber by dilution of blood to 1 in

200 dilutions with a diluent which is isotonic to blood. The diluent used prevents
clotting, clumping and rouleaux formation and does not destroy WBCs.

DILUTING FLUIDS
Two types of diluting fluids are used for RBC counting: Hayem’s fluid and Dacie’s fluid.
HAYEM’S FLUID (Mercuric chloride: 0.25 g, Sodium chloride: 0.5 g, Sodium sulphate:
2.5 g and Distilled water: 100 ml)
DACIE’S FLUID (40% Formaldehyde: 5 ml and 3% Trisodium citrate: 495 ml)

PROCEDURE
 Draw anticoagulated blood or blood from finger prick upto mark 0.5 in RBC pipette.
 Wipe tip and outside of the pipette.
 Draw diluting fluid upto mark 101 in the RBC pipette.
 Mix well by rotating the pipette for 2-3 minutes.
 Charge the Neubauer’s chamber after discarding 1-2 drops of mixture from the RBC
pipette.
 Allow the cells to settle down for 2 minutes.
 Count RBCs under high power 40X in 80 tiny squares (5 × 16 tiny squares) in the
centre of the chamber.

CALCULATIONS
 Volume of area in which
 RBCs counted in 5 squares = (1/5X1/5 X0.1) X 5
 Number of RBCs in volume (1X1X0.1)mm 3= n 5
 Number of RBCs in 1 cubic mm = nx10x5
 Dilution factor = 200
 RBC count per mm3 (μl) = nx50x200 = nx10000

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PLATELET COUNT: Platelets are thin discs 2-4 μm in diameter. They function in
haemostasis, in maintaining vascular integrity and in the process of blood coagulation.
Their life span is 7-10 days.

VISUAL METHOD
TYPE OF BLOOD USED: Use only venous blood as the blood obtained from finger prick
causes clumping of platelets.
DILUTING FLUID: 1% ammonium oxalate is prepared as under: Ammonium oxalate: 1g
and Distilled water: 100 ml. Filter it and keep in a refrigerator at 40c.

PROCEDURE
 Using an RBC pipette, prepare a 1:200 dilution as for RBC method
 Mix for 2 minutes, charge the Neubauer’s counting chamber.
 Place the charged Neubauer’s chamber into a petri dish having a moist filter paper at
bottom for allowing the platelets to settle down.
 Count the platelets as for red cell count using 40x objectives with reduced condenser
aperture.
 If platelet count is low, a WBC pipette can be used for charging the Neubauer’s
chamber.

CALCULATIONS
CALCULATIONS
 Volume of area in which
 Number of platelets in 5 squares = (1/5X1/5 X0.1) X 5
 Number of plateletsin volume (1X1X0.1)mm3= n 5
 Number of platelets in 1 cubic mm = nx10x5
 Dilution factor = 200
 Platelets count per mm3 (μl) = nx50x200 = nx10000

BLEEDING TIME

Bleeding time is duration of bleeding from a standard puncture wound on the skin which
is a measure of the function of the platelets as well as integrity of the vessel wall. This is
one of the most important preliminary indicators for detection of bleeding disorders. This
is also the most commonly done preoperative investigation in patients scheduled for
surgery.

192 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

PRINCIPLE

A small puncture is made on the skin and the time for which it bleeds is noted. Bleeding
stops when platelet plug forms and breach in the vessel wall has sealed.

METHODS FOR BLEEDING TIME

 Fingertip method
 Duke’s method
 Ivy’s method

FINGER TIP METHOD PROCEDURE

 Clean the tip of a finger with spirit.

 Prick with a disposable needle or lancet.
 Start the stop-watch immediately.
 Start gently touching the pricked finger with a filter paper till blood spots continue to
be made on the filter paper.
 Stop the watch when no more blood spot comes on the filter paper and note the time.

DISADVANTAGES

 It is a crude method.
 Bleeding time is low by this method.

Normal bleeding time is 1-3 minutes.

DUKE’S METHOD PROCEDURE

 Clean the lobe of a ear with a spirit swab.

 Using a disposable lancet/needle, puncture the lower edge of the ear lobe to a depth of
approximately 3 mm.
 Start the stop-watch immediately.
 Allow the drops of blood to fall on a filter paper without touching the ear lobe and then
slowly touching the blood drop gently on a new area on the filter paper.
 Stop the watch when no more blood comes over the filter paper and note the time.

ADVANTAGES OF THE METHOD

 The ear lobule has abundant subcutaneous tissue and is vascular.

 Flow of blood is quite good.

Normal bleeding time is 3-5 minutes

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IVY’S METHOD PROCEDURE

 Tie the BP apparatus cuff around the patient’s upper arm and inflate it upto 40 mmHg
which is maintained throughout the test.
 Clean an area with spirit over the flexor surface of forearm and let it dry.
 Using a disposable lancet or surgical blade make 2 punctures 3 mm deep 5-10 cm
from each other taking care not to puncture the superficial veins.
 Start the stop-watch immediately.
 Go on blotting each puncture with a filter paper as in Duke’s method.
 Stop the watch, note the time in each puncture and calculate average bleeding time.

ADVANTAGES OF THE METHOD

 This is the method of choice.

 It is a standardized method.
 Bleeding time is more accurate.

Normal bleeding time is 3-8 minutes

CLINICAL APPLICATION OF BLEEDING TIME

The bleeding time is prolonged in:

 Thrombocytopenia
 Disorders of platelet functions
 Acute leukaemias
 Aplastic anaemias
 Liver disease
 von Willebrand’s disease
 DIC
 Abnormalilty in the wall of blood vessels
 Administration of drugs prior to test e.g. aspirin

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 CLOTTING TIME

This is also known as whole blood clotting time and is a measure of the plasma clotting
factors. It is a screening test for coagulation disorders. Various other tests for
coagulation disorders include: prothrombin time (PT), partial thromboplastin time (PTTK)
or activated partial thromboplastin time with kaolin (APTTK), and measurement of
fibrinogen.

WHOLE BLOOD CLOTTING TIME METHODS

CAPILLARY TUBE METHOD PROCEDURE

 Clean the tip of a finger with spirit.
 Puncture it upto 3 mm deep with a disposable needle.
 Start the stop-watch.
 Fill two capillary tubes with free flowing blood from the puncture after wiping the first
drop of blood.
 Keep these tubes at body temperature.
 After 2 minutes start breaking the capillary tube at 1 cm distance to see whether a
thin fibrin strand is formed between the two broken ends.
 Stop the watch and calculate the time from average of the two capillary tubes.
 Normal clotting time is 1-5 minutes.

ADVANTAGES DISADVANTAGES

Can be performed when venous blood  Method is insensitive

cannot be obtained.  Method is unreliable

LEE AND WHITE METHOD PROCEDURE

 After cleaning the forearm, make a venepuncture and draw 3 ml of blood in a

siliconised glass syringe or plastic syringe.
 Start the stop-watch.
 Transfer 1 ml of blood each into 3 glass tubes which are kept at 37oC in a waterbath.
 After 3 minutes tilt the tubes one by one every 30 seconds.
195 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 The clotting time is taken when the tubes can be tilted without spilling of their
contents.
 Calculate the clotting time by average of 3 tubes.
 Normal clotting time is 5-10 minutes

ADVANTAGES DISADVANTAGES

 More accurate and standard method.  It is also a rough method.

 Test can be run with control.  There can be contamination of syringe or
tubes.

CLINICAL APPLICATIONS

 Clotting time is prolonged in:

 Severe deficiency of coagulation factors.
 Afibrinogenaemia.
 Administration of heparin.
 Disseminated intravascular coagulation (DIC).
 Administration of drugs such as anticoagulants.

PROTHROMBIN TIME (PT)

The patient’s blood is quickly oxalated (or citrated) to remove calcium ions so that
prothrombin cannot be converted to thrombin. The sample is then centrifuged. Then to
the oxalated plasma, a large excess of calcium ions (as calcium chloride solution) and
rabbit brain suspension (to provide tissue thromboplastin; tissue factor, TF) is added.
The excess calcium neutralizes the effect of oxalate and the TF converts prothrombin to
thrombin via the extrinsic clotting pathway (i.e. factor VII).

The time required for clotting to occur is called the prothrombin time (PT).

Normal PT = 15–20 seconds.

CLINICAL SIGNIFICANCE: Since the potency of tissue thromboplastin (TF) may vary,
blood from a normal person is used as a control when the test is used for controllin g
anticoagulant dose, or in a haemorrhagic disease. Bleeding tendency is present when the
prothrombin level falls below 20% of normal (normal plasma prothrombin = 30–40
mg/dl). Prolonged PT suggests the possibility of deficiency of factors II (prothrombin), V,
VII and X. Prothrombin level is low in vitamin K deficiency and various liver and biliary
diseases.

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 BLOOD GROUPING

Blood group is a classification of blood based on the presence/absence of inherited

antigenic substances present on the surface of the red blood cells. Presence of these
antigens is decided by genes from both parents.

Karl Landsteiner discovered human blood groups.

ABO system is the most important blood group system.

There are two types of antigens which can produce four blood groups.

Rhesus blood group system is the second most significant blood group system. It is
based on presence/absence of antigen D on the red blood cells. RBCs which express this
D antigen are termed Rh positive (Rh+). About 85% of population is Rh positive and 15%
is Rh negative.

ABO SYSTEM
PRINCIPLE: ABO system was discovered by Landsteiner in 1900. The red cells contain
different types of antigens (agglutinogen), while plasma contains antibodies (agglutinins).
In order to determine the blood group of a subject, the red cells are allowed to react with
a sera containing known antibody (agglutinin).

METHODS FOR ABO GROUPING: Slide method and Tube method

SLIDE METHOD

 Take a clean glass slide.

 Divide one slide into two halves with a glass marking pencil and mark these areas as A
and B.
 Place a drop of serum anti-A (blue) on the slide in area marked A and a drop of serum
anti-B (yellow) in the area marked B.
 Make a finger prick with a disposable needle after cleaning the area.
 Place a drop of blood near anti-A and anti-B serum and mix them with a stick or with
the end of a glass slide.
 Wait for 5 minutes and look for agglutination.
OBSERVATIONS: If any agglutination occurs it is visible with naked eyes as dark
reddish clumps of different sizes. If agglutination is minimal it can be confirmed by
examining it under a microscope

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TUBE METHOD: In this method cells and serum of the unknown blood sample to be
tested are separated. Cells as well as serum grouping are done.
CELL GROUPING
 Prepare a 2-5% cell suspension in saline from the unknown blood sample.
 Take 3 test tubes 1,2,3 and put a drop of anti-A, anti-B and anti-AB serum (pink) to
them.
 Add one drop of red cell suspension in each test tube.
 Centrifuge at 1500 rpm for one minute.
 Look for agglutination either with naked eye or under the microscope.
SERUM GROUPING
 Let the unknown blood sample stand for some time and separate the serum.
 Add 2 drops of unknown serum in test tubes 4, 5, 6.
 Add 1 drop of 2-5% cell suspension of known blood of A, B and O group into these test
tubes.
 Centrifuge at 1500 rpm for one minute.
 Look for agglutination either with naked eye or under the microscope.
Tube method is more accurate because both red cell and serum grouping is done.
The interpretation of ABO grouping by any of the above methods is given in Table
Blood group of Agglutination with Agglutination with
person anti-A serum anti-B serum
A + -
B - +
AB + +
O - -
Note
 Red blood cells from person with blood group O contain no antigen; so no
agglutination occurs and thus such a person is a universal donor.
 Red blood cells from persons with blood group AB contain both A and B antigens,
so agglutination occurs in both as no antibodies are present in their serum and
thus such individual is a universal recipient.

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 RHESUS (RH) SYSTEM
Rh blood group system was first reported by Landsteiner and Weiner in 1940. In
contrast to ABO system, Rh antigens are present on red blood cells only and Rh
antibodies develop only in response to a known stimulus (e.g. blood transfusion, or after
first pregnancy). Rh factor is present in 85-95% of human beings.

METHODS FOR RH GROUPING: Slide method and Tube method

SLIDE METHOD
 Take a clean glass slide.
 Place a drop of anti-D serum on the slide.
 Place a drop of blood near anti-D serum and mix them as for ABO grouping.
 Wait for 5 minutes and see for agglutination.
TABLE OF Rh GROUPING
AGGLUTINATION Rh Group
Present +
Absent -

TUBE METHOD
 Prepare a 2-5% cell suspension in saline from the blood to be tested.
 Take a test tube and put a drop of anti-D serum.
 Add one drop of red cell suspension in the tube.
 Centrifuge at 1500 rpm for 1 minute.
 Look for agglutination either with naked eye or under the microscope.

NOTE
 Rh positive subjects have Rh antigen on their red blood cells but no Rh antibody in
their serum.
 Rh negative subjects have neither Rh antigen on their red blood cells nor Rh antibody
in their serum. The most common Rh antigen is D.

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 CROSS MATCHING

Cross matching is a direct test of compatibility of donor cells and recipient serum. It is
mandatory to do cross matching before all transfusions.
Major cross matching: Donor’s cells are mixed with patient’s serum
Minor cross matching: Patient’s cells are mixed with donor’s serum

Uses of blood grouping and cross matching

Blood transfusion
Organ transplantation
Hemolytic disorder in newborn
Medicolegal cases

Complications of blood transfusion

Hemolytic reactions
Allergic reactions
Circulatory overload
Air embolism
Hyperkalemia
Iron overload
Transmission of infections

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 BONE MARROW EXAMINATION

Bone marrow examination is a medical procedure in which a sample of bone marrow

tissue is collected and examined to diagnose various hematological disorders, including
blood cancers (such as leukemia and multiple myeloma), anemias, and other conditions
affecting the blood-forming cells in the bone marrow.

ARTICLES REQUIRED

 Needles and syringes: Various sizes of needles and syringes are used for bone marrow
aspiration and biopsy. The needles used for bone marrow aspiration are salah needle
and kilma needle

 Local anesthetic: Typically, a local anesthetic is used to numb the skin and underlying
tissue at the aspiration site.

 Antiseptic solution: An antiseptic solution is used to clean the skin over the aspiration
site to reduce the risk of infection.

 Sterile drapes: Sterile drapes are used to maintain a sterile field during the procedure.

 Gloves and gowns: Healthcare professionals performing the procedure should wear
sterile gloves and gowns to prevent contamination.

 Biopsy needle: A specialized needle is used to obtain a core biopsy sample of bone
marrow.

 Slides and containers: Slides and containers are used to collect and transport the
bone marrow samples for examination in a laboratory.

 Microscope: A microscope is necessary for the examination of the collected bone

marrow samples.

SITES OF BONE MARROW ASPIRATION

Iliac Crest: The posterior superior iliac spine is a common site for bone marrow
aspiration. It's located in the pelvic region, just above the hip bone.

Sternum (Breastbone): The flat bone in the center of the chest, known as the sternum,
is another site where bone marrow aspiration can be performed.

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Tibia (Shinbone): In children, bone marrow aspiration can be done from the tibia, which
is the large bone in the lower leg.

INDICATIONS

Diagnosis of blood disorders: To determine the cause of unexplained anemia, leukopenia

(low white blood cell count), or thrombocytopenia (low platelet count).

Cancer diagnosis: To diagnose and stage hematologic cancers, such as leukemia,

lymphoma, and multiple myeloma.

Monitoring treatment: To assess the effectiveness of treatment in patients with blood

cancers and to detect any relapse.

Evaluation of infections: In certain infections, especially those affecting the bone marrow,
a bone marrow examination may be necessary to identify the causative organism.

Evaluation of bone marrow disorders: To investigate bone marrow disorders like

myelodysplastic syndromes.

PROCEDURE

The procedure for bone marrow examination typically involves two main components:

Bone Marrow Aspiration:

 The patient is positioned comfortably, and the skin over the chosen aspiration site

(usually the iliac crest) is cleaned and numbed with a local anesthetic.
 A needle is then inserted through the skin and into the bone marrow cavity.

 A syringe is used to aspirate (withdraw) a sample of liquid bone marrow.

 The collected bone marrow fluid is examined under a microscope.

Bone Marrow Biopsy:

 After aspiration, a larger needle is used to obtain a core biopsy sample of bone

marrow.
 This needle is inserted into the same site, and a small piece of bone and marrow is

removed.
 The bone marrow biopsy sample is also examined under a microscope.

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BLOOD CULTURE

Bacteria have to be grown (cultured) for their identification, because they cannot be
diagnosed by their morphology alone. A blood culture is a laboratory test in which blood
is microbiologically cultured to find bacteria or other microorganisms in a blood sample.
The blood normally does not have any bacteria or fungi. A blood culture can identify the
type of bacteria or fungi causing the infection in the blood. The transient presence of
bacteria (or other microorganisms) in the blood is called Bacteraemia. Blood culture
helps the physician to determine the best course of treatment. There are numerous
culture medias. They are classified as solid, Liquid or semi-solid media. Agar is the most
universally used to prepare solid media. Media can also be aerobic or anaerobic.

SEROLOGICAL AND IMMUNOLOGICAL TESTS

Antigens are substances which when introduced parenterally into the body stimulate the
production of antibodies. Antigens and antibodies combine with each other. The reaction
between antigen and antibody may show different patterns.

PRECIPITATION REACTION

When a soluble antigen combines with antibody, the antigen – antibody complexes may
form insoluble precipitates in liquid media or in gel and named as precipitation reaction.
The amount of precipitates formed depends on the relative proportion of antigen and
antibody. Precipitation occurs rapidly and abundantly when the antigen and antibody
are present in equivalent proportions.

AGGLUTINATION REACTION

When an antigen is mixed with antibody, the antigen – antibody may form clumping or
agglutinated. Agglutination is more sensitive than precipitation for the detection of
antibodies.

COMPLEMENT FIXATION TEST (CFT)

Complement takes part in many antigen antibody reactions. In the presence of the
appropriate antibodies, complement lyses RBCs and in some cases lyses bacteria,
immobilizes motile organisms, promotes phagocytosis. The ability of antigen – antibody
complexes to ‘fix’ complement is used in the complement fixation test.

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 EXAMINATION OF BODY FLUIDS

(PLEURAL, PERICARDIAL AND ASCITIC (PERITONEAL) FLUID

SPECIMEN COLLECTION: The body fluid is collected in a clean, dry container under
aseptic precautions and traumatically to avoid mixing with fresh blood. The fluid is
collected in the following three sterile test tubes:

 CHEMICAL EXAMINATION: Fluoride tube.

 MICROSCOPIC EXAMINATION: EDTA tube
 BACTERIOLOGICAL EXAMINATION: Plain tube (without anticoagulant)

They should be examined as early as possible to prevent chemical changes, growth of

bacteria and disintegration of cells.

EXAMINATION OF BODY FLUIDS

PHYSICAL EXAMINATION: Note volume, colour and appearance.

COLOUR: Pleural, pericardial and ascetic (peritoneal) fluids are usually clear and straw
coloured. Uniform blood stained fluid suggests malignancy involving the organs/ tissues
surrounding the respective body cavity. TURBID Fluid may be due to high cell count or
high protein content. CHYLOUS with milky appearance usually indicates high lipid
content due to lymphatic obstruction.

TRANSUDATE Vs EXUDATE: It is important to differentiate where the fluid is a

transudate or exudate. TRANSUDATE is usually seen in all body cavities with disease
like heart failure and hypoalbuminemic conditions (e.g. nephrotic syndrome). Cirrhosis
results in prominent ascities, but may also cause pleural effusion. EXUDATE usually
suggests infection or malignancy.

CHEMICAL EXAMINATION
PROTEIN ESTIMATION: This helps to differentiate transudate and exudate.
GLUCOSE ESTIMATION: Low glucose in the body fluids usually suggests bacterial
infection (including tuberculosis), malignancy or nonspecific inflammation.
MEASUREMENT OF AMYLASE IN ASCITIC FLUID: It is useful in patients with
pancreatic lesions.

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MICROSCOPIC EXAMINATION

CELL COUNT: It is done similar to total WBC count using improved Neubauer chamber.
Normally, few mesothelial cells (lining cells of body cavities) and lymphocytes are seen.

DIFFERENTAIL WBC COUNT

PROCEDURE: Centrifuge the body fluid and from the sediment prepare the smears.

Leishman’s stain: Stain one smear with Leishman’s stain and count 100 cells and
express the differential count. Gram’s stain/ Acid fast stain: These stains are useful in
suspected cases of infective / tubercular infections.

CYTOLOGICAL EXAMINATION FOR MALIGNANT CELLS

PROCEDURE: The body fluid is centrifuged; Smears are made from the sediment and
fixed immediately in absolute alcohol. The smears are stained by Pap stain. Hematoxylin
and eosin stain or Giemsa may also be used.

MICROBIOLOGICAL EXAMINATION: Culture is done to identify the organism in cases

of effusion due to infections.

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 EXAMINATION OF SYNOVIAL FLUID

Examination of synovial fluid is useful in the diagnosis of joint disorders.

 Infective arthritis (Septic arthritis, Rheumatic)

 Gouty arthritis (Metabolic disorders)

 Rheumatoid arthritis (Autoimmune disorders)

 Degenerative arthritis.

EXAMINATION: It consists of Physical Examination, Microscopic Examination, Chemical

Examination and Microbiological Examination.

PHYSICAL EXAMINATION
APPEARANCE CONDITION
NORMAL Clear, straw coloured and viscous. It does not clot.
TURBID Infection and Inflammation of the joint space, due to
the presence of crystals, amyloid and cartilage
fragments.
PURULENT Septic arthritis
RED OR BROWN SUPERNATANT Hemarthrosis or in a traumatic tap.

VISCOSITY TEST: Synovial fluid is viscous due to presence of hyaluronic acid. The
viscosity of the synovial fluid decreases in inflammatory joint disorders due to the
breakdown of hyaluronic acid by the enzyme hyaluronidase.
MUCIN CLOT TEST: Hyaluronic acid forms a compact clot when mixed with acetic acid.
Low concentration of hyaluronic acid does not allow the formation of a firm clot. Add few
drops of synovial fluid to 20 ml of 5 % acetic acid in a small beaker. A g ood clot is formed
if the synovial fluid is normal.
 In inflammatory diseases of the joint, there is poor clot formation due to degrading

enzymes from the inflammatory cells. (e.g. tuberculous arthritis).

 Non inflammatory joint disorders show good clot formation, whereas hemorrhagic

synovial fluid prevents clot formation due to dilatation of fluid.

 Fair to poorly formed clot is seen in rheumatoid arthritis, gout and pseudogout.

MICROSCOPIC EXAMINATION: The total leukocyte count is estimated similar to total

WBC count using improved Neubauer chamber. If polymorphs are more than 70%, it

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indicates bacterial arthritis. Non inflammatory arthropathies (osteoarthritis) are
associated with lymphocytes and macrophages.

WET SMEAR EXAMINATION: Centrifuge the synovial fluid and take the sediment on a
glass slide and cover it with a coverslip. Observe the slide first under low power objective,
then under high power objective with reduced light and carefully note for the presence of
the following crystals:
 Urate crystals are needle shaped, highly birefringent and are seen in gouty arthritis.

 Rhomboid calcium pyrophosphate crystals are seen in pseudo – gout.

 Cholestrol crystals are seen in rheumatoid arthritis.

Crystals can be confirmed using polarized microscopy.

CHEMICAL EXAMINATION: Glucose and protein estimation

MICROBIOLOGICAL EXAMINATION: Synovial fluid culture is recommended in

suspected cases of pyogenic / tubercular arthritis.

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 CSF ANALYSIS

Cerebrospinal fluid (CSF) is a clear, colorless fluid that surrounds the brain and spinal
cord. It is produced, circulated, and absorbed in the central nervous system.

CSF Secretion:CSF is primarily produced by the choroid plexus, a structure in the

ventricles of the brain. It is continuously formed at a rate of about 500 ml per day.

CSF Flow: CSF flows through the ventricular system of the brain and then into the
subarachnoid space surrounding the brain and spinal cord. It is eventually absorbed
into the bloodstream.

CSF Composition: The composition of CSF includes water, electrolytes, proteins,

glucose, and small molecules. The normal values for CSF composition can vary slightly,
and changes may indicate various neurological disorders.

Functions of CSF
 Protection: CSF provides a cushioning effect, protecting the brain and spinal cord from
mechanical shocks.
 Nutrient Transport: It delivers nutrients and removes waste products from the brain.
 Maintaining Intracranial Pressure: CSF helps maintain a stable pressure within the
skull.
 Immune Function: It contributes to the immune defense of the central nervous
system.
Importance of CSF examination: Analysis of the CSF is of diagnostic importance in
conditions like meningitis or primary/ metastatic tumour of CNS with CSF involvement.

COLLECTION OF CSF
CSF is usually obtained by Lumbar puncture (LP) using an LP needle under strict
aseptic conditions.
Lumbar puncture needle: The needle measures 10 – 20 cm in length. In children a
shorter needle is used. It has a needle and a stillete.
Lumbar puncture sites: In Adults, CSF is normally collected in the midline of the lower
back in the 3rd lumbar space and in children in the 4th lumbar space.
Method of collection: Normally, CSF is collected in 3 sterile test tubes. The amount of
CSF collected should not exceed 6 – 8 ml.

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GROSS EXAMINATION

Color: Normal CSF is colorless

 Normal CSF does not have clots
 Yellow color or xanthochromia is due to severely jaundiced
 Orange color is due to dietary hypercarotenemia
 Brown color is due to meningeal metastatic melanoma
 Red to orange color in patients on rifampacin therapy
 Pink to red indicates presence of blood in CSF sample

pH: Normal pH of CSF is 7.28-7.32

Appearance: Normal CSF is crystal clear without presence of any clots. Turbidity or
cloudiness of CSF in increased cell and bacterial counts. Smoky CSF indicates increased
number of WBCs in CSF.

MICROBIOLOGICAL EXAMINATION & CULTURE

The first few drops of CSF are collected for culture in the first tube. CSF can be cultured
for bacteria, tuberculosis and fungal infections.
Neutrophils in CSF: Bacterial meningitis and Brain abscess
Lymphocytes in CSF: Viral meningitis
Plasma cells in CSF: Tuberculous meningitis and meningoencephalitis

BIOCHEMICAL TESTS & IMMUNOLOGICAL STUDIES

Collect about 2.5 ml of CSF in the second tube for biochemical tests.

Estimation of Protein in CSF: Normal CSF protein level is 15-45mg/dl. Increased

protein in CSF is a sensitive indicator and if the level is more than 150mg/dl indicates
bacterial meningitis.

Estimation of Glucose in CSF: Normal CSF glucose is two thirds of blood glucose.
Normal range of glucose in CSF is 45-80mg/dl. Less than 40mg/dl is abnormal and
indicates bacterial meningitis, brain abscess, malignancy and autoimmune disorders.

INDICATIONS FOR LUMBAR PUNCTURE

 Meningeal infection: Bacterial(Pyogenic, Tuberculosis), Syphilitic, Viral, Fungal

 Encephalitis
 Subarachnoid Hemorrhage
 Primary or Metastatic malignancy (e.g. Acute leukemia, Lymphoma)
209 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
 Demyelinating diseases: Multiple Sclerosis, Guillian – Barre Syndrome
 Spinal canal blockage leading to elevated intracranial tension (Spinal cord tumors)
 Injecting the radio – opaque dye for myelography
 Spinal Anesthesia
 Intrathecal injection of chemotherapeutic drugs for CNS Prophylaxis/ relapse of ALL,
Lymphomas.

ANALYSIS AND INTERPRETATION

 Physical Examination: Color, clarity, and pressure are assessed.
 Chemical Analysis: Includes glucose, protein, and electrolyte levels.
 Cell Count: Presence and count of white blood cells (pleocytosis) and red blood cells.
 Microbiological Culture: To identify infections.
 Cytology: Examination of cell types for cancerous or abnormal cells.

CONTRAINDICATIONS:
 Increased Intracranial Pressure: Lumbar puncture may be contraindicated in
conditions where it could worsen intracranial pressure.
 Bleeding Disorders: Increased risk of bleeding complications.

COMPLICATIONS:
 Headache: Post-lumbar puncture headache is a common complication.

 Infection: Risk of introducing infection during the procedure.

 Bleeding: Hemorrhage can occur, especially in patients with clotting disorders.

INTERPRETATION OF CSF FINDINGS:

Abnormal findings in CSF may indicate various conditions, including:
 Infection: Elevated white blood cell count.

 Inflammation: Elevated protein levels.

 Bleeding: Presence of blood in the CSF.

 Tumor or Meningitis: Abnormal cell types.

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 SPUTUM EXAMINATION

Sputum is a thick mucus produced in the lungs. It is also known as phlegm and,
because of its thickness, can contain infectious germs. In a sputum culture test, a
laboratory uses a sample of this mucus to try to encourage the growth of any bacteria or
other germs that may be causing an infection.

A sputum culture test can reveal whether there is an infection in the lungs and, if so, the
type of bacteria or fungus involved. It is often used in the diagnosis and follow-up care of
people with respiratory diseases like pneumonia and tuberculosis.

SPUTUM COLLECTION
 The patient is instructed to cough up to get the sputum proper and the same is
collected in a wide mouthed sterile glass / plastic container with screw.
 In those patients who cannot produce sputum spontaneously by deep coughing, a
specimen of sputum may be induced. This is done by inhalation of appropriate
solvents which are aerosolized to stimulate sputum production.
 Early morning sputum sample is preferred for routine examination and 24 hours
sample for the demonstration of tubercle bacilli by concentration method.

PHYSICAL EXAMINATION
QUANTITY: In bronchiectasis, large amount of purulent sputum is coughed out. Large
amount of watery sputum with pink tinge suggests pulmonary edema.
APPEARANCE/ COLOUR CAUSES
White, viscid, mucoid Asthma
Serous, Clear, Watery Pulmonary edema
Clear or Mucoid, Gray, Glassy, Tenacious Chronic bronchitis
Acute Lower Respiratory Tract (Pulmonary)
Yellow due to pus / Neutrophils
Infections
Long standing infection (Bronchiectasis,
Green
lung abscess)
Pneumonia (e.g. Pneumococcal) and
Rusty due to lysis of red cells
pulmonary infarction
Pulmonary tuberculosis, Lung tumours,
Bright red due to fresh blood
Pulmonary infarction.
Coal workers pneumoconiosis or in heavy
Black due to coal dust
smokers
Anchovy sauce (Chocolate brown) Rupture of amoebic liver abscess into lung
Mitral stenosis, Pulmonary tuberculosis,
Blood tinged sputum
Carcinoma lung, Pulmonary infarction.

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ODOUR OR SMELL: Foul smelling sputum is observed in Bronchiectasis and lung
abscess and is due to anaerobic bacterial infections.

MICROSCOPIC EXAMINATION
Staining of Sputum: Two to Three smears are made on a clean dry glass slides and are
stained with:
 Leishman stain or Wright stain for differential count.
 Other stains (Depends on the clinical / Pathological features)
 Gram’s stain for microorganisms.
 Ziehl – Nielsen stain for acid fast tubercle bacilli
 Special stains for fungi
 Papanicolaou stain for study of malignant cells.

CELLS: Normal sputum consists of a few neutrophils, few lymphocytes, carbon laden
macrophages, occasional eosinophils and red cells. Various types of cells seen in sputum
and their significance are shown below:

TYPE OF CELL SIGNIFICANCE

Pus cells (neutrophils) Pyogenic infection of the respiratory tract
Eosinophils Asthma and parasitic infections of the lungs
Lymphocytes Early pulmonary tuberculosis
Hemorrhage (bleeding) into the lungs or the
Red blood cells
bronchi
Chronic venous congestion of the lungs,
Heart failure cells
Pulmonary infarction and Hemorrhage
Antharacotic (carbon) pigment – laden Coal workers pneumoconiosis and those who
cells live in smoky polluted atmosphere

OTHER STRUCTURES
 Curschmann spiral: They appear as spiral structures with a central thread found in
the sputum of patients with bronchial asthma.
 Charcot–leyden crystals: These appear as fine needle shaped or hexagonal colourless
crystals found in bronchial asthma.

PARASITES
 Larvae of Strongyloides stercoralis and Round worms may be seen.
 Entamoeba histolytica: Cysts or the trophozoites may be found when an amoebic liver
abscess ruptures into the lungs.
 Echinococcus Granulosae: Scolices and hoocklets of the larval form may be seen with
the rupture of the Hydatid cyst of the lungs into the bronchus.

CULTURE STUDY: Sputum culture may demonstrate the causative infectious agent.

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 SEMEN ANALYSIS

 Semen analysis measures the quantity and quality of semen and sperm.
 Semen is the thick, white fluid released during sexual intercourse.
 Release of semen is called ejaculation.
 Semen contains spermatozoa or sperms
 Semen is derived from seminal vescicles which is neutral or slightly alkaline.
 Prostate gland contributes 20% of the semen volume which is milky fluid is citric acid
with a PH of 6.5.
 Prostate secretion is also rich in proteolytic enzymes
 Proteolytic enzymes are responsible for the coagulation and liquefaction of semen.
 Less than 10% of semen volume is contributed by epididymis, vas deferens,
bulbourethral and urethral glands.

INDICATIONS

 Infertility
 Success of vasectomy
 Medicolegal cases e.g. rape

SAMPLE COLLECTION

Patient is instructed to collect the specimen by masturbation after 4-7 days of sexual
abstinence. The sample is collected in a clean glass tube, wide-mouthed container or in a
properly washed dry condom. Use of lubricant during collection should not be
recommended. Sample should be kept at body temperature. The sample is submitted in
the laboratory immediately but preferably within one hour of collection for examination.
Two specimens collected at 2-3 weeks interval are used for evaluation.

GROSS EXAMINATION

 COLOUR: Normally it is whitish, grey-white or slightly yellowish.

 VOLUME: Normally, volume of semen is between 2.5 and 5 ml. The volume is slightly
more in patients of infertility. The volume does not vary with the period of abstinence.
 VISCOSITY: When ejaculated, semen is fairly viscid and it falls drop by drop.
 REACTION: Normally it is slightly alkaline with pH between 7 and 8.
 LIQUEFACTION: Liquefaction occurs because of presence of fibrinolysin. Normally
liquefaction occurs within 10-30 minutes.

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MICROSCOPIC EXAMINATION

MOTILITY: Place a drop of liquefied semen on a clean glass slide. Put a coverslip over it
and examine it under the microscope, first under low power and then under high power.
Normally within 2 hours of ejaculation more than 60% of spermatozoa are vigorously
motile, and in 6-8 hours 25-40% is still motile. If motility is less than 50%, a stain for
viability such as eosin Y with nigrosin as counterstain can be done. Red dye
accumulates in the heads of non-motile sperms. Motility is graded on -4ranking system.

 Grade1: Sluggish and little progress

 Grade2: Move forward, but slow and do not move in straight line.
 Grade3: Move in a straight line with good speed and can reach the ovum.
 Grade4: Move at terrific speed and reach the ovum accurately.

COUNT: This is done in Neubauer’s chamber using a WBC pipette. Draw liquefied semen
in WBC pipette up to mark 0.5 and then draw the diluting fluid up to mark 11. The
composition of diluting fluid is as under: Sodium bicarbonate 5 gm Formalin (neutral) 1
ml Distilled water 100 ml After mixing it properly, charge the Neubauer’s chamber. Allow
the spermatozoa to settle down in 2 minutes. Examine under microscope and count the
number of spermatozoa in two large peripheral squares (used for TLC counting) and
multiply the number by 1 lakh (100,000) which gives number of spermatozoa per
milliliter. Normal value = > 60 million/ml. Abnormal value = < 20 million/ml is
considered a strong indicator of infertility.

MORPHOLOGY: Prepare a thin smear from liquefied semen on a glass slide. Stain it with
any of the Romanoswky stains, Pap or H&E stain. Observe at least 200 spermatozoa for
any abnormality in their morphology. Normally 80% of spermatozoa are normal. The
abnormal forms of spermatozoa are with double head, swollen and pointed head, double
tail and rudimentary forms. Also look for the presence of RBCs or WBCs, if any.
Computer- mediated morphologic screening is particularly useful in samples with very
low numbers of normal sperm count which may otherwise remain undetected.

CHEMICAL EXAMINATION

FRUCTOSE TEST: This test determines androgen deficiency or ejaculatory obstruction

to semen; the level of seminal fructose is low in both these conditions. Normal seminal
fructose level is 150-600 mg/dl. Fructose is measured qualitatively by resorcinol test.
Procedure:Take 5 ml of dilute HCl in a test tube. Add 1 ml of semen then add 5 mg of
resorcinol and boil. Interpretation: Appearance of red colour indicates presence of
fructose which can be measured by spectrophotometer.

ACID PHOSPHATASE TEST: This test is used for seminal stain and on vaginal aspirate
in medicolegal cases. Normally semen has 2500 KA units/ml of acid phosphatase.

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IMMUNOLOGICAL ASSAYS: The presence of sperm antibody binding to head or tail
antigens is considered specific for immunologic infertility. The antibodies are usually of
immunoglobulin A (IgA) or IgG, and rarely of IgM class. These are detected by direct or
indirect mixed agglutination reaction tests.

MICROBIOLOGICAL ASSAYS: Genital tract infections by bacteria, yeast and sexually

transmitted diseases may have significant adverse effect on male infertility. If the
concentration of bacteria exceeds 1000 CFUs per ml, the colonies should be identified
and tested for antibiotic sensitivity.

SPERM FUNCTION TESTS: Defective sperm function may affect various fertilising
activities such as the transport of sperm in the male and female reproductive tracts and
thus events directly related to fertilization such as specific zona binding, penetration and
formation of male pronucleus, and accordingly function assays are devised.

215 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 URINALYSIS

Urinalysis is a basic procedure which enables the clinician to determine existence of a

metabolic disturbance in the body or conditions that affect the kidneys and the urinary
tract.

COMPOSITION OF NORMAL URINE

Water constitutes 95% of urine. The remaining5% of urine is composed of urea (2%) and
organic and inorganic substances (3%). The important inorganic constituents include
chloride, phosphorous, sulfur, sodium and potassium. The important organic
constituents are urea, creatinine, uric acid and ammonia.

COLLECTION OF URINE SPECIMEN

Urine should be collected in a proper way to make the test more meaningful. Urine is
collected in containers which are quite variable in type. Wide mouthed glass bottles are
most commonly used. It requires proper cleaning with soap and water. It must be
thoroughly dried before the sample is collected. It should be properly labeled. A freshly
voided, clean catch, midstream sample of urine is collected for most of the tests. The
patient should be instructed to void directly into a clean, dry container. All the
specimens should be covered immediately and brought without delay to the laboratory.
For bacterial examination a clean voided midstream specimen is essential. Bladder
catheterization and percutaneous suprapubic aspiration of the bladder may be used in
rare circumstances.

PHYSICAL EXAMINATION
 Volume of urine: The normal urine excretion ranges from 600 to 2400ml/day.
Polyuria is increase in the urine excretion. Oliguria is a decrease in urinary output.
Anuria refers to absent urinary output or volume less than 125ml/day.

 Color: The urochrome pigments give normal urine an amber color or pale yellow color.
Color of urine is affected by various factors like fluid intake, diet, medicines and
diseases. It becomes colorless in polyuria and becomes dark yellow orange in oliguria.
Presence of red blood cells gives urine a smoky color and hemoglobin gives cola

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 colored urine. Urine is yellow orange in jaundice and milky in the presence of pus.
Vitamin B supplements turn the urine bright yellow.

 Transparency and turbidity: normal urine is clear. Turbidity of the urine is caused
by phosphate, presence of mucus, bacterial growth or formation of amorphous or
crystalline deposits.

 Odor: Freshly voided urine is faintly aromatic. Presence of acetone imparts a fruity
odor and bacterial decomposition results in ammonical odor.

 Reaction of urine: The PH of the urine varies from 5.5 to 6.8. Commonly it is acidic.
The PH of the urine is measured using litmus paper, PH indicator strips and strip
multistix method.

 Specific gravity: The normal specific gravity of urine varies from 1.008 to 1.030. It is
measured by a urinometer, a refractometer or by dipstick methods. Increased specific
gravity is seen in dehydration, diarrhea, vomiting, diabetes mellitus and excessive
sweating. Decreased specific gravity is seen in excessive fluid intake and diabetes
inspidus

CHEMICAL EXAMINATION
Urine chemical examination is done for proteins, sugar, ketones, bile pigments, bile salts
and blood.

TESTS FOR PROTEINURIA: If urine is not clear, it should be filtered or centrifuged

before testing. Urine may be tested for proteinuria by qualitative tests and quantitative
methods.
HEAT AND ACETIC ACID TEST
Heat causes coagulation of proteins. The procedure is as under:
 Take a 5 ml test tube.
 Fill 2/3rd with urine.
 Acidify by adding 10% glacial acetic acid if urine is alkaline.
 Boil upper portion for 2 minutes (lower part acts as control).

217 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 If precipitation or turbidity appears add a few drops of 10% acetic acid.
Interpretation: If turbidity or precipitation disappears on addition of acetic acid, it is
due to phosphates; if it persists after addition of acetic acid then it is due to proteins.
Depending upon amount of protein the results are interpreted as under:
 No cloudiness = negative.
 Cloudiness against dark background = traces (less than 0.1 g/dl).
 Cloudiness without granularity = +(0.1 g/dl).
 Granular cloudiness=++(0.1-0.2 g/dl)
 Precipitation and flocculation = +++(0.2-0.4 g/dl).
 Thick solid precipitation = ++++ (0.5 g/dl).

SULFOSALICYLIC ACID TEST

This is a very reliable test. The procedure is as under:
 Make urine acidic by adding acetic acid.
 To 2 ml of urine add a few drops (4-5) of 20% Sulphosalicylic acid.
Interpretation: Appearance of turbidity which persists after heating indicates presence
of proteins.

HELLER’S TEST
 Take 2 ml of concentrated nitric acid in a test tube.
 Add urine drop by drop by the side of test tube.
Interpretation: Appearance of white ring at the junction indicates presence of protein.

REAGENT STRIP METHOD

Bromophenol coated strip is dipped in urine. Change in colour of strip indicates
presence of proteins in urine and is compared with the colour chart provided for semi
quantitative grading

TEST FOR BENCE-JONES PROTEINURIA

Bence--globulin. These are excreted in multiple myeloma and other paraproteinaemias.

In heat and acetic acid test performed under temperature control, these proteins are
precipitated at lower temperature (56oC) and disappear on further heating above 90oC

218 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

but reappear on cooling to lower temperature again. In case both albumin as well as
Bence-Jones proteins are present in urine, the sample of urine is heated to boiling.
Precipitates so formed due to albumin are filtered out and the test for Bence-Jones
proteins is repeated under temperature control.

TEST FOR GLUCOSURIA: Glucose is by far the most important of the sugars which may
appear in urine. Normally approximately 130 mg of glucose per 24 hours is passed in
urine which is undetectable by qualitative tests. Tests for glucosuria may be qualitative
or quantitative. Qualitative tests are Benedict’s test and Reagent strip test. Causes of
glucosuria are:
 Diabetes mellitus
 Renal glucosuria
 Severe burns
 Administration of corticosteroids
 Severe sepsis
 Pregnancy

BENEDICT’S TEST

In this test cupric ion is reduced by glucose to cuprous oxide and a coloured precipitate
is formed.

Procedure

 Take 5 ml of Benedict’s qualitative reagent in a test tube.

 Add 8 drops (or 0.5 ml) of urine.
 Heat to boiling for 2 minutes
 Cool in water bath or in running tap water.
Interpretation
 No change of blue colour = Negative
 Greenish colour = traces (< 0.5 g/dl)
 Green/cloudy green precipitate = + (1g/dl)
 Yellow precipitate = ++ (1-1.5g/dl)
 Orange precipitate= +++ (1.5-2g/dl)
 Brick red precipitate = ++++ (> 2g/dl)
219 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
Benedict’s test is for reducing substances excreted in the urine; the test is positive for all
reducing sugars (glucose, fructose, maltose, lactose but not sucrose) and other reducing
substances (e.g. ascorbic acid, salicylates, antibiotics, L-dopa).

REAGENT STRIP TEST

These strips are coated with glucose oxidase and the test is based on enzymatic reaction.
This test is specific for glucose. The strip is dipped in urine. If there is change in colour
of strip it indicates presence of glucose. The colour change is matched with standard
colour chart provided on the label of the reagent strip bottle.

QUANTITATIVE TEST FOR GLUCOSE

Procedure: Take 25 ml of quantitative Benedict’s reagent in a conical flask. Add to it 15

gm of sodium carbonate (crystalline) and some pieces of porcelain and heat it to boil.
Add urine to it from a burette slowly till there is disappearance of blue colour of
Benedict’s reagent. Note the volume of urine used. Calculate the amount of glucose
present in urine as under:

0.05 × 100
Amount of urine
(0.05 gm of glucose reduces 25 ml of Benedict’s reagent)

TESTS FOR KETONURIA: These are products of incomplete fat metabolism. The three
ketone bodies excreted in urine are: Acetoacetic acid (20%), acetone (2%), and
hydroxybutyric acid (78%). Causes of Ketonuria are
 Diabetic ketoacidosis
 Dehydration
 Hyperemesis gravidarum
 Fever
 Cachexia
 After general anaesthesia

TESTS FOR KETONURIA are

 Rothera’s test
 Gerhardt’s test
 Reagent strip test

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ROTHERA’S TEST Principle: Ketone bodies (acetone and acetoacetic acid) combine with
alkaline solution of sodium Nitroprusside forming purple complex.
Procedure
 Take 5 ml of urine in a test tube.
 Saturate it with solid ammonium sulphate salt.
 Add a few crystals of sodium nitroprusside and shake.
 Add liquor ammonia from the side of test tube.
Interpretation Appearance of purple coloured ring at the junction indicates presence of
ketone bodies.

GERHARDT’S TEST: It is not a very sensitive test.

Procedure
Take 5 ml of urine in a test tube.
Add 10% ferric chloride solution drop by drop.
Filter it and add more ferric chloride.
Interpretation: Brownish red colour indicates presence of ketone bodies.

REAGENT STRIP TEST: These strips are coated with alkaline sodium nitroprusside.
When strip is dipped in urine it turns purple if ketone bodies are present.

TEST FOR BILE DERIVATIVES IN URINE: Three bile derivatives excreted in urine are:
Urobilinogen, bile salts and bile pigments. While Urobilinogen is normally excreted in
urine in small amounts, bile salts and bile pigments appear in urine in liver diseases
only.

TESTS FOR BILE SALTS: Bile salts excreted in urine are cholic acid and
chenodeoxycholic acid. Tests for bile salts are Hay’s test and strip method. The main
cause for bile salts in the urine is obstructive jaundice.

HAY’S TEST Principle: Bile salts if present in urine lower the surface tension of the
urine.
Procedure: Fill a 50 or 100 ml beaker 2/3rd to 3/4th with urine and sprinkle finely
powdered sulphur powder over it.

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Interpretation: If bile salts are present in the urine then sulphur powder sinks,
otherwise it floats.

STRIP METHOD: Coated strips can be used for detecting bile salts as for other
constituents in urine

TESTS FOR UROBILINOGEN: Normally a small amount of Urobilinogen is excreted in

urine (4 mg/24 hr). The sample should always be collected in a dark coloured bottle as
Urobilinogen gets oxidised on exposure to light. Causes of increased urobilinogen in
urine are Haemolytic jaundice and haemolytic anaemia. Cause for absence of
urobilinogen in urine is obstructive jaundice. Tests for Urobilinogen in urine are
Ehrlich’s test and reagent strip test.

EHRLICH’S TEST Principle: Urobilinogen in urine combines with Ehrlich’s aldehyde

reagent to give a red purple coloured compound.
Procedure: Take 10 ml of urine in a test tube and add 1 ml of Ehrlich’s aldehyde reagent
then wait for 3-5 minutes.
Interpretation: Development of red purple colour indicates presence of Urobilinogen. A
positive test is subsequently done in dilutions; normally it is positive in up to 1:20
dilution.

REAGENT STRIP TEST: These strips are coated with p-dimethyl-aminobenzaldehyde.

When strip is dipped in urine, it turns reddish-brown if urobilinogen is present.

TESTS FOR BILIRUBIN (BILE PIGMENT) IN URINE: Bilirubin is breakdown product of

haemoglobin. Normally no bilirubin is passed in urine. Causes of bilirubinuria are
obstructive jaundice and hepatocellular jaundice. Following tests are done for detection
of bilirubin in urine: Fouchet’s test, Foam test and Reagent strip test

222 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

FOUCHET’S TEST Principle: Ferric chloride oxidises bilirubin to green biliverdin.
Procedure
 Take 10 ml of urine in a test tube.
 Add 3-5 ml of 10% barium chloride.
 Filter through filter paper.
 To the precipitate on filter paper, add a few drops of Fouchet’s reagent (ferric chloride
+ trichloroacetic acid).
Interpretation: Development of green colour indicates bilirubin.

FOAM TEST: It is a non-specific test.

Procedure: Take 5/10 ml of urine in a test tube and shake it vigorously.
Interpretation: Presence of yellow foam at the top indicates presence of biluribin.

REAGENT STRIP TEST (Principle): It is based on coupling reaction of bilirubin with

diazonium salt with which strip is coated. Dip the strip in urine; if it changes to blue
colour then bilirubin is present.

TESTS FOR BLOOD IN URINE: Causes of blood in urine are renal stones, renal
tumours, polycystic kidney, bleeding disorder and trauma. Tests for detection of blood in
urine are as under:
 Benzidine test
 Orthotoluidine test
 Reagent strip test

BENZIDINE TEST procedure: Take 2 ml of urine in a test tube. Add 2 ml of saturated

solution of benzidine with glacial acetic acid. Add 1 ml of H2O2 to it.
Interpretation: Appearance of blue colour indicates presence of blood. Benzidine is,
however, carcinogenic and this test is not commonly used.

ORTHOTOLUIDINE TEST PROCEDURE: Take 2 ml of urine in a test tube. Add a

solution of 1 ml of orthotoluidine in glacial acetic acid. Add a few drops of H2O2.
Interpretation: Blue or green colour indicates presence of blood in urine.

REAGENT STRIP TEST: The reagent strip is coated with orthotoluidine. Dip the strip in
urine. If it changes to blue colour then blood is present.

223 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 URINE MICROSCOPY
COLLECTION OF SAMPLE: Early morning sample is the best specimen. It provides an
acidic and concentrated sample which preserves the formed elements (RBCs, WBCs and
casts) which otherwise tend to lyse in a hypotonic or alkaline urine. The specimen
should be examined fresh or within 1-2 hours of collection. But if some delay is
anticipated, the sample should be preserved as described in the preceding exercise.

PREPARATION OF SEDIMENT
 Take 5-10 ml of urine in a centrifuge tube.
 Centrifuge for 5 minutes at 3000 rpm.
 Discard the supernatant.
 Re-suspend the deposit in a few ml of urine left.
 Place a drop of this on a clean glass slide.
 Place a coverslip over it and examine it under the microscope.

EXAMINATION OF SEDIMENT: Urine is an unstained preparation and its microscopic

examination is routinely done under reduced light using the light microscope. This is
done by keeping the condenser low with partial closure of diaphragm. First examine it
under low power objective, then under high power and keep on changing the fine
adjustment in order to visualize the sediments in different planes and report as
…..cells/HPF (high power field). Phase contrast microscopy may be used for more
transluscent formed elements. Rarely, polarizing microscopy is used to distinguish
crystals and fibres from cellular or protein casts. Following categories of constituents
are frequently reported in the urine on microscopic examination:
 Cells (RBCs, WBCs, epithelial cells)
 Casts
 Crystals
 Miscellaneous structures

224 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

 EXAMINATION OF CELLS
RBCs: These appear as pale or yellowish, biconcave, double contoured, disc-like
structures, and when viewed from side they have an hour-glass appearance. In
hypotonic urine, RBCs swell up while in hypertonic urine they are crenated. They can be
confused with WBCs, yeast and air bubbles/oil droplets but can be distinguished as
under:
 The WBCs are larger in size and are granular.
 Yeast cells appear round but show budding.
 Air bubbles and oil droplets vary in size. When edge of the cover slip is touched
with a pencil, oil droplets tumble while RBCs do not.
SIGNIFICANCE: Normally 0-2 RBCs/HPF may be passed in urine. RBCs in excess of this
number are seen in urine in the following conditions:
PHYSIOLOGICAL: Following severe exercise, Smoking and Lumbar lordosis
PATHOLOGICAL: Renal stones, Tumours, Glomerulonephritis, Polycystic kidney, UTI
and Trauma.

WBCs: These appear as round granular 12-14 in diameter. In fresh urine nuclear details
are well visualised. WBCs can be confused with RBCs. For differentiating, add a drop of
dilute acetic acid under coverslip. RBCs are lysed while nuclear details of WBCs become
clearer. WBCs can also be stained by adding a drop of crystal violet or safranin stain.
SIGNIFICANCE: Normally 0-4 WBCs/HPF may be present in females. WBCs are seen in
urine in following conditions: UTI, cystitis, prostatitis, chronic pyelonephritis, renal
stones and renal tumours.

EPITHELIAL CELLS: These are round to polygonal cells with a round to oval, small to
large nucleus. Epithelial cells in urine can be squamous epithelial cells, tubular cells
and transitional cells i.e. they can be from lower or upper urinary tract, and sometime it
is difficult to distinguish between different types of these cells. At times, these cells can
be confused with cancer cells.
SIGNIFICANCE Normally a few epithelial cells are seen in normal urine, more common
in females and reflect normal sloughing of these cells. When these cells are present in
large number along with WBCs, they are indicative of inflammation.

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CASTS IN URINE: These are formed due to moulding in renal tubules of solidified
proteins. Their shape depends upon their site of origin. In general casts are cylindrical in
shape with rounded ends. The basic composition of casts is Tamm- Horsfall protein
which is secreted by tubular cells. Casts appear in urine only in renal diseases.
CALCIUM OXALATE: These are colourless refractile and have octahedral envelope-like
structure. They can also be dumb-bell shaped.
URIC ACID: They are yellow or brown rhomboid-shaped seen singly or in rosettes. They
can also be in the form of prism, plates and sheaves.
AMORPHOUS URATE: They appear as yellowish brown granules in the form of clumps.
They dissolve on heating. When they are made of sodium urate, they are needle -like in
the form of thorn-apple. They are passed more often in patients having gout.
TYROSINE: They are yellowish in the form of silky needles or sheaves. They are passed
in urine in jaundice.
CYSTINE: They are colourless, hexagonal plates which are highly refractile. They are
passed in urine in an inborn error of metabolism, cystinuria.
CHOLESTEROL CRYSTALS: These are rare and are seen in urinary tract infection,
rupture of lymphatic into renal pelvis or due to blockage of lymphatics.
SULPHONAMIDE: They appear as yellowish sheaves, rosettes, or rounded with radial
striations. They appear in urine after administration of sulphonamide drugs.

CRYSTALS IN ALKALINE URINE

AMORPHOUS PHOSPHATE: They are seen as colourless granules in the form of clumps
or irregular aggregates. They dissolve when urine is made acidic.
TRIPLE PHOSPHATE: They are in the form of prisms and sometimes in fern leaf
pattern. They dissolve when urine is made acidic.
CALCIUM CARBONATE: They are in the form of granules, spheres or rarely dumbbell-
shaped. They again dissolve in acidic urine.
AMMONIUM BIURATE: They are round or oval yellowish-brown spheres with thorns on
their surface giving ‘thorn apple’ appearance. They dissolve on heating the urine or by
making it acidic

226 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]

MISCELLANEOUS STRUCTURES IN URINE
SPERMATOZOA: They can be seen in normal urine in males. They have a head and tail
and can be motile.
PARASITES: Urine may contain Trichomonas vaginalis which is more common in
females. Eggs of Schistosoma hematobium or Entamoeba histolytica can also be seen in
urine.
FUNGUS: Candida which are budding yeast cells can be seen in urine in patients with
UTI or as contaminant.
TUMOUR CELLS: Tumour cells having all the characteristics of malignancy may be seen
singly or in groups in urine. These tumour cells could be from kidney, ureter, bladder or
urethra. These cells are examined after staining of urine sediment.

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 CHARACTERISTICS OF FAECES
The characteristics of stool, also known as feces or bowel movements, can provide
valuable information about digestive health. Here are some key characteristics to
consider:

COLOR
Normal: Typically varies from light to dark brown, influenced by the presence of bile
pigments.
Abnormal: Unusual colors, such as black (may indicate bleeding in the upper digestive
tract), pale or clay-colored (may suggest issues with bile flow), or red (may indicate
bleeding in the lower digestive tract or from certain foods).

CONSISTENCY
Normal: Soft, formed, and easy to pass.
Abnormal: Diarrhea (loose or watery stools) may indicate an issue with absorption or
rapid transit through the intestines. Constipation (hard, difficult-to-pass stools) may
suggest a lack of fiber, dehydration, or other factors.

FREQUENCY
Normal: Can vary from person to person, but typically ranges from three times a day to
three times a week.
Abnormal: Significant changes in bowel habits, such as increased frequency or
prolonged constipation, may indicate underlying issues.

SHAPE
Normal: Stools are usually cylindrical and well-formed.
Abnormal: Narrow or pencil-thin stools may indicate a potential obstruction in the
colon.

ODOR
Normal: Has a distinct but not overpowering odor.
Abnormal: Foul or extremely strong odors may be associated with certain dietary factors
or digestive issues.

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PRESENCE OF BLOOD
Normal: Stool should not contain visible blood.
Abnormal: Presence of blood in the stool (hematochezia or melena) may indicate
bleeding in the digestive tract.

MUCUS
Normal: Small amounts of mucus are generally normal and help with the passage of
stool.
Abnormal: Increased amounts of mucus may be associated with inflammation or
infection.

FLOATING OR SINKING
Normal: Stools may float or sink, influenced by factors like gas content and fat
absorption.
Abnormal: Persistent floating stools may be associated with malabsorption.

UNDIGESTED FOOD
Normal: Small amounts of undigested food particles may be present.
Abnormal: Large, noticeable pieces of undigested food may suggest malabsorption or
rapid transit through the digestive tract.

SIZE
Normal: Stools vary in size, but drastic changes may indicate an issue.
Abnormal: Very small or very large stools may be associated with certain conditions.

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 STOOL EXAMINATION
Examination of sample of Stool is easily done and is very useful in the evaluation of
diarrheal diseases, parasitic infestations, colorectal carcinoma and malabsorption.

COLLECTION
Container: Stool sample is collected either in a wide mouthed glass or plastic jars with a
screw cap. Container should be clean and dry.
Method of collection: The sample is transferred from a clean bed pan or toilet into the
container.
Amount of sample: Stool required is small and about 2 – 5 gms of the stool sample is
adequate.
Precautions in collection:
 Morning sample is preferred.
 Sample should be labeled and the time of collection to be mentioned.
 The container after sample collection should be closed to avoid drying.
 Contamination with either urine or other substances in the bed pan or toilet should be
avoided.
 Stool must be fresh, Examine within one hour of collection.
 If blood / Mucous/ any other abnormal gross features are present in stool, it should
be included in the sample collected.
Preservation: Formal – Saline can be used as preservative which preserves morphology
of protozoa and helminthic eggs.

PHYSICAL EXAMINATION
Quantity: The quantity of stool varies from 100 – 250g/ day depending on the type of
diet consumed.
Consistency and form:
 Normal feces is well – formed.
 Extensively hard stool is observed during constipation.
 Large bulky, frothy, pale, foul smelling stool which floats on water is characteristic of
stratorrhea (poor fat digestion)
 Rice watery stool is typical of cholera.
 Watery / Semisolid stool in diarrhea, dysentery and following use of laxative/ enema.
230 PATHOLOGY NOTES KIRAN+91 9880268562 [email protected]
Colour
 Normal: Golden brown due to stercobilin, a pigment derived from bilirubin
metabolism.
 Black tarry stools: It is usually due to altered blood in stool and known as melena. The
source of blood is bleeding from the upper gastrointestinal tract (GIT). But black tarry
stool may also be observed following iron administration.
 Bright red colour: It is due to bleeding from the lower GIT like bleeding piles.
 Clay coloured stools: They are observed in obstructive jaundice.
Odour: Normal odour of stool is due to Indole and Skatole formed by intestinal
fermentation and putrefaction. The odour varies according to the pH of the stool.
Blood & mucous in stool: This is observed in either amoebic dysentery or Bacillary
dysentery. It may also be seen in Ulcerative colitis, neoplasms or tuberculosis of
intestine.
Parasites: Stool sample may show adult worms/ segments of worms (e.g. round worm,
pin worm, whip worm, hood worm or tape worm).

CHEMICAL EXAMINATION OF STOOL

The chemical examination of stool includes:
Reaction and pH:
 Normal stool pH: It ranges from 5.8 to 7.5
 Strong Acidic Stool: Observed with excess carbohydrate diet or fermentation due to
lactose intolerance.
 Strong Alkaline Stool: Observed with excess proteins in diet.

Occult blood: Small amount of blood in stool cannot be seen on gross examination.
Chemical tests are necessary to detect occult blood in stool. Presence of blood /
Hemoglobin in the stool which is detected by a ‘chemical test’ and not by the naked eye
is known as ‘occult (hidden) blood’.
BENZIDINE TEST: It is sensitive test for detecting occult blood.
Procedure:
 The benzedine reagent consists of 4g benzedine base in 10 ml glacial acetic acid. It is
stable for 2 - 4 months.
 Emulsify a bit of stool in 5ml water.

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 Mix 1 ml of emulsion with 1 ml of benzedine reagent in a test tube.
 Add several drops of 3% hydrogen peroxide.
Interpretation: The appearance of blue colour indicates the presence of blood.

MICROSCOPIC EXAMINATION OF STOOL

A fresh sample of stool without any contamination with disinfectants is used for
microscopic examination. On microscopy, examine the stool for:
 Leukocytes (pus cells), red blood cells, muscle fibres, fat globules, crystals, cysts, and
yeast cells and are expressed as number seen per high power field.
 Protozoa, eggs, larvae and cysts of parasites, flagellates and cillates. They are
reported as scanty, few, moderate or many.

METHODS FOR THE PREPARATION OF STOOL FOR MICROSCOPY

Saline preparation: A Small amount of stool sample is picked up with the help of tooth
prick and taken on a glass slide. Mix with normal saline to make a thin emulsion so that
the fine print can be seen through it. Cover with a cover slip. This is useful for the
demonstration of motility especially of E.histolytica.
Iodine preparation: In this, Gram’s Iodine is used instead of saline. Iodine imparts
brown colour to chromatin granules (nuclei) of amoebic cysts and also glycogen vacuole.
But iodine kills living parasites thereby preventing identification of motility.

STOOL CONCENTRATION METHODS: When ova and cysts are few in number and not
detected by routine methods, concentration method will be of help.
Floatation method: The stool sample is mixed with either zinc sulphates or magnesium
sulphates which has a high specific gravity and causes the parasite to float in the
solution. It is used for concentration of cysts, Larvae and most of the helminthic eggs.
Sedimentation methods: In this method, the parasites sediment and get deposited at
the bottom by centrifugation. It can be done by either simple sedimentation method or
by formal saline ether sedimentation method.
 Simple sedimentation method: A small amount of stool sample is mixed with saline
in a tube or bottle and sieved through a strainer. The sieved contents are centrifuged
and the supernatant fluid discarded. The deposit is resuspended in more saline, mixed

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 and centrifuged. This is repeated till the supernatant fluid appears clear. The deposit
is examined directly on a glass slide.
 Formal saline ether sedimentation method: This yields a good concentration of
parasites and is recommended for routine work. But this method cannot be used to
concentrate living parasites because the formalin used kills the parasites.

STOOL CULTURE AND SENSITIVITY

Collection: Stool sample for culture should be collected in a sterile wide mouthed
container.
Culture media used: MacConkey’s agar, nutrient agar or selective media depending on
the suspected organism.
Procedure:
 Take a stool in culture media and incubate at 370 for 18 – 20 hours.
 Suspected colonies are tested by using oxidase test.
 The causative organisms are identified by using biochemical tests.
 The organism may be confirmed by agglutination using specific antisera.
Antibiotic sensitivity test is done for the identified pathogenic organism.

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