INTRODUCTION TO

PATHOLOGY
H.A.NGGADA MD, FMCPath.
PROFESSOR OF PATHOLOGY
DEPARTMENT OF HUMAN PATHOLOGY
FACULTY OF BASIC CLINICAL SCIENCES
COLLEGE OF MEDICAL SCIENCES
UNIVERSITY OF MAIDUGURI
NIGERIA
DEFINITION
• Pathology is the branch of medical science that deals with the study
of morphologic (structural) changes caused by disease in cells, tissues,
organs, body fluids or whole body (Autopsy Pathology)
• There are two main branches of Pathology
• General Pathology – study of basic, common reactions of cells and
tissues to abnormal stimuli that underlie all diseases e.g. Acute
inflammation (similar to all types of tissue)
• Systemic Pathology – study of specific responses of specialized organs
and tissues to abnormal stimuli e.g. Cerebral infarction
The Process of Disease
• Aetiology (Cause) – Genetic & Acquired
• Pathogenesis (Mechanism of Development) – sequence of events in
response of cells or tissues to the aetiologic agent, from the initial
stimuli to the expression
• Morphologic Changes (Biochemical & Structural alterations induced
in cells)
• Clinical Significance (Functional consequences of morphologic
changes) – symptoms and signs
HOMEOSTASIS
• Is when a cell is able to handle the normal physiologic demands,
maintaining a steady state
CELL CYCLE
Cell cycle
Definition: The stages
through which a cell
passes from one cell
division to the next
Durations
G1 – phase – 10hrs
S – phase – 9hrs
G2 – Phase – 4hrs
M -phase – 1hr
Definition
• Cell cycle is also known as Cell Division Cycle .
• Is a series of events that take place in a cell leading to its
division and duplication of its DNA to produce two daughter
cells.
Types of TISSUES/CELLS
1. Continuously dividing cells – Proliferate throughout life
e.g. Surface epithelia – skin, oral cavity, vagina,cervix
- Lining mucosa of all the excretory ducts of the glands – salivary glands, pancreas, biliary duct
- Columnar of the GI tract, uterus, transition epithelium of the urinary bladder
- Cells of the bone marrow and haemopoietic tissues
2. Stable or quiescent cells – low level of replication
e.g Parenchymal cells of the liver, Kidney, Panreas, fibroblast
3. Nondividing (Permanent) cells – Cannot undergo mitotic division in postnatal life
e.g. Neurons, skeletal and cardiac muscles
CELLULAR ADAPTATION
• Hyperplasia
• Hypertrophy
• Atrophy
• Metaplasia
TYPES OF CELLULAR
ADAPTATIONS
HYPERPLASIA
• It is defined as the increase number of cells in an organ or tissue
leading to increased size/mass of the tissue or organ
• It take place in cells that are capable of synthesizing DNA
• In nondividing cells, only hypertrophy occurs
Mechanism:
• Hormones acts as growth factors and trigger transcription of genes
• Proliferation of remaining cells and development of new cells from
stem cells
.
Types
1. Physiologic hyperplasia
a. Hormonal Hyperplasia – Hormonal stimulation increases the
functional capacity of the tissue when needed e.g. Breast and Uterus
in puberty, pregnancy and lactation
b. Compensatory Hyperplasia – increase in tissue mass after
damage or partial resection e.g. regeneration of liver after partial
hepatectomy
.
2. Pathologic Hyperplasia – Hyperplasia due to excessive hormonal
stimulation or excessive effect of growth factors on target cells e.g.
Endometrial hyperplasia (occurs when balance between progesterone
and oestrogen is disturbed) and Benign Nodular Prostatic Hyperplasia
(occurs due to androgen excess)
Hypertrophy
• Definition: Is the increase in size of the cell due to increased synthesis
of structural components and not due to cellular swelling
• Hypertrophy occurs in nondividing cells e.g. myocardial fibres
• Dividing cells – (stable cells or quiescent cells) undergo both
hyperplasia and hypertrophy)
Mechanism:
• Induction of genes stimulate the synthesis of cellular proteins which is
responsible for hypertrophy
.
Types
• Physiological Hypertrophy – Occurs due to increase functional
demand and stimulation by growth factors and hormones e.g. Uterine
enlargement in pregnancy and breast hypertrophy during lactation
• Pathological Hypertrophy – Hypertrophy of cardiac muscle in
systemic hypertension and aortic valve stenosis in chronic
haemodynamic overload leading to left ventricular hypertrophy
ATROPHY
Definition – is the decrease in the size of a body organ, tissue or cell along
with decreased function, owing to disease, injury or lack of use
Mechanism:
Decreased protein synthesis or increased protein degradation by lysosomal
Types:
• Physiological atrophy – during development e.g. atrophy of the notochord
or thyroglossal duct during fetal development and uterus after parturition
• Pathological atrophy -
a. Decrease workload due to immobilization and prolonged functional
inactivity leading to disuse atrophy
.
b. Loss of innervation of muscle which induces its wasting e.g.
Poliomyelitis and motor neuron disease
c. Atherosclerosis – can cause ischaemic atrophy
d. Nutritional deficiency – marasmus, cancer cachexia
e. Loss of endocrine stimulation after menopause induce atrophy of the
reproductive organs
f. Senile atrophy in an aging especially the Brain, Heart and Testes
METAPLASIA

• Definition: Is the replacement of an adult/differentiated epithelial or

mesenchymal cell type by another adult/differentiated cell type and is
reversible
E.g.
• Columnar to squamous metaplasia- e.g. in respiratory tract due to
chronic irritation (cigarette smoking) and Vitamin A deficiency; Stones in
excretory ducts of salivary glands, pancreas and gall bladder; Endocervix
due to chronic infection
• Squamous to columnar metaplasia (Barrett’s oesophagus) – e.g. in
oesophagus due to reflux oesophagitis ( Note: may progress to
adenocarcinoma)
.
• Connective tissue metaplasia – Formation of cartilage, bone or
adipose tissue in tissue that normally does not contain these
elements e.g myositis ossifican
• Metaplasia is mostly reversible and the tissue reverts to its normal
state after removal of the stimulus or irritant.
• If the irritant or stimuli persist, metaplasia may progress to DYSPLASIA
and then to neoplasia (Malignant), which is irreversible
DYSPLASIA
• Is define as the disorder of cellular development that is characterized
by:
 Architectural disorientation (disorderly arrangement of cells)
 Lack uniformity of individual cells (cellular pleomorphism)
• Causes of dysplasia: Cellular insults – physical, chemical and
biological
• Typically seen in epithelial cells and may reverse in early stage
• Severe dysplasia may progress to carcinoma in situ and invasive
carcinoma
DIFFERENCES BETWEEN METAPLASIA
AND DYSPLASIA
METAPLASIA DYSPLASIA
• Replacement of one adult • Disorderly cellular development
epithelial or mesenchymal cell characterized by: i) lost of
type by another orientation of cells with respect
• Type: Squamous, columnar to one another ii) lack of
(epithelial); Osseous, uniformity
cartilaginous (Mesenchymal) • Type: Epithelial only
• No pleomorphism • Pleomorphism present
• Reversible on withdrawal of • May regress or progress to high
stimuli grade or carcinoma
CELL INJURY
• Definition: When the cell cannot adapt anymore or when the limits of
adaptive response to a stimulus are exceeded, a sequence of events
labelled cell injury follows.
Types of cell injuries
• 1. Reversible – If the structural and functional changes, induced by an
injurious stimulus, can revert to normal on removal of the same
• 2. Irreversible - If the structural and functional changes, induced by
an injurious stimulus, cannot be reverse even after removal of the
same
Causes of cell injury
• Genetic
• Development defects – errors in morphogenesis
Radiation – Atomic weapons and Radioiodine
Infections – CMV, Herpes virus, Syphilis, Toxoplasma, Rubella virus
Maternal metabolic factors – Alcoholism, DM, Folic acid deficiency
Drugs – Thalidomide, Busulfan, Cocaine, Cyclophosphamide
• Cytogenetic defects – chromosomal abnormalities
Down’s syndrome – Trisomy 21
Klinefelter syndrome - XXY
• Single gene defects
Mendelian disorders - SCD
• Multifactorial inheritance disorders
Cleft lip, cleft palate
Cont.
• Acquired
• Hypoxia -Ischaemia, anaemia, CO poisoning, Cardiorespiratory failure
• Physical agents - Trauma, Thermal injury, Radiation, Electric shock, pressure
changes
• Chemical agents/Drugs - Heavy metals, acids/alkalies, insecticides/herbicides,
alcohol, smoking
• Microbial agents - Bacteria, viruses, fungi, rickettsiae, parasite
• Immunological agents - autoimmunity, hypersensitivity
• Nutritional imbalance - Deficiency of protein, calories, trace elements,
vitamins, excess cholesterol
Responses to Pathological
stimuli
a. Type, duration and severity of the injury
b. Type, status and adaptability of the target cell

Injuries to:-
• Mitochondrial - Aerobic respiration
• Cell membrane
• Protein synthesis
• Cytoskeleton
• Genetic apparatus
Biochemical basis of cell injury
• Cell injury occurs due to the following mechanisms:
• ATP depletion – ATP is required for
• Membrane transport
• Protein synthesis
• Lipogenesis
• Phospholipid turnover

• Damage due to oxygen and oxygen-derived free radicals

• Loss of calcium homeostasis
• Normal cytosolic free calcium levels are very low
• Most intracellular calcium sequestered in ER and Mitochondria
• Injury causes influx of calcium across cell membrane and its release into cytosol from
mitochondria and ER
• Increase in cytosolic calcium leads to activation of enzymes initiating cell injury
CELL INJURY

REVERSIBLE CELL INJURY IRREVERSIBLE CELL INJURY

• Cell Membrane: Blebbing, blunting, • CM: More prominent
distortion, outpouching
• Rupture of lysosomes
• Hydropic ER and Mitochondria swelling
• Swelling of ER and detachment of • Rupture or fragmentation of cell
ribosome membrane
• Myelin figures – large masses of • Fragmentation of nucleus
degraded phospholipids
• Apoptosis
• Nuclear chromatin clumping
• Mitochondria densities • Necrosis
NECROSIS
• Definition: Is cell death in a tissue or organ and where continuity with
neighboring viable tissue is preserved
TYPES OF MORPHOLOGICAL
PATTERN OF NECROSIS
• COAGULATIVE NECROSIS
• LIQUEFACTIVE (COLLIQUATIVE) NECROSIS
• CASEOUS NECROSIS
• ENZYMATIC FAT NECROSIS
• FIBRINOID NECROSIS
• GANGRENOUS NECROSIS
COAGULATIVE NECROSIS

• The cell maintains its outline (architecture) for days, resulting in a

well-defined, anuclear mass of pink cytoplasm
• Protein denaturation
• This is seen in all cells that have undergone hypoxia, except for the
brain
 Mechanism of Coagulative
Necrosis
Decrease pH
Denaturation of structural and enzymatic proteins

Lack of Enzymatic proteins blocks proteolysis

Preservation of Basic Architecture of Cell/Tissue

LIQUEFACTIVE NECROSIS
• The cell is transformed into a thick liquid without a defined shape
(the cellular outline is destroyed)
• Enzymatic degradation
• This is seen in bacterial infection, some fungal infection and brain
hypoxia

• Macroscopically, thick yellowish fluid is seen

MECHANISM OF EVOLUTION OF
GANGRENE NECROSIS
Bacterial infection and accumulation of inflammatory cells

Release of enzymes

Autolysis and heterolysis

FAT NECROSIS
• The fat cell is broken down, but maintains its outline
• A bluish calcium layer is deposits around the cell and the fat cell
become surrounded by neutrophils, lymphocytes and macrophages
• This is seen in the pancreas and fatty tissues (Breast, Abdomen and
subcutaneous tissue)
• Macroscopically, White chalky areas are seen which is known as fat
saponification
MECHANISM OF EVOLUTION OF ENZYMATIC
FAT NECROSIS
Release of activated pancreatic lipase into pancreas and peritoneal cavity

Focal areas of destruction of fat and release of fatty acids

Released fatty acids combine with calcium (Saponification)

Chalky white areas

CASEOUS NECROSIS
• This is a typical form of coagulative necrosis
• The cell becomes amorphous and loses its outline
• The tissue loses its architecture
• Surrounding the necrotic area, a granulomatous inflammatory border
is formed primarily by macrophages and lymphocytes
• Example in Tuberculous lung infections
• Macroscopically: Yellowish cheesy area is seen
FIBRINOID NECROSIS
• The cell loses its outline and becomes homogenous
and pink like-fibrin, but there no fibrin involvement
• This is seen in blood vessels of patients with
malignant Hypertension and those that have
autoimmune diseases e.g Systemic lupus
erythematosus (SLE), Polyarteritis nodosa (PN) and
Rheumatic fever, Rheumatoid arthritis and HBV
infection
GANGRENE NECROSIS
• This is a clinical term and not a specific pattern of
necrosis
• It is usually used in context of the lower limbs which
has lost blood supply and has undergone necrosis
• Initially coagulative (Dry gangrene)
• Later liquefactive (Wet gangrene) due to secondary
bacterial infection and immigrating leucocytes
MECHANISM OF EVOLUTION OF
GANGRENE NECROSIS
Bacterial infection and accumulation of inflammatory cells

Release of enzymes

Autolysis and heterolysis

APOPTOSIS
• Apoptosis is programmed cell death
• In apoptosis, enzymes are activated to hydrolyze :
• Proteins via – Caspases
• Crosslink Proteins via – Transglutaminases
• Cleave DNA via – Endonucleases
• The exact trigger of this mechanism is unknown
• The signal takes its cue from the apoptotic environment in the form of
feedback mechanism
APOPTOSIOS
• Is a form of genetically programmed cell death design to eliminate
unwanted host cells through activation of a coordinated series of
events
• It occurs in Physiological and Pathological conditions
• Physiological apoptosis
• During development/Embryogenesis (implantation and organogenesis)
• Hormone-dependent involution (regression of lactational changes in breast
and prostatic atrophy)
• Cell ageing
Pathological apoptosis
• Cellular damage by diseases
• Pathological atrophy in hormone-dependent organs e.g prostate
• Cell death in tumours
• Low doses of thermal injury, radiation and anticancer drugs
Sequence of Morphological changes in
Apoptosis
• Cell shrinkage
• Chromatin condensation and nuclear fragmentation
• Formation of cytoplasmic plebs
• Fragmentation into apoptotic bodies
• Fragmentation into membrane-bound apoptotic bodies
• Phagocytosis of apoptotic bodies (Digestion by macrophages and
lysosomal degradation)
‘

INTRACELLULAR ACCUMULATION
Degenerative changes
• Def: It is a retrogressive change which is visible in living cell. The
manifest changes consist of accumulation of a normal substance in
excess in the cytoplasm or the appearance of an abnormal substance
in the cytoplasm or in the intercellular spaces.
• Mild damage – Biochemical lesion
• Moderate damage – Degeneration
• Severe damage - Necrosis
Types of Degeneration
• Cloudy swelling
• Hydropic or vacuolar degeneration
• Fatty change
• Mucoid
• Myxomatous
• Hyaline
• Calcareous or calcification
CLOUDING SWELLING
• Characterized by the appearance of protein granules – a normal
substance in excess within the cytoplasm of parenchymatous cells.
• The change is of short duration
• It is reversible or may progress to hydropic degeneration or fatty
change.
• Causes: Bacterial toxin
Chemical – Chloroform, Arsenic, carbolic acid, CCl4
Eg. Liver, Kidney, Heart
. Organ is paler than the normal
. Consistency is soft
. Cut surface is blurred
HYDROPIC (VACUOLAR)
• It is an extension of cloudy degeneration.
• It is reversible
• Causes: Infective Hepatitis; Chloroform; CCL4, Shock.
• Liver, Kidney, Skin, Pancreas
• The Cells appears ballooned, cytoplasm is pale, watery and
shows vacuoles (Negative for glycogen and fat).
FATTY CHANGE (STEASTOSIS)

• Characterized by fat in the cytoplasm of parenchymatous

cells
• It is reversible in its early stage.
• Causes: Alcohol, DM, Obesity, Toxins, Anoxia, CCL4,
choloform, Ether, phosphorus.
• Liver, heart.
• Organ is enlarged, pale, soft
.
Cut surface is yellowish
Fat in the cytoplasm of parenchymatous cells
H&E stain – clear vacuoles in the cytoplasm
Frozen section – Sudan IV or Oil Red – O = orange red colour.
Yellow/Red-brown colour = Tigered effect (Heart)
PIGMENTS
• Definition: are coloured substances some of which are normal
constituents of cells (eg Melanin), where as others are
abnormal and collect in cells only under special circumstances.
• Types
1. Endogenous pigments:
E.g. Lipofuscin (lipochrome); Melanin; Derivatives of Hb
(Bilirubin, Haemosiderin, Hemozoin, Porphyrin)
Cont.
2. Exogenous pigments:
eg. Carbon or Coal dust (lung)-Anthracosis
Tattooing (skin)- localized
LIPOFUSCIN (LIPOCHROME)
• ‘‘Wear and tear’’ or Aging pigment
• Insoluble pigment
• Composed of polymers of lipids and phospholipid complexed with protein
• Derived from lipid peroxidation of polyunsaturated lipid of subcellular membrane
• Lipofuscin is not injurious to the cell or its function.
• It is yellow brown, finely granular, intracytoplasmic, often perinuclear pigment.
• Liver and Heart of aging pt, malnutrition,cachetic cancer pt.
• Organ is usually shrunken.
MELANIN
• Melas – Black
• Brown Black Pigments
• Tyrosine – DOPA – Melanin (Melanocytes)
DISORDERS

1. VITILIGO – Partial or complete loss of pigment – producing

melanocytes within the epidermis
Causes – Autoimmunity (Addison’s dx)
Asymptomatic, flat, well dermacated zones (macules) of pigment
loss.
Distribution: Wrist, Perioral, Periorbital, anogenital skin, axillae
Cont.
2. ALBINISM – lack or defect in the tyrosinase, enzyme (No melanin
pigment) -Albino
3. FRECKLE
4. MELASMA (MASK-LIKE)
5. LENTIGO
6. NEVUS
7. MELANOMA
EXOGENOUS PIGMENTS
• Inhaled, ingested, absorbed from the mucous membrane.
1. COAL DUST (ANTHRACOSIS)
Carboneous particles seen in alveolar lumen within macrophages.
Pigments may either be intra or extracellular
Black lines outlining the alveolar or lymphatic network.
Coal miner’s pneumoconiosis
Anthracosis
2. Tatooning
PATHOLOGIC CALCIFICATION
• 1. DYSTROPHIC – Is the deposition of calcium salt in altered
or necrotic tissue despite normal serum level of calcium and
in the absence of derangements in calcium metabolism.
• Predisposing factors:
Hyaline change in fibrous tissue –Uterine fibroid
Death tissue – Caseous necrosis
Cont.
• 2. METASTATIC – Is the deposition of calcium salt in vital or normal
tissues which almost always reflects some disturbance in calcium
metabolism, leading to hypercalcaemia
• Causes:
1. Increased secretion of parathyroid hormone (PTH) – tumour of
parathyroid gland.
2. Destruction of bone tissue – multiple myeloma
3. Renal failure – retention of phosphate
Special stain for calcium – von kossa
 Q&A

END OF THE LECTURE TOPICS