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PATHOLOGY

F-Pa-001 Pathology (Cell Injury) Learning Objectives

 Discuss the significance of pathology
 Discuss the causes of cell injury.
 Identify the types of cell injury.
 Describe the mechanism of cell injury.
 Identify the types of cell death.
 Define necrosis and apoptosis.
 Describe different types of necrosis.
 Compare apoptosis with necrosis.
 Identify different types and mechanisms of cellular adaptations to stress
 Discuss the mechanism and types of intracellular accumulations and
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pathological calcifications

Pathology plays a crucial role in medicine by providing insights into the causes,
mechanisms, and manifestations of diseases.
1. Disease Etiology Understanding
2. Disease Pathogenesis Insight
3. Diagnosis and Treatment
4. Rational Treatment Development
5. Preventive Medicine
6. Scientific Foundation
Cell injury:
Cell damage also known as cell injury is a variety of changes of stress that cells
suffer due to external as well as internal environmental changes.

Causes of cell injury:

Causes of cell injury Examples
1. Hypoxia and - Oxygen deficiency, reduced blood supply, Arterial obstruction,
Ischemia inadequate oxygenation, Reduction in oxygen-carrying capacity
(e.g., anemia and carbon monoxide poisoning)
2. Toxins - Air pollutants, insecticides, asbestos, Cigarette smoke,
ethanol, drugs
3. Infectious Agents - Viruses, bacteria, fungi, protozoans
4. Immunologic - Autoimmune reactions, allergic reactions
338 Reactions
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5. Genetic - Congenital malformations (e.g., Down syndrome), Single
Abnormalities amino acid substitution (e.g., sickle cell anemia)
6. Nutritional - Protein–calorie insufficiency, vitamin deficiencies
Imbalances
7. Physical Agents - Trauma, extremes of temperature, radiation, Electric shock,
sudden changes in atmospheric pressure
8. Aging - Cellular senescence
Types of cell injuries:
 Reversible
 Irreversible
Reversible cell injury EXPRESS HIT
Reversible injury is the stage of cell injury at which the deranged function and "Ischemic cell injury leads to
morphology of the injured cells can return to normal if the damaging stimulus is ATP depletion—triggering
removed. Na+/K+ pump failure and
Morphology: swelling!"
Cellular swelling:

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 It is commonly seen in cell injury associated with increased permeability
of the plasma membrane.
 When it affects many cells in an organ, it causes pallor (as a result of
compression of capillaries),
 Increased turgor
 An increase in organ weight.
 Microscopic examination may show small, clear vacuoles within the
cytoplasm; these represent distended and pinched-off segments of the
endoplasmic reticulum (ER). This pattern of nonlethal injury is sometimes
called hydropic change or vacuolar degeneration
Fatty change:
 It is manifested by the appearance of triglyceride-containing lipid
vacuoles in the cytoplasm. It is principally encountered in organs that are
involved in lipid metabolism, such as the liver.
Other Intracellular Changes Associated with Cell Injury
1. Plasma Membrane - Blebbing, blunting, or distortion of microvilli
Alterations - Loosening of intercellular attachments
2. Mitochondrial Changes - Swelling
- Appearance of phospholipid- rich amorphous densities
3. Dilation of the - Detachment of ribosomes
Endoplasmic - Dissociation of polysomes
Reticulum
4. Nuclear Alterations - Clumping of chromatin

Irreversible injury: 339

Irreversible responses to cell injury refer to changes that lead to a new equilibrium
with the environment. Types of irreversible responses include:
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 Interruption of membrane integrity;
 Hydrolysis of phospholipids, proteins, and nucleic acids
Cell death:
There are two major patterns of cell death:
1. Necrosis
2. Apoptosis
Other pathways of cell death:
1) Necroptosis
2) Pyroptosis
PAST SEQ:
Compare and contrast apoptosis and necrosis in terms of their causes,
mechanisms, and morphological changes.
Define and classify GANGRENE NECROSIS. Give description with examples of
each type.
(a) Do-define CALCIFICATION.
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(b) What are various types of calcification?

(c) Describe and differentiate between DYSTROPHIC and METASTATIC
CALCIFICATION.

Difference between apoptosis and necrosis

Feature Apoptosis Necrosis
Definition Programmed and coordinated cell Cell death along with
death degradation of tissue by
hydrolytic enzymes
Causative agents Physiologic and pathologic processes Hypoxia, toxins
Morphology
i) Inflammatory No Always present
reaction
ii) Death of cells Single cells Many adjacent cells
iii) Cell size change Cell shrinkage Cell swelling initially
iv) Membrane Cytoplasmic blebs on the Membrane disruption
changes membrane
v) Organelles Intact Damaged organelles /
(lysosomes) hydrolytic enzymes
released
vi) Nucleus Chromatin condensation Nuclear disruption
vii) Phagocytosis Phagocytosis of apoptotic bodies Phagocytosis of cell
by macrophages debris by macrophages
Agarose gel Step ladder DNA pattern Diffused DNA pattern
electrophoresis
Molecular changes
i) Organelles Lysosomes and other organelles Lysosomal breakdown
intact with liberation of
hydrolytic enzymes
ii) Genetic Genetic activation by proto- Lysosomal breakdown
activation oncogenes and oncosuppressor with liberation of
genes, and cytotoxic T cell- hydrolytic enzymes
mediated target cell killing
iii) Initiation of Initiation of apoptosis by intra- and Cell death by ATP
apoptosis extracellular stimuli, followed by depletion, membrane
activation of caspase pathway damage, free radical
(FAS-R, BCL-2, p53) injury
Cell Size Reduced (shrinkage) Enlarged (swelling)
Nucleus Fragmentation into nucleosome- Pyknosis -> karyorrhexis
340 sized fragments -> karyolysis
Plasma Membrane Intact; altered structure, especially Disrupted
orientation of lipids
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Cellular Contents Intact; may be released in apoptotic Enzymatic digestion may
bodies leak out of the cell
Physiologic or Often physiologic means of Invariably pathologic
Pathologic Role eliminating unwanted cells; may be (culmination of
pathologic after some forms of cell irreversible cell injury)
injury, especially DNA and protein
damage

Necrosis
Necrosis is a form of cell death in which cellular membranes fall apart, and cellular
enzymes leak out and ultimately digest the cell
Severe disturbances, such as loss of oxygen and nutrient supply and the actions
of toxins, cause a rapid and uncontrollable form of death that has been called EXPRESS HIT
“accidental” cell death. "Necrosis spills intracellular
Mechanism: contents—activating
inflammation, unlike
 Failure of energy generation in the form of ATP because of reduced apoptosis!"
oxygen supply or mitochondrial damage;
 Damage to cellular membranes, including the plasma membrane and

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lysosomal membranes, which results in leakage of cellular contents
including enzymes;
 Irreversible damage to cellular lipids, proteins, and nucleic acids, which
may be caused by reactive oxygen species (ROS);
Morphology:
Cytoplasmic Characteristics
Changes
Eosinophilia Increased in necrotic cells
Glassy Homogeneous Compared with viable cells, often due to the loss of lighter
Appearance staining glycogen particles
Prominent Myelin More noticeable in necrotic cells than in cells with reversible
Figures injury
Vacuolated Results from enzyme digestion of cytoplasmic organelles,
Cytoplasm giving a "moth-eaten" appearance
Electron Microscopy - Discontinuities in plasma and organelle membranes, marked
Characteristics dilation of mitochondria with large amorphous intra-
mitochondrial densities, disruption of lysosomes, presence of
intracytoplasmic myelin figures

Nuclear Characteristics
Changes
Pyknosis - Nuclear shrinkage, increased basophilia, DNA condenses into a
dark, shrunken mass
Karyorrhexis - Fragmentation of the pyknotic nucleus
Karyolysis The nucleus undergoes karyolysis, and basophilia fades due to the
digestion of DNA by deoxyribonuclease (DNase) activity, in 1 to 2
days, the nucleus in a dead cell may completely disappear
Fate of necrotic cells:
Necrotic Cells Characteristics
Persistence This may persist for some time
Disappearance It may be digested by enzymes and disappear
Replacement Dead cells may be replaced by myelin figures

Fate of Myelin Figures Characteristics

Phagocytosis Phagocytosed by other cells
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Degradation Further degraded into fatty acids
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Calcification Process Characteristics

Binding of Fatty Acids Fatty acids bind calcium salts
Ultimate Fate Dead cells may ultimately become calcified
Types of necrosis
Necrosis Type Definition Causes Morphological Cellular
Features Response
Coagulative Denaturation of Ischemia (lack of Tissue retains its Inflammation is
Necrosis proteins; blood flow), shape; nucleus usually absent
architecture infarction disappears; ghost
maintained initially outlines of cells;
occurs in solid
organs

Liquefactive Tissue becomes Bacterial/fungal Rapid degradation Inflammatory

Necrosis liquid, forming infections, some of tissue; response;
cystic spaces ischemic events formation of a macrophage
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liquid mass; influx

common in the
brain (abscess
formation)
Caseous Necrosis Cheese-like Tuberculosis, Distinct Granulomatous
appearance due to fungal infections granuloma inflammation
amorphous formation; tissue
granular debris appears "cheese-
like"; no cellular
outlines

Fat Necrosis Focal destruction of Trauma, acute Formation of Inflammatory

fat cells pancreatitis chalky white response;
areas macrophage
(calcification); influx
saponification of
fat; inflammation
of surrounding
tissue

Gangrenous Death of tissue Ischemia, Dry gangrene: Varies based on

Necrosis involving multiple infection, coagulative the underlying
tissue layers diabetes necrosis; wet cause
gangrene:
liquefactive
necrosis; gas
gangrene:
bacterial infection

Fibrinoid Deposition of fibrin- Immune Bright pink Immune

Necrosis like material in reactions, staining with H&E; response;
walls of vessels vasculitis deposition of inflammation
fibrin-like material
in vessel walls;
immune complex
involvement

Apoptosis:
Apoptosis is a pathway of cell death in which cells activate enzymes that degrade
the cells’ nuclear DNA and nuclear and cytoplasmic proteins
342 Features:
 It is a regulated cell death
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 Apoptosis is a process that eliminates cells with a variety of intrinsic
abnormalities and promotes clearance of the fragments of the dead cells
without eliciting an inflammatory reaction. This “clean” form of cell suicide
occurs in pathologic situations
 Unlike necrosis, which is always an indication of a pathologic process,
apoptosis also occurs in healthy tissues
Causes:
Physiologic conditions:
1. During normal development
2. In these situations, cell death is always by apoptosis, ensuring that
unwanted cells are eliminated without eliciting potentially harmful
inflammation.
3. In the immune system, apoptosis eliminates excess leukocytes left at the
end of immune responses
Condition Mechanism of Apoptosis
During embryogenesis Loss of growth factor signaling
Turnover of proliferative tissues (e.g., Loss of growth factor signaling

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intestinal epithelium, lymphocytes in bone
marrow, and thymus)
Involution of hormone-dependent tissues Decreased hormone levels lead to reduced
(e.g., endometrium) survival signals
Decline of leukocyte numbers at the end Loss of survival signals as stimulus for
of immune and inflammatory responses leukocyte activation is eliminated
Elimination of potentially harmful self- Strong recognition of self-antigens induces
reactive lymphocytes apoptosis by both the mitochondrial and
death receptor pathways

Pathologic conditions:
1. Apoptosis eliminates cells that are damaged beyond repair.
2. For example, after exposure to radiation and cytotoxic drugs
Condition Mechanism of Apoptosis
DNA damage Activation of proapoptotic proteins by BH3-only sensors
Accumulation of Activation of proapoptotic proteins by BH3-only sensors,
misfolded proteins possibly direct activation of caspases
Infections, especially Activation of the mitochondrial pathway by viral proteins
certain viral infections Killing of infected cells by cytotoxic T lymphocytes, which
activate caspases

Pathways of apoptosis:
1. Mitochondrial (Intrinsic) Pathway
2. Death receptor (Extrinsic) Pathway

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Morphology:
EXPRESS HIT  The nuclei of apoptotic cells show various stages of chromatin
condensation and aggregation and, ultimately, karyorrhexis
"Mitochondrial damage
releases cytochrome c—  The cells rapidly shrink, form cytoplasmic buds, and fragment into
activating apoptosis via apoptotic bodies that are composed of membrane-bound pieces of cytosol
caspases!" and organelles
Necroptosis
 In some instances, regulated cell death shows features of both necrosis
and apoptosis and has been called necroptosis.
Pyroptosis:
 This form of cell death is associated with the activation of a cytosolic
danger-sensing protein complex called the inflammasome. The net result
of inflammasome activation is the activation of caspases, some of which
induce the production of cytokines that induce inflammation, often
manifested by fever, and others trigger apoptosis
Cellular adaptations
Adaptations are reversible changes in the number, size, phenotype, metabolic
activity, or functions of cells in response to changes in their environment.
 Hypertrophy
 Hyperplasia
 Atrophy
 Metaplasia
Hypertrophy:
Hypertrophy is an increase in the size
of cells increasing the size of the
organ.
in pure hypertrophy, there are no new
cells, just bigger cells containing
increased amounts of structural
proteins and organelles.
Hypertrophy can be physiologic or
pathologic and is caused either by
344 increased functional demand or by
growth factor or hormonal stimulation.
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Examples:
Type Example
Physiologic 1) Uterine Enlargement During Pregnancy: Massive enlargement due
Hypertrophy to estrogen-stimulated smooth muscle hypertrophy and hyperplasia
2) Uterine Enlargement During Pregnancy: Massive enlargement due
to estrogen-stimulated smooth muscle hypertrophy and hyperplasia

Pathologic 1) Cardiac Enlargement in Hypertension or Aortic Valve Disease:

Hypertrophy

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Hyperplasia:
Hyperplasia is an increase in the number of cells in an organ that stems from
increased proliferation, either of differentiated cells or, in some instances, less
differentiated progenitor cells.
Hyperplasia occurs in cells capable of replication, whereas hypertrophy occurs in
tissues incapable of cell division.
Hyperplasia can be physiologic or pathologic; in both situations, cellular
proliferation is stimulated by growth factors that are produced by a variety of cell
types
Examples:
Type Example
Physiologic 1) Hormonal Hyperplasia: Proliferation of glandular epithelium in
Hyperplasia the female breast at puberty and during pregnancy
2) Compensatory Hyperplasia: Residual tissue growth after
removal or loss of part of an organ. Ex. Liver Regeneration after
Resection
Pathologic 1) Endometrial Hyperplasia
Hyperplasia
2) Benign Prostatic Hyperplasia

Atrophy:
Atrophy is shrinkage in the size of cells by the loss of cell substance. The main
cause of death in atrophy is apoptosis.
Physiological Atrophy:
 Aging (senile atrophy).
 Notochord and thyroglossal duct undergo atrophy during development
Pathological Atrophy
 Disuse atrophy: due to decreased workload (e.g., immobilization of a limb
345
to permit healing of a fracture
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 Ischemic atrophy: ischemia due to atheroma or diminished blood supply
 Denervation atrophy: loss of innervation due to nerve damage
 Pressure atrophy: atrophy of renal parenchyma in hydronephrosis due to
increase increased pressure
 Starvation atrophy: malnutrition
Cellular atrophy results from a combination of decreased protein synthesis and
increased protein degradation.
 Protein synthesis decreases because of reduced metabolic activity.
 The degradation of cellular proteins occurs mainly by the ubiquitin-
proteasome pathway. Nutrient deficiency and disuse may activate
ubiquitin ligases, which attach multiple copies of the small peptide ubiquitin
to cellular proteins and target them for degradation in proteasomes
 In many situations, atrophy also is associated with autophagy, resulting in
increases in the number of autophagic vacuoles.
Mataplasia:
Metaplasia is ta change in which one adult cell type (epithelial or mesenchymal)
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is replaced by another adult cell type.

Examples:
1) Epithelial metaplasia is exemplified by the change that occurs in the
respiratory epithelium of habitual cigarette smokers, in whom the normal
ciliated columnar epithelial cells of the trachea and bronchi often are
replaced by stratified squamous epithelial cells. (vitamin A is essential for
normal epithelial differentiation, its deficiency also may induce squamous
metaplasia in the respiratory epithelium.)
2) In chronic gastric reflux, the normal stratified squamous epithelium of the
lower esophagus may undergo metaplastic transformation to gastric or
intestinal-type columnar epithelium
PAST SEQ:
1 A 45-year-old male bodybuilder has been undergoing intense resistance
training for the past six months. Upon examination, his skeletal muscles
have significantly increased in size.
 What type of cellular adaptation is occurring in his muscles?
 Explain the underlying mechanism of this adaptation.
 How does this differ from hyperplasia?
2 A 60-year-old chronic smoker develops a persistent cough. A biopsy of
his bronchial tissue shows a replacement of normal columnar epithelium
with stratified squamous epithelium.
 What type of cellular adaptation has occurred?
 Explain the possible cause and the consequences of this adaptation.
 How can this condition progress if the irritant (smoking) continues?
3 (a) Define and differentiate between HYPERPLASIA and METAPLASIA.
(b) What is pathological calcification?
(c) Enlist four causes of metastatic calcification and give one example of each.
4 A multigravida delivers a baby babe. Because of her good experience of
breastfeeding in the past, she wants to breastfeed the baby during
pregnancy that will enable this.
(a) What changes occur in the mother to nurse her baby? Define this type of
cellular adaptation.
5 (a) Massive enlargement of the uterus during pregnancy is a type of
cellular adaptation?
346 (b) What is the mechanism of atrophy?
 PHARMACOLOGY AND PATHOLOGY
Aspect Hypertrophy Hyperplasia Atrophy Metaplasia
Definition Increase in cell Increase in the Decrease in Conversion of
size or tissue number of cell size or one mature cell
mass due to cells in an tissue mass type into another
enlargement of organ or tissue due to cell mature cell type
existing cells shrinkage
Cellular Increased Increased cell Decreased Reprogramming
Mechanism protein division protein of stem cells or
synthesis synthesis or existing cells to a
increased different cell type
protein
degradation
Causes Physiological Physiological Reduced Chronic irritation,
(e.g., exercise- (e.g., workload, inflammation, or
induced muscle hormonal loss of adaptation to
hypertrophy) or changes) or innervation, stress
pathological pathological decreased
(e.g., cardiac (e.g., blood supply,
hypertrophy in excessive aging
response to hormonal

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hypertension) stimulation)
Examples Enlargement of Breast Muscle Barrett's
skeletal muscles enlargement wasting due esophagus, or
in response to during to disuse or squamous
the exercise pregnancy aging metaplasia in the
respiratory tract
due to smoking
Reversibility Potentially Potentially Reversible to May be reversible
reversible if the reversible if the some extent if the stimulus is
underlying underlying if the cause removed, but can
cause is cause is is addressed progress to
removed removed irreversible
changes

Intracellular accumulations:
Pathways:
1) Inadequate removal and degradation of endogenous substances,
2) Excessive production of an endogenous substance,
3) Deposition of an abnormal exogenous material
Fatty Change:
Fatty change, also called steatosis, refers to any accumulation of triglycerides
within parenchymal cells.
Organs involved:
 liver, since this is the major organ involved in fat metabolism,
 heart,
 skeletal muscle,
 kidney, and other organs.
Cause:
 Steatosis may be caused by toxins,
 protein malnutrition,
 diabetes mellitus,
 obesity,
 anoxia.
 Alcohol abuse and diabetes associated with obesity are the most common 347
causes of fatty change in the liver (fatty liver)
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Cholesterol and Cholesteryl esters:

phagocytic cells may become overloaded with lipids (triglycerides, cholesterol, and
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cholesteryl esters) in several different pathologic processes most important of

which is atherosclerosis.
Proteins:
In disorders with heavy protein leakage across the glomerular filter (e.g., nephrotic
syndrome), much more of the protein is reabsorbed in kidneys, and vesicles
containing this protein accumulate, giving the histologic appearance of pink,
hyaline cytoplasmic droplets.
Glycogen:
Excessive intracellular deposits of glycogen are associated with abnormalities in
the metabolism of either glucose or glycogen.
Example:
1) In poorly controlled diabetes mellitus
2) Glycogen storage diseases
Pathologic Accumulation of Proteins in the Cytoplasm:
Proteinuria:
 Excessive renal tubular reabsorption of proteins by proximal tubular
epithelial cells.
 Pink hyaline droplets appear in the cytoplasm.
 Reversible condition; protein droplets disappear with control of proteinuria.
Plasma Cells:
 Actively functioning plasma cells exhibit pink hyaline inclusions known as
Russell’s bodies.
 Represent synthesized immunoglobulins.
α1-Antitrypsin Deficiency:
 Hepatocytes' cytoplasm shows eosinophilic globular deposits of a mutant
protein.
Mallory’s Body (Alcoholic Hyalin):
 In hepatocytes, intracellular accumulation of intermediate filaments of
cytokeratin.
 Appears as amorphous pink masses.
Intracellular Accumulation of Glycogen:
Diabetes Mellitus:
348
 Intracellular accumulation of glycogen in different tissues due to impaired
cellular uptake of glucose.
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 Glycogen deposits in diabetes mellitus are observed in:
 Epithelium of the distal portion of the proximal convoluted tubule and
descending loop of Henle.
 Hepatocytes.
 Beta cells of pancreatic islets.
 Cardiac muscle cells.
 Glycogen deposits produce clear vacuoles in the cytoplasm.
 Best’s carmine and periodic acid-Schiff (PAS) staining may confirm the
presence of glycogen.
Glycogen Storage Diseases (Glycogenosis):
 Defective metabolism of glycogen due to genetic disorders.
Pigments:
Pigments are colored substances that are either exogenous, coming from outside
the body, such as carbon (most common), or are endogenous, synthesized within
the body itself, such as lipofuscin, melanin, and certain derivatives of hemoglobin.
Aggregates of the pigment blacken the draining lymph nodes and pulmonary

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parenchyma (anthracosis)
A. Exogenous pigments
1. Inhaled pigments
2. Ingested pigments
3. Injected pigments
(Tattooing)
B. Endogenous pigments
1. Melanin
2. Melanin-like pigment
 Alkaptonuria
 Dubin-Johnson
syndrome
3. Haemoprotein-derived
pigments
 Haemosiderin
 Acid haematin
(Haemozoin)
4. Bilirubin
5. Porphyrins
6. Lipofuscin (Wear and tear pigment)
1. Lipofuscin (Indicator of Free-radical injury):
 “wear-and-tear pigment,”
 It is an insoluble brownish-yellow granular intracellular material
 accumulates in a variety of tissues (particularly the heart, liver,
and brain) with aging or atrophy.
 Lipofuscin represents complexes of lipids and proteins that are
produced by the free radical–catalyzed peroxidation of
polyunsaturated lipids of subcellular membranes
 The brown pigment when present in large amounts, imparts an
appearance to the tissue that is called brown atrophy.
2. Melanin
 Is an endogenous, brown-black pigment
 Synthesized by melanocytes located in the epidermis and acts as 349
a screen against harmful UV radiation.
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
Although melanocytes are the only source of melanin, adjacent
basal keratinocytes in the skin can accumulate the pigment (e.g.,
in freckles), as can dermal macrophages.
3. Hemosiderin:
 It is a hemoglobin-derived granular pigment.
 It is golden yellow to brown and accumulates in tissues when
there is a local or systemic excess of iron.

Excessive deposition of hemosiderin, called hemosiderosis, and
more extensive accumulations of iron seen in hereditary
hemochromatosis
4. Homogentisic acid
 Black pigment present in the patients of alkaptonuria, that is found
in the skin and connective tissue, while pigmentation is known as
ochronosis
Pathological calcifications:
Pathologic calcification, a common process in a wide variety of disease states, is
the result of an abnormal deposition of calcium salts, together with smaller
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amounts of iron, magnesium, and other minerals.

It can occur in two ways, it begins in mitochondria of all the organs except
kidney. Kidney’s calcification starts from the basement membrane.
 Dystrophic calcification
 Metastatic calcification
Aspect Dystrophic Calcification Metastatic Calcification
Definition Deposition of calcium salts Deposition of calcium salts in normal
in dead and degenerated tissue
tissues
Calcium Normal Deranged
Metabolism
Serum Normal Hypercalcemia
Calcium
levels
Site of Necrotic tissue, thrombi, Blood vessels, lungs (most
deposition dead parasite, old scars, common), kidney, gastric mucosa
atheroma, infarcts
Mechanism Initiated by extracellular Associated with hypercalcemia,
deposition of crystalline influenced by factors like increased
calcium phosphate or parathyroid hormone secretion, bone
intracellular deposition in destruction, vitamin D disorders, and
dying cell mitochondria renal failure
Crystalline Crystals deposited in Crystalline deposition due to systemic
Formation membrane-bound vesicles hypercalcemia
or mitochondria; propagated
to form larger deposits
Causes Local factors like tissue Hyperparathyroidism, accelerated
injury or inflammation, bone turnover (e.g., Paget disease),
necrosis, infract, thrombi, immobilization, tumors, vitamin D
hematoma, dead parasite, disorders, milk-alkali syndrome,
old scars, atheroma, renal failure leading to secondary
monckebrg’s sclerosis, hyperparathyroidism
calcinosis cutis
pathology Initiation and propagation High pH at certain sites e.g., lungs,
stomach, blood vessel, cornea
Example Calcification in aging or Soft tissue calcification in renal
damaged heart valves failure, pulmonary alveolar damage
350 in hyperparathyroidism
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Relevance in Commonly observed in Associated with metabolic disorders
Clinical chronic inflammatory affecting calcium homeostasis
Settings diseases or areas of tissue
damage
Management Focuses on addressing Addresses the underlying cause of
underlying tissue damage or hypercalcemia and may involve
inflammation treating the primary disorder causing
elevated serum calcium

MEDICO EXPRESS SUMMARIES LO 001

1. Pathology in Medicine – Essential for understanding disease etiology,
pathogenesis, diagnosis, treatment, and prevention.
2. Causes of Cell Injury – Includes hypoxia, toxins, infections, immune
reactions, genetic abnormalities, nutritional imbalances, physical agents,
and aging.
3. Types of Cell Injury – Can be reversible (temporary cellular dysfunction)
or irreversible (leading to cell death).
4. Reversible Cell Injury – Characterized by cellular swelling (hydropic

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change) and fatty change, affecting plasma membrane, mitochondria, ER,
and nucleus.
5. Irreversible Cell Injury – Leads to permanent membrane damage,
enzyme leakage, and breakdown of phospholipids, proteins, and
nucleic acids.
6. Cell Death Mechanisms – Includes necrosis (uncontrolled, inflammatory)
and apoptosis (programmed, non-inflammatory), along with necroptosis
and pyroptosis.
7. Differences Between Apoptosis and Necrosis – Apoptosis is regulated
and affects single cells, while necrosis is unregulated and involves large
areas of tissue with inflammation.
8. Mechanisms and Morphology of Necrosis – Caused by ATP depletion,
ROS damage, and membrane disruption, leading to cytoplasmic
eosinophilia, nuclear fragmentation (pyknosis, karyorrhexis,
karyolysis), and organelle breakdown.
9. Fate of Necrotic Cells – Can persist, disappear through enzymatic
digestion, be replaced by myelin figures, or undergo calcification
(binding of fatty acids with calcium salts).
10. Types of Necrosis – Includes:
 Coagulative (ischemia, protein denaturation)
 Liquefactive (bacterial/fungal infections)
 Caseous (TB, granulomas)
 Fat (pancreatitis, trauma)
 Gangrenous (dry, wet, gas gangrene)
 Fibrinoid (immune-mediated, vasculitis)
11. Apoptosis Pathways – Occurs via intrinsic (mitochondrial) or extrinsic
(death receptor) pathways, removing damaged or unnecessary cells.
12. Necroptosis & Pyroptosis – Necroptosis shares features of both necrosis
and apoptosis, while pyroptosis involves inflammasome activation,
leading to inflammation and cell death.
13. Cellular Adaptations – Cells adapt to stress through hypertrophy
(increase in size), hyperplasia (increase in number), atrophy (shrinkage),
and metaplasia (change in cell type).
14. Hypertrophy vs. Hyperplasia – Hypertrophy occurs in non-dividing cells
(e.g., muscle), while hyperplasia occurs in dividing cells (e.g., breast 351
tissue during pregnancy).
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15. Atrophy – Shrinkage due to reduced workload, ischemia, denervation,
or malnutrition, often involving protein degradation and autophagy.
16. Metaplasia – A reversible change where one cell type replaces another
due to chronic irritation (e.g., squamous metaplasia in smokers).
17. Intracellular Accumulations – Cells accumulate lipids, proteins,
glycogen, and pigments due to metabolic dysfunctions or exposure to
harmful substances (e.g., fatty liver from alcohol abuse).
18. Pigments in Cells – Can be:
 Exogenous (carbon from pollution, tattoo ink)
 Endogenous (melanin, bilirubin, lipofuscin, indicating oxidative stress and
aging)
19. Glycogen Storage & Protein Accumulation – Excess glycogen in
diabetes, while protein buildup occurs in nephrotic syndrome and α1-
antitrypsin deficiency.
20. Pathologic Calcifications – Dystrophic calcification occurs in damaged
tissues, while metastatic calcification results from systemic calcium
imbalances.
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F-Pa-002 Microbiology (Introduction to Microorganisms)

Learning Objectives
 Describe the basic structure of bacteria and virus.
 Enlist medically important microbes causing infectious diseases.
 Differentiate cell walls of gram positive and gram negative bacteria.
 Compare the structure of bacterial cell and virus
 Discuss the growth curve of bacteria and virus.
 Enlist steps of viral replication Enlist stages of infectious diseases
 Enlist stages of bacterial pathogenesis
 Discuss the determinants of bacterial pathogenesis

Bacteria
Shape & size of Bacteria
Bacterial Classification by Shape: EXPRESS HIT

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 Cocci: Spherical. "Gram-positive bacteria
 Bacilli: Rod-shaped. have a thick peptidoglycan
wall—targeted by penicillin!"
 Spirochetes: Spiral-shaped.
 The shape of a bacterium is determined by its rigid cell wall.
Pleomorphism and Arrangement:
 Some bacteria exhibit pleomorphism, displaying multiple shapes.
 Cocci can be found:
 In pairs (Diplococci).
 In chains (Streptococci).
 In grape-like clusters (Staphylococci).
 Bacterial arrangement is determined by orientation and attachment
during cell division.
Size Variation:
 Bacteria range in size from 0.2 to 5 micrometers.
 Mycoplasma, lacking a cell wall, represents the smallest bacteria.
 This wide size range underscores the diversity within the bacterial
kingdom.

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 MEDICO EXPRESS BLOCK 1
Structure of bacterial cell wall:
 The outermost component present in most bacteria (excluding
Mycoplasma species).
 Location: External to the cytoplasmic membrane.
 Composition: Primarily composed of peptidoglycan.
 Function: Provides structural support and maintains cell shape.
PAST SEQ:
1 Classify GRAM POSITIVE BACILLI.
2 Write short notes on:
 (a) What are sulphur granules?
EXPRESS HIT
 (b) How do the following bacterial structures contribute in pathogenesis?
"Viruses lack ribosomes—
forcing them to hijack host o (i) Pili
machinery for replication!" o (ii) Catalase
o (iii) Slime layer
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Viruses
A virus is a microscopic infectious agent that requires a living host cell to replicate.
It consists of genetic material, either DNA or RNA, enclosed in a protein coat called
a capsid. Some viruses also have an outer lipid envelope derived from the host
cell membrane.
Structure
Size and Shape of Viruses:
 Viruses range from 20 to 300 nm in diameter.
 Shapes include spheres, rods, bullets, or bricks, but are complex
structures of precise geometric symmetry.
 Shape is determined by the arrangement of repeating subunits forming the
capsid.
 Shapes and sizes vary among different viruses.

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 PHARMACOLOGY AND PATHOLOGY
Viral Nucleic Acids:
 Located internally within virus particles.
 Can be single- or double-stranded DNA or RNA.
 DNA can be linear or circular; RNA can be single molecule or segmented.
 Almost all viruses are haploid; the exception is the retrovirus family.
 Retroviruses are diploid, containing two copies of the RNA genome.
Viral Capsid & Symmetry:
 Capsid surrounds nucleic acid and is composed of capsomers.
 Capsomers give virus structure geometric symmetry.
 Symmetry can be icosahedral (20 triangles forming a sphere-like figure)
or helical (rod-shaped).
EXPRESS HIT
 Helical viruses are enveloped; icosahedral viruses can be enveloped or
"Obligate anaerobes (e.g.,
naked.
Clostridium) lack superoxide
Viral Proteins: dismutase & catalase—
 Capsid proteins protect the genome from degradation. oxygen is toxic to them!"
 Surface proteins mediate attachment to host cell receptors.
 Outer viral proteins induce immune responses and determine species and

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organ specificity.
 Different viruses have various internal proteins, some structural and others
enzymatic.
 Some viruses produce superantigens, activating T cells for replication.
Viral Envelope:
 Composed of lipoprotein membrane derived from host cell.
 Contains virus-specific proteins and glycoproteins for host cell attachment.
 Matrix protein mediates the interaction between capsid proteins and
envelope.
 Acquisition of envelope occurs during viral exit from host cell through
budding process.
Clinical Correlates:
 Enveloped viruses are less stable and sensitive to heat, drying, and lipid
solvents.
 Enveloped viruses are often transmitted by direct contact, insect bite,
respiratory droplets, or animal bite.
 Naked nucleocapsid viruses commonly transmitted by fecal-oral route.
 Surface proteins of viruses are principal antigens and determinants of
serotype specificity.
 Limited cross-protection between different serotypes, enhancing the
virus's ability to evade host defenses.
Microbe Type Examples
Bacteria Escherichia coli (E. coli), Staphylococcus aureus, Streptococcus
(prokaryotic) pneumoniae, Mycobacterium tuberculosis, Salmonella spp., Vibrio
cholera
Viruses Influenza virus, Human immunodeficiency virus (HIV), Hepatitis
viruses (e.g., Hepatitis A, B, C), Herpes simplex virus, Human
papillomavirus (HPV), SARS-CoV-2 (COVID-19)
Fungi (eukaryotic) Candida albicans, Aspergillus spp., Cryptococcus neoformans,
Histoplasma capsulatum
Protozoa Plasmodium spp. (causing malaria), Giardia lamblia, Entamoeba
(eukaryotic) histolytica, Toxoplasma gondii
Helminths (worm) Taenia solium (causing cysticercosis), Ascaris lumbricoides,
(eukaryotic) Schistosoma spp., Necator americanus (hookworm)
Ectoparasites Sarcoptes scabiei (causing scabies), Pediculus humanus (causing
lice infestation)
355
Prions Creutzfeldt-Jakob disease (CJD), variant CJD, kuru
 MEDICO EXPRESS BLOCK 1
1. Cell Envelope:
 Cell Wall: The cell wall provides structural support and shape to the
bacterial cell. It also helps protect the cell from osmotic lysis. In Gram-
positive bacteria, the cell wall is composed mainly of peptidoglycan, while
in Gram-negative bacteria, it consists of a thin layer of peptidoglycan
surrounded by an outer membrane containing lipopolysaccharides (LPS).
 Cell Membrane (Plasma Membrane): The cell membrane is a
phospholipid bilayer that surrounds the cytoplasm. It regulates the
passage of substances into and out of the cell and is involved in various
cellular processes, including nutrient uptake and energy production.
2. Cytoplasm:
 The cytoplasm is a gel-like substance that fills the interior of the cell. It
contains various structures and molecules necessary for cellular
metabolism and growth.
 Ribosomes: Bacterial ribosomes are the site of protein synthesis. They
consist of RNA and protein and float freely in the cytoplasm or may be
attached to the cell membrane.
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 Nucleoid: The nucleoid is a region in the cytoplasm where the bacterial

chromosome (circular DNA molecule) is located. Unlike eukaryotic cells,
bacteria typically have a single, circular chromosome.
 Plasmids: Some bacteria contain extrachromosomal DNA molecules
called plasmids, which may carry genes that confer antibiotic resistance
or other advantageous traits.
3. Appendages:
 Flagella: Flagella are long, whip-like structures that extend from the cell
surface. They are involved in bacterial motility, allowing the cell to move
towards or away from stimuli.
 Pili (Fimbriae): Pili are shorter, hair-like appendages that protrude from
the cell surface. They are involved in adherence to surfaces, including host
tissues, and in bacterial conjugation (the transfer of genetic material
between bacterial cells).
4. Inclusions:
 Some bacterial cells contain inclusions, which are storage granules or
compartments that store nutrients or other substances. Examples include
glycogen granules, lipid droplets, and sulfur granules.
5. Capsule and S-layer (in some bacteria):
 Some bacteria have an outer layer known as a capsule, which is
composed of polysaccharides or glycoproteins. The capsule helps protect
the cell from phagocytosis by immune cells and may also facilitate
attachment to surfaces.
 In addition to or instead of a capsule, some bacteria have a surface layer
(S-layer) composed of protein or glycoprotein subunits. The S-layer
provides additional protection and structural support to the cell.

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 PHARMACOLOGY AND PATHOLOGY
Difference between Gram-Positive and Gram- Negative cell wall
Aspect Gram-Positive Bacteria Gram-Negative Bacteria
Composition A thick layer of A thin layer of peptidoglycan
peptidoglycan (murein), (murein), surrounded by an
makes up about 90% of outer membrane
the cell wall
Peptidoglycan Thick, multi-layered Thin, single-layered
Structure structure structure
Teichoic Acids Present, covalently Generally absent
bound to peptidoglycan
or cell membrane
Outer Membrane Absent Present, composed of
lipopolysaccharides (LPS),
phospholipids, and proteins
Porins Absent Present in the outer
membrane, allowing the
passage of small molecules
Lipopolysaccharides Absent Present in the outer
(endotoxins) membrane, contributing to

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bacterial pathogenicity
Periplasmic Space Limited or absent Prominent, containing
periplasmic enzymes and
proteins
Staining Response Retains crystal violet stain Loses crystal violet stain
during Gram staining, during Gram staining, appears
appears purple pink

Difference between Bacteria and Viruses

Aspect Bacterial Cell Virus
Size Much larger, typically in the Much smaller, typically in the
range of 0.5 to 5 micrometers range of 20 to 300 nanometres
Cellularity Unicellular Acellular
Genetic Material DNA or RNA (usually a single DNA or RNA (can be single- or
circular chromosome) double-stranded, linear or
circular)
Cellular Contains ribosomes (70S), Lacks cellular machinery and
Machinery organelles, and a cytoplasmic organelles
membrane
Reproduction Reproduces through binary Replicates inside host cells
fission or other forms of cell using host cellular machinery
division
Metabolism Metabolically active, capable of Lack metabolic machinery and
independent metabolism and are obligate intracellular
growth parasites
Cell Wall May have a cell wall composed Lack a cell wall, although some
of peptidoglycan (in bacteria) have protein coats or
envelopes
Proteins Contains proteins encoded by Contains proteins encoded by
its genetic material its own genetic material and/or
acquired from the host cell
Envelope May have a cell membrane, but Some viruses have a lipid
lacks a lipid envelope envelope derived from the host
cell membrane
Host Interaction Can interact with other cells Requires a host cell to replicate
and tissues independently and propagate
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 MEDICO EXPRESS BLOCK 1

Bacterial Growth curve

Growth Description Metabolism
Phase
Lag Phase Initial period of adjustment and Limited metabolic activity
preparation for growth, minimal
increase in population size
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Exponential Rapid and exponential growth of Active metabolism, synthesis of

Phase (log bacterial population, maximum proteins
phase) growth rate
Stationary The growth rate slows down, and Reduced metabolic activity,
Phase equilibrium reached between cell adaptation to stress. Nutrient
division and death. Birth = death depletion
Death Population declines due to Decreased metabolism, cell
Phase unfavorable conditions, exponential death
decrease in population density.
Death > Birth

Viral Growth Curve

1. Rapid Replication
 A single virion can replicate within ~10 hours, producing hundreds of new
virions.
 The time for the viral growth cycle varies between minutes (bacterial
viruses) to hours (human viruses).
2. Eclipse Period
 The virus seemingly "disappears" as the solid line on the graph drops to
the x-axis.
 The viral nucleic acid continues to function but no complete virions are
detected inside the cell.
 Ends when new virions start to appear.
3. Latent Period
358
 Defined as the time from infection onset to the appearance of
extracellular virus.
 PHARMACOLOGY AND PATHOLOGY
 Includes both the eclipse period and early stages of virion production.
4. Viral Reproduction
 Unique replication method where one virion infects a cell and produces
hundreds of new virions.
5. Cytopathic Effect (CPE)
 Occurs towards the end of the latent period.
 Leads to alterations in cell morphology and function.
6. Cell Lysis and Death
 The CPE culminates in the destruction of infected cells.
 Causes significant cellular damage and dysfunction.
7. Laboratory Diagnosis
 CPE can be observed under a light microscope.
 Serves as an important diagnostic feature in detecting viral infections.
8. Non-Cytopathic Viruses
 Some viruses do not cause visible cell damage.

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 These viruses can replicate without inducing major morphological
changes.

Steps of viral replication

1. Attachment: Virus binds to host cell receptors.
2. Penetration: The virus enters the host cell.
3. Uncoating: Viral genetic material is released.
4. Replication and Transcription: The viral genome is copied and transcribed.
5. Translation: Viral proteins are synthesized.
6. Assembly: New virions are assembled.
7. Maturation: Virions acquire final structure.
8. Release: Viruses exit the host cell.
9. Propagation: Released virions infect new cells.
Types of bacterial infections
1. Respiratory Infections:
 Pneumonia: Infection of the lungs leading to inflammation and
fluid buildup. 359
 Sinusitis: Inflammation of the sinuses causing nasal congestion,
pain, and discharge.
 MEDICO EXPRESS BLOCK 1
 Bronchitis: Inflammation of the bronchial tubes causing coughing
and difficulty breathing.
2. Skin and Soft Tissue Infections:
 Cellulitis: Infection of the deeper layers of the skin causing
redness, swelling, and pain.
 Impetigo: Contagious skin infection characterized by blisters and
crusts.
 Abscess: Collection of pus within tissues, often resulting from
bacterial infection.
3. Gastrointestinal Infections:
 Gastroenteritis: Inflammation of the stomach and intestines
causing diarrhea, vomiting, and abdominal pain.
 Food Poisoning: Illness caused by consuming food contaminated
with pathogenic bacteria such as Salmonella or Escherichia coli
(E. coli).
4. Urinary Tract Infections (UTIs):

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Cystitis: Infection of the bladder leading to frequent and painful

urination.
 Pyelonephritis: Infection of the kidneys causing fever, flank pain,
and urinary symptoms.
5. Sexually Transmitted Infections (STIs):
 Gonorrhoea: Bacterial infection affecting the genital tract, throat,
or rectum.
 Chlamydia: Common STI caused by the bacterium Chlamydia
trachomatis.
 Syphilis: A sexually transmitted infection caused by the bacterium
Treponema pallidum.
6. Bacterial Meningitis: Infection of the membranes covering the brain and
spinal cord, leading to symptoms such as headache, fever, and neck
stiffness.
7. Bloodstream Infections:
 Sepsis: A life-threatening condition resulting from the body's
response to infection, often caused by bacteria entering the
bloodstream.
Typical Stages of an Infectious Disease
1. Incubation Period
 Time between acquiring the organism (or toxin) and the onset of
symptoms.
 Duration varies from hours to weeks depending on the organism.
2. Prodrome Period
 Characterized by nonspecific symptoms such as:
o Fever
o Malaise
o Loss of appetite
3. Specific-Disease Period
 Overt signs and symptoms of the disease appear.
 Symptoms vary depending on the infection.
4. Recovery (Convalescence) Period
 Illness resolves, and the patient returns to a healthy state.
360
 IgG and IgA antibodies protect against reinfection by the same organism.
 PHARMACOLOGY AND PATHOLOGY
Post-Recovery Outcomes
1. Chronic Carriers
 Some individuals continue to harbor and shed the organism while
remaining clinically well.
2. Latent Infections
 The infection may persist in a dormant state and reactivate later.
 Recurrence can present either as:
o The same form as the primary infection.
o A different manifestation with new signs and symptoms.
3. Subclinical Infections
 Some infections do not cause symptoms but still result in antibody
production.
 The presence of antibodies can confirm past infection, even if no
symptoms were experienced.
Stages of bacterial pathogenesis
1. Source or Reservoirs: Bacteria originate from various sources like

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humans, animals, soil, water, and contaminated objects.
2. Entry into the Host: Bacteria enter the host via ingestion, inhalation, direct
contact, or vector transmission.
3. Attachment & Colonization: Bacteria attach to host cells or surfaces and
establish colonization, initiating infection.
4. Invasion of Host Tissues/Evading Host Defences: Bacteria invade tissues
and evade host immune responses using virulence factors.
5. Growth and Multiplication: Bacteria multiply rapidly within host tissues,
leading to tissue damage and disease progression.
6. Leaving the Host: Some bacteria disseminate from the initial site of
infection to other parts of the body via the bloodstream, lymphatic system,
or direct extension.
7. Enter into New Host: Bacteria exit the infected host and enter new hosts
through various routes, completing the transmission cycle.
Determinants of bacterial pathogenesis
1. Adherence and Colonization Factors:
 Bacteria possess adhesins or surface structures that facilitate
attachment to host cells or tissues.
 Adherence factors allow bacteria to establish colonization at the
site of infection, promoting bacterial survival and growth.
2. Invasion Factors:
 Some bacteria possess mechanisms for invading host tissues or
penetrating epithelial barriers.
 Invasins, secreted proteins, or surface structures help bacteria
breach host cell barriers and access deeper tissues, contributing
to disease progression.
3. Toxins:
 Bacteria produce toxins that damage host cells, disrupt cellular
function, and contribute to tissue damage and disease symptoms.

Toxins may be exotoxins (secreted by bacteria) or endotoxins
(components of the bacterial cell wall), each exerting specific
effects on host cells and tissues.
4. Enzymes and Degradative Factors:
 Bacteria secrete enzymes such as proteases, lipases, and 361
hyaluronidases that degrade host tissues and extracellular matrix
components.
 MEDICO EXPRESS BLOCK 1
 Degradative factors facilitate tissue invasion, nutrient acquisition,
and evasion of host immune responses.
5. Capsules and Surface Structures:
 Capsular polysaccharides or surface structures protect host
immune defenses, phagocytosis, and complement-mediated
lysis.
 Surface structures such as pili, flagella, or outer membrane
proteins may contribute to adherence, motility, or evasion of host
immune recognition.
6. Antimicrobial Resistance:
 Bacteria may acquire resistance to antimicrobial agents through
genetic mutations or horizontal gene transfer.
 Antimicrobial resistance determinants enable bacteria to survive
and proliferate in the presence of antimicrobial drugs,
complicating treatment and increasing the risk of treatment failure.
7. Host Immune Status:
 Host-related factors, such as immune competence, underlying
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health conditions, and genetic susceptibility, influence the

outcome of bacterial infections.
Immune deficiencies, immunosuppressive therapies, or chronic
diseases may predispose individuals to severe or recurrent
bacterial infections.
8. Quorum Sensing and Regulatory Systems:
 Bacteria utilize quorum sensing and regulatory systems to
coordinate gene expression, virulence factor production, and
adaptation to the host environment.
 Quorum sensing allows bacteria to sense population density and
regulate virulence gene expression in response to environmental
cues.

MEDICO EXPRESS SUMMARIES LO 002

 Bacterial Shape & Size: Bacteria vary in shape—cocci (spherical), bacilli
(rod-shaped), and spirochetes (spiral). Sizes range from 0.2 to 5 µm.
 Bacterial Arrangement: Bacteria form pairs (diplococci), chains
(streptococci), or clusters (staphylococci) based on cell division orientation.
 Bacterial Cell Wall: Composed mainly of peptidoglycan, it provides
structural support. Mycoplasma lacks a cell wall.
 Virus Structure: Viruses contain DNA or RNA within a protein capsid; some
have lipid envelopes derived from the host cell.
 Viral Shape & Size: Viruses range from 20 to 300 nm and exhibit varied
shapes—icosahedral, helical, or complex.
 Viral Nucleic Acids: Can be single- or double-stranded DNA or RNA;
retroviruses are diploid with two RNA copies.
 Viral Capsid & Symmetry: Made of capsomers, exhibiting icosahedral or
helical symmetry; helical viruses are always enveloped.
 Viral Envelope: Derived from the host cell membrane, containing
glycoproteins for attachment and entry into cells.
 Bacterial Cell Components: Include cell membrane, cytoplasm,
ribosomes, nucleoid, plasmids, flagella (motility), and pili (attachment).
 Capsule & S-layer: Some bacteria have capsules (protection from
362 phagocytosis) or S-layers (additional protection).
 PHARMACOLOGY AND PATHOLOGY
 Gram-Positive vs. Gram-Negative Bacteria: Gram-positive bacteria have
a thick peptidoglycan layer, while Gram-negative bacteria have a thin layer
with an outer membrane containing LPS.
 Bacteria vs. Viruses: Bacteria are larger, unicellular, metabolically active,
and divide by binary fission; viruses are smaller, acellular, and rely on host
cells for replication.
 Bacterial Growth Curve: Phases include lag (adjustment), log (rapid
growth), stationary (equilibrium), and death (decline).
 Viral Growth Curve: Includes eclipse (no complete virions), latent
(intracellular replication), and cytopathic effects (cell damage and death).
 Viral Replication Steps: Attachment → Penetration → Uncoating →
Replication → Translation → Assembly → Maturation → Release →
Spread.
 Bacterial Infections: Affect respiratory (pneumonia, bronchitis), skin
(cellulitis, abscess), and gastrointestinal (food poisoning, gastroenteritis)
systems.
 Viral Transmission: Enveloped viruses spread via direct contact or
droplets, while non-enveloped viruses spread via the fecal-oral route.

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 Microbe Classification: Includes bacteria (e.g., E. coli, Staphylococcus),
viruses (HIV, influenza), fungi (Candida), protozoa (Plasmodium), helminths
(Ascaris), ectoparasites (scabies), and prions (CJD).
 Bacterial Resistance: Some bacteria acquire resistance through plasmids,
making treatment challenging.
 Clinical Relevance: Viral and bacterial infections require different
treatments—antibiotics for bacteria, while antivirals or vaccines target
viruses.

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 MEDICO EXPRESS BLOCK 1

F-Pa-003 Microbiology (Sterilization & Disinfection)

Learning Objectives
 Define sterilization and disinfection.
 Describe the principles of sterilization and disinfection.
 Describe clinical uses of common disinfectants and their mode of
sterilization
 Discuss physical and chemical agents of sterilization

EXPRESS HIT Sterilization

"Autoclaving = Microbe’s The process of eliminating or destroying all forms of microbial life, including
worst nightmare—121°C bacteria, viruses, fungi, and spores, from surfaces, instruments, or environments
steam under pressure kills Example:
even spores!" 1. Autoclaving
2. Dry Heat Sterilization
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3. Ethylene Oxide (ETO) Sterilization

4. Gamma Irradiation
5. Sterilization by Filtration
6. Electron Beam Sterilization
PAST SEQ:
1.Differentiate between DISINFECTION and STERILIZATION.

Disinfection
Disinfection is the process of reducing the number of microorganisms on surfaces,
instruments, or in the environment to a level that is considered safe for public
health.
1. Chemical Disinfectants  Chlorine bleach
 Alcohol-based solutions
 Quaternary ammonium compounds
2. Ultraviolet (UV) Light:  Ultraviolet germicidal irradiation (UVGI)
3. Heat:  Boiling water or steam
 Pasteurization

Principles of sterilization and disinfection

1. Sterilization:  Aim: Complete elimination of all forms of microbial life.
 Objective: Render objects or areas completely free from
viable microorganisms.
 Methods: Utilize physical or chemical processes to achieve
high levels of microbial kill.
 Determinants: Factors such as temperature, pressure,
exposure time, and nature of the material being sterilized.
2. Disinfection:  Aim: Reduce the number of microorganisms to a safe level for
public health.
 Objective: Lower microbial contamination without necessarily
eliminating all microbial life.
 Methods: Employ chemical disinfectants, ultraviolet light, or
heat to reduce microbial load.
364  Determinants: Concentration of disinfectant, contact time,
temperature, and presence of organic matter or biofilms
 PHARMACOLOGY AND PATHOLOGY
Clinical uses of common disinfectants and their mode of sterilization
Clinical Use Commonly Used Disinfectant or
Method of Sterilization
Disinfect the surgeon’s hands before surgery Chlorhexidine
Disinfect the surgical site before surgery Iodophor
Disinfect skin before venipuncture or immunization 70% ethanol
Disinfect skin before blood culture or inserting a Tincture of iodine followed by 70%
vascular catheter ethanol, iodophor, or chlorhexidine
Clinical thermometer disinfection Isopropyl alcohol
Cleanse wounds Thimerosal, chlorhexidine,
hydrogen peroxide
EXPRESS HIT
Cleanse burn wounds Silver sulfadiazine
"Alcohol-based disinfectants
Cleanup of blood spill from a patient with hepatitis Hypochlorite (bleach, Clorox) work best on viruses with
B or C (disinfect area) envelopes—bare viruses
Sterilize surgical instruments and heat- Ethylene oxide or glutaraldehyde survive better!"
sensitive materials (e.g., endoscopes,
respiratory therapy equipment)

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Sterilize non–heat-sensitive materials (e.g., Autoclave
surgical gowns, drapes)
Sterilize intravenous solutions Filtration
Disinfect air in the operating room (when not in Ultraviolet light
use)
Disinfect the floor of the operating room Benzalkonium chloride (Lysol)
Disinfect stethoscope 70% ethanol
Preservative in vaccines Thimerosal

Physical and chemical agents of sterilization

Physical Agents:
Physical Mechanism of Action Common Use
Agent
Heat Kills by denaturing proteins, Autoclaving: Moist heat sterilization
damaging membranes, and (121°C at 15 lb/in^2 for 15-20 minutes)
enzymatic cleavage of DNA. Dry heat sterilization (180°C for 2
hours)
Radiation Ultraviolet (UV) light damages UV irradiation, Infrared (non-ionizing):
DNA by forming thymine dimers, Airborne organism sterilization (250-260
inhibiting DNA replication and nm)
cell growth. X-rays, cosmic rays and gamma rays
(ionizing): Sterilization of heat-sensitive
items
Filtration Filters physically trap particles Sterilizing solutions with heat-sensitive
larger than the pore size and components (common pore size: 0.22
retain smaller particles via μm)
electrostatic attraction.

Chemical Agents:
Chemical Agent Mechanism of Action Common Use
Alcohol Disorganizes lipid structure in Skin antisepsis, cleaning
membranes, denatures proteins the skin before procedures
Detergents Disrupt cell membranes by Skin antisepsis, surface
interaction with lipid and polar disinfection
groups 365
Phenols Damage membranes, denatured Hand disinfection before
proteins surgery, wound cleansing
 MEDICO EXPRESS BLOCK 1
Chlorine Cross-links sulfhydryl groups in Water purification, surface
enzymes, rendering them inactive disinfection
Iodine Inactivates enzymes bind to Skin antiseptic,
tyrosine residues in proteins preparation before
procedures
Heavy Metals Bind to sulfhydryl groups, Skin antiseptics,
blocking enzymatic activity prevention of infection
Hydrogen Peroxide Attacks sulfhydryl groups, Wound cleaning, contact
inhibiting enzymatic activity lens disinfection
Formaldehyde & Denatures proteins and nucleic Sterilization of medical
Glutaraldehyde acids equipment

EXPRESS HIT Ethylene Oxide Alkylates proteins and nucleic Sterilization of heat-
acids sensitive materials
"Filtration is the go-to for
Acids & Alkalis Denature proteins, bacteriostatic Disinfection, preservation
heat-sensitive solutions—
think IV fluids & vaccines!" Modification of Inhibit microbial growth by binding Skin antiseptics, microbial
Nucleic Acids to nucleic acids' phosphate culture media
groups
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MEDICO EXPRESS SUMMARIES LO 003

 Sterilization vs. Disinfection: Sterilization eliminates all microbial life,
while disinfection reduces microbial load to safe levels.
 Sterilization Methods: Includes autoclaving, dry heat, ethylene oxide,
gamma irradiation, filtration, and electron beam sterilization.
 Disinfection Methods: Uses chemical agents (alcohol, chlorine, iodophor),
UV light, and heat (boiling, pasteurization).
 Principles of Sterilization: Involves complete microbial elimination using
physical or chemical methods, influenced by temperature, pressure, and
exposure time.
 Principles of Disinfection: Aims to lower microbial contamination using
disinfectants, UV light, or heat, with effectiveness depending on
concentration and contact time.
 Clinical Uses of Disinfectants: Alcohol, iodine, chlorhexidine, and
hypochlorite are used for skin antisepsis, wound cleaning, blood spill
cleanup, and surgical preparation.
 Sterilization of Medical Equipment: Autoclaving is used for non-heat-
sensitive items, while ethylene oxide and glutaraldehyde sterilize heat-
sensitive instruments.
 Physical Sterilization Agents: Heat denatures proteins, radiation
damages DNA, and filtration removes microbes from solutions.
 Chemical Sterilization Agents: Alcohol disrupts membranes, chlorine and
iodine inactivate enzymes, and formaldehyde denatures proteins.
 Hospital Disinfection: UV light disinfects air, benzalkonium chloride cleans
floors, and 70% ethanol sanitizes stethoscopes.

366
 PHARMACOLOGY AND PATHOLOGY
D) stimulation of ATP synthesis
PAST MCQs E) activation of DNA repair
F-PA-001 | CELL INJURY Correct Answer: C (activation of destructive
1. What mechanism is responsible for reduction in enzymes)
tumor size after chemotherapy? 7. the irreversible cell injury is characterized by?
A) Apoptosis A) pyknosis
B) necrosis B) cell membrane destruction
C) Atrophy C) autolysis
D) autophagy D) mitochondrial swelling
E) calcification E) ribosomal disappearance
Correct Answer: A (Apoptosis) Correct Answer: A (pyknosis)
2. The histopathology report of patient suffering 8. the acquired cause of cell injury is?
from ovarian carcinoma showed that epithelial A) single gene defect
tumor has laminated calcified bodies (psammoma B) hypoxia
bodies). What type of cellular changes is this?
C) chromosomal aberration
A) metastatic calcification
D) cytogenic abnormalities

MEDICO EXPRESS-MBBS
B) dystrophic calcification
E) inheritance disorder
C) idiopathic calcification
Correct Answer: B (hypoxia)
D) metaplasia
9. hypoxic cell injury result into which type of
E) hyperplasia necrosis?
Correct Answer: B (dystrophic calcification) A) fibrinoid necrosis
3. calcification of tissue without disturbing calcium B) liquefactive necrosis
metabolism is defined as?
C) fat necrosis
A) dystrophic calcification
D) caseous necrosis
B) metastatic calcification
E) coagulative necrosis
C) atrophic calcification
Correct Answer: E (coagulative necrosis)
D) idiopathic calcification
10. the four core aspects of disease in pathology
E) pathological calcification are represented as?
Correct Answer: A (dystrophic calcification) A) etiology, pathogenesis, morphological changes,
4. the programmed cell death is referred as? clinical significance
A) necrosis B) etiology, pathogenesis, morphological changes,
B) apoptosis genetic changes
C) apoptosis C) morphological changes, clinical significance,
D) autophagy tissue repair, inflammation
E) phagocytosis D) tissue repair, inflammation, etiology, tissue
growth
Correct Answer: B (Apoptosis)
E) genetic mutation, genetic repair, pathogenesis,
5. What is the role of Reactive Oxygen Species tissue repair
(ROS) in cell injury?
Correct Answer: A (etiology, pathogenesis,
A) cause DNA damage morphological changes, clinical
B) neutralize reactive free radicals significance)
C) induce lipid peroxidation in cell membrane
D) activate proteolytic enzyme F-PA-002 | INTRODUCTION TO
E) enhance glycolysis MICROORGANISMS
Correct Answer: C (induce lipid peroxidation in 11. Penicillin is most effective in which phase of
cell membrane) bacterial growth curve?
6. Intracellular calcium overload during cell injury A) lag phase
results into activation of which mechanism?
B) log phase
A) activation of glycolysis
C) stationary phase
B) inhibition of gluconeogenesis 367
D) decline phase
C) activation of destructive enzymes
E) death phase
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Correct Answer: B (log phase) 17. Which of the following are obligate intracellular
12. what is the major structural difference between parasite?
gram-negative and gram-positive cell wall? A) bacteria
A) gram-negative bacteria have plasmids, B) protozoa
whereas gram positive has not C) fungi
B) gram-negative bacteria have thick D) viruses
peptidoglycan, whereas gram positive have thin
E) helminths
layer
Correct Answer: D (viruses)
C) gram-negative bacteria have capsules,
whereas gram positive has not 18. Which of the following are prokaryotic
microorganism?
D) gram-negative bacteria are spore forming,
whereas gram positive are not A) bacteria
E) gram-negative bacteria have thin B) protozoa
peptidoglycan, whereas gram positive have thick C) fungi
layer D) viruses
Correct Answer: E (gram-negative bacteria have E) helminths
thin peptidoglycan, whereas gram positive
Correct Answer: A (Bacteria)
MEDICO EXPRESS-MBBS

have thick layer)

13. in comparison to gram-negative, gram-positive 19. which of the following reproduce by binary
fission?
bacteria have?
A) bacteria
A) chitin
B) protozoa
B) starch
C) fungi
C) thin peptidoglycan
D) cellulose D) viruses
E) thick peptidoglycan E) helminths
Correct Answer: A (Bacteria)
Correct Answer: E (thick peptidoglycan)
20. in which of the following microorganism, the cell
14. bacteria prepares itself for division in which
wall is absent?
phase of growth curve?
A) bacteria
A) lag phase
B) log phase B) protozoa
C) stationary phase C) fungi
D) viruses
D) decline phase
E) helminths
E) death phase
Correct Answer: D (viruses)
Correct Answer: A (lag phase)
15. the characteristic feature of gram-negative
bacteria is? F-PA-003 | STERALIZATION &
A) presence of outer membrane DISINFECTION
B) thick peptidoglycan 21. for sterilization of endoscope used in gastric
C) lack of cell wall clinic, we will use?
D) ability to form spores A) formaldehyde
E) resistance to antibiotic B) iodine
Correct Answer: A (presence of outer C) glutaraldehyde
membrane) D) chlorohexidine
16. which organism contain both DNA & RNA in its E) hydrogen peroxide
genome? Correct Answer: C (glutaraldehyde)
A) bacteria 22. For disinfection of heat-sensitive agent, the
B) protozoa most commonly used agent is?
C) fungi A) hydrogen peroxide
D) viruses B) iodine
368 E) helminths C) phenol
Correct Answer: A (bacteria) D) alcohol
E) ethylene oxide
 PHARMACOLOGY AND PATHOLOGY
Correct Answer: E (ethylene oxide) Explanation: Pili allow bacteria to attach to
23. Which agent is used to sterilize hospital surfaces and to each other, playing a role in
surfaces? adhesion and horizontal gene transfer.
Flagella help in motility, while cilia are found
A) formaldehyde
in eukaryotic cells.
B) benzalkonium chloride
28. A surgeon uses a sterilization method that
C) glutaraldehyde involves high-pressure steam to sterilize surgical
D) chlorohexidine gloves. Which method is being used? Annual 2024
E) hydrogen peroxide A) Ethylene oxide gas
Correct Answer: B (benzalkonium chloride) B) Dry heat
24. the most common agent used for sterilization of C) Autoclave
IV Solutions is? D) Radiation
A) filtration Ans: C) Autoclave
B) autoclaving Explanation: Autoclaving uses moist heat
C) UV light under pressure to kill all microorganisms,
D) radiation while ethylene oxide gas is used for heat-
sensitive materials.
E) alcohol
29. A patient diagnosed with a bacterial infection is

MEDICO EXPRESS-MBBS
Correct Answer: A (Filtration)
given antibiotics. At which bacterial growth phase
25. the process of sterilization is defined as? will they be most effective? Annual 2024
A) killing of maximum microorganisms A) Lag phase
B) killing of all microorganism except spores B) Log phase
C) killing of all viruses C) Stationary phase
D) killing of all microorganisms including spores D) Death phase
E) killing of all spores Ans: B) Log phase
Correct Answer: D (killing of all Explanation: Bacteria are most metabolically
microorganisms including spores) active and dividing in the log phase, making
26. A drug has a pH of 7.8. Where will it be them most susceptible to antibiotics.
maximally absorbed across the membrane? Annual 30. Which enzyme is the most specific marker of
2024 acute pancreatitis? Annual 2024
A) Stomach A) Amylase
B) Duodenum B) Lipase
C) Jejunum C) Alkaline phosphatase
D) Colon D) Lactate dehydrogenase
Ans: C) Jejunum Ans: B) Lipase
Explanation: Weak bases (like a drug with pH Explanation: Lipase is the most specific marker
7.8) are best absorbed in a more alkaline for acute pancreatitis, as it remains elevated
environment, where they remain unionized longer than amylase. Amylase is also
and lipid-soluble. The jejunum (pH ~7.5-8) elevated but can be elevated in other
provides the optimal absorption site. The conditions like salivary gland disease.
stomach (pH ~1-2) and duodenum (pH ~6) Alkaline phosphatase is a marker for liver
are too acidic, leading to ionization and and bone diseases, and lactate
poor absorption. The colon is less efficient dehydrogenase (LDH) is elevated in tissue
for most drug absorption due to its thicker damage but is nonspecific.
mucus layer and reduced surface area. 31. Programmed cell death is known as? Annual
27. A researcher observes bacteria forming clusters 2024
via small hair-like projections. Which structure is
A) Necrosis
responsible for this? Annual 2024
B) Apoptosis
A) Flagella
C) Autophagy
B) Cilia
D) Pyroptosis
C) Pili
Ans: B) Apoptosis
D) Capsule
Ans: C) Pili
Explanation: Apoptosis is a highly regulated 369
form of programmed cell death,
characterized by cell shrinkage, chromatin
 MEDICO EXPRESS BLOCK 1
condensation, and caspase activation. Explanation: Statins competitively inhibit HMG-
Necrosis is uncontrolled cell death due to CoA reductase, reducing cholesterol
injury. Autophagy is a survival mechanism synthesis. Non-competitive inhibitors bind
where cells degrade and recycle at different sites, not the active site.
components. Pyroptosis is an inflammatory Irreversible inhibitors permanently
form of cell death triggered by infections. deactivate enzymes, and allosteric
32. Which of the following occurs in reversible cell activators enhance enzyme activity, which
injury? Annual 2024 statins do not.
A) Nuclear fragmentation 35. A drug (likely Sugammadex) binds directly with
rocuronium instead of interacting with its receptor.
B) Mitochondrial rupture
This drug is a: Annual 2024
C) Microvilli damage
A) Physiological antagonist
D) Cell membrane rupture
B) Pharmacological antagonist
Ans: C) Microvilli damage
C) Non-competitive inhibitor
Explanation: In reversible cell injury, there is
D) Chemical antagonist
cell swelling, loss of microvilli, and
ribosomal detachment due to ATP Ans: B) Pharmacological antagonist
depletion. Nuclear fragmentation and Explanation: Sugammadex is a
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mitochondrial rupture occur in irreversible pharmacological antagonist as it directly

cell injury, and cell membrane rupture is a binds rocuronium, reversing its effects
hallmark of necrosis, leading to cell death. without acting on the receptor.
33. Vibrio cholerae affects which secondary Physiological antagonists produce
messenger pathway? Annual 2024 opposite effects via different receptors.
Non-competitive inhibitors reduce receptor
A) cGMP
activity without direct binding to the ligand.
B) cAMP Chemical antagonists inactivate drugs by
C) IP3 chemical reactions, which is not the case
D) Calcium here.
Ans: B) cAMP 36. A drug that increases heart rate will bind to:
Annual 2024
Explanation: Cholera toxin activates adenylate
cyclase, leading to an increase in cyclic A) Gi-coupled M2 receptors
AMP (cAMP). This causes chloride and B) Gq-coupled α1 receptors
water secretion, resulting in severe watery C) Gs-coupled β-adrenergic receptors
diarrhea. cGMP is involved in heat-stable
D) Gi-coupled D2 receptors
toxin of E. coli, IP3 in calcium mobilization,
and calcium signaling plays a role in muscle Ans: C) Gs-coupled β-adrenergic receptors
contraction but is not the primary pathway Explanation: β1-adrenergic receptors (Gs-
for cholera toxin. coupled) increase heart rate by activating
34. Statin drugs act as: Annual 2024 adenylate cyclase, raising cAMP levels. M2
receptors (Gi-coupled) slow heart rate. α1
A) Non-competitive inhibitors
receptors (Gq-coupled) mediate
B) Competitive inhibitors vasoconstriction, not heart rate. D2
C) Irreversible inhibitors receptors (Gi-coupled) inhibit dopamine
D) Allosteric activators signaling but do not regulate heart rate.
Ans: B) Competitive inhibitors

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