HISTOLOGY

(FOUNDATION MODULE BLOCK 1)

F-A- • Describe different types of microscopies Basic Introduction to

040 • Describe Staining methods and their Technique microscopy &
significance in Histology Basic staining
technique

MICROSCOPY

There are two basic types of microscopies:

1. Light Microscopy:
a) Bright-field Microscopy (most common): Utilizes ordinary light and staining
techniques to visualize tissue components. It's commonly used for observing stained
cells and tissues but may lack contrast for unstained specimens.
b) Phase Contrast Microscopy: Exploits differences in refractive index to produce
contrast without staining, allowing observation of living cells. This method enhances
visualization of cell boundaries, nuclei, and cytoplasmic structures.
c) Fluorescence Microscopy: Utilizes UV light to visualize specific molecules such as
DNA and RNA by labeling them with fluorescent dyes or fluorescent proteins. It
enables precise localization of targeted molecules within the specimen.
d) Polarizing Microscopy: Reveals materials with repetitive, periodic macromolecular
structures, such as collagen fibers, through birefringence. Collagen fibers exhibit
intense yellow or orange birefringence under polarized light.
e) Confocal Microscopy: Involves 3D scanning of specimens at successive focal planes
using a focused light beam, typically from a laser. It produces detailed 3D
reconstructions of the specimen from the acquired images.

2. Electron Microscopy:
a) Transmission Electron Microscopy (TEM): Achieves high resolution (up to 3nm)
by transmitting electrons through thin specimens, which are then projected onto an
objective lens to form a magnified image. TEM allows for detailed visualization of
cellular ultrastructure.
b) Cryofracture and Freeze Etching: Techniques allowing TEM study of unfixed
frozen cells. Fractured membranes or cut surfaces are coated with carbon and heavy
metal to create replicas for analysis.
c) Scanning Electron Microscopy (SEM): In SEM, the beam of electrons is directed
onto the surface of the specimen, rather than passing through it. The specimen's
surface is dried and coated with a thin layer of heavy metal to enhance conductivity

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 and image quality. SEM provides detailed, high-resolution images of surface
morphology.

STAINING TECHNIQUES

Chemical Fixation:
• Chemical fixatives like formalin are used to preserve tissue structure by cross-linking
proteins, inactivating enzymes, and preventing autolysis. T
• his step is crucial for maintaining the integrity of cellular and tissue structures during
subsequent processing and staining.
Dehydration and Clearing:
• Fixed tissues are dehydrated in alcohol and cleared in organic solvents to prepare
them for embedding.
• Dehydration removes water from tissues while clearing agents remove alcohol and
render tissues transparent, facilitating embedding in a solid medium for sectioning.
Staining Techniques:
1. Hematoxylin and Eosin (H&E) Staining:
H&E staining is the most commonly used staining method in histology. Hematoxylin
stains basophilic structures, such as DNA-rich nuclei, dark blue or purple, while eosin
stains acidophilic structures, such as cytoplasm and collagen, pink. This staining
allows for the visualization of tissue architecture and differentiation between cellular
components.
2. Fluorescent Dye Staining:
Fluorescent dyes, when used in fluorescence microscopy, allow for
the specific labeling of molecules within the specimen. This
technique enables the visualization of specific cellular structures or
molecules with high sensitivity and specificity, such as DNA and
RNA.
3. Periodic Acid-Schiff (PAS) Staining:
PAS staining is used to detect carbohydrates and glycoproteins in
tissues. It involves the transformation of glycol groups present in
sugars into aldehyde residues, which then react with the Schiff reagent to produce a
purple or magenta color. PAS-positive material can be further identified by enzyme
digestion to distinguish between glycogen and glycoproteins.

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 4. Metal Impregnation Techniques:
Metal impregnation techniques, often using solutions of silver salts, are employed to
visualize certain extracellular matrix (ECM) fibers and specific cellular elements,
particularly in nervous tissue. These techniques enhance the contrast and visibility of
structures that may be difficult to visualize with conventional staining methods.
Significance of Staining:
• Staining methods allow for the visualization of cellular and tissue
structures under the microscope by imparting color to otherwise
colorless components.
• Different staining methods target specific cellular components or
molecules, allowing for the identification and characterization of
tissues at the microscopic level.
• Staining enhances contrast, making it easier to distinguish between
different tissue components and structures, thereby aiding in
histological analysis and interpretation.
• By revealing specific cellular features, staining methods contribute to our
understanding of tissue morphology, organization, and function in health and
disease.
MCQ PEARLS
1. Most commonly used histology staining method? → Hematoxylin and Eosin (H&E)
2. Microscopy that uses UV light to visualize DNA/RNA? → Fluorescence Microscopy
3. Staining method for carbohydrates and glycoproteins? → Periodic Acid-Schiff (PAS)
4. Microscopy for high-resolution surface images? → Scanning Electron Microscopy
(SEM)
5. Microscopy that reveals birefringent materials like collagen? → Polarizing
Microscopy
6. Common fixative used to preserve tissue structure? → Formalin
7. Staining technique using silver salts for ECM fibers? → Metal Impregnation
8. Microscopy for 3D scanning of specimens? → Confocal Microscopy
9. Microscopy for detailed cellular ultrastructure? → Transmission Electron
Microscopy (TEM)
10. Step involving tissue dehydration and clearing? → Dehydration and Clearing

F-A- • Describe the electron microscopic structure and Basic Cell

041 fluid mosaic model of plasma membrane Histology membrane
• Draw the fluid mosaic model of plasma membrane
• Describe the structure of glycocalyx coat and lipid
raft and correlate it with function
• Describe different types of membrane proteins and
their functions

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 • Explain different modes of transport across the
cell membrane

PLASMA MEMBRANE

Electron Microscopic Structure:

• The plasma membrane is approximately 7.5 nm thick and consists of a lipid bilayer.
• The lipid bilayer is composed of phospholipids, cholesterol, proteins, and
oligosaccharide chains covalently linked to phospholipid and protein molecules.
• When examined by transmission electron microscopy, the plasma membrane displays
a trilaminar (unit membrane) structure.
• The lipid bilayer has two leaflets: the inner leaflet facing the cytoplasm and the outer
leaflet facing the extracellular environment.
• Associated with the lipid bilayer are integral and peripheral proteins, which play
various roles in membrane function.
Fluid Mosaic Model:
The fluid mosaic model describes the dynamic and fluid nature of the plasma membrane.
1. Molecular Structure:
• Phospholipids constitute the highest percentage of the lipid bilayer. They are
amphipathic molecules with a hydrophilic head and two hydrophobic fatty acyl
tails.
• Glycolipids, found primarily on the extracellular aspect of the outer leaflet,
contribute to the glycocalyx and cell recognition.
• Cholesterol, present in both leaflets, helps maintain the structural integrity of the
membrane and regulates fluidity.
2. Organization:
• The lipid bilayer is asymmetrical, with the polar heads of phospholipids facing the
membrane surfaces and the hydrophobic tails oriented toward the interior.
• Microdomains called lipid rafts, enriched in cholesterol and glycosphingolipids,
are less fluid and thicker than the surrounding membrane.
3. Fluidity:
• Fluidity of the lipid bilayer is crucial for various cellular processes, including
exocytosis, endocytosis, and membrane trafficking.
• Fluidity increases with temperature and decreased saturation of fatty acyl tails.
• Cholesterol content in the membrane affects fluidity, with higher cholesterol
content leading to decreased fluidity.

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 Fluid Mosaic Model of plasma membrane

STRUCTURE OF GLYCOCALYX COAT

• The glycocalyx (cell coat) is located on the outer surface of the outer leaflet of the
plasma membrane. It varies in appearance (fuzziness) and thickness (up to 50 nm).
• Composed of polar oligosaccharide side chains, it is covalently linked to most
proteins and some lipids (glycolipids) of the plasma membrane, proteoglycans, which
are glycosaminoglycans bound to integral proteins.
Function of Glycocalyx Coat:
1. Cell Attachment: Facilitates the attachment of certain cells, such as fibroblasts, to
extracellular matrix components, aiding in tissue structure and integrity.
2. Binding: Binds antigens and enzymes to the cell surface, contributing to immune
response and enzymatic activity regulation.
3. Cell-Cell Recognition and Interaction: Plays a crucial role in cell-cell recognition and
interaction, which is essential for processes like cell signaling, development, and
immune response.
4. Protection: Protects cells from injury by preventing contact with inappropriate
substances, serving as a physical barrier.
5. Alignment and Enzymatic Cleavage: Assists T cells and antigen-presenting cells in
aligning properly and prevents inappropriate enzymatic cleavage of receptors and
ligands, ensuring proper immune response and cellular function.
6. Endothelial Lining: Lines the endothelial surface of blood vessels, decreasing
frictional forces as blood rushes by and diminishing fluid loss from the vessel,
contributing to vascular integrity and function.

STRUCTURE OF LIPID RAFT

• Lipid rafts are microdomains of the plasma membrane that are thicker than the
surrounding membrane and protrude slightly into the extracellular space.
• They contain a higher concentration of cholesterol and glycosphingolipids, making
them less fluid than the surrounding membrane.
Correlation with Function:
• Specific Signaling Events
• Enhanced Cell Signaling
• Cellular Communication
• Membrane Integrity

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 TYPES OF MEMBRANE PROTEINS

Integral Proteins:
a. Transmembrane Proteins:
• Structure: Span the entire thickness of the plasma membrane and have
hydrophilic and hydrophobic regions.
• Functions: Serve as membrane receptors, enzymes, cell adhesion molecules,
recognition proteins, molecules for message transduction, and transport
proteins.
• Characteristics: Most are glycoproteins, amphipathic, and folded to pass
back and forth across the membrane, also known as multipass proteins.
• Anchoring: Can also be anchored to the inner or outer leaflet via fatty acyl or
prenyl groups.
b. Associated Functions:
• Act as receptors for extracellular signals.
• Participate in cell-cell communication and adhesion.
• Facilitate transport of molecules across the membrane.
• Serve as enzymes catalyzing specific biochemical reactions.
• Play roles in cell signaling and intracellular message transduction.
Peripheral Proteins:
Location: Do not extend into the lipid bilayer and are located on the cytoplasmic and extracellular
aspects of the cell membrane.

Anchoring: Can be anchored to glycolipids or bind to phospholipid polar groups or integral proteins
via noncovalent interactions.

Functions:
• Serve as electron carriers, cytoskeletal components, or part of intracellular
second messenger systems.
• Modify the relationships of other peripheral proteins with the lipid bilayer.
• Participate in membrane trafficking and the formation of ion channels.
• Examples include annexins, synapsin I, and spectrin.

Functional Characteristics of Membrane Proteins:

a. Lipid-to-Protein Ratio: Varies in different cell types, ranging from 1:1 to 4:1. This ratio
reflects the diverse functions of the membrane proteins in different cellular contexts.
b. Lateral Diffusion: Some membrane proteins can diffuse laterally in the lipid bilayer,
allowing for dynamic interactions and flexibility in response to environmental cues.
c. Immobilization: Other membrane proteins are immobile and are held in place by
cytoskeletal components, ensuring stability and organization within the membrane.

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 DIFFERENT MODES OF TRANSPORT ACROSS THE CELL MEMBRANE

Passive Transport:
1. Simple Diffusion:
• Description: Involves the movement of small nonpolar molecules (e.g., O2,
N2) and small, uncharged polar molecules (e.g., H2O, CO2, glycerol) down
their concentration gradient.
• Specifics: Exhibits little specificity, and the rate of diffusion is proportional to
the concentration gradient.
2. Facilitated Diffusion:
• Description: Occurs via ion channels or carrier proteins, facilitating the
movement of specific molecules across the membrane down their
concentration gradient.
• Ion Channels: Form small aqueous pores across the membrane for the
passage of specific ions.
• Carrier Proteins: Undergo reversible conformational changes to transport
specific molecules across the membrane.
Active Transport:
1. Na⁺-K⁺ Pump:
• Description: Antiport transport of Na⁺ and K⁺ ions against their concentration
gradient via the Na⁺-K⁺ ATPase carrier protein.
• Function: Maintains cell volume, osmotic pressure, and membrane potential
by pumping Na⁺ out and K⁺ into the cell.
2. Glucose Transport:
• Description: Symport movement of glucose across epithelium, often powered
by an electrochemical Na⁺ gradient.
• Function: Facilitates the uptake of glucose into cells by coupling its transport
to the electrochemical gradient of Na⁺.
3. ATP-binding Cassette (ABC) Transporters:
• Description: Transmembrane proteins with nucleotide-binding and
membrane-spanning domains, utilizing ATP as an energy source to export
materials from the cytoplasm.
• Function: Export toxins, drugs, and other substances from the cytoplasm into
the extracellular space.

Facilitated Diffusion of Ions:

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 1. Selective Ion Channel Proteins:
• Description: Permit specific ions to traverse them, often gated and regulated
by various stimuli.
• Examples: K⁺ leak channels, voltage-gated channels, mechanically gated
channels, and ligand-gated channels.
2. Ionophores:
• Description: Lipid-miscible molecules that form complexes with ions and
transport them across the membrane.
• Mechanism: Insert into the lipid
bilayer to facilitate the movement of
ions across the membrane.
Vesicular Transport:
1. Endocytosis:
• Phagocytosis: Engulfment of large
particles such as bacteria or dead cell
remnants by specialized cells like
macrophages and neutrophils.
• Pinocytosis: Ingestion of extracellular fluid and dissolved contents through
smaller invaginations of the cell membrane.
• Receptor-mediated Endocytosis: Ligand-induced internalization of specific
substances through membrane receptors.
2. Exocytosis:
• Description: Release of large molecules from the cell by fusion of
cytoplasmic vesicles containing the molecules with the plasma membrane.
• Trigger: Often triggered by a transient increase in cytosolic Ca2+.
• Regulation: Highly regulated process involving specific interactions between
membrane proteins.

Types and Characteristics of Movement Across Membranes

Types Transport Requires Examples
ATP
Diffusion With the concentration No O2,CO2,Cl-,urea
gradient through the lipid

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 protion of the cell
membrane or htrough
membrane channels
Osmosis With the concentration No Water
gradient (for water)
through the lipid portion
of the cell membrane or
through membrane
channels
Carrier-mediated
transport
mechanisms
• Facilitated With the concentration No Glucose in most cells
diffusion gradient by carrier
• Acitve molecules
transport Against the concentration Yes Na+,K+,Ca2+,H+and
• Secondary gradient by carrier amino acids
active molecules
transport Against the concentration
gradient by carrier Yes Glucose, amino acids
moleculaes:the energy for
secondary active
trabnsport of one
substance comes from the
concentration gradient of
another
Endocytosis Movement into cells by Yes Ingestion of particles by
vesicles phagocytosis or receptor-
mediated endocytosis and
liquids by pinocytosis
Exocytosis Movement out of cells by Yes Secretion of proteins
vesicles
Pinocytosis Ingestion of small fluid - Uptake of enzyme &
droplets and solutes hormones
Receptor-mediated Specific uptake of ligands - Uptake of LDL
endocytosis bound to cell surface
receptors
Phagocytosis Engulfment of large - Bacteria engulfment by
particles or whole cells by WBCs
phagocytes

MCQ PEARLS
1) Thickness of the plasma membrane? → 7.5 nm
2) Plasma membrane examined by which microscopy? → Transmission Electron
Microscopy
3) Lipid bilayer's two primary leaflets are? → Inner and outer leaflets
4) Model describing the plasma membrane? → Fluid Mosaic Model
5) Highest percentage of the lipid bilayer is made up of? → Phospholipids

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 6) Phospholipids are molecules with a hydrophilic head and? → Two hydrophobic fatty
acyl tails
7) Cholesterol in the membrane helps regulate? → Fluidity
8) Microdomains of the plasma membrane are called? → Lipid rafts
9) Glycolipids are primarily found in which leaflet? → Outer leaflet
10) Glycocalyx is also known as? → Cell coat
11) Thickness of the glycocalyx? → Up to 50 nm
12) Glycocalyx assists in cell? → Attachment
13) Glycocalyx helps protect cells from? → Injury
14) Lipid rafts are enriched with? → Cholesterol and glycosphingolipids
15) Function of lipid rafts? → Cell signaling
16) Integral proteins span? → Entire plasma membrane
17) Peripheral proteins are anchored to? → Glycolipids
18) Simple diffusion moves molecules? → Down their concentration gradient
19) Facilitated diffusion occurs via? → Ion channels or carrier proteins
20) Na⁺-K⁺ pump maintains? → Cell volume and membrane potential

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 F-A- • List the membranous and non-membranous cellular Integrate Cell
042 organelles with organelles
• Describe the structure of the following cellular Pathology
organelles and correlate with their function:
1. Ribosomes 2. Endoplasmic reticulum (rough &
smooth) 3. Golgi apparatus 4. Lysosomes 5.
Proteasomes 6. Mitochondria 7. Peroxisomes
• Describe the structural components of the
cytoskeleton, and correlate them with their
functions
• Explain the histological basis of immotile cilia
syndrome
• Describe the histological features of cytoplasmic
inclusions
• Describe the structure of the nuclear envelope Integrate
and nuclear pores with
physiology

CELL ORGANELLES
Organelles are metabolically active units of the cellular matrix. They are of following two
types:
Membranous Organelles Non-Membranous Organelles
• Endoplasmic Reticulum (ER) • Ribosomes
• Golgi Apparatus • Centrosomes and Centrioles
• Mitochondria • Cytoskeleton
• Nucleus • Nucleolus
• Chloroplast (plants only) • Spliceosomes
• Lysosomes • Chromatin
• Vacuoles • Glyoxysomes (plants only)
• Peroxisomes

RIBOSOMES
1. Structure:
Ribosomes are nonmembranous organelles composed of RNA and
proteins, consisting of two subunits: small and large.
• The small subunit binds to mRNA and activated tRNAs,
enabling the ribosome to read mRNA's genetic information.
• The large subunit contains peptidyl transferase, which
catalyzes peptide bond formation, leading to polypeptide
synthesis.
Ribosomes’ lack of membranes allows flexibility and versatility in
function.
2. Function:
Ribosomes are the sites of protein synthesis, translating mRNA into
amino acid sequences that define protein structure and function.
• They can be free in the cytoplasm or bound to the
endoplasmic reticulum (ER). Free ribosomes synthesize

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 proteins for use within the cell, while bound ribosomes produce proteins for secretion
or localization in organelles.
• During translation, the small subunit binds mRNA, and the large subunit catalyzes
peptide bond formation, requiring tRNAs and initiation factors.
• After translation, ribosomes dissociate from mRNA and can be reused for further
synthesis.
• Abnormal ribosomal function can lead to disorders called ribosomopathies, such as
Diamond-Blackfan anemia, characterized by impaired red blood cell production.

ENDOPLASMIC RETICULUM
Rough Endoplasmic Reticulum (RER)
Structure:
• The RER has a rough appearance due to ribosomes on its cytoplasmic surface and
consists of interconnected membrane-bound sacs called cisternae.
• The large surface area of the RER facilitates efficient protein synthesis.
Function:
• Protein Synthesis: Ribosomes on the RER synthesize proteins for secretion, plasma
membrane incorporation, or localization in organelles.
• Posttranslational Modifications: Newly synthesized proteins undergo modifications,
such as glycosylation and folding, essential for their functionality.
• Quality Control: The RER ensures proper protein folding and targets misfolded
proteins for degradation.
Smooth Endoplasmic Reticulum (SER)
Structure:
• The SER appears smooth due to the absence of ribosomes and consists of tubular or
saclike structures interconnected by channels.
• It is continuous with the RER and is abundant in cells specializing in lipid metabolism
and detoxification.
Function:
• Lipid Synthesis: The SER synthesizes phospholipids and steroids, key components
of cellular membranes.
• Carbohydrate Metabolism: It plays a role in carbohydrate metabolism, though less
significant than the RER.
• Detoxification: Enzymes in the SER, particularly cytochrome P450, catalyze
detoxification reactions for drugs and harmful substances.
• Calcium Storage and Release: In muscle cells, the SER, known as sarcoplasmic
reticulum, stores and releases calcium ions (Ca²⁺) to regulate muscle contraction.
Characteristic Smooth Endoplasmic Reticulum Rough Endoplasmic Reticulum
(SER) (RER)
Presence of Does not bear ribosomes over the Possesses ribosomes attached to
Ribosomes surface its membrane
Main Function Synthesis of lipids Synthesis of proteins
Structure Formed of vesicles and tubules Formed of cisternae and few
tubules
Location Usually found deep inside the Found in the periphery of the
cytoplasm cytoplasm

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 Development May develop from the nuclear May develop from the RER
envelope

Integration with Pathology

Endoplasmic Reticulum (ER):
• Mutations affecting ER function can lead to ER stress and the unfolded protein
response (UPR), contributing to diseases like cystic fibrosis and diabetes mellitus.
• An underdeveloped smooth endoplasmic reticulum (SER) in liver cells can result
in jaundice in newborns. This condition impedes bilirubin metabolism and other
pigmented compounds, leading to their accumulation and causing yellowish
discoloration of the skin.

GOLGI APPARATUS
Structure:
• The Golgi apparatus consists of smooth membranous saccules, some vesicular and
others flattened, containing enzymes and proteins for processing.
• It has two functional sides: the cis face (where material enters from the RER) and the
trans face (where processed proteins are dispatched).
• Material moves from the RER to the Golgi in transport vesicles that merge with the
cis face. At the trans face, larger saccules or vacuoles accumulate and generate
vesicles carrying completed protein products.
Function:
• Enzymes within the Golgi perform posttranslational modifications (glycosylation,
sulfation, phosphorylation, limited proteolysis).
• It initiates packing, concentration, and storage of secretory products.
• The Golgi is involved in the formation of transport and secretory vesicles, regulated
by coat proteins (e.g., clathrin).
• Secretory granules from condensing vesicles in the Golgi store products until release
via exocytosis, triggered by metabolic, hormonal, or neural signals.
Integration with Pathology:
• Dysfunction of the Golgi apparatus is implicated in various diseases, including
neurodegenerative disorders like Alzheimer's disease, where structural and
functional abnormalities contribute to pathological protein aggregation.

LYSOSOMES
Structure:
• Lysosomes are membrane-limited vesicles containing approximately 40 different
hydrolytic enzymes, abundant in phagocytic cells (e.g., macrophages, neutrophils).
• They contain acid hydrolyases (proteases, nucleases, phosphatases, phospholipases,
sulfatases, β-glucuronidase).

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 • Enzymes are segregated in the rough endoplasmic reticulum (RER), modified in the
Golgi apparatus, and packaged into vacuoles to form lysosomes.
Function:
• They perform intracellular digestion and turnover of cellular components.
• Digest materials from outside the cell through endocytosis.
• Maintain an acidic pH (~5.0) for optimal enzymatic activity.
• Remove indigestible material, forming residual bodies.
• Facilitate autophagy by removing excess or non-functional organelles.
Integration with Pathology:
• Lysosomal storage disorders arise from mutations causing deficiencies in lysosomal
enzymes or errors in their posttranslational processing, leading to the accumulation of
undigested macromolecules.
• Symptoms result from disrupted cellular metabolism and homeostasis due to vacuole
accumulation within affected cells.

Disease Faulty Enzyme Main Organs Affected

Hurler syndrome α-L-Iduronidase Skeleton and nervous
system
McArdle Muscle Skeletal muscles
syndrome phosphorylase
Tay-Sachs GM2-gangliosidase Nervous system
Gaucher Glucocerebrosidase Liver and spleen
I-cell disease Phosphotransferase Skeleton and nervous
for M6P formation system

PROTEASOMES
Structure:
• Proteasomes are small, membrane-free protein complexes.
• Approximately the size of the small ribosomal subunit, they are cylindrical
structures made of four stacked rings.
• Each ring consists of seven proteins, including proteases.
• At each end of the cylinder is a regulatory particle containing ATPase, which
recognizes proteins marked with ubiquitin.
Function:
• Proteasomes degrade denatured or nonfunctional polypeptides.
• They remove proteins that are no longer needed by the cell.
• Proteasomes restrict the activity of specific proteins to defined time windows.
• Unlike lysosomes that digest organelles through autophagy, proteasomes primarily
process free proteins as individual molecules.
Integration with Pathology:
• Dysfunction of the proteasome system is linked to cancer and neurodegenerative
diseases such as Parkinson's, Alzheimer's, and Huntington's diseases.
• Proteasome failure allows protein aggregates to accumulate within cells, disrupting
function and leading to cell death. These aggregates can also accumulate in the
extracellular matrix, worsening tissue damage.

MITOCHONDRIA
Structure of Mitochondria:

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 Aspect Description
Shape and Size Rod-shaped organelles, approximately 0.2 μm wide and up to 7 μm
long
Membranes Outer membrane surrounds the organelle, Inner membrane contains
cardiolipin and forms cristae
Compartments Intermembrane compartment between outer and inner membranes,
Inner matrix compartment contains enzymes and genetic apparatus
Enzymes and Genetic Enzymes of Krebs cycle primarily in the matrix, ATP synthase
Apparatus embedded in inner membrane
Protein Import Specific presequence recognition by translocase of the outer
Mechanism mitochondrial membrane (TOM) and inner mitochondrial membrane
complexes (ITM)
Origin and May have originated as symbionts and proliferate by division of
Proliferation preexisting mitochondria

Function of Mitochondria:
Aspect Description
ATP Production Generate adenosine triphosphate (ATP) through oxidative
phosphorylation
Cellular Respiration Convert glucose and nutrients into ATP and carbon dioxide
Metabolism Break down fatty acids, amino acids, and other metabolites for
Regulation energy and biosynthesis
ROS Regulation Control and neutralize reactive oxygen species (ROS) to prevent
oxidative stress
Calcium Regulate intracellular calcium levels for cellular processes and
Homeostasis signaling
Apoptosis Participate in programmed cell death pathways
Regulation
Heat Production Generate heat in specialized cells, such as brown adipose tissue
Synthesis of Produce molecules like heme and certain lipids for cellular
Molecules functions

Integrated with pathology:

• Mitochondrial dysfunction is linked to various disorders such as mitochondrial
myopathies, neurodegenerative diseases like Alzheimer's and Parkinson's, and metabolic
disorders like diabetes.
• Myoclonic epilepsy with ragged red fibers (MERRF) is a rare condition where specific
tissues, particularly skeletal muscle regions, inherit mitochondrial DNA with a mutated
lysine-tRNA gene. This results in defective synthesis of respiratory chain proteins,
leading to structural abnormalities in muscle fibers and other cells.

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PEROXISOMES
Structure
Aspect Description
Shape and Size Spherical organelles enclosed by a single membrane
Enzymes Contains oxidases and peroxidases that produce and degrade hydrogen
peroxide (H2O2)
Protein Import Peroxisomal proteins synthesized on free polyribosomes and imported
Mechanism via targeting sequences recognized by receptors in the peroxisomal
membrane
Formation Peroxisomes form by budding of precursor vesicles from the
endoplasmic reticulum (ER) or through growth and division of
preexisting peroxisomes

Function
Aspect Description
Detoxification Break down harmful substances like hydrogen peroxide
(H2O2)
Fatty Acid Oxidation Convert fatty acids into energy through β-oxidation
Plasmalogen Synthesis Synthesize important phospholipids for cell membranes
Antioxidant Activity Neutralize harmful reactive oxygen species (ROS)
Bile Acid Synthesis Contribute to the production of bile acids for digestion
D-Amino Acid Participate in the breakdown of certain amino acids
Breakdown

Integration with Pathology:

• Peroxisomal disorders, like Zellweger syndrome and X-linked
adrenoleukodystrophy, stem from defects in peroxisome biogenesis or enzyme
function. This leads to metabolic imbalances and tissue damage.
• Neonatal adrenoleukodystrophy is caused by defective peroxisomal proteins
necessary for transporting very long-chain fatty acids into the peroxisome for β-
oxidation. Accumulation of these fatty acids in body fluids can disrupt myelin sheaths
in nerve tissue, resulting in severe neurologic symptoms.

CYTOSKELETON
Structural Components of Cytoskeleton:
1. Microtubules: Hollow tubes composed of tubulin protein subunits.
2. Microfilaments: Thin filaments made of actin protein subunits.
3. Intermediate Filaments: Fibrous proteins with intermediate diameter between
microtubules and microfilaments.

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Correlation with Functions:
1. Microtubules:
• Provide structural support and serve as tracks for intracellular transport of
organelles and vesicles.
2. Microfilaments:
• Involved in cell movement, cytokinesis, and maintenance of cell shape.
3. Intermediate Filaments:
• Provide mechanical support and help maintain cell shape and integrity.
Integration with Pathology:
The presence of specific intermediate filament proteins in tumors can often indicate the
cellular origin of the tumor, crucial for diagnosis and treatment.
Immunocytochemical methods routinely identify these proteins. The use of GFAP helps
identify astrocytomas, the most prevalent type of brain tumor.

Immotile cilia syndrome

Aspect Description
Structural - Defects observed in cilia ultrastructure.
Abnormalities - Electron microscopy reveals missing or shortened dynein arms, central
microtubular pair abnormalities, or disorganized axonemal structures.
Impaired Ciliary - Primary defect causing immotile cilia syndrome.
Beating - Dysfunction of dynein arms and microtubular structures disrupts
coordinated movement of ciliary axoneme.
- Results in inability of cilia to beat or move rhythmically.
Mucociliary - Dysfunction affects mucociliary clearance in respiratory tract.
Clearance - Impaired clearance leads to retention of inhaled particles, pathogens, and
Dysfunction mucus in airways.
- Manifests as chronic respiratory symptoms like recurrent infections,
sinusitis, bronchiectasis, and chronic cough.
Other - Affected organs include reproductive tract, brain ventricles, and
Manifestations embryonic nodal cilia.
- Dysfunction in reproductive tract leads to infertility.
- Dysfunction in brain ventricles causes hydrocephalus.
- Dysfunction in embryonic nodal cilia leads to situs inversus (mirror-
image reversal of organ positioning).

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 Clinical - Essential for accurate diagnosis and management of immotile cilia
Implications syndrome.
- Provides insights into underlying pathology and manifestations affecting
multiple organ systems.

CYTOPLASMIC GRANULES
1. Lipid Droplets:
• Histologically, lipid droplets appear as clear vacuoles within the cytoplasm,
often displacing the cellular organelles.
• They can be stained with lipid-specific stains such as Oil Red O or Sudan
Black, appearing as red or black granules, respectively.
• In tissues with high lipid content, such as adipose tissue, lipid droplets can
occupy a significant portion of the cytoplasm.
2. Glycogen Granules:
• Histologically, glycogen granules appear as irregular clumps of PAS-positive
or electron-dense material.
• They can be visualized under light microscopy using PAS staining, where they
stain pink or magenta.
• In tissues with high glycogen content, such as liver cells, glycogen granules
can be abundant and contribute to the characteristic appearance of the tissue.
3. Pigmented Deposits:
• Melanin: Histologically, melanin appears as dark brown granules within
melanocytes or keratinocytes.
• Lipofuscin: Histologically, lipofuscin appears as pale brown granules within
the cytoplasm of stable, non-dividing cells.
• Hemosiderin: Histologically, hemosiderin appears as dense brown aggregates
within phagocytic cells, such as macrophages.
• These pigmented deposits can be identified using special stains or by their
characteristic appearance under light microscopy.
Integration with Pathology:
Hemosiderosis, characterized by the presence of iron-containing hemosiderin in various
organs, may result from increased dietary iron uptake, impaired iron utilization, or excessive
red blood cell breakdown. While hemosiderosis typically does not impair cell or organ
function, excessive accumulation of iron in cellular hemosiderin can lead to disorders like
hemochromatosis and iron overload syndrome, causing tissue damage in organs like the liver.

Structure of Cell Nucleus

Component Description
Nuclear - Double membrane structure surrounding the nucleus.
Envelope - Contains nuclear pores for the exchange of molecules between the
nucleus and cytoplasm.
- Associated with a meshwork of proteins called the nuclear lamina,
which provides structural support.

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 Nuclear Pores - Large protein complexes that penetrate the nuclear envelope.
- Allow for the bidirectional movement of proteins and RNA molecules
between the nucleus and cytoplasm.

Function of Cell Nucleus

Function Description
Protein Synthesis - Directs protein synthesis in the cytoplasm through the production
of ribosomal RNA (rRNA), messenger RNA (mRNA), and transfer
RNA (tRNA).
Chromatin - Facilitates the folding of DNA into a condensed structure to fit
Organization within the nucleus.
- Protects DNA from physical damage during cell division and
between divisions.
- Controls the activity of DNA by regulating transcription and
duplication.
Gender - Identification of Barr bodies (sex chromatin) assists in determining
Determination gender in individuals with ambiguous external genitalia.

Diagnostic - Analysis of sex chromatin helps identify anomalies involving sex

Marker chromosomes, aiding in the diagnosis of conditions such as
Klinefelter syndrome.

MCQ PEARLS
1) What are the two types of organelles? ➔ Membranous and non-membranous
organelles.
2) Which organelle is responsible for protein synthesis? ➔ Ribosomes.
3) What structure characterizes the rough endoplasmic reticulum (RER)? ➔ Ribosomes
on its surface.
4) What is the primary function of the smooth endoplasmic reticulum (SER)? ➔ Lipid
synthesis.
5) Which organelle is involved in posttranslational modifications of proteins? ➔ Golgi
apparatus.
6) What do lysosomes contain that aids in digestion? ➔ Hydrolytic enzymes.
7) What is the main function of proteasomes? ➔ Degrade damaged proteins.
8) Which organelle is known as the powerhouse of the cell? ➔ Mitochondria.
9) What is a key function of mitochondria in cellular processes? ➔ ATP production.
10) What is the role of peroxisomes in the cell? ➔ Detoxification.
11) What condition is associated with mitochondrial dysfunction? ➔ Alzheimer’s disease.
12) What do abnormalities in ribosomal function lead to? ➔ Ribosomopathies.
13) What is the characteristic of microtubules in the cytoskeleton? ➔ Hollow tubes of
tubulin.
14) How do intermediate filaments contribute to cell structure? ➔ Provide mechanical
support.
15) What is a symptom of immotile cilia syndrome? ➔ Chronic respiratory infections.
16) What do lysosomal storage disorders result from? ➔ Deficiencies in lysosomal
enzymes.

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 17) Which organelle initiates packing and concentration of secretory products? ➔ Golgi
apparatus.
18) What role does the SER play in muscle cells? ➔ Calcium storage.
19) What is a characteristic of ribosomes? ➔ Involved in protein synthesis.
20) Which organelle is implicated in neurodegenerative disorders? ➔ Mitochondria.

PAST UHS QUESTIONS

Q1. a) What are organelles? Name FIVE of them and give the difference between
cytoplasmic organelles and inclusions. (Annual 2016)
b)Draw and label microscopic structure of a Bronchiole.

F-A- • Describe the structure of chromatin Histology Cell

043 • Describe the structure of chromosome nucleus
• Describe the structure of nucleolus
• Describe the structure and types of DNA (Deoxy
Ribonucleic Acid) and RNA (Ribonucleic Acid)
• Describe the histological basis for apoptosis and
necrosis
• Describe the structure of different types of cell Integrated
junctions with
• Describe the cell cycle & cell division pathology
• Define important clinicopathological terms: Atresia,
Hypertrophy, Atrophy, Hyperplasia, Metaplasia,
Anaplasia, Neoplasia, Inflammation, Metastasis

CELL NUCLEUS

Chromatin
Chromatin is a complex structure composed of DNA, histone proteins, and nonhistone
proteins. It exists in two forms: euchromatin and heterochromatin, each with distinct
structural characteristics.
Characteristic Euchromatin Heterochromatin
Composition Approximately 10% of Approximately 90% of total
total chromatin chromatin
Transcriptional Transcriptionally active Transcriptionally inactive
Activity
Appearance (Light Lightly stained region Basophilic clumps of
Microscopy) within nucleus nucleoprotein within nucleus
Ultrastructure (TEM) Electron-lucent regions Folded into 30-nanometer-thick
among heterochromatin filaments

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 Composition (TEM) Composed of 10- Densely packed nucleosomes
nanometer strings of
nucleosomes
Function Active transcription and Maintenance of chromosomal
gene expression integrity, centromeres, telomeres;
involved in chromosomal
segregation and interactions during
meiosis

Chromosomes
Aspect Description
Composition Consists of chromatin extensively folded into loops
Nucleosome Basic unit of chromatin packaging, composed of a core of eight
histones wrapped by DNA

Linker DNA Thin string-like regions of DNA connecting adjacent nucleosomes

Chromosome During mitosis and meiosis, chromatin condenses to form visible
Condensation chromosomes

Extended When not condensed, chromatin appears as beads on a string, with

Chromatin nucleosomes as beads and linker DNA as the string
Chromosome Condensed chromatin forms 30-nm-diameter filaments of helical
Structure coils, the structural unit of the chromosome

Karyotype Refers to the number and morphology of chromosomes,

characteristic for each species
Chromosome Haploid number (n) is the number of chromosomes in germ cells,
Number while diploid number (2n) is the number in somatic cells

Genetic Total genetic complement of an individual is stored in its

Complement chromosomes
Centromere Small point where two chromatids of a chromosome are joined
together

Nucleolus
Aspect Description
Shape Generally spherical
Staining Highly basophilic due to densely concentrated ribosomal RNA (rRNA)
Ultrastructure Reveals fibrillar and granular subregions with different staining
characteristics reflecting stages of rRNA maturation
Composition Site of rRNA synthesis, processing, and assembly into ribosomal
subunit precursors, as well as primary processing of microRNAs

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 Function Involved in the synthesis of rRNA and its assembly into ribosome
subunits, primary processing of microRNAs, and sequestration of
nucleolar proteins
Nucleolar Certain proteins, such as nucleostemin, are sequestered in the
Proteins nucleolus and function as cell cycle checkpoint signaling proteins

DNA and RNA

Aspect DNA RNA
Structure Double-stranded helical linear Single-stranded molecule composed of
molecule composed of multiple riboses instead of deoxyribose sugar and
nucleotide sequences uracil instead of thymine

Components Nucleotides composed of a base Nucleotides composed of ribose sugar,

(purine or pyrimidine), deoxyribose phosphate group, and one of four bases:
sugar, and a phosphate group adenine, cytosine, guanine, or uracil

Types of Adenine (A), cytosine (C), guanine Adenine (A), cytosine (C), guanine (G),
Bases (G), thymine (T) uracil (U)
Strands Double-stranded with Single-stranded
complementary base pairing (A-T
and G-C)
Synthesis Does not undergo transcription; Synthesized by transcription from DNA
serves as a template for RNA template
synthesis
Types of Does not directly produce RNA mRNA, tRNA, rRNA, microRNAs
RNA molecules (miRNAs), small nuclear RNA
(snRNA), and others
Function Stores genetic information and acts Carries genetic information from DNA
as a template for RNA synthesis to direct protein synthesis, regulates gene
expression, splicing, and other cellular
processes

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HISTOLOGICAL ASPECT OF APOPTOSIS AND NECROSIS
Apoptosis:
1. Chromatin condensation: One of the early signs of apoptosis is the condensation
of chromatin within the nucleus, resulting in a dense, aggregated appearance under
the microscope.
2. Nuclear fragmentation: As apoptosis progresses, the nucleus undergoes
fragmentation into multiple smaller fragments, each containing condensed
chromatin.
3. Plasma membrane blebbing: The cell membrane develops irregular protrusions or
blebs, giving the cell a "bubbly" appearance.
4. Cell shrinkage: Apoptotic cells typically undergo shrinkage due to cytoplasmic
and organelle condensation.
5. Formation of apoptotic bodies: The cell breaks up into smaller membrane-bound
vesicles known as apoptotic bodies, each containing cellular fragments.
6. Minimal inflammatory response: Apoptotic cells are rapidly engulfed by
neighboring phagocytic cells, such as macrophages, without eliciting an
inflammatory response.

Necrosis:
1. Cell swelling: Necrotic cells often exhibit swelling due to increased permeability of
the cell membrane and influx of fluid.
2. Rupture of the cell membrane: The integrity of the cell membrane is
compromised, leading to the release of cellular contents into the extracellular space.
3. Release of cellular contents: Necrotic cells release their contents, including
enzymes, proteins, and other molecules, into the surrounding tissue.
4. Inflammatory response: The release of cellular contents triggers an inflammatory
response, characterized by infiltration of immune cells and tissue damage.
5. Loss of cellular architecture: Necrotic cells lose their structural integrity, and the
overall tissue architecture is disrupted.
6. Formation of necrotic lesions: In severe cases, areas of necrotic tissue, known as
necrotic lesions, may develop within the affected tissue.

CELL JUNCTION
Junction Major Cytoskeletal Major Functions Medical
Type Transmembrane Components Significance
Link Proteins

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 Tight Occludins, Actin Seals adjacent cells Defects in
Junction claudins, ZO filaments to one another, occludins may
proteins controlling passage compromise the
of molecules fetal blood-brain
between them; barrier, leading to
separates apical severe neurologic
and basolateral disorders
membrane
domains
Adherent E-cadherin, catenin Actin Provides points Loss of E-cadherin
Junction complexes filaments linking the in epithelial cell
cytoskeletons of tumors
adjacent cells; (carcinomas)
strengthens and promotes tumor
stabilizes nearby invasion and the
tight junctions shift to malignancy
Desmosome Cadherin family Intermediate Provides points of Autoimmunity
proteins filaments strong intermediate against desmoglein
(desmogleins, (keratins) filament coupling I leads to dyshesive
desmocollin) between adjacent skin disorders
cells, strengthening characterized by
the tissue reduced cohesion
of epidermal cells
Integrins None Intermediate Anchors Mutations in the
filaments cytoskeleton to the integrin-ẞ4 gene
basal lamina are linked to some
types of
epidermolysis
bullosa, a skin
blistering disorder
Gap Connexin None Allows direct Mutations in
Junction transfer of small various connexin
molecules and ions genes have been
from one cell to linked to certain
another types of deafness
and peripheral
neuropathy

Integration with Pathology:

• Cell junction abnormalities can lead to various pathological conditions. Malfunctioning
tight junctions in the epithelial lining of the intestines can result in increased intestinal
permeability, leading to conditions like inflammatory bowel disease.
• Defects in desmosomes are associated with skin disorders like pemphigus vulgaris, where
autoantibodies target desmosomal proteins, causing loss of cell-cell adhesion and
blistering. Aberrant gap junction function can contribute to cardiac arrhythmias, as
impaired electrical signaling between cardiac cells disrupts the heart's rhythm.

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Cell cycle
The cell cycle is the series of events that occur in a eukaryotic cell leading to its division and
duplication. It can be broadly divided into two main phases: interphase and cell division.
Interphase:
1. G1 (Gap 1) Phase: During G1 phase, the cell grows and carries out its normal
functions. It synthesizes proteins and prepares for DNA replication.
2. S (Synthesis) Phase: In S phase, DNA replication occurs, resulting in the duplication
of the cell's genetic material. Each chromosome is replicated, forming sister
chromatids.
3. G2 (Gap 2) Phase: G2 phase is characterized by continued growth and preparation
for cell division. The cell synthesizes organelles and proteins necessary for mitosis.
Integrated with pathology:
• Proto-oncogenes, regulating cell growth, can become oncogenes, driving cancer.
Alterations in these genes are linked to tumors and hematologic cancers, affecting growth
factors and their receptors.
• Retinoblastoma, an eye cancer, reveals insights into cell cycle control. Inherited forms
involve the Rb gene, halting cell cycle progression until stimulated by growth factors.
Phosphorylation of Rb releases the E2F transcription factor, triggering DNA replication.
• Disruptions in cell cycle regulation, often involving proto-oncogenes like Rb, contribute
to cancer. Understanding these molecular mechanisms aids in cancer diagnosis and
treatment.
Cell Division:
1. Mitosis (M Phase): Mitosis is the process by which the nucleus of the cell divides
into two identical nuclei. It is divided into several stages:
• Prophase: Chromosomes condense, the nuclear envelope breaks down, and
spindle fibers begin to form.
• Metaphase: Chromosomes line up at the metaphase plate in the center of the
cell, and spindle fibers attach to the centromeres of each chromosome.
• Anaphase: Sister chromatids separate and move to opposite poles of the cell,
pulled by the spindle fibers.
• Telophase: Chromatids reach the poles, the nuclear envelope reforms around
each set of chromosomes, and chromosomes begin to decondense.
• Cytokinesis: Cytokinesis is the division of the cell's cytoplasm, resulting in the
formation of two daughter cells. In animal cells, this involves the formation of
a cleavage furrow, while in plant cells, a cell plate forms to divide the
cytoplasm.
2. Meiosis
• Prophase I: Homologous chromosomes pair up (synapsis), exchange genetic
material (crossing-over), and form tetrads. The nuclear envelope breaks down.
• Metaphase I: Tetrads align at the equatorial plane randomly, increasing genetic
diversity.
• Anaphase I: Homologous chromosomes separate, moving to opposite poles.
• Telophase I: Cell divides, resulting in two haploid daughter cells, each with
duplicated chromosomes.
• Prophase II: Nuclear envelope breaks down again, and spindle apparatus forms.
• Metaphase II: Sister chromatids align at the equator.
• Anaphase II: Sister chromatids separate and move to opposite poles.

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 • Telophase II: Chromosomes arrive at poles, and nuclear envelopes form.
• Cytokinesis: Cell division yields four haploid daughter cells, genetically diverse
due to random assortment and crossing-over.

Integrated with pathology:

During meiosis, chromosome 21 may fail to separate properly, leading to nondisjunction,
especially in older oocytes or sperm progenitor cells. If a gamete retains an extra
chromosome 21, the resulting zygote develops into an individual with Down syndrome. This
condition is characterized by morphological and cognitive impairments.

CLINICOPATHOLOGICAL TERMS
Term Definition
Atresia Absence or closure of a normal body orifice or tubular structure,
occurring naturally during embryonic development or due to pathological
processes, leading to obstruction.
Hypertrophy Increase in the size of cells or tissues in response to stimuli such as
workload, hormonal stimulation, or pathological conditions, characterized
by enlarged individual cells.
Atrophy Decrease in the size or function of cells, tissues, or organs due to
reduction in cell size, number, or both, resulting from disuse, aging,
decreased blood supply, or pathology.
Hyperplasia Increase in the number of cells in a tissue or organ, leading to
enlargement, occurring in response to hormonal stimulation, chronic
irritation, or other stimuli.
Metaplasia Reversible change where one differentiated cell type is replaced by
another in response to chronic irritation or inflammation, better suited to
the new environment.
Anaplasia Loss of cellular differentiation and organization, leading to abnormal
morphology and function, commonly seen in cancerous tumors,
characterized by loss of normal architecture.
Neoplasia Abnormal and uncontrolled cell growth resulting in tumor formation,
which can be benign or malignant, characterized by proliferation of cells
that disregard normal growth controls.

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 Inflammation Body's response to injury, infection, or irritation, characterized by redness,
heat, swelling, pain, and loss of function, aimed at eliminating the cause
of injury and initiating healing.
Metastasis Spread of cancer cells from a primary tumor to distant sites, establishing
secondary tumors, involving tissue invasion, entry into circulation, and
colonization at new sites.

MCQ PEARLS
1. What is chromatin composed of? ➔ DNA, histone proteins, and nonhistone
proteins.
2. What are the two forms of chromatin? ➔ Euchromatin and heterochromatin.
3. Which type of chromatin is transcriptionally active? ➔ Euchromatin.
4. What is the basic unit of chromatin packaging? ➔ Nucleosome.
5. What characterizes heterochromatin? ➔ Transcriptionally inactive and densely
packed nucleosomes.
6. What is the function of the nucleolus? ➔ Synthesis of rRNA and assembly into
ribosome subunits.
7. What type of RNA does DNA produce during transcription? ➔ mRNA, tRNA, rRNA,
and others.
8. What indicates the early stages of apoptosis? ➔ Chromatin condensation.
9. How do necrotic cells differ from apoptotic cells? ➔ Necrotic cells swell and release
cellular contents.
10. What defines tight junctions? ➔ Seals adjacent cells and controls passage of
molecules.
11. Which proteins are major transmembrane link proteins in adherent junctions? ➔ E-
cadherin.
12. What occurs during the G1 phase of the cell cycle? ➔ Cell growth and normal
functions.
13. What phase involves DNA replication? ➔ S phase.
14. What characterizes mitosis? ➔ Division of the nucleus into two identical nuclei.
15. What is the result of meiosis? ➔ Four genetically diverse haploid daughter cells.
16. What can cause Down syndrome during meiosis? ➔ Nondisjunction of chromosome
21.
17. What is hypertrophy? ➔ Increase in the size of cells or tissues.
18. What is atrophy? ➔ Decrease in the size or function of cells or tissues.
19. What defines neoplasia? ➔ Abnormal and uncontrolled growth of cells.
20. What is metastasis? ➔ Spread of cancer cells from the primary tumor to distant
sites.

F-A- • Describe the histological structure and function of the Histology Epithelium
044 basement membrane (light and electron)
• Draw and label a diagram illustrating the electron
microscopic structure of the basement membrane
• Describe the basal surface modifications of epithelia

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 • Describe the electron microscopic structure and functions
of intercellular junctions (lateral surface modifications)
and give their locations
• Describe the Biochemical composition of the basolateral
modifications

• Describe the electron microscopic structure & functions of Integrate

the following apical cell surface specializations: 1. with
Microvilli 2. Stereocilia 3. Cilia Biochemistry
• Classify and exemplify the epithelia with their histological Integrate
structure, locations, and functions with
Pathology
• Describe the structure of exocrine glands Histology
• Explain the mechanism of transport across the epithelial
• Describe the classification of exocrine glands based on:
1. Shape of secretory portions and ducts 2. Mode of
secretion 3. Type of secretion

Epithelium: Basement Membrane

The basement membrane is a specialized extracellular matrix that provides structural support,
regulates cell behavior, and separates different tissue layers.
Light Microscopy:
• Appears as a thin, eosinophilic line beneath epithelial or endothelial layers, best
visualized with special stains (e.g., PAS, silver stains).
• Main Layers:
1. Basal Lamina:
▪ Lamina Densa: Thicker layer composed primarily of type IV
collagen, providing structural stability.
▪ Lamina Lucida: Thinner, less electron-dense layer containing
laminins, nidogens, and proteoglycans; interfaces with cell plasma
membranes.
2. Reticular Lamina: Located beneath the basal lamina, consisting of collagen
fibers (primarily type III) that anchor the basement membrane to connective
tissue.
Electron Microscopy:
1. Basal Lamina:
▪ Appears as a dense, electron-dense layer with a meshwork of type IV
collagen fibrils.
▪ Lamina lucida shows laminin-rich structures and integrin receptors.
2. Reticular Lamina: Loosely arranged type III collagen fibers embedded in
glycoprotein and proteoglycan-rich ground substance.
Functions:
• Structural Support: Maintains tissue integrity.
• Barrier Function: Regulates movement of cells, macromolecules, and ions.
• Cell Adhesion and Migration: Facilitates interactions with cell surface receptors
(e.g., integrins).
• Tissue Organization: Contributes to the compartmentalization of tissues.

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Diagram illustrating the electron microscopic structure of basement membrane

BASAL SURFACE MODIFICATIONS OF EPITHELIA

Basal Surface Description
Modification
Basal infoldings Inward extensions of the basal cell membrane into the
cytoplasm, increasing surface area for molecule transport.
Hemidesmosomes Cell adhesion structures anchor epithelial cells to the
basement membrane, providing structural stability.
Focal adhesions Protein complexes link the cytoskeleton to the extracellular
matrix, enabling cell signaling and migration.
Basal lamina attachment Transmembrane proteins facilitate cell-matrix adhesion and
proteins signaling, crucial for cell survival and function.
Basal membrane Proteins regulate ion, nutrient, and waste molecule movement
transporters between epithelial cells and underlying tissue.
Basal membrane Receptors interact with signaling molecules and extracellular
receptors matrix components, regulating cell behavior.

Intercellular junctions
Junction Structure Function Location
Type

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 Tight Strands of Regulate paracellular transport, The blood-brain
Junctions transmembrane proteins create a barrier preventing barrier, intestinal
from adjacent cells passage of substances between epithelium
interact to form a seal. cells Renal tubules,
epithelial linings
Adherens Electron-dense plaques Provide mechanical strength Epithelial and
Junctions along lateral surfaces. and stability to tissues; link endothelial tissues
Actin filaments anchored neighboring cells; regulate cell
by transmembrane signaling and shape
cadherins
Desmosomes Electron-dense Provide strong adhesion and Skin, heart,
desmosomal plaques on resistance to mechanical stress; bladder, uterus
the cytoplasmic side anchor intermediate filaments
Intermediate filaments
extend into the cytoplasm
Gap Arrays of transmembrane Facilitate direct exchange of Cardiac muscle,
Junctions protein channels ions, small molecules, and nervous tissue,
Connexons composed of signaling molecules between epithelium
six connexin subunits cells

Basolateral Modifications of Epithelial Cells

Basolateral modifications refer to structural and biochemical adaptations on the basal and
lateral surfaces of epithelial cells, essential for maintaining cell polarity, facilitating
communication, and supporting specialized functions.
1. Proteins:
o Transport Proteins: Facilitate ion and nutrient movement, regulating
absorption and secretion.
o Receptors: Mediate cell signaling by binding to hormones or growth factors.
o Adhesion Proteins: Cell adhesion molecules (CAMs) promote cell-cell
adhesion and interactions with the extracellular matrix (ECM).
o Enzymes: Participate in metabolic processes and signal transduction.
2. Lipids:
o Major constituents (phospholipids, cholesterol, glycolipids) provide membrane
stability, fluidity, and signaling roles.
3. Carbohydrates:
o Covalently attached to membrane proteins and lipids as glycoproteins and
glycolipids, facilitating cell recognition, adhesion, and signaling.
4. Cytoskeletal Components:
o Connected to the cytoskeleton (actin and intermediate filaments) for structural
support and intracellular transport.
Apical Cell Surface Specializations
1. Microvilli:
o Structure: Finger-like projections with actin filaments bundled by actin-
binding proteins.
o Functions:

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 ▪ Increase surface area for enhanced absorption (e.g., intestinal epithelial
cells).
▪ May contain receptors for detecting external chemical signals.
2. Stereocilia:
o Structure: Long, non-motile microvilli found in the male reproductive tract
and sensory hair cells.
o Functions:
▪ Mechanosensory role in hair cells for sound transduction.
▪ Aid in fluid and nutrient absorption in the male reproductive tract.
3. Cilia:
o Structure: Hair-like protrusions with microtubule-based axonemes (9+2 or
9+0 arrangements).
o Functions:
▪ Motile cilia propel mucus in the respiratory tract.
▪ Primary cilia function as sensory organelles in signaling pathways.
Integration with Biochemistry
• Microvilli: Contain actin-binding proteins (villin, fimbrin) for stability.
• Stereocilia & Cilia: Contain microtubule-associated and motor proteins for assembly
and motility.
• Membrane Proteins: Localized to structures for nutrient absorption, sensory
transduction, and motility.
• Signaling Molecules: Facilitate cell-cell communication and responsiveness to
extracellular cues.
Classification of epithelium

Epithelial Type Histological Locations Functions Pathological

Structure Integration
Simple Single layer of flat, Alveoli of Facilitates Injury or inflammation
Squamous scale-like cells; lungs; diffusion and can lead to increased
Epithelium flattened nuclei endothelium filtration; permeability, as seen in
of blood reduces pulmonary edema.
vessels friction
Stratified Multiple layers of Epidermis; Protects Chronic irritation can
Squamous squamous cells; oral cavity; against lead to hyperplasia and
Epithelium basal cells esophagus; mechanical dysplasia, increasing the
cuboidal/columnar vagina stress and risk of cancer
abrasion
Simple Cuboidal A single layer of Glands Involved in Damage or loss of
Epithelium cube-shaped cells; (e.g., secretion and cuboidal epithelium in
centrally located thyroid, absorption renal tubules can impair
nuclei pancreas); kidney function, leading
kidney to renal failure.
tubules
Simple A single layer of GI tract; Facilitates Inflammatory bowel
Columnar tall, column- gallbladder; absorption and diseases like ulcerative
Epithelium shaped cells; some respiratory secretion; colitis or Crohn's disease
may have tract provides can disrupt the integrity
microvilli or cilia protection of the columnar

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 epithelium, leading to
symptoms such as
diarrhea and abdominal
pain.
Pseudostratified A single layer of Respiratory Secretes Chronic exposure to
Columnar varying height tract mucus; propels cigarette smoke can
Epithelium columnar cells; (trachea, mucus and damage pseudostratified
nuclei at different bronchi) debris by columnar epithelium,
levels ciliary action leading to impaired
mucociliary clearance
and chronic obstructive
pulmonary disease
(COPD).
Transitional Variable Urinary Allows Chronic inflammation or
Epithelium appearance bladder; stretching and infection can lead to
(cuboidal/columnar ureters; distension metaplasia and
when relaxed, urethra without dysplasia, increasing the
flattened when compromising risk of bladder cancer.
stretched) the barrier

Structure of Exocrine Glands

Exocrine glands are glandular epithelia that secrete substances onto surfaces or into ducts,
essential for lubrication, protection, and physiological functions. Their structure includes:
1. Parenchyma:
o Functional portion composed of secretory epithelial cells responsible for
producing and releasing secretions.
2. Ductal System:
o Pathways for transport of secretions, varying in complexity and length.
Components include:
▪ Interlobar Ducts: Between lobes
▪ Intralobular Ducts: Within lobes
▪ Interlobular Ducts: Between lobules
▪ Intralobular Ducts: Within lobules
3. Basal Lamina:
o Thin extracellular matrix separating parenchyma from surrounding connective
tissue, providing structural support.
4. Stroma:
o Connective tissue surrounding the parenchyma, consisting of fibroblasts,
collagen fibers, and blood vessels, providing support and organization.
5. Secretory Units:
o Functional units producing specific substances, classified by shape:
▪ Acinar: Rounded or sac-like
▪ Alveolar: Flask-like
▪ Tubular: Straight or coiled
6. Secretory Cells:
o Specialized epithelial cells that synthesize, store, and release secretions, with
morphological variations based on the secretion type (e.g., mucous or serous
cells).

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 7. Connective Tissue Capsule and Septa:
o Some glands have a connective tissue capsule for support, with septa dividing
the gland into lobes and lobules for compartmentalization.
Mechanism of transport
Mechanism of Description
Transport
Active Transport Movement of ions or molecules against their concentration gradients,
requiring energy expenditure (e.g., Na^+/K^+-ATPase pump).
Passive Transport Movement of ions or molecules along their concentration gradients,
without the need for energy (e.g., facilitated diffusion through
aquaporins).
Endocytosis and Processes involving the internalization (endocytosis) and release
Exocytosis (exocytosis) of molecules and fluids by epithelial cells through vesicular
transport.
Transcytosis Transport of molecules or fluids across epithelial cells through
endocytosis on one side and exocytosis on the other side, facilitating
bidirectional movement.
Tight Junctions Junctional complexes between adjacent epithelial cells seal the
intercellular spaces, regulating paracellular transport and maintaining
epithelial integrity.
Lateral Structural features of epithelial cells, such as microvilli or lateral folds,
Membrane Folds increase the surface area for transport and facilitate exchange with the
environment.

Classification of Exocrine Glands

Simple glands (Do not branch)

Class Simple Branched Coiled Acinar (or Branched
Tubular Tubular Tubular Alveolar) Acinar
Features Elongated Several long The Rounded, Multiple
secretory secretory secretory saclike saclike
portion; duct parts join to portion is secretory secretory
usually short or drain into 1 very long portion parts
absent duct and coiled entering the
same duct
Examples Mucous glands Glands in Sweat Sebaceous Small
of the colon; the uterus glands glands of mucous
intestinal glands and stomach the skin glands along
or crypts (of the urethra
Lieberkühn)

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 COMPOUND Glands (Ducts from Several Secretory Units Converge into Larger
Ducts)
Class Tubular Acinar (Alveolar) Tubuloacinar
Features Several elongated coiled Several saclike Ducts of both
secretory units secretory units tubular and acinar
Several ducts converge at a Small ducts secretory units
larger duct converge to form Larger ducts
larger ducts
Examples Submucosal mucous glands Exocrine pancreas Salivary glands
(of Brunner) in the
duodenum

Mode of Examples
Secretion
Merocrine Salivary glands, Sweat glands, Pancreatic acinar cells, Eccrine glands of
the skin
Apocrine Apocrine sweat glands, Mammary glands (during lactation), Ceruminous
glands of the ear
Holocrine Sebaceous glands of the skin, Meibomian glands of the eyelids, Glands in
the mucous membrane of the digestive tract

Type of Examples
Secretion
Mucous Goblet cells in the respiratory tract and gastrointestinal tract, Mucous
glands of the esophagus, Mucous glands in the urethra

Serous Parotid salivary glands (serous acini), Pancreatic acinar cells (zymogen-
secreting cells), Serous cells in the submandibular and sublingual salivary
glands
Mixed Submandibular salivary glands (both mucous and serous acini), Sublingual
salivary glands (mixed acini), Lacrimal glands (produce both mucous and
serous components of tears)

MCQ PEARLS
1. What is the primary function of the basement membrane? ➔ Provides structural
support.
2. What are the two main layers of the basement membrane? ➔ Basal lamina and
reticular lamina.
3. What type of collagen predominates in the lamina densa? ➔ Type IV collagen.
4. What staining technique best visualizes the basement membrane? ➔ Periodic acid-
Schiff (PAS) stain.

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 5. What is a key characteristic of microvilli? ➔ They increase the surface area for
absorption.
6. What junction type provides mechanical strength to epithelial tissues? ➔ Adherens
junctions.
7. Which epithelium type is found in the alveoli of the lungs? ➔ Simple squamous
epithelium.
8. What function does transitional epithelium serve? ➔ Allows stretching and
distension.
9. What is the main role of cilia? ➔ Facilitate motility through coordinated beating.
10. What type of secretion is characteristic of sebaceous glands? ➔ Holocrine secretion.
11. What are hemidesmosomes? ➔ Structures that anchor epithelial cells to the
basement membrane.
12. What is the main function of tight junctions? ➔ Regulate paracellular transport.
13. Which type of gland is characterized by a branched structure? ➔ Branched tubular
gland.
14. What do stereocilia primarily facilitate in the inner ear? ➔ Mechanotransduction.
15. What is the function of focal adhesions? ➔ Link the cytoskeleton to the extracellular
matrix.
16. What type of epithelium is found in the respiratory tract? ➔ Pseudostratified
columnar epithelium.
17. What is the role of basolateral membrane transporters? ➔ Regulate movement of ions
and nutrients.
18. What is the structural feature of simple cuboidal epithelium? ➔ A single layer of
cube-shaped cells.
19. What type of secretion do goblet cells produce? ➔ Mucous secretion.
20. Which exocrine gland is classified as tubuloacinar? ➔ Salivary glands.

PAST UHS QUESTIONS

Q1. An infant with frequent attacks of sinusitis and lung infections was diagnosed by
a pediatrician as having dysfunction of cilia. (Supple 2019 held in 2020)
a) What is the most common disorder of ciliary dysfunction?
b) Explain the histological causes of abnormalities in this disorder.
c) Briefly give the normal structure of Cilia.

Q2. a) Name the various types of Specializations of the apical cell surface of the
epithelium. (Supply 2022 held in 2023)
b) Draw and label the light microscopic structure of the spleen.
Q3.Define and classify compound exocrine glands quoting one example of each. Draw the
diaphragmatic outline of these glands to support your answer. (Supple 2010)
b)Name three viscera in the body which are both endocrine and exocrine glands.

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 F-A- • Describe the composition and list the Histology Connective
045 constituents of connective tissue tissue
• Classify the connective tissue with
examples
• Describe the composition of the ground
substance of connective tissue
• Describe the composition, distribution, and
function of glycosaminoglycans in
connective tissue
• Describe connective tissue fibers and cells.
• Define Fibrosis
• Describe the structure, distribution, and Integrate with
functions of the cells of the macrophage Biochemistry/
mononuclear phagocytic system Physiology
• Describe the role of macrophages in innate
immunity & formation of foreign body
Giant cell
• Describe the structure & functions of Mast
cells.
• Role of Mast cells in immediate
hypersensitivity reactions.
• Describe the structure of Plasma cells and
their role in antibody formation
• Describe the types of adipose tissue (white Histology
& brown), their histogenesis, locations, and
function
• Describe lipid storage and mobilization in
• and from adipocytes and compare the Integrate with
brown and white adipose tissue Pathology

Connective tissue
Composition of Connective Tissue:
Connective tissue is composed primarily of extracellular matrix (ECM), which consists of
ground substance and fibers, along with various connective tissue cells embedded within this
matrix.
1. Extracellular Matrix (ECM):
• Ground Substance: A gel-like material in which cells and fibers of connective
tissue are embedded. It is composed of glycosaminoglycans, proteoglycans,
and glycoproteins.
• Fibers:
• Collagen Fibers: Predominant fibers in connective tissue, consisting
mainly of types I and III collagen. They provide tensile strength and
flexibility to tissues.
• Reticular Fibers: Composed primarily of type III collagen, forming a
framework in certain organs and glands.
• Elastic Fibers: Coiled branching fibers composed of elastin
surrounded by microfibrils, providing elasticity to tissues.
2. Connective Tissue Cells:

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 • Fibroblasts: Predominant cells in connective tissue, responsible for producing
collagen, elastic fibers, and ground substance.
• Pericytes: Found along capillaries, involved in blood vessel formation and
repair, and may differentiate into fibroblasts or smooth muscle cells.
• Adipose Cells (Adipocytes): Responsible for fat synthesis, storage, and
release. Can be unilocular (containing a single large fat droplet) or
multilocular (containing many small fat droplets).
• Mast Cells: Large cells containing metachromatic granules, involved in
inflammatory and allergic reactions.
Classification of Connective tissue

Connective General Organization Major Functions Examples

Tissue Type
Connective tissue proper
Loose (areolar) Much ground substance; Supports Lamina propria
connective many cells and little microvasculature, nerves, beneath the epithelial
tissue collagen, randomly and immune defense cells lining of the digestive
distributed tract
Dense irregular Little ground substance; Protects and supports Dermis of skin, organ
connective few cells (mostly organs; resists tearing capsules, submucosa
tissue fibroblasts); much layer of the digestive
collagen in randomly tract
arranged fibers
Dense regular Almost filled with parallel Provide strong connections Ligaments, tendons,
connective bundles of collagen; few within the musculoskeletal aponeuroses, corneal
tissue fibroblasts, aligned with system; strong resistance stroma
collagen to force
Embryonic connective tissue
Mesenchyme Sparse, undifferentiated Contains stem/progenitor A mesodermal layer
cells, uniformly distributed cells for all adult of the early embryo
in a matrix with sparse connective tissue cells
collagen fibers
Mucoid Random fibroblasts and Supports and cushions Matrix of the fetal
(mucous) collagen fibers in a large blood vessels umbilical cord
connective viscous matrix
tissue
Specialized Connective Tissues
Reticular Delicate network of Supports blood-forming Bone marrow, liver,
connective reticulin/collagen III with cells, many secretory cells,pancreas, adrenal
tissue attached fibroblasts and lymphocytes in most glands, all lymphoid
(reticular cells) lymphoid organs organs except the
thymus
Adipose Tissue Large, closely packed Stores energy in the form Subcutaneous tissue,
adipocytes with minimal of triglycerides, provides around organs (e.g.,
ground substance insulation, cushions organs kidneys, heart), bone
marrow
Cartilage Firm, flexible matrix Provides support, Articular cartilage,
containing chondrocytes resilience, and cushioning costal cartilage, nasal
embedded in lacunae cartilage, tracheal

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 for joints and other rings, intervertebral
structures discs

Bone A dense network of Provides structural Bone

collagen fibers embedded support, protection of vital
in a mineralized ground organs, mineral storage,
substance and blood cell production
Blood Fluid matrix (plasma) with Transport of oxygen, Blood
various types of cells nutrients, hormones, and
(erythrocytes, leukocytes, waste products; immune
platelets) defense

Composition of Ground Substance in Connective Tissue

The ground substance of connective tissue is a gel-like material filling the spaces between
cells and fibers in the extracellular matrix (ECM). It primarily consists of:
1. Water:
o The largest component, serving as a medium for nutrient, gas, and waste
diffusion between cells and blood vessels.
2. Glycosaminoglycans (GAGs):
o Long, unbranched polysaccharide chains made of repeating disaccharide units
(e.g., hyaluronic acid, chondroitin sulfate).
o Highly negatively charged, they attract and bind positive ions and water,
contributing to the gel-like consistency.
3. Proteoglycans:
o Large molecules consisting of a core protein with attached GAG chains.
o Important for maintaining ECM structure and hydration, and they interact with
collagen to enhance tissue stability.
4. Glycoproteins:
o Proteins with attached carbohydrate chains (e.g., fibronectin, laminin).
o Provide structural support, promote cell adhesion, and facilitate cell signaling
within the ECM.
Composition, distribution, and function of glycosaminoglycans

Glycosaminoglycan Hexuronic Hexosamine Distribution Electrostatic Function

Acid Interaction with
Collagen
Hyaluronic acid D-glucuronic D-glucosamine The umbilical High levels of Provides
acid cord, interaction, mainly hydration
synovial with collagen type and
fluid, II lubrication
vitreous to tissues,
humor, contributes
cartilage to tissue
resilience
and shock
absorption

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Chondroitin 4- D-glucuronic D-galactosamine Cartilage, High levels of Provides
sulfate acid bone, cornea, interaction, mainly structural
skin, with collagen type support and
notochord, II elasticity to
aorta connective
tissues
Chondroitin 6- D-glucuronic D-galactosamine Cartilage, High levels of Similar
sulfate acid umbilical interaction, mainly function to
cord, skin, with collagen type chondroitin
aorta (media) II 4-sulfate
Dermatan sulfate L-iduronic D-galactosamine Skin, tendon, Low levels of Provides
acid or D- aorta interaction structural
glucuronic (adventitia) support and
acid elasticity to
connective
tissues
Heparan sulfate D-glucuronic D-glucosamine Aorta, lung, Intermediate levels Involved in
acid or L- liver, basal of interaction, cell
iduronic acid laminae mainly with adhesion,
collagen types III basement
and IV membrane
formation,
and
regulation
of growth
factor
signaling
Keratan sulfate D-galactose D-glucosamine Cartilage, None Provides
nucleus resistance to
pulposus, compressive
annulus forces in
fibrosus cartilage
and
maintains
tissue
structure

Fibrosis
Definition: Fibrosis is a pathological condition characterized by the excessive accumulation
of fibrous connective tissue in an organ or tissue, leading to scarring and impaired function.
Causes:
• Chronic inflammation
• Tissue injury or damage
• Persistent infections
• Autoimmune reactions
• Environmental factors (e.g., toxins, radiation)
Types of Fibrosis
1. Pulmonary Fibrosis
2. Liver Cirrhosis

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 3. Cardiac Fibrosis
4. Renal Fibrosis
Structure, Distribution, and Functions of Cells of the Mononuclear Phagocytic System
Structure:
• Macrophages are large, irregularly shaped cells with abundant cytoplasm.
• They contain a single, centrally located nucleus that may vary in shape.
• The cytoplasm often contains vacuoles, lysosomes, and phagosomes.
Distribution:
• Macrophages are found throughout the body in various tissues and organs.
• They are particularly abundant in tissues involved in immune surveillance and
defense, such as the spleen, lymph nodes, liver, lungs, and bone marrow.
Tissue/Organ Specific Macrophage
Names
Spleen Splenic Macrophages
Liver Kupffer Cells
Lungs Alveolar Macrophages
Skin Langerhans Cells (in
epidermis)
Bone Marrow Sinusoidal Macrophages
Central Microglia
Nervous
System
Lymph Nodes Sinus Macrophages
Kidneys Mesangial Cells (in
glomeruli)
Functions of Macrophages
1. Phagocytosis:
o Macrophages engulf and digest
foreign particles, microorganisms,
and cellular debris, aiding in
pathogen removal and tissue repair.
2. Antigen Presentation:
o They process and present antigens from engulfed pathogens to T cells,
initiating adaptive immune responses.
3. Cytokine Production:
o Macrophages secrete cytokines (e.g., interleukins, TNF-alpha) that regulate
inflammation, immune responses, and tissue repair.
4. Tissue Repair and Remodeling:
o They promote wound healing by removing damaged cells and stimulating
fibroblast and endothelial cell proliferation.
5. Homeostasis:
o Macrophages help maintain tissue integrity by clearing apoptotic cells and
modulating immune responses to prevent excessive inflammation.
Integration with Biochemistry/Physiology
• Receptors:
o Macrophages express pattern recognition receptors (PRRs), including toll-like
receptors (TLRs), to detect pathogens.

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 • Signaling Pathways:
o Recognition of pathogens activates signaling pathways that produce pro-
inflammatory cytokines and chemokines.
• Lipid Metabolism:
o Scavenger receptors facilitate the uptake of modified lipoproteins and other
molecules.
• Metabolic States:
o Macrophage functions are linked to metabolic profiles, with M1 (pro-
inflammatory) and M2 (anti-inflammatory) states associated with glycolysis
and oxidative phosphorylation, respectively.

Role of macrophages in innate immunity

Role Description
Phagocytosis Engulfment and digestion of pathogens, foreign particles, and
cellular debris.
Antigen Presentation Processing and presentation of antigens on MHC molecules to
activate the adaptive immune response.
Cytokine Production Production and release of cytokines to regulate the immune
response, including inflammation, recruitment of immune cells, and
activation of immune functions.
Tissue Remodeling Contribution to tissue repair and remodeling through the release of
and Repair growth factors and MMPs to promote healing and resolution of
inflammation.
Formation of Multinucleated giant cell formation in response to large foreign
Foreign Body Giant bodies or materials that cannot be phagocytosed individually,
Cells aiming to isolate and encapsulate the foreign material.

Mast Cells:
Aspect Description
Structure Mast cells are large, granulated cells found in connective tissue.
They contain numerous granules filled with various inflammatory
mediators. Their structure includes:
- Cytoplasm filled with granules
- Centrally located nucleus
- Surface receptors, including FcεRI receptors

Functions Mast cells perform various functions in the body, including:

- Release of inflammatory mediators stored in granules
- Modulation of immune responses
- Promotion of inflammation
- Contribution to tissue repair and remodeling
- Defense against pathogens

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 Role in Mast cells play a central role in immediate hypersensitivity reactions,
Immediate also known as type I hypersensitivity reactions.
Hypersensitivity - Sensitization: Mast cells become sensitized to specific allergens
Reactions through the binding of IgE antibodies to FcεRI receptors on their
surface.
- Activation: Upon re-exposure to the allergen, cross-linking of IgE-
FcεRI complexes triggers mast cell degranulation, releasing
inflammatory mediators.
- Immediate Reaction: The released mediators lead to rapid
vasodilation, increased vascular permeability, smooth muscle
contraction, and allergic symptoms characteristic of hypersensitivity
reactions.
Plasma Cells
Aspect Description
Structure of • Plasma cells have abundant cytoplasm packed with rough
Plasma Cells endoplasmic reticulum (RER).
• eccentrically located nucleus due to RER accumulation.
• Well-developed Golgi apparatus for post-translational
modification and packaging of antibodies.
• Increased number of mitochondria for energy demands.
• Expression of specific markers such as CD38, CD138
(Syndecan-1), and MHC class II molecules.
Role in Antibody • Derived from activated B cells upon exposure to specific
Formation antigens.
• Dedicated to producing antibodies with specificity for particular
antigens.
• Synthesize large quantities of antibodies, which are
glycoproteins with two heavy chains and two light chains.
• Transport antibodies through the endoplasmic reticulum and
Golgi apparatus for post-translational modifications.
• Secretion of antibodies into extracellular space for immune
defense.
• Formation of memory B cells for long-lasting immunity.

Adipose Tissue

Aspect White Adipose Tissue (WAT) Brown Adipose Tissue (BAT)

Structure Contains a single large lipid Contains multiple small lipid droplets
droplet surrounded by a thin rim and numerous mitochondria, giving it
of cytoplasm. a brown appearance.
Histogenesis Derived from mesenchymal stem Develops from myogenic progenitor
cells that differentiate into cells expressing specific transcription
preadipocytes, then adipocytes. factors under the influence of
PRDM16 and PGC-1α.
Locations Predominantly found in Predominantly found in interscapular,
subcutaneous tissue, visceral cervical, and axillary regions, also
depots (around organs), bone around the neck, thorax, and kidney
marrow, and breast tissue. areas in humans.

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 Function Stores energy in the form of Specializes in thermogenesis to
triglycerides, acts as an insulator, generate heat by uncoupling oxidative
provides mechanical cushioning, phosphorylation, and helps in energy
and secretes adipokines. expenditure, and metabolic
regulation.

Lipid Storage:
1. Triglyceride Accumulation: Adipocytes primarily store energy in the form of
triglycerides. These triglycerides are synthesized from fatty acids and glycerol
through a process called lipogenesis.
2. Lipid Droplet Formation: Lipid droplets, containing triglycerides, cholesterol esters,
and other lipids, accumulate within the cytoplasm of adipocytes. These droplets are
surrounded by a phospholipid monolayer and associated proteins such as perilipins.
3. Regulation of Lipogenesis: Lipogenesis is regulated by various hormones and
signaling pathways. Insulin promotes lipogenesis by stimulating glucose uptake and
conversion to fatty acids. Conversely, hormones like glucagon and catecholamines
inhibit lipogenesis and promote lipolysis.
Lipid Mobilization (Lipolysis):
1. Activation of Lipolytic Pathways: During times of energy demand, lipolysis is
activated to mobilize stored triglycerides. Hormones such as catecholamines (e.g.,
epinephrine, norepinephrine), glucagon, and growth hormone stimulate lipolysis.
2. Activation of Lipases: Lipolysis involves the hydrolysis of triglycerides into glycerol
and fatty acids. This process is catalyzed by lipases, particularly hormone-sensitive
lipase (HSL) and adipose triglyceride lipase (ATGL).
3. Release of Fatty Acids: Fatty acids released from adipocytes are released into the
bloodstream, where they can be taken up and utilized as energy substrates by other
tissues such as muscle and liver.
4. Energy Production: The released glycerol can be used as a substrate for
gluconeogenesis in the liver, contributing to blood glucose levels during fasting or
prolonged exercise.
Integration with Pathology:
1. Obesity: Dysregulation of lipid storage and mobilization in adipocytes contributes to
obesity, characterized by excessive adipose tissue accumulation. In obesity, adipocyte
hypertrophy and hyperplasia, lead to metabolic dysfunction and associated health
risks such as insulin resistance, type 2 diabetes, and cardiovascular disease.
2. Lipodystrophy: Disorders characterized by abnormal adipose tissue distribution or
function, such as lipodystrophy syndromes, can result in metabolic disturbances and
insulin resistance.
3. Lipid Disorders: Dysfunction in lipid metabolism within adipocytes can lead to lipid
disorders such as hyperlipidemia, characterized by elevated levels of circulating
lipids, including triglycerides and cholesterol.
MCQ PEARLS
1. What is the primary component of connective tissue? → Extracellular Matrix (ECM)
2. Which type of fiber provides tensile strength and flexibility in connective tissue? →
Collagen Fibers
3. What cells are responsible for producing collagen and ground substance? →
Fibroblasts

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 4. Which connective tissue type has much ground substance and supports
microvasculature? → Loose (areolar) connective tissue
5. What type of connective tissue resists tearing and protects organs? → Dense irregular
connective tissue
6. Which type of connective tissue is primarily filled with parallel bundles of collagen? →
Dense regular connective tissue
7. Which embryonic connective tissue contains stem/progenitor cells? → Mesenchyme
8. What is the major function of adipose tissue? → Stores energy as triglycerides
9. Which glycosaminoglycan provides hydration and lubrication to tissues? →
Hyaluronic acid
10. What is fibrosis characterized by? → Excessive accumulation of fibrous tissue
11. Which type of fibrosis affects the liver? → Liver Cirrhosis
12. What is the role of macrophages in the immune system? → Phagocytosis
13. Which cells are involved in immediate hypersensitivity reactions? → Mast Cells
14. What type of adipose tissue specializes in thermogenesis? → Brown Adipose Tissue
15. Which factor regulates lipogenesis in adipocytes? → Insulin
16. What do plasma cells produce in response to specific antigens? → Antibodies
17. Which type of connective tissue forms a framework for blood-forming cells? →
Reticular connective tissue
18. What is the main component of the ground substance in connective tissue? → Water
19. What is the function of glycoproteins in the ground substance? → Provide structural
support
20. What is the primary role of cytokines produced by macrophages? → Regulate immune
responses

PAST UHS QUESTIONS

Q1. a) Name the cells found in loose areolar connective tissue (Supple 2008)
b) What are distinguishing features of plasma cells?

Q2. a) Draw and label light microscopic pictures of white adipose tissue stained with
haemotoxyline and eosin.
b. List any four functions of adipocytes (Annual 2010)

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