Cytology & Histology Doctoral Module

LESSON 4
HISTOLOGY

The definitive compendium of Epithelial, Connective, Nervous, and Muscle tissue — from molecular architecture to clinical pathology.

Animal Tissue Types
PART I: EPITHELIALClassification, Polarity, Junctions, Basement Membrane, Renewal.
PART II: CONNECTIVEAdipose, Cartilage, Bone Cells, Bone Structure, Ossification.
PART III: NERVOUSNeurons, Glia, Myelin, Nerves, Electrophysiology, Synapses.
PART IV: MUSCLESkeletal, Cardiac, Smooth, Sarcomere, NMJ, Clinical.
Part I

EPITHELIAL TISSUE

Covering, Lining, and Glandular Tissue — Exploring polarity, junctions, and classification.

Overview & Origin

Definition and Embryogenesis.

What is Epithelium?

Epithelial tissue covers body surfaces, lines body cavities, and forms glands. It creates a selective barrier between the external environment and the underlying connective tissue.

Key Properties

  • Cellularity: Cells are in close mutual contact (little intercellular matrix).
  • Polarity: Exhibits functional and morphologic polarity (Apical vs Basal).
  • Avascular: Contains no blood vessels; nutrients diffuse from connective tissue.
  • Basement Membrane: Separated from connective tissue by a specialized layer.

Embryological Origin

Epithelia are unique as they derive from all three embryonic germ layers.

EctodermMesodermEndodermEpidermis, CorneaMesothelium, EndotheliumGut Lining, Respiratory

Classification

Lining Epithelia Types.

Classification is descriptive and based on two factors: the number of cell layers and the shape of the surface cells.

Epithelial Tissue Classification
1. Simple Epithelia (One Layer)

Simple Squamous

Flat, Scale-like

Function: Exchange, Lubrication.
Location: Endothelium (vessels), Mesothelium (body cavities), Alveoli.

Simple Cuboidal

Cube-shaped

Function: Secretion, Absorption.
Location: Kidney tubules, Thyroid follicles, Duct linings.

Simple Columnar

Tall, Rectangular

Function: Absorption, Secretion.
Location: Stomach, Intestine, Gallbladder.

Special Case: Pseudostratified Columnar

Appears stratified because nuclei are at different levels, but all cells rest on the basement membrane. Found in the Trachea and Bronchial tree (often ciliated).

2. Stratified Epithelia (Multiple Layers)

Classified by the shape of the cells in the superficial (apical) layer.

1

Stratified Squamous

Keratinized: Epidermis (dry, protective, dead surface cells).
Non-Keratinized: Oral cavity, Esophagus, Vagina (moist, protective).

2

Stratified Cuboidal/Columnar

Rare. Found in large ducts of exocrine glands (sweat glands, salivary glands).

3

Transitional (Urothelium)

Specialized for distension. Surface cells are large and dome-shaped ("umbrella cells"). Found in Bladder, Ureters.

Cell Polarity

Apical, Lateral, and Basal Domains.

Cell Polarity

Apical Domain

Faces the lumen or external environment.

Modifications
  • Microvilli: Actin core. Increase absorption (e.g., Intestine).
  • Stereocilia: Long microvilli. Sensory (Ear) or absorption (Epididymis).
  • Cilia: Microtubule core (9+2). Movement of fluid (e.g., Trachea).

Lateral Domain

Contacts adjacent cells.

Features
  • Occluding Junctions: Tight seals.
  • Anchoring Junctions: Mechanical strength.
  • Gap Junctions: Communication.

Basal Domain

Rests on the basement membrane.

Structures
  • Basement Membrane: Attachment & filtration.
  • Hemidesmosomes: Anchor cell to matrix.
  • Infoldings: Increase surface area (Ion transport).

Junctional Complex

Cell-to-Cell Adhesion and Communication.

Specialized structures in the lateral domain that adhere cells together and allow communication.

1

Tight Junction

Zonula Occludens

Most apical. Seals intercellular space to prevent leakage. Formed by Claudins and Occludins. Defines cell polarity.

2

Adherens Junction

Zonula Adherens

Below tight junctions. Encircles cell. Mediated by E-Cadherin (Ca++ dependent). Links to Actin filaments via Catenins.

3

Desmosome

Macula Adherens

Spot-like adhesion. Mediated by Desmogleins. Links to Intermediate Filaments (Keratin). Provides mechanical resistance.

4

Gap Junction

Communicating

Formed by Connexons (6 connexins). Allows passage of ions and small molecules. Coordinates activity (e.g., heart beat).

Tight JunctionAdherens JunctionDesmosomeGap Junction

Basal Domain

Interaction with the underlying tissue.

Basement Membrane

A specialized layer of extracellular matrix that separates the epithelium from the connective tissue.

  • Lamina Lucida: Electron-lucent layer just below the cell. Contains Integrins, Laminin.
  • Lamina Densa: Electron-dense layer. Contains Type IV Collagen, Perlecan.
  • Reticular Lamina: Produced by connective tissue. Type III (Reticular) and Type VII (Anchoring) Collagen.

Hemidesmosomes

Junctions that anchor the basal domain of the epithelial cell to the basal lamina.

  • Transmembrane Protein: Integrins (α6β4).
  • Intracellular Link: Plectin (connects to Intermediate Filaments).
  • Extracellular Link: Laminin-332 and Collagen IV.

Cell Renewal

Turnover and Stem Cells.

Epithelia belong to the category of continuously renewing cell populations. The rate depends on the tissue.

Small Intestine

Turnover Rate4-6 Days

Stem cells in crypts.

Skin (Epidermis)

Turnover Rate~47 Days

Stem cells in Stratum Basale.

Epithelial Review

Key Terminology.

TermDefinition
EndotheliumSimple squamous epithelium lining blood vessels.
MicrovilliApical projections containing actin; increase surface area for absorption.
ConnexonThe functional unit of a gap junction, formed by 6 connexins.
MesotheliumSimple squamous epithelium lining body cavities (Pleura, Peritoneum).
Part II

CONNECTIVE TISSUE

The Support System — From Fat Cells to Bone Matrix.

Overview & Classification

The Matrix and Cells.

Connective tissue comprises a diverse group of cells embedded within a tissue-specific Extracellular Matrix (ECM). Unlike epithelium, cells are widely separated by this matrix.

Connective Tissue Types

Components

  • Cells: Fibroblasts, Adipocytes, Immune cells.
  • Fibers: Collagen (Strength), Elastic (Stretch), Reticular (Support).
  • Ground Substance: Amorphous gel (GAGs, Proteoglycans).

Classification

1. Connective Tissue Proper
Loose, Dense (Regular/Irregular)
2. Specialized Connective Tissue
Adipose, Cartilage, Bone, Blood

Adipose Tissue

Energy Storage & Insulation.

A specialized connective tissue where Adipocytes predominate. It is the largest energy reservoir in the body.

Adipose Tissue
Unilocular

White Adipose Tissue

  • Structure: Single huge lipid droplet. Nucleus flattened at periphery ("Signet ring").
  • Function: Energy storage, Insulation, Cushioning.
  • Location: Hypodermis, around organs (kidneys).
Multilocular

Brown Adipose Tissue

  • Structure: Multiple small lipid droplets. Central nucleus. Many mitochondria (Iron = Brown color).
  • Function: Thermogenesis (Heat production) via UCP1 (Thermogenin).
  • Location: Newborns, Hibernating animals.

Cartilage

Flexible Support.

Avascular tissue. Cells (Chondrocytes) reside in lacunae within a firm gel-like matrix.

Cartilage

Hyaline

Glassy Appearance

  • Matrix: Type II Collagen (invisible), Aggrecan, Water (60-80%).
  • Location: Articular surfaces, Trachea, Nose, Fetal skeleton.
  • Perichondrium: Present (except articular).

Elastic

Flexible

  • Matrix: Elastic fibers + Type II Collagen.
  • Location: External Ear (Pinna), Epiglottis.
  • Perichondrium: Present.

Fibrocartilage

Tough

  • Matrix: Thick Type I Collagen bundles + Type II.
  • Location: Intervertebral discs, Pubic symphysis, Menisci.
  • Perichondrium: Absent.

Bone Cells

The Architects of Bone.

Bone Cells

Osteoblast

The Builder

Secretes organic matrix (Osteoid) including Type I Collagen. Initiates mineralization. Located on bone surfaces.

Osteocyte

The Sensor

Mature bone cell trapped in lacunae. Senses mechanical stress. Communicates via canaliculi.

Osteoclast

The Destroyer

Large, multinucleated cell derived from monocytes. Resorbs bone using acid and enzymes. Sits in Howship's lacunae.

Bone Structure

Compact vs. Spongy Bone.

Compact Bone: The Osteon

The functional unit of compact bone is the Osteon (Haversian System).

Structural Components

  • Haversian Canal
    Central channel containing blood vessels and nerves.
  • Lamellae
    Concentric rings of calcified matrix.
  • Lacunae
    Small cavities containing Osteocytes.
  • Canaliculi
    Tiny channels connecting lacunae for nutrient exchange.
  • Volkmann's
    Perpendicular channels connecting Haversian canals.

Ossification

Bone Formation Types.

Types of Ossification

Intramembranous

Direct formation of bone from mesenchymal connective tissue.

  • Mechanism: Mesenchymal cells differentiate directly into osteoblasts.
  • Examples: Flat bones of the skull, Clavicle, Mandible.

Endochondral

Bone forms by replacing a hyaline cartilage model.

  • Mechanism: Cartilage calcifies and is replaced by bone.
  • Growth Plate: Epiphyseal plate allows longitudinal growth.
  • Examples: Long bones (Femur, Humerus), Vertebrae.

Epiphyseal Plate Zones (Top to Bottom)

1. Resting Zone (Cartilage reserve)
2. Proliferation Zone (Mitosis)
3. Hypertrophic Zone (Cell enlargement)
4. Calcification Zone (Matrix hardens)
5. Ossification Zone (Bone deposition)

Connective Tissue Review

Key Terminology.

TermDefinition
ECMExtracellular Matrix; ground substance + fibers (collagen, elastic, reticular).
ChondrocyteMature cartilage cell maintaining the matrix.
PeriosteumDense connective tissue covering bone (except articular surfaces). Essential for growth/repair.
LacunaA small cavity in bone or cartilage containing an osteocyte or chondrocyte.
HydroxyapatiteCalcium phosphate crystals that give bone its hardness.
Part III

NERVOUS TISSUE

Neurons, Glia, Nerves, and Electrophysiology.

Overview & Organization

The Master Control System.

Nervous tissue allows for rapid and specific communication between different areas of the body. It receives sensory input, processes information (integration), and dictates motor output. It is derived from the Ectoderm (specifically the Neural Tube and Neural Crest).

Central Nervous System
CNS

Central Nervous System

  • Components: Brain (Encephalon) and Spinal Cord.
  • Function: Integration and command center.
  • Tissue: Contains neurons and glial cells (Astrocytes, Oligodendrocytes, Microglia, Ependymal).
  • Environment: Protected by the Blood-Brain Barrier (BBB).
PNS

Peripheral Nervous System

  • Components: Cranial nerves (12 pairs), Spinal nerves (31 pairs), and Ganglia.
  • Function: Communication lines between the CNS and the rest of the body.
  • Tissue: Neurons (Ganglia), Schwann cells, Satellite cells.

The Neuron

The Functional Unit.

Neurons are highly specialized for excitability (generating action potentials) and conductivity. They are "post-mitotic" cells (do not divide).

Neuron Structure
1. Soma (Perikaryon)

The metabolic center.

  • Nucleus: Large, spherical, euchromatic (pale), with a prominent nucleolus ("Owl's eye" appearance).
  • Nissl Bodies: Large granules of Rough ER and free ribosomes. Site of intense protein synthesis. Absent in the axon hillock.
  • Cytoskeleton: Neurofilaments (intermediate filaments) for structure, Microtubules for transport.
2. Dendrites

The Input Zone.

  • Short, tapering, branching extensions.
  • Receive signals from other neurons.
  • Dendritic Spines: Small protrusions that increase surface area for synapses. Plasticity of spines is key to memory/learning.
  • Contain Nissl bodies in proximal parts.
3. Axon

The Conducting Zone.

  • Single, long process. Arises from the Axon Hillock (trigger zone).
  • Axoplasm: Contains mitochondria and microtubules but NO rough ER (no protein synthesis).
  • Initial Segment: Site where Action Potential is generated. High density of Na+ channels.
  • Ends in Terminal Boutons.

Axonal Transport

The Neuron's Highway System.

Since the axon contains no machinery for protein synthesis, everything must be shipped from the soma. This occurs via Microtubules acting as tracks and Motor Proteins carrying the cargo.

Axonal Transport

Anterograde Transport

Direction: Soma → Axon Terminal

Motor Protein: Kinesin (+ end directed)

  • Fast Component: (400 mm/day). Carries mitochondria, vesicles with neurotransmitters, channel proteins.
  • Slow Component: (1-5 mm/day). Carries cytoskeletal elements (actin, neurofilaments) and soluble enzymes.

Retrograde Transport

Direction: Axon Terminal → Soma

Motor Protein: Dynein (- end directed)

  • Fast Only: (200 mm/day).
  • Carries worn-out organelles for degradation (lysosomes).
  • Carries growth factors (NGF) and signal molecules to the nucleus.
Clinical Correlate

Viruses & Toxins: Rabies, Polio, Herpes simplex, and Tetanus toxin hitch a ride on Retrograde Transport to reach the CNS from the periphery.

Neuronal Classification

Structural & Functional.

Structural (Number of Processes)

  • Multipolar
    1 Axon + Many Dendrites. The most common type. Includes motor neurons and interneurons.
  • Bipolar
    1 Axon + 1 Dendrite. Rare. Found in special senses: Retina, Olfactory epithelium, Vestibulocochlear ganglia.
  • Pseudounipolar
    Single process that splits into a peripheral branch (receptor) and central branch (CNS). Sensory neurons in Dorsal Root Ganglia.

Functional (Signal Direction)

  • Sensory (Afferent)
    Transmit impulses TO the CNS from receptors. Usually pseudounipolar.
  • Motor (Efferent)
    Transmit impulses FROM the CNS to effectors (muscles, glands). Multipolar.
  • Interneurons
    Connect sensory and motor neurons within the CNS. 99% of all neurons. Responsible for integration and reflex arcs.

Neuroglia (Glia)

The Support Crew.

Glia ("Glue") are non-neuronal cells that support, nourish, and protect neurons. They are mitotic (can divide) and outnumber neurons significantly.

Types of Neuroglia

Central Nervous System (CNS)

1. Astrocytes

Most abundant.

  • Star-shaped with "perivascular feet".
  • Form the Blood-Brain Barrier (BBB) by wrapping capillaries.
  • Regulate ionic environment (K+ buffering).
  • Recycle neurotransmitters (Glutamate/GABA).
  • Form scar tissue (gliosis) after injury.
2. Oligodendrocytes

"Few tree branches".

  • Form the Myelin Sheath in the CNS.
  • One cell can wrap up to 50 different axon segments.
  • Inhibits axon regeneration.
3. Microglia

Small, thorny processes.

  • Derived from Monocytes (Mesoderm), unlike others (Neuroectoderm).
  • Phagocytic: The immune defense (macrophages) of the CNS.
  • Activated by inflammation/injury.
4. Ependymal Cells

Cuboidal/Columnar epithelial-like.

  • Line the ventricles of the brain and central canal of the cord.
  • Possess cilia and microvilli.
  • Produce and circulate Cerebrospinal Fluid (CSF) (Choroid plexus).

Peripheral Nervous System (PNS)

Schwann Cells (Neurolemmocytes)
  • Form the Myelin Sheath in the PNS.
  • 1 cell = 1 axon segment.
  • Vital for axon regeneration (form a regeneration tube).
Satellite Cells
  • Small, flat cells surrounding neuron cell bodies in Ganglia.
  • Regulate nutrient/waste exchange (similar to astrocytes).

The Myelin Sheath

Insulation for Speed.

Myelin is a whitish, fatty (lipid-rich) substance formed by concentric wrapping of glial plasma membranes around axons. It acts as an electrical insulator, preventing charge leakage.

Myelin Sheath

Structure

  • Composition: 80% Lipid, 20% Protein.
  • Nodes of Ranvier: Gaps in the sheath (approx 1 μm wide). High density of Voltage-Gated Na+ channels. Site of action potential regeneration.
  • Internodes: The insulated segments between nodes.

Saltatory Conduction

In myelinated axons, the action potential "jumps" (saltare) from node to node. This is:

  • Faster: Up to 120 m/s (vs 1-2 m/s in unmyelinated).
  • Energy Efficient: Na+/K+ pumps only need to work at the nodes.
Clinical Correlate: Demyelination
  • Multiple Sclerosis (MS): Autoimmune destruction of Oligodendrocytes (CNS). Leads to visual disturbances, muscle weakness, speech issues.
  • Guillain-Barré Syndrome: Autoimmune attack on Schwann cells (PNS). Ascending paralysis.

Peripheral Nerve Structure

Organization of Nerve Fibers.

A "nerve" in the PNS is a cable-like bundle of axons enclosed by successive layers of connective tissue, similar to skeletal muscle organization.

Peripheral Nerve Anatomy
1
Epineurium

Dense irregular connective tissue wrapping the entire nerve. Provides tensile strength and protection.

2
Perineurium

Specialized connective tissue wrapping fascicles (bundles of axons).
Crucial: Forms the Blood-Nerve Barrier via tight junctions.

3
Endoneurium

Loose delicate connective tissue (reticular fibers) wrapping individual fibers (outside the myelin/Schwann cell). Electrically isolates fibers.

Electrophysiology

The Spark of Life.

1. Resting Membrane Potential (-70 mV)

The neuron is polarized (inside is negative relative to outside).

  • Na+/K+ Pump: Actively pumps 3 Na+ OUT and 2 K+ IN (electrogenic). Creates gradients.
  • Leak Channels: Membrane is much more permeable to K+ than Na+. K+ leaks out down its gradient, leaving negative anions behind. This is the primary determinant of RMP.

2. The Action Potential

Action Potential Graph

An "All-or-None" electrical event propagating down the axon.

Threshold(-55 mV). Point of no return. Voltage-gated Na+ channels open.
DepolarizationNa+ rushes IN rapidly. Potential spikes to +30 mV.
RepolarizationNa+ channels inactivate. Voltage-gated K+ channels open. K+ rushes OUT. Potential drops.
HyperpolarizationK+ channels close slowly. Membrane becomes more negative than RMP (-90 mV).
Toxins

Tetrodotoxin (Pufferfish): Blocks Voltage-gated Na+ channels. Prevents depolarization -> Paralysis.

Local Anesthetics (Lidocaine): Also block Na+ channels, stopping pain signals.

The Synapse

Signal Transmission.

The specialized junction where a neuron communicates with another cell. Most are Chemical Synapses.

Chemical Synapse

Transmission Steps:

  1. Action potential reaches the Presynaptic Terminal.
  2. Voltage-gated Calcium (Ca2+) channels open. Ca2+ enters.
  3. Ca2+ triggers synaptic vesicles to fuse with membrane (Exocytosis).
  4. Neurotransmitter is released into the Synaptic Cleft (20-30 nm gap).
  5. Neurotransmitter binds to receptors on the Postsynaptic Membrane.
  6. Ion channels open, causing a Graded Potential.
  7. Neurotransmitter is removed (reuptake, enzymatic degradation, or diffusion).
Excitatory (EPSP)

Opens Na+ channels. Depolarizes postsynaptic cell. Increases chance of AP. (e.g., Glutamate, ACh).

Inhibitory (IPSP)

Opens K+ or Cl- channels. Hyperpolarizes postsynaptic cell. Decreases chance of AP. (e.g., GABA, Glycine).

Part IV

MUSCLE TISSUE

From the Angstrom-scale sliding filaments to the macroscopic generation of force. Skeletal, Cardiac, and Smooth muscle biology.

Classification of Muscle Tissue

The contractile machinery of the body. Muscle tissue converts chemical energy (ATP) into mechanical energy (Force).

Skeletal

Voluntary • Striated

  • Morphology: Long, cylindrical, multinucleated syncytium.
  • Nuclei: Peripheral (under sarcolemma).
  • Regeneration: Satellite cells (limited).
  • Function: Posture, movement, heat.

Cardiac

Involuntary • Striated

  • Morphology: Branched, short cylinders.
  • Nuclei: Single, central (halo of glycogen).
  • Junctions: Intercalated Discs.
  • Regeneration: None (fibrosis).

Smooth

Involuntary • Non-Striated

  • Morphology: Fusiform (spindle).
  • Nuclei: Single, central (corkscrew).
  • Structure: Dense bodies (no sarcomeres).
  • Regeneration: Active (mitosis).

SKELETAL MUSCLE

Structure, Organization, and the Molecular Engine.

Connective Tissue Hierarchy

The transmission of force relies on the continuity of connective tissue layers, which merge to form tendons (Myotendinous Junction). These layers also convey neurovascular bundles.

Skeletal Muscle Structure Hierarchy
  • EpimysiumDense irregular connective tissue surrounding the entire muscle.
  • PerimysiumConnective tissue surrounding fascicles (bundles of fibers). Main route for larger nerves/vessels.
  • EndomysiumDelicate reticular fibers (Type III Collagen) surrounding individual fibers. Supports capillaries and synaptic terminals.

Microanatomy & Organelles

Muscle Fiber Anatomy
  • Sarcolemma: Plasma membrane. Forms T-Tubules.
  • Sarcoplasm: Cytoplasm. Contains Myoglobin (O2 storage) and Glycogen.
  • Sarcoplasmic Reticulum (SR): Specialized SER. Forms Terminal Cisternae. Stores Ca2+ (bound to Calsequestrin).
  • Triad: 1 T-Tubule + 2 Terminal Cisternae. Located at the A-I Junction. Crucial for E-C coupling.
  • Satellite Cells: Stem cells located between the basal lamina and sarcolemma. Responsible for limited regeneration.

The Sarcomere

Functional Unit: Z-line to Z-line (2.5 μm relaxed)

Z-DiscZ-DiscM-LineA Band (Dark, Anisotropic)I Band (Light, Isotropic)I BandH ZONE
Sarcomere Structure Diagram

Note: During contraction, the I-Band and H-Zone shorten. The A-Band length remains constant.

Excitation-Contraction Coupling

Excitation-Contraction Coupling

The Sequence of Events

  1. Neuromuscular Transmission: Action Potential travels down motor neuron axon -> Voltage-gated Ca2+ channels open -> Ca2+ entry triggers exocytosis of synaptic vesicles containing Acetylcholine (ACh).
  2. Sarcolemma Depolarization: ACh diffuses across synaptic cleft -> Binds Nicotinic ACh receptors on the motor end plate -> Na+ influx generates End Plate Potential (EPP) -> Action Potential sweeps across sarcolemma. ACh is degraded by Acetylcholinesterase.
  3. T-Tubule Transmission: AP dives into T-tubules. The voltage change is sensed by Dihydropyridine Receptors (DHPR) (L-type Ca2+ channels).
  4. Mechanical Coupling: In skeletal muscle, DHPR is mechanically coupled to the Ryanodine Receptor (RyR1) on the SR. The conformational change of DHPR physically pulls RyR1 open (like a cork).
  5. Calcium Flood: Ca2+ rushes out of SR into sarcoplasm (increasing from 0.1μM to 10μM).
  6. Cross-Bridge Activation: Ca2+ binds to Troponin C -> Troponin complex changes shape -> Moves Tropomyosin away from actin active sites -> Myosin binds Actin -> Power Stroke (ATP hydrolysis).
  7. Relaxation: SERCA pumps (Ca2+-ATPase) actively pump Ca2+ back into SR. Calsequestrin binds Ca2+ in SR to reduce free Ca2+ gradient.

Rigor Mortis

After death, ATP production stops.
1. Without ATP, SERCA pumps fail -> Ca2+ leaks from SR -> Binding sites exposed -> Cross-bridges form.
2. Crucially: ATP is required for the Myosin head to detach from Actin. Without ATP, myosin stays locked (Rigor complexes).
3. Muscles remain stiff until proteolytic enzymes break down the sarcomeres (15-24 hours).

Duchenne Muscular Dystrophy (DMD)

Defect: Mutation in Dystrophin gene (X-linked).
Function: Dystrophin links actin cytoskeleton to ECM (Dystroglycan complex), stabilizing the membrane during contraction.
Pathology: Membrane tears -> Ca2+ influx -> Protease activation -> Necrosis. Muscle is replaced by fat (Pseudohypertrophy).

Innervation & Proprioception

The Motor Unit

Defined as one alpha-motor neuron and all the muscle fibers it innervates. Fibers of a unit are scattered throughout the muscle.

  • Fine Control: 1 neuron : 5-10 fibers (Eye, Finger).
  • Coarse Control: 1 neuron : 1000+ fibers (Back, Thigh).
  • Recruitment: Small units (Type I) are recruited first; larger units (Type II) recruited for more force (Size Principle).

Myasthenia Gravis

Autoimmune disease where antibodies block/destroy Nicotinic ACh receptors at the NMJ. Causes progressive weakness (ptosis, diplopia). Treatment: AChE inhibitors.

The Muscle Spindle (Stretch Sensor)

The Muscle Spindle

Detects changes in length. Activates stretch reflex.

CARDIAC MUSCLE

Endurance, Automatism, and Intercalated Discs.

Structural Unique Features

  • Cardiocytes: Short, cylindrical, and branched cells (Y-shaped). This allows for a complex 3D network.
  • Nucleus: Typically single, pale, large, and centrally located. Occasionally binucleated.
  • Metabolism: Mitochondria are huge (40% vol). Depends on aerobic metabolism (Fatty acids > Glucose). Very little glycogen compared to skeletal.
  • Diads: T-tubules are wider and located at the Z-line (not A-I junction). They associate with only one terminal cisterna (Diad).

Endocrine Function

Atrial cells contain specific granules producing Atrial Natriuretic Peptide (ANP).

Atrial Natriuretic Peptide
Stimulus: Atrial Stretch (High Blood Volume).
Action: Acts on Kidney -> Increases Na+ and H2O excretion -> Decreases Blood Volume/Pressure.

The Intercalated Disc

The structural and electrical bridge between cardiomyocytes.

The Intercalated Disc
Transverse Region (Force)

Perpendicular to contraction. Holds cells together mechanically.

Lateral Region (Communication)

Parallel to contraction. Low electrical resistance for AP propagation.

Conduction & Physiology

CICR Mechanism

  1. Trigger: Action Potential opens L-type Ca2+ channels (DHPR) in T-tubule.
  2. Influx: Extracellular Ca2+ enters. (Note: Not enough for contraction by itself).
  3. Activation: This "Trigger Calcium" binds to RyR2 on the SR.
  4. Release: RyR2 opens (Calcium-Induced Calcium Release). Massive Ca2+ flood.
  5. Regulation: Sympathetic system phosphorylates Phospholamban on the SR, speeding up SERCA pumps -> Faster relaxation (Lusitropy) and stronger contraction (Inotropy).

Purkinje Fibers (Conduction)

Modified cardiomyocytes specialized for electrical conduction, not contraction.

  • Structure: Larger diameter than ordinary myocytes. Paler cytoplasm (High Glycogen, few myofibrils).
  • Location: Subendocardial layer.
  • Function: Rapid transmission of impulse from AV bundle to ventricular myocardium.
  • Junctions: Massive number of gap junctions.
Myocardial Infarction: Cardiac cells do not divide. Dead cells are replaced by fibroblasts forming a collagen scar. This scar creates an electrical block (arrhythmia risk) and mechanical weakness (heart failure).

SMOOTH MUSCLE

Visceral Control. Plasticity, Economy, and the Latch State.

Ultrastructure

  • Shape: Fusiform (spindle). Tapered ends overlap.
  • Filaments: No sarcomeres. Actin and Myosin criss-cross the cell, anchored to Dense Bodies (functional Z-lines).
  • Dense Bodies: Located in cytoplasm and plasma membrane. Contain α-actinin. Anchor Intermediate Filaments (Desmin/Vimentin) which transmit force.
  • Caveolae: Membrane invaginations rich in Ca2+ channels. Analogous to T-tubules but less organized.
  • Regeneration: Unique among muscles. Retains mitotic activity. Example: Uterus during pregnancy (Hypertrophy + Hyperplasia). Pericytes can also differentiate into smooth muscle.

Innervation: "En Passant"

No structured Neuromuscular Junction.

Varicosities

Autonomic axons have swellings (varicosities) containing neurotransmitters (NE, ACh). They release transmitter into the general vicinity of the muscle sheet (Diffuse Junction).

  • Single-Unit (Visceral): Cells connected by Gap Junctions. Contract as a wave (Gut, Uterus). Pacemaker activity.
  • Multi-Unit: Independent cells. Rich nerve supply. Precise control (Iris, Vas deferens).

Contraction Mechanism

The "Corkscrew" Shortening.

RelaxedContracted

Molecular Regulation

The Calmodulin-MLCK Pathway

Smooth muscle lacks Troponin. It relies on Myosin-based regulation.

  1. Stimulation: Neural (ANS), Hormonal (Oxytocin, Histamine), or Stretch.
  2. Ca2+ Increase: Influx + SR Release (IP3 pathway).
  3. Calmodulin: 4 Ca2+ ions bind to Calmodulin (CaM).
  4. Activation: Ca2+-CaM complex activates Myosin Light Chain Kinase (MLCK).
  5. Phosphorylation: MLCK phosphorylates the Myosin Light Chain. This unfolds the myosin tail and activates the ATPase.
  6. Contraction: Cycling occurs (slower ATP hydrolysis than skeletal).
The Latch State
The Latch State

Unique to smooth muscle. Once contracted, Myosin Phosphatase can remove the phosphate while myosin is still attached to actin. This creates a "Latch Bridge" that maintains tension with near-zero ATP consumption. Essential for tonic contraction (sphincters, blood vessels).

Asthma & Bronchoconstriction

Bronchioles have smooth muscle walls. In asthma, mast cells release Histamine/Leukotrienes. These bind GPCRs on smooth muscle -> IP3 pathway -> Ca2+ Release -> Sustained contraction (Bronchospasm).
Treatment: β2-Agonists (Albuterol) increase cAMP -> PKA -> Inhibits MLCK -> Relaxation.

The Grand Comparison

Summary of key histological and physiological differences.

FeatureSkeletalCardiacSmooth
Cell ShapeLong CylindricalBranched CylindricalFusiform (Spindle)
NucleusMany, Peripheral1-2, Central1, Central
StriationsYes (Sarcomeres)Yes (Sarcomeres)No (Dense Bodies)
T-TubulesYes (Triads at A-I)Yes (Diads at Z-line)No (Caveolae)
Ca2+ SensorTroponin CTroponin CCalmodulin
Ca2+ SourceSR OnlyExtracellular (Trigger) + SRExtracellular + SR
ControlVoluntary (Somatic)Involuntary (Autonomic)Involuntary (Autonomic)
RegenerationLimited (Satellite Cells)None (Fibrosis)High (Mitosis/Pericytes)
SecretoryNoYes (ANP)Yes (ECM molecules)