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PHYSIOLOGY

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UNIT 1: NERVE MUSCLE PHYSIOLOGY

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Q. What is a Nerve Fiber? Classify it.

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Q. What is Resting Membrane Potential (RMP)? Explain its mechanism.

1. Selective permeability - at rest, membrane is more permeable to K+ than Na+
2. K+ diffuses out along concentration gradient → inside becomes negative
3. Na+ is kept out - Na+/K+ ATPase pump actively transports 3 Na+ out and 2 K+ in
4. Large negatively charged proteins remain inside the cell → maintain negativity
5. Donnan equilibrium - K+ distribution reaches equilibrium between chemical and electrical forces

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Q. Describe the Action Potential of a nerve fiber with a diagram.

• Stimulus opens voltage-gated Na+ channels
• Na+ rushes INTO the cell (Na+ influx)
• Membrane potential rises from -70 mV to +35 mV
• This is called "overshoot"

• Na+ channels close (inactivation)
• Voltage-gated K+ channels open → K+ flows OUT
• Membrane potential falls back toward -70 mV

• K+ channels close slowly → membrane goes below -70 mV (about -90 mV)
• Na+/K+ pump restores ionic balance → returns to -70 mV

• Absolute refractory period - No stimulus can generate another AP (Na+ channels inactivated)
• Relative refractory period - Only a stronger than normal stimulus can generate AP

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Q. What is Saltatory Conduction?

1. Myelinated fibers have insulating myelin sheath between Nodes of Ranvier
2. Ionic current can only flow at the nodes (where membrane is exposed)
3. Depolarization at one node creates local current that jumps to the next node
4. The impulse "jumps" from node to node

• Much faster conduction velocity (up to 120 m/s in myelinated vs. 0.5 m/s in unmyelinated)
• Energy efficient (only nodes depolarize, less Na+/K+ pump activity needed)

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Q. Describe Neuromuscular Transmission (NMJ - Neuromuscular Junction).

• Motor nerve terminal (presynaptic)
• Synaptic cleft (gap of ~20-50 nm)
• Motor end plate (postsynaptic - thickened muscle membrane with junctional folds)
• Synaptic vesicles contain Acetylcholine (ACh)
• Nicotinic receptors (NM type) on postsynaptic membrane at tops of junctional folds

1. Nerve action potential arrives at the motor nerve terminal
2. Depolarization opens voltage-gated Ca2+ channels → Ca2+ enters the terminal
3. Ca2+ triggers exocytosis of synaptic vesicles → ACh is released into synaptic cleft
4. ACh diffuses across the cleft and binds to nicotinic receptors on motor endplate
5. Receptor activation opens Na+/K+ channels → Na+ influx → produces Endplate Potential (EPP)
6. EPP depolarizes adjacent muscle membrane → generates muscle action potential
7. Muscle action potential spreads along muscle fiber and causes contraction
8. ACh is broken down by Acetylcholinesterase (AChE) → choline is taken back up (reuptake)

• Curare / Tubocurarine - competitive blocker (non-depolarizing)
• Succinylcholine - depolarizing blocker
• Neostigmine - inhibits AChE (increases ACh)

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Q. Describe the mechanism of Muscle Contraction (Sliding Filament Theory).

1. Muscle AP spreads down the T-tubules into the muscle fiber
2. T-tubules are connected to the Sarcoplasmic Reticulum (SR)
3. SR releases Ca2+ into the sarcoplasm
4. Ca2+ binds to Troponin C (on thin filament)
5. Troponin-tropomyosin complex shifts → actin active sites exposed
6. Myosin cross-bridge attaches to actin active site
7. Power stroke - myosin head rotates (uses ATP hydrolysis) → thin filament slides inward
8. New ATP binds to myosin → cross-bridge detaches → myosin returns to original position
9. Cycle repeats → sarcomere shortens → muscle contracts
10. When stimulation stops, Ca2+ pumped back into SR → Troponin-Tropomyosin covers actin sites again → relaxation

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UNIT 2: SYNAPSE

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Q. Define Synapse. Describe the types and properties of synapses.

• Presynaptic terminal (knob): Contains mitochondria and synaptic vesicles with neurotransmitters
• Synaptic cleft: Gap between pre and postsynaptic membranes (~20-50 nm)
• Postsynaptic membrane: Has specific receptors for neurotransmitters

1. One-way conduction - impulse passes only from pre to post synaptic neuron
2. Synaptic delay - 0.3 to 0.5 ms delay due to release and diffusion of neurotransmitter
3. Fatigue - repeated stimulation depletes neurotransmitter stores
4. Summation - EPSP's can summate (spatial and temporal)
5. Convergence - many neurons synapse on one neuron
6. Divergence - one neuron synapses on many neurons
7. After-discharge - continued discharge after stimulus ends

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Q. What are Excitatory Post-Synaptic Potentials (EPSP) and Inhibitory Post-Synaptic Potentials (IPSP)?

• When an excitatory neurotransmitter (e.g., Glutamate) is released and binds to receptors
• Opens Na+/K+ channels → Na+ influx → depolarization of postsynaptic membrane
• Membrane potential moves from -70 mV toward threshold (-55 mV)
• Does NOT generate AP by itself, but brings membrane closer to threshold

• When an inhibitory neurotransmitter (e.g., GABA) is released
• Opens Cl- channels (or K+ channels) → Cl- influx (or K+ efflux) → hyperpolarization
• Membrane potential moves further from threshold (e.g., -70 to -80 mV)
• Makes it harder to fire an AP

• Temporal summation - repeated impulses from ONE neuron arrive rapidly → EPSPs add up
• Spatial summation - impulses from MANY neurons arrive simultaneously → EPSPs add up
• When summated EPSP reaches threshold (-55 mV) → Action Potential is generated

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Q. Write about important neurotransmitters.

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UNIT 3: SPECIAL SENSES

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Q. Describe the mechanism of Vision / Photoreception.

• Rods - for dim light / black & white vision; contain Rhodopsin (visual purple)
• Cones - for bright light / color vision; contain Iodopsin; 3 types (Red, Green, Blue)

1. Rhodopsin = Opsin (protein) + 11-cis-retinal (Vitamin A derivative)
2. Light hits rhodopsin → 11-cis-retinal converts to all-trans-retinal (bleaching)
3. This conformational change activates Transducin (G-protein)
4. Transducin activates Phosphodiesterase (PDE)
5. PDE breaks down cGMP → cGMP levels fall
6. Fall in cGMP → Na+ channels close → Na+ entry stops
7. Membrane hyperpolarizes (from -40 mV to -70 mV)
8. This hyperpolarization is the receptor potential → transmitted as visual signal
9. In dark: Na+ channels open (dark current) → rod is depolarized
10. Recovery: all-trans-retinal is converted back to 11-cis-retinal (needs Vitamin A)

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Q. Describe the mechanism of Hearing / Auditory Physiology.

1. Sound waves cause vibration of tympanic membrane
2. Vibration transmitted through ossicular chain (Malleus → Incus → Stapes)
3. Stapes vibrates against oval window → produces waves in perilymph of cochlea
4. Perilymph waves cause movement of basilar membrane
5. Basilar membrane movement deflects hair cells of the Organ of Corti
6. Stereocilia of hair cells bend → K+ channels open → K+ enters from endolymph
7. Hair cell depolarizes → releases neurotransmitter (Glutamate)
8. Cochlear nerve (CN VIII) transmits impulse to brain

• High frequency sounds cause maximum vibration at the base of cochlea
• Low frequency sounds cause maximum vibration at the apex of cochlea

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Q. Write about Taste (Gustation) and Smell (Olfaction) briefly.

• Receptor: Taste buds on tongue (papillae - fungiform, circumvallate, foliate)
• 5 primary tastes: Sweet, Sour, Salty, Bitter, Umami (savory)
• Nerve supply: Anterior 2/3 tongue - Chorda tympani (CN VII); Posterior 1/3 tongue - CN IX
• Pathway: → Nucleus Tractus Solitarius → Thalamus → Gustatory cortex (parietal lobe)

• Receptor: Olfactory receptor neurons in olfactory epithelium (superior nasal cavity)
• Mechanism: Odorant binds to receptor → G-protein → adenylyl cyclase → cAMP → opens cation channels → depolarization
• Pathway: Olfactory nerve (CN I) → Olfactory bulb → Olfactory cortex (pyriform cortex)
• Only sense that does NOT relay through thalamus (direct to cortex)
• Anosmia = loss of smell (seen in COVID-19, head injury)

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BIOCHEMISTRY

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UNIT 4: VITAMINS

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Q. Classify vitamins. Write about Fat-Soluble Vitamins.

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FAT-SOLUBLE VITAMINS

VITAMIN A (Retinol)

1. Vision - component of Rhodopsin (11-cis-retinal + opsin); essential for dark adaptation
2. Growth and differentiation - regulates gene expression via nuclear receptors (RAR, RXR)
3. Epithelial integrity - maintains mucus-secreting epithelium (prevents keratinization)
4. Immune function - anti-infective vitamin
5. Reproduction - spermatogenesis, fetal development

• Night blindness (Nyctalopia) - earliest sign
• Xerophthalmia - dryness of conjunctiva and cornea
• Bitot's spots - triangular foamy patches on conjunctiva (pathognomonic)
• Keratomalacia - corneal softening → blindness
• Xerosis - dry, scaly skin
• Follicular hyperkeratosis - toad skin appearance
• Increased susceptibility to infections

• Headache, vomiting, skin desquamation
• Pseudotumor cerebri (raised intracranial pressure)
• Teratogenic in pregnancy

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VITAMIN D (Calciferol)

• Dietary: Fatty fish, egg yolk, dairy, fish liver oil
• Skin synthesis (major source): 7-dehydrocholesterol → UV light → Cholecalciferol (Vitamin D3)

1. Increases Ca2+ absorption from intestine (induces calcium-binding protein - Calbindin)
2. Increases phosphate absorption from intestine
3. Renal reabsorption of Ca2+ and phosphate
4. Bone mineralization - works with PTH
5. Immune regulation, cell differentiation

• Children: Rickets
  • Bowing of legs, knock knees, frontal bossing
  • Rachitic rosary (beading of ribs at costochondral junction)
  • Harrison's groove, Pigeon chest
  • Delayed closure of fontanelle
  • Craniotabes (softening of skull)
• Adults: Osteomalacia - softening of bones, bone pain, fractures
• Elderly: Risk of Osteoporosis
• Hypocalcemic tetany (carpopedal spasm, Chvostek's sign, Trousseau's sign)

• Low serum calcium, Low phosphate
• Raised Alkaline Phosphatase (ALP)
• Low 25-OH Vitamin D

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VITAMIN E (Tocopherol)

1. Antioxidant - major lipid-soluble antioxidant, protects polyunsaturated fatty acids (PUFA) from peroxidation
2. Protects RBC membrane from hemolysis
3. Protects cell membranes generally

• Hemolytic anemia in premature infants
• Peripheral neuropathy (posterior column degeneration)
• Ataxia, areflexia
• Retinopathy in premature infants

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VITAMIN K (Phylloquinone / Menaquinone)

• K1 (Phylloquinone) - from plants
• K2 (Menaquinone) - from gut bacteria
• K3 (Menadione) - synthetic

1. Blood coagulation - cofactor for gamma-carboxylation of clotting factors II (Prothrombin), VII, IX, X, Protein C, Protein S
2. Bone metabolism - carboxylation of osteocalcin

• Bleeding tendency - prolonged Prothrombin Time (PT)
• Hemorrhagic disease of newborn - newborns lack gut bacteria to synthesize K2 (Prevented by Vitamin K injection at birth)
• Deficiency with fat malabsorption (bile salt deficiency, liver disease)

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WATER-SOLUBLE VITAMINS (Key ones)

VITAMIN B1 (Thiamine)

1. Pyruvate dehydrogenase (Pyruvate → Acetyl CoA)
2. Alpha-ketoglutarate dehydrogenase (Krebs cycle)
3. Transketolase (HMP shunt)
4. Branched-chain keto acid dehydrogenase

• Dry Beriberi - peripheral neuropathy (sensory > motor)
• Wet Beriberi - cardiac failure + peripheral neuropathy + edema
• Wernicke's Encephalopathy - confusion, ataxia, ophthalmoplegia (3 triad)
• Korsakoff's Psychosis - confabulation, anterograde amnesia (chronic)
• Common in alcoholics and polished rice eaters

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VITAMIN B2 (Riboflavin)

• Cheilosis (cracks at angles of mouth = angular stomatitis)
• Glossitis (magenta/raw tongue)
• Corneal vascularization
• Seborrheic dermatitis
• 3 C's: Cheilosis, Corneal vascularization, Confusion

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VITAMIN B3 (Niacin / Nicotinic acid)

• Dermatitis - photosensitive skin lesions (Casal's necklace - rash around neck)
• Diarrhea
• Dementia
• Death (if untreated)

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VITAMIN B6 (Pyridoxine)

• Peripheral neuropathy (also caused by INH - Isoniazid which is treated with B6)
• Sideroblastic anemia
• Convulsions in infants

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VITAMIN B9 (Folic Acid)

• Megaloblastic anemia (macro-ovalocytes, hypersegmented neutrophils)
• Neural tube defects (anencephaly, spina bifida) in fetus if deficient in mother during pregnancy
• Glossitis, diarrhea

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VITAMIN B12 (Cobalamin)

1. Methylcobalamin - Methionine synthesis (methyl-THF + homocysteine → methionine; recycles THF)
2. Adenosylcobalamin - Methylmalonyl-CoA → Succinyl-CoA (important in odd-chain FA metabolism)

• Megaloblastic anemia (similar to B9 but also has neurological features)
• Subacute Combined Degeneration (SACD) of spinal cord - posterior column + corticospinal tract
  • Symptoms: Loss of proprioception and vibration, spastic weakness
• Causes: Pernicious anemia (lack of Intrinsic Factor), vegan diet, gastrectomy
• Schilling test used to diagnose cause

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VITAMIN C (Ascorbic Acid)

1. Collagen synthesis - hydroxylation of proline and lysine (requires Vitamin C as cofactor for prolyl hydroxylase and lysyl hydroxylase)
2. Antioxidant
3. Iron absorption - reduces Fe3+ to Fe2+ (better absorbed)
4. Dopamine-beta-hydroxylase (norepinephrine synthesis)
5. Immune function

• Bleeding gums (gingivitis, gum hemorrhage)
• Perifollicular hemorrhages (around hair follicles)
• Corkscrew hairs
• Subperiosteal hemorrhage → bone pain
• Poor wound healing
• Scorbutic rosary - costochondral junction beading
• Woody leg (brawny edema of legs)

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UNIT 5: MINERAL METABOLISM

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Q. Describe Calcium Metabolism.

• 40% protein-bound (mainly albumin)
• 10% complexed (citrate, phosphate)
• 50% ionized Ca2+ (physiologically active)

1. Bone: Increases osteoclast activity → bone resorption → Ca2+ released
2. Kidney: Increases Ca2+ reabsorption (DCT); decreases phosphate reabsorption → phosphaturia
3. Kidney: Stimulates 1-alpha hydroxylase → activates Vitamin D (indirect ↑ Ca2+)
4. Intestine: Indirect increase via Vitamin D

• Causes: Hypoparathyroidism, Vitamin D deficiency, Hypomagnesemia, Chronic renal failure
• Features: Tetany - carpopedal spasm
  • Trousseau's sign - carpal spasm on inflating BP cuff
  • Chvostek's sign - facial twitch on tapping facial nerve
  • Perioral tingling, muscle cramps, convulsions, QT prolongation on ECG

• Causes: Hyperparathyroidism, Malignancy, Vitamin D toxicity, Sarcoidosis
• Features: "Bones, Stones, Groans, Psychic Moans"
  • Bones - bone pain, pathological fractures
  • Stones - renal calculi, nephrocalcinosis
  • Groans - abdominal pain, constipation, peptic ulcer
  • Psychic Moans - confusion, depression, weakness, polyuria

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Q. Describe Iron Metabolism.

• Occurs mainly in duodenum and upper jejunum
• Ferrous (Fe2+) form is better absorbed than ferric (Fe3+)
• Vitamin C promotes absorption (reduces Fe3+ → Fe2+)
• Inhibitors: Phytates, oxalates, tannins (in tea), antacids

• In blood: bound to Transferrin (beta-1 globulin; binds 2 Fe3+ per molecule)
• TIBC (Total Iron Binding Capacity) = reflects transferrin level
• Transferrin saturation = Serum Iron / TIBC × 100 (normal: 25-35%)

• Ferritin - major intracellular storage protein (reflects body iron stores)
• Hemosiderin - insoluble iron storage (in macrophages)

• Hepcidin (liver) - main regulator
  • High iron → High hepcidin → blocks ferroportin → ↓ iron absorption
  • Iron deficiency → Low hepcidin → ↑ iron absorption

1. Component of Hemoglobin (oxygen transport) - 70% of body iron
2. Component of Myoglobin (oxygen storage in muscle)
3. Component of Cytochromes (electron transport chain)
4. Enzyme cofactor (catalase, peroxidase, ribonucleotide reductase)

• Most common nutritional deficiency worldwide
• Stages: Iron depletion → Iron deficiency without anemia → Iron deficiency anemia
• Lab: Low serum iron, Low ferritin, High TIBC, Microcytic hypochromic anemia
• Features: Fatigue, pallor, koilonychia (spoon nails), glossitis, angular stomatitis
• Pica (eating non-food items like clay, ice)
• Plummer-Vinson syndrome = iron deficiency + dysphagia + esophageal web

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Q. Write about Iodine and Thyroid Hormone Metabolism.

1. Trapping - Thyroid gland actively traps I- (sodium-iodide symporter, NIS)
2. Oxidation - I- → I2 (by thyroid peroxidase, TPO, using H2O2)
3. Organification - I2 added to tyrosine residues on Thyroglobulin → MIT, DIT
4. Coupling - MIT + DIT → T3; DIT + DIT → T4 (by TPO)
5. Storage - as Thyroglobulin colloid in follicles
6. Release - Thyroglobulin proteolysis → T3 and T4 released into blood

• Goiter (enlarged thyroid) - most common manifestation
• Hypothyroidism
• In pregnancy/children: Cretinism (mental retardation, stunted growth, deaf-mutism)
• Prevention: Iodization of salt

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Q. Write about Zinc, Copper, Fluoride (Trace Minerals).

ZINC

• Functions: Cofactor of 300+ enzymes (carbonic anhydrase, alcohol dehydrogenase, RNA polymerase), wound healing, immune function, sexual maturation, taste and smell, insulin storage
• Deficiency: Dwarfism, hypogonadism (Prasad's syndrome), acrodermatitis enteropathica, delayed wound healing, ageusia (loss of taste), anosomia, poor immunity

COPPER

• Functions: Ceruloplasmin (ferroxidase), cytochrome c oxidase, superoxide dismutase, lysyl oxidase (collagen/elastin crosslinking), tyrosinase (melanin synthesis)
• Deficiency: Hypochromic anemia, neurological features, depigmentation
• Excess (Wilson's disease): Copper accumulation in liver, brain, Kayser-Fleischer rings in eyes

FLUORIDE

• Functions: Strengthens tooth enamel (fluorapatite) and bone
• Deficiency: Dental caries
• Excess (Fluorosis): Dental fluorosis (mottled brown teeth); Skeletal fluorosis (osteosclerosis, bone deformities)

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QUICK REVISION TABLE - Vitamin Deficiency Mnemonics

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• Always write definition first, then classification/types, then mechanism, then clinical relevance
• Use tables wherever possible - examiners love them
• Draw neat labeled diagrams for action potential, synapse, NMJ, rhodopsin cycle
• End answers with clinical significance / deficiency / disease - this gets bonus marks
• Use bold headings for each point in long answers