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📋 Comprehensive Physiology Notes

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1. ELECTROMYOGRAPHY (EMG) & NERVE CONDUCTION STUDIES

Nerve Conduction Studies

• Principle: Stimulating electrodes placed over a nerve; recording electrodes placed distally over the nerve or an innervated muscle.
• CMAP (Compound Motor Action Potential): Recorded from muscle belly; reflects summated electrical activity of muscle cells.
• SNAP (Compound Sensory Nerve Action Potential): Recorded from nerve; from summated sensory neuron axon activity.
• Proximal lesions (proximal to dorsal root ganglia): SNAP preserved (cell bodies intact), but CMAPs reduced (motor axon degeneration).
• Demyelination: Slowed conduction velocity; reduced SNAP/CMAP latency or velocity vs. standard values.
• Axonal damage: Decreased SNAP amplitude.

Repetitive Stimulation (Neuromuscular Junction Testing)

• Slow stimulation depletes presynaptic ACh stores; fast stimulation raises presynaptic Ca²⁺.

EMG (Needle Electromyography)

• Electrode inserted directly into muscle → records Motor Unit Action Potentials (MUPs).

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2. MYASTHENIA GRAVIS

Epidemiology

• Affects 25–125 per million; bimodal distribution: young women (20s) with thymic hyperplasia; older men (60s) with thymoma.

Pathophysiology

• Autoimmune disorder: spontaneous anti-AChR antibodies → progressive loss of nicotinic AChRs at neuromuscular junction.
• Antibodies target the MIR (main immunogenic region) of the AChR α subunit.
• Mechanism: antibodies bind → activate complement → accelerate receptor destruction + degenerate postjunctional folds.
• MEPP (miniature end-plate potential) amplitude ↓; quantal release frequency normal.

Clinical Features

• Fluctuating fatigable skeletal muscle weakness, worst at end of day or after exertion.
• Ocular form: only extraocular muscle weakness (ptosis, diplopia).
• Generalized form: all skeletal muscles; severe cases → respiratory muscle paralysis → death.

Diagnosis

• EMG: decremental CMAP on slow repetitive stimulation.
• Anti-AChR antibodies positive.
• Tensilon (edrophonium) test: rapid transient improvement.

Treatment

⚠️ Overdose of AChE inhibitors → excess ACh → prolonged depolarization → Na⁺ channel inactivation → cholinergic crisis (paradoxical paralysis).

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3. LYMPHATIC CIRCULATION

Lymph Formation & Flow

• Fluid efflux from capillaries exceeds influx → excess enters lymphatics → returns to blood.
• Normal 24-h lymph flow: 2–4 L.

Types of Lymphatic Vessels

Functions

1. Fluid balance: Returns excess interstitial fluid to blood.
2. Protein return: 25–50% of total circulating plasma protein returned daily (from liver/intestine interstitium).
3. Lipid transport: Dietary fats absorbed via lacteals (chylomicrons → chyle).
4. Immune function: Lymph nodes filter lymph; transport lymphocytes.

Interstitial Fluid & Edema

• Interstitial fluid volume depends on: capillary pressure, oncotic pressure, lymph flow, capillary filtration coefficient, ECF volume, pre/postcapillary resistance ratio.
• Edema = abnormal accumulation of interstitial fluid.
• Causes: ↑ capillary pressure, ↓ plasma oncotic pressure, ↑ capillary permeability, lymphatic obstruction.

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4. COMPARISON OF SKELETAL, CARDIAC & SMOOTH MUSCLE

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5. PERIODIC BREATHING & DROWNING

Periodic Breathing (Cheyne-Stokes Respiration)

• Caused by increased controller gain in the respiratory control system.
• During apnea: CO₂ builds up → powerful stimulus drives ventilation (hyperpnea).
• Hyperpnea washes out CO₂ below threshold → apnea resumes.
• Key factor: prolonged circulation time between lungs and brain chemoreceptors (>5 sec delay).

1. Heart failure (most common — prolonged circulation time).
2. Cerebrovascular disease / brain stem lesions.
3. High altitude (hypoxia → hyperventilation → hypocapnia → apnea).
4. Uremia, severe anemia.
5. Normal in newborns and during sleep in some adults.

Drowning & Near-Drowning

• Wet drowning (~80–90%): Water aspirated into lungs → surfactant disruption → hypoxia, bronchospasm, electrolyte disturbances.
• Dry drowning (~10–20%): Laryngospasm prevents water entry; asphyxia from hypoxia/CO₂ retention.
• Salt water drowning: Hypertonic water draws fluid into alveoli → haemoconcentration, pulmonary edema.
• Fresh water drowning: Hypotonic water absorbed rapidly → haemodilution, haemolysis, hyponatremia, VF risk.
• Diving reflex (triggered by cold water on face): Bradycardia + peripheral vasoconstriction → redistributes blood to heart and brain → can prolong survival (especially in children).
• Secondary drowning: Delayed pulmonary edema hours after submersion.

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6. PHYSIOLOGY OF DEEP SEA DIVING (Applied)

Relevant Laws

• Boyle's Law: P × V = constant → at depth, gas compresses; on ascent, gas expands.
• Dalton's Law: Total pressure = sum of partial pressures of all gases.
• Henry's Law: Gas dissolved in liquid ∝ its partial pressure → at depth, more N₂ dissolves in tissues.

Problems at Depth

A. Nitrogen Narcosis ("Rapture of the Deep")

• At >30 m depth, high partial pressure of N₂ causes CNS depression.
• Symptoms: Euphoria, impaired judgment, hallucinations (anesthetic effect, similar to alcohol/N₂O).
• Mechanism: Membrane expansion theory (dissolved N₂ expands neuronal membranes).
• Treatment/Prevention: Replace N₂ with helium (trimix/heliox) — helium is inert, doesn't cause narcosis.

B. Decompression Sickness ("The Bends") — Caisson Disease

• Cause: Rapid ascent → ambient pressure ↓ → dissolved N₂ comes out of solution → bubbles form in tissues/blood.
• Bubbles form in: joints (bends), spinal cord, inner ear (staggers), lungs (chokes), skin.
• Symptoms: Severe joint pain, paresthesia, paralysis, vertigo, pulmonary edema, air embolism.
• Prevention: Slow staged ascent; decompression stops.
• Treatment: Hyperbaric oxygen (HBO₂) chamber → recompress to dissolve bubbles, then slow decompression.

C. Oxygen Toxicity

• At PO₂ > 1.6 atm (diving below 6 m on 100% O₂):
  • Pulmonary toxicity (prolonged exposure): ↑ ROS → inflammation, alveolar damage, ARDS-like picture.
  • CNS toxicity (high PO₂): Seizures, visual disturbances → drown.

D. High-Pressure Nervous Syndrome (HPNS)

• Below ~120–200 m depth with helium.
• Symptoms: Tremors, dizziness, nausea, drowsiness, visual disturbances.
• Reduced by slow staged pressurization; adding small amounts of N₂.

E. Barotrauma

• Ear squeeze: Pressure difference across tympanic membrane.
• Pulmonary barotrauma: Breath-holding on ascent → lung overexpansion → pneumothorax, arterial gas embolism (AGE).

F. High-Altitude (Applied)

• ↓ ambient PO₂ → hypoxia → hyperventilation → respiratory alkalosis.
• Acclimatization: ↑ RBCs/Hb (EPO from kidneys), ↑ 2,3-DPG (right shifts O₂ curve), cardiovascular adjustments.

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7. PINEAL GLAND PHYSIOLOGY

Structure

• Small endocrine gland in epithalamus; composed of pinealocytes.

Hormones

• Primary: Melatonin (N-acetyl-5-methoxytryptamine) — synthesized from tryptophan → serotonin → melatonin.

Regulation

• Light suppresses melatonin secretion; darkness stimulates secretion.
• Light signal: Retina → suprachiasmatic nucleus (SCN) → superior cervical ganglion (sympathetic) → NE release → stimulates pinealocyte melatonin synthesis at night.
• Peak secretion: 2–3 AM.

Functions of Melatonin

1. Circadian rhythm regulation — master clock hormone; promotes sleep (acts on SCN).
2. Suppresses gonadotropin secretion → ↓ LH/FSH → inhibits reproductive activity (antigonadotrophic).
3. Seasonal reproduction: In seasonal animals, long-night melatonin signals inhibit breeding; in humans, role is less prominent.
4. Antioxidant properties.
5. Immune modulation.

Applied

• Jet lag treatment: Exogenous melatonin helps reset circadian rhythm.
• Pineal tumors in children:
  • Destructive lesion → ↓ melatonin → precocious puberty (removes gonadal inhibition).
  • Secreting tumor → ↑ melatonin → delayed puberty.

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8. THYMUS PHYSIOLOGY

Structure

• Bilobed lymphoid organ in anterior mediastinum; most active in childhood, involutes after puberty.
• Has cortex (T-cell maturation) and medulla (Hassall's corpuscles).

Functions

1. T-lymphocyte maturation (education): Thymic selection → positive + negative selection → self-MHC restriction + self-tolerance.
2. Hormonal secretion:
   • Thymosin α1: Promotes T-cell differentiation; enhances immune response.
   • Thymopoietin: Induces T-cell differentiation from stem cells.
   • Thymulin (FTS): Zinc-dependent; promotes T-cell maturation.
3. Immunological competence: Provides cells that colonize peripheral lymphoid organs.

Role in Myasthenia Gravis

• Thymic cells express nicotinic AChRs → become source of autoantigens.
• Thymoma or thymic hyperplasia → anti-AChR antibody production.
• Thymectomy improves MG in ~75% of patients with thymoma.

Applied

• DiGeorge syndrome: Thymic aplasia → absent T-cells → profound cellular immunodeficiency (T⁻ B⁺ SCID type).
• Thymus transplant can correct this.

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9. DIABETES MELLITUS

Classification

Diagnosis

• Urinary glucose: Glucosuria (renal threshold ~180 mg/dL).
• Fasting blood glucose: Normal 80–90 mg/dL; >115 mg/dL = upper limit; >126 mg/dL × 2 = DM.
• Glucose Tolerance Test (OGTT): 1 g/kg glucose orally.
  • Normal: peaks ~120–140 mg/dL, returns below normal in 2 hours.
  • Diabetic: Peaks much higher, fails to normalize in 4–6 hours.
• HbA1c: Glycated hemoglobin reflects average blood glucose over 3 months (life of RBC ~120 days). ≥6.5% = DM.

Complications

• Macrovascular: Atherosclerosis, MI, stroke, peripheral arterial disease.
• Microvascular: Retinopathy, nephropathy (most common cause of end-stage renal disease), neuropathy.
• Acute: DKA (Type 1), HHS (Type 2), hypoglycemia (insulin excess).

Insulin Shock (Hypoglycemia)

• BG 50–70 mg/dL: CNS excitation → nervousness, tremor, diaphoresis.
• BG 20–50 mg/dL: Seizures, loss of consciousness.
• BG <20 mg/dL: Coma (without ketoacidosis unlike diabetic coma).
• Treatment: IV glucose (immediate) or glucagon/epinephrine.

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10. SEX DETERMINATION & DIFFERENTIATION

Sex Determination

• Genetic sex: 46,XX (female) or 46,XY (male) — set at fertilization.
• SRY gene (Sex-determining Region on Y chromosome): Encodes TDF (Testis-Determining Factor) → induces undifferentiated gonad → testis.
• Without SRY (XX): Gonad develops into ovary by default (requires RSPO1, WNT4, FOXL2 pathways).

Gonadal Sex

• Indifferent gonad present in both sexes up to week 7.
• XY + SRY → Sertoli cells → AMH (Anti-Müllerian Hormone) + Leydig cells → testosterone.
• XX → Granulosa cells → no AMH, no testosterone → ovary forms.

Phenotypic Sex Differentiation

• DHT (5α-reductase converts T → DHT) is required for external male genitalia.
• 5α-reductase deficiency: Normal internal male genitalia but female-appearing external genitalia → virilization at puberty.

Applied (Disorders of Sex Development)

• Congenital Adrenal Hyperplasia (CAH): 21-hydroxylase deficiency → excess androgens → virilized female (46,XX).
• Androgen Insensitivity Syndrome (AIS): 46,XY; androgen receptor defect → female phenotype; testes present (risk of malignancy).
• Turner syndrome (45,XO): Streak gonads, no estrogen, no puberty without HRT.
• Klinefelter syndrome (47,XXY): Male phenotype; small testes, azoospermia, gynecomastia.

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11. PUBERTY & APPLIED

Definition

• Period of sexual maturation: gonads become functional, secondary sexual characteristics develop, growth spurt occurs.

Hormonal Cascade

1. ↑ GnRH pulses from hypothalamus (pulsatile — critical).
2. → ↑ LH + FSH from anterior pituitary.
3. → ↑ Sex steroids (testosterone in males, estradiol in females).
4. → Development of secondary sexual characteristics.

Timing

• Girls: Puberty 8–13 years; menarche ~12.5 years average.
• Boys: Puberty 9–14 years.
• First sign in girls: Thelarche (breast development).
• First sign in boys: Testicular enlargement.

Tanner Stages (I–V)

• Stage I = prepubertal; Stage V = adult.
• Assesses breast/genital development and pubic hair separately.

Growth Spurt

• Girls: Before menarche (estrogen → bone maturation + GH synergy).
• Boys: Later (testosterone → linear growth + muscle mass).
• Epiphyseal closure: Estrogen causes closure of growth plates → end of linear growth.

Applied

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12. INFERTILITY: CAUSES & ROLE OF IVF

Definition

• Failure to conceive after 12 months of regular unprotected intercourse (6 months if woman >35 years).
• Affects ~10–15% of couples.

Causes

Investigations

• Male: Semen analysis (WHO criteria: volume >1.5 mL, sperm >16 million/mL, motility >42%, morphology >4% normal).
• Female: Hormonal panel (FSH, LH, AMH, estradiol, prolactin, TSH), HSG (tubal patency), pelvic USS, laparoscopy.

Role of IVF (In Vitro Fertilization)

1. Ovarian stimulation: GnRH agonist/antagonist + FSH/LH injections → superovulation (multiple follicles).
2. Trigger: hCG injection → mimics LH surge → oocyte maturation.
3. Oocyte retrieval: Transvaginal ultrasound-guided aspiration (36 hours post-trigger).
4. Fertilization: Oocytes mixed with prepared sperm (or ICSI — intracytoplasmic sperm injection if severe male factor).
5. Embryo culture: 3–5 days in incubator; blastocyst stage preferred.
6. Embryo transfer: 1–2 embryos transferred to uterus; rest frozen.
7. Luteal support: Progesterone supplementation → supports endometrial preparation.
8. Pregnancy test: β-hCG at 14 days post-transfer.

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13. PHYSIOLOGY OF MENOPAUSE

Definition

• Natural menopause: Permanent cessation of menstruation for ≥12 consecutive months due to loss of ovarian follicular function; average age 51 years (range 45–55).
• Perimenopause (climacteric): Transitional phase 2–8 years before menopause; irregular cycles begin.

Pathophysiology

• Ovarian follicle depletion: Born with ~2 million oocytes → ~400,000 at puberty → <1,000 at menopause.
• As follicles deplete: ↓ inhibin B (→ loss of negative feedback on FSH) → FSH rises markedly (best early marker).
• ↓ Estradiol production → ↑ FSH, ↑ LH (loss of negative feedback).
• Residual estrogen: Peripheral aromatization of androgens (from adrenal cortex) → estrone (weak estrogen) in adipose tissue.

Hormonal Profile at Menopause

Symptoms & Effects

Management

Premature Ovarian Insufficiency (POI)

• Menopause before age 40; affects ~1% of women.
• Causes: Autoimmune, chromosomal (Turner's), iatrogenic (chemotherapy/radiation), idiopathic.
• ↑ FSH + ↓ estradiol confirms diagnosis.
• Fertile at times (intermittent ovarian function in 5–10%) — IVF with donor eggs is the main fertility option.

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Topic Index