Last Day Revision

Nerve & Cell Physiology

Resting membrane potential (RMP) and channels

• Neuronal RMP: approximately −70 mV.
• Mainly due to K⁺ leak channels, intracellular impermeant anions and Na⁺/K⁺-ATPase.
• Na⁺/K⁺-ATPase: 3 Na⁺ out, 2 K⁺ in per ATP → electrogenic.

Action potential and refractory periods

• Threshold: approximately −55 mV.
• Threshold → rapid opening of voltage-gated Na⁺ channels → depolarization via positive feedback.
• All-or-none: stronger stimuli increase firing frequency, not action potential amplitude.
• Accommodation: slowly rising depolarization can inactivate Na⁺ channels before threshold is reached.

Nerve fibres and myelination

• Myelin enables saltatory conduction between nodes of Ranvier.
• MS: CNS demyelination; oligodendrocytes.
• GBS: PNS demyelination; commonly ascending flaccid weakness, involving peripheral myelin/Schwann cells.

Electrolytes and local anaesthetics

• Hyperkalaemia: depolarizes RMP; initially increases excitability, but sustained depolarization inactivates Na⁺ channels → conduction failure.
• Hypocalcaemia: increases neuronal excitability → tetany; Chvostek and Trousseau signs.
• Local anaesthetics: block intracellular voltage-gated Na⁺ channels; use-dependent block.

Sensitivity order: C > B > A-δ > A-α — pain fibres generally blocked before large motor fibres.

Cell membrane and transport

• Small nonpolar molecules such as O₂, CO₂ and steroids cross the lipid bilayer readily.
• Ions and glucose generally require membrane transport proteins.
• Digoxin: inhibits Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → reduced Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ → positive inotropy.
• Cystic fibrosis: defective CFTR Cl⁻ channel → impaired salt/water movement → thick secretions.

Organelles and cytoskeleton

Final 20-second recall

• RMP −70 mV; threshold −55 mV.
• Na⁺ influx → depolarization; K⁺ efflux → repolarization.
• Absolute refractory = Na⁺ channels inactivated.
• C fibres = unmyelinated, slow pain.
• MS = CNS; GBS = PNS.
• Hypocalcaemia → tetany; hyperkalaemia → depolarization and eventual conduction block.
• Digoxin → ↑ intracellular Ca²⁺ → ↑ contractility.
• Facilitated diffusion is saturable; simple diffusion is not.
• Nissl bodies = RER; microtubules = tubulin; microfilaments = actin.

Muscle

Sarcomere and skeletal muscle

• Sarcomere: functional contractile unit; actin and myosin slide past each other without shortening.
• During contraction:
  • I band ↓
  • H zone ↓
  • A band remains constant

Cross-bridge cycle and rigor mortis

• Myosin binds actin → P_i release triggers power stroke.
• ATP binding detaches myosin from actin.
• ATP hydrolysis re-cocks the myosin head.
• Rigor mortis: ATP depletion after death → myosin cannot detach from actin → rigidity.

Neuromuscular junction (NMJ)

Excitation–contraction coupling

Troponin and muscle mechanics

• Cardiac muscle cannot be tetanized because its long absolute refractory period prevents summation and allows filling between beats.
• Skeletal muscle can undergo summation and tetanus.

Smooth muscle

• No troponin.
• Ca²⁺ binds calmodulin → activates MLCK → phosphorylates myosin light chains → contraction.
• Latch state: maintains sustained tension with low ATP consumption.

Cardiac action potential and ECG

• Ventricular phase 2 plateau: inward Ca²⁺ current through L-type channels balanced by outward K⁺ current.
• Prolonged action potential and refractory period prevent tetanus.

Pacemaker and conduction system

• SA node: no stable resting membrane potential; spontaneous phase 4 depolarization produces automaticity.
• Funny current: contributes to phase 4 depolarization.
• Fastest conduction: Purkinje fibres (~1.5–4 m/s).
• Slowest conduction: AV node → delay permits ventricular filling before ventricular systole.

Final 15-second recall

• I band and H zone decrease; A band stays constant.
• ATP detaches myosin; ATP depletion causes rigor mortis.
• Botulinum blocks ACh release; curare blocks nicotinic receptors.
• Skeletal muscle: mechanical DHP–RyR coupling.
• Cardiac muscle: CICR.
• Smooth muscle: Ca²⁺–calmodulin–MLCK.
• Cardiac muscle cannot tetanize.
• Hyperkalaemia → peaked T waves; hypocalcaemia → prolonged QT.
• SA node → automaticity; AV node → slowest conduction; Purkinje → fastest conduction.

Homeostasis

Examples

• Negative: baroreceptor reflex, glucose and temperature regulation.
• Positive: childbirth (oxytocin), blood clotting, action potential upstroke.
• Pathological positive feedback: haemorrhagic shock → ↓ CO → ↓ coronary perfusion → weaker heart → further ↓ CO.
• Feed-forward: seeing or smelling food → cephalic phase of gastric secretion.
• Temperature regulation gain: approximately 33.

Reflex arc

Stimulus → Receptor → Afferent pathway → Integrating centre → Efferent pathway → Effector → Response

The response feeds back to regulate the original disturbance.

Body fluid compartments — 60–40–20 rule

Indicator dilution method

Ionic composition

Na⁺/K⁺-ATPase: uses 1 ATP to pump 3 Na⁺ out and 2 K⁺ in.

Osmosis and fluid shifts

Water moves toward the compartment with higher effective osmolarity.

Urea trap: A 300 mOsm/L urea solution is iso-osmolar but effectively hypotonic because urea crosses cell membranes, promoting cellular swelling.

Final 20-second recall

• Homeostasis = dynamic, not fixed.
• Negative feedback opposes; positive feedback amplifies; feed-forward anticipates.
• 60–40–20: TBW 60%, ICF 40%, ECF 20% of body weight.
• ECF = Na⁺; ICF = K⁺.
• 3 Na⁺ out, 2 K⁺ in per ATP.
• Hypertonic ECF → cells shrink; hypotonic ECF → cells swell.
• Oedema = hydrostatic pressure ↑, plasma oncotic pressure ↓, permeability ↑, or lymphatic drainage ↓.

Cardiology

Hemodynamics: must-know formulas

• Greatest pressure drop: arterioles.
• Radius reduced by 50% → resistance increases 16-fold.
• Stiff arteries in elderly → isolated systolic hypertension + widened pulse pressure.
• Turbulent flow → murmurs/bruits; promoted by high velocity and low viscosity, e.g. aortic stenosis and severe anaemia.

Cardiac output and venous return

• ↑ Blood volume or venous tone → ↑ mean systemic filling pressure (MSFP) → ↑ venous return → ↑ preload → ↑ SV.
• ↑ Right atrial pressure (RAP) → ↓ venous return.
• Frank–Starling: ↑ ventricular filling/stretch → ↑ force of contraction.
• Sympathetic inotropy: ↑ contractility at the same preload.
• SVT/severe tachycardia: ↓ diastolic filling and coronary perfusion → ↓ SV; CO may fall despite ↑ HR.

Autonomic receptors

• MAP = CO × TPR.
• Sympathetic stimulation can increase both CO and TPR to support BP.

Cardiovascular reflexes

Valsalva manoeuvre

• Strain → ↓ venous return/CO/BP → reflex tachycardia.
• Release → BP overshoot → reflex bradycardia.
• Absent HR response may indicate autonomic dysfunction.

Baroreceptors can reset in chronic hypertension, shifting their operating point upward.

Regional circulation — favourite MCQs

Note: Autoregulation organs = H-B-K (Heart, Brain, Kidneys).

• Lewis triple response: red line → flare → wheal.
• Raynaud phenomenon: excessive digital vasoconstriction triggered by cold or stress.
• Exercise: ↑ HR, contractility and venous return; active muscle vasodilation → overall TPR falls.

Starling forces and oedema

Four major mechanisms of oedema:

1. ↑ Capillary hydrostatic pressure — heart failure, venous obstruction.
2. ↓ Plasma oncotic pressure — nephrotic syndrome, cirrhosis, malnutrition.
3. ↑ Capillary permeability — inflammation, burns, histamine.
4. Impaired lymphatic drainage — filariasis, lymph node dissection, lymphedema.

Hormonal regulation of BP

Three triggers of renin release:

• ↓ Renal perfusion pressure.
• ↓ NaCl delivery to macula densa.
• ↑ Renal sympathetic stimulation via β₁ receptors.

Standing, haemorrhage and exercise

Orthostatic hypotension: fall in SBP ≥20 mmHg or DBP ≥10 mmHg within 3 minutes of standing.

Final 60-second recall

• Largest resistance change: arterioles; resistance varies with \(1/r^4\).
• Largest pressure drop: arterioles.
• Coronary perfusion: predominantly diastolic.
• Highest resting O₂ extraction: myocardium (~75%).
• Bainbridge: atrial stretch → tachycardia.
• Cushing triad: hypertension, bradycardia, irregular respiration.
• Angiotensin II: preferential efferent arteriolar constriction.
• ACEi/ARB: efferent dilation → possible creatinine rise.
• Exercise: muscle blood flow rises dramatically; total TPR falls.
• Oedema: ↑ hydrostatic pressure, ↓ plasma oncotic pressure, ↑ permeability, or lymphatic obstruction.
• ANP opposes RAAS.
• Haemorrhage compensation: neural first, fluid shift next, renal/hormonal mechanisms later.

For any CVS clinical scenario, reason in this order:

Trigger → venous return/preload → stroke volume/CO → BP and tissue perfusion → compensatory reflex or hormonal response.

Blood

WBC differential — memorise the order

• Left shift = increased immature neutrophils (bands).
• Rolling: selectins.
• Firm adhesion: integrins.
• Diapedesis: passage through endothelium.
• Chemotaxis: migration toward chemical signals.

3. Lymphocytes

• T cells: ~70–80% of lymphocytes.
• B cells: ~10–15%.
• NK cells: ~5–15%.
• Normal CD4:CD8 ratio: approximately 2:1.
• HIV targets CD4⁺ T helper cells.

Platelets and haemostasis

Primary haemostasis: platelet plug.

Secondary haemostasis: fibrin formation and clot stabilisation.

• Platelet disorders → petechiae and mucosal bleeding.
• Coagulation-factor disorders → deep bleeding and haemarthroses.
• vWD = most common inherited bleeding disorder; impaired platelet adhesion and sometimes reduced factor VIII.

Coagulation cascade — rapid recall

• Thrombin (IIa): converts fibrinogen to fibrin; activates platelets and several clotting factors.
• Vitamin K-dependent: II, VII, IX, X, proteins C and S.
• Factor XIII deficiency: bleeding can occur despite normal PT and aPTT.

Coagulation tests

Mixing study: correction suggests factor deficiency; failure to correct suggests an inhibitor.

Anticoagulants and fibrinolysis

Fibrinolysis: tPA → plasminogen → plasmin → fibrin breakdown → D-dimer.

Dry socket: premature breakdown of the extraction socket clot → exposed bone and severe pain, typically 2–4 days after extraction.

Blood groups and transfusion

• O negative: universal packed-RBC donor principle.
• AB positive: universal packed-RBC recipient principle.
• AB plasma: universal ABO plasma donor.
• ABO antibodies are naturally occurring; anti-D usually develops after sensitisation.

Coombs tests

• Direct Coombs (DAT): antibodies/complement already attached to RBCs.
• Indirect Coombs: free serum antibodies.

Transfusion reactions

Endocrinology

Last second recall

• EPO = kidney; TPO = mainly liver.
• RBC lifespan = 120 days.
• Hepcidin inhibits ferroportin.
• Iron deficiency: ↓ ferritin, ↑ TIBC.
• G6PD: oxidative haemolysis.
• Neutrophils: bacteria; eosinophils: parasites/allergy.
• GPIb–vWF = adhesion; GPIIb/IIIa–fibrinogen = aggregation.
• PT = extrinsic; aPTT = intrinsic.
• Haemophilia A = VIII; B = IX.
• DIC = consumption of platelets and factors → thrombosis + bleeding.
• Direct Coombs = bound antibodies; indirect = free antibodies.
• TRALI = lung injury; TACO = volume overload.

LAST-MINUTE FCPS RECALL

Remember: short pathways

Hypothalamus → CRH → anterior pituitary ACTH → adrenal fasciculata cortisol → negative feedback to CRH/ACTH.

Hypothalamus → TRH → anterior pituitary TSH → thyroid T3/T4 → negative feedback to TRH/TSH.

Low calcium → chief cells release PTH → renal Ca²⁺ retention + phosphaturia + calcitriol activation → calcium rises.

Low renal perfusion → renin → angiotensin I → ACE → angiotensin II → aldosterone → Na⁺ retention and K⁺ secretion.

β-cell glucose metabolism → ATP rises → KATP channel closes → depolarization → Ca²⁺ influx → insulin release.

Insulin lowers glucose and shifts K⁺ into cells; glucagon raises glucose in fasting.

Exam tips: classic contrasts

Dental exam safety pearls

Uncontrolled hyperthyroidism: avoid elective care and epinephrine; stress can precipitate thyroid storm.

Suspected thyroid storm: stop treatment, call emergency services, oxygen/cooling and immediate transfer.

Diabetic patient: avoid prolonged fasting; ask about meals and medication; have glucose available.

Unconscious hypoglycemic patient: never give oral glucose because of aspiration risk.

Known adrenal insufficiency/long-term steroid exposure: assess adrenal-crisis risk and follow a clinician-guided steroid-cover plan for significant stress/invasive procedures.

Diabetes is linked bidirectionally with periodontitis; poor glycemic control worsens infection and healing.

Hyperparathyroidism may cause loss of lamina dura on dental radiographs.

One-minute final sweep

Peptides: membrane receptor, rapid; steroids/thyroid: intracellular receptor, slower genomic effects.

Gs = cAMP; Gq = IP3/DAG; insulin = tyrosine kinase; ANP/NO = cGMP.

GH is diabetogenic; IGF-1 mediates linear growth. Prolactin is inhibited by dopamine.

ADH V2 saves water; V1 constricts vessels. Oxytocin ejects milk; prolactin makes milk.

TPO = oxidation + organification + coupling; T3 is more potent than T4.

GFR layers: salt, sugar, sex. Cortisol peaks in the morning; aldosterone retains Na⁺ and loses K⁺/H⁺.

Insulin is anabolic and moves K⁺ into cells; glucagon is fasting/catabolic.

PTH increases calcium but decreases phosphate; vitamin D increases both; calcitonin opposes bone resorption.

Respiratory

Rapid Numerical Recall

These are standard approximate reference values, not fixed values for every individual.

MCQ Tips — Must Memorize

Remember — Essential Physiologic Relationships

Ventilation

• Increased alveolar ventilation → decreased PaCO₂.
• Decreased alveolar ventilation → increased PaCO₂.
• Increased dead-space ventilation → less effective alveolar ventilation for a given minute ventilation.

Compliance and surfactant

• Compliance = ease of lung expansion.
• Elastance = tendency to recoil.
• Surfactant lowers surface tension.
• Emphysema: high compliance, low recoil.
• Fibrosis: low compliance, increased elastic stiffness.

Gas exchange

• Oxygen moves from alveoli to pulmonary capillary blood.
• CO₂ moves from blood to alveoli.
• Diffusion improves with greater surface area and pressure gradient.
• Diffusion worsens with increased membrane thickness.
• V/Q mismatch is a common mechanism of hypoxemia.

Oxygen transport

• PaO₂ measures dissolved oxygen pressure.
• SaO₂ measures the proportion of hemoglobin binding sites occupied by oxygen.
• CaO₂ measures total oxygen content.
• Anemia reduces oxygen content even if PaO₂ is normal.
• Carbon monoxide reduces oxygen carriage and impairs tissue unloading.

V/Q matching

• Apex: relatively high V/Q.
• Base: relatively low V/Q.
• Shunt: perfusion without effective ventilation.
• Dead space: ventilation without effective perfusion.
• Hypoxic pulmonary vasoconstriction redirects blood toward better-ventilated alveoli.

Respiratory regulation

• Central chemoreceptors respond primarily to CO₂-induced changes in brain fluid pH.
• Peripheral chemoreceptors detect low arterial PO₂ and also respond to CO₂ and pH.
• High altitude causes hypoxemia and stimulates hyperventilation.
• Chronic hypercapnia can lead to adaptation of the central CO₂ response.

Exam Tips — Classic Contrasts

High-Yield Clinical Scenarios