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Premedical Physiology
Cell → systems → bedside: mechanisms, equations, control loops, and clinical reasoning for high-yield exams. 🔥
🔢 Key Areas of Study
- Cell & Membranes: Ion gradients, membrane transport (simple/facilitated diffusion, primary/secondary active), channels vs carriers, Nernst/Goldman, osmosis & tonicity.
- Excitable Tissues: Action potentials (neurons, skeletal & cardiac muscle), refractory periods, conduction velocity, synaptic transmission (chemical/electrical), summation.
- Muscle: Skeletal (length–tension, force–velocity, motor units), cardiac (Frank–Starling, calcium-induced calcium release), smooth (MLCK/MLCP, latch state).
- Cardiovascular: Cardiac cycle & pressure–volume (PV) loops, preload/afterload/contractility, valves & heart sounds, vascular compliance, Poiseuille flow, microcirculation & Starling forces, autonomic/baroreflex control.
- Respiratory: Mechanics (compliance, surfactant, work of breathing), spirometry & volumes, gas exchange (Fick), alveolar gas equation, V/Q mismatch & shunt, O\(_2\)/CO\(_2\) transport, control of ventilation (chemoreceptors).
- Renal: Clearance & GFR, filtration fraction, tubular handling (Na\(^+\), K\(^+\), HCO\(_3^-\), water, urea), concentrating–diluting mechanisms (countercurrent), acid–base.
- Gastrointestinal: Motility (slow waves, peristalsis, MMC), secretion (salivary, gastric, pancreatic, bile), digestion & absorption, splanchnic circulation, enterohepatic cycling.
- Endocrine & Metabolism: Hormone classes & receptors (GPCR/RTK/steroid), hypothalamic–pituitary axes, insulin/glucagon, thyroid, adrenal, calcium–phosphate (PTH, calcitonin, vitamin D), reproductive physiology.
- Neurophysiology: Sensory transduction, receptive fields, pain pathways & modulation, motor systems & reflexes, autonomic physiology (SNS/PSNS), sleep & circadian basics.
- Blood & Immunophysiology: RBCs & O\(_2\) content, haemostasis (primary/secondary), coagulation cascade checks, inflammation mediators, fever & thermoregulation.
- Integrative Physiology: Exercise, altitude, diving, pregnancy & foetal circulation, temperature homeostasis, shock states.
🧫 Cell membranes & electrophysiology
- Driving forces: Each ion has an equilibrium potential \(E_{ion}\) from Nernst; membrane potential \(V_m\) sits near ions with highest permeability (Goldman). Current \(I=g(V_m-E_{ion})\).
- AP templates: Neurons: fast Na\(^+\) upstroke → K\(^+\) repolarisation; absolute then relative refractory. Cardiac fast AP (0–4 phases) vs nodal slow AP (If funny current, Ca\(^{2+}\) upstroke).
- Conduction: Myelination ↑ length constant, saltatory at nodes; larger diameter ↑ velocity. Local anaesthetics block open/inactivated Na\(^+\) channels (use-dependence).
💪 Muscle physiology – compare three types
- Skeletal: Troponin–tropomyosin Ca\(^{2+}\) regulation; summation & tetanus as firing rate ↑; optimal sarcomere length maximises cross-bridges.
- Cardiac: L-type Ca\(^{2+}\) influx triggers SR release; force ∝ intracellular Ca\(^{2+}\) & sarcomere length (Frank–Starling). β\(_1\) agonism ↑ cAMP → PKA → more Ca\(^{2+}\) entry & reuptake (lusitropy).
- Smooth: Calmodulin-MLCK phosphorylation of myosin; slow cycling → energy-efficient latch state. Autonomic, hormonal, myogenic inputs integrate.
❤️ Cardiovascular control
- CO & BP: \( \text{MAP}\approx \text{DBP}+ \tfrac{1}{3}\text{PP} \). \( \text{CO}=HR\times SV \). \( \text{Flow}= \Delta P/R \). Arterioles dominate TPR; veins hold most blood (capacitance).
- Reflexes: Arterial baroreceptors buffer beat-to-beat BP (↑ stretch → ↓ SNS, ↑ PSNS). Chemoreceptors (↓O\(_2\), ↑CO\(_2\), ↓pH) drive ventilation & sympathetic tone.
- Microcirculation: Filtration \(J_v=K_f[(P_c-P_i)-\sigma(\pi_c-\pi_i)]\). ↑ venous pressure or ↓ plasma proteins → oedema; lymphatics return interstitial fluid & protein.
🌬️ Respiratory essentials
- Ventilation: \( \dot V_A=(V_T-V_D)f \). PaCO\(_2\) ∝ CO\(_2\) production / alveolar ventilation. Dead space ↑ in embolism; shunt in pneumonia/oedema (doesn’t correct with O\(_2\)).
- Gas exchange: Fick \( \dot V_{gas}=D_L (P_1-P_2) \). DLCO ↓ in fibrosis/emphysema/anaemia. Alveolar gas: \(P_{AO_2}=P_{IO_2}-\frac{P_{aCO_2}}{R}\) (≈ \(150-\frac{PaCO_2}{0.8}\) at sea level).
- O\(_2\) carriage: \(C_{aO_2}=1.34\,\text{Hb}\cdot S_{aO_2}+0.003\,P_{aO_2}\). Right shift (↑H\(^+\), ↑CO\(_2\), ↑Temp, ↑2,3-BPG) favours unloading (Bohr effect).
💧 Renal logic
- Clearance: \(C_x=\frac{U_x V}{P_x}\). Inulin/creatinine ≈ GFR; PAH (at low [ ]) approximates RPF. FF=GFR/RPF.
- Handling along nephron: Prox tubule bulk reabsorption (incl. HCO\(_3^-\) via CA), thick ascending limb (Na-K-2Cl; water-impermeable), early distal (Na-Cl), late distal/collecting (ENaC; aldosterone/ADH regulation).
- Concentration: Countercurrent multiplier creates medullary gradient; ADH inserts aquaporin-2; urea recycling augments gradient.
🍽️ GI physiology
- Motility: ICC slow waves set rhythm; PSNS ↑ motility; sympathetic ↓. Migrating motor complex sweeps fasting gut.
- Secretion: Gastric acid (parietal: H\(^+\)/K\(^+\) ATPase) ↑ by histamine (H\(_2\)), ACh, gastrin; ↓ by prostaglandins, somatostatin.
- Absorption: Na\(^+\)/glucose cotransport (SGLT1), fat via micelles → chylomicrons; bile acids reabsorbed terminal ileum (enterohepatic cycle).
🧯 Endocrine axes
- Receptors: Peptides → GPCR/RTK (fast); steroids/thyroid → nuclear receptors (slow transcriptional). Spare receptors explain high potency.
- HPA: CRH→ACTH→cortisol (diurnal; stress). Negative feedback at pituitary & hypothalamus.
- Glucose: Insulin (tyrosine kinase) ↑ uptake (GLUT4), glycogenesis, lipogenesis; glucagon/epi oppose in fasting; cortisol permissive.
- Ca–P: PTH ↑ Ca\(^{2+}\) (bone, kidney) & ↓ phosphate; calcitriol ↑ gut Ca\(^{2+}\)/P; calcitonin minor.
📏 Core Equations – Learn or Locate
| Topic | Equation | Use / Memory Tip |
|---|---|---|
| Nernst | \(E_{ion}=\frac{RT}{zF}\ln\frac{[\text{ion}]_o}{[\text{ion}]_i}\) | At 37 °C, ≈ \(61\,\text{mV}\cdot\frac{1}{z}\log_{10}\frac{o}{i}\). |
| Goldman (GHK) | \(V_m=\frac{RT}{F}\ln\frac{\sum P_i[\text{ion}]_o}{\sum P_i[\text{ion}]_i}\) | Weighted by permeability \(P\). |
| Ohm / driving force | \(I=g(V_m-E_{ion})\) | Sign shows ion entry/exit. |
| Flow | \(Q=\frac{\Delta P}{R}\) | Series ↑R, parallel ↓R. |
| Poiseuille | \(R=\frac{8\eta L}{\pi r^4}\) | Radius rules (×2 radius → 16× flow). |
| MAP | \(\text{MAP}\approx \text{DBP}+\tfrac13(\text{SBP}-\text{DBP})\) | At normal HR; shifts with tachy. |
| Laplace | \(T=\frac{P\cdot r}{2}\) (sphere) | Aneurysm risk ↑ with radius. |
| Alveolar ventilation | \(\dot V_A=(V_T-V_D)f\) | PaCO\(_2\) ∝ \( \frac{\dot V_{CO_2}}{\dot V_A}\). |
| Alveolar gas | \(P_{AO_2}=P_{IO_2}-\frac{P_{aCO_2}}{R}\) | Sea level: \(P_{IO_2}\approx150\) mmHg on air. |
| O\(_2\) content | \(C_{aO_2}=1.34\,\text{Hb} \cdot S_{aO_2}+0.003\,P_{aO_2}\) | Hb dominates O\(_2\) content. |
| Clearance | \(C_x=\frac{U_x V}{P_x}\) | Inulin/Cr ≈ GFR; PAH ≈ RPF. |
| Filtration fraction | \(\text{FF}=\frac{\text{GFR}}{\text{RPF}}\) | Normal ≈ 0.2. |
| Free water clearance | \(C_{H_2O}=\dot V - C_{osm}\) | Sign shows dilute vs concentrated urine. |
| Henderson–Hasselbalch | \(\mathrm{pH}=6.1+\log\frac{[\mathrm{HCO_3^-}]}{0.03\,P_{aCO_2}}\) | Lungs (CO\(_2\)) vs kidneys (HCO\(_3^-\)). |
| Winter’s | \(P_{aCO_2}^{\,\mathrm{exp}}=1.5[\mathrm{HCO_3^-}]+8\pm2\) | Expected compensation in metabolic acidosis. |
| Starling filtration | \(J_v=K_f[(P_c-P_i)-\sigma(\pi_c-\pi_i)]\) | Capillary vs interstitial pressures & oncotic forces. |
| Dose–response | \(E=\frac{E_{max}[A]}{EC_{50}+[A]}\) | Spare receptors shift left. |
📝 Quick self-quiz (hover to reveal answers)
- Double arteriole radius: what happens to resistance? Ans: ↓ by 16× (Poiseuille).
- Right shift of Hb–O\(_2\) curve – two causes? Ans: ↑Temp, ↑H\(^+\) (acidosis), ↑CO\(_2\), ↑2,3-BPG.
- Creatinine: \(U=10\,\mathrm{mmol/L},\,P=100\,\mu\mathrm{mol/L},\,V=2\,\mathrm{mL/min}\). CrCl? Ans: \(C=\frac{10\times2}{0.1}=200\,\mathrm{mL/min}\) (units matched).
- Metabolic acidosis with HCO\(_3^-\)=12: expected \(P_{aCO_2}\)? Ans: \(1.5\times12+8=26\pm2\) mmHg.
- Alveolar gas at sea level with PaCO\(_2\)=40: \(P_{AO_2}\)? Ans: \(150-\frac{40}{0.8}\approx100\) mmHg.
📈 Systems & Curves – What They Mean & How to Shift Them
| Curve / Diagram | What it shows | Shift / Interpretation |
|---|---|---|
| Left ventricular PV loop | Isovolumic lines, ejection, filling; stroke work = area | ↑Preload → wider loop; ↑Afterload → higher ESP line, lower SV; ↑Contractility → steeper ESPVR, ↑SV at same preload. |
| Starling (ventricular function) | SV/CO vs EDV/RAP | Positive inotropy shifts up; HF shifts down; venoconstriction ↑ preload (moves along curve). |
| Venous return curve | VR vs RAP; intercept = mean systemic filling pressure | ↑Blood volume/venoconstriction → curve up/right; ↑TPR flattens slope. |
| Hb–O\(_2\) dissociation | Sat vs \(P_{O_2}\); sigmoid from cooperativity | Right shift (↑T, ↑H\(^+\), ↑2,3-BPG, ↑CO\(_2\)); Left shift (↓T, ↓H\(^+\), CO, fetal Hb). |
| Compliance curves (lung/chest wall) | Volume vs pressure | Emphysema ↑ compliance; fibrosis ↓. FRC at lung+chest wall equilibrium. |
| Spirometry loops | Obstructive vs restrictive patterns | Obstructive: scooped expiratory limb (↓FEV\(_1\)/FVC); restrictive: small but similar shape (FEV\(_1\)/FVC normal/high). |
| V/Q distribution | Base > apex for both V and Q; V/Q↑ at apex | Dead space (V/Q→∞): PE; shunt (V/Q→0): consolidation/oedema. O\(_2\) fixes dead space better than shunt. |
| Glucose titration (renal) | Filtered, reabsorbed, excreted vs \(P_{glc}\) | Splay between threshold and T\(_m\); glucosuria when filtered load > T\(_m\). |
| Endocrine dose–response | Effect vs ligand concentration | Affinity (EC\(_{50}\)) shifts curve left/right; efficacy alters \(E_{max}\); competitive antagonists shift right. |
🧑🏫 Exam hack: State the axis labels, normal landmarks, then describe a single parameter change (preload/afterload/contractility or compliance) and its effect on the curve.
Worked example – aortic stenosis on PV loop
↑Afterload (narrow valve) → steeper ESP line, higher systolic pressure, ↓SV (narrower loop). Concentric LVH ↑ end-systolic volume; often preserved EF early with elevated pressures → systolic murmur + slow upstroke pulse.
Worked example – obstructive vs restrictive spirometry
Obstructive: ↓FEV\(_1\) > ↓FVC → ↓FEV\(_1\)/FVC; ↑TLC/RV (air-trapping). Restrictive: ↓FEV\(_1\) & ↓FVC proportionally → normal or ↑ ratio; ↓TLC.
🩺 Clinical Integration – Patterns, Numbers & Pitfalls
- Shock states: Hypovolaemic (↓preload, cold), cardiogenic (pump failure, ↑PCWP), distributive (↓SVR, warm early), obstructive (tamponade/PE/tension PTX). Give mechanism → targeted fix.
- Respiratory failure: Type 1 (hypoxaemia ± normocapnia; V/Q mismatch/shunt), Type 2 (hypercapnia; hypoventilation). O\(_2\) helps V/Q but not pure shunt; ventilate for hypoventilation.
- Hyponatraemia: Check osmolality & volume status; SIADH = euvolaemic, low serum osm, high urine Na\(^+\)/osm; treat water restriction ± vaptans after cause addressed.
- Hyperkalaemia: ECG changes (peaked T → wide QRS). Stabilise membrane (IV Ca\(^{2+}\)), shift K\(^+\) in (insulin+glucose, β\(_2\)), remove (loop diuretic, resin, dialysis).
- Acid–base steps: 1) pH? 2) Primary disturbance? 3) Expected compensation (Winter’s/others). 4) Anion gap? 5) Mixed disorders?
🩸 ABG compensation cheatsheet
- Metabolic acidosis: Winter’s \(P_{aCO_2}=1.5[\mathrm{HCO_3^-}]+8\pm2\).
- Metabolic alkalosis: \(P_{aCO_2}^{\,exp}=0.7[\mathrm{HCO_3^-}]+20\pm5\).
- Acute resp acidosis: HCO\(_3^-\) ↑ ~1 mmol/L per 10 mmHg ↑PaCO\(_2\). Chronic: ~3.5–4 per 10.
- Acute resp alkalosis: HCO\(_3^-\) ↓ ~2 per 10 ↓PaCO\(_2\). Chronic: ~4–5 per 10.
🌬️ A–a gradient & V/Q vs shunt
\(A\!-\!a = P_{AO_2}-P_{aO_2}\). Normal increases with age; ↑ in diffusion/VQ mismatch/shunt. 100% O\(_2\) improves V/Q mismatch but not shunt (bypassed alveoli).
🧠 Murmurs & loops
- Aortic stenosis: Crescendo–decrescendo systolic; ↑afterload pattern (see PV loop).
- Mitral regurgitation: Holosystolic; PV loop with absent true isovolumic contraction (backflow to LA).
- Aortic regurgitation: Wide pulse pressure; no isovolumic relaxation (retrograde flow into LV).
💧 Pre-renal vs intrinsic AKI
| Feature | Pre-renal | Intrinsic (ATN) |
|---|---|---|
| Urine Na\(^+\) | <20 mmol/L | >40 mmol/L |
| FeNa | <1% | >2% |
| Osmolality | >500 mOsm/kg | <350 mOsm/kg |
| Urine sediment | Bland | Granular “muddy brown” casts |
🏃 Exercise, altitude, pregnancy
- Exercise: ↑CO (HR > SV at high work), vasodilation in muscle (metabolites), ↓TPR; ventilation ↑ to match CO\(_2\) production; A–a small.
- Altitude: ↓PIO\(_2\) → hyperventilation (resp alkalosis) → renal HCO\(_3^-\) loss; ↑2,3-BPG shifts Hb curve right; polycythaemia later.
- Pregnancy: ↑Plasma volume > RBC mass (physiological anaemia), ↑GFR, mild resp alkalosis (progesterone-driven hyperventilation).
🧠 Study & Exam Tips
- State the loop: For any system, name sensor → integrator → effector → variable. Examiners reward control-system language.
- Equation → estimate: Plug plausible numbers (order of magnitude) to sanity-check MCQ stems quickly.
- Curve literacy: Be able to draw Hb–O\(_2\), PV loops, compliance curves, Starling/venous return, and annotate a single shift.
- Integrate with path: Link physiology derangements to common diseases (COPD, HF, CKD, sepsis) and predict lab/bedside findings.
- Active recall: Daily 10-minute drills on equations and graphs; teach a peer the story of one axis (e.g., HPA) each day.
🚀 Rapid drill (answers hidden)
- What happens to PaCO\(_2\) when dead space rises but total minute ventilation stays constant? Ans: PaCO\(_2\) ↑ (effective alveolar ventilation falls).
- How does β\(_1\) agonism change PV loop? Ans: Steeper ESPVR, ↑SV & EF at same preload/afterload.
- Give two mechanisms for oedema besides ↑hydrostatic pressure. Ans: ↓Plasma oncotic pressure (hypoalbuminaemia), ↑capillary permeability (inflammation), lymphatic obstruction.
- Why does anaemia cause ↓CaO\(_2\) with normal PaO\(_2\)? Ans: O\(_2\) content depends mainly on Hb concentration.
- Predict acid–base in prolonged vomiting. Ans: Metabolic alkalosis (H\(^+\) loss, volume contraction → ↑aldosterone → H\(^+\)/K\(^+\) renal loss).
Final thought: Physiology is cause-and-effect. Name the variable, the controller, and the effector, then use the right equation - the answer usually writes itself. 💪