Physiology — High-Yield — USMLE Step 1 Notes

Cardiovascular

• Cardiac output = stroke volume × heart rate; SV set by preload, afterload, contractility
• Frank-Starling: increased preload (venous return) increases stroke volume
• Pulse pressure ∝ stroke volume; widens in aortic regurgitation, narrows in tamponade/failure
• Baroreceptor reflex: ↑BP → carotid sinus stretch → ↓sympathetic → ↓HR

Respiratory

• Oxygen-dissociation curve: right shift (unload O2) with ↑CO2, ↑temp, ↑2,3-BPG, ↓pH (Bohr)
• Left shift: CO, fetal haemoglobin, methaemoglobin, alkalosis, cold
• A-a gradient: normal in hypoventilation and low FiO2; raised in V/Q mismatch, shunt, diffusion limit
• Shunt does not correct with 100% oxygen; V/Q mismatch does

Renal & acid-base

• Anion gap = Na − (Cl + HCO3); high-gap acidosis = MUDPILES
• Winter's formula: expected PaCO2 = 1.5×HCO3 + 8 (±2)
• Aldosterone: retains sodium and water, excretes potassium and hydrogen
• ADH: inserts aquaporins in the collecting duct (water reabsorption)

Endocrine signalling

• cAMP hormones (FLAT ChAMP): FSH, LH, ACTH, TSH, CRH, hCG, ADH(V2), MSH, PTH, calcitonin, GHRH, glucagon
• Steroid/thyroid hormones act on intracellular receptors (lipophilic)
• Insulin and growth factors use receptor tyrosine kinase (MAP kinase pathway)

Cross-cutting physiology worth over-learning

• Nernst vs Goldman: the Nernst equation gives the equilibrium potential of a single ion; the Goldman equation combines the permeabilities of several ions to give the membrane potential.
• Fick principle: flow can be calculated from consumption divided by the arteriovenous difference — the basis for measuring cardiac output from oxygen use.
• Laplace's law: wall tension rises with radius — relevant to aneurysms, dilated ventricles and alveolar stability (why surfactant matters).
• Compliance vs elastance are reciprocals; a stiff (non-compliant) ventricle or lung needs more pressure for the same volume.
• Diffusion (Fick's law) is faster with more surface area and a steeper gradient, and slower across a thicker membrane — why fibrosis and oedema impair gas exchange.

Written by StepSherpa in our own words, grounded in Human Physiology (Wikibooks), used under CC BY-SA 3.0.

Integrating the systems

• Feedback: negative loops dominate homeostasis (thermoregulation, glucose, osmolality); positive loops are rare and self-limiting (LH surge, clotting, labour).
• Membrane transport: primary active (Na/K ATPase), secondary active (SGLT, Na/Ca exchange), facilitated (GLUT), and channels. The Na/K ATPase (3 out, 2 in) underlies resting potential; digoxin inhibits it.
• Signal transduction: Gs raises cAMP, Gi lowers it, Gq raises IP3/DAG/Ca; tyrosine-kinase receptors (insulin, growth factors); nuclear receptors (steroid, thyroid).