Homeostasis & Cell Physiology
Usually week 1 of a medical physiology coursePhysiology courses open here because every later lecture is a variation on one idea: the body defends set points, and it defends them with negative feedback loops built from a sensor, an integrating center, and an effector. The exam lives at the loop components (which is the sensor? what happens when the effector overshoots?), the fluid compartments and what moves the water between them, and the handful of cell structures whose jobs become disease when they fail. Get the vocabulary exact now — gradient, flux, set point, gain — because the cardiovascular and renal weeks will use it without slowing down to redefine it.
This guide is the frame. The exams are written from your lectures— drop this unit's slides on the dashboard to get flashcards and board-style questions from your own course, and quiz them all semester (a course whose exams re-test earlier units rewards nothing more than early, repeated self-testing). The physiology playbook has the weekly loop.
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AI-authored study notes, not faculty-reviewed and not medical advice. Verify every mechanism against your course materials and faculty; programs differ in emphasis.
High-Yield Pearl
Ask two questions of any transported substance — which way is it moving relative to its gradient, and what pays for the trip? — and you can classify every transporter and predict every fluid shift the exam can write.
What the exam asks
Mechanisms, curves, and what happens when each one fails.
- Homeostasis and the set point. Homeostasis is the maintenance of a relatively constant internal environment (Claude Bernard's milieu intérieur) — not a frozen state but a regulated one, with each variable oscillating around a set point. Regulated variables the exam favors: core temperature (~37 °C), arterial pressure, blood glucose, plasma osmolarity (~290 mOsm/L), pH (7.35–7.45), and PaO2/PaCO2. A question that asks 'which variable is being defended' is asking you to find the set point in the vignette.
- Negative feedback — the universal loop. Sensor (receptor) detects the change → afferent signal → integrating center compares against the set point → efferent signal → effector opposes the original disturbance. The response REDUCES the error, which is what makes it negative. Examples to have cold: baroreceptor reflex (pressure), hypothalamic thermoregulation (temperature), insulin/glucagon (glucose), ADH and thirst (osmolarity), chemoreceptors and ventilation (PaCO2). The loop's 'gain' is how completely it corrects a disturbance — high-gain systems (pH) barely move; low-gain systems (glucose) swing more.
- Positive feedback — rare, self-amplifying, and terminated from outside. The response AMPLIFIES the stimulus instead of opposing it, so the loop runs to completion and must be ended by an outside event. The three classics: oxytocin in labor (contraction → cervical stretch → more oxytocin, ended by delivery), the clotting cascade (activated factors activate more factors, ended by the clot sealing the vessel), and the depolarization phase of the action potential (Na+ entry opens more Na+ channels, ended by inactivation). If a vignette describes escalation rather than correction, it is positive feedback.
- Feedforward (anticipatory) control. A response launched BEFORE the regulated variable changes, on a predictive cue: salivation and insulin release at the sight and taste of food (the cephalic phase), the rise in heart rate at the start of exercise before any metabolite accumulates. Distinguish it from negative feedback by timing — feedforward acts on the prediction, feedback acts on the error.
- Body fluid compartments and the 60-40-20 rule. Total body water ≈ 60% of body weight (less in women and the obese — fat is anhydrous). Two-thirds of it is intracellular fluid (40% of body weight); one-third is extracellular (20%), which splits roughly 3:1 into interstitial fluid and plasma. The major ECF cation is Na+ (with Cl− and HCO3−); the major ICF cation is K+ (with proteins and organic phosphates). Water crosses freely between compartments, so at steady state ICF and ECF osmolarities are EQUAL — the volumes shift until they are.
- Osmosis, osmolarity, and tonicity. Osmosis is water moving across a semipermeable membrane toward the higher solute concentration. Osmolarity counts ALL solute particles; tonicity counts only the EFFECTIVE (non-penetrating) ones, because a solute that crosses the membrane (urea, and glucose once insulin lets it in) drags no sustained water with it. That is why isosmotic is not always isotonic: a urea solution at 290 mOsm/L is isosmotic but hypotonic — cells in it swell. Infuse isotonic saline and it stays in the ECF; infuse pure water (as D5W after the glucose is metabolized) and it distributes across total body water, two-thirds of it entering cells.
- Transport across membranes — the taxonomy. Simple diffusion: down-gradient, through the lipid, no protein, never saturates (O2, CO2, steroids). Facilitated diffusion: down-gradient through a carrier or channel, saturable, no ATP (glucose via GLUT transporters). Primary active transport: directly ATP-powered, against the gradient (Na+/K+-ATPase, Ca2+-ATPase, H+/K+-ATPase). Secondary active transport: rides the Na+ gradient the pump built — cotransport/symport when the partner moves the same direction (SGLT glucose, Na+-K+-2Cl−), countertransport/antiport when opposite (Na+/Ca2+ exchanger, Na+/H+ exchanger). 'Saturable' and 'inhibitable' are the exam's code words for protein-mediated.
- The Na+/K+-ATPase — one pump, four exam jobs. Three Na+ out, two K+ in, per ATP — electrogenic (net positive charge leaves). It (1) maintains the Na+ and K+ gradients underlying the resting potential and every action potential, (2) powers all secondary active transport, (3) keeps the cell from swelling (the pump-leak hypothesis — poison it and cells take on Na+, then water), and (4) is the pharmacologic target of digoxin, which by raising intracellular Na+ blunts the Na+/Ca2+ exchanger and raises contractile Ca2+.
- Cell structures the exam actually asks about. Rough ER + ribosomes: proteins for export and membranes — abundant in secretory cells. Smooth ER: lipid and steroid synthesis, drug detoxification, and Ca2+ storage (as the sarcoplasmic reticulum in muscle). Golgi: modifies, sorts, and ships (the mannose-6-phosphate tag routes enzymes to lysosomes — lost in I-cell disease). Lysosomes: acid-hydrolase digestion (storage diseases when an enzyme is missing). Mitochondria: oxidative phosphorylation, with their own maternal DNA. Cytoskeleton: microtubules for transport and cilia (defective dynein = immotile cilia), actin for shape and motility, intermediate filaments for strength.
- Cell junctions. Tight junctions (zonula occludens) seal the paracellular path and make an epithelium 'tight' or 'leaky' — the difference between the collecting duct and the proximal tubule. Adherens junctions and desmosomes bolt cells together mechanically (autoantibodies against desmosomal proteins = pemphigus). Gap junctions are connexon channels that couple cells electrically and chemically — the reason cardiac muscle and single-unit smooth muscle contract as a syncytium.
Worth drilling · 26 concepts
Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.
- 1Negative feedback — sensor, integrating center, effector opposing the disturbance; the body's default control loop
- 2Positive feedback — response amplifies the stimulus until an outside event ends it (labor, clotting, AP upstroke)
- 3Feedforward control — anticipatory response launched before the variable changes (cephalic-phase insulin)
- 4Set point — the defended value a negative feedback loop oscillates around
- 5Gain — how completely a feedback loop corrects a disturbance
- 660-40-20 rule — body water 60% of weight; ICF 40%, ECF 20%
- 7Intracellular fluid — two-thirds of body water; K+ is its major cation
- 8Extracellular fluid — one-third of body water; Na+ is its major cation; splits 3:1 interstitium to plasma
- 9Plasma osmolarity — ~290 mOsm/L, defended by ADH and thirst
- 10Tonicity — osmotic effect of NON-penetrating solutes only; what decides whether a cell swells
- 11Isosmotic urea solution — same osmolarity, still hypotonic: urea crosses, cells swell
- 12Simple diffusion — down-gradient through the lipid, no protein, never saturates (O2, CO2, steroids)
- 13Facilitated diffusion — down-gradient through a protein, saturable, no ATP (GLUT glucose uptake)
- 14Primary active transport — pump burns ATP directly against the gradient (Na+/K+-ATPase)
- 15Secondary active transport — rides the Na+ gradient the pump built (SGLT, Na+/Ca2+ exchanger)
- 16Na+/K+-ATPase — 3 Na+ out, 2 K+ in per ATP; electrogenic; digoxin's target
- 17SGLT cotransporter — moves glucose uphill INTO the cell using the Na+ gradient (gut, proximal tubule)
- 18GLUT transporter — facilitated diffusion of glucose DOWN its gradient into cells
- 19Rough endoplasmic reticulum — ribosome-studded; makes proteins for export and membranes
- 20Smooth endoplasmic reticulum — lipid/steroid synthesis, detoxification, Ca2+ storage
- 21Golgi apparatus — modifies and sorts proteins; mannose-6-phosphate tags lysosomal enzymes
- 22Lysosome — acid-hydrolase digestion; missing enzymes cause storage diseases
- 23Mitochondrion — oxidative phosphorylation; maternally inherited DNA
- 24Tight junction — seals the paracellular path; makes an epithelium tight or leaky
- 25Gap junction — connexon channel electrically coupling cells; why heart muscle beats as one
- 26Desmosome — mechanical spot-weld between cells; the pemphigus autoantigen
Practice it
Active recall over the drill list — flip and claim, match the pairs, produce the answers cold, fill in the diagram.
Every concept on the drill list, one card at a time — the name up front, the fact that identifies it on the flip. Claim each card honestly and the deck learns what to lead with next time. Progress lives in this browser only.
What everyone misses
The distinctions that lose points on this material, year after year.
- Osmolarity and tonicity are not synonyms. Every year the isosmotic-urea question catches students who learned 'same osmolarity = no water shift.' Tonicity only counts solutes that CANNOT cross the membrane. Urea crosses, equilibrates, and contributes nothing to sustained water movement — so an isosmotic urea solution behaves like pure water and the red cell in it lyses. Ask of every solute in the stem: does the membrane let it through?
- Positive feedback is not 'bad feedback'. Students file positive feedback under pathology, then miss the three physiologic examples the exam loves: labor, clotting, and the action potential upstroke. The discriminator is the response's direction relative to the stimulus — amplifies it — not whether the outcome is healthy.
- Facilitated diffusion needs no ATP — and still saturates. The two properties get mismatched in both directions: 'it uses a protein, so it must use energy' (no — glucose enters muscle down its gradient) and 'it's passive, so it can't saturate' (no — a finite number of carriers means a Tm). Protein-mediated is what saturates; ATP is only for the ACTIVE transporters.
- Secondary active transport moves its passenger UPHILL. SGLT questions are missed by students who see 'down the Na+ gradient' and conclude the whole process is passive. The Na+ half runs downhill; the glucose half runs uphill, powered by that Na+ energy — which the Na+/K+-ATPase paid for one step earlier. Poison the pump and secondary transport dies with it, one step delayed.
- The ECF's cation is Na+ even though the pump exports it. A tempting inversion: the pump pushes Na+ out, so students place Na+ inside the cell. The pump is WHY Na+ is outside — it keeps bailing against the leak. High Na+ outside, high K+ inside is the geography every membrane-potential and action-potential question assumes.
- Water follows osmoles, not the other way around. When a vignette adds solute to one compartment, the exam wants water to MOVE toward it and both compartments to end at the same osmolarity. Students instead try to move the solute. In fluid-shift problems, treat solute as fixed to its compartment (unless it's a penetrating solute) and let water do all the traveling.
Clinical correlations
Where this unit shows up again — in clinic, on rotations, and on the boards.
- Hypernatremia and the shrinking brain. A dehydrated patient who lost water (not salt) concentrates the ECF; water leaves the ICF — including neurons — and the brain shrinks, producing the confusion and lethargy of hypernatremia. Correct it too fast and water rushes back in: cerebral edema. The compartment arithmetic from week one is the whole mechanism, which is why correction rates are capped.
- IV fluid choice is a tonicity question. Isotonic (0.9%) saline stays in the ECF — the resuscitation fluid for volume loss. D5W is effectively free water once the glucose is metabolized, distributing across total body water — a treatment for free-water deficits, never for shock. Hypertonic 3% saline pulls water out of cells — reserved for symptomatic hyponatremia. Every fluid order is applied compartment physiology.
- Digoxin and the coupled transporters. Digoxin inhibits the Na+/K+-ATPase; intracellular Na+ rises; the Na+/Ca2+ exchanger, deprived of its Na+ gradient, extrudes less Ca2+; contractility rises. The same chain explains its toxicity in hypokalemia — less K+ competing at the pump's binding site means more inhibition at the same dose.
- Oral rehydration therapy rides SGLT. In secretory diarrhea (cholera), the gut still absorbs Na+ and glucose TOGETHER through SGLT1 even while Cl− secretion pours fluid out. Glucose-plus-salt solution drives Na+ (and water) absorption and turns a lethal disease into an outpatient one — the highest-impact application of cotransport in medicine.
- Cystic fibrosis as a channel disease. One defective Cl− channel (CFTR) produces thick airway mucus, pancreatic insufficiency, and a salty sweat test — the template 'channelopathy' vignette. The sweat gland runs the logic in reverse of the airway (fails to REABSORB Cl−), which is why sweat chloride is high and diagnostic.
- SGLT2 inhibitors — a transporter as a drug target. Blocking the proximal tubule's Na+-glucose cotransporter forces glucosuria, lowering blood glucose (and, through natriuresis, benefiting heart failure). The predictable side effects come straight from the mechanism: glycosuric urinary tract infections and volume depletion.
- Pemphigus vs bullous pemphigoid — junction biology at the bedside. Autoantibodies against desmosomes (desmoglein) let keratinocytes pull apart: flaccid, rupturing blisters and a positive Nikolsky sign (pemphigus vulgaris). Antibodies against the hemidesmosome anchoring the epithelium to its basement membrane give tense, intact blisters (bullous pemphigoid). Which junction fails predicts the blister.