⚡ Physiology

What you’ll learn

1. The Only Thing You Are Really DoingEstablish the one idea the whole course runs on: life is the active maintenance of gradients against a levelling universe.A body a second before and after death has the same atoms and architecture — nothing left, something stopped. Your ion concentrations, blood pressure, oxygen levels, 37 °C core and mitochondrial proton stores are all differences, and physics does not permit differences to persist. So they are being actively held, and paid for, every second. Every function is therefore either building a gradient or spending one, which is the question to ask of anything unfamiliar.
2. Homeostasis Is a Thermostat, Not a Set PointUnderstand homeostasis as continuous correction rather than constancy, and learn to spot the sensor–comparator–effector loop anywhere.Cannon chose homeo- (similar), not homo- (same), deliberately: nothing in you is constant, everything oscillates and is dragged back. Every regulatory system has a sensor, a comparator holding a set point, and an effector, with the loop closed by the effector changing what the sensor measures. Negative feedback opposes change and cannot be perfect by its own logic — the error must occur before it can be corrected, so the wobble is evidence the system works. Positive feedback is rare and always completes an event rather than maintaining a state.
3. The Battery in Every Cell You OwnMeet the Na⁺/K⁺ pump as the body's master gradient-builder, and confront what it costs.In nearly every cell, a pump throws 3 Na⁺ out and drags 2 K⁺ in per ATP — both uphill, which is why it costs. The result is two stored concentration gradients plus a membrane voltage of about –70 mV in a resting neuron, which across a 5 nm membrane is a field in the region of ten million volts per metre. It never stops, because ions leak back constantly. A typical cell spends on the order of 30% of its ATP on it; nerve cells up to ~70%; in grey matter Na⁺/K⁺-ATPases have been estimated to take up to about three-quarters of the energy.
4. The Action Potential Spends It All at OnceSee the action potential as stored gradient released through a switch, made digital by a positive feedback loop.Nothing is pumped during an impulse — the pump banked the work in advance, and channels are the sluice gate. Voltage-gated Na⁺ channels create a positive feedback loop (depolarisation opens channels, sodium entry depolarises further), so past a ~–55 mV threshold the avalanche runs to completion regardless of the stimulus: the all-or-none law, which forces intensity to be coded as firing rate. Inactivation and K⁺ channels terminate it; the refractory period caps rate and enforces one-way travel. Myelin makes conduction jump between nodes — faster and cheaper.
5. Muscle: Turning a Gradient Into ForceFollow the gradient chain from nerve to force, and use rigor mortis to prove that relaxation is what costs.Calcium (some 10,000× more concentrated outside than in) triggers acetylcholine release; the muscle fires its own action potential; internal stores dump calcium, which drags the blocker off actin's binding sites. Calcium is the actual command. Myosin heads then ratchet the filaments past each other — sliding, not shortening. And ATP's job is to make the head LET GO, not to power the stroke, which is why a muscle with no ATP locks rather than going limp. That is rigor mortis, exactly.
6. The Heart Makes a Pressure GradientReframe circulation as a pressure gradient built and spent, and meet the loop with no sensor.The heart doesn't move blood; it makes a pressure difference, and blood moves because a difference exists — flow is the pressure difference over resistance, so equal pressures would mean no flow however hard the heart worked. Cardiac output = heart rate × stroke volume, about 5 L/min at rest. And the Frank–Starling law matches two series pumps to within a fraction of a percent with no controller at all: stretch cardiac muscle and it contracts harder, so a fuller ventricle ejects more and the imbalance erases itself.
7. Breathing Is Pressure All the Way DownShow that breathing and gas exchange are pressure differences and geometry, not machinery.You cannot pull air. The diaphragm flattens, the ribs swing out, volume rises, Boyle's law drops the pressure a couple of mmHg below atmospheric, and air falls in — while the lung, which has no muscle, follows the chest wall only because the pleural layers won't separate. Exhalation at rest is free elastic recoil. Gas exchange has no machinery whatsoever: both gases diffuse down opposing partial-pressure gradients across the same membrane, and the lung's whole geometry exists to let diffusion win. Haemoglobin's cooperativity makes it a switch; the Bohr effect makes hard work its own unloading signal.
8. The Kidney's Strange EconomicsExplain why filtering everything and buying it back is the only strategy that survives a molecule you've never met.The kidneys take ~1 L of blood a minute — about 20% of a resting cardiac output — and filter ~125 ml/min in men (~180 L/day; ~105 ml/min and ~150 L/day in women), then reabsorb about 99% to make 1–2 L of urine. That looks insane until you notice that extracting waste directly would require knowing in advance every substance that will ever need removing. A whitelist ('keep the known, discard the remainder') handles novel drugs automatically. And the loop of Henle builds a salty medulla at great cost purely so ADH-gated channels can spend it on water.
9. The Slow Loops: Hormones and HeatContrast the two signalling systems, and work thermoregulation through as a complete loop — including fever.Nerves are a telephone: private line, milliseconds, stops when you stop. Hormones are a radio broadcast, because Anatomy II's endocrine glands lost their ducts — so specificity moved to the receiver, and only cells with the matching receptor respond. That buys the ability to change the whole body's mode at once with no wiring. Thermoregulation runs the full loop: hypothalamic sensors and set point, effectors from vasoconstriction and shivering (muscle at deliberate zero efficiency) to sweating and thyroid hormone. Fever is the set point being moved, which is why you feel freezing in an unchanged room.
10. Coda: The BillTotal the energy bill, and name the design principle that explains why it is what it is.Basal metabolic rate is almost entirely maintenance: the Na⁺/K⁺ pump, 99% reabsorption of 180 L/day, a pressure gradient rebuilt 100,000 times a day, 37 °C held against a room. You eat in order to keep not being at equilibrium. And notice the pattern: the kidney discards the unrecognised rather than recognising poisons, the lung arranges a geometry where diffusion wins, Starling's law has no sensor, the Bohr effect needs no signal. Physiology's answer is repeatedly to arrange a situation where a spontaneous process works for free — you pay for the setup, not the work.

Questions this course answers

Grounded in trusted sources

• Walter F. Boron and Emile L. Boulpaep, 'Medical Physiology', 3rd edition (Elsevier, 2017)
• Walter B. Cannon, 'The Wisdom of the Body' (W. W. Norton, 1932) — homeostasis
• A. L. Hodgkin and A. F. Huxley, 'A quantitative description of membrane current and its application to conduction and excitation in nerve', Journal of Physiology 117, 500 (1952)
• A. F. Huxley and R. Niedergerke, Nature 173, 971 (1954); H. E. Huxley and J. Hanson, Nature 173, 973 (1954) — the sliding filament model
• Otto Frank (1895) and Ernest Starling (1918) — the Frank–Starling law of the heart
• John B. West and Andrew M. Luks, 'West's Respiratory Physiology: The Essentials', 11th edition (Wolters Kluwer, 2020)
• Christian Bohr, Karl Hasselbalch and August Krogh (1904) — the Bohr effect
• Eric R. Kandel et al., 'Principles of Neural Science', 6th edition (McGraw Hill, 2021)

Every Wunder lesson is built from real, reputable sources — never invented.

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