Applied Physiology: the mechanisms the clinical chapters assume
The same fluid bolus saves one patient and drowns another. Physiology is what tells you which is which.
Physiology examined as isolated theory is difficult to retain and rarely useful. Examined as the reason a treatment works or harms, it becomes the most practical subject in the course.
This chapter covers the four areas the clinical chapters lean on hardest: how the circulation fails, how the kidney filters, how acid-base results are read, and how endocrine feedback locates a lesion.
Cardiac output: one equation, four kinds of shock
Everything about circulatory failure follows from two relationships:
A patient is shocked when tissue perfusion fails. Ask which term has broken and the classification writes itself:
Not enough volume to fill the heart. Stroke volume falls because there is nothing to eject — haemorrhage, dehydration, burns. Hypovolaemic shock.
The pump cannot eject what it receives. Stroke volume falls despite adequate filling — infarction, arrhythmia, severe valve disease. Cardiogenic shock.
The vessels have dilated. Resistance collapses, so pressure falls even when output is high or normal — sepsis, anaphylaxis, spinal cord injury. Distributive shock.
Something is stopping the heart filling from outside it — tension pneumothorax, cardiac tamponade, massive pulmonary embolism. Obstructive shock.
This matters because the treatments differ and some are harmful in the wrong category. Fluid is the treatment for hypovolaemia and dangerous in cardiogenic shock. A vasoconstrictor helps distributive shock and does little for a heart that cannot eject. Naming the mechanism chooses the treatment — which is why an examiner asks for the type of shock before asking what you would give.
Starling: why the same bolus helps one patient and harms another
Cardiac muscle has a useful property: stretching a fibre before it contracts makes the contraction stronger. So in a normal heart, more filling produces more output, automatically and without any nervous signal. That is the Frank–Starling relationship, and it is why a healthy circulation self-adjusts.
The relationship is a curve, not a straight line, and it flattens. In a failing heart it is flat almost from the start.
The clinical consequence is the whole point. Give fluid to a hypovolaemic patient and you move up the steep part of the curve — output rises and the patient improves. Give the same fluid to a patient in heart failure and output barely changes, because the curve is flat there — but the pressure behind the failing ventricle still rises, and that pressure is transmitted back into the lungs.
The fluid becomes pulmonary oedema instead of cardiac output. Same intervention, opposite result, and the difference is a physiological curve.
Glomerular filtration: two taps, and the drugs that turn them
Filtration at the glomerulus is driven by pressure. Blood arrives through the afferent arteriole and leaves through the efferent, and the balance of tone in those two vessels sets the pressure inside the glomerulus.
That gives the kidney a neat trick — it can defend filtration when blood pressure falls, by constricting the efferent (holding pressure in) and dilating the afferent (letting more blood through). Both responses depend on locally produced mediators.
And that is exactly what two very common drug groups interfere with:
NSAIDs block the prostaglandins that dilate the afferent arteriole. Less blood enters, so filtration falls.
ACE inhibitors and ARBs block angiotensin II, which constricts the efferent arteriole. The efferent dilates, pressure inside the glomerulus falls, and filtration falls.
Put an NSAID and an ACE inhibitor together with a diuretic — which reduces the volume arriving in the first place — and all three supports of filtration are removed simultaneously. The "triple whammy" that causes acute kidney injury is not a coincidence to memorise; it is three drugs each disabling a different part of one mechanism.
This also explains why these drugs are held during acute illness: a dehydrated patient is already relying on those compensations to maintain filtration.
Acid-base: three questions, no memorised tables
Blood gas interpretation is usually taught as a table to memorise. It does not need to be — three questions answer any result.
Question 1: is the pH low or high? Low is acidosis, high is alkalosis. This names the primary problem, whatever else the numbers show.
Question 2: which value moved in the same direction as the pH? This identifies the culprit system, and it works because the primary disorder always drags the pH with it:
A low pH with a high CO₂ means the lungs are not clearing CO₂ — respiratory acidosis.
A low pH with a low bicarbonate means acid is being produced or base lost — metabolic acidosis.
Question 3: has the other system compensated? The lungs can compensate within minutes by changing ventilation; the kidneys take days. Compensation reduces the pH change but does not reverse it — compensation never overshoots, so if the pH has crossed to the other side of normal, there is a second disorder.
💡 The trap worth knowing: a normal pH with markedly abnormal CO₂ and bicarbonate is not a normal result. It means either a fully compensated single disorder, or two opposing disorders cancelling each other out. Report what the individual values show rather than being reassured by the pH.
Endocrine feedback: the pattern tells you where the lesion is
Most endocrine axes work the same way. The pituitary releases a hormone that drives a peripheral gland; the gland's hormone then restrains the pituitary. So in health the two move in opposite directions — that is what negative feedback means.
The diagnostic power comes from asking whether that opposition still holds.
The gland has failed (primary problem). Gland hormone is low. The pituitary is no longer restrained, so its hormone rises. Low gland hormone, high pituitary hormone — the pituitary is shouting at a gland that cannot respond.
The pituitary has failed (secondary problem). Gland hormone is low because nothing is driving it — and the pituitary hormone is low too. Both low: nobody is shouting.
So the two hormones moving together — both low, or both high — is the abnormal pattern. It means the controller itself is broken, or something outside the axis is producing hormone independently. That single rule replaces a page of memorised combinations, and it applies to the thyroid, adrenal and gonadal axes alike.
Two more mechanisms worth carrying
Oxygen delivery is not the same as oxygen saturation. Delivery depends on cardiac output and haemoglobin concentration and saturation. A profoundly anaemic patient can have a saturation of 100% and still be delivering far too little oxygen — because saturation describes the percentage of available haemoglobin that is loaded, not how much haemoglobin there is. This is why saturation alone can be falsely reassuring.
Potassium sits mostly inside cells, and its movement is affected by pH. In acidosis, potassium tends to shift out of cells, so the measured serum potassium can look adequate while total body potassium is depleted. Correcting the acidosis moves potassium back into the cells and the serum level falls — which is why potassium is monitored closely when treating a severe acidosis, as covered in the diabetic emergencies chapter.
Putting it together
Output = stroke volume × rate; pressure = output × resistance. Ask which term broke and the type of shock follows.
Starling explains why fluid helps one patient and drowns another.
Afferent and efferent arterioles set filtration pressure — which is why NSAIDs, ACE inhibitors and diuretics together cause kidney injury.
Three questions read any blood gas, and compensation never overshoots.
In a working axis the two hormones move in opposite directions. Moving together locates the lesion in the controller.
Saturation is not delivery, and potassium moves with pH.
No reference ranges, ECG intervals or absolute values appear in this chapter: they differ between laboratories and conventions. Use the ranges your laboratory reports.
Syllabus points
Cardiac output equation and the four types of shock
Frank-Starling: why the same fluid helps or harms
Afferent and efferent arterioles set filtration
The triple whammy as mechanism, not coincidence
Three questions that read any blood gas
Compensation never overshoots
Endocrine feedback locates the lesion
Saturation is not delivery; potassium moves with pH
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