The Lab / Core medicine / Lesson 5
Three chemical messengers passed along like a relay: the kidney’s way of raising blood pressure and holding on to salt. Build the chain one link at a time, then see where four kinds of drugs cut it.
Educational, not for clinical use
Build the chain
Your two kidneys clean the blood and make urine. They also feel the blood pressure, the push of blood against artery walls, in the vessel that feeds them. The dotted line shows that sensing; the dial shows the push. Lesson 4 covers pressure itself.
Build the chain
When pressure falls, or less salt reaches them, cells in the kidney release more renin into the blood. Renin is an enzyme: a protein that makes one chemical change happen, here cutting another protein. The bar shows how much renin is released.
Build the chain
The liver keeps angiotensinogen, a long protein, in the blood all the time. Renin snips a short piece off its end. That piece is angiotensin I (“angiotensin one”), which does very little by itself. More renin means more angiotensin I.
Build the chain
In the lungs, angiotensin-converting enzyme (ACE for short), on the inner lining of the vessels, trims angiotensin I shorter. The result is angiotensin II (“angiotensin two”), a hormone: a chemical messenger carried in the blood that changes what distant organs do.
Build the chain
Angiotensin II only works where it can dock. A receptor is a cell’s docking site for one particular messenger, shaped to fit it like a lock fits a key. When angiotensin II docks, the cell answers. Cells without the receptor ignore it.
Build the chain
Arterioles are the smallest arteries, wrapped in muscle. Angiotensin II docks on their receptors and the muscle tightens, so they narrow. Blood finds it harder to get through, called higher resistance, and the pressure behind it rises within minutes.
Build the chain
Angiotensin II also reaches the adrenal glands, two small glands sitting on top of the kidneys. Docking on their receptors makes them release aldosterone, the third messenger in the relay. Aldosterone travels in the blood back to the kidneys.
Build the chain
Each kidney makes urine in tiny tubes called nephrons. Near their end, aldosterone makes them take more sodium, the main part of table salt, back into the blood, and send more potassium, another mineral carried in the blood, out in the urine. Lesson 2 follows the nephron.
Build the chain
Where sodium goes, water follows. Keeping salt keeps water, so blood volume, the amount of blood in the circulation, grows. A fuller circulation pushes harder on artery walls, so pressure rises. This is the slow arm: it works over hours to days.
Build the chain
As pressure climbs back, the kidney feels the push and releases less renin, so each later link makes less. This is negative feedback: a result that turns down its own cause. It holds pressure steady even when you eat more or less salt.
Build the chain
Low pressure releases renin. Renin cuts angiotensinogen into angiotensin I; ACE makes angiotensin II. It squeezes arterioles and calls out aldosterone, which keeps salt and water. Pressure rises, and feedback eases renin. Key measures: blood pressure, blood volume and potassium.
What changes it
An inhibitor is a drug that stops an enzyme working. ACE inhibitors stop ACE, so little angiotensin II is made: arterioles relax, aldosterone falls and pressure drops. The kidney answers with more renin, so angiotensin I piles up unused. Potassium rises.
What changes it
Angiotensin receptor blockers (ARBs) block the receptor angiotensin II uses to squeeze arterioles and call out aldosterone. Arterioles relax, aldosterone falls and pressure drops. The kidney releases more renin, so the blood holds more angiotensin II, but it cannot use that receptor. Potassium rises.
What changes it
An antagonist blocks a receptor without switching it on. Aldosterone antagonists, such as spironolactone, block aldosterone’s receptor in the nephron. Less sodium and water are kept, so volume and pressure fall, and potassium builds up. The body makes more aldosterone, to little effect.
What changes it
Direct renin inhibitors stop renin itself, so angiotensinogen is barely cut. Every later link falls: less angiotensin I, less angiotensin II, less aldosterone, and pressure drops. The kidney releases even more renin, but the drug keeps it from working. Potassium rises.
Start with Next, or use the arrow keys. Bars are illustrative amounts, not measurements.
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Normal teaching baseline.
The blue line on each bar is an illustrative teaching model, not a patient measurement. A shaded band is the textbook normal range; a black line is a textbook typical value where the source gives no range. Arrows show the expected direction from the cited source; real responses vary.
An illustrative teaching model of the whole chain. Weaken one link, change the salt you eat, or switch the feedback off, and watch the rest of the chain answer. The faint dashed outlines are the normal state.
Everything is relative to a normal resting state, where every quantity equals 1. The kidney releases renin; with feedback working, the amount rises steeply when pressure is below normal and falls when it is above. Renin’s working share (set by the renin slider) cuts angiotensinogen, which the model treats as never running out, so angiotensin I follows working renin. ACE’s working share turns angiotensin I into angiotensin II, and the free share of angiotensin II receptors sets the signal reaching cells. That signal tightens arterioles (resistance) and, with a resting floor, sets aldosterone release; an adrenal tumor can add aldosterone on top. Aldosterone’s free receptors set its effect. Salt kept is the average of aldosterone’s effect and the angiotensin II signal (angiotensin II also helps the kidney keep sodium directly). Blood volume rises gently with salt kept and with salt eaten, and pressure rises with the square of volume times resistance. Potassium falls as aldosterone’s effect rises, and sodium moves only very slightly, because water follows the salt. The model finds the steady state where the pressure the kidney senses equals the pressure the chain produces. It omits thirst, the brain’s water-holding hormone, nerves, kidney filtering and anything about timing. In the Clinical values tab the relative results are multiplied by the textbook typical values to show illustrative numbers.