Long-term blood pressure regulation

Neurons in the hypothalamus make ADH and carry it down their axons to the posterior pituitary, which releases it into the blood.

• Made in the adrenal cortex, released from the adrenal medulla:
• Correct: Made in the hypothalamus, released from the posterior pituitary:
• Made in the kidneys, released from the kidneys:

Aldosterone, from the adrenal cortex, makes kidney cells reabsorb sodium into the blood and secrete potassium into the urine. Water follows the sodium by osmosis.

• Correct: Makes the kidneys reabsorb more sodium and secrete more potassium:
• Makes the kidneys excrete more sodium and keep more potassium:
• Raises blood glucose by breaking down glycogen:

MAP is the product of cardiac output and total peripheral resistance. If cardiac output falls and TPR is unchanged, MAP falls in proportion.

• It rises:
• It stays the same:
• Correct: It falls:

2.9 g ÷ 58.5 g/mol ≈ 0.05 mol, or 50 mmol of sodium. Thirst and ADH add water until that sodium sits at the normal 140 mmol/L. 50 ÷ 140 ≈ 0.36 L of extra fluid outside the cells.

• About 0.05 L: This is the amount of salt in moles, 0.05 mol, not a volume of fluid. The next step is to divide 50 mmol by 140 mmol/L.
• About 2.8 L: This divides 140 by 50 instead of 50 by 140. Holding 50 mmol at 140 mmol/L needs less than half a liter.
• About 0.07 L: This is about a fifth of 0.36 L, the part that ends up in the plasma, not the whole extra volume outside the cells.
• Correct: About 0.36 L: Correct. 50 mmol ÷ 140 mmol/L ≈ 0.36 L.

Water loss raises osmolarity and lowers volume. The nervous system, the kidneys, the adrenal cortex, the hypothalamus and the heart all respond: ADH, renin and aldosterone rise, ANP falls, and her kidneys make a small volume of concentrated urine while she waits for a drink.

• Plasma osmolarity: up. She lost more water than salt, so the solutes left in her plasma are more concentrated.
• ADH release: up. Hypothalamic osmoreceptors sense the higher osmolarity, and the fall in volume adds to the signal.
• Renin release: up. Lower pressure in the kidney's small arteries and more sympathetic stimulation both increase renin release.
• Aldosterone: up. More renin means more angiotensin II, which makes the adrenal cortex release aldosterone.
• ANP release: down. With less blood volume, venous return falls and the atria are stretched less.
• Urine volume: down. ADH makes the kidneys keep water, and aldosterone makes them keep sodium, which water follows.

With ACE blocked, less angiotensin II is made. Arterioles relax, and the adrenal cortex releases less aldosterone, so the kidneys keep less sodium and water. Blood volume and TPR both fall, which lowers pressure.

• Renin release from the kidneys falls sharply: Angiotensin II normally holds back renin release. With less angiotensin II and lower pressure, renin release rises.
• Angiotensin I in the plasma falls to near zero: Angiotensin I is made by renin, which still works. With the conversion step blocked, angiotensin I builds up.
• Correct: Aldosterone falls, and more sodium is excreted: Correct. Less angiotensin II means less aldosterone, so more sodium and water leave in the urine.
• Plasma potassium falls below its normal range: Aldosterone makes the kidneys secrete potassium. With less aldosterone, they secrete less, so plasma potassium tends to rise.

A fall in volume of more than about 5 to 10 percent reduces stretch of the arterial baroreceptors and of the stretch sensors in the atria and large veins. That drives ADH release steeply, to levels far above those osmolarity produces, and the volume signal overrides a normal osmolarity.

• His osmoreceptors are reporting a hidden rise in osmolarity: Losing whole blood removes plasma and its solutes together, so osmolarity stays normal. The osmoreceptors are not the source of this signal.
• Correct: The large fall in volume and pressure drives ADH release: Correct. A large volume loss is a powerful ADH trigger in its own right.
• Pain releases ADH, and pain is the main trigger after injury: Pain and stress can raise ADH somewhat, but the rise after a large bleed is driven mainly by the loss of volume.
• His kidneys release ADH when their blood flow falls: ADH comes from hypothalamic neurons and is released from the posterior pituitary. The kidneys are its target, not its source.

Adding fluid that matches plasma raises volume but not osmolarity. The atria sense the extra volume and release ANP, the RAAS switches down, and the kidneys excrete the extra sodium and water over the next hours.

• Atrial stretch: up. More blood volume raises venous return, which fills and stretches the atria more.
• ANP release: up. Stretched atrial muscle cells release ANP.
• Renin release: down. Higher pressure in the kidney's small arteries, less sympathetic stimulation and ANP all reduce renin release.
• Aldosterone: down. Less renin means less angiotensin II, and ANP also reduces aldosterone release directly.
• Plasma osmolarity: no change. Saline matches the concentration of plasma, so it adds volume without changing osmolarity.
• Urine sodium excretion: up. More ANP and less aldosterone make the kidneys keep less sodium, so more leaves in the urine with water.

Right after the bleed, pressure falls and the reflex speeds the heart. Over the next hours, renin, angiotensin II, aldosterone and ADH rise, urine output falls and thirst increases. Over one to two days, kept and drunk fluid restores plasma volume, so the fast reflex no longer has to work hard and heart rate settles.

• Mean arterial pressure, first minutes: down. Less volume means less venous return, stroke volume and cardiac output, so MAP falls before the reflexes fully catch up.
• Renin release, first hour: up. Lower pressure in the kidney's small arteries and sympathetic stimulation of the renin-making cells both increase renin.
• ADH, first hour: up. A loss of this size lowers stretch of the baroreceptors and the atrial sensors, which drives ADH release steeply.
• Urine volume, first day: down. Aldosterone keeps sodium and ADH keeps water, so less of both reaches the urine.
• Plasma volume two days later, compared with just after the bleed: up. Kept salt and water, plus thirst-driven drinking, refill the plasma.
• Heart rate two days later, compared with the first hour: down. With volume restored, venous return and stroke volume recover, baroreceptor firing returns, and sympathetic drive to the SA node eases.

Extra volume stretches the atria, so ANP rises. It also raises pressure in the kidney's small arteries, and ANP itself inhibits renin, so renin and angiotensin II fall, and aldosterone falls with them. Every signal pushes the kidneys to excrete sodium and water.

• ANP high, renin high, aldosterone high: Renin and aldosterone rise when volume is low. With extra volume and high ANP, both are turned down.
• ANP low, renin high, aldosterone high: This is the pattern for low volume. Extra volume raises ANP and lowers renin and aldosterone.
• Correct: ANP high, renin low, aldosterone low: Correct. High ANP with low renin and aldosterone is the response to too much volume.
• ANP low, renin low, aldosterone low: ANP is released by atrial stretch, which extra volume increases, so ANP would be high, not low.