Adrenal & Fluid-Balance Disorders

BCH 130 β€” Advanced Human Biochemistry Β· Dr. Radi

build Jul 18 Β· 08:24 Β· CC BY-NC-SA 4.0 Β· owned figures (RDKit / matplotlib)
Dr. Radi

By the end of this unit, you can…

  • Walk the renin-angiotensin-aldosterone system and diagnose primary aldosteronism (Conn) via the aldosterone-to-renin ratio.
  • Distinguish endocrine causes of secondary hypertension (primary aldosteronism, renovascular, Cushing, pheochromocytoma) and their labs.
  • Explain RAAS-blocking pharmacology: ACE inhibitors, ARBs, mineralocorticoid-receptor antagonists, and direct renin inhibitors.
  • Explain vasopressin (ADH) physiology β€” osmoreceptor control, V2/aquaporin-2 β€” and the biochemistry of water reabsorption.
Dr. Radi

Today's route πŸ—ΊοΈ

  1. RAAS Disorders & Secondary Hypertension
  2. Vasopressin & Water-Balance Disorders
  3. Catecholamine Excess & the Adrenal Medulla
Dr. Radi

1 Β· RAAS Disorders & Secondary Hypertension

"Most high blood pressure is 'essential' β€” no single cause. But a slice of it is endocrine, and that slice is CURABLE if you name the hormone. Today we walk the renin-angiotensin-aldosterone system, catch primary aldosteronism with one ratio, and block the pathway at four different points."

Dr. Radi

The RAAS, one enzyme at a time

The body's blood-pressure thermostat. Low renal pressure releases renin, which clips angiotensinogen to angiotensin I; ACE (lung) makes angiotensin II β€” a vasoconstrictor that drives adrenal aldosterone (holds Na⁺ and water). Pressure and volume climb β€” and that climb feeds back to shut renin off.

Dr. Radi

One ratio catches Conn

The most under-diagnosed curable hypertension. In Conn, an adrenal adenoma makes aldosterone autonomously β€” volume climbs, potassium drops, and the high volume suppresses renin to the floor. High aldosterone with low renin is the tell: the aldosterone-to-renin ratio (ARR) shoots up. Screen positive β†’ hunt the adenoma.

Dr. Radi

Four endocrine causes β€” sorted by lab

When hypertension is young, severe, or drug-resistant, think endocrine β€” and the labs sort the four culprits. Renin is the first fork: low in Conn (aldosterone-driven), high in renovascular disease. Cushing shows cortisol that won't suppress with dexamethasone; pheochromocytoma shows sky-high metanephrines.

Dr. Radi

Block it in four places

Now the payoff β€” every RAAS drug is a ⊣ on the cascade. Direct renin inhibitors (aliskiren) cap the top. ACE inhibitors (-prils) stop angiotensin II forming. ARBs (-sartans) block its AT1 receptor. MR antagonists (spironolactone, eplerenone) block aldosterone itself. One pathway, four levers.

Dr. Radi

2 Β· Vasopressin & Water-Balance Disorders

"Aldosterone handled the salt; now meet the hormone that handles the WATER. Vasopressin (ADH) lets the kidney reclaim free water on demand β€” and when it's too loud, too quiet, or ignored, the serum sodium tells you exactly which. Learn to read osmolality and the diagnosis falls out."

Dr. Radi

How the body claws back water

When plasma turns too concentrated, hypothalamic osmoreceptors fire and the posterior pituitary releases ADH. ADH hits the V2 receptor β†’ Gs β†’ cAMP β†’ and the cell inserts aquaporin-2 into its apical membrane. Water flows back, urine concentrates, plasma osmolality falls β€” quieting the osmoreceptors. Fast and self-correcting.

Dr. Radi

Serum vs urine: three diseases

Break it three ways and the osmolality pair names each. SIADH = too much ADH β†’ water trapped β†’ dilute serum (Na⁺ < 135), wrongly concentrated urine. Both DI types lose water (dilute urine, concentrated serum): central DI makes no ADH; nephrogenic DI makes plenty but the kidney ignores it.

Dr. Radi

Same receptor, opposite drug

Management is beautifully logical β€” aim at V2. For SIADH (hyponatremia), fluid-restrict and add a vaptan that blocks V2, dumping free water. For central DI (hypernatremia), give desmopressin β€” a V2 agonist replacing the missing ADH. Nephrogenic DI resists V2, so desmopressin fails: use a thiazide + low salt, stop the offender.

Dr. Radi

3 Β· Catecholamine Excess & the Adrenal Medulla

"The adrenal cortex made steroids; the adrenal MEDULLA makes catecholamines. Follow tyrosine all the way to epinephrine, see how it's broken down into the metanephrines we measure β€” and meet pheochromocytoma, the tumor that comes in spells and can kill you if you block the wrong receptor first."

Dr. Radi

Tyrosine to epinephrine β€” and back down

One amino acid builds them all. Tyrosine β†’ (tyrosine hydroxylase, rate-limiting) β†’ L-DOPA β†’ dopamine β†’ norepinephrine β†’ (PNMT, needs cortisol) β†’ epinephrine, stored in chromaffin granules. Breakdown matters too: COMT and MAO convert them to metanephrines and finally VMA β€” the stable products we measure.

Dr. Radi

The tumor that comes in spells

Pheochromocytoma is a chromaffin-cell tumor of the adrenal medulla (paraganglioma if extra-adrenal). It fires catecholamines in paroxysms β€” the P's: Pressure (episodic HTN), Pain (headache), Palpitations, Perspiration, Pallor. It leaks continuously, so plasma free or 24-h urine metanephrines stay high even between spells β€” the best test.

Dr. Radi

Alpha before beta β€” always

The one on every exam and every ward. Catecholamines drive Ξ±1 (vasoconstriction) and Ξ²2 (vasodilation). Block Ξ² first and you strip the dilating brake β€” leaving Ξ±1 unopposed, vessels clamp, hypertensive crisis. So the order is fixed: Ξ±-blocker first (phenoxybenzamine, doxazosin), then the Ξ²-blocker for rate.

Dr. Radi

Can you…?

  • ☐ walk the renin-angiotensin-aldosterone system and diagnose primary aldosteronism (Conn) via the aldosterone-to-renin ratio.?
  • ☐ distinguish endocrine causes of secondary hypertension (primary aldosteronism, renovascular, Cushing, pheochromocytoma) and their labs.?
  • ☐ explain RAAS-blocking pharmacology: ACE inhibitors, ARBs, mineralocorticoid-receptor antagonists, and direct renin inhibitors.?
  • ☐ explain vasopressin (ADH) physiology β€” osmoreceptor control, V2/aquaporin-2 β€” and the biochemistry of water reabsorption.?

If any box stays empty, the practice site has a drill for it. πŸ§ͺ

Dr. Radi