Adrenal glands

The adrenal medulla behaves like a sympathetic ganglion: preganglionic fibers release acetylcholine onto its chromaffin cells, which release epinephrine into the blood.

• ACTH from the anterior pituitary:
• Correct: Sympathetic preganglionic fibers releasing acetylcholine:
• Low blood potassium:

Steroids are lipid-soluble. They diffuse into the cell, bind an intracellular receptor protein, and the complex acts on DNA, so the cell makes different proteins over hours.

• It binds a membrane receptor protein and raises cyclic AMP within seconds:
• Correct: It crosses the plasma membrane, binds an intracellular receptor protein and changes which genes are transcribed:
• It opens ion channels directly:

Long-loop negative feedback: the target gland's hormone travels back in the blood and inhibits both the releasing hormone and the tropic hormone.

• Correct: The final hormone from the target gland feeds back and inhibits them:
• The target gland runs out of hormone:
• Nerves from the target gland signal the pituitary directly:

The zona fasciculata (fascicul- = little bundle) is the thickest layer of the cortex. Its cells line up in columns, and it makes cortisol, the main glucocorticoid.

• Zona glomerulosa; aldosterone: The zona glomerulosa is the thin outer layer of rounded clusters (glomerul- = little ball). It makes aldosterone.
• Zona reticularis; androgens: The zona reticularis is the inner layer of branching cords (reticul- = little net). It makes androgens such as DHEA.
• Medulla; epinephrine: The medulla is the core, with larger round chromaffin cells, not columns. It makes epinephrine.
• Correct: Zona fasciculata; cortisol: Correct. Columns of cells in the thickest layer: the zona fasciculata, making cortisol.

Low pressure in the kidney triggers renin release. Renin makes angiotensin I from angiotensinogen; ACE makes angiotensin II; angiotensin II releases aldosterone; aldosterone makes the kidney keep sodium, and water follows by osmosis, restoring volume.

• Correct order: 1. Pressure falls in the kidney's small arteries 2. Kidney cells release renin into the blood 3. Renin converts angiotensinogen from the liver into angiotensin I 4. ACE, mostly in the lungs, converts angiotensin I into angiotensin II 5. Angiotensin II makes the zona glomerulosa release aldosterone 6. The kidneys reabsorb more sodium, and water follows

During treatment, feedback from the drug suppresses ACTH and the zona fasciculata shrinks. When the drug stops suddenly, glucocorticoid activity crashes: blood glucose and blood pressure fall, the picture of an adrenal crisis. ACTH stays low at first, and it rises only over weeks to months, while the shrunken cortex recovers more slowly still. That is why long courses of glucocorticoids are tapered.

• ACTH, during treatment: down. The drug acts like cortisol on the hypothalamus and pituitary, so long-loop feedback suppresses CRH and ACTH.
• Size of his zona fasciculata, during treatment: down. ACTH keeps the zona fasciculata large; without it, the layer shrinks over weeks.
• His own cortisol release, during treatment: down. With little ACTH, the shrunken zona fasciculata makes little cortisol.
• Total glucocorticoid activity, in the days after stopping: down. The drug is gone, and his shrunken adrenal cortex cannot make up for it quickly.
• Blood glucose, in the days after stopping: down. Without glucocorticoid, the liver makes less glucose by gluconeogenesis.
• Blood pressure, in the days after stopping: down. Cortisol is permissive for the vessels' response to norepinephrine and epinephrine; without it, vessels constrict poorly.
• ACTH, in the days after stopping: no change. The hypothalamus and pituitary were suppressed for months and take weeks to restart, so ACTH stays low at first; that is why the crisis comes on so fast.

This is Addison disease, primary adrenal insufficiency. Low cortisol explains the weakness, weight loss and low glucose; low aldosterone explains the salt loss, high potassium and faintness. Feedback no longer holds back the pituitary, so ACTH rises very high, and high ACTH darkens the skin.

• Her anterior pituitary is releasing too little ACTH: Her ACTH is very high, not low. Pituitary failure would also spare aldosterone and would not darken her skin.
• Correct: Her adrenal cortex has been destroyed: Correct. Both cortisol and aldosterone are low, and ACTH is high, so the cortex itself has failed.
• Her adrenal medulla has stopped releasing epinephrine: Losing epinephrine alone causes little, because sympathetic nerves cover its effects. It cannot explain the high potassium or dark skin.
• Her hypothalamus is releasing too much CRH: Too much CRH would raise ACTH and so raise cortisol, giving high glucose, not low.

Blocking ACE lowers angiotensin II, so the zona glomerulosa releases less aldosterone. With less aldosterone, the kidney secretes less potassium into the urine, and plasma potassium rises. Clinicians check potassium after starting these drugs.

• Correct: It rises: Correct. Blocking ACE lowers angiotensin II, so the zona glomerulosa releases less aldosterone. With less aldosterone, the kidney secretes less potassium into the urine, and plasma potassium rises. Clinicians check potassium after starting these drugs.
• It falls: Potassium excretion falls, not rises, when aldosterone falls, so plasma potassium cannot fall for this reason.
• It does not change: Aldosterone is a main control of potassium excretion, so lowering it changes potassium.

Cortisol raises blood glucose by driving gluconeogenesis, breaking down muscle protein for its amino acids and making tissues resist insulin. It is permissive for the vessels' response to sympathetic signals. It damps inflammation and slows bone building.

• Correct: More gluconeogenesis in the liver: Correct. Cortisol switches on gluconeogenesis.
• Correct: Breakdown of muscle protein: Correct. The amino acids feed gluconeogenesis; in excess, muscles waste.
• Stronger inflammatory responses: Cortisol damps inflammation, which is why glucocorticoid drugs treat inflammatory diseases.
• Correct: Blood vessels that respond normally to norepinephrine: Correct. This permissive effect is why low cortisol causes low blood pressure.
• Faster bone building: Cortisol slows bone building; long-term excess thins bone.
• Correct: Less response of muscle and fat to insulin: Correct. Muscle and fat take up less glucose, which leaves more in the blood; in excess this causes high blood glucose.

In pituitary failure, ACTH is low, so nothing darkens the skin. Cortisol falls, but the zona glomerulosa still answers angiotensin II and potassium, so aldosterone is mostly spared and potassium stays normal. In Addison disease the cortex itself is destroyed, so aldosterone falls too, and very high ACTH darkens the skin.

• The pituitary tumor releases aldosterone in place of ACTH: The pituitary does not make aldosterone; only the zona glomerulosa does.
• Correct: ACTH is low, and aldosterone has its own main controls: Correct. Low ACTH means no darkening, and aldosterone keeps its own controls.
• The adrenal medulla takes over making cortisol: The medulla makes epinephrine and norepinephrine. It cannot make steroids.
• The skin and kidneys stop responding to adrenal hormones: Nothing changes the tissues' responses. The difference lies in which hormones are low.

The alarm reaction is the fight-or-flight response, acting in seconds through sympathetic nerves and epinephrine from the adrenal medulla. Epinephrine speeds the heart and switches on glycogenolysis in the liver.

• Resistance; cortisol: Cortisol acts over hours through new proteins. It carries the stage of resistance, not the first seconds.
• Correct: Alarm reaction; epinephrine: Correct. The seconds-long response is sympathetic and epinephrine-driven.
• Alarm reaction; aldosterone: Aldosterone takes hours to act and handles sodium and potassium, not heart rate.
• Stage of exhaustion; ACTH: The stage of exhaustion comes after weeks or months of unrelieved stress.