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Flashcards in Adrenal Pathology Deck (40)
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What is the 2 basic components of the adrenal gland?

Composed of the cortex, which secretes cholesterol derived hormones, and adrenal medulla which secretes the catecholamines.


What are the three components of the adrenal cortex?

GFR, Glomerulosa, Fasiculata and Reticularis.


What are the different hormones produced by the adrenal cortex that are derived from cholesterol?

In the glomerulosa of the AC, Mineralocorticouids (like aldosterone, for salt maintenance) is made, in the Fasciculata makes glucocorticoids (like cortisol for sugar maintenance among others) and in the reticularis the sex steroids are made. "It gets sweeter as you get deeper," i.e. from salt (aldesterone) to cortisol (sugar) to sex (deeper?)


What is the basic problem of hyperaldosteronism?

Too much aldosterone production by the adrenal cortex, specifically by the Granulosa of the AC.


How would hyperaldosteronism present?

Increased Na, decreased K, and metabolic alkalosis. Also HTN due to water retention.


Where does aldosterone work?

Late Distal Tubule and Collecting duct, where 2 cell types are found: principal cells and alpha intercalated cells.


What do the principal cells and alpha intercalated cells do to respond to aldosterone? How does this manifest?

Principal cells will reabsorb Na but dump K back into the tubules thereby excreting them. Alpha intercalated cells will dump H+ and excrete that. Net result: increased Na and HTN results, decreased K and hypokalemia results, and decreased H+ so metabolic alkalosis results.


What is the main reason and two lesser reason for primary hyperaldosteronism?

Most commonly due to adrenal adenoma, but also sporadic hyperplasia and carcinoma can cause this as well.


How is primary hyperaldosteronism characterized by in terms of hormones?

High aldosterone, which increases body fluids that will be detected by the juxtaglomerular cells of the kidney, and they respond by lowering renin because there is no need to raise BP when there is so much fluid.


What defines a secondary hyperaldosteronism?

High aldosterone however not due to the adrenal, but due to the RAS activation.


Why does the RAS activate in young women?

Fibromuscular dysplasia, which will thicken the walls of the BV's of renal arteries, making the JG cells detect low blood flow and respond by secreting renin to increase blood flow.


Why does the RAS activate in older men?

Atherosclerosis of the renal artery, which will basically block the blood flow into the kidneys and the JG will think there is low blood flow, respond with renin secretion.


What is secondary hyperaldosteronism characterized by hormone wise?

High aldosterone, high renin (because the JG's detect low blood flow and tries to compensate by raising BP, and does so by secreting renin which converts angiotensiongen to angiotension I, which turns into angiotensiotensin II, which makes adrenal gland make aldosterone.


What is the reasoning behind "Congenital adrenal Hyperplasia?"

Excess sex steroids with hyperplasia of both adrenal glands, as a result of congenital abnormalities.


What is the most common enzyme deficiency that causes the congenital adrenal hyperplasia?

21-hydroxylase deficiency.


Why is the enzyme 21-hydroxylase important?

It is necessary to convert pregnenolol into mineralocorticoids or to cortisol.


What does a congenital adrenal hyperplasia with 21-hydroxylase deficiency result in?

Since no 21-hydroxylase is available, no conversion of pregnenolol to cortisol or mineralocorticoids happen, so all the pregnenolol gets converted to the third pathway, conversion of sex hormones. This results in enlarged clit for females, precocious puberty for males. Low cortisol will result in life threatening hypotension (because cortisol hits the alpha 1 vascular receptors to maintain vascular tone). Also low cortisol makes AP think it needs more cortisol so it secretes excess ACTH, resulting in b/l adrenal hyperplasia.


Congenital adrenal hyperplasia has this consequence in mineralocorticoids if due to 21-hydroxylase deficiency:

No conversion of pregnenolol into mineralocorticoids, no aldosterone = salt wasting (hyponatremia) and retension of K (hyperkalemia), as aldosterone would retain Na and excrete K if it were present. Also can cause hypovolumia because no water retention due to aldosterone.


If it is not a 21 hydroxylase deficiency induced congenital adrenal hyperplasia, and there is no salt wasting hypovolumia or hyperK, what is it? How would this present?

Due to a deficiency in 11ß Hydroxylase. Pregnenolol turns into a weak mineralocorticoid via 21 hydroxylase, and that product is converted to a strong mineralocorticoid via 11ß hydroxylase. Also 11ß hydroxylase is needed to turn pregnenolol into cortisol (second step after 21 hydroxylase). This results in the same cortisol induced problems, but there will be some mineralocorticoids so no salt wasting, no hyper K, no hypovolumia, but yes b/l adrenal hyperplasia, life threatening hypovolumia, enlarged clit/precocious puberty.


What would happen if there is a 17 hydroxylase deficiency instead for congenital adrenal hyperplasia?

17 Hydroxylase is needed to initiate both the cortisol and sex steroid pathways (before 21 and 11 can come into play). Deficiency in 17 hydroxylase will result in increased mineralocorticoids with no sex steroids or cortisol, thus still resulting in adrenal hyperplasia, along with probably hypervolumia, hypo K and hyper Na, as well as late puberty and late development of female clit.


What is the classic disease for inducing adrenal insufficiency?

Waterhouse-Friderichsen syndrome. This is due to lack of adrenal hormones.


What is the progression of Waterhouse-Friderichsen syndrome?

Occurs in a young child with Neisseria Meningitidis infection, which then develops into DIC, and gets b/l necrosis of both adrenal glands. Results in acute lack of cortisol, and thus exacerbate the hypotension.


How would acute adrenal insufficiency and Waterhouse-Friderichsen syndrome present?

The adrenal glands will look like a "sac of blood."


What is chronic insufficiency and what causes it?

Progressive and slow destruction of adrenal glands, can be caused by 3 things: autoimmune, TB, or metastatic carcinoma, particularly lung cancer.


Where does lung cancer love to metastasize?

It loves to go to the adrenals.


What are the clinical features of Adrenal insufficiency?

Hypotension, hyponatremia, hyper K, hypovolumia. Weakness, hyperpigmentation of oral mucosa and skin, and vomitting, diarrhea.


Why would chronic insufficiency present as hyperpigmentation?

Lack of cortisol will result in the AP secreting ACTH, which is derived from POMC. POMC also produces melanocyte simulating hormone (MSH), which stimulates the melanocytes to induce hyperpigmentation.


Where is the adrenal medulla derived from?

Neural crest derived.


What is the adrenal medulla composed of?

Chromaffin cells.


What 2 hormones are secreted by the adrenal medulla?

Epi and NorEpi.


What is "Pheochromocytoma?"

A tumor of the chromaffin cells of the adrenal medulla.


What color does pheochromocytoma present as?

It will be a brown tumor because the adrenal medulla is brown, as compared to the adrenal cortex which will be yellow.


What are the clinical features of Pheochromocytoma and what causes it?

All the symptoms are caused due to Epi and NorEpi production, which results in episodic HTN, headaches, palpitations, tachycardia and sweating.


How would we diagnose Pheochromocytoma?

Increased serum metanephrines and increased 24 hr urine metanephrines and VMA.


How is Pheochromocytomas Tx-ed? What must be administered before tx?

Surgical excision. Must administer phenoxybenzamine before tx, which is an irreversible blocker of alpha receptors, thus when the tumor is removed there is a potential for a massive release of epi and norepi. Phenoxybenzamine will block the alpha receptors so no effect of that will take place.


How are both Epi and NorEpi metabolized?

Epinephrine gets metabolized into metanephrine, norepi turns into normetanephrine. Both of these compounds get further converted into VMA due to the Monoamine Oxidase (MAO).


What are the 4 rule of 10's in relation to pheochromocytoma?

10% are b/l, 10% familial, 10% (90% benign) malignant and 10% located outside the medulla (90% in medulla).


What is a classic site of pheochromocytoma if it is outside of the medulla?

In the bladder wall.


What is Pheochromocytoma associated with?

MEN2A (medulla carcinoma of thyroid, pheychromocytoma and parathyroid adenoma) and 2B (Medullary Carcinoma of thyroid, Pheochromocytoma, mucosal ganglio neuromas esp in oral mucosa) VHL disease, and NF type I.


What is Von Hippel Lindau disease (VHL disease)?

AD condition where VHL tumor suppressor is lost, resulting in an increased risk of hemangioblastoma of cerebellum, renal cell carcinoma, and Pheochromocytoma.