Flashcards in 15.8 - 15.10: Parathyroid gland, Endocrine pancreas, adrenal cortex / medulla Deck (171):
What is the key cell within the parathyroid gland? What does this do?
-Regulates *free* ionized calcium in the serum via PTH secretion
What percent of the Ca in the body is bound to proteins?
What is the effect of PTH on the bones? How?
Increases osteoclast activity, by first activating osteoBLASTS, which then activate osteoclasts
What is the effect of PTH on the small bowel? How?
Increases small bowel reabsorption of Ca and Phosphate through vitamin D
What is the effect of PTH on the kidneys?
Increases renal calcium reabsorption, and decreases phosphate reabsorption
What are the cells that secrete bone? Resorb bone?
Secrete = Osteoblasts
Resorb = Osteoclasts
How are osteoclasts activated?
Osteo*blasts* receive PTH signal, which then activate osteoclasts
Why is it important that PTH increases the excretion of phosphate?
Phosphate binds free Ca, so getting rid of it increases free Ca levels within the serum
What is primary hyperparathyroidism?
Excess PTH d/t a disorder of the parathyroid gland itself
What is the most common cause of primary hyperparathyroidism?
True or false: a parathyroid adenoma is benign
Do parathyroid adenomas usually involve more than one gland?
What is the most common presentation of a parathyroid adenoma?
What are the kidney problems that can arise from a parathyroid adenoma? (2)
-Nephrolithiasis (Ca oxalate stones)
What are the GI problems that can arise from a Parathyroid adenoma? (3)
What is nephrocalcinosis?
Deposition of Ca into the tubules of the kidney, resulting in polyuria
What are some of the CNS disturbances that can be caused by hypercalcemia from a parathyroid adenoma?
How can hypercalcemia cause acute pancreatitis?
Ca activates the enzymes in the pancreas
What is osteitis fibrosa cystica?
Resorption of Ca from the bone causes cyst formation in the bones
What happens to the following lab values with hyperparathyroidism:
-Serum alk phos
-Serum Ca (increased)
-Serums phosphate (decrease)
-Urinary cAMP (increase)
-Serum alk phos (increase)
How does hyperparathyroidism cause increased urinary cAMP?
Gs coupled protein activation by PTH
What is the role of alk phos in bone normally? Why is it increased in hyperparathyroidism?
-Normally aids in the deposition of Ca onto bone by generating an alkaline environment
-Since PTH first activates osteoblasts, these cells secrete alk phos
What is the treatment for a hyperparathyroidism secondary to a parathyroid adenoma?
Surgical removal of the affected gland
What is secondary hyperparathyroidism?
Excess production of PTH d/t disease process extrinsic to the parathyroid gland
What is the most common cause of secondary hyperparathyroidism?
Chronic renal failure
How does chronic renal failure lead to hyperparathyroidism?
Decreased phosphate excretion leads to increased serum levels of phosphate, which binds Ca. Lower Ca levels then stimulate the parathyroid gland
What is the effect of a lack of phosphate excretion in chronic renal disease in terms of PTH secretion?
Higher phosphate leads to lower Ca, leading to increased PTH levels
What happens to the following lab values with secondary hyperparathyroidism:
-Decreased serum Ca
-Increased serum phosphate
-Increased alk phos
What are the three major causes of hypoparathyroidism?
Which pharyngeal pouches fail to develop in DiGeorge syndrome? What is the genetic cause of this?
3rd and 4th
chr 22q del
What are the s/sx of hypoparathyroidism?
-Numbness and tingling
-Muscle spasms (tetany)
What happens to serum PTH and Ca levels with pseudohypoparathyroidism?
Where specifically does the numbness/tingling start with hypoparathyroidism?
What is the trousseau sign?
a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm.
What is Chvostek sign?
a clinical sign of existing nerve hyperexcitability (tetany) seen in hypocalcemia. It refers to an abnormal reaction to the stimulation of the facial nerve. When the facial nerve is tapped at the angle of the jaw (i.e. masseter muscle), the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcemia
What is pseudohypoparathyroidism?
When end-organs do not respond to PTH d/t a mutation in the Gs protein
What are the PTH and Ca levels with pseudohypoparathyroidism?
Hypocalcemia and increased PTH levels
What is the inheritance of pseudohypoparathyroidism? What are the physical deformities that can present with this?
Short stature + short 4th and 5th digits
What are the cells that comprise the endocrine pancreas called?
Islets of Langerhans
What does a single islet of Langerhans contain?
multiple cells types, each producing one hormone type
What cells of the pancreas secrete insulin? Where are these cells in the islets?
-Center of islets
What cells of the pancreas secrete glucagon?
Where in the islets of langerhans do the beta cells lie?
What is the MOA of insulin?
Increases the movement of GLUT 4 receptors to the surface of cells
What type of hypersensitivity rxn occurs in type I DM?
What are the HLA haplotypes associated with DM I?
DR3 and DR4
What is the classic histological finding of DM I?
Inflammation of the islets
What are the autoantibodies that can be seen with DM I?
What causes the muscle wasting with untreated DM I?
Increased gluconeogenesis from amino acids
What are the risk factors for DKA?
How does stress cause DKA?
Epinephrine increases glucagon, exacerbating lipolysis
What are the three ketone bodies that are found in DKA?
What, besides hyperkalemia, are the lab findings with DKA?
-Anion gap metabolic acidosis
What are the s/sx of DKA? What type of respirations?
-mental status changes
Why the anion gap metabolic acidosis with DKA?
Increased ketonic acids
Why is there hyperkalemia with DKA? (2)
-Insulin causes K to go into cells, but there is none
-K is exchanged for H+ in the serum
True or false: despite having high potassium levels in the serum, DKA pts actually have lower K levels overall
What are the three measures to take to treat DKA?
How can treating DKA lead to hypokalemia?
-Insulin will force K into cells
-Reversal of the acidosis
What is the classic DM II pt?
Obese middle aged adult
True or false: there is a strong genetic predisposition for DM II
How does DM II arise?
Decreased numbers of insulin receptors
Which has a stronger genetic inheritance, type 1 or 2 DM?
What are the histological findings of DM II?
Islets of Langerhans are filled with amyloid
What are the ssx of DM II, if any?
What are the clinical values for random and fasting glucose levels to diagnose DM II?
-Random more than 200 mg/dL
-Fasting more than 126 mg/dL
What is the glucose tolerance test?
More than 200 mg/dL two hours after glucose load
What is the first line therapy for DM II?
What are the pharmacological treatments for DM II? (2)
-Drug therapy to counter insulin resistance
When in the progression of DM II do pts become insulin dependent?
What is hyperosmolar nonketotic coma? Why are there no ketones with this?
-High glucose levels cause dehydration, leading to hypotension and coma.
-No ketones since there is still a small amount of insulin to counter glucagon
What are the two major ways that complications from DM arise?
-Non-enzymatic glycosylation of BM
How is CVD mediated in DM II?
NEG of large and medium sized vessels leads to atherosclerosis
NEG of small vessels in DM II leads to what?
What is HbA1c?
How does DM II mediated CKD?
Efferent arteriole of the kidney preferentially undergoes NEG, causing a hyperfiltration state, causing sclerosing of the mesangium
What happens if there is hyaline deposition in the afferent arteriole of the kidney?
Diffuse sclerosis of the glomerulus from loss of blood supply
How does peripheral neuropathy develop in DM?
Schwann cells take up glucose independent of insulin. This glucose is converted to sorbitol, which leads to osmotic damage.
Recall that schwann cells myelinate peripheral nerves
What is the enzyme that converts glucose to sorbitol?
What are the three cells in the body that can take up glucose without insulin?
-Pericytes of the retinal blood vessels
How can DM cause blindness?
Pericytes of the retinal blood vessels take up glucose, convert it to sorbitol, and die. Aneurysms and bleeding then form
How do cataracts result from DM?
Lens cells take up glucose, convert it to sorbitol via aldose reductase, which causes osmotic damage
What cells do pancreatic endocrine tumors arise from?
Pancreatic endocrine tumors are often a component of what genetic malignancy? What other malignancies are associated with this?
What are the s/sx of an insulinoma?
Episodic hypoglycemia with mental status changes and are relieved by glucose
What are the levels of the following in an insulinoma:
What is Zollenger-Ellison syndrome?
gastrinoma that produces gastrin to increased HCl from parietal cells
What are the GI findings of a somatostatinoma?
-Achlorhydria (inhibition of gastrin)
-Cholelithiasis and steatorrhea (inhibition of CCK)
How do somatostatinomas cause cholelithiasis?
Somatostatin inhibits CKK action on the gallbladder
What is a VIPoma?
Tumor that causes and excessive vasoactive intestinal peptide to be produced
What are the findings of a VIPoma? (2) What electrolyte disturbance?
What is the effect of VIP on gastric acid secretion?
What is the effect of VIP on potassium levels?
What does the adrenal cortex secrete? Medulla?
-Cortex = hormones derived from cholesterol
-Medulla = catecholamines
What are the three layers of the adrenal cortex (from superficial to deep)?
What part of the adrenal cortex secretes aldosterone?
What part of the adrenal cortex secretes cortisol?
What part of the adrenal cortex secretes the sex hormones?
What does the mnemonic "it gets sweeter as it gets deeper" mean when applied to the adrenal cortex?
-Aldosterone controls salt
-Cortisol controls sugar
-Sex steroids are the sweetest
What are the findings of the extremities with cushing's syndrome? Why?
Muscle weakness with thin extremities, due to gluconeogenesis stimulation by cortisol
What areas of the body deposit fat with cushing's syndrome?
What, besides obesity, are the superficial abdominal findings with cushing's? Why?
-Cortisol impairs the synthesis of collagen
What are the CV findings of Cushing's? Why?
-Upregulation of alpha 1 receptors
What are the bone problems caused by Cushing's?
What happens to the immune system with cushing's syndrome?
What causes the muscle weakness with Cushing's?
Breakdown of amino acids for gluconeogenesis
What causes the abdominal striae with Cushing's?
Cortisol impairs the synthesis of collagen, leading to weak vessels, and thus vessel hemorrhage
How does Cushing's cause HTN?
Upregulates alpha 1 receptors on arterioles
Why is cortisol essential for life?
Maintains vascular tone
What are the three major mechanisms through which cortisol causes immune suppression?
-Inhibits phospholipase A2
-Inhibits histamine release from mast cells
What is the role of phospholipase A2?
converts arachidonic acid to generate proinflammatory prostaglandins
What is the role of IL-2?
T cell growth factor (switch to Th2)
How do you diagnose Cushing's syndrome?
24 hours cortisol level monitoring
What are the four major causes of Cushing's?
-Exogenous corticosteroids (iatrogenic)
-Primary adrenal adenoma, hyperplasia, or carcinoma
-ACTH secreting pituitary adenoma
-Paraneoplastic ACTH secretion
What is the most common cause of Cushing's syndrome?
Iatrogenic 2/2 exogenous corticosteroids
What causes the adrenal atrophy with exogenous corticosteroids?
No ACTH to maintain them
What are the three types of primary growths that can cause Cushing's syndrome?
What will happen to the adrenal gland that is not producing excess cortisol?
Decrease in size
What type of pituitary disease can cause Cushing's?
What is the classic example of a paraneoplastic syndrome that secretes ACTH?
Small lung cell carcinoma
What is the thinking behind the high dose dexamethasone test?
-Administering dexamethasone inhibits the production of ACTH by the pituitary adenoma
-but FAILs to suppress ectopic ACTH production by SCLC
What are the metabolic disturbances with hyperaldosteronism?
What happen to BP with hyperaldosteronism?
Where in the nephron does aldosterone work? MOA?
Late distal tubule of the collecting duct
What are the two cell types in the late distal collecting duct?
What is the role of the principal cell?
Absorbs Na, and secretes K in response to aldosterone
What is the role of the alpha-intercalated cell?
Secretes H+ ion in response to aldosterone
What are the metabolic disturbances that are seen with hyperaldosteronism?
What is the most common cause of primary aldosteronism? What are the two other, less common, causes?
What happens to renin levels in primary hyperaldosteronism? Why?
Increased blood flow to the kidney as a result of increased Na uptake
What is the cause of secondary hyperaldosteronism?
Activation of the renin-angiotensin system, leading to increased aldosterone
What happens to aldosterone and renin with secondary hyperaldosteronism?
Increased blood pressure in a young women can be cause be what effect on the kidney?
Fibromuscular Dysplasia of the renal artery
What is the primary pathophysiological process that occurs with secondary hyperaldosteronism?
Some insult to the renal arteries decrease blood flow to the kidneys, and therefore increase renin.
Increased renin increases ang II, which increases aldosterone
What is congenital adrenal hyperplasia?
Excess sex steroids with hyperplasia of both adrenal glands, due to a defect in the enzymes responsible for steroidogenesis
What is the most commonly affected enzyme in congenital adrenal hyperplasia? What is the effect of this? Why?
Pregnenolone is shunted down the sex hormone pathway, since, since 21-hydroxylase is necessary for the genesis of mineralocorticoids, and cortisol
What is cholesterol turned into in the genesis of hormones? What are the three pathways that this molecule can be shunted down?
What is the enzyme that is necessary for the production of both mineralocorticoids and cortisol? What happens when this enzyme is deficient/defective?
Pregnenolone is shunted down the sex hormone synthesis pathway
What are the physical consequences of 21-hydroxylase deficiency (males and females)?
Clitoral enlargement in female
Precocious puberty in males
What causes the adrenal hyperplasia with 21-hydroxylase deficiency?
Since no cortisol is produced, ATCH is upregulated, causing hyperplasia of the adrenals
What are the two metabolic/hemodynamic effects of 21-hydroxylase deficiency (congenital adrenal hyperplasia)?
-salt wasting (hyponatremia and hyperkalemia)
-Clitoromegaly if female
What causes the hyponatremia and hyperkalemia with 21 hydroxylase deficiency (congenital adrenal hyperplasia)?
No mineralocorticoids (aldosterone) is produced d/t the lack of enzyme. No aldosterone leads to these two electrolyte disturbances
What are the two major enzymes that can cause congenital adrenal hyperplasia? What is the major difference between the two?
11 hydroxylase deficiency does not present with salt wasting, since some mineralocorticoids are able to be produced
What is the enzyme that is necessary for the conversion of pregnenolone into either sex hormones or cortisol? What are the problems if there is a deficiency in this enzyme?
No sex hormones and no cortisol produced, but an overabundance of mineralocorticoids, leading to HTN, hypernatremia, and hypokalemia
Why is there always adrenal hyperplasia with any sort of enzymatic deficiency of the pregnenolone conversion pathway?
All enzymes needed to produce cortisol.
No cortisol = increased ACTH production = adrenal hyperplasia
What is Waterhouse-Friderichsen syndrome?
Acute adrenal insufficiency caused by DIC and necrosis of adrenal glands (usually by Neisseria meningitidis)
What is the classical presentation of Waterhouse-Friderichsen syndrome?
Child who gets neisseria meningitis who develops DIC, leading to bilateral necrosis of both adrenal glands, leading to a lack of cortisol and hypotension
What is the classic gross finding of the adrenal glands with Waterhouse-Friderichsen syndrome?
Adrenal glands with a large pool of coagulated blood
What is chronic adrenal insufficiency? Causes (3)?
Progressive destruction of the adrenal glands, caused by:
Cancer from what organ system commonly metastasizes to the adrenal glands to produce chronic adrenal insufficiency?
Lung cancer that metastasizes to the adrenal glands
What type of cancer loves to metastasize to the adrenal glands, and cause chronic adrenal insufficiency?
What are the findings of chronic adrenal insufficiency, and what causes them?
All caused by a lack of aldosterone
What causes the hyperpigmentation seen with chronic adrenal insufficiency?
ACTH will increase, which is derived from POMC.
POMC breaks down to form ACTH and MSH. Thus increased MSH results in hyperpigmentation
What are the two hormones that POMC is broken down into?
MSH (melanocyte stimulating hormone)
What causes the n/v/d with chronic adrenal insufficiency?
lack of cortisol
What type of cells comprise the adrenal medulla? What are these derived from embryologically?
Neural Crest derived chromaffin cells
What is the function of the adrenal medulla
Main physiologic source of epi and norepi
What is a pheochromocytoma?
Tumor of the chromaffin cells that leads to excess epi and NE production
What is the classic gross findings of a pheochromocytoma? Why?
-Brown tumor of the adrenal glands
-Adrenal medulla is normally brown, but huge size of it
What are the clinical features of a pheochromocytoma?
How do you diagnose a pheochromocytoma?
Increase serum metanephrines and increased urine metanephrines and VMA
What is the treatment for a pheochromocytoma?
What are the breakdown products of epi and norepi? What is the next step (enzyme and product) for each of these?
Metanephrine and normetanephrine respectively
Both converted to VMA by MAO
What is the MOA of phenoxybenzamine? Use?
Irreversible blocker of alpha receptors used in the treatment of a pheochromocytoma
Why is phenoxybenzamine given to patients prior to surgical excision of a pheochromocytoma?
If surgeon squeezes on the tumor, then will release a lot of epi/NE. This counteracts that
What are the four "rules of 10" for pheochromocytomas?
-10% are bilateral
-10% located outside of the adrenal medulla
What is the classic exogenous location of a pheochromocytoma? S/sx of this?
Urination causes HTN, HA, etc
If urination causes HTN, HA, etc, what should you suspect?
Pheochromocytoma of the bladder
What are the four genetic disorders that are associated with pheochromocytomas?
-MEN2A and MEN 2B
-NF type 1
What is the gene that is the cause of MEN?