Endocrinology Flashcards
ADH release signal
Cell bodies in the supraoptic nuclei of the hypothalamus send axons to the posterior pituitary and release ADH (hypothalamic neurons synthesize ADH)
Signals that trigger ADH release
Low BP - carotid (CNIX) and aortic (CNX) baroreceptors
Decreased arterial stretch due to low blood volume
Increased osmolality - hypothalamic osmoreceptors
Sympathetic stimulation
Angiotensin II secretion
Low blood volume
Secretion of ADH is most sensitive to what trigger
Plasma osmolality changes
ADH method of action in kidney
ADH binds V2 receptors in distal tubule and collecting duct activating GPCR-cAMP-PKA sequence
This causes more aquaporin channels to be inserted in the membrane for more water uptake
Diabetes insipidus and ADH
ADH lacks its normal effect on the collecting duct
Causes frequent urination
Large volume of urine is diluted
Central vs nephrogenic diabetes insipidus (DI)
Central- lack of ADH- could be from damage to pituitary or hypothalamus. Treat with desmopressin (antidiuretic)
-will have decreased plasma ADH in labs
Nephrogenic- Kidneys unable to respond to ADH
-Can be caused by drugs like lithium, or kidney disease
-Desmopressin will not work
Water deprivation test for DI
Drink fluids over night, give breakfast w/o fluids
Weigh patient
No fluid during day, weigh patient every 1-2 hrs
Empty bladder, measure volume and osmolality of urine as well as plasma osmolality
If results suggest DI, patient drinks and desmopressin is administered
Remeasure plasma osmolality and urine osmolality/volume
Syndrome of inappropriate ADH secretion SIADH
Excessive ADH secretion
Excessive water retention
Hypoosmolality fails to inhibit ADH release
-Hyponatremia, decreased plasma osmolality, increased urinary osmolality
Factors causing aldosterone production and sequence of events
Decreased Na, Increased K+ in blood
Decreased blood volume or blood pressure
Kidney signaled to release renin
Liver releases angiotensinogen which is converted to angiotensin I by renin
AT1–>AT2 –> adrenal cortex –> Aldosterone–> water/Na+ reabsorption
Aldosterone effect on kidney
Aldosterone combines with cytosolic receptor in distal tubule
Hormone/receptor complex travels to nucleus and new protein channels/pumps are synthesized
Increased Na reabsorption and K+ secretion in ascending limb, distal tubule, collecting duct
Other effects of angiotensin II besides Aldosterone secretion
Increased sodium/hydrogen exchange causing increased sodium reabsorption along nephron
Increased thirst
Vasoconstriction
Increased ADH secretion
Primary adrenal insufficiency
Both cortisol and aldosterone secretion decreased
Secondary or tertiary adrenal insufficiency
Cortisol decreased but renin-angiontensin-aldosterone axis still exists
ANP
When atria are distended, ANP is released
Increases excretion of NaCl/water by kidneys
-vasodilation of afferent and vasoconstriction of efferent arterioles- increasing GFR and filtration load
-Inhibit renin/aldosterone secretion and ADH action on distal tubule/collecting duct
-inhibit NaCl reabsoprtion
Ventricles produce BNP (brain natriuretic peptide) that has a similar function
-both decrease total peripheral resistance
Urodilatin
Encoded by the same gene as ANP
Secreted by the distal tubule and collecting duct
Influences only the function of the kidneys
Stimulated by increased BP and ECF volume
Inhibits NaCl and water reabsorption by medullary portion of collecting duct
Sympathetic nerve activity and regulation of NaCl/water reabsorption
Catecholamines released from sympathetic nerves stimulate reabsorption of Na and water by proximal tubule, thick ascending limb, distal tubule and collecting duct
Increase renin secretion
Decrease GFR (vasoconstrict afferents)
Addisons disease
Atrophy of adrenal gland
Decreased cortisol and aldosterone secretion
Causes increased CRH release from hypothalamus
Causing increased ACTH release from pituitary
Hyperpigmentation
Response to increased sodium intake
Decreased sympathetic activity
Increased ANP
Decreased peritubular capillary osmotic pressure
Decreased renin/angiotensin/aldosterone system
Causes of K+ shifts out of cells–>hyperkalemia
Insulin deficiency B2 adrenergic antagonist a-adrenergic agonists Acidosis Hyperosmolarity Cell lysis Exercise
Causes of K+ shift into cells–>hypokalemia
Insulin B2 adrenergic agonists a-adrenergic antagonists Alkalosis Hypoosmolarity
Insulin effect on K+ balance
Stimulates K+ uptake into cells by increasing Na/K pump activity
Ensures ingested K does not remain in ECF
Deficiency of insulin like in type I diabetes causes decreased K+ uptake and hyperkalemia
Three pathways triggering aldosterone release
Hypothalamus CRH–>pituitary ACTH–> adrenal cortex aldosterone
High plasma K+–> adrenal cortex secrete aldosterone
Renin-angiotensin system
Increased ENaC: Liddle syndrome lab results (renin, aldosterone, EC volume or BP)
Low renin
Low aldosterone
High EC volume/BP
Decreased B-hydroxysteroid dehydrogenase: apparent mineralocorticoid excess, licorice lab results (renin, aldosterone, EC volume or BP)
Low renin
Low aldosterone
High EC volume or BP
Adrenal tumor or hyperplasia lab results (renin, aldosterone, EC volume or BP)
Low renin
High aldosterone
High EC volume or BP
Congenital adrenal hyperplasia 17-hydroxylase deficiency lab results (renin, aldosterone, EC volume or BP)
Low renin
High aldosterone
High EC volume or BP
Renin-secreting tumor lab results (renin, aldosterone, EC volume or BP)
High renin
High aldosterone
High EC volume or BP
11B-HSD2 enzyme effect in aldosterone/cortisol pathways
Cortisol has the ability to bind mineralocorticoid receptors and carry out aldosterones function
This is prevented by enzyme 11B-HSD2, which converts cortisol to cortisone so it must be converted back to cortisol in a glucocorticoid specific target cell
17a Enzyme deficiency (mineralcorticoid, cortisol, sex hormones, BP, K+, labs)
MC- increased Cortisol- decreased Sex hormones- decreased BP- increased K+- decreased Labs: decreased androstenedione
21B enzyme deficiency (mineralcorticoid, cortisol, sex hormones, BP, K+, labs)
MC- decreased Cortisol- decreased Sex hormones- increased BP- decreased K+- increased Labs: increased renin activity, increased 17-hydroxy progesterone
11B enzyme deficiency (mineralcorticoid, cortisol, sex hormones, BP, K+, labs)
MC- decreased aldosterone, increased DOC (^^BP) Cortisol- decreased Sex hormones- increased BP- increased K+- decreased Labs: decreased renin activity
B-blockers, autonomic neuropathy effect on renin system
Hyporenin-hypoaldosteronism can result
Hypocalcemia symptoms/indicators
Hyperreflexia, spontaneous twitching, muscle cramp, numbness/tingling
Chvostek sign- twitching of facial muscles when tap on facial nerve
Trousseau sign- carpopedal spasm upon inflation of BP cuff
Hypercalcemia symptoms
Decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness/hyporeflexia, lethargy, coma
Changes in phosphate concentration effect on calcium
Increased phosphate will decrease ionized calcium
Same hormones that regulate calcium also regulate phosphate
Acidemia/alkalemia effect on calcium-albumin binding
Acidemia will increase ionized calcium by decreasing Ca-albumin binding
Alkalemia has opposite effect
Calcitonin
Decreases bone resorption- opposite effect of PTH
PTH effects on bone/kidney/intestine
Increased bone resorption
Decreased phosphate reabsorption, increase calcium reabsorption and increase urinary cAMP in kidney
Increase calcium absorption in intestine (via vitamin D)
PTH in kidneys
PTH activates GPCR in proximal tubule, increasing cAMP, causing inhibition of Na/phosphate pump which decreases sodium/phosphate reabsorption
Stimulates calcium reabsorption in thick ascending limb and distal tubule
Vitamin D and PTH gene expression
Vitamin D inhibits PTH gene expression and activates Calcium receptor on parathyroid cell which senses calcium and activates another pathway to further inhibit PTH gene activation
Cholecalciferol processing
25-hydroxylase in liver converts it to 25-OH-cholecalciferol
1a-hydroxylase (CYP1-a) in kidney converts 25-OH-C to 1,25-OH2-cholecalciferol active form
24-hydroxylase in kidney converts to 24,25-OH2-cholecalciferol inactive form
CYP1-a gene regulation
Transcription activated by PTH
Inhibited by Calcium and active vitamin D or the 25-OH form
Vitamin D activates CYP24 gene for 24 hydroxylase
Familial hypocalciuric hypercalcemia FHH
Caused by mutation that inactivates CaSR in parathyroid glands and parallel calcium receptors in ascending limb of kidney
Results in decreased urinary calcium excretion and increased serum calcium
Normal/high PTH, high serum Ca, low urine Ca, normal phosphate and normal vitamin D
