Lecture 12: Renal Endocrinology Flashcards
ADH is critical for which function?
Water reabsorption
What is the pathway of ADH release?
paraventricular/supraoptic nuclei synthesizes ADH > travels though the hypothalamic hypophyseal tract > released as vesicles by the posterior pituitary > targets kidneys and arterioles
What is the pathway of ADH synthesis?
Prepropressophysin cleaved to propressophysin in hypothalamus
Travel to posterior lobe where it is cleaved to ADH > released
Very simply, what is osmolarity and how does ADH relate to it?
What is blood volume and how does ADH relate to it?
- How concentrated the ECF is. ADH wants to “dilute” concentrated blood
- How much fluid is in the ECF. Directly proportional to BP. ADH reabsorbs water to add to the blood volume if it is low
How does the hypothalamus detect body osmolarity?
How does the hypothalamus detect blood pressure?
Osmoreceptors (relays info to PVN and SON
Baroreceptors (relays info to PVN and SON via CN Ix/x
____ blood pressure, _____ arterial stretch, ______ osmolarity trigger ADH release
Low; low (due to blood volume), high
ADH secretion is most sensitive to _______ changes
Plasma osmolality (small changes affects regulation a lot compared to other variables)
What receptors does ADH bind in the arterioles?
In the kidneys?
V1
V2
What does ADH specifically do in the collecting duct that allows water reabsorption?
Increase in aq2 expression on the luminal side to let more water through
During dehydration/hyperosmolarity, what happens to …
BV
Osmolarity
Urine
Low
High, can lead to hypernatremia
Low volume and more concentrated urine (body attempts to keep as much water in)
During hypervolemia/hypoosmolarity, what happens to …
BV
Osmolarity
Urine
High
Low
High volume, diluted (body gets rid of excess water)
What is the characterizing symptom of diabetes insipidus?
Losing water/low water (polyuria, polydipsia)
Central DI vs Nephrogenic DI (causes, treatments)
- Central: no ADH so you can’t keep the water. Damage to pituitary or hypothalamus. Tx with desmopressin which inhibits water excretion
- Nephrogenic: kidney not responding to ADH so you can’t keep water. Kidney disease/damage.
How does the water deprivation test for DI work?
Patient stops drinking water but still makes high urine volume/diluted urine.
Syndrome of inappropriate ADH secretion (SIADH)
Cause
What disease is this associated with usually?
High ADH secretion leading to water retention and diluted blood
Small lung cell carcinoma
What is the main purpose of aldosterone?
Na+ reabsorption and K+ excretion (direct) Water reabsorption (indirect, water follows the salt)
What does aldosterone specifically control at the nephron tubule?
Increases expression of ATPases/channels that change the passage of K+ and Na+
What is the RAAS?
Renin-angiotensin-II-aldosterone system
Activated during conditions of low BP and BV > Na+ resorption
What does primary adrenal gland insufficiency mean?
What does secondary or tertiary adrenal gland insufficiency mean?
- Defect at Adrenal cortex leading to low aldosterone and cortisol
- Defect at pituitary or hypothalamus leading to low cortisol (area responsible for aldosterone not affected)
Myocytes produce ______ which _________
ANP and BNP; reduce workload on the heart by decreasing blood volume
What is urodilatin?
Released by the kidney at the distal tubule and collecting duct. Similar functions to ANP and BNP by inhibiting resorption at the nephron > decrease blood volume
How do natriuretic peptides regulate renal vasculature?
Goal is to excrete Na+ so increases GFR by vasodilation of afferent arterioles and vasoconstriction of efferent arterioles
What other processes control salt and water regulation?
SNS > renin > promote resorption
What effect does sodium intake have on the body?
More sodium intake = water is reabsorbed as it follows it = increases blood volume
And vice versa
What is the major regulator of K+ concentration in cells and ECF?
Insulin - keeps K+ in the cell by stimulating the Na/K ATPase
Deficiency in insulin causes hyperkalemia, since K+ accumulates in the ECF
What is the aldosterone paradox?
There is negative feedback between K+excretion and aldosterone release that stops its actions when body is losing too much K+
What are some major causes of hypokalemia?
E-Nac increase Decreased B-hydroxysteroid dehydrogenase Adrenal tumor/hyperplasia Congenital renal hyperplasia Renin secreting tumor
_______ prevents mineralocorticoid receptor activation by cortisol
Enzyme 11B-HSD2
17a hydroxylase deficiency leads to…
21B hydroxylase deficiency leads to …
11B hydroxylase deficiency leads to…
Low cortisol
Low mineralocorticoids and cortisol
Low mineralocorticoids and cortisol
What are some major causes of hyperkalemia?
Decrease E-Nac
Hypoaldesteronism
Insulin deficiency
What are the major symptoms of hypocalcemia and why is this so?
Too much muscle activity. Due to increased ICF Ca2+ that increases AP threshold = easier AP’s = more frequent muscle activity
Chvostek and Trousseau signs are indicative of….
hypocalcemia
What are the major symptoms of hypercalcemia and why is this so?
Less muscle activity. Due to increased Ca2+ in the ECF, keeping membrane potential more negative = harder to make AP’s = harder to generate muscle activity
How can you change plasma Ca2+ concentration?
- Change protein bound calcium directly (proportional)
2. Increase anions for Ca2+ to pair with so that there’s less Ca2+ floating in the blood (Inverse)
Acidemia leads to _______. Why?
Alkalemia leads to _______. Why?
Hypercalcemia. More H+ bound to albumin, leaving more Ca2+ in blood
Hypocalcemia. Less H+ bond to albumin, allowing Ca2+ to bind and escape from the blood
Vitamin D leads to …
PTH leads to ….
Calcitonin leads to…
- Ca2+ absorption at intestines (active at low Ca2+)
- bone resorption/Vitamin D activation/Ca2+ increase (secreted at low Ca2+)
- bone deposition/Ca2+ decrease
The concentration of phosphate in the blood is _______ proportional to Ca2+ concentration
inversely
How does PTH act on the kidneys?
PTH binds to receptor at thick ascending, PCT and DCT > AMP to cAMP > Protein kinase activation > Ca2+ channel upregulation and NPT2 (phosphate transporter) inhibition
How is PTH regulated?
CasR senses Ca2+ levels and inhibits more PTH production
Vice versa if Ca2+ is low
What enzyme produces the active vitamin D (1,25, dihydroxycholecalciferol and where does this happen?
1a hydroxylase in the PCT
How is the 1a hydroxylase enzyme regulated on the transcriptional level?
CYP12 gene (transcribed when Vit. D is low)
Familial hypocalciuric hypercalcemia (FHH)
Autosomal dominant. CasR is inactivated so cell cannot sense Ca2+ levels accurately. Ca2+ is not regulated and concentration in blood is high.
