Flashcards in Week 2: Regulation of bp, Kidney in HTN Deck (11):
Summarize the chain of events known as pressure natriuresis- the effects of arterial bp on renal excretion of NaCl.
In response to increased arterial bp
-increased renal perfusion pressure-->decreased NaCl reabsorption in the PT (mechanism unclear)-->more NaCl to macula densa -->TGF -->afferent arteriole constriction -->keeps GFR from increasing
-decrease in Na and volume reabsorption in PT and DCT culminates in pressure induced natriuresis, diuresis.
Diagram the 6 feedback relationships connecting ECFV, BP, and AngII/SNS.
1. BP --AngII/SNS
-Increased bp-->decreased renin and SNS
-decreased bp-->increased AngII and SNS-->vasoconstriction
2. BP -- ECFV
-increased BP-->decreased NA reabsorption
-decreased BP-->increased CO and tissue vasoconstriction
3. ECFV -- AngII, SNS
-Increased ECFV-->decreased renin and SNS, increased ANP
-decreased ECFV-->increased AngII, SNS-->increased Na reabsorption.
Summarize the homeostatic mechanisms governing "escape" from mineralocorticoid excess: transport along nephron, endocrine adjustments.
-escape from sodium retaining effects of increased aldosterone
-Aldosterone increases Na reabsorption along CD, persistent and uncorrected-->increased ECF volume
-increases in mean arterial bp and central venous pressure
1. response to central venous pressure increases
-->atrial stretch-->ANP increases and SNS decreases-->decreased RAS, ADH, decreased IMCD Na transport-->decreased tubular Na reabsorption along nephron except aldosterone sensitive region of CD
2. response to increases in mean arterial bp
-->increased renal perfusion pressure-->decreased renin, RAS, pressure/natriuresis-->decreased tubular Na reabsorption except in aldosterone sensitive region of CD
What is Gitelman's syndrome?
-mutation leading to inactive NCC co transporter in DCT.
-Hypotension, hypokalemia, and alkalosis
-mimicked by thiazide diuretics
What is Bartter's syndrome?
-mutations leading to inactivation of transporters in TALH: can be NaK2Cl, apical K+ channels, basolateral Cl- channels
-hypotension, hypokalemia, alkalosis
Describe pseudohypoaldosteronism (PHA).
Type 1 autosomal dominant
-loss of function mutations in mineralocorticoid receptor with high aldosterone
-leads to hypotension, hyperkalemia, and acidosis
Type 1 autosomal recessive
-loss of function mutations in ENac subunits with similar but more severe symptoms because ENac is affected
What are lesions that cause hypertension? List 1
1. hyperaldosteronism: excess NaCl reabsorption in distal nephron
2. pseudohyperaldosteronism type 2: mutations in kinase cascade or degradation pathways that lead to activation (phosphorylation) of DCT NCC
3. defect of 11B-OH SD: glucocorticoids saturate also-receptors. excess Na reabsorption. (excess licorice consumption inhibits this enzyme and can do the same)
4. Liddle's syndrome: mutation in beta or y subunit of epithelial Na channel, leads to prolonged channel retention in apical membrane and open in-->excess Na reabsorption in CDs
5. Mineralocorticoid receptor mutation: binds progesterone-->HTN in pregnant females
6. Renovascular HTN: renal artery stenosis of one kidney-->decreased renal perfusion-->increased renin from stenotic kidney-->increased AngII and aldosterone-->unregulated increased Na reabsorption from both kidneys
What are lesions that cause hypertension? List 2
7. Renin secreting tumor in JGA-->high AngII generated
8. elevated plasma angiotensinogen
9. adducin mutation
10. WNK and SPAK kinase mutations-->constitutive activation of NCC by phosphorylation=Gordan's syndrome
11. Calcineurin inhibitors: immunosuppressive drugs that inhibit calcineurin, preventing dephospho rylation of NCC, leading to increased NCC-P and activation of Na reabsorption in DCT
Of the renal mechanisms, what is the most important in physiologic control of bp?
-regulation of Na excretion and blood volume
What are mechanisms that regulate renal renin secretion?
1. perfusion pressure in renal afferent arterioles
3. macula densa mechanism
5. angiotensin II exerts a negative feedback
6. serum glucose