Renal Diseases - RM Flashcards
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What 3 things characterize nephrotic syndrome?
proteinuria, hypoalbuminemia, edema
What is anasarca?
generalized systemic edema
What is minimal change disease?
nephrotic syndrome where there is diffuse loss of podocyte foot processes, causing loss of electrical charge so proteins and fluids can leak
What is the underfill hypothesis for edema?
glomerular disease–>increased filtration of plasma proteins–>tubular catabolism of albumin and excretion of albumin–>hypoalbuminemia–>reduced oncotic pressure–>edema
What is the overfill hypothesis for edema?
glomerular disease–>primary renal Na retention–>plasma volume expansion–>increased capillary hydrostatic pressure–>edema
What is puromycin aminonucleoside used for (PAN)?
can selectively infuse it into one kidney to make it nephrotic for experimental model
What occurs in a PAN- model of nephrotic syndrome where one kidney is affected and one is fine? What does this suggest?
- get proteinuria even without hypoalbuminemia
- Na excretion is normal or even high in good kidney, but significantly reduced in PAN-perfused kidney
- suggests that there is an intrarenal factor promoting Na retention by nephrotic kidney
How is the ANP response to water immersion different in healthy patients and those with nephrotic syndrome (NS)?
in NS pts, the effect is blunted
-can measure a lot of ANP in response to stretch from increased central vascular volume due to water diffusing into body, but the effect in the kidney is reduced and there is not as much diuresis
What is the normal transcapillary gradient of oncotic pressure?
12 mmHg
Why doesn’t the normal transcapillary oncotic pressure gradient change with hypoalbuminemia until plasma albumin level falls below 2?
there is a compensatory fall in interstitial oncotic pressure along with the fall in plasma oncotic pressure in hypoalbuminemia, but the mechanism fails when levels of albumin fall below 2
-at that point, fluid will shift into interstitial space
What are the arguments against hypoalbuminemia causing edema in nephrotic sydnrome patients?
- most patients have normal or increased plasma volume
- Na retention in PAN-perfused kidney has edema without changes in albumin
- edema may resolve without changes in albumin levels
- no edema in congential analbuminemia patients
- variable natriuresis in pts with volume expansion (should have increased to increase water outflow too)
In which case (underfill or overfill) is the renin-angiotensin-aldosterone system activated? suppressed?
- in underfill, RAAS activated, high renin
- in overfill, RAAS suppressed, low renin
In which case is it appropriate to use diuretics? what can you measure first to be sure?
- use in overfill cases
- measure renin to make sure levels are low
How can increased glomerular permeability cause hyperlipidemia?
reduced albumin–>compensatory hepatic synthesis–> hepatic lipoprotein synthesis as well as reduced lipoprotein lipase activity–>hyperlipidemia
What is the signaling path for ADH?
ADH–> V2 receptors –> adenyl cyclase –> increased cAMP –> PKA –> insertion of aquaporin channels into apical membrane and synthesis of more aquaporins
What are nonosmotic factors that influence ADH release?
volume, blood pressure, nausea, pain, stress, hypoglycemia, narcotics, angiotensin II, ethanol, caffeine, prostaglandins, ANP
What type of patients are frequently hyponatremic?
people recoverying from surgery
What is SIADH?
inappropriate secretion of ADH
-hypoosmolar plasma with inappropriately concentrated urine (that should be dilute)
What is vasopressin escape?
eventually develop a new steady state of ADH activity–>have a decrease in aquaporin mRNA since it is not longer tied to ADH quantity
What is the positive feedback that occurs in CHF?
CHF is hypervolemic state but with decreased effective circulating volume, so that is sensed by kidneys as hypoosmotic due to decreased afferent arteriole flow, causes renin release to increase water retention in edematous patient even more
What segment of the nephron does angiotensin II preferentially cause vasoconstriction of?
efferent arterioles
How do ACE inhibitors affect GFR in normal patients and those with underlying vascular disease or CHF?
- in normal patients, increases renal blood flow and GFR
- in pts with vascular disease or CHF, decreases GFR due to reduction in efferent arteriole constriction
What 4 things stimulate renin secretion by macula densa?
baroreceptors/myogenic reflexes in afferent arteriole
SNS
catecholamines
decreased Cl in macula densa
What 3 things inhibit renin secretion by macula densa?
ADH
ANP
BNP
What do prostaglandins cause dilation of?
afferent arterioles
What is the effect of NSAIDS?
inhibit cyclooxygenase enzymes that produce vasodilation (PGE2 and PGI2)
What is the effect of NSAIDS in the kidneys of normal patients?
in normal patients, renal prostaglandin production is low so NSAIDS have little effect
What is the effect of NSAIDS in the kidneys of a patient with acute kidney injury/compromise of renal perfusion (volume depletion, CHF, cirrhosis, diuretics, advanced age)
many vasodilatory prostaglandins are secreted in these kidneys to keep blood flow to kidney
-if you give dose of NSAID it can put patient into renal failure by blocking the prostaglandin-mediated vasodilation
What causes dysautoregulation?
NSAID + ACE inhibitor + intravascular volume depletion
drug induced acute renal failure
