Renal Flashcards
Renal Clearance
Cx = renal clearance of substance X Cx = Ux * V / Px where Ux is the urine concentration of substance X, V is urine flow rate, and Px is the plasma concentration of substance X
Cx = GFR, no net reabsorption or secretion of substance X
Cx < GFR, net reabsorption of substance X
Glomerular filtration
Estimated w/ insulin clearance as insulin is near absorbed or secreted and freely filtered
GFR = Uinsulin * V / Pinsulin
GFR normal approximately 100 mL/min
Creatinine clearance is an approximate measure of GFR
Slightly overestimates GFR because creatinine is moderately secreted by renal tubules
Effective renal plasma flow
Can be estimated by using para-amniohippuric acid (PAH) clearance because it is both filtered and actively secreted in proximal tubule (not all PAH entering kidney is filtered, but all is excreted)
ERPF = Upah * V / Ppah = Cpah RBF = ERPF / (1-Hct)
Filtration fraction (FF)
FF = GFR/RPF
Normal FF = 20%
Glomerular dynamics
Afferent arteriole constriction: decreased RPF, GFR, no change in FF
Efferent arteriole constriction: decreased RPF, increased GFR (increased plasma hydrostatic pressure), increased FF
Increased plasma protein concentration: no change in RPF, decreased GFR (increased plasma oncotic pressure), decreased FF
Constriction of ureter: no change in RPF, decreased GFR, decreased FF
Glucose clearance
Glucose at normal plasma level ~ 100 is completed reabsorbed at the proximal tubule but Na/glucose cotransport
Glucose plasma level of ~ 200 glycosuria begins
Glucose plasma level of ~ 375 all transporters are saturated
Early proximal convoluted tubule
Reabsorbs all of the glucose and amnio acids and most ions (HCO3, Na, Cl, K, PO4) and water
Secretes NH3 to buffer H+ in tubule lumen
PTH inhibits PO4 absorption
ATII stimulates Na and HCO3 absorption
65-80% of Na reabsorbed
Thin descending loop of Henle
Passively reabsorbs H20 via medullary hypertonicity (impermeable to Na)
Concentrating segment making urine more hypertonic
Thick ascending loop of Henle
Actively reabsorbs Na, K, and Cl
Indirectly induces the paracellular reabsorption of Mg and Ca
Impermeable to water, making urine less concentrated
10-20% Na reabsorbed
Loop diuretics prevent absorption of Na at this region (NaK/2Cl cotransporter into cell lumen)
Early distal convoluted tubule (DCT)
Actively reabsorbs Na and Cl, making urine more hypotonic
PTH increased Ca/Na exchange and increasing Ca reabsorption
5-10% Na reabsorbed
Thiazide diuretics prevents absorption of Na at this region (NaCl cotransporter) and decreases Ca excretion
Collecting tubule
Reabsorbs Na in exchange for secreting K and H (regulated by aldosterone which inserts Na channel on luminal side) —-> principle cells
ADH acts to insert aquaporin H2o channels on luminal side to increase water reabsorption –> principle cells
Amiloride blocks Na channels –> principle cells
3-5% Na reabsorbed
Fanconi syndrome
Reabsorption defect in PCT
Associated w/ increased excretion of nearly all amnio acids, glucose, bicarb, and phosphate
Can result in metabolic acidosis (proximal renal tubular acidosis)
Causes include hereditary (Wilson), ischemia, and nephrotoxins
Bartter syndrome
Reabsorption defect in thick ascending loop of Henle
Affects NaK/2Cl co transporter
Results in hypokalemia and metabolic alkalosis
Gitelman syndrome
Reabsorption defect of NaCl in distal convoluted tubule
Less severe than Bartter but can still lead to hypokalemia and metabolic alkalosis
Liddle syndrome
Increased Na reabsorption in distal and collection tubules due to increased activity of epithelial Na channels
Results in hypertension, hypokalemia, metabolic alkalosis
Renal tubular acidosis type 1
Defect in ability of alpha intercalated cells (collecting ducts) to secret H, and thus no new HCO3 generated, leading to non-anion gap metabolic acidosis
Causes: amphotericin B toxicity, analgesic nephropathy, MM
Renal tubular acidosis type 2
Defect in proximal tubule bicarb reabsorption resulting in increased bicarb excretion in urine leading to metabolic acidosis
Causes: Falconi syndrome, carbonic anhydrase inhibitors
Renal tubular acidosis type 4
Hypoaldosteronism, aldosterone resistance, or K+ sparing diuretics
Resulting hyperkalemia impaires ammoniagenesis in proximal tubule leading to decreased H+ buffering capacity and decreased H+ excretion into urine –> metabolic acidosis
Focal segmental glomerulosclerosis
LM: segmental sclerosis (only parts of glomerulus is sclerosed)
IF: none
EM: effacement of foot processes similar to MCD
Associated with sickle cell, HIV, CKD
Membranous nephropathy
LM: diffuse capillary and GBM thickening
IF: granular as result of immune complex deposits
EM: spike and dome appearance
Associated with NSAIDs, SLE
Minimal change disease
LM: normal
IF: none
EM: effacement of foot processes
Most common in children, triggered by recent infection, immunization
Renal amyloidosis
LM: congo red stain shows apple-green birefringence under polarized light
Associated w/ chronic conditions such as MM or TB
Membranoproliferative glomerulonephrtis
LM: tram-track appearance due to GMB splitting and thickening
IF: Immune complex with granular appearance
Associated with HBV, C3 nephritic factor
Diabetic glomerulonephropathy
LM: mesangial expansion, GBM thickening, Kimmelstiel-Wilson lesion (eosinophilic nodular glomerulosclerosis)
Glycosylation of GMB
Acute post streptococcal glomerulonephritis
LM: glomeruli enlarged and hyper cellular
IF: starry sky granular appearance (lumpy bumpy) due to IgG, IgM, and C3 deposition along GBM
EM: subepithelial IC humps
Often ~2 wks after strep A infection leading to type III hypersensitivity
Decreased serum C3 level
Rapidly progressive glomeruloneprhitis (RPGN)
Crescentic
LM and IF: crescent-moon shaped glomerulus, linear deposits along GBM
Result of Goodpasture syndomre (type II hypersensitivity against GBM), Wegner (PR3ANCA/cANCA), microscopic polyangiitis (MPOANCA/pANCA)
Diffuse proliferative glomerulonephritis
LM: wire looping of capillaries
IF: granular deposits
EM: subendothelial IgG based ICs w/ C3
Most commonly associated w/ SLE and MPGN
IgA nephropathy (Berger disease)
LM: mesangial proliferation
EM: mesangial IC deposits
IF: IgA based IC deposits
Associated w/ HSP
