Renal Flashcards
pronephros develops by
Week 4, then degenerates
Mesonephros
interim kidney during 1st trimester, later contributes to male genital system
metanephros
permanent kidney
When does metanephros appear? contiues through
5th week of gestation. Nephrogenesis continues through 32-36 weeks.
When is ureteric bud fully canalized by?
10th week
What is ureteric bud derived from?
caudal end of mesonephric duct
What does ureteric bud give rise to?
ureter + pelvises + calyces + collecting ducts
what does metanephric mesenchyme give rise to?
Glomerulus through to DCT.
what are congenital malformations of kidney often due to?
aberrant interaction between ureteric bud and metanephric mesenchyme.
causes of Potter disease
ARPKD + obstructive uropathy (posterior urethral valves) + bilateral renal agenesis + chronic placental insufficiency
Potter sequence presentation
POTTER (pulmonary hypoplasia, Oligohydramnios (trigger), Twisted face, Twisted Skin, Extremity defects, Renal failure (in utero.
horseshoe kidney assocations
1) hydronephrosis (ureteropelvic junction obstruction.
2) renal stones
3) infection
4) chromosomal aneuploidy syndromes (13,18,21)
5) renal cancer (rarely)
Diagnosis of unilateral renal agenesis
US
cause of unilateral renal agenesis
Ureteric bud fails to develop and induce differentiation of metanephric mesenchyme.
kidney consisting of cysts and connective tissue
multicystic dysplastic kidney
cause of multicystic dysplastic kidney
ureteric bud fails to induce differentiation of metanephric mesenchyme
Causes of duplex collecting system
1) 2 ureteric buds reaching and interacting with metanephric blastema
2) bifurcation of ureteric bud before it enters the metanephric blastema, creating a Y-shpaed bifid ureter.
Why do duplex collecting systems create problems?
1) vesicoureteral reflux
2) ureteral obstruction
3) increased risk for UTIs
what usually happens with congenital solitary functioning kidney?
1) majority asymptomatic
2) compensatory hypertrophy of kidney
3) anomalies in contralateral kidney common though.
which kidney is usually taken during donor transplantation?
left (longer renal vein)
Renal blood flow
renal artery –> segmental artery –> interlobar artery –> arcuate artery –> interlobular artery –> afferent arteriole –> glomerulus –> efferent arteriole –> vasa recta/peritubular capillaries –> venous outflow
angiotensin II affects
1) Potent vasoconstrictor with preferential affects on the efferent arteriole, thus increasing FF to preserve GFR in low vlume states.
2) increases NE release by renal sympathetic nerves, thus stimulating aldosterone release
3) secondary effect is to increase HCO3- reabsorption (permitting contraction alkalosis)
4) Affects baroreceptor function; limits reflex bradycardia.
5) stimulates hypothalamus –> thirst
6) Acts at AT II receptor on vascular smooth muscle –> vasoconstriction –> increased BP.
8) stimulates ADH release from anterior pituitary.
9) increases PCT Na/H activity –> Na, HCO3, H2O reabsorption (can permit contraction alkalosis).
macula densa location
Lines the wall of the cortical thick ascending limb, at the transition to the DCT.
function of macula densa
when GFR drops, NaCl presentation to the macula is reduced , macula densa signals to juxtaglomerular cells in the afferent arteriole, causing them to release renin and activate the RAAS. Thus causing efferent arteriole vasoconstriction and increased GFR.
common complication of gynecologic procedures (ligation of uterine or ovarian vessels)
Damage to ureter, leaking to ureteral obstruction or leak.
relation of ureter to vas
Ureter passes UNDER vas deferens
percent of total body weight of total body water, ICF, ECF
60-40-20. 60% of your body water is total body water, of which 40% is ICF and 20% is ECF.
How is plasma volume measured?
Radiolabeling albumin.
How is ECF volume measured?
Inulin or mannitol
osmolality
285-295 mOsm/kg H2O
How to calculate HCT
roughly 3 x [Hb] in g/dL
RBC volume
2.8 L
ECF breakdown
interstitial fluid comprises 75% of ECF, Plasma comprises 25% of ECF
what component of the glomerular filtration barrier is lost in nephrotic syndrome?
Charge barrier
Composition of glomerular filtration barrier
1) fenestrated capillary endothelium (size barrier)
2) Fused BM w/ heparan sulfate (negative charge and size barrier)
3) epithelial layer consisting of podocyte foot processes (negative charge barrier)
Renal clearance equation
Cx = Ux V/Px (FA 556)
clearance and GFR relationship
Cx net reabsorption
Cx>GFR –> net secretion
Cx = GFR –> no net secretion or reabsorption
How to calculate GFR
1) Clearance of inulin. (given by above equation)
2) creatinine clearance
Normal GFR
100 mL/min
Describe creatinine clearance as a measure of GFR
Approximate. Slightly overestimates GFR because creatinine is moderately secreted by renal tubules.
How to estimate effective renal plasma flow (eRPF)? why?
PAH clearance. This is because between filtration and secretion there is nearly 100% excretion of all PAH that enters the kidney. It rises rapidly and is not reabsorbed anywhere.
eRPF as an estimate of RPF
It UNDERestimates true renal plasma flow slightly.
Normal FF
20%
How to calculate filtered load (mg/min)
GFR (mL/min) x plasma concentration (mg/mL)
How do prostaglandins affect FF?
No effect on FF because they increase both RPF and GFR
angiotensin II affect on FF
Increase FF because they decrease RPF and increase GFR by constricting efferent arteriole.
Effect of ureter constriction on GFR and FF
Decrease GFR + FF (backup causes increased hydrostatic pressure)
Effect of dehydration on GFR, RPF, and FF
Decrease GFR and decrease RPF BUT increase FF (RPF decreased to a greater degree than GFR).
Filtered load equation
Filtered load = GFR x Px
Excretion rate equation
V x Ux
Reabsorption/secretion
just difference between filtered and excreted
FEna
Na+ excreted/Na+ filtered
Glucose clearance
at a normal plasma level, glucose is completely reabsorbed in PCT by Na+/glucose ACTIVE cotransport.
When does glucosuria begin?
around 200 mg/dL
when do glucose glucose transporters become fully saturatd (Tm)?
375 mg/min
Why are glucosuria and aminoaciduria common in pregnancy?
pregnancy decreases ability of PCT to reabsorb glucose and amino acids.
What is “splay”?
Region of substance clearance between threshold and Tm. Basically, individual nephrons vary in absorptive capacity, so beyond the threshold there are still some nephrons capable of reabsorption.
PCT functions
1) reabsorbs all glucose and amino acids and most HCO3-, Na+, Cl-, PO4, K+, H2O, uric acid
2) generates and secretes NH3, which acts as a buffer for secreted H+ (which is secreted when Na+ is absorbed)
PTH action in the proximal tubule
Inhibits Na+/PO4 cotransport, cauisng phosphate excretion.
Fraction of Na+ reabsorbed in the proximal tubule
65-80%
Function of thin descending loop of henle
passive reabsorption of H2O via medullary hypertonicity (impermeable to Na). Thus, this is a concentrating segment.
Fraction of Na reabsorbed in the thick ascending limb
10-20%
Ca2+ and Mg2+ transport
Paracellular absorption in thick ascending limb through positive lumen potential generated by K+ backleak.
Thick ascending limb and affect on tonicity
Impermeable to H2O. Makes urine less concentrated as it ascends.
Early DCT affect on tonicity
Reabsorbs Na, Cl- thus diluting urine.
PTH action in the early DCT
Increases Ca/Na exchange leading to Ca reabsorption.
Fraction of Na absorbed in the DCT
5-10%
triamterene
K+-sparing diuretic
collecting tubule function
Reabsorbs Na+ in exchange for secreting K+ and H+ (regulated by aldosterone).
Sodium absorption in the collecting tubule
3-5%
Fanconi syndrome defect
Generalized reabsorptive defect in PCT. Associated with increased excretion of nearly all amino acids, glucose, HCO3-, and PO4.
Causes of fanconi syndrome
Wilson disease, tyrosinemia, glycogen storage disease, cystinosis, ischemia, MM, nephrotoxins/drugs (ifosfamide, cisplatin, tenofovir, expired tetracyclines), lead poisoning.
Which is more severe, gitelman’s or bartter’s syndrome?
Barter’s
differentiating barter’s from gitelman’s in metabolic profile
gitelman’s causes hypocalciuria, Bartter’s causes hypercalciuria
Example of a gain of function mutation
Liddle syndrome
Syndrome of apparent mineralocorticoid excess
1) pathophys
2) presentation
3) treatment
hereditary deficiency of 11beta-hydroxysteroid dehydrogenase, which normally converts cortisol into cortisone in mineralocorticoid receptor-containing cells before cortisol can act on the mineralocorticoid receptors. /excess cortisol in these cells from enzyme deficiency leads to increased mineralocorticoid receptor activity. /presentation = hypertension + hypokalemia + metabolic alkalosis. /low serum aldosterone. /can acquire disorder from glycyrrhetic acid (present in licorice), which blocks activity of 11beta-hydroxystroid dehydrogenase. /treatment = corticosteroids (exogenous corticosteroids decrease endogenous cortisol production, leading to decreased mineralocorticoid receptor activation).
Components of the juxtaglomerular apparatus + function
Mesangial cells + JG cells + macula densa (NaCL sensor, part of DCT). Function is maintain GFR via RAAS.
JG cells + function
Modified smooth muscle cells of afferent arteriole. Secrete renin in response to decreased renal blood pressure and increased sympathetic tone (B1)
ANP, BNP effects
1) check on RAAS.
2) relaxes vascular smooth muscle via cGMP –> increased GFR + decreased renin
3) dilates afferent ateriole; constricts efferent
4) promotes natriuresis.
What activates RAAS?
1) Decreased BP
2) decreased Na+ delivery (macula densa cells)
3) increased sympathetic tone (B1-receptors)
angiotensin 1 –> angiotensin II
occurs in lungs
