renal Flashcards
what do you use to measure plasma volume?
radiolabeled albumin
what do you use to measure extracellular volume?
inulin
normal osmolality?
285-295 mOsm/kg H2O
what does the fenestrated capillary endothelium of the glomerulus do?
acts as a size barrier
what does the basement membrane of the glomerulus do?
acts as a negative charge barrier
** has heparan sulfate
what component of the glomerulus is lost in nephrotic syndrome?
charge barrier
formula for renal clearance?
Cx = UxV/Px
where V = urine flow rate (mL/min)
what can you use to calculate GFR?
inulin clearance (neither reabsorbed nor secreted) creatinine clearance - slightly overestimates bc of moderate tubular secretion
what is normal GFR?
100 mL/min
what can you use to estimate effective renal plasma flow?
PAH - filtered and secreted in PCT, near 100% excretion
formula for eRPF?
eRPF = U(PAH) * V/P(PAH)
in other words, eRPF = PAH clearance
** understimates RPF by 10%
formula for renal blood flow?
RBF = RPF/(1 - Hct)
formula for filtration fraction?
FF = GFR/RPF
what is normal FF?
20%
formula for filtered load?
filtered load (mg/min) = GFR * plasma concentration
how do prostaglandins affect RPF, GFR, FF?
dilate afferent arteriole –> increased RPF and GFR, so FF remains the same
how does ATII affect RPF, GFR, FF?
constrict efferent arteriole –> decreased RPF and increased GFR –> increased FF
how does a change in plasma protein affect RPF, GFR, FF?
increase: decreased GFR, RPF remains same –> FF decreases
decrease: increased GFR, RPF remains same –> FF increases
how does constriction of the ureter affect RPF, GFR, FF?
decreases GFR, no change in RPG –> FF decreases
formula for excretion rate?
excretion rate = V * Ux
how to calculate reabsorption and secretion rates?
reabsorption = filtered - excreted = (GFR * Px) - (V * Ux) secretion = excreted - filtered
how is glucose reabsorbed in the kidneys?
in PCT
Na/glucose cotransport
what are thresholds of glucose reabsorption?
200 mg/dL - begin to have glucosuria
375 mg/dL - all transporters saturated (reached Tm)
pregnancy and glucose/AA reabsorption?
decrease PCT ability to reabsorb
how are AAs reabsorbed in kidneys?
PCT
Na-dependent transporters
Hartnup dz?
AR
deficiency in neutral AA transporters in PCT and enterocytes –> decreased tryptophan –> decreased niacin production –> pellagra
** tx: high-protein diet and niacin
what happens in the PCT?
all glucose and AA reabsorption
most reabsorption of other electrolytes
secretion of NH3 - buffer for H+ secretion
** isotonic absorption
where does PTH act on the kidney?
PCT: inhibits Na/P cotransport –> increases P excretion
DCT: increases Na/Ca exchange –> increases Ca reabsorption
where does ATII act on the kidney?
PCT: stimulates Na/H exchange –> increased Na, H2O, HCO3 reabsorption
** contraction alkalosis!
where does acetazolamide act on the kidney?
PCT: inhibits carbonic anhydrase, increases HCO3 excretion in urine
what happens in the thin descending loop of Henle?
passive reabsorption of water
concentration of urine –> hypertonic
** impermeable to Na
what happens in the thick ascending loop of Henle?
Na/K/Cl reabsorption via cotransporter
paracellular reabsorption of Ca and Mg (via K+ backleak–>membrane potential)
- impermeable to H2O
- urine becomes less concentrated
where do loop diuretics act on the kidney?
thick ascending LOH
inhibit Na/K/Cl transporter
what happens in the DCT?
Na, Cl reabsorption (via cotransporter)
Ca reabsorption
urine becomes hypotonic
where do thiazide diuretics act on the kidney?
DCT - inhibit Na/Cl transporter
what happens in the collecting tubule?
- principal cells: Na reabsorbed in exchange for K and H secretion via Na/K pump, ENaC, apical K loss
- H2O reabsorption via aquaporins (apical side of principal cells)
- alpha-intercalated cells: HCO3/Cl exchange via H+ ATPase, H/K exchanger
where does aldosterone act on the kidney?
collecting tubule
1) principal: upregulates apical K, Na/K pump, ENaC
2) alpha-intercalated: upregulates H+ ATPase –> increases HCO3/Cl exchanger activity
where does ADH act on the kidney?
V2 receptor of collecting tubule
insertion of AQP on apical side
generalized reabsorptive defect in PCT?
Fanconi syndrome
increased excretion of AAs, glucose, HCO3, Phos
may cause RTA2
** causes: hereditary, ischemia, MM, nephrotoxins/drugs, lead poisoning
reabsorptive defect in thick ascending LOH?
Bartter syndrome - AR
affects Na/K/Cl cotransporter
** hypokalemia, metabolic alkalosis with hypercalciuria
reabsorptive defect in DCT?
Gitelman - AR
affects Na/Cl cotransporter
** hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
gain of function mutation in collecting tubule?
Liddle syndrome - AD
affects ENaC channel
- HTN, hypokalemia, metabolic alkalosis, low aldosterone
- tx: amiloride
where do amiloride and triamterene act on the kidney?
collecting tubule - block ENac
K sparing diuretics
syndrome of apparent mineralocorticoid excess?
11beta-hydroxysteroid DH deficiency - can’t convert cortisol to cortisone
excess cortisol –> increased mineralocorticoid receptor activity
HTN, hypokalemia, metabolic alkalosis; low aldosterone
what does glycyrrhetic acid do to you?
(found in licorice)
blocks 11beta-hydroxysteroid DH –> gives you syndrome of apparent mineralocorticoid excess
why does tubular inulin concentration increase along PCT?
bc of water reabsorption
which solutes are reabsorbed at about the same rate as water in the PCT?
Na, K
how does Cl concentration change in PCT?
initially reabsorbed slower than Na –> relative concentration in PCT increases
then rate increases to match Na rate –> concentration plateaus
what makes angiotensinogen?
the liver
what makes ACE?
the lungs
what activates RAAS?
JG cells sense BP decrease
macula densa cells sense decreased Na delivery
B1 receptors sense increased sympathetic tone
what cells make renin?
JG cells (in afferent arteriole)
functions of ATII?
1) AT1 receptor on vascular smooth mm –> constriction
2) constriction of efferent arteriole –> increased FF
3) stimulates aldosterone and ADH release
4) increases PCT Na/H activity
5) stimulates thirst center in hypothalamus
how do ANP and BNP interact with RAAS?
may act as “check” - relax vascular smooth mm via cGMP, causing increase in GFR without concurrent absorption of Na/H2O
where is the macula densa?
DCT
what do macula densa cells do?
sense decreased Na delivery to DCT
release renin –> vasoconstriction
where is EPO made?
interstitial cells in peritubular capillary bed
released in response to hypoxia
where is vitD converted to active form?
PCT
** enzyme: 1alpha hydroxylase
Henderson Hasselbach?
pH = 6.1 + log ([HCO3-]/(0.03*PCO2))
Winters formula?
PCO2 = 1.5[HCO3] + 8 +/- 2
metabolic acidosis, hypokalemia, calcium phosphate kidney stones?
type I RTA
- distal: alpha intercalated cells can’t secrete H+ so no HCO3 generated
** causes: amphoB, analgesic nephropathy, congenital anomalies (e.g. obstruction)
metabolic acidosis, hypokalemia, hypophosphatemic rickets?
type II RTA
- proximal: PCT can’t reabsorb HCO3
** causes: Fanconi, carbonic anhydrase inhibitors
hypoaldo, hyperkalemia, decreased ammonia in urine?
type IV RTA
- decreased aldo –> hyperkalemia –> decreased PCT NH3 synthesis
** causes: decreased aldo production (diabetes, mx, adrenal insufficiency), aldo resistance (K+ sparing diuretics, obstructive nephropathy, bactrim)
