Flashcards in Quiz 1 Deck (45):
1
urine flow
1ml/min
2
Glomerularfiltration rate:
125ml/min 180L/day
3
Filtration fraction
FF= GFR/RPF
125/660 ~~20%
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filtration barriers
capillary
endothelium (cells)
basement
membrane
(charge)
podocyteslit
(protein)
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pressure differences in glomeruli
In glomerulus Starling forces favor filtration:
Δ hydrostatic pressure ~ 40 mm Hg
Δ oncotic pressure ~22 mm Hg
net filtration pressure ~ 18 mm Hg
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Control of Bladder
low volume: sympathetic signals dominate • bladder relaxed • internal sphincter contracted
Filling : Sensory signals trigger parasympathetic response • bladder contracts • internal sphincter relaxes • external sphincter contracted (somatic override)
Emptying (micturition): external sphincter relaxes parasympathetic responses dominate • contract detrusor • relax internal sphincter
Detrusor muscle:
- during filling - relaxed via sympathetic B2
- during emptying, contracted via parasym M
INternal schincter:
- during filling: contracted via sympath A1
- during emptying, relaxed via parasym M
External schinter:
- during filling - contracted - volun
- during emptying - relaxed also voluntary
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measuring GFR
Inulin is
• filtered and excreted
• not reabsorbed by tubules
• not secreted by tubule
rate of excretion = rate of filtration
GFR = Uinulin•V’/Pinulin
urine inulin levels times urine flow rate divided by plasam inulin levels
same with creatine (a little secreted)
GFR ≈ C/Pcr = eGFR
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regulation of GFR
Constrict afferent arteriole:
DECREASE capillary pressure
DECREASE GFR
Constrict efferent arteriole:
INCREASE capillary pressure
INCREASE GFR
decreased during exercise, heart failure and shock
increased sympathetic tone, consstriction of afferent arteriole, decrease in GFR
increased during volume expansion - increased atrial pressure signals the release of ANP - dilates afferent arteriole
decreased in chronic kidney disease
decreases with normal aging
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glucose
normally no excretion in urine
SGLT2: early proximal tubule (PCT = S1, S2)
1 Na/glucose
reabsorbs most of filtered glucose
(drugs inhibit this to treat T2D - excrete excess sugar)
SGLT1: late proximal tubule (PST = S3)
2 Na/glucose
reabsorbs remaining glucose
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Urea
liver converts NH3 to urea - kidneys excrete it
Urea is partially absorbed in prox tubule by passibe diffusion (through tight junctions)
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PAH
PAH: amount entering kidney via renal artery
=amount excreted in urine
RPF • RA(PAH)= U(PAH) * V
RPF = U(PAH) * V/ RA(PAH)
Renal plasma flow equals the urine PAH con times the urine flow divided by the plasma PAH con
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clearance
“Clearance” of any substance S is its rate of excretion normalized to its plasma concentration:
Cs = excretion/PS= US•V’/PS
clearance of glucose = 0
clearance of CR = GFR
clearance of PAH = RPF
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development
kidneys come from intermediate mesoderm
ureteric bud and mesenteric blastema are important
** Kidney development is dependent on reciprocal induc.ve interac.ons between the met mess and ub***
The ureteric bud gives rise to the ureter, renal pelvis, calyces and collec.ng ducts
the metanephric mesenchyme: nephron epithelia (from the renal corpuscle to distal convoluted tubule)
kidneys normally ascend during development
bladder comes from endoderm
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renal development problems
Congenital anomalies of the kidney and urinary tract (CAKUT)
--renal agenesis- absence of kidney
--renal hypodysplasia- small and/or abnormal tubules (cystic)
--urinary tract obstruction – hydronephrosis
--reflux–infection and parenchymal damage
if no ureteric bud - renal agenesis - not enough ammniotic fluid - oligohydramnios (- potter syndrome - usually fatal
if too many UBs - multiple ureters, not hte end of the world - only a problem if they insert at a weird place - cause an obstruction
- RET and ROBO are important signaling factors
obstructions - hydropnephrosis - renal pelvis is enlarged
- could have pelvic kidney if one or both dont ascend normally
Polycystic kidney disease : Abnormal control of tubule diameter PKD1 PKD2
Renal hypoplasia : Premature cessation of nephrogenesis
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normal levels
Na: 140
Cl: 100
K: 4.5
HCO3: 24
pH: 7.35-7.45
osmolarity (290 mOsM)
creatinine: 1.2
pCO2 = 40
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Sodium
consume 100meq daily
filter 1.5 kg/day
excrete .1 moles/ day
reaborbed in cells via: exchangers (H+), channels, and cotransport (K)
-- these driven by low cell Na conce (pumped out other side using ATP) and also neg cell voltage
17
Na transport in proximal tublule
Na+ transport by the proximal tubule •cotransportwith nutrients •exchange for H+ (HCO3- reabsorption) •Cl- reabsorption coupled to Na+ coupled anion exchange paracellular transport •water follows (isotonic reabsorption)
•diuretics --> • acetazolamide • mannitol
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NaClreabsorption in TALH
co transporter: Na/K/Cl
k is receycled
-- furosemide blocks this transporter
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Na reabsprot in DCT
Na/ Cl cotransporter blocked by thiazides
• cotransportwith Cl• Cl- reabsorption coupled directly • water does not follow NaCl: urine diluted • diuretics - thiazides
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Na transport through CD
•transport through channels
•coupled to K+ secretion
•Cl- reabsorption
•electrical coupling(paracellular)
•exchange with HCO3- (ICs)
•water reabsorption depends on ADH
•highly regulated (aldosterone)
•diuretics -K-sparing diuretics
- •amiloride
- •angiotensin receptor antagonists/ACE inhibitors - •mineralocorticoid receptor blockers
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summary of diuretics
proximal tubule: carbonic anhydrase inhibitors acetazolamide/altitude sickness, glaucoma
thick ascending limb: NaKCl2 inhibitor furosemide/acute CHF, hypertension
distal convoluted tubule: NaCl inhibitor thiazides/hypertension
connecting tubule/collecting duct: Na channel blockers amiloride/hypokalemia, with thiazides for hypertension connecting tubule/collecting duct: RAA antagonists captopril, losartan/hypertension, heart failure spironolactone/edema with CHF, nephrotic syndrome
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Potasium
hyperkalemia: muscle weakness cardiac arrhythmias •widened QRS •shortened QT •fibrillation metabolic acidosis
hypokalemia: •muscle weakness •cardiac arrhythmias •reduced renal blood flow, GFR •metabolic alkalosis
- compensate for loss of K during exercise with increase in sympathetic tone
K transport in PCT
•Na reabsorption drives Cl, water reabsorption. •K in lumen is concentrated, reabsorbed through tight junctions. •In late proximal tubule, + voltage in lumen is added driving force.
K transport in TALH
•cotransport through Na/K/2Cl (furosemide). •Partial recycling across luminal membrane (K channels). •Reabsorption through tight junctions (+ lumen p.d.)
K transport in DCT - principal :
•K uptake through Na/K pump. •K efflux through apical channels •Coupled to Na reabsorption •K can be concentrated in urine (tight junctions, large voltage)
transport in intercalated cells:
•connecting tubule, cortical and outer medullary collecting ducts •K reabsorption through H/K pump (similar to stomach). •Stimulated by low dietary K.
aldostrerone helps balance K levels - high K intake, increased aldosterone, increased Na retention which is exhcanged and gets rid of excess K
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summary of K
K excretion increased by:
• high dietary K
• mineralocorticoids
• Na delivery to distal nephron
• loop and thiazide diuretics
K excretion decreased by:
•low dietary K
•acidosis
•K-sparing diuretics (amiloride)
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calcium and magnesium regualtion
---•Paracellular reabsorption in proximal tubule
•Na reabsorption drives Cl, water reabsorption. •Ca2+ and Mg2+ in lumen are concentrated, reabsorbed through tight junctions. •In late proximal tubule, + voltage in lumen is added driving force.
---•Paracellular reabsorption in TALH
Reabsorption through tight junctions driven by + lumen voltage
•Regulated reabsorption in distal nephron
•uptake across luminal membrane through specific channels. •efflux across basolateral membrane through pumps, exchange with Na •regulated (PTH for Ca2+)
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The CO2/HCO3- buffer system
H+ + HCO3- CO2 + H2O
pH = 6.1 + log([HCO3- ]/0.03xPCO2)
[HCO3- ] = 24 mM PCO2 = 40 mm Hg
pH = 6.1 + log((24)/0.03x40) = 7.40 (NORMAL)\
diadventage off this buffer sysstem: HCO3- must be replenished (in response to an acid load) or excreted (in response to a base load) (kidneys)
- advantage is that Co2 is easy to blow off in lungs
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acid excretion
most acid excreted bound to buffers titratable acids (H2PO4-) NH4+
- excreting H+ only gets you so far
Phoshate:
--- Proton secretion in the distal nephron • αintercalated cells
•increased with acidosis
--- HCO3-secretion in the distal nephron • βintercalated cells
•increased with alkalosis
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NH4+/HCO3- production by the kidney
in liver: glutamine production goes up in acidosis and down in alkalosis
in kidney: NH4+ production goes up in acidosis and down in alkalosis
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Acid/base issues
met - acid:
pH: low
HCO3- : VERY low
PCO2 low
resp- acid:
pH low
HCO3- high
PCO2 VERY high
met-alka:
pH: high
HCO3-: VERY high
PCO2: high
resp-alka:
pH: high
HCO3- : low
PCO2: VERY low
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production of dilute urine
NaCl (but not H2O) reabsorption in the TALH, DCT
NaCl (but not H2O) reabsorption in the CD (low ADH)
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NaCl extraction from thin ascending limb
1. Urea concentrated in CD
2. Urea --> interstitium of inner medulla (UTA1, UTA3) 3. H2O: thin descending limb --> interstitium (AQP1)
4. NaCl thin ascending limb --> interstitium
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Countercurrent exchange in the vasa recta minimizes solute loss from the inner medulla
descending limb: • water lost • solute gained
ascending limb: • water gained • solute lost
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ADH
ADH release controlled by osmoreceptors in the hypothalamus
Plasma ADH is secreted by the posterior pituitary
Plasma ADH increases urine osmolality.
diuresis(low ADH): water channels in cytoplasm antidiuresis(high ADH): water channels in apical membrane
Actions of ADH
- INCREASE H2O permeability in collecting duct
- INCREASE NaCl transport in TALH
- INCREASE urea transport in collecting duct`
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volume expansion
increased hydrostatic pressure
decreased oncotic pressure
---> decreased fluid reabsorption
lots of fluid, won't reabsorb much sodium
34
Autonomic control of Na excretion
low ECV
low arterial pressure
baroreceptors respond by turning on and activate sympathetic repsonse
--> increased Na reabsorption
also activation of RAAS which does the same thing but indirectly
ANS regulates proximal and distal tubule Na transport
35
ANP effects
act via cGMP
released in response to high volume
§ systemic vasodilation
§ afferent arteriole vasodilation (GFR)
§ decreased aldosterone secretion (adrenal)
leads to increased Na excretion (don't need it)
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Renin
stimuli for secretion
1.Decrease in renal perfusion pressure via baroreceptors in the afferent arteriole
2. Decrease in sodium load to the macula densa
3. Direct adrenergic stimulation of JG cells via beta adrenergic receptors
37
emergency treatment of hypertension
Esmolol,a short-acting β-blocker
Nicardipine,an intermediate-acting Ca2+-channel blocker
Nitroprusside,a short-acting NO releaser
Fenoldopam, a short-acting dopamine DA1R agonist
38
equations
filtered load = GFR x plasma concentration
fractional excretion = amount excreted/amount filtered
excretion rate = urine concentration x urine volume
39
net acid excretion
= excretion of titratable acid + excretion of NH4+ - excretion of HCO3-
40
free water clearance
Solute clearance: Cosm= Uosm•V’/Posm
Free water clearance:
CH2O= V’-Cosm= V’•(1-Uosm/Posm)
When Uosm< Posm, CH2O is positive
Distilled H2O added to urine (diuresis)
When Uosm> Posm, CH2Ois negative
Distilled H2O removed from urine (antidiuresis)
41
three factors that impact the release of renin
1. decreased renal perfusion pressures sensed by the JG cells - baroreceptors
2. sympathetic stimulation - beta receptors
3. decreased Na load as sensed by the macula densa
42
Carbonic anhydrase inhibitors (acetazolamide)
Proximal tubule
Inhibition of carbonic anhydrase
↑ HCO3- excretion
43
loop diuretics - furosemide
Thick ascending limb of the loop of Henle
Inhibition of Na+–K+− 2Cl− cotransport
↑ NaCl excretion ↑ K+ excretion (↑ distal tubule flow rate) ↑ Ca2+ excretion (treat hypercalcemia) ↓ ability to concentrate urine (↓ corticopapillary gradient) ↓ ability to dilute urine (inhibition of diluting segment)
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thiazide diuertetics
Early distal tubule (cortical diluting segment)
Inhibition of Na+–Cl−cotransport
↑ NaCl excretion ↑ K+ excretion (↑ distal tubule flow rate) ↓ Ca2+ excretion (treatment of idiopathic hypercalciuria) ↓ ability to dilute urine (inhibition of cortical diluting segment) No effect on ability to concentrate urine
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