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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%

4

filtration barriers

capillary
 endothelium (cells)

basement
 membrane
  (charge)

podocyteslit
  (protein)

5

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

6

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

7

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

8

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

9

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

10

Urea

liver converts NH3 to urea - kidneys excrete it

Urea is partially absorbed in prox tubule by passibe diffusion (through tight junctions)

11

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

12

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

13

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

14

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

15

normal levels

Na: 140
Cl: 100
K: 4.5
HCO3: 24
pH: 7.35-7.45
osmolarity (290 mOsM)
creatinine: 1.2
pCO2 = 40

16

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

18

NaClreabsorption  in  TALH

co transporter: Na/K/Cl
k is receycled
-- furosemide blocks this transporter

19

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

20

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

21

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

22

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

23

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)

24

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+)

25

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



26

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

27

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

28

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

29

production of dilute urine

NaCl (but not H2O) reabsorption in the TALH, DCT

NaCl (but not H2O) reabsorption in the CD (low ADH)

30

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

31

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

32

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`

33

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)

36

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)

44

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

45

k - sparing - spironolactone, amiloride

Late distal tubule and collecting duct

Inhibition of Na+ reabsorption Inhibition of K+ secretion Inhibition of H+ secretion

↑ Na+ excretion (small effect) ↓ K+ excretion (used in combination with loop or thiazide diuretics) ↓ H+ excretion