Lec 2/3 Renal Physiology Flashcards
What percent of body mass it total water?
total body water is 60%
What percent of total body water is extracellular vs intracellular?
1/3 extracellular [20% total body]
2/3 intracellular [40% total body]
What percent of total extracellular water is plasma volume vs interstitial?
1/4 plasma volume [5% total body weight]
3/4 interstitial [15% total body weight]
What is total body fluid in liters?
40 liters
What is the function of glomerulus?
bulk filtration of urine
What is the function of proximal tubule?
bulk reabsorption of whats filtered [reabsorbs 2/3 of filtered fluid]
What is the function of the loop of henle?
to reasborb eletrolytes without water –> creates longitudinal gradient to allow potential for concentrating urine or secreting dilute urine
What is function of distal tubule and collecting duct?
fine tune what we excrete and acidification of urine
What are the two types of nephrons?
cortical and juxtamedullary
What are properties of cortical nephrons?
- glomerulus near surface of kidney
- shorter loop of henle –> Na and H2O wasting [excrete more]
- efferent: peritubular capillaries that stay in cortex
What parts of kidney structures are contained in cortex?
- glomeruli
- the convoluted portions of loop of henle = proximal and distal convoluted tubules
What are the 4 parts of the loop of henle?
- thick descending limb
- thin descending limb
- thin ascending limb
- thick ascending limb
What is the function of glomerulus?
form primary urine which is filtrate from plasma; filters plasma
What are properties of juxtomedullary nephrons?
- glomerulus in cortex near medulla junction
- longer loop of henle –> allows for more concentration [Na and H20 conserving]
- efferent: vasa recta that follows loop of henle
What is the function of peritubular capillaries?
associated with cortical nephrons; stays in cortex exclusively and puts Na and H2O reabsorbed in prox and distal tubules back into circulation
What is function of vasa recta?
associated with juxtomedullary nephrons; network of long looping capillaries that follow path of loops of henle; aids in creating longitudinal gradient
What are characteristics of the content of bowman’s space?
exactly like plasm except not proteins, cells, or large macromolecules
What is the main function of the efferent arteriole?
down stream resistor; backs up fluid into the capillary to drive filtration/fluid into bowman’s space
What is the difference in glomerular vs systemic capillaries?
glomerular capillaries are in parallel not in series –> lower resistance than in systemic so lower pressure drop [only 2-3 mmHg drop] –> mean there is a much higher filtration pressure across the glomerulus compared to systemic circulation so filtration occurs across the entire length [vs in systemic filtration in beginning and reabsorption at the end]
What two structures make up the juxtaglomerular apparatus?
- juxtaglomerular cells [JG cells] that secrete renin
- macula densa: in distal tubule; sensitive to NaCl conc in distal tubule and feedback to control renin secretion and resistance of afferent arteriole to maintain constant GFR
What are the 3 layers of glomerular filtration barrier?
- fenestrated capillary endothelim [size]
- fused basement membrane with heparan sulfate [neg charge barrier]
- epithelial layer of podocyte foot processes [filtration slits]
Is pos, neutral, or neg charged protein more likely to be able to pass glomerular filtration barrier?
positive charge can more easily pass filtration barrier b/c it has an inherent negative charge
What is the equation for GFR in terms of starlings forces?
GFR = K([Pgc - Pbs] - [PIgc-PIbc])
Pgc = hydrostatic P in glomerular capillary Pbs = hydrostatic pressure in bowmans space PIgc = oncotic pressure in glomerular capillary PIbs = oncotic pressure in bowman space = normal 0
What is the equation for clearance of a substance?
C = UxV/Px Ux = urine conc X V = urine flow rate Px = plasma conc X
What does it mean if Cx < GFR?
net tubular reabsorption
What does it mean if Cx > GFR?
net tubular secretion
What does is mean if Cx = GFR?
no net secretion or absorption
Clearance of what substance[s] can be used to calculate GFR?
inulin
creatinine is approximate but slightly overestimates
What is difference in Kf systemic vs glomerular capillary?
glomerular = much higher Kf
Clearance of what substance equals effective renal plasma flow?
PAH
What is the equation for filtration fraction [FF]?
FF = GFR / RPF RPF = renal plasma flow
What happens to GFR if you constrict the afferent artery?
increased resistance –> more pressure dissipates by the time you reach glomerular capillary so less hydrostatic P –> lower GFR and less blood flow into capillary [lower renal blood flow]
in sum: lower RBF, lower GFR
What happens to GFR if you dilate the afferent artery?
decreased resistance –> higher hydrostatic P –> higher GFR and more blood flow into capillary [lower renal blood flow]
in sum: higher RBF, higher GFR
What happens to GFR if you constrict the efferent artery?
- higher resistance to blood flow so pressure builds up –> rise in Pgc and increase in GFR
- decrease RBF, increase GFR
What happens to GFR if you dilate the efferent artery?
- low resistance to blood flow so lower pressure –> decrease in Pgc and decrease in GFR
- increase RBF, decrease GFR
What are two non-vascular regulators of GFR?
- contraction of mesangial cells causes decrease K/GFR [vs relaxation causes increases]
- contraction of podocytes decreases K/GFR [vs relaxation increases]
How does kidney autoregulate constant GFR [despite changes in MAP]? [2 mech]
- myogenic mechanism: vascular smooth muscle stretched –> increase in contractile force leads to vessel contracting down to smaller diameter
- tuboglomerular feedback: macula densa of distal tubule has contact w/ afferent arterole; senses luminal fluid in distal tubule and causes afferent arteriole contraction/relaxation
When does kidney autoregulation fail?
at MAP < 60 an’t maintain perfusion pressure –> thus hypotension can cause renal failure
What is the equation for filtered load of a substance?
FLx = Px * GFR
FL = filtered load P = plasma conc
What is equation for urinary excretion of a substance?
UEx = Ux * V
UE = urinary excretion U = urine conc V = urine flow
What is equation for fractional excretion of a substance?
FEx = UEx / FLx
FEx = fractional excretion UEx = urinary excretion FLx = filtered load
What is normal GFR?
125 mL/min or 180L/day
What happens to H2O in the proximal tubule?
- isosmotic reabsorption of water mediated by leaky tight junctions
- primarily Na-driven/dependent
- paracellular and transcellular
What happens to water in descending loop of henle?
water permeable; passive reabsorption due to medullary hypertonicity
What happens to water in ascending loop of henle?
ascending loop of henle is water impermeable
What happens to water in early distal convoluted tubule?
water impermeable
What happens to water in late distal tubule and collecting tubule?
permeability depends on ADH level; ADH acts at V2 recepro and inserts aquaporin H2O channels on luminal side
In what part of the loop of henle does Na/K reabsorption occur?
occurs in thick ascending loop via Na/K/2Cl cotransporter
What is important about function of Na/K/2Cl cotransporter?
only unctions if it contains all 3 ions
conc of Na > > K so have apical transport of K back into lumen to recycle for continued function of the Na/K/2Cl cotransport [otherwise you would be limited by the amount of K]
What happens to glucose in the proximal tubule?
100% of glucose gets reabsorbed in the proximal tubule
What is the osmolarity of the fluid at end of the distal prox tubule?
same as serum = very leaky/permeably
What happens to conc of lumen in thick ascending limb?
have solute transport but it is water impermeable so get hypotonic solution that is delivered to the distal tubule
How is Na handled in early proximal tubule?
- lumen potential -4 mV
- Na linked co-transporter reabsorbs Na/glucose; Na/AA, etc
- each Na absorbed with a bicarbonate
- basolateral side of cell has Na/K ATPase [3 Na out of cell; 2 K in = electrogenic]
65-80% of Na reabsorbed in prox tubule
How is Na handled in late proximal tubule?
- Na reabsorbed transcellular and pericellularly
- pericellular = Cl driven Na reabsorption
- transcelluar = Na/H exchanger then Na/K ATPase on basolateral side
How is Na handled in descending loop of Henle
s
What happens to Na in ascending loop of Henle?
10-20% of Na actively reabsorbed in thick ascending limb via Na/K/2Cl transporter
What happens to Na in early distal convoluted tubule?
5-10% of Na reabsorbed
actively reabsorbed via Na/Cl cotransporter on apical; Na/K ATPase on basolateral side
further dilutes the urine b/c water impermeable
What happens to Na in late distal tubule and collecting duct?
3-5% of Na reabsorbed
under hormonal regulation
principle cells: reabsorb Na and secrete K
overall: reabsorption of Na in exchange for secreting K and H
What happens to K in the proximal tubule?
2/3 of filtered K reabsorbed in proximal tubule via paracellular = solvent drag; flows with H2O
What happens to K in the thick ascending loop?
actively reabsorb via Na/K/2Cl
leaks back into lumen to recycle for use in Na/K/2Cl transporter thus creating + potential in the lumen which causes indirect paracellular reabsorption of Mg and Ca
What happens to K in the late distal tubule and collecting duct?
alpha-intercalated cells: secrete H and reabsorb K
principle cells: reabsorb Na and secrete K
What happens to Cl in early proximal tubule?
s
What happens to Cl in late proximal tubule?
s
What happens to Cl in late proximal tubule?
- pericellular diffuses out of lumen down concentration gradient
- transcellular enters cell via Cl/anion exchanger and leaves via Cl/K co-transporter
What happens to Cl in descending loop of henle?
s
What happens to Cl in ascending loop of henle?
s
What happens to Cl in early distal convoluted tubule?
ss
What happens to Cl in collecting duct?
s
What happens to bicarbonate in the proximal tubule?
can’t be reabsorbed as bicarbonate; need to convert via carbonic anhydrase to CO2 and H2O; then back to HCO3 once in the cell
What happens to bicarbonate in the proximal tubule?
s
What happens to bicarbonate in the thick ascending limb?
reabsorbed as CO2 via carbonic anhydrase reaction in lumen/cell
What happens to extra H in lumen when there is not bicarb left to reabsorb with it?
- excreted as titratable acid
- excreted as NH4
if pH is low in lumen –> will inhibit H ATPase so as to prevent even lower luminal pH which might injure epithelium; instead secrete H and NH4 which does not contribute to the pH
What happens to acid-base handling in the distal tubule and collecting duct?
alpha intercalated cell
- K/H ATPase on apical membrane to secrete H and reabsorb K
- regenerates bicarb from intracellular CO2/H2o [also reabsorbs a small amount from lumen]
What is the function of principle cells in the distal tubule and collecting duct? regulation?
principle cells reabsorb Na and secrete K
regulated by aldosterone and ADH
What is the function of alpha intercalated cells in distal tubule and collecting duct?
secrete H and reabsorb K
What is the function of beta intercalated cells in distal tubule and collecting duct?
secrete bicarbonate
What two hormones regulate proximal tubule Na reabsorption?
- epinephrine
- angiotensin II
What who hormones regulate distal tubule reabsorption?
- ANP [decreases reasborption]
- aldosterone
What is the target for aldosterone?
principle cell –> increases K secretion
What is the driving force for counter current multiplier?
Na/K/2Cl cotransporter is driving force; higher activity of cotransporter and longer the loop = larger the longitudinal gradient
What are the 3 roles of ADH?
- inserts water pores into apical membrane of principle cells
- increases activity of Na/K/2Cl co-transporter to increase longitudinal gradient to create driving force for H2O reabsorption
- increases permeability of urea in inner-medullary collecting duct
What stimulates ADH release?
hyper-osmolarity and hypervolemia
How is HCO3 reabsorbed basolaterally from alpha intercalated cells?
Cl/HCO3 countertransport
How is HCO3 reabsorbed basolaterally from prox tubule and thick ascending limb cells?
via 1Na/3HCO3 cotransporter
How is H secreted apically from prox tubule and thick ascending limb cells?
Na/H exchanger
How is H secreted apically in alpha intercalated cells?
H/K ATPase exchanger
What happens to HCO3, pCO2 in metabolic acidosis?
- low HCO3
- low pCO2
What happens to HCO3, pCO2 in metabolic alkalosis?
- high HCO3
- high pCO2
What happens to HCO3, pCO2 in respiratory acidosis?
- high pCO2
- high HCO3
What happens to HCO3, pCO2, in respiratory alkalosis?
- low pCO2
- low HCO3