what are the 6 major functions of the kidney?
1) regulation of water and electrolyte balance
2) excretion of metabolic waste products/foreign chemicals
3) regulation of blood pressure
4) secretion of erythropoietin
5) secretion of 1,25-dihydroxyvitamin D3
6) regulation of extracellular pH
What are the kidneys?
2 retroperitoneal organs about the size of a fist (wt = 150g)
what is a nephron?
filtering units of the kidney each containing a selective filtering unit (glomerulus)
what percentage of volume is reabsorbed in the kidneys?
99%
what is urethritis?
inflammation of urethra
what is cystitis?
inflammation of bladder
what is pyelonephritis?
infection of kidney
what is the glomerulus?
highly specialized membrane for selective filtration, containing a network of capillaries between an afferent and efferent arteriole
what allows effective filtration at glomerulus?
large surface area that allows fluids and small molecules across but not protein
what is glomerular filtration rate? what is the normal range?
total movement of fluid across the glomerular membrane for all nephrons
100-125mL/min
What is the flow of blood through the glomerulus?
afferent arteriole glomerular capillaries (filtration site) efferent arteriole peritubular capillars and vasa recta venules
where are the two capillary beds (glomerulus and peritubular) located in relation to one another?
two capillar beds in parallel
where is bowman’s capsule?
surrounding glomerulus
what are the 3 layer of the glomerular membrane?
endothelial cells basement membrane (basal lamina) podocytes (foot processes)
describe the endothelial cells
perforated and have pores
contain fenestrations
describe the basal lamina
acellular
contains collagen and glycoprotein
describe podocytes
epithelial cells that encircle glomerular tuft
there are narrow slits between podocytes
what is the glomerular membrane sensitive to?
changes in BP and P sub GC
changes in Glc levels
what are the 3 glomerular cell types?
mesangial cells
macula densa
juxtaglomerular apparatus
what are the mesangial cells?
muscle cells between capillary loops that are able to contract and decrease GFR
what are the mesangial cells?
muscle cells between capillary loops that are able to contract and decrease GFR
where is the macula densa? what is its function?
located in early distal tubule and between afferent/efferent arterioles
detects changes in tubular fluid
what is the function of the JGA?
contain granule cells that secrete renin and other vasoactive chemicals
how are the JGA and macula densa related?
macula densa can detect changes in tubular fluid and tell JGA to release agents to regulate GFR accordingly (through vasoconstriction/dilation)
what drives filtration?
starling forces
what is P sub GC?
pressure in glomerular capillary
acts on bowman’s capsule
what is pi sub BC?
oncotic pressure of filtrate in Bowman’s capsule
what is P sub BC?
pressure in bowman’s capsule
acts on glomerulus
what is pi sub GC?
oncotic pressure of plasma in glomerular capillary
what is Kf?
filtration coefficient (leakiness)
what 2 forces favour filtration?
P sub GC
pi sub BC
what 2 forces oppose filtration?
P sub BC
pi sub GC
what is the main determinant of GFR? what happens if you increase or decrease it?
P sub GC
incr: GFR increases (leads to damage of glomerular membrane)
decr: GFR decreases
what controls P sub GC?
afferent and efferent arterioles
what controls P sub GC? what hormones are involved?
afferent and efferent arterioles
ang 2 and NE
what happens to PsubGC if you constrict afferent arteriole? efferent arteriole?
aff = decr PsubGC eff = incr PsubGC
what happens to PsubGC if you constrict afferent arteriole? efferent arteriole?
aff = decr PsubGC eff = incr PsubGC
what are two intrarenal mechanisms and what is their overall function?
1) myogenic (generated within muscle)
2) tubuloglomerular feedback
keep RBF (renal blood flow) and GFR constant of wide range of BP
how does myogenic mechanism keep RBF and GFR constant?
prevents increase in PsubGC and GFR by constricting the muscle when theres increased BP
how does tubuloglomerular feedback help keep RBF and GFR constant?
tubules talk to glomerulus
macula densa detects changes in fluid flow/content in distal tubule and tells JGA to release constrictor/dilator accordingly
how does tubuloglomerular feedback help keep RBF and GFR constant?
tubules talk to glomerulus
macula densa detects changes in fluid flow/content in distal tubule and tells JGA to release constrictor/dilator accordingly
what does the myogenic and tubular glomerular feedback mechanisms do when there is an increase in RBF?
protect PsubGC
myogenic contstricts afferent
tubular glomerular feedback reduces flow to prevent PsubGC from going up
what does the myogenic and tubular glomerular feedback mechanisms do when there is an increase in RBF?
protect PsubGC
myogenic contstricts afferent
tubular glomerular feedback reduces flow to prevent PsubGC from going up
what 3 substances are released when there is volume depletion/low BP? what causes each release?
baroreceptor reflex incr NE
decr renal perfusion incr ang 2
decr BP incr ADH
use of NE, Ang 2 and ADH may cause severe vasoconstriction. what do the kidneys do to prevent that?
release of vasodilatory prostaglandins
use of NE, Ang 2 and ADH may cause severe vasoconstriction. what do the kidneys do to prevent that?
release of vasodilatory prostaglandins
how are prostaglandins formed?
membrane phospholipids are converted to arachidonic acid
cyclooxygenase, COX1 and COX2 convert arachidonic acid to prostaglandin intermediates which go on to become prostaglandins
how are prostaglandins formed?
membrane phospholipids are converted to arachidonic acid
cyclooxygenase, COX1 and COX2 convert arachidonic acid to prostaglandin intermediates which go on to become prostaglandins
how could aspirin cause renal failure?
prostaglandins prevent intence constriction of afferent/efferent caused by Ang 2 and NE
aspirin can block prostaglandin and allow severe constrition
what is creatinine?
natural product of muscle metabolism and constant from day to day and freely filtered (not secreted or reabsorbed)
estimates GFR
what are 3 values to know the importance of?
1) creatinine clearance
2) MDRD eGFR equation to estimate GFR
3) blood urea/creatinine ratio to determine volume depletion
what is the problem with eGFR?
only accurate with patients who have GFR less than 60 and have been stable for a period of time
what can blood urea:creatinine ratio tell us?
early volume depletion
if over 0.07, then hypovolemia
what is the relationship between plasma creatinine and GFR? why is this significant?
inverse relationship (filtration goes down, plasma Cr goes up) a small change in plasma Cr may reflect a large change in GFR
what is the relationship between plasma creatinine and GFR? why is this significant?
inverse relationship (filtration goes down, plasma Cr goes up) a small change in plasma Cr may reflect a large change in GFR
how much is reabsorbed in the proximal tubule?
95%
what does the negatively charged barrier of the glomerulus do
repel proteins, making the filtrate protein free
what is reabsorbed at proximal tubule?
water/Na (55-70%)
HCO3 (85%)
Glucose (100%)
small amount of filtered protein (95%)
what does volume depletion do to proximal tubule? How?
increases reabsorption since there is a decre in water and solute
increases constriction of afferent and efferent (dec. RBF but efferent constriction corrects drop in PsubGC)
decreases plasma osmotic pressure in peritubular capillaries
what can volume depletion do to drug/metabolites?
increase reabsorption which can be toxic
what is different about the blood going to peritubular capillaries when there is volume depletion?
increased protein conc and increased osmolality
what does less blood flow mean in terms of RBF?
greater fraction of RBF is filtered and protein is left behind in blood
what is the equation for excretion?
exc = filtration - reabsorption + secretion
when reabsorption is 100%, then filtration = reabsorption
what happens to excretion, reabsorption, filtration with increase plasma Glc?
filtration goes up
excretion does not go up until there is quite a big incr in plasma glc (transport maximum = Tm)
reabsoprtion goes up until certain point (Tm) is reached
what happens to excretion, reabsorption, filtration with increase plasma Glc?
filtration goes up
excretion does not go up until there is quite a big incr in plasma glc (transport maximum = Tm)
reabsoprtion goes up until certain point (Tm) is reached
what is the function of descending loop of henle?
reabsorbs water
increases concentration of electrolytes in filtrate
what 2 conditions are required to pull water out from lumen of descending tubule?
high water permeability so water can freely pass but not ions
hypertonic interstitum causing osmotic forces to pull water from lumen
what is the function of the ascending loop of henle?
Na, Ca, Cl, Mg, and Ca are reabsorbed
Water is left behind (dilutes)
what is the function of the distal tubule?
Na and Ca (PTH activated) reabsorption
water left behind (dilutes)
what is the function of collecting ducts?
Na reabsorbed, K secreted (as a loss)
water reabsorbed if ADH present
H+ excreted
concentrates urine
what parts of the nephron segments are in the adrenal medulla? cortex?
cortex: distal tubule, proximal tubule and part of collecting duct
medulla: loop of henle, part of collecting duct
what causes renin release?
decreased RA pressure, decr Na load, decr renal perfusion pressure, beta-adrenergic receptor stimulation
what is the function of ang 2?
vasoconstrictor release aldosterone increase thirst increase Na appetite increase ADH increase NE release
what happens when BP decreases?
baroreceptors increase Sym nerve activity (incr HR and contractility)
renin release leads to ang 2 formation, leading to aldosterone release and Na retention
how does converting enzyme affect bradykinin?
causes it to be inactive, leading to decreased vasodilation and increased TPR
how does converting enzyme affect bradykinin?
causes it to be inactive, leading to decreased vasodilation and increased TPR
what increases aldosterone?
ang 2
potassium
ACTH
what does aldosterone do?
incr Na reabsorption but incr K loss
incr H loss
what does ADH do?
opens water channels (incr water reabsorption in collecting ducts)
vasoconstriction
thirst
what causes ADH release?
incr in osmolality of plasma
decr blood volume
what two receptors activate ADH?
osmoreceptors
baroreceptors
what two receptors activate ADH?
osmoreceptors
baroreceptors
what is the major prostaglandin in the kidney? what triggers PG production?
PGE2
NE and ang 2
what are 3 sources of calcium?
GI tract
kidneys
bone
how much caclium is reabsorbed in kidneys and where is it reabsorbed the most?
99%
60% proximal tubule
(distal tubule under PTH control)
what does PTH do in GI?
stimulates activation of vit D to increase interstinal Ca absorption
what does PTH do in kidneys?
incr calcium reabsorption in distal tubule and decr phosphate reabsorption in proxminal tubule
what does PTH do in bone?
mobilizes Ca from bone to ECF
what does Vit D do in GI?
incr Ca and phosphate absorption in gut
what does Vit D do in bone?
incr responsiveness of bone to PTH to incr Ca mobilization
what does Calcitonin do?
works primarily in bone to decr Ca movement from bone fluid to plasma and decr bone resoprtion (inhibits osteoclasts)
what does erythropoietin do?
increases hemoglobulin synthesis and production of RBCs when there is hypoxia