review session 1 Flashcards
osmosis
solutes suck - solutes draw fluid in direction of higher solute concentration
counteracted by hydrostatic pressure - the hydrostatic pressure that stops the water flow is the oncotic pressure
this tendency to draw water can be counteracted by applying the hydrostatic pressure and that hydrostatic pressure that stops the water flow is the osmotic pressure
osmotic pressure and particles
doesn’t matter what the nature of the particle is - a particle is a particle - all exert the same osmotic pressure
reflection coefficient
how much of a pressure is exerted by a particle
of the membrane - if totally impermeable, molecule always reflected back from the membrane = reflection coefficient of 1
if reflection coefficent of .5, 50% of the particles get through - ineffective osmole in a stationary system - eventually solute will leak out and equilibrium is released so eventually will be no gradient in the long term - in dynamic system like capillaries, reflection coefficient below 1 is relevant
problem of maintaining cell volume
without regulation, eventually cells would fill so much with water that they would rupture
have Na/K ATPase pump to prevent this - sot that intracellular osmotic concentration equals extracellular osmotic concentration so that there’s no driving force for water entry
requires lots of energy - up to 20% of cells energy to this
composition of body fluids
na main extracellular ion
K main intracellular
established by na/k atpase - makes the system behave as though there were no na or k permeability - also creates sidedness:
na an effective osmole only from extracellular side and k only an effective osmole from the intracellular side
calculation of plasma osmolality
osmolality = 2[na] + [glucose]/18 + [BUN]/2.8
multiply na by 2 cause there’s always an equal number of counterions
osmolar gap
difference between measured and calculated osmolality
when changes, alerts you to some unusual osmole being present
use to detect methanol and ethylene glycol poisioning
60-40-20 rule
60% of body weight is water
40% of body weight is ICFV
20% of body weight is ECFV
5% of body weight is plasma volume (part of ECFV)
changes in total body water
reflected by changes in body weight
1 liter of fluid = 1 kg of water
changes in ICFV
changes reflected by alterations in plasma osmolality and plasma [Na]
changes in ECFV
associated with changes in blood volume, blood pressure will be low
can see changes in plasma protein concentration and hematocrit
forces driving fluid movement between plasma and ISF
oncotic pressure due to plasma proteins in the blood (same as colloid osmotic pressure)
hydrostatic pressure established by pumping of the heart pushes fluid into interstitial space
lymph
washes away proteins in the interstitial space
most capillaries somewhat permeable to protein so there’s always some protein in the interstitium
doesn’t come to an equilibrium even though most of the fluid is reabsorbed because of lymph
if lymph flow is blocked then protein that accumulates in interstitial space can’t be carried away - protein concentration in interstitium becomes equal to that in the capillary - get continuous filtration into interstitial space because there’s nothing to oppose the hydrostatic pressure => severe edema
venous pressure
if increased due to central venous failure or heart failure or something like that will be transmitted to the capillaries => increased filtration and tendency to develop edema
vasodilation (shock)
capillary pressure will also increase => further filtration out of capillaries => exacerbates hydrostatic shock even further
hypertension
if capillary pressure inappropriately high, fluid seeps out of the capillaries to mitigate it
capillary pressure declines
eg in shock
fluid drawn from ISFC into PV to support circulation
edema
develops when capillary pressure significantly exceeds oncotic pressure or if capillary permeability increases
to expand ecfv
use isotonic saline
will only expand ecfv
to expand icfv
use pure water - but can’t be infused cause causes hemolysis
so use isoosmotic glucose solution or hypoosmotic glucose solution
glucose will be metabolized and the solution you’ve added will turn into pure water eventually
to expand both ECFV and ICFV
use hypotonic saline
to remove water from cells
use hyper tonic saline - increases osmolarity of excf and will draw fluid out
to expand only plasma volume
colloid can be used (such as albumin)
ensures that remains in vascular space
won’t result in changes to ISFV
energy use in kidneys
filtration does not require energy, but reabsorption does because requires ATPases
therefore O2 consumption is determined primarily by GFR - changes in parallel with RBF
why is kidney main regulator of RBC production?
over wide range in blood flows, there’s no significant change in the areteral venous O2 difference so no change in the partial pressure of O2 in the tissue
therefore the main determinant of tissue partial pressure is O2 of incoming blood
ultrafiltration
occurs in glomerular capillary bed
bounded by afferent arteriole and efferent arteriole
reabsorption
in peritubular capillary bed
efferent arteriole before
efferent arteriole
determines balance be reabsorption and filtration
if constricts, pressure in front of it increases, favors more filtration but also favors reabsorption in peritubular capillaries because hydrostatic pressure has declined there
determinants of GFR
glomerular capillary pressure - much higher than it is in other types of capillaries - main driving force for filtration
hydrostatic pressure of bowman’s space opposes that - generally remains consistent physiologically
filtration fraction
amount of arriving plasma that becomes ultrafiltrate
usually about 20%
= GFR/RPF
consequence of high filtration fraction - as blood flows through glomeruli and protein free ultrafiltrate is formed the protein concentration inside the capillaries gradually increases => limits further filtration
hydrostatic pressure along glomerular capillaries
remains relatively the same - declines by only 1-2 mm Hg because resistance of these capillaries negligable
oncotic pressure increases substancially and if flow is sluggish filtration may come to a standstill because oncotic pressure buildup stops further filtration
determinants of filtration
main determinant is hydrostatic pressure in glomeruli
blood flow less important determinant but changes in afferent and efferent tone still alter Pgc and thus GFR in opposite directions
surface area under regulation too - mesangeal cells are contractile, can change surface area available for filtration
arteriole effects on filtration
if afferent arteriole constricts, RPF goes down, Pgc goes down and GFR therefore goes down
if efferent arteriole constricts, then pressure in front of it is going to increase, so Pgc goes up, RPF goes down, and GFR goes up
filtration fraction increases - favors reabsorption
clearance
(Us x V)/Pas
urine flow rate x concentration of substance
divided by plasma concentration of substance
arterial input = venous output + urine output
PAH
filtered by glomeruli and also actively secreted into tubules by peritubular capillaries
therefore all blood that passes through the kidney is cleared of PAH in a single passage
whatever goes into the urine is equal to what came in the afferent arteriole
concentration ratio tells you how much more concentrated the urine is for PAH = can then extrapolate to what the renal plasma flow is
inulin
to determine GFR
need something that’s freely filtered just as well as water is
freely filtered and tubules are completely impermeable to it so whatever has entered the tubule through the glomerular filtration is all that will be excreted in the urine
advantages = accurate
disadvantages = requires infusion and short-timed urine collection during infusion (Foley catheter)
partial workaround for inulin and PAH
infuse inulin or PAH at a constant rate
know rate of infusion = rate of excretion
creatinin
produced endogenously - degradation product of creatinin phosphate
still need to do time collection
not perfect cause there’s some secretion - glomerular filtration increases as disease progresses though, so not that accurate
overestimates GFR with failure?
autoregulation of RBF and GFR
in normal operating range, GFR practically doesn’t change due to corresponding increase in resistance of the vessels to keep GFR from changing
if this weren’t the case, normal changes in blood pressure due to everyday activities would create huge changes in kidney function
autoregulation breaks down at BP lower than 70 - get pre renal failure
also breaks down when pressure gets very high
mechanisms = myogenic mechanism and tuboglomerular mechanism
myogenic mechanism
smooth muscle cells stretched, contract more forcefully and increase frequency of their contractions
very pronounced in kidney cause long afferent arteriole - mainly occurs in proximal region of afferent arteriole
tuboglomerular feedback
in distal portion of afferent arteriole - if high rate of filtration, more fluid delivered to loop, more arrives at macula densa (thick ascending limb) - glomerulus then sends signal to afferent arteriole of that glomerulus and that constricts it - so prevents too much na from getting to distal part of nephron, where there’s limited reabsorption capacity
but this also regulates GFR and RBF
mechanism of TGF
in macula densa:
via sensing [NaCl]:
if more na delivered, macula densa cell forced to reabsorb more (vie Na/2Cl/K transporter) => turnover rate of Na/K transporter has to increase => ATP production has to increase => signals in cell recognize high Na
via cilia: have primary cilia that sense how much fluid is passing by
sympathetic tone to kidney
under normal conditions, vasoconstrictor tone is negligable
only when blood pressure declines a lot does it matter - only when low pressure receptors deactivated
vasoactive substances
even during large changes in ECFV, effect of vasoactive substances is small because the effect of vasoconstrictors is bufferend by simultaneous release of vasodilators and vice versa
GFR needs to be stabilized cause small change in GFR could lead to huge change in filtration
vasoactive substances change set point or sensitivity of autoregulation
also have direct effects on tubules of kidney - change Na reabsorption
generally, vasodilators are natriuretic and vasoconstrictors are antinatriurretic
this effect is much more relevant than the effect on GFR
things that regulate secretion of renin (4)
increased afferent arteriole pressure results in decreased renin
increased beta-adrenergic/sympathetic tone activity results in increased renin
increased NaCl load at the macula densa results in decreased renin
increased levels of pressor hormones results in decreased renin (negative feedback)
hemodynamic affects of AII
acts primarily by increasing efferent tone, only constricts afferent at very high doses
also decreases medullary blood flow
decreases auto regulation
increases sensitivity of TGF
decreases renin secretion
NSAIDs
prostaglandins are one of main substances that buffer afferent tone - vasodilators
production of them inhibited by NSAIDs
when sympathetic tone to kidney is high, such as in heart failure, can result in pronounced effect of NSAIDs - by unmasking full vasoconstrictor effect - can result in renal failure
proximal tubule
- transport capacity - driving force - leakiness - energy efficiency
- highest
- very small
- highest
- highest
loop of henle
- transport capacity - driving force - leakiness - energy efficiency
- little less than PT
- little more than PT
- little less than PT
- little less than PT
distal tubule
- transport capacity - driving force - leakiness - energy efficiency
- much smaller than PT or LH
- much larger than PT or LH
- much smaller than PT or LH
- much smaller than PT or LH
cortical CD
- transport capacity - driving force - leakiness - energy efficiency
- little smaller than DT
- about twice as big as DT, largest
- little smaller than DT
- little smaller than DT
medullary CD
- transport capacity - driving force - leakiness - energy efficiency
- little smaller than cortical CD
- about the same as cortical CD, twice as big as DT
- little smaller than cortical CD
- about as big as cortical CD
functions of PT
reabsorbs 70% of filtered na and h2o
reclaims all of nutrients (glucose, AA, lactate, etc.)
reabsorbs about 80% of filtered bicarbonate and phosphate
secretes xenobiotics (detox)
degrades and reabsorbs filtered proteins and peptides
nutrient uptake in PT
coupled to reabsorption of Na
makes it more efficient
bicarbonate uptake in PT
Na/H exchanger in apical membrane
drives indirect reabsorption of bicarbonate
secreted H+ ions join with HCO3 to make carbonic acid
luminal C.A. IV converts carbonic acid to CO2 and H2O, which can diffuse through the membrane
C.A. II converts back into carbonic acid
carbonic acid splits into bicarbonate and H+
H+ goes back into filtrate through Na/H exchanger and bicarbonate excreted back into blood through Na/HCO3 cotransporter
acetazolamide
blocks carbonic anhydrase on lumen that converts carbonic acid into H2O and CO2 so that it can be reabsorbed
inhibit significant fraction of Na reabsorption in proximal tubule because eliminate a lot of the H+ that’s used in the Na/H+ exchanger
therefore these are diuretics
water reabsorption in PT
by osmosis
as cells reabsorb solutes, there’s a slightly higher solute concentration in cell and blood, resulting in slightly higher osmolality
change in osmolality needed to drive water through is minimal cause the water permeability of the PT is very high
partially because they have aquaporin channels present and also because tight junctions are very water permeable (leaky)
solvent drag
as water goes through tight junctions due to osmotic pressure, some solutes are taken with it
results in further solute reabsorption
paracellular transport in PT
30-50% of the filtered Na and water reabsorbed by this method
since na and water are reabsorbed with HCO3 and other anions in the early part of the PT, Cl- is left behind
its concentration increases - since the paracellular pathway is leaky, Cl diffuses down its concentration gradient and negatively charged ions move out of tubule => tubule ends up with positive voltage - voltage then drives passage of cations (Na) out of lumen as well - so there’s na/cl reabsorption without input of energy
reabsorption is a two-step process
1: transport from tubular fluid to peritubular interstitial space
2: uptake into peritubular capillary
typically step 1 is rate limiting
but PT is so leaky and its transport so high that step 2 can become ratelimiting
na can go back through paratubular junction too - how much goes back depends on starling forces that dictate entry into the peritubular capillaries
glomerulartubular balance
if glomerulus filters more, tubules respond by reabsorbing more
mechanisms involved:
if more filtration, especially due to efferent constriction (so hydrostatic pressure in glomerular capillaries increases and RBF decreases) - hydrostatic pressure in peritubular capillaries declines, oncotic pressure in peritubular capilaries increases, since more filtrate is formed from less blood - favors reabsorption
secretion of xenobiotics in PT
many toxins bind to plasma albumin - limits their filtration
these toxins are taken up into the PT by high-affinity basolateral transporters and are then secreted into the tubular fluid
3 types of transporters:
- organic anion
- organic cation
- multidrug resistance proteins
transporters are non-specific and saturable (allows for drug-drug interactions)
reabsorption of oligopeptides in PT
degraded by intracellular brush boarder ectopeptidases
resulting AA then reabsorbed in cotransport with Na
reabsorption of albumin in PT
a little bit enters filtrate despite high permselectivity of filtration barrier
filtered albumin taken up by PT cells via receptor-mediated endocytosis
degraded intracellularly and returned to blood as AA
defects in endocytic uptake of proteins in PT can result in tubular proteinuria
main functions of loop of henle
reabsorbs 25% of filtered Na but only 15% of filtered H2O - water reabsorbed in descending limb, na reabsorbed in ascending limb
dilution of urine (direct) - reabsorb more na than water
concentration of urine (indirect, permissive effect) - because segment responsible for generating hyperosmotic medullary enviornment that’s a prerequisite for concentraiton
main site of Mg reabsorption, important site of ca reabsorption
participates in the regulation of acid/base balance - permissive effect - NH4 reabsorption
ion transport in TAL
still has Na/H exchange mechanism, but that’s a small fraction
most of reabsorption due to Na/2Cl/K cotransporter
limited amount of K in tubular fluid, so K recycled through channels on luminal side => lumen positive voltage
this voltage drives Na, Ca, Mg, K, and NH4 though paracellular pathway
always water impermeable so buildup of salt in the interstitium in the medulla - how urine will eventually become concentrated when it passes through that enviornment
loop diuretics (furosemide, bumetanide)
block Na/2Cl/K cotransporter
main functions of distal tubule
reabsorbe about 5% of filtered NaCl
water impermeable, so doesnt reabsorb any water at all
contributes to dilution of urine
doesn’t contribute to ability of kidney to dilute the urine because it’s in the renal cortex and in the renal cortex, blood flow is very high and there’s no countercurrent there so salt that secreted into the interstitium gets washed away instantly
regulation of Ca balance
NaCl transport in DT
Na/Cl cotransporter => larger concentration difference than cotransporter in Na/Cl/K cotransporter
also water impermeable
thiazide diuretics
block Na/Cl cotransporter in DT
main functions of CD
where regulation of Na balance takes place
regulation of H2O balance
regulation of K balance
fine regulation of acid/base balance
ion transport in CD
na entry through na channel
driven by gradient established by Na/K atpase
mechanism can practically eliminate all the na from the urine if necessary
entry of Na into cell creates lumen negative voltage - this drives Cl through paracellar pathway
K leaves through K channel in lumen so that gradient can be maintained
means that reabsorption of Na leads to secretion of K
paracellular pathway in CD
permeable only to Cl
K sparing diuretics
inhibit Na channel in CD
because reabsorption of Na in this section is coupled to the secretion of K
if block Na entry mechanism, we also block K secretion and thereby K loss
ADH
regulates water permeability of CD
increases H2O permeability in all CD segments
increases urea permeability of medullary CD
Na and H2O handling summary
in PT - 65% Na and H2O descending LH - no Na but 15% H2O ascending LH - 25% Na but no H2O DT - 6% Na but no H2O CD - 4% Na and 0-20% H2O depending on ADH
regulators of Na/H2O reabsorption
in PT: GT balance, AII, sympathetic nerves, dopamine
in descending LH - medullary osmolality (medullary blood flow), unreabsorbed osmoles
in ascending LH, thin - medullary blood flow
in ascending LH, thick - Na load, Ca/Mg, prostaglandins, NO
DT - Na load (chronic), aldosterone
CD - aldosterone, anp, ADH, Ca/Mg, prostaglandins
renal handling of urea
in water-diuresis
50% in PT
5% in thin descending LH
5% in ascending LH
in antidiuresis 50% in PT 30% in thin descending LH 30% in ascending LH 90% in CD
central DI
inadequate release of ADH
nephrogenic DI
kidney is resistant to ADH
primary polydipsia
compulsive water drinking
SIADH
ADH secretion (often ectopic) that is not suppressed by low plasma osmolality
