review session 1

Question 1

osmosis

Answer 1

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

Question 2

osmotic pressure and particles

Answer 2

doesn’t matter what the nature of the particle is - a particle is a particle - all exert the same osmotic pressure

Question 3

reflection coefficient

Answer 3

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

Question 4

problem of maintaining cell volume

Answer 4

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

Question 5

composition of body fluids

Answer 5

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

Question 6

calculation of plasma osmolality

Answer 6

osmolality = 2[na] + [glucose]/18 + [BUN]/2.8

multiply na by 2 cause there’s always an equal number of counterions

Question 7

osmolar gap

Answer 7

difference between measured and calculated osmolality
when changes, alerts you to some unusual osmole being present
use to detect methanol and ethylene glycol poisioning

Question 8

60-40-20 rule

Answer 8

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)

Question 9

changes in total body water

Answer 9

reflected by changes in body weight

1 liter of fluid = 1 kg of water

Question 10

changes in ICFV

Answer 10

changes reflected by alterations in plasma osmolality and plasma [Na]

Question 11

changes in ECFV

Answer 11

associated with changes in blood volume, blood pressure will be low
can see changes in plasma protein concentration and hematocrit

Question 12

forces driving fluid movement between plasma and ISF

Answer 12

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

Question 13

lymph

Answer 13

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

Question 14

venous pressure

Answer 14

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

Question 15

vasodilation (shock)

Answer 15

capillary pressure will also increase => further filtration out of capillaries => exacerbates hydrostatic shock even further

Question 16

hypertension

Answer 16

if capillary pressure inappropriately high, fluid seeps out of the capillaries to mitigate it

Question 17

capillary pressure declines

Answer 17

eg in shock

fluid drawn from ISFC into PV to support circulation

Question 18

edema

Answer 18

develops when capillary pressure significantly exceeds oncotic pressure or if capillary permeability increases

Question 19

to expand ecfv

Answer 19

use isotonic saline

will only expand ecfv

Question 20

to expand icfv

Answer 20

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

Question 21

to expand both ECFV and ICFV

Answer 21

use hypotonic saline

Question 22

to remove water from cells

Answer 22

use hyper tonic saline - increases osmolarity of excf and will draw fluid out

Question 23

to expand only plasma volume

Answer 23

colloid can be used (such as albumin)
ensures that remains in vascular space
won’t result in changes to ISFV

Question 24

energy use in kidneys

Answer 24

filtration does not require energy, but reabsorption does because requires ATPases
therefore O2 consumption is determined primarily by GFR - changes in parallel with RBF

Question 25

why is kidney main regulator of RBC production?

Answer 25

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

Question 26

ultrafiltration

Answer 26

occurs in glomerular capillary bed | bounded by afferent arteriole and efferent arteriole

Question 27

reabsorption

Answer 27

in peritubular capillary bed | efferent arteriole before

Question 28

efferent arteriole

Answer 28

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

Question 29

determinants of GFR

Answer 29

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

Question 30

filtration fraction

Answer 30

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

Question 31

hydrostatic pressure along glomerular capillaries

Answer 31

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

Question 32

determinants of filtration

Answer 32

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

Question 33

arteriole effects on filtration

Answer 33

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

Question 34

clearance

Answer 34

(Us x V)/Pas urine flow rate x concentration of substance divided by plasma concentration of substance arterial input = venous output + urine output

Question 35

PAH

Answer 35

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

Question 36

inulin

Answer 36

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)

Question 37

partial workaround for inulin and PAH

Answer 37

infuse inulin or PAH at a constant rate | know rate of infusion = rate of excretion

Question 38

creatinin

Answer 38

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?

Question 39

autoregulation of RBF and GFR

Answer 39

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

Question 40

myogenic mechanism

Answer 40

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

Question 41

tuboglomerular feedback

Answer 41

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

Question 42

mechanism of TGF

Answer 42

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

Question 43

sympathetic tone to kidney

Answer 43

under normal conditions, vasoconstrictor tone is negligable | only when blood pressure declines a lot does it matter - only when low pressure receptors deactivated

Question 44

vasoactive substances

Answer 44

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

Question 45

things that regulate secretion of renin (4)

Answer 45

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)

Question 46

hemodynamic affects of AII

Answer 46

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

Question 47

NSAIDs

Answer 47

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

Question 48

proximal tubule - transport capacity - driving force - leakiness - energy efficiency

Answer 48

- highest - very small - highest - highest

Question 49

loop of henle - transport capacity - driving force - leakiness - energy efficiency

Answer 49

- little less than PT - little more than PT - little less than PT - little less than PT

Question 50

distal tubule - transport capacity - driving force - leakiness - energy efficiency

Answer 50

- much smaller than PT or LH - much larger than PT or LH - much smaller than PT or LH - much smaller than PT or LH

Question 51

cortical CD - transport capacity - driving force - leakiness - energy efficiency

Answer 51

- little smaller than DT - about twice as big as DT, largest - little smaller than DT - little smaller than DT

Question 52

medullary CD - transport capacity - driving force - leakiness - energy efficiency

Answer 52

- 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

Question 53

functions of PT

Answer 53

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

Question 54

nutrient uptake in PT

Answer 54

coupled to reabsorption of Na | makes it more efficient

Question 55

bicarbonate uptake in PT

Answer 55

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

Question 56

acetazolamide

Answer 56

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

Question 57

water reabsorption in PT

Answer 57

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)

Question 58

solvent drag

Answer 58

as water goes through tight junctions due to osmotic pressure, some solutes are taken with it results in further solute reabsorption

Question 59

paracellular transport in PT

Answer 59

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

Question 60

reabsorption is a two-step process

Answer 60

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

Question 61

glomerulartubular balance

Answer 61

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

Question 62

secretion of xenobiotics in PT

Answer 62

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)

Question 63

reabsorption of oligopeptides in PT

Answer 63

degraded by intracellular brush boarder ectopeptidases | resulting AA then reabsorbed in cotransport with Na

Question 64

reabsorption of albumin in PT

Answer 64

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

Question 65

main functions of loop of henle

Answer 65

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

Question 66

ion transport in TAL

Answer 66

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

Question 67

loop diuretics (furosemide, bumetanide)

Answer 67

block Na/2Cl/K cotransporter

Question 68

main functions of distal tubule

Answer 68

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

Question 69

NaCl transport in DT

Answer 69

Na/Cl cotransporter => larger concentration difference than cotransporter in Na/Cl/K cotransporter also water impermeable

Question 70

thiazide diuretics

Answer 70

block Na/Cl cotransporter in DT

Question 71

main functions of CD

Answer 71

where regulation of Na balance takes place regulation of H2O balance regulation of K balance fine regulation of acid/base balance

Question 72

ion transport in CD

Answer 72

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

Question 73

paracellular pathway in CD

Answer 73

permeable only to Cl

Question 74

K sparing diuretics

Answer 74

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

Question 75

ADH

Answer 75

regulates water permeability of CD increases H2O permeability in all CD segments increases urea permeability of medullary CD

Question 76

Na and H2O handling summary

Answer 76

``` 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 ```

Question 77

regulators of Na/H2O reabsorption

Answer 77

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

Question 78

renal handling of urea

Answer 78

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 ```

Question 79

central DI

Answer 79

inadequate release of ADH

Question 80

nephrogenic DI

Answer 80

kidney is resistant to ADH

Question 81

primary polydipsia

Answer 81

compulsive water drinking

Question 82

SIADH

Answer 82

ADH secretion (often ectopic) that is not suppressed by low plasma osmolality