review session 2

Question 1

short-term regulation of BP

Answer 1

control of HR, SV and vasomotor tone by autonomic nervous system
MAP = CO x TPR
not good for long term, carotid sinus adapts to continual increase in BP (discharge rate of receptors goes back to normal after a few days of continually high BP)

Question 2

long-term regulation of BP

Answer 2

by regulating cardiac output and by changes in blood volume
increase in CO increase general peripheral resistance
kidneys regulate PV by regulating Na concentration

Question 3

na output/losses

Answer 3

105 mmol through urine
10 mmol through feces
5 mmol through skin
all routes regulated
if on high na diet, kidney key regulator
if low na diet all routes of Na loss are curtailed

Question 4

factors that regulate Na balance

Answer 4

antinaturetic mechanisms:
RAAS
renal sympathetics

natriuretic mechanisms:
ANP
intrinsic pressure natriuresis

Question 5

how does body measure na content?

Answer 5

senses blood volume
high pressure receptors - those in afferent arteriole most important - don’t adapt
also ones in cardiac sinus and aortic arch but these are less important
low pressure receptors - cardiac atria, vena cava, large pulmonary vessels

Question 6

carotid sinus/aortic arch

Answer 6

cause changes in sympathetic/parasympathetic tone
response mainly direct cardiovascular with no or little renal participation
high pressure receptors

Question 7

renal baroreceptors

Answer 7

changes in renin-angiotensin-aldosterone cascade

Question 8

P receptors in the atria

Answer 8

changes in secretion of ANPs

changes in sympathetic tone (including renal)

Question 9

effects of renal sympathetic nerves

Answer 9

renin secretion increases

na reabsorption in PT increases

Question 10

main effects of AII in kidney

Answer 10

na reabsorption in PT increases
renin secretion decreases
also increases efferent tone a lot
and increases sensitivity of TGF

Question 11

extrarenal effects of AII

Answer 11

huge increase in aldosterone secretion
increase in arteriolar tone (vasoconstrictor)
small increase in thirst

Question 12

biological activities of aldosterone

Answer 12

increases na reabsorption primarily in CD but also in late DT
increases Na reabsorption in sweat glands
increases Na reabsorption in colon
increases K excretion
increases acid excretion

Question 13

renal effects of ANP

Answer 13

in intermedullary CD, decreases NA reabsorption - not very important for this
decreases afferent tone => increased GFR
decreases renin secretion
decreases ADH sensitivity of CD

Question 14

extrarenal effects of ANP

Answer 14

decreases cardiac contractility
decreases venous tone
increases capillary permeability - reduces circulating BV by allowing more of fluid to seem out into interstitium

decreases sympathetic tone
decreases arteriolar tone
decreases aldosterone secretion
decreases ADH secretion

Question 15

what happens to segmental Na reabsorption if there’s a decrease in Na intake

Answer 15

typically regain 99% of secreted Na
if low na, every segment responds
70% in PT
25% in ascending LH
3% in DT
3% in CD
only excrete about .1% now

Question 16

what mechanisms are regulated by catecholamines andgiotensin II?

Answer 16

Na/H exchange mechanism in early PT

so also bicarbonate

Question 17

acetezolamide

Answer 17

blocks C.A. IV on PT - acts as potent diuretic

Question 18

loop diuretics

Answer 18

target Na/Cl/K+ channels in TALH
can see the same effects from bartters’s disease
get Na, Ca, Mg wasting

Question 19

thiazide diuretics

Answer 19

the Na/Cl cotransporter in the DT is more powerful than the previous ones b/c transports 1 Na for just 1 Cl
same effects as loss of function in Gitelman’s
get hypotension and hypokalemia

Question 20

ENaC channels

Answer 20

most powerful Na collection
3 Na enters cell in CD
driven in due to low intracellular [Na] and because cell is negative inside

Question 21

aldosterone on CD

Answer 21

aldosterone main regulator of CD Na uptake
acts on MR
up regulates abundance of ENaC channels and of the Na/K atpase

Question 22

k sparing diuretics

Answer 22

inhibit Na+ channels in CD
blocking Na channel blocks associated K secretion as well
antagonists for MR receptor also act like this

Question 23

gain of function mutation in ENaC

Answer 23

get hypertension, hypokalemia becuase too many Na channels in membrane - can’t be removed
too much na uptake and too little k excretion

Question 24

aldosterone deficiency

Answer 24

results in severe hypotension and hyperkalemia because can’t increase ENaC channels and so can’t increase amount of Na reabsorbed or K secreted

Question 25

11beta-HSD

Answer 25

MR can't distinguish between cortisol and aldosterone, and cortisol at much higher concentration in blood, so MRs would always be saturated by cortisol but 11b-HSD converts cortisol to cortisone which doesn't bind to MR can be inhibited by licorice - would bet situation of apparent mineralocorticoid excess - hypertension and hypokalemia

Question 26

clinical importance of K

Answer 26

too much or too little results in arrhythmias

Question 27

effects of exercise on K

Answer 27

longer increase in K conductance and short increase in Na conductance end result is that K is lost from cells get hyperkalemia

Question 28

catecholamines on K (epi - beta-receptors)

Answer 28

epi acts on beta2-receptors increases activity of Na/K atpase enhances K uptake into cell allows prevention of large hyperkalemia associated with exercise can also be stimulated pharmacologically - asthmatics receive beta receptor agonists - makes them prone to developing hypokalemia can also use b-receptor agonists to treat acute hyperkalemia

Question 29

catecholamines on K (norepi - alpha-receptors)

Answer 29

inhibits Na/K atpase results in K leaving cell - hyperkalemia contributes to minimizing rebound hypokalemia after exercise less important than opposing effect of beta receptors but can become more pronounced in patients taking beta blockers

Question 30

effects of insulin on K

Answer 30

enhances activity of Na/K atpase - potent inducer of k uptake into cell so in diabetes mellitus get hyperkalemia - get significant fall in plasma K following insulin treatment in DM refeeding with a carbohydrate rich meal following a period of starvation may result in fatal hypokalemia can be exploited for the correction of hypokalemia due to other causes by giving insulin with glucose

Question 31

effect of hypertonicity on K

Answer 31

as there's hyperosmosis, cell shrinks cause water leaves but k amount stays the same so concentration goes up - k leaves cell a hyperglycemic, hyperosmolar state contributes to hyperkalemia in DM

Question 32

acid/base balance on K

Answer 32

mineral acids: cell behaves as though it has a H/K exchange mechanism (a little more complicated than that, but easier to remember this way) so large effect on K organic acids: are lipophilic and so can cross the membrane without the charge movement - so small change in K respiratory acidosis where CO2 can enter the cell in unionized form doesn't affect K much either

Question 33

sites of K reabsorption and secretion

Answer 33

``` 65% reabsorbed in PT 10% passively tranported in ascending LH 30% reabsorbed in ascending LH regulated in CT - if k depletion, only about 2% reabsorbed, if K loading, about 20% secreted mostly regulated in cortical CD though if k depletion, 2% reabsorbed if K loading, up to 160% secreted in medullary CD, if k depletion, 10% reabsorbed, if K loading, 20% reabsorbed ``` creates buildup of K gradient in medulla so that K isn't reabsorbed from CD when we want to excrete it

Question 34

ion transport in CD - aldosterone

Answer 34

na reabsorbed and k secreted into tubule because of more na ions reabsorbed for number of k ions secreted, creates negative charge in lumen cl then goes through paracellular pathway and also creates more favorable voltage for K secretion if force CD to reabsorb more na by delivering more to it then mechanism of K excretion will be enhanced aldosterone also upregulates K secretion

Question 35

diuretic action before or after macula densa

Answer 35

if diuretic acts proximal to macula densa, more na will be delivered to CD and more K will be secreted all diuretics that act proximal to macula densa therefore produce K wasting

Question 36

effect of tubular flow rate on K

Answer 36

in CD, how much K is in tubular fluid depends on flow rate - if flow is low and equilibirum is reached between the cell and the tubular fluid if flow is high then k secretion can occur throughout full length of cortical CD

Question 37

ADH and K

Answer 37

if flow is high then k secretion can occur throughout full length of cortical CD - creates potential problem with ADH since ADH affects flow in CD - but need to regulate water balance and K balance independently - so in the absence of ADH, have a high flow rate - maintains K secretion when ADH acts, CD becomes water permeable, H2O reabsorbed, flow is reduced , but ADH also has direct effect on open probability of luminal K channels - allows the effect of slower tubular flow rate to be canceled out and for water to be regulated separately from K

Question 38

pH and K

Answer 38

alkalosis increases open probability of K channels on luminal side fo CD acidosis inhibits opening of channels

Question 39

aldosterone and K

Answer 39

hyperkalemia stimulates aldosterone secretion directly | when aldosterone secretion is stimulated by hyperkalemia, the main effect is an increase in K excretion in cortical CD

Question 40

aldosterone and Na

Answer 40

na depletion stimulates aldosterone secretion indirectly via renin and AII when aldosterone secretion is stimulated by Na deficiency, Na delivery to the cortical collecting duct is decreased by enhanced reabsorption in preceding nephron segments - prevents K wasting get increase in Na reabsorption in PT which results in decreased Na load in cortical CD => K secretion unchanged

Question 41

what generates base?

Answer 41

exogenous organic acids

Question 42

sources of endogenous acids

Answer 42

incomplete metabolism of carbohydrates => lactic acid incomplete metabolism of lipids => ketoacids 2 main sources of endogenous acids

Question 43

sources of bases

Answer 43

carboxyl group on AA - also generates NH4 - not acidic but can be converted to H+ and urea

Question 44

NH4

Answer 44

not generally acidic but cna be converted into urea and H+

Question 45

how body protects itself from dietary acid

Answer 45

``` physiochemical buffering (instantaneous) - CO2/bicarbonate buffer system respiratory compensation (seconds to hours) - pH is determined by ratio of bicarbonate to PCO2 - if we alter them both in the same direction, the pH isn't going to change - so in acidosis, we hyperventilate to blow off CO2 and thereby return pH toward normal renal compensation (days) ```

Question 46

buffering of acid

Answer 46

by HCO3 CO2 can be blown away but bicarboanate doesn't buffer respiratory acidosis/alkalosis so ICF and bone must buffer all renal compensations are slow

Question 47

respiratory acidosis

Answer 47

too much CO2 - retention of H2CO2 directe effect on blood = decreased pH, increased PCO2 compensate by increasing HCO3 concentration - kidney does this

Question 48

respiratory alkalosis

Answer 48

due too little H2CO3 - if we hyperventilate direct effect on blood = pH increases, PCO2 decreases compensate by decreasing HCO3 - kidney does this can differentiate acute change from chronic change by amount of bicarbonate produced

Question 49

metabolic acidosis

Answer 49

due to addition of fixed acid or removal of alkali causes decreased blood pH and decreased blood HCO3 compensate by decreasing PCO2 - hyperventilate

Question 50

metabolic alkalosis

Answer 50

due to addition of alkali or loss of fixed acid increases blood pH and increases blood HCO3 compensate by increasing PCO2 - hypoventilate

Question 51

at high elevation

Answer 51

erythropoietin goes up but won't change PO2 - will breathe harder - hyperventilate - if chronic kidney will adjust and lower bicarbonate concentration - so kidney generated metabolic acidosis (essentially) come down to sea level - bicarbonate concentration is still low, so there will be a respiratory response to that - lower PCO2

Question 52

anion gap

Answer 52

no true gap difference between cations and anions that are not measured by this formula used to detect the presence of organic acid formation

Question 53

general scheme for acid excretion

Answer 53

has to be excreted in buffered form main buffer is phosphate need to reclaim all of bicarbonate first

Question 54

HCO2 reabsorption along nephron

Answer 54

80% from PT 10% from ascending LH 5% from DT 5% from CD

Question 55

alpha ICC

Answer 55

cell responsible for regulating acid base balance acid secreting has H ion pump - secretes H ions at expense of ATP hydrolysis - electrogenic so sensitive to voltage in lumen also has electroneutral H/K exchanger - sensitive to luminal K concentration source of H ions = intracellular carbonic acid - C.A. enzyme combines OH+CO2 to make HCO3 and H+ H+ pumped into lumen HCO3 pumped into blood through HCO3/Cl exchanger - same exchanger mutated in RBCs

Question 56

phosphate and ammonia

Answer 56

buffers H+ that's excreted but there's not enough to buffer entire acid load so liver makes urea and we eliminate ammonia glutamine converted to alphaketoglutarate and ammonium in kidney - ammonium excreted

Question 57

NH4/NH3 handling in PT

Answer 57

in PT K/Na exchanger puts NH4 into filtrate - NH4 substitutes for K - in these cells, glutamine take up from blood - this is converted to alphaketoglutarate which generate bicarbonate which is sent back into blood through HCO3/Na cotransporter

Question 58

NH4/3 handling in ascending LH

Answer 58

has Na/Cl/K cotransporter but NH4 can substitute for K NH4 splits into NH3 and H+ H+ sent back into urine via Na/H exchanger NH3 can't get through membrane into urine but can get into interstitium so diffuses into interstitum - get ammonium gradient

Question 59

NH3/4 handling in medulla of CD

Answer 59

highly permeable to NH3, but impermeable to NH4 NH3 diffuses into cells and into urine here it's combined with H+ that's pumped out since the cell is impermeable to NH4, the NH4 is stuck in the urine and can now be excreted

Question 60

k depletion and acid/base balance

Answer 60

K depletion creates metabolic alkalosis potassium ions leave cells in exchange for H+ therefore K exit leads to intracellular acidification a low intracellular pH stimulates H+ secretino throughout the nephron and also increases NH4 production by the PT K+ and NH4+ compete with each other on several transporters and therefore hypokalemia also facilitates NH4 excretion

Question 61

Na balance and acid/base balance

Answer 61

in PT and LH, Na reabsorption and H+ secretion are directly coupled (via Na/H exchange) in the CD Na reabsorption and H+ secretion are linked indirectly because of the coupling of Na reabsorption to H+ secretion, ECFV depletion promotes the development of metabolic alkalosis

Question 62

aldosterone on A/B balance

Answer 62

in CD, get increase in Na transport in CD - increases lumen negative voltage - increases H ion secretion by alpha-ICC cells also directly activates ICC cell pumps some K secretion increase too from CD cells, so get more K to fuel ICC cell H/K exchanger

Question 63

urinary anion gap

Answer 63

Na + K concentrations - cl concentration looking for cation = ammonium becomes negative if the gut is the problem