Lecture 6: Sodium Homeostasis (and part of Lecture 7)

Question 1

what hormones regulate extracellular fluid voluem by altering Na excetion by the kidney?

Answer 1

angiotensin II (increase reabsorption)
arginine vasopressin (increase reabsorption)
aldosterone (increase reabsorption)
natriuretic factors (ANP, dopamine, endothelin, ouabain, and ouabain analogues) (increase renal excretion)

Question 2

describe the reabsorption of Na at different parts of the nephron.

Answer 2

65% proximal tubule
25-30% at loop of henle
3-5% at distal tubule
1-3% at collecting tubule

Question 3

How does the kidney alter the amount of Na exretion?

Answer 3

changin in the filtered load or

change in graction of filtered Na that is reabsorbed

Question 4

Describe filtration of Na at the glomerulus

Answer 4

freely filtered
starling forces determine GFR
glomerular capillary flow important determinant of GFR
higher oncotic pressure less filtration
more rapid flow, slower rise in oncotic pressure

Question 5

Describe reabsorption of Na at the proximal tubule

Answer 5

65% reabsorbed
Na crosses apical membrane via co-transporters (especially with HCO3- in early proximal tubule)
Na absorption is isoosmotic
Na-k-ATPase provides driving force for Na reabsorption
Some Na transport occurs with chloride via paracellular pathway in late proximal tubule

Question 6

what are the major Na transporters on the apical plasma membrane?

Answer 6

Na/H exchanger
Na/glucose co-transporter
Na/amino acid co-transporter
Na/PO4 co-transporter

Question 7

How does Na enter the interstitial space?

Answer 7

crosses basolateral membrane via Na/K ATPase and Na/HCO3- costransporter (uses electromotive force despite chemical gradient)

Question 8

Describe Cl reabsortption at the proximal tubue

Answer 8

facilitated by anion exchangers: Cl/HCO3- exchanger, Cl/formate, Cl/oxalate

Question 9

Describe the paracellular pathway of Na transport

Answer 9

in late proximal tubue, Cl- concentration in tubular lumen is greater than in interstitial space, Cl- moves across tight junctions creating a lumen positive potention that drives Na through the tigh junctions

Question 10

What happens to Na in the interestitial space?

Answer 10

enters peritubular capillaries (rate limiting of Na reabsorption)
leaks back across tight junctions into the tubular lumen

Question 11

How is Na reabsorption affected by oncotic and hydrostatic pressure of the peritubular capillary?

Answer 11

increasing oncotic pressure or decreasing hydrostatis pressure in peritubular capillary will increase Na reabsorption

Question 12

Describe reabsorption of Na in the loop of henle

Answer 12

25-35% reabsorption of filtered Na occurs here
50% of the reabsorbed Na travels thru the transccellular pathway and 50% through the paracellular patway
Na crosses apical via Na,K,2Cl co-transporter
loop diuretics block Na reabsorption in the segment by blocking Na.K,2Cl transporter
Paracellular transport of Ca2+ and Mg2+ occur here
no active transport across descending limb and thin ascending limb
some passive transport in the thin ascending limb
active transport across the thick ascending limb**
Crosses basolateral via the Na-K-ATPase and enters interstitial space

Question 13

Describe the paracellular pathway in the loop of henle

Answer 13

depends on developing positive charge in tubule as K is recycled across apical plasma membrane via ROMK
this drives Na, Mg2+ and Ca2+ uptake

Question 14

describe reabsorption in the distal nephron

Answer 14

4-8% of filtered Na reabsorbed
early distal convoluted tubule reabsorbs Na via the Na,Cl co-transporter (activated by aldosterone, inhibited by thiazide diuretics)
late distal convoluted tubule uses ENaC (activated by aldosterone and arginine vasopressin and inhibited by K sparing diuretics [amiloride, triamterene], trimethoprim, and spironolactone)
Na crosses basolateral membrane via Na-K-ATPase to enter interstitial space

Question 15

What is absorbed in the early distal convoluted tubule?

Answer 15

Na+, Ca++, Mg++
Ca++ and Mg++ reabsorbed transcellularly
when Na,Cl co transporter inhibited, reabsorption of filtered Ca++ and Mg++ is inreased due to enhanced proximal tubular reabsorption

Question 16

Describe conversion of angiotensinogen to angiotensin II

Answer 16

renin (excreted by JG cells) cleaves angiotensinogen to angiotensin I
ACE cleaves angiotensin I to angiotensin II

Question 17

what does angiotensin II do?

Answer 17

constricts efferent arteriole
reduces renal plasma flow and glomerular palsma flow
increases glomerular hydrostatic pressure
increase filtration fraction while maintaining GFR
increase peritubular oncotic pressure + decrease peritubular hydrostatic pressure –> increase Na and H2O reabsorption in proximal tubule
increases systemic BP (arterial vasoconstriction, increasing proximal tubular Na reabsorption, release aldosterone increasing distal tubular Na reabsorption)

Question 18

filtration fraction equation

Answer 18

FF = GFR/RPF

Question 19

What regulates renin release?

Answer 19

amount of solute delived to macula densa
stretch of the afferent arteriole
sympathetic nervous system
prostaglandins

Question 20

how does angiotensin II effect gfr?

Answer 20

selective efferent arteriolar constriction –> increases GFR by increasing hydrostatic pressure
however there is a decrease in renal plasma flow leading to rise in oncotic pressure –> reduce GFR
net result = little change in GFR

Question 21

Describe arginine vasopressin

Answer 21

it is secreted in response to osmotic stimuli or non-osmotic stimuli like volume deption or reduced effective arteriolar volume
activates Na,K,2Cl cotransporter in thick ascending limb –> increasing Na transport across cells
activats NCC and ENaC in distal nephron

Question 22

Describe aldosterone

Answer 22

secreted in response to angiotensin II and increased plasma K
increases Na reabsorption by activating Na-Cl cotransporter, ENaC and increasing basolateral NaKATPase in distal nephron
increases K and H secretion in distal nephron

Question 23

Secretion of aldosterone from adrenal cortex is a response to what?

Answer 23

ang II

increased plasma [K]

Question 24

how does aldosterone affect ENaC?

Answer 24

effects levels of ENac mRNA in kidney (alpha subunit expression increased)
regulates ENaC post-translational mechanisms

Question 25

Describe ANP

Answer 25

secreted by atrial myocytes in response to stretch
increases GFR and inhibits NA reabsorption in inner medullary collecting tubule due to inhibition of the Na/K-ATPase –> increasing urinary Na excretion

Question 26

Describe ouabain analogues

Answer 26

inhibits NaKATPAse –> increase renal Na excretion

secreted by hypothalamus

Question 27

Describe dopamines effect on Na excretion

Answer 27

increases urinary Na excretion due to inhibition of Na/H exchanger and Na/K ATPase in proximal tubule
inhibits Na reabsorption in more distal nephron sements

Question 28

Describe endothelin’s effect on Na excretion

Answer 28

increases urinary Na excretion by inhibiting ENaC

Question 29

Describe PGs effect on Na reabsorption

Answer 29

prostacyclin and PGE2 enhance renin secretion by JG apparatus
specific PGs affect glomerular hemodynamics by dilating the afferent and efferent arterioles
renal Pgs (PGE2) promote urinary Na excretion by inhibiting Na reabsorption in the thick ascending limb and cortical collecting duct

Question 30

Describe the effect of the activation of the sympathetic nervous system on Na reabsorption

Answer 30

enhances renin secretion leading to increase in Ang II and aldosterone
enhances Na reabsorption (proximal tubule)

Question 31

Describe Gitelman’s Syndrome

Answer 31

loss of function mutation from the Na,Cl co transporter in early distal tubule
resembles treatment with a thiazide diuretic
clinically presents with
low-normal ECF volume
low-normal BP
elevated renin and aldosterone
low K+
hypocaciuria

Question 32

Describe pseudohypoaldosteronism Type I

Answer 32

loss of function mutation of ENaC or mineralocorticoid receptors –> making collecting tubule unable to respond to aldosterone
AR disorder
characterised by:
volume depletion, hypotension
hyperkalemia despite elevated plasma aldosterone

Question 33

What are some common causes of volume overload?

Answer 33

advanced renal failure
heart failure
liver failure
nephrotic syndrome

Question 34

How does an increase in Na and H2O in the IT space manifest?

Answer 34

edema
lung –> dyspnea
extremities –> swelling
abdomen –> ascites

Question 35

how does an increase in Na and H2O in the IV space manifest?

Answer 35

hypertension

Question 36

what are two factors that drive the formation of edema?

Answer 36

renal retention of Na and water?

change in capillary starling forces (net movement of fluid out of capillary bed and into interstitial space)

Question 37

what are some characteristics of ESRD?

Answer 37

volume overload, retention of Na and H2O and increased hydrostatic pressure

Question 38

what disorders will you see an expansion of the extracellular fluid volume and underfilling of the arterial bed: “decreased effective arterial volume”

Answer 38

CHF, cirrhosis, some nephrotic syndromes

Question 39

describe volume overload in heart failure

Answer 39

decreased CO –> decreased pressure at baroreceptors and decreased flow to kidneys –> RAAS activation –> renal retention of Na and water