Renal: Physiology 2

Front 1

Describe the isotonic water transport at the proximal tubule.

Back 1

- high Lp
- only need small osmotic gradient: Na+ uptake leads to slight decrease in hypo-osmolarity of luminal fluid.
- fluid uptake by peritubular capillaries driven by Starling forces

Front 2

Where is glucose absorbed in the nephron?

Back 2

proximal tubule (100%)
- early part: apical SGLT2 (Na+/Glu) and basalateral GLUT transporter
- late part: apical SGLT1 and SGLT2 (Na+/Glu) and basalateral GLUT transporter.
- Tmax = 1.9mMol/min

Front 3

What is the Tm and threshold for plasma [glucose]?

What explains the splay?

Back 3

- Tm = 350 mg/dl
- threshold = 250 mg/dl
- difference is called splay which is explained by heterogeneity of nephrons and the relatively low affinity of the Na/Glu transporter.

Front 4

What type of diabetes is this?

- glucosuria
- normal plasma [glucose]
- diuresis
- thirst

Back 4

renal diabetes mellitus
- reduced Tmax, reduced threshold, increased splay

Front 5

Where is PAH absorbed/secreted?

Back 5

- PAH is secreted in the proximal tubule
- at low [PAH], secretion rate increases
- at high [PAH] above Tmax, scretion rate is constant

Front 6

PAH can be used to measure the size of which fluid compartment?

Back 6

RPF

Front 7

How to calculate the fraction of H2O reabsorbed using inulin method?

Back 7

1 - 1/(U/P)inulin

Front 8

What % filtered K+ remains in the tubular fluid given that U/P(K+) / U/P (inulin) is 0.3?

Back 8

30%

Front 9

Where are Na+ reabsorbed? by what transporters?

Back 9

1) 67% at proximal tubule
- Na+/glu cotransporter
- Na+/H+ exchanger
- Na+/HCO3- cotransporter
- Na+/AA cotransporter
- Na+/phosphate cotransporter
- Na+/lactate cotransporter
- Na+/Cl- cotransporter in late proximal tubule
2) 25% at thick ascending limb of loops of Henle:
- Na+/K+/2Cl- transporter
3) 8% at distal tubule and collecting duct
- early distal tubule: Na+/Cl- transporter
- late distal tuble and collecting duct: Na+/K+ channels which are stimulated by aldolsterone

Front 10

What is the action of ouabain?

Back 10

block Na+/K+ ATPase that set up the diffusion gradient

Front 11

What is the action of phlorizin?

Back 11

Block SGLT2 (Na+/Glu) in proximal tubule

Front 12

What is the action of acetazolamide?

Back 12

carbonic anhydrase inhibitor
- diuretics that act in proximal tubule by inhibiting reabsorption of HCO3-.

Front 13

What is the action of furosemide?

Back 13

Loop diuretics
- block Na+/K+/2Cl- cotransporter in the thick ascending limb of the Loop of Henle

Front 14

What stimulates Na+/K+/2Cl- cotransporter in the thick ascending limb of the Loop of Henle? what inhibits it?

Back 14

- ADH stimulates it
- Loop diuretics (furosemide) inhibits it

Front 15

What is the action of thiazide?

Back 15

diuretics
- block Na+/Cl- cotransporter at the cortical diluting segment (early distal tubule)

Front 16

What is the action of spironolactone and amiloride?

Back 16

K+ sparing diuretics
- inhibits Na+ transporter in the principle cells of the collecting duct
- inhibit K+ secretion in the principle cells of collecting duct

Front 17

What are some actions of aldolsterone on distal tubules and collecting duct?

Back 17

1) on principle cells:
- increases Na+ reabsorption
- increase K+ secretion
2) on intercalated cells
- increases H+ secretion

Front 18

List some drugs that act directly on Na+ reabsorption.

Back 18

- loop diuretics: block Na+/K+/2Cl- on thick ascending loops of Henle
- thiazide diuretics: block Na+/Cl[ on early distal tubule
- K+ sparing diuretics: block Na+ absorption and K+ secretion on principle cells

Front 19

ECF volume contraction ___ (increase/decrease) reabsorption in proximal tubules.

Back 19

increase
- volume contraction -> increase peritubular capillary osmolarity and decrease Pcap -> reabsorption

Front 20

ECF volume expansion ___ (increase/decrease) reabsorption in proximal tubules.

Back 20

decrease
- volume expansion -> decrease peritubular capillary osmolarity and increase Pcap -> less reabsorption

Front 21

Cell types on late distal and collecting duct and their specialzed transporters.

Back 21

1) principle cells:
- Na+ reabsorption
- K+ secretion
- H2O reabsorption in the presence of ADH
2) Type A intercalated cells
- apical: H+ pump, K+ reabsorption during K+ depletion
- basalateral HCO3-/Cl- exchanger
3) Type B intercalated cells
- apical HCO3-/Cl- exchanger
- basalateral H+ pump

Front 22

What is this disease?

- impaired reabsorption of di-basic AA such as lysine, arginine, ornithine, cystein

Back 22

cysinuria (AR)
- see cystein stones (calculi)

Front 23

What is this disease?

- defective AA transport resulting in Tryptophan deficiency

Back 23

Hartnup's disease (AR)

Front 24

Describe K+ reabsorption/secretion along the nephron and the specific transporters.

Back 24

1) proximal tubule: 67% reabsorption
2) thick ascending limb of the loop of Henle: 20%
- Na+/K+/2Cl- cotransport
3) distal tubule and collecting duct
- reabsorption by type A intercalated cell:
- secretion by principle cells: determined by concentration gradient

Front 25

Factors that increase K+ secretion by the principal cells.

Back 25

- high K+ diet: high intracellular [K+] -> high driving force
- aldolsterone: stimulate Na+, K+ channels on principal cells
- alkalosis: too little H+ in blood -> H+ leaves the cells and K+ enters the cell from basalateral membrane -> increased driving force
- thiazide and loop diuretics: increase flow rate in distal tubule -> dilution of luminal [K+] -> increased driving force
- luminal anions: negativity of the lumen drives K+ out

Front 26

Factors that decrease K+ secretion by the principal cells.

Back 26

- low K+ intake: low intracellular [K+] -> small driving force
- hypoaldolsterone: no stimulation of Na+, K+ channels on principal cells
- acidosis: excess H+ in blood -> H+ enters cell and K+ leaves through basalateral membrane -> low intracellular [K+] -> small driving force
- K+ sparing diuretics: decrease K+ secretion by blocking K+ channel on principal cells

Front 27

Specialized transporters on type B intercalated cells in the late distal tubule and collecting duct.

Back 27

- apical: Cl-/HCO3- exchanger
- basalateral: H+(out) and Cl(out) transporter.

Front 28

T/F: There is no active transport in thin loop of Loops of Henle.

Back 28

T.

Front 29

How does PTH affect phosphate transport in proximal tubule?

Back 29

PTH lowers Tmax for phosphate thus increases excretion and leads to low level of phosphate in the body.

Front 30

What can you do to treat barbituates poisoning?

Back 30

HCO3- infusion to make the tubular fluid more alkaine
- barbituric acid in charged form -> absorption of barbituric acid blocked

Front 31

How are weak organic acids secreted in the late proximal tubules?

Back 31

- basalateral side: transporter takes up the acid
- apical: anion transporter to secrete the acid (site where different drug may compete)

Front 32

How are weak organic bases secreted in the late proximal tubule?

Back 32

- basalateral: transporter taken up the base
- apical: organic cation/H+ exchanger

ex. creatinine, EPI, NE, atropine, amiloride

Front 33

Where is urea reabsorbed?

Back 33

- proximal tubule: passively
- inner medullary collecting duct: in the presence of ADH, contributes to corticopapillary osmotic gradient.

Front 34

Where is phosphate reabsorbed?

Back 34

- 85% in proximal tubule by Na+/PO4- cotransporter
- 15% excreted

* PTH decreases Tmax thus decreases reabsorption and increase excretion (phosphaturia and urinary cAMP)

Front 35

Mechanism of action of PTH on phosphate reabsorption.

Back 35

PTH decreases Tmax thus decreases reabsorption and increase excretion (phosphaturia and urinary cAMP)
- activate adenylate cyclase -> increase cAMP -> inhibit Na+/PO4- cotransport.

Front 36

Mechanism that contributes to corticopapillary osmotic gradient.

Back 36

- countercurrent multiplication in loops of Henle: Na+/K+/2Cl- cotransport(augmented by ADH) in thick ascending loop with no H2O permeability.
- increased urea concentration in inner medulla: ADH increase urea absorption in inner medullary collecting duct
- countercurrent system of vasa recta in medulla: minimize washout of osmolytes from medullary interstitium

Front 37

Where does ADH act on the nephron?

Back 37

- thick ascending limb: stimulate Na+/K+/2Cl- cotranport
- distal tubule and collecting duct: stimulate V2 receptor on basalateral membrane -> adenylate cyclase -> increase cAMP -> PKA -> insertion of aquaporins
- inner medullary collecting duct: increase urea absorption thus aid in corticopapillary osmotic gradient

* also stimulate V1 receptor in vasculature: vasoconstriction

Front 38

What stimulate ADH release from posterior pituitary gland? what inhibits it?

Back 38

Stimulate ADH:
- stimulation of osmoreceptors in the wall of 3rd ventricle

Inhibition of ADH:
- stimulation of volume receptors in atria
- caffeine
- alcohol

Front 39

Where is ADH released?

Back 39

posterior pituitary gland
- neucleus supraopticus
- nucleus paraventricularis

Front 40

What happens when there is 1% reduction in plasma osmolarity?

Back 40

complete ADH block

Front 41

What happens when there is 1-2% increase in plasma osmolarity?

Back 41

maximum antidiuresis

Front 42

What happens when plasma osmolarity is > 294 mOsM?

Back 42

exceeded thirst threshold, drink water

Front 43

Equation for osmotic clearance.

Back 43

Cosm = UFR x (U/P)osm

Front 44

Equation for free H2O clearance.

Back 44

C(H2O) = UFR - Cosm = UFR x (1 - (U/P)osm)

Front 45

Compare H2O clearance during diuresis and antidiuresis.

- % reabsorption
- urine osmolarity
- UFR
- Cosm
- C(H2O))

Back 45

Diuresis (absence of ADH)
- 1% reabsorption in distal tubule
- 4% reabsorption in collecting duct
- urine osmolarity: 50-60 mOsM
- UFR: 12mL/min
- Cosm: 2.4 mL/min
- C(H2O)): 9.6 mL/min

Antidiuresis (presence of ADH)
- 10% reabsorption in distal tubule
- 4.6% reabsorption in collecting duct
- urine osmolarity: 1200 mOsM
- UFR: 0.5mL/min
- Cosm: 12 mL/min
- C(H2O)): -1.5 mL/min

Front 46

When is C(H2O) zero?

Back 46

under treatment with loop diuretics
- no diluting effect
- no role in setting up corticopapillary gradient.