Lecture 4: Glomerular and tubular function 2

Question 1

What are the roles of the loop of henle?

What are the parts?

How does it work?

Answer 1

• Allows urine to be concentrated
• 50 –> 1200mOsm/kg water
• parts:
  
  • proximal straight tubule
  • thin descending limb
  • thin ascending limb
  • thick ascending limb
• Works by 2 propsed mechanisms:
  
  • Countercurrent mechanism
  • Passive hypothesis

Question 2

How do ions move through the descending loop of henle?

Answer 2

• Na+ extruded by means of the Na+/K+ ATPase
• mediated by the NKCC2 which brings in one sodiuma and potassium and 2 Cl
• ROMK recylces K+ and puts back in the lumen
• Tight junctions are water tight, so osmolality in interstitium is raised.
• (NOTE furosemide targets NKCC2, is a diuretic)
• this is the single effect

Question 3

How does countercurrent multiplication work?

Answer 3

• in TAL, salt extrusion into medulla causes an increases in ECF osmollaity and decrease in TAL osmolality
• In TDL, water will move out, raising the TDL osmolality.
• As fluid from the TDL moves through to the TAL, the higher osmalality fluid has its salt extruded. The further up the TAL the less salt extruded. This will cause more water to be absorbed from the TDL. This is Continuous.

Question 4

Role of the vasa recta?

Answer 4

• The vasa recta carry blood opposite to the direction of tubular flow. As blood flow descends, loses water due to gradient
• but as it ascends, water is reabsorbed as it is by TDL where water is extruded from the tubule
• note that slow blood flow offers optimal exchange, and increased flow causes wash out (takes away salt from the gradient), as in decreased concentrating ability.

Question 5

What occurs in the early distal convoluted tubule?

Answer 5

• Further dilution occurs here, driven by Na/K pump and Na+/Cl- symporter
• Water cant move accross due to water tight tight junctions
• Na/Cl transpoter blocked by thiazide diuretics (hypertension and heart failure meds) (lower ECF sodium, less water so lowers BP)

Question 6

What is Gittleman’s syndrome?

Answer 6

• Defect in Na/Cl symport resulting in Na+ and Cl- wasting, hyperaldosteronism, and resultant hypokalemic alkalosis.

Question 7

What are the cell types in the late DCT, collecting tubule and collecting duct?

Answer 7

• Principal cells
• Intercalated cells

Question 8

What do principal cells do?

How are they affected by thiazide diuretics?

Answer 8

• Allow Na+ to be rebsorbed via electrogenic sodium channel ENaC which is driven by Na/K pump
• This makes lumen electronegative and causes K+ to be secreted through ROMK channel
• Thiazide diuretics deliver more Na+ to late DCT meaning that more K+ is lost causing hypokalemia

Question 9

What is liddle’s syndrome?

Answer 9

• Mutation causes increased numbers of ENaC
• too much NaCl is reabrobed –> increased ECF volume –> hypertension

Question 10

What effect does aldosterone have on principle cells?

What blocks it?

Answer 10

• Stimulates Na+ reabsorption and K+ secretion by gene expression changes
• Upregulates ENaC
• spirolactone blocks aldosterone and is a weak K+ sparing diuretic

Question 11

What do intercalated cells do?

Answer 11

• Important for acid base balance and K+ absorption
• Usually secrete H+ via H+ ATPase and K+/H+ antiporter
• Some H+ used to reabsorb HCO3- (excess peed out)
• Acid removed drops pH of filtrate

Question 12

What is diffusion trapping?

Answer 12

• NH3 can freely diffuse into flitrate where it will bind to H+ –> NH4+
• NH4+ cant diffuse back across the cell thus excreting H+

Question 13

How does water absorption occur in the DCT and collecting ducts?

Answer 13

• depends on ADH levels which inserts apical aquaporin 2 receptors. reabsorbs water
• High ADH causes conc urine. rapid response far greater in medulla due to greater osmolality in ECF

Question 14

How is the osmotic gradient established in the inner medulla/ long loop nephrons (passive hypothesis)?

Answer 14

1. At high ADH, water is reabsorbed and urea conc is high in collecting duct
2. ADH increases urea and water permeability in the collecting duct of the inner medulla (CD is always permeable to urea)
3. urea deposited in interstitium. Water causes salt conc to lower
4. NaCl moves out of the tip of ascending limb into ECF
5. vasa recta helps preserve osmotic gradient.

Question 15

What is the Low ADH passive hypothesis?

Answer 15

• Low ADH means little water is reabsorbed so urea conc does not increase
• inner medullary collecting duct is permeable to urea still
• urea of ECF will exceed CD urea so urea will be lost, and wash out occurs
• hence as long as ADH is low inner medulla urea conc is low.

Question 16

I have an E question thanks joe:

do the 2 proposed hypothesis’s, the counter current and passive hypothesis, occur in short loop neprhons and loop nephrons respectively?

Can someone pls explain this lecture

Answer 16

• i think this lecture went through me head cause i was mindlessly doing it…