Lecture 6: Nephron function 2

Question 1

What are the two types of cells in the LATE distal convoluted tubule, connecting tubule and collecting duct?

Answer 1

• Principal cells and intercalated cells

Question 2

Whats happening in the LATE distal convoluted tubule, connecting tubule and collecting duct?

Answer 2

• Principal cells are reabsorbing Na (ENAC) and secrete K (ROMK)

Question 3

How are Na and K linked in the LATE distal convoluted tubule, connecting tubule and collecting duct?

Answer 3

• Reabsorption of Na makes the lumen more electronegative which drives K secretion (ROMK)

Question 4

Whats a complication that can occur during treatment with diuretics in the DCT, CT and CD?

Answer 4

Thiazide diuretics block Na/Cl transporter, thus delivering more Na to the LATE DCT and K loss (hypokalemia) can occur here.

This can lead to ventricular arrhythmias

Question 5

What targets ENAC?

Answer 5

K sparring diuretics such as Amiloride

Question 6

Whats the relationship of Aldosterone and principal cells?

Answer 6

Aldosterone stimulates Na reabsoprtion and K secretion via gene expresion changes:
- Upregulates activators that open ENAC and induces more ENAC + Na/K ATPase expression

Question 7

What are the intercalated cells of the LATE DCT, CT, CD?

Answer 7

• Imp. for acid base balance and K absoprtion
• Usually secrete H (H ATPase and H/K ATPase)
• Some H+ used to reabsorb HCO3
• Some H+ can be freely secreted generating new HCO3

Question 8

What is the impact of aldosterone on LATE DCT, CT, CD?

Answer 8

• Directly: stimulates the activity of H ATPase

- Indirectly: Electronegative lumen caused by increased Na uptake via ENaC drives H secretion

Question 9

Describe what causes the changes in pH throughout the nephron:

Answer 9

• PT: H+ used to reabsorb HCO3

- Late DCT+CD: Some H+ secreted w/o HCO3 reabsorbed

Question 10

What role does the kidney play in acid:base balance of the kidney:

Answer 10

• H+ can be secreted into urine
• CO2 and thus HCO3 can be released into filtrate
• HCO3 can be reclaimed by kidney
• Kidney can make HCO3 thats reabsorbed

Question 11

Describe diffusion trapping of ammonium in the collecting duct:

Answer 11

• Excess H+ (after all HCO3 reabsorbed) combines with NH3 to form NH4. (this cant diffuse and thus trapped in filtrate)

This happens because at pH4.5 this is the max H+ conc attainable so much sequester it another way

Question 12

What happens to water in the Late DCT, CT and cortical CD?

Answer 12

• ADH determines aquaporin channel expression in apical membrane and thus water reabsorption

Very rapid transient function of ADH to remove water from filtrate

Question 13

What happens to water in the outer medulla collecting duct?

Answer 13

THE SAME

ADH determines aquaporin channel expression in apical membrane and thus water reabsorption

Very rapid transient function of ADH to remove water from filtrate

High ADH = high reasborption and concentrated urine

Question 14

What is the simplified model of passive hypothesis when it comes to loop of henle?

Answer 14

Applies to the long loop

1) Urea becomes very high in cortical CD when ADH present due to water reasorption
2) ADH increases urea and water premability of inner medulla collecting duct (premeable too in absence of CD)
3) Urea deposited in intersitium (H2O) causes NaCl conc. to drop
4) NaCl moves out of tip and ascending limb. down its conc. gradient.

Countercurrent exchange by vasa recta helps preserve osmotic gradient and carries water away

Question 15

What happens to the passive loop hypothesis when ADH is low?

Answer 15

• Water is not reabsorbed in distal nephron and cortical collecting duct so urea does not increase
• BUT the inner medullar CD is permeable to urea when ADH is low
• [urea] ISF > [urea] CD -> urea diffusing into CD and wash out
• Thus if ADH is low then urea of the inner medulla will be low
• ADH high will deposit urea again

Question 16

Describe the loop of henle conc. gradient with the two mechanisms:

Answer 16

Outer medulla: NaCl gradient formed by countercurrent multiplication mechanism

Inner medulla: NaCl and Urea gradient formed by passive mechansim. Dependant on high ADH levels.

Question 17

Summarise what happens in the PT:

Answer 17

Proximal tubule reabsorbs 2/3 of filtered water, Na+ and Cl-,90% of HCO3-, and 100% of glucose. Na+ coupled transport dominates. Filtrate remains at 300 mOsm (as water follows the Na+). pH drops only slightly as most H+’s are used to reabsorb HCO3-. Some new HCO3- made from glutamine.

Question 18

Summarise what happens in the loop of henle:

Answer 18

Loop of Henle. Thick ascending limb pumps out NaCl but water cannot follow. Countercurrent multiplier established by short loops in outer medulla (300-600 mOsm gradient). In long loops, when ADH is high: NaCl moves from tip and ascending thin limb into inner medulla by osmosis, urea is deposited in inner medulla by collecting duct. Inner medulla gradient established (600-1200 mOsm) and draws water from descending thin limb and collecting duct to concentrate the urine.

Question 19

Summarise what happens in the early DCT:

Answer 19

Early distal convoluted tubule: impermeable to water. More NaCl absorbed (blocked by thiazide diuretics). Urea becomes concentrated.

Question 20

Summarise what happens in the LATE DCT, CT and CD:

Answer 20

Late distal convoluted tubule, connecting tubule and cortical collecting duct: what happens depends on ADH. Absence of ADH: No aquaporins inserted, tubule is impermeable to water. NaCl continues to be reabsorbed by ENaC (target of K+ sparing diuretics). Urine stays dilute. Presence of ADH: tubule becomes water permeable. Urine concentrated (300 mOsm). Intercalated cells secrete H+ (some used to reabsorb HCO3- some freely excreted (pH balance).

Question 21

Summarise what happens in the medullary CD

Answer 21

Medullary collecting duct: what happens depends on ADH. Absence of ADH: No aquaporins inserted, tubule is impermeable to water. NaCl continues to be reabsorbed. Urine stays dilute. Presence of ADH: tubule becomes water permeable and more urea permeable. Urea deposited into medullary interstitium. NaCl moves from long thin loops to interstitium. Urine becomes concentrated (max 1200 mOsm). Intercalated cells secrete H+ (some used to reabsorb HCO3- some freely excreted (pH balance). pH can drop to 4.5. Additional H+ excreted by NH4+ ‘diffusion trapping’.

Question 22

Describe what happens in chronic kidney disease:

Answer 22

Diabetic nephropathy or hypertension can lead to:

1. Damage to glomerulus = proteinuria
2. Damage to tubulues = Chronic inflam, excessive fibrosis, Hypoxia
3. Progressive nephron loss
4. Renal failure