Glom and Tubular Function 2

Question 1

How are these things reabsorbed in the Proximal Convoluted tubule?

Answer 1

..

Question 2

What is the set role of the Loop of Henle and by how much can this vary?

Answer 2

To produce urine at a set concentration specific to the bodies needs (water reabsorbtion) . Ranges from
Conc: 50 to 1200mOsm/kg water

Volume: 0.5-20 L/day

Question 3

What are the two hypotheses on how the Loop of Henle works?

Answer 3

1. Countercurrent Multiplication
2. Passive Hypothesis

Question 4

Why do we always pee out some urine no matter what?

Answer 4

As this is our main mechanism for Nitrogenous waste removal

Question 5

How is the Medulla sub-divided?

Answer 5

Into the ‘outer’ and ‘inner’ regions that are dependent on the varied looping of the short and long loop nephrons.

Outer medulla: Nacl

Inner Medulla: NaCl + urea

Question 6

What does the salt gradient created by the inner and outer medulla affect?

Answer 6

Affects how water + solutes move in/out of the Loop of Henle!

Question 7

How does the Counter current “single effect” in the short loop nephrons work?

Answer 7

1. In the ascending limb Na+/K+/2Cl^- and Na+/K+ ATPase mediate Na+ ⇒ ECF
2. ROMK (K+ channel) recycles some K+ back into lumen
3. Tight junctions are water tight to stop water following Na+
4. ECF becomes HYPERTONIC (“single effect”)

• This happens many many times!!’*
• **the ascending limb is immpermeable to water!*

Question 8

What is Na+/K+/2Cl^- the target of?

Answer 8

The drug Furosemide

Question 9

Whats the “multiple effect” of the short nephron LOH?

Answer 9

Following the active reabsorbtion of Na+, Cl- etc in the ascending limb (which is impermeable to water), water can be passively drawn out/reabsorbed from the descending limb (impermeable to solutes).

Question 10

Once reabsorbed, where does the water reabsorbed from the descending limb go?

Answer 10

The arterial vasa recta.

This carries blood counter to the direction of tubular fluid flow, ensuring no ‘wash out’ of the gradient.

Water goes out and solute enters as blood descends, vice versa as it ascends

Question 11

Why is slow flow more favourable for the arterial vasa recta?

Answer 11

Allows for optimal exchange.

Increased flow (eg; large increases in arterial pressure) cause ‘wash-out’, where salt is taken away from the gradient. and the patient can’t concentrate the urine.

Question 12

What type of fluid enters the early DCT and what is its role?

Answer 12

Dilute fluid from the TAL (where salt was reabs.) enters. This fluid is further diluted via the Na+/Cl- symporters (and the DCT being impermeable to water) and osm → 50mOsm/L.

**Na+/Cl- symporters are blocked by _thiazide diuretics_ used to treat hypertension and HF

Question 13

The ‘Diluting segment’?

Answer 13

TAL + early DCT

Where salt (NOT water) is removed/reabsorbed from the lumen

Question 14

Role of ‘Principle Cells’, why are these important to know about?

Answer 14

In the late DCT, connecting tubule and CD.

Reabsorb Na+ via ENaC which drives secretion of K+ via ROMK (as lumen is left negatively charged)
“More Na+ → more K+ secretion”

Importance: if we take thiazide diuretics → more Na+ to DCT → more K+ secretion → hypokalemia → ventricular arrhythmias

Question 15

Whats Liddles syndrome? and what targets ENaC?

Answer 15

LS: mutation → increased ENaC → too much NaCl reabs. → increased ECF vol and hypertension

**ENaC is the target of potassium-sparing diuretics eg amiloride

Question 16

How does aldosterone affect principal cells?

Answer 16

Aldosterone stimulates Na+ reabs. and K+ secretion by up-regulating (via gene-expression changes) activators that

1. Open ENaC channels (early effect)
2. Induce more ENaC and Na/K ATPase (late effect)

within principal cells

Question 17

What blocks Aldosterone?

Answer 17

Spirolactone

Question 18

The role of Intercalated cells?

Answer 18

Found in the l_ate DCT_, connecting tubule and CD.

• For acid-base balance and K⁺ absorption
• Secrete H+ (via H⁺ ATPase and H⁺/K⁺ ATPase)

Some of this H+ is used to reabsorb HCO3^{<strong>-</strong>} and some is freely secreted to remove acid!!!

This is why the pH in the lumen drops here!

Question 19

Body fluid pH is determined by?

Answer 19

CO₂/HCO₃^- buffer system

Question 20

How do we deal/process the Acids in our body

Answer 20

H+ can be buffered by HCO3- → HCO3- eventually depleted

1. Reclaim/reabsorb HCO3- from kidney
2. Make more HCO3- via glutamine in PCT
3. Secrete H+ into urine and excrete (there’s a limit to this!)
4. Diffusion Trapping

Question 21

Diffusion Trapping

Answer 21

Excess H⁺ after all HCO₃^- has been used combines with NH₃ → NH₄⁺

Whereas ammonia (NH₃) can freely diffuse, NH₄⁺ is charged and therefore trapped and excreted (removing the H⁺)

Question 22

What happens to water in the late DCT, CT and cortical collecting duct?

Answer 22

• The level of water reabsorbtion depends on the level of ADH/Vasopression.
• ADH → Aquaporin-2 water channels inserted into apical membrane from vesicles in the cell → increased water reabsorbtion*
• In the absense of ADH, water remains in the tubule lumen.
• Response to ADH is rapid.

Question 23

Why can you move far more water in the outer medulla collecting duct in comparison to other ducts.

Answer 23

Still uses the same ADH/aquaporin mechanism but it can also utilise the outer medulla salt gradient

Question 24

Simply explain the Passive Hypothesis

Answer 24

..

Question 25

What happens in regards to the passive Hypothesis when ADH is low?

Answer 25