Renal 6

Question 1

how does the nephron respond to respiratory acidosis?

Answer 1

Respiratory relies on renal compensation to reestablish normal PH

Acidosis: acid coming from respiratory disturbance

- Hypoventilation
- Obstructive lung disease 

Fix this: retain bicarbonate (gets pH back to normal)

1. Increase bicarbonate reabsorption along tubule
2. Increase generation of new bicarbonate (titratable acids and ammonium)
- Adds more bicarb into system to buffer
- Excretes protons
3. In extreme cases: increase secretion of protos from the collecting duct (major regulation point) 

In alpha intercolated (IC cells-not principle cells) H+ATP ase is on apical membrane and secretes H+ into tubular lumen
AE1 is on basalateral membrane and reabsorbs bicarbonate.

Question 2

How does the nephron respond to respiratory alkalosis?

Answer 2

Alkolosis:
hyperventilationg, or high altitude
Reduced amount of co2 that we have
- Fix this: Need to eliminate bicarbonate

1. Reduce bicarbonate reabsorption
2. Reduce bicarbonate generation (both types) 
3. Secrete bicarbonate from collecting duct in extreme cases 

In beta IC cells (collecting duct) to reabsorp H+ on basolateral membrane
Pendrin is on apical membrane and secretes bicarbonate.

Question 3

What is the renal medullary osmotic gradient?

Answer 3

You have a gradient that goes from 300 - 1200 mOsm/kg/h20.

- Allows us produce hyperosmotic urine (osmololity within urine is greater than that of the plasma) 
- SECRETE A LOT OF SOLUTES (LIKE UREA NITROGENOUS WASTE) WITHOUT LOSING A LOT OF WATER

Countercurrent multiplier

- Establishes the gradient moving inward between sections 
- Between tubule and surrounding interstitium

Countercurrent exchanger

- Maintains the gradient 
- Involved vasa recta (vessels into medulla and come back up) and interstitum

Question 4

What is countercurrent multiplication?

Answer 4

Countercurrent multiplication

Coordination between multiple segments of the nephron.
- Starting at descending thin limb to collecting ducts is involved in this

Gradient establishment depends on
1. Different transport abilities for different molecules in different regions (water, sodium, urea is different in different regions

Transport and permeability allows for

1. Generation of meduallary osmotic gradient
2. Regulation of urine osmolality. 

Allows for regulation. Sensitivity allows us to alter permiabilitty of things ilke water and urea.
Generation happens in the entire region.

AVP* vasopressin
Thick Ascending limb: key player in generation of gradient
- Short limb nephrons not rlly a thin ascending limb.
- Handling urea in the deep section of the medulla increases and handles the gradient.

Question 5

How is the gradient established with countercurrent multiplication? IN short loop nephrons

Answer 5

Generation of gradient (medulllary osmotic gradient

write out this mechansim cause it is rlly helpful

Left: thin decending limb (allows water but not sodium movement)
Right: thick ascending limb (actively reabsorb sodium but not water)

1. Initially, osmolality is 300 everywhere 
2. NCKK actively transport sodium from tubule to surrounding interstitium (increase osmolality of interstitium and decrease it in the tubule cause sodium is leaving) 
3. Osmolaltiy stays lowers (200) on the right cause not h20 permeable. But left IS PERMEABLE TO WATER. 
4. Water moves into interstital space to equibilrate descending limb and interstitium both to around 400. 

Tubular fluid flow:

- New fluid enters desending thin limb with 300 osmolality , hyperosmottic fluid has move down into ascending limb, and the hypoosmotic fluid is up and out. 
- Then MORE active transport of sodium from thick ascending limb for reabsorption to interstitium. 
- 200 gradient is the largest that the NKCC pumps can establish. 
- Then more passive water movement (from descending to interstitium 
- Isoosmotic tubular fluid to interstitium at ANY level along descending part of the loop. 

As you keep going through steps, you have a gradeint from 300-1200 from top to bottom.

VERY COOL!

Question 6

How does countercureent multiplication work in long loop nehrons?

Answer 6

IN long loop nephrons (rather than short ones)
- They lack active transport of sodium. So how do they do it!?

Relies on urea handling.
Regions are not permeable to urea (only area in whole body)
- Thick ascendnig limb, distal tubule, cortical medullary collecting duct.

1. Cortical ollecting ducts allows for reabsorption of water and sodium. Does not allow urea to pass. Urea trapped, water leaves, concentration of urea increases. Increases as you move down tubule. 
2. Urea transports (some permeability) in MEDULLARY collecting duct. Urea leaves the tubule passivly and goes into interstitial space, which increases the concentration in interstitum. 
3. The end of loop of henle is super close, so water leaves from decsending portion of loop of henle, which is sodium impermeable and sodium is diluted in interstitium. 

4. Greater urea concentration and lower sodium concentration outside of the thin limb of descending tubule 
5. Movement of urea into ascendig thin limb
6. Sodium chloride out of asending thin limb
	Ascending thin limb (sodium permeability is greater than urea permeability) 
	More sodium will leave than urea will enter. This INCREASES OSMOLALITY in this region.

Question 7

Summarize countercurrent multiplication

Answer 7

• Generates medullary osmotic gradient
  
  • Driven by active na reabsorptin in TAL
  • Osmotic gradient needed for hyperosmotic urine
  • WE can get rid of solute (urea, nitrogenous waste) with minimal H20 loss