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S2B5 Physiology > Renal Regulation H+ and Urea > Flashcards

Renal Regulation H+ and Urea Flashcards

1
Q

What is the fractional excretion of urea?

What characteristics determine urea’s movement in the nephron?

A
  • 20%
  • Urea is freely filtered
  • Although small, it is highly polar & does not freely permeate lipid bylayers
    • medullary interstitial space contributes to osmotic gradient that allows us to concentrate urine
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2
Q

Describe what happens to urea in each of the following locations:

Proximal tubule

Loop of Henle

Medullary collecting ducts

How does ADH affect this?

A
  • Proximal tubule
    • urea is reabsorbed- dependent on the development of a favorable concentration gradient through paracellular paths
  • Loop of Henle
    • urea is secreted passively down its concentrtion gradient
  • Medullary collecting ducts
    • urea is reabsorbed by urea transporters (UT)
  • ADH
    • increases the permeability of MCD to water and urea
    • stimulates urea transporter activity in MCD
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3
Q

What is azotemia?

What situations cause this?

A
  • Azotemia
    • increased nitrogen in the blood (BUN)
  • Can occur with
    • decreased GFR (urea production > urea excretion)
    • elevated urea production (high protein diet, steroid therapy)
    • excessive urea reabsorption in proximal tubule (hypovolemia)
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4
Q

What is uremia?

A

uremia- used to describe pathologic increases in urea

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5
Q

What clinical presentaitons would indicate a renal cause of decrease in GFR?

A
  • Renal failure
    • decrease in Cr urea excretion
    • increase plasma creatinine
    • increase BUN
    • BUN / PCr (10-1 - 20/1)
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6
Q

What is the renal physiologic response to a hypovolemic state?

A
  • Hypovolemic
    • sympathetic stimulation and angiotensin II
      • decreases GFR and decreases Cr excretion
      • increase PCr and increase BUN
      • increases reabsorption Na+, solutes, and water in the proximal tubule
        • further enhances urea reabsorption secondary to the development of a favorable concentration gradient (increase BUN)
    • THUS – increases BUN/PCr ration >20/1
      • referred to as prerenal azotemia
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7
Q

How can you differentiate between Renal Failure & Prerenal Azotemia?

A

decrease GFR

  • Renal Failure
    • both BUN and PCr increase
    • BUN / PCr remains normal (10/1 - 20/1)
  • Prerenal Azotemia
    • both BUN & PCr increase
    • BUT, the BUN / PCR increase to >20/1
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8
Q

What types of acid are generated by daily metabolism?

How does the body maintain acid-base balance?

A
  • Volatile (CO2) and non-volatile (50-150 mEq / day)
    • The lungs “blow-off” CO2 getting rid of the volatile acid
    • To maintain acid-base balance, the kidneys
      • must excrete an amout of H+ equat to the daily production of nonvolatile (fixed) acids
      • must prevent the loss of HCO3- in the urine, while replacing HCO3- that is lost in the buffering process
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9
Q

How is H+ secreted?

What enzye is responsible for producing a source of H+? What is this equation?

What other components are required for successful H+ secretion?

A
  • An active process that moves H+ across the luminal membran into the tubule
    • Carbonic anhydrase
  • Requires:
    • a H+ transporter (Na+ / H+ exchanger)
    • proton acceptors in the tubular fluid
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10
Q

Describe what H+ does int eh proximal tubule.

A
  • Na+- H+ exchanger
    • Na+ is coming down its concentration gradient in exchange for protons
  • Na+- HCO3
    • bicarbonate generated by carbonic anhydrase is being reabsorbed
  • Carbonic anhydrase
    • in cell
    • in lumen brush border
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11
Q

Describe what H+ does in the intercalated cells

A
  • H+- ATPase
    • proton pump (into lumen)
  • H+- K+ ATPase
    • Hydrogens to lumen & potassium in
  • HCO3- reabsorption
  • Carbonic anhydrase
    • for every proton that gets pumped out, a bicarbonate is reabsorbed
  • lumen (-) potential
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12
Q

What is the major source of H+?

A
  • derived from the dissociation of H2CO3
    • requires the enzyme carbonic anhydrase (CA)
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13
Q

What is the general shape of this graph?

What is normal PaCO2?

A
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14
Q

What is the minimum pH?

What can happen if it decreases below this minimum?

How do we continue to secrete H+ without reaching this minimum?

A
  • Minimum: pH 4.5 (32 microM [H+])
    • if [H+] is greater than this, H+ can leak out of the tubule & inhibit the proton pump
  • Continued secretion of H+ requires proton pump acceptors in the tubular fluid
    • actuall excrete ~100,000 microM H+/day
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15
Q

What are the three primary tubular H+ acceptors?

A
  • Bicarbonate (HCO3- –> CO2 + H2O)
    • reabsorb CO2 & water and go back into the cycle
  • Phosphate (HPO42-–> H2PO4-)
    • because the phosphate, even when protonated, is charged, it gets diffusion trapped
  • Ammonia (NH3–> NH4+)
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16
Q

What percent of bicarbonate is reabsorbed in the proximal tubule?

How does this happen?

A
  • 90% filtered load of HCO3-
    • H++ HCO3- = H2CO3= H2O + CO2 (volatile)
    • reabsorption is coupled to Na+ reabsorption via H+ secretion
  • Na+ enters the cell down its concentration gradient
    • one H+ is secreted
    • one HCO3- “disappears” from the tubular filtrate
    • one HCO3- is produced int he cell and reabsorbed
  • Excrete basicaly no bicarbonate, & have relatively acidic urine
17
Q

Why is the “tubular transport maximum” of bicarbonate not a true one?

What is it actually a measure of?

A
  • Not a true “transport maximum” b/c there is not carrier
  • really a measure of hte capacity to secrete H+
  • Normal plasma HCO3- is just slightly below the “renal threshold”
18
Q

How much acid is produced in the body a day?

How do we excrete this much acid?

A

50-100 mEq acid / day

becasue this acid load is in excess of the H+ so it must be excreted as titratalbe acid adn ammonium (NH4+) & plasma bicarbonate levels must be restored

19
Q

What is the principle titratable acid?

How does this lead to excretion of H+?

A
  • Phosphate (HPO42-) is the principle titratable acid
  • For each H+ that is secreted
    • H+ titrates HPO42- to H2PO4- and is diffusion trapped and excreted
    • one “new bicarbonate” is reabsorbed
20
Q

What is the pKa of phosphate?

How does this impact its ability to act as a titratable acid?

A
  • pKa is 6.8 - limited buffering capacity
    • phosphate is largely used up before bare minimum urin pH (~4.5) can be achieved … so,
    • other bases with lower pKa can accept protons
21
Q

If the pKas of other bases are more suited to being buffers around pH 4.5, why are they not the prinicple titratable acids?

A
  • they are only present in small amounts or not at al
  • some have pKa values that are unfavorable for protonation within the normal range of urinary pH
22
Q

What is the second most abundant buffer in the urine (after HCO3)?

A

NH3

23
Q

How is NH3 synthesized?

Its synthesis is upregulated under what conditions?

How is it secreted?

A
  • NH3 is synthesized in tubular cells from glutamine
    • glutamine –> (glutaminase) –> NH3 + glutamate
    • glutamate —> (glutamate dehydrogenas) –> NH3 + alpha-ketoglutarate2-
  • NH3 production is up-regulated in acidosis
  • Secreted as NH3 (or NH4+) by all segments of the nephron
    • NH3 islipid soluble adn is secreted by passive diffusion
    • Because NH4+ is charged, it is “diffusion trapped” and excreted
24
Q

Describe the excretion of NH4+

A
  • pKa for NH3 + H+ –> NH4+
  • for each H+ that is secreted:
    • one NH4+ is diffusion trapped and excreted
    • one “new bicarbonate” is formed and reabsorbed
25
Q

How can you determine the the amount of new HCO3- produced?

This is equal to what other value?

A
  • The amount of H+ secreted beyond that needed ot reabsorb all the HCO3- is equal to the…
    • the sum of the titratable acid and NH4+ in the urine
  • For each titratable acid and NH4+ formed, one “new HCO3-” is formed and reabsorbed to restore the HCO3- levels in the plasma and body fluids
    • New HCO3- production = Titratable acid + NH4+
  • The amount of H+ secreted beyone that needed to reabsorb all the HCO3- is equal to the new HCO3-
26
Q

How can you calculate the total H+ secreted?

A

the amount of H+ that was secreted to reabsorb the entire filtered load of HCO3- and to form the amount of titratable acid & NH4+ in the urine

27
Q

What are they typical values for the indicated substances?

A
28
Q

What factors influence the rate and extent of H+ secretion?

A
  • the availability of urinary bases (H+ acceptors)
  • Changes in arterial PCO2
  • Aldosterone excess or deficit
  • Hyperkalemia (K+- H+ exchange)
    • and secondarily aldosterone
  • Increased delivery of Na+ to the distal nephron
    • eg. overuse of loop or thiazide diuretics; increases H+ secretion

S2B5 Physiology (10 decks)

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