Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

GI and Renal Exam 1 > 5 - Acid Base Regulation by the Kidney I > Flashcards

5 - Acid Base Regulation by the Kidney I Flashcards

1
Q

What is a buffer?

A

A buffer is a solution of a weak acid and its conjugate base - resists changes in pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the major buffer system in the blood?

A

The bicarbonate buffer system is the major buffer system operating in the blood

Hemoglobin also plays important role here

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What equation allows you to calculate the degree of dissociation of a weak acid in a given pH?

A

The Henderson-Hasselbalch equation allows one to calculate the degree of dissociation of a weak acid at a given pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the H-H equation?

A

pH = pKa + log ([A-]/[HA])

where HA is the weak acid and A- is the conjugate base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the H-H equation for the bicarbonate buffer system specifically?

A

pH = 6.1 + log ([HCO3-]/(0.03)xPCO2)

KNOW THIS ***

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why is acid base balance needed in the first place?

A

Typical American diet generates 50 - 100 mmol of H+ per day ***

  • Oxidation of nutrients generates CO2
  • Oxidation of methionine/cysteine
  • Some phosphate-containing compounds
  • Metabolism of glutamate/aspartate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the formation of carbonic acid increasing pH

A
  • Oxidation of nutrients generates CO2
  • This forms carbonic acid
  • This is volatile and needs to be removed as CO2 by lungs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the formation of sulfuric acid increasing pH

A
  • Oxidation of methionine/cysteine and other sulfur-containing compounds form sulfuric acid
  • This is non-volatile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the formation of phosphoric acid increasing pH

A
  • Some phosphate-containing compounds form phosphoric acid

- This is non-volatile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe what glutamate and aspartate do to pH

A

Metabolism of glutamate/aspartate and use of certain organic anions generates base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the state of respiratory acidosis

A
  • hypoventilation (not blowing off enough CO2)
  • increased PCO2
  • point on normal buffer slope below pH 7.4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the state of respiratory alkalosis

A
  • hyperventilation (blowing off too much CO2)
  • decreased PCO2
  • point on normal buffer slope above pH 7.4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the state of metabolic (kidney) acidosis

A
  • loss of HCO3- (too much base lost in the urine)

- point on 40 torr isobar below pH 7.4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the state of metabolic alkalosis

A
  • increase in HCO3- concentration (not losing enough base in the urien)
  • point on 40 torr isobar above pH 7.4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is compensation in terms of acid base balance?

A

Changes in one buffer component lead to compensatory changes in the other component

  • ratio of HCO3- to PCO2 remains close to normal
  • pH remains close to normal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe respiratory compensation

A
  • hypo or hyperventilation regulates PCO2

- rapid (hours)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe renal compensation

A
  • regulation of HCO3- concentration
  • regulation of H+ excretion
    slow (days)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do the kidneys carry out this pH regulation function?

A
  • Kidneys regulate H+ excretion and HCO3- reabsorption

- Kidney must dispose of 50 - 100 mmol of H+ per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does H+ leave in the urine?

A

Cannot leave as free H+ (urine pH typically 5.5 to 6.5)

H+ ions removed by

  • binding to filtered buffers (H2PO4-)
  • binding to NH3 (NH4+)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the elimination of HCO3- in the urine

A

* Elimination of HCO3- in urine is equivalent to adding H+ to the body*

Cannot eliminate the H+ load unless virtually all filtered HCO3- is reabsorbed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the secretion of H+ by renal tubule cells into the tubular lumen in the proximal region

A

This process is called proximal acidification

  • The sodium-potassium ATPase, present in the basolateral membrane of proximal tubule cells, generates a transmembrane sodium electrochemical gradient.
  • The energy of this sodium gradient is used to drive efflux of protons into the tubular lumen via an H+/Na+ exchanger.
  • An H+-transporting ATPase is also present, which contributes to H+ secretion but the major player is the H+/Na+ exchanger.
22
Q

Describe the secretion of H+ by renal tubule cells into the tubular lumen in the distal region

A

This is called distal acidification

  • An H+-transporting ATPase is found in the plasma membrane of the intercalated cells of the collecting duct.
  • This transporter is responsible for active secretion of H+ into the tubular lumen.
  • * In response to low pH, cytoplasmic vesicles that contain the H+-transporting ATPase fuse with the luminal membrane (they insert into the wall), increasing the cell’s ability to secrete H+*
  • ** Conversely, an alkali load (high pH) stimulates recycling of these transporters from the luminal membrane back to cytoplasmic vesicles **
23
Q

So, what happens in distal acidification in response to LOW pH?

A

Insertion of ATPase into luminal membrane stimulated by low pH

24
Q

And, what happens in distal acidification in response to HIGH pH?

A

High pH stimulates recycling of ATPase back to the cytoplasm

25
Q

Describe the resorption of bicarbonate in a normal, healthy individual

A
  • filters ~ 4300 mmol HCO3- per day (~ 260 g or 0.57 lb)
  • virtually ALL bicarb is reabsorbed
  • 90% reabsorbed in proximal tubule
  • 10% reabsorbed in collecting duct system
26
Q

How is the bicarb reabsorbed?

A

Reabsorption is not by simple transport of HCO3- back from the tubular lumen into the filtrate

It is more complicated…

27
Q

Describe how bicarbonate is reabsorbed in the proximal tubule

A
  • H+ secreted into tubule lumen
  • Reacts with HCO3- in filtrate, forming carbonic acid
  • Carbonic anhydrase converts carbonic acid to H2O and CO2
  • H2O and CO2 diffuse into renal tubular cell
  • Carbonic anhydrase converts H2O and CO2 to carbonic acid
  • Carbonic acid dissociates, H+ exported to tubule lumen and HCO3- exported to blood
28
Q

What is the net effect of bicarbonate reabsorption in the proximal tubule?

A

Net effect: movement of NaHCO3 FROM the filtrate TO the blood

29
Q

Describe the reabsorption of bicarbonate in the collecting duct

A

Slightly different system operates in the collecting duct

Very similar to the proximal tubule, but in the collecting duct, a chloride/bicarbonate antiport system appears to operate (rather than the sodium/bicarbonate co-transporter seen in the proximal tubule)

30
Q

So what are the types of transporters in the proximal tubule and collecting duct for bicarbonate reabsorption?

A

Proximal tubule = sodium/bicarbonate co-transporter

Collecting duct = chloride/bicarbonate antiport system

31
Q

Describe the process of active bicarbonate secretion into the filtrate

A

This is a bit of a side note, FYI

Kidney actively secretes bicarbonate when needed

  • B-type intercalated cells of collecting tubule
  • polarity of membrane transporters can be reversed
  • becomes important during metabolic alkalosis
32
Q

What is the “limiting urine pH”?

A

In the proximal tubule…
- [H+] increased 4-fold from 4 x 10-8 mol/L to 1.6 x 10-7 mol/L

In the collecting duct…

  • H+ translocating ATPase stimulated by acid load
  • This increases [H+] further to 4 x 10-5 mol/L maximum value
  • This corresponds to limiting urine pH of 4.4 ***
  • H+ translocating ATPase now inhibited ***

NOTE: the limiting urine pH is therefore a [H+] of 0.04 mmol/L

Daily acid load from normal diet is 50 - 100 mmol, which would require 1250 - 2500 liters of urine/day and obviously this does NOT happen

33
Q

What is the value of “limiting urine pH” again?

A

Limiting urine pH of 4.4 or [H+] of 0.04 mmol/L

34
Q

How does the body accommodate for this?

A

Excretion of H+ as H2PO4-

35
Q

Describe the process of excretion of H+ as H2PO4-

A
  • Secreted H+ is buffered in filtrate and the buffer is excreted
  • Phosphate typically major non-bicarbonate urinary buffer
  • H+ secretion increases [H+] in tubular lumen
  • Shifts equilibrium leftward
  • This drives formation of H2PO4-, eliminated in urine
36
Q

What limits the body’s ability to excrete H+ as H2PO4-?

A

Ability to excrete H+ as H2PO4- limited by…

  • amount of HPO42- in filtrate
  • requirement of body to retain phosphate
  • ~75% filtered phosphate reabsorbed even during acidosis
37
Q

What is the KEY POINT for the concept of excretion of H+ as H2PO4-?

A

For each newly-formed H2PO4- excreted in urine…

  • One H+ eliminated, and
  • One new HCO3- formed and added to the blood***

This contributes to the pH of the blood **

38
Q

What is titratable acid?

A
  • Measure of H+ excreted in urine as undissociated weak acid (generally H2PO4- most abundant)
39
Q

How do you determine the titratable acid value?

A
  • 24 hr urine collection

- Measure amount of NaOH required to back-titrate urine pH to 7.4

40
Q

What is the normal value for titratable acid?

A

Normal value: ~20 mmol/day

41
Q

What is the value for titratable acid in the state of acidosis?

A

Acidosis: ~40 mmol/day

42
Q

What other weak acids may be quantitatively important in this calculation?

A

Remember, the main one was H2PO4-

Others include:

  • β-hydroxybutyric acid (during ketoacidosis)
  • lactic acid (during lactic acidosis)

Note efficiency is a function of the pKa of the weak acid, concentration of the weak acid, and urine pH
- Example: pKa of β-hydroxybutyric acid is ~4.7 but acetoacetic acid is ~ 3.6

43
Q

Describe the excretion of H+ as NH4+

A

First step is generation of NH4+ within renal tubule cells

  • kidney expresses glutaminase
  • converts glutamine to glutamate
  • glutamate then converted to α-ketoglutarate by glutamate dehydrogenase
  • glutamate metabolism ultimately yields 2 HCO3-
44
Q

What is the net effect of H+ as NH4+?

A

Net effect is excretion of protons into the lumen and addition of NEW molecules of HCO3- to the blood

45
Q

What signals H+ secretion as NH4+ in the urine?

A
  • NH4+ excretion increases rapidly in response to increased urine acidity
  • NH4+ reaches maximum in a few days
46
Q

How does the body compensate to allow this increase capacity to excrete H+ as NH4+

A

The body compensates fro this increased need for NH4+ excretion by increasing glutamine uptake by kidney/increased glutaminase activity

In severe acidosis, NH4+ production contributes up to 250 mmol/day of new bicarbonate to the blood

47
Q

What does the rate of H+ secretion depend on?

A
  • Rate of H+ secretion is pH dependent

- Reduced pH activates Na+/H+ antiporter and H+-ATPase

48
Q

Describe the secretion of H+ in a normal, healthy individual

A

Healthy individual eating standard Western diet secretes enough H+ to allow reabsorption of most bicarbonate

  • some titratable acid (mainly H2PO4- excreted)
  • some NH4+ secreted
49
Q

Describe the secretion of H+ in the state of acidosis

A
  • H+ secretion increased
  • all HCO3- reabsorbed
  • substantial titratable acid excreted
  • NH4+ production increased
    • –> increased glutamine uptake/glutaminase activity
    • –> increased NH4+ excretion in urine
50
Q

Describe the secretion of H+ in the state of alkalosis

A
  • H+ secretion insufficient to allow HCO3- reabsorption
  • HCO3- is secreted in urine
  • B-type intercalated cells of collecting duct actively secrete bicarbonate into tubular lumen
  • no titratable acid or ammonium ions excreted in urine

GI and Renal Exam 1 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions