Role of the Kidneys in Acid/Base Balance Flashcards Preview

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Flashcards in Role of the Kidneys in Acid/Base Balance Deck (44):

What determines pH?

Concentration of H+

pH = -log [H+]


What is a normal range for pH?

7.35 to 7.45


True or False: Concentration of Hin blood at a normal pH is much lower than other things that are in the blood.


True. (despite the small concentration, they are very powerful)

at a pH of 7.40, [H+] is 40 nmol/L or 0.00004 mmol/L


True or False: There is less bicarbonate than protons in blood.


There is about a million times greater concentration of bicarbonate than protons in blood.

protons is about 40 nmol/L or 0.00004 mmol/L

bicarbonate is 24 mmol/L


Why is it important to keep H+ concentration controlled in a tight range?

Excess H+ will bind to important compounds (proteins) and affect protein charge, shape, and function


What is the difference between acidemia and acidosis? alkalemia and alkalosis?

Acidemia is an increase in concentration of H+ in the body and acidosis is the process in which there is an addition of H+ to the body (respiratory acidosis with increases in PCO2 and metabolic acidosis with decreases in HCO3-)

Alkalemia is a decrease in concentration of H+ in the body and alkalosis is the process in which there is a subtraction of H+ from the body (respiratory alkalosis with decreases in PCO2 and metabolic alkalosis with increases in HCO3-)


Typically, generation of organic acids is equal to utilization/elimination. What are 2 exceptions that we learned about having to do with incomplete oxidation of carbohydrates or fat?

1. With hypoxia, glucose is incompletely oxidized and causes acidosis.

2. With lack of insulin, triglycerides are incompletely oxidized and causes acidosis.


The kidney plays a role in acid/base balance primarily by handling _____ acids that come from _____ and _____.

Non-volatile, protiens, nucleic acids


True or False: The metabolism of proteins and nucleic acids generates "nonvolatile" acid that must be eliminated by the kidneys.



What non-volatile acid is typically formed from consuming protein? how about nucleic acid?

Proteins (sulfur containing amino acids) are metabolized into sulfuric acid (H2SO4).

Nucleic acids are metabolized into phosphaturic acid (H3PO4).


The average westerner consumes _____ mmol of nonvolatile acid daily.

60-70 mmol


Nonvolatile acid intake is mostly from _____ in diet



The acid forming amino acids and alkali forming amino acids in meat is typically balanced. So, what causes net acid intake when eating meat?

Sulfur containing amino acids are metabolized into sulfuric acid (H2SO4)


An average western diet consumes 60-70 mmol of nonvolatile acid daily. What would happen to serum H+ if the body didn't have acid/base balancing mechanisms?

Normal [H+] is about 0.0001 mol/L. Adding 70mmol to an avg ECF volume of 15 liters results in a concentration of 4.7 mmol/L, about 47,000 times normal [H+]. pH would be about 2.4


What is the primary way that the body handles nonvolatile acid intake to maintain a proper pH?

Buffering. Buffering binds to protons but do not eliminate them.

ECF proteins

  • albumin
  • immunoglobulins

Other buffers

  • amines
  • carboxylates
  • histidines
  • Bone


Buffering of acid helps the body to maintain proper pH when ingesting non-volatile acids. However, buffering doesn't eliminate the acids. What system helps to eliminate these acids through the lungs?

Bicarbonate buffering system (BBS)

H+ + HCO3- → H2CO3 → CO2 + H2O

CO2 is then removed by the lungs via expiration.


Does a high CO2 or low CO2 level drive the function of the bicarbonate buffering system for elimination of H+ from the body? How about high or low blood pH?

H+ + HCO3- → H2CO3 → CO2 + H2O

Low CO2. With a low CO2, the reaction is driven to the right which takes H+ from the body and eliminates through the lungs in the form of CO2.

Low pH. With a low pH, there is a high H+ which wil also drive the reaction to the right. Acidemia stimulates ventilation which lowers PCO2


At the tissue level, O2 consumption results in an addition of CO2 to the capillaries. However, there are 2 conditions that will result in an accumulation of CO2 in the tissues instead of being eliminated. What are these conditions? Why is this bad?

1. Rise in metabolic rate without a proportional increase in blood flow

2. Decrease in blood flow without a change/decrease in metabolic rate


Either one of these conditions imparis the function of the Bicarbonate Buffering System because CO2 builds up and drives the reaction to the left causing less H+ to be removed by the system. Excess H+ then binds to proteins and disrupts function.

H+ + HCO3- ← H2CO3 ← CO2 + H2O


What are the 3 tasks of the kidney for acid/base balance?

  • Eliminate acid anions
    • HSO4- and H2PO4- are filtered by the glomerulus and excreted
  • Reabsorb all of the filtered bicarbonate
    • Freely filtered by the glomerulus and avidly reabsorbed in the proximal tubule (85-90% of it)
  • Synthesize/generate new bicarbonate
    • Since HCO3- is continuously consumed via H+ buffering (60-70mmol/day), the kidneys must synthesize/generate 60-70mmol of HCO3- daily to maintain HCO3- balance.
    • This occurs primarily at the distal tubule by the intercalated cells in the collecting duct.
    • There is only about 360mmol of total HCO3- in the ECF so that's a 5-6 dady supply of bicarbonate if there was no synthesis or generation of HCO3-


Explain the bicarbonate reabsorption mechanism in the proximal tubules.

Bicarbonate and Na are traveling in the tubule.

Na+ is taken into the proximal tubule cell in exchange for a H+. This is done through an Na+/Hexchanger on the apical membrane of the proximal tubule cell.

The H+ reacts with HCO3- to form H2CO3. The H2CO3 is turned into water and carbon dioxide by the carbonic anhydrase enzyme.

The carbon dioxide and water are absorbed into the proximal tubule where they are turned back into H2CO3 by carbonic anhydrase which splits back into H+ and HCO3-. The H+ is used for the exchanger mentioned above to bring in more Na+ and the HCO3- is taken across the basolateral membrane with Na+ by a cotransporter.

If you follow the H+s, you can see that they leave the cell and come back in a cycle. However, the bicarbonates are being taken in from lumen and put into the blood (bicarbonate reabsorption).


True or False: There is a net loss of ECF HCO3- due to the proximal tubule bicarbonate reabsorption.

FALSE. There is no net gain or loss of ECF H+ or HCO3-. There is no change in acid-base balance.


What is proximal renal tubular acidosis? How does this happen?

Proximal renal tubular acidosis (RTA) happens if the proximal tubule bicarbonate reabsorption system is impaired. If bicarbonate is not reabsorbed, it is eliminated. This causes acidosis.


How does renal bicarbonate synthesis/generation work?

Carbon dioxide from the peritubular capillaries enter the intercalated cells where they join with water to create H2CO3 (via carbonic anhydrase). H2CO3 then dissociates into H+ and HCO3-. The His secreted into the lumen of the collecting duct by ATPase and the HCO3- is exchanged for Cl- across the basolateral membrane by a bicarbonate/chloride exchanger.

This results in H+ being secreted and HCO3- being reabsorbed.

Note that this mechanism only happens if there isn't HCO3- in the tubular lumen. As long as there is bicarbonate in the tubular lumen, bicarb will be reabsorbed but not synthesized


Is more bicarbonate reabsorbed or synthesized in the nephrons?

Reabsorbed. Daily reabsorption is about 4,320 mmol while daily synthesis is only 60-70 mmol.

Compared to synthesis, reabsorption requires 60 times the capacity of exchangers, channels, and proton pumps.


True or False: Essentially no bicarbonate synthesis can take place until bicarbonate reabsorption is complete.



True or False: Urine has an acid buffering system so that it doesn't get too acidic.


Without a buffering system, urine would be about 1.4 pH. This would be way too toxic for the epithelial cells lining the urinary tract and secretion of H+ would be energetically expensive/impossible.

With a buffering system, the lowest urine pH is around 4.5.


What are the two main urinary buffering systems to make sure urine pH doesn't get too low?

Titratable acid and ammonia trapping


What is titratable acid and how does this maintain a normal urine pH?

When H+ are secreted from the intercalated cells, they react with HPO42- to form H2PO4and excreted. The protons are also buffered by creatinine and urate.

About 30-40mmol of protons are titrated this way.


What is ammonia trapping?

In the proximal tubule cells, glutamine is converted to ammonia (NH3) by glutaminase. Ammonia freely passes across the apical membrane ending up in the tubular lumen. In the distal part of the nephron, H+ that is secreted from intercalated cells combines with the ammonia to form ammonium (NH4+).

Ammonia has a very high affinity for protons so it is favorable to turn into ammonium.  While ammonia can freely diffuse around, once it turns into ammonium it cannot permeate the membranes so it is trapped in the urine and excreted.


What is ammoniagenesis and where does it happen?

Ammoniagenesis is the generation of ammonia. It happens in the proximal tubule cells where glutamine is metabolized into ammonia (NH3) and bicarbonate. The ammonia ends up in the tubular lumen and the bicarbonate is reabsorbed into the peritubular capillary.


When can ammoniagenesis increase?

Ammoniagenesis typically titrates around 40 mmol of protons under normal conditions. When there is a high concentration of protons in the proximal tubule cells (during chronic acidosis or hypokalemia), ammoniagenesis can increase and titrate up to 200 mmol of protons per day.


True or False: Titratable acid excretion can increase in situations of acidosis


Titratable acid excretion is relatively stable and has to do with the amount of protein ingested in a diet. It is the ammoniagenesis that can increase in situations of chronic acidosis.


How do you calculate net acid excretion (NAE)?

NAE = (NH4+ excretion) + (Titratable acid excretion) - (HCO3- excretion)

About 40-50% of NAE is typically titratable acid. This is a relatively constant depending on protein intake of diet.

About 50-60% of NAE is ammonium excretion. This can increase with an increase in ammoniagenesis in response to chronic metabolic acidosis.

Bicarbonate excretion is essentially zero in normal circumstances.


How do the 3 factors of NAE change in chronic metabolic acidosis?

  1. NH4+
  2. Titratable acid excretion
  3. Bicarbonate excretion

NH4+ excretion increases because ammoniagenesis increases to titrate more acid.

Titratable acid excretion is unchanged because it is relatively constant and depends on protein ingestion in diet.

Bicarbonate excretion remains at zero.


How do the 3 factors of NAE change in chronic metabolic alkalosis?

  1. NH4+
  2. Titratable acid excretion
  3. Bicarbonate excretion

In states of chronic metabolic alkalosis, bicarbonate excretion increases because the body has an excess of bicarbonate in alkalosis and needs to eliminate the excess. Bicarbonate excretion can go up to 80 mmol/day which happens by decreased bicarbonate reabsorption.

NH4+ and titratable acid excretion both decrease because there is no need to titrate as much acid in a state of alkalosis.


Upregulation/downregulation of apical and basolateral transporters is dependent on ECF _____ and _____

pH and CO2 levels


In states of acidosis, what happens to ECF [H+] and [HCO3-]? How are apical and basolateral transporters regulated in reaction to acidosis?

In acidosis (both metabolic and respiratory),

ECF [H+] increases and [HCO3-] decreases.

This causes an increase in apical H+ and basolateral HCO3- transporters so that more protons can be eliminated and more bicarbonate can be reclaimed.


In states of alkalosis, what happens to ECF [H+] and [HCO3-]? How are apical and basolateral transporters regulated in reaction to acidosis?

In states of alkalosis (both respiratory and metabolic),

ECF [H+] is decreased and [HCO3-] is increased.

This results in decreased apical H+ transporters and basolateral HCO3- transporters. This causes less H+ to be eliminated and less HCO3- to be reclaimed.


Understand this flow chart of metabolic acidosis


Explain this flow chart for the renal response to respiratory acidosis


How can hypokalemia cause metabolic alkalosis?

When there is decreased ECF [K+], K+ will shift out of cells into the ECF. This is done in exchange for H+. So, you end up with higher intracellular H+ in all cells, including the renal tubule cells.

This increases ammoniagenesis which allows for more H+ trapping and excretion.

In the intercalated cells, the cells will preferentially reabsorb K+ in exchange for H+. This is done by an H+/K+-ATPase on the apical membrane of the intercalated cells. (Remember that in the intercalated cells, when H+ is secreted, HCO3- is reclaimed).

This all results in more proton secretion/excretion and more HCO3- synthesis which causes metabolic alkalosis. Hypokalemia is often associated with metabolic alkalosis but this isn't always the case.


How can metabolic alkalosis cause hypokalemia?


True or False: In hyperkalemia, K+ shifts into cells from the ECF



Hypokalemia is related to metabolic alkalosis. Hyperkalemia is related to metabolic acidosis but to a lesser degree. Explain the mechanism and why it's not such a clear cut relationship.

Potassium shifts into cells from the ECF in exchange for protons which shift out of the cells (this happens in all cells including those of the renal tubules). Less intracellular protons are available in the renal tubules for secretion. This decreases ammoniagenesis which decreases ability for H+ trapping and excretion. Less H+ secretion/excretion results in less HCO3- synthesis.

However, this is not a clear cut relationship because hyperkalemia also stimulates aldosterone. Aldosterone increases H+ secretion and HCO3- synthesis. This causes a counteractive effect so we don't always see metabolic acidosis from hyperkalemia.