Lecture #19: Renal Acid-Base Regulation

Question 1

Distinguish between volatile and non-volativle acids and give examples.

Answer 1

> Volatile Acid -> excreted from lungs

• carbon dioxide
  
  • product of cellular aerobic metabolism
  • H2CO3 is a weak acid

> Non-volatile Acids (fixed acids) -> excreted from kidneys

• sulfuric acid (product of protein catabolism)
• phosphoric acid (product of phospholipid catabolism)
• ketoacids, lactic acid, salicylic acid

Question 2

Define pH and know the normal pH range of venous and arterial blood.

Answer 2

arterial blood pH = 7.37 - 7.44

venous blood pH = 7.35 - 7.45

Question 3

Define equilibrium constant for the dissociation reaction and explain what pKa refers to.

Answer 3

Ka is the equilibrium constant for the dissociation reaction. Ka = [H][A]/[HA]

Question 4

Define acid and base.

Answer 4

Acid Definition -> compounds that release H+ ions. 
     - Strong Acids: 
          > dissociate completely 
     - Weak Acids (conjugate acid) 
          > do not dissociate completely 
          > dissociate into:
               - hydrogen ions (H+)
               - conjugate base

Bases -> compounds that accept H+ ions

Question 5

List the major systems in the body that regulate pH.

Answer 5

> chemical acid/base buffer systems of the body fluids

> respiratory center

> kidneys

Question 6

Define “buffer” and list the important buffer systems in the body.

Answer 6

A buffer is a substance that can reversibly bind H+.

> bicarbonate buffer system
phosphate buffer system
proteins as buffers (NOT covering)

Question 7

Which buffer system is the most important extracellular buffer system?

Answer 7

Extracellular Buffer System

• This buffer system consists of:
  
  • weak acid (H2CO3)
  • bicarbonate salt (NaHCO3)
• NOTE:
  
  • bicarbonate concentration is regulated mainly by kidneys
  • pCO2 is controlled by rate of respiration

Question 8

Explain how the bicarbonate buffer system works when a strong acid or a strong base is added.

Answer 8

> add a strong acid to the system:

increase H + HCO3 -> H2CO3 -> CO2 + H20

Question 9

What is the organ that primarily regulates the bicarbonate buffer system?

Answer 9

Bicarbonate concentration is regulated mainly by the kidneys.

Question 10

Distinguish between metabolic acid/base disorders.

Answer 10

Metabolic Acid/Base Disorders:
- Result from primary change in bicarbonate concentrations in extracellular fluid.
> metabolic acidosis = decreased HCO3- (bicarbonate)
> metabolic alkalosis = increased HCO3- (bicarbonate)

Question 11

Distinguish between respiratory acid/base disorders.

Answer 11

Respiratory acid/base disorders:
- Result from primary change in pCO2.
> respiratory acidosis = increased pCO2
> respiratory alkalosis = decreased pCO2

Question 12

How does the normal operating pH point for the bicarbonate buffer system compare to its pKa?

Answer 12

normal operating point in body = 7.4 pH, and the pKa is 6.1
Thus, by examining figure 30-1 you can see that the normal operating point in the body is at the type range of the buffer capacity for bicarbonate.

*Note that pH of 6.1 occurs when concentrations of both bicarbonate ions and carbon dioxide are equal;

**Therefore, pH at this point = pKa of the buffer system.

Question 13

Describe the phosphate buffer system and explain why it is more important as a buffer in the kidney tubular fluids.

Answer 13

> Plays major role in buffering renal tubular fluid and intracellular fluids.

> What area the two reasons for its importance as a buffer in kidney tubular fluids?

 - usually becomes greatly concentrated in the tubules 
 - lower pH of the tubular fluid brings the operating range of the buffer closer to the pK of the buffer system. 

> HCl + Ha2HPO4 -> Na H2PO4 + NaCl
- strong acid is replaced by an additional amount of weak acid and pH change is minimal.

Question 14

What is the primary method for removing non-volatile acids?

Answer 14

Renal Excretion -> primary method for removing non-volatile acids.

Question 15

True or False:

The kidneys can excrete either an acidic or basic urine?

Answer 15

True

Question 16

What must happen before filtered bicarbonate is reabsorbed?

Answer 16

Almost all filtered bicarbonate is reabsorbed, but it must react with secreted hydrogen ion to form carbonic acid before it can be reabsorbed.

*must form carbonic acid before it can be reabsorbed.

Question 17

How many mEq of hydrogen must be secreted each day by the kidneys?

Answer 17

4320 mEq of hydrogen ion must be secreted each day just to reabsorb the 4320 mEq of filtered bicarbonate.

Question 18

What are the 3 mechanisms by which the kidneys regulate extracellular hydrogen ions?

Answer 18

1) Kidneys reabsorb filtered bicarbonate ions.
2) Kidneys can secrete hydrogen ions.
3) Kidneys produce new bicarbonate ions.

Question 19

Review each of the below mechanisms for regulating hydrogen ion concentration ad study the below figures and accompanying information in the text book in detail for the exam!

> kidneys reabsorb filtered bicarbonate ions. 
     - figures 30-4 and 30-5 
> kidneys can secrete hydrogen ions 
     - figures 30-5 and 30-6 
> kidneys produce new bicarbonate ions
     - figures 30-7 through 30-9

Answer 19

Dr. Anderson said to know this.

Question 20

Where in the kidney tubules does hydrogen ion secretion and bicarbonate reabsorption occur?

Answer 20

H+ Secretion -> almost all parts of the tubules via secondary active transport (coupled with sodium ion transport) except the descending and ascending thin limbs of the loop of Henle

Primary active hydrogen secretion begins in late distal tubules in intercalated cells and involves a hydrogen-transporting ATPase.

Bicarbonate Reabsorption -> about 80-90% of bicarbonate reabsorption occurs in the proximal tubule

Question 21

Describe the mechanism by which bicarbonate ion is reabsorbed.

Answer 21

Bicarbonate is joined with H+ and dissolves into CO2 + H20 in the tubular lumen. The CO2 + H20 diffuse (reabsorbed) into the cell and are turned back into carbonic acid by carbonic anhydrase. Carbonic Acid dissolves into bicarbonate and hydrogen ion and the bicarbonate ion is reabsorbed into renal interstitial fluid by a sodium/bicarbonate symporter.

Question 22

What role is played by carbonic anhydrase?

Answer 22

Turns CO2 + H20 in the cell into carbonic acid so that bicarbonate can be regenerated.

Question 23

Explain why the bicarbonate ion returned to the extracellular fluid is not the same as that filtered into the tubular lumen.

Answer 23

Because the bicarbonate in the tubular lumen dissociates into CO2 + H20 to diffuse back into the cell. Those reactants are then turned into carbonic acid via carbonic anhydrase, which then dissociates into bicarbonate and hydrogen ion. This is the bicarbonate that is then returned to the extracellular fluid.

Question 24

Explain how bicarbonate ion is normally titrated against hydrogen ion and how incomplete titration can be used to correct acidosis or alkalosis.

Answer 24

> Use of incomplete titration to correct acidosis or alkalosis:

 - normally each time a H+ is formed in tubular epithelial cells, a bicarbonate ion is also formed and released back into the blood. 
 - in metabolic acidosis new bicarbonate ion is added to the extracellular fluid
 - in metabolic alkalosis, bicarbonate ions are removed from extracellular fluid by renal excretion. 

**talking about incomplete titration to correct acidosis or alkalosis. It is not a 1:1 process.

Question 25

What is the role of intercalated cells in hydrogen ion transport, and where are these cells found?

Answer 25

Active transport resulting in hydrogen ion secretion is carried out by intercalated cells.

Found -> only in late distal renal tubules

2-step process of H+ secretion in intercalated cells:

 - dissolved CO2 in intercalated cells combines H20 to from carbonic acid. 
 - carbonic acid then dissociates into bicarbonate, which is rapidly reabsorbed into the blood, and hydrogen ion, which is secreted into the tubular lumen by means of the hydrogen-ATPase transporters.

Question 26

What is the lower limit of pH that can be achieved in normal kidneys?

Answer 26

pH =4.5

Question 27

Explain how excess hydrogen ion is generated.

Answer 27

> each day the body produces about 80 mEq of non-volatile acids, mostly from the metabolism of proteins. Because these are non-volatile acids, they cannot be excreted by the lungs. They are primarily removed via renal excretion.

> Note also that loss of bicarbonate ions is the same as adding hydrogen ions to the extracellular fluid.

Question 28

What limits the amount of free hydrogen ion that can be excreted?

Answer 28

> only a small part of the excess H+ secreted in excess of the filtered bicarbonate ion can be excreted in ionic form in the urine.
- this is because the minimal urine pH is about 4.5

> to excrete the 80 mEq of non-volatile acid formed by metabolism per day, about 2667 L of urine would have to be excreted if all the excess H+ remained free in solution.

**Buffers are important in allowing larger amounts of H+ to be excreted ** (phosphate buffer system and ammonia buffer system)

Question 29

What buffers are important in allowing larger amounts of H+ to be excreted?

Answer 29

Phosphate Buffer System

Ammonia Buffer System

Question 30

How does the excretion of excess hydrogen ions lead to the formation of new bicarbonate ions?

Answer 30

Bottom Line: if H+ are combining with other buffers in the tubular lumen, then excess bicarbonate ion is available to be returned to the blood. This bicarbonate ion is referred to as “new bicarbonate ion”.

> Excess H+ are eliminated through binding with phosphate or ammonia ions.
- this means that the bicarbonate ions formed when carbon dioxide combines with water in the tubular cells and then dissociates into H+ and bicarbonate ions can be returned to the extracellular fluid and blood, while the H+ are buffered with the phosphate and ammonia buffer systems.

Question 31

How does the kidneys (renal) handle excess base?

Answer 31

> reduction in the extracellular fluid H+ concentration leads to alkalosis.

• kidneys can correct this by failing to reabsorb all the filtered bicarbonate ion.
  
  • this is the same as adding H+ to the extracellular fluid:
• extracellular fluid pH returns to normal.

Question 32

How can the respiratory system produce acidosis?

Answer 32

• caused by hypoventilation

Acidosis occurs when the ratio of bicarbonate ion to CO2 in extracellular fluid decreases.
- decrease in bicarbonate ion = metabolic acidosis

• increase in CO2 = respiratory acidosis

Question 33

How can the respiratory system produce alkalosis?

Answer 33

• Respiratory alkalosis occurs when there is a decrease in C)2 concentration = caused by hyperventilation

Alkalosis occurs when there is an increase in the ratio of bicarbonate to H+ concentration:

• excess bicarbonate is excreted in urine
• effect is to add H+ to extracellular fluid

Question 34

How does the respiratory system compensate for acid/base disturbances?

Answer 34

Metabolic Acidosis: 
  - primary compensatory:
     > increased ventilation rate
     > renal compensation 
          -> adds new bicarbonate ion to extracellular fluid

Metabolic Alkalosis is caused by a rise in the extracellular fluid bicarbonate ion concentration.
- compensatory response:
> decreased ventilation
> increased renal bicarbonate ion excretion

Question 35

I recommend looking at figure 30-10 to bring lecture 19 all together.

Answer 35

Dr. Anderson really liked this figure.