L11: acid base regulation

Question 1

Normal pH range and deviations

Answer 1

Normal: 7.35-7.45
Acidosis: 6.8-7.35
Alkalosis: 7.45-8
Deviations outside of these ranges result in death.

Question 2

What happens if pH goes outside the normal range?

Answer 2

• proteins are denatured, enzyme function lost, nerves hypersensitive, muscle spasms, heart rate changes etc,
• our daily metabolic processes produce (and consume) substantial volumes of free H+ ions/acids that are effectively removed from the body.

Question 3

Sources of H+ ions

Answer 3

• ingested protein metabolism
• cell metabolism - produce CO2
• food products - processed foods, sodas, meats etc
• medications - aspirin, warfarin, indomethacin
• metabolic intermediate by-products e.g. exercise produces lattice acid
• disease processes - e.g., diabetes may c improper breakdown of fats and generation of keto-acids

Question 4

Buffer systems in the body

Answer 4

• Intracellular fluid (in cells): phosphates can collect H+ to become phosphoric acid; amino acids also accept H+
• Interstitial fluid (part of ECF): carbonic acid/bicarbonate buffer system
• Blood (part of ECF): haemoglobin, plasma proteins, carbonic acid/bicarbonate buffer system

Question 5

Issue with buffering

Answer 5

Buffering is good but it is a temporary short-term fix to the problem. They will bind to H+ when they are in excess and pH is low and release them when there are too few H+ and pH is high. Ultimately excess acids and bases must be eliminated from the body.
The carbonic acid/bicarbonate buffer is a great ECF buffer because both the lungs and kidneys can be used to restore pH.

Question 6

The carbonic acid / bicarbonate buffer system

Answer 6

CO2 + H2O H2CO3 H+ + HCO3-
Lungs can alter the depth and rate of ventilation to alter arterial PCO2.
Tubular excretion or reabsorption of H+ and HCO3-.
Unique because it works both ways.

Question 7

What are the 3 defence mechanisms in the body that buffer against or prevent pH changes?

Answer 7

1st defense: chemical buffering - seconds (<1second)
2nd defense: respiratory - minutes
3rd defense: renal days (5-7)

If any one organ is unable to do their job, the other one can compensate for it,

Question 8

Normal ABG values

Answer 8

CO2 and bicarbonate levels in the blood need to be kept constant for pH to remain unaltered. Arterial blood gases (ABG) can be easily obtained from the radial artery to provide values for:

• pH: 7.4 (7.35-7.45)
• PCO2: 40mmHg (35-40)
• HCO3-: 24mmol/L (22-26)

Question 9

What are the 4 ways of renal acid-base regulation?

Answer 9

1. Reabsorb HCO3- back into the blood when H+ levels are too high and pH is too low.
2. Excrete H+ when H+ is too high and pH is too low.
3. Generate HCO3- when H+ is too high and pH is too low.
4. Excrete HCO3- when HCO3- is too high and pH is too high.

Question 10

What happens if there is too much H+ in the blood (acidosis)?

Answer 10

If HCO3- has been reabsorbed and it is still too acidic then H+ is excreted. If this keeps happening it will change the pH of the urine and will cause pain and discomfort to urinate due to acidity, and eventually the lining of the bladder and urethra would become damaged. If acidity reaches 4.4-4.5 or below, the renal phosphate or renal ammonia buffer systems are used.

Question 11

Renal phosphate buffer system

Answer 11

HPO42- + H+ H2PO4-
In the kidney tubules:
- filtered phosphates (HPO42-) can buffer excess H+ in the filtrate
- phosphoric acid is excreted in the urine (called titratable acid)
- limited supply because 75% of phosphates that are filtered are also reabsorbed
- in this process new bicarbonate can be generate by the renal tubules and reabsorbed into the blood
- (this buffer is also an intracellular buffer)

Question 12

Renal ammonia buffer system

Answer 12

• renal tubular buffer only
• glutamine in PCT cell is converted to ammonia (NH3) which accepts H+ to become ammonium (NH4+)
  NH3 + H+ NH4+

In the kidney tubules:

• NH4+ is excreted in the urine
• in this process new bicarbonate can be generated by the renal tubules which is reabsorbed by the blood
• NH3 buffers and excreted 50% of excess H+ in urine and contributes to generation of 50% of the new bicarbonate
• most effective because there are no means of absorbing ammonium once it is made

Question 13

What are the two types of acid-base imbalance?

Answer 13

1. Respiratory dysfunction - change in PCO2

2. Metabolic dysfunction - change in [HCO3-]

Question 14

Relationship between pH and bicarbonate and CO2

Answer 14

pH is directly proportional to [HCO3-] / pCO2

So pH is directly proportional to bicarbonate concentration and indirectly proportional to partial pressure of carbon dioxide.

Question 15

What is respiratory acidosis?

Answer 15

• pH is too low - below 7.35

- pCO2 is too high - above 45mmHg

Question 16

Causes of respiratory acidosis?

Answer 16

• respiratory patterns that cause hypoventilation
• holding CO2 in the body - most common A-B disorder
• lung problems - emphysema, oedema, obstruction
• trauma to respiratory centre
• dysfunction of respiratory muscles
• overuse of sedatives, barbiturates, or narcotics such as Valium, heroin etc or other drugs which make you sleepy

Question 17

What does respiratory acidosis mean for the buffer equation?

Answer 17

Accumulation of CO2 in the bloodstream increases H+ and bicarbonate, because reaction is being driven to the right

Question 18

Renal compensatory mechanism for respiratory acidosis

Answer 18

• peripheral chemoreceptors will sense the change in pH and try to change rate of ventilation
• however the lungs are unresponsive due to the problem causing the respiratory acidosis
• so the kidneys remove excess H+ in an acidic urine and conserve bicarbonate in the ways discussed before

Davenport diagram and explanation at 13:30

Question 19

What is respiratory alkalosis?

Answer 19

• pH is too high - above 7.45

- pCO2 is too low - below 35mmHg

Question 20

Causes of respiratory alkalosis?

Answer 20

• respiratory patterns that cause hyperventilation
• removing CO2 from the body too quickly
• anxiety, fear, pain - hysterical over-breathing not just panting
• lung problems, e.g. pneumonia
• aspirin overdose/ toxicity; too much caffeine
• over-ventilation on mechanical respirator
• ascent to high altitude, fever…

Question 21

Effect of respiratory alkalosis on the buffer equation

Answer 21

Loss of CO2 from the blood stream decreases H+/bicarbonate, driving the reaction to the right

Question 22

Renal compensation for respiratory alkalosis

Answer 22

Peripheral chemoreceptors will sense the change in oH and try to alter the rate of ventilation, but the lungs are unresponsive as this is where the problem is. So the kidneys retain H+ and excrete bicarbonate.

Question 23

What is metabolic acidosis?

Answer 23

• pH lower than normal - below 7.35

- bicarbonate levels too low - below 24mEq/L

Question 24

Causes of metabolic acidosis

Answer 24

• loss of bicarbonate due to severe diarrhoea (most common)
• accumulation of acid e.g., ketone bodies in uncontrolled diabetes mellitus (ketoacidosis) and starvation
• renal dysfunction leading to impaired H+ excretion
• excess protein consumption (broken down to amino acids)
• ingestion of an acid (aspirin, ethanol, or antifreeze)
• exercise - mild, transient acidosis because of lactic acid

Question 25

How does metabolic acidosis affect the buffer equation?

Answer 25

Addition of H+ or loss of bicarbonate reduces bicarbonate. So pH rises.

Question 26

Respiratory/pulmonary compensation for metabolic acidosis

Answer 26

Peripheral chemoreceptors sense the change in pH and the lungs hyperventilate to remove CO2 (and thus H+) from the body. This will lower the bicarbonate even more too. Kidneys eventually remove excess H+ in an acidic urine and conserve bicarbonate.

Question 27

What is metabolic alkalosis?

Answer 27

• pH is higher than normal - above 7.45

- bicarbonate is higher than normal - above 24mEq/L

Question 28

Causes of metabolic alkalosis?

Answer 28

• loss of acid due to severe vomiting (most common)
• gastric suction
• use of diuretics leading to renal dysfunction
• excessive intake of alkaline drugs - antacids
• excessive intake of fruits (fad-diets rich in fruits)

Question 29

How does metabolic alkalosis affect the buffer equation?

Answer 29

Bicarbonate levels rise and H+ levels decrease.

Question 30

Respiratory/pulmonary compensation for metabolic alkalosis?

Answer 30

Peripheral chemoreceptors sense the change in pH and the lungs hypoventilate to retain CO2 (and thus H+) in the body. This will raise the bicarbonate even more too. Kidneys eventually remove excess bicarbonate in the urine and conserve H+.