Physiology 6 - Acid Base

Question 1

Why is Acid/Base Balance crucial?

Answer 1

• Metabolic reactions are exquisitely sensitive to the pH of the fluid in which they occur
  
  • Relates to the high reactivity of H+ ions with Pr- ⇒ changes in configuration and function, especially enzymes
  • Acid/Base disturbances ⇒ all sorts of metabolic disturbances

Question 2

What is the normal arterialized blood pH?

Answer 2

7.4 = free [H+] of 40 x10^-9moles/l or 40 x10^-2mmoles/l

Question 3

What are the major sources of H+?

Answer 3

• Respiratory Acid (CO₂ + H₂O ⇔ H₂CO₄ ⇔ H⁺ + HCO₃^-)
  
  • Formation of carbonic acid not normaly a net contributor to increased acid because any increase in production ⇒ increase in ventilation
    
    • Problem if lung function impaired
• Metabolic Acid (Non-respiratory acid)
  
  • Inorganic
    
    • Sulphuric acid from Amino acids
    • Phosphoric acid from Phospholipids
  • Organic e.g. fatty acids/lactic acid
    
    • Normal diet = no net gain to body of 50-100 mmoles H+/day

Question 4

What do buffers do?

Answer 4

Minimise changes in pH when H+ ions are added or removed

Question 5

What does the quantity of H₂CO₃ depend on?

Answer 5

The quantity of H₂CO₃ depends on the amount of CO₂ dissolved in plasma

• This depends on solubility of CO₂ and Pco₂

Question 6

What does the Henderson-Hasselbalch equation define pH in terms of?

Answer 6

In terms of the ration of [A-]/[HA] NOT the absolute amounts

pH = pK + log[A-]/[HA]

Question 7

What is the most important extracellular buffer?

Answer 7

Bicarbonate buffer system

H₂CO₃ ⇔ H⁺ + HCO₃^-

pH = pK + log[HCO₃^-]/[H₂CO₃]

7. 4 = 6.1 + log[HCO₃^-]/[H₂CO₃]
8. 3 = log 20

So ratio of [HCO₃^-]/[H₂CO₃] at pH 7.4 = 20:1

Question 8

What is the normal concentration of bicarbonate?

Answer 8

Solubility of CO₂ in blood at 37^oc

= 0.03 mmoles/l/mmHg Pco₂

= 0.225 mmoles/l/kPa Pco₂

So at a normal Pco₂ of 40mmHg, 5.3kPA, [H₂CO₃] = 40 x 0.03mmoles/l or 5.3 x 0.225 mmoles/l

= 1.2 mmoles/l

Since ration of [HCO₃^-]/[H₂CO₃] in blood at pH 7.4 is 20:1

[HCO₃^-] = 24mmoles/l = “Standard bicarbonate”

Question 9

What are the normal values are ranges?

Answer 9

• pH = 7.4
  
  • Range 7.37 - 7.43
  • (Range compatible with life = 6.8-7.8 (US) 7.0-7.6(UK)
• pCO₂ = 5.3kPa = 40mmHg
  
  • Range 4.8 - 5.9 = 36 - 44

Question 10

What are the major H+ buffer systems of the body?

Answer 10

1. Bicarbonate
2. Plasma proteins
3. Dibasic ⇒ Monobasic phosphate
   
   • HPO4 {2-} + H{+} ⇒ H2PO4{-}
4. Intracellular buffers
5. Bone carbonate

Question 11

Whats the consequence of using intracellular buffers?

Answer 11

H+ ions moved into the cells must either come with Cl- or be exchanged with K+ to maintain electrical equilibrium. In acidosis this can cause Hyperkalemia –> Vfib & death

Question 12

Whats the consequence of using bone carbonate as a buffer?

Answer 12

Occurs mainly in chronic renal failure when H+ can’t be excreted. Causes bone wasting due to the chronic acid load

Question 13

How much H+ do you take in a day?

Answer 13

50-100mmoles/day

Question 14

BY what mechanisms do the kidneys regulate acid/base balance?

Answer 14

1) Reabsorption of Bicarbonate 2) Excretion of H+ as titratable acids 3) Excretion of H+ with ammonium

Question 15

Explain the process of HCO3- reabsorption?

Answer 15

1) H+ ions actively secreted into proximal tubule (coupled to passive Na+ Reabsorption) 2) H+ & filtered bicarbonate form carbonic acid 3) dissociates to CO2/H2O which are then reabsorped 4) forms carbonic acid again in proximal tubule cell 5) dissociates to H+ & bicarbonate 6) bicarbonate is reabsorped and H+ secreted again for the same purpose

Question 16

How is H+ excreted as a titrable acid?

Answer 16

Excess (Exceeding Tm) dibasic PO4{2-} ions reach distal tubule. H+ secreted into distal tubule (coupled to passive Na+ reabsorption) and binds to dibasic phosphate Making monobasic phosphate (HPO4{-}) Which is then excreted This process is dependant on blood PaCO2 Also works with uric acid and creatinine

Question 17

What else is produced when H+ ions are excreted as titratable acids?

Answer 17

New bicarbonate. Blood CO2 is absorbed into distal tubule cells +water –> Carbonic acid Then dissociates to H+ (for secretion) and HCO3- (absorped into blood)

Question 18

Whats different about ammonium excretion compared to other methods of regulating Acidity?

Answer 18

It is variably active. Normally it excretes 30-50mmoles H+/day but during a chronic acid load the kidneys can synthesize new proteins over 4–5 days and up that to 250mmoles/day

Question 19

How does ammonium excretion work in the distal tubule?

Answer 19

Ammonium (NH3) is lipid soluble but ammonia (NH4+) is not. Distal Tubule: 1) Renal glutaminase deaminates amino acids producing NH3 2) NH3 moves into lumen, combines with H+ –> NH4+ and is excreted The H+ ions are secreted from the distal tubule cells after being produced from blood CO2 (So this process is also reliant on PaCO2)

Question 20

How does ammonium excretion work in the proximal tubule?

Answer 20

Almost the same as in the distal. But H+ and NH3+ combine in the cell and are actively excreted using a NH4+/Na+ exchanger

Question 21

What else is produced during ammonium excretion?

Answer 21

HCO3- is produced when you make H+ from blood CO2 to secrete. The bicarbonate is then reabsorped into the blood

Question 22

Summary of renal regulation:

Answer 22

1) HCO3- reabsorption # No new HCO3- # No net excretion of H+ # Proximal tubule 2) H+ excretion as titrable acids # New HCO3- produced # Net loss of H+ as monobasic phosphate # Distal tubule 3) Ammonium excretion # New HCO3- # Net loss of H+ as NH4+ # Proximal and distal tubule

Question 23

Describe the blood gasses of Respiratory Acidosis?

Answer 23

High PaCO2 = Directly High HCO3- = Kidney’s regulating pH Slightly acidic pH

Question 24

What could cause respiratory alkalosis?

Answer 24

Acute- aspirin or high altitude Chronic - Low PaO2 or high altitude

Question 25

Describe the bloods of respiratory alkalosis?

Answer 25

Low PaCO2 = directly Low HCO3- = because less H+ means less secretion which means less HCO3- reabsorption/production Slightly raised pH

Question 26

What can cause metabolic acidosis?

Answer 26

Excess H+ or loss of HCO3-: 1) Increased H+ production e.g. DKA 2) Decreasd H+ excretion e.g. renal failure 3) Decreased intestinal HCO3- reabsorption e.g. Diarrhoea

Question 27

Describe the bloods of metabolic acidosis?

Answer 27

Low PaCO2 = kussmauls respiration blows off CO2 to lower H+ Low HCO3- = Directly (either lost or used up buffering extra H+) pH slightly low

Question 28

What can cause metabolic alkalosis?

Answer 28

H+ ion loss in vomit Excess aldosterone –> Na+ reabsorption in exchange for H+ –> More H+ excretion and also less H+ available for HCO3- reasborption. Excess HCO3- administration in the renally impaired Massive blood transfusions (contain citrate for anticoagulation)

Question 29

Describe the bloods of metabolic alkalosis?

Answer 29

High PaCO2 = to raise acidity High HCO3- = Directly Slightly high pH

Question 30

What is the anion gap?

Answer 30

A measure of the difference between the principle cations (Na+/K+) and anions (Cl-/HCO3-). Usually about 14-18mmoles/l more cations than anions.

Question 31

When is the anion gap a useful measurment?

Answer 31

In acidosis It increases when bicarbonate is used up by lactic acidosis/DKA It stays the same when HCO3- is lost in the gut as its compensated by extra Cl-

Question 32

Patient with pH = 7.32, [HCO-3]= 15 mM, PCO2 = 30mmHg (4kPa) What Acid/base disturbance is this?

Answer 32

Metabolic acidosis pH low = Acidosis HCO3- & PaCO2 are low = metabolic acidosis

Question 33

Patient with pH = 7.32, [HCO-3]= 33 mM, PCO2 = 60mmHg (8kPa) What acid/base disturbance is this?

Answer 33

pH low = Acidosis PaCO2 high = Respiratory acidosis High HCO3- = Chronic Crhonic because more H+ means more HCO3- production and reabsorption. In the acute form HCO3- would not be elevated

Question 34

Patient with pH = 7.45, [HCO-3] = 42 mM, PCO2 = 50mmHg (6.7kPa) What they got?

Answer 34

high pH = alkalosis High HCO3- & PaCO2 = metabolic

Question 35

pH = 7.45, [HCO-3]= 21 mM, PCO2 = 30mmHg (4kPa) What they got?

Answer 35

high pH = alkalosis Low PaCO2 = Respiratory Normal HCO3- = acute (chronically it would adjust downward)

Question 36

Patient with pH = 7.31, PCO2 = 7.7.kPa, (58mmHg), [HCO3-] =36mmoles/l. Which of the following is true: 1. It is likely that he has renal disease. 2. He may have an acute respiratory infection. 3. It is possible that he may have chronic bronchitis. 4. There will be a decrease in his excretion of ammonium ions. 5. His plasma potassium will be reduced.

Answer 36

3!! 1) He’s acidotic but his HCO3- is still raised so hes not losing to renal disease 2) Hes in respiratory acidosis, we know its not acute due to the high HCO3- so it not a resp infection 3) His High HCO3- indicates it a chronic respiratory acidosis as its compensating with more HCO3- 4) False it will increase 5) False it will go up as H+ is exchanged into cells for K+ in order to be buffered

Question 37

The following acid/base values were obtained: pH = 7.25, [HCO3-] = 12mmoles/l, PCO2 = 3.3kPa (25mmHg) Which of the following are true? 1) They are indicative of a respiratory acidosis 2) The reduction in Pco2 is a result of under-breathing 3) The subject has probably been taking bicarbonate of soda 4) It could be related to impaired renal function 5) The subject may have been vomiting very badly

Answer 37

4!! They’re in metabolic acidosis 1) Low HCO3- and PaCO2 indicates its metabolic 2) False, you hyperventilate in response to acidosis 3) Why would their bicarbonate be so low 4) True, thats where the HCO3- might be going 5) that would cause alkalosis (So a high pH)