43. Acid-Base Balance

Question 1

What is a conjugate base?

What is the acid dissociation constant?

What is pH7 in terms of ions?

Answer 1

When an acid HA dissociates it yields H⁺ and its conjugate base A^-

K_a, measure of an acid in solution: K_a= [H⁺][A^-]/[HA]. Strong acid = high K_a and low pK_a (pK_a = -log₁₀K_a). And pH = -log₁₀[H⁺]

Equal numbers of H⁺ and OH^- i.e. a neutral solution

Question 2

What is the Henderson-Hasselbalch equation?

What is the pH range compatible with life? What happens if you go above/below this?

What pH levels cause death if you go above/below? Why?

Answer 2

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

7.35 - 7.45, alkalosis (alkalaemia)/acidosis (acidaemia)

8/6.8. Denatures proteins, enzyme systems and ETC disrupted -> organ failure

Question 3

What are the 2 different classes of acids produced by the body?

Answer 3

1) Respiratory (volatile): H2CO3 (carbonic acid)

2) Metabolic (fixed): lactic acid. Harder to regulate.

Question 4

Production of Respiratory (volatile) acids

A normal adult metabolism produces how much CO₂/day?

What is the equilibrium equation showing how CO₂ is carried in the blood?

Answer 4

300L (end product of complete oxidation of carbs and FAs)

H₂O + CO₂ <=> H₂CO₃ <=> HCO₃^- + H⁺

Carbonic acid dissociates into hydorgen and bicarbonate ions. CO₂ must be rapidly excreted.

Question 5

What are the 3 ways metabolic (fixed) acids are produced?

Answer 5

1) Incomplete oxidation of carbohydrates and fats produces non-volatile acids e.g. actic acid
2) Metabolism (oxidation) of proteins and aas produces strong acids e.g. HCl and H₂SO⁴
3) Incomplete FA oxidation in disease states produces non-volatile acid e.g. diabetes: keto acids

Question 6

What does a chemical pH buffer solution contain?

What 3 mechanisms does the body have to limit changes in pH?

Answer 6

A weak acid (HA) and its conjugate base (A^-)

1) chemical buffer systems (1st line of defence)
2) respiratory control systems (2nd line)
3) renal control of pH (3rd line)

Question 7

Describe some chemical buffers in intracellular and extracellular fluid.

What is carbonic anhydrase?

What buffer systems contribute most to the buffer?

Answer 7

Intracellular: protein (acidic and basic side chains can give/take up H⁺), phospate (H⁺ + HPO₄^2- <=> H₂PO^4-, buffers H⁺ in urine with ammonia), bicarbonate/CO₂ system (imp in acid-base physiology, controlled by lungs and kidney)

Extracellular: Hb (buffers changes in H⁺ caused by CO₂: H⁺ + Hb -> HHb in tissues and releases it in lungs to take up O₂), phosphate, bicarbonate

Catalyses conversion of CO₂ and H₂O to carbonic acid and back.

Bicarbonate and Hb

Question 8

Describe respiratory control of pH.

Answer 8

Any increase in blood H⁺ driven by changes in CO₂ triggers activation of central chemoreceptors -> medullary respiratory neurons -> generates breathing. (H⁺ can’t cross BBB directly so CO₂ combines with it to cross.) This blows off CO₂ and removes acid. Response = minutes.

Question 9

Describe renal control of pH.

What are the 2 main sites where H⁺ excretion can be regulated, and how in each?

Answer 9

Filtered bicarbonate reabsorbed. Titratable acids (e.g. phoshoric, H₂SO₄) are formed. Ammonia (NH₃ and NH₄⁺) added to urine. All involves H⁺ secretion by tubular epithelium so urine is acidified. The H⁺ excretion is buffered by phosphate and ammonia.

1) PCT: CO₂ diffuses from blood to tubular cell -> carbonic anhydrase converts it to H₂CO₃ which dissociates to H⁺ and HCO₃^- -> H⁺ transported out of cells into urine via Na⁺/H⁺ exchanger -> HCO₃^- returned to blood

2) CD: H⁺ secreted via electrogenic H⁺ ATPase pump and electroneutral H⁺/K⁺ ATPase exchanger which can acidfy urine to pH 4.5. Bicarbonate absorption too.

Question 10

In renal control of pH, how is bicarbonate reabsorbed?

What is the renal response to alkalosis?

Answer 10

Filtered from blood but can’t be reabsorbed b/c impermeable renal tubule cells. Reacts with secreted H⁺ to form H₂CO₃. Extracellular carbonic anhydrase converts it to H₂O and CO₂. CO₂ diffuses into tubule cells where intracellular CA converts it to H₂CO₃ -> dissociates to HCO₃^- and H⁺. H⁺ is excreted in urine and HCO₃^- diffuses into blood.

H⁺ excretion by Na⁺/H⁺ antiport is inhibited, allowing filtered bicarbonate to be lost in urine. If extreme, mechanism can reverse, excreting Na⁺ and retreiving H⁺ = alkaline urine.

Question 11

What is the [HCO₃^-]:[CO₂] ratio in normal pH?

How would respiratory acidosis be caused in COPD?

Why are the measurements of the following important:

a) pH
b) pCO₂
c) HCO₃^-

Answer 11

20:1 (HCO₃^- = 24mM, CO₂ = 1.2mM), keeps blood at pH7.4 according to henderson hasselbalch equation

CO₂ retained = increased [H⁺] (CO₂ = 2.4mM so pH = 7.1)

a) acidosis or alkalosis?
b) respiratory indicator
c) metabolic indicator

Question 12

List 4 simple acid-base disturbances, the primary cause for them, and compensation type.

Answer 12

1) respiratory acidosis: CO₂ retention e.g hypoventilation -> renal compensation (H⁺ excretion, HCO₃^- gain)
2) respiratory alkalosis: CO₂ loss e.g. hyperventilation -> renal compensation (HCO₃^- loss, H⁺ retention)
3) metabolic acidosis: gain of acid, loss of base e.g. diarrhoea, keto(or lacto)-acidosis -> respiratory compensation (CO₂ loss, HCO₃^- falls)
4) metabolic alkalosis: loss of acid, gain of base e.g. vomiting, hypokalaemia, ingestion of HCO₃^- -> respiratory compensation (CO₂ rises, HCO₃^- rises)

Question 13

What is a Davenport diagram used for?

What is the anion gap?

Answer 13

To interpret mixed acid-base disturbances

Difference between primary measured cations (Na⁺) and primary measured anions (Cl^- and HCO₃^-). Useful in determining some conditions. [Na⁺] - ([Cl^-] + [HCO₃^-]) = [anion gap]. Normally = 8-14mEg/L