Acid-Base Inbalance

Henderson-Hasselbach: pH = 6.1 + log ( [HCO₃^-]/0.03 pCO₂ )

Henderson: [H⁺] = 25 pCO₂ / [HCO₃^-]

	pH	[H⁺]	1° disorder	2° response
Metabolic acidosis	ß	Ý	ß ß HCO₃^-	ß pCO₂ (hyperventilation)
Metabolic alkalosis	Ý	ß	Ý Ý HCO₃^-	Ý pCO₂ (hypoventilation)
Respiratory acidosis	ß	Ý	Ý Ý pCO₂	Acute: Ý HCO₃^- Chronic:ÝÝ HCO₃^-
Respiratory alkalosis	Ý	ß	ß ß pCO₂	Acute: ß HCO₃^- Chronic:ßß HCO₃^-

Metabolic Acidosis – ß HCO₃^-

Causes:

(1) Excess production of acids.

endogenous (lactic acid, keto acids, etc.)
exogenous (methyl alcohol, formic acid, etc.)

(2) Inability of kidney to excrete normal amount of acid (i.e. inability to reabsorb bicarbonate in proximal tubule).
(3) Loss HCO₃^- from body – GI track (diarrhea).

Responses:

(1) Recruit non-bicarbonate buffers which offset the severity of acidosis. (instantaneous)

(2) Respiratory: Hyperventilation – in acidosis the H⁺ levels are high, hyperventilation gets rid of the excess protons. (minutes)

This works via chemoreceptors which increase minute ventilation thus ß CO₂.

(3) Renal response: (2-4 days). This won’t happen if the kidneys are the problem.

Ý ammonia excretion = Ý HCO₃^- regeneration

Ý urinary acidification, this drives more hydrogen ions to the buffers, so excrete more H⁺ without paying for it with ß pH.

Metabolic Alkalosis – Ý HCO₃^-

Causes: There are two phases to metabolic alkalosis:

(1) The generation of the metabolic alkalosis is by either a loss of non-carbonic acid from the body or an addition of base to the body.

(2) The maintenance of the alkalosis, i.e. maintenance of Ý T_m, is by an elevation in the rate of tubular reabsorption of bicarbonate.

Maintenance is the pathological aspect because normally the kidney would maintain HCO₃^- levels by excreting any excess HCO₃^-).

Responses:

(1) Respiratory: Hypoventilation – in alkalosis the H⁺ levels are low, hypoventilation replenishes the protons.
(2) Renal: HCO₃^- excretion by the kidney

Example: vomiting Þ loss of H^{+ and}Cl^- Þ Ý HCO₃^-. Also, loss of ECF Þ ß ECFV which will result in increased aldosterone to compensate for the lost volume. In order to do this need to hold on to Na⁺. As a result K⁺ is exchanged for Na⁺ and thus KHCO₃(potassium bicarbonate) appears in the urine. When potassium depletion occurs (hypokalemia) filtered sodium ions are reabsorbed in exchange for hydrogen ions. Urine pH falls, and net urinary acid excretion increases. As urinary acid excretion increases, more HCO₃^- is added to the extracellular fluid. Plasma HCO₃^- concentration rises and the alkalosis is maintained. This acidic urine is paradoxical in light of an extracellular alkalosis. It occurs because the stimulus to reabsorb sodium exceeds the stimulus to maintain acid-base homeostasis.

Example #2: If a tumor causes the excess production of aldosterone there will be similar responses to those above. Na⁺ will be exchanged for H⁺, and K⁺ will be lost in the urine.

Relationship of Plasma HCO₃^- to HCO₃^- reabsorption:

Respiratory Acidosis – Ý pCO₂

Causes: decrease in respiratory rate and retention of CO₂, increase [H⁺] and [HCO₃^-] by mass action

(1) brain – coma, etc.
(2) chest – chest wall defect
(3) lungs – COPD, etc.

Responses:

(1) Initially, there is a small Ý in HCO₃^- due to non HCO₃^- buffers (proteins, etc).

(2) Respiratory: no respiratory compensation for respiratory acidosis.

(3) Renal:

Acute respiratory acidosis – none yet occurred.

Chronic respiratory acidosis - kidneys will make more bicarbonate in the long term by Ý ammonia excretion and/or Ý urinary acidification.

Respiratory Alkalosis – ß pCO₂

Causes: increase in respiratory rate and loss of CO₂, decrease [H⁺] and [HCO₃^-] by mass action

(1) chronic hypoxia – V/Q mismatch, shunt, restrictive disease, ß FIO₂ (high altitutde). Of these only shunt is acute, while all the rest are chronic.

(2) Acute causes can be anxiety, fever, intoxication.

Responses:

(1) Respiratory: no respiratory compensation for respiratory alkalosis.

(2) Renal:

Acute respiratory alkalosis – none yet occurred.

Chronic respiratory alkalosis – kidneys will Ý HCO₃^- excretion, thus arterial pH is decreased towards normal.

(3) Symptoms of hypocalcemia may occur because H⁺ and Ca²⁺ compete for binding sites on plasma proteins. Decreased [H⁺] causes increased protein binding of Ca²⁺ and decreased free ionized Ca²⁺.