Acid-Base Disorders

Question 1

SIMPLE ACID-BASE DISTURBANCES

Answer 1

metabolic acidosis
metabolic alkalosis
respiratory acidosis
respiratory alkalosis

Question 2

Metabolic acidosis: definition, primary lesion and compensation

Answer 2

DEFINITION: ≈ characterised by a low [HCO3−] and a low pH (and, if compensation has occurred, a low Pco2).
PRIMARY LESION - a low plasma [HCO3−] due either to the addition of hydrogen ions to the ECF or loss of bicarbonate from the body.
COMPENSATION - The low [HCO3−] results in a low pH which stimulates the respiratory centre and increases carbon dioxide excretion. This results in a lowered Pco2 and hence an increase in the pH which returns towards normal but rarely to normal.

Question 3

metabolic acidosis - CAUSES/PATHOPHYSIOLOGY

Answer 3

Addition of H+

Increased production: Ketoacidosis, Lactic acidosis, Toxins* (ethanol, methanol, salicylate, ethylene glycol), Ingestion/Infusions (HCI, NH4CI, arginine/lysine)
Decreased renal excretion: Renal failure*, Obstructive uropathy, Renal tubular acidosis Type I, Mineralocorticoid deficiency

Loss of HCO3−

Extrarenal losses: Acute diarrhoea, Drainage from pancreatic fistulae, Diversion of urine to gut
Renal losses: Renal tubular acidosis Type II
*These conditions are associated with a high anion gap (see below). The others have a normal anion gap (hyperchloraemic metabolic acidosis).

Question 4

The following conditions are associated with a high anion gap

Answer 4

Ketoacidosis
Lactic acidosis
Toxins
Renal failure

Question 5

hyperchloraemic metabolic acidosis is associated with

Answer 5

normal anion gap

Question 6

Causes of plasma anion gap metabolic acidosis

Answer 6

AKI and CKD
Ketosis e.g. DKA, ethanol excess or prolonged starvation
Lactic acidosis
Intoxicants
Salicylates
Methanol
Ethanol
Ethylene glycol
Paracetamol
Propylene glycol, Paraldehyde
Massive rhabdomyolysis
Organic acidurias

Question 7

Causes of normal plasma anion gap metabolic acidosis (Hyperchloraemic acidosis)

Answer 7

Ingestion of ammonium chloride, arginine, lysine, sulphuric or hydrochloric acid
Drugs such as acetazolamide or anion-binding resins, e.g. cholestyramine
Renal tubular acidosis
Gastrointestinal disease, e.g. fistula or diarrhoea
Ureteric diversion, e.g. ileal bladder or ureterosigmoidostomy
Intravenous saline excess

Question 8

Clinical effect of metabolic acidosis

Answer 8

• Increased [H+] stimulates the respiratory centre and causes hyperventilation. This causes deep, rapid and gasping respiration known as Kussmaul breathing. This is a physiological compensatory response which decreases pCO2 and returns the pH towards normal.
• Increased [H+] commonly causes hyperkalaemia. Intracellular polyanions such as proteins and glycogen normally bind H+ and K+. In an acidosis, excess H+ move into cells, displacing K+.
• Increased [H+] causes increased neuromuscular irritability. There is thus a risk of cardiac arrhythmias, especially in the presence of hyperkalaemia. Acidaemia impairs myocardial contraction which could result in cardiac failure; however, acidaemia also releases catecholamines which block the pH effect.
• Increased [H+] enhances the mobilisation of calcium from bone, decreases the binding of ionised calcium to albumin, and decreases the renal reabsorption of calcium producing hypercalciuria. Thus chronic acidaemia, as in renal tubular acidosis, is associated with a negative calcium balance, and can result in nephrocalcinosis and urolithiasis.
  *Increased [H+] depresses consciousness, which can progress to coma and death.

Question 9

metabolic acidosis - INVESTIGATION

Answer 9

Arterial blood gases analysis
determination of plasma anion gap
Other tests are indicated according to the clinical situation
plasma glucose estimation,
plasma urea and creatinine estimation,
blood lactate determination,
tests for ketones in urine,
tests for drugs or poisons, for example ethanol, paracetamol, salicylate (if indicated),
specialized tests for renal tubular acidosis

Question 10

metabolic acidosis - TREATMENT

Answer 10

1. Treat the primary cause.
2. Treat any dehydration and hyperkalaemia which are commonly present.
3. Treat the acidosis if severe (pH < 7.0) by administering NaHCO3
   7

Question 11

Metabolic alkalosis: definition, primary lesion and compensation

Answer 11

DEFINITION: ≈ characterised by a high bicarbonate, a high pH (and, if compensation has occurred, a high Pco2).

PRIMARY LESION - high [HCO3−] which may be due to
(a) exogenous ingestion or infusion, or
(b)to endogenous production as a consequence of H+ loss.

COMPENSATION
- A high plasma [HCO3−] results in a high pH which suppresses respiration and consequently retention of carbon dioxide and a high Pco2.

The high Pco2 returns the pH towards normal but rarely to normal

Question 12

metabolic alkalosis - CAUSES/PATHOPHYSIOLOGY

Answer 12

Excessive bicarbonate generation reflects 2 basic causes:
(1) Increased exogenous bicarbonate, and

(2) Loss of hydrogen ions which results in generation of bicarbonate by the body.

A. Increased exogenous bicarbonate
Oral/intravenous bicarbonate
Antacid therapy, e.g. magnesium carbonate
Organic acid salts, eg, lactate, acetate, citrate

B. Loss of hydrogen ions
Gastrointestinal tract losses:
Stomach: vomiting, gastric suction
Bowel: chloride diarrhoea
Kidney losses: Diuretic therapy, Mineralocorticoid excess

Question 13

metabolic alkalosis - CLINICAL EFFECTS

Answer 13

• Tetany: The major effect of alkalosis is enhanced binding of calcium ions (Ca2+) to protein. The lowered ionised calcium results in increased neuromuscular activity and the characteristic Chvostek and Trousseau signs may occur.
  Other clinical effects of metabolic alkalosis are:
• Hypokalaemia, due to decreased distal tubular hydrogen ion secretion (increased renal potassium excretion and uptake of potassium ions by the cells in exchange for cellular hydrogen ions). In turn hypokalaemia worsens and prolongs the alkalosis.
• Increased renal calcium reabsorption
• Enhanced glycolysis (stimulation of phosphofructokinase by a high intracellular pH)

Question 14

metabolic alkalosis - TREATMENT

Answer 14

1. Treat the primary cause.
2. Treat any dehydration and hypochloraemia which are present with normal saline (NaCl).
3. Treat any hypokalaemia present with KCl.

Question 15

metabolic alkalosis - INVESTIGATION

Answer 15

A clinical and drug history and physical examination may reveal the cause of the metabolic alkalosis.
Useful laboratory investigations include:
● arterial blood gases
● plasma Na+, K+, Cl –, Mg2+
● urea and creatinine
● spot urine [Cl –] <20 mmol/L suggests the saline-responsive form (volume depletion or contraction) of metabolic alkalosis, and >20 mmol/L the saline-non- responsive form.

Other tests are indicated according to the clinical situation, e.g., if primary hyperaldosteronism (Conn’s syndrome) or Cushing’s syndrome is suspected.

Question 16

respiratory acidosis: definition, primary lesion (and its cause) & compensation

Answer 16

DEFINITION: ≈ characterised by an increased Pco2 (hypercapnia). The blood pH may be decreased in the acute uncompensated case, or normal in the chronic fully compensated case. There is usually an associated decrease in the Po2 (hypoxia).

PRIMARY LESION - The primary lesion (increased Pco2) is due to decreased respiratory exchange which may be a consequence of (a) decreased respiration, or (b) decreased respiratory exchange because of local lung disease.

COMPENSATION - The response to hypercapnia is two-fold:

An acute increase in the plasma [HCO3−] during the first 10 minutes (the lower curve) followed by,
A chronic, sustained, rise in the plasma [HCO3−] over the next 2 to 4 days (the upper curve), providing the hypercapnia remains.

Question 16

respiratory acidosis - CLINICAL EFFECTS

Answer 16

Brain: Hypercapnia induces cerebral vasodilation and increased blood flow which can increase the intracerebral pressure producing drowsiness, headaches, stupor, and coma.
Potassium: Theoretically acidaemia could result in the release of potassium from the cells (exchange for H+) but this is not a consistent feature of respiratory acidosis.

Question 16

respiratory acidosis - TREATMENT

Answer 16

1. Treat the underlying cause, e.g., remove any physical airway obstruction.
2. Improve alveolar ventilation and lower the Pco2 by using physiotherapy, bronchodilators, antibiotics and assisted ventilation if necessary. Beware of lowering the pCO2 too rapidly in chronic conditions, since the renal compensatory changes takes several days to reverse - otherwise the patient would develop a residual metabolic alkalosis.
3. Improve the hypoxia. In acute conditions, this must be done urgently by using oxygen at high concentrations, or even assisted ventilation. In chronic conditions, beware of removing the hypoxia which may be the only stimulus to which the respiratory centre still responds

Question 16

respiratory acidosis CAUSES/PATHOPHYSIOLOGY

Answer 16

CAUSES/PATHOPHYSIOLOGY - Hypercapnia, which is tantamount to alveolar hypoventilation, may be due to `
Thoracic disease
Restrictive defects: hydrothorax, pneumothorax, flail chest
Obstructive disease: bronchitis, emphysema, pneumonia, infiltrations, oedema, foreign body obstruction
Neuromuscular disease
Poliomyelitis, Guillain-Barre syndrome, multiple sclerosis, myopathies
Central depression
Trauma, cerebrovascular accidents, CNS infections, CNS tumours, drug overdose.

Question 17

respiratory acidosis - INVESTIGATION

Answer 17

In many cases the cause of the respiratory acidosis can be deduced from the clinical history and examination in conjunction with a chest radiograph and lung function tests, if indicated.
Laboratory tests include: ● arterial blood gases

Question 18

respiratory alkalosis: definiton, primary lesion and compensation

Answer 18

DEFINITION: ≈ characterised by low Pco2 (hypocapnia) due to increased ventilation. The blood pH may be increased in the acute uncompensated case, or normal in the chronic fully compensated case.
PRIMARY LESION - The primary lesion is a low blood Pco2 due to increased ventilation as a consequence of either (a) central stimulation of the respiratory centre, or (b) reflex stimulation from lung pathology.
COMPENSATION - The compensatory response to a low Pco2 is a decrease in plasma [HCO3−] which occurs in two phases; acute and chronic.

Question 19

respiratory alkalosis CAUSES/PATHOPHYSIOLOGY

Answer 19

CAUSES/PATHOPHYSIOLOGY - Hyperventilation and increased CO2 excretion can be due to central (CNS) or pulmonary mechanisms. It is never due to decreased CO2 production.
Hyperventilation, e.g. anxiety states, increased mechanical ventilation
Exogenous agents that increase respiratory drive, e.g. salicylates, theophylline, catecholamines, thyroxine, progestogen, etc
Hypoxaemia due to early and non-severe pulmonary disease, e.g. asthma, pulmonary embolus, pneumonia, or high altitude
Increased cerebral respiratory centre drive, e.g. head injury, cerebral tumour, meningitis, cerebrovascular accidents
Increased non-cerebral causes of respiratory centre drive, e.g. pregnancy, heat exposure, hepatic failure, septicaemia

Question 20

respiratory alkalosis - CLINICAL EFFECTS

Answer 20

1. Calcium metabolism: main clinical feature of respiratory alkalosis is tetany (carpopedal spasm) due to a lowering of the plasma ionised calcium level (alkalaemia causes increased binding of calcium ions to protein).
2. Potassium: mild (initially) hypokalaemia due to increased cellular uptake (exchange with cellular H+) but generally the plasma K remains normal.
3. Phosphate: Transient severe hypophosphataemia (e.g.,< 0.4 mmol/L) is not uncommon. This is due to alkalaemia-induced cellular phosphate uptake (stimulation of phosphofructokinase).
4. Glucose metabolism: A low intracellular [H’] stimulates phosphofructokinase activity and hence glycolysis. This produces increased lactate production and may result in an increase in the plasma lactate concentration.
5. Brain: Hypocapnia induces cerebral vasoconstriction which may result in light-headedness.

Question 21

respiratory alkalosis - INVESTIGATION

Answer 21

The cause of the hyperventilation may be obvious from the clinical history and examination.
A chest radiograph and lung function tests may be indicated.

Laboratory tests include:

● arterial blood gases,

● plasma [K+] and ionized [Ca2+] may be low,

● liver function tests when hepatic failure is suspected,

● exclude salicylate overdose and respiratory stimulants,

● elevated white cell count and relevant cultures may point to sepsis as a cause of hyperventilation,

● full blood count to exclude anaemia.

Question 22

respiratory alkalosis - TREATMENT

Answer 22

Treat the underlying cause

Question 23

mixed acid-base disturbances

Answer 23

In hospital practice about 40% of the blood gas reports reveal a mixed disorder, i.e., two or more simple disturbances occurring together.
Characteristically they present in one of two ways:
a severe acidaemia or alkalaemia
a normal, or near normal, pH associated with abnormal levels of Pco2 and [HCO3−] (suggesting complete compensation of simple disorder)