Whenever the plasma bicarbonate rises above 24mmols/l, bicarbonate is excreted by the kidney. This response is reasonably prompt and effective so a metabolic alkalosis will be rapidly corrected.
Causes : Classification of Initiating Processes for Metabolic Alkalosis
Gain of alkali in the ECF
* from an exogenous source (eg IV NaHCO3 infusion, citrate in transfused blood)
* from an endogenous source (eg metabolism of ketoanions to produce bicarbonate)
Loss of H+ from ECF
* via kidneys (eg use of diuretics)
* via gut (eg vomiting, NG suction)
'Causes' of clinically significant chronic metabolic alkalosis are usefully divided into 2 major groupings based on the major factor involved in the maintenance of the disorder:
* The chloride depletion group
* The potassium depletion group
A Common Hybrid Classification of 'Causes' of Metabolic Alkalosis
A: Addition of Base to ECF
* Milk-alkali syndrome
* Excessive NaHCO3 intake
* Recovery phase from organic acidosis (excess regeneration of HCO3)
* Massive blood transfusion (due metabolism of citrate)
B: Chloride Depletion
* Loss of acidic gastric juice
* Excess faecal loss (eg villous adenoma)
C: Potassium Depletion
* Primary hyperaldosteronism
* Cushing’s syndrome
* Secondary hyperaldosteronism
* Some drugs (eg carbenoxolone)
* Kaliuretic diuretics
* Excessive licorice intake (glycyrrhizic acid)
* Bartter's syndrome
* Severe potassium depletion
D: Other Disorders
* Laxative abuse
* Severe hypoalbuminaemia
Loss of gastric acid (vomiting, NG drainage) and diuretic use account for 90% of clinical cases of metabolic alkalosis
Gastric alkalosis is most marked with vomiting due to pyloric stenosis or obstruction because the vomitus is acidic gastric juice only. Vomiting in other conditions may involve a mixture of acid gastric loss and alkaline duodenal contents and the acid-base situation that results is more variable. Histamine H2-blockers also decrease gastric H+ losses despite continued vomiting or nasogastric drainage and alkalosis will not occur if the fluid lost is not particularly acidic - indeed loss of alkaline small intestinal contents can even result in an acidosis if gastric acid secretion is suppressed.
Diuretics such as frusemide and thiazides interfere with reabsorption of chloride and sodium in the thick ascending limb. Urinary losses of chloride exceed those of bicarbonate. The patients on diuretics who develop an alkalosis are those who are also volume depleted (increasing aldosterone levels) and have a low dietary chloride intake ('salt restricted' diet). Hypokalaemia is common in these patients. If dietary chloride intake is adequate then an alkaosis is unlikely to develop. This is the main reason why every patient taking diuretics such as thiazides or lasix does not develop a metabolic alkalosis. The effect of diuretic use on urinary chloride levels depends on the relationship of the time of urine collection to diuretic effect: it is high while the diuretic is acting, but drops to low levels afterwards.
Villous adenomas typically excrete bicarbonate and can cause a hyperchloraemic metabolic acidosis. Sometimes they excrete chloride predominantly and the result is then a metabolic alkalosis.
Chloride diarrhoea is a rare congenital condition due to an intestinal transport defect, where the chronic faecal chloride loss can (if associated with volume depletion and K+ loss as maintenance factors) result in a metabolic alkalosis.
Without a second mechanism acting to maintain it, the alkalosis would be only transitory.
Why? This is because the kidney normally has a large capacity to excrete bicarbonate and return the plasma level to normal
The four factors that cause maintenance of the alkalosis (by increasing bicarbonate reabsorption in the tubules or decreasing bicarbonate filtration at the glomerulus) are:
* Chloride depletion (most common factor)
* Reduced glomerular filtration rate (GFR)
* Potassium depletion
* ECF volume depletion
Hypoxaemia may occur and oxygen delivery to the tissues may be reduced. Factors involved in impaired arterial oxygen content are:
* Hypoventilation (due respiratory response to metabolic alkalosis)
* Pulmonary microatelectasis (consequent to hypoventilation)
* Increased ventilation-perfusion mismatch (as alkalosis inhibits hypoxic pulmonary vasoconstriction)
Peripheral oxygen unloading may be impaired because of the alkalotic shift of the haemoglobin oxygen dissociation curve to the left. The body’s major compensatory response to impaired tissue oxygen delivery is to increase cardiac output but this ability is impaired if hypovolaemia and decreased myocardial contractility are present.
The need for administration of supplemental oxygen to patients with metabolic alkalosis is a neglected part of therapy.
If hypoventilation is sufficient to cause hypoxaemia, this also may stimulate respiration via the peripheral chemoreceptors. As mentioned above, associated hypoxaemia is probably responsible for variability in the measured arterial pCO2 in patients who also have a sufficiently low arterial pO2. Patients who present with hypoxaemia and hypercapnia may be diagnosed with respiratory failure if the association with metabolic alkalosis is not appreciated. It is usually best in these patients to administer oxygen and to avoid intubation and ventilation.
The expected pCO2 due to appropriate hypoventilation in simple metabolic alkalosis can be estimated from the following formula:
Expected pCO2 = 0.7 [HCO3] + 20 mmHg (range: +/- 5)
Note the wide variation allowed (ie a 10 mmHg range) because of the conflicting factors that affect ventilation (discussed above). This formula is used to determine if a coexistent respiratory acid-base disorder is present. For example, if pCO2 is much lower than expected, a respiratory alkalosis is also present.
The main principles are:
* Correct the primary cause of the disorder
* Correct those factors which maintain the disorder (esp chloride administration)
Repletion of chloride, potassium and ECF volume will promote renal bicarbonate excretion and return plasma bicarbonate to normal.
Must Give Chloride
Hydrochloric Acid Infusion
An infusion of hydrochloric acid (HCl) can be given via a central line. This will selectively correct the deficiency of Cl- and H+ and the infusion can be titrated to an end-point of a specific bicarbonate level. The H+ will consume HCO3- provided the excess CO2 can be ventilated off.
Use of Acetazolamide
Acetazolamide is a carbonic anhydrase inhibitor which has also been used to speed the rapidity of correction of alkalosis. It is usually more readily available than sterile hydrochloric acid solutions and is a more acceptable therapeutic option. It causes renal bicarbonate loss to increase and plasma bicarbonate levels fall. Only one or two doses probably should be used. Some problems with acetazolamide are:
* Renal losses of water, Na+ and K+ increase (so appropriate adjustments in IV fluids and K+ supplementation are necessary)
* It interferes with CO2 transport
* It is slower acting and more difficult to titrate to a given bicarbonate level
Treatment Outline -Metabolic Alkalosis
1. Correct cause if possible (eg correct pyloric obstruction, cease diuretics)
2. Correct the deficiency which is impairing renal bicarbonate excretion (ie give chloride, water and K+)
3. Expand ECF Volume with N/saline (and KCl if K+ deficiency)
4. Rarely ancillary measures such as:
* HCl infusion
* Acetazolamide (one or two doses only)
* Oral lysine hydrochloride
5. Supportive measures (eg give O2 in view of hypoventilation; appropriate monitoring and observation)
6. Avoid hyperventilation as this worsens the alkalaemia