Disorders, in which arterial pH and partial pressure of carbon dioxide (Pco2) with serum bicarbonate (HCO3−) levels are disturbed abnormally, are called Acid Base Disorders.
- State of blood in which pH is < 7.35 is Acidemia.
- State of blood with serum pH > 7.45 is taken as alkalemia.
All those processes in which acid accumulation or alkali loss leads to decrease of pH fall in Acidosis. Alkalosis includes all the processes or a condition in which alkali production is increased, or the acid is lost in one way or the other.
Physiologic compensatory mechanisms are activated in the body; pH change depends on the degree of these compensatory mechanisms.
On the basis of clinical and the primary mechanism of change in pH, i.e. due to the change in serum HCO3− or in Pco2, the primary disorder in acid-base balance can be:
Metabolic acidosis and metabolic alkalosis are caused by an imbalance in the production of acids or bases and their excretion by the kidneys.
Respiratory acidosis and respiratory alkalosis are caused primarily by changes in carbon dioxide exhalation due to lung or breathing disorders.
If serum HCO3− is less than 24 mEq/L, it will be labeled as metabolic acidosis. The body compensates by hyperventilation, i.e. the rate of breathing increases and CO2 is lost from the body. The body tries to maintain pH though compensatory mechanisms.
Before discussing the causes of acidosis, we need to know about anion gap.
Anion gap: It is the sum of concentration of all the major cations (sodium + potassium ion concentration) minus the sum of concentration of all the anions (chloride + bicarbonate ions). Positive ions are more in concentration than the negative ions by roughly 14 mmol/L. The normal anion gap is 8-16 mmol/L when not including potassium in the equation, and 10-20 mmol/L when including potassium.
The anion gap exists because there are more unmeasured anions (mostly albumin, but others include lactate and sulfate) than cations (includes calcium and magnesium).
Metabolic acidosis is divided into increased and normal anion gap.
- Increased anion gap:
- Lactic acidosis: shock, infection, hypoxia.
- Renal failure.
- Raised ketones (diabetes mellitus (DKA), alcohol).
- Drugs or toxins: salicylates, metformin, ethylene glycol, methanol, cyanide.
- Normal anion gap (due to loss of bicarbonate or ingestion hydrogen ions):
- Renal tubular acidosis.
- Addison’s disease.
- Pancreatic fistulae.
- Drugs or toxins: acetazolamide, ammonium chloride
DKA is a complication of uncontrolled type I diabetes mellitus in which surplus ketone bodies are produced as a result of gluconeogenesis.
Lactic acidosis is due to surplus lactic acid production in the body as a result of:
- Prolonged exercise and lack of oxygen
- Low blood sugar, or hypoglycemia
- Alcohol use
- Liver failure
- Severe dehydration or shock
Hyperchloremic acidosis occurs after the loss of bicarbonate through the stools in severe watery diarrhea.
In mild metabolic acidosis, people may have no symptoms but usually experience:
Kussmaul breathing is a typical breathing pattern in metabolic acidosis i.e. deeper and slightly faster (the body tries to correct acidosis by removing CO2). In extreme cases, cardiac issues may develop and the blood pressure falls, leading to shock, coma and even death.
If the arterial blood gas and electrolyte shows alkalemia and serum HCO3− is more than 24 mEq/L, it will be labeled as metabolic alkalosis.
- Hypokalaemia – e.g., diuretics. See also the separate article on Hypokalaemic Alkalosis.
- Excessive alkali drugs, such as for acid dyspepsia.
A major cause of metabolic alkalosis is the loss of stomach acid after persistent vomiting.
The body compensates by reducing the respiratory rate and retaining CO2, which tries to maintain body pH.
Respiratory acidosis is a state of the body in which partial pressure of the CO2 is more than 40 mm Hg (hypercapnia), along with acidic arterial pH.
- Acute Onset Acidosis:
- Depression of the central respiratory center by cerebrovascular disease or drugs. (Comma)
- Inability to ventilate adequately due to neuromuscular disease e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome (GBS,) muscular dystrophy.
- Airway obstruction related to asthma or exacerbation of chronic obstructive pulmonary disease (COPD).
- Chronic Onset Acidosis:
Chronic respiratory acidosis can occur secondary to COPD, obesity hypoventilation syndrome (Pickwickian syndrome), neuromuscular disorders and restrictive ventilatory defects, such as in interstitial fibrosis or thoracic deformities.
When Pco2 falls below 40 mm Hg (hypocapnia) along with alkalemia in the arterial blood, it is called respiratory alkalosis.
Increase in minute ventilation (persistent hyperventilation) due to any cause like anxiety, stroke, meningitis, altitude and pregnancy can lead to respiratory alkalosis.
Diagnosis of Acid Base Disturbance
For the diagnosis of acidosis or alkalosis, the following investigations are needed:
- Arterial blood Gasses – ABG with pH, Pco2, Po2
- Serum electrolytes
- Anion gap calculated
The ABG directly measures arterial pH and Pco2. In case of CVS failure, venous blood gasses VBG may more accurately reflect conditions at the tissue level, and may be a more useful guide to bicarbonate administration and adequacy of ventilation.
Renal Tubular Acidosis
Renal tubular acidosis (RTA) is a type of acidosis in which an electrolyte disturbance in the body occurs leading to a chronic metabolic acidosis with a normal anion gap. RTA can occur after abnormal renal H+ ion excretion (type 1 RTA) or impaired bicarbonate resorption (type 2 RTA), or abnormal aldosterone production or response (type 4 RTA). Type 3 RTA is a very rare condition, so it is not discussed. RTA, if not managed properly, can complicate into chronic renal failure CRF.
Type I – Distal RTA
H+ ion secretion in the DCT is impaired in type I RTA, resulting in a high urine pH (>5.5) and metabolic acidosis. In distal RTA, serum HCO3 <15 mEq/L along with hypokalemia, hypercalciuria, and decreased citrate excretion. Nephrocalcinosis and nephrolithiasis are possible complications and presentation of many patients of distal RTA.
It can be primary or secondary; familial cases manifest in childhood and are autosomal dominant AD. Secondary causes include:
- Autoimmune disease with hypergammaglobulinemia, particularly Sjögren syndrome or RA
- Kidney transplantation
- Medullary sponge kidney
- Chronic obstructive uropathy
- Drugs (mainly amphotericin B, ifosfamide and lithium)
- Sickle cell anemia
Type 2 (Proximal) RTA
The main etiology behind this is the inability to reabsorb bicarbonate in the PCT with urine pH > 7 if plasma bicarbonate concentration is normal, and urine pH < 5.5 if plasma bicarbonate concentration is already depleted due to ongoing losses. These patients can have an increased urinary excretion of glucose, uric acid, phosphate, amino acids, citrate, calcium, potassium and proteins as well. Patients develop osteomalacia or osteopenia (rickets in children). Hypercalciuria, hyperphosphaturia, disturbed Vitamin D metabolism and secondary hyperparathyroidism are the major complications.
- Fanconi syndrome
- Light chain nephropathy due to multiple myeloma
- Various drug exposures (usually acetazolamide, sulfonamides, ifosfamide, outdated tetracycline or streptozocin)
Type 4 RTA
Aldosterone deficiency or loss of sensitivity of DCT to aldosterone is the main cause of type 4 RTA. Reduced potassium excretion leads to hyperkalemia and reduced acid excretion leading to metabolic acidosis. This is the most common type of RTA. It secondary to impairment in the renin-aldosterone-renal tubule axis in:
Other factors that can contribute to type 4 RTA include the following:
- ACE inhibitor use
- Aldosterone synthase type I or II deficiency
- Angiotensin II receptor blocker use
- Chronic kidney disease, usually due to diabetic nephropathy or chronic interstitial nephritis
- Congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency
- HIV nephropathy (due, possibly in part, to infection with Mycobacterium avium complex or cytomegalovirus)
- Interstitial renal damage (e.g., due to SLE, obstructive uropathy or sickle cell disease)
- Potassium-sparing diuretics (e.g, amiloride, eplerenone, spironolactone, triamterene)
- Obstructive uropathy
- Primary adrenal insufficiency
- Pseudohypoaldosteronism (type I or II)
- Volume expansion (e.g., in acute glomerulonephritis or chronic kidney disease)
Different Types of Renal Tubular Acidosis
|Feature||Type 1||Type 2||Type 4|
|Mechanism||Impaired hydrogen ion excretion||Impaired bicarbonate resorption||Decrease in aldosterone secretion or activity|
|Plasma bicarbonate (mEq/L)||Frequently <15, occasionally < 10||Usually 12–20||Usually > 17|
|Plasma potassium||Usually low but tends to normalize with alkalinization||Usually low and decreased further by alkalinization||High|
|Urine pH||> 5.5||> 7 if plasma bicarbonate is normal
< 5.5 if plasma bicarbonate is depleted (e.g., <15 mEq/L)