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Lactic acidosis: Causes, Types, Symptoms and Treatment

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  • Clinical Chemistry
  • 2020-10-19 22:22:55

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lactic acidosis is a serum lactate concentration above 4 mmol/L. It is the most common cause of metabolic acidosis among hospitalized patients. It occurs due to excessive production of lactic acid or a decreased excretion or sometimes both. This derangement is a high anion gap metabolic acidosis secondary to elevated blood lactate.

Lactic acidosis is one of the four principal causes of a high-AG acidosis. Other causes include; ketoacidosis, acute and chronic renal failure and toxins.

What is lactic acid?

Lactate is a normal byproduct of glucose and amino acid metabolism. lactic acid is a carbohydrate within cellular metabolism whose levels rise with an increase in the metabolism rate during exercise and with catecholamine secretion.

Glucose-6-phosphate is converted anaerobically to pyruvate via the pathway known as Embden-Meyerhof. In this pathway, Pyruvate is in equilibrium with lactate with a ratio of about 25 lactate molecule to 1 pyruvate molecule. Therefore, lactate is the endpoint of the anaerobic metabolism of glucose in the tissues.

The lactate then gets out of the cells and is transported to the liver, where it undergoes oxidation to form pyruvate and then it is converted back to glucose via the Cori cycle.

Lactic acid is known to exist in two optical isomeric forms, that is, L-lactate and D-lactate.

Of the two, L-lactate is the most commonly measured level, as it is the only form that is produced in human metabolism. Whenever the level of L-Lactate is high, it represents an increased anaerobic metabolism due to tissue hypoperfusion.

On the other hand, D-lactate is a byproduct of bacterial metabolism. This form can occur in excess in patients with short-gut syndrome or in those patients who have an history of gastric bypass  surgery.

What are the types of lactic acidosis?

Lactic acidosis is divided into two types according to Cohen and Woods

  1. Type A, tissue hypoperfusion
  2. Type B, non-hypoxic

Type A lactic acidosis

Type A (tissue hypoperfusion lactic acidosis) occurs in association with clinical evidence of poor tissue perfusion or oxygenation of blood such as, hypotension, cyanosis, cool and mottled extremities. This poor tissue perfusion is caused by shock such as septic shock, severe anaemia, severe hypoxia, excess catecholamine release or excess exercise.

Generally this type occurs due to tissue hypoxia and peripheral generation of lactate, such as the one in patients with circulatory failure and shock.

This type can be caused by the overproduction of lactate or the underutilization of the produced  lactate. Circulatory, pulmonary, and hemoglobin transfer disorders are are the ones responsible in the  cases of overproduction whereas liver disease, inhibition of gluconeogenesis and thiamine deficiency are responsible for the cases of underutilization of lactate.

Type B lactic acidosis

Type B lactic acidosis (non hypoxic lactic acidosis) occurs due to an impaired metabolism of lactate. This impairment occurs in conditions such as sepsis with mitochondrial impairment, renal failure, liver disease, uncontrolled diabetes mellitus, cancer such as leukemia and lymphoma, acute pancreatitis or thiamine deficiency.

This one can also be caused by a number of drugs and toxins, such as metformin, that work by inhibiting lactate metabolism.

Type B is lactic acidosis occurring when there is no any clinical evidence of poor tissue perfusion or oxygenation.

There are three subtypes of type 3 lactic acidosis based on underlying etiology.

  1. Type B1 is associated withsystemic disease, like renal failure and hepatic failure, diabetes mellitus and malignancy. 
  2. Type B2 results due todrugs and toxins, such as biguanides, alcohols,isoniazid, zidovudine, iron, and salicylates.
  3. Type B3 occursdue to inborn errors of metabolism.

Septic shock may move from category A to type B. this is because the initial presentation is usually associated with hypoperfusion, and with aggressive fluid resuscitation there is little evidence of tissue hypoperfusion but lactic acidosis often persists because of an  altered oxidative phosphorylation and leukocyte production of lactate caused by sustained increased inflammatory stimuli

Causes of lactic acidosis

Like it was mentioned above,increased anion gap  metabolic acidosis is most commonly seen in renal failure, ketoacidosis, and lactic acidosis. This is because there is an endogenous production of anions that are distinct from chloride ions and hidrogen carbonate ions.

Ketoacidosis is caused by insulin deficiency and is exacerbated by catecholamine and stress hormone excess, which combine to cause lipolysis and the formation of acidic ketones (acetoacetate, 3-hydroxybutyrate and acetone).

Starvation ketoacidosis occurs when there is reduced food intake in situations of high glucose demand, such as in neonates, and in pregnant or breastfeeding women. In alcoholic ketoacidosis, there is usually a background of chronic malnutrition and a recent alcohol binge.

Unrecognized bowel ischemia or infarction in a patient with severe atherosclerosis or cardiac decompensation receiving vasopressors is a common cause of lactic acidosis.

Pyroglutamic acidemia has been reported in critically ill patients receiving acetaminophen, which is  associated with depletion of glutathione. d-Lactic acid acidosis, which may be associated with jejunoileal bypass, short bowel syndrome, or intestinal obstruction, is due to formation of d-lactate by gut bacteria.

in tissues where sequestered parasites interfere with microcirculatory flow,lactate production by the parasites, and a failure of hepatic and renal lactate clearance. The prognosis of severe acidosis is poor.

Drugs causing lactic acidosis

Drug induced lactic acidosis results from drugs such as paracetamol  overdose, salycylate, metformin, methanol, ethanol, ethylene glycol, or cyanide.

Other causes are:

Hereditary enzyme defects, such as glucose 6 phosphate deficiency and fructose-,6- diphosphate deficiency,

Heat stroke. This is a very severe and potentially life-threatening condition where patients lose the ability to remove heat from the body because of the impairment in their ability to sweat. This makes body temperature to be severely elevated up to above 41°C, causing  confusion, disorientation, blurred vision, and seizures. In this condition there is a serious derangement in lab values such as hemoconcentration, rhabdomyolysis, and elevated BUN. Anuria, and diseminated intravascular coagulation may eventually develop.

Here are examples of drugs and toxins that are known to cause type B2 lactic acidosis,

  • Paracetamol (Acetaminophen)
  • Alcohols and glycols such as methanol, ethanol, ethylene glycoland, propylene glycol
  • Antiretroviral nucleoside analogs such as zidovudine, didanosine, lamivudineand zalcitabine.
  • Beta-adrenergic agents ie epinephrine, ritodrine, terbutaline
  • Biguanides ie metformin and phenformin
  • Diethyl ether
  • 5-Fluorouracil
  • Cocaine
  • Halothane
  • Iron
  • Isoniazid
  • Propofol
  • Sugars and sugar alcohols (fructose, sorbitol, and xylitol)
  • Salicylates
  • Cyanogenic compounds
  • Strychnine
  • Sulfasalazineand
  • Valproic acid

Signs and symptoms
 

The onset of acidosis may be rapid or progressive.

It usually occurs during strenuous exercise among healthy people,with no consequence.

However, development of lactic acidosis in disease states indicates a critical illness with recent onset. Therefore, the clinician should take a careful history to evaluate the underlying cause of shock which contributed to lactic acidosis.

A detailed history of drug of toxin ingestion should also be obtained.

The signs and symptoms of lactic acidosis are depend on the underlying cause.

Lactic acidosis is usually present in patients who are critically ill from hypovolemic shock, septic shock, or cardiogenic shock. It should be suspected in the presence of elevated anion gap metabolic acidosis.

From pharmacology, Lactic acidosis is a serious complication of antiretroviral therapy. Therefore you will need to obtain a history of antiretroviral treatment.

lactic acidosis,is aunique form of lactic acidosis, that can occur in patients with jejunoileal bypass or small bowel resection causing what is known as short bowel syndrome. In these patients, the glucose and car

References

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