METABOLIC MEDICINE MADE SIMPLE : METABOLIC ACIDOSIS

METABOLIC ACIDOSIS

Metabolic acidosis is a sinister acid base disorder in which there is accumulation of excessive acid in the blood and body tissues.It is a serious and life threatening condition

PATHOPHYSIOLOGY OF METABOLIC ACIDOSIS

OCCURS DUE TO THREE MAIN MECHANISMS:

1. EXCESSIVE PRODUCTION OF ACID IN THE BODY

2. LOSS OF ACID BUFFERING SYSTEM WHICH IS LACK OF BICARBONATE IN THE BODY

3 . INABILITY OF KIDNEYS TO GET RID OF EXCESSIVE ACID FROM THE BODY

PATHOPHYSIOLOGY

Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35

Acute metabolic acidosis, lasting from minutes to several days, often occurs during serious illnesses or hospitalizations, and is generally caused when the body produces an excess amount of organic acids (ketoacids or lactic acid).

Chronic metabolic acidosis, lasting several weeks to years, can be the result of impaired kidney function (Chronic Kidney Disease) and/or bicarbonate wasting.

CAUSES OF METABOLIC ACIDOSIS

There are several types of metabolic acidosis:

Diabetic acidosis (also called diabetic ketoacidosis and DKA) develops when substances called ketone bodies (which are acidic) build up during uncontrolled diabetes.

Hyperchloremic acidosis is caused by the loss of too much sodium bicarbonate from the body, which can happen with severe diarrhea.

Kidney disease (uremia, distal renal tubular acidosis or proximal renal tubular acidosis).

Lactic acidosis.

Poisoning by aspirin, ethylene glycol (found in antifreeze), or methanol.

Severe dehydration.

MECHANISM OF METABOLIC ACIDOSIS

Metabolic acidosis is characterized by a low concentration of bicarbonate (HCO−3), which can happen with increased generation of acids (such as ketoacids or lactic acid), excess loss of HCO-3 by the kidneys or gastrointestinal tract, or an inability to generate sufficient HCO−3.

 

The body regulates the acidity of the blood by four buffering mechanisms.

Bicarbonate buffering system.

Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.

Respiratory compensation. Hyperventilation will cause more carbon dioxide to be removed from the body and thereby decrease pH.

Kidney compensation

SYMPTOMS OF METABOLIC ACIDOSIS

Symptoms

Most symptoms are caused by the underlying disease or condition that is causing the metabolic acidosis.

Metabolic acidosis itself most often causes rapid breathing.

Acting confused or very tired may also occur.

Severe metabolic acidosis can lead to shock or death.

In some situations, metabolic acidosis can be a mild, ongoing (chronic) condition.

INVESTIGATIONS

These tests can help diagnose acidosis. They can also determine whether the cause is a breathing problem or a metabolic problem. Tests may include:

 

Arterial blood gas

Basic metabolic panel, (a group of blood tests that measure your sodium and potassium levels, kidney function, and other chemicals and functions)

Blood ketones

Lactic acid test

Urine ketones

Urine pH

Other tests may be needed to determine the cause of the acidosis.

MANAGEMENT OF METABOLIC ACIDOSIS

Treatment of metabolic acidosis depends on the underlying cause, and should target reversing the main process.

 

When considering course of treatment, it is important to distinguish between acute versus chronic forms.

Bicarbonate therapy is generally administered In patients with severe acute acidemia (pH < 7.11), or with less severe acidemia (pH 7.1-7.2) who have severe acute kidney injury.

Bicarbonate therapy is not recommended for people with less severe acidosis (pH ≥ 7.1), unless severe acute kidney injury is present.

In the BICAR-ICU trial,bicarbonate therapy for maintaining a pH >7.3 had no overall effect on the composite outcome of all-cause mortality and the presence of at least one organ failure at day 7.

However, amongst the sub-group of patients with severe acute kidney injury, bicarbonate therapy significantly decreased the primary composite outcome, and 28-day mortality, along with the need for dialysis.

Currently, the most commonly used treatment for chronic metabolic acidosis is oral bicarbonate.

The NKF/KDOQI guidelines recommend starting treatment when serum bicarbonate levels are <22 mEq/L, in order to maintain levels ≥ 22 mEq/L.

 Studies investigating the effects of oral alkali therapy demonstrated improvements in serum bicarbonate levels, resulting in a slower decline in kidney function, and reduction in proteinuria – leading to a reduction in the risk of progressing to kidney failure.

However, side effects of oral alkali therapy include gastrointestinal intolerance, worsening edema, and worsening hypertension.

 Furthermore, large doses of oral alkali are required to treat chronic metabolic acidosis, and the pill burden can limit adherence.

Veverimer (TRC 101) is a promising investigational drug designed to treat metabolic acidosis by binding with the acid in the gastrointestinal tract and removing it from the body through excretion in the feces, in turn decreasing the amount of acid in the body, and increasing the level of bicarbonate in the blood