Acid-Base Balance

An acid is any compound that can donate H+ when dissolved in water. A base is any compound that can donate OH- ions. A buffer system is a combination of a weak acid or base and its salt or conjugate that resists changes in pH. The human body has incredible mechanisms to maintain an acid-base balance. Changes in pH put the body in different physiological states that can cause an array of problems. Acidosis is when the pH falls below the reference range of 7.34. Alkalosis is when the pH increases above the reference range of 7.44.


The most important buffer system in the body is the bicarbonate (HCO3)/carbonic acid (H2CO3) system. Carbonic acid works to allow the human body to rid of toxic CO2 via respiration to maintain a normal pH of 7.4. There normally is a 20:1 ratio of bicarbonate to carbonic acid.

The red cells pick up CO2 from tissues and throughout its travel through the blood vessel its converted to carbonic acid. That carbonic acid is then broken down into bicarbonate and hydrogen. The excess hydrogen ions are buffered by hemoglobin. Bicarbonate leaves the red cell and goes into circulation. Bicarbonate enters the plasma through an exchange mechanism with chloride to maintain a state of electroneutrality in the cell. When the red cells reach the lung the hemoglobin will release the excess hydrogen ions by the binding of oxygen to hemoglobin. The excess hydrogen ions bind to bicarbonate to form carbonic acid. Carbonic acid then dissociates into H20 and CO2 which is expelled.

As mentioned above, an individual can be in a state of acidosis or alkalosis. This can be caused by ventilation and is called respiratory acidosis or respiratory alkalosis or it can either be caused by HCO3-. This is called metabolic acidosis or alkalosis.

Respiratory acidosis is an increase in PCO2. Conversely respiratory alkalosis is a decrease in PCO2. Metabolic acidosis is a loss of HCO3- or an addition of H+. Metabolic alkalosis is a loss of H+ or an increase of HCO3-. The body will naturally compensate for the pH changes. Some of the compensatory mechanisms are increasing respiration in metabolic acidosis. Hyperventilation increases the amount of CO2 that is expelled and raising the pH. In respiratory acidosis the kidney will increase its reabsorption of HCO3-.

Metabolic acidosis can be caused by multiple different disease states. Excessive loss of HCO3- by diarrhea can cause metabolic acidosis. Diabetic ketoacidosis can cause it. Other causes are ingestion of acids or renal tubular failure where there is no renal reabsorption of HCO3-.

Metabolic alkalosis is caused by excess or an overdose of HCO3-. Excessive vomiting causes a loss of hydrochloric acid with the stomach contents. Vomiting also results in hypokalemia and hyponatremia which are both positively charged ions (acids) leading to an increase in the pH. Excessive diuretic use can sometimes initially cause an increase in chloride, but most commonly results in hyponatremia and causing a contractile alkalosis.

Respiratory acidosis is most commonly caused by CO2 retention usually due to ventilation failure. Decreased cardiac output and hypotension also cause acidosis. Less blood is pumped to the heart so less CO2 is getting transported to the lungs to be expelled. Chronic lung conditions such as COPD result in an inability to ventilate properly and to expel CO2. Certain drugs cause depression of the respiratory center in the brain and can cause respiratory acidosis. Some of these drugs are barbiturates, opiates and ethanol (alcohol).

Respiratory alkalosis is primarily caused by hyperventilation (increased alveolar ventilation). This results in a decreased arterial PCO2. Any condition which decreases pulmonary compliance causes a sensation of dyspnea. Dyspnea is not a single sensation and there are at least three distinct sensations including air hunger, work/effort, and chest tightness. These sensations cause a state of hypoxia which is caused by the hyperventilation.



Lactate Dehydrogenase

Lactate dehydrogenase (LD, LDH) is an enzyme that is found in all cells in all tissues of the body. It catalyzes the reversible conversion of lactate to pyruvic acid in glycolysis and gluconeogenesis. It is released from various anatomical sites of the body in response to cellular injury and damage. It is used as a common marker for tissue damage and disease such as heart failure. Its down-fall is that it isn’t very specific to which tissue is damaged, but there are subtle hints that can clue a physician in particular directions.

Lactate dehydrogenase is structurally composed of four subunits, but the two common subunits are LDHA known as LDH-M, and LDHB, known as LDH-H. The only difference between the two subunits is that their is an amino acid substitution of alanine with glutamine within the H subunit. This amino acid change slightly changes the biochemical properties of the two subunits slightly in that the H subunit can bind faster, but the catalytic activity of the M subunit does not deteriorate at the same rate as the H subunit, it holds well.


The two subunit of LDH can form five isomers which are found in various sites within the body;

LDH-1 (4H)- Found in the heart, RBCs, and the brain.

LDH-2 (3H1M)- Found in the RES.

LDH-3 (2H2M)- Found in the lungs.

LDH-4 (1H3M)- Found in the kidneys, placenta, and the pancreas.

LDH-5 (4M)- Found in the liver and striated muscle.

LDH is a protein that is found in small amounts normally in the body and there are various conditions that can cause an elevation. Cancer can raise the LDH levels within the body. Cancer cells rely on increased glycolysis due to their high energy demand. LDH elevation in cancer is often times referred to the Warburg effect which allows malignant cells to convert glucose stores into lactate even in the presence of aerobic respiration. This shifts glucose metabolism from simple energy production to accelerate cell growth and proliferation.

Hemolysis can be measured as LDH is abundant in RBCs and can be measured. Although measures should be taken to correctly receive the sample as incorrect procedures an cause hemolysis and a false-positive elevation in LDH levels among other substrates and electrolytes.

It can also be used as a marker for myocardial infarction. Normally LDH-2 is at a higher level than LDH-1. When someone experiences a myocardial infarction, levels of LDH-1 will be significantly elevated to a level higher than LDH-2. This is known as the LDH flip and is diagnostic in patients who have experienced myocardial infarction. Elevation of LDH peaks 3-4 days after MI, and can remain elevated for up to 10 days. LDH has since been replaced by the troponin test, which is a much more specific and sensitive test in diagnosing MI.

High levels of LDH in the cerebrospinal fluid (CSF) can indicate bacterial meningitis. Elevated LDH levels in viral meningitis is indicative of a poor prognosis.

LDH is an important tool that physicians don’t always utilize to its lack of specificity, but it can still be helpful in a diagnosis. Its important not to ignore any test and any result as it still contributes to the whole picture.