What is lactate dehydrogenase
Lactate dehydrogenase (LDH) is an enzyme involved in energy production that is found in almost all of the body’s cells, with the highest levels found in the cells of the heart, liver, muscles, kidneys, lungs, and in red blood cells; bacteria also produce lactate dehydrogenase. Serum lactate dehydrogenase is elevated in a number of clinical conditions.
Many things can affect lactate dehydrogenase results that are not necessarily a cause for concern. For example:
- Strenuous exercise can cause temporary elevations in lactate dehydrogenase.
- Hemolysis of the blood specimen can cause falsely elevated results. This may happen if the specimen is handled roughly, stored in extreme temperatures, or if the sample was difficult to collect.
- If a person’s platelet count is increased, serum lactate dehydrogenase can be artificially high and not reflective of the lactate dehydrogenase actually present in the circulation.
Lactate dehydrogenase levels
- Normal lactate dehydrogenase value range is 105 to 333 international units per liter (IU/L).
Normal lactate dehydrogenase value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your provider about the meaning of your specific results.
Blood lactate dehydrogenase
Only a small amount of lactate dehydrogenase is usually detectable in the fluid portion of the blood (serum or plasma). Lactate dehydrogenase is released from the cells into the serum when cells are damaged or destroyed. Thus, a lactate dehydrogenase blood level is a non-specific marker for the presence of tissue damage somewhere in the body. By itself, lactate dehydrogenase cannot be used to identify the underlying cause or location of the cellular damage. However, lactate dehydrogenase may be used, in conjunction with other blood tests, to help evaluate for and/or monitor conditions that lead to tissue damage, such as liver or blood diseases or cancer.
Fluid lactate dehydrogenase
Sometimes when there is injury, inflammation, or infection within a specific area of the body, such as the brain, heart or lungs, fluid will accumulate or constituents of the fluid present will change. The level of lactate dehydrogenase present in the fluid may be useful in determining the cause. For example, lactate dehydrogenase is typically high in cerebrospinal fluid when an individual has bacterial meningitis. The lactate dehydrogenase test can also be used, along with other tests, to determine whether fluid accumulation, for example around the heart or lungs or in the abdominal cavity, is due to injury or inflammation (exudate) or due to an imbalance of fluid pressure inside blood vessels and the protein level in blood (transudate).
Lactate dehydrogenase isoenzymes
A test for lactate dehydrogenase isoenzymes is rarely ordered and not widely available nowadays. In the past, the test was used to help diagnose and monitor heart attacks, but it has been replaced by the test for troponin. Though not a routine test, it may be used in differential diagnosis to help determine which organs are likely affected by tissue damage when the cause of an elevated total lactate dehydrogenase is not clear and cannot be determined using other specific tests.
lactate dehydrogenase exists in five different forms called isoenzymes. Although there is some overlap, each of the five lactate dehydrogenase isoenzymes tends to be concentrated in specific body tissues. In general, the isoenzyme locations tend to be:
- Lactate dehydrogenase-1: heart, red cells, kidneys, germ cells
- Lactate dehydrogenase-2: kidneys, red blood cells, lungs, heart (lesser amounts than lactate dehydrogenase-1)
- Lactate dehydrogenase-3: lungs and other tissues
- Lactate dehydrogenase-4: white blood cells, lymph nodes, muscles, liver (lesser amounts than lactate dehydrogenase-5)
- Lactate dehydrogenase-5: liver, skeletal muscle
Determining which isoenzyme is elevated in the blood may give clues to where tissue damage is occurring in the body and/or which organs may be affected.
Lactate dehydrogenase test
Lactate dehydrogenase test measures the level of lactate dehydrogenase in the blood or sometimes other body fluids. The lactate dehydrogenase test can be useful because it can alert a healthcare practitioner that cellular injury is occurring. In a similar fashion, tests such as a C-reactive protein (CRP) warn that inflammation is occurring somewhere in the body.
Red blood cells contain much more lactate dehydrogenase (LDH) than serum. A hemolyzed specimen is not acceptable. Lactate dehydrogenase activity is one of the most sensitive indicators of in-vitro hemolysis. Causes can include transportation via pneumatic tube, vigorous mixing, or traumatic venipuncture.
While increases in serum lactate dehydrogenase also are seen following a heart attack (myocardial infarction), the test has been replaced by the determination of troponin.
Lactate dehydrogenase test is used to investigate a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood.
Lactate dehydrogenase test is also used in monitoring changes in tumor burden after chemotherapy, although, lactate dehydrogenase elevations in patients with cancer are too erratic to be of use in the diagnosis of cancer.
Lactate dehydrogenase normal range
- Age 1-30 days old: 135-750 U/L
- Age 31 days-11 months: 180-435 U/L
- Age 1-3 years: 160-370 U/L
- Age 4-6 years: 145-345 U/L
- Age 7-9 years: 143-290 U/L
- Age 10-12 years: 120-293 U/L
- Age 13-15 years: 110-283 U/L
- Age 16-17 years: 105-233 U/L
- Age > or =18 years: 122-222 U/L
How is lactate dehydrogenase test used?
A lactate dehydrogenase (LDH) test is a non-specific test that may be used in the evaluation of a number of diseases and conditions.
An lactate dehydrogenase blood test may be used:
- As a general indicator of the existence and severity of acute or chronic tissue damage
- To detect and monitor progressive conditions such as anemia, including hemolytic anemia and megaloblastic anemia, or severe infections
- To help stage, determine prognosis, and/or monitor treatment (i.e., chemotherapy) of cancers, such as germ cell tumors (e.g., some types of testicular cancer and ovarian cancer), lymphoma, leukemia, melanoma, and neuroblastoma
An lactate dehydrogenase test is performed on body fluids for a few different reasons:
- To help evaluate cerebrospinal fluid and distinguish between bacterial or viral meningitis
- To evaluate other body fluids such as pleural, peritoneal or pericardial fluid and help determine whether the accumulation of fluid is due to injury and inflammation (exudate) or due to an imbalance of pressure within blood vessels and the amount of protein in the blood (transudate). This information is helpful in guiding treatment.
When is lactate dehydrogenase test ordered?
Blood lactate dehydrogenase test
An lactate dehydrogenase level may be ordered, along with other tests such as a comprehensive metabolic panel (CMP), when a healthcare practitioner suspects that a disease or condition is causing some degree of cellular or tissue damage. If lactate dehydrogenase is elevated, then more specific tests, such as alanine aminotransferase (ALT), aspartate amino transferase (AST) or alkaline phosphatase (ALP), may help diagnose the condition and help determine which organs are involved. Once the acute or chronic problem is diagnosed, total lactate dehydrogenase levels may be ordered at regular intervals to monitor its progress and/or resolution.
Lactate dehydrogenase levels may also occasionally be ordered when an individual has experienced muscle trauma or injury or when a person has signs and symptoms of hemolytic anemia.
Lactate dehydrogenase testing may be ordered on a regular basis when an individual has been diagnosed with cancer.
Body fluid lactate dehydrogenase test
Body fluid lactate dehydrogenase test may be ordered, for example, when a person has signs and symptoms of meningitis or when someone has a buildup of fluid around the heart, lungs or in the abdomen.
What does the lactate dehydrogenase test result mean?
Blood lactate dehydrogenase test
Elevated levels of blood lactate dehydrogenase usually indicate some type of tissue damage. Lactate dehydrogenase levels typically will rise as the cellular destruction begins, peak after some time period, and then begin to fall. lactate dehydrogenase levels are elevated in a wide variety of conditions, reflecting its widespread tissue distribution.
An elevated level of lactate dehydrogenase may be seen with:
- Hemolytic anemia
- Pernicious anemia (megaloblastic anemia)
- Infections such as infectious mononucleosis (mono), meningitis, encephalitis, HIV
- Sepsis
- Intestinal, myocardial (heart) and lung (pulmonary) infarction
- Acute kidney disease
- Acute liver disease
- Acute muscle injury
- Pancreatitis
- Bone fractures
- Testicular cancer, lymphoma or other cancers
- Severe shock
- Lack of oxygen (hypoxia)
A high lactate dehydrogenase in the blood may indicate that treatment for cancer (e.g., chemotherapy) has not been successful. A high level is predictive of a poorer outlook for survival for those with cancer.
With some chronic and progressive conditions, moderately elevated lactate dehydrogenase blood levels may persist.
Low and normal levels of lactate dehydrogenase do not usually indicate a problem. Low levels are sometimes seen when someone ingests large amounts of ascorbic acid (vitamin C).
Body fluids lactate dehydrogenase:
- Cerebrospinal fluid—a high lactate dehydrogenase indicates that meningitis is likely caused by bacteria, while a low or normal level indicates viral meningitis is more likely.
- A high lactate dehydrogenase indicates that pericardial fluid, peritoneal or pleural fluid is an exudate, while a low level indicates it is transudate. Transudates are usually caused by congestive heart failure or cirrhosis. Exudates have several possible causes and usually require additional testing to determine the cause.
Elevated lactate dehydrogenase
Marked elevations in lactate dehydrogenase (LDH) activity can be observed in megaloblastic anemia, untreated pernicious anemia, Hodgkin disease, abdominal and lung cancers, severe shock, and hypoxia.
A higher-than-normal lactate dehydrogenase level may indicate:
- Blood flow deficiency (ischemia)
- Heart attack
- Hemolytic anemia
- Infectious mononucleosis
- Leukemia or lymphoma
- Liver disease (for example, hepatitis)
- Low blood pressure
- Muscle injury
- Muscle weakness and loss of muscle tissue (muscular dystrophy)
- New abnormal tissue formation (usually cancer)
- Pancreatitis
- Stroke
- Tissue death
If your lactate dehydrogenaseH level is high, your provider may recommend an lactate dehydrogenaseH isoenzymes test to determine the location of any tissue damage.
Moderate to slight increases in lactate dehydrogenase levels are seen in myocardial infarction (heart attack), pulmonary infarction, pulmonary embolism, leukemia, hemolytic anemia, infectious mononucleosis, progressive muscular dystrophy (especially in the early and middle stages of the disease), liver disease, and renal disease.
In liver disease, elevations of lactate dehydrogenase are not as great as the increases in aspartate amino transferase (AST) and alanine aminotransferase (ALT).
Increased levels of the enzyme are found in about one-third of patients with renal disease, especially those with tubular necrosis or pyelonephritis. However, these elevations do not correlate well with proteinuria or other parameters of renal disease.
On occasion a raised lactate dehydrogenase level may be the only evidence to suggest the presence of a hidden pulmonary embolus.
Is there anything I can do to lower my lactate dehydrogenase?
No, it is an indicator of injury that will typically return to normal when the underlying condition resolves. If someone has a chronic condition with ongoing tissue damage, such as may occur with liver disease, then increased lactate dehydrogenase concentrations may persist.
Lactate dehydrogenase deficiency
Lactate dehydrogenase deficiency also called metabolic muscle disorder, is a rare inherited disorder that affects how the body breaks down carbohydrates to use as energy in cells, primarily muscle cells. In Japan, lactate dehydrogenase deficiency affects 1 in 1 million individuals; the prevalence of lactate dehydrogenase deficiency in other countries is unknown.
There are two types of this condition 1:
- Lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and
- Lactate dehydrogenase-B deficiency
People with lactate dehydrogenase-A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). In some people with lactate dehydrogenase-A deficiency, high-intensity exercise or other strenuous activity leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Some people with lactate dehydrogenase-A deficiency develop skin rashes. The severity of the signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly.
People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not have difficulty with physical activity or any specific physical features related to the condition. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity.
Lactate dehydrogenase deficiency has its onset in early adulthood and does not progress 2.
Lactate dehydrogenase deficiency causes
Mutations in the LDHA gene cause lactate dehydrogenase-A deficiency, and mutations in the LDHB gene cause lactate dehydrogenase-B deficiency. These genes provide instructions for making the lactate dehydrogenase-A and lactate dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four protein subunits. Various combinations of the lactate dehydrogenase-A and lactate dehydrogenase-B subunits make up the different forms of the enzyme.
The version of lactate dehydrogenase made of four lactate dehydrogenase-A subunits is found primarily in skeletal muscles, which are muscles used for movement. Skeletal muscles need large amounts of energy during high-intensity physical activity when the body’s oxygen intake is not sufficient for the amount of energy required (anaerobic exercise). During anaerobic exercise, the lactate dehydrogenase enzyme is involved in the breakdown of sugar stored in the muscles (in the form of glycogen) to create additional energy. During the final stage of glycogen breakdown, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate.
Mutations in the LDHA gene result in the production of an abnormal lactate dehydrogenase-A subunit that cannot attach (bind) to other subunits to form the lactate dehydrogenase enzyme. A lack of functional subunit reduces the amount of enzyme that is formed, mostly affecting skeletal muscles. As a result, glycogen is not broken down efficiently, leading to decreased energy in muscle cells. When muscle cells do not get sufficient energy during exercise or strenuous activity, the muscles become weak and muscle tissue can break down, as experienced by people with lactate dehydrogenase-A deficiency.
The version of lactate dehydrogenase made of four lactate dehydrogenase-B subunits is found primarily in heart (cardiac) muscle. In cardiac muscle, lactate dehydrogenase converts lactate to pyruvate, which can participate in other chemical reactions to create energy. LDHB gene mutations lead to the production of an abnormal lactate dehydrogenase-B subunit that cannot form the lactate dehydrogenase enzyme. Even though lactate dehydrogenase activity is decreased in the cardiac muscle of people with lactate dehydrogenase-B deficiency, they do not appear to have any signs or symptoms related to their condition. It is unclear why this type of enzyme deficiency does not cause any health problems.
Lactate dehydrogenase deficiency inheritance pattern
Lactate dehydrogenase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
It is rare to see any history of autosomal recessive conditions within a family because if someone is a carrier for one of these conditions, they would have to have a child with someone who is also a carrier for the same condition. Autosomal recessive conditions are individually pretty rare, so the chance that you and your partner are carriers for the same recessive genetic condition are likely low. Even if both partners are a carrier for the same condition, there is only a 25% chance that they will both pass down the non-working copy of the gene to the baby, thus causing a genetic condition. This chance is the same with each pregnancy, no matter how many children they have with or without the condition.
- If both partners are carriers of the same abnormal gene, they may pass on either their normal gene or their abnormal gene to their child. This occurs randomly.
- Each child of parents who both carry the same abnormal gene therefore has a 25% (1 in 4) chance of inheriting a abnormal gene from both parents and being affected by the condition.
- This also means that there is a 75% ( 3 in 4) chance that a child will not be affected by the condition. This chance remains the same in every pregnancy and is the same for boys or girls.
- There is also a 50% (2 in 4) chance that the child will inherit just one copy of the abnormal gene from a parent. If this happens, then they will be healthy carriers like their parents.
- Lastly, there is a 25% (1 in 4) chance that the child will inherit both normal copies of the gene. In this case the child will not have the condition, and will not be a carrier.
These possible outcomes occur randomly. The chance remains the same in every pregnancy and is the same for boys and girls.
Figure 1 illustrates autosomal recessive inheritance. The example below shows what happens when both dad and mum is a carrier of the abnormal gene, there is only a 25% chance that they will both pass down the abnormal gene to the baby, thus causing a genetic condition
Figure 1. Lactate dehydrogenase deficiency autosomal recessive inheritance pattern
Lactate dehydrogenase deficiency treatment
For many people with metabolic muscle diseases, the only treatment needed is to understand what activities and situations tend to trigger attacks of rhabdomyolysis. In addition, some people with metabolic disorders have benefited from dietary changes. For instance, there is evidence that those with carbohydrate-processing problems may be helped by a high-protein diet, while those with difficulty processing fats may do well on a diet high in carbohydrates and low in fat 3.
We encourage you to consult with your healthcare provider for more information about management of lactate dehydrogenase A deficiency. A professional staff member through a Muscular Dystrophy Association (http://www.mdausa.org/) clinic can also help you design a specific plan suited for your metabolic disorder and individual needs.
References
