LD 4 (or LDH-4)

check icon Optimal Result: 5 - 13 %.

When illness or injury damages your cells, LDH may be released into the bloodstream, causing the level of LDH in your blood to rise.

LDH-4: liver and skeletal muscle

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Measuring LDH acan be a useful tool for doctors when evaluating and treating certain medical conditions. Normal ranges vary with age. As scientists continue to learn more about the role of LDH in the body, the usefulness of monitoring LDH levels in certain diseases and conditions will likely increase.

What is lactate dehydrogenase?

Lactate dehydrogenase (LDH) is an enzyme required during the process of turning sugar into energy for your cells. LDH is present in many kinds of organs and tissues throughout the body, including the liver, heart, pancreas, kidneys, skeletal muscles, lymph tissue, and blood cells.

When illness or injury damages your cells, LDH may be released into the bloodstream, causing the level of LDH in your blood to rise. High levels of LDH in the blood point to acute or chronic cell damage, but additional tests are necessary to discover its cause. Abnormally low LDH levels only rarely occur and usually aren’t considered harmful.

What are the types of LDH isoenzymes?

There are five different forms of LDH that are called isoenzymes. They are distinguished by slight differences in their structure.

The isoenzymes of LDH are LDH-1, LDH-2, LDH-3, LDH-4, and LDH-5.

Different LDH isoenzymes are found in different body tissues.

The areas of highest concentration for each type of isoenzyme are:

LDH-1: heart and red blood cells
LDH-2: heart and red blood cells
LDH-3: lymph tissue, lungs, platelets, pancreas
LDH-4: liver and skeletal muscle
LDH-5: liver and skeletal muscle

Typical ranges for LDH levels:

LDH levels vary based on age and the individual laboratory. Infants and young children will have much higher normal LDH levels than older children or adults. LDH is often reported in units per liter (U/L). In general, normal ranges for LDH levels in the blood are as follows:

Age Normal LDH level
0 to 10 days 290–2000 U/L
10 days to 2 years 180–430 U/L
2 to 12 years 110–295 U/L
Older than 12 years 100–190 U/L

Links:

Clinical laboratory tests: Normal values. (2017). apps.mcc.ca/objectives_online/objectives.pl?lang=english&loc=values

Faloppi L, et al. (2016). The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy. -- ncbi.nlm.nih.gov/pmc/articles/PMC4827080/

Lactate dehydrogenase deficiency. (2015). ghr.nlm.nih.gov/condition/lactate-dehydrogenase-deficiency

Lactate dehydrogenase isoenzymes. (n.d.). urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=lactate_dehydrogenase_isoenzymes

LD. (2016). labtestsonline.org/understanding/analytes/ldh/tab/test

Mecabo G, et al. (2015). Lactate dehydrogenase isoenzyme 3 and hemolysis in sickle cell anemia: a possible correlation? bloodjournal.org/content/125/24/3821?sso-checked=true

TABLE 27.1: REFERENCE VALUES | Harriet Lane Handbook. (n.d.). unboundmedicine.com/harrietlane/view/Harriet_Lane_Handbook/309269/all/TABLE_27_1:_Reference_Values

References:

Rotenberg Z, Davidson E, Weinberger I, Fuchs J, Sperling O, Agmon J. The efficiency of lactate dehydrogenase isoenzyme determination for the diagnosis of acute myocardial infarction. Arch Pathol Lab Med. 1988; 112(9):895-897. PubMed 3415440

Loughlin JF, Krijnen PM, Jablonsky G, Leung FY, Henderson AR. Diagnostic efficiency of four lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction. Clin Chem. 1988 Oct; 34(2):1960-1965. PubMed 3168204

Rotenberg Z, Weinberger I, Sagie A, Fuchs J, Sperling O, Agmon J. Lactate dehydrogenase isoenzymes in serum during unstable angina. Clin Chem. 1986 Aug; 32(8):1566-1567. PubMed 3731454

Jablonsky G, Leung FY, Henderson AR. Changes in the ratio of lactate dehydrogenase isoenzymes 1 and 2 during the first day after acute myocardial infarction. Clin Chem. 1985 Oct; 31(10):1621-1624. PubMed 4042327

Rotenberg Z, Weinberger I, Sagie A, Fuchs J, Sperling O, Agmon J. Lactate dehydrogenase isoenzymes in serum during recent acute myocardial infarction. Clin Chem. 1987 Aug; 33(8):1419-1420. PubMed 3608159

Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction. Clin Chem. 1988 Jun, 34(6):1096-1098. PubMed 3378325

Jacobs DS, Robinson RA, Clark GM, Tucker JM. Clinical significance of the isomorphic pattern of the isoenzymes of serum lactate dehydrogenase. Ann Clin Lab Sci. 1977 Sep-Oct; 7(5):411-421. PubMed 900865

Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Patterns of lactate dehydrogenase isoenzymes in serum of patients with acute pulmonary edema. Clin Chem. 1988 Sep; 34(9):1882-1884. PubMed 3416439

Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Significance of isolated increases in total lactate dehydrogenase and its isoenzymes in serum of patients with bacterial pneumonia. Clin Chem. 1988 Jul; 34(7):1503-1505. PubMed 3390929

Gorus F, Aelbrecht W, Van Camp B. Circulating IgG-LD complex, dissociable by addition of NAD.+. Clin Chem. 1982 Jan; 28(1):236-239. PubMed 7055917

Pesce MA. The CK and LD macroenzymes. Lab Management. 1984 Nov 29; 22:29-41.

Podlasek SJ, Dufour DR, McPherson RA. Alterations in lactate dehydrogenase isoenzyme patterns after therapy with streptokinase or streptococcal infection. Clin Chem. 1989 Aug; 35(8):1763-1766. PubMed 2758647

Vladutiu AO. Cathodic lactate dehydrogenase (LDH 6): A sign of ominous prognosis? Arch Pathol Lab Med. 1983 Nov; 107(11):612-613. PubMed 6688723

Wolf PL. Lactate dehydrogenase-6: A biochemical sign of serious hepatic circulatory disturbance. Arch Intern Med. 1985 Aug; 145(8):1396-1397. PubMed 4026470

Von Eyben FE, Blaabjerg O, Petersen PH, et al. Serum lactate dehydrogenase isoenzyme 1 as a marker of testicular germ cell tumor. J Urol. 1988 Nov; 140(5):986-990. PubMed 2845154

Schwartz PE, Morris JM. Serum lactic dehydrogenase: a tumor marker for dysgerminoma. Obstet Gynecol. 1988 Sep; 72(3 Pt 2):511-515. PubMed 3405571

Yoshimura T, Takemori K, Okazaki T, Suzuki A. Serum lactic dehydrogenase and its isoenzymes in patients with ovarian dysgerminoma. Int J Gynaecol Obstet. 1988 Dec; 27(3):459-465. PubMed 2904916

Rotenberg Z, Weinberger I, Sagie A, et al. Total lactate dehydrogenase and its isoenzymes in serum of patients with non-small-cell lung cancer. Clin Chem. 1988 Apr; 34(4):668-670. PubMed 2834116

Manzo V, Sun T, Lien YY. Misdiagnosis of acute myocardial infarction. Ann Clin Lab Sci. 1990 Sep-Oct; 20(5):324-328. PubMed 2256660

Galbraith LV, Leung FY, Jablonsky G, Henderson AR. Time-related changes in the diagnostic utility of total lactate dehydrogenase, lactate dehydrogenase isoenzyme-1, and two lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction. Clin Chem. 1990 Jul; 36(7):1317-1322. PubMed 2372944

Clark CP 3rd, Foreman ML, Peters GN, Cheek JH, Sparkman RS. Efficacy of preoperative liver function tests and ultrasound in detecting hepatic metastasis in carcinoma of the breast. Surg Gynecol Obstet. 1988 Dec; 167(6):510-514. PubMed 3055370

Giannoulaki EE, Kalpaxis DL, Tentas C, Fessas P. Lactate dehydrogenase isoenzyme pattern in sera of patients with malignant diseases. Clin Chem. 1989 Mar; 35(3):396-399. PubMed 2920405

What does it mean if your LD 4 (or LDH-4) result is too high?

Because LDH is present in so many types of cells, high levels of LDH may indicate a number of conditions.

Elevated levels of LDH can include:

  • blood flow deficiency
  • cerebrovascular accident, also known as a stroke
  • certain cancers
  • heart attack
  • hemolytic anemia
  • infectious mononucleosis
  • liver disease, such as hepatitis
  • muscle injury
  • muscular dystrophy
  • pancreatitis
  • tissue death
  • use of alcohol or certain drugs
  • sepsis and septic shock

High levels of LDH indicate some form of tissue damage. High levels of more than one isoenzyme may indicate more than one cause of tissue damage. For example, a patient with pneumonia could also have a heart attack. Extremely high levels of LDH could indicate severe disease or multiple organ failure.

Because LDH is in so many tissues throughout the body, LDH levels alone won’t be enough to determine the location and cause of tissue damage. A diagnosis will also require the use of other tests and images in addition to measuring the levels of LDH. For example, high LDH-4 and LDH-5 may mean either liver damage or muscle damage, but liver disease can’t be confirmed without a full liver panel.

Before the discovery of other blood markers for heart injury, LDH was used to monitor people with heart attacks. Now, troponin, a protein produced more specifically in heart cells, is often a more accurate indicator of a heart attack.

Once your doctor diagnoses your particular condition, they may measure your LDH levels regularly to track the progress of your treatment.

LDH levels are also often used during the treatment of certain cancers to predict outcomes and monitor the body’s response to medications.

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What does it mean if your LD 4 (or LDH-4) result is too low?

LDH deficiency affects how the body breaks down sugar for use as energy in cells, particularly muscle cells. It’s very rare for a person to have low LDH levels.

Two types of genetic mutations cause low LDH levels. People with the first type will experience fatigue and muscle pain, especially during exercise. While those with the second type may have no symptoms at all. You may also have low LDH levels if you’ve consumed a large amount of ascorbic acid (vitamin C).

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