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Ammonia (NH3), Hyperammonia

April 3, 2025Chemical pathologyLab Tests

Table of Contents

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  • Ammonia (NH3)
        • What sample is needed for Ammonia (NH3)?
        • What are the precautions for Ammonia (NH3)?
        • What are the Indications for Ammonia (NH3)?
        • How will you define ammonia (NH3)?
        • What are the sources of Ammonia (NH3)?
        • What are the Properties of Ammonia (NH3)?
        • What are the toxic effects of Ammonia (NH3)?
        • What are the uses of ammonia (NH3) gas?
        • What are the signs and symptoms of hyperammonemia (Ammonia, NH3)?
        • What are the normal levels of Ammonia (NH3)?
      • What is the critical value of ammonia (NH3)?
        • What are the causes of raised Ammonia (NH3) levels?
        • What are the causes of decreased Ammonia (NH3) levels?
      • Questions and answers:

Ammonia (NH3)

What sample is needed for Ammonia (NH3)?

  1. Whole blood is needed to estimate ammonia.
    1. Plasma is prepared in EDTA or heparin other than ammonium heparinate.
  2. Fasting AM  samples are preferred.
  3. There should be no smoking after 12 midnight.
    1. Avoid smoking in the vicinity of the test sample place.
  4. There should be no clinching of the hand.
  5. Ammonia is a volatile gas that should be transported in ice or tested immediately.
  6. The specimen may be centrifuged at 4 °C.
  7. Perform the test within 20 minutes or freeze the plasma immediately.
  8. A urine 24-hour sample is preferred.

What are the precautions for Ammonia (NH3)?

  1. Analyze the sample as soon as possible.
  2. Avoiding hemolyzed samples that increase the ammonia level because the RBCs contain more than three times more than plasma.
  3. Avoid clenching the fist.
  4. Avoid exercise before taking the blood sample because it increases the level.
  5. Don’t smoke at least 8 hours before this test.
    1. One cigarette smoked one hour before the sample can raise the blood ammonia concentration to 100 to 200 µg/L.
    2. Smokers need a shower and new clothing.
    3. The technician should also be a non-smoker.
  6. The use of the tourniquet may increase the ammonia level.
  7. Avoid contamination of urine by bacteria or ammonia.
  8. Glassware should be cleaned and washed with a hypochlorite solution.
  9. EDTA and heparin are acceptable anticoagulants.
  10. The arterial blood sample is more reliable than venous blood but is difficult to obtain, so venous blood is taken.
  11. Drugs that increase the level are:
    1. Acetazolamide.
    2. Alcohol.
    3. Barbiturates.
    4. Ammonium chloride.
    5. Narcotics.
    6. Parenteral nutrition.
    7. Diuretics.
  12. Drugs that decrease the level are:
    1.  Broad-spectrum antibiotics (neomycin).
    2. Levodopa.
    3. Potassium salt.
    4. Lactobacillus.

What are the Indications for Ammonia (NH3)?

  1. To find the progression of liver disease and its response to treatment (Fulminant hepatitis or cirrhosis).
  2. To diagnose Reye’s syndrome.
  3. To follow the hepatic encephalopathy.
  4. To monitor the patient in the case of hyperalimentation, high-calorie I/V nutrition.
  5. The newborn’s advice is when the infant has irritability, vomiting, lethargy, and develops seizures in the early days of birth.

How will you define ammonia (NH3)?

  1. Ammonia (NH3) is a colorless gas with a pungent odor. It has one nitrogen and three hydrogen atoms.
    1. It is highly soluble in water, forming ammonium hydroxide (NH4OH).
  2. Ammonia (NH3) is derived mainly from amino acids in the liver via the urea cycle.
  3. Humans excrete nitrogen from the amino acids and other sources (proteins) as one of the three end products:
    1. Ammonia (NH3): It is highly toxic, particularly for the brain.
    2. Urea: Humans are ureotelic (excrete mainly urea as the end product of nitrogenous compounds).
    3. Uric acid:  Birds are uricotelic (excrete mainly uric acid as the end product of nitrogenous compounds).

What are the sources of Ammonia (NH3)?

  1. Ammonia is the end product of protein metabolism.
  2. Ammonia in the peripheral blood is present in a very small amount of 10 to 20 µg/dL.
  3. The main sources of ammonia are skeletal muscles (urea cycle) and the gut, which are derived from the intestinal bacteria that break down proteins.
  4. Ammonia is produced in the liver, intestine, and kidneys as the end product of protein metabolism.
    1. Ammonia is a by-product of protein catabolism.
    2. The major source of NH3 is the gastrointestinal tract.
    3. In the hepatic portal vein, NH3 concentration is 5 to 10 times higher than the systemic circulation.
  5. Most ammonia is caused by bacteria acting on proteins in the intestine.
  6. This intestinal ammonia enters the blood and reaches the liver through the portal vein.
    1. In portal hypertension, ammonia cannot reach the liver to be catabolized.

What are the Properties of Ammonia (NH3)?

  1. Ammonia is an inorganic compound of hydrogen and nitrogen with the formula of NH 3.
  2. NH3 is a colorless, alkaline gas with a pungent smell.
  3. Ammonia (NH3) is lighter than air and easily liquefied under pressure.
  4. Ammonia is an irritating gas to the skin, eyes, throat, nose, and lungs.
  5. Ammonia is the most abundant nitrogen-containing compound in the atmosphere.
  6. Ammonia is neurotoxic; it causes brain edema, which may lead to death.
  7. The liver is the major site for detoxifying ammonia (NH3).
Ammonia (NH3) metabolism

Ammonia (NH3) metabolism

What are the toxic effects of Ammonia (NH3)?

  1. The liver converts ammonia into urea, which is then excreted by the kidneys.
  2. If the liver is damaged, then its level increases in the blood.
  3. It helps diagnose hepatic encephalopathy, and serial estimation may be done to follow the disease.
  4. Accumulation of ammonia is toxic to the central nervous system.
    1. The entry of NH3 into nervous tissue depends upon the pH. As the pH increases, the rate of entry of the NH3 into the nervous tissue increases.
    2. Ammonia (NH 3) crosses the blood-brain barrier more easily than ammonium (NH 4) ions.
Ammonia (NH3) metabolism

Ammonia (NH3) metabolism

What are the uses of ammonia (NH3) gas?

  1. It is used as fertilizer in the form of ammonium nitrate and urea.
  2. It is used as a cleaning agent and a household cleaner.
  3. It acts as a refrigerant gas.
  4. It is used in the manufacturing of plastics, explosives, and dyes.

What are the signs and symptoms of hyperammonemia (Ammonia, NH3)?

  1. Hyperammonemia exerts toxic effects on the central nervous system.
  2. Hyperammonemia Causes may be:
    1. Inherited. The urea cycle enzyme is deficient and common in infants.
    2. Acquired. The causes are liver diseases and renal failure.
  3. There is fatigue.
  4. There is a loss of appetite.
  5. Nausea and vomiting.
  6. There is a loss of strength.
  7. Ultimately, the patient will become confused.
  8. The patient may have pain in the abdomen or back.
  9. Precipitating causes of encephalopathy are:
    1. Dietary protein.
    2. Constipation.
    3. Drugs.
    4. Infection.
    5. Electrolytes and acid-base imbalance.
Ammonia (NH3) metabolism and its effect on brain

Ammonia (NH3) metabolism and its effect on the brain

What are the normal levels of Ammonia (NH3)?

Source 2

  • Adult = 10 to 80 µg /dL
  • Child = 40 to 80 µg /dL
  • Newborn = 90 to 150 µg /dL

Another reference

  • Normal range  = 19 to 60 µg /dL
  • Urine   =  140 to 1500 µg /dL

Another source

  • 19 to 60  µg NH3 /dL (by Du Pont automated clinical analyzer)
  • By Ektachem:
    • 0 to 10 days = 170 to 341 µg NH3 /dL
    • 10 days to 2 years = 68 to 136 µg NH3 /dL
    • > 2 years = 19 to 60 µg NH3 /dL

Another source

  • Adult = 15 to 56 µg /dL (9 to 33 µmol/L)
  • Birth to 10 days = 109 to 182 µg /dL  (64 to 107 µmol/L).
  • 10 days to 2 years = 95 to 157 µg /dL (56 to 92 µmol/L)
  • Children = 36 to 85 µg /dL (21 to 50 µmol/L).

What is the critical value of ammonia (NH3)?

  • Ammonia low value = None
  • Ammonia high value = >40 µmol//L

What are the causes of raised Ammonia (NH3) levels?

  1. Raised level of ammonia has toxic effects on the nervous system.
    1. Hyperammonemia may be due to the lack of the urea cycle enzyme in infants.
    2. Genetic metabolic disorder of the urea cycle.
  2. The acquired causes of hyperammonemia are:
    1. Hepatic coma.
    2. Reye’s syndrome.
    3. Hemorrhages like GIT (Gastrointestinal) bleeding.
      1. Gastrointestinal obstruction with mild liver disease.
    4. Severe congestive heart failure.
      1. With congestive hepatomegaly.
    5. Hemolytic diseases of the newborn (HDN).
      1. Erythroblastosis fetalis.
    6. Renal diseases.
    7. Asparagine toxication.
    8. Portal hypertension.
    9. Diuretics and antibiotics may increase the ammonia level.
    10. Alcohol abuse.
    11. High temperature (Hyperthermia).
    12. In the case of hypokalemia (low potassium level).
    13. Metabolic alkalosis.
    14. Congenital metabolic disorder of the urea cycle.
  3. Drugs that increase the level are:
    1. Alcohol.
    2. Barbiturates.
    3. Ammonium chloride.
    4. Acetazolamide.

What are the causes of decreased Ammonia (NH3) levels?

  1. Essential or malignant hypertension.
  2. Drugs that decrease the level are:
    1. Levodopa.
    2. Broad-spectrum antibiotic (neomycin).
    3. Potassium salt.
    4. Lactobacillus.
  3. Hyperornithinemia.

Questions and answers:

Question 1: What is the critical value of ammonia (NH3)?
Show answer
Ammonia critcal velue is >40 µmol/L .
Question 2: What is the role of bacteria in the ammonia formation?
Show answer
Bacteria in the intestine form ammonia (NH3), that is the major source.
Question 3: Is there any role of pH on ammonia (NH3) toxicity?
Show answer
When pH increases, then ammonia (NH3) toxicity also increases.

Possible References Used
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