Ammonia (NH3), Hyperammonia, Ammonia level

Sample

1. Whole blood is needed for the estimation of 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, so it should be transported in ice or test 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 hours sample is preferred.

Precautions

1. Analyze the sample as soon as possible.
2. Avoid hemolyzed samples increases the ammonia level because the RBCs contain more than three times 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. Use of the tourniquet may increase the ammonia level.
7. Avoid contamination of urine by bacteria or ammonia.
8. Glassware should be clean and wash with a hypochlorite solution.
9. EDTA and heparin are acceptable anticoagulants.
10. The arterial blood sample is more reliable than venous but 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.

Purpose of the test (Indications)

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. In the case of a patient with hyperalimentation, taking high-calorie I/V nutrition.
5. The newborn’s advice when the infant has irritability, vomiting, lethargy, and develops seizures in the early days of birth.

Pathophysiology

1. The main source of ammonia is skeletal muscles (urea cycle) and the gut, where the ammonia is derived from the intestinal bacteria that breakdown proteins.
2. Ammonia is an inorganic compound of hydrogen and nitrogen with the formula of NH ₃^. It is colorless alkaline gas with a pungent smell.
   1. Ammonia is irritating gas to the skin, eyes, throat, nose, and lungs.
   2. Ammonia is the most abundant nitrogen-containing compound in the atmosphere.
3. 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.
4. Most of the ammonia is made by bacteria acting on protein present in the intestine.
5. This intestinal ammonia enters the blood and reaches the liver; by way of the portal vein.
   1. In portal hypertension, ammonia cannot reach the liver to be catabolized.

5. The liver converts ammonia into urea, which is then excreted by the kidneys.
6. If the liver is damaged, then its level increases in the blood.
7. It’s raised level diagnose hepatic encephalopathy, and serial estimation may be done to follow the disease.
8. 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.

Signs and Symptoms of hyperammonemia:

1. Hyperammonemia exerts toxic effects on the central nervous system.
2. Causes may be:
   1. Inherited. The urea cycle enzyme is deficient, 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. There are nausea and vomiting.
6. There is a loss of strength.
7. Ultimately patient will have confusion.
8. The patient may have pain abdomen or back.
9. Precipitating causes of encephalopathy are:
   1. Dietary protein.
   2. Constipation.
   3. Drugs.
   4. Infection.
   5. Electrolytes and acid-base imbalance.

Normal level

Source 2

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

Other reference

• Normal range  = 19 to 60 µg /dL

• Urine   =  140 to 1500 µg /dL

Another source

• 19 to 60  µg NH_³ /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
  • Birth to 10 days =109 to 182 µg /dL
  • 10 days to 2 years = 95 to 157 µg /dL
  • Children = 36 to 85 µg /dL

Raised level is seen in (Hyperammonemia):

1. Raised level of ammonia has toxic effects on the nervous system.
   1. In infants, hyperammonemia may be due to the lack of the urea cycle enzyme.
   2. Genetic metabolic disorder of the urea cycle.
2. The acquired causes of hyperammonemia are:
   1. Hepatic coma.
   2. Reye’s syndrome.
   3. Hemorrhage 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.

The decreased level is seen in:

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.

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