Dr. Lee was born in Shanghai, China, and received his college and medical training in the United States. He is fluent in English and three Chinese dialects. He graduated with chemistry departmental honors from Harvey Mudd College. He was appointed president of AOA society at UCLA School of Medicine. He underwent internal medicine residency and gastroenterology fellowship training at Cedars Sinai Medical Center.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
How is acetaminophen processed (metabolized) in
the body?
The liver is the primary site in the body where acetaminophen is metabolized.
In the liver, acetaminophen first undergoes sulphation (binding to a sulphate
molecule) and glucuronidation (binding to a glucuronide molecule) before being
eliminated from the body by the liver. The parent compound, acetaminophen, and
its sulphate and glucuronide compounds (metabolites) are themselves actually not
harmful. An excessive amount of acetaminophen in the liver, however, can
overwhelm (saturate) the sulphation and glucuronidation pathways. When this
happens, the acetaminophen is processed through another pathway, the cytochrome
P-450 system. From acetaminophen, the P-450 system forms an intermediate
metabolite referred to as NAPQI, which turns out to be a toxic compound.
Ordinarily, however, this toxic metabolite is rendered harmless (detoxified) by
another pathway, the glutathione system.
How does an overdose of acetaminophen cause
liver injury?
The answer is that liver damage from acetaminophen occurs when the
glutathione pathway is overwhelmed by too much of acetaminophen's metabolite,
NAPQI. Then, this toxic compound accumulates in the liver and causes the damage.
Furthermore, alcohol and certain medications such as phenobarbital, phenytoin
(Dilantin), or carbamazepine
(Tegretol)
(anti-seizure medications) or isoniazid
(INH, Nydrazid, Laniazid) - (anti-tuberculosis drug) can significantly
increase the damage. They do this by making the cytochrome P-450 system in the
liver more active. This increased P-450 activity, as you might expect, results
in an increased formation of NAPQI from the acetaminophen. Additionally,
chronic
alcohol use, as well as the fasting state or poor nutrition, can each deplete
the liver's glutathione. So, alcohol both increases the toxic compound and
decreases the detoxifying material. Accordingly, the bottom line in an
acetaminophen overdose is that when the amount of NAPQI is too much for the
available glutathione to detoxify, liver damage occurs.
Abdominal pain is pain in the belly and can be acute or chronic. Causes include inflammation, distention of an organ, and loss of the blood supply to an organ. Abdominal pain can reflect a major problem with one of the organs in the abdomen such as the appendix, gallbladder, large and small intestine, pancreas, liver, colon, duodenum, and spleen.
Liver disease can be cause by a variety of things including infection (hepatitis), diseases such as gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause; however, common symptoms may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
Alcoholism is a disease that includes alcohol craving and continued drinking despite repeated alcohol-related problems, such as losing a job or getting into trouble with the law.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Coma is the inability to waken or react to the surrounding environment. The Glasgow Coma Scale is frequently used to measure the depth of coma. Causes of coma include trauma, bleeding, edema, lack of oxygen, poisoning, or hypoglycemia. Prognosis for a patient in a coma depends on the cause of the coma.
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