abdominal pain, liver toxicity
TRANSCRIPT
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By
Logeshwaran.K &
Rajasri.M
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Just about everybody at one point or another will
experience abdominal pain.
Most of the causes are not serious and can be readily diagnosed and treated.
However, pain can also be a sign of a serious illness.
It's important to be able to recognize symptoms that are severe and know when to call a doctor.
Abdominal pain is pain that is felt in the abdomen.
Introduction
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Abdominal pain is caused by
inflammation (for example, appendicitis, diverticulitis, colitis),
by stretching or distension of an organ (for example, obstruction of the intestine, blockage of a bile duct by gallstones, swelling of the liver with hepatitis),
or by loss of the supply of blood to an organ (for example, ischemic colitis).
Causes
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To complicate matters, it is believed to be due either
to abnormal contractions of the intestinal muscles (for example, spasm) or abnormally sensitive nerves within the intestines that give rise to painful sensations inappropriately (visceral hyper-sensitivity).
These latter types of pain are often referred to as functional pain because no recognizable (visible) causes for the pain have been found - at least not yet.
Other causes
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Doctors determine the cause of abdominal pain by
relying on:
characteristics of the pain,
findings on physical examination,
laboratory, radiological, and endoscopic testing, and
surgery.
Diagnosing the cause
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The way the pain begins.
The location of the pain.
The pattern of the pain.
The duration of the pain.
What makes the pain worse.
What relieves the pain.
Determining the cause
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The presence of fever suggests inflammation.
Diarrhoea or rectal bleeding suggests an intestinal cause of the pain.
The presence of fever and diarrhoea suggest inflammation of the intestines that may be infectious or non-infectious (for example, ulcerative colitis or Crohn's disease).
Associated signs and symptoms
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The presence of sounds coming from the intestines that
occur when there is obstruction of the intestines,
The presence of signs of inflammation (by special maneuvers during the examination),
The location of any tenderness
The presence of a mass within the abdomen that suggests a tumor, enlarged organ, or abscess (a collection of infected pus)
The presence of blood in the stool that may signify an intestinal problem such as an ulcer, colon cancer, colitis, or ischemia.
Physical examination
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Laboratory tests such as the complete blood
count (CBC), liver enzymes, pancreatic enzymes (amylase and lipase), and urinalysis are frequently performed in the evaluation of abdominal pain.
Laboratory test
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The liver is the second largest organ in the body
(after the skin), and is essential in keeping the body functioning properly.
The liver is located in the upper right-hand side of the abdomen.
It performs many functions in the body, including processing the body's nutrients, manufacturing bile to help digest fats, synthesizing many important proteins, regulating blood clotting, and breaking down potentially toxic substances into harmless ones that the body can use or excrete.
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Inflammation of the liver may, in severe cases, interfere
with these processes and allow potentially toxic substances to accumulate.
Inflammation can occur while the liver is performing its functions, such as metabolizing drugs.
The liver is able to regenerate or repair up to two-thirds of injured tissue, including hepatocytes, biliary epithelial cells, and endothelial cells.
Healthy cells take over the function of damaged cells, either indefinitely or until the damage is repaired.
Liver function
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But no matter what type the individual has, the
damage to the liver is likely to progress in a similar way.
Viruses cause some of them, like hepatitis A, hepatitis B, and hepatitis C.
Other types of liver damage can be the result of drugs (such as acetaminophen), poisons (such as the death cap mushroom), or
drinking too much alcohol for a long period of time.
Different types of liver disease
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If the liver forms scar tissue because of an illness, it is called cirrhosis.
Jaundice, or yellowing of the skin and eyes, can be one sign of liver disease.
Cancer can also affect the liver. Individuals may inherit a liver disease such as hemochromatosis, which is a liver condition causing iron overload.
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The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents.
Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ.
Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins) and herbal remedies can also induce hepatotoxicity.
Chemicals that cause liver injury are called hepatotoxins.
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Alternative names
Toxic liver diseaseToxin induced liver diseaseDrug induced liver diseaseDrug induced liver damageHepatogenous poisoning
Subordinate terms
Toxic hepatitisToxin induced hepatitisDrug induced hepatitisDrug-induced hepatic necrosisDrug induced hepatic fibrosisDrug induced hepatic granulomaToxic liver disease with hepatitisToxic liver disease with cholestasis
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Drug metabolism in liver
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Drug metabolism is usually divided into two phases: phase 1 and phase 2.
Phase 1 reaction is thought to prepare a drug for phase 2. However many compounds can be metabolized by phase 2 directly.
Phase 1 reaction involves oxidation, reduction, hydrolysis, hydration and many other rare chemical reactions.
phase 2 reactions take place in cytosol and involve conjugation with endogenous compounds via transferase enzymes
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Age
Ethnicity and race
Gender
Nutritional status
Underlying liver disease
Renal function
Pregnancy
Duration and dosage of drug
Enzyme induction
Drug-to-drug interaction
Factors influencingdrug induced hepatotoxicity
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Type of injury: Hepatocellular Cholestatic Mixed
ALT ≥ Twofold rise Normal ≥ Twofold rise
ALP Normal ≥ Twofold rise ≥ Twofold rise
ALT: ALP ratio High, ≥5 Low, ≤2 2-5
Examples
AcetaminophenAllopurinolAmiodaroneHAARTNSAID
Anabolic steroidChlorpromazineClopidogrelErythromycinHormonal contraception
Amitriptyline,EnalaprilCarbamazepineSulfonamidePhenytoin
Pattern of injury
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Normal blood test results for typical liver function tests include:
ALT. 7 to 55 units per litre (U/L)
AST. 8 to 48 U/L
ALP. 45 to 115 U/L
Albumin. 3.5 to 5.0 grams per decilitre (g/dL)
Total protein. 6.3 to 7.9 g/dL
Bilirubin. 0.1 to 1.0 mg/dL
GGT. 9 to 48 U/L
LD. 122 to 222 U/L
PT. 9.5 to 13.8 seconds
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Zonal necrosis
Hepatitis
Cholestasis
Steatosis
Granuloma
Vascular lesions
Neoplasm
Specific histo-pathological patterns of liver injury from drug-induced damage
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Adverse drug reactions are classified as type A (intrinsic
or pharmacological) or type B (idiosyncratic). Type A drug reaction accounts for 80% of all toxicities.
Drugs or toxins that have a pharmacological (type A) hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity, such as directly damaging liver tissue or blocking a metabolic process.
Idiosyncratic (type B) injury occurs without warning, when agents cause non-predictable hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period.
Adverse drug reactions
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Acetaminophen
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Glucocorticoids
Isoniazid
Other hydrazine derivative drugs
Natural products
Industrial toxin
Herbal and alternative remedies that could contribute to liver failure
Specific drug or toxin
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During the first phase, that is, the initial 12 to 24 hours or
so after ingestion, the patient experiences nausea and vomiting.
For the next perhaps 12 to 24 hours, which is the second phase or the so-called inactive (latent) phase, the patient feels well.
In the third phase, which begins about 48 to as late as 72 hours after the ingestion of acetaminophen, liver blood test abnormalities begin to appear. Most notably, extremely high (abnormal) levels of the liver blood tests, AST and ALT, are common with this type of liver injury.
Symptoms and signs of acetaminophen-induced liver
damage
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In most cases, liver function will return to normal if the
offending drug is stopped early. Additionally, the patient may require supportive treatment.
In acetaminophen toxicity, however, the initial insult can be fatal.
Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation.
An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign.
This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped.
Administration of antihepatocytotoxic serum helps in regeneration of liver’s cellular mechanism
Treatment and prognosis
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