Causes of Reye's Syndrome

• Inflammatory disorders, resulting in tender hepatomegaly
  –Hepatitis (viral or drug-induced): Associated with jaundice, fever, nausea, vomiting, fatigue, diarrhea, weight loss
  –Alcoholic liver disease: Associated with liver failure and portal hypertension (e.g., caput medusae, spider angiomata, hemorrhoids, testicular atrophy, ALT is more than two times higher than AST)
• Infiltrative disorders
  –Fatty liver (NASH): Predisposing factors include middle age, obesity, female gender, diabetes, and hyperlipidemia
  –Sarcoidosis: Associated with cough, hilar lymphadenopathy; more common in blacks, women, ages 30–40
  –Hemochromatosis: Iron overload resulting in bronzed skin color, diabetes, abnormal iron panel
  –Wilson's disease: Copper excess resulting in liver failure, lenticular degeneration, and Kayser-Fleischer rings in cornea
• Neoplasms present with focal enlargement, arterial bruit and/or hepatic rub, and constitutional symptoms (e.g., fever, night sweats, weight loss)
  –Metastatic cancer is more common than primary liver cancers (colon, lung, breast)
  –Hepatocellular carcinoma is most common primary liver cancer (often due to chronic hepatitis or cirrhosis)
  –Hepatic adenoma or hepatic cysts
  –Leukemia/lymphoma

• Liver abscess
• Less common causes (“zebras”) include tricuspid regurgitation, Budd-Chiari syndrome, schistosomiasis, amyloidosis, kala-azar (visceral leishmaniasis), and HIV/AIDS

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Source: In a Page: Signs and Symptoms, 2004

Hepatomegaly: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Inflammation
  –Most common infections: EBV; hepatitis A, B, C; CMV; TORCH
  –Less common infections: HIV, malaria, amebiasis, tuberculosis, toxocariasis, Borrelia burgdorferi
  –Drugs: Acetaminophen (commonly used in overdoses among adolescents), NSAIDs, isoniazid, sodium valproate, propothiouracil, halothane
  –Toxins: Tyrosinemia, galactosemia, vitamin A toxicity
  –Autoimmune hepatitis
  –Systemic lupus erythematosus

• Inappropriate storage
  –Glycogen storage diseases I–V
  –Lipids: Gaucher disease, Wolman disease, Niemann-Pick disease
  –Fat: Fatty acid oxidation defects, mucopolysaccharidoses
  –Metals: Wilson disease (copper), hemochromatosis (iron)
  –Abnormal proteins: α-1 antitrypsin deficiency (store abnormal protein product)
  –Peroxisomal disease: Zellweger
  –Mucopolysaccharidoses, types I–IV

• Infiltration
  –Hepatoblastoma
  –Hepatocellular carcinoma
  –Hemangioma
  –Histiocytosis
  –Extramedullary hematopoiesis
  –Chronic granulomatous disease
• Vascular congestion
  –Congestive heart failure
  –Budd-Chiari syndrome
  –Veno-occlusive disease
  –Suprahepatic web
• Biliary obstruction
  –Biliary atresia represents the most common cause of pediatric liver transplantation
  –Alagille syndrome
  –Cystic fibrosis
  –Primary sclerosing cholangitis
  –Inspissated bile syndrome
• Miscellaneous
  –Reye syndrome, bile acid synthetic disorder

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Source: In A Page: Pediatric Signs and Symptoms, 2007

Hepatomegaly: Medical causes
(Handbook of Signs & Symptoms (Third Edition))

Amyloidosis

Amyloidosis is a rare disorder that may cause hepatomegaly and mild jaundice as well as renal, cardiac, and other GI effects.

Cirrhosis

Late in cirrhosis, the liver becomes enlarged, nodular, and hard Other late signs and symptoms affect all body systems

Respiratory findings include limited thoracic expansion due to abdominal ascites, leading to hypoxia. Central nervous system findings include signs and symptoms of hepatic encephalopathy, such as lethargy, slurred speech, asterixis, peripheral neuritis, paranoia, hallucinations, extreme obtundation, and coma. Hematologic signs include epistaxis, easy bruising, and bleeding gums. Endocrine findings include testicular atrophy, gynecomastia, loss of chest and axillary hair, or menstrual irregularities. Integumentary effects include abnormal pigmentation, jaundice, severe pruritus, extreme dryness, poor tissue turgor, spider angiomas, and palmar erythema.

The patient may also develop fetor hepaticus, enlarged superficial abdominal veins, muscle atrophy, right upper quadrant pain that worsens when he sits up or leans forward, and a palpable spleen. Portal hypertension — elevated pressure in the portal vein — causes bleeding from esophageal varices.

Diabetes mellitus

Poorly controlled diabetes in overweight patients commonly produces fatty infiltration of the liver, hepatomegaly, and right upper quadrant tenderness along with polydipsia, polyphagia, and polyuria

These features are more common in type 2 than in type 1 diabetes A chronically enlarged fatty liver typically produces no symptoms except for slight tenderness.

Granulomatous disorders

Sarcoidosis, histoplasmosis, and other such disorders commonly produce a slightly enlarged, firm liver.

Hepatic abscess

Hepatomegaly may accompany a fever (a primary sign), nausea, vomiting, chills, weakness, diarrhea, anorexia, an elevated right hemidiaphragm, and right upper quadrant pain and tenderness.

Hepatitis

In viral hepatitis, early signs and symptoms include nausea, anorexia, vomiting, fatigue, malaise, photophobia, a sore throat, a cough, and a headache Hepatomegaly occurs in the icteric phase and continues during the recovery phase

Also, during the icteric phase, the early signs and symptoms diminish and others appear: liver tenderness, slight weight loss, dark urine, clay-colored stools, jaundice, pruritus, right upper quadrant pain, and splenomegaly.

Leukemia and lymphomas

Leukemia and lymphomas are proliferative blood cell disorders that typically cause moderate to massive hepatomegaly and splenomegaly as well as abdominal discomfort

General signs and symptoms include malaise, a low-grade fever, fatigue, weakness, tachycardia, weight loss, bleeding disorders, and anorexia.

Liver cancer

Primary tumors commonly cause irregular, nodular, firm hepatomegaly, with pain or tenderness in the right upper quadrant and a friction rub or bruit over the liver Common related findings are weight loss, anorexia, cachexia, nausea, and vomiting

Peripheral edema, ascites, jaundice, and a palpable right upper quadrant mass may also develop. When metastatic liver tumors cause hepatomegaly, the patient’s accompanying signs and symptoms reflect his primary cancer.

Mononucleosis (infectious)

Prodromal symptoms include a headache, malaise, and fatigue. After 3 to 5 days, the patient typically develops a sore throat, cervical lymphadenopathy, and temperature fluctuations. He may also develop stomatitis, palatal petechiae, periorbital edema, splenomegaly, exudative tonsillitis, pharyngitis and, possibly, a maculopapular rash.

Obesity

Hepatomegaly can result from fatty infiltration of the liver

Weight loss reduces the liver’s size.

Pancreatic cancer

In pancreatic cancer, hepatomegaly accompanies such classic signs and symptoms as anorexia, weight loss, abdominal or back pain, and jaundice Other findings include nausea, vomiting, a fever, fatigue, weakness, pruritus, and skin lesions (usually on the legs).

Pericarditis

The usual signs of cardiac disease typically are absent; other features include peripheral edema, ascites, fatigue, and decreased muscle mass.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Signs & Symptoms (Third Edition), 2006

Reye's syndrome: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

Reye’s syndrome typically begins within 1 to 3 days of an acute viral infection, such as an upper respiratory tract infection, type B influenza, or varicella (chickenpox). Incidence commonly rises during influenza outbreaks and may be linked to salicylate use. For this reason, use of aspirin for children younger than age 15 isn’t recommended. The Reyes Syndrome Foundation warns against the use of salicylates, even in topical preparations, when a viral illness is suspected.

In Reye’s syndrome, damaged hepatic mitochondria disrupt the urea cycle, which normally changes ammonia to urea for its excretion from the body. This results in hyperammonemia, hypoglycemia, and an increase in serum short-chain fatty acids, leading to encephalopathy. Simultaneously, fatty infiltration occurs in renal tubular cells, neuronal tissue, and muscle tissue, including the heart.

Reye’s syndrome affects children from infancy to adolescence and occurs equally in boys and girls. Peak incidence is at age 6.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Diseases (Eighth Edition), 2005

Viral hepatitis: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

The major forms of viral hepatitis result from infection with the causative viruses: A, B, C, D, E, or G.

Type A hepatitis is highly contagious and is usually transmitted by the fecal-oral route. However, it may also be transmitted parenterally. Hepatitis A usually results from ingestion of contaminated food, milk, or water. Many outbreaks of this type are traced to ingestion of seafood from polluted water. In 2001, there were more than 10,000 acute cases of hepatitis A infection reported in the United States.

Type B hepatitis, once thought to be transmitted only by the direct exchange of contaminated blood, is now known to be transmitted also by contact with human secretions and feces. As a result, nurses, physicians, laboratory technicians, and dentists are frequently exposed to type B hepatitis, in many cases as a result of wearing defective gloves. Transmission also occurs during intimate sexual contact as well as through perinatal transmission. An estimated 200,000 new cases of hepatitis B virus (HBV) and 5,000 deaths from HBV occur annually in the United States.

Although specific type C hepatitis viruses have been isolated, only a small percentage of patients have tested positive for them — perhaps reflecting the test’s poor specificity. Usually, this type of hepatitis is transmitted through transfused blood from asymptomatic donors. Hepatitis C accounts for 30,000 new infections and 8,000 to 10,000 deaths each year in the United States. Most exposures (60%) occur through the use of illicit I.V. drugs. However, sexual transmission is responsible for 20% of cases. More than 170 million people have the hepatitis C virus worldwide.

Type D hepatitis is found only in patients with an acute or chronic episode of hepatitis B and requires the presence of HBsAg. The type D virus depends on the double-shelled type B virus to replicate. For this reason, type D infection can’t outlast a type B infection. About 15 million people are infected with hepatitis D worldwide. It’s more common in adults than in children. People with a history of illicit I.V. drug use and people who live in the Mediterranean basin have a higher incidence.

Type E hepatitis is transmitted enterically, much like type A. Because this virus is inconsistently shed in feces, detection is difficult. In the United States, the prevalence of hepatitis E is less than 2%. It’s typically found in developing countries that lie near the equator. Incidence is highest among people ages 15 to 40.

Type G may be transmitted in a manner similar to that of hepatitis C. It may also be transmitted by sexual contact, and its incidence may be higher than previously suspected. It’s associated with acute and chronic liver disease, but studies haven’t clearly implicated the hepatitis G virus as an etiologic agent.

Other proposed causative factors, such as non-ABCDE viral hepatitis and type F, are under investigation.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Nonviral hepatitis: Causes
(Professional Guide to Diseases (Eighth Edition))

Various hepatotoxins — carbon tetrachloride, acetaminophen, trichloroethylene, poisonous mushrooms, and vinyl chloride — can cause the toxic form of this disease. Following exposure to these agents, liver damage usually occurs within 24 to 48 hours, depending on the size of the dose or degree of exposure. Alcohol, anoxia, and preexisting liver disease exacerbate the toxic effects of some of these agents.

Drug-induced (idiosyncratic) hepatitis may stem from a hypersensitivity reaction unique to the affected individual, unlike toxic hepatitis, which appears to affect all people indiscriminately. Among the drugs that may cause this type of hepatitis are niacin, halothane, sulfonamides, isoniazid, methyldopa, and phenothiazines (cholestasis-induced hepatitis). In hypersensitive people, symptoms of hepatic dysfunction may appear at any time during or after exposure to these drugs but usually emerge after 2 to 5 weeks of therapy. Not all adverse drug reactions are toxic. Hormonal contraceptives, for example, may impair liver function and produce jaundice without causing necrosis, fatty infiltration of liver cells, or hypersensitivity.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Hepatic encephalopathy: Causes
(Professional Guide to Diseases (Eighth Edition))

Hepatic encephalopathy follows rising blood ammonia levels. Normally, the ammonia produced by protein breakdown in the bowel is metabolized to urea in the liver. When portal blood shunts past the liver, ammonia directly enters the systemic circulation and is carried to the brain. Such shunting may result from the collateral venous circulation that develops in portal hypertension or from surgically created portosystemic shunts. Cirrhosis further compounds this problem because impaired hepatocellular function prevents conversion of ammonia that reaches the liver.

Other factors that predispose rising ammonia levels include excessive protein intake, sepsis, excessive accumulation of nitrogenous body wastes (from constipation or GI hemorrhage), and bacterial action on protein and urea to form ammonia. Certain other factors heighten the brain’s sensitivity to ammonia intoxication: hypoxia, azotemia, impaired glucose metabolism, infection, and administration of sedatives, narcotics, and general anesthetics. Depletion of the intravascular volume, from bleeding or diuresis, reduces hepatic and renal perfusion and leads to contraction alkalosis. In turn, hypokalemia and alkalosis increase ammonia production and impair its excretion.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Fatty liver: Causes
(Professional Guide to Diseases (Eighth Edition))

Chronic alcoholism is the most common cause of fatty liver in the United States and in Europe, with the severity of hepatic disease directly related to the amount of alcohol consumed. (Fatty liver can occur in people who consume as little as 10 oz of alcohol per week.) Other causes include malnutrition (especially protein deficiency), obesity, diabetes mellitus, jejunoileal bypass surgery, Cushing’s syndrome, Reye’s syndrome, pregnancy, large doses of hepatotoxins such as I.V. tetracycline, carbon tetrachloride intoxication, prolonged parenteral nutrition, and DDT poisoning. Whatever the cause, fatty infiltration of the liver probably results from mobilization of fatty acids from adipose tissues or altered fat metabolism.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Hepatomegaly: Medical causes
(Professional Guide to Signs & Symptoms (Fifth Edition))

Amyloidosis

This rare disorder can cause hepatomegaly and mild jaundice as well as renal, cardiac, and other GI effects.

Cirrhosis

Late in this disorder, the liver becomes enlarged, nodular, and hard. Other late signs and symptoms affect all body systems. Respiratory findings include limited thoracic expansion due to abdominal ascites, leading to hypoxia. Central nervous system findings include signs and symptoms of hepatic encephalopathy, such as lethargy, slurred speech, asterixis, peripheral neuritis, paranoia, hallucinations, extreme obtundation, and coma. Hematologic signs include epistaxis, easy bruising, and bleeding gums. Endocrine findings include testicular atrophy, gynecomastia, loss of chest and axillary hair, and menstrual irregularities. Integumentary effects include abnormal pigmentation, jaundice, severe pruritus and dryness, poor tissue turgor, spider angiomas, and palmar erythema.

The patient may also develop fetor hepaticus, enlarged superficial abdominal veins, muscle atrophy, right-upper-quadrant pain that worsens when he sits up or leans forward, and a palpable spleen. Portal hypertension—elevated pressure in the portal vein—causes bleeding from esophageal varices.

Diabetes mellitus

Poorly controlled diabetes in overweight patients commonly produces fatty infiltration of the liver, hepatomegaly, and right-upper-quadrant tenderness along with polydipsia, polyphagia, and polyuria. These features are more common in type 2 than in type 1 diabetes. A chronically enlarged fatty liver typically produces no symptoms except for slight tenderness.

Granulomatous disorders

Sarcoidosis, histoplasmosis, and other granulomatous disorders commonly produce a slightly enlarged, firm liver.

Heart failure

This disorder produces hepatomegaly along with jugular vein distention, cyanosis, nocturia, dependent edema of the legs and sacrum, steady weight gain, confusion and, possibly, nausea, vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites is a late sign. Massive right-sided heart failure may cause anasarca, oliguria, severe weakness, and anxiety. If left-sided heart failure precedes right-sided heart failure, the patient exhibits dyspnea, paroxysmal nocturnal dyspnea, orthopnea, tachypnea, arrhythmias, tachycardia, and fatigue.

Hemochromatosis

This rare disease of iron metabolism causes hepatomegaly, altered skin pigmentation and, possibly, cardiac failure.

Hepatic abscess

Hepatomegaly may accompany fever (a primary sign), nausea, vomiting, chills, weakness, diarrhea, anorexia, elevated right hemidiaphragm, and right-upper-quadrant pain and tenderness.

Hepatitis

In viral hepatitis, early signs and symptoms include nausea, anorexia, vomiting, fatigue, malaise, photophobia, sore throat, cough, and headache. Hepatomegaly occurs in the icteric phase and continues during the recovery phase. Also, during the icteric phase, the early signs and symptoms diminish and others appear: liver tenderness, slight weight loss, dark urine, clay-colored stools, jaundice, pruritus, right-upper-quadrant pain, and splenomegaly.

Leukemia and lymphomas

These proliferative blood cell disorders commonly cause moderate to massive hepatomegaly and splenomegaly as well as abdominal discomfort. General signs and symptoms include malaise, low-grade fever, fatigue, weakness, tachycardia, anorexia, weight loss, and bleeding disorders.

Liver cancer

Primary tumors commonly cause an enlarged, irregular, nodular, firm liver with pain or tenderness in the right upper quadrant and a friction rub or bruit over the liver. Common related findings are anorexia, weight loss, cachexia, nausea, and vomiting. Peripheral edema, ascites, jaundice, and a palpable right-upper-quadrant mass may also develop. When metastatic liver tumors cause hepatomegaly, the patient’s signs and symptoms reflect his primary cancer.

Mononucleosis (infectious)

Occasionally, this disorder causes hepatomegaly. Prodromal symptoms include headache, malaise, and fatigue. After 3 to 5 days, the patient typically develops a sore throat, cervical lymphadenopathy, and temperature fluctuations. He may also develop stomatitis, palatal petechiae, periorbital edema, splenomegaly, exudative tonsillitis, pharyngitis and, possibly, a maculopapular rash.

Obesity

Hepatomegaly can result from fatty infiltration of the liver. Weight loss reduces the liver’s size.

Pancreatic cancer

In this disease, hepatomegaly accompanies such classic signs and symptoms as anorexia, weight loss, abdominal or back pain, and jaundice. Other findings include nausea, vomiting, fever, fatigue, weakness, pruritus, and skin lesions (usually on the legs).

Pericarditis

In chronic constrictive pericarditis, an increase in systemic venous pressure produces marked congestive hepatomegaly. Distended jugular veins (more prominent on inspiration) are a common finding. The usual signs of heart disease typically are absent; other features include peripheral edema, ascites, fatigue, and decreased muscle mass.

Other causes

Drugs

Hepatomegaly is a rare but serious side effect of drugs used to treat HIV-positive hepatitis, such as tenofovir and lamivudine.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Hepatomegaly: Differential Overview
(Field Guide to Bedside Diagnosis)

❑ Acute hepatitis

❑ Chronic hepatitis

❑ Cirrhosis

❑ Right heart failure

❑ Fatty liver

❑ Hepatocellular carcinoma

❑ Metastatic cancer

❑ Lymphoma/leukemia

❑ Liver cysts

❑ Hepatic vein obstruction (Budd-Chiari)

❑ Primary biliary cirrhosis

❑ Hemochromatosis

❑ Amyloidosis

❑ Gaucher

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Source: Field Guide to Bedside Diagnosis, 2007

Reye's syndrome: Causes
(Handbook of Diseases)

Incidence of Reye’s syndrome usually rises during influenza outbreaks and is linked to aspirin use. It almost always follows within 1 to 3 days of an acute viral infection, such as an upper respiratory tract infection, type B influenza, or varicella (chickenpox).

With Reye’s syndrome, damaged hepatic mitochondria disrupt the urea cycle, which normally changes ammonia to urea for its excretion from the body. This results in hyperammonemia, hypoglycemia, and an increase in serum short-chain fatty acids, leading to encephalopathy. Simultaneously, fatty infiltration is found in renal tubular cells, neuronal tissue, and muscle tissue, including the heart.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Diseases, 2003

Hepatitis, viral: Causes
(Handbook of Diseases)

The major forms of viral hepatitis result from infection with the causative viruses: A, B, C, D, E, or G.

Type A hepatitis

Hepatitis A is highly contagious and usually transmitted by the fecal-oral route. It may also be transmitted parenterally.

Clinical tip  I.V. drug abusers and recipients of multiple blood product transfusions are at increased risk for hepatitis A.

Hepatitis A usually results from ingestion of contaminated food, milk, or water. Outbreaks of this type are commonly traced to ingestion of seafood from polluted water.

Type B hepatitis

Once thought to be transmitted only by the direct exchange of contaminated blood, hepatitis B is now also known to be transmitted by contact with human secretions and stool passed by health care workers, recipients of plasma-derived products, and hemodialysis patients. As a result, nurses, physicians, laboratory technicians, and dentists are frequently exposed to type B hepatitis, commonly as a result of wearing defective gloves.

Transmission also occurs during intimate sexual contact and through perinatal transmission.

Type C hepatitis

Although hepatitis C viruses have been isolated, only a small percentage of patients have tested positive for them, perhaps reflecting the test’s poor specificity. Usually, this type of hepatitis is transmitted through transfused blood from asymptomatic donors and receiving tattoos.

Clinical tip  Most patients with hepatitis C are asymptomatic. Hepatitis C virus is associated with a high rate of chronic liver disease (chronic hepatitis, cirrhosis, and an increased risk of hepatocellular carcinoma), which develops in 50% to 80% of those infected. People who have chronic hepatitis C are considered infectious.

Type D hepatitis

Hepatitis D is found only in patients with an acute or a chronic episode of hepatitis B and requires the presence of HBsAg. The type D virus depends on the double-shelled type B virus to replicate. For this reason, a type D infection can’t outlast a type B infection.

Hepatitis D is rare in the United States, except in I.V. drug abusers.

Type E hepatitis

Hepatitis E is transmitted enterically (oral-fecal and waterborne routes), much like type A. Because this virus is inconsistently shed in feces, detection is difficult.

Type G hepatitis

Hepatitis G, a newly identified virus, is transmitted by the blood-borne route, similar to hepatitis C.

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Source: Handbook of Diseases, 2003

Hepatitis, nonviral: Causes
(Handbook of Diseases)

Nonviral hepatitis results from various causes, including:

❑ alcohol overuse — follows heavy alcohol consumption

❑ direct hepatotoxicity — hepatocellular damage and necrosis usually caused by toxins; it’s dose-dependent and occurs primarily in connection with acetaminophen overdose

❑ idiosyncratic hepatotoxicity — follows a sensitization period of several weeks; caused by a host hypersensitivity to medications (isoniazid, methyldopa, mercaptopurine, lovastatin, pravastatin, dipyridamole, and halothane)

❑ cholestatic reactions — caused by lack of bile excretion; possibly direct hepatotoxicity from hormonal contraceptives or anabolic steroids; hypersensitivity to phenothiazine derivatives, such as chlorpromazine, antibiotics, thyroid medications, antidiabetic drugs, and cytotoxic drugs

❑ metabolic and autoimmune disorders — acute exacerbations of subclinical liver disease, such as autoimmune hepatitis and Wilson’s disease

❑ infectious agents — systemic viruses, such as cytomegalovirus, mononucleosis or Epstein-Barr virus, measles virus, varicella zoster, adenovirus, herpes simplex virus, coxsackievirus, and human immunodeficiency virus; spirochetes such as those that cause syphilis and leptospirosis.

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Source: Handbook of Diseases, 2003

Hepatic encephalopathy: Causes
(Handbook of Diseases)

Hepatic encephalopathy develops as a result of rising blood ammonia levels. Several factors cause these levels to rise.

Improper shunting of blood

Normally, the ammonia produced by protein breakdown in the bowel is metabolized to urea in the liver. When portal blood shunts past the liver, ammonia directly enters the systemic circulation and is carried to the brain.

Such shunting may result from the collateral venous circulation that develops in portal hypertension or from surgically created portal-systemic shunts. Cirrhosis further compounds this problem because impaired hepatocellular function prevents conversion of ammonia that reaches the liver.

Other factors

Other factors that predispose to rising ammonia levels include excessive protein intake, sepsis, excessive accumulation of nitrogenous body wastes (from constipation or GI hemorrhage), and bacterial action on protein and urea to form ammonia.

Certain other factors heighten the brain’s sensitivity to ammonia intoxication, including fluid and electrolyte imbalances (especially metabolic alkalosis), hypoxia, azotemia, impaired glucose metabolism, infection, and administration of sedatives, narcotics, and general anesthetics.

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Source: Handbook of Diseases, 2003

Fatty liver: Causes
(Handbook of Diseases)

The most common cause of fatty liver in the United States and Europe is chronic alcoholism, with the severity of liver disease directly related to the amount of alcohol consumed. Other common, non-alcohol-related causes include acquired immunodeficiency syndrome, drug toxicity, and pregnancy.

Other causes include malnutrition (especially protein deficiency), obesity, diabetes mellitus, jejunoileal bypass surgery, Cushing’s syndrome, Reye’s syndrome, carbon tetrachloride intoxication, prolonged total parenteral nutrition (TPN), and DDT poisoning.

Whatever the cause, fatty infiltration of the liver probably results from mobilization of fatty acids from adipose tissues or from altered fat metabolism.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Diseases, 2003

Hepatomegaly: Medical causes
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Cirrhosis

In late cirrhosis, the liver becomes enlarged, nodular, and hard. Other late signs and symptoms affect all body systems. Respiratory findings include limited thoracic expansion due to abdominal ascites, leading to hypoxia. Central nervous system findings include signs and symptoms of hepatic encephalopathy, such as lethargy, slurred speech, asterixis, peripheral neuritis, paranoia, hallucinations, extreme obtundation, and coma. Hematologic signs include epistaxis, easy bruising, and bleeding gums. Endocrine findings include testicular atrophy, gynecomastia, loss of chest and axillary hair, or menstrual irregularities. Integumentary effects include abnormal pigmentation, jaundice, severe pruritus, extreme dryness, poor tissue turgor, spider angiomas, and palmar erythema.

The patient may also develop fetor hepaticus, enlarged superficial abdominal veins, muscle atrophy, right-upper-quadrant pain that worsens when he sits up or leans forward, and a palpable spleen. Portal hypertension — elevated pressure in the portal vein — causes bleeding from esophageal varices.

Diabetes mellitus

Poorly controlled diabetes in overweight patients can produce fatty infiltration of the liver, hepatomegaly, and right-upper-quadrant tenderness along with polydipsia, polyphagia, and polyuria. These features are more common in type 2 than in type 1 diabetes. A chronically enlarged fatty liver typically produces no symptoms except for slight tenderness.

Heart failure

Heart failure produces hepatomegaly along with jugular vein distention, cyanosis, nocturia, dependent edema of the legs and sacrum, steady weight gain, confusion and, possibly, nausea, vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites is a late sign. Massive right-sided heart failure may cause anasarca, oliguria, severe weakness, and anxiety. If left-sided heart failure precedes right-sided heart failure, the patient exhibits dyspnea, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, arrhythmias, tachycardia, and fatigue.

Hepatitis

In viral hepatitis, early signs and symptoms include nausea, anorexia, vomiting, fatigue, malaise, photophobia, sore throat, cough, and headache. Hepatomegaly occurs in the icteric phase and continues during the recovery phase. Also, during the icteric phase, the early signs and symptoms diminish and others appear: liver tenderness, slight weight loss, dark urine, clay-colored stools, jaundice, pruritus, right-upper-quadrant pain, and splenomegaly.

Leukemia and lymphomas

Leukemia and lymphomas are proliferative blood cell disorders that commonly cause moderate to massive hepatomegaly and splenomegaly as well as abdominal discomfort. General signs and symptoms include malaise, low-grade fever, fatigue, weakness, tachycardia, weight loss, bleeding disorders, and anorexia.

Liver cancer

Primary tumors commonly cause irregular, nodular, firm hepatomegaly, with pain or tenderness in the right upper quadrant and a friction rub or bruit over the liver. Common related findings are weight loss, anorexia, cachexia, nausea, and vomiting. Peripheral edema, ascites, jaundice, and a palpable right-upper-quadrant mass may also develop. When metastatic liver tumors cause hepatomegaly, the patient’s accompanying signs and symptoms reflect his primary cancer.

Mononucleosis (infectious)

Occasionally, infectious mononucleosis causes hepatomegaly. Prodromal symptoms include headache, malaise, and fatigue. After 3 to 5 days, the patient typically develops sore throat, cervical lymphadenopathy, and temperature fluctuations. He may also develop stomatitis, palatal petechiae, periorbital edema, splenomegaly, exudative tonsillitis, pharyngitis and, possibly, a maculopapular rash.

Obesity

Hepatomegaly can result from fatty infiltration of the liver. Weight loss reduces the liver’s size. Obesity may also produce findings related to respiratory difficulties, hypertension, cardiovascular disease, diabetes, renal disease, gallbladder disease, and psychological difficulties.

Pancreatic cancer

In pancreatic cancer, hepatomegaly accompanies such classic signs and symptoms as anorexia, weight loss, abdominal or back pain, and jaundice. Other findings include nausea, vomiting, fever, fatigue, weakness, pruritus, and skin lesions (usually on the legs).

» READ BOOK EXCERPT ONLINE »

Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Hepatomegaly: Principal Causes of Hepatomegaly
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

1. Infection/inflammation
   1. Hepatitis
      1. Viral
      2. Bacterial
      3. Other infections
      4. Toxic
      5. Autoimmune
   2. Cholangitis
2. Hemolytic anemia
3. Cardiac disorders
4. Trauma
5. Bile duct obstruction
   1. Biliaryatresia
   2. Caroli disease
6. Vascular disorders
   1. Budd-Chiarisyndrome
   2. Venoocclusive disease
7. Neoplasia
8. Metabolic disorders
   1. Disordersof carbohydrate metabolism
      1. Galactosemia
      2. Hereditary fructose intolerance
      3. Glycogen storage disease
         1. Glycogenstorage disease type I
         2. Glycogen storage disease type III
         3. Glycogen storage disease type IV
         4. Glycogen storage disease type VI
   2. Disorders of amino acid metabolism
      1. Tyrosinemia
      2. Urea cycle defects
   3. Disorders of lysosomal storage
      1. Mucopolysaccharidoses
      2. Lipidoses
         1. Gaucher disease (Types I, II, III)
         2. Nieman-Pick disease (Types A, B, C)
         3. GM-1 gangliosidosis
         4. GM-2 gangliosidosis (Sandhoff disease)
      3. Glycoprotein disorders
         1. Fucosidosis(Types I, II)
         2. Sialidosis type II
      4. Wolman disease and cholesterol esterdisease
   4. Disorders of fatty acid oxidation
   5. Disorders of bile acid synthesis andtransport
   6. Alpha1-antitrypsin deficiency
   7. Wilson disease
   8. Reye syndrome
   9. Zellweger syndrome
9. Systemic disorders
   1. Obesity
   2. Diabetes mellitus
   3. Cystic fibrosis
   4. Malnutrition
   5. Connective tissue diseases
   6. Histiocytoses
   7. Total parenteral nutrition

» READ BOOK EXCERPT ONLINE »

Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Hepatomegaly: Medical causes
(Nursing: Interpreting Signs and Symptoms)

Amyloidosis.Amyloidosis is a rare disorder that may cause hepatomegaly and mild jaundice as well as renal, cardiac, and other GI effects.

Cirrhosis.Late in cirrhosis, the liver becomes enlarged, nodular, and hard. Other late signs and symptoms affect all body systems. Respiratory findings include limited thoracic expansion due to abdominal ascites, leading to hypoxia. Central nervous system findings include signs and symptoms of hepatic encephalopathy, such as lethargy, slurred speech, asterixis, peripheral neuritis, paranoia, hallucinations, extreme obtundation, and coma. Hematologic signs include epistaxis, easy bruising, and bleeding gums. Endocrine findings include testicular atrophy, gynecomastia, loss of chest and axillary hair, or menstrual irregularities. Integumentary effects include abnormal pigmentation, jaundice, severe pruritus, extreme dryness, poor tissue turgor, spider angiomas, and palmar erythema.

The patient may also develop fetor hepaticus, enlarged superficial abdominal veins, muscle atrophy, right upper quadrant pain that worsens when he sits up or leans forward, and a palpable spleen. Portal hypertension—elevated pressure in the portal vein—causes bleeding from esophageal varices.

Diabetes mellitus.Poorly controlled diabetes in overweight patients commonly produces fatty infiltration of the liver, hepatomegaly, and right upper quadrant tenderness along with polydipsia, polyphagia, and polyuria. These features are more common in type 2 than in type 1 diabetes. A chronically enlarged fatty liver typically produces no symptoms except for slight tenderness.

Granulomatous disorders.Sarcoidosis, histoplasmosis, and other such disorders commonly produce a slightly enlarged, firm liver.

Hepatic abscess.Hepatomegaly may accompany a fever (a primary sign), nausea, vomiting, chills, weakness, diarrhea, anorexia, an elevated right hemidiaphragm, and right upper quadrant pain and tenderness.

Hepatitis.In viral hepatitis, early signs and symptoms include nausea, anorexia, vomiting, fatigue, malaise, photophobia, a sore throat, a cough, and a headache. Hepatomegaly occurs in the icteric phase and continues during the recovery phase. Also, during the icteric phase, the early signs and symptoms diminish and others appear: liver tenderness, slight weight loss, dark urine, clay-colored stools, jaundice, pruritus, right upper quadrant pain, and splenomegaly.

Leukemia and lymphomas.Leukemia and lymphomas are proliferative blood cell disorders that typically cause moderate to massive hepatomegaly and splenomegaly as well as abdominal discomfort. General signs and symptoms include malaise, a low-grade fever, fatigue, weakness, tachycardia, weight loss, bleeding disorders, and anorexia.

Liver cancer.Primary liver tumors commonly cause irregular, nodular, firm hepatomegaly, with pain or tenderness in the right upper quadrant and a friction rub or bruit over the liver. Common related findings are weight loss, anorexia, cachexia, nausea, and vomiting. Peripheral edema, ascites, jaundice, and a palpable right upper quadrant mass may also develop. When metastatic liver tumors cause hepatomegaly, the patient's accompanying signs and symptoms reflect his primary cancer.

Mononucleosis (infectious).Occasionally, infectious mononucleosis causes hepatomegaly. Prodromal symptoms include a headache, malaise, and fatigue. After 3 to 5 days, the patient typically develops a sore throat, cervical lymphadenopathy, and temperature fluctuations. He may also develop stomatitis, palatal petechiae, periorbital edema, splenomegaly, exudative tonsillitis, pharyngitis and, possibly, a maculopapular rash.

Obesity.Hepatomegaly can result from fatty infiltration of the liver. Weight loss reduces the liver's size.

Pancreatic cancer.In pancreatic cancer, hepatomegaly accompanies such classic signs and symptoms as anorexia, weight loss, abdominal or back pain, and jaundice. Other findings include nausea, vomiting, a fever, fatigue, weakness, pruritus, and skin lesions (usually on the legs).

Pericarditis.In chronic constrictive pericarditis, an increase in systemic venous pressure produces marked congestive hepatomegaly. Distended jugular veins (more prominent on inspiration) are a common finding. The usual signs of cardiac disease typically are absent; other features include peripheral edema, ascites, fatigue, and decreased muscle mass.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

Chronic Hepatitis: Chronic Hepatitis - pathophysiology
(The 5-Minute Pediatric Consult)

Pathology has been traditionally classified as chronic persistent hepatitis, chronic aggressive hepatitis, and chronic lobular hepatitis. The hepatocytes are damaged, with inflammatory cellular infiltration accompanied by liver regeneration.

• Chronic persistent hepatitis:
  • Minimal portal tract fibrosis
  • Slightly widened portal tracts
  • Limiting plate is intact and inflammation does not extend beyond this.
  • No bridging fibrosis between portal tracts
• Chronic aggressive hepatitis:
  • Perilobular hepatitis, with inflammatory cells extending from portal tracts into parenchyma with fibrosis
  • Piecemeal necrosis: Necrotic hepatocytes surrounded by lymphocytes and fibroblasts
  • In advanced disease, fibrosis bridges the portal tracts (bridging fibrosis).
  • Cirrhosis occurs when there is loss of architecture owing to fibrosis.
• Chronic lobular hepatitis:
  • Liver architecture is preserved with scattered changes of acute hepatitis with hepatocyte necrosis in the lobules (perivenular regions).
  • These changes are most often associated with hepatitis B and non-A, non-B hepatitis.

Chronic Hepatitis - etiology

• Autoimmune liver disease
• Viral hepatitis
• Obesity (NASH)
• Progressive familial intrahepatic cholestasis syndromes
• Congenital hepatic fibrosis
• Cystic fibrosis
• Metabolic disease:
  • Mitochondrial disease
  • Lysosomal storage disorders
  • Peroxisomal disease
  • Lipid storage disease
  • Glycogen storage disease
  • Wilson disease and others
• Drug hepatotoxicity:
  • Methotrexate
  • Isoniazid
  • Thioguanine
  • 6-Mercaptopurine
  • Valproate
• Liver disease associated with other chronic diseases:
  • Cardiac disease
  • Autosomal recessive polycystic kidney disease
  • Diabetes mellitus
  • Langerhans cell histiocytosis
  • Immunodeficiency
  • Total parenteral nutrition cholestasis

» READ BOOK EXCERPT ONLINE »

Source: The 5-Minute Pediatric Consult, 2008

Hepatomegaly: Hepatomegaly - etiology
(The 5-Minute Pediatric Consult)

• Most cases of hepatic failure in children are owing to acute viral hepatitis.
• Toxic exposure accounts for 25% of cases, with the most common drug being acetaminophen.

» READ BOOK EXCERPT ONLINE »

Source: The 5-Minute Pediatric Consult, 2008

Reye Syndrome: Reye Syndrome - pathophysiology
(The 5-Minute Pediatric Consult)

• Mitochondrial injury of unknown etiology in a viral-infected host results in dysfunction of oxidative phosphorylation and fatty acid oxidation.
• Mitochondrial toxins, usually salicylates, exacerbate the condition when ingested after mitochondrial injury.

Postmortem:

• Liver: Grossly yellowish-white, due to increased triglyceride levels; foamy cytoplasm with increased microvesicular fat, decreased glycogen
• Brain: Marked edema with increased intracellular fluid and loss of neurons
• Abnormal-looking mitochondria can be detected in many tissues.

» READ BOOK EXCERPT ONLINE »

Source: The 5-Minute Pediatric Consult, 2008

Hepatitis: Epidemiology and Etiology
(Pediatric Infectious Disease)

Hepatitis A is the most common viral etiology of pediatric hepatitis. The mode of transmission is person to person, resulting from fecal contamination of food. Sexual contact and nosocomial transmission have also been documented.

» READ BOOK EXCERPT ONLINE »

Source: Pediatric Infectious Disease, 2004

 » Next page: Symptoms of Reye's Syndrome

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