Causes of Alcoholic liver disease

• 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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Jaundice: Differential Diagnosis
(In a Page: Signs and Symptoms)

• Viral hepatitis
  –Fatigue, anorexia, fever, nausea, vomiting, dark urine, light-colored (acholic) loose stools, RUQ pain, hepatomegaly, and/or pruritis

• Alcoholic hepatitis
  –Associated with fever, leukocytosis, and AST:ALT ratio >2

• Nonalcoholic steatohepatitis or nonalchoholic fatty liver disease
  –Associated with obesity, diabetes, hyperlipidemia and medications

• Cholecystitis
  –RUQ pain, fever, leukocytosis
  –Female, fertile, fat, forty
  –Murphy's sign: Pain upon palpation of the
  gallbladder while taking a deep breath

• Drugs and toxins
  –Acetaminophen, alcohol, estrogens, isoniazid, chlorpromazine, erythromycin, nitrofurantoin, rifampin

• Gilbert's syndrome
  
  –Decreased conjugation of bilirubin, especially with dehydration, fasting, infection

• Bile ascites (bile peritonitis): Spontaneous rupture of the common bile duct
• Renal
  –Nephrotic syndrome
  –Urinary ascites (due to bladder rupture)
  –Obstructive uropathy: Congenital ascites may be seen with bilateral hydronephrosis
• Peritoneal dialysis
• Cardiac
  –Congestive heart failure
  –Chronic constrictive pericarditis
  –Inferior vena cava web
  –Erythroblastosis fetalis
• Peritonitis
  –Tuberculous peritonitis
  –Schistosomiasis (Mansoni)
  –Tularemia
  –Abscess
• Gastrointestinal disorders
  –Infarcted bowel
  –Bowel perforation
  –Pancreatitis, ruptured pancreatic duct
  –Protein-losing gastroenteropathy
• Chylous ascites
  –Collection of lymph within the abdominal cavity; secondary to lymphatic obstruction from trauma, surgery, tumor, tuberculosis, or filariasis
• Gynecologic
  –Ovarian tumors, cyst torsion or rupture
• Malignancy
  –Leukemia, lymphoma, neuroblastoma
• Systemic lupus erythromatosus
• Ventriculoperitoneal shunt
• Hypothyroidism

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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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Jaundice in Infants – Direct: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Bile duct obstruction
  –Biliary atresia: Represents the most frequent cause for liver transplantation in the pediatric patient; prompt diagnosis is crucial, as patient outcome is better if intervention comes before 60 days of life
  –Choledochal cyst
  –Common bile duct gallstone
  –Choledochocele
  –Bile duct stricture
  –Alagille syndrome
  –Caroli disease
  –Congenital hepatic fibrosis

• Neonatal hepatitis
  –Idiopathic hepatitis: Diagnosis of exclusion that should be made only when other causes are excluded; accounts for 60% of patients with neonatal cholestasis
  –Infections: TORCH, hepatitis B, HIV, E. coli, adenovirus, enterovirus, parvovirus B16, tuberculosis, listeriosis, malaria

• Metabolic disorders
  –α-1 antitrypsin deficiency
  –Cystic fibrosis
  –Hypothyroidism
  –Neonatal iron storage disease
  –Amino acids: tyrosinemia
  –Carbohydrates: Galactosemia, fructosemia
  –Lipids: Niemann-Pick, Gaucher, Wolman, cholesterol ester storage disease
  –Mitochondropathies
  –Bile acid synthetic disorders
  –Peroxisomal: Zellweger syndrome
  –Urea cycle defects
• Toxins
  –Total parenteral nutrition
  –Drugs: Trimethaprim-sulfamethoxazole, anticonvulsants
• Miscellaneous
  –Sepsis/hypoperfusion
  –Erythrophagocytic lymphohistiocytosis
  –Extracorporeal membrane oxygenation
  –Trisomy 17, 18, 21
  –Neonatal lupus erythematosus
  –Donohue syndrome
  –Rotor syndrome
  –Dubin-Johnson syndrome
  –Byler disease (PFIC type 1)
  –Cholestasis of North-American Indians
  –Nielsen syndrome

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Jaundice in Infants – Indirect: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Icterus neonatorum (physiologic jaundice)
  –The most common form of indirect jaundice in infants under 14 days of age
  –Caused by increased bilirubin production with transient limited conjugation abilities
• Breast-feeding jaundice
  –Occurs in first week of life in 13% of breast-fed infants
  –Secondary to poor volume intake
• Breast-milk jaundice
  –Occurs in about 2% of breast-fed infants after day 7 of life
  –Secondary to glucuronidase in breast milk
• Hematologic: Hemolysis increases bili load
  –Rh incompatability
  –ABO incompatability
  –Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  –Pyruvate kinase deficiency
  –Hereditary spherocytosis
  –Elliptocytosis
  –Thalassemia
  –Polycythemia
• Extravascular blood
  –Cephalohematoma
  –Trauma
  –Swallowed maternal blood
• Endocrinologic
  –Hypothyroidism
  –Maternal diabetes
• Sepsis
• Metabolic
  –Crigler-Najjar I
  –Crigler-Najjar II (Arias syndrome)
  –Crigler-Najjar III
• Cardiopulmonary
  –Congestive heart failure
  –Patent ductus arteriosus
  –Portal vein thrombosis
• Anatomic
  –Pyloric stenosis
  –Duodenal atresia/stenosis
  –Duodenal web
• Drugs
  –Oxytocin
  –Sulfonamides
  –Ceftriaxone
  –Chuen-Lin
• Lucey-Driscoll syndrome

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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.

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

Carcinoma

Cancer of the ampulla of Vater initially produces fluctuating jaundice, mild abdominal pain, a recurrent fever, and chills

Occult bleeding may be its first sign. Other findings include weight loss, pruritus, and back pain.

Hepatic cancer (primary liver cancer or another cancer that has metastasized to the liver) may cause jaundice by causing obstruction of the bile duct. Even advanced cancer causes nonspecific signs and symptoms, such as right upper quadrant discomfort and tenderness, nausea, weight loss, and a slight fever. Examination may reveal irregular, nodular, firm hepatomegaly; ascites; peripheral edema; a bruit heard over the liver; and a right upper quadrant mass.

Withpancreatic cancer,progressive jaundice — possibly with pruritus — may be the only sign. Related early findings are nonspecific, such as weight loss and back or abdominal pain. Other signs and symptoms include anorexia, nausea and vomiting, a fever, steatorrhea, fatigue, weakness, diarrhea, pruritus, and skin lesions (usually on the legs).

Cholangitis

Obstruction and infection in the common bile duct cause Charcot’s triad: jaundice, right upper quadrant pain, and a high fever with chills.

Cholecystitis

Cholecystitis produces nonobstructive jaundice in about 25% of patients

Biliary colic typically peaks abruptly, persisting for 2 to 4 hours. The pain then localizes to the right upper quadrant and becomes constant. Local inflammation or passage of stones to the common bile duct causes jaundice. Other findings include nausea, vomiting (usually indicating the presence of a stone), a fever, profuse diaphoresis, chills, tenderness on palpation, a positive Murphy’s sign and, possibly, abdominal distention and rigidity.

Cholelithiasis

Cholelithiasis commonly causes jaundice and biliary colic

It’s characterized by severe, steady pain in the right upper quadrant or epigastrium that radiates to the right scapula or shoulder and intensifies over several hours. Accompanying signs and symptoms include nausea and vomiting, tachycardia, and restlessness. Occlusion of the common bile duct causes a fever, chills, jaundice, clay-colored stools, and abdominal tenderness. After consuming a fatty meal, the patient may experience vague epigastric fullness and dyspepsia.

Cirrhosis

With Laënnec’s cirrhosis, mild to moderate jaundice with pruritus usually signals hepatocellular necrosis or progressive hepatic insufficiency

Common early findings include ascites, weakness, leg edema, nausea and vomiting, diarrhea or constipation, anorexia, weight loss, and right upper quadrant pain. Massive hematemesis and other bleeding tendencies may also occur. Other findings include an enlarged liver and parotid gland, clubbed fingers, Dupuytren’s contracture, mental changes, asterixis, fetor hepaticus, spider angiomas, and palmar erythema. Males may exhibit gynecomastia, scanty chest and axillary hair, and testicular atrophy; females may experience menstrual irregularities.

With primary biliary cirrhosis,fluctuating jaundice may appear years after the onset of other signs and symptoms, such as pruritus that worsens at bedtime (commonly the first sign), weakness, fatigue, weight loss, and vague abdominal pain. Itching may lead to skin excoriation. Associated findings include hyperpigmentation; indications of malabsorption, such as nocturnal diarrhea, steatorrhea, purpura, and osteomalacia; hematemesis from esophageal varices; ascites; edema; xanthelasmas; xanthomas on the palms, soles, and elbows; and hepatomegaly.

Dubin-Johnson syndrome

With Dubin-Johnson syndrome, which is a rare, chronic inherited syndrome, fluctuating jaundice that increases with stress is the major sign, appearing as late as age 40

Related findings include slight hepatic enlargement and tenderness, upper abdominal pain, nausea, and vomiting.

Heart failure

Jaundice due to liver dysfunction occurs in patients with severe right-sided heart failure

Other effects include jugular vein distention, cyanosis, dependent edema of the legs and sacrum, steady weight gain, confusion, hepatomegaly, nausea and vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites are a late sign. Oliguria, marked weakness, and anxiety may also occur. If left-sided heart failure develops first, other findings may include fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, arrhythmias, and tachycardia.

Hepatic abscess

Multiple abscesses may cause jaundice, but the primary effects are a persistent fever with chills and sweating

Other findings include steady, severe pain in the right upper quadrant or midepigastrium that may be referred to the shoulder; nausea and vomiting; anorexia; hepatomegaly; an elevated right hemidiaphragm; and ascites.

Hepatitis

Dark urine and clay-colored stools usually develop before jaundice in the late stages of acute viral hepatitis

Early systemic signs and symptoms vary and include fatigue, nausea, vomiting, malaise, arthralgia, myalgia, a headache, anorexia, photophobia, pharyngitis, a cough, diarrhea or constipation, and a low-grade fever associated with liver and lymph node enlargement. During the icteric phase (which subsides within 2 to 3 weeks unless complications occur), systemic signs subside, but an enlarged, palpable liver may be present along with weight loss, anorexia, and right upper quadrant pain and tenderness.

Pancreatitis (acute)

Edema of the head of the pancreas and obstruction of the common bile duct can cause jaundice; however, the primary symptom of acute pancreatitis is usually severe epigastric pain that commonly radiates to the back

Lying with the knees flexed on the chest or sitting up and leaning forward brings relief. Early associated signs and symptoms include nausea, persistent vomiting, abdominal distention, and Turner’s or Cullen’s sign. Other findings include a fever, tachycardia, abdominal rigidity and tenderness, hypoactive bowel sounds, and crackles.

Severe pancreatitis produces extreme restlessness; mottled skin; cold, diaphoretic extremities; paresthesia; and tetany — the last two being symptoms of hypocalcemia. Fulminant pancreatitis causes massive hemorrhage.

Sickle cell anemia

Hemolysis produces jaundice in the patient with sickle cell anemia

Other findings include impaired growth and development, increased susceptibility to infection, life-threatening thrombotic complications and, commonly, leg ulcers, swollen (painful) joints, a fever, and chills. Bone aches and chest pain may also occur. Severe hemolysis may cause hematuria and pallor, chronic fatigue, weakness, dyspnea (or dyspnea on exertion), and tachycardia. The patient may also have splenomegaly. During a sickle cell crisis, the patient may have severe bone, abdominal, thoracic, and muscular pain; a low-grade fever; and increased weakness, jaundice, and dyspnea.

Other causes

Drugs

Many drugs may cause hepatic injury and resultant jaundice

Examples include acetaminophen, phenylbutazone, I.V. tetracycline, isoniazid, hormonal contraceptives, sulfonamides, mercaptopurine, erythromycin estolate, niacin, troleandomycin, androgenic steroids, 3-hydroxy-3-methylglutaryl reductase inhibitors, phenothiazines, ethanol, methyldopa, rifampin, and dilantin.

Treatments

Upper abdominal surgery may cause postoperative jaundice, which occurs secondary to hepatocellular damage from the manipulation of organs, leading to edema and obstructed bile flow; from the administration of halothane; or from prolonged surgery resulting in shock, blood loss, or blood transfusion.

A surgical shunt used to reduce portal hypertension (such as a portacaval shunt) may also produce jaundice.

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Alcohol-related disorder: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

Numerous biological, psychological, and sociocultural factors appear to be involved in alcohol addiction. An offspring of one parent with alcohol-related disorder is seven to eight times more likely to become an alcoholic than is a peer without such a parent. Biological factors may include genetic or biochemical abnormalities, nutritional deficiencies, endocrine imbalances, and allergic responses.

Psychological factors may include the urge to drink alcohol to reduce anxiety or symptoms of mental illness; the desire to avoid responsibility in familial, social, and work relationships; and the need to bolster self-esteem.

Sociocultural factors include the availability of alcoholic beverages, group or peer pressure, an excessively stressful lifestyle, and social attitudes that approve of frequent drinking.

More than 15% of American adults have a problem with alcohol use, and about 5% to 10% of male and 3% to 5% of female drinkers are alcohol dependent, accounting for about 12.5 million people. Alcohol-related disorder cuts across all social and economic groups, involves both sexes, and occurs at all stages of the life cycle, beginning as early as elementary school.

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Cirrhosis and fibrosis: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

These clinical types of cirrhosis reflect its diverse etiology:

❑ Portal, nutritional, or alcoholic (Laennec’s) cirrhosis, the most common type, occurs in 30% to 50% of cirrhotic patients, up to 90% of whom have a history of alcoholism. Liver damage results from malnutrition, especially of dietary protein, and chronic alcohol ingestion. Fibrous tissue forms in portal areas and around central veins.

❑ Biliary cirrhosis (15% to 20% of patients) results from injury or prolonged obstruction.

❑ Postnecrotic (posthepatic) cirrhosis (10% to 30% of patients) stems from various types of hepatitis.

❑ Pigment cirrhosis (5% to 10% of patients) may result from disorders such as hemochromatosis.

❑ Cardiac cirrhosis (rare) refers to liver damage caused by right-sided heart failure.

❑ Idiopathic cirrhosis (about 10% of patients) has no known cause.

Noncirrhotic fibrosis may result from schistosomiasis or congenital hepatic fibrosis or may be idiopathic.

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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.

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Jaundice [Icterus]: Medical causes
(Professional Guide to Signs & Symptoms (Fifth Edition))

Agnogenic myeloid metaplasia

This myeloproliferative disorder of the bone marrow may cause jaundice. Its typical effects, however, are associated with anemia, including fatigue, weakness, anorexia, massive splenomegaly, hepatomegaly, purpura, and bleeding tendencies.

Carcinoma

Cancer of the ampulla of Vater initially produces fluctuating jaundice, mild abdominal pain, recurrent fever, and chills. Occult bleeding may be its first sign. Other findings include weight loss, pruritus, and back pain.

Hepatic cancer (primary liver cancer or another cancer that has metastasized to the liver) may cause jaundice by causing obstruction of the bile duct. Even advanced cancer causes nonspecific signs and symptoms, such as right-upper-quadrant discomfort and tenderness, nausea, weight loss, and slight fever. Examination may reveal irregular, nodular, firm hepatomegaly, ascites, peripheral edema, a bruit heard over the liver, and a right-upper-quadrant mass.

With pancreatic cancer, progressive jaundice—possibly with pruritus—may be the only sign. Related early findings are nonspecific, such as weight loss and back or abdominal pain. Other signs and symptoms include anorexia, nausea and vomiting, fever, steatorrhea, fatigue, weakness, diarrhea, pruritus, and skin lesions (usually on the legs).

Cholangitis

Obstruction and infection in the common bile duct cause Charcot’s triad: jaundice, right-upper-quadrant pain, and high fever with chills.

Cholecystitis

This disorder produces nonobstructive jaundice in about 25% of patients. Biliary colic typically peaks abruptly, persisting for 2 to 4 hours. The pain then localizes to the right upper quadrant and becomes constant. Local inflammation or passage of stones to the common bile duct causes jaundice. Other findings include nausea, vomiting (usually indicating the presence of a stone), fever, profuse diaphoresis, chills, tenderness on palpation, a positive Murphy’s sign, and, possibly, abdominal distention and rigidity.

Cholelithiasis

This disorder commonly causes jaundice and biliary colic. It’s characterized by severe, steady pain in the right upper quadrant or epigastrium that radiates to the right scapula or shoulder and intensifies over several hours. Accompanying signs and symptoms include nausea and vomiting, tachycardia, and restlessness. Occlusion of the common bile duct causes fever, chills, jaundice, clay-colored stools, and abdominal tenderness. After consuming a fatty meal, the patient may experience vague epigastric fullness and dyspepsia.

Cholestasis

With benign, recurrent intrahepatic cholestasis, the patient experiences prolonged attacks of jaundice (sometimes spaced several years apart) accompanied by pruritus. Other signs and symptoms are similar to those of hepatitis—fatigue, nausea, weight loss, anorexia, pale stools, and right-upper-quadrant pain.

Cirrhosis

With Laënnec’s cirrhosis, mild to moderate jaundice with pruritus usually signals hepatocellular necrosis or progressive hepatic insufficiency. Common early findings include ascites, weakness, leg edema, nausea and vomiting, diarrhea or constipation, anorexia, weight loss, and right-upper-quadrant pain. Massive hematemesis and other bleeding tendencies may also occur. Other findings include an enlarged liver and parotid gland, clubbed fingers, Dupuytren’s contracture, mental changes, asterixis, fetor hepaticus, spider angiomas, and palmar erythema. Males may exhibit gynecomastia, scanty chest and axillary hair, and testicular atrophy; females may experience menstrual irregularities.

With primary biliary cirrhosis, fluctuating jaundice may appear years after the onset of other signs and symptoms, such as pruritus that worsens at bedtime (commonly the first sign), weakness, fatigue, weight loss, and vague abdominal pain. Itching may lead to skin excoriation. Associated findings include hyperpigmentation; indications of malabsorption, such as nocturnal diarrhea, steatorrhea, purpura, and osteomalacia; hematemesis from esophageal varices; ascites; edema; xanthelasmas; xanthomas on the palms, soles, and elbows; and hepatomegaly.

Dubin-Johnson syndrome

With this rare, chronic inherited syndrome, fluctuating jaundice that increases with stress is the major sign, appearing as late as age 40. Related findings include slight hepatic enlargement and tenderness, upper abdominal pain, nausea, and vomiting.

Glucose-6-phosphate dehydrogenase deficiency

Acute intravascular hemolysis following ingestion of such drugs as quinine or aspirin causes jaundice, pallor, dyspnea, tachycardia, and malaise. Palpation may reveal splenomegaly and hepatomegaly.

Heart failure

Jaundice due to liver dysfunction occurs in patients with severe right-sided heart failure. Other effects include jugular vein distention, cyanosis, dependent edema of the legs and sacrum, steady weight gain, confusion, hepatomegaly, nausea and vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites is a late sign. Oliguria, marked weakness, and anxiety may also occur. If left-sided heart failure develops first, other findings may include fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, arrhythmias, and tachycardia.

Hemolytic anemia (acquired)

This disorder may produce prominent jaundice along with dyspnea, fatigue, pallor, tachycardia, and palpitations. Rapid hemolysis causes chills, fever, irritability, headache, and abdominal pain; severe hemolysis causes signs of shock.

Hepatic abscess

Multiple abscesses may cause jaundice, but the primary effects are persistent fever with chills and sweating. Other findings include steady, severe pain in the right upper quadrant or midepigastrium that may be referred to the shoulder; nausea and vomiting; anorexia; hepatomegaly; elevated right hemidiaphragm; and ascites.

Hepatitis

Dark urine and clay-colored stools usually develop before jaundice in the late stages of acute viral hepatitis. Early systemic signs and symptoms vary and include fatigue, nausea, vomiting, malaise, arthralgias, myalgias, headache, anorexia, photophobia, pharyngitis, cough, diarrhea or constipation, and a low-grade fever associated with liver and lymph node enlargement. During the icteric phase (which subsides within 2 to 3 weeks unless complications occur), systemic signs subside, but an enlarged, palpable liver may be present along with weight loss, anorexia, and right-upper-quadrant pain and tenderness.

Leptospirosis

Severe leptospirosis (Weil’s disease) may cause jaundice. This disorder begins suddenly with a frontal headache, severe muscle aches in the thighs and lumbar area, cutaneous hyperesthesia, abdominal pain, nausea, conjunctival suffusion, and vomiting. Chills and a rapidly rising fever follow. Signs and symptoms of meningeal irritation include drowsiness, decreased mentation, stiff neck, and positive Kernig’s and Brudzinski’s signs. Right-upper-quadrant tenderness, hepatomegaly, and jaundice indicate hepatic involvement; proteinuria, pyuria, and hematuria indicate renal involvement. Epistaxis, hematemesis, melena, and hemoptysis may also occur.

Pancreatitis (acute)

Edema of the head of the pancreas and obstruction of the common bile duct can cause jaundice; however, this disorder’s primary symptom is usually severe epigastric pain that commonly radiates to the back. Lying with the knees flexed on the chest or sitting up and leaning forward brings relief. Early associated signs and symptoms include nausea, persistent vomiting, abdominal distention, and Turner’s or Cullen’s sign. Other findings include fever, tachycardia, abdominal rigidity and tenderness, hypoactive bowel sounds, and crackles.

Severe pancreatitis produces extreme restlessness; mottled skin; cold, diaphoretic extremities; paresthesia; and tetany—the last two being symptoms of hypocalcemia. Fulminant pancreatitis causes massive hemorrhage.

Sickle cell anemia

Hemolysis produces jaundice in patients with this disorder. Other findings include impaired growth and development, increased susceptibility to infection, life-threatening thrombotic complications and, commonly, leg ulcers, (painful) swollen joints, fever, and chills. Bone aches and chest pain may also occur. Severe hemolysis may cause hematuria and pallor, chronic fatigue, weakness, dyspnea (or dyspnea on exertion), and tachycardia. The patient may also have splenomegaly. During a sickle cell crisis, the patient may have severe bone, abdominal, thoracic, and muscular pain; low-grade fever; and increased weakness, jaundice, and dyspnea.

Zieve syndrome

Caused by alcohol abuse, this relatively rare disorder produces abdominal pain and a sudden onset of severe jaundice. However, spider angiomas, ascites, and other signs of advanced liver disease are absent.

Other causes

Drugs

Many drugs may cause hepatic injury and resultant jaundice. Examples include acetaminophen, I.V. tetracycline, isoniazid, hormonal contraceptives, sulfonamides, mercaptopurine, erythromycin estolate, niacin, troleandomycin, androgenic steroids, HMG-CoA reductase inhibitors, phenothiazines, ethanol, methyldopa, rifampin, and phenytoin.

Treatments

Upper abdominal surgery may cause postoperative jaundice, which occurs secondary to hepatocellular damage from the manipulation of organs, leading to edema and obstructed bile flow; from the administration of halothane; or from prolonged surgery resulting in shock, blood loss, or blood transfusion.

A surgical shunt used to reduce portal hypertension (such as a portacaval shunt) may also produce jaundice.

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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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Jaundice: Differential Overview
(Field Guide to Bedside Diagnosis)

Conjugated

❑ Viral hepatitis

❑ Gallstone obstruction

❑ Drugs

❑ Carotinemia

❑ Alcohol-induced hepatitis

❑ Cirrhosis

❑ Pregnancy (cholestatic)

❑ Postoperative

❑ Metastatic cancer

❑ Pancreatic cancer

❑ Ampullary carcinoma

❑ Hepatoma

❑ Sclerosing cholangitis

❑ Primary biliary cirrhosis

❑ Leptospirosis

❑ Hepatic vein obstruction (Budd-Chiari)

❑ Hemochromatosis

Unconjugated

❑ Hemolysis

❑ Gilbert syndrome

❑ Sepsis

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Alcoholism: Causes
(Handbook of Diseases)

Numerous biological, psychological, and sociocultural factors appear to be involved in alcohol addiction. An offspring of one alcoholic parent is seven to eight times more likely to become an alcoholic than is a peer without an alcoholic parent. Biological factors include genetic and biochemical abnormalities, nutritional deficiencies, endocrine imbalances, and allergic responses.

Psychological factors include the urge to drink alcohol to reduce anxiety or symptoms of mental illness; the desire to avoid responsibility in family, social, and work relationships; and the need to bolster self-esteem.

Sociocultural factors include the availability of alcoholic beverages, peer pressure, an excessively stressful lifestyle, and social attitudes that approve of frequent drinking.

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Cirrhosis: Causes
(Handbook of Diseases)

Cirrhosis has various causes, depending on the type.

Hepatocellular disease

Postnecrotic cirrhosis accounts for 10% to 30% of patients and stems from various types of hepatitis (such as types A, B, C, D viral hepatitis) or toxic exposures.

Laënnec’s cirrhosis — also called portal, nutritional, or alcoholic cirrhosis — is the most common type and is commonly caused by hepatitis C. Liver damage results from malnutrition (especially dietary protein) and overuse of alcohol. Fibrous tissue forms in portal areas and around central veins.

Autoimmune disease, such as sarcoidosis and chronic inflammatory bowel disease, may result in cirrhosis.

Cholestatic diseases

Cholestatic diseases include diseases of the biliary tree (biliary cirrhosis resulting from bile duct diseases suppressing bile flow) and sclerosing cholangitis.

Metabolic diseases

Metabolic diseases include disorders such as Wilson’s disease, alpha₁-antitrypsin deficiency, and hemochromatosis (pigment cirrhosis).

Other types of cirrhosis

Other types of cirrhosis include Budd-Chiari syndrome, cardiac cirrhosis, and cryptogenic cirrhosis. Cardiac cirrhosis is rare; the liver damage results from right-sided heart failure. Cryptogenic refers to cirrhosis of unknown cause.

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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).

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

Carcinoma

Cancer of the ampulla of Vater initially produces fluctuating jaundice, mild abdominal pain, recurrent fever, and chills. Occult bleeding may be its first sign. Other findings include weight loss, pruritus, and back pain.

Hepatic cancer (primary liver cancer or metastases to the liver) may cause jaundice by causing obstruction of the bile duct. Even advanced cancer causes nonspecific signs and symptoms, such as right-upper-quadrant discomfort and tenderness, nausea, weight loss, and slight fever. Examination may reveal irregular, nodular, firm hepatomegaly, ascites, peripheral edema, a bruit heard over the liver, and a right-upper-quadrant mass.

With pancreatic cancer, progressive jaundice — possibly with pruritus — may be the only sign. Related early findings are nonspecific, such as weight loss and back or abdominal pain. Other signs and symptoms include anorexia, nausea and vomiting, fever, steatorrhea, fatigue, weakness, diarrhea, pruritus, and skin lesions (usually on the legs).

Cholangitis

Obstruction and infection in the common bile duct cause Charcot’s triad: jaundice, right-upper-quadrant pain, and high fever with chills. The patient may also report pruritus. Acholic or hypocholic stools may be present.

Cholecystitis

Cholecystitis produces nonobstructive jaundice in about 25% of patients. Biliary colic typically peaks abruptly, persisting for 2 to 4 hours. The pain then localizes to the right upper quadrant and becomes constant. Local inflammation or passage of stones to the common bile duct causes jaundice. Other findings include nausea, vomiting (usually indicating the presence of a stone), fever, profuse diaphoresis, chills, tenderness on palpation, a positive Murphy’s sign and, possibly, abdominal distention and rigidity.

Cholelithiasis

Cholelithiasis commonly causes jaundice and biliary colic. It’s characterized by severe, steady pain in the right upper quadrant or epigastrium that radiates to the right scapula or shoulder and intensifies over several hours. Accompanying signs and symptoms include nausea and vomiting, tachycardia, and restlessness. Occlusion of the common bile duct causes fever, chills, jaundice, clay-colored stools, and abdominal tenderness. After consuming a fatty meal, the patient may experience vague epigastric fullness and dyspepsia.

Cholestasis

With benign, recurrent intrahepatic cholestasis, the patient experiences prolonged attacks of jaundice (sometimes spaced several years apart) accompanied by pruritus. Other signs and symptoms are similar to those of hepatitis — fatigue, nausea, weight loss, anorexia, pale stools, and right-upper-quadrant pain.

Cirrhosis

With Laënnec’s cirrhosis, mild to moderate jaundice with pruritus usually signals hepatocellular necrosis or progressive hepatic insufficiency. Common early findings include ascites, weakness, leg edema, nausea and vomiting, diarrhea or constipation, anorexia, weight loss, and right-upper-quadrant pain. Massive hematemesis and other bleeding tendencies may also occur. Other findings include an enlarged liver and parotid gland, clubbed fingers, Dupuytren’s contracture, mental changes, asterixis, fetor hepaticus, spider angiomas, and palmar erythema. Males may exhibit gynecomastia, scanty chest and axillary hair, and testicular atrophy; females may experience menstrual irregularities.

With primary biliary cirrhosis, fluctuating jaundice may appear years after the onset of other signs and symptoms, such as pruritus that worsens at bedtime (commonly the first sign), weakness, fatigue, weight loss, and vague abdominal pain. Itching may lead to skin excoriation. Associated findings include hyperpigmentation; indications of malabsorption, such as nocturnal diarrhea, steatorrhea, purpura, and osteomalacia; hematemesis from esophageal varices; ascites; edema; xanthelasmas; xanthomas on the palms, soles, and elbows; and hepatomegaly.

Glucose-6-phosphate dehydrogenase deficiency

Acute intravascular hemolysis following ingestion of such drugs as quinine or aspirin causes jaundice, pallor, dyspnea, tachycardia, and malaise. Palpation may reveal splenomegaly and hepatomegaly.

Heart failure

Jaundice due to liver dysfunction occurs in patients with severe right-sided heart failure. Other effects include jugular vein distention, cyanosis, dependent edema of the legs and sacrum, steady weight gain, confusion, hepatomegaly, nausea and vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites is a late sign. Oliguria, marked weakness, and anxiety may also occur. If left-sided heart failure develops first, other findings may include fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, arrhythmias, and tachycardia.

Hemolytic anemia (acquired)

Acquired hemolytic anemia may produce prominent jaundice along with dyspnea, fatigue, pallor, tachycardia, and palpitations. Rapid hemolysis causes chills, fever, irritability, headache, and abdominal pain; severe hemolysis causes signs of shock.

Hepatitis

Dark urine and clay-colored stools usually develop before jaundice in the late stages of acute viral hepatitis. Early systemic signs and symptoms vary and include fatigue, nausea, vomiting, malaise, arthralgias, myalgias, headache, anorexia, photophobia, pharyngitis, cough, diarrhea or constipation, and a low-grade fever associated with liver and lymph node enlargement. During the icteric phase (which subsides within 2 to 3 weeks unless complications occur), systemic signs subside, but an enlarged, palpable liver may be present along with weight loss, anorexia, and right-upper-quadrant pain and tenderness.

Pancreatitis (acute)

Pancreatitis can cause jaundice; however, this disorder’s primary symptom is usually severe epigastric pain that commonly radiates to the back. Lying with the knees flexed on the chest or sitting up and leaning forward brings relief. Early associated signs and symptoms include nausea, persistent vomiting, abdominal distention, and Turner’s or Cullen’s sign. Other findings include fever, tachycardia, abdominal rigidity and tenderness, hypoactive bowel sounds, and crackles.

Severe pancreatitis produces extreme restlessness; mottled skin; cold, diaphoretic extremities; paresthesia; and tetany — the last two being symptoms of hypocalcemia. Fulminant pancreatitis causes massive hemorrhage.

Sickle cell anemia

Hemolysis produces jaundice in patients with sickle cell anemia. Other findings include impaired growth and development, increased susceptibility to infection, life-threatening thrombotic complications and, commonly, leg ulcers, swollen joints (sometimes painful), fever, and chills. Bone aches and chest pain may also occur. Severe hemolysis may cause hematuria and pallor, chronic fatigue, weakness, dyspnea (or dyspnea on exertion), and tachycardia. The patient may also have splenomegaly. During a sickle cell crisis, the patient may have severe bone, abdominal, thoracic, and muscular pain; low-grade fever; and increased weakness, jaundice, and dyspnea.

Other causes

Drugs

Many drugs may cause hepatic injury and resultant jaundice. Examples include acetaminophen, phenylbutazone, I.V. tetracycline, isoniazid, hormonal contraceptives, sulfonamides, mercaptopurine, erythromycin estolate, niacin, troleandomycin, androgenic steroids, HMG-CoA reductase inhibitors, phenothiazines, ethanol, methyldopa, rifampin, and dilantin.

Treatments

Upper abdominal surgery may cause postoperative jaundice, which occurs secondary to hepatocellular damage from the manipulation of organs. Postoperative jaundice may lead to edema and obstructed bile flow from the administration of halothane or from prolonged surgery resulting in shock, blood loss, or blood transfusion. A surgical shunt used to reduce portal hypertension (such as a portacaval shunt) may also produce jaundice.

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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

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Jaundice: Principal Causes of Unconjugated Hyperbilirubinemia
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

1. Neonatalonset
   1. Increasedbilirubin production
      1. Physiologic
      2. Hemolytic anemia
         1. Isoimmunization
         2. Red cell enzyme defects
            1. Glucose-6-phosphatedehydrogenase deficiency
            2. Pyruvate kinase deficiency
            3. Other enzyme defects
         3. Red cell membrane defects
            1. Hereditaryspherocytosis
            2. Hereditary elliptocytosis
            3. Hereditary stomatocytosis
            4. Infantile pyknocytosis
         4. Septicemia
      3. Polycythemia
      4. Enclosed hematoma
   2. Decreased bilirubin uptake, storage,or metabolism
      1. Physiologic
      2. Hypoxia and acidosis
      3. Hypoalbuminemia
      4. Increased serum fatty acids
      5. Septicemia
      6. Drugs
      7. Hypothyroidism
      8. Lucey-Driscoll syndrome (transientfamilial neonatal hyperbilirubinemia)
      9. Crigler-Najjar syndrome (types I andII)
   3. Increased enterohepatic circulation
      1. Physiologic
      2. Breast-feeding–related jaundice
      3. Intestinal obstruction
2. Postneonatal onset
   1. Increasedbilirubin production
      1. Hemolytic anemia
      2. Septicemia
   2. Decreased bilirubin uptake, storage,or metabolism
      1. Gilbertsyndrome
      2. Septicemia

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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.

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Jaundice [Icterus]: Medical causes
(Nursing: Interpreting Signs and Symptoms)

Carcinoma.Cancer of the ampulla of Vater initially produces fluctuating jaundice, mild abdominal pain, a recurrent fever, and chills. Occult bleeding may be its first sign. Other findings include weight loss, pruritus, and back pain.

Hepatic cancer (primary liver cancer or another cancer that has metastasized to the liver) may cause jaundice by causing obstruction of the bile duct. Even advanced cancer causes nonspecific signs and symptoms, such as right upper quadrant discomfort and tenderness, nausea, weight loss, and a slight fever. Examination may reveal irregular, nodular, firm hepatomegaly; ascites; peripheral edema; a bruit heard over the liver; and a right upper quadrant mass.

With pancreatic cancer, progressive jaundice—possibly with pruritus—may be the only sign. Related early findings are nonspecific, such as weight loss and back or abdominal pain. Other signs and symptoms include anorexia, nausea and vomiting, a fever, steatorrhea, fatigue, weakness, diarrhea, pruritus, and skin lesions (usually on the legs).

Cholangitis.Obstruction and infection in the common bile duct cause Charcot's triad: jaundice, right upper quadrant pain, and a high fever with chills.

Cholecystitis.Cholecystitis produces nonobstructive jaundice in about 25% of patients. Biliary colic typically peaks abruptly, persisting for 2 to 4 hours. The pain then localizes to the right upper quadrant and becomes constant. Local inflammation or passage of stones to the common bile duct causes jaundice. Other findings include nausea, vomiting (usually indicating the presence of a stone), a fever, profuse diaphoresis, chills, tenderness on palpation, a positive Murphy's sign and, possibly, abdominal distention and rigidity.

Cholelithiasis.Cholelithiasis commonly causes jaundice and biliary colic. It's characterized by severe, steady pain in the right upper quadrant or epigastrium that radiates to the right scapula or shoulder and intensifies over several hours. Accompanying signs and symptoms include nausea and vomiting, tachycardia, and restlessness. Occlusion of the common bile duct causes a fever, chills, jaundice, clay-colored stools, and abdominal tenderness. After consuming a fatty meal, the patient may experience vague epigastric fullness and dyspepsia.

Cirrhosis.With Laënnec's cirrhosis, mild to moderate jaundice with pruritus usually signals hepatocellular necrosis or progressive hepatic insufficiency. Common early findings include ascites, weakness, leg edema, nausea and vomiting, diarrhea or constipation, anorexia, weight loss, and right upper quadrant pain. Massive hematemesis and other bleeding tendencies may also occur. Other findings include an enlarged liver and parotid gland, clubbed fingers, Dupuytren's contracture, mental changes, asterixis, fetor hepaticus, spider angiomas, and palmar erythema. Males may exhibit gynecomastia, scanty chest and axillary hair, and testicular atrophy; females may experience menstrual irregularities.

With primary biliary cirrhosis, fluctuating jaundice may appear years after the onset of other signs and symptoms, such as pruritus that worsens at bedtime (commonly the first sign), weakness, fatigue, weight loss, and vague abdominal pain. Itching may lead to skin excoriation. Associated findings include hyperpigmentation; indications of malabsorption, such as nocturnal diarrhea, steatorrhea, purpura, and osteomalacia; hematemesis from esophageal varices; ascites; edema; xanthelasmas; xanthomas on the palms, soles, and elbows; and hepatomegaly.

Dubin-Johnson syndrome.With Dubin-Johnson syndrome, which is a rare, chronic inherited syndrome, fluctuating jaundice that increases with stress is the major sign, appearing as late as age 40. Related findings include slight hepatic enlargement and tenderness, upper abdominal pain, nausea, and vomiting.

Heart failure.Jaundice due to liver dysfunction occurs in patients with severe right-sided heart failure. Other effects include jugular vein distention, cyanosis, dependent edema of the legs and sacrum, steady weight gain, confusion, hepatomegaly, nausea and vomiting, abdominal discomfort, and anorexia due to visceral edema. Ascites is a late sign. Oliguria, marked weakness, and anxiety may also occur. If left-sided heart failure develops first, other findings may include fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, tachypnea, arrhythmias, and tachycardia.

Hepatic abscess.Multiple liver abscesses may cause jaundice, but the primary effects are a persistent fever with chills and sweating. Other findings include steady, severe pain in the right upper quadrant or midepigastrium that may be referred to the shoulder; nausea and vomiting; anorexia; hepatomegaly; an elevated right hemidiaphragm; and ascites.

Hepatitis.Dark urine and clay-colored stools usually develop before jaundice in the late stages of acute viral hepatitis. Early systemic signs and symptoms vary and include fatigue, nausea, vomiting, malaise, arthralgia, myalgia, a headache, anorexia, photophobia, pharyngitis, a cough, diarrhea or constipation, and a low-grade fever associated with liver and lymph node enlargement. During the icteric phase (which subsides within 2 to 3 weeks unless complications occur), systemic signs subside, but an enlarged, palpable liver may be present along with weight loss, anorexia, and right upper quadrant pain and tenderness.

Pancreatitis (acute).Edema of the head of the pancreas and obstruction of the common bile duct can cause jaundice; however, the primary symptom of acute pancreatitis is severe epigastric pain that commonly radiates to the back. Lying with the knees flexed on the chest or sitting up and leaning forward brings relief. Early associated signs and symptoms include nausea, persistent vomiting, abdominal distention, and Turner's or Cullen's sign. Other findings include a fever, tachycardia, abdominal rigidity and tenderness, hypoactive bowel sounds, and crackles.

Severe pancreatitis produces extreme restlessness; mottled skin; cold, dia-phoretic extremities; paresthesia; and tetany—the last two being symptoms of hypocalcemia. Fulminant pancreatitis causes massive hemorrhage.

Sickle cell anemia.Hemolysis produces jaundice in the patient with sickle cell anemia. Other findings include impaired growth and development, increased susceptibility to infection, life-threatening thrombotic complications and, commonly, leg ulcers, swollen (painful) joints, a fever, and chills. Bone aches and chest pain may also occur. Severe hemolysis may cause hematuria and pallor, chronic fatigue, weakness, dyspnea (or dyspnea on exertion), and tachycardia. The patient may also have splenomegaly. During a sickle cell crisis, the patient may have severe bone, abdominal, thoracic, and muscular pain; a low-grade fever; and increased weakness, jaundice, and dyspnea.

Other causes

Drugs.Many drugs may cause hepatic injury and resultant jaundice. Examples include acetaminophen, phenylbutazone, I.V. tetracycline, isoniazid, hormonal contraceptives, sulfonamides, mercaptopurine, erythromycin estolate, niacin, troleandomycin, androgenic steroids, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, phenothiazines, ethanol, methyldopa, rifampin, and dilantin.

Treatments.Upper abdominal surgery may cause postoperative jaundice, which occurs secondary to hepatocellular damage from the manipulation of organs, leading to edema and obstructed bile flow; from the administration of halothane; or from prolonged surgery resulting in shock, blood loss, or blood transfusion.

A surgical shunt used to reduce portal hypertension (such as a portacaval shunt) may also produce jaundice.

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Alcoholic liver disease as a symptom:

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