SOAP. – Jaundice – SỔ TAY LÂM SÀNG

Jaundice

Jill C. Cash and Cheryl A. Glass

Definition

A.Jaundice is a yellow tinge of the skin or mucous membranes. It is a symptom, not a disease. The diagnostic approach begins with gathering a comprehensive history, physical examination, and screening labs. The differential diagnosis is formulated, and further testing may be warranted. The onset of jaundice usually prompts the patient or family to seek medical attention. Jaundice can reflect a medical emergency secondary to massive hemolysis, ascending cholangitis, unconjugated hyperbilirubinemia in the neonatal period, and fulminant liver failure.

Incidence

A.Incidence is variable according to pathogenesis, age, and population.

Pathogenesis

The mechanism responsible for jaundice includes excess bilirubin production, decreased hepatic uptake, impaired conjugation, intrahepatic cholestasis, extra-hepatic obstruction, and hepatocellular injury (see Table 14.21). However, it is important to recognize that more than one mechanism can be operating in a given case (i.e., sickle cell anemia and HIV).

A.Excess bilirubin production results from accelerated red cell destruction. The excessive amounts of hemoglobin (Hgb) and resultant bilirubin released into the bloodstream overwhelm the liver’s normal capacity for uptake, and an unconjugated hyperbilirubinemia ensues.

B.With decreased uptake and conjugation there is often a concurrent, acquired illness such as infection, cardiac disease, or cancer. Hereditary conditions, such as Gilbert and Crigler–Najjar syndromes, are responsible.

C.Intrahepatic cholestasis may occur at a number of levels: intracellularly (e.g., hepatitis), at the canalicular level (when estrogen-induced), at the ductule (phenothiazine exposure), at the septal ducts (primary biliary cirrhosis), and at the intralobular ducts (cholangiocarcinoma).

TABLE 14.21 Classification of Jaundice According to Bile Pigment and by Mechanism

Unconjugated Hyperbilirubinemia	Conjugated Hyperbilirubinemia
Increased/overproduction of bilirubin	Hepatocellular injury/disease
Impaired/decreased hepatic uptake of bilirubin	Intrahepatic cholestasis
Impaired/decreased conjugation	Extrahepatic cholestasis (biliary obstruction)

D.Extrahepatic obstruction occurs when stone, stricture, or tumor blocks the flow of bile within the extrahepatic biliary tree. A history of gallstones, biliary tract surgery, or malignancy may be elicited.

Predisposing Factors

A.Previous blood transfusion.

B.Travel to an area endemic for hepatitis.

C.Raw shellfish consumption.

D.Intravenous (IV) drug abuse.

E.High-risk sexual practices.

F.Family history of episodic jaundice.

G.History of gallstones.

H.Biliary obstruction/previous biliary tract surgery.

I.Alcoholism.

J.Chemical exposure.

K.Sickle cell disease.

L.Pregnancy (intrahepatic cholestasis).

M.Cancer.

Common Complaints

A.Pruritus.

B.Dark, tea-colored urine, from conjugated bilirubinuria.

C.Light, clay-colored stools, from absence of bile.

D.Fatigue.

E.Right upper quadrant (RUQ) pain.

Other Signs and Symptoms

A.Enlarged liver.

B.Splenomegaly.

C.Fever.

D.Chills.

E.Gastrointestinal (GI): Appetite loss, weight loss, abdominal pain, nausea, or vomiting.

F.Ascites.

G.Shortness of breath.

H.Palpitations.

I.Ecchymosis.

J.Steatorrhea, severe.

K.Asterixis (tremor).

L.Myalgias.

M.Malaise.

Subjective Data

A.Review onset, duration, and course of symptoms.

TABLE 14.22 Drugs and Herbals Associated With Jaundice

ACE inhibitors Acetaminophen (Tylenol) Alkylated steroids Aminobenzoic acid Antibiotics Antidiabetic drugs Arsenic Barbiturates Chlorpromazine Ethinyl estradiol/OCPs/hormone replacement Herbal medications (e.g., Jamaican bush tea) INH Mercaptopurine (Purinethol) Methyldopa (Aldomet) Monoamine oxidase inhibitors Paracetamol (acetaminophen) Perphenazine (Trilafon) Phenothiazine derivatives PTU Probenecid Rifampin Sulfonamides Tamoxifen TPN

ACE, angiotensin-converting enzyme; OCPs, oral contraceptives; INH, isoniazid; PTU, propylthiouracil; TPN, total parenteral nutrition.

B.Review medication history for drugs/herbals that may induce jaundice (see Table 14.22).

C.Inquire about recent blood transfusions. Are there any known blood disorders in the patient’s family history?

D.Ask about contact with a person who has an infection, such as infectious hepatitis.

E.Ask about unprotected sexual activity/HIV status.

F.Review ingestion of potentially contaminated food or water, including Amanita mushrooms, milk, or shellfish.

G.Ask about the patient’s exposure to any toxic chemicals, such as carbon tetrachloride, chloroform, phosphorus, arsenic, ethanol, or halothane (Fluothane).

H.Review the patient’s history of nonsterile needle punctures.

I.Review the patient’s medical/surgical history for gallstones, hepatitis, tumor, pancreatitis, Wilson’s disease, Budd–Chiari syndrome, liver surgery, or transplantation. Is there a family history of gallstones?

J.Ask how much alcohol the patient has ingested over the years, as well as daily intake of alcohol.

K.Ask about dark urine or white or clay-colored stool.

L.Inquire about dyspepsia, anorexia, nausea, vomiting, RUQ or epigastric pain, or pain radiating to the back or shoulder blade. Ask what the relationship of pain is to eating.

M.Inquire about fever, fatigue, malaise, loss of vigor and strength, easy bruising, and weight loss.

N.Review travel history.

Physical Examination

A.Check temperature, pulse, respirations, blood pressure (BP), and weight. Marked weight loss accompanied by jaundice suggests carcinoma of the head of the pancreas or metastatic disease obstructing the common duct. Note breath odor for fetor hepaticus (breath of the dead).

B.Inspect:

1.Inspect skin, mouth, palms, and sclera for yellow tinge. Severe jaundice may cause greenish tinge from oxidation of bilirubin to biliverdin:

a.In fair-skinned people, discoloration is most evident on the face, trunk, and sclera (sclera icterus).

b.In dark-skinned people, discoloration is most evident in sclera and roof of mouth.

c.Jaundice is most noticeable in natural sunlight. In artificial or poor light, it may be hard to detect.

2.Inspect the skin for spider angiomata, rashes, or scratches from severe itching due to pruritus, and for bruising or petechiae.

3.Inspect the palms for erythema or overt bleeding.

4.Inspect the chest for gynecomastia.

C.Palpate the abdomen for tenderness, masses, liver enlargement in RUQ, and ascites:

1.Extrahepatic obstruction and intrahepatic cholestasis may be identical in presentation.

2.Tenderness is minimal unless cholangitis or rapid distension occurs.

3.Splenomegaly is unlikely except in primary biliary cirrhosis.

4.Gallbladder may be palpable (Courvoisier sign) when there is gradual development of the biliary tree. Sudden onset of pain results from passage of stone that becomes wedged into common duct; fever and sepsis shortly thereafter indicate cholangitis.

5.Malignancy usually presents as a rock-hard mass.

6.Absence of abdominal pain does not rule out obstruction, especially when it develops slowly from tumor growth or primary biliary cirrhosis.

7.Advanced hepatocellular disease is indicated by a small liver, signs of portal hypertension (ascites, splenomegaly, prominent abdominal venous pattern), asterixis, peripheral edema (from hypoalbuminemia), spider angiomata, gynecomastia, palmar erythema, and testicular atrophy.

D.Percuss the abdomen.

E.Auscultate the heart, lungs, and abdomen for bowel sounds.

F.Neurologic exam:

1.Note level of consciousness.

2.Note asterixis, or flapping tremor elicited when arms are extended and wrists are dorsiflexed.

G.Rectal exam: Check for masses and occult blood.

Diagnostic Tests

The diagnostic approach begins with a careful history and physician examination, and screening laboratory studies. A differential is formulated, and appropriate further testing is performed to narrow the diagnosis.

A.Initial laboratory tests:

1.Serum bilirubin: Direct, indirect (unconjugated), and total; clinically, jaundice becomes noticeable when levels reach 2.0 to 2.5 mg/dL:

a.Intrahepatic cholestasis and extrahepatic obstruction: Elevated conjugated bilirubin, elevated serum alkaline phosphatase (ALP); mild to moderate rise in transaminase.

b.Gilbert’s syndrome is the most common cause of decreased uptake and unconjugated hyperbilirubinemia. It is a benign disorder that produces recurrent self-limited episodes of mild jaundice. Typically, the unconjugated fraction rises to no more than 1.5 to 3.0 mg/100 mL. In Gilbert’s syndrome, fasting and minor illness can precipitate jaundice.

2.ALP, biliary obstruction or intrahepatic cholestatis is commonly exhibited by increased ALP out of proportion to aminotransferases.

3.Aspartate transaminase (AST)/alanine transaminase (ALT):

a.Elevation of ALT and AST may indicate liver cell damage or may be caused by opiates and aspirin.

b.Aspirin may also decrease AST and ALT.

4.Prothrombin time (PT):

a.PT may be prolonged due to malabsorption, but it is reversible by vitamin K injection.

b.Prolonged PT unresponsive to parenteral vitamin K strongly suggests hepatocellular failure.

c.Cholestasis and obstruction may also produce prolongation of PT but can be reversed by vitamin K.

d.Phenazopyridine (Pyridium) may cause a false-positive bilirubin result.

B.Other laboratory testing as needed:

1.Total serum protein.

2.Serum albumin and globulin:

a.Albumin decreases with cirrhosis and chronic hepatitis.

b.Globulin increases with cirrhosis, chronic obstructive jaundice, and viral hepatitis.

c.To interpret albumin level, consider dietary intake and sources of possible protein loss.

3.Cholesterol.

4.Lactate dehydrogenase (LDH).

5.Gamma-glutamyl transpeptidase (GGT).

6.Serum ammonia.

7.Bile acids radioimmunoassay: Elevated levels indicate hepatic disease.

8.Serologic tests for viral hepatitis.

9.Serum iron, transferrin, and ferritin to evaluate hemochromatosis.

10.Serum ceruloplasmin levels to evaluate Wilson’s disease.

11.Alpha-1 antitrypsin activity to evaluate alpha-1 antitrypsin deficiency.

12.Urine for bilirubin—bilirubinuria may be an early sign of liver disease:

a.Collect specimens over a 2-hour period after lunch.

b.Place specimen in a dark brown container and send to lab immediately to prevent decomposition.

C.Abdominal ultrasound is considered the screening procedure of choice. More selective imaging procedures are ordered based on clinical evaluation.

D.Other imaging procedures:

1.Endoscopic ultrasound.

2.Hepatobiliary iminodiacetic acid (HIDA) scan: Uses radioactive isotopes.

3.Oral cholecystography.

4.Endoscopic retrograde cholangiopancreatography (ERCP).

5.Percutaneous transhepatic cholangiography (PTC).

6.Helical CT.

7.Magnetic resonance cholangiopancreatography (MRCP) is an alternative to ERCP.

8.Liver biopsy may be indicated for definitive diagnosis.

Differential Diagnoses

A.Jaundice is a symptom, not a diagnosis.

B.Cancer of pancreas.

C.Obstruction of biliary tract.

D.Icteric phase of hepatitis.

E.Cirrhosis.

F.Right-sided heart failure (HF).

G.Chronic hemolysis from prosthetic heart valve.

Plan

A.Management depends on primary diagnosis. Most patients can be managed on an ambulatory basis, unless they are unable to maintain hydration or begin to show evidence of severe hepatocellular failure.

B.Pharmaceutical therapy.

1.Cholestyramine 2 to 8 g orally twice a day may be used to help relieve itching. Cholestyramine is ineffective with complete biliary obstruction.

Follow-Up

A.See the patient 2 to 4 weeks after initial diagnosis and referral.

B.Subsequent routine evaluations are related to primary diagnosis.

Emergent Issues/Instructions

Hospital admission is mandatory when jaundice is complicated by a fever and peritoneal signs are indicative of cholangitis. IV antibiotics and prompt surgical consultation are required.

Consultation/Referral

A.Consult with a gastroenterologist familiar with liver disease and needle biopsy techniques when hepatocellular disease is suspected; when there is evidence of hepatic failure, portal hypertension, or encephalopathy; or when jaundice persists longer than 3 months.

B.Consultation with a gastroenterologist, surgeon, or radiologist experienced in evaluation of jaundice can be very useful when there is clinical suspicion of extrahepatic obstruction.

Individual Considerations

A.Pregnancy:

1.Viral hepatitis is the most frequent cause of jaundice in pregnancy.

2.Intrahepatic cholestasis in pregnancy is associated with modest maternal risks, including increased risk of peripartum bleeding and increased likelihood of subsequent cholelithiasis.

3.Cholestyramine resin, generally 4 g every 4 to 6 hours, has been reported to afford some relief of pruritus in 50% of affected women, presumably by removing a portion of the bile acids by irreversible binding in the gut.

4.Pregnant women who take cholestyramine are at increased risk for depletion of vitamin K–dependent coagulation factors and should be followed with serial PT times. Such women should also receive prophylactic vitamin K supplementation. If PT becomes prolonged, medication should be discontinued.

B.Geriatrics:

1.The most frequent cause of jaundice in patients older than 65 years is cholelithiasis.

2.The second most frequent cause of jaundice for patients 65 years and older is cancer, especially of the gallbladder.

3.Painless jaundice in the elderly with weight loss and a mass, but with minimal pruritus, suggests biliary obstruction caused by cancer.

4.Drugs that are highly metabolized by cytochrome P450 or similar liver enzymes may result in competitive inhibition of each other, resulting in slow clearance, drug accumulation, and toxicity. Due to polypharmacy a full review of medications, herbals, and over-the-counter (OTC)

should be done for medications (monotherapy or in combination) that are hepatoxic and should be avoided in the geriatric population.