Introduction

-A bile duct stricture is an abnormal narrowing of the common bile duct. 

-Most benign strictures of the extrahepatic bile ducts result from surgical trauma (95% of cases) 

-Causes: injury to the bile ducts, cancer of the bile duct, liver or pancreas, pancreatitis, primary sclerosing cholangitis 

Symptoms & Signs

RUQ abdominal pain, fever, chills, itching, jaundice, pale or clay-colored stools 

Diagnosis 

Labs: bilirubin level is higher than normal, elevated serum alkaline phosphatase 

Imaging: Ultrasound, CT, ERCP, MRCP, Percutaneous cholangiography  

Treatment 

-The goal of treatment is to correct the narrowing. This will allow bile to flow from the liver into the intestine.

-Fluid resuscitation, antibiotic coverage 

-ERCP, MRCP, Sphincterotomy to allow closure of a bile leak, dilation of the stricture and stent placement

-Surgery in select cases 

Prognosis 

Long-term success depends on the cause of the stricture. Good prognosis with benign causes and bad prognosis with malignant causes. 

Introduction

-Choledocholithiasis is the presence of gallstones in the common bile duct.

-The vast majority of ductal stones are formed within the gallbladder and migrate down the cystic duct into the common bile duct. But they may also form spontaneously in the bile duct after cholecystectomy.

-About 15% of patients with gallstones have choledocholithiasis

-About 60% of common duct stones are cholesterol stones and 40% are pigment stones.

Symptoms & Signs

-Most patients with gallstones are asymmptomatic while most patients with choledocholithiasis are symptomatic.

-Biliary colic from common duct obstruction cannot be distinguished from that caused by stones in the gallbladder, but lasts longer (>5 hours).

-Choledochal stones may be silent and asymptomatic or they may cause complete or incomplete obstruction, cholangitis or gallstone pancreatitis.

-Associated symptoms:  nausea, vomiting, jaundice, pruritis (intense in warm weather and common on extremities than on trunk)

–Courvoisier sign:  A palpable gallbladder due to CBD obstruction, but is also found in obstruction from malignancy.

Diagnosis

Labs: Elevated ALT, AST, amylase, lipase, alkaline phosphatase  

Imaging: Hepatobiliary ultrasound, CT, Magnetic Resonance Cholangiopancreatography, Endoscopic Retrograde Cholangiopancreatography, Percutaneous Transhepatic Cholangiogram, Endoscopic Ultrasound

-A dilated CBD on ultrasound is suggestive of choledocholithiasis.

Treatment

-The treatment is cholecystectomy with evaluation of the biliary tree and clearance of all stones within the ductal system.

-CBD stones can be removed by endoscopy or surgery.

-ERCP with sphincterotomy

– The most commonly used therapy for treatment of choledocholithiasis: Sphincterotomy

Prognosis

Major complications of choledocholithiasis: Obstructive jaundice, cholangitis, pancreatitis, and secondary biliary cirrhosis.

Q.What is the most common cause of obstructive jaundice? Bile duct stone

Q. What is the most common complication associated with endoscopic sphincterotomy? Pancreatitis

Introduction

-Acute cholecystitis is 90% calculous; 10% acalculous

-Cholecystitis is associated with gallstones occurs when a stone becomes impacted in the cystic duct and inflammation develops behind the obstruction.

-The acute attack is often precipitated by a large or fatty meal

Symptoms & Signs

-the sudden appearance of steady pain localized to the epigastrium or right hypochondrium, vomiting, fever, jaundice, muscle guarding, rebound tenderness

-Murphy sign: Positive when deep inspiration or cough during palpation of the RUQ produces increased pain or inspiratory arrest.

-In contrast to biliary colic of gallstone disease, the pain of acute cholecystitis does not subside. It is unremitting and may last for several days. It is usually more severe than the pain associated with uncomplicated gallstone disease.

-Peritonitis suggests gallbladder perforation.

-Emphysematous cholecystitis may produce abdominal wall crepitus.

Diagnosis

-Ultrasonography is considered the most useful initial radiologic test for diagnosing acute cholecystitis.  Findings suggestive of acute cholecystitis are gallbladder wall thickening, pericholecystic fluid, and a sonographic Murphy sign (Focal tenderness over the gallbladder when compressed by the sonographic probe (sonographic Murphy’s sign)

-HIDA Scan is useful in demonstrating an obstructed cystic duct

Labs: normal or elevated WBC,serum bilirubin levels, serum aminotransferase, alkaline phosphatase, serum amylase

Treatment

-All patients with acute cholecystitis should be hospitalized.

-They should receive IV fluids, broad-spectrum antibiotics, and analgesia.

-Cholecystectomy is the definitive treatment for acute cholecystitis.

Prognosis

-Excellent after cholecystectomy

Complications: Empyema, hydrops, gangrene, perforation, fistulization, gallstone ileus, porcelain gallbladder.

-Mirizzi syndrome: A stone in the neck of the gallbladder may compress the common hepatic duct and cause jaundice

1. What is the procedure of choice for acute cholecystitis? Laparoscopic cholecystectomy
2. What is the most frequent complication of acute cholecystitis? Gangrene.

Introduction

-Gallstones are hardened deposits of cholesterol, calcium salts, proteins and mucin.

-They are broadly classified into cholesterol stones and pigment stones.  

–Pigment stones can be further classified as either black or brown.

-In Western countries, about 80% of gallstones are cholesterol stones.

-Parasitic infection with Ascaris lumbricoides or Clonorchis sinensis can cause brown stones.

-Typical patient with gallstones is female, who is on a high dietary fat intake, has had prior pregnancies.

-Risk factors for gallstones: Female sex, increasing age, pregnancy, diabetes mellitus, rapid weight loss, obesity, certain medications, Native American (Pima Indians) and Hispanic heritage

–Rapid weight loss following bariatric surgery or lifestyle changes can  precipitate gallstone formation

Signs & Symptoms:

-The majority of patients with gallstones are asymptomatic.

-Symptomatic patients present with biliary colic (an intense discomfort in the right upper quadrant which may radiate to the right shoulder blade), nausea, vomiting,  abdominal bloating, early satiety, belching, and diaphoresis

–The biliary colic develops when a stone obstructs the cystic duct, resulting in a progressive increase of tension in the gallbladder wall as it contracts in response to a meal.

– Th pain is severe and comes on abruptly, typically during the night or after a fatty meal.

Diagnosis: Transabdominal ultrasound (the most sensitive imaging modality to detect gall stones)

Labs:  WBC, LFTs are usually normal; Amylase and lipase levels may be increased if stone obstruction occurs at the ampulla hepatopancreatica.

X rays: Most cholesterol stones (>90%) are radiolucent

Treatment:

Asymptomatic Incidental gallstones: Expectant management

Symptomatic:

-Pain control with NSAIDS

-Nonsurgical: Oral bile acid dissolution therapy (Ursodeoxycholic acid); Abdominal ultrasound every 6 to 12 months to assess the response, Percutaneous stone extraction, lithotripsy

-Surgical: Cholecystectomy

Prognosis:

-The prognosis is excellent after cholecystectomy

–Cholecystectomy & Cancer: Cholecystectomy may increase the risk of esophageal, proximal small intestinal, and colonic adenocarcinomas because of increased duodenogastric reflux and changes in intestinal exposure to bile.

-Complications of gallsones: Acute cholecystitis, obstructive choledocholithiasis, gallstone pancreatitis, gallstone ileus

-Gallstones in pregnancy: Pregnancy is a risk factor for the development of cholesterol gallstones and biliary sludge. Both progesterone and estrogen increase bile lithogenicity; progesterone decreases gallbladder contractility.

1. What is the chief symptom associate with cholelithiasis? Biliary colic
2. What is the most sensitive imaging test to detect gallstones: Ultrasonography

Benign liver neoplasms

General Considerations

-Cavernous hemangiomas, focal nodular hyperplasia, hepatic adenomas are the most common benign tumors of the liver.

-Cavernous hemangioma: The most common benign neoplasm of the liver; more than 80% occur in women

-Focal nodular hyperplasia: second most common after cavernous hemangiomas; occurs at all ages

-Hepatocellular adenoma occurs most commonly in women aged 20-40; usually caused by oral contraceptives

Symptoms & Signs

Most benign neoplasms are aymptomatic; Palpable abdominal mass, bleeding, nausea, vomiting, early satiety

Diagnosis

Cavernous hemangioma: Ultrasound, CT, MRI

FNH: lesions are identified by the presence of a central scar; CT, Ultrasound shows

Spoke-wheeling

Hepatic adenoma: Ultrasound show hyperechoic mass; Hepatic angiography is the most valuable diagnostic tool.

Treatment

Cavernous hemangioma: if symptomatic, surgical resection

Focal nodular hyperplasia & OCPs: no need to discontinue OCPs; annual ultrasonography for 2-3 years; if symptomatic, resection

Hepatocellular adenoma: resection, percutaneous radiofrequency ablation

-Resection is advised in all patients in whom the tumor causes symptoms or measures > 5 cm in diameter, even in the absence of symptoms

-Resection is also recommended even for an adenoma measuring < 5 cm in diameter if a beta-catenin gene mutation is present in a biopsy sample

General Considerations

-Hepatic abscesses may be bacterial, parasitic, or fungal in origin.

-the most common identifiable cause of hepatic abscess is acute cholangitis resulting from biliary obstruction due to a stone, stricture or neoplasm

-Pyogenic liver abscesses are the most common liver abscesses seen in the United States.

-Abscesses are most commonly single, but more than one may be present.

-The right lobe is usually involved.

Causes: suppurative process, infection from appendicitis, diverticulitis, bacterial endocarditis, renal infection, lung infection, infected indwelling catheters,

Symptoms & Signs

Fatigue,fever, right upper quadrant pain, chills, jaundice, weight loss, elevated hemidiaphragm

Diagnosis

Labs: Leukocytosis with a left shift, positive blood cultures, elevated AP level  

Imaging: Chest radiographs, Ultrasonography, CT, or MRI of the liver

Hepatic candidiasis: CT liver shows multiple ‘bulls-eyes’

Treatment

Bacterial abscess: Empiric antibiotic therapy should cover gram-negative and anaerobic organisms

Fungal abscess: Amphotericin B, Fluconazole

Amebiasis: Metronidazole or tinidazole

Surgery: percutaneous drainage, open debridement, lobectomy

Prognosis

-With drainage and antibiotics, the cure rate is about 90%.

-The overall mortality rate of 15%

-The mortality rate is about 40% in patients with malignant disease.

Fungal abscesses are associated with mortality rates of up to 50%

1. What is the most common presenting sign of liver abscess? Fever
2. What is the single most reliable laboratory finding in patients with liver abscess? Elevated serum alkaline phosphatase
3. What is the most useful diagnostic aid in evaluating liver abscess? Ultrasound liver

Hepatic vein obstruction (Budd-Chiari syndrome)

General Considerations

Budd-Chiari syndrome is defined as hepatic venous outflow tract obstruction, independent of the level or mechanism of obstruction.

-Obstruction can occur anywhere from the small hepatic venous tributaries within the liver parenchyma to the major hepatic venous trunks to the inferior vena cava up to the level of the right atrium.

-The obstruction is not due to cardiac disease, pericardial disease, or sinusoidal obstruction syndrome (veno-occlusive disease).

–The most common reason is thrombosis.

-Causes of Budd-Chiari syndrome: Polycythemia rubra vera, pregnancy, oral contraceptives, coagulation disorders, and factor V Leiden.

Symptoms & signs

Fever, right upper quadrant abdominal pain, anorexia, postprandial bloating, jaundice, lower extremity edema, gastrointestinal bleeding

Diagnosis

-The screening test of choice is contrast-enhanced, color, or pulsed-Doppler abdominal ultrasonography

-The definitive radiographic study to confirm the diagnosis: Hepatic venography

Treatment

All patients with hepatic vein obstruction should be hospitalized.

Treatment goals: prevent the propagation of the clot, prevent and manage the complications, decompress the congested liver and restore the patency of thrombosed veins

Anticoagulation, thrombolytic therapy, percutaneous angioplasty, TIPS

Prognosis

Without treatment, the prognosis is poor

General Considerations

Wilson disease is a hereditary condition in which defective cellular copper transport leads to excessive deposition of copper in several organs—most commonly the liver, brain, and cornea.

-It is an autosomal recessive disorder caused by mutations in the ATP7B gene on chromosome 13.  

-It usually presents in childhood or young adult life with mean age of onset is between 12 and 23 years of age

Symptoms & Signs

-Wilson disease tends to present as liver disease in adolescents and neuropsychiatric disease in young adults

Hepatic features: acute or chronic liver failure, jaundice, hepatomegaly, cirrhosis, portal hypertension

Neurologic features: basal ganglia dysfunction, tremor, ataxia, incoordination, spasticity, ataxia, migraines, seizures, dysarthria, dysphagia

Psychiatric features: behavioral, personality changes, depression

Miscellaneous: Sunflower cataracts, KF rings, splenomegaly may cause hemolytic anemia and thrombocytopenia.

Kayser-Fleischer ring: Pathognomonic sign of Wilson’s disease; Brownish or gray-green pigmented granular deposits in Descemet membrane in the cornea

Diagnsois

-Decreased serum copper concentration despite the presence of copper overload

-Elevated hepatic copper concentration

-Low serum ceruloplasmin (the plasma copper-carrying protein) level

-Elevated urinary copper excretion

-Testing for mutations in ATP7B can be done and is recommended for a definitive diagnosis.

-Liver biopsy with quantitative copper assays: gold standard for diagnosis

-MRI Brain:  “face of the giant panda” sign in the midbrain and a “face of the miniature panda” in the pontine tegmentum.

Treatment

-Treatment of choice: Copper chelation with D-penicillamine or trientine hydrochloride

Drug of choice: Oral Penicillamine; always add pyridoxine to penicillamine

-Oral zinc acetate (interferes with intestinal absorption of copper)

-Administration of trientine and zinc should be separated by at least 1 hr because trientine chalates zic and forms ineffective complexes

-Tetrathiomolybdate for neurologic therapy

-Patients with Wilson disease require lifelong therapy.

-Liver transplantation for advanced liver disease

Prognosis

-The prognosis of untreated Wilson disease is poor, but it is good if effective treatment occurs before liver or brain damage

1. What is the most common presentation of Wilson disease? Chronic liver disease
2. What is the most common ocular finding of Wilson disease? Kayser–Fleischer rings

General Considerations

Hemochromatosis refers to a group of genetic diseases that predispose to iron overload, potentially leading to fibrosis and organ failure

-Increased accumulation of iron as hemosiderin in the liver, pancreas, heart, testes,adreanls, pituitary, and kidneys

-Major clinical manifestations: Cirrhosis of the liver, diabetes mellitus, arthritis, cardiomyopathy, and hypogonadotropic hypogonadism

-The quantity of total iron is 3 g in women and 5 g in men. Most iron resides in red blood cells.

-Almost all iron absorption occurs in the duodenum.

-Hepcidin normally functions as a regulatory protein which controls iron absorption

-In hemochromatosis, mucosal absorption is greater than body requirements and amounts to ≥4 mg/d.

-Most common autosomal recessive disease in Caucasians

–HFE gene mutation (usually C282Y/C282Y) is found in most cases

-C282Y is the major mutation and H63D the minor mutation of the HFE gene

-The onset is usually after age 50

-The disease is more common in men than in women

Symptoms & Signs

-Most patients are aymptomatic

-Lethargy, arthralgia, skin pigmentation, loss of libido, loss of body hair, jaundice, hepatomegaly, cirrhosis, diabetes mellitus, increased pigmentation, spider angiomas, splenomegaly, arthropathy, ascites, cardiac arrhythmias, congestive heart failure, testicular atrophy

Diagnosis

-Measure serum iron, tranferrin saturation, ferritin concentration, liver biopsy, MRI liver

-Hepatic iron index generally > 1.9

-An elevated plasma iron with > 45% transferrin saturation

-An elevated serum ferritin

-A TSAT ≥45 percent and/or a serum ferritin >200 ng/mL (>200 mcg/L) in men or >150 ng/mL (>150 mcg/L) in women is consistent with iron overload

-Test for HFE mutations when serum iron/total iron-binding capacity and/or serum ferritin are elevated

-Genetic testing is not recommended for the general population.

Treatment

-therapy involves removal of the excess body iron and supportive treatment of damaged organs

Iron removal: therapeutic Phlebotomy (mainstay of treatment), Chelating agents (Deferoxamine, Dererasirox)

-counsel and screen other family members

-Stop alcohol consumption

-Liver transplantation for advanced cirrhosis

Prognosis

-Survival appears normal in those with a serum ferritin <2000 ng/mL at the time of diagnosis.

-The principal cause of death are cardiac failure, portal hypertension, liver cancer

Q.What is the most common autosomal-recessive disorder in Caucasians? HFE-related hemochromatosis

1. What is the single best screening test for hereditary hemochromatosis? Transferrin saturation
2. What is the key regulatory hormone that controls iron metabolism? Hepcidin
3. What is the first organ to be affected by hemochromatosis? Liver
4. What is the most common cardiac manifestation of hemochromatosis? Congestive heart failure
5. What are the most common endocrine manifestaions of hemochromatosis? Diabetes mellitus and hypogonadism
6. What is the classic presentation of arthropathy in hemochromatosis? the second and third metacarpophalangeal and proximal interphalangeal joints of the hands