Chapter 15 & 16 - Liver, Gall bladder, Biliary Tract

Question 1

Liver

Answer 1

Organ found in vertebrates

Detoxifies various metabolites, synthesizes proteins, and produces biochemical necessary for digestion and growth

Located in upper right quadrant of the abdomen, below the diaphragm

Question 2

Bilirubin

Answer 2

Brownish-yellow pigment secreted by the liver

Produced in bone marrow cells and liver as the end product of red-blood-cell (hemoglobin) breakdown
Amount of bilirubin manufactured relates directly to quantity of blood cells destroyed
About 0.5 to 2 grams produced daily

Question 3

Unconjugated Bilirubin (Indirect Bilirubin)

Answer 3

Fat-soluble form of bilirubin, formed during the initial chemical breakdown of hemoglobin
While being transported in blood, it is mostly bound to albumin (binding affinity for albumin to bilirubin is extremely high, and under ideal conditions, no free [non-albumin bound] unconjugated bilirubin is seen in the plasma)

Question 4

Conjugated Bilirubin (Direct Bilirubin)

Answer 4

When albumin-unconjugated bilirubin complex reaches the liver, sugars are attached to the unconjugated bilirubin to form water soluble conjugated bilirubin (direct bilirubin)
Then excreted in the bile and passes from the liver to the small intestines
(water-soluble)

Question 5

Jaundice (hyperbilirubinemia)

Answer 5

Yellow discoloration of skin and sclerae occurring at a serum bilirubin of 2.0 mg/dl (normal is < 1.2)

Question 6

Pathophysiology of Jaundice

Answer 6

Hemolytic anemia - excess production of bilirubin

Drug interference - Reduced hepatocellular uptake

Newborn jaundice, viral hepatitis - Impaired conjugation

Drug-induced damage, viral hepatitis - Decreased hepatic excretion of bile

Intrahepatic or extrahepatic bile duct damage, common duct obstruction by gallstones - Impaired bile flow

Question 7

Hepatic Failure

Answer 7

Inability of the liver to perform its normal functions, life-threatening condition; urgent medical care
Acute or chronic (cirrhosis)
Recently, a 3rd form of liver failure known as acute-on-chronic liver failure (ACLF) is increasingly being recognized
Clinical Consequences: 80-90% of hepatic function lost (Jaundice, Hypoalbuminemia, Coagulopathy, Encephalopathy)

Question 8

Acute Liver Failures

Answer 8

Rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient w/out known prior liver disease
Usually drug-related or fulminant (fast and strong) viral hepatitis
Resulting in massive hepatic necrosis

Question 9

Chronic Liver Failure

Answer 9

End point of chronic liver injury
Causes of cirrhosis: alcoholism, chronic hepatitis B or C, autoimmune hepatitis, hereditary and metabolic causes, metabolic derangements

Question 10

Acute on chronic Liver Failure

Answer 10

occurs when a patient w/ chronic liver disease develops features of liver failure, underlying precipitating causes include: alcohol misuse, infection

Question 11

Hepatic Encephalopathy

Answer 11

Loss of brain function as a result of failure in the removal of toxins from the blood due to liver damage, inc blood ammonia levels, liver flap
Symptoms: jaundice, must or sweet breath odor, problems in mvmt w/ abnormal tendon reflexes, altered loss of consciousness, changes in moods, personality changes
Diagnosis: Complete blood count, liver function test, CT Scan

Question 12

Cirrhosis of Liver

Answer 12

Degenerative disease of the liver resulting in scarring and liver failure, asymptomatic until advanced stages

Causes: alcoholic liver disease: 60-70%, viral hepatitis: 10%, Biliary tract diseases: 5-10%

Symptoms: weakness, fatigue, muscle cramps, weight loss, nausea, vomiting, upper abdominal pain

Clinical features: anorexia, debilitation, abdominal swelling due to ascites

Classification: best system based upon etiology, fibrosis and conversion of liver architecture into structurally abnormal nodules
Macronodular - larger nodules (greater than 3 mm)
Micronodular - usually alcoholism, obesity, diabetes mellitus

Causes of Death - progressive hepatic failure, portal hypertension w/ esophageal bleeding, hepatocellular carcinoma

Question 13

Portal Hypertension

Answer 13

Increase in the blood pressure within a system of veins called the portal venous system
Cirrhosis accounts for most cases of intrahepatic portal hypertension
Complications: Ascites, Portosystemic shunts (esophagogastric varices, hemorrhoidal varices, periumbilical and abdominal wall collaterals), Splenomegaly (congestive)

Question 14

Hepatitis A

Answer 14

Vaccine-preventable liver infection caused by HAV
Found in the stool and blood of people who are infected
Highly contagious
HAV can live outside the body for months
HAV is killed when exposed to temperatures of >185 degrees F for 1 min

Incubation Period: range: 15-50 days
*Does not become a chronic, long-term infection

Transmission: Close person-to-person contact w/ an infected person, sex contact w/ infected, ingestion of contaminated food or water

At risk individuals: international travelers, ppl who anticipate close personal contact w/ international adoptee

Signs & Symptoms: Fever, fatigue, loss appetite, nausea, vomiting, abdominal pain, dark urine, diarrhea, jaundice
symptoms last less than 2 months, 10-15% of symptomatic persons have prolonged or relapsing disease for up to 6 mo

Diagnosis: Antibody to hep a virus, nucleic acid amplification test

Prevention: Vaccination, Immune globulin, Good hand hygiene

Vaccination: Children (all aged 12-23 mo, unvaccinated children and adolescents aged 2-18 yrs)

Question 15

Hepatitis B

Answer 15

Vaccine-preventable liver infection caused by HBV, spreads when blood, semen, or other body fluids from a person infected w/ virus

Incubation Period: average of 90 days (range: 60-150 days)

Transmission: sexual contact, sharing syringes, other drug-injection equipment, mother to baby
Virus can live on objects for 7 days or more

Symptoms: last several weeks, persist up to 6 mo, pain in area of liver or abdominal pain, fever, loss of appetite, extreme fatigue and weakness, itching, dark urine, joint pain, jaundice

Infections: acute or chronic

Diagnosis: Hep B surface antigen, Hep B surface antibody, total hep B core antibody

Treatment: Acute infection - less than 6 mo, Chronic infection - more than 6 mo

Meds: Antivirals - stop replication of virus, Immunomodulators - reduces viral load by preventing replication of viruses

Vaccination schedules: 3 intramuscular injections, second and third doses administered at 1 and 6 mo

Question 16

Acute Hep B

Answer 16

Ranges from asymptomatic or mild disease to fulminant hepatitis, although the latter occurs only rarely

Disease is more severe among adults age >60 yrs

Question 17

Chronic Hep B

Answer 17

Risk for chronic infection is related to age at infection

90% of infants w/ hepatitis B develop chronic infection
2-6% of adults w/ hep B develop chronic infection

*Best way to prevent hep B is to get vaccinated

Question 18

Hepatitis C

Answer 18

Liver infection caused by hep C virus

Incubation Period: 2-12 weeks (range: 2-26 weeks), > 50% of infected patients get a chronic infection

Transmission: parenteral exposures to infectious blood or body fluids that contain blood

Exposure: injection-drug use, birth, sex, sharing personal items, Health-care procedures that involve invasive procedures, needlestick injuries

Acute Signs & Symptoms: Fever, fatigue, dark urine, clay-colored stool, abdominal pain, loss of appetite, nausea, jaundice

Chronic Hepatitis C: Signs & Symptoms: Asymptomatic or non-specific symptoms (chronic fatigue and depression), chronic liver disease, HCV-positive when screened for blood donation or when elevated alanine aminotransferase (ALT, liver enzyme)

Treatment: Acute - exception of pregnant women and children under 3, treated, Chronic - 90% of people can be cured of infection, 8-12 weeks oral therapy

Vaccination: no vaccine

Question 19

Hepatitis D

Answer 19

Liver disease caused by hep D virus, “satellite virus” b/c only infect ppl who are infected by HBV, acquired either simultaneously w/ HBV as coinfection or as a superinfection, uncommon in US

Transmission: mainly transmitted through activities that involve percutaneous, mucosal contact w/ infectious blood or body fluids

Signs and symptoms: acute - fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, jaundice

Diagnosis: presence of antibodies against HDV and/or HDV RNA

Treatment: no treatment available, but liver transplantation may be considered

Question 20

Chronic Hep D

Answer 20

likelihood of progression to chronic depends on whether the initial infection occurred by HBV/HBV coinfection or HDV superinfection

More than 95% clear both HBV and HDV infections when they are acquired at the same time

Becomes chronic in more than 80% of people w/ HDV superinfection (chronic HDV generally causes more aggressive and rapid progression of liver disease

Question 21

Hepatitis E

Answer 21

Liver disease caused by hep E, HEV infection results in a self-limited, acute illness, not commonly acquired in the US

Incubation Period: symptoms develop 15-60 days after exposure

Transmission: developing countries, spread by the fecal-oral route (contaminated drinking water), sporadic cases occur following consumption of uncooked/undercooked pork or deer meat

Signs and Symptoms: (many people don’t have symptoms of acute infection) fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, Jaundice, dark urine

Duration: virus excretion in stool has been demonstrated from 1 week prior to onset to 30 days after onset of jaundice, chronically infected persons shed virus as long as remain infected

Prognosis: most people recover completely, no report of progression of acute hep e to chronic hep e

Diagnosis: presence of antibody against HEV or HEV RNA

Treatment: no specific antiviral therapy for acute hep e, supportive therapy

Question 22

Alcoholic Liver Disease

Answer 22

3 forms of injury - steatosis (fatty liver - moderate ethanol intake, more fat, greater effect on function), alcoholic hepatitis, cirrhosis

Alcoholic Hepatitis - heavy intake, hepatocyte necrosis, Mallory bodies, Fibrosis
Alcoholic Cirrhosis - final and irreversible, initially liver is enlarged, brown, shrunken, and nonfatty, End-stage cirrhosis

Question 23

Hemochromatosis

Answer 23

Primary type inherited genetic disorder
Most are AR (mutations in HFE gene)
Excessive iron absorption (deposition in liver, pancreas, and heart)

Cirrhosis predisposes to hepatocellular carcinoma, secondary type seen w/ iron overload multiple transfusion, chronic hemolysis

Question 24

Wilson Disease

Answer 24

Copper plays key role in development of healthy nerves, bones, collagen and the skin pigment melanin, total body copper is 50-150 mg, Free copper dissociates and is transferred to hepatocytes, where it is incorporated into an alpha2 globulin to form ceruloplasmin and resecreted into plasma

99% of plasma copper is bound to ceruloplasmin
Most affected patients have different mutations of ATP7B that cause defective biliary excretion of copper

Long term copper chelation therapy w/ D-penicillamine, liver transplantation
Kayser-Fleischer rings

Question 25

Reye Syndrome

Answer 25

Encephalopathy and fatty degeneration of liver in children due to mitochondrial dysfunction after febrile viral-like illness treated w/ aspirin
Current cases are more common in adults

Question 26

Hepatocellular carcinoma

Answer 26

Malignant tumor w/ hepatocellular differentiation
Uncommon in N. America and W. Europe

Pathophysiology: Aflatoxins (mycotoxins), Cirrhosis, Hepatitis B virus, Hepatitis C virus

Symptoms: abdominal pain, ascites, hepatomegaly, obstructive jaundice, systemic manifestations
Laboratory: elevated serum AFP

Prognosis: 5 yr survival: 10% overall to 50% in tumors < 5 cm w/ resection

Question 27

Cholelithiasis (Gall Stones)

Answer 27

Affects 10% of adults, 80% of gallstones in West are cholesterol stones, 20% of gallstones in W are pigment stones

Risk Factors: 80% have no factors other than age and sex, obesity, western diet, family history, quick weight loss or fasting, pregnancy, women on birth control

Symptoms: usually none, may have biliary colic

Treatment: laparoscopic cholecystectomy if symptomatic, in children, native americans, pts w/ sickle cell disease, stones 3 cm +

Question 28

Acute Cholecystitis

Answer 28

90% of cases, mean age of 60 yrs, 60% women
Abdominal pain, right upper quadrant tenderness, nausea, vomiting, fever, leukocytosis, & mild jaundice
50% of those w/ jaundice have coexisting choledocholithiasis, 50% have bacterial infection

Question 29

Chronic Cholecystitis

Answer 29

Typically secondary to gallstones, female predominance, associated w/ cholelithiasis in > 90% of cases, can be a sequela of recurrent acute cholecystitis

Question 30

Carcinoma of Gallbladder

Answer 30

associated w/ gallstones
infections and parasites
prognosis poor
mostly elderly pts

Question 31

Pancreas

Answer 31

Glandular organ in the digestive system and endocrine system located in abdominal cavity behind stomach
Endocrine gland producing several important hormones (insulin, glucagon, somatostatin, pancreatic polypeptide)

Question 32

Acute Pancreatitis

Answer 32

medical emergency of great magnitude, severe abdominal pain, elevated serum levels of pancreatic enzymes (amylase, lipase), extensive peripancreatic fat necrosis, associated w/ alcoholism & biliary tract disease
gallstones
increased pressure in ductal system thought to initiate the release of enzymes triggering acute pancreatitis

Systemic Complications: shock, disseminated intravascular coagulation, ARDS, acute renal failure

Question 33

Chronic Pancreatitis

Answer 33

Chronic alcohol abuse, seen w/ cystic fibrosis

exocrine and endocrine functions severely compromised leading to malabsorption and diabetes mellitus

Question 34

Carcinoma of Pancreas

Answer 34

Most are ductal adenocarcinomas, 25% 1 yr survival rate, 5 yr survival = 6%

Risk Factors: 40% sporadic, 30% smoking, 30% dietary factors (high fat/meat diet especially processed)

Question 35

Insulinoma

Answer 35

Beta cell tumor

May produce intractable hypoglycemia (20%)

10% behave in a malignant fashion

Question 36

Gastrinoma

Answer 36

Inc. gastrin causes gastric hypersecretion and intractable ulcers = “Zollinger-Ellison syndrome”

Most common in duodenum

60% behave in a malignant fashion

May be part of MEN-1 syndrome