Chapter 15 & 16 - Liver, Gall bladder, Biliary Tract Flashcards
Liver
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
Bilirubin
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
Unconjugated Bilirubin (Indirect Bilirubin)
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)
Conjugated Bilirubin (Direct Bilirubin)
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)
Jaundice (hyperbilirubinemia)
Yellow discoloration of skin and sclerae occurring at a serum bilirubin of 2.0 mg/dl (normal is < 1.2)
Pathophysiology of Jaundice
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
Hepatic Failure
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)
Acute Liver Failures
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
Chronic Liver Failure
End point of chronic liver injury
Causes of cirrhosis: alcoholism, chronic hepatitis B or C, autoimmune hepatitis, hereditary and metabolic causes, metabolic derangements
Acute on chronic Liver Failure
occurs when a patient w/ chronic liver disease develops features of liver failure, underlying precipitating causes include: alcohol misuse, infection
Hepatic Encephalopathy
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
Cirrhosis of Liver
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
Portal Hypertension
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)
Hepatitis A
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)
Hepatitis B
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
Acute Hep B
Ranges from asymptomatic or mild disease to fulminant hepatitis, although the latter occurs only rarely
Disease is more severe among adults age >60 yrs
Chronic Hep B
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
Hepatitis C
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
Hepatitis D
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
Chronic Hep D
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
Hepatitis E
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
Alcoholic Liver Disease
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
Hemochromatosis
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
Wilson Disease
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
Reye Syndrome
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
Hepatocellular carcinoma
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
Cholelithiasis (Gall Stones)
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 +
Acute Cholecystitis
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
Chronic Cholecystitis
Typically secondary to gallstones, female predominance, associated w/ cholelithiasis in > 90% of cases, can be a sequela of recurrent acute cholecystitis
Carcinoma of Gallbladder
associated w/ gallstones
infections and parasites
prognosis poor
mostly elderly pts
Pancreas
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)
Acute Pancreatitis
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
Chronic Pancreatitis
Chronic alcohol abuse, seen w/ cystic fibrosis
exocrine and endocrine functions severely compromised leading to malabsorption and diabetes mellitus
Carcinoma of Pancreas
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)
Insulinoma
Beta cell tumor
May produce intractable hypoglycemia (20%)
10% behave in a malignant fashion
Gastrinoma
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
