Hepatobiliary Diseases Flashcards
Liver Anatomy
- weights 1200-1500g , divided into two main lobes (right and left lobes)
- dual blood supply - 1.) Hepatic artery (ex celiac artery, oxygenated blood from the heart) and 2.) portal vein (deoxygenated blood from GI tract)
- bile leaves the body via the left and right hepatic ducts that join to form the common hepatic duct. CBD joined by the pancreatic duct just before it enters the duodenum at the ampulla of Vater, which is guarded by the sphincter of Oddi.
Liver Histology
- divided into hexagonal lobules
- At the center of each lobule is the central vein which joins the hepatic veins
- portal tracts are at the periphery of the lobules, each containing a hepatic artery, portal vein, and bile duct
- the parenchyma is comprised of lobules and consists of anastomosing sheets or cords of liver cells (hepatocytes)
- vascular sinusoids are between the cords
- arterial and veinous blood enters the liver via the hepatic artery and portal veins through the sinusoids, during which it washes over the hepatocytes and then exits through the central veins to the hepatic veins and vena cava
Liver Function
Metabolic
- glucose and lipid physiology
- uses things
- excess blood glucose is stored in the liver as glycogen. Glucose is released into the blood through glycogenolysis, glucose made from AAs - during fasting, the liver converts free fatty acids to triglycerides which is secreted as lipoproteins
Synthetic
- most serum proteins (albumin, clotting factors, complement, iron and copper-binding proteins) made in the liver, with the exception of immunoglobulins
Storage
- liver stores glycogen, triglycerides, irons, copper, and lipid-soluble vitamins
Catabolic
- endogenous (hormones, serum proteins) by the liver to maintain their levels - Exogenous (drugs) substances too
Excretory
- bile (most important for fat absorption in small intestine)
Diagnosis Liver Disease
Liver function tests
- bilirubin, albumin, INR (blood clotting test)
- liver clearing toxins, producing proteins, clotting factors
- Not clearing toxins - bilirubin in blood increases
- not producing proteins - albumin in the blood decreases
- not making clotting factors/too long to clot - INR test abnormal (elevated INR)
Liver Enzyme Test
- ALT, AST, GGT, LDH
- when liver cells are inflamed - more enzymes are excreted into the blood, levels increase
Liver Ultrasound
- lesion in liver, screen for cancer
Liver Biopsy
Common Hepatotrophic Viruses
- viral hepatitis is the inflammation of the liver caused by viruses
- can affect the liver directly (hepatitis viruses) or affect the liver secondary due to a systematic infection (cytomegalovirus or Epstein Barr Virus)
- Histology - inflamed liver (inflammation amount = grade), dense aggregates of inflamed cells, lymphocyte infiltrate centred on portal tract (chronic appearance), a large quantity of fibrotic tissue (amount determines stage)
Hepatitis A
- causes mild or asymptomatic hepatitis
- spread via fecal-oral route (food and water contamination)
- epidemics common, high association with oro-anal sexual practices
- serology for diagnosis - anti-HAV IgM is indicative of current infection, anti-HAV IgG is indicative of past infection
- the disease is mild and self-limited, it is protracted and relapsing
- Few develop fulminant or chronic hepatitis, no carriers of hepatitis A
Hepatitis B
- blood and body fluid-borne disease
- 400 million, 75% in South-East Asia
High-Risk Individuals
- blood transfusions
- IV drug abusers
- healthcare workers
- hemodialysis patients
- high-risk sex practices
Spread - parenteral (injection), close contact, sexual, vertical
The concentration of body fluids
- high = blood, serum, wound exudates
- Medium = semen, vaginal fluid, saliva
- low = urine, sweat, tears, breastmilk
Serum Antigens and Antibodies
- HBsAg - surface antigen, first appearing marker - >4-6 months = chronic
- HBsAb - normally persists for life and is the protective, the basis of vaccine, which means you have success vaccine or are immune
Infection rates
- 30-40% know they have it
- 5-10% are carriers
- 5-10% chronic, low rate, most clear - 1% recovery, 20% cirrhosis, 2-3% carcinoma
- 25% acute - 99% recover, 1% -> fulminant -> death or transplant
- HCC is 200x risk
Hepatitis C
Transmission
- blood transfusion
- parenteral transmission - most common is an IV drug
- sporadic hepatitis
- HBV method higher % than needle
Serological Diagnosis
- Anti-HCV Antibodies or PCR for viral RNA detection
Treatment
- interferon and related drugs, antivirals
- no vaccine
infection
- few have acute hepatitis
- rare fulminant
- chronic is 80% - takes years/decades
- 80% of carrier state
- cirrhosis in 20% of chronic patients
Hepatitis D
- defective virus - HDV can only replicate in the presence of HBV
- Modifier of acute and chronic hepatitis B
- presentation depends on the presence of hepatitis B concurrently (co-infection) or after (super-infection)
- transmitted parenterally
Needle stick Injury
Risk of transmission after needle prick
- Hepatitis B - 30%
- Hepatitis - 3% (0-10)
- HIV - 0.3%
Follow up after needle
- HBV - vaccine if unvaccinated
- post-exposure prophylaxis with HBV immunoglobulin (HBIg) considered
HCV - baseline, follow up testing for anti-HCV antibodies and ALT activity (inflamed hepatocytes)
Cirrhosis
- end-stage in the evolution of many chronic liver diseases - includes viral hepatitis
The diffuse process involves:
- deposition of fibrous tissue (fibrosis)
- conversion of moral architecture into regenerative nodules
Etiology of Cirrhosis
- infections - HBV, HCB, schistosomiasis
- drugs/toxins - alcohol, methotrexate, amiodarone
- Metabolic - NAFLD/NASH, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency
- autoimmune - primary biliary cirrhosis
- biliary obstruction - calculi, sclerosing cholangitis
- venous - veno-occlusion disease, Budd-chiari syndrome
- Miscellaneous - neonatal hepatitis syndromes
- cryptogenic
3 Major Causes of Cirrhosis
1.) Cell death
- initiating factors occurs continuously over a long period of time
- mild = can recover, cirrhosis does not occur
- MUST be recurrent to be cirrhosis
2.) Regeneration
- Completes the reparative process
- Hepatocytes will try to regenerate to restore normal function
- End up with Regenerative nodules - due to fibrous tissue present
3.) Fibrosis
- Repair mechanism that follows cell death
- When cells cannot repair quickly enough to repair damaged tissue
- Lay down fibrous tissue - provides structure and stability
Complications of Cirrhosis
abnormal blood flow - Problematic
- leads to portal hypertension
- portal vein drains blood from the entire GI tract through the liver - back pressure = problems
- esophageal varices (rupture -> hematemesis) - vomit blood, vital
- splenomegaly (enlargement of spleen) and ascites (build-up of fluid in the abdominal cavity that leaked out of the vascular system)
Parenchymal Insufficiency
- impaired protein synthesis - decrease in albumin (keep blood plasma in the vascular system, clotting factors)
- inadequate deactivation of drugs and hormones
- jaundice
- Clotting abnormalities
- Hepatic encephalopathy - altered mental state
Hepatocellular carcinoma
- can be a late complication
Stages of Alcoholic Liver Disease
Steatosis (fat)
- earliest manifestations - least serious
- fat in the liver
- few symptoms or signs
- usually disappears in 4-6 weeks of abstinence
- pink hepatocytes, purple nuclei, large white fat droplets in cytoplasm, no inflammation
Alcoholic Hepatitis (steatohepatitis)
- elevated liver enzymes
- Triad (inflammation, steatosis, liver cell damage)
- elevated aminotransferase, alkaline phosphatase, and jaundice
- fat droplets, small purple dots (inflammation cells), Mallory bodies (damaged hepatocytes, a marker)
Cirrhosis
- often due to alcohol - 80 g (8 beers) is mild and reversible,
- hepatitis Cellular Cirrhosis (HCC) - 5-15%, may act as a promoter or co-carcinogen related to the induction of microsomal enzymes.
Fatty Liver Disease
- most common liver abnormality disease in NA
- the hepatic expression of the metabolic syndrome - increased associated with obesity
Two main morphological Types
- Non-alcoholic fatty liver
- Non-alcoholic Steatohepatitis
Non-alcoholic Fatty Liver
steatosis
- usually macrovascular (admixed with micro)
- Zone 3 or diffuse
- Quantified as <5%, 5-33%, 33%-65%, >66%
No hepatocellular injury
NAFL does not always -> NASH
–> Steatosis without hepatobiliary injury - just fat in liver
Non-alcoholic Steatohepatitis
Steatohepatitis
- steatosis
- hepatocyte ballooning
- inflammation (lobular +/- portal) - +/- Mallory Denk bodies (Mallory bodies, Mallory hyaline) - +/- fibrosis
Grading
- depends on inflammation and cellular damage
Staging
- quantity of fibrosis
20-25% get cirrhosis, risk increase with more liver diseases
–> steatosis with inflammation and hepatic injury - +/- fibrosis
CANNOT tell if fatty liver cause by NASH or alcohol
Metabolic Diseases
Most important (excluding NASH):
- Hemochromatosis
- Wilson’s Disease
- Alpha-1-antitrypsin (ATT) deficiency
- maybe non-inherited iron overload
Hemochromatosis
- one of the most common hereditary/genetic diseases in the West
- individuals homozygous for C282Y mutation for the HFE gene (chromosome 6)
- life long excess iron absorption (duodenum)
- deposition of iron cells and tissues - liver (cirrhosis), heart (cardiac failure), pancreas (diabetes mellitus), joints (arthropathy), bronze skin
- increased risk of HCC - abnormal iron in hepatocytes, brown pigment
Treatment
- removal of iron from phlebotomy - remove blood and iron at regular intervals
Wilson’s Disease
- copper accumulation in the liver and multiple other organs
- patients develop hepatitis and cirrhosis
- degenerative neurological disease from brain involvement - neuropsychiatric symptoms
Alpha-1-Antitrypsin Deficiency
- A1AT is a protein which inhibits proteinase digestion, synthesized in the liver
- deficiency = abnormal proteins produced and accumulated in the liver - > difficulty excreting hepatocytes
- main consequences to liver and lungs - chronic hepatitis and cirrhosis (children), emphysema (adults, alveolar membranes broken down by proteinases)
Metabolic Syndrome X
- increased in obesity and in metabolic syndromes
- a cluster of metabolic abnormalities that are risk factors for cardiovascular disease
- insulin resistance, diabetes mellitus, obesity, dyslipidemia, and systemic hypertension
- NAFLD is considered a hepatic expression of metabolic syndromes
Cholestasis
- impaired excretion of bile -> hyperbilirubinemia -> manifests as jaundice (+/-) prurtis
