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6. HDS GI Repro > Hepatic Disorders > Flashcards

Hepatic Disorders Flashcards

1
Q

Liver
Gross Anatomy

A
  • Location:
    • From right 5th intercostal space in midclavicular line to just below right costal margin
  • Size/Weight:
    • 10-12cm span
    • 1,400-1,600gm (adult weight)
  • Lobes:
    • Visually divides as:
      • Right ⇒ includes right lobe, caudate and quadrate lobes
      • Left
    • Physiologic division:
      • Divide into 2 equal parts w/ line extending from IVC to gallbladder
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2
Q

Liver
Connections

A
  • Glisson’s capsule: CT covering liver
  • Falciform ligament: connects liver → diaphragm & anterior abdominal wall
    • Fetal life: carries umbilical vein
    • Later life: carries paraumbilical vein
      • May serve as collateral vessels in portal HTN
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3
Q

Liver
Vascular Supply

A
  • Inflow:
    • Hepatic artery: usually from celiac artery
      • Supplies 30-40% of blood flow
    • Portal vein: formed from convergence of superior mesenteric and splenic veins (i.e. most of venous drainage of abdomen)
      • Supplies 60-70% of blood flow
    • True infarcts rare d/t dual supply of blood
  • Venous drainage:
    • Extrahepatic veins drain into inferior vena cava
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4
Q

Liver
Biliary System

A

Intrahepatic ducts (lobular and septal) → right and left hepatic ducts (extrahepatic) ⇒ unite to form common hepatic duct

Cystic duct from gallbladder enters ⇒ forms common bile duct (CBD)

Ampulla of Vater: slightly dilated portion of CBD as it empties into second portion of duodenum

Pancreatic duct drains into ampulla in two-thirds of population

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5
Q

Liver

Functional Unit Models

A

Zonation of the parenchyma

  • Gradient of activity displayed by many hepatic enzymes
  • Zonal distribution of certain types of hepatic injury
  • Acinar model ⇒ describes physiologic relationship b/t hepatocytes & vascular supply
  • Classic lobular model ⇒ describes histopathology of the liver
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6
Q

Liver

Lobular Model

A
  • Hexagon shaped
    • Center ⇒ terminal hepatic veins (“central vein, efferent vein”)
      • Hepatocytes near terminal hepatic vein ⇒ “centrilobular”
    • Periphery ⇒ portal tracts
      • Hepatocytes near portal tract ⇒ “periportal”
  • Pros: easy to define
  • Cons: not physiologic
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7
Q

Liver

Acinar Model

A
  • Triangle shaped
    • Apex ⇒ central vein
    • Distal apices ⇒ terminal hepatic veins (“central vein, efferent vein”)
    • Base ⇒ formed by septal venules from portal vein that extend out from portal tracts
  • Based on blood flow
  • Parenchyma is divided into three zones
    Zones numbered higher as blood flows toward central vein
    • Zone 1: adjacent to portal vein
      • Freshest blood flow
    • Zone 2: between 1 & 3
    • Zone 3: closest to central v.
      • Furthest from afferent blood supply
      • Most susceptible to blood supply problems
        • Ischemia d/t poor portal flow
        • Congestion/ischemia d/t problems w/ blood exiting liver
      • Most susceptible to drug/toxin insults
        • Hepatocytes tend to have active drug metabolizing enzyme systems
        • Susceptible to buildup of toxic metabolite byproducts and injury from toxins in general
  • Pros: physiologic
  • Cons: harder to visualize
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8
Q

Liver
Portal Tract

A
  • Contains 3 structures
    • Hepatic artery branch
    • Portal vein branch
    • Bile duct branch
  • Connective tissue matrix
  • Others
    • Lymphatic branch
    • Scant inflammation
  • Limiting plate
    • Hepatocytes that abut portal tract
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9
Q

Hepatocytes

A
  • Polygonal eosinophilic cell
  • Central nucleus, prominent nucleolus
  • Arranged as 1 cell thick cord after 5 y/o w/ occasional interanastomosis
  • Surfaces:
    • 2 sinusoidal surfaces w/ numerous microvilli facing into Space of Disse
    • 1 canalicular surface
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10
Q

Hepatocyte and Sinusoids

Arrangement

A
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11
Q

Liver

Bile Flow

A

Bile flow: canaliculus → bile duct

  • Bile canaliculus: formed by apposition of two adjacent hepatocytes
  • Held together by tight junctional complexes
  • Bile actively transported into canaliculus
  • Canaliculus → canals of Hering @ border of portal tract → portal bile duct branch
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12
Q

Liver

Sinusoid

A
  • Formed by fenestrated endothelium w/ no basement membrane
  • Space of Disse:
    • Space between hepatocyte and endothelial cell
    • Usually not seen on routine histology
    • Contains fibronectin and type I collagen
      • Scaffold of liver architecture
  • Kupffer cell:
    • Resident macrophage sits either on top or between endothelial cells
  • Ito cells:
    • Stellate cells in space of Disse
    • Can function as facultative fibroblasts and secrete extracellular matrix components and growth factors
      • When activated, see liver fibrosis and can go on to cirrhosis
    • Can store fat
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13
Q

Liver Functions

A
  • Metabolic
  • Synthetic
  • Storage
  • Catabolic
  • Excretory
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14
Q

Liver Disease

Overview

A
  • Mechanisms of injury: metabolic, toxic, microbial, circulatory, and neoplastic
  • Main primary diseases of the liver: viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC)
  • Liver can also be damaged by: cardiac decompensation, disseminated cancer, and extrahepatic infections
  • High functional reserve ⇒ masks impact of mild liver damage
    • Insidious process (other than fulminant hepatic failure)
      • Takes place over weeks, months, years
    • Hepatic decompensation ⇒ symptoms
  • Injury is detectable w/ lab tests
  • Chronic liver disease causes 27k deaths/yr in the US
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15
Q

Liver

Response to Injury

A
  • Hepatocyte degeneration and intracellular accumulations
  • Hepatocyte necrosis and apoptosis
  • Inflammation
  • Regeneration
  • Fibrosis
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16
Q

Liver Function Tests (LFTs)

Overview

A
  • Serologic tests used in the evaluation of liver disease
  • Commonly include: ALT, AST, Alkaline Phosphatase, GGTP, Total & Direct Bilirubin, Albumin & Total Protein
  • Many reflect the health of the liver and are not direct measures of its function
  • Commonly used LFTs may be abnormal even in pts w/ a healthy liver
  • Liver injury tests (enzymes):
    • Serum alanine aminotransferase (ALT)
    • Serum aspartate aminotransferase (AST)
    • Serum alkaline phosphatase (ALP)
    • Serum gamma glutamyl-transferase (GGTP)
  • Tests of hepatic synthetic function:
    • Albumin
    • Prothrombin time
  • Marker of hepatic transport:
    • Serum bilirubin
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17
Q

Patterns of LFT Abnormalities

A

Clinically observed patterns of biochemical tests:

  • Hepatocellular Injury Pattern
    • AST/ALT elevated > 5x upper limit of normal
      • Normal for females: < 19 IUs
      • Normal for males: < 30 IUs
    • ALP levels elevated ≤ 2-3x upper limit of normal
      • Normal = 38-126
  • Cholestatic Pattern
    • ALP levels elevated 3-5x upper limit of normal
      • AST/ALT elevation minor
  • Mixed pattern
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18
Q

Serum Aminotransferases

A

Most accurate markers of hepatocellular necrosis

Part of gluconeogenic pathway

Normal levels: < 40 IU/ml

  • AST: Aspartate Aminotransferase
    • Oxaloacetate → Malate
    • Found in the mitochondria and cytosol
    • Not specific for liver disease
    • Found in the liver, heart, skeletal muscles, kidney, brain, pancreas, lungs, leukocytes and erythrocytes
  • ALT: Alanine Aminotransferase
    • Pyruvate → Lactate
    • Primarily found in the liver cytosol
    • More specific indicator of liver injury than AST
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19
Q

Elevated AST/ALT

Interpretation

A
  • Mild ⇒ < 3x ULN
    • NAFLD; NASH
    • Chronic Viral Hepatitis B & C
  • Moderate ⇒ 3-20x ULN
    • Alcoholic Hepatitis (2-3:1 ratio AST:ALT)
    • Acute Viral Hepatitis (1:1 ratio)
    • Autoimmune hepatitis
  • High ⇒ > 20x ULN
    • Drug toxicity (acetaminophen)
    • Acute Viral Hepatitis
    • Ischemia
    • Autoimmune Hepatitis
    • Wilson’s Disease
  • Ratio AST > ALT
    • Alcoholic liver disease
    • Cirrhosis of any etiology
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20
Q

Serum Alkaline Phosphatase (ALP)

A
  • Family of isoenzymes which catalyze hydrolysis of phosphate esters @ alkaline pH
    • Reaction requires zinc
    • Function in the liver unknown
  • Four different genes:
    • 1 = liver, bone, 1st trimester placenta and kidney
    • 2 = 3rd trimester placenta and intestine
    • 3 = intestine
    • 4 = fetal intestine
  • ↑ ALP in liver diseases that involve:
    • Inflammation
    • Destruction or blockage of large and small intra- and extrahepatic bile ducts
  • If ALP ↑ ⇒ must ID source
    • Gel electrophoresis to separate the various types of ALP
    • Measure 5’ nucleotidase or GGTP ⇒ elevated along w/ ALP when 2/2 liver disorder
    • ↑ ALP + nl GGTP ⇒ more likely 2/2 bone disorder
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21
Q

Elevated Serum Alkaline Phosphatase

Hepatic Etiologies

A
  • Chronic cholestatic or infiltrative diseases
  • Partial bile duct obstruction
  • Primary biliary cholangitis (PBC) (previously called primary biliary cirrhosis)
  • Primary sclerosing cholangitis (PSC)
  • Idiopathic adulthood ductopenia
  • Drugs ⇒ androgenic steroids; phenytoin
  • Infiltrative diseases ⇒ sarcoidosis; other granulomatous diseases; metastases
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22
Q

Serum Gamma Glutamyltransferase (GGT)

A
  • Found in hepatocytes and biliary epithelial cells
  • Very sensitive indicator of hepatobiliary disease
  • Usefulness limited by lack of specificity
    • Elevated levels also seen in a wide variety of other clinical conditions: pancreatic disease, MI, CKD, COPD, DM, Alcoholism, Phenytoin and Barbiturates
  • Occult alcohol use ⇒ sensitivity ranges from 52-94%
  • Clinical uses:
    • Evaluate a cause for ↑ ALP
    • Support a suspicion of alcohol abuse w/ AST:ALT ratio > 2:1
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23
Q

Hepatic Synthetic Function

Tests

A

Tests measure how well the liver is working:

  • Serum Albumin
    • Most important protein in plasma synthesized by the liver
    • Total pool = 500 grams, 12-15 gm synthesized daily
    • T ½ = 20 days
      • Not helpful in acute liver disease
    • Influenced by nutritional status, hormone balance and osmotic pressure
  • Prothrombin Time
    • Liver synthesizes most coagulation factors
      • Factors II, VII, IX, X, (vitamin K)
    • < 50% of normal levels are needed to prolong PT
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24
Q

Bile Physiology

A
  • Secreted by hepatocytes
  • Functions:
    • Emulsify dietary fats in the duodenum
    • Facilitates transport of fat-soluble vitamins (A, D, E, K)
    • Rids body of bilirubin
    • Enables excretion of cholesterol, lipophilic wates (drugs, toxins)
  • Contains:
    • Water
    • Bile salts
    • Bilirubin (pigmented)
    • Electrolytes (isotonic to plasma)
    • Phospholipids and cholesterol
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25
Q

Bilirubin

Synthesis & Transport

A
  • Heme derived end product
    • 85% from senescent RBCs
    • 15% from other sources
      • Breakdown of other hepatic hemoproteins
        • Cytochrome P-450 enzymes
      • Premature RBC breakdown in bone marrow
  • RBC phagocytosed by MΦ in reticuloendothelial system (RES)
    • Heme porphyrin ring → biliverdin by microsomal heme oxygenase
    • Biliverdin → bilirubin by biliverdin reductase
  • Unconjugated BRN is released into the plasma
    • Majority bound to albumin
      • Insoluble in water ⇒ cannot be excreted in urine or bile
      • Transported to the liver
      • BRN released by albumin and taken up by hepatocytes
    • Unbound (free) bilirubin
      • Toxic to brain of newborns ⇒ kernicterus
      • Drugs competing w/ bilirubin for albumin binding sites ↑ free bili
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26
Q

Bilirubin

Metabolism & Excretion

A
  • Hepatic BRN metabolism__:
    • Uptake:
      • Bilirubin dissociates from albumin in the space of Disse
      • Carrier mediated transport of unconjugated BRN across hepatocyte membrane
      • Glutathione-S-Transferase (ligandin) binds bilirubin in the cell
    • Conjugation:
      • BRN conjugated w/ glucuronic acid by UDP glucoronyltransferase (UGT) in the ER
      • Forms BRN mono- and diglucuronide ⇒ both water soluble
    • Excretion into the bile:
      • Conjugated BRN excreted into bile canaliculus via active transport by MRP2 transport protein
        • Rate limiting step for transhepatic transport of bilirubin
  • Transport of conjugated BRN__:
    • Bile → biliary system → ampulla of Vater → 2nd portion of the duodenum → large intestine (colon)
    • Bacteria convert conjugated BRN → colorless urobilinogens → excreted in the feces
      • Urobilinogens → colored urobilins ⇒ gives stool its color
    • 20% of urobilinogens deconjugated by colonic bacteria and reabsorbed by enterohepatic circulation
    • 1% is excreted in the urine
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27
Q

Bilirubin

Measurement

A
  • Total bilirubin = 0.1-1.5 mg/dL
  • Unconjugated or “indirect” = 0.1-1.0 mg/dL
    • Not soluble in water
    • Not measured directly in serum
    • Indirect BRN = Total – Direct BRN
  • Conjugated or “direct” = 0-0.3 mg/dL
    • Water soluble
    • Small amount leaks out from liver
    • Directly measured in the serum
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28
Q

Excess Bilirubin

A
  • Hyperbilirubinemia: ↑ bilirubin concentration in blood (> 1.0 mg/dL)
  • Jaundice (icterus): yellow skin and sclerae (> 2-2.5 mg/dL)
  • Cholestasis: visible bile plugs and bile by microscopic examination of liver
  • Cholestatic jaundice: Cholestasis and hyperbilirubinemia
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29
Q

Jaundice

A

“Icterus”

  • Yellow discoloration of skin, sclera and mucous membranes
  • Excess serum bilirubin ⇒ deposited in tissues
    • Tissues w/ high [elastin] ⇒ ↑ affinity for serum bilirubin
      • E.g., sclera of the eye
  • Normal serum bilirubin 0.3-1.5 mg/dL
  • ↑ BRN becomes clinically evident when > 2-4 mg/dL
  • Other conditions can cause yellow discoloration of the skin but not scleral icterus
    • Carotenemia (excess serum carotene from carrots)
    • Tanning products
    • Side effects of medication (e.g., quinacrine or busulfan)
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30
Q

Unconjugated Hyperbilirubinemia

A

Disorders are not usually ass. w/ significant hepatic disease

  • Displacement of BRN from albumin by drugs
    • Rifampin
  • Overproduction__:
  • *Overproduction of BRN** ⇒ exceeds hepatic conjugative capability
    • BRN rarely > 5mg/dL
    • Jaundice usually mild
    • Hemolytic disorders
      • Sickle cell anemia, thalassemia, G6PD deficiency, paroxysmal nocturnal hemoglobinuria
    • Ineffective erythropoiesis
      • Fe deficiency, vitamin B12 deficiency, sideroblastic anemia, lead toxicity
    • Resorption of large hematomas
  • Impaired uptake__:
    • 1°: Gilbert’s syndrome
    • 2°: Certain drugs, e.g., rifampin, may compete w/ BRN uptake
  • Impaired conjugation__:
    • 1°: Crigler-Najjar syndrome
    • 2°: Acquired defects in conjugation
      • Drugs (e.g. chloramphenicol)
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31
Q

Gilbert’s Syndrome

A
  • AD disorder, 3-8% of population
  • Mutation of bilirubin UDP-GT
    • ↓ Uptake of unconjugated BRN by hepatocytes
    • Partial defect in BRN conjugation (50% of normal)
  • Mild unconjugated hyperbilirubinemia
    • BRN levels ≤ 6mg/dL
    • No other biochemical/histological abnormalities
  • Pts asymptomatic at baseline
  • Occasionally exhibit jaundice w/ illness, stress, fatigue, premenstrual state and alcohol abuse
  • Liver biopsy is not indicated, no specific therapy
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32
Q

Crigler-Najjar Syndrome

A

Unconjugated Hyperbilirubinemia

Impaired conjugation of BRN caused by ∆ UDP glucoronyltransferase activity.

  • Type 1
    • AR disorder
    • No UDPGT activity
    • Fatal for neonates
      • Severe unconjugated hyperbilirubinemia (> 20 mg/dL)
      • Often die by 18 m/o w/ kernicterus
    • Tx: phototherapy, plasmapheresis, liver transplantation
  • Type 2
    • AD disorder
    • ↓ UDPGT activity (10% of normal)
    • BRN levels 10-16 mg/dL
    • No kernicterus
    • Tx: Phenobarbital to induce UDPGT activity
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33
Q

Neonatal Jaundice

A
  • Seen in 70% of full-term newborns
  • Physiologic in first 5 days of life
  • D/t incompletely developed hepatic BRN metabolism
    • ↓ Ligandin and ↓ UGT
  • Result in unconjugated hyperbilirubinemia
  • UGT ↑ by 2 wks of life to adult levels
  • Bilirubin crosses placenta and is dealt w/ by mom in utero
  • Other factors:
    • RH and ABO blood incompatibilities: hemolytic anemia ⇒ pathologic + physiologic jaundice in newborn
    • Hypothyroidism
    • Breast milk jaundice resulting from an inhibitor of UDPGT activity in maternal breast milk
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34
Q

Conjugated Hyperbilirubinemia

A
  • Definition: conjugated BRN level > 30% of total BRN
  • Congenital causes:
    • Dubin-Johnson syndrome
    • Rotor’s syndrome
    • Progressive familial intrahepatic cholestasis (PFIC) (“Byler’s disease”)
  • Acquired causes:
    • Cholestasis: impaired formation or excretion of all components of bile
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35
Q

Dubin-Johnson Syndrome

A

Conjugated Hyperbilirubinemia

  • AR condition
  • Mutated MRP2 transporter
  • Impaired storage and excretion of BRN
  • Serum BRN levels 2-5mg/dL
  • Histological exam reveals a darkly pigmented (black) liver
  • No specific therapy
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36
Q

Rotor’s Syndrome

A

Conjugated Hyperbilirubinemia

  • AR condition
  • Impaired intracellular storage of BRN
  • Bile salt excretion is normal
  • BRN levels 2-5mg/dL
  • Liver is not pigmented
  • Liver function unaffected
  • No specific therapy
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37
Q

Progressive Familial Intrahepatic Cholestasis (PFIC)

“Byler’s Disease”

A

Conjugated Hyperbilirubinemia

  • AR condition
  • Defective hepatic secretion of bile acids across the canalicular membrane
  • Particularly affecting the Amish kindred
  • Pts present w/ severe watery diarrhea, cholestatic jaundice, fat-soluble vitamin deficiency and occasionally pancreatitis
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38
Q

Cholestasis

Overview

A
  • Impaired formation or excretion of all components of bile
  • ↑ Serum and tissue bilirubin
  • 2 major mechanisms:
    • Defect in excretion of BRN from hepatocytes into bile ⇒ intrahepatic cholestasis
    • Mechanical obstruction to the flow of bile through the bile ducts ⇒ extrahepatic cholestasis
  • Biochemical pattern:
    • ↑ Serum BRN (usually conjugated)
    • ↑ ALP
    • ↑ GGTP
    • Mild ↑ AST/ALT (≤ 2x ULN)
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39
Q

Differentiating

Cholestasis

A
  • Considerable overlap in biochemical pattern seen in intrahepatic and extrahepatic causes
  • Additional testing to look for an extrahepatic cause
    • Abdominal US
    • CT
    • MRCP (magnetic resonance cholangiopancreatography)
      • MRI of the biliary and pancreatic trees
    • ERCP (endoscopic retrograde cholangiopancreatography)
      • Endoscopic contrast study of the biliary tree
  • Obstruction in the biliary tree (gallstone, pancreatic tumor or malignant biliary tract CA) ⇒ bile ducts will appear dilated on imaging
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40
Q

Intrahepatic Cholestasis

Etiologies

A
  • Bile canaliculus
    • Hepatocellular injury
      • Viral and alcoholic hepatitis
      • Sepsis
      • Prolonged total parenteral nutrition
      • Congestive hepatopathy (from right heart failure)
      • Infiltrative disorders (sarcoidosis, amyloidosis, lymphoma etc.)
      • Graft-versus-host disease (after bone marrow transplant)
    • Drugs
      • Steroid hormones, chlorpromazine, OCP, NSAIDs etc.
    • Benign post-operative cholestasis
    • Pregnancy
  • Bile ductule
    • ? Drugs
  • Portal tract bile duct
    • Primary biliary cholangitis (PBC) (“Primary biliary cirrhosis”)
    • Intrahepatic biliary atresia
  • Medium and large interlobular bile ducts
    • Sclerosing cholangitis
    • Cholangiocarcinoma
    • Parasite
    • Vanishing bile duct syndrome (idiopathic adulthood ductopenia, chronic rejection)
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41
Q

Intrahepatic Cholestasis

Morphologic Features

A

Cholestasis & cell necrosis

  • Early cholestasis
    • Preferential localization in zone 3
    • See bile in hepatocytes
  • Late cholestasis
    • Bile plugs in zone 1
    • Feathery degeneration
      • Swelling
      • Bile pigment
      • Reticulation of cytoplasm
    • Mallory hyaline
    • Fibrosis/Cirrhosis
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42
Q

Extrahepatic Cholestasis
Etiologies

A
  • Choledocholithiasis (gallstones impacted in common bile duct)
  • Sclerosis and strictures of biliary tree
    • Sclerosing cholangitis
    • Secondary causes
  • Neoplasia
    • Cholangiocarcinoma (bile ducts)
    • Pancreatic adenocarcinoma
    • Ampullary carcinoma
    • Duodenal neoplasm
    • Metastases to hepatic hilum
    • Portal LN involvement by any neoplasm
  • HIV cholangiopathy
  • Haemobilia (blood clots in biliary tree)
  • Infectious cholangiopathy: worms impacted in bile ducts (Clonorchis, Ascaris, Fasciola)
  • Chronic pancreatitis
  • Benign biliary strictures (post-cholecystectomy, post liver transplant, related to PSC, ischemic)
  • Pediatric pts
    • Extrahepatic biliary atresia
    • Choledochal cysts
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43
Q

Extrahepatic Cholestasis

Morphologic Features

A

Cholestasis & Cell Necrosis

Plus

  • Portal tract edema
  • Bile duct proliferation
  • Neutrophils
  • Bile infarct
  • Extravasated bile
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44
Q

Cholestasis

Clinical Manifestations

A
  • Dark urine ⇒ “tea colored”
  • Light stools ⇒ “clay colored”
  • Pruritus
    • D/t retention of bile salts and other products
    • Tx w/ bile salt binders (cholestyramine)
  • Abd pain
  • Weight loss
  • Fat malabsorption (steatorrhea)
  • Fat soluble vitamin deficiency states:
    • Vit A ⇒ night blindness
    • Vit D ⇒ osteomalacia
    • Vit K ⇒ coagulopathy
  • High cholesterol ⇒ xanthomas
  • Secondary biliary cirrhosis
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45
Q

Predictable

Hepatotoxins

A
  • Fundamental property of toxin
  • Injury in majority of people
  • Dose dependent
  • Zonal necrosis
  • Two mechanisms:
    • Direct
    • Indirect
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46
Q

Carbon Tetrachloride Toxicity

A
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47
Q

Unpredictable

Hepatotoxins

A
  • Idiosyncratic reaction
  • Host dependent
  • Non-dose dependent
  • Non-zonal
  • Two mechanisms:
    • Hypersensitivity
    • Metabolic aberration
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48
Q

Acute and Chronic Hepatitis

Common Causes

A
  • Viral
  • Drug/Toxin
  • Alcohol
  • Non-Alcoholic Fatty Liver
  • Autoimmune Related Disorders
  • Metabolic Disorders
  • Ischemic/Congestive
  • Extrahepatic biliary obstruction
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49
Q

Hepatic Injury

Morphologic Patterns

A
50
Q

Confluent Necrosis

Subtypes

A
  • Bridging: Bands of necrosis linking landmark structures (portal tracts and central veins)
  • Submassive: Necrosis of entire lobules or groups of lobules
  • Massive: Necrosis of virtually all the hepatocytes
51
Q

Acute Viral Hepatitis

Pathology

A

Similar in all forms of viral hepatitis:

  • Lobular disarray
  • Liver cell necrosis
    • Apoptosis
    • Ballooning degeneration
  • Inflammation
    • Lymphocytes
    • Macrophages
    • Neutrophils
  • Regeneration
  • ± Cholestasis and phlebitis
52
Q

Chronic Hepatitis

A
  • Definition: Presence of necrosis and inflammation in the liver for > 6 months
  • Liver biopsy can be done to establish degree of disease
  • Expressed as ‘grade’ and ‘stage’
    • Grade describes the amount of acute disease and takes into account:
      • Interface necrosis
      • Lobular activity
      • Portal inflammation
    • Stage describes the level of fibrosis:
      • No fibrosis
      • Portal fibrosis
      • Bridging fibrosis
      • Cirrhosis
53
Q

Autoimmune Hepatitis

A

Chronic hepatitis of unknown cause

  • ~20% of all cases of chronic hepatitis in Western countries
  • More common in women, usually middle age
  • Ass. w/ circulating auto-Ab and high levels of immunoglobulins
  • Ass. w/ other autoimmune diseases
  • Suspected mechanism of injury:
    • Ab-dependent cell-mediated cytotoxicity
    • Defective suppressor T cell function
  • Type I: Anti-smooth muscle, Anti-actin, anti-asiaoglycoprotein receptor Ab
  • Type II: Liver/kidney microsomes and anti-liver cytosolic protein Ab
  • Pathology: Like chronic viral hepatitis, often plasma cell rich infiltrate
  • Clinical features: Ranges from asymptomatic to fulminant disease
  • Treatment: steroid and immune suppression responsive
  • Must distinguish from other causes of chronic hepatitis
54
Q

Drug-related Chronic Hepatitis

A
  • Many drugs reported to cause chronic hepatitis
  • May be indistinguishable from viral and autoimmune disease histologically
  • Requires exclusion of other causes serologically and clinical history
55
Q

Alcoholic Liver Disease

Stages

A
  • Fatty Liver (Steatosis)
    • Yellow, enlarged, heavy liver
    • Fat first accumulates in zone 3
    • Enlarged mitochondria, SER hyperplasia
    • If discontinue drinking, can lose the fat
    • Cause of progression to next step is unclear
  • Steatohepatitis
    • 10-30% mortality
    • > 30% who continue to drink for 1-2 yrs more will develop next step
    • Necrosis of hepatocytes
    • Neutrophilic infiltrate
    • Mallory hyaline and fat
    • Perivenular and pericellular fibrosis
  • Cirrhosis
    • Thin and thick bands of fibrosis circumscribing nodules of regenerating hepatocytes
    • Central and pericellular fibrosis

Important to realize that any of these manifestations may coexist

Do not need to see one to proceed to the next

56
Q

Non-Alcoholic Fatty Liver (NAFL)

Associations

A
  • Obesity
  • Diabetes
  • Drug related: corticosteroids
  • Metabolic disease/disorder
    • Wilson’s disease
    • Kwashiorkor
57
Q

Primary Biliary Cholangitis (PBC)

Overview

A

“Primary Biliary Cirrhosis”

Chronic progressive cholestatic liver disease characterized by destruction of intrahepatic bile ducts

  • Autoimmune disease (presumably)
  • > 85% have at least one other autoimmune disease:
    • Chronic thyroiditis, RA, scleroderma, Sjogren’s, SLE
  • > 95% have elevated antimitochondrial Ab
    • Elevated Ig, other Abs present
  • Presumed attack of ducts by cytotoxic T cells
  • Middle age women (range 30-65yrs)
  • F:M ratio is 10:1
  • Other labs: elevated alkaline phosphatase, ↑ serum cholesterol
58
Q

Primary Biliary Cholangitis (PBC)

Stages

A
  • Stage I: Destruction of small and medium sized bile ducts (focal, segmental)
    • Granulomas are the characteristic portal infiltrate
    • All types of inflammatory cells are seen
    • Plasma cell and eosinophils may be prominent
  • Stage II: Periportal inflammation and ductular proliferation
  • Stage III: Bridging fibrosis
    • Mallory hyaline
    • ↑ Copper deposition
  • Stage IV: Cirrhosis
59
Q

Primary Sclerosing Cholangitis (PSC)

A

Chronic cholestatic liver disease of unknown cause

Inflammatory and fibrosing process narrows and eventually obstructs intrahepatic and extrahepatic bile ducts

  • Associations:
    • Ulcerative colitis (seen in 2/3)
    • Less commonly: Crohn’s disease, lymphoma, retroperitoneal fibrosis
  • Hypergammaglobulinemia
  • Antineutrophilic cytoplasmic Ab (ANCA)
  • More common in men in 3-4th decade
  • ↑ risk of cholangiocarcinoma
    • Up to 10% of PSC patients
  • Liver transplant is curative
60
Q

Iron Overload

Etiologies

A
  • ↑ Iron absorption
    • HHC
    • Chronic liver disease
    • Porphyria cutanea tarda
    • Congenital diseases
    • Dietary iron overload
    • Excess medicinal iron
  • Parenteral iron overload
    • Multiple blood transfusions
    • Injectable medicinal iron
  • Focal iron overload
    • Idiopathic pulmonary hemosiderosis
    • Renal hemosiderosis
61
Q

Hereditary Hemochromatosis (HHC)

Pathogenesis

A
  • Inherited disorder of iron metabolism
  • Iron deposition toxic to involved organs
  • Autosomal recessive
  • HFE gene on short arm of chromosome 6
  • Linked to the HLA locus of the MHC
    • 70% of homozygotes have HLA-A3
62
Q

Hereditary Hemochromatosis (HHC)

Clinical Features

A
  • ↑ Iron absorption in duodenum
  • ↑ Serum iron, ferritin, and transferrin saturation
  • Clinical manifestations:
    • Diabetes
    • Skin pigmentation
    • Cardiac failure
    • Cirrhosis
63
Q

Wilson Disease

A

Genetic disorder in which excess copper builds up in the body.

Symptoms are typically related to the brain and liver.

64
Q

Cystic Fibrosis

Hepatic Effects

A
  • Tenacious bile due to CF
  • Similar change in viscosity seen in other bodily secretions
  • Newborns may present w/ obstructive jaundice
  • 15% of young adults w/ CF have symptomatic liver disease, can develop cirrhosis
65
Q

Alpha 1 Antitrypsin Deficiency

A
  • Defective secretion of mutant protein made in the liver
  • Co-dominant inheritance: > 75 variants
    • PIMM normal
    • PIZZ phenotype ⇒ abnormal folding
  • Liver and lung disease
    • Emphysema: due to lack of protease inhibitor
    • Hepatitis, Cholestasis and Cirrhosis: due to accumulation of abnormal protein
      • Seen as globules in hepatocyte
      • ↑ risk of hepatocellular carcinoma
  • Most common genetic cause of liver disease in infants and children
    • 1/2000 live births
    • Only 10-15% of those develop liver dz
  • Liver transplant curative
66
Q

Ischemic Hepatopathy

A
  • Cardiac disease: any disease ass. w/ right heart failure
    • Congestive heart failure (most common cause)
    • Tricuspid valvular disease
    • Constrictive pericarditis
  • Venous obstruction
    • Budd-Chiari: occlusion of intra and/or extrahepatic veins w/ congestive liver damage
      • Hypercoagulable states
    • Hepatic veno-occlusive disease: occlusion of the central venules and small branches of the hepatic veins
      • Bush tea
      • Chemotherapeutic agents
67
Q

Hepatic Failure

Overview

A
  • Definition: Liver cannot perform metabolic, synthetic, detoxifying activities sufficiently for body’s needs
  • Usually end-stage of chronic progressive damage
    • Steady destruction of hepatocytes
    • Repetitive waves of parenchymal damage
  • Rarely d/t sudden, massive liver destruction ⇒ fulminant hepatic failure
  • Criterion: Need to lose 80-90% of liver functional capacity
  • Without a transplant, 80% of pts w/ hepatic failure will die
68
Q

Acute Liver Failure

A
  • Acute liver illness w/ encephalopathy within 6 months after dx
    • Fulminant if within 2 weeks jaundice onset
    • Sub-fulminant if within 3 months of jaundice onset
  • Caused by massive hepatic necrosis
    • Mechs include direct toxic damage or combo of toxicity and immune-mediated hepatic destruction
  • Etiologies:
    • Usu. from drugs or toxins
      • Halothane, antimycobacterial drugs, chemicals
    • Hepatitis A, Hepatitis B, autoimmune hepatitis
69
Q

Chronic Liver Disease

A

Most common route

End point of chronic hepatitis that ends in cirrhosis

70
Q

Hepatic Dysfunction without Overt Necrosis

A

Hepatocytes are viable, but can’t function normally

Examples: Tetracycline toxicity, pregnancy

71
Q

Cirrhosis

Etiologies

A
  • Fatty liver disease
    • Alcohol (ASH), Non-alcoholic steatohepatitis (NASH) / Non-alcoholic fatty liver disease (NALD)
  • Viral hepatitis
    • Hep C, B (w/ or w/o D)
  • Autoimmune diseases
    • Autoimmune hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis
  • Genetic liver diseases
    • Hemochromatosis, Wilson’s disease, α-1 anti-trypsin deficiency, cystic fibrosis
  • Vascular causes
    • R heart failure, Budd Chiari syndrome, veno-occlusive disease
  • Rare causes
    • Drugs
      • Methotrexate, amiodarone, methyldopa
    • Toxins, herbal supplements
    • Secondary biliary cirrhosis
      • Ass. w/ chronic cholestasis
  • Cryptogenic (unknown)
    • 10-15% of cases
72
Q

Cirrhosis

Overview

A
  • Irreversible end result of chronic liver disease
    • Death of hepatocytes, ECM deposition, vascular reorganization
  • Characterized histologically by regenerative nodules surrounded by fibrous tissue
  • Caused by a variety of inflammatory, toxic, metabolic and/or congestive insults
    • Hepatitis, hepatopathy, cholestasis
73
Q

Cirrhosis

Classification

A
  • Pathologically ⇒ gross pattern of architectural distortion
    • Micronodular
      • Regenerative nodules < 3 mm
      • Often due to alcoholic cirrhosis
    • Macronodular
      • Nodules > 3 mm
      • Commonly related to chronic viral hepatitis
    • Mixed
  • Clinically
    • Compensated
      • No complications
    • Decompensated
      • One or more complications (ex. ascites, encephalopathy or variceal bleeding)
      • Liver transplantation considered
74
Q

Cirrhosis

Clinical Manifestations

A
  • May be dx @ at the asymptomatic stage
  • General decline in health (most ubiquitous feature)
  • Non-specific complaints:
    • Anorexia, wt loss, malaise, fatigue, weakness
  • Loss of normal bile flow
    • Jaundice
    • Pruritus
  • Loss of detoxification
    • Neurological sx
    • Hepatorenal
  • Loss of synthetic function
    • Albumin
    • Clotting factors
  • Advanced disease may present w/ complications of portal HTN
    • Esophageal varices
    • Ascites
    • Splenomegaly
    • Portosystemic shunting (varicosities)
    • Encephalopathy
  • Cancer risk
    • Hepatocellular Carcinoma
75
Q

Cirrhosis

Physical Examination

A

Cutaneous stigmata and endocrine features:

  • Jaundice
  • Splenomegaly and ascites ⇒ suggest portal HTN
  • Spider angiomata
  • Palmar erythema
  • Leukonychia (white nails)
  • Gynecomastia
  • Testicular atrophy
  • Caput medusae
76
Q

Cirrhosis

Laboratory Findings

A
  • Hepatic insufficiency (synthetic dysfunction):
    • Low serum albumin
    • Prolonged prothrombin time (INR)
    • High bilirubin
  • Portal HTN (due to hypersplenism):
    • Thrombocytopenia
    • Anemia
    • Leukopenia
77
Q

Cirrhosis

Radiologic Features

A

US, CT, and MRI may all be used

Characteristic features include:

  • Small, shrunken, nodular liver
  • Recanalized paraumbilical vein
  • Enlarged caudate lobe of the liver
  • Prominent vessels (varices) around the esophagus, stomach or in the mesentery
  • Splenomegaly
  • Free abdominal fluid (ascites)
  • Enlarged portal vein
78
Q

Cirrhosis

Diagnostic Tests

A
  • Non-invasive:
    • Bloodwork
      • HCV – fibrosure
      • NASH – fibrosure
    • Imaging
      • US w/ elastography
      • Fibroscan
      • MR elastography
  • Invasive:
    • Liver biopsy
      • Gold standard
      • Often not necessary if complications (e.g. varices or ascites) present or radiologic imaging diagnostic
      • Performed percutaneously or via trans-jugular route (allows for measurement of portal pressures)
79
Q

Cirrhosis

Natural History

A
  • Cirrhosis = end histological stage resulting from chronic liver injury of various etiologies
  • Initially, cirrhosis is compensated
    • Median survival 10-12 yrs
  • Decompensated stage marked by onset of variceal hemorrhage, ascites, hepatic encephalopathy and/or jaundice
    • 60% risk over 10 yrs
    • Ascites most common
    • ↑ risk of death from liver disease
    • Median survival 2-4 yrs
80
Q

Liver Failure

Severe Effects

A
  • Portal HTN
  • Hepatic encephalopathy
    • Variety of neurological signs and sx in pts who suffer chronic liver failure or in who the portal circulation is diverted –has 4 stages, ending in coma
  • Hepatorenal syndrome
    • Renal failure featuring renal hypoperfusion: oliguria, azotemia and ↑ plasma creatinine levels
    • Usually kidneys function normally
    • Seems to be d/t ↓ in renal blood flow
  • Hepatopulmonary Syndrome
    • Clinical liver disease, hypoxemia, intra-pulmonary vascular dilations
81
Q

Portal Hypertension (PHTN)

Characteristics

A
  • Portal circulation follow Ohm’s Law: P = R x F
  • Portal venous system ⇒ low-pressure system
  • Cirrhosis:
    • Nodular regeneration and fibrosis in the space of Disse
      • ↑ resistance to flow
    • ↓ tone in the splanchnic arterioles (possibly related to nitric oxide) ⇒ ↑ splanchnic blood flow
      • ↑ portal venous inflow
  • Portal pressure gradient = effective intrasinusoidal pressure
    • Difference between hepatic vein and portal vein pressure
    • Normally < 5 mmHg
    • Clinically significant elevation: > 12 mmHg
  • Not all PHTN is due to cirrhosis
  • PHTN is classified according to the site of increased resistance
82
Q

Portal Hypertension (PHTN)

Etiologies

A
  • Pre-hepatic causes:
    • Portal vein thrombosis, splenic vein thrombosis, splenomegaly, arterioportal fistula
  • Intra-hepatic causes:
    • Presinusoidal (Schistosomiasis), sinusoidal (cirrhosis), post-sinusoidal (veno-occlusive disease)
    • Primary Biliary Cirrhosis (pre-cirrhosis)
    • Congenital hepatic fibrosis
    • Cystic disease of the liver
    • Nodular transformation
    • Metastatic or primary carcinoma
    • Toxins
  • Post-hepatic causes:
    • Budd-Chiari syndrome (thrombosis of hepatic v.), IVC web/obstruction, constrictive pericarditis, right heart failure
  • Idiopathic
83
Q

Varices

Pathophysiology

A
  • Portal HTN ⇒ dilation of pre-existing connections ⇒ portal-systemic collaterals
  • Most important: Esophago-gastric collaterals (Esophagogastric varices)
    • Coronary vein ↔︎ esophageal veins
    • Drains blood into azygos vein
    • Could cause life-threatening hemorrhage
  • Other sites of portosystemic collaterals:
    • Umbilicus (caput medusae)
      • Splenic bed via short gastric veins (gastric fundic varices)
      • Retroperitoneum
    • Rectum (rectal varices)
    • Small and large intestine (ectopic varices)
84
Q

Variceal

Management

A
  • > 50% of pts w/ cirrhosis develop gastroesophageal varices
  • Varices form and enlarge at a rate of 7-8%/year
  • Endoscopy to ID pts w/ medium-large varices @ high risk for bleeding
  • Primary prophylaxis (prevention of first bleed)
    • Non-selective β-blocker (e.g. nadolol or propranolol) ⇒ ↓ intra-variceal pressure
    • Endoscopic banding
85
Q

Variceal

Hemorrhage

A
  • Medical emergency
  • 10-30% of pts every year
  • Each episode associated w/ up to 50% mortality
  • Presentation:
    • Hematemesis
    • Melena and/or hematochezia
    • Typically leads to hemodynamic compromise
  • Predictors of bleeding:
    • Larger variceal size
    • Red signs on the varices
    • More advanced liver disease (Childs B-C)
  • Treatment:
    • Hemodynamic resuscitation w/ IV fluid
    • Blood and/or FFP transfusion
    • Pharmacologic therapy
      • Somatostatin or its synthetic analog (octreotide)
      • Abx
    • Endoscopic therapy
      • Band ligation or injection sclerotherapy
    • Transjugular intrahepatic portosystemic shunt (TIPS stent)
      • Creates a communication between portal (portal vein) and systemic (hepatic vein) circulation
      • For refractory bleeding
86
Q

Ascites

Overview

A
  • Pathological accumulation of excess fluid in the peritoneal cavity
  • Cirrhosis causes 75% of cases
  • Classification: serum ascites-albumin gradient (SAAG)
    • Elevated SAAG > 1.1 g/dL ⇒ portal HTN, right heart failure, massive liver metastases
  • Clinically detectable w/ > 500 mL
    • Shifting dullness to percussion
    • Fluid wave
    • Bulging of the flanks
    • Everted umbilicus
    • Umbilical hernia
  • Detectable w/ US @ > 250 mL
87
Q

Serum ascites-albumin gradient

(SAAG)

A
88
Q

Ascites

Pathogenesis

A

Cirrhosis (portal HTN):

  • Hepatic venous outflow block
    • Anatomical: fibrosis and regenerative nodules
    • Functional: ↑intrahepatic vascular tone, predominantly post-sinusoidal ⇒ ↑ sinusoidal pressure
  • Splanchnic and systemic arteriolar vasodilation
    • Decreased effective arterial blood volume
    • Upregulation of sodium-retaining hormones
    • Sodium and water retention
    • Plasma volume expansion
    • Dilutional hyponatremia and renal failure from hepatorenal syndrome
  • Sinusoidal hypertension
    • Drives fluid out of the sinusoids and into peritoneal cavity
    • Intravascular fluid continuously replenished by plasma volume expansion
89
Q

Ascites

Treatment

A
  • Sodium restriction (< 2g/day)
  • Fluid restriction [when hyponatremia (Na < 125mEq/L) occurs]
  • Diuretics
    • Spironolactone (aldosterone antagonist)
    • Furosemide (loop diuretic)
  • Refractory ascites (~10% of pts w/ cirrhosis)
    • Fluid overload that recurs rapidly after therapeutic paracentesis
    • Unresponsive to high dose diuretic treatment and sodium restricted diet
    • Treatment includes repeated large-volume paracentesis, TIPS or liver transplantation
90
Q

Spontaneous Bacterial Peritonitis (SBP)

Overview

A
  • Ascitic fluid infection w/ growth of a single organism and ascitic fluid neutrophil count > 250 cells/μL w/o e/o a surgically remediable intra-abd cause
  • Dx by paracentesis w/ analysis of fluid cell count and culture
  • For all practical purposes, SBP occurs only in the setting of liver disease
91
Q

Spontaneous Bacterial Peritonitis (SBP)

Pathogenesis

A
  • Severe liver disease ⇒ failure of local and systemic immune defenses ⇒ ↑ bacterial translocation
  • RES = main defense system vs bacteremia and other hematogenous infectious
    • Most RES activity located in the liver
    • Kupffer cells (tissue MΦ) are the major components
  • Cirrhosis ⇒ ↓ bactericidal activity of Kupffer cells and impaired reticuloendothelial system (RES) activity
    • Porto-systemic shunting bypasses the liver
      • Escaping the action of the RES
  • Impaired RES ⇒ prolonged bacteremia
  • In the presence of ascites, bacterial colonization occurs
  • In pts w/ ↓ local defense mechanisms (e.g. low ascites complement levels) ⇒ overt ascites infection develops (SBP)
92
Q

Spontaneous Bacterial Peritonitis (SBP)

Clinical Manifestations & Treatment

A
  • Predominant sx: fever, jaundice and abdominal pain
    • Pts can present atypically w/ encephalopathy, shock or renal failure
    • Up to ⅓ of pts may be entirely asymptomatic
  • Treatment:
    • Third generation cephalosporin (e.g. cefotaxime) IV for 5 days
    • High rates of SBP recurrence (70% at 1 year w/o abx)
    • Secondary prophylaxis w/ long-term abx is indicated
93
Q

Hepatorenal Syndrome (HRS)

A
  • Occurs in pts w/ advanced cirrhosis
  • Functional renal failure
    • Extreme peripheral vasodilatation ⇒ renal vasoconstriction
    • Kidneys w/o significant histological abnl
  • Renal dysfunction characterized by:
    • ↓ GFR
    • Oliguria
    • Low urine sodium (<10mEq/L)
    • Absence of intrinsic renal disease or other renal insults ⇒ nl urinary sediment & nl renal US
  • Tx:
    • Withdrawing diuretics and nephrotoxins
    • Volume expansion w/ saline or albumin
    • Liver transplantation is the only effective cure
      • If liver transplant is done early enough, kidneys should begin working properly again
94
Q

Hepatic Encephalopathy (HE)

A

Neuropsychiatric manifestations of hepatic cirrhosis

  • Proposed pathogenesis:
    • ↓ Clearance of gut-derived neurotoxins, including ammonia
    • Ammonia ⤭ BBB ⇒ ↑ astrocytic peripheral-type benzodiazepine receptors
      • Most potent stimulants of neurosteroid production
    • Neurosteroids ⇒ major modulators of GABA
    • GABA ⇒ cortical depression and hepatic encephalopathy
  • Dx: based on hx and PE findings
    • Ammonia levels are unreliable
      • Poor correlation b/t stage of encephalopathy and serum [ammonia]
  • Clinical features: subtle changes in personality/affect → deep coma
    • Flapping tremor or “asterixis” ⇒ cardinal feature
      • Due to inability to maintain posture of the outstretched hands
  • Treatment:
    • ID and address precipitating factors
      • GI hemorrhage, infections, electrolyte abnl, new-onset renal insufficiency, TIPS placement, medication non-compliance
    • Therapy is directed at altering the colonic microenvironment
      • ↓ ammonia production in the gut
        • Lactulose
        • Non-absorbable abx such as rifaximin
95
Q

Hepatic Metastases

A
  • 98% of Hepatic Malignancies in US
  • Carcinoma
    • Lung, Breast, Colon, Pancreas
  • Hematopoietic Malignancies
    • Non-Hodgkin lymphoma
    • Hodgkin lymphoma
    • Leukemia
    • Sarcoma
96
Q

Primary Hepatic Tumors

A
97
Q

Hepatocellular Carcinoma (HCC)

Overview

A

Malignant tumor that arises from hepatocytes

  • Low incidence regions: Western industrialized countries
    • Age of onset: 6-7th decade
    • M:F ratio: 3:1
    • % CA deaths: 0.5-2
  • High incidence regions: Sub-Saharan Africa, Southeast Asia, Japan
    • Age of onset: 3-5th decade
    • M:F ratio: 9:1
    • % CA deaths: 20-40%
  • Worldwide – Hepatocellular Carcinoma is either the #1 or #2 most common malignancy
98
Q

Hepatocellular Carcinoma (HCC)

Pathogenesis

A

Incidence of HCC ↑↑↑ in pts w/ cirrhosis

  • Viral
    • Hepatitis B Virus
    • Hepatitis C Virus
      • HCC in 1-3% of HCV-infected pts over 20-30 yr follow up
  • Metabolic disorders
    • Hemochromatosis
    • α-1 antitrypsin
  • Exposures
    • Alcohol
    • Thorotrast
    • Aflatoxins
    • Anabolic steroids
99
Q

Hepatocellular Carcinoma (HCC)

Clinical Features

A
  • Symptoms
    • Abdominal pain
    • Fullness
    • Mass
    • Decompensated cirrhosis
    • Paraneoplastic sx
  • Serology
    • ↑ alpha-fetoprotein
  • Outcome
    • Poor
    • 50% have metastases @ autopsy
100
Q

Hepatocellular Carcinoma

Appearance

A

Microtrabecular vs Macrotrabecular

101
Q

Hepatocellular Carcinoma

Screening & Treatment

A
  • Screen at-risk individuals w/ US every 6 months
  • Treatment:
    • Pts w/ well-compensated disease ⇒ surgical resection
    • Pts w/ advanced cirrhosis ⇒ liver transplantation
    • Non-surgical options:
      • Microwave or radiofrequency ablation
      • Trans-arterial chemotherapy
102
Q

Fibrolamellar Carcinoma

A

Variant of HCC w/ unique features

  • Arises in normal liver (not a cirrhotic liver like other HCC)
  • Affects adolescents and young adults
  • Not ass. w/ elevated AFP
  • Better prognosis
  • Histology:
    • Large eosinophilic hepatocytes
    • Delicate collagen in lamellar arrangement
103
Q

Cholangiocarcinoma

Overview

A
  • Adenocarcinoma of bile duct origin
  • Affects primarily 6th-7th decade, M=F
  • Location:
    • Intrahepatic (Peripheral): within the liver
    • Extrahepatic: outside the liver
      • R & L hepatic duct
        • If @ convergence ⇒ hilar or Klatskin tumor
      • CBD
      • Cystic duct
  • Differential diagnosis (microscopic look-alikes, i.e. other adenocarcinomas)
    • Pancreatic carcinoma
    • Ampullary carcinoma
    • Gallbladder carcinoma
104
Q

Cholangiocarcinoma

Clinical Features

A
  • Signs and symptoms related to site:
    • Painless jaundice
    • Pruritus
    • Palpably enlarged gallbladder
    • Pancreatitis
    • Anorexia, weight loss
  • Clinical course
    • Similar to gallbladder carcinoma
  • Outcome
    • Dismal
105
Q

Cholangiocarcinoma

Risk Factors

A
  • Biliary disease
    • PSC/UC
    • Chronic biliary infection
    • C. sinensis (liver fluke)
    • Choledochal cysts
    • Caroli’s disease
    • Congenital hepatic fibrosis
  • Other exposures
    • Hemochromatosis
    • Thorotrast
106
Q

Cholangiocarcinoma

Morphology

A
  • Intrahepatic
    • Glands within desmoplastic stroma
    • May combine w/ HCC, results in cholangiohepatocellular carcinoma
  • Extrahepatic
    • Small sclerosing tumor obliterating lumen
    • Tumor spreading along wall of duct
    • Intraductal papillary variant
107
Q

Hepatoblastoma

A
  • Malignant tumor of the liver
  • Seen mainly in young children, age 0-3 yrs
  • Clinical manifestations:
    • Abdominal enlargement
    • Vomiting
    • Failure to thrive
    • Paraneoplastic syndromes
  • Elevated AFP
  • May be cured by resection
  • Pathology
    • Hemorrhagic, circumscribed mass, up to 25cm
    • Epithelial cells
      • Embryonal appearance
      • Fetal appearance
    • Mesenchymal component
    • Extramedullary hematopoiesis
108
Q

Hepatic Sarcomas

A
  • Rare (< 1% of all hepatic malignancies)
  • Angiosarcoma
    • Malignant neoplasm of blood vessels
  • Risk factors (present in ~ 1/3)
    • Thorium dioxide
    • Vinyl chloride
    • Inorganic arsenic
    • Anabolic steroids
  • Clinical:
    • Peak: 6-7th decade
    • Rapidly fatal
109
Q

Cavernous Hemangioma

A

Benign neoplasm of blood vessels

110
Q

Hepatocellular Adenoma

Overview

A

Benign neoplasm of hepatocytes

  • Women in reproductive yrs
    • Highly ass. w/ oral contraceptives
      • Incidence ↓ w/ low dose oral contraceptives
  • Rare cases in men w/ anabolic steroid use
  • Complication:
    • Bleeding into peritoneal cavity
  • Treatment:
    • Resection
    • May disappear w/ discontinuation of OCPs
111
Q

Hepatocellular Adenoma

Pathology

A
  • 75% solitary, 25% multiple
  • Up to 40cm size
  • Mass lesion composed of compressed benign hepatocytes without normal portal areas
  • Prominent vascular spaces
112
Q

Focal Nodular Hyperplasia

A
  • Non-neoplastic nodular lesion that looks like cirrhosis
    • Mass lesion: must be distinguished from others
  • F>M
  • Pathology:
    • Central fibrous scar containing large vessels w/ radiating septa
    • No portal areas, proliferating bile ductules
  • Treatment: None required
113
Q

Nodular Transformation

Overview

A

Hyperplastic nodules without fibrous scarring

  • Two forms:
    • Partial nodular transformation
      • Partially involves liver
      • Located predominantly in hilar region
    • Nodular regenerative hyperplasia
      • Diffuse involvement of liver
  • Clinical Importance:
    • Portal Hypertension in the absence of cirrhosis
114
Q

Nodular Transformation

Associations

A
115
Q

Von Myenburg Complex

A

Bile duct microhamartomas

Anomalous, small cystic bile ducts in stroma

116
Q

Liver

Simple Cysts

A

Solitary or multiple simple cysts (Polycystic Liver Disease)

Sporadic or can be ass. w/ adult polycystic disease of the kidney

117
Q

Congenital Hepatic Fibrosis

A
  • Autosomal recessive
  • Enlarged portal tracts w/ extensive fibrosis w/o regenerative nodules
  • Numerous bile ductules that communicate w/ the biliary tree
  • Complication: portal hypertension
118
Q

Caroli’s Disease

A
  • Larger ducts are segmentally dilated
  • May contain thickened bile
  • ↑ risk of cholangiocarcinoma
119
Q

Liver Transplantation

A
  • Highly successful procedure in pts w/ advanced liver disease
  • Indications:
    • Cirrhosis (all causes)
    • Intrahepatic malignancy (ex. localized hepatocellular carcinoma)
    • Acute liver failure
    • Metabolic diseases (ex. Wilson’s disease)
  • 1-year post transplant pt survival is ~90%
  • LT evaluation includes detailed medical and psychosocial assessment
  • Several prognostic indicators have been developed
120
Q

Liver Transplantation

Complications

A
  • Rejection
    • Early
      • Cholangitis
      • Cholestasis
      • Endothelialitis (inflammatory response within endothelium of vessels)
    • Late
      • Paucity of bile ducts
      • Arteropathy
      • Subintimal foam cells
      • Myointimal hyperplasia
  • Infection
    • CMV
    • HSV
  • Disease recurrence
  • EBV ass. lymphoproliferative disease

6. HDS GI Repro (30 decks)

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