Accessory GI Flashcards
Describe the difference between the classic hepatic lobule and the hepatic acinus
- Hepatic lobule
- Hexagonal
- Central vein in center
- 6 portal tracts at periphery
- Hepatic acinus
- Triangle
- 2 portal tracts at periphery extending towards central vein
- Describes zones of blood supply
Describe the zones of blood supply in the hepatic acinus version of organization
- Zone 1: Periportal hepatocytes
- closest to blood supply
- doing most of the work
- First to be damaged by toxin in the blood
- Zone 2: Midzoneal
- Zone 3: Centrilobular hepatocytes
- around central vein
- Farthest from blood supply
- Recruited when needed
- First to be damaged by ischemia or lack of blood flow
What is the role of the following cells:
- Kupfer cells
- Stellate cells
- Kupfer cells
- phagocyte
- Stellate cells
- Myofibroblasts
- role in liver fibrosis
- Store Vit A
- Located in Space of Disse
- Myofibroblasts
Ballooning degeneration of hepatocytes is found in what types of liver damage?
Ischemic / hypoxic injury
Feathery degeneration of hepatocytes is found in what types of liver damage?
Cells have foamy cytoplasm
- cholestatic injury
- Bile accumulation
What macromolecule is accumulated in hepatocytes with steatosis?
Triglyceride accumulation
Microvesicular steatosis is found in what types of liver damage?
Fatty liver of pregnancy
Macrovesicular steatosis is found in what types of liver damage?
- Obesity
- Diabetes
- Hep C
- Found with microvesicles in Alcohol fatty liver
Mallory bodies are most likely associated with which liver disease?
Alcoholic hepatitis
How much liver function must be lost to have Liver Failure?
80-90%
What are the features of Hepatic Failure?
- Portal HTN
- ascites
- Congestive splenomegaly / hypersplenism
- ingests more RBCs and platelets
- Portosystemic shunts
- Esophageal varicies, hemorrhoids, caput medusae
- Secondary renal failure
- Decreased detox
- Increased ammonia
- Mental status changes
- Hyperestrinism
- gynecomastia, spider angiomata
- Jaundice
- Increased ammonia
- Decreased protein synthesis
- Hypoalbuminemia
- edema
- Decreased clotting factors
- Increased PT
- Hypoalbuminemia
What is the size difference between micronodular and macronodular cirrhosis?
- Micro: <3mm
- Macro: >3mm
What are the histologic changes that occur in Cirrhosis?
- Deposition of collagen I and III in space of Disse
- Normally only small amout of type II and IV
- Loss of fenestrations in sinusoid endothelial cells
- obliterates biliary channels
What is the main cell responsible for cellular architecture found in cirrosis?
Cell of ido (forms a myofibroblast when activated
Where are the regenerative cells of the liver located?
Bile ductules
May cause regeneration of cells and regain function following cirrhosis
What outcomes are associated with acute HBV infxn?
HBV Ag and significance
What is the first serologic marker to rise in HBV?
HBsAg (surface Ag)
Which HBV markers indicate acute stage?
- HBsAg = surface Ag
- first to rise
- HBeAg / HBV DNA
- HBcAb = Core Ab
- IgM
Which HBV markers indicate chronic stage?
- HBsAg (surface Ag)
- Presence > 6 months
- HBeAg and HBV DNA
- may or may not be present
- HBcAb (Core Ab)
- IgG
What markers indicate infectivity in HBV?
- HBV DNA
- HBeAg (Envelope)
- Need an envelope to mail a letter
- (mail = transfer to another person)
Which HBV marker indicates immunization or resolution of disease?
HBsAb IgG
(Surface Ab)
What is the most common cause of chronic liver disease?
HCV
What is the most common indication for liver transplant?
HCV
Whic HCV is associated with metabolic syndrome?
Genotype 3
What is the serology confirmation of coinfection of HBV and HDV?
- IgM anti-HDAg
- new infxn HDV
- IgM anti-HBcAg
- new infxn HBV
What is the serology confirmation of HBV/HDV superinfection?
- IgG or IgM anti-HDV
- BHsAg present
Outcomes of HDV/HBV Coinfection
Nearly all: Recovery with immunity
Outcomes of HDV/HBV Superinfection
Most become chronic => cirrhosis
Characteristics Hepatitis viruses
(HOV’s chart)
Hepatitis diagnosis chart
(HOV’s chart)
What are the characteristics of Acute Asymptomatic infxn with Recovery?
- Minimally elevated serum transaminases
- Anti-HAV or anti-HBV Abs
What are in characteristics of each stage of Acute Symptomatic Infxn with Recovery (Hepatitis)?
- Incubation
- Preicteric
- Icteric
- Convalescence
- Incubation
- Infectivity in last days
- Preicteric
- non-specific symptoms
- Serum sickness-like syndrome
- immune complex-mediated
- Urticaria, arthritis, glomerulonephritis
- Icteric
- Conjugated Hyperbilirubinemia
- Nearly all HAV
- 1/2 HBV
- Absent in HCV
- Conjugated Hyperbilirubinemia
- Convalescence
- Strong immune response
Acute Hepatitis Morph. Changes
Chronic Hepatitis
Ground glass cytoplasm is most characteristic of which type of Hepatitis?
HBV
What is the most common cause of Chronic Hepatitis?
- HCV
- HBV
- determined by age of exposure
Steatosis is most characteristic of which type of hepatitis?
HCV
What would be found in a serumtest of an inactive Hepatitis carrier?
- (+) HBsAg
- (-) HBeAg
- b/c can’t transmit
- (+) anti-HBe
- Normal transaminase
What are the most common causes of Fulminant Hepatitis globally?
- HAV
- HEV
Fulminant Hepatitis
- Histo
- Symptoms
- Histo
- Loss of hepatocytes
- Collapsed reticulin framework
- Symptoms
- Jaundice
- Coagulopathy
- Hepatic encephalopathy
- Sepsis
The rosettes pictured below are characteristically associated with which form of hepatitis?
Autoimmune Hepatitis
- Should also have prominent plasma cells
The eosinophilic inclusions in hepatocytes are characteristically associated with which type of hepatitis? What are they called?
Mallory Bodies
Alcoholic Hepatitis
What comorbidities are associated with progression of Alcoholic Hepatitis to cirrhosis (or more severe forms)?
- Iron overload
- HBV infxn
- HCV infxn
What is the physiopathology associated with hepatic steatosis and the formation of vesicular inclusions?
- Hepatocytes shunt normal substrates to lipid biosynthesis
- (increased lipid)
- Impaired production of lipoproteins
- (can’t get rid of them)
- Increased peripheral fat catabolism
- Increased FAs
- Go to liver
- Increased lipid
What is the most common presentation of Hepatic steatosis?
- Hepatomegaly
- Mild elevation of
- bilirubin
- alkaline phosphatase
What are the physiological changesthat lead to Hepatic Steatosis?
- Shunting of normal stubstrates to lipid biosynthesis in hepatocytes
- Impaired assembly of lipoproteins
- Increased peripheral fat catabolism
- Releases FFA
What is the mechanism of hepatic injury in Alcoholic Hepatitis?
- Acetaldehyde disrupts cytoskeleton
- Generation of P450
- Decreased glutathione
- more susceptible to oxidative injury
- Release of bacterial endotoxins
- activates NF-kß
- Release of endothelins
- contraction of stellate cells
What is the limit of alcohol consumption for Nonalcoholic Fatty Liver Disease / Steatohepatitis?
less than 20gm/wk
What is the two hit model for NAFLD / NASH?
- Insulin resistance causes accumulation of fat in liver
- Formation of lipid peroxides and ROS
- Oxidative damage
What is the difference in Morphology between NAFLD and NASH?
- Nonalcoholic Fatty Liver Disease
- Macro / micro vesicular steatosis
- No inflammation
- NA Steatohepatitis
- Macro / micro vesicular steatosis
- Inflammation
- Mallory bodies
- Fibrosis of:
- portal tract
- central vein
- sinusoids
What disease process is pictured below?
Nonalcoholic Steatohepatitis
What disease process is pictured below?
Nonalcoholic Fatty Liver Disease
What gene is mutated in Hereditary Hemochromatosis? What is the most common mutation in the US?
- Gene
- HFE
- Regulates hepcidin => reg. iron absorption
- Mutation
- C282 more common in US (european origin)
- Poorer outcome
- H63D
- Mild accumulation
- C282 more common in US (european origin)
What disease process is pictured below?
Secondary hemochromatosis
- Iron primarily in Kupfer cells
- Accumulation not as great as in primary disease
What disease process is pictured below?
Primary Hemochromatosis
- Greater accumulation of iron
- Accumulates toward the center of hepatocytes
Where is copper normally absorbed? How is it stored? What happens to the excess?
- Absorbed in the duodenum
- Stored in ceruloplasmin
- Excess is secreted into bile
***ceruloplasmin and secretion into bile is decreased in Wilson disease
What accumulates in cells in Wilson’s disease? What stain is used to visualize this accumulation in cells?
Copper
Rhodamine Stain
What enzyme conjugates bilirubin? Where does this occur?
- Enzyme:
- UDP-glucuronosyl transferase
- adds glucuronic acid
- Location:
- Liver ER
Is unconjugated bilirubin soluble? Conjugated bilirubin?
- Unconjugated: NO
- bound to albumin before arriving to the liver
- Conjugated: Yes
- excreted in bile into the gut
What does bilirubin become once it is metabolized in the gut? What is responsible for metabolism?
- Metabolism
- Gut bacteria glucuronidases deconjugate bilirubin
- Becomes Urobilinogen
- 80% to feces
- 20% reabsorbed by bloodstream and enters urine
From what molecule is bilirubin derived originally?
Heme
What is the role of bile acids? What are they composed of?
- function
- detergents: solubilize wate-insoluble lipids
- composition
- cholesterol
- taurine or glycine
Which form of bilirubin is referred to as Delta or Indirect Bilirubin?
Unconjugated
(More abundant than conjugated)
Which form of bilirubin is referred to as Direct Bilirubin?
conjugated bilirubin
In intrahepatic and extrahepatic obstruction of bilirubin release:
- How do enzyme levels change?
- How do enzyme levels change?
- Increased Alkaline phosphatase
- greater for extrahepatic
- Increased ALT
- Increased GGT
- Increased AST
- greater for intrahepatic
- Increased Alkaline phosphatase
In intrahepatic and extrahepatic obstruction of bilirubin release:
- How is digestion affected?
- Decreased bile
- Malabsorption of fat-soluble vitamins
- Decreased Vit K:
- Increased PT and PTT
- Decreased Vit K:
- Decreased urobilinogen
- Acholic (light) stools
- Malabsorption of fat-soluble vitamins
What disease process is pictured below?
Cholestasis
Bile lake formation from cell degeneration
What disease process is pictured below?
Cholestasis
- Front: bile plugs
- Back: ductular proliferation
- tries to accomodate bile
What are the causes and symptoms of cholestasis?
- Causes:
- Intrahepatic obstruction
- Extrahepatic obst.
- Symptoms
- Jaundice
- Pruritis
- Xanthomas
- Dark urine possible
- elevated conjugated bilirubin
- water soluble
Neonatal Cholestasis
- Unique histologic features
- Symptoms
- Histo
- Lobular disarray
- focal hepatocyte apoptosis
- Rosettes
- multinuclear giant cells
- Extramedullary hematopoiesis
- Lobular disarray
- Symptoms
- Jaundice
- Dark Urine
- Light stools
- Hepatomegaly
What histologic changes are associated with primary biliary cirrhosis?
- Lymphocytic infiltrate in portal tracts
- Noncaseating granulomatous destruction of intrahepatic bile ducts
- Fibrosis
- Cirrhosis
- Increased hepatocellular cancer
What disease process is pictured below?
Primary Sclerosing Cholangitis
- Front: onion-skin around bile duct
- Back: beading sign on radiography
In secondary biliary cirrhosis, what important findings occur before cirrhosis?
- Bile stasis
- Ductular proliferation
- neutrophil infiltrate
- Portal Tract Edema
In primary biliary cirrhosis, what important findings occur before cirrhosis?
- Dense lymphocytic PT infiltrate
- Granulomatous destruction of bile ducts
In primary sclerosing cholangitis, what important findings occur before cirrhosis?
- Periductal PT onion-skin fibrosis
- Pattern of stenosis then beading of intra- and extra-hepatic ducts
What are von Meyenburg Complexes? What symptoms occur?
- Small clusters of dilated bile ducts
- detached from biliary tree
- located in portal tract
- Symptoms:
- clinically insignificant
What causes Polycystic Liver Disease? With what other disease is it associated?
- Cause
- Inherited
- AD
- Disease
- Strong association with polycystic kidney disease
Congenital Hepatic Fibrosis
- Appearance
- Cause
- Associated with what other disease?
- Appearance
- PT enlargement
- abnormal bile ducts in CT
- continuous with biliary tree
- Develops portal HTN
- Cause
- Inherited
- AR
- Associated with what other disease?
- Polycystic Kidney Disease
Caroli Syndrome
- Appearance
- Cause
- Associated with what other disease?
- What complications can occur?
- Appearance
- Dilated bile ducts
- Cause
- Inherited
- AR
- Associated with what other disease?
- Risk of cholangiocarcinoma
What complications arise from cysts in the liver?
- Intrahepatic cholelithiasis
- Cholangitis
- Hepatic abscess
- Portal HTN
Manifestations of problems in Hepatic Blood Flow
What complication can occur with acute portal vein obstruction?
Congestion of liver and bowel infarction
What is the most common intrahepatic obstruction to blood flow?
Cirrhosis
Peliosis Hepatis
- Histology
- Associated conditions
- Severe outcomes
- Histology
- Dilation of Sinusoids
- Due to apoptosis
- Associated conditions
- Cancer
- TB
- HIV
- Anabolic Steroids
- Severe outcomes
- Intra-abdominal hemorrhage
- Hepatic Failure
What symptoms are associated with Hepatic Vein Outflow Obstruction syndromes?
- Tender hepatomegaly
- Ascites
- Jaundice
What type of liver damage is caused by Right sided vs Left sided Heart Failure?
- Right sided
- Sinusoidal congestion
- Blood backs up due to lack of pumping
- Left sided
- Ischemic necrosis
- Lack of pumping causes reduced systemic blood pressure
What effect can chronic CHF have on the liver?
Centrilobular fibrosis
What potentially life-threatening pathology of the liver can occur during eclampsia?
Hepatic hematoma
Can rupture if under the Glisson capsule
Intrahepatic cholestasis of pregnancy
- Symptoms
- Complications
- Symptoms
- Jaundice
- conjugated bilirubin
- Dark urine
- Light stools
- elevated transaminases
- Jaundice
- Complications
- Gallstones
- Small risk of fetal distress
What disease process is pictured below?
Acute Fatty Liver of Pregnancy
Microsteatosis
What symptoms of acute bone marrow transplant graft vs host disease occur in the liver?
- Donor lymphocytes attack liver
- Hepatitis
What symptoms of chronic bone marrow transplant graft vs host disease occur in the liver?
Selective bile duct destruction
What symptoms occur in chronic liver allograft rejection?
Vanishing Bile Duct Syndrome
Obliterative arteritis => loss of blood flow to bile duct (w/ immune response) => disappears
Nodular Regenerative Hyperplasia of the Liver
- Definition
- Common cause of what hepatic condition?
- Definition
- cirrhosis like nodules
- no fibrosis present
- Cause
- decreased intrahepatic blood flow
- Condition
- non-cirrhotic portal HTN
Focal Nodular Hyperplasia
- Population
- Cause
- Appearance
- Population
- Women
- 20-40
- Cause
- Exogenous estrogens
- Appearance
- White, central, stellate scar
What is the most common benign liver tumor?
Cavernous Hemangioma
What genes are associated with Hepatocellular Carcinoma?
- p53
- Inactivation
- WNT/beta catenin pathway
- Activation
- IL6/JAK/STAT pathway
What is the difference in prognosis between large cell and small cell dysplastic change of the liver?
- Large cell
- Marker forincreased surveillance
- Small cell
- Directly premalignant
What are the differences between a low grade and high grade dysplastic nodules?
- Low
- No atypia
- PT present
- High
- Small cell change
- Atypia
- Few PT
- Subnodules w/i nodules
What disease process is pictured below?
Fibrolamellar variant of SCC of liver
What congenital anomaly is pictured below?
Phrygian cap
Folded fundus
What causes Acute Acalculous Cholecystitis?
Ischemia most common
Cystic artery
What causes Chronic Cholecystitis? What bugs may initiate an attack?
- Cause
- Unknown
- Important: Supersaturation of bile
- Bugs
- E. coli
- Enterococci
Rokitansky-Aschoff sinuses occur in what pathology of the gallbladder?
Chronic Cholecystitis
(due to reactie proliferation of buried crypts)
What disease process is pictured below?
Porcelain gallbladder
Dystrophic calcification
(increased risk cancer)
occurs w/ Chronic Cholecystitis
What disease process is pictured below?
Xanthogranulomatous cholecystitis
Due to Chronic Cholecystitis
What disease process is pictured below?
Hydropic Gallbladder
Due to Chronic cholecystitis
What are the clinical features of chronic Cholecystitis?
Recurrent attacks
Nausea / vomiting
***Intolerance to fatty food***
What is the most common form of Carcinoma of the Gallbladder?
Adenocarcinoma
Carcinoma of the Gallbladder is more common in which population?
- Females
- Countries
- Chili
- Bolivia
- N India
Which form of CA of the Gallbladder has the best prognosis?
Papillary
What mutation can result in Pancreas agenesis?
PDX1
(homozygous loss of function)
What is the pathology and treatment of autoimmune pancreatitis?
Lymphoplasmacytic sclerosing pancreatitis
- Path:
- IgG4 secreting plasma cells in the pancreas
- Treatment:
- responds to steroid therapy
What genes are important in the progression to Pancreatic Carcinoma?
- K-RAS
- p16
- p53
- SMAD4
