Liver Disease Flashcards
Clinical indications of cytoplasmic accumulation of material
- accumulation ==> cell damage and death
- Fat – Steatosis
- Bile – Cholestasis
- Iron – Hemosiderosis
- Copper – Wilson’s Disease/cholestasis
- Viral particles – Viral hepatitis
Pathologic findings in hepatocyte death
- balooning degeneration =
- hepatocyte swelling
- clumping of organelles and keratin filaments
- clearing of cytoplasm
- necrosis & apoptosis
- decreaseing cells size
- increased eosinophilia @ cytoplasm
- small dark nucleus
Ballooning degeneration indicates…
steatohepatitis
necrosis/apoptosis @ confluent zone 3 indicates…
- wide spread ischemia
acidophils @ interface zone indicate…
- acidophils = single necrotic/apoptotic cell w/in liver parenchyma
- DDx:
- autoimmune hepatitis
- viral hepatitis
Neutrophils indicate…
steatohepatitis
Eosinophils indicate…
drug reaction
Plasma cells indicate…
autoimmune hepatitis
Portal based inflammation indicates…
biliary disease
Interface inflammation indicates…
- autoimmune hepatitis
- viral hepatitis
Zone 3 inflammation indicates…
- autoimmune hepatitis
- acute cellular rejection (transplant pts)
Pathologic findings of cholestasis
- cholestasis = bile accumulation @ hepatic parenchyma
- obstructive vs. non-obstructive causes
- ==> ballooning degeneration
Pathologic findings of bile ductular reaction
- obstructive outflow ==> bile build up @ canilliculi of zone 1 hepatocytes
- hepatocytes ==metaplasia==> ~bile duct cells
- ==> bile duct-like structures @ interface zone + PMNs + edema
Progressive fibrosis ==>
cirrhosis
Clinicopathologic patterns in Acute Hepatitis
- Clinical
- new onset sx lasting < 6 mo.
- labs = evelated AST & ALT
- Causes
- acute viral
- autoimmune
- adverse drug rxn
- indiopathic
- Pathology
- marked lobular disarray
- inflammation
- numerous single necrotic hepatocytes
- no significant fibrosis
Clinicopathologic patterns in Chronic Hepatitis
- Clinical
- hepatic injury/inflammation > 6 mo.
- Causes
- viral, autoimmune, drug rxn, idiopathic
- Pathologic
- less lobular disarray and inflammation
- rare single necrotic hepatocytes
- slow progression of fibrosis
Scales used to assess severity of chronic hepatitis
- GRADE = assessment of necroinflammatory activity
- = ~current liver damage
- STAGE = degree of fibrosis
- = ~cumulative injury over time
- both scales use 0-4 scale
Cirrhosis characteristics
- end stage of chronic liver disease
- pathologic findings
- fibrous septa
- distortion of architecture
- regeneration nodules
- clinical/laboratory findings
- portal HTN
- poor synthetic fxn
- ==> increased risk for hepatocellular carcinoma
Characteristics of cholestatic liver disease
- acute or chronic jaundice
- laboratory findings
- elevated alkaline phosphatase
- elevated GGT (gamma glutamyl transpeptidase)
- elevated bilirubin
- obstructive vs. nonobstructive causes
- pathologic
- interface ductular rxn + edema + PMNs
Viral Hepatitis: types of virus
- Hep A = ssRNA
- Hep B = dsDNA
- Hep C = ssRNA
- Hep D = ssRNA
- Hep E = ssRNA
Viral Hepatitis: Routes of transmission
- Hep A = fecal-oral
- Hep B
- parenteral
- sexual contact
- perinatal
- Hep C
- parenteral
- IV drugs, intranasal cocaine = risks
- parenteral
- Hep D = parenteral
- Hep E = fecal-oral
Viral Hepatitis: risk for chronicity
- Hep A = never
- Hep B = 10%
- Hep C = 80%
- Hep D = rare
- Hep E = never
Hep A: Serology/Dx
- detected by serum IgM (and sometimes IgG) specific antibodies
Hep B: Serology/Dx
- HBsAg (antigen)
- antibody (IgM or IgG) HBcAg
- IgM = acute/initial infection
- IgG = ~chronic/indicates past infection
Hep C: Serology/Dx
- PCR for HCV RNA
- ELISA for antibody to HCV
HCV: presentation/histology
- rarely presents as acute hepatitis
- histo
- interface and lobular necroinflammatory activity
- progressive fibrosis
- nodular lymphocytic aggregates @ portal areas
HBV: presentation/histology
- histology
- ground glass hepatocytes = viral particles @ cytplasm
- sanded nuclei = viral particles @ nucleus
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Non-hepatotropic viruses that infect the liver
- HSV
- CMV
- adenovirus
Presentation of autoimmune hepatitis
- lab tests
- high AST, ALT
- normal ALP
- positive autoantibody (ANA, ASMA)
- histology
- interface and centrolobular necrainflammation
- hepatocyte necrosis
- prominent plasma cells
Clinical Presentation of Primary biliary cirrhosis (PBC) vs. Primary Sclerosing Cholangitis (PSC)
- PBC = autoimmune destruction of intrahepatic bile ducts
- insidious
- pruritis
- jaundice (later)
- females
- liver fxn = high ALP, GGT, & bilirubin
- positive AMA; elevated IgM
- PSC = idiopathic ==> inflammation and fibrosis of (mostly) extrahepatic bile ducts
- liver fxn = high ALP, GGT, bilirubin
- no other signs/symptoms
- progression ==> fatigue, pruritis, jaundice
- males
- strong association w/ulcerative colitis
Pathologic Presentation of Primary biliary cirrhosis (PBC) vs. Primary Sclerosing Cholangitis (PSC)
- PBC
- plasma cell rich inflammation @ portal areas
- lymphocytic cholangitis
- bile duct destruction
- ==> duct loss (ductopenia)
- PSC
- beading of extra- (and intra-) hepatic bile ducts
- lymphocytic periductular inflammation
- progressive fibrosis ==> onion skin fibrosis
Characteristics of drug-induced liver injury
- varied presentations
- varied histology
- necrosis, cholestatis, acute hepatitis, etc.
- most common cause = acetominophen
Histologic findings of steatohepatitis
- non-alcoholic steatohepatitis (NASH) vs. alcoholic steatohepatitis
- triad =
- steatosis
- lobular inflammation
- ballooning degeneration
- alcoholic SH
- mallory hyaline
- prominent PMNs
- chronic changes
- chicken-wire fibrosis (=sinusoidal pattern)
- secondary micronodular fibrosis
Clinical presentation of alcoholic steatohepatitis
- Hx = alcohol
- Labs
- AST: ALT = 2(+) : 1
- normal ALP
- high GGT
Presentation of Hemochromatosis
- genetic disorder (Auto Rec.)
- males > females
- pathophsyiology = abnormal regulation of iron absorption ==> excess/deposition of iron
- clinical
- liver disease
- diabetes
- heart failure
- histology
- iron deposition @ hepatocytes
- initially @ periportal region
- ==> hepatic injury & fibrosis
- iron deposition @ hepatocytes
Presentation of Wilson’s disease
- genetic (auto rec) dz of copper overload
- clinical
- neuro sx
- Kayser-Fleischer rings on opthalm exam
- histology
- copper accumulation @ hepatocytes
- steatosis or acute/chronic hepatits-like changes possible
Presentation of Alpha-1-Antitrypsin
- genetic (auto rec) of decreased production of protease inhibitor (that limits tissue damage)
- clinical
- mostly ==> emphysema
- liver disease (10%)
- histology
- intracytoplasmic acculumulation of PAS positive hyaline globules
- progressive fibrosis
Presentation/characteristics of hepatocellular carcinoma
- most common primary malignant tumor of liver
- exclusively in pts w/ chronic liver disease and cirrhotic liver
- prognosis
- size
- macroscopic & microscopic vascular invasion
- focality
- invasion
Common benign liver tumors + characteristics
- hemangioma
- most common
- vascular spaces
- ==> vague GI sx
- well-circumscribed
- focal nodular hyperplasia (FH)
- hyperplastic parenchyma due to vascular anomaly
- histo = central stellate scar, ductular rxn
- hepatocellular adenoma
- proliferation of benign hepatocytes
- assoc. w/OCPs
- risk of rupture
- well-circumscribed
Characteristics of hepatocellular carcinoma
- Hepatocellular carcinoma (HCC)
- patients have cirrhotic/chronic liver dz.
- Distinct mass in a cirrhotic liver
- May have green-yellow color (bile)
- Thickened hepatic plates
- Endothelialization of sinusoids
- No true portal areas
Characteristics of cholangiocarcinoma
- May be intra- or extrahepatic
- PSC is a major risk factor
- Usually presents at an advance stage
- Densely fibrotic mass in the hilar region with infiltrative edges
- Tan-white in color
- Invasive gland forming tumor with abundant desmoplastic response
