Wk5 Liver Path pt2 Flashcards by Weston Tardy

early EtOH abuse

enlarged, lipid filled liver

How does it look microscopically?

Alcoholic steatosis–fatty liver

large lipid vacuoles

**reverses with abstinence

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Alcoholic hepatitis = steatosis + ?

hepatocyte injury and/or inflammation

“steatohepatitis”

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Cytokeratin aggregates in hepatocytes:

Associated with?

Mallory bodies

Alcoholic hepatitis

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Usually seen surrounding Mallory bodies:

neutrophilic inflammation

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Alcoholic hepatitis occurrence

pre-cursor to cirrhosis

steatofibrosis

**perivenular and pericellular

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Grossly: fibrosis + nodules

cirrhosis

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Liver in early stages of alcoholic cirrhosis

enlarged

fatty

micronudular (less 3 mm)

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Liver in late stages of alcoholic cirrhosis:

shrunken

non-fatty

variable nodule size

cholestasis usually present

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5 major causes of death from alcoholic liver disease:

hepatic encephalopathy and coma
Massive GI tract hemorrhage (esophageal varicies)
infx
hepatorenal syndrome
hepatocellular carcinoma

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NAFLD?

Patient profile?

Non-alcoholic fatty liver disease

metabolic syndrome
obesity
DM2
dyslipidemia
insulin resistance

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autoimmune cholangiopathy

progressive destruction of small and medium sized INTRAhepatic bile ducts

extrahepatic ducts are spared

middle age females

Primary biliary cirrhosis

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AMA (antimitochondrial antibodies)

associated with other autoimmune disorders

Primary biliary cirrhosis

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fatigue

anicteric pruritis

xanthomas

steatorrhea

vit D malabsorption

Primary biliary cirrhosis

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Tx for PBC:

urodeoxycholic acid

liver transplant

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Dx of PBC:

liver biopsy

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Damage due to prolonged EXTRAhepatic bile duct obstruction

Secondary biliary cirrhosis

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progressive

RANDOM

autoimmune

uneven fibroinflammatory

extra/intrahepatic bile ducts

Primary sclerosing cholangitis (PSC)

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pANCA

IBD association

Primary sclerosing cholangitis

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“beaded” appearance on cholangiogram

PSC

primary sclerosing cholangitis

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disorders of excessive iron absorption resulting in accumulation of iron in tissues producing organ injury

hemochromotosis

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Inheritance pattern of primary hemochromotosis

autosomal recessive

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Liver protein decreased in hemochromotosis

hepcidin –> excessive intestinal iron absorption

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Most common genetic mutation in hereditary hemochromotosis

HFE – chromosome 6

C282Y – 80% of cases in adults

**most common in male of northern european descent

low penetrance so not all homozygotes express disease

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Causes of secondary hemochromotosis

parenteral Fe overloads (transfusions)

ineffective erythropoesis –> increased Fe absorption
-(B-thalassemis, sideroblastic anemia)

increased oral intake of Fe

Chronic EtOH liver disease

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Reread slide 42

distribution of excess Fe

Early pathological finding of primary hemochromotosis:

periPORTAL iron deposits in hepatocytes

Early pathological finding of secondary hemochromotosis (different from primary):

Fe accumulates in Kupffer cells not hepatocytes

Classic triad for hemochromotosis presentation:

1. cirrhosis 2. diabete 3. skin pigmentation "Bronze diabetes" **also may see sx in other organ systems (heart, joints, etc.)

Best screening test for hemochromotosis:

fasting transferrin saturation if greater than 45% --> serum ferritin if ferritin elevated --> HFE gene test

Reason for liver bx in hemochrmatosis:

concern for cirrhosis

Tx for hemochromatosis:

chelating agents / phlebotomy

Autosomal recessive disorder of copper metabolism

Wilson's disease

Genetic defect in Wilson's disease

ATP7B gene chromosome 13

ATP7B?

gene for liver copper transporting ATPase protein impaired secretion as ceruloplasmin and impaired secretion into bile --> toxic levels of Cu in tissues

Dx test for Wilson's

plasma ceruloplasmin level 24 hr urine copper excretion

When to consider Wilson's in your Ddx:

liver disease in anyone under 30 yo

Presenting sx of Wilson's disease:

neurpsychiatric KAYSER-FLEISCHER rings -copper deposits at limbus of cornea

What is alpha-1-antitrypsin?

a protease inhibitor (primarily neutrophils elastase) **without it, tissues get degraded unchecked

A1AT gene location

ch 14

Pathogenesis of liver disease in A1AT deficiency:

intracellular misfolding --> accumulation --> apoptosis of hepatocytes

Most commonly dx hepatic disorder in infants and childrren:

A1AT deficiency

PAS stain

A1AT deficiency

Always include what in Ddx of any form of liver disease?

Toxins

CPC -- chronic passive congestion

slide 73

nutmeg liver

centrilobular hemorrhagic necrosis

thrombosis of two or more hepatic vein branches classic triad: hepatomegaly ascites abd pain

Budd-Chiari syndrome

most common causes of Budd-Chiari syn:

hyercoaguable states

Dx for Budd-Chiari

Doppler US MRI/CT looking for clots

obstructive, NONthrombotic lesions of small (central) hepatic veins radiation/hepatotoxin exposure BM tx

Sinusoidal obstruction syndrome

sudden weight gain hepatomegaly increased serum bilirubin

Sinusoidal obstruction syndrome (ACUTE)

prolonged conjugated hyperbilirubinemia in the neonate

neonatal cholestasis

Two causes of neonatal cholestasis

1. biliary atresia (extrahepatic) | 2. neonatal hepatitis

Causes of granulomatous hepatitis:

idiopathic 50% sarcoid 22% drugs 6% TB 3% other 19%

HELLP syndrome?

pregnancy Hemolysis Elevated Liver enzymes Low Platelets

microvesicular steatosis in pregnancy

Acute fatty-liver of pregnancy

mild increase in conjugated bilirubin in pregnancy

Intrahepatic cholestasis of pregnancy

portal inflammation lymphocytic cholangitis "vanishing bile ducts"

chronic GVHD from BM tx

Tests that reflect hepatocellular damage NOT hepatic function

AST/ALT

Reflect injury to bile ducts/canalicular membranes markers of cholestasis

Alk Phos GGT

Markers of hepatic function

Albumin PT clotting factors

Most specific test for liver damage

ALT **AST is found in other tissues

Why is AST elevated preferentially in EtOH disease?

found in mitochondria EtOH is mitochondrial toxin

Increased Alk Phos usually due to? How to help differentiate?

bone or liver GGT from biliary epithelium

Two purposes of Liver biopsy:

1. determine possible cause of disease | 2. determine extent of liver damage

Liver bx: ground glass hepatocytes

chronic viral HBV

Liver bx: plasma cells

autoimmune hepatitis PBC (primary biliary cirrhosis)

Liver bx: lymphocytic/granulomatous cholangitis

PBC (primary biliary cirrhosis)

Liver Bx: Fibrous obliterative cholangitis

PSC (primary sclerosing cholangitis)

Liver Bx: periportal hepatitis mild steatosis

chronic viral HCV

Liver bx: Globular hepatocyte inclusions

A1AT deficiency