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GI II Block 2 > Liver Pathology > Flashcards

Liver Pathology Flashcards

1
Q

Reversible Changes to Hepatocytes (2)

A

Steatosis: accumulation of fat

Cholestasis: accumulation of bile

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2
Q

Irreversible Damage to Hepatocytes Descriptions
Necrosis: Process (2) and Types (2)
Apoptosis: Process (3) and Morphology

A

Necrosis:
Response to oxidative stress, death due to ischemia
Cells die via lysis due to swelling from osmosis disruption
Confluent happens around Central V
Bridging connects 2 or more lobules

Apoptosis:
Pyknosis (shrinking), Karyorrhexis (fragmentation) and Apoptotic body formation
Acidophil bodies called Councilman bodies

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3
Q

Liver Scar Formation

Principal Cell Description and Pathogenesis (3)

A

Myofibroblastic hepatic stellate cells

Stellate cells release PDGFR-beta
Kupffer cells release TGF-beta, MMPR2, TIMP1/2
Fibrous septa formed where parenchyma is lost

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4
Q 
Tests for Hepatocytes
Integrity Tests (3) and Synthetic Functioning Tests (3)
A

ALT
AST
LDH (Lactate dehydrogenase)

Serum albumin
Coagulation factors
Serum ammonia

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5
Q 
Tests for Biliary System
Excretory Function (3) and Canaliculi Damage (2)
A

Serum bilirubin
Urine bilirubin
Serum bile acids

Serum ALP
Serum GGT

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6
Q

Acute Liver Failure

Timeline, Causes (8), Clinical Features (6), Labs (3)

A

Failure happens within 26 weeks of initial injury

Massive hepatic necrosis from:
Acetaminophen/Hep A/Autoimmune Hepatitis
Hep B
Hep C
Hep D
Hep E/Esoteric (WIlson's, Budd Chiari)
N/V and jaundice followed by:
Encephalopathy (Asterixis)**
Coagulopathy**
Portal HTN
Hepatorenal Syndrome

Elevated conjugated bilirubin
Elevated ALT/AST
Elevated IgM

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7
Q

Chronic Liver Failure

Causes (4), Symptoms/Signs (7) and Association

A

Alcoholic liver disease
Hep B
Hep C
Nonalcoholic liver disease

Spider Telangiectasias
Palmar erythema
Hypogonadism
Gynecomastia
Pruritis
Dupuytren's Contracture
Asterixis and Coagulopathies

Often associated with Cirrhosis

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8
Q

Liver Cirrhosis

Description, Child Pugh Classifications (3), Sequelae (6)

A

Diffuse transformation of liver into regenerative parenchymal nodules surrounded by fibrous bands

Class A: Well compensated
Class B: Partially compensated, with varices
Class C: Decompensated

Chronic liver failure
Intrahepatic Portal HTN (most common cause)
Ascites
Splenomegaly
Esophageal Varices
Encephalopathy
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9
Q 
Hep A Virus
Clinical Features (4), Transmission, Diagnosis (2)
A

Benign process that doesn’t produce chronic hepatitis
Smoking aversion
Elevated ALT/AST
Elevated Bilirubin/ALP (cholestasis)

Fecal-oral transmission

anti-HAV IgM if active infection
anti-HAV IgG shows immunity

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10
Q 
Hep B Virus
Clinical Features (3) Disease Associations (2) Transmission (3), Diagnosis (5), Morphology
A

Smoking Aversion
Elevated ALT/AST
Can progress to chronic

Polyarteritis nodosa
Risk of Hepatocellular carcinoma if chronic

Parenteral, sexual or perinatal transmission

HBsAg seen in infected people
HBsAb seen in immunized or prior infected
HBcAb IgM if Acute infection
HBcAb IgG if Chronic infection
HBeAg shows infectivity (actively replicating)

Ground glass hepatocytes with HBsAg
(diagnostic for chronic HBV)

*HBcAb IgM is the only (+) lab finding during the window period

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11
Q 
Hep C Virus
Clinical Features (5) Disease Associations (3) Transmission, Diagnosis (2), Morphology (2)
A

Generally asymptomatic but persistent infection
Fluctuating levels of AST/ALT
Decreased serum cholesterol
Mixed Cryoglobulinemia
Most progress to chronic and show cirrhosis

Metabolic syndrome
Coinfection with HIV
Risk of Hepatocellular carcinoma

Blood transmission (IVDU, Intranasal DU, Fighters)

HCV RNA PCR during active
anti-HCV Ab if immune

Lymphoid aggregates or lymphoid follicles
Scattered steatosis

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12
Q 
Hepatitis D Virus
Clinical Features (4), Transmission, Diagnosis (2)
A

Seen either as a coinfection or superinfection of Hep B
Superinfections more likely to progress to chronic
Higher rate of acute liver failure if IVDU
Hep B vaccine also prevents Hep D

Parenteral transmission

Serum HDV IgM/IgG**
Serum HDV RNA

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13
Q 
Hepatitis E Virus
Clinical Features (3), Transmission, Diagnosis (2)
A

Seen in immunocompromised patients
Only progresses to chronic if treated with Tacrolimus
Causes fulminant hepatitis in pregnant women

Fecal-oral transmission (via pigs)

anti-HEV IgG/IgM
PCR for HEV RNA

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14
Q

Autoimmune Hepatitis Type 1 vs Type 2

Population and Antibody

A

Type 1
Adults
anti-Smooth Muscle Abs

Type 2
Kids and Teenagers
anti-LKM1 Abs

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15
Q

Autoimmune Hepatitis

Morphology (3), Clinical Features (4) and Treatment

A

Mononuclear infiltrate of plasma cells
Hepatocyte rosettes in inflammatory regions
Eventual cirrhosis with little inflammatory activity

HLA DRB1 association
Female predominance
Acute fulminant hepatitis
Hepatic encephalopathy

Glucocorticoids

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16
Q

Acetaminophen-Induced Hepatitis

Pathogenesis (2) Morphology and Clinical Features (2)

A

**Most common heptotoxin in acute liver failure
Toxic metabolite from CYTP450 in Zone 3 acinar cells

Causes massive hepatocellular necrosis

Rumack Matthew Nomogram for severity of toxicity
N-acetylcysteine used as antidote

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17
Q

Toxin-Induced Hepatitis Morphology

Anabolic Steroids and Aspirin

A

Steroids:
Bland hepatocellular cholestasis without inflammation

Aspirin:
Microvascular steatosis (diffuse small droplet fat)
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18
Q

Agents that Cause Hepatic Neoplasia

Adenoma (2), Carcinoma (2), Cholangiocarcinoma (1) and Angiosarcoma (3)

A

Hepatocellular Adenoma:
Oral contraceptives, Anabolic steroids

Hepatocellular carcinoma:
Alcohol, Thorotrast

Cholangiocarcinoma:
Thorotrast

Angiosarcoma:
Thorotrast, Vinyl chloride, Arsenic

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19
Q

Steatosis

Pathogenesis (3), Morphology and Clinical Features (3)

A

Upregulation of lipid generation, dysfunction of lipoprotein synthesis and peripheral fat catabolism

Microvesicular lipid droplets within hepatocytes

Hepatomegaly
Mildly elevated ALP and Bilirubin

20
Q

Steatohepatitis

Pathogenesis (3), Morphology (3) and Clinical Features (4)

A

Acetaldehyde induces lipid peroxidation and protein adduct formation
Induces CYTP450 which creates ROS
Inhibits methionine metabolism which decreases glutathione that is ROS protective

Hepatocyte swelling and necrosis
Mallory-Denk Bodies (damaged intermediate filaments)
Cytokeratin within Hepatocytes

Tender hepatomegaly
Hyperbilirubinemia
AST:ALT is 2:1
Elevated ALP

21
Q

Alcoholic Liver Disease (Steatofibrosis)

Pathogenesis (4) Morphology (2) and Clinical Features (2)

A

Chronic disorder of steatosis, hepatitis, progressive fibrosis and deranged perfusion

Chicken wire fence pattern of scarring
Laennec cirrhosis signals end stage ALD

Hypoproteinemia
Coagulation abnormalities

22
Q

Metabolic Syndrome Criteria (8)

A 
One of:
Diabetes Mellitus or
Impaired glucose tolerance or
Impaired fasting glucose or
Insulin resistance
And two of:
BP > 140/90
Dyslipidemia
Central obesity
Microalbuminuria
23
Q

Nonalcoholic Fatty Liver Disease

Pathogenesis (3), Risk Factors (4) Morphology (4) and Clinical Features (3)

A

Insulin resistance leading to hepatic steatosis
Hepatocellular oxidative injury leading to necrosis and inflammation

Diabetes
Obesity
Hypertriglyceridemia
Hispanic ethnicity

Pathologic steatosis
Mononuclear cell infiltrates
Portal fibrosis
Some mallory denk bodies

RUQ pain
Mildly elevated AST/ALT
Death via cardiovascular event

24
Q

Hemochromatosis

Pathogenesis (3), Morphology (3), Clinical Features (5), Treatment (2)

A

HFE gene mutation alters hepcidin functioning
Increased intestinal iron absorption
Iron deposition causes lipid peroxidation and DNA damage

Shrunken liver with micronodular cirrhosis
Golden-yellow hemosiderin granules on liver
Pigmented pancreas/heart

Cirrhosis with Hepatomegaly
Gray-slate skin color
Diabetes
Cardiac dysfunction
Increased risk of hepatocellular carcinoma

Weekly phlebotomy
Deferoxamine

25
Q

Wilson Disease

Pathogenesis (3), Morphology (3) Clinical Features (5) and Treatment

A

Autosomal recessive ATP7B mutation
Decreased copper secretion via cerruloplasmin
Toxic liver damage via ROS

Mallory-Denk bodies
Basal ganglia atrophy/cavitation
Kayser-Fleischer rings

Elevated urine copper
Decreased plasma cerruloplasmin
Movement disorders/Rigid dystonia
Psychiatric symptoms
Hemolytic anemia causing elevated bilirubin

Penicillamine

26
Q

alpha-1 Antitrypsin Deficiency

Pathogenesis (3), Morphology (2) and Clinical Features (3)

A

Autosomal recessive PiMM/PiZZ defect
Causes AAT to be trapped in endoplasmic reticulum
ER stress leads to hepatocyte apoptosis

PAS (+) periportal hepatocytes with globular cytoplasmic inclusions

Panacinar emphysema
Cirrhosis/Cholestasis
Neonatal hepatitis

27
Q

Unconjugated Hyperbilirubinemia Etiologies (6)

A 
Hemolytic Anemia
Ineffective erythropoiesis (Pernicious anemia)
Crigler-Najjar Syndrome
Gilbert Syndrome
Hepatitis
Physiologic Jaundice of the Newborn
28
Q

Conjugated Hyperbilirubinemia Etiologies (4)

A

Dubin-Johnson Syndrome
Rotor Syndrome
Bile duct obstruction
Autoimmune cholangiopathy

29
Q

Crigler-Najjar Syndrome

Types (2) with Defect and Clinical Course

A

Type 1
Autosomal Recessive absence of UGT1A1
Neonatal fatality

Type 2
Autosomal Dominant decrease in UGT1A1
Mild clinical course, occasional kernicterus

30
Q

Dubin-Johnson Syndrome

Pathogenesis (2) and Morphology

A

Autosomal recessive MRP2 gene defect
Causes impaired bilirubin glucuronides secretion

Pigmented cytoplasmic globules makes liver black

31
Q

Cholestasis

Definition, Symptoms (4) and Labs (3)

A

Impaired bile formation/flow from obstruction or defective secretion causing bile pigment to accumulate

Jaundice
Pruritis
Xanthomas
Malabsorption and Vit ADEK deficiency

Elevated gamma-glutamyl transferase (GGT)**
Elevated ALP
Normal AST/ALT

32
Q

Primary Biliary Cirrhosis (AI Cholangiopathy)

Demographic, Disease Associations (2), Serology (2), Morphology (2), Clinical Features (2)

A

Middle aged women

Sjogren’s syndrome
Hashimoto Thyroiditis

anti-Mitochondrial Ab Positive
ANA Positive

Florid duct lesions with loss of small ducts only
Mallory-Denk bodies

Isolated increased ALP
Hypercholesterolemia causing Xanthelasmas

33
Q

Primary Sclerosing Cholangitis (AI Cholangiopathy)

Demographic, Disease Association, Complication, Serology, Morphology (2), Presentation (4)

A

Men in their 30s

Ulcerative colitis

Cholangiocarcinoma

May be ANCA positive

Strictures and beading of large bile ducts
(Beads on a string on ERCP)
Onion skin fibrosis of smaller ducts (biopsy)

Jaundice
Pruritis
Elevated ALP and Conjugated Bilirubin

34
Q

Biliary Tree Cystic Abnormality Descriptions

Choledochal (2) and Fibropolycystic (4)

A

Choledochal cysts:
Congenital dilations of common bile duct
Present in kids with jaundice and biliary colic

Fibropolycystic Disease:
Congenital malformations of biliary tree
Von Meyenburg Complexes: hamartomatous cysts
Caroli Disease: simple cysts
Caroli Syndrome: Congenital Hepatic Fibrosis

35
Q

Intrahepatic Flow Disorders

Etiologies (2) and Clinical Manifestations (4)

A

Cirrhosis,
Sinusoidal occlusion

Ascites,
Varices,
Hepatomegaly,
Increased AST/ALT

36
Q

Preeclampsia and Eclampsia

Clinical Features of Each (4/2) and Subclinical Features (3)

A 
Preeclampsia:
Maternal HTN
Proteinuria
Peripheral edema
Coagulation abnormalities

Eclampsia:
Hyperrelfexia (clonus)
Convulsions

HELLP Syndrome:
Hemolysis
Elevated liver enzymes
Low platelet count

37
Q 
Acute Fatty Liver Disease of Pregnancy
Clinical Features (2) Morphology and Treatment
A

Presents in 3rd trimester with symptoms of liver failure
Elevated AST/ALT

Characteristic diffuse microvesicular steatosis of hepatocytes

Treat with pregnancy termination

38
Q

Focal Nodular Hyperplasia

Etiology, Prognosis, Morphology (2)

A

Spontaneous lesion in otherwise normal liver

Benign

Single well demarcated lesion
Central stellate scar

39
Q

Nodular Regenerative Hyperplasia

Associations (2), Prognosis (2) and Morphology (2)

A

HIV and Autoimmune Disease

Benign but can lead to Portal HTN

Plump hepatocytes surrounded by atrophic hepatocytes
Multiple nodules (like cirrhosis without fibrous septa)
40
Q

Hepatocellular Adenomas
Clinical Features (2)
Types with Risk for Malignancy (3)

A

Incidentally discovered, present with some pain
Associated with anabolic steroid and oral contraceptives

HNF1-alpha Activated:
No risk, completely benign

Inflammatory Adenomas:
Small but definite risk of malignancy

Beta-catenin Activated:
Very high risk for malignancy

41
Q

Hepatoblastoma

Genetics (2), Morphology Types (2) and Clinical Features (3)

A

APC gene mutation
WNT pathway activation

Epithelial Type: Polygonal fetal or embryonal cells
Mixed Type: Mesenchymal foci of osteoid, cartilage and striated muscle

Most common liver tumor in kids
Associated with FAP and Beckwith-Wiedemann Syndrome

42
Q

Hepatocellular Carcinoma

Genetics (2), Clinical Features (3), Risk Factors (4)

A 
Beta-catenin activation
p53 activation (by aflatoxin)

Hepatomegaly
Elevated alpha-fetoprotein (AFP)
Death via cachexia, bleeding, liver failure

Aflatoxin (Aspergillus)
HBV in Asia
HCV in US
Any condition causing cirrhosis

43
Q 
Hepatocellular Carcinoma Precursor Characteristics
High Grade (3), Low Grade (2), Large Change (2), Small Change (2)
A

High Grade Dysplasia:
Cellular Atypia
Definitely Premalignant
Viral hepatitis and Alcoholic liver disease pathway

Low Grade Dysplasia:
Clonal but lacking sign of atypia
Maybe Premalignant

Large Cell Change:
Large scattered hepatocytes with normal cytoplasm ratio
Premalignant in HBV

Small Cell Change:
High cytoplasm ratio with nuclear hyperchromasia
Definitely Premalignant

44
Q

Hepatic Lymphoma

Population, Associations (4) and Cancer Course (2)

A

Middle aged men

HBV
HCV
HIV
Primary Biliary Cirrhosis

Diffuse Large B cell Lymphomas followed by MALTomas

45
Q

Cholangiocarcinoma
Morphology (2), Risk Factors (3), Precursor Lesion
Clinical Features of Intrahepatic (2) and Extrahepatic (3)

A

Adenocarcinomas that incite desmoplasia
Perihilar (Klatskin) tumors are hepatic duct junction

Liver flukes in Southeast Asia
Primary sclerosing cholangitis
Cholelithiasis

Biliary Intraepithelial Neoplasia

Intrahepatic:
Obstruction to bile flow
Symtpomatic liver mass

Extrahepatic:
RUQ pain
Biliary obstruction
Cholangitis

46
Q

Sites of Tumors that Metastasize to Liver (5)

A 
Colon*  
Breast*
Lung*
Pancreas*
Melanoma

Secondary liver tumors far more common than primary
*=most common sites

GI II Block 2 (4 decks)

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