Drug Induced Liver Disease, Hepatobiliary Neoplasia, GI/Liver Miscellaneous Flashcards
(89 cards)
1
Q
DILD
A
Drug Induced Liver Disease
2
Q
DILD Important?
A
- 10% of acute hepatitis admissions
- 6% of drug side effects
- 15-20% of fulminant & subfulminant hepatitis
- 20% of patients with jaundice & DILD will progress to fulminant failure
3
Q
When does DILD happen?
A
- within 5-90 days
- after prolonged use
- triad of rash, eosinophilia & fever rare
4
Q
Clinical Setting of DILD?
A
-asymptomatic
-fatigue
-abnormal liver enzymes
-jaundice
-hepatic failure
(repeated exposure not required, even small doses)
5
Q
Intrinsic Hepatotoxin
A
- predictable injury
- dose dependent
- easily reproduced in animals
- carbon tetrachloride
6
Q
Idiosyncratic Hepatotoxin
A
- unpredictable
- not in animals
- not dose dependent
- most medications
7
Q
Hepatocellular Injury
A
acute hepatitis fulminant hepatitis chronic hepatitis steatohepatitis cirrhosis
8
Q
Cholestatic Injury
A
Cholestasis-impariment of bile flow bland cholestasis acute & chronic cholangitis sclerosing cholangitis vanishing bile duct syndrome
9
Q
Oral Contraceptives
A
-Idiosyncratic
-bland cholestasis
-estrogen decreases membrane fluidity
-dec. Na+, K+ ATPase activity & bile salt transport
vascular complications
hepatic vein thrombosis (Budd-Chiari)
Peliosis hepatis
Focal nodular hyperplasia
Hepatic Adenomas
Hepatocellualr carcinoma: rare with current doses
10
Q
Occupational Chemicals
A
- obtain exposure history
- inhaled & contact
11
Q
Angiosarcoma
A
25 patients per year
-hepatomegaly, inc. alkaline phosphatase
>70% pathogenesis is unknown
(polyvinyl chloride exposure?)
12
Q
Acetaminophen in US
A
- 85% of OTC poisonings
- with ethanol, dec. glutathione, inc. P450 induction, inc. toxic metabolites, 2.5-4g may be hepatotoxic in alcoholics (unsafe at low doses with alcoholics)
- well tolerated in patients with non-alcoholic liver disease
- patients w/cirrhosis from other causes often have decreased P450 activity & normal glutathione level
13
Q
Acetaminophen/Alcohol/Hospital
A
- discontinue ethanol
- hold acetaminophen
- N-acetylcysteine give 140mg/kg then 70mg/kg q 4 hrs x 17 doses
14
Q
N-Acetylcysteine
A
- Therapeutic even with late presentation
- Dosing within 10-36hrs lowers mortality from 58 to 37% (acetaminophen)
- helpful in acute liver failure from non-acetaminophen etiologies `
15
Q
Paracetamol
A
- restricted to 16 500mg tablets per patient in stores (32 tablets in UK)
- 72% drop in hospitalizations
- 74% dec. in deaths/transplantation
16
Q
Hepatocellular Carcinoma
A
- most common primary cancer of liver (75%)
- 5th most common neoplasm world wide
- common in areas with viral hep B is endemic
- 24,000/year in US due to inc. hep C
- bad prognosis, 5 year survival is less than 5%
- malignant epithelia neoplasm of liver composed of cells resembling hepatocytes
17
Q
Hepatocellular Carcinoma Epidemology
A
- 3x more common in males
- 3x more common in Asian Americans & 1.5x more common in blacks
- 50-60 years old
- usually in patients with chronic liver disease (80% chronic viral hepatitis)
18
Q
Common Sites for Liver Mets?
A
-colon, lung, breast, pancreas & stomach
19
Q
Most common neoplasms in liver?
A
metastatic tumors
20
Q
Presentation of Hepatocellular Carcinoma
A
- decompensation of chronic liver disease
- jaundice, encephalopathy, ascites, bleeding
- others: mild-moderate upper abdominal pain, weight loss, diarrhea, bone pain, dyspnea
21
Q
Classifications of Hepatocellular Carcinoma
A
- based on microscopic/macroscopic appearance (doesn’t predict behavior)
- Predictors: size, differentiation, invasion & metastasis, presence or absence of cirrhosis
22
Q
Gross Pathology of Hepatocellular Carcinoma
A
highly variable
- yellow (from bile production), invasive
- multiple nodules (tumor originating in multiple sites), cholestasis (tumor obstruct ducts)
- 20% arise without cirrhosis
- highly vascularized (biopsy cause hemorrhage)
23
Q
Hepatocellular Carcinoma: Histologic patterns
A
- Micro-Trabecular
- MacroTrabecular
- Acinar
- Solid
24
Q
Hepatocellular Carcinoma Pain
A
from stretching of capsule
25
Hepatocellular Carcinoma Microscopy: 1
-well differentiated with trabeculae of cells resembling normal hepatocytes
26
Hepatocellular Carcinoma Microscopy: 2
-moderately differentiated hepatocellular carcinoma with bigger cells less resembling normal hepatocytes and very abnormal architecture
27
Hepatocellular Carcinoma Microscopy: 3
-moderately differentiated (still) but very large neoplastic cells and even more disturbed architecture
28
Hepatocellular Carcinoma Microscopy: 4
-poorly differentiated hepatocellular carcinoma with pleomorphic dyscohesive neoplastic cells invading non-neoplastic liver from below
29
Hepatocellular Carcinoma Microscopy: 5
-anaplastic hepatocellular carcinoma with markedly pleomorphic cells with huge nuclei, some multinucleated, some bizarre
30
Alpha-Fetoprotein
-major fetal serum globulin
>20mcg/L in 60% of patients with hepatocellular carcinoma (also elevated with acute/chronic liver injury, gonadal tumors, pregnancy, gastric cancers)
-specificity 91%
>200mcg/L specificity 99% (sen. 22%)
31
Treatment of Hepatocellular Carcinoma
- surgical resection
- majority of patients not eligible due to tumor extent or underlying liver dysfunction
- various other treatments including injecting poison into the tumor (ethanol)
32
Hepatic Adenomas (Hepatomas)
- more common in patients who have taken or are taking anabolic steroids, androgenic steroids of estrogenic steroids
- commonly compress surrounding normal liver, which may cause some necrosis of it, with repair response forming a capsule
33
Hemangioma
- most common benign tumor in liver
- usually <2cm, commonly sucapsular
- composed of blood-filled vascular spaces
34
Hepatoblastoma
- rare malignant epithelial neoplasms in children
| - malignant tumors in children have more primitive appearance, similar to embyronal appearance of site (blastoma)
35
Cholangiocarcinoma
- malignant epithelial neoplasm with biliary differentiation, arising from cholangiocytes
- uncommon (7,000/year in US) (3,000 extrahepatic)
- males, 50-70
- associated with primary sclerosing cholangitis (PSC)
- extrahepatic 2/3 at bifurcation of common hepatic bile duct (Klatskin tumors)
- KRAS mutation in 50% of intra and 15% of extrahepatic, p53 mutation in 33%
36
Cholangiocarcinoma Appearance/Spread
- tan-white & firm b/c they have a desmoplastic reaction and they don't make bile
- more tendency to spread via lymphatics
- less tendency to spread via blood vessels than hepatocellular carcinoma
- embedded in dense fibrous matrix, abnormal tubular structures
37
Symptoms of Extrahepatic Cholangiocarcinoma
-pruritus (66%), RUQ abdominal pain (constant dull ache 50%), weight loss 50%, fever 20%, clay-colored stools and dark urine
38
Signs of Extrahepatic Cholangiocarcinoma
-jaundice (90%), hepatomegaly (40%), RUQ mass (10%
39
Labs of Extrahepatic Cholangiocarcinoma
high bilirubin (>10)
high alkaline phosphatase (2-10x normal)
initially normal ALT & AST
40
Symptoms of Intrahepatic Cholangiocarcinoma
dull RUQ pain & weightloss
41
Signs of Intrahepatic Cholangiocarcinoma
only those of underlying liver disease
42
Labs of Intrahepatic Cholangiocarcinoma
normal or slightly elevated bilirubin
| elevated alkaline phosphatase
43
Cholangiocarcinoma Diagnosis
biopsy (cytology)
44
Cholangiocarcinoma Treatment
surgical resection (poor results)
45
Cholangiocarcinoma Prognosis
bad, 5 year survival 5-10%
46
Gallbladder Carcinoma
```
-7,000per year in US
females, hispanics & Native Americans
exophytic or infiltrating patterns of growth
microscopic (usually glandular)
-70 year old
```
47
Symptoms of Gallbladder Carcinoma
-abdominal pain, jaundice anorexia, nausea, vomiting, malaise, weight loss
SIGN: RUQ mass
48
Diagnosis/Treatment of Gallbladder Carcinoma
-biopsy (cytology)
-surgery (rarely feasible)
prognosis bad (5% 5 year survival)
49
Jaundice (hyperbilirubinemia)
Conjugated (direct): obstruction, hepatitis, Dubin-Johnson
| Unconjugated (indirect): hemolysis, hepatitis, Gilbert
50
Jaundice in Neonates
- common, "physiologic" due to liver immaturity (hepatic machinery for conjugating & excreting bilirubin not fully operational until 2 weeks old)
- severe can injure brian, treated with UV light
51
Biliary Atresia
- progressive inflammatory & fibrosing disease of extrahepatic bile ducts, of unknown etiology, with gradually complete obstruction of bile flow caused by destruction of extrahepatic bile ducts
- 1:10,000 live births
- causes 1/2 of neonatal cholestasis
- most common cause of death from liver disease in early childhood
52
Biliary Atresia Microscope
-Fibrosis obliterating on extrahepatic bile duct
53
Biliary Atresia Progression
- typically become jaundiced at 3-6 weeks of age
- have conjugated hyperbilirubinemia
- disproportionately high GGT
- mild-moderately high ALT & AST
- poor prognosis improved by early surgery (hepatoportoenterostomy) but many still need liver transplant
54
Alagille Syndrome
- syndrome paucity of intrahepatic bile ducts
- neonatal jaundice, pruritis and cholestasis
- "arteriohepatic dysplasia"
- autosomal dominant
- 70% sporadic new mutations
- dut to mutation in JAGGED 1 gene for ligand for NOTCH 1 receptor
55
Alagille Syndrome: Microscopy
-trichrome stain of portal triad, blood vessels but no bile ducts
-
56
Alagille Syndrome: Prognosis
-good unless misdiagnosed and surgerized
57
Dubin-Johnson Syndrome
- hereditary conjugated hyperbilirubinemia
| - defective excretion of bilirubin conjugates and other organic anions across hepatocyte canalicular membrane
58
Dubin-Johnson Syndrome: Microscope
-brown-black pigment in the liver: lysosomes containing polymers of epinephrine metabolites
59
Dubin-Johnson Syndrome: Symptoms
-usually asymptomatic, with normal life expectancy, but may have recurring or fluctuating chronic jaundice
60
Gilbert Syndrome
- autosomal recessive deficiency of uridine diphosphate-glucuronyltransferase (UGT) enzyme conjugates bilirubin
- 9% of population homozygous
- males
- usually diagnosed in young adults with mild, primarily unconjugated hyperbilirubinemia (febrile illness, physical exertion, fasting or hemolysis) and no other manifestations of this disease
61
Gilbert Syndrome: Prognosis
-benign, maybe better than average because have slightly higher bilirubin than average & incidence of colon cancer, cancer mortality in general and atherosclerotic heart disease are inversely proportional to bilirubin level
62
Primary Biliary Cirrhosis
- auto-immune, slowly progressive cholestatic disease
- typically in late middle-aged women
male: female 1:6
- usually present with pruritis, fatigue, hepatomegaly, elevated alkaline phosphatase eventually get jaundice, xanthomas, steatorrhea
63
Primary Biliary Cirrhosis: Pathology
- dense lymphocytic inflitrate in and around interlobular bile ducts with granulomas and bile duct destruction and loss, and progressive portal fibrosis
- associated with anti-mitochondrial antibodies (90%)
64
Primary Biliary Cirrhosis: Microscopy
-dense lymphocytic infiltrate in and around interlobular bile ducts, with granulomas and bile duct destruction and loss
65
Primary Sclerosing Cholangitis
- probably auto-immune fibrosing cholangitis of intra & extra hepatic bile ducts
- associated with inflammatory bowel disease (70%)
- early middle-aged men, male:female 2:1
66
Primary Sclerosing Cholangitis: Pathology
-onion-skinning fibrosis of bile ducts
67
Primary Sclerosing Cholangitis: Presentation
- ususally fatigue, pruitis, jaundice
- commonly have endoscopic retrograde cholangio-pancreatography showing characteristic "beading" of bile ducts due to strictures & dilatations
68
Budd-Chiari Syndrome
- portal hypertension due to thrombosis of hepatic veins
- manifestations: hepatomegaly, ascites, abdominal pain
- due to polycythemia vera, other myeloproliferative disease, pregnancy, postpartum state, oral contraception, paroxysmal nocturnal hemoglobinuria, abdominal cancer
69
Budd-Chiari Syndrome Cause
- 30% idiopathic
- associated with hypertrophy of caudate lobe
- commonly fatal in develops acutely
- 50% 5 year survival if develops chronically
70
Acute Cholecystitis
common (middle aged females)
| 90% have gallstones obstructing neck of gallbladder or cystic duct
71
Acute Cholecystitis: symptoms
-steady severe abdominal pain (RUQ), fever, anorexia, nausea
72
Acute Cholecystitis: signs
- patients lie still b/c pain is aggravated by movement
| - voluntary/involuntary guarding
73
Murphy's Sign
acute cholecystitis
- while palpating the area of the gallbladder, patient asked to inspire deeply causing increased pain
(sen. 97%, spec. 48%)
74
Acute Cholecystitis: Labs
leukocytosis
| inc. alkaline phosphatase
75
Acute Cholecystitis: Complications
gangrene 20%
| rupture 2%
76
Acute Cholecystitis: Treatment
cholecystectomy
77
Acute Acalculous Cholecystitis
10% of gallbladders removed for Acute Cholecystitis contain no gallstones
- usually seriously ill patients with
1. postoperative state after major surgery
2. severe trauma
3. severe burns
4. sepsis
- stasis & sludging of bile in gallbladder probably = major etiological factors
78
Chronic Cholecystitis
-associated with gallstones (almost always) infection with E. coli or enterococci (1/3)
79
Chronic Cholecystitis: Symptoms
biliary cholic or indolent RUQ pain, epigastric distress, nausea, intolerance for fatty foods
80
Chronic Cholecystitis: Diagnosis
ultrasound: gallstones & thickened gallbladder wall
81
Chronic Cholecystitis: Treatment
cholecystectomy
82
Choledocholithiasis
gallstones in bile ducts (obstruction)
83
Choledocholithiasis: Complications
biliary obstruction, acute/chronic pancreatitis, acute/chronic cholangitis, acute/chronic cholecystitis (if cystic duct), liver abscess, chronic liver disease, secondary biliary cirrhosis
84
White Bile
-biliary secretion w/high mucus content being aspirated from the gallbladder intraoperatively in a case of biliary obstruction
85
Cholangitis
inflammation of the biliary tree (often with infection)
- almost always caused by choledocholithiasis complicated by bacterial infection of the normally sterial biliary lumen
- uncommon: tumors, stents, acute pancreatitis, benign strictures
86
Ascending Cholangitis
-infection of intrahepatic biliary ducts
Acute: usually due to bacteria (E. coli, Klebsiella, Clostridium, Bacteroides, Enterobacter, Enterococcus)
Chronic: usually due to parasites (Cryptosporidium, Fasciola hepatica, Schistosoma or Clonorchis sinensis)
87
Symptoms of Ascending Bacterial Cholangitis
-fever, chills, abdominal pain, jaundice
88
Pathology of Ascending Bacterial Cholangitis
-purulent bile fills and distends bile ducts, can get liver abscess formation
89
Treatment of Ascending Bacterial Cholangitis
-relief of obstruction and antibiotics
