Waters Flashcards
1
Q
complications of liver disease
A
- synthetic impairment
- cholestasis
- decreased clearance
- portal HTN
2
Q
Tests of liver synthetic capacity
A
clotting factors
albumin
cholesterol: late complication of severe dysfunction
3
Q
cholestasis
A
impairment of bile flow
4
Q
Tests that measure liver clearance
A
bilirubin: imperfect
ammonia
5
Q
portal HTN
A
portal blood is shunted around liver rather than processed by the liver
6
Q
bilirubin
A
balance btwn input and removal by liver
increases with intrahepatic/extrhepatic obstruction
normal: 1
7
Q
Tests that detect liver injury
A
aminotransferases: ALT, AST
ALP
8
Q
AST (aspartate aminotransferase))
A
liver and muscle injury
9
Q
ALT (alanine aminotransferase)
A
more specific for liver
10
Q
ALP (alkaline phosphatase)
A
bile ducts: correlates with intrahepatic and extra hepatic injury or obstruction
level associated with increases synthesis
isoenzymes: Gut, Liver, Bone
11
Q
Cholylglycine
A
serum bile salt
correlates with degree of cholestasis, intrahepatic of extra hepatic obstruction to bile flow
12
Q
GGT (Gamma Glutamyl Transferase/Transpepidase)
A
many tissues
biliary
increased: cholestasis, biliary obstruction; Phenytoin and ethanol
limited clinical utility: many meds and chemicals increase it
13
Q
isolated GGT elevation
A
due to medications or ETHANOL
14
Q
ammonia
A
detoxified in liver by urea cycle and glutamine synthetase
correlation: hepatic encephalopathy
15
Q
prolonged prothrombin time
A
clotting factor deficiency: I, II, V, VII, X
Vit. K deficiency
correlates with hepatic synthetic function
16
Q
international standardized ratio (INR)
A
correlates with hepatic synthetic function
17
Q
albumin
A
correlates with hepatic sun.
half life 20 days
rapidly changes with acute illness, malnutrition
18
Q
Child Pugh score
score 1; 2; 3
A
prognosis after vatical bleeding
1. albumin: greater than 3.5; 2.8-3.5; less than 2.8
2. bilirubin: less than 2; 2-3; greater than 3
3. ascites: none; mild; mod.-sev.
4. encephalopathy: none; 1-2; 3-4
5. PT/INR: less than 1.71; 1.71-2.2; greater than 2.2
Grade A: 5-6
Grade B: 7-9
Grade C: 10-15
prognosis: grade A better survival (C nearly half die in 1-2 months)
19
Q
Model of End-Stage Liver Disease (MELD)
A
predictor of ALD survival 1. INR 2. bilirubin 3. creatinine: high is bad (should be low due to muscle wasting and malnutrition in liver disease) High MELD: increase 90 day mortality
20
Q
Where does the majority of liver blood flow come from?
A
Portal vein (splenic vein, splanchnic circulation)
rest: hepatic artery
21
Q
How does chronic portal HTN lead to increased splanchnic blood flow and perfused capillary density?
A
- increased transvascular pressure gradient
- portosystemic shunting
- increase circulating levels of Glucagon and other vasodilators: decreases catecholamine sensitivity
- decreases splanchnic arteriolar resistance
22
Q
How does chronic portal HTN lead to increased lymph flow?
A
- venous stasis
- capillary and postcapillary venule pressure (also due to decreased splanchnic arteriolar resistance)
- increase capillary filtration rate (also due to increased perfused capillary density)
23
Q
What do venous collaterals in portal HTN cause (via what vein)?
- anterior
- posterior
- superior
- inferior
A
- caput medusa (via umbilical vein)
- splenorenal shunt (via retroperitoneal veins)
- esophageal varcies (azygous)
- hemorrhoids/ anorectal varices
24
Q
varices
- how many have them in newly Dx cirrhosis
- how many bleed within 2 year
- why do they bleed
- Tx
A
tortuous venous collaterals under high pressure
1. half (increases each year after Dx)
2. 1/3
3. high pressure, thrombocytopenia, impairment of clotting factors
4. volume resuscitation, correct coagulopathy, splanchnic vasoconstriction (decrease blood flow to intestine, stomach, collaterals); VASOPRESSIN, SOMATOSTATIN (blocks vasodilators like Glucagon)
MAJOR CAUSE of DEATH in liver disease
25
Tx of variceal hemorrhage
1. endoscopic therapy to sclerose or band varices
2. decrease portal pressure: Beta blockers, portosystemic shunt (surgical or transjugular intrahepatic), liver transplant
26
What causes ascites (3 pathways)?
1. increased resistance to portal venous flow, increased flow to portal vein, increased lymphatic flow, leakage of lymphatic flow from the liver and intestines
2. increased portosystemic shunting of vasodilators, systemic vasodilation
3. decreased renal perfusion, increased renal vasoconstriction, increased Renin-Angiotensin, increased Na reabsorption
27
Hypotheses of Ascites
1. traditional underfill concept
2. overflow hypothesis
3. revised underfill theory
1. ascites formation, decreased effective volume, renal Na retention, ascites and edema
2. primary renal tubular retention of Na, increase plasma volume, translocation of fluid out of splanchnic circulation as ascites
3. primary peripheral vasodilation, imbalance of capacitance and volume (relative underfilling), renal Na retention
28
complications of ascites
1. tense ascites: pressure on diaphragms and stomach, difficulty breathing and eating
2. hepatic hydrothorax
3. spontaneous bacterial peritonitis
4. spontaneous bacterial peritonitis
29
spontaneous bacterial peritonitis
due to ascites (therefore liver disease)
1. large amount of undrained fluid, low protein and complement
2. bacterial translocation from intestines to blood, bacteremia infects ascites
30
Tx of ascites
1. Na restriction
2. diuretics
3. Tx the underlying liver disease
4. large volume paracentesis
correct portal HTN
other: transjugular/surgical portosystemic shunt, liver transplant
31
Two important effects of portal HTN
1. ascites
| 2. varices
32
normal serum lab values
1. ALT, AST, GGT
2. ALP
1. 10-60 U/L
| 2. 45-150 U/L
33
normal serum lab values
| albumin
3.5-5.2 g/dL
34
normal serum lab values
| alpha-1 antitrypsin
100-200 mg/dL
35
normal serum lab values
| ammonia
7-27 micromol/L
36
normal serum lab values
| amylase
30-110 U/L
37
normal serum lab values
| bilirubin (total)
0.2-1.9 mg/dL
38
normal serum lab values
| ceruloplasmin
25-63 mg/dL
39
normal serum lab values
| copper
26-190 mcrgm/dL
40
normal serum lab values
| creatinine
0.7-1.4 mg/dL
41
What population has a very high prevalence of alcoholic liver disease?
Native American
42
stages of alcoholic liver disease
1. steatosis
2. alcoholic hepatitis
3. alcoholic cirrhosis
43
What can liver cirrhosis lead to?
1. hepatocellular carcinoma
| 2. cholangiocarcinoma
44
How many drinks/day for alcoholic liver disease and how many years?
5 yrs
men: more than 6 drinks
women: 3 drinks
45
Why do women require less drinking than men to get alcoholic liver disease?
1. differences in volume of distribution
2. decreased alcohol dehydrogenase activity
3. differences in first pass metabolism
46
alcoholic hepatitis
40-60 yrs old
Sx: jaundice, muscle wasting, ascites, tender hepatomegaly, FEVER
AST over 2x ALT (both are rarely over 300)
also: elevated INR, leukocytosis
47
normal prothrombin time (PT)
10.7-15 s
48
normal INR
below 1.1
| 2-3 if on warfarin
49
ADH2*1 polymorphism
East Asian
| increased susceptibility to alcoholic liver disease (flushing due to acetaldehyde build up)
50
TNF a-238 polymorphism
Caucasians
| increased susceptibility to alcoholic liver disease
51
Mechanism of ALD pathogenesis
1. ethanol, acetylaldehyde cause intestinal injury and increased permeability
2. results in endotoxemia
3. results in inflammatory response by Kupffer cells
52
Two hit theory of ALD
Hit 1: Fatty Liver: oxidative stress, increased NADH/NAD ratio, obesity/DM
fat sensitizes liver to 2nd hit
Hit 2: inflammation and necrosis; oxidative stress/hypoxia/immunological rxn
53
Maddrey score
modified discriminant function: predictor of survival in ALD
[4. 6 (PT- control)] + bilirubin
greater than 32: one month mortality is 1/3 to 1/2
54
Glasgow Alcoholic Hepatitis Score
| score: 1, 2, 3
predictor of survival in ALD
greater than 9: bad
1. age: less than 50, greater than 50; no 3 score
2. WBC: less than 15,000, more than 15,000; no 3 score
3. BUN: less than 14, more than 14; no 3 score
4. INR: less than 1.5, 1.5-2, greater than 2
5. bilirubin: less than 7.4, 7.4-14.7, more than 14.7
55
C282Y mutation
location: HFE gene
missense: Cys to Tyr
hemochromatosis
decreased sensing of iron stores leads to excess iron absorption in intestine
decreases hepcidin
56
HFE gene
type I hemochromatosis
| defect: can't sense iron: absorb iron you don't need
57
ALD patients with C282Y mutations had?
increased hepatic iron scores
| higher rates of HCC
58
MZ or SZ
heterozygous
| alpha-1 antitrypsin deficiency
59
ZZ
homozygous
| alpha-1 antitrypsin deficiency
60
most important environmental factors in determining ALD risk
ethanol pattern
| obesity and hyperglycemia
61
ALD Tx
1. ABSTINENCE
2. nutrition
3. pentoxifylline
4. immunosuppression with corticosteroids in some
liver transplant
62
How does heptaocellular steatosis occur in ALD?
1. shunt substrates away from catabolism and toward lipid biosynthesis: increased generation of NADH by alcohol dehydrogenase and acetaldehyde dehydrogenase
2. impaired assembly and secretion of lipoproteins
3. increased peripheral fat catabolism of fat, releasing FFA into circulation
63
nonalcoholic fatty liver disease (NAFLD)
obesity, T2DM, hyperlipidemia, metabolic syndrome
64
Two conditions of NAFLD
1. steatosis (limited progression)
| 2. NASH
65
non-alcoholic steatohepatitis (NASH)
fatty liver, fibrosis, cirrhosis
| increases risk of: HCC
66
BMI of obesity
greater than 30
67
Who has the highest rate of NAFLD? Lowest?
high: Mexican American
low: AA
gender equal
68
Leading cause of pediatric liver disease?
NAFLD
69
Other causes of NAFLD (besides obesity)
1. nutrition abnormalities: total parenteral nutrition, starvation then re-feeding
2. metabolic diseases: abetalipoproteinemia, hypobetalipoproteinemia
3. occupational chemical exposure
4. drugs
5. surgery (with rapid, excessive wt. loss): jejunoileal bypass, gastric bypass
70
drugs that cause NAFLD
```
tamoxifen
corticosteroids
amiodarone
methotrexate
antiretrovirals
```
71
pathogenesis of steatosis in NAFLD
normal: TG in chylomicrons travel via lymph to peripheral fat, hydrolyzed to FFA (stored in liver and oxidized by mitochondria)
disturbance of this
1. more lipogenesis
2. increased FFA from periphery to liver
72
pathogenesis of insulin resistance in NAFLD
1. insulin promotes uptake of glucose (stored as glycogen)
2. inhibit lipolysis (increase in adipose tissue lipolysis?)
3. increased insulin leads to increased lipogenesis: increased FFA
4. increased mitochondrial FA oxidation: free radical formation and damage
73
NAFLD: two hit hypothesis
1. hepatic fat accumulation
| 2. oxidative stress via lipid peroxidation and free radicals
74
Dx of NAFLD
Sx of most: NONE
nonspecific: fatigue
PE: obesity, hepatomegaly, SPIDER ANGIOMATA, PALMER ERYTHEMA
lab:
moderately elevated AST and ALT (up to 4x normal)
ALP up to 2x normal
can have normal LFTs but may have low platelets
Biopsy is the ONLY definitive way to Dx: controversial
75
Histo definitions in fatty liver
1. steatosis
2. steatohepatisis
3. fibrosis
4. cirrhosis
1. macro vesicular fat
2. inflammation, hepatocyte degeneration, Ballooning and Mallory bodies
3. pericellular then bridging
4. 20% of patients within 10 yrs
76
NAFLD/NASH Tx
WEIGHT REDUCTION
1. optimize diabetic Tx
2. must Tx hyperlipidemia to reduce cardiac risk
3. BMI greater than 35: bariatric Sx: improves inflammation and fibrosis
4. liver transplant
77
most frequent genetic condition in Caucasians
hemochromatosis
78
hepcidin
decreases iron absorption
normally: iron excess leads to up regulation; iron def. leads to down regulation
HEMOCHROMATOSIS: decreased hepcidin: leads to up increased intestinal iron absorption via upregulation of ferroportin
79
HFE mutations
1. C282Y homozygous
2. C282Y/H63D or S65C
3. homozygous for H6D3 or S65C
1. most patients with hereditary hemochromatosis
2. may have iron overload
3. NOT associated with iron overload
80
What organs is serum Fe in hemochromatosis loaded into and why?
What happens to these organs?
tissues with High Transferrin Receptors
liver, heart, pancreas, thyroid
increased oxidative stress and free radicals
81
Hemochromatosis Sx
over 40 yrs in men; 50 yrs in women
general: fatigue, ARTHRITIS (most common)
liver: cirrhosis, HCC
heart: restrictive cardiomyopathy
skin: hyperpigmented
pancreas: bronze DM
82
Type I hemochromatosis
HFE gene
adults
chromosome 6
83
Type II hemochromatosis
Juvenile: 10-15yrs
defect in: HJV, HAMP gene
NO HEPCIDIN
more CARDIAC involvement
84
HJV gene (hemojuvelin)
Type II hemochromatosis
85
HAMP gene (hepacidin anti-microbial peptide)
Type II hemochromatosis
86
Type III hemochromatosis
transferrin receptor mutation
87
Type IV hemochromatosis
ferroportin mutation
88
Dx of hemochromatosis
1. transferrin saturation (serum Fe/TIBC) greater than 45%: suspect iron overload
2. serum Ferritin more than 1000 mcg/l predicts advanced fibrosis/cirrhosis
TIBC: transferrin
3. gene test for homo C282Y
4. biopsy: confirm HIC/age greater than 1.9; assess liver injury; Dx those without HFE mutation (type II, III)
89
Screening for HFE
1. who
2. how
3. for children of hemochromatosis parent
if have
4. hetero or homo C282Y and elevated ferritin
5. hetero or homo C282Y and normal ferritin
1. all 1st degree relatives
2. check ferritin/TS and HFE mutation
3. check other parent: don't have it, then children are heterozygotes and don't need further testing
4. start Tx: phlebotomies
5. monitor Fe normally
90
Other causes of iron overload (other than hemochromatosis)
1. ineffective erythropoiesis (Thalassemia, sideroblastic anemia)
2. parenteral iron overload from transfusions
3. chronic liver disease
4. aceruloplasminemia
5. congenital atransferrinemia
91
Hemochromatosis Tx
1. phlebotomy (until ferritin is less than 50g/ml)
2. Fe chelation: desferoxamine, deferasirox
3. avoid Vit. C (increases Fe absorption), undercooked seafood (risk of infection with Vibrio; also at risk of Listeria, Yersinia)
4. decrease: alcohol and iron intake (no longer recommended)
92
Results of hemochromatosis Tx do?
1. improve survival if initiated before cirrhosis/DM
2. reversal of fibrosis (but not cirrhosis)
3. improved glycemic control and cardiac function
4. reduction in portal HTN
5. elimination of HCC risk (if before cirrhosis)
6. reduction in skin pigmentation
93
1. What can hemochromatosis NOT reverse?
| 2. What should cirrhotic hemochromatosis pts. be screened for?
1. hypogonadism, arthropathy, cirrhosis
| 2. HCC
94
Wilson's Sx
1. liver
2. brain
3. kidney
4. blood
AR
presents EARLY in life
excess Cu
ATP7b defect
1. chronic hepatits, cirrhosis, acute liver failure
2. psych Sx, basal ganglia (parkinson like: tremor, dystonia, lack of coordination, dysphasia, spasticity, etc)
3. proximal tubular disease
4. hemolytic anemia
other: cardiomyopathy, pancreatitis, osteoporosis, arthritis, nephrolithiasis
KAYSER-FLEISCHER RING
95
Cu metabolism
intestinal Cu transported to hepatocyte
1. into circulation bound to ceruloplasmin
2. biliary Cu excretion into feces
96
ATP7b gene
encodes ATPase that transports Cu in hepatocytes
reduced/absent: WILSON'S: reduced Cu excretion in bile and inability to incorporate Cu into ceruloplasmin
chromosome 13
97
Where does Cu go in Wilson's?
increase in serum free Cu
| some goes to: urine and extra-hepatic sites
98
Labs in Wilson's
1. low ceruloplasmin
2. high free Cu in plasma
3. high Cu in liver
99
Kayser-Fleischer Ring
Cu in Descemet's membrane of cornea
WILSON'S
can be absent in isolated hepatic Wilson's
also seen in: PBC, PSC
100
Wilson's: fulminant liver failure
1. liver failure
2. encephalopathy
3. coagulopathy: hemolytic anemia (Coomb's neg)
4. low serum ALP
5. ALP/Bil less that 2
6. AST/ALT less than 2000
Tx: LIVER TRANSPLANT only
101
When to suspect Wilson's
1. less than 40 with elevated AST/ALT
2. Neuropsychiatric disease with liver disease
3. young patient with liver failure
102
Dx of Wilson's
1. ceroloplasmin less than 5 mg/dl
2. free Cu greater than 25 ugm/dl
3. 24 hour Cu urine greater than 100 mg
4. liver Cu concentration greater than 250 ugm/gram (can get false neg if have severe fibrosis)
too many mutations for genetic mutation (unless family member already Dx)
103
Tx of Wilson's
1. chelating agent: penicillamine, trientene, tetrathiomolybdate
2. Zinc
3. Liver transplant
104
Rx of choice for Wilson's
trientene and zinc
105
Alpha-1 anti-trypsin
neutralized neutrophil elastase
106
SERPINA1 gene
chromosome 14
alpha1 antitrypsin deficiency
alleles: M, S, Z
only Z
107
alpha-1 anti-trypsin
1. M
2. S
3. Z
1. normal
2. mutated: slow moving
3. mutated: slowest: disease; cannot be secreted by liver (excess in liver, low in lung and serum)
108
alpha-1 antitrypsin deficiency
Sx
Dx
Tx
1. lung: EARLY EMPHYSEMA (uncontrolled elastase activity)
2. liver: accumulation: liver injury, neonatal jaundice
can have either one or both
Dx: ZZ phenotype, liver biopsy
Tx: if smoke STOP, replace aAT (useful for emphysema only)
liver transplant for cirrhosis
109
Risk of HCC in
1. hemochromatosis
2. Wilson's
3. Alpha-1 AT def.
1. HIGH
2. low
3. middle
110
impact of liver transplant in
1. hemochromatosis
2. Wilson's
3. Alpha-1 AT def.
1. can theoretically recur (rare); no impact on extra hepatic sites
2. cures disease, may improve neurological disease
3. cures hepatic disease, emphysema irreversible
111
causes of hepatic encephalopathy
1. acute liver failure
2. portosystemic shunt without liver failure
3. chronic liver failure
112
proposed mechanisms of hepatic encephalopathy
1. ammonia, nitrogenous waste
2. increased intracellular glutamine
3. astrocyte swelling, cerebral edema
4. inflammatory cytokines alter BBB
5. increased benzodiazepine receptors
6. increase neurosteroids, increased GABA receptor activity
7. manganese: neurotoxin that deposits in basal ganglia
113
acute hepatic encephalopathy
1. coagulopathy and altered mental status within 2 weeks of jaundice
2. alteration of BBB
3. associated with acute cerebral edema resulting in cerebral herniation
MAJOR cause of death in acute liver injury
114
chronic hepatic encephalopathy
slow and subtle
milder Sx
missed by coworkers or physicians (often noticed by family)
REVERSIBLE (possibly mild decrease in mentation)
115
stages of hepatic encephalopathy
1. Grade I
2. Grade II
3. Grade III
4. Grade IV
1. irritable, insomnia, agitation
2. indefferent, personality change, short term memory impairment, mildly disoriented about time or place
3. drowsy but arousable, significantly confused and disoriented to time and place
4. coma
116
Sx of hepatic encephalopathy
asterixis, myoclonus (jerking) with hyperextension of ankles
confusion
NO tachycardia, HTN, other sensory/motor/cerebellar deficient to suggest other causes
117
asterixis
hyperextend wrist and observe flap motion
| inability to sustain grip
118
conditions that need to be treated in hepatic encephalopathy
1. hypovolemia
2. hypokalemia
3. GI bleed
4. remove some medications (sedatives), substance abuse
5. infection: MENINGITIS
6. exclude INTRACRANIAL HEMORRHAGE (falls with thrombocytopenia, coagulopathy)
119
Tx of hepatic encephalopathy
1. lactulose: decreases glutamine absorption, reduced syn. and absorption of NH3
2. zinc sulfate: cofactor in NH3 metabolism (def. is common in liver disease)
3. antibiotics: alter intestinal flora; decrease NH3, intestinal glutaminase, coliform bacteria that produce NH3
4. NUTRITION
do NOT restrict protein
120
chronic neuropsychiatric complications of cirrhosis
1. decreased functional capacity despite medical therapy
2. dementia
3. Parkinson's like syndrome
4. cerebral edema
121
hepatic Parkinsonism
symmetrical
| rigidity, lack tremor
122
hepatic dementia
flutuating Sx
| attention deficit, dysarthia, apraxia (inability to carry out learned movements)
123
hepatic cerebral edema
ACUTE liver failure or decompensated cirrhosis
| worsened with hyponatremia, rapid fluid shifts
124
hepatic myelopathy
demyelination of pyramidal tract
progressive spastic paraparesis
hyper-reflexia
dementia
125
hepatocerebral degeneration
```
risk with recurrent hepatic encephalopathy
neuropsych disorders
movement disorders, myoclonus
cerebellar Sx
myelopathy
```
126
hepatocerebral degeneration MRI
increased intensity in globus pallidus with T1
associated with severity and worsened NH3 levels
IMPROVED within 3 mo. of LIVER TRANSPLANT, IMPROVEMENT in BASAL GANGLIA ABNORMALITIES (his publication)
127
renal complication associated with liver disease
1. hepatorenal syndrome
2. IgA nephropathy
3. membranoproliferative glomerulonephritis
4. membranous glomerulomephritis
128
hepatorenal syndrome
liver failure causes renal arterial vasoconstriction and renal failure
Sx: cirrhosis and ascites; serum Cr greater than 1.5 mg/dL
Dx: exclusion; lack of return of renal function with intravascular volume depletion
reversed with Tx of liver failure
129
hepatorenal syndrome
1. Type 1
2. Type 2
1. rapid worsening Cr greater than 2.5 mg/dL or decrease in CrCl less than 20 ml/min within 2 wks
2. slow progression, often with worsening liver disease
130
Mechanism of hepatorenal syndrome
1. peripheral artery vasodilation
2. stimulation of renal sympathetic nervous system, renin-angiotensin-aldosterone
3. cardiac dysfunction
4. cytokinees, vasoactive mediators
131
hepatorenal syndrome Tx
1. intravascular volume repletion
2. Tx underlying infection
3. AVOID NSAIDs and CONSTRAST
4. optimize renal perfusion with midodrine and octreotide
5. hemodialysis until liver transplant
132
IgA nephropathy
most common secondary cause: liver disease
IgA, C3 deposition (decreased clearance)
IFN worsens dysfunction
association: HEP C and B
133
membranoproliferative glomerulonephritis
associated with: CHRONIC HEPATITIS C
| CRYOGLOBULINEMIA
134
cryoglobulinemia
proteins precipitate in chilled tube of blood
| see bruises in distal extremeties
135
drug-induced liver disease
| Sx
RASH, EOSINOPHILIA, FEVER
| other: asymptomatic, fatigue, abnormal liver enzymes, jaundice, liver failure
136
intrinsic vs. idiosyncratic hepatotoxin
1. predictability
2. dose dependency
3. reproducibility in animals
4. what drugs
```
intrinsic
1. predictable
2. dose dependent
3. easily reproduced in animals
4. carbon tetrachloride, acetaminophen
idiosyncratic
1. unpredictable
2. not reproduced in animals
3. not dose dependent
4. MOST medications
```
137
Drug induced liver disease: what do you see on histo (not sure if correlate)
1. amiodarone
2. CCl4
3. androgens
4. chlorpromazine
5. floxuridine
6. azathioprine
7. sulfonamides
8. chlorpromazine
9. halothane
1. ALD
2. fatty liver
3. cholestasis
4. bile duct injury
5. sclerosing cholangitis
6. veno-occlusive Dis
7. granulomas
8. cholestasis
9. fatal immune-mediated hepatitis
138
hepatocellular injury in drug induced liver disease
acute and chronic hepatitis
fulminant hepatitis
steatohepatitis
cirrhosis
139
cholestatic injury in drug induced liver disease
cholestasis
acute and chronic cholangitis
sclerosing cholangitis
vanishing bile duct syndrome
140
oral contraceptive drug induced liver disease
idiosyncratic
bland cholestasis
estrogen decreases membrane fluidity
decrease Na/K ATPase activty and bile salt transport
vascular complications, Budd-Chiari, peliosis hepatitis, focal nodular hyperplasia, hepatic adenomas, HHC (rare)
141
acetaminophen and ethanol
1. decreased glutathione
2. increase CYP induction
3. increase toxic metabolites
Tx: N-acetylcysteine; discontinue alcohol and tylenol
LOW dose acetaminophen in alcoholic is all it takes
142
fulminant hepatic failure
massive necrosis of liver cells without preceding liver disesae
HIGH MORTALITY
LESS THAN 2 WEEKS
143
Causes of fulminant hepatic failure
1. viral
2. drug/toxin
3. ischemic
4. metabolic
5. misc.
1. Hep. A, B, D, E; herpes, CMV, EBV, varicella, adeno
2. acetaminophen, halothane, NSAIDs, herbals
3. hypoxia, shock, budd-chiari
4. wilson, fatty liver of pregnancy, Reye's
5. CA, bactierial infection
MOST are viral or toxic
144
viral fulminant hepatic failure
1. pregnancy
2. immunocompromised
3. rare, usually greater than 40 yrs
4. other
MOST COMMON cause
1. HEV
2. HSV, CMV, EBV, varicella, adeno
3. HAV
4. HBV (most common of virus; half infected with HDV)
145
second most common cause of fulminant hepatic failure
drugs
| halothane, NSAID, ISONIAZID, acetaminophen, mushroom, herbals, alcohol
146
acetaminophen liver toxicity
oxidation causes the problem, sulfonation, glucoronidation help fix
metabolized by CYP to NAPQI (toxic)
glutathione detoxifies NAPQI
147
HBsAg
Hep. B surface antigen
| ongoing infection
148
anti-HBc
```
Ab to Hep B core antigen
prior infection (IgM indicates recent)
```
149
anti-HBs
Ab to Hep B surface protein
| immunity and/or recovery
150
Hep. B
1. type 1
2. type 2
3. type 3
1. clear
2. chronic (greater than 6 mo)
3. fulminant hepatic failure
151
Wilson's Tx in acute liver failure
transplant
| don't bother with chelating
152
Sx of acute hepatic failure
1. general
2. bad/late
3. if was from chronic
1. Jaundice, large liver (or small with collapse), vomit
2. increased HR and BP, fever
if do to chronic: no liver Hx, small 3. hard liver, splenomegaly, vascular collaterals
