Liver Flashcards
(217 cards)
1
Q
blood supply liver
A
2/3 portal vein
1/3 hepatic artery
2
Q
liver functions
A
metabolism synthesis catabolism storage excretion blood reservoir
3
Q
serum transaminases
A
present in hepatocytes
involved in amino acid metabolism
elevated in hepatic injury
4
Q
alkaline phosphatase
A
removes PO4
borders bile canaliculi cells
also found in placenta and bone
elevated in cholestatic disorders
5
Q
gamma glutamyl transpeptidase
A
enzyme in bile canaliculus
involved in glutathione metabolism, drug detoxification
most sensitive indicator
elevated with ALP=hepatobiliary disease
6
Q
albumin
A
produced in liver
maintains normal oncotic pressure
decreased in liver disease-does not correlate to severity of disease
7
Q
causes of acute hepatitis
A
viruses excessive alcohol consumption acetaminophen overdose response to medications autoimmune metabolic disorders circulatory disorders
8
Q
clinical manifestations acute hepatitis
A
acute encephalopathy coagulopathy acute renal failure gastrointestinal bleeding infection, sepsis respiratory failure cardiovascular collapse
9
Q
outcomes acute hepatitis
A
resolve spontaneously
proceed to acute liver failure
develop into chronic hepatitis
10
Q
regenerative power of liver
A
mature hepatocytes divide even in presence of confluent necrosis or chronic injury
can regenerate from 25% but need normal framework
11
Q
acute hepatic failure
A
80-90% reduction of liver functional capacity-either diminished cell number of impaired function
12
Q
decompensated acute hepatic failure
A
from compensated chronic disease with sudden flare of activity
13
Q
pathology acute hepatic failure
A
acute massive hepatic necrosis
non-necrotic liver failure
chronic liver disease/cirrhosis
14
Q
hepatic encephalopathy
A
neuropsychiatric abnormalities
altered metabolism-shunting of blood from portal to systemic circulation, bypassing liver
hyperammonemia leading to rigidity, hyperreflexia, behavioral changes
15
Q
microvesicular steatosis
A
seen in fatty liver of pregnancy, toxic reaction to tetracycline, valproate
16
Q
laboratory findings acute liver failure
A
elevated AST, ALT
hypoalbuminemia
hyperammonemia
17
Q
hepatorenal syndrome
A
decreased renal perfusion in cirrhotic patients
portal HTN leading to vasodilation and renal vasoconstriction
18
Q
hepatopulmonary syndrome
A
pulmonary vasodilation causing ventilation-perfusion mismatch
hypoxia, SOB
19
Q
non-necrotic liver failure
A
acute fatty liver of pregnancy
Reye syndrome
20
Q
cause of acute fatty liver of pregnancy
A
microvesicular steatosis
due to abnormal fatty acid metabolism-accumulation of toxic products from placenta and fetus in mother
21
Q
clinical manifestations acute fatty liver of pregnancy
A
malaise, N/V, RUQ pain, jaundice, fever, pruritus
22
Q
treatment acute fatty liver of pregnancy
A
supportive care, fluids, delivery of baby
23
Q
Reye syndrome
A
acute metabolic encephalopathy in babies following acute viral illness and aspirin intake
abnormal fatty acid and carnitine metabolism
24
Q
liver biopsy Reye syndrome
A
microvesicular steatosis
25
clinical manifestation Reye syndrome
acute encephalopathy
pernicious vomiting
evidence of dysfunctional liver
26
etiologies chronic liver disease
```
non-alcoholic fatty liver disease
hep C, B
hereditary hemochromatosis
alcoholic liver disease
A1AT deficiency
Wilson disease
PBC, PSC
autoimmune hepatitis
```
27
appearance of cirrhosis
fibrosis with delicate bands or broad scars surrounding multiple adjacent regenerative lobules
portal-portal, portal-central, central-central fibrosis
28
regenerative nodules
<3mm micro, >3mm macro
| regeneration of liver cells in canals of Hering (progenitors of parenchymal and bile duct cells)
29
role of stellate cell in cirrhosis
stimulated by reactive oxygen species, growth factors, TNF, IL-1
become myofibroblast like to produce smooth muscle actin and GFAP
30
pathology of cirrhosis
loss of functional integrity
loss of sinusoidal cell fenestrations
shunt development
high pressure vessels without solute exchange
31
clinical manifestations cirrhosis
liver failure
| portal HTN-ascites, shunts, congestive splenomegaly, hepatic encephalopathy
32
result of impaired estrogen metabolism
gynecomastia, spider angiomas
33
bile
complex fluid of bile acids and bilirubin produced by liver
| flows through biliary tract into small intestine where bile acids are reabsorbed and returned to liver and re-secreted
34
functions bile
emulsification and micelle formation
bicarbonate for neutralizing gastric acid
eliminate cholesterol, highly protein bound organic molecules, heavy metals, lipophilic drug metabolites
protects gut from infection
35
bile salts
bile acids conjugated with taurine or glycine
| detergents-solubilize water-insoluble lipids cholic acid, chenodeoxycholic acid
36
bilirubin
breakdown product of heme from spleen
37
unconjugated bilirubin
water insoluble bound to albumin, toxic to cells
38
conjugated bilirubin
water soluble, occurs in liver, nontoxic, secreted in bile ducts
39
bilirubin in the gut
converted to urobilinogen
excreted as stercobilinogen
reabsorbed in gut, recirculated, metabolized in liver or excreted via kidneys in urine
40
cholestasis
decreased bile flow accompanied by accumulation of substances normally excreted in bile (bilirubin, bile acids, cholesterol)
41
prehepatic causes jaundice
hemolysis
42
hepatic causes jaundice
hepatitis
cirrhosis
malignancy
defect in bilirubin metabolism
43
posthepatic causes jaundice
gallstones
tumors, strictures
compression by tumor (pancreatic head)
44
bilirubin product in feces
urobilinogen
| due to beta glucuronidases of bacteria in gut making pyrroles and urobilinogen
45
clinical manifestation increased bilirubin
jaundice
46
clinical manifestation serum bile acids
pruritis
47
clinical manifestation malabsorption of fats
steatorrhea
48
malabsorption of ADK
hemorrhagic, clotting disorders
49
increased serum cholesterol
xanthomas
50
non-hepatitis viruses causing hepatitis
EBV
CMV
adenvirus-neonates
yellow fever
51
most common chronic
hep C
52
symptoms pre-icteric
malaise, fatigue, anorexia, nausea, fever
| 2 weeks post-exposure
53
symptoms icteric phase
jaundice, dark color, clay colored stools, hepatomegaly
54
convalescence
diminishing jaundice, 6-8 weeks post-exposure
55
most infectious time with hepatitis
last asymptomatic days of incubation period
56
laboratory signs hepatitis
high levels ALT, AST
hyperbilirubinemia
viral serology
57
hepatocellular damage hepatitis
host adaptive immune response to viral proteins
| T cells cause necroinflammatory activity and apoptosis
58
transmission hep A
oral-fecal route
ingested through contaminated water, food
contaminated shellfish concentrates virus, can infect if undercooked
59
serology acute infection hep A
IgM
60
immunity against reinfection hep A
IgG
61
shedding hep A
shedding 2-3 weeks before and 1 week after jaundice
62
transmission hep B
vertical-childbirth
horizontal
sex/iv in low prevalence regions
63
chronic hep B
small % progress to cirrhosis and/or develop HCC
| age at infection predicts chronicity (younger more likely)
64
early response to hep B
innate immune response protects
| IF gamma to clear infected cells
65
most variable portion hep C
E2 envelope protein
| new virus strains can escape neutralizing antibodies
66
anti HCV IgG and future infection
does not protect due to high rate of chronicity
| also mutated strain
67
incubation period HCV
4-26 weeks
68
laboratory HCV
HCV RNA in blood 1-3 weeks
| elevated AST and ALT
69
treatment hep C
pegylated IFN alpha, ribavirin
| response depends on genome (2 and 3 best response), host genome IL28B gene for IF lambda
70
superinfection
severe acute hepatitis
| worse than coinfection
71
Hep D
requires B for replication
72
demographics Hep E
India-sporadic
pig farms in developed world
high mortality in pregnant women
73
clinical serology Hep E
elevated AST, ALT, IgM anti-HEV
| RNA and virions in stool, serum before symptoms appear
74
histology hep B
ground glass appearance
75
histology hep C
inflamed portal tract
76
serology autoimmune hep
elevated AST, ALT
autoantibodies
necorinflammatory activity on biopsy
77
type 1 autoimmune hepatitis
middle aged and older
| ANA, ASMA mostly
78
type 2 autoimmune hepatitis
children
anti-LKM-1 and ACL-1
LKM-1 attacks CYP2D6 on plasma membrane of cells
79
genetic predispositions hepatitis-autoimmune
HLA-DR3/4
80
clinical presentation autoimmune heptatitis
flu like symptoms, fatigue, jaundice, anorexia, hepatomegaly
| concurrent autoimmune conditions-thyroiditis, arthritis, Sjogren
81
overlap syndrome
clinical and histologic features of both autoimmune hepatitis and primary biliary cirrhosis or primary sclerosing cholangitis
chronic disease
82
laboratory findings autoimmune hep
elevated AST ALT
autoantibodies
polyclonal serum Ig
liver biopsy
83
histology autoimmune hep
rosette formation
plasma cells
lobular inflammation
84
treatment autoimmune hep
need to treat early
| good response to immunosuppresion
85
xenobiotics
therapeutic agents, environmental toxins
| liver turns them into active toxin
86
attributing drug to liver damage
temporal association
| recovery on withdrawal of suspected agent
87
direct cytotoxicity liver
chlorpromazine
| halothane
88
xenobiotics causing steatohepatitis
methotrexate and alcoholic beverages
89
leading cause of liver disease in Western world
alcoholic liver disease
90
hepatic steatosis
liver may be enlarged
micro and macrovesicular
reversible with abstinence
91
pathogenesis hepatic steatosis
increased synthesis of lipid
abnormal lipoproteins
increased peripheral fat catabolism
92
Mallory body
thick, ropy perineuclear eosinophilic inclusions composed of cytokeratin intermediate filaments
93
neutrophilic reaction
infiltrate in areas of hepatic necrosis and produce free radicals
94
effects of alcohol
steatosis
| dysfunction of mitochondrial, cellular membranes, hypoxia, oxidative stress
95
hepatocellular steatosis
shunting of normal substrates towards lipid synthesis
more reduced NADH leads to more lipogenesis
increased peripheral catabolism of fat
96
labs alcoholic liver disease
elevated bilirubin, ALP, neutrophilia
| AST>ALT
97
factors dictating severity of alcoholic liver disease
gender-women have less AlcDH
AA more cirrhosis than white
Asian ALDH2 variant and acetaldehyde
98
gross appearance alcoholic cirrhosis
liver is shrunken, diffusely nodular, firm
99
non-alcoholic fatty liver disease
most common chronic liver disease in US
| growing due to obesity, T2DM, and metabolic syndrome
100
steatosis
greater than 5% fat cells in liver parenchyma
| elevated liver enzymes without inflammation, cell death, or fibrosis
101
steatohepatitis
steatosis and necroinflammatory changes of hepatitis
102
clinical manifestation non-alcoholic fatty liver disease
fatigue, RUQ pain
103
non-alcoholic fatty liver disease in individuals with insulin resistance
decreased adiponectin
increased TNF alpha, IL-6
promote fat cell apoptosis
104
pediatric NAFLD
more diffuse
more portal fibrosis
mononuclear inflammatory cells in portal and lobule (neutrophils in adult)
105
neonatal hyperbilirubinemia
unconjugated bilirubinemia
| conjugation and excretion immature until 2 weeks
106
treatment neonatal hyperbilirubinemia
phototherapy to convert water soluble isomers Z-lumirubin, E bilirubin
excreted without conjugation
107
breastmilk jaundice
beta-glucuronidase deconjugates conjugated bilirubin
108
kernicterus
excessive levels of UCB crosses blood brain barrier-toxic to brain
109
Crigler-Najjar type 1
AR UDGPT deficiency
kernicterus-hypotonia, deafness, oculomotor palsy, lethargy
fatal-unless transplant
110
Crigler-Najjar type 2
AD UGT1A1 activity (monoglucuronide only)
| mild jaundice, non-fatal
111
Dubin Johnson syndrome
AR mutated gene for MRP2 (transports glucuronate conjugated bilirubin from liver cell to canaliculi)
benign relapsing conjugated hyperbilirubinemia
112
lab findings Dubin Johnson
normal liver transaminases and conjugated hyperbilirubinemia
non-pruritic jaundice in teens, asymptomatic
pigmented liver
113
Rotor syndrome
AR liver not pigmented
| increased urinary coproporphyrin excretion
114
Gilbert syndrome
AR
intermittent unconjugated hyperbilirubinemia
precipitated by stress, calorie reduction, fasting, drug intake
115
lab findings Gilbert syndrome
increase ratio urinary coproporphyrin I to III
116
causes of large bile duct obstruction
gallstones
malignancies (biliary tree or head of pancreas)
strictures from surgery
117
surgery for large bile duct obstruction
only works if extrahepatic
| intrahepatic may develop biliary cirrhosis
118
ascending cholangitis
subtotal/intermittent obstruction
| secondary bacterial infection from gut
119
suppurative cholangitis
bile pus fills bile ducts
| sepsis dominates
120
canalicular cholestasis
centrilobular canalicular bile plugs
Kupffer cell activation, mild portal inflammation
scant/absent hepatocyte necrosis
121
forms of sepsis associated cholestasis
canalicular cholestasis and ductular cholestasis
122
ductular cholestasis
worse pathology
| dilated canals of Hering and bile ducts
123
neonatal cholestasis
prolonged conjugated hyperbilirubinemia in newborn
124
causes neonatal cholestasis
neonatal hepatitis
| cholangiopathies-biliary atresia
125
neonatal hepatitis
giant cell transformation
| necrosis
126
biliary atresia
complete/partial obstruction extrahepatic biliary tree in first 3 months
127
clinical manifestations biliary atresia
asymptomatic
| jaundice, dark urine, pale stools
128
associations perinatal biliary atresia
viruses-rotavirus, reovirus, echovirus, CMV
129
hereditary hemochromatosis
iron overload in tissues, organs such as liver due to AR genetic mutations
130
secondary hemochromatosis
iron accumulates from excess iron-multiple transfusions, ineffective erythropoiesis, increased iron intake
131
HFE hemochromatosis
decreased hepcidin leads to increased absorption
| defect in regulation of intestinal absorption of dietary iron
132
C282Y mutation
AA 282 cystine to tyrosine
133
organs iron deposition
```
liver
pancreas-interstitial fibrosis
heart-interstitial fibrosis
pituitary gland, adrenal gland, thyroid, parathyroid, joints (pseudogout)
skin
```
134
hepatic iron index
iron concentration in liver biopsy measured tissue iron >1.9
135
clinical manifestations hereditary hemochromatosis
hepatomegaly, abdominal pain
pancreas-diabetes
skin pigmentation-bronze, slate grey
cardiac dysfunction-arrhythmias, cardiomyopathy
136
treatment hereditary hemochromatosis
regular phlebotomy
| monitor serum ferritin level
137
secondary iron overload disorders
```
multiple transfusions
thalassemia
ineffective erythropoiesis (thalassemia, myelodysplasic syndrome)
chronic liver disease
cirrhosis
increased iron intake-Bantu siderosis
```
138
Wilson disease
AR mutation in ATP7B gene
impaired copper excretion into bile
copper not incorporated into ceruloplasmin
139
ATPase and ATP7B gene
copper transporting ATPase in trans-Golgi network in canalicular area of hepatocyte
140
absorbed copper
complexed with albumin and histidine
| should be excreted in bile or incorporated into ceruloplasmin
141
histology Wilson disease
resemble viral hepatitis and fatty changes
glycogenated nuclei
copper granules
rhodamine, rubeanic stains
142
brain lesions Wilson disease
lenticular-basal ganglia
143
clinical manifestations Wilson disease
depression, behavioral abnormalities, liver failure, Kayser-Fleischer rings, arthritis, tubular
144
A1AT deficiency
AR defect
serine protease inhibitor mutated ch 14
SERPINA1
145
PiMM
most common
146
PiZZ
10% A1AT levels
| defective migration from ER to golgi
147
PiMZ
codominant expression
148
clinical manifestation PiZZ
neonatal hepatitis, cholestasis, fibrosis
chronic hepatitis
childhood or adult cirhosis
149
PiZ polypeptide
glu to lys at AA 342
| fold abnormally
150
primary biliary cirrhosis
autoimmune non-suppurative inflammation and destruction of medium-sized intrahepatic bile ducts
results in chronic progressive, often fatal cholestatic liver disease
151
portal stage primary biliary cirrhosis
portal infalmmation, bile duct damage
152
peripheral stage primary biliary cirrhosis
ductular proliferation, periportal inflammation, fibrosis
153
septal stage primary biliary cirrhosis
bridging fibrosis, ductopenia
154
labs primary biliary cirrhosis
elevated ALP
GGT
AMA
155
treatment primary biliary cirrhosis
ursodiol
156
primary sclerosing cholangitis
chronic cholestatic disorder characterized by inflammation and fibrosis that obliterates intrahepatic and extrahepatic bile ducts up to ampulla
creates beading, common with UC
157
histology primary sclerosing cholangitis
onion skin scar-periductal fibrosis, preserved ducts dilated due to obstruction down stream
158
clinical manifestation primary sclerosing cholangitis
elevated alk phos
| jaundice, pruritus
159
primary bile acids
made in liver with cholesterol and AA
| cholic acid and chenodeoxycholic acid
160
secondary bile acids
made in colon from primary bile acids (bacterial metabolites)
deoxycholate, lithocholate
161
risk factors cholelithiasis
```
middle age
females
hypersecretion of cholesterol
metabolic syndrome
obesity
```
162
estrogen role in cholelithiasis
increase LDL receptors
stimulate hepatic HMG CoA reductase
enhances cholesterol uptake, synthesis
163
hereditary cholelithiasis
ABC transporters have associations with gallstone formation
164
cholesterol stones
ca carbonate, phosphates
radiolucent
more common in NA
165
formation cholesterol stones
cholesterol becomes water soluble by aggregation with water-soluble bile salts
supersaturated, nucleates into solid monohydrate crystals
166
pigment stones
beta glucuronidases hydrolyze bilirubin glucuronides
167
complications of gallstones
```
empyema
perforation
gallstone ileus
fistula formation
obstructive cholestasis
cholangitis
pancreatitis
```
168
acute cholecystitis
90% caused by stone obstructing neck
| most important complication of gallstones
169
appearance acute cholecystitis
serosa with fibrinous exudate
170
clinical manifestations acute cholecystitis
RUQ epigastric pain
fever, nausea, tachy, sweating, N/V
if jaundice-common bile duct is obstructed
171
lab findings acute cholecystitis
leukocytosis
| mildly elevated ALP
172
acute calculous cholecystits
surgical emergency if sudden
173
histology chronic cholecystitis
subserosal fibrosis
gray-white wall
lumen with green-yellow mucoid bile
174
clinical chronic cholecystitis
N/V, intolerance for fatty foods
175
complications cholecystitis
bacterial superinfection
gallbladder perforation
gallbladder rupture
176
porcelain gallbladder
due to dystrophic calcifications
| associated with increased risk for cancer
177
Caroli disease
```
chronic recurrent fever, pain, jaundice
cholangitis
elevated ESR
dilated bile duct
risk of cholangiocarcinoma
```
178
Alagille syndrome
paucity of interlobualr bile ducts
mutations in JAGI
leads to deficient bile flow, malabsorption, growth retardation, osteoporosis, neuro deficits
179
laboratory findings Alagille syndrome
conjugated hyperbilirubinemia
GGT, ALP elevation
hyperlipidemia
180
pathology alagille syndrome
```
peripheral stenosis pulmonary artery
hypoplastic pulmonary tree
vertebral arch defects
posterior embryotoxon
hypertelic facies
```
181
right sided decompensation
passive congestion of liver, congestion of centrilobar sinusoids
atrophic liver cell plates
182
left sided decompensation
centrilobular necrosis
| ischemic coagulative necrosis
183
systemic circulatory decompensation
centrilobular necrosis
ischemic coagulative necrosis
central vein red, surrounding parenchyma tan/brown
184
peliosis hepatitis
blood filled cysts with incomplete endothelial lining
185
etiology peliosis hepatitis
tamoxifen, corticosteroids, methotrexate, thorotrast, AIDS, bartonella, hairy cell leukemia
186
Budd-Chiari syndrome
thrombosis of two or more major hepatic veins or IVC
| results in increased intrahepatic blood pressure
187
causes Budd-Chiari syndrome
myeloproliferative disorders
deficiencies antithrombin, S,C, V
antiphospholipid syndrome, malignancies (HCC)
pregnancy, OCP
188
sinusoidal obstruction syndrome
fibrotic occlusion of small hepatic veins with secondary hepatic congestion
endothelial cell injury, destruction
189
etiology sinusoidal obstruction syndrome
herbal teas, pyrrolizidine alkaloids, chemo agents, bone marrow transplant
190
focal nodular hyperplasia
20-40 yo women
OC cause tumor to enlarge
no malignant potential
191
nodular regenerative hyperplasia
transformation of entire liver into multiple nodules without fibrous septa between nodules
due to heterogenous microcirculation-obliteration of small portal veins and arterialization
192
clinical manifestations nodular regenerative hyperplasia
RA, SLE, sclerosis, PAN, polycythemia vera, chronic granulomatous disease, cystinosis, mastocytosis, amyloidosis
193
lab findings nodular regenerative hyperplasia
mildly elevated ALP, GGT
194
hepatocellular adenoma
benign tumor of hepatocytes
young women of reproductive age OCP and men on androgen therapy
can rupture during pregnancy or change into carcinomas (especially in glycogen stroage disease)
195
cavernous hemangioma
most common
| discrete subcapsular red-blue soft nodules less than 2 cm
196
complications cavernous hemangioma
Kasabach-Merritt syndrome
197
Kasabach-Merritt syndrome
MAHA with consumption coagulopathy
| erythrocytosis (EPO secretion)
198
liver met adult
colon, breast, lung, pancreas
199
liver met children
neuroblastoma, Wilms, rhabdomyosarcoma
200
hepatocellular carcinoma
malignant tumor of liver from hepatocytes
201
risk factors hepatocellular
NASH, hemochormatosis, aflatoxin
202
laboratory findings hepatocellular carcinoma
increase AFP
203
biopsy hepatocellular carcinoma
paler than surroudning parenchyma
| propensity for vascular invasion-intrahepatic mets
204
fibrolamellar HCC
young
better prognosis than HCC
large eosinophilic cells
205
cholangiocarcinoma
arises from ducts within and outside liver
206
risk factors cholangiocarcinoma
PSC, gallstones, liver fluke, thorotrast, choledochal cysts
207
Klatskin tumor
hilar location choloangiocarcinoma causes symptoms of biliary obstruction
208
lab cholangiocarcinoma
elevated 19.9 (no specific)
209
histology liver angiosarcoma
pleomorphic spindle and epithelioid cell with bizarre multinucleated cells
210
liver hepatoblastoma
malignant pediatric tumor
epithelial-best prognosis
associated with Beckwith-Wiedemann syndrome, FAP
211
lab findings preeclampsia and eclampsia
elevated aminotransferases, ALP, bilirubin
212
pathology pre-eclampsia and eclampsia
hematoma may dissect under Glisson's capsule and rupture
| biopsy-periportal sinusoidal deposits fibrin, coagulative hepatocyte necrosis
213
treatment seizures
MgSO4
214
HELLP syndrome
hemolysis, elevated liver enzymes, low platelets
215
acute fatty liver of pregnancy
defects in mitochondrial fatty acid beta-oxidation
216
intrahepatic cholestasis of pregnancy
pruritus, jaundice, darkening urine, lightening stool
| bile salts increased-cause of pruritus
217
genetics cholestasis of pregnancy
mutations in phospholipid translocator B4
