LIVER Flashcards
1
Q
What is hepatic steatosis? Steatohepatitis? What are the major causes?
A
hepatic steatosis: fatty changes in the liver
steatohepatitis: fatty liver with inflammatory changes
from alcohol consumption –> alcoholic steatohepatitis
microvesicular (small droplet) or macrovesicular (large droplet)
2
Q
What is this section? What is A-D?
A
normal liver histology
A: bile duct
B: hepatic artery
C: hepatic vein
D: central vein
3
Q
What type of cell death is caused by hepatic artery thrombosis?
A
necrosis
4
Q
What type of cell death is caused by hepatic ischemic injury?
A
necrosis
5
Q
What type of cell death is caused by viral hepatitis?
A
apoptosis
6
Q
What is the time course of acute liver failure?
A
failure within 6 months
- fulminant liver failure < 2 weeks from onset*
- sub-fulminant liver within 3 months*
7
Q
What are common causes of acute liver failure?
A
drugs (acetaminophen)
toxin ingestion
viruses
autoimmune hepatitis
8
Q
What does this histology section suggest?
A
acetaminophen toxicity in hepatic tissue
9
Q
What are major causes of chronic liver failure?
A
alcohol, non-alcoholic steatohepatitis, viruses, autoimmune hepatitis, biliary disease, genetic metabolic diseases
10
Q
What does this histology section suggest?
A
cirrhosis
trichrome stain
11
Q
What does this histology section suggest?
A
steatohepatitis
12
Q
What does this histology section represent?
A
mallory bodies in alcoholic hepatitis
13
Q
What are the three ways that fatty acids can get into the liver?
A
1) peripheral adipose tissue breakdown (FFAs enter from systemic circulation)
2) dietary intake (portal circulation)
3) de novo synthesis in hepatocytes from acetyl-CoAs
14
Q
What are major causes of macrovesicular fatty changes in liver?
A
nutritional: obesity, parenteral nutritions, intestional bypass surgery
metabolic: diabetes, hyperlipidemia, Wilson’s disease
drug-related: alcohol, corticosteroids
15
Q
What are major causes of microvesicular fatty changes in the liver?
A
acute fatty liver of pregnancy, Reye’s syndrome, tetracycline toxicity
16
Q
What is cryptogenic cirrhosis?
A
cirrhosis that cannot be explained by HBV, HCV, alcoholism, genetic diseases, etc.
major cause: non-alcoholic steatohepatitis
17
Q
What level of alcohol consumption increases risk of cirrhosis?
A
40-60 g daily
steady daily drinking more harmful, but regular binge drinking also bad
18
Q
How is ethanol oxidized for elimination?
A
ethanol –(ADH)–> acetaldehyde –(ALDH2)–> acetate
19
Q
What are the three major pathways of ethanol metabolism?
A
1) oxidation of ethanol by alcohol dehydrogenase
2) microsomal ethanol oxidizing system (via a CYP)
3) catalase mediated (via catalase)
20
Q
What is the effect of genetic variation in alcohol dehydrogenase?
A
more common in Chinese/Japanese populations
ethanol is converted rapidly to acetaldehyde but is not quickly metabolized to acetate
leads to flushing, palpitations, sweating
21
Q
What are the major metabolic effects of alcohol?
A
increased lipoprotein synthesis
increased serum triglycerides
increased liver triglycerides
increased blood and tissue acetaldehyde
increased testosterone breakdown
increased drug metabolism
22
Q
What are the three stages of alcoholic liver disease?
A
1) hepatic steatosis
2) alcoholic steatohepatitis
c) cirrhosis
23
Q
What are mallory bodies?
A
bodies composed of intermediate filaments plus ubiquitin that are common in centrizonal areas of alcoholic hepatitis
24
Q
What is the mechanism of fibrosis in alcoholic steatohepatitis?
A
stellate cell activation
25
What is the continuum of fibrosis in alcoholic injury?
1) pericellular fibrosis (around hepatocytes and central veins)
2) perivenous fibrosis
3) portal fibrosis
4) septal fibrosis
26
What type of cancer is associated with alcoholic cirrhosis?
hepatocellular carcinoma
27
How do liver cells die?
necrosis, apoptosis
28
Can you distinguish alcoholic from nonalcoholic steatohepatitis by a liver biopsy?
nope
29
How does obesity/metabolic syndrome cause liver injury?
buildup of triglycerides in hepatocytes, plus esterification of fatty acids and/or reactive oxygen specias causes inflammation which leads to steatohepatitis
30
How is ethanol metabolized?
ethanol --\> acetaldehyde --\> acetate
31
What is total body iron in normal individuals?
3-5 g
35% stored in ferritin, 65% in hemoglobin
32
What is the form of iron in the body in iron overload conditions (ex. hemochromatosis)?
iron deposits in various tissues (liver, heart, pancreas), stored as ferritin or aggregated ferritin (hemosiderin)
33
How is iron absorption regulated?
absorbed in intestinal mucosal cells, physiologically regulated
## Footnote
*only about 10% of daily iron is absorbed to maintain iron balance and make up for daily iron loss*
34
How is iron excreted from the body?
via desquamated/dead cells
35
What is the major iron storage compound in the body? Where in the body is it stored?
ferritin
stored in liver (Kupffer cells, hepatic parenchymal cells), reticuloendothelial system, bone marrow, muscle
36
What does a serum ferritin level of \< 10 ug/L indicative of?
iron deficiency
37
What is a ferritin level of \> 300 ug/L (in men) or \> 200 ug/L (in women) indicative of? What is the major risk of an iron level \> 1000 ug/L?
indicative of iron overload (hemochromatosis)
\> 1000 puts patients at risk of cirrhosis
38
What is hemochromatosis?
a group of disorders where there is a progressive increase in total body iron stores + a deposition of iron in the parenchymal cells of the liver, heart, pancreas, and other organs
39
What genetic mutation is associated with primary (hereditary) hemochromatosis?
hemochromatosis (HFE) gene C282Y mutation
40
What is the triad of symptoms associated with hemochromatosis?
diabetes mellitus (pancreas)
hyperpigmentation (bronzing of skin)
cirrhosis of liver (secondary to iron overload)
41
How is hemochromatosis diagnosed?
increased total body iron stores (esp in parenchymal cells) in absence of other known causes of iron overload
can also identify the HFE C282Y mutation
42
What is hepcidin? How does it function?
a peptide hormone produced by the liver that regulates body iron metabolism
it controls extracellular iron concentrations by binding to and degrading cellular iron exporter ferroportin
*hepcidin levels inversely related to iron absorption --\> low hepcidin means iron absorption cannot be stopped*
43
What is the mechanism of tissue injury in iron overload?
excess iron deposited in lysosomes as hemosiderin --\> leads to increased acid hydrolase activity and lysosomal fragility --\> release of lysosomal enzymes --\> cell death --\> fibrosis
44
What tests are used to diagnose hemochromatosis?
invasive: liver biopsy and measurement of iron concentration (most reliable, but not often feasible)
non-invasive: serum iron concentration high, elevated transferrin saturation, elevated seurm ferritin, screen for HFE mutations
45
How is hemochromatosis managed?
goal = keep transferrin saturation below 55%
weekly phlebotomy to remove iron, medicinal leeches, desferrioxamine B (chelating agent) injected twice daily
46
What is PiMM vs. PiZZ?
variations of alpha-1 antitrypsin genes
PiMM is normal PiZZ is abnormal
homozygous PiZZ leads to risk of developping liver disease and emphysema
47
What is the function of wild type alpha-1 antitrypsin? How is it produced and circulated?
a serum protease inhibitor that inhibits elastase, trypsin, chymotrypsin, thrombin, and bacterial proteases to prevent lung damage
produced by the liver and then secreted into the blood where it travels to the lung
48
What is the mechanism of damage associated with mutant alpha-1 antitrypsin?
1) mutant protein cannot be secreted from hepatocytes, so it accumulates and leads to hepatitis and cirrhosis
2) protein cannot reach lungs, leading to emphysema from failure to prevent lung damage
49
What is the pathophysiology of Wilson's disease?
excessive accumulation of copper in tissues due to increased absorption or decreased elimination in feces
very low ceruloplasmin levels
50
What is the genetic cause of Wilson's disease?
genetic defect in ATP7B, which encodes a copper-transporting ATPase 2
normally transports copper into bile and plasma and attaches copper to ceruloplasmin
51
What are the clinical manifestations of Wilson's disease?
liver: cirrhosis, chronic inflammation
brain: degeneration and cavitation of putamen, globus pallidus, caudate nuclei, thalamus, brain stem
eye: Kayser-Fleisher rings
52
What are the treatments for Wilson's disease?
oral chelation therapy with D-penicillamine or trientine
zinc administration (blocks copper absorption
53
What type of virus is Hep A? How is it transmitted?
RNA
food-borne, water-borne, shellfish, possible sexual transmission, fecal-oral
54
What type of virus is Hep E? How is it transmitted?
RNA
fecal-oral, possible sexual transmission, water-borne epidemics
55
What type of virus is Hep B? How is it transmitted?
DNA
sexual, transfusion, needle stick, drug abuse, etc.
56
What type of virus is Hep C? How is it transmitted?
RNA
sexual, transfusion, needle-stick, drug abuse, etc.
57
What type of virus is Hep D? How is it transmitted?
RNA (needs HepB antigen to infect)
sexual, transfusion, needle-stick, drug abuse, etc.
58
What serotypes of hepatitis are likely to cause chronic changes?
Hep C most likely, also Hep B (and subsequently Hep D)
59
What types of hepatitis can cause hepatocellular carcinomas?
Hep B and Hep C (when chronic)
60
What is the hepatitis B virion?
dane particle (encodes a bunch of proteins that cause disease)
61
What antibodies are associated with HBsAg? HBcAg? HBeAg?
HBs: IgM and IgG anti-HBsAg
HBc: IgM and IgG anti-HBcAg
HBe: anti-HBeAg
62
What Hep C genotype is associated with hepatic steatosis?
genotype 3
63
What are the lab characteristics of chronic Hep C?
elevated ALT, AST, and HCV RNA in serum
64
How is Hep A replicated?
replicates in intestinal mucosa first, then liver parenchymal cells
increase in IgM at onset that lasts for months, increase in IgG at onset that lasts for life
65
What is the pathology of acute viral hepatitis?
lobular disarray --\> smudging of cellular outlines
ballooning and acidophilic hyaline bodies
focal hepatic necrosis
lymphocytic parenchymal and portal inflammation
cholestasis
kupffer cell and macrophage hypertrophy/hyperplasia
66
What is the clinical presentation of acute viral hepatitis?
malaise, fatiguability, nausea, fever, muscle joint pains, jaundice phase
ALT and AST increased
67
What is the clinical course of acute hep A and hep E?
rarely becomes fulminant hepatitis, no chronicity
68
What is the chronic carrier state of acute viral hepaitis?
persistence of Hep B as an asymptomatic carrier
69
What is the progression of chronic hep B?
asymptomatic carrier --\> chronic hepatitis --\> cirrhosis of liver --\> hepatocellular carcinoma
70
What phase of infection is suggested by IgM anti-HAV? IgG?
IgM: acute hep A
IgG: recovered, immunity
71
What is the significance of anti-HbsAg? Absent antibody in the presence of hep B infection?
anti-HbsAg: total recovery, immune to HBV
absent: acute disease/chronic carrier
72
What is the significance of IgM anti-HBcAg? IgG?
IgM: acute HBV
IgG: past exposure, cured or carrier
73
What are major causes of chronic hepatitis?
hep B, hep C, autoimmune hepatitis, drug-induced hepatitis, metabolic disorders
74
What type of hepatitis is suggested by ground glass cells in liver?
hepatitis B infection
75
What type of hepatitis is suggested by lymphoid follicles in portal areas, fatty change and bile duct damage?
hep c infection
76
What type of hepatitis is suggested by cholestasis, eosinophilic infiltration, bile duct damage, granulomas?
drug-induced hepatitis
77
What type of hepatitis is suggested by prominent plasma cell infiltrate?
autoimmune hepatitis
78
What does this section suggest?
iron accumulation
* brown pigment on left = iron*
* blue pigment on right = hemosiderin stain*
79
What do these sections suggest?
alpha-1 antitrypsin mutation
## Footnote
* top image = round inclusions of mutated protein*
* bottom image = prominent round deposits, cirrhotic scars*
80
What does this section suggest?
Wilson disease
## Footnote
*glycogenated nuclei, steatosis*
81
What does the section on the right suggest?
chronic portal inflammation associated with chronic viral hepatitis
82
What diagnosis does this section suggest?
chronic hep B
## Footnote
*ground-glass hepatocytes*
83
What does this section suggest?
cirrhosis (nodular)
84
What is the dietary composition of fat? How much of it is absorbed?
diet: triacylglycerol, cholesterol esters, phospholipids, unsaturated fatty acids, fat soluble vitamins
almost all (98%) is absorbed
85
What is the structure of a triglyceride?
glycerol backbone + three fatty acids
86
What is a saturated vs. unsaturated fatty acid?
saturated = no double bonds
unsaturated = 1+ double bonds
87
Lingual and gastric lipases hydrolyze __________ from triacylglycerol, generating \_\_\_\_\_\_\_\_\_\_\_\_
one fatty acid; diacylglycerol and one free fatty acid
88
Pancreatic lipases hydrolyze __________ from triglyceride to generate \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
2 faty acids; 2-monoacylglyerol plus 2 free fatty acids
89
How does bile get into the intestine?
liver makes bile --\> stored in gallbladder until a meal --\> gallbladder contracts causing bile to enter the duodenum through the sphincter of Oddi
90
How do bile salts act on fats?
promote formation of mixed micelles to the brush border of the intestinal mucosal cells
91
What happens to fat after it reaches enterocytes?
taken up into enterocytes by passive diffusion --\> long-chain fatty acids resynthesize triglycerides --\> packaged with ApoB48 + cholesterol esters + phospholipids into chylomicrons and transfered to lymphatics via exocytosis
## Footnote
*short and medium chain fatty acids are absorbed directly into portal circulation*
92
Describe enterohepatic circulation of bile acids.
bile salts transfer lipids to enterocytes and then remain in intestinal lumen --\> some get passively reabsorbed, most are taken up in the ileum (via a transporter), some are lost to fecal excretion (5%)
93
Where are bile salts reabsorbed?
small intestine (ileum)
colon
94
How is bile acid synthesis regulated?
bile acids bind to a nuclear receptor (FXR) in intestine in liver --\> triggers cascade that suppresses an enzyme that makes bile acids (CYP7a1) and releases FGF19 (suppresses bile acid synthesis)
95
Which one of the following statements is true? Digestion of triglycerides by pancreatic lipase:
a) produces 2-monoacylglycerol (MAG) and free fatty acids
b) yields products which are less soluble in water than the triglycerides
c) requires fatty acyl-CoA before lipase can attack the triglycerides
d) produces only glycerol and short-chain fatty acids
e) is followed by simple diffusion of the digestion products and released into the portal circulation
a) produces 2-monoacylglycerol (MAG) and free fatty acids
96
Which one of the following statements is true? Bile salts act to:
a) emulsify dietary lipids and form chylomicrons
b) aid in the absorption of short-chain fatty acids
c) prevent resynthesis of triglycerides in the enterocyte
d) convert VLDL particles to LDL particles
e) emulsify triglycerides and form mixed micelles
e) emulsify triglycerides and form mixed micelles
97
Which of the following is not true of bile?
a) the major organic molecules in bile are bile acids, cholesterol, and phospholipids
b) hepatic bile is more concentrated than gallbladder bile
c) excretion in bile is a major source of elimination of cholesterol from the body
d) cholecystokinin stimulates the release of bile into the duodenum after a fatty meal
e) an excess of biliary cholesterol relative to bile acids and phospholipids promotes gallstone formation
b) hepatic bile is more concentrated than gallbladder bile
98
Which of the following is true of enterohepatic circulation of bile salts?
a) the enterohepatic circulation allows the return of bile acids to the liver through the systemic circulation
b) about 95% of bile salts are absorbed in the colonvia passive uptake
c) bile acids returning to the liver stimulate synthesis of new bile acids from cholesterol
d) uptake of bile acids in intestinal cells stimulate release of FGF19
e) the bile acid pool recirculates about once daily
d) uptake of bile acids in intestinal cells stimulate release of FGF19
99
What does the gallbladder do to bile?
concentrates and acidifies it
100
What is the difference between absorption of short/medium chain and long chain fatty acids?
short/medium: transported directly in enterocytes
long: re-esterified to triglycerides and transported in chylomicrons
101
What are the primary bile acids in humans? How are they synthesized?
cholic acid, chenodeoxycholic acid
synthesized from cholesterol with CYP7A1
102
What are intrahepatic causes of cholestasis? Extrahepatic causes?
intrahepatic: impaired flow of bile acids out of hepatocytes into bile canaliculi
extrahepatic: blockage of extrahepatic bile ducts
103
What are the consequences of cholestatic liver disease?
liver toxicity (excess bile acids in hepatocytes)
itching (from bile acids) and jaundice (bilirubin)
fat malabsorption
104
Where does the common hepatic duct arise?
from the confluence of left and right hepatic ducts
105
What are cholangioles?
terminal bile ducts that pass through portal tracts to become interlobular ducts
106
How is the common bile duct formed?
common hepatic duct + cystic duct from gallbladder join together
107
What is the function of the choledochoduodenal junction?
regulates flow of bile and pancreatic enzymes and filling of gallbladder
108
What is the ampulla of vater?
the location where the common bile duct and pancreatic duct join at the duodenum
109
What is the extrahepatic phase of bilirubin formation?
aged RBCs are broken down and heme is catabolized to unconjugated bilirubin --\> unconjugated bilirubin binds to albumin and travels to liver
110
What is the hepatic phase of bilirubin formation?
unconjugated bilirubin is conjugated (by UGT1A1) and becomes water soluble
111
How is bilirubin excreted?
conjugated bilirubin is water soluble and diffuses through cytoplasm to bile canaliculi and excreted into bile by an energy-dependent mechanism
112
What is the mechanism of prehepatic jaundice?
excess production of unconjugated bilirubin --\> hemolysis, hemolytic anemia, ineffective erythropoiesis
113
What is the mechanism of hepatic jaundice?
liver conditionsthat lead to buildup of bilirubin
114
What is Gilbert syndrome?
a genetic defect in the promoter region of the gene encoding UDP-glucuronosyltransferase 1 (enzyme that conjugates bilirubin) leading to impaired clearance of unconjugated bilirubin
115
What is Crigler-Najjar syndrome?
mutations in the UDP glucuronosyltransferase 1 gene leading to severe unconjugated hyperbilirubinemia
## Footnote
*milder if heterozygous*
116
What is the mechanism of posthepatic jaundice?
cholestasis due to extrahepatic biliary tree problems
117
What is the clinical presentation of cholestasis?
1) impaired bile formation/flow
2) conjugated hyperbilirubinemia
3) increased serum bile acids
4) increased serum lipids
5) increased serum alk phos levels (disproportionate to serum transaminase levels)
118
What is the mechanism of pruritis associated with cholestasis?
retention of pruritogens, bile acids in the skin
119
What is primary biliary cholangitis? Who does it typically affect?
chronic cholestatic disease of unknown etiology
mostly occurs in white, middle aged females
120
What is the pathophysiology of primary biliary cholangitis?
unknown etiology, involves immunologic-autoimmune components
includes antibodies to anti-mitochondrial antibodies (AMA)
121
What are the clinical features of primary biliary cholangitis?
pruritis (itching), fatigability, jaundice, xanthomas (cholesterol tumors), osteoporosis, osteomalacia
122
What are the laboratory findings of primary biliary cholangitis?
- elevated alk phos
- antimitochondrial antibodies (AMA)
- antibodies against 2-oxo acid dehydrogenase complex
123
What pathological findings are associated with primary biliary cholangitis?
- chronic, non-suppurative destructive cholangitis (septal and interlobular bile ducts)
- epithelioid granulomas with cytotoxic T cells and inflammation in portal tracts
- loss of ducts
- progression to biliary cirrhosis
- increased risk of liver cancer
124
What is primary sclerosing cholangitis?
chronic liver disease with persistently elevated serum alk phos
125
What gastric condition is associated with primary sclerosing cholangitis?
inflammatory bowel disease (specifically ulcerative colitis)
126
What are the findings of primary sclerosing cholangitis on cholangiopgraphy?
stricture, beading, irregularities of the intrahepatic and extrahepatic biliary system
127
What are the liver biopsy findings associated with primary sclerosing cholangitis?
imflammation, cholangitis, fibrosis, obliteration of intralobular and septal bile ducts, ductopenia, biliary cirrhosis
128
What complications are associated with primary sclerosing cholangitis?
cholestasis, cholangiocarcinoma, colorectal cancer, colitis, hepatocellular carcinoma
129
What are the basic morphologic patterns of extrahepatic biliary atresia?
1) obstruction of common bile duct with patent hepatic ducts
2) obstruction of hepatic ducts with patent porta hepatis ducts
3) obstruction of bile ducts at the porta hepatis
130
What are the 5 "F"s associated with cholelithiasis?
female, fat, fair (white), fertile, fifty
131
What are the major types of gallstones?
pure cholesterol stones: solitary, round/oval, radiating crystalline structure
pigment stones: predominantly calcium bilirubinate, trace cholesterol
mixed stones
132
What are the three steps of cholesterol gallstone formation?
1) cholesterol in bile in an unstable state, making it susceptible to precipitation
2) cholesterol must be nucleated (either alone - homogenous, or with other substances - heterogenous)
3) nucleated structure grows into a stone
133
What causes cholecystitis?
obstruction of the cystic duct, often by a gallstone
leads to distended, tense, and discolored duct and possible perforation
134
What are the complications of calculous cholecystitis?
pancreatitis, hydrops/emphyema, porcelain gallbladder, perforation, bile peritonitis, fistulas
135
What is the most common type of carcinoma of the gallbladder?
adenocarcinoma
136
A patient dies shortly after a diagnosis of primary sclerosing cholangitis. What was the neoplasm?
cholangiocarcinoma
137
What are possible causes of extra-hepatic cholestasis?
primary sclerosing cholangitis, stones, carcinoma, congenital (atresia), trauma/stricture
138
What does this histology suggest?
primary biliary cholangitis
139
What does this histology show?
primary sclerosing cholangitis
## Footnote
*bile ductules with onion-skin concentric fibrosis*
140
What populations are at risk of hep A? How do they contract it?
more common in underdeveloped areas without access to vaccines
fecal/oral is main route of transmission; associated with poor hygiene, IV drug use, etc.
141
What is the pathogenesis of hepatitis A infection?
HAV enters via small intestine --\> travels to liver where it replicates --\> travels through biliary system to small intestine --\> sheds in feces to infect more people
142
What are the signs/symptoms of hep A?
jaundice, fever, fatigue, abdominal pain, nausea, vomiting, arthralgias
can also be asymptomatic
143
How is hep A diagnosed?
HAV IgM detection for active infection
no viral load test
IgG detection defines immunity
144
Is there a vaccine for hep A?
yes
145
Who is at risk of catching hep B? how is it transmitted?
prevalant globally, blood-borne virus and sexually transmitted
146
What are the major virulent proteins produced by hep B?
1) sAg --\> marker of carrier status
2) polymerase (reverse transcriptase)
3) core Ag --\> nucleocapsid
4) protein X --\> gene activation
147
What is the pathogenesis of hep B?
exists mainly in hepatocyte nuclei
148
What are the symptoms of hep B?
determined by age of acquisition
can be asymptomatic or present with jaundice, fatigue, abdomoinal discomfort, etc.
149
What are the main serologies associated with hep B?
sAg and total antibodies (IgG and IgM)
viral load can also be measured
150
What serologies are associated with resolved hep B infection?
clearance of sAg while Ab is still present in the serum
151
What is the treatment for hep B?
usually not needed, only recommended if viral load is high and there is advanced fibrosis
treat with: reverse transcriptase inhibitors (low cure rate)
152
What is the risk of maternal-to-child transmission in hep B?
correlated to viral load, risk with c-section or vaginal delivery
153
What cancer screenings are needed for hep B?
hepatocellular carcinoma
monitor semi-annually with CT or MRI and alpha-fetal protein
154
How is hep C transmitted?
IV, intranasal drug use, tattoos, etc.
155
What is the pathogenesis of hep c?
mostly in hepatocytes, but can have extra-hepatic reservoirs
liver damage is due to viral cytotoxicity and immune mechanisms
most patients will have chronic disease
156
What is the treatment for hep C infection?
most patients spontaneously resolve
in patients that do not resolve, use oral anti-viral cocktail with a high cure rate (but very expensive)
157
Is there a vaccine for Hep C?
no
158
What cancer screenings are required after hep c diagnosis?
hepatocellular carcinoma screening semi-annually
159
How is hep D transmitted?
parenteral transmission (IV drug use, sex)
co-infection with hep B
160
What is the serological difference between Hep D co-infection and superinfection?
co-infection: HDV IgM and viral load with typical acute HBV serologies
super-infection: HDV IgM/IgG and a viral load with markers of crhonic HBV
161
How is Hep D treated?
treat hep B --\> hep D cannot survive without hep B
162
Is there a hep D vaccine?
no, but the hep B vaccine acts as a de facto hep D prevention mechanism
163
How is hep E transmitted?
fecal oral transmission, under cooked food, poor sanitation
mostly occurs in central america, africa, and asia
164
How is hep E diagnosed?
elevated liver injury tests with symptoms
sometimes IgM and viral load can be measured
165
What are three risk factors for hepatitis A?
poor sanitation, IV drug use, homelessness
166
How do you determine the status of a suspected HBV patient?
serologies are the first-order tests
cAb (IgM/total) and sAg (and sAb)
viral load is measured to determine infectivity
167
Why is treatment not given to all chronic HBV patients?
current therapy is effective at viral suppression, but not immune-activation --\> medication will be needed for life and is not curative
168
How do you differentiate between HCV exposure and active disease?
exposure: positive Ab test
viral load suggests active disease
169
Who should be tested for HCV infection?
all individuals 18+ should have antibody testing once
170
What is the essential HBV component for HDV replication?
HDV cannot replicate without sAg from HBV
171
Which population has high risk mortality if exposed to HEV?
HEV is generally an acute viral infection
can have high risk mortality in pregnant patients or in solid organ transplants
172
What phase of hep B illness is this:
positive IgM anti-HBc
positive HBeAg
high HBV DNA
increased ALT
acute hbv
173
What phase of hep B illness is this:
negative IgM anti-HBc
positive HBeAg
high HBV DNA
normal ALT
chronic, immune tolerant HBV
174
What phase of hep B illness is this:
negative IgM anti-HBc
positive HBeAg
high HBV DNA
increased ALT
chronic, immune active hbv
175
What phase of hep B illness is this:
negative IgM anti-HBc
negative HBeAg
low HBV DNA
normal ALT
chronic hbv, inactive carrier
176
Which serotype of hepatitis does this describe:
acute illness, controlled through sanitation/vaccination
HAV
177
Which serotype of hepatitis does this describe:
serologies key to assessment, treatment determined by liver status/risk and viral load
HBV
178
Which serotype of hepatitis does this describe:
screen if \> 18 and/or pregnant, pan-genotypic, treatment with high cure rate and low-side effects (but expensive)
HCV
179
Which serotype of hepatitis does this describe:
requires sAg for viability
HDV
180
Which serotype of hepatitis does this describe:
acute illness, high pregnancy fatality rate
HEV
181
What enzyme conjugates bilirubin?
UGT1A1
182
What vitamin deficiencies are seen in cholestasis? Symptoms?
malabsorption of fat soluble vitamins (due to lack of bile flow)
vitamin D --\> rickets
vitamin K --\> coagulopathy
vitamin A --\> night blindness
vitamin E --\> neuropathy
183
What are the general mechanisms of neonatal jaundice?
increased production of bilirubin
decreased excretion of bilirubin
combination
184
What are causes of neonatal jaundice secondary to increased bilirubin production?
fetal-maternal bloodgroup incompatibilities
extravascular blood in body tissues
polycythemia
red blood cell abnormalities
induction of labor
185
What are causes of neonatal jaundice secondary to decreased excretion of bilirubin?
breast feeding
increased enterohepatic circulation
inborn errors of metabolism
hormones and drugs
prematurity
hepatic hypoperfusion
cholestatic syndromes
biliary tree obstruction
186
What are causes of neonatal jaundice secondary to increased production and decreased excretion of bilirubin?
sepsis
intrauterine infection
congenital cirrhosis
187
When is neonatal jaundice abnormal?
- before 36 h of age
- persists beyond 10 days of age
- higher than 12 mg/dL
- elevation of direct-reacting fraction of bilirubin
188
189
What is Gilbert's syndrome?
a rare genetic syndrome due to alteration in promoter for the bilirubine uridine diphosphage glucuronyl transferase (UDP-GT) gene
leads to mild indirect hyperbilirubinemia and a benign clinical course
190
What is Crigler-Najjar syndrome?
type 1: severe, complete absence of UDP-GT, high bilirubins, can lead to brain damage (kernicterus)
type 2: partial activity of UDP-GT, less severe, responsive to phenobarbital
191
What is dubin johnson syndrome?
genetic deficiency in cMOAT/MRP2 gene, which encodes the transporter of conjugated bilirubin
manifests as mild conjugated hyperbilirubinemia with no evidence of hepatocellular/canalicular injury
192
What is idiopathic neonatal hepatitis?
idiopathic liver disease characterized by multi-nucleated giant cells
presents with jaundice and hepatosplenomegaly
diagnosis of exclusion
193
What is gestational alloimmune liver disease/neonatal hemochromatosis?
a rare condition associated with extrahepatic siderosis caused by maternal antibodies crossing the placenta and attacking the neonatal liver
poor survival rate, treated by treating the mother
194
What are the neonatal symptoms of alpha 1 antitrypsin deficiency?
neonatal cholestasis, juvenile cirrhosis, chronic hepatitis, hepatocellular carcinoma
195
What is galactosemia?
a defect in galactose-1-phosphate uridyl transferase that leads to accumulation of toxic metabolites of galactose
clinical manifestations: lethargy, vomiting, acidosis, cataracts, UTI, jaundice, hemolytic anemia
196
What is tyrosinemia?
an autosomal recessive deficiency of fumarylacetoacetate hydrolase that leads to build up of tyrosine metabolites
clinical presentation: acute liver dysfunction, jaundice, hepatomegaly, ascites, rickets, predisposition to hepatocellular carcinoma
197
What is the treatment for galactosemia? Tyrosinemia?
dietary avoidance
tyrosinemia can also be treated with NTBC to reduce formation of metabolites
198
What is intrahepatic alagille's syndrome?
characterized by reduced interlobular bile ducts with associated multi-system abnormalities
caused by genetic disruptions of chromosome 20 affecting the NOTCH signaling pathway
presents as jaundice and conjugated hyperbilirubinemia
199
What are choledochal cysts?
female \> male, more prevalent in asians
anatomic cyst that presents as abdominal pain, jaundice, palpable RUQ mass
can also present with fever, nausea, vomiting, and pancreatitis
200
What is biliary atresia? What are the two major types?
extrahepatic obstruction of the bile ducts that presents with jaundice, pale color stools
two types: splenic malformation (embryonic origin), perinatal viral infection leading to inflammation of bile ducts
201
What is the treatment for biliary atresia?
surgical correction to circumvent the biliary tree
may need transplant later on
202
A patient has jaundice, mild RUQ tenderness (without Murphy's sign), bilirubinemia, elevated alk phos with normal ALT/AST. What is on the differential? How would you distinguish between etiologies?
cholestasis
use imaging (ultrasound) to determine if there is biliary obstruction (extrahepatic) or no obstruction (intrahepatic)
203
What is the likely diagnosis for a patient with fatigue, pruritis, abdominal pain, and jaundice with elevated alk phos and GGT? What antibody is likely positive in this patient?
primary biliary cholangitis
AMA
204
What is the genetic pattern associated with Gilbert's disease?
TATA box mutation --\> 7+ TAs in the TATA box leads to Gilbert's disease
mutation in promoter region for the gene of interest
205
What genetic mutations cause intrahepatic cholestasis of pregnancy?
mutations in the Abcb4 gene (liver transporter)
206
What type of cancer is associated with cirrhosis?
hepatocellular carcinoma
207
(micronodular or macronodular) cirrhosis has a greater predisposition to hepatocellular carcinoma
**macronodular** cirrhosis has a greater predisposition to hepatocellular carcinoma
208
What is cirrhosis?
a diffuse disease process where fibrous septa and regenerative liver nodules distort the normal lobular architecture
209
What components contribute to fibrosis in cirrhotic livers?
increases in all types of collagen (especially type I)
*via increased synthesis and decreased degradation*
also stellate cell activation
210
\_\_\_\_\_\_\_ cell activation, initiation, and perpetuation contributes to fibrosis in cirrhosis
**stellate** cell activation, initiation, and perpetuation contributes to fibrosis in cirrhosis?
211
What are the characteristics of liver nodules in cirrhosis?
hyperplastic, regenerative, and pre-neoplastic
caused by proliferation of surviving hepatocytes
can be micronodular or macronodular
212
What is the difference between the pathology of micronodular and macronodular liver nodules?
micronodular: small, uniform, no portal triads
macronodular: large, irregular, coarse, contain portal triads and/or central veins
213
What viruses can cause cirrhosis?
hep B and C
214
What toxins can cause cirrhosis?
plant, fungal toxins, synthetic chemicals, some drugs
215
What are metabolic causes of cirrhosis?
hemochromatosis, wilson's disease, alpha-1 antitrypsin deficiency
216
What are causes of prehepatic portal hypertension?
portal vein thrombosis or compression
217
What are hepatic causes of portal hypertension?
cirrhosis, parenchymal disease
218
What are post-hepatic causes of portal hypertension?
budd-chiari syndrome, heart failure
219
What complications of portal hypertension are associated with increased collateral circulation?
esophageal varices, hemorrhoids, umbilical vein
220
When cancer metastasizes to the liver, where does it come from?
frequently from stomach, colon, lung, breast, pancreas
## Footnote
*tumors from organs that drain into portal circulation*
221
Liver metastases are usually (singluar or multiple)
Liver metastases are usually **multiple**
222
What are the major types of primary liver tumors?
hepatocellular carcinoma (most common)
tumors of bile duct epithelium (ex. cholangiocarcinoma)
223
\_\_\_\_\_\_\_\_\_ and ________ (drugs) predispose to hepatic adenoma
oral contraceptives and contraceptive steroids
224
What are the major characteristics of hepatic adenoma?
benign tumor
often asymptomatic
highly vascular, risk of rupture
225
What factors predispose to hepatocelluar carcinoma?
alcohol, cirrhosis, aflatoxin B, hep B or C, non-alcoholic fatty liver disease (and obesity)
226
What lab value can be used to assess for hepatocellular carcinoma?
increased alpha fetoprotein
227
What is cholangiocarcinoma?
adenocarcinoma arising from bile duct epithelium, leads to obstructive symptoms
higher incidence in elderly
228
What are the general mechanisms that lead to cirrhosis and hepatocellular carcinoma?
chronic inflammation, fibrosis, reactive oxygen species, oxidative damage
229
What does the thickness of liver cell plates indicate?
one cell thick --\> normal liver
two cells thick --\> regeneration of damaged liver
three + cells thick --\> hepatocellular carcinoma
230
The image on the left represents normal liver histology. What is the image on the right?
neoplasm --\> no normal liver architecture or portal tracts
231
What does the image on the left represent?
cholangiocarcinoma
232
What differentiates compensated and decompensated cirrhosis?
compensated: asymptomatic for the most part, may have lab anomalies
decompensated: overt clinical complications (ex. jaundice, ascites)
233
What is the pathophysiology of portal hypertension?
fibrosis of hepatic sinusoids + inflammation + increased blood volume + clot formation + increased vascular tone
234
How does blood volume contribute to portal hypertension?
increase in nitric oxide increases splanchnic arterial flow --\> increased cardiac output from decreased peripheral vascular resistance --\> overall total body volume overload (into third spaces)
235
What role does vascular tone play in the pathophysiology of portal hypertension?
SNS alpha1 receptor stimulation leads to increased vascular tone in intrahepatic vessels
236
What symptoms are associated with decompensated cirrhosis?
cognitive errors/slow thinking
abdominal fullness, leg swelling, weight gain
fatigue
237
What physical exam findings are associated with decompensated cirrhosis?
cognitive errors or asterixis
volume overload (ascites, pitting edema)
malnutrition (muscle wasting)
238
What lab findings are associated with decompensated cirrhosis?
low albumin, sodium, platelets, cholesterol, and BUN
high INR, ammonia, and bilirubin
variable liver test findings
239
What is ascites? How is it diagnosed?
excessive fluid into the peritoneal cavity
diagnosis: consistent symptoms, fluid wave or shifting dullness on exam, fluid on imaging, paracentesis
240
What is the pathophysiology of ascites?
cirrhosis leads to splanchnic vasodilation --\> reduces effective arterial circulating volume (including to kidneys) --\> to renal vasoconstriction and activation of RAA system, sympathetic nervous system, and vasopressin --\> water retention, increased thirst response, vasoconstriction, increased cardiac output
eventually the liver can't hold all the blood it is getting, so ultrafiltrate of blood weeps into peritoneum
241
What are the treatments for ascites?
sodium restriction
diuretics
paracentesis
transjugular intrahepatic portosystemic shunt (TIPS)
liver transplant
242
What is spontaneous bacterial peritonitis?
infected ascitic fluid in the peritoneal cavity
243
What are the symptoms of spontaneous bacterial peritonitis?
may be asymptomatic or may have confusion and intense abdominal pain with guarding
244
What peracentesis findings are associated with spontaneous bacterial peritonitis?
\> 250 neutrophils/mm3
245
What is the pathophysiology?
occurs only in the setting of ascites
bacteria enters the ascitic fluid through intestinal wall or lymphatics
normal ascitic fluid has anti-infectious properties, but as it gets worse (and if there is malnutrition) infection is more likely
246
What is the treatment for spontaneous bacterial peritonitis?
antibiotics with broad spectrum coverage IV for 5 days
247
What is hepatic hydrothorax?
abnormal collection of ascitic fluid in the thoracic cavity, often right-sided
248
What are the physical exam findings on hepatic hydrothorax?
diminished breath sounds on auscultation, hypoxemia
249
How is hepatic hydrothorax diagnosed?
symptoms (dyspnea), physical exam (decreased breath sounds), opacities on chest x-ray, fluid on thoracentesis (used to determine etiology)
250
What is the pathophysiology of hepatic hydrothorax?
same pathophysiology of ascites --\> ascitic fluid travels from peritoneal space into pleural space through holes in the diaphram (driven by negative intra-thoracic pressure)
251
What are the treatments for hepatic hydrothorax?
sodium restriction, diuretics, thoracentesis, transjugular intrahepatic portosystemic shunt, pleurodesis, liver transplantation
252
What is hepatopulmonary syndrome?
a secondary lung disorder caused by intrapulmonary shunting due to intrapulmonary vascular dilation and neo-angiogenesis
253
How is hepatopulmonary syndrome diagnosed?
symptoms (platypnea), spider angiomata on chest, low PaO2, positive bubble study on echo (vessels dilated enough for bubbles to pass through)
254
What is portopulmonary hypertension?
A sub-type of pulmonary arterial hypertension that is caused by excessive vasoconstrictors leading to smooth muscle hyperplasia/hypertrophy, thrombosis, and fibrosis in pulmonary arteries
255
What is hepatorenal sydrome?
a syndrome caused by decreased renal perfusion caused by reduced effective circulating volume as a sequelae of portal hypertension
diagnosis of exlusion
256
How is hepatorenal syndrome diagnosed?
symptoms: increased weight gain, decreased urine output
exam: ascites, edema
labs: oliguria, increased creatinine, urine studies (pre-renal etiology)
257
What is the treatment for hepatorenal syndrome?
vasoconstrictor + vasodilator inhibitor (octeotride), oncotic support
## Footnote
*not curative*
258
What are esophageal varices?
enlarged natural or neo-angiogenic veins that are caused by portal hypertension
caused by hepatofugal flow from the liver that backs up in smaller vessels
259
What are the treatments for esophageal varices?
volume control, coagulopathy, control of portal hypertension, octreotide (splanchnic vasoconstriction), acid suppression, antibiotics to prevent infection, TIPS, liver transplant
260
What is hepatic encephalopathy?
altered mental status due to toxin build up in the brain
nostly due to ammonia that is unable to be effectively cleared due to liver damage
261
What are the symptoms of hepatic encephalopathy?
altered mental status, disorientation, errors in comprehension/memory, decreased bowel movements
262
How do NSbetaB medications work to reduce portal hypertension in patients with varices?
they lower cardiac ouptut (beta1 blockade) and constricting the splanchnic nerves (beta2 blockade) that feed the portal system
263
Why does hyper-ammonemia develop in patients with cirrhosis?
ammonia is produced throughout the body by host and bacterial processes and is normally metabolized by liver, kidney, and muscle
in cirrhosis, metabolic efficiency is compromised leading to build up of nitrogenous compounds
264
What is the basis for treatments for hepatocellular carcinoma?
HCCs are fed by the hepatic artery, which is the main target of treatment
