Chapter 18-Liver Flashcards
1
Q
What is the main blood supply for the liver
A
The portal vein provides 60-70% of blood flow
2
Q
What are the three components of the portal triad
A
- Portal veins
- Hepatic arteries
- Bile ducts
3
Q
Ischemic and hypoxic events are most likely to affect which zone of the hepatic lobule
A
Zone 1
4
Q
Drugs and toxins in the liver are most likely to damage which lobular zone
A
3
5
Q
What are the main primary diseases of the liver
A
- Viral hepatitis
- NAFLD
- Alcoholic liver disease
- hepatocellular carcinoma
6
Q
What are the cytosolic serum measurements that can be ordered to investigate the integrity of the liver
A
AST
ALT
Lactate dehydrogenase (LDH)
7
Q
What is the serum measurement that can be take for testing the biliary excretory function
A
- Serum bilirubin
- Urine bilirubin
- Serum bile acids
8
Q
What is direct serum bilirubin looking at
A
The amount of conjugated bilirubin
9
Q
Which tests can be ordered to evaluate the love of damage to the bile canaliculus
A
Serum alkaline phosphatase
Serum gamma-glutamic transpeptidase (GGT)
10
Q
Which serum level can be used to test for the amount of hepatic demethylation
A
Aminopyrine breath test
11
Q
What are the two major hepatic changes that are reversible
A
Steatosis and cholestasis
12
Q
What is the process and condition if there are councilman bodies or acidophil bodies present
A
Hepatic apoptosis
13
Q
What is confluent necrosis and where does it normally begin
A
Widespread necrosis where there is zonal loss due to toxic or ischemic events, usually starting around a central vein
14
Q
What is a bridging necrosis event
A
Zone of necrosis that links central veins to portal tracts or bridges them
15
Q
IN the regeneration of the liver, which cytokines are present in the priming phase
A
TNF and IL6
16
Q
IN the regeneration of the liver, which cytokines are present in the growth phase
A
HGF and TGF-alpha
17
Q
What is the principal cell involved in the hepatic scar deposition
A
Hepatic stellate cell
18
Q
What is the function of the stellate cell in a quiescent form
A
Lipid Vitamin A storage
19
Q
What does the stellate cell become in the phase of hepatic repair
A
Highly fibrotic myofibroblasts
20
Q
What is the process that initiates the stellate cells to become myofibroblasts
A
- Increased production of platelet derived growth factor Beta receptor (PDGFR-Beta) in the stellate cells
- Increased production of TGF-Beta and receptors
- increased metalloproteinase 2 (MMP2)
- Increased tissue inhibators of metalloproteinase 1 and 2 inhibators (TIMP2)
21
Q
Once stellate cells become myofibroblasts, what is their function
A
Are contractile cells and are activated by endothelin-1 (ET-1)
22
Q
What percentage of the liver functional capacity must be affected to cause hepatic failure
A
80 to 90%
23
Q
What defines a case of acute hepatic liver failure
A
Acute liver illness with encephalopathy and coagulation that occurs 26 weeks after an initial liver injury, and must in the absence of pre-existing liver disease
24
Q
What is the most common cause of acute liver failure
A
Massive hepatic necrosis, most often induced by drugs or toxins
25
Ingestion of which toxic is the most common cause of acute liver toxicity
50% occur due to ingestion (accidental or purposefully) of acetaminophen
26
IN Asia, what is the most common cause of acute liver toxicity
Hepatitis B and E
27
What is the time frame that acetaminophen causes liver toxicity
Within a week
28
IN the case of direct liver toxicity like with acetaminophen, what is the size and characteristic of the liver
Small and shrunken, without signs of scarring or regeneration due to the quick nature of the toxicity and failure.
29
What are the feature of the liver when damage is caused by viral infection
Failure is due to weeks or months of injury, so while the attack is acute, it will still show signs of regeneration and scarring
30
What are the conditions that can cause poisoning of the liver cells without any evidence of cell death and parenchymal collapse
Diffuse microvascular steatosis related to fatty liver of pregnancy and reactions to toxins
31
Which toxins can cause diffuse microvascular steatosis
Valproate and tetracycline
32
What is the general clinical presentation of acute liver failure
- Nausea, vomiting, and jaundice
| - Followed by encephalopathy and coagulation defects
33
Cholestasis increases the risk of which condition
Life threatening bacterial infections
34
Hepatic encephalopathy is characterized by what presentations
- Confusion, stupor, coma or death
- Rigidity and hyperreflexia
* asterixis (rapid extension/flexion of the head and extremities)
35
How will Asterixis present and is characteristic of which condition
Rapid flexion/extension of the head and extremities, best seen with arms are in extension and wrists are dorsiflexed.
-Indicative of hepatic encephalopathy
36
The encephalopathies seen in hepatic failure are due to abnormal levels of what in the serum
Ammonia leading to neural dysfunction
37
What is the relation between hepatic failure and coagulation issues
Liver produces vitamin K dependent and independent clotting factors, so impaired hepatic function decreases, there is a decrease in the ability to clot, along with the development of DIC
38
What is hepatorenal syndrome defined as
Renal failure that is occurring in patients with hepatic failure, with no appearance or reason for kidney failure
39
What is the result of hepatorenal function on the serum concentrations
Decreased GFR and renal perfusion pressure due to:
- Systemic vasodilation
- activation of SNS
- Increased renin/angiotensin axis
- Increased renal vasoconstriction
40
What is chronic liver failure most associated with and what is the morphology of the result
Liver cirrhosis, characterized by regenerative parenchymal nodules surrounded by fibrous bands and vascularization
41
How do cirrohosis livers appearances during a biopsy tend to not develop portal hypertension
-narrow, dense, and compacted septa which are separated by large islands of intact parenchyma
42
How do cirrohosis livers appearances during a biopsy tend develop portal hypertension
-Broad bands of dense scarring, with dilated lymphatic spaces, with less intervening healthy parenchyma
43
How will patients with cirrhosis present in the clinic
Anorexia, weight loss, weakness
44
What are the normal causes of fatality in those patients with cirrhosis
- Hepatic encephalopathy
- Bleeding of esophageal varicose veins
- Bacterial infections
45
During chronic liver injury, even if the cause is removed, which risks factors still remain
- Portal hypertension due to formation of irreversible shunts
- Hepatocellular carcinoma
46
What are common effects seen in chronic liver failure with regards to hormones and their result
Impaired estrogen metabolism, leading to hyperestrogenemia:
- palmar erythema (local vasodilation)
- spider angiomas
- hypogonadism and gynocomastia
47
What are the common causes of prehepatic conditions leading to portal hypertension
Obstructive thrombosis
Narrowing of the portal vein
Increased splenic venous blood flow
48
What are the common causes of posthepatic conditions that lead to portal hypertension
Right sided heart failure
Constructive pericarditis
Hepatic vein outflow obstruction
49
What is the main cause of intrahepatic conditions leading to portal hypertension
Cirrhosis
50
What is the leading cause of hepatic hypertension
Cirrhosis
51
Alteration in sinusoidal endothelial cells contribute to intrahepatic vasoconstriction and Portal Hypertension through which chemicals
- Decrease in NO
- Increased endothelin-1 (ET-1)
- Angiotensinogen
- Eicosanoid
52
What is the correlation between splanchnic circulation changes and portal hypertension
- Increased portal venous blood flow from hyperdynamic circulation caused by vasodilation in the Splanchnic circulation
- Overall leads to increased venous efflux
53
What is the most common cause of ascites
Cirrhosis
54
In the case of patients with ascites, what does the presence of neutrophils in the fluid mean
Infection
55
In the case of patients with ascites, what does the presence of blood in the fluid point to
Disseminated intra-abdominal cancer
56
With long standing ascities, what is the process of hydrothroax and which side is it more common on
-Seepage of peritoneal fluid through trans-diaphragmatic lymphatics, usually on the right side
57
What are the three mechanism that can lead to ascites pathogenesis
1-sinusiodal hypertension
2-percolation of hepatic lymph into the peritoneal cavity
3-Splanchnic vasodilation and hyperdynamic circulation
58
What is happening in the sinusoidal hypertension as a result of ascities pathogensis
Alterations in Starling’s forces, which drive fluid into space of Disse (also promoted by hypoalbumininemia), where it is removed by hepatic lymphatics
59
What is the happening in the percolation of hepatic lymph into the peritoneal cavity as a result of portal hypertension and formation of ascites
With cirrhosis, normal lymph flow is far exceeding what is normally does, so there is more than the thoracic duct can handle. As a result, protein rich and triglyceride poor fluid accumulates as part of the ascites fluid
60
In the case of patients with ascites, what does the presence of splanchnic vasodilation and hyper-dynamic circulation as a result of portal hypertension that results in ascites
Arterial vasodilation in the splanchnic circulation and reduces that arterial blood pressure. The CO is unable to compensate and as a result vasoconstrictors are activated,leading to excess fluid leaving into the abdominal cavity
61
What is the result on the spleen as a result of liver congestion
Splenomegaly, leading to hypersplenism, such as thrombocytopenia and pancytopenia
62
What is hepatopulmonary syndrome and what is a common cause
Seen in 30% of patients with cirrhosis and portal hypertension:
-When the intrapulmonary vasculature dilates, including capillaries, resulting in hypoxia
63
What is mechanism of hepatopulmonary syndrome
-Intrapulmomsry vasculature, including capillaries, dilate. This results in ventilation/perfusion mismatch and hypoxia, creates and right to left shunt
64
What position that exacerbates hepatopulmonary syndrome
Dyspnea in the upright position
65
What are the clinical findings of portopulmonary hypertension and what is the common cause
Caused by liver disease and portal hypertension, leading to vasoconstriction and vascular remodeling of the pulmonary arteries
-dyspnea upon exertion and clubbing of the fingers
66
What is a cause of acute on chronic liver failure with regards to hepatitis origin
-Chronic Hepatitis B infection in a patients who become infected with hepatitis D
67
What is the cause of acute on chronic liver failure with regards to ascending cholagitis
Ascending cholagitis in a patients with primary sclerosing cholagitis is fibropolycystic liver disease
68
Overall, what is the very general mechanism of acute on chronic liver disease
-A well compensated chronic liver disease undergoes distress when an acute and new toxin/event causes changes that the remaining parenchyma can not handle
69
What is the usually clinical course and outcome of Hepatitis A infection
Usually benign, self limited disease with 2-6 weeks of incubation period
70
What are the common locations that Hepatitis A infections are occuring
Places with poor hygiene and sanitation with a fecal oral transmission
71
Which marker is a reliable indication for an acute hepatitis A infection
Anti HAV IgM titer, as a rise in this also indicates lack of fecal shedding
72
What are the five potential outcomes from a hepatitis B infection
1-Acute hepatitis with recovery and clearance
2-nonprogressive chronic hepatitis
3-progressive chronic disease with cirrhosis
4-acute hepatic failure with massive liver necrosis
5-asympatmatic healthy carrier
73
Which cancer is hepatitis B an important precursor for
Hepatocellular carcinoma (even in the absence of cirrhosis)
74
The carrier rate for hepatitis B is largely determined by which factor
The age of infection, as infection in children leads to a higher carrier rate
75
What is the main transmission route for hepatitis B
90% is due to transmission during childbirth
76
In areas of low levels of Hepatitis B prevalence, what is the most common route of transmission
Sexual contact or drug use
77
How are most hepatitis B infections prevented
Use of the vaccine as it is 95% successful
78
What is the location of hepatitis B during active and chronic infections
In the Blood
79
What percentage of patients with chronic hepatitis due to hepatitis B recover
1-2% of the patients spontaneously clear the infection
80
What is the result of most patients with an acute or subclinical disease
Recovery
81
What is the result of the majority of patients who develop chronic hepatitis
Cirrhosis
82
What is the function of the hepatitis B preform region
Directs the secretion of the core region aka HBeAg
83
What is the activity of the Pol portion of hepatitis B
A polymerase that is a DNA polymerase and reverse transcriptase
84
What portion of the hepatitis B virus has been indicated in cancer and which cancer is it
HBx (activates transcription) in hepatocellular carcinoma
85
What are the levels of HBsAg over the course of a hepatitis B infection
HBsAg:
- Appears before onset of symptoms
- Peaks during disease
- Undetectable by week 12
86
What are the levels of anti-HBs antibody over the course of a hepatitis B infection
Anti-HB antibodies:
- Rises after acute distress
- Usually after the disappearance of HBsAg
87
What are the levels of HBeAg, HBV-DNA, and DNA polymerase over the course of a hepatitis B infection
Appear in serum after HBsAg, and present during viral replication
88
What marker is the HBeAg used to monitor
Continues viral replication, infectivity, and progression to chronic hepatitis
89
What does the presence of anti-HBe antibodies imply
Acute infection has peaked and is winding down
90
What is the main determinant of the result of a hepatitis B viral infection
Host immune response
91
During the hepatitis B infection, what is causing the destruction to the liver
CD8 T cells
92
What is the best predictor of chronicity of hepatitis B infection
Age (the younger at onset, more likely to develop)
93
What are the common risk factors for hepatitis C
- IV drug users (54%)
- Sexual partners (36%)
- Surgury in last 6 months (16%)
- Needle stick (10%)
- Contact with infected with HCV (10%)
94
What is the target of the hepatitis C antibodies and what is the characteristic of that target
-E2 protein is the target, but serves to be the most variable portion of the virus
95
Why is there no vaccine to hepatitis C
-Genomic instability and antigenic variability as even the presence of IgG does not incur lifelong immunity
96
What is a typical feature of the clinical infection course of disease for hepatitis C
-Repeated bouts of hepatic damange due to the reactivation of preexisting infection or the emergence of an endogenous, new strain
97
Which condition is very commonly associated with hepatitis C infected patients
Chronic disease in (80-90%), resulting in cirrhosis in 20% of them
98
In those patients with chronic hepatitis, which test should be run for diagnosis and what is it evaluating
Hepatitis C RNA testing for assessment of viral replication and conformation of diagnosis
99
In patients with chronic hepatitis C viral infection, what is a characteristic serum finding
Persistent elevations in serum aminotransferases
100
Which syndrome is highly associated with hepatitis C infection
Metabolic syndrome, as it can cause insulin resistance and NAFLD, particularly with genotype 3
101
Treatment of hepatitis C infection with what can possibly provide a cure
Pegylated IFN
| Ribavirin
102
Patients with which hepatitis C genotype are generally likely to have a better response to treatment
2 or 3
103
Which polymorphism can result in better responses to hepatitis C treatment
Polymorphism in the IL28B gene
104
What is the general clinical outcome in a patient who is infected with a co-infection of the Hepatitis B and D
Usually self limiting and there is clearance of both viruses in healthy non-IV drug users
105
Which population is at a higher risk of acute hepatic failure when co-infected with hepatitis B and D
IV drug users
106
What is the result in patients who are infected with chronic hepatitis B and are inoculated with hepatitis D
Superinfection, resulting in chronic hepatitis D in almost all patients
107
What is the most reliable indicator of hepatitis D viral infection
IgM anti-HDV antibodies
108
What is the route of infection of hepatitis E and what is the common patient population affected
Zoonotic disease (pigs) that is a water Bourne infection primarily occurring in young to middle aged adults
109
Which patients are at an increased risk of poor prognosis as a result of infection with hepatitis E
Pregnant women as mortality is 20%
110
What is the relationship between hepatitis E and immunocompetent patients with regards to chronic conditions
Does not cause chronic liver disease or persistence of viremia
111
What are the clinical features of hepatitis infections with acute asymptomatic infection with recovery
- Subclinical and only found accidental
| - Minimally elevated serum transaminases
112
What are the clinical features of hepatitis infections with scute symptomatic infection with recovery
1) Incubation period
2) symptomatic preicteric phase
3) symptomatic icteric phase
4) Convalescence
113
What are the clinical features of hepatitis infections with acute liver failure
Hepatitis A and E are most common causes
| -activation of stem cells from canal of Hering, no other real symptoms/treatments other than supportive
114
What are the clinical features of hepatitis infections with chronic hepatitis
All Changes continuing or relapsing diseases for longer than 6 months:
- Elevations in transaminases
- prolonged prothrombin time
- fatigue
- hepatomegaly, hepatic tenderness and mild splenomegaly
115
Which condition is commonly found to have cyroglobulemia
Chronic hepatitis C infection (in 35% of patients)
116
What percentage of patients with an acute hepatitis C viral infection with progress to a chronic hepatitis
80%
117
The presence of spotty necrosis or lobular hepatitis are indicative of which kind of injury
Acute viral hepatitis
118
In severe acute hepatitis, where is the damage seen and what are the common histological findings
Occurs around the central veins and accompanying severity are central-portal bridging necrosis, along with even worse parenchymal collapse
119
What is the characteristic histological feature of chronic viral hepatitis
Mononuclear portal infiltration
120
What condition is found to have interface between the hepatocellular parenchyma and portal tract stroma, along with scarring
Progressive chronic hepatitis
121
What is the histological progression of chronic hepatitis infection histologically
- Only the portal ducts exhibit fibrosis at first
| - Over time, there is increasing ductular reaction, which reflects the stem cell action
122
Which condition is characterized by histological feature of ground glass hepatocytes
Hepatitis B, caused by ER swelling by HBsAg
123
Which condition shows lymphoid aggregates or fully formed lymphoid follicles, commonly with fatty changes
Hepatitis C
124
Which parasite is the common cause of cholangiocarcinoma in Southeast Asia
Liver flukes
125
What are hydatid cysts caused by and what is usually used to confirm the diagnosis
Caused by echinococcal infections and are confirmed by their calcification in the cyst walls
126
Autoimmune hepatitis is commonly associated with which HLA
DRB1 alleles
127
What are the common patient populations seen to have autoimmune hepatitis
White females
128
Which autoimmune hepatitis is known to affect middle aged to older individuals
Type 1
129
Which autoimmune hepatitis is known to affect individuals in their teens and children
Type 2
130
Type 2 autoimmune hepatitis are known have antibodies against which antigens
- antinuclear (ANA)
- antismooth muscle actin (SMA)
- anti-soluble liver antigen/liver-pancreas (SLA/LP)
- anti-mitochondrial (AMA)
131
Type 1 autoimmune hepatitis are known have antibodies against which antigens
- Anti-liver Kidney microsomes 1(LKM-1)
- Anti-CYP2D6
- Anti-liver cytosol-1 (ACL-1)
132
How is autoimmune hepatitis distinguished from viral hepatitis
The time frame, as viral hepatitis is a slower longer period of destruction and subsequent scarring. Autoimmune hepatitis is rapid damage, followed by rapid scarring
133
Which condition is characterized histologically by plasma cell predominance in inflammatory infiltrates and “rosettes” in ares of activity
Autoimmune hepatitis
134
How would acute hepatic damage be differentiated as the origin from drug toxicity or autoimmune hepatitis
Both will have little/no scarring:
Autoimmune hepatitis- Confluent necrosis
Drug toxicity- Lobule necrosis
135
Which patient population tends to have a better prognosis with regards to autoimmune hepatitis
Adults over children
136
What is the result of liver transplantation in patients with autoimmune hepatitis
-High 10 year survival, but there is a 20% chance of recurrence
137
What conditions are autoimmune gastritis associated with
Autoimmune conditions, particularly primary biliary cirrhosis (more common) or primary sclerosing cholangitis
138
What is the most common agent the produces toxic liver injury
Alcohol
139
What is the manner in which predictable reactions affect all people
Dose dependent manner
140
What is the most common toxins causing acute hepatic failure and the need for a liver transplant
Acetaminophen
141
What aspect of acetaminophen is toxic and where is it formed
CYP450 in the liver creates a toxic byproduct
142
What are two examples of idiosyncratic reactions that cause liver damage
- chlorpromazine
| - halothane
143
What is the leading cause of liver disease in most western countries
Excessive alcohol consumption
144
What are the three distinctive forms of alcoholic liver injury
1-Hepatocellular steatosis or fatty change
2-Alcoholic hepatitis
3-Steatofibrosis
145
What are the morphological findings in hepatic steatosis (fatty liver)
-Lipid begins as small droplets that coalesce into large droplets which distend the hepatocytes and push the nucleus aside, but is completely reversible
146
What does the presence of hepatocytes swelling and necrosis, Mallory Denk bodies, and Neutrophilic reactions signify
Alcoholic (steato-) hepatitis
147
What is the histological findings of the hepatocytes swelling and necrosis that is seen in alcoholic hepatitis
Ballooning of cells and necrosis due to the accumulation of fat and water
148
What is the histological findings of Mallory-Denk bodies
Clumped, amorphous, eosinophilia material in ballooned hepatocytes, leaving almost an “empty” cytoplasm
-characteristic of alcoholic liver disease
149
What are the contents of the Mallory Denk bodies made of
Keratins 8 and 18 in complex with proteins such as ubiquitin
150
What are the morphological characteristics of the neutrophil reaction seen in alcoholic hepatitis
Neutrophils penetrate the lobule and accumulate around the Mallory Denk bodies
151
What are the histological findings of alcoholic steatofibrosis
- Fibrosis of the central vein and space of Disse, resulting in a chicken wire pattern
- Continues use results in perisinusoidal scarring leading to mucronodular or Leanne’s cirrhosis
- Can have the loss of hepatocytes and fatty accumulation
152
Which gender is more likely to develop hepatic injury and what is the cause
Women, because the estrogen dependent response to LPS in the liver
153
Which nationalities are more likely to develop cirrhosis
African Americans
154
Polymorphisms in which genes can cause the increased risk for hepatic injury
ALDH2
155
What is the response on cells during exposure to alcohol
-Steatosis, mitochondrial and cellular membrane dysfunction, hypoxia, and oxidative stress
156
What is the reasoning behind alcohol causing steatosis
Shunting of substrates from catabolism toward lipid biosynthesis due to increased NADH
157
What are the biochemical results of alcohol ingestion
- Increased NADH
- Decreased assembly and secretion of lipoproteins
- Increased free fatty acids
158
What are the methods in which alcohol can cause cellular dysfunction
- Acetaldehyde causes lipid peroxidation and skeletal membrane dysfunction
- CYP450 metabolism causes production of ROS
- impaired methionine production and decreased glutathione
159
Alcoholic hepatitis can usually arise following which event
Heavy bout of drinking
160
What are the common serum finding of alcoholic liver disease that can differentiate it from other chronic liver diseases
-AST elevated 2:1 over ALT
161
What are the common causes of death in end stage alcoholics
- Hepatic coma
- massive GI bleed
- Intercurrent infection
- Hepatorenal syndrome
- Hepatocellular carcinoma
162
What is the most common cause of chronic liver disease in the US
NAFLD
163
What condition does NAFLD increase the risk for and how is it different from the other forms that cause it
Increased risk for hepatocellular carcinoma, but does so without the presence of scarring like the other causes
164
What about the cells in NAFLD place it at a higher risk for dysfunction
- Increased production of proinflammatory cytokines
| - Increased risk for lipid peroxidation generated by oxidative stress
165
Which pathway correlates with the amount/stage of fibrosis in NAFLD
Shh
166
What are the 4 conditions that at least one must be present to be considered for metabolic syndrome
- DM
- Impaired glucose tolerance
- Impaired fasting glucose
- insulin resistance
167
What are the conditions that 2 must be present to be considered for metabolic syndrome
- BP >140/90
- waist/hip > .9
- BMI >30
- dyslipidermia (TG > 1.965, HDL 20 microgram/min)
168
pathological steatosis is defined as having what
More than 5% of hepatocytes
169
In NASH, how is it differentiated from NAFLD
Mononuclear cells are more prominent, Mallory-Denk bodies are less prominent
170
Previous cryptogenic cirrhosis cases are now being thought to represent which condition
Burned out NAFLD
171
How does pediatric NAFLD different from adult cases
- More diffuse steatosis
- Portal rather than central fibrosis
- Portal and parenchymal mononuclear inlitration rather than neutrophils
172
What is the most reliable diagnosis for NAFLD and NASH
Liver biopsy
173
What serum levels are elevated in 90% of patients with NASH
ALT and AST
174
What is the frequent cause of death in patients with NASH
Cardiovascular disease
175
What is the name of the stain that is used to show the chicken wire pattern in steatosis
Masson trichromatic stain
176
What is the general mechanism of hemochromatosis
Excessive iron absorption that gets deposited in the parenchymal organs such as liver pancreas, as well as heart, joints and endocrine organs
177
What occurrence leads to secondary hemochromatosis
Excess blood transfusions or other parenteral administration of iron
178
Which three findings are exhibited in fully developed cases of hemochromatosis
- Micronodular cirrhosis in all patients
- DM in 75 % of patients
- Abnormal skin pigment in 75% of patients
179
What is the common age that hemochromatosis will emerge in men, and what about women
40s and 50s for men
| Later for women due to menstration
180
What are the mechanism that excessive iron in hemochromatosis causes damage
- Lipid peroxidation bur iron catalyzed free radicals
- Stimulation of collagen formation by the activation of stellate cells
- Integration of reactive oxygen species with DNA, leading to injury and HCC
181
What is the main regulator of iron absorption and the gene responsible for it
Hepcidin, which is coded by HAMP game
182
What are the conditions that will increase the coding of hepcidin
Inflammatory cytokines and iron
183
What are the conditions that will decrease the amount of coding for hepcidin
- Iron deficiency
- Hypoxia
- ineffective erythropoiesis
184
What is the mechanism of action for hepcidin
Binds to the efflux channel ferroportin, which causes the internalization and proteolysis and the inhibition of release from intestinal cells and macrophages. Overall, this results in the lower plasma levels of iron
185
What are the proteins that regulate the level of hepcidin
- HJV
- TFR2
- HFE
186
Most adult forms of hemochromatosis are caused by which mutation and what is the function of that protein
HFE, which codes and HLA class 1 like molecule that controls intestinal absorption of dietary iron by regulating the levels of hepcidin synthesis.
187
What is the mutation in the HFE gene that causes hemochromatosis
Cytosine to tyrosine at 282 (aka C282Y)
188
Which hemochromatosis most common mutation gene is most common in which patient group
HFE mutation most common in white patients
189
Which mutations causing hemochromatosis is more likely to cause severe juvenile hemochromatosis
HAMP and HJV
190
Which condition is characterized by the following conditions:
- Deposition of hemosiderin in liver, pancreas, myocardium etc
- Cirrhosis
- pancreatic fibrosis
Hemochromatosis
191
What is the stain used to identify hemochromatosis and what is being identified
-Prussian blue stain looking for hepatocellular iron
192
What are secondary conditions seen with hemochromatosis
- Pseudogout
| - Testes are small and atropic
193
What are the clinical manifestations of hemochromatosis
- Hepatomegaly
- abdominal pain
- abnormal skin color
- DM due to pancreatic damage
194
What are the two causes of death usually in patients with hemochromatosis
HCC and cardiac disease
195
Which condition does hemochromatosis predispose patients for
200x more likely to develop HCC
196
What is the effect of fixing the iron overloading in hemochromatosis
Risks still remain for the HCC because of the DNA damage already being done
197
What is the presenting features of neonatal hemochromatosis and what is the cause
Cause is not hereditary, but normally damage to the liver in utero
- Severe liver disease
- Extrahepatic hemosiderin Deposition
198
How is neonatal hemochromatosis detected
Buccal biopsy for extra hepatic deposition
199
What are the most common causes of secondary hemochromatosis
Ineffective erythropoiesis:
- thalassemia
- myelodyspastic syndromes
200
Wilson’s disease is caused by a mutation in which gene
ATP7B
201
What is the heritability of Wilson’s disease
Autosomal recessive
202
In Wilson disease, what is being deposited and in what common locations
-Copper, normally in the eye, brain, liver
203
What is the mechanism of disease in Wilson disease
ATP7B gene loss results in the decreased expression of copper transporters that eliminate excess copper
204
What are the three mechanisms that excess copper causes toxicity
1-Formation of free radicals by the Fenton reaction
2-Binding to sulfhydryl groups of proteins
3-Displacing other metals in hepatic metalloenzymes
205
Which stains are used for the identification of copper in Wilson disease
```
Rhodamine stain (copper)
Orcein stain (copper assoacited proteins)
```
206
Wilson’s disease primarily affects which portion of the brain
Basal ganglia, mainly the putamen
207
Which conditions may be confused with Wilson disease
Parkinson
208
What are the diagnostic features of Wilson disease
- Decreased serum ceruloplasm
- Increased hepatic copper content (most sensitive/accurate)
- increased urinary excretion of copper (most specific)
209
What is the heritability of alpha-1 antitrypsin deficiency
Autosomal recessive
210
What the organs affected in alpha-1 antitripsin deficiency
Liver (over accumulation of misfolded proteins)
| Lungs (lack of Alpha1AT to inhibit elastase)
211
What is the most common clinically significant mutations
PiZ coding for the PIZZ protein
212
What is the most commonly diagnosed inherited hepatic disorder in infants and children
Alpha1- Antitrypsin deficiency
213
Where in the liver does the misfolded PIZZ protein accumulate
ER of the hepatocytes
214
What is the stain used for identifying alpha-1 antitrypsin deficiency
PAS stain with diastase
215
Which histological feature is characterized in alpha 1 antitrypsin
Cytoplasmic globular inclusions in the hepatocytes, which will stain magenta
216
In patients with alpha1 AT deficiency, which activity should be avoided at all costs
Smoking, as it will increase the rate of emphysema
217
What are the properties of unconjugated bilirubin properties with the solubility, toxicity, and ability to be excreted
Insoluble in water, so is tightly bound to albumin
No not be excreted in urine
Toxic
218
What are the properties of conjugated bilirubin with regards to solubility, toxicity, and ability to be excreted in urine
- Water soluble, and loosely bound to albumin
- Non-toxic
- Can be excreted via urine (when levels are high)
219
What is the function of the protein UGT1A1
Hepatic conjugating enzyme
220
What are the heritability of the diseases that results in excess conjugated bilirubin
Autosomal recessive
221
What are the only conditions that result in predominantly conjugated hyperbilirubinemia, and was is the result
Usually innocuous
- Dubin Johnson syndome
- Rotor Syndrome
222
What is cholestasis
Impaired bile formation and bile flow that gives rise to accumulation of bile pigment in the hepatic parenchyma
223
What are the clinical presentations of a patient with cholestatis
- Jaundice
- Pruritus
- Skin xanthomas
- intestinal malabsorption of vitamins A,D,K,E
224
What are the clinical lab findings that would indicate cholestasis
Elevated alkaline phosphate
| Elevated glutamyl transpeptidase (GGT)
225
Which conditions may histologically have fine foamy appearance, looking like “feathery degeneration” as a result of bile pigmentation accumulation
Cholestasis
226
What is the most common cause of bile duct obstruction in adults
-Extrahepatic cholelithiasis
227
What are the three main causes of bile duct obstruction
- Extrahepatic cholelithiasis
- Malignancies of biliary tree/head of pancreas
- strictures from procedures
228
What is ascending cholangitis
Secondary bacterial infection of the biliary tree
229
What is the clinical presentation of cholangitis
Fever, chills, abdominal pain, and jaundice
230
What is the most severe form of cholangitis
Suppurative, where the purulent bile fills and distends the bile ducts
231
What is the histological hallmark of ascending cholangitis
Influx of peridcutal neutrophils directly into the bile duct epithelium and lumen
232
What are the histological findings seen in acute biliary obstruction
- neutrophil influx into the bile duct epithelium
- feathery degeneration (from cholestasis)
- Mallory-Denk bodies
- formation of bile infarcts
233
Which condition is most likely to cause cholestasis of sepsis
-Response to circulating microbial products, especially those in gram neg bacteria
234
What is the most common form of cholestasis
Canalicular cholestasis (around the centrilobular canaliculi)
235
What is the prognosis of ductular cholestasis
Poor, especially if there are bile plugs present, causing the dilation of tracts, often accompanying or proceding septic shock
236
What is hepatolithiasis
Disorder of intrahepatic gallstones that leads to repeated cases of ascending cholangitis, leading to progressive inflammatory destruction of hepatic parenchyma
237
Which condition is more likely to develop during hepatolithiasis
Cholangiocarcinoma
238
What is the only common location for hepatolithiasis
Asia, aka oriental cholangitis
239
What is the morphology for hepatolithiasis
Pigmented calcium bilirubinate stones in a distended intrahepatic bile duct
240
Which condition produces histological findings that look like irregular shapes, similar to jigsaw puzzle shapes
Biliary cirrhosis
241
What are the major causes of prolonged conjugated hyperbilirubinemia in neonates
- biliary atresia
| - neonatal Hepatitis
242
Why is it crucial to differentiate between biliary atresia and neonatal hepatitis
Because the treatments are different:
- Biliary atresia (Kasai procedure to fix)
- Neonatial hepatitis (procedures may cause complications)
243
What are the clinical presentations of neonatal hepatitis
- Jaundice
- Dark urine
- acholic stools
- hepatomegaly
244
What are the histological findings of neonatal hepatitis
- Giant cell transformation of hepatocytes
- hepatocellular and canalicular cholestasis
- mononuclear infiltrates of portal areas
- reactive changes in Kupffer cells
- extramedullary hepatopoiesis
245
What is biliary atresia
Complete or partial obstruction of the lumen of the Extrahepatic biliary tree within the first 3 months of life
246
What is the number one cause of death from liver disease in early childhood and accounts for 50% of children referred for liver transplants
Biliary atresia
247
What are the common conditions seen in association with the fetal form of biliary atresia
Abnormal development of organs:
- lack of laterality of Thoracic duct
- inversus malrotation of abdominal viscera
- interrupted IVC
- polyspenia
- Congentical eart disease
248
What is the overall cause of fetal form of biliary atresia
Aberrant intrauterine development of the extrahepatic biliary tree
249
What is the most common cause of biliary atresia
Perinatal form
250
What is the pathogensis of the perinatal form of biliary atresia
Normal development of the biliary tree, but is destroyed following birth.
251
Which conditions of biliary atresia are correctable
- Limited to the common duct (Type 1)
| - Limited to the right and left hepatic bile ducts (Type 2)
252
Which condition of biliary atresia is not correctable
Type 3, obstruction of the ducts at or above the porta hepatic
253
What are the clinical presentations of biliary atresia
- Normal north weight and postnatal weight
- Normal stools will begin to change to acholic stool
- Death within 2 years without transplant
254
What is the primary biliary cirrhosis characterized by
No suppurative, inflammatory destruction of small and medium sized hepatic bile ducts. Large ducts are not involved
255
Where is primary biliary cirrhosis most prevalent geographically
Northern European and Minnesota
256
How related is primary biliary cirrhosis in families
Increased risk
257
What is the most characteristic laboratory finding in primary biliary cirrhosis
Antimitochondrial antibodies
258
What are the target of the most commonly seen antibodies in primary biliary cirrhosis
E2 of the pyruvate dehydrogenase complex
259
What is the histological finding in the condition of primary biliary cirrhosis
- Florid duct lesions, where the interlobular bile ducts are actively being destroyed by lymphocytes
- Periportal/periseptal cholestasis
260
What is a distinguished organ size characteristic of primary biliary cirrhosis
Hepatomegaly
261
What is a treatment for primary biliary cirrhosis that slows down the progression of the disease
Ursodeoxychilic acid
262
What are the symptoms seen as primary biliary cirrhosis progresses
- Skin hyper pigmentation
- xanthelasmas
- steatorrhea
- Vitamin D osteomalacia
263
What is primary sclerosing cholangitis characterized by
Inflammation and obliterative fibrosis of the intrahepatic and extrahepatic bile ducts
264
Which conditions are commonly associated with primary sclerosing cholangitis
IBD, and UC
265
Which HLA is associated with primary sclerosing cholangitis
HLA-B8
266
Which conditions is commonly seen when there are degenerating bile ducts entrapped in an “onion skin” scar
primary sclerosing cholangitis
Aka a tombstone scar
267
What is the laboratory finding that may accidentally find primary sclerosing cholangitis
Elevated levels of alkaline phosphate
268
What are choledochal cysts
Congenital dilations of the common bile duct
269
Which patient group is commonly seen to have choledochal cysts
Female Children before age of 10
270
The development of Choleductal cysts increase the risk of which condition in older patients
Bile duct carcinoma
271
What are the common conditions seen with fibropolycystic disease
1-Von meyeberg complexes (bile duct hamartomas)
2- Small biliary cysts (Caroli disease)
3- Congentical hepatic fibrosis
272
What are the conditions assoacited with fibropolycystic disease caused by
Ductal plate malformations
273
Fibropolycystic liver disease commonly occurs with which condition
Autosomal recessive polycystic renal Disease
274
Which gene is involved in polycystic kidney disease as well as fibrocystic liver disease
Polycystin
275
Patients with fibrocystic liver disease are at a higher risk for which condition
-Cholangiocarcinoma
276
When will a hepatic artery thrombosis cause infarction
In transplanted patients because there is only arterial supply to the biliary ducts
277
In those patients with extrahepatic portal vein obstruction, which condition is assoacited 25% of the time, and which underlying condition is commonly present
Cirrhosis is present in 25% of cases, with an underlying thrombophlebitis genotype
278
What can the intrahepatic portal vein radicle be abstracted by
Acute thrombosis
279
What is the result of intrahepatic portal vein radicles being blocked by an acute thrombosis
- Does not cause an ischemic infarction
- Causes a sharply demarcated area of red/blue discoloration called the infarct of Zahn
- Results in severe hepatocellular atrophy and stasis around the sinusoids
280
WHich condition is going to result in the infart of Zahn
Acute Thrombotic event in the intrahepatic portal vein radicles
281
What are the results of a small portal vein branch disease
Noncirrhotic portal hypertension with portal fibrosis and obliteration of the small portal vein branches
282
What is the most common small portal vein branch obstruction
Schistosomiasis, where the eggs lodge and obstruct
283
Small portal vein branch disease seen in East Asia is commonly in which patient group and with which associated condition
Female, Japanese, and rheumatologist diseases
284
Which treatments or conditions increase the risk of small portal vein branch disease
- Untreated HIV
| - anti-retroviral treatment
285
What is the most common intrahepatic cause of blood flow obstruction
Cirrhosis
286
Which conditions can cause sinusoidal occlusion through the liver
- Sickle cell
- DIC
- Eclampsia
- metastatic cancer
287
What is the condition of peliosis hepatis
Sinusoidal dilation that causes the efflux of hepatic blood to be impeded
288
What are some causes of peliosis hepatis
- Bartonella
| - Sex hormone administration
289
What are fetal outcomes of peliosis hepatis if the underlying cause is not treated
-Intraabdominal hemorrhage or hepatic failure
290
Which condition is defined as obstruction of two or more major hepatic veins producing liver enlargement, pain, and ascites
Budd Chiari syndrome
291
During Budd-chiari Syndrome, what is the actual mechanism causing damage
Increased intrahepatic blood pressure
292
Which conditions are hepatic vein thrombosis associated with
myeloproliferative disorders:
- polycythemia Vera
- coagulation disorders
- antiphospholipid antibody syndrome
- paroxysmal nocturnal hemoglobinuria
- HCC
293
What is the morphology seen during budd-Chiari syndrome
Liver is swollen with a red-purple, tense capsule
| -Alternating pattern of hemorrhagic places with those that are regenerating
294
What is the mortality rate in untreated acute hepatic vein thrombosis
High
295
What are the primary settings that sinusoidal obstructive syndrome develops
- Following allogenic hematopoietic stem cell transplantation within the first 3 weeks
- cancer patients receiving chemotherapy
296
What is the pathogenesis of sinusoidal obstructive syndrome
Toxic injury to the sinusoidal endothelium, which obstructs the blood flow
297
What is the histological characteristic of sinusoidal obstruction syndrome
Obliteration of the terminal hepatic venules by subendothelial swelling and collagen deposition
298
What is the cause of passive congestion of the liver
Right sided heart failure
299
What is the morphology of the liver following right sided heart failure
Congestion of the centrilobular sinusoids
300
What is the cause of the appearance of the nutmeg liver
Right sided heart failure provides the passive congestion (red portion) while the left sided heart failure results in hypoxia (orange color)
301
How many days after transplantation does graft versus host disease occur with liver transplantation
10 to 50 days following
302
What are the morphological changes seen in graft versus hosts disease in the liver
Hepatitis with necrosis of hepatocytes and bile duct epithelial cell, inflammatory cells in the bile duct epithelium
303
What is the final pathogenesis of chronic rejection of a liver
Obliterative arteriopathy of the small and large arteries, which lead to the ischemic changes in the liver parenchyma, ultimately resulting in vanishing bile duct syndrome
304
What is the most common cause of jaundice in pregnancy
Viral hepatitis
305
How does pregnancy change the course of a viral hepatitis infection, and what is the exception
Does not change the course of the viral hepatitis infection, except for HEV, which causes more severe of a cause in pregnant women, leading to 20% fatality
306
What are the presentations of preeclampsia
- Maternal hypertension
- Proteinuria
- Peripheral edema
- Coagulataive abnormalities
307
What are the clinical presentations of eclampsia
Hyperreflexia and convulsions
308
What are the histological findings of preeclampsia
Periportal sinusoids containing fibrin deposits associated with hemorrhage into the space of Disse, which leads to Periportal coagulative necrosis
309
When do pregnant women usually present with acute fatty liver of pregnancy
latter half, usually the third trimester
310
What histological and morphological finding can occur and usually resulting in fatality
Subscapular hematoma under the Glisson capsule, which can rupture
311
What is the proposed cause of acute fatty liver of pregnancy
Mother lacks long chain 3-hydroxyacyl CoA dehydrogenase, so when it is produced by the fetus, it causes damage to the mother
312
What is the onset of intrahepatic cholestatis of pregnancy
Third trimester
313
What are the clinical presentations of intrahepatic cholestasis of pregnancy
Darkening of the urine
Occasional light stools
Jaundice
Large increase in the level of bile salts
314
What is focal nodal hyperplasia and it’s characteristic
- Well demarcated, but poorly encapsulated nodule
- In young to middle age adults
- Central stellate scaring
315
Nodular regenerative hyperplasia is most commonly associated with which conditions
HIV infected people
| Rheumatic diseases such as SLE
316
What is the most common type of benign liver tumors
Cavernous hemangioma
317
What are the types of benign liver neoplasm
- Cavernous hemangiomas
| - Hepatocellular adenomas
318
What is the medical emergency associated with hepatocellular adenomas
Intraabdominal bleeding
319
What would place a patient at a higher risk for hepatocellular adenomas
Oral contraceptives
| Anabolic steroids
320
What is the increased risk factor of the oral contraceptives for hepatocellular adenoma
30-40x
321
The majority of hepatocellular adenomas have a mutation of what
Inactivating somatic mutation of HNF1-alpha
322
How many mutations are required for the patients with hepatocellular adenoma tumors with the MODY3
A second somatic mutation
323
Which form of the hepatocellular adenomas are at the highest risk of becoming malignant
Beta-catenin activated hepatocellular adenomas
324
Which condition are inflammatory hepatocellular adenomas associated with
NAFLD
325
What is the only hepatocellular adenoma that does not have a risk of becoming malignant
HNF1 alpha
326
The inflammatory hepatocellular adenoma is associated with which factors
Gp130, IL6
| Via JAKSTAT signaling
327
Which tumor is present if there is complete absence of Liver Fatty acid binding protein (LFABP)
HNF1-alpha hepatocellular adenoma, and immunostaining for it is diagnostic
328
Which tumor is present if with immunostaining, there is a high presence of glutamine synthetase
Beta catenin hepatocellular adenoma (targets downstream GLU synthetase)
329
Which factors are overexpressed in the inflammatory hepatocellular adenomas
-CRP and serum amyloid A
330
What is the most common tumor of early childhood
Hepatoblastoma
331
What are the cell types present in the epithelial type of hepatoblastoma
-small polygonal fetal cells that form acini, tubules
332
What are the cells included in the mixed epithelial and mesenchymal type of hepatoblastoma
-osteosarcoma, cartilage, or striated muscle
333
What is the characteristic pathway activated in hepatoblastoma
WNT
334
Which genes are commmonly mutated in hepatoblastoma
- APC
- Beta catenin
- FOXG1
335
Which familial conditions normally can develop hepatocellular adenomas
- Familial adenomastous polyposis
| - Beckwith-Wildemann syndrome
336
Most hepatocellular carcinomas are associated with areas with this endemic infection
HBV
337
In cases with patients who have HCV, what comes before the malignancy HCC
Cirrhosis
338
What gender is more likely to develop hepatocellular carcinoma
Male
339
What are the most common setting for the emergence of HCC
Chronic liver diseases
340
In Asian and African countries, what can HBV synergize with to increase the risk of HCC
Aflatoxin
341
Which metabolic diseases increase the risk of hepatocellular carcinoma
- Metabolic syndrome, with the obesity, DM, NAFLD
- Hemochromatosis
- alpha1-AT
342
What are the two most common early mutations in the development of hepatocellular carcinoma
P53 and Beta catenin
343
Which mutation in HCC are more likely to be associated with non HBV and more genetic instability
Beta catenin
344
What mutation in HCC is strongly assocaited with aflatoxin
P53
345
What cell size change is directly a premalignant sign
Small cell change
346
What cell size change associated with hepatitis B is a premalignant
Large cell size change
347
What are the histological findings of large cell changes
Normal nuclear to cytoplasmic ratio but scattered normal hepatocytes with larger than normal nuclei
348
What are the histological changes seen in small cell changes
High nuclear to cytoplasmic ratio and the cells are separated by a thickened plates
349
In high grade dysplasia can nodules, what is the characteristic of the blood supply and how does this compare to the low grade
High grade- arteries dominate
| Low grade- arteries and veins
350
What is the most likely route of extrahepatic masses to spread
Arterial supply
351
Where do primary liver tumors preferentially spread
Lungs, usually very late in the course
352
What are the clinical presentation of hepatocellular carcinomas
Fatigue, weight loss, hepatomegaly, abdominal pain in the URQ
353
Elevations of which serum component is elevated in advanced hepatocellular carcinomas
Serum alpha-fetoprotein
354
What are the histological findings of fibrolamellar carcinoma
Large, hard “scirrhous” tumor with fibrous bands
| -Cords and nests of oncocytic hepatocytes separated by dense bundles of collagen
355
What are the 4 causes of death in those patients with hepatocellular carcinoma
1-cachexia
2-GI or esophageal varices bleeding
3-liver failure and coma
4-rupture of the tumor
356
What is the cholangiocarcinoma
Primary malignant tumor of the biliary tree/ducts
357
What areas and which parasite are associated with higher levels of cholagiocarcinoma
in the southeast Asian countries where the liver flukes are endemic
358
Which conditions have an increased risk of developing cholangiocarcinoma
- NAFLD
- HBV and HCV
- liver flukes (opisthorchis and Clonorchis)
- Chronic inflammation ofthe bile ducts
359
The majority of choleangiocarcinomas are what type and in which location
50 to 60% are Klatskin tumors, which are at the junction of the right and left hepatic ducts (aka perihilar)
360
What is the prognosis of choleangiocarcinomas
very very bad
361
What is the most common premalignant lesion for cholangiocarcinoma
Biliary intraepithelial neoplasia 3 (BilIN-3)
362
What type of tumor is choleangiocarcinomas and which product is secreted
Adenomas, which secrete mucin
363
What are the typical histological findings of a choleangiocarcinoma
- Desmoplasia
| - lymphovascular and perineural invasion
364
Which liver malignancy will form a wreath like patter around a central trapped nerve
Perineural
365
What are the causes of a liver angiosarcoma forming
- Vinyl chloride
- Arsenic
- Thorotrast
366
What are hepatic lymphomas associated with and which form do most take
- HCV, HBV, HIV, PBC
| - Diffuse B cell lymphomas
367
What are the common locations that metastasizing to the liver is common
-Colon, Breast, lung, pancreas
