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Flashcards in Liver Pathophys Deck (198):
1

psychometric testing

sensitive for detecting impairment in mild HE 

lead to the identificaltion of minimal HE

2

Wilson's Disease 

inadequate copper excretion and failure of copper to ener circulation as ceruloplasmin --> multiorgan Cu accumulation

ATP7B genetic defect with Autosomal recessive (in hepatocytes, transfers Cu into secretory pway by binding it to ceruloplasmin and facilitates biliary excretion) 

Basal ganglia degernation - depression, parkinsons

Ceruloplasmin decreases, Cirrhosis, Corneal deposits (KF rings) Copper accumulation, Caricnoma (hepatocellular)

Dementia

3

interface hepatitis - AIH

mononuclear infiltrate invading through the limiting plate

4

lab tests to assess liver disease progression 

fibrosis, cirrhosis, seerity 

proteins involved in EC matrix modeling and other blood tests

not gret yet

 

5

Hepatopulmonary Syndrome

present when this triad:

1. Liver disease 

2. impaired oxygenation

3. intrapulmonary vascular dilations (IPVDS) 

decreased GFR 

decreased renal perfusion 

absence of identifiable cause 

6

Labs in Wilson's

low serum ceruloplasmin (if not bound to copper, short half life and degraded quickly) 

low serum Cu (serum Cu actually means Cu bound to ceruloplasmin which is low) 

high urinary Cu (unbound Cu excreted by kidneys) 

High heaptic Cu (biopsy)

7

portal htn in portal vein? 

hypercoag 

trauma 

malignancy

8

direct bilirubin

conjugated Bb is water soluble and can be measred "directly" using colorimetric methods - dye in serum, measure normally 

Normal value is very low. It is about .1-.3mg/dL because the liver is putting out that conjugated bilirubin. So it is not circulating.

9

unconjugated hyperbilirubinemia 

defective uptake and conjugation 

inhereted (defects in UDPGT) 

liver immaturing (physiologic jaundice of newborns Bb = 4-5)

10

Natural history of NAFLD

20% progress to NASH

11% progress to cirrhosis (possible decompensation)

both can progress to HCC 

increased mortality

80% have fatty liver

min progression to cirrhosis 

increased CV, diabetes risk

11

Hepatitis C labs

mostly becomes chronic 

develop anti-HCV but it's not protective

can have ab and may be chronically infected

•You can measure in the acute phase as well as the chronic phase the virus. The antibodies doesn’t tell you that the patient isn’t immune any longer. It is just evidence that they have been affected as some point. It is not like the surface antibodies in HBV that tells you the patient is immune. Most of these people don’t recover

12

treatment of HDV

treat HBV 

if clear HBV will clear HDV 

interferon is only therapy against HDV! 

13

HCV genotype

6! 

1a/1b in US 

imp for treatment

14

labs in liver failure

increased Bb (T and D) 

hypoalbuminemia 

increased PT (INR) 

increased ammonia --> encephalopathy

15

NAFLD

30% of americans have NAFLD

dyslipidemia 

obesity

T2D

comprises "fatty liver" and NASH 

fat droplets in the hepatocytes

16

PSC and IBD

80% have concimitent IBD 

IBD patients have increased risk of PSC

more colitis = greater risk 

must do colo to evaluated for IBD 

17

Treatment for herediatry hemochromatosis 

goal is ferritin <50

phlebotomy is gold standard - improes fatigue, liver enzymes, skin, varices 

does not improve arthralgias 

may imrpove diabetes or cardiac 

weekly for 2 years then maintenence every 3 months for life 

screening of relatives

18

prescott nomogram

risk of toxicity for acetaminophen 

19

primary sclerosing cholangitis 

chronic progressive cholestatic disease of both intra and extra hepatic ducts

inflammation and fibrosis of bile ducts - stricutres and dilation 

80% have concomitant IBD (UC more) 

progressive risk of cholangicarcinoma, HCC, gallbladder cancer 

only treatment is liver transplant

 

20

conjugated bilirubin

direct - water soluble

•Conjugated bilirubin: the bilirubin has already been glucuronized and can be excreted into the bile

21

Course of herediatry hemocrhomatosis 

22

Autoimmune sclerosing cholangitis 

AIH = PSC

like PSC

23

transient elastography

measures liver tissue elasticity by measuring speed of vbrations through parenchma 

detect advanced fibrosis

24

Clinical manifestations of herediary hemochromatosis

1. biochemical - steady increase in Fe stores from birth, clinically quiescent 

2. parenchymal accumulation - elevated ferritin, clinically quiescent 

3. end organ toxicity/failure - 30-50 years, cirrhosis and HCC, CCA, arrithymias and CHF, diabetes 

25

Tx of Wilsons

drugs: goal of negative copper balance 

1. Cu chelators (trientene or D-penicillamine) 

2. maintanence - Zinc, low dose chelators 

3. liver transplant if acute liver failure or cirrhosis

26

hepatorenal syndrope mechanism

cirrhosis 

PHTN

splanchnic vaodilation

reduced EABV 

incrased vasoconstriction/antinaturesisi

renal vasoconstriction

HRS

27

pathogenesis of ascietes

1. PHTN

increased hep sinusoidal P 

vasodilation (esp splanchnic) 

effective vol depletion 

2. activation of endogenous vasocontrictors 

ADH

RAAS 

Sympathetic NS 

3. NET: Na + water retention

increased total body Na with a dilutional hyponaturemia

28

normal ranges for ALT and AST

< 40 IU/L

 

29

TIPS

transjugular intrahepatic porto-systemic shunt 

btwn hepatic vein and portal vein

decreases P 

30

LFTs for cholestasis (altered bile flow) 

bilirubin (also uptake and conjugation) 

alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) 

 

31

GGT

produced by biliar epithelial cells of small interlobular bile ducts and SRE of hepatocytes

increases when induction by toxins, drugs, alcohol

non-specific (high in many conditions)

mostly used to determine if ALP is of liver origin when both elevated - request both together

•So the main use GGT is to see if the ALP that is elevated is from the liver origin.

If both elevated, the most likely reason for the elevation is that they are coming from the biliary tree. So they can be associated to liver disease.

32

type I AIH autoantibodies

ANA 

ASMA 

33

Hepatorenal syndrome

reversible renal failure that occurs in patients w advanced cirrhosis and portal hypertension

marked reduction in GFR 

decreased renal perfusion

absence of identifiable cause

34

Lab Findings in ALD

AST/ALT >2:1

elevated GGT 

high ferratin (inflam marker)

high bili, INR

35

Autoimmune cholangitis

AIH + AMA-negative PBC

UDCA +/- steroids (variable response)

36

AIH pathogenesis

1. env trigger 

2. genetics 

3. autoantigen is cyp4502D6 (anti-LKM ab responds to it) 

4. auto reactivity (molec mimicry, T cell med cascade) 

5. inflammation --> cirrhosis

37

autoimmune hepatitis

chronic hepatitis in young to middle aged women

elevation of aminotransferases

positive ANA and anti-smooth muscle antibodies (type 1) 

or 

mostly in children abs to liver-kidney (type 2) 

•They may have elevation of aminotransferases. But as I said, there is test, not very specific, that could tell you there is hypergammaglobulinemia

•These patients have hypergammaglobulinemia in addition to having autoantibodies like antinuclear antibody or anti smooth muscle antibody

•So middle age women presenting with liver enzyme elevation that has a family of autoimmune diseases. perhaps you can do this type of work up: electrophoresis or autoantibody detection

38

HBV DNA level

PCR 

marker of acute or chronic infection

who to treat and response to treatment

39

how much bilirubin produced daily? 

250-300 mg/dL daily 

 

40

HBV reactive phase

Rise in ALT and High HBV DNA leels 

i.e. if start on immunosuppression, small amt can stay in liver even if cleared

41

what do LFTs assess

hepatocellular injury (aminotransferases - ALT, AST) 

cholestasis -- altered bile flow (biliubin, alkaline phosphatase - ALP, GGT) 

synthetic functio

42

management of alcoholic hepatitis

abstinence 

support/ntrition

steroids and/or pentoxifylline; NAC

43

synthetic liver functions

albumin

clotting factors 

acute phase reactants 

bile acids 

other proteins

44

transferrin

transports iron in the blood 

can only bind 2 Fe atoms at a tome 

20-45% of transferrin is bound to Fe (transferrin saturation) 

45

albumin synthesis in the liver

only made in the liver!

half life= 18-20 

decreased synthesis in chronic liver disease and index of disease severity

46

Medictions for HBV

1. Entecavir 

2. Tenofovir 

^nucletide analogs - inhibit viral DNA pol, less side effects but longer treatment 

don't use interferons as much anymore (side effects)

47

Treatmetn of PBC?

UDCA is the only therapy that slows the progression of PBC and reduces need for transplant 

less bile acid pool hepatotoxicity and decreases inflammation

give bile acid resins or rifampin for pruritis 

48

How do you distinguish between superinfection vs coinfection with HDV? 

superinfection: IgM anti-HBc is negative 

chronic HBV! 

coinfection: IgM anti-HBc is positive 

acute HBV!

49

outcomes of chronic HCV

cirrhosis 

HCC 

extrahepatic

50

splanchnic vasodilation in portal HTN

NO is the mediator 

NO synthesis stimulated by inflammatory mediators, endo toxin, bacterial products 

51

treatment of HEV

supportive care 

may require transplant if severe liver disease

52

primary biliar cirrhosis

chronic autoimmune disease targeting small intrahepatic bile ducts 

middle aged women of northern european descent 

AMA is highly specific!! 95% - on inner mitochondrial membrane for all cells 

progressive destruction of small intrahepatic bile ducts - chronic cholestasis - hepatocyte inflammation and necrosis - regen nodules and cirrhosis - liver failure and death

53

Natural history of NASH

steatosis

NASH

fibrosis

cirrhosis

HCC 

54

Lab findings in cirrhosis

T and D bili 

ALT/AST 

albumin

Alk Phos

also platelets+INR (coag), sodium (hyponautremia), markers of cirrhosis 

55

Clinical presentation of WIlson's disease

younger 

either: 

acute hepatitis: malaise, janudice, high ALT/AST, coagulopathy

chronic liver disease: hepatosplenomegaly, portal hypertension, coagulopathy

acute LF: coagulopathy, encephalopathy (lower ALT./AST - higher bili due to hemolysis, **low alk phos)

56

how do you diagnose hepatic cause of ascites

diagnostic paracentesis

Serum Ascites Albumin Gradient > 1.1

Total protein (low) 

cell conut

57

How do you diagnose PBC? 

Cholestatic LFTs 

asymptomatic elevation in alk phos is the most common presentation - related to degree of inflammation and ductopenia 

detectable serum AMA 

marked hypercholesterlemia (HDL - no MI risk) 

High serum IgM 

osteoporosis

liver biopsy

58

HEV IgM

acute infection

 

59

symptoms of HAV

incubation = 2-4 wks 

fever, malaise, fatigue, nausea and vomiting

self limted infection! increased mortality in old and liver disease pts 

occasional relapse w/in 6 mo - no chronic! 

can cause fulminant hepatits --> liver transplant

60

ALT vs AST

ALT = more specific (in cytosol) - [AST is in many organs - increses in hemolysis, MI] 

ALT has a much longer halflife (takes longer to decrease after injury) 

61

bilirubin synthesis pathway

•Bilirubin comes from heme of hemoglobin.

•There are steps that takes place outside the liver. Takes place in reticular endothelium, spleen and other organs.

•The heme is subject to an enzyme oxygenation that opens up this tetrapyrrol ring and is converted into something called biliverdin

•Then another step is [catalyzed by] biliverbin reductase and now biliverdin is converted in bilirubin. It has been reduced

•All three steps here takes place outside the liver

•In the liver it gets conjugated. And this is bilirubin diglucuronide that we are going to mention in a few minutes. One of the important steps in the elimination of bilirubin is to conjugate it.

•All of these steps. The iron is taken back in this reaction [the one catalyzed by heme oxygenase]. As the tetrapyrrol opens, it releases CO2 and Fe and it breaks down O2 etc.

62

perinatal exposure to HBV

95% will develop chronic HBV 

post-exposure prophylaxis with HBG and Hep B vaccine 

increase Hep B surface ab 

vaccine = long term immunity 

63

alcoholic hepatitis 

fever

janudice

abdominal dysfunction

coagulopathy, encepholpathy, edema

64

Who to treat with HBV? 

High ALT 

High BBV DNA levels (lower if HBeAg is negative) 

chronic HBV starting immunosuppressants

coinfection with HIV

PEP

decompensated cirrhosis

65

HBV genetic material 

DNA

66

Pathogenesis of Hepatic encephalopathy

gut derived toxins are absorbed and metabolized by the liver 

cirrhosis - incrased systemic delivery due to inadequate metabolism, portosystemic collaterals, 

GI tract is primary source of ammonia (anterocytes, colonic bacteria) 

liver clears all NH4 converting it to urea or glutamine 

ammonia crosses BBB

67

Mechanism of Wilson's disease

ATP7B genetic defect 

located in golgi in hepatocytes 

transfers copper into secretory pway by binding it to ceruloplasmin and facilitates biliar copper excretion

defect - Cu over  load - free/unprotected Cu attacks cell membranes, enzymes, DNA - oxidative stress and disruption of cell functions 

68

Anti-HBsAb

History of HBV infection OR vaccination

May not be detectable right after the disappearance of HBsAg (window period)

69

spectrum of alcoholic liver disease 

alcoholic steatosis 

fatty deposition in liver without inflammation (benign reversible) 

alcoholic hepatitis 

inflammatory cell infiltrates in context of fatty change 

alcoholic cirrhosis 

fibrosis and scarring from chronic inflammation 

70

NAFLD spectrum

Fatty Liver, NASH, Cirrhosis

80% have simple fatty liver 

20% have NASH 

15-30% of NASH will develop cirrhosis over 15 years 

7% will develop HCC

71

neuro presentation of wilson's disease

20s, 30s 

movement (remor) 

gait (dysarthria, dysphagia) 

psych - depression, compulsion, phobias

72

HBV inactive carrier state 

normal ALT and low HBV DNA

73

primary biliary cirrhosis

autoimmune

in women in their 50s 

fibrosis of bile canaliculi in portal triad 

anti-mitochondrial antibodies 

74

HBeAg

marker of high rate of viral replication

 

75

Anti-HBc IgG

marker of cleared or chronic HBV infection

76

HDV replication

ssRNA 

encodes HDAg

needs the HBV envelope proteins to enter hepatocytes 

host rna pol helps HDV replicate in the hepatocyte nucleus 

co infection w HDV will often lead to more rapid rogression

77

UDPGT

•The bilirubin comes with albumin to the liver to be conjugated

•Once it gets to the hepatocytes, inside the hepatocytes, the bilirubin binds to several carrier proteins and gets conjugated via that enzyme UDPGT. This is the crucial enzyme that makes it soluble and able to come out of the biliary tree and excreted into the intestinal tract.

78

Type I HRS

severe, rapidly progressing renal failure 

2 wk survival 

precipitated by EtOH/viral Hep, surgery

79

bilirubin

product of breakdown of hemoglobin

A very important function of the liver is to conjugate bilirubin- to make it go into the bile. If the liver can not conjugate it, it can not be excreted. This is the way the body gets rid of break down products of hemoglobin

•We produce about 300mg of bilirubin per day. Normally it is excreted. The liver takes it, conjugates it, goes down into the intestinal tract via the biliary tree

•If there is an increase in production or the liver can not conjugated it easily, now the bilirubin goes up in blood and that is called hyperbilirubinemia. Also known as jaundice.

•Jaundice is that coloration that is due to the increased concentration of the bilirubin. It is seen on the skin and easily on the sclera because the sclera is normally not as colored as skin, you can easily see that coloration

80

Treatment for HRS

albumin (increase reduced EABV) 

vasoconstrictors (splanchnic vasodilation) 

TIPS and transpolant

81

bariatric surgery as treatment

not effective in reversing advanced fibrosis in the long term

restrictive (intragastric balloon, restrictive devices, gastroplasty) 

malabsorptive (duodenal sleeve, magnets)

82

aminotransferases

ALT (alanine) 

AST (aspartate) 

tested by measuring enzymatic activity

important enzymes in AA metabolism, can assess liver cell injury because it's in the hepatocytes 

how much is in disease depends on how much damage (and previous damage) 

83

intrinsic hepatotoxins

predictable injury - direct chemical reaction

i.e. Acetomenophen 

dose dependent 

necrosis of hepatocytes

very high AST/ALT!

high mortality

 

84

detox/excretory liver functions

exogenous (drugs) endogenous (billirubin)

85

treatment of AIH? 

prednisone and/or AZA first line 

goals: normalize LFTs and gamma globulins 

may be lifelong treatment 

86

MDRP-2

protein that allows conjugated bilirubin to be excreted into bile canaliculi into billiary tree and Sb 

87

Hepatitis A labs

acute only!!

first fecal HAV (infectious!!) 

then IgM anti-HAV

then IgG anti-HAV (immune)

•For example in our lab, if you find a patient who possibly have HAV, then IgM is a critical value in the sense that we have to communicate it immediately to the providers that the individual is transmitting HAV. Many times food handlers, restaurants, or somebody handling food in a restaurant and they have IgM anti-HAV. It is transmitted easily by oral-enteral route.

88

AIH-PBC overlap

if have AIH + AMA-positive PBC

steroids+azathiprine

89

portal htn in hepatic feins? 

CHF

budd chiari - OCP clotting 

clots 

90

hepatic encephalopathy

spectrum of potentially reversible impairment in brain function in patients w liver failure, cirrhosis of the liver, or portosystemic shunts 

91

liver failure threshold

when >80% of liver function has been lost 

as end stage of chronic liver disease or acute form (massive destruction)

92

occular presentation of wilson's 

granular Cu deopsition in Descemet's membrane - where cornea meets sclera 

first as a crescent and ultimately a circle 

95% also have neuro symptoms

93

ALP

produced by biliary epithelial cells, canalicular hepaocyte membrane 

also by bone (osteoblasts), placenta, and intestine 

nl values according to age (vary as growing, pregnancy) 

•We were talking before about normal ranges. This is one of those enzymes that we have to provide the reference ranges.

• Ranges for children: as children are growing, born, they are releasing more ALP. So in children, ALP is higher.

•Pregnant women: ALP is produced by the placenta. So again ALP will be normal high in pregnancy [so a high ALP is normal is pregnant women]

•These are things to consider when looking at laboratory parameters.

94

HCV replication 

ssRNA 

enveloped 

detectable 7-21 d after transmission, ALT RAISES 4-12 WKS later!

95

LFTs for hepatocellular injury

Aminotransferases (ALT, AST)

96

Hepatitis B labs 

•the earlier indicators of hepatitis will be the surface antigen circulating, the DNA circulating

•Later on the antibodies to the core appear

•Once antibodies to the surface appear, this individual is already immune meaning this individual will not be transmitting this disease and will not be a carrier. This is very important

•All of you here have probably been vaccinated. We should all have antibodies to the surface which means we are immune

97

IgG Anti-HAV

resolved or vaccinated

long term resistance

can't tell which!

 

98

hepatic hyperbilirubinemia

defects in uptake (drugs) 

defects in conjugation

hepatocellular damage (hep, drugs, hypoxia) 

intrahepatic cholesitasis 

increased unconjugated and conjugated

99

esophageal varices

dilated submucosal veins in the lower 1/3 of the esophagus 

HVPG>10 - blood flow redirected to collaterals 

superficial esophageal veins become distended and tortuous

50% of pts w cirrhosis have varices and 5-15% will bleed 

decompensated cirrhosis - mortality

100

bilirubin breakdown 

•Coming again from the spleen and bone marrow and all these reticulo endothelium in which now the bilirubin comes into the liver and gets conjugated and excreted in the bile duct. Once it gets to the intestine there are several steps that break down this conjugated bilirubin.

•First by bacteria. These products of this metabolism by bacteria leads to that fecal urobilinogen and other products that are colored.

•The reason why our stools are colored is due to this particular mechanism. This is bilirubin that has been metabolized and gives color to the stools

•Some of that fecal urobilinogen is reabsorbed from the intestine and could circulate and go to the kidney and we have urinary urobilinogen that is usually colorless. It is not a colored compound.

101

vaccination for HBV? 

yes! 

102

clinical presentation of PSC

1. asymptomatic - normal LFTs and no clinical symptoms, incidental on imaging

2. biochemical: elevated LFTs including AP, bili, transaminases 

3. symptomatic: fatigue, pruritis, weight loss, cholangitis

4. cirrhosis

103

corticosteroids for alcoholic hepatitis 

prednisolone improves survival in the beginning

still high mortality

not in infections or w GI bleeds!!

104

presentation of AIH 

asymp to debilitating to fulminant 

40% with acute hep 

wax and wane

non specific 

abnormal LFTs, autoabs

105

HDV

depends on HBV!

coinfection or superinfection in a patient w chronic HBV 

superinfections --> severe hepatitis and decompensation of liver disease

106

lab findings in AIH

increased AST

hypergammaglobulnemia 

increased IgG

107

Hepatic Venous Pressure Gradient

indirect measurement of portal pressure 

gradient between the portal vein and the abdominal IVC 

greater than 5 - PHTN 

greater than 10 - clinically signif PHTN

greater than 12 vericeal rupture 

WHVP - FHVP

108

How to diagnose Wilsons? 

1. does the patient have low serum ceruloplasmin? 

2. Are KF rings present? 

3. is the 24 h urinary Cu elevated

if yes - def wilsons

if no to all 3 - unlinkly wilsons 

if unusre, liver biopsy or genotyping

109

type 1 hemochromatosis

HFE-related hemochromatosis

mutant HFE --> hepcidin not functional --> uncontrolled release of Fe into circulation through ferroportin --> multi rgan Fe deposition 

vary in genetic alterations in hepcidin reg pway that causes iron homeostasis mech to fail 

intestinal and macrophage iron unchecked 

rate of damage determined by gene involved and role in hepcidin biology 

 

110

threshold for alcoholic liver diesaes

no level or duration is directly associated w appearance of clinically significant liver disase

risk begins at low leves

women more vulnerable

111

steatosis

112

type II AIH autoantibodies 

anti-LKM

113

transmissionof HCV

IVDU 

blood infusions

healthcare workers 

sex 

perinatal 

hemodyalisis

114

Clinical findings in PBC

fatigue 

pruritis 

Sicca syndrome (xerostomia) 

Crest

portal HTN/varices (even without cirrhosis) 

115

Clinical manifestations of acetaminophen overdise 

to 24h - nausea, vomiting, malaise, half of injury in 24h

36 h - all aminotransferae elevations - 

72-96h - liver abnormalities peak, crazy high AST/ALT

if survive - recovery by 7d 

116

transmission of HAV

fecal-oral - contaminated food and water 

person-person

sex

oysters and shellfish!

117

How do you diagnose PSC? 

1. 80% have elevated pANCA 

2. MRCP is first test - non invasive - "beaded pattern" with short strictures and dilations

118

How do you determine if chronic HBV infection? 

•In a few cases, HBV patients do that recover that way. They don’t develop antibodies to surface. They will remain excreting the antigen. They will have antibody anti-core but they will not have anti-surface. You can detect the virus and e antigen. These are the individuals that may go into chronicity.

119

Progression of Alcoholic Liver Disease

Fatty liver to either steatohep or fibrosis

120

treatment for acetaminophen OD

within 4h give activated charcoal 

NAC - stimuates hepatic synthesis of glutathione!! 

after 16h - may be point of no return, but still can help up to 36h

121

diagnosis of HCV

ALT levels fluctuate

HCV Ab = active or past infection

HCV RNA level confirms active infection 

used to monitor response to HCV treatment 

viral load is unrelated to the degree of fibrosis 

122

cholangiocarcinoma and PSC

in 10-15%, 5 month survival

worsening LFT and functional status warrent evaluation

not a mass lesion - try to brush cells off if see lengthy structure 

123

How do you diagnose hemochromatosis? 

1. Fe studies 

Elevated TF Saturation > 45%

Ferritin > 1000 

2. HFE Genetic testing 

C282Y homozygote = diagnosis confirmed 

if not confirmed - consider liver biopsy

3. Liver biopsy 

assess damage and exclude cirrhosis 

measure hepatic iron concentration via prussian blue stain

 

124

crigler-najjar type I

inhereted UDPGT disorder 

unconjugated hyperbilirubinemia >20 can kill 

125

when is jaundice? 

>2-3 mg/dL hyperbilirubinemia 

(usually about 1 mg circulating) 

jaundice or icterus of skin, sclera, mucus membranes

126

treatment of HCV 

ribavirin w interferon (side effects!!) 

now we use protease inhibitors - a ton of them in the HCV rep cycle

127

HDV IgM

acute infection with HDV! 

can persist in chronic infection

128

What enzymes are in cytosol

AST

ALT 

 

129

symptoms of HEV 

flu like symptoms (most contagious before symptoms)

self limited (chronic can occur if immunosuppressed) 

can cause jaundice 

high mortality rate in pregnant women w fulminant hep!! 

130

Anti-HBc Igm

marker of acute infection

131

gold standard for diagnosing cirrhosis? 

liver biopsy

invasive, bleeding, pain, sampling error 

132

coagulation protein synthesis in the liver 

most (except VIII) are made in the liver 

liver disease may also affect Vit K absorption and this factors 

magnitidue of prothrmobin time (PT) elevation correlates w degree of liver failure

133

nl total bilirubin

.2-.9

134

ferritin

stored iron in liver and heart 

1 mlecule can store 4000 Fe atons 

when excess iron is absorbed, body makes more ferratin

135

wilson's disease

genetic disorder of biliary copper excretion 

measure Cu in urine and liver biopsy

136

HBV immune tolerant phase

in patientsinfected with HBV at birth/early childhood

min inflammation or fibrosis of the liver 

used to seeing virus so let live in liver - no inflam

137

treatment of HAV

symptomatic treatment

fulminant hep may require liver transplant 

vaccine for PEP or if traveling!

138

HBV replication

  1.  envelope surrounds partially dsDNA 
  2. converted to covalently closed circular DNA (cccDNA - dsDNA that's super coiled 
  3. RT will make RNA that will be translated into proteins that make HBV

139

Treatment for NAFLD/NASH

right now only weight loss through lifestyle modifications! 

weight loss of 5% can improve liver enzymes 

no fructose 

exercise alone can improve liver statosis (without affect on weight or ALT) 

coffee! decreases fibrosis

all drugs have really bad side effects- don't work well enough

140

nl direct bilirubin

.1-.3

141

unconjugated bilirubin

indirect - has not been made water soluble

•Unconjugated bilirubin: the bilirubin that is produced from the breakdown of hemoglobin that is coming to the liver to be conjugated. So prior to being conjugated, obviously it is called unconjugated, in the lab we measure by a method called the indirect detection of bilirubin 

142

Type II HRS

moderate steady decline in renal function

relatively preserved lvier function

survival 6-12 months

143

symptoms of herediatry hemochromatosis

bronze diabetes 

cirrhosis 

bronze skin

diabetes 

joint inflammation (victory sign)

heart disease 

fatigue 

hepatomegaly (increase ALT, cirrhosis, HCC) 

144

DeRitis ratio

AST/ALT

ratio > 2 in alcoholic liver disase

•Alcohol induced injury: AST will always be higher than ALT and that helps to distinguish alcohol injury versus others.

•AST: has higher concentration inside the hepatocyte. The other thing I wanted to mention is that AST is not only present in the cytoplasm of the hepatocyte but also in the mitochondria. The majority (80%) is in the mitochondria of hepatocyte. Ethanol releases that mitochondrial AST.

So it is a very useful test to do is to compare the concentration you receive in your blood test of AST versus ALT. If AST is much higher than the ALT, most likely reason for the injury is alcohol-ethanol. That ratio is called the DeRitis ratio- seen in alcoholic liver disease

145

HBV active phase

elevated aminotransferase levels 

signs of chronic hep

146

PSC management

no drugs

liver transpant is best chance - high recurrance rate soon after 

147

primary sclerosing cholangitis 

middle-aged men

autoimmune destruction of intra and extrahepatic bile ducts 

P-ANCA, ANA or SMA

148

Where is iron absobed?  

duodenum

149

idiosyntratic reactions

necrotic or cholestatic 

no dose relationship

unpredictable

hypersensitivity (immuno - augmentin) 

metabolic (amiodarone) 

majority!

150

HBsAg

HBV surface ag 

marker of acute and chronic HBV infection

persistance in blood for 6 mo means chronic infection

151

hemochromatosis

mutant HFE 

uncontrolled release of iron from duodenal enterocytes

unregulated Fe absorption - in all tissues 

toxic accumulation of excess iron in multiple irons 

defect in hepcidin regulatory pway

autosomal recessive 

152

hemochromatosis and malignancy

cirhosis ALWAYS precursor 

HCC is most common

CCA also 

some HCC-CCA

153

outcomes of chronic HBV

1/3 of patients with chronic HBV acquired in childhood will develop cirrhosis 

HCC can develop with and without cirrhosis 

glomerularnephritis

154

Histology of AIH

liver biopsy!

mononuclear infiltrate invading throught he limiting plate (interface hepatitis)

abundance of plasma cells

fibrosis

155

Names of copper chelators? 

trientene 

d-penicillamine

156

HBeAb

seroconversion to LOW replation state 

not as infevtive

157

mallory bodies

condensation of cytoskeletal intermediary filaments that results when tubulin acetaldehyde adducts form

look like red intracellular clumps

 

158

alcoholic hepatitis

clinical syndrome of janudice and liver function abnormalities in alcohol abusers 

associated w fast progression to cirrhosis w liver failure 

pahtology = steatosis, hepatocellular balloooning, neutro[hilic infiltrates, perisinusoidal fibrosis 

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hepcidin 

binds to ferroportin to inhibit iron export --> reduction in intestinal iron absoprption

if too much iron --> high hepcidin --> blocks export from duodenum --> don't absorb any more iron! 

160

processing/storage liver functions

dietary amino acids 

carbs

lipids

vitamins

161

delta bilirubin 

Bb tightly bound to albumin (reacts like direct) 

•Some patients with high direct bilirubinemia because of diseases that direct bilirubinemia builds up in blood. That bilirubin may bind to albumin and that is called delta billirubin. The difference between the delta bilirubin and the unconjugated bilirubin is that this delta bilirubin has a much longer half life because it is bound to albumin. Albumin has a 3wks half life. By being attached to albumin, delta bilirubin gets in circulation for a lot longer.

162

HEV IgG 

past infection

163

ascites

pathologic accumulation of fluid in the peritoneal cavity 

most common comp of cirrhosis

distention and pain

SOB (push on diaphragm) 

Early satiety (stomach can't expand) 

impired quality of life

164

replication of HAV

ssRNA 

HAV RNA pol copies RNA genome 

most common cause of acute viral hepatitis 

vaccinations for HAV have lead to a decrease

165

transient elastography

noninvasive mesure of liver stiffness 

painless risk free

sends sound waves 

to determine minimal and advanced fibrosis 

 

166

HEV replication

ssRNA 

no envelope 

elevation in ALT corresponds with the appearance of HEV abs

167

How to manage variceal bleeding? 

1. vasoconstrictors (reduces splanchnic flow)

BB, ADH, somatostatin

2. venodilators (reduce hepatitic resistance 

Nitrates 

3. endoscopic treatment 

band ligation

sclerotherapy

4. TIPS and shunts (decreased resistance) 

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NASH

non-alcoholic statoheptaitis

fat with inflammation, may progress to more advanced disease 

need a liver biopsy to diagnose

169

LFTs for synthetic function

 

albumin

prothrombin time

170

acetaminophen hepatotoxicity

90% metabolized to conjugates and excreted in urine 

remainder excreted unchanged in urine or metabolized via CYP to NAPQU (highly reactive and toxic) 

NAPQI is rapidly conjugated w glutathione and excreted in urine (non toxic) 

if OD: saturated primary pway, more NAPQU produced - depleted glutathione stores --> hepatic injury 

171

bilirubin in biliary obstruction

high - mostly direct 

172

petoxifylline 

inhibits synthesis and activity of TNF 

decreased mortality from hepatorenal syndrome 

use when steroids contraindicated 

173

why is too much iron a bad thing? 

target organ damage due to redox activity 

excesse iron - toxic iron free radicals - oxidative stress - cell damage - fibrosis - cirrhosis 

174

What enzymes are in the bile cannaliculi? 

GGT

ALP

175

transmission of HDV

exposudre to infected blood or other bodily fluids 

IVDU 

hemodialysis 

hemophiliacs

176

hemochromatosis

excessive Fe accumulation

uncommon - screening with Fe/TIBC - suspicious when >45%

177

fibrosis/cirrhosis

178

NAPQI

from acetomenophin - byproduct

irreversibly binds to hepatic macromolecules - oxidative injury and centrilobular necrosis - ck release from damaged hepatocytes - extension of zone of hepatic injury

179

indirect bilirubin

measuring Bb after adding accelerator substances that solubiliz unconjugated Bb and make it total bilirubin

nl: .2-.9

•We have to do some steps in between to solubilize it.

•Once we do that, we measure the bilirubin again by the colorimetric assay. Now the bilirubin is going to be higher than the 1st direct step. This one here is the total bilirubin. If we subtract the direct bilirubin from the total that will be our indirect, unconjugated bilirubin.

•>90% of the time, the direct bilirubin represents the conjugated bilirubin. But it is just a way in the lab to help as measure the different fractions of bilirubin

180

conjugated hyperbilirubinemia 

defects in bilirubin excretion and bile flow 

extrahepatic (tubors, choangitis) 

intrahepatic (viral, alcoholic, drugs, cirrhosis)

 

bc conjugated Bb is water soluble it will be excreted in stools 

if biliary obstruction --> absence on Bb in intestine --> lack of pigment in stools (acholia) 

 

181

two mutations in HFE? 

1. C282Y - Common

homozygotes = type I DM, liver disease etc 

low penetrance 

2. H63D (rare) - often normal Fe stores 

C282Y/C282Y > C282Y/H638 > H63D/H63D

182

Markers of HBV infection

incubation: HBsAg

acute: HBsAg, anti-HBc

after cleared: Anti-HBs

183

hepatocellular carcinoma 

aggressive primary liver tumor 

many associated w HBV or cirrhosis 

hepatocarcinogenesis linked to chronic liver damage 

 

184

IgM Anti-HAV

acue infection

185

transmission of HEV

fecal-oral route (most are drinking water) 

186

LDH

very ubiquitious (muscle, heart, lungs, RBCs)

• Can be used to determine certain diseases of the liver; particularly when LDH and ALP go together  without affecting much bilirubin is usually seen in space occupying lesions in the liver like tumors for example. So it can also help
•Malignant cells that have a very high level of proliferation , they may release very high concentrations of LDH
•So even though it is not useful by itself, as part of picture it is of use.

187

ferroportin

Fe is released from enterocytes into plasma through transporter

188

NASH

189

what enzyme is on mitochondria? 

AST

(EtOH affects)

190

insulin resistance in NAFLD

almost all patients w NAFLD have insulin resistance 

lipid overload leads to inappropriate accumulation of lipids in muscle, liver, beta cells 

lipid metabolites interefere w action of insulin R in the liver

can't suppress glucogenesis 

can't suppress lipolysis 

decreased uptake of glucose 

high glucose, high fatty acids

191

exposure to children vs adults of HBV

children - 30% will develop chronic 

adults - 2-5 will develop chronic 

192

pre-hepatic hyperbilirubinemia 

increased heme production 

hemolysis 

sickle cell

ineffective erythropoesis (Fe, folate deficiencies) 

high unconjugated bilirubin

193

Transmission of HBV

percutaneous/mucus membrane exposure 

healthcare 

hemodialysis

blood transfusion

perinatal

IVDU

sex 

tattoos 

194

treatment of hepatic encephalopathy

1. ammonia reduction

non absorbable disaccharides - lactulose - ammonium ion trapping 

oral abx

2. correct nutritional deficiencies 

3. reduce systemic inflammation

4. institution of lifelong secondary prophylaxis

195

MRI-PDFF

protein density fat fraction

quantify changes in liver fat - correlation w biopsy and more sensitive to changes

196

HDV IgG

active or past HDV infection

197

post hepatic hyperbilirubinemia 

obstruction to bile flow (cholestasis) 

malignancies 

high conjugated bilirubin

198

autoimmune hepatitis

self perpetuating idiopathic liver inflammation 

1. interface hepatitis 

2. hypergammaglobulinemia 

3. autoantibodies 

hard to daignose