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GI2 > Liver Pathophys > Flashcards

Liver Pathophys Flashcards

1
Q

psychometric testing

A

sensitive for detecting impairment in mild HE

lead to the identificaltion of minimal HE

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2
Q

Wilson’s Disease

A

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

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3
Q
A

interface hepatitis - AIH

mononuclear infiltrate invading through the limiting plate

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4
Q

lab tests to assess liver disease progression

A

fibrosis, cirrhosis, seerity

proteins involved in EC matrix modeling and other blood tests

not gret yet

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5
Q

Hepatopulmonary Syndrome

A

present when this triad:

1. Liver disease

2. impaired oxygenation

3. intrapulmonary vascular dilations (IPVDS)

decreased GFR

decreased renal perfusion

absence of identifiable cause

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6
Q

Labs in Wilson’s

A

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)

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7
Q

portal htn in portal vein?

A

hypercoag

trauma

malignancy

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8
Q

direct bilirubin

A

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.

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9
Q

unconjugated hyperbilirubinemia

A

defective uptake and conjugation

inhereted (defects in UDPGT)

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

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10
Q

Natural history of NAFLD

A

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

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11
Q

Hepatitis C labs

A

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

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12
Q

treatment of HDV

A

treat HBV

if clear HBV will clear HDV

interferon is only therapy against HDV!

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13
Q

HCV genotype

A

6!

1a/1b in US

imp for treatment

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14
Q

labs in liver failure

A

increased Bb (T and D)

hypoalbuminemia

increased PT (INR)

increased ammonia –> encephalopathy

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15
Q

NAFLD

A

30% of americans have NAFLD

dyslipidemia

obesity

T2D

comprises “fatty liver” and NASH

fat droplets in the hepatocytes

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16
Q

PSC and IBD

A

80% have concimitent IBD

IBD patients have increased risk of PSC

more colitis = greater risk

must do colo to evaluated for IBD

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17
Q

Treatment for herediatry hemochromatosis

A

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

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18
Q

prescott nomogram

A

risk of toxicity for acetaminophen

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19
Q

primary sclerosing cholangitis

A

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

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20
Q

conjugated bilirubin

A

direct - water soluble

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

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21
Q

Course of herediatry hemocrhomatosis

A
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22
Q

Autoimmune sclerosing cholangitis

A

AIH = PSC

like PSC

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23
Q

transient elastography

A

measures liver tissue elasticity by measuring speed of vbrations through parenchma

detect advanced fibrosis

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24
Q

Clinical manifestations of herediary hemochromatosis

A
  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
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25
Q

Tx of Wilsons

A

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

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26
Q

hepatorenal syndrope mechanism

A

cirrhosis

PHTN

splanchnic vaodilation

reduced EABV

incrased vasoconstriction/antinaturesisi

renal vasoconstriction

HRS

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27
Q

pathogenesis of ascietes

A

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

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28
Q

normal ranges for ALT and AST

A

< 40 IU/L

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29
Q

TIPS

A

transjugular intrahepatic porto-systemic shunt

btwn hepatic vein and portal vein

decreases P

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30
Q

LFTs for cholestasis (altered bile flow)

A

bilirubin (also uptake and conjugation)

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

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31
Q

GGT

A

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.

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32
Q

type I AIH autoantibodies

A

ANA

ASMA

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33
Q

Hepatorenal syndrome

A

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

marked reduction in GFR

decreased renal perfusion

absence of identifiable cause

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34
Q

Lab Findings in ALD

A

AST/ALT >2:1

elevated GGT

high ferratin (inflam marker)

high bili, INR

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35
Q

Autoimmune cholangitis

A

AIH + AMA-negative PBC

UDCA +/- steroids (variable response)

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36
Q

AIH pathogenesis

A
  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
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37
Q

autoimmune hepatitis

A

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
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38
Q

HBV DNA level

A

PCR

marker of acute or chronic infection

who to treat and response to treatment

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39
Q

how much bilirubin produced daily?

A

250-300 mg/dL daily

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40
Q

HBV reactive phase

A

Rise in ALT and High HBV DNA leels

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

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41
Q

what do LFTs assess

A

hepatocellular injury (aminotransferases - ALT, AST)

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

synthetic functio

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42
Q

management of alcoholic hepatitis

A

abstinence

support/ntrition

steroids and/or pentoxifylline; NAC

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43
Q

synthetic liver functions

A

albumin

clotting factors

acute phase reactants

bile acids

other proteins

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44
Q

transferrin

A

transports iron in the blood

can only bind 2 Fe atoms at a tome

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

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45
Q

albumin synthesis in the liver

A

only made in the liver!

half life= 18-20

decreased synthesis in chronic liver disease and index of disease severity

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46
Q

Medictions for HBV

A
  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)

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47
Q

Treatmetn of PBC?

A

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

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48
Q

How do you distinguish between superinfection vs coinfection with HDV?

A

superinfection: IgM anti-HBc is negative

chronic HBV!

coinfection: IgM anti-HBc is positive

acute HBV!

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49
Q

outcomes of chronic HCV

A

cirrhosis

HCC

extrahepatic

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50
Q

splanchnic vasodilation in portal HTN

A

NO is the mediator

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

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51
Q

treatment of HEV

A

supportive care

may require transplant if severe liver disease

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52
Q

primary biliar cirrhosis

A

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

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53
Q

Natural history of NASH

A

steatosis

NASH

fibrosis

cirrhosis

HCC

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54
Q

Lab findings in cirrhosis

A

T and D bili

ALT/AST

albumin

Alk Phos

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

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55
Q

Clinical presentation of WIlson’s disease

A

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)

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56
Q

how do you diagnose hepatic cause of ascites

A

diagnostic paracentesis

Serum Ascites Albumin Gradient > 1.1

Total protein (low)

cell conut

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57
Q

How do you diagnose PBC?

A

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

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58
Q

HEV IgM

A

acute infection

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59
Q

symptoms of HAV

A

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

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60
Q

ALT vs AST

A

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)

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61
Q

bilirubin synthesis pathway

A
  • 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.
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62
Q

perinatal exposure to HBV

A

95% will develop chronic HBV

post-exposure prophylaxis with HBG and Hep B vaccine

increase Hep B surface ab

vaccine = long term immunity

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63
Q

alcoholic hepatitis

A

fever

janudice

abdominal dysfunction

coagulopathy, encepholpathy, edema

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64
Q

Who to treat with HBV?

A

High ALT

High BBV DNA levels (lower if HBeAg is negative)

chronic HBV starting immunosuppressants

coinfection with HIV

PEP

decompensated cirrhosis

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65
Q

HBV genetic material

A

DNA

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66
Q

Pathogenesis of Hepatic encephalopathy

A

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

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67
Q

Mechanism of Wilson’s disease

A

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

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68
Q

Anti-HBsAb

A

History of HBV infection OR vaccination

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

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69
Q

spectrum of alcoholic liver disease

A

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

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70
Q

NAFLD spectrum

A

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

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71
Q

neuro presentation of wilson’s disease

A

20s, 30s

movement (remor)

gait (dysarthria, dysphagia)

psych - depression, compulsion, phobias

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72
Q

HBV inactive carrier state

A

normal ALT and low HBV DNA

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73
Q

primary biliary cirrhosis

A

autoimmune

in women in their 50s

fibrosis of bile canaliculi in portal triad

anti-mitochondrial antibodies

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74
Q

HBeAg

A

marker of high rate of viral replication

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75
Q

Anti-HBc IgG

A

marker of cleared or chronic HBV infection

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76
Q

HDV replication

A

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

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77
Q

UDPGT

A
  • 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.
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78
Q

Type I HRS

A

severe, rapidly progressing renal failure

2 wk survival

precipitated by EtOH/viral Hep, surgery

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79
Q

bilirubin

A

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
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80
Q

Treatment for HRS

A

albumin (increase reduced EABV)

vasoconstrictors (splanchnic vasodilation)

TIPS and transpolant

81
Q

bariatric surgery as treatment

A

not effective in reversing advanced fibrosis in the long term

restrictive (intragastric balloon, restrictive devices, gastroplasty)

malabsorptive (duodenal sleeve, magnets)

82
Q

aminotransferases

A

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
Q

intrinsic hepatotoxins

A

predictable injury - direct chemical reaction

i.e. Acetomenophen

dose dependent

necrosis of hepatocytes

very high AST/ALT!

high mortality

84
Q

detox/excretory liver functions

A

exogenous (drugs) endogenous (billirubin)

85
Q

treatment of AIH?

A

prednisone and/or AZA first line

goals: normalize LFTs and gamma globulins

may be lifelong treatment

86
Q

MDRP-2

A

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

87
Q

Hepatitis A labs

A

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
Q

AIH-PBC overlap

A

if have AIH + AMA-positive PBC

steroids+azathiprine

89
Q

portal htn in hepatic feins?

A

CHF

budd chiari - OCP clotting

clots

90
Q

hepatic encephalopathy

A

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

91
Q

liver failure threshold

A

when >80% of liver function has been lost

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

92
Q

occular presentation of wilson’s

A

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
Q

ALP

A

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
Q

HCV replication

A

ssRNA

enveloped

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

95
Q

LFTs for hepatocellular injury

A

Aminotransferases (ALT, AST)

96
Q

Hepatitis B labs

A
  • 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
Q

IgG Anti-HAV

A

resolved or vaccinated

long term resistance

can’t tell which!

98
Q

hepatic hyperbilirubinemia

A

defects in uptake (drugs)

defects in conjugation

hepatocellular damage (hep, drugs, hypoxia)

intrahepatic cholesitasis

increased unconjugated and conjugated

99
Q

esophageal varices

A

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
Q

bilirubin breakdown

A
  • 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
Q

vaccination for HBV?

A

yes!

102
Q

clinical presentation of PSC

A
  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
Q

corticosteroids for alcoholic hepatitis

A

prednisolone improves survival in the beginning

still high mortality

not in infections or w GI bleeds!!

104
Q

presentation of AIH

A

asymp to debilitating to fulminant

40% with acute hep

wax and wane

non specific

abnormal LFTs, autoabs

105
Q

HDV

A

depends on HBV!

coinfection or superinfection in a patient w chronic HBV

superinfections –> severe hepatitis and decompensation of liver disease

106
Q

lab findings in AIH

A

increased AST

hypergammaglobulnemia

increased IgG

107
Q

Hepatic Venous Pressure Gradient

A

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
Q

How to diagnose Wilsons?

A
  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
Q

type 1 hemochromatosis

A

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
Q

threshold for alcoholic liver diesaes

A

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

risk begins at low leves

women more vulnerable

111
Q
A

steatosis

112
Q

type II AIH autoantibodies

A

anti-LKM

113
Q

transmissionof HCV

A

IVDU

blood infusions

healthcare workers

sex

perinatal

hemodyalisis

114
Q

Clinical findings in PBC

A

fatigue

pruritis

Sicca syndrome (xerostomia)

Crest

portal HTN/varices (even without cirrhosis)

115
Q

Clinical manifestations of acetaminophen overdise

A

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
Q

transmission of HAV

A

fecal-oral - contaminated food and water

person-person

sex

oysters and shellfish!

117
Q

How do you diagnose PSC?

A
  1. 80% have elevated pANCA
  2. MRCP is first test - non invasive - “beaded pattern” with short strictures and dilations
118
Q

How do you determine if chronic HBV infection?

A

•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
Q

Progression of Alcoholic Liver Disease

A

Fatty liver to either steatohep or fibrosis

120
Q

treatment for acetaminophen OD

A

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
Q

diagnosis of HCV

A

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
Q

cholangiocarcinoma and PSC

A

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
Q

How do you diagnose hemochromatosis?

A
  1. Fe studies

Elevated TF Saturation > 45%

Ferritin > 1000

  1. HFE Genetic testing

C282Y homozygote = diagnosis confirmed

if not confirmed - consider liver biopsy

  1. Liver biopsy

assess damage and exclude cirrhosis

measure hepatic iron concentration via prussian blue stain

124
Q

crigler-najjar type I

A

inhereted UDPGT disorder

unconjugated hyperbilirubinemia >20 can kill

125
Q

when is jaundice?

A

>2-3 mg/dL hyperbilirubinemia

(usually about 1 mg circulating)

jaundice or icterus of skin, sclera, mucus membranes

126
Q

treatment of HCV

A

ribavirin w interferon (side effects!!)

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

127
Q

HDV IgM

A

acute infection with HDV!

can persist in chronic infection

128
Q

What enzymes are in cytosol

A

AST

ALT

129
Q

symptoms of HEV

A

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
Q

Anti-HBc Igm

A

marker of acute infection

131
Q

gold standard for diagnosing cirrhosis?

A

liver biopsy

invasive, bleeding, pain, sampling error

132
Q

coagulation protein synthesis in the liver

A

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
Q

nl total bilirubin

A

.2-.9

134
Q

ferritin

A

stored iron in liver and heart

1 mlecule can store 4000 Fe atons

when excess iron is absorbed, body makes more ferratin

135
Q

wilson’s disease

A

genetic disorder of biliary copper excretion

measure Cu in urine and liver biopsy

136
Q

HBV immune tolerant phase

A

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
Q

treatment of HAV

A

symptomatic treatment

fulminant hep may require liver transplant

vaccine for PEP or if traveling!

138
Q

HBV replication

A
  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
Q

Treatment for NAFLD/NASH

A

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
Q

nl direct bilirubin

A

.1-.3

141
Q

unconjugated bilirubin

A

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
Q

Type II HRS

A

moderate steady decline in renal function

relatively preserved lvier function

survival 6-12 months

143
Q

symptoms of herediatry hemochromatosis

A

bronze diabetes

cirrhosis

bronze skin

diabetes

joint inflammation (victory sign)

heart disease

fatigue

hepatomegaly (increase ALT, cirrhosis, HCC)

144
Q

DeRitis ratio

A

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
Q

HBV active phase

A

elevated aminotransferase levels

signs of chronic hep

146
Q

PSC management

A

no drugs

liver transpant is best chance - high recurrance rate soon after

147
Q

primary sclerosing cholangitis

A

middle-aged men

autoimmune destruction of intra and extrahepatic bile ducts

P-ANCA, ANA or SMA

148
Q

Where is iron absobed?

A

duodenum

149
Q

idiosyntratic reactions

A

necrotic or cholestatic

no dose relationship

unpredictable

hypersensitivity (immuno - augmentin)

metabolic (amiodarone)

majority!

150
Q

HBsAg

A

HBV surface ag

marker of acute and chronic HBV infection

persistance in blood for 6 mo means chronic infection

151
Q

hemochromatosis

A

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
Q

hemochromatosis and malignancy

A

cirhosis ALWAYS precursor

HCC is most common

CCA also

some HCC-CCA

153
Q

outcomes of chronic HBV

A

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

HCC can develop with and without cirrhosis

glomerularnephritis

154
Q

Histology of AIH

A

liver biopsy!

mononuclear infiltrate invading throught he limiting plate (interface hepatitis)

abundance of plasma cells

fibrosis

155
Q

Names of copper chelators?

A

trientene

d-penicillamine

156
Q

HBeAb

A

seroconversion to LOW replation state

not as infevtive

157
Q

mallory bodies

A

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

look like red intracellular clumps

158
Q

alcoholic hepatitis

A

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

159
Q

hepcidin

A

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
Q

processing/storage liver functions

A

dietary amino acids

carbs

lipids

vitamins

161
Q

delta bilirubin

A

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
Q

HEV IgG

A

past infection

163
Q

ascites

A

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
Q

replication of HAV

A

ssRNA

HAV RNA pol copies RNA genome

most common cause of acute viral hepatitis

vaccinations for HAV have lead to a decrease

165
Q

transient elastography

A

noninvasive mesure of liver stiffness

painless risk free

sends sound waves

to determine minimal and advanced fibrosis

166
Q

HEV replication

A

ssRNA

no envelope

elevation in ALT corresponds with the appearance of HEV abs

167
Q

How to manage variceal bleeding?

A

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)

168
Q

NASH

A

non-alcoholic statoheptaitis

fat with inflammation, may progress to more advanced disease

need a liver biopsy to diagnose

169
Q

LFTs for synthetic function

A

albumin

prothrombin time

170
Q

acetaminophen hepatotoxicity

A

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
Q

bilirubin in biliary obstruction

A

high - mostly direct

172
Q

petoxifylline

A

inhibits synthesis and activity of TNF

decreased mortality from hepatorenal syndrome

use when steroids contraindicated

173
Q

why is too much iron a bad thing?

A

target organ damage due to redox activity

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

174
Q

What enzymes are in the bile cannaliculi?

A

GGT

ALP

175
Q

transmission of HDV

A

exposudre to infected blood or other bodily fluids

IVDU

hemodialysis

hemophiliacs

176
Q

hemochromatosis

A

excessive Fe accumulation

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

177
Q
A

fibrosis/cirrhosis

178
Q

NAPQI

A

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
Q

indirect bilirubin

A

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
Q

conjugated hyperbilirubinemia

A

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
Q

two mutations in HFE?

A
  1. C282Y - Common

homozygotes = type I DM, liver disease etc

low penetrance

  1. H63D (rare) - often normal Fe stores

C282Y/C282Y > C282Y/H638 > H63D/H63D

182
Q

Markers of HBV infection

A

incubation: HBsAg
acute: HBsAg, anti-HBc

after cleared: Anti-HBs

183
Q

hepatocellular carcinoma

A

aggressive primary liver tumor

many associated w HBV or cirrhosis

hepatocarcinogenesis linked to chronic liver damage

184
Q

IgM Anti-HAV

A

acue infection

185
Q

transmission of HEV

A

fecal-oral route (most are drinking water)

186
Q

LDH

A

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
Q

ferroportin

A

Fe is released from enterocytes into plasma through transporter

188
Q
A

NASH

189
Q

what enzyme is on mitochondria?

A

AST

(EtOH affects)

190
Q

insulin resistance in NAFLD

A

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
Q

exposure to children vs adults of HBV

A

children - 30% will develop chronic

adults - 2-5 will develop chronic

192
Q

pre-hepatic hyperbilirubinemia

A

increased heme production

hemolysis

sickle cell

ineffective erythropoesis (Fe, folate deficiencies)

high unconjugated bilirubin

193
Q

Transmission of HBV

A

percutaneous/mucus membrane exposure

healthcare

hemodialysis

blood transfusion

perinatal

IVDU

sex

tattoos

194
Q

treatment of hepatic encephalopathy

A

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
Q

MRI-PDFF

A

protein density fat fraction

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

196
Q

HDV IgG

A

active or past HDV infection

197
Q

post hepatic hyperbilirubinemia

A

obstruction to bile flow (cholestasis)

malignancies

high conjugated bilirubin

198
Q

autoimmune hepatitis

A

self perpetuating idiopathic liver inflammation

1. interface hepatitis

2. hypergammaglobulinemia

3. autoantibodies

hard to daignose

GI2 (7 decks)

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