Liver Pathophys Flashcards

Question

Tx of Wilsons

Answer 1

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

Answer 2

cirrhosis PHTN splanchnic vaodilation reduced EABV incrased vasoconstriction/antinaturesisi renal vasoconstriction HRS

Answer 3

**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

Answer 4

\< 40 IU/L

Answer 5

transjugular intrahepatic porto-systemic shunt btwn hepatic vein and portal vein decreases P

Answer 6

bilirubin (also uptake and conjugation) alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)

Answer 7

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.

Answer 8

reversible renal failure that occurs in patients w advanced cirrhosis and portal hypertension ## Footnote **marked reduction in GFR** **decreased renal perfusion** **absence of identifiable cause**

Answer 9

AST/ALT \>2:1 elevated GGT high ferratin (inflam marker) high bili, INR

Answer 10

AIH + AMA-negative PBC UDCA +/- steroids (variable response)

Answer 11

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

Answer 12

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

Answer 13

PCR marker of **acute or chronic** infection who to treat and response to treatment

Answer 14

250-300 mg/dL daily

Answer 15

Rise in ALT and High HBV DNA leels i.e. if start on immunosuppression, small amt can stay in liver even if cleared

Answer 16

hepatocellular injury (aminotransferases - ALT, AST) cholestasis -- altered bile flow (biliubin, alkaline phosphatase - ALP, GGT) synthetic functio

Answer 17

abstinence support/ntrition steroids and/or pentoxifylline; NAC

Answer 18

albumin clotting factors acute phase reactants bile acids other proteins

Answer 19

transports iron in the blood can only bind 2 Fe atoms at a tome 20-45% of transferrin is bound to Fe (transferrin saturation)

Answer 20

only made in the liver! half life= 18-20 decreased synthesis in chronic liver disease and index of disease severity

Answer 21

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)

Answer 22

**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 resin**s or rifampin for pruritis

Answer 23

**superinfection:** IgM anti-HBc is negative chronic HBV! **coinfection:** IgM anti-HBc is positive acute HBV!

Answer 24

cirrhosis HCC extrahepatic

Answer 25

NO is the mediator NO synthesis stimulated by inflammatory mediators, endo toxin, bacterial products

Answer 26

supportive care may require transplant if severe liver disease

Answer 27

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

Answer 28

steatosis NASH fibrosis cirrhosis HCC

Answer 29

**T and D bili** **ALT/AST** **albumin** **Alk Phos** also platelets+INR (coag), sodium (hyponautremia), markers of cirrhosis

Answer 30

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**)

Answer 31

diagnostic paracentesis Serum Ascites Albumin Gradient \> 1.1 Total protein (low) cell conut

Answer 32

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

Answer 33

acute infection

Answer 34

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

Answer 35

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)

Answer 36

* 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.

Answer 37

95% will develop chronic HBV post-exposure prophylaxis with HBG and Hep B vaccine increase Hep B surface ab vaccine = long term immunity

Answer 38

fever janudice abdominal dysfunction coagulopathy, encepholpathy, edema

Answer 39

High ALT High BBV DNA levels (lower if HBeAg is negative) chronic HBV starting immunosuppressants coinfection with HIV PEP decompensated cirrhosis

Answer 40

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

Answer 41

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

Answer 42

History of HBV infection OR vaccination May not be detectable right after the disappearance of HBsAg (window period)

Answer 43

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

Answer 44

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

Answer 45

20s, 30s movement (remor) gait (dysarthria, dysphagia) psych - depression, compulsion, phobias

Answer 46

normal ALT and low HBV DNA

Answer 47

autoimmune in women in their 50s fibrosis of bile canaliculi in portal triad anti-mitochondrial antibodies

Answer 48

marker of high rate of viral replication

Answer 49

marker of cleared or chronic HBV infection

Answer 50

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

Answer 51

* 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.

Answer 52

severe, rapidly progressing renal failure 2 wk survival precipitated by EtOH/viral Hep, surgery

Answer 53

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

Answer 54

albumin (increase reduced EABV) vasoconstrictors (splanchnic vasodilation) TIPS and transpolant

Answer 55

not effective in reversing advanced fibrosis in the long term restrictive (intragastric balloon, restrictive devices, gastroplasty) malabsorptive (duodenal sleeve, magnets)

Answer 56

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)

Answer 57

predictable injury - direct chemical reaction i.e. Acetomenophen dose dependent necrosis of hepatocytes very high AST/ALT! high mortality

Answer 58

exogenous (drugs) endogenous (billirubin)

Answer 59

prednisone and/or AZA first line goals: normalize LFTs and gamma globulins may be lifelong treatment

Answer 60

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

Answer 61

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.

Answer 62

if have AIH + AMA-positive PBC steroids+azathiprine

Answer 63

CHF budd chiari - OCP clotting clots

Answer 64

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

Answer 65

when \>80% of liver function has been lost as end stage of chronic liver disease or acute form (massive destruction)

Answer 66

granular Cu deopsition in **Descemet's membrane** - where cornea meets sclera first as a crescent and ultimately a circle 95% also have neuro symptoms

Answer 67

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.

Answer 68

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

Answer 69

Aminotransferases (ALT, AST)

Answer 70

* 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

Answer 71

resolved or vaccinated long term resistance can't tell which!

Answer 72

defects in uptake (drugs) defects in conjugation hepatocellular damage (hep, drugs, hypoxia) intrahepatic cholesitasis **increased unconjugated and conjugated**

Answer 73

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

Answer 74

* 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.

Answer 75

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**

Answer 76

prednisolone improves survival in the beginning still high mortality not in infections or w GI bleeds!!

Answer 77

asymp to debilitating to fulminant 40% with acute hep wax and wane non specific abnormal LFTs, autoabs

Answer 78

depends on HBV! coinfection or superinfection in a patient w chronic HBV superinfections --\> severe hepatitis and decompensation of liver disease

Answer 79

increased AST hypergammaglobulnemia increased IgG

Answer 80

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**

Answer 81

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

Answer 82

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

Answer 83

no level or duration is directly associated w appearance of clinically significant liver disase risk begins at low leves women more vulnerable

Answer 84

IVDU blood infusions healthcare workers sex perinatal hemodyalisis

Answer 85

fatigue pruritis Sicca syndrome (xerostomia) Crest portal HTN/varices (even without cirrhosis)

Answer 86

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

Answer 87

fecal-oral - contaminated food and water person-person sex oysters and shellfish!

Answer 88

1. 80% have elevated pANCA 2. MRCP is first test - non invasive - "beaded pattern" with short strictures and dilations

Answer 89

•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.

Answer 90

Fatty liver to either steatohep or fibrosis

Answer 91

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

Answer 92

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

Answer 93

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

Answer 94

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

Answer 95

inhereted UDPGT disorder unconjugated hyperbilirubinemia \>20 can kill

Answer 96

\>2-3 mg/dL hyperbilirubinemia (usually about 1 mg circulating) jaundice or icterus of skin, sclera, mucus membranes

Answer 97

ribavirin w interferon (side effects!!) now we use protease inhibitors - a ton of them in the HCV rep cycle

Answer 98

acute infection with HDV! can persist in chronic infection

Answer 99

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!!

Answer 100

marker of acute infection

Answer 101

liver biopsy invasive, bleeding, pain, sampling error

Answer 102

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

Answer 103

stored iron in liver and heart 1 mlecule can store 4000 Fe atons when excess iron is absorbed, body makes more ferratin

Answer 104

genetic disorder of biliary copper excretion measure Cu in urine and liver biopsy

Answer 105

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

Answer 106

symptomatic treatment fulminant hep may require liver transplant vaccine for PEP or if traveling!

Answer 107

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

Answer 108

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

Answer 109

indirect - has not been made water soluble ## Footnote •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

Answer 110

moderate steady decline in renal function relatively preserved lvier function survival 6-12 months

Answer 111

**bronze diabetes** cirrhosis **bronze skin** **diabetes** joint inflammation (**victory sign**) **heart disease** fatigue **hepatomegaly** (increase ALT, cirrhosis, HCC)

Answer 112

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

Answer 113

elevated aminotransferase levels signs of chronic hep

Answer 114

no drugs liver transpant is best chance - high recurrance rate soon after

Answer 115

middle-aged men autoimmune destruction of intra and extrahepatic bile ducts P-ANCA, ANA or SMA

Answer 116

necrotic or cholestatic no dose relationship unpredictable hypersensitivity (immuno - augmentin) metabolic (amiodarone) majority!

Answer 117

HBV surface ag marker of **acute and chronic** HBV infection persistance in blood for 6 mo means chronic infection

Answer 118

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

Answer 119

cirhosis ALWAYS precursor HCC is most common CCA also some HCC-CCA

Answer 120

1/3 of patients with chronic HBV acquired in childhood will develop cirrhosis HCC can develop with and without cirrhosis glomerularnephritis

Answer 121

liver biopsy! mononuclear infiltrate invading throught he limiting plate (**interface hepatitis)** **abundance of plasma cells** **fibrosis**

Answer 122

trientene d-penicillamine

Answer 123

seroconversion to LOW replation state not as infevtive

Answer 124

condensation of cytoskeletal intermediary filaments that results when tubulin acetaldehyde adducts form look like red intracellular clumps

Answer 125

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

Answer 126

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!

Answer 127

dietary amino acids carbs lipids vitamins

Answer 128

Bb tightly bound to albumin (reacts like direct) ## Footnote •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.

Answer 129

past infection

Answer 130

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

Answer 131

ssRNA HAV RNA pol copies RNA genome most common cause of acute viral hepatitis vaccinations for HAV have lead to a decrease

Answer 132

noninvasive mesure of liver stiffness painless risk free sends sound waves to determine minimal and advanced fibrosis

Answer 133

ssRNA no envelope elevation in ALT corresponds with the appearance of HEV abs

Answer 134

**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)**

Answer 135

non-alcoholic statoheptaitis fat with inflammation, may progress to more advanced disease need a liver biopsy to diagnose

Answer 136

albumin prothrombin time

Answer 137

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

Answer 138

high - mostly direct

Answer 139

inhibits synthesis and activity of TNF decreased mortality from hepatorenal syndrome use when steroids contraindicated

Answer 140

target organ damage due to redox activity excesse iron - toxic iron free radicals - oxidative stress - cell damage - fibrosis - cirrhosis

Answer 141

**exposudre to infected blood or other bodily fluids** IVDU hemodialysis hemophiliacs

Answer 142

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

Answer 143

fibrosis/cirrhosis

Answer 144

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

Answer 145

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

Answer 146

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)

Answer 147

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

Answer 148

incubation: HBsAg acute: HBsAg, anti-HBc after cleared: Anti-HBs

Answer 149

aggressive primary liver tumor many associated w HBV or cirrhosis hepatocarcinogenesis linked to chronic liver damage

Answer 150

acue infection

Answer 151

fecal-oral route (most are drinking water)

Answer 152

very ubiquitious (muscle, heart, lungs, RBCs) ## Footnote * 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.

Answer 153

Fe is released from enterocytes into plasma through transporter

Answer 154

AST | (EtOH affects)

Answer 155

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**

Answer 156

children - 30% will develop chronic adults - 2-5 will develop chronic

Answer 157

increased heme production hemolysis sickle cell ineffective erythropoesis (Fe, folate deficiencies) **high unconjugated bilirubin**

Answer 158

**percutaneous/mucus membrane exposure** healthcare hemodialysis blood transfusion perinatal IVDU sex tattoos

Answer 159

**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**

Answer 160

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

Answer 161

active or past HDV infection

Answer 162

obstruction to bile flow (cholestasis) malignancies **high conjugated bilirubin**

Answer 163

self perpetuating idiopathic liver inflammation **1. interface hepatitis** **2. hypergammaglobulinemia** **3. autoantibodies** hard to daignose