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Laboratory evaluation of liver cell injury

Bilirubin metabolism and jaundice

 Ucb conjugated o glucuronic acid by ugt

 Intestinal bacteria convert cb to urobilinogen ( some use the term stercobilinogen )
 Ubg is spintaneosly oxidized to urobilin ( stercobilin)
 Approximately 20% of ubg is recycled to the liver (90% of 20%) and kidneys (10% of 20%)
 Jaundice is due to increase in ucb or/and cb
 Sclera has a high affinity for bilirubin
 %CB = cb/total bilirubin
 Mcc of jaundice is hep , 2nd mcc is gilbert(more in man , mc hereditary cause of jaundice)
 Criggler najjar with 0 ugt activity is incompatible woth life – needs liver transplantation
 Physiological jaundice of nb begins on day 3
 Breast milk jaundidce – due to preg nane 3 , 30 diol , which inhibits ugt – no treatment required

Liver function tests

 Alcohol increase ggt

 Alp can be increased by osteoblastic activity
 Hepatocyte functions
o Serum albumin
o Pt
o Factor 5
o Bun
o Serum ammonia – ammonia derived from large bowel and amino acid degradation
 Immune function
o Igm increased in PBC
o Ama increased in pbc
o Antismooth muscle ab and ana increased In AI hep

Viral hepatitis

 Phases of acute viral hepatitis

o Prodrome
 Fever , painful splenomegaly , distaste for cig and alcohol
 Steady increase in serum transaminases just before jaundice occur
 Atypical lymphocytosis
o Jaundice
o Recovery – jaundice resolves
 Microscopic finding in acute viral hepatitis
o Lymphocytic infilteration and destruction of hepatocytes
 Apoptosis of hepatocytes( councilmen bodies )
o Persistent inflame and fibrosis is a bad sign – sign of chronic hepatitis progressing to
postnecrotic cirrhosis
o Epidemiology
 HAV – 2nd mcc of acute hep in us , mc hep producing jaundice (70%),
 HBV – mc acute hep in US , 2nd mcc of fulminant hepatitis
 Comp – fulminant hepatitis , HCC secondary to postnecrosis cirrhosis
 HCV – mcc of hep due to ivda .
 hemophilcs transfused before 1987 ,
 Mc chronic blood bourne inf in us (85%)
 3rd mcc of acute hepatitis
 Comp – hcc due to postnecrosis cirrhosis (3%)
 No vaccine
 HDV – incomplete virus that req hbsag to replicate
 Cytolytic virus so fulminant hep can occur
 HEV – only produces fulminant hepatisis esp in pregnant
o Serological studies in viral hepatitis
 HAV – igm – active infection .
 Igg – recovery or immunization ( protective )
 HBsAg
o First marker of infxn
o Appears 2-8 weeks after exposure
 HBeAg and HBV DNA – infective paraticle
o Appears after HBsAg and disappeares before HBsAg
 Anti HB c IgM
o Non protective ab > remains positive in acute infection
o Only ag/ab + during window phase
o Converts entirely to igG by 6m regardless of hbsag state
 Anti HBs ab
o Protective ab – marker of immunization
 Infective chronic carrier (+ HBeag /hbv dna ) are at a greater risk for
postnecrosis cirrhosis and hcc compared to healthy chronic carrier
 Screen with eia
o + Anti HCV igG indicates active infxn or recovery (97%
 does not differentiate between acute , chronic ,
resolved infxn
 NOT a protective ab
 Confirmatory tests
o RIBA – ordered if eia +
o Hcv rna using pcr detects viral load
 Gold standard for diagnosing hcv
 To confirm active infxn and to montor pt on therapy
 + riba and + hcv rna indicatae active infxn
 + riba and – hcv rna indicate cure from treatment
 Anti hdc igM or igG indicates active infection
 Igg is NOT protectoive
 + anti HEV IgM = active infxn
 Anti hev igg indicates recovery ( protective)
o Alt is more specific for liver necrosis than ast . also alt is the last liver enzyme to return
to normal
 Infectious liver disorders
o Ascending cholangitis – llife threatening . triad of fever , jaundice , ruq pain
 Mcc cause of multiple liver abces
o Liver abcess – causes : ascending cholangitis (mcc) , intraabd infxn , direct extension ,
hematogenous . jaundice is uncommon
o Granulomatous hepatitis – tb – military spread
o Spontaneous peritonitis – develops in ascites
o Leptospirosis – biphasic ( weil ) disease – septicemic and immune phase
o Amebiasis – mcc of liver abcess worldwide ( not in us)
o Clonorchiasis – becomes adult in cbd
o Schistosomiasis – pipestem cirrhosis
o Echinococcus – hyatid cyst
 Autoimmune hepatitis
o Type 1 mc
o Young women
o Range of Clx – symptomatic with increased transaminases , fulminant hepatitis ,
o HLA dr3 and dr4
o Fever jaundice hepatosplenomegaly
o + antiSM ab , + ana
 Neonatal hepatitis
o Idiopathic . ass with cong infxn (cmv) . ass with inborn errors of metabolism (A1AT def))
o Biopsy shows multinucleated giant cells i.e giant cell hepatitis
 Reye syndrome
o Postinfectious triad to define reye syndrome include
 Encephalopathy
 Microvesicular fatty change
 Serum transaminase elevation
o Often follows chickenpox or influenza
o Path
 Mito damge
 Disruption of urea cycle
 Def b oxi in damaged mito > more fa becomes TAG > fatty change
 Microvesicular – small cytoplasmic globules that do not displace nucleus
o Clx
 Encephalopathy ( cerebral edema woth increased cerebral pressure) finding in
progression from sleepy to death
o Hypoglycemia ( liver not working )
o Csf is normal
o Tx is supportive – mannitol , glycerol , hyperventilation to reduce cerebral edema
 Acute fatty liver of pregnancy
o Abnormality in beta oxidation
o Fatal to mother and fetus unless baby is delivered
 Preeclampsi
o Htn , proteinuria , dep pitting edema in 3rd trimester
o Liver cell necrosis around the portal triads (Z1) > increased serum transaminases
o HELLP syndrome
o Acute liver failure with encephalopathy within 8 weeks of hepatic dysfunction
o Causes
 Drugs ( acetaminophen mcc ), hepatotos (2nd mcc)
 Reye , Wilson , AI hepatitis
o Wrinkled capsular surfaces due to loss of hepatic parenchyma
o Clx – hep encephalopathy , jaundice
o Decrease transaminases since less parenchyma
 ---
Circulatory disorders of the liver
 Prehepatic obstruction to blood floe
o Hepatic artery thrombosis with infarction
 Liver infarction is uncommon
 Causes – liver transplant rejection , PAN
o Portal vein thrombosis
 Causes –
 Pyelophlebitis ( mc due to acute appendicitis , air in PV)
 Polycethemia vera
 HCC – tumor invasion of pv
 PHTN , ascites , splenomegaly
 Intrahepatic obstruction – intrahepatic obstrucciton to sinusoidal blood flow
o Causes – cirrhosis , centrilobular hemmoragic necrosis , peliosis hepatis , SC disease
o Centrilobular hemmoragic necrosis – mc by HF
 Z3 ischemic necrosis due to hypoperfusion - LHF
 Enlarged liver with mottled red appearance
 Painful hepatomegaly
 May progress to cardiac cirrhosis
 Fibrosis around central venules
o Peliosis hepatis
 Sinusoidal dilation due to blood
 Causes
 Anabolic steroid
 Bartonella henselae in aids
 Potential for intraperitoneal hemmorage
 Posthepatic obstruction
o Hepatic vein thrombosis
 Budd chiari syndrome
 Causes
 PV – MCC
 Hypercoagualable state
o OCP , Protein c and s def , APLA
 HCC – invades hepatic vein
 Enlarged painful liver , Phtn , ascites , splenomegaly
 u/s with pulsed Doppler is first line test
 mri
o venoocclusive disease
 complication of BM transplantation
 collaagaen develops around central venules
 hematobilia

alcohol , drug , and chemical induced trauma to liver

 alcohol
o fatty change – mc type
 tender hepatomegaly without fever or neutrophilic leukocytosis
o alcoholic hepatitis
 stimulation of collagen synthesis around central venules
 fatty change with neutrophilic infilteration
 Mallory bod
 Painful helpatomegaly with fever , neutrophilic leukocytosis
o cirrhosis –
 chemical and drug
obstructive – cholestatic – liver disease
 intrahepatic cholestatis
o cause
 drugs ( ocp , anabolic steroids) MCC
 neonatal hepatitis
 preg induced cholestasis
 extrahepatic cholestasis
o stones
o Extrahepatic bilary atresia
o Ca of head of pancreas
 Enlarged greenish liver
 Clx in cholestatis liver disease
o Jaundice with pruritis (bile salts)
o Malabsorption
o Cholesterol deposits in skin
o Ligh stool
 Increase in serum ch
 Benign intrahepatic cholestasis of preg
o Due to estrogen inhibition of intrahepatic bile secretion
o NOT dangerous to fetus or mother
 Extrahepatic biliary atresia
o Cause of jaundice in nb
o Common indication for lliver transplantation in a child
 PSC – obliterative fibrosis of intrahepatic and extrahepatic bile ducts
o Hla dr52a and hlaCw7 , male dom ,
o Ass with ibd ( uc more)
o Ass with other sclerosing conditions ( retroperitoneal and mediastinalsclerosing fibrosis)
o Comp – cirrhosis and choliangiocarcinoma
o Jaundice , pruritis , hepatosplenomegaly
o Dx – ercp shows beading
o Tx req a liver transplant


 Irreversible fibrosis diffuse of liver with formation of regenerative nodules

 In regenerative nodules , liver lacks normal liver architecture of portal triads and sinusoids
o Nodules compress sinusoids and crntral venules
 Intrasinusoidal htn
 Reduciton in the number of functioning sinusoids
 Increase in hydrostatic pressure In poral vein
 Cause of cirrhosis
o Alcoholic liver disease (mc)
o Galactosemia
o Autoimmune hepatitis
 Comp with cirrhosis
o Hepatic failure – end point of progressive damage to the liver
 Coag prob – hyper or hypo
 Hypoalbuminemia
 Hep encephalopathy – reversible
 Increase in serum ammonia > urea cycle disfuncrion
 Increase in aromatic AA ( phenylalanine , tyrosine , tryptophan )
o These are converted to false neurotransmitters ( eg gamma
aminobutyric acid)
 Amino comes from metabolism of amino acid and from the release of
ammonia from amino acids by bacterial ureaeses in the bowel .
ammonia (nh3) is diffusible and is reabsorbes into the portal vein for
delvery to the urea cycle where it is metabolized into urea . .
ammonium isnot reabsorbed . methods of reducing ammonia
o Restrict protein (most cost effective)
o Oral neomycin – kills bacteria that synthesizes urease
o Lactulose – H+ ions released which combine with nh3 to
become nh4+
 Factors precipitating encephalopathy
o Increased protein ( most important)
 Diatary sources or blood in gi > leads to increase
bacterila conversion of urea into ammonia
o Alkalosis keeps ammonia in the nh3 statae
 Diuretics produce metabolic alkalosis ( less h
ions )
o Sedatives
o Portosystemic shunts - shunts ammonia away from liver
 Clx – aloc , asterixis , coma
o Portal htn
 Path – resistance to intrahepatic blood flow due to intrasinusoidal htn
 > anastomoses between portal vein tributaries and arterial system
 Compo
 Ascites
 Congestive splenomegaly > hyperslpenism with vadrious cytopenias
 Eso varices , caput medusa , hemmoroids
 Shnts used to treat ph
 Portocaval , mesocaval , splenorenal , TIPS
o Ascites
 Path
 Portal htn – increases portal vein hydrostatic pressure
 Hypoalbunemia – decreases oncotic pressure
 2nd hyperaldosteroism – salt retension
o CO is decreased du rot 3rd spcing > more raas
o Liver cant metabolize aldo
 Clx abd distension with fluid wave . increased risk of SBP
o Hepatorenal syndorome
 Condition of intense renal vasoconstriction dur to loss of renal autoregulation
occurring as a complication of severe , chronic liver disease i.e cirrhosis
 Reversiibble renal failure without parenchymal disease
 Renal tubular function is preserved
 Absence of significant proteiniuria/hematuria
 Tx
 Supportive care including dialysis
 Vasopressin analogues
 Vasoconstrictors
 Albumin for volume expansion
 Liver transplantation only curative treatment
o Hyperesterinism in males
 Liver cannot degrade estrogen and 17 KS
 KS ( androstenedione )is aromatized to estrogen in adipose cells
 Gynecomastia
 Spider telangiectasias
 Female distribution of hairs
 Impotence and erectile dysfunction
 Increae estrogen increases synthesis of sex hormone binding protein .
ehich increases binding of free testosterone
 Postnecrosis cirrhosis
 Most often caused by chronic hepatitis due to hbv and hcv
 Increased HCC
 Incidence of which virus is most common varied around the world
o Cirrhosis due to granulomatous destruction of bile ducts in the portal triads .
o AI , bitches mid age
o Ama
o Clx – pruritis – unknown etiology ( not bile salts inskin)
 Painful hepatosplenomegaly
 Jaundice – late finding after a lot of destruction
 Inflammatory arthropathy
 Xanthelaesma – increase ch
 KF rings in cornea – dep of copper
o Ana+ in 50%
o Increae serum igm
o Tx
 Budesonide + ursodeoxycholic acid
 Cholestyramine for pruritis
 Liver trsndplsntstoin
 Secondary biliary cirrhosis
o Complication of chronic extrahepatic bile duct obstruction
 Eg CF ehere bile duct is dehydrated
 Hereditary hemochromatosis
o 6p , hlaa3
o Most common genetic disorder in people of northeren European ancestery
o Male dominant disorder
 Cuz chicks lose iron in menses
o Unrestricted reabsorption of iron iin small intestine
o 2 missense mut on 6 ( c282y , h63d)
o Sec hemochromatosis : transfusion , alcohol ( alcohol increase iron absorption ), well
water )
o Clx –
 Cirrhosis
 Bronze diabetes
 Iron dep in beta cells > T1 DM
 Hyperpigmentation by deposit in skin AND increased melanin
 Malabsorption – destruction of exocrine pancreas
 Restrictive cardiomyopathy
 Hypogonadism – pit
 Loss of libido
 Amennorhea
 Degenerative joint disease – chondrocalcinosis
o Increased serum iron , percent saturation , and ferritin .
o Transferrin saturation is the best screening test . values >45% needs further workup
o Decreased tibc
o Serum ferritin is primarily used to follow therapy
o Liver biopsy to confirm
o Gene screening for relatives
o Treatment – phlebotomy until serum ferritin <50ug/ml sat <30%
 Deferoximine
o Normal life expectancy if no cirrhosis present
 Wilson
o Onset usually late childhood
o Liver disease progresses from acute hepatitits to cirrhosis and portal htn
o Unbound copper eventually accumulates in blood – copper is loosely attached to
albumin > deposits in tissues
o Clx – KF rings – not pathonemonic tho cuz also seen in pbc
 Cns disease
 Deposit in putamen (parkinism ) , subthalamic nuceli (hemibalismus) ,
cerebral cortex ( dementia)
 Hepatosplenomegaly – bx shows increased copper and fibrosis
 Hemolytic anemia
 Renal failure and fanconi
o Lab shows DECRESED total serumc copper due to decreaed ceruloplasmin
o Decreased serum ceruloplasmin – early stage diagnosis
o Increased seruma dn urine free copper – late stage dx
o Tx – pemicilalmine , zinc , ammonium tetrathiomollybdate , transplant
 A1at def
o AD
o ZZ – presents as neonatal hepatitis with intrahepatic cholestatsis
 Progresses to cirrhosis - a mcc of cirrhosis in children
o Tx – pooled a1at iv . liver and lung transplant
 Lab test abnormalities in cirrhosis
o Decreased bun , increased ammonia
o Fasting hypoglycemia
o Chronic resp alkalosis
o Lactic acidosis
o Hyponatremia
o Hypokalemia
o Increase pt
o Hypoallbunemia
o Hypocalcemia
o MILD serum trransmenemia

Liver tumors and tumor like disorders

 Focal nodular hyperplasia

o Tumor like condition
o More common in women , usually an incidental finding
o Poorly encapsulatead nodule . central depressed stellate scar contains large blood
vessels . fibrous septa radioating to the periphery
o Ct scan – hypervascular mass
 Benigh tumors of the liver
oCavernous hemangioma
 Mc benign tumor of the liver
 Dx with enhanced ct
o Hepatic cell adenoma
 More in women
 Ocp mcc
 Anabolic steroids
 Von gierke glycogneolysis
 Highly vascular tumors – tendency to rupture during preg and cause
intraperitoneal hem
 Malignant tumors of liver
o Met more common , lumg mcc
o Hcc
 Causes
 Cirrhosis , aflatoxin ,
 Mc by hbv/hcv
 Focal , multifocal or diffusely infilterating cancer – with or without preexisting
 Portal and hepatic vein invasion is common
 Characteristic finding is prsensce of bile in neoplastic cells
 Clx
 Over 1/3 are asymx
 Abd pain is the common initial presentation
 Liver cell necrosis causes fever
 Sudden increase In alp and ggt is a characteristic finding in hcc
 Production of ectopic hormones
 Epo ,insulin llike factor , pthrp
 Ct and u/s llocallizez hcc , angiography shows pooling and increased vascularity
o Angiosarcoma
 Exposure to vinul chloride (mcc) , arsenic , thorium dioxide

Gallblasser and biliary tract disease

 Cystic disesaes of the biliary tract

o Choledochal cyst
 Mc cyst in biliary tract in children <10y
 Abd pain with persistant or intermittent jaundice
 u/s screening test of choice . ercp or transhepatic chaolangiography may be
o caroli disease
 AD and AR types
 Segmental dilation of intrahepatic bile ducts and portal tract fibrosis
 Ass with pkd
 Tx – surgical resection of the involved lobe and liver transplantation

 Cholangiocarcinoma
o Causes
 Psc – mcc in us
 Clonorchis sinensis
 Thorotrast
 Choledechal cyst , caroli disease
o Mc site is ampulla or CBD
o Junction of r and l hepatic duct aka klatskin tumor
o Can also be intrahepatic
o Clx – obs jaundice
 Palpable gallbladder ( only if in middle portion of cbd ? or in ampulla
 Hepatomegaly
 Gallstones
o Bile acid/salts ( 67%) , phospholipid ( 22%) , protein , CH , CB , wate , electrolyte , bicarb
o In gall bladder come CB is conv to ucb which combines calcium to forn calcium
bilirubinatae stones
o Cholesterol
 Usually mixed – ch , calcium carbonate (makes it opaque if present) , bilirubin
o Pigment
 Bilirubin – chronic eha . excess cb is ocnv to ucb , ehich combines with calcium
to produce calcium bilirubinate stones
 Brown – infection in cbd , Asians , bacteria conv cb to ucb
o Estrogen increases stone formation by 3 mechanism
 Increase hdl formation – brings ch from periphery
 Upregulates LDL r –
 Inc hmgcoa reductase
o RF
 Obesity , rapid weight loss , lipid lowering drug , native maericans
o Comp , cholecystitis ( mc) , cbd obstruction , gb cancer , pancreatitis
 Acute cholecystits
o Women – 55y
o Ass with gallstones 95% of cases
o Other causes – AIDS (cmv , cryptosporidium ) , severe volume depletion
o Stages of development of acute cholecystitis
 1 – lodges in cytic duct – midepigastric colicky pain
 2- stone impacted in cystic duct > bacterial growth > pain shifts to ruq
 3- invasion – localized peritonitis with rebound tenderness ,
 4 – perforation – bv sompressed by high pressure in gb
o Clx
 Fever , vomiting , boas sign , murphy , jaundice ,
o Lab –
 Absolute neutrophilic leukocytosis with left shift
 increased alp/ ast – indicates stone in cbd
 amylase suggest pancreatitis
 bilirubin indicates stone in cbd
o test
 u/s ppreffered initial test - gold (98%)
 not effective in ifentifying cbd stones
 plain film – only 20% radiopaque
 HIDA scan – identifies stoen in cystic duct – no visualization of gb
 No tracer in duodenum means cbd stone
o Indication for cbd exploration
 Haundice , cbd >12mm , acute pancreatitis , no stones in gb ?
o Tx
 Cholesystectomy
 Ercp with sphincterotomy ro extract the stone in the cbd
 Meperepine for pain - do not use morphine cuz it contracts oddi and worsens
 Pip taz

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