P A O 5600 Lecture 5 Liver Fx Tests (1hr) Dave

LIVER FUNCTION TESTS

CLINICAL LAB MEDICINE ICLINICAL LAB MEDICINE IPAO 5600

The Liver• Largest Gland

– Weighs 1 5 KgWeighs 1.5 Kg– Inf edge is usually

subcostal– Synthesizes and

detoxifies

By Dave Kotun for NSU Orlando 2

OBJECTIVES• List the tests which aid in the assessment of theList the tests which aid in the assessment of the

detoxification function of liver• List tests which aid in the assessment of hepatic injury

and necrosisand necrosis• Explain why the gamma-glutamyl-transpeptidase

(GGT) and alkaline phosphatase tests aid in the assessment of biliary tract obstructiony

• Recall what effect the liver function has on the y the prothrombin time and serum albumin

• Compare and contrast the lab findings in theCompare and contrast the lab findings in the hepatitises and what impact these conditions have on individual and community health

• Trace the bilirubin pathway and the lab findings in ace e b ub pa ay a d e ab d gsbilirubin abnormalities and biliary tract obstruction.

• Describe etiologies, lab findings, and complications associated with the effect of alcohol on the liver


LIVER FUNCTION TESTS• Tests which can assess the synthetic function of liver

– Prothrombin time– Serum albumin

Ch l t l– Cholesterol• Tests which can assess the detoxification function of liver

– Serum bilirubin: total; direct briefly describe the metabolic pathway of bilirubin, indicating where unconjugated and conjugated bilirubin exist in the pathwaypathway

– Serum ammonia• Tests which may be indicative of liver injury

– Aminotransferases• Aspartate aminotransferase (AST)• Aspartate aminotransferase (AST)• Alanine aminotransferase (ALT)• Gamma- glutamyl-transpeptidase ( GGT )

• Tests which may be indicative of biliary tract obstructionAlk li h h t (ALP)– Alkaline phosphatase (ALP)

– Gamma- glutamyl-transpeptidase (GGT)


• HEPATITIS

HEPATOBILIARY DISEASE

• Definition and important causes (viral; alcoholic; drug induced; toxic or ischemic induced; autoimmune)

– VIRAL HEPATITIS• Distinguishing between hepatitis A, B, and C in terms

of: mode of transmission; complications; diagnostic screening

• Liver function test findings• Liver function test findings• Clinical presentation

– Why hepatitis C is of particular health concern in the US todaytoday


HEPATOBILIARY DISEASEHEPATOBILIARY DISEASE

• Hepatitis ( cont )• Hepatitis ( cont.)– ALCOHOLIC HEPATITIS

– Clinical presentation and diagnostic findingsp g g

– DRUG-INDUCED HEPATITIS• Examples of drugs which may cause hepatitis

AUTOIMMUNE HEPATITIS– AUTOIMMUNE HEPATITIS– Definition

– ACUTE FULMINANT HEPATITIS CU U S– Causes and diagnostic findings


HYPERBILIRUBINEMIA• Causes

– Elevation of unconjugated bilirubin– Elevation of conjugated bilirubin

• Lab findings associated with biliary tract obstructionComplete: early and chronic findings– Complete: early and chronic findings

– Partial or intrahepatic obstruction• CIRRHOSIS

– Definition– Major causes

• Lab findings• Complications

» portal hypertension (gastroesophageal varices etc.),


p yp (g p g ),ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, coagulopathy

OVERVIEW OF LIVER ANATOMY

• FUNCTIONAL UNIT: liver lobule– Hexagonal structure with rows of liver cells ( hepatocytes ), a vein in

center (central vein), and “ portal triad “ (hepatic artery and portal

ANATOMY

vein branch, bile duct) in each corner• CIRCULATION

– hepatic artery brings blood rich in O2 to liver; blood flows from portal triad to central einportal triad to central vein

– portal vein drains GI tract and spleen and carries blood rich in nutrients to liver

• BILIARY TRACT: passageway of bile excretion (bile has bile• BILIARY TRACT: passageway of bile excretion (bile has bile acids, bilirubin, and cholesterol)

– Bile is excreted by hepatocytes into adjacent small passageways (canaliculi ) bile flows to bile duct in portalpassageways (canaliculi ) bile flows to bile duct in portal triad intrahepatic ducts converge into R and L hepatic ducts which converge into common hepatic duct cystic duct from gall bladder joins common hepatic duct common bile duct enters duodenum at ampulla of Vater


enters duodenum at ampulla of Vater

FUNCTIONS OF LIVER• Liver is the “major metabolic factory and disposal plant

“– PLASMA PROTEIN SYNTHESIS

FUNCTIONS OF LIVER

– PLASMA PROTEIN SYNTHESIS• Albumin

– major carrier of substances in blood– most abundant plasma protein so maintains

plasma oncotic pressure• most clotting factorsmost clotting factors

– BILIRUBIN METABOLISM ( figure 1 )• Metabolic pathway of bilirubin:• RBC breakdown ( typically inRBC breakdown ( typically in

spleen) heme biliverdin unconjugated bilirubin carried by albumin to liver liver conjugates bilirubin to glucuronic acid

conjugated bilirubin excreted into small intestine reduced by bacteria into urobilinogen urobilinogen excreted in feces or


bacteria into urobilinogen urobilinogen excreted in feces or reabsorbed and excreted in urine

FUNCTIONS OF LIVER• Why must unconjugated bilirubin be conjugated by liver and excreted

from body:– Bilirubin is toxic if accumulates– Unconjugated bilirubin is insoluble in water and can’t be excretedUnconjugated bilirubin is insoluble in water and can t be excreted– Conjugated bilirubin is water soluble and can be excreted in bile

• BILE ACID PRODUCTION– Bile consists of : cholesterol, bile acids, conjugated bilirubin

F ti f bil– Functions of bile:– Absorption of fat soluble vitamins ( A, D, E, K )– Excretion of cholesterol and bilirubin

• DETOXIFICATION– Converts nitrogenous wastes (ammonia) into urea, and

excretes urea (ammonia is toxic to brain)– Metabolizes drugs and toxins in microsomes

Conjugates bilirubin to detoxify and excrete it– Conjugates bilirubin to detoxify and excrete it• CARBOHYDRATE METABOLISM

– Synthesizes and stores glucose as glycogen– Releases glucose into blood upon appropriate neural and


g p pp phormonal stimulation

FUNCTIONS OF LIVER

• MAJOR SITE OF HORMONAL BREAKDOWN AND RECYCLYING

– Monitors plasma hormone levels• Estrogen levels increase in chronic liver failure

and males develop gynecomastia ( to be discussed )discussed )


LIVER FUNCTION TESTS• INDICATORS OF HEPATIC SYNTHETIC FUNCTION

– Prothrombin time ( nml: 10- 12.5sec)• Reflects ability to make clotting factors with very short half• Reflects ability to make clotting factors with very short half

lives (several hours) therefore reflects acute changes in synthetic function (may also reflect chronic changes)

– Albumin ( nml: 3 0 - 5 5gm/dL )Albumin ( nml: 3.0 5.5gm/dL )• Indicative of chronic changes in synthetic function

due to long half life S t i l t h i b d t• Serum protein electrophoresis can be used to evaluate albumin and other proteins made by the liver

– Cholesterol synthesis– Gluconeogenesis


Cholesterol BiosynthesisCholesterol Biosynthesis


Liver Function TestsLiver Function Tests• INDICATORS OF HEPATIC DETOXIFICATION FUNCTION

– Ammonia Level• End product of protein metabolism

– Bacterial action in the intestine with glutamine hydrolysis in the kidneys

M t i d b th li ’ t l i i l ti d• Most is removed by the liver’s portal vein circulation and converted to urea

• Almost any ammonia (NH3) affects acid-base balance and brain function

• Uses– Diagnose Reye’s syndrome– Evaluate metabolism– Evaluate progress of liver disease and treatment– Monitor hyperalimentation patients

• Values– Adults 15 – 56 μg/dL– (nml: 12-47umol/L)


• For reference: false increase in ammonia may result from smoking; certain diuretics; tourniquet on too tight or too long

INDICATORS OF HEPATIC DETOXIFICATIONLIVER FUNCTION TESTS

• INDICATORS OF HEPATIC DETOXIFICATION FUNCTION

– Bilirubin• Total ( unconjugated and conjugated bilirubin ): 0.2-1.2

mg/dL• Direct ( conjugated bilirubin ): 0 – 0.3 mg/dLDirect ( conjugated bilirubin ): 0 0.3 mg/dL• Term “direct” refers to manner of measurement in lab

– Gamma-glutamyl-transpeptidase (GGT )Definition: enzyme which catalyzes transfer of glutamic acid• Definition: enzyme which catalyzes transfer of glutamic acid joined at a “gamma” carboxyl group

• Most sensitive indicator of hepatic injury, but nonspecific for type of injuryfor type of injury

• Can be used to monitor alcohol consumption in alcoholics because is located in microsomes, and alcohol activates microsomal enzymes


microsomal enzymes• Males: 15-85 U/L; females: 5-55 U/L

LIVER FUNCTION TESTS• TEST WHICH MAY REFLECT HEPATIC INJURY AND

NECROSIS– Aminotransferases

• Definition: enzymes which catalyze interconversion of amino acids

– Alanine aminotransferase (ALT): (formerly SGOT)– 0-48 U/L (U = units ) more specific for liver than AST

(formerly SGPT)(formerly SGPT)– Aspartate aminotransferase (AST): 0-41 U/L nonspecific

for liver: e.g. increased in MI

• Significant increase in both AST and ALT (>10x)• Significant increase in both AST and ALT (>10x) indicates severe hepatocyte damage


LIVER FUNCTION TESTS• TEST WHICH WHICH MAY REFLECT HEPATIC

INJURY AND NECROSIS– ALKALINE PHOSPHATASE ( nml: 30-117 U/L )

• Different forms of ALP in different organs ( isoenzymes ): liver is major source, then bone

• Isoenzyme analysis can help determine source of elevated ALPelevated ALP


LIVER FUNCTION TESTS• USE OF LIVER FUNCTION TESTS TO

DIAGNOSE HEPATOBILIARY DISEASE– HEPATITIS

• Definitions:H titi i fl ti d i f li ll– Hepatitis: inflammation and necrosis of liver cells resulting from different types of injury ( e.g. viruses; toxins )Antigen: biochemical component of a microbial– Antigen: biochemical component of a microbial pathogen or body tissue recognized as foreign by one’s immune systemAntibody: protein produced by plasma cells which– Antibody: protein produced by plasma cells which forms complex with antigen to destroy microbial pathogens or body tissueAutoimmunity: immune reaction to one’s own tissue


– Autoimmunity: immune reaction to one s own tissue and cells

LIVER FUNCTION TESTS

• ACUTE VIRAL HEPATITIS• Comprise 80-90% of cases of acute hepatitis• Types: Hepatitis A B C D E• Types: Hepatitis A, B, C, D, E• Mode of transmission; complications; serological screening

• PHASES OF ACUTE VIRAL HEPATITIS– Incubation period ( weeks: depends on virus )p ( p )– Prodromal phase: variable, systemic symtoms decreased

appetite ( anorexia ); nausea and vomiting; fatigue; arthralgia ( ache in joints ); myalgia ( muscle ache );headache; cough; sore throatthroat

– Clinical jaundice phase• occurs 1-2 weeks after onset of prodromal phase• serum blirubin > 2.5mg/dL to note signs of jaundiceg g j• many patients do not develop jaundice ( anicteric hepatitis )• liver enlarged and tender

– Recovery phase: constitutional symptoms disappear but liver i till l d d l b t t till b l


is still enlarged, and some lab tests are still abnormal (aminotransferases )

• LABORATORY FINDINGS IN C SACUTE VIRAL HEPATITIS

– AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are increased 10 100(alanine aminotransferase) are increased 10 –100 x upper limit normal ( 400-4000 U/L )

– AST/ALT ratio < 1 (ALT > AST)– Increased total bilirubin ( 5-20 mg/dL ) both

conjugated and unconjugated bilirubin increased (necrotic liver cells have decreased ability to both ( yconjugate unconjugated bilirubin and excrete conjugated bilirubin )

– ALP (alkaline phosphatase): 2x upper limit normalALP (alkaline phosphatase): 2x upper limit normal (ULN)

– GGT (gamma- glutamyl-transpeptidase): 5 x ULNP th bi ti t t i ll l t d l


– Prothrombin time: not typically elevated unless acute fulminant hepatitis (to be discussed)

CHRONIC ACTIVE HEPATITIS (CAH)(CAH)

• HEPATITIS B ( HBV ): 5% patients develop CAH Criteria- if the following occur longer than 6 months– Hepatitis B surface antigen ( HBsAg ) present ALT increased– HBV resolves when HBsAg disappears and hepatitis B surface

antibody ( anti-HBs ) appears HEPATITIS C ( HCV ) 60 80% ti t d l CAH• HEPATITIS C ( HCV ): 60-80% patients develop CAH– IS A MAJOR HEALTH CONCERN IN US TODAY

• results in 8,000-13,000 deaths annually in US• 20-30% patients develop cirrhosis which may progress to

primary liver cancer ( hepatocellular carcinoma )• 75% patients asymptomatic, so: silenty, over many decades,

HCV destroys liver cells resulting in cirrhosisHCV destroys liver cells resulting in cirrhosis • AST and ALT may be normal intermittently making detection

more difficult• Annual cost related to hepatitis C in US is very high: In 1997


• Annual cost related to hepatitis C in US is very high: In 1997 cost was approximately $5.46 billion

CHRONIC ACTIVE HEPATITIS (CAH)

– MODE OF TRANSMISSON OF HEPATITIS ( for reference )• Blood:

IV drug addicts sharing needles ( most efficient means of

(CAH)

IV drug addicts sharing needles ( most efficient means of transmission ) transfusions before 1992; needle stick accidents in health care professionals (1/2000 infection rate )

• Intranasal cocaine• Sexual contact • Tatooing or body piercing: with unsanitary conditions• Perinatal transmission

Sh i t th b h f i f t d• Sharing razor or tooth brush from an infected person– DETECTION ( for reference )

• often diagnosed incidentally on routine exam• screening serology: detection of hepatitis C antibody (enzyme• screening serology: detection of hepatitis C antibody (enzyme

immunoassay )• confirmation: recombinant immunoblot assay ( RIBA )• HCV RNA: confirmation and determination of viral load to monitor


treatment response – TREATMENT: interferon alpha and ribavirin ( for reference )

CHRONIC ACTIVE HEPATITIS (CAH)(CAH)

– ALCOHOLIC HEPATITISexcessive alcohol intake is the leading cause of liver disease in most Western countries

– some reasons why alcohol is hepatotoxic: ( for reference )l h l d h d ( t b li l h l ) f tt h• alcohol dehydrogenase ( metabolizes alcohol ) causes fatty change

which is initial pathologic change in alcoholic liver disease: fatty change alcoholic hepatitis ( continuous destruction with acute episodes of hepatic decompensation ) cirrhosisp p p )

• toxic products of alcohol metabolism: free radicals and acetaldehyde ( disrupt cell membrane function )fatty change is reversible, and alcoholic hepatitis is reversible to a point if patient abstains from alcohol


Alcoholic HepatitisAlcoholic Hepatitis

• CLINICAL FEATURES OF ACUTE ALCOHOLIC• CLINICAL FEATURES OF ACUTE ALCOHOLIC HEPATITIS

– Variable presentation: mild fatal hepatic p pdecompensation

– Clinical findings similar to viral hepatitis anorexia weight loss abdominal pain nausea andanorexia, weight loss, abdominal pain, nausea and vomiting, jaundice, fever, tender hepatomegaly ( due to fatty liver and swelling of injured liver cells ), splenomegaly ( in 1/3 ); ascites in 1/3 due to transient portal venous obstruction or cirrhosis ( hepatic scarring )


hepatic scarring )

Alcoholic HepatitisAlcoholic Hepatitis

• LABORATORY FINDINGS IN ALCOHOLIC HEPATITIS– AST and ALT elevated up to 10 x ULN ( less than viral

hepatitis; AST often < 300 U/L )– classically AST/ALT ratio > 1 ( or 2 ), but not always

this disproportionate increase in AST ( with AST/ALT ratio > 2 ) is rarely seen in other forms of liver disease remember: with viral hepatitis AST/ALT ratio < 1ratio < 1

– GGT is increased– MCV > 100 fL

• direct alcohol toxicitydirect alcohol toxicity• megaloblastic anemia secondary to folate deficiency (

MCV > 110 fL in diagnostic range; macroovalocytes; hypersegmented neutrophils )

H bili bi iBy Dave Kotun for NSU Orlando 26

– Hyperbilirubinemia

DRUG INDUCED HEPATITISDRUG INDUCED HEPATITIS

Drugs:g• isoniazid ( anti-tuberculous drug ) – elevated

aminotransferases in 10%; illness like viral h titi i 1% ith 10% f t lit thepatitis in 1% with 10% fatality rate

• Methyldopa• “ alternative meds “• alternative meds

– some herbal meds ( e.g. senna, mistletoe; herbal teas with toxic alkaloids; chaparral; kava kava; comfrey; germander; Jin Bu Huan; Ma-Huang )megadoses of vitamin A


– megadoses of vitamin A

AUTOIMMUNE HEPATITIS• Definition: chronic hepatocellular necrosisDefinition: chronic hepatocellular necrosis

and inflammation usually with scarring which tends to progress to cirrhosis and liver failure ( i th h t t d i( in those who are untreated or unresponsive to therapy )

• Clinical presentation variable: mayClinical presentation variable: may resemble acute viral hepatitis, but patients may be asymptomatic and diagnosed on routine examroutine exam

• Diagnosis: a diagnosis of exclusion ( exclude other causes of hepatitis ) serologic


p ) gtesting helps make diagnosis: to be discussed in serology lecture

Acute Fulmanant Hepatitis and Liver Failure Causes

• Acetaminophen overdose (suicide; accidental in children)Vi l h i i• Viral hepatitis

• Halothane (anesthetic gas) - may also cause no or mild symptoms and increase in serum aminotransferases is no longer used in adults in US, but still in children,

• Poisonous mushroom (Amanita phalloides)• Hypotension caused by MI, arrhythmia or sepsis• Rare: anti-seizure drugs- sodium valproate; phenytoin (may also

l b liti i li f ti )cause less severe abnormalities in liver function)• Some herbal meds

– Chaparral: native to southwest US; thought to have broad anti-microbial properties and is used for many conditions such asmicrobial properties and is used for many conditions such as veneral skin lesions; popular among patients with HIV

– Jin Bu Huan: used as sedative and analgesic– Ma- Huang ( has ephedrine ): used for weight loss and to treat

i di l diti ( h b hiti j i tBy Dave Kotun for NSU Orlando 29

various medical conditions (e.g. cough; bronchitis; joint symptoms)

Acute Fulmanant Hepatitis and Liver Failure

LAB FINDINGS• abrupt extreme elevation of ALT and AST: > 100 x ULN (> 4000 units/L)• abrupt, extreme elevation of ALT and AST: > 100 x ULN (> 4000 units/L)• prothrombin time significantly prolonged ( > or = 4 sec above

normal)• elevated serum ammonia may be seen: due to inability of necrotic

hepatocytes to convert ammonia to urea for excretion alterations inhepatocytes to convert ammonia to urea for excretion alterations in consciousness which may ultimately result in coma can occur: called hepatic encephalopathy ( to be discussed )

SUMMARY OF KEY LAB FINDINGS IN DIFFERENT FORMS OF HEPATITISSUMMARY OF KEY LAB FINDINGS IN DIFFERENT FORMS OF HEPATITIS• FEATURE VIRAL ALCOHOLIC TOXIC/ISCHEMIC• AST/ALT RATIO < 1 > 1 or 2 > 1 • PEAK AST 10-100 1-10 > 100 ( x normal )( )• PT normal nml or inc. usually > 15 sec


Hyperbilirubinemia and J diJaundice

• Jaundice, also known as icterus, is noted asJaundice, also known as icterus, is noted as yellowing of sclera and skin, due to increased serum bilirubin ( > 2.5 mg/dL )


Hyperbilirubinemia and Jaundice

CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIAU j d bili bi i 80 85% f l bili biUnconjugated bilirubin is > 80-85% of total bilirubin• BILIRUBIN OVER PRODUCTION

– Hemolytic anemias ( e.g. sickle cell anemia )Hemolytic transfusion reaction– Hemolytic transfusion reaction

– Resorption of major hemorrhages• DECREASED BILIRUBIN CONJUGATION

– Gilbert’s syndrome:Gilbert s syndrome: • Inherited in 6% population; presents in adolescence or

adulthood with illness, strenuous exercise, fasting, lack of sleep, stress ( bilirubin rarely > 3-4 mg/dL )Si ifi f Gilb t’ d iti id• Significance of Gilbert’s syndrome: recognition avoids expensive work-up and reassures patient

– Physiologic neonatal jaundice:Liver too immature to conjugate bilirubin in neonatal period (


Liver too immature to conjugate bilirubin in neonatal period ( especially if neonate is premature )

Hyperbilirubinemia and J diJaundiceCAUSES OF CONJUGATED ( DIRECT ) HYPERBILIRUBINEMIAOBSTRUCTION TO FLOW OF BILE WITHIN THE BILIARY TREEConjugated ( direct ) bilirubin is > 50% of total bilirubin• GALLSTONES

Cause > 95% biliary tract diseaseTypes:

– Cholesterolmajority stones in Western countries

• pigmented ( salts of unconjugated bilirubin ) caused by:– chronic hemolysis ( sickle cell disease )– parasitic infections in non-Western countries

• TUMORS– Cancer of head of pancreas

C f ll f V– Cancer of ampulla of Vater– Cancer of bile duct

• BILIARY ATRESIA– destruction or absence of all or part of extrahepatic biliary tree in

infants


infants– most common cause of death due to liver disease in early childhood

Hyperbilirubinemia and Jaundice

LAB VALUES IN BILIARY TRACT OBSTRUCTION

• early, complete obstruction– increasing conjugated bilirubin ( direct

bilirubin )l i i ALP ( lk li– slow increase in ALP ( alkaline

phosphatase ) over several days ( < 3-4 x ULN )U )

– increase in AST ( aspartate aminotransferase ) and ALT

By Dave Kotun for NSU Orlando 34– ( alanine aminotransferase )

Hyperbilirubinemia and J diJaundice

• Persistent ( chronic ), complete obstructionPersistent ( chronic ), complete obstruction– ALP and GGT ( gamma-glutamyl-

transpeptidase) markedly increased: p p ) yoften 10 –30x ULN

– Progressive increase in total bilirubing• Partial or intrahepatic obstruction

– Progressive increase in ALP and GGT: og ess e c ease a d GGoften 10-30x ULN

– Minimal increase in direct bilirubinBy Dave Kotun for NSU Orlando 35– Normal AST and ALT

Hyperbilirubinemia and JaundiceJaundiceEXPLANATION OF LAB VALUES FOR CONJUGATEDHYPERBILIRUBINEMIA:HYPERBILIRUBINEMIA:• Complete obstruction to bile flow results in the

following:– Some bile which is not excreted diffuses back into

ththe serum– Pressure increases in biliary tract; to overcome

pressure in biliary tract, enzymes found at surface of smallest bile ducts ( ALP and GGT ) increase( )

– Toxic waste ( e.g. bilirubin ) builds up in liver cells ( hepatocytes ) due to accumulation of backed up bile in the cells the liver cells are damaged AST and ALT increaseALT increase

• Partial obstruction of biliary tract– Obstruction is enough to cause pressure in biliary tract

and increase in enzymes ( ALP; GGT ) near small bile d cts


ducts– Obstruction is NOT enough to cause significant

diffusion of bilirubin back into serum

CirrhosisCirrhosisDEFINITION: diffuse injury and scarring of liver tissue

icausing total disruption of liver architecture and function

• CAUSES OF CIRRHOSIS IN WESTERN WORLD:– ALCOHOLIC LIVER DISEASE 60-70%– Viral hepatitis 10%– Biliary disease 5-10%– Biliary disease 5-10%– Primary hemochromatosis 5%– Remainder: 10-15%

A t i h titi l h ti t i• Autoimmune hepatitis; alpha anti-trypsin deficiency; Wilson's disease;

– Unknown causeLook up the symptoms of Wilson’s disease


– Look up the symptoms of Wilson’s disease

CirrhosisCirrhosisCONSEQUENCES OF CIRRHOSIS• PORTAL HYPERTENSION

Definition: increased pressure in portal circulation due to resistanceto portal blood flow in scarred liver Consequences Of Portal Hypertension:– Engorgement of veins where systemic and portal circulation

share common capillary beds• Gastroesophageal varices: in 2/3 patients with advanced

cirrhosis; fatal rupture and hemorrhage occurs in half of patients with varices

• Hemorrhoids: veins in rectum• Hemorrhoids: veins in rectum• Periumbilical veins: “ caput medusae”

– Congestive splenomegaly Ascites


– Ascites

ASCITESASCITESDefinition: at least 500 ml of excess fluid in abdominal cavityCauses:• Portal hypertension ( hydrostatic pressure driving fluid out of vessel )• Low serum albumin ( decreased serum oncotic pressure) secondary

to:– Decreased synthetic ability of cirrhotic liver– Decreased portal blood flow and supply of amino acids to liver

• Consequence of ascites:SPONTANEOUS BACTERIAL PERITONITIS abrupt onset of fever,chills, and generalized abdominal pain without obvious source ofInfection (bacteria can be grown from ascitic fluid )


CoagulopathyCoagulopathy• Definition - increased bleeding tendencyDefinition increased bleeding tendency• Causes:

– Decreased ability of liver to make clottingDecreased ability of liver to make clotting factors

– Decreased ability of liver to make bile acids yto absorb vitamin K from small intestine (vitamin K needed to make some clotting factors)factors)

– Decreased platelets because are sequestered in enlarged spleen (due to


q g p (portal hypertension)

Hepatic EncephalopathyHepatic Encephalopathy• Definition: complex neuropsychiatric syndrome with disturbances in

consciousness mood and behavior along with fluctuatingconsciousness, mood, and behavior along with fluctuating neurologic signs

• Presentation of hepatic encephalopathy: varies- acute and reversible vs. chronic and progressive; 4 stages with last stage being coma which may result in deathbeing coma which may result in death

• Cause of hepatic encephalopathy: decreased detoxification of neurotoxic substances ( like ammonia ) by liver ( may occur in setting of cirrhosis or acute, fulminant liver failure )

• Precipitating factors: ( for reference )– Increased nitrogen load ( e.g. GI bleeding )

El t l t i b l– Electrolyte imbalance– Infection– Surgery


Hepatorenal SyndromeHepatorenal Syndrome

• Definition: acute renal failure occurring in• Definition: acute renal failure occurring in the setting of severe liver disease, in which there is no structural abnormality of ythe kidney

• Precipitating factors ( for reference )p g ( )– An obvious cause may not be present– Severe GI bleeding ( e.g. ruptured

)gastroesophageal varices )– Sepsisoverly vigorous attempts to treat

ascites ( present in cirrhotic patients ) withBy Dave Kotun for NSU Orlando 42

ascites ( present in cirrhotic patients ) with diuretic agents or paracentesis (fluid drainage)

Impaired Estrogen Metabolism• Symptoms

– In males: breast tissue development ( gynecomastia ), testicular atrophy

• LAB VALUES IN CIRRHOSIS– Decreased serum albumin– Prolonged prothrombin time– Slight elevation of alkaline phosphatase, GGT and total

bilirubin due to some obstruction to bile flow within liver frombilirubin due to some obstruction to bile flow within liver from scarring

– AST and ALT nml or slightly elevated due to liver cell injury Not significantly elevated because significant acute liver cellNot significantly elevated because significant acute liver cell necrosis is not occurring, and much liver tissue is already lost


NORMAL LAB VALUES:• Serum albumin 3-5.5 gm/dL• Prothrombin time 10 - 12.5sec• Total bilirubin 0.2-

1 2mg/dL1.2mg/dL• Conjugated ( direct ) bilirubin 0.0-0.3 mg/dL• Serum ammonia 12- 47 umol/L• Alanine aminotransferase• Alanine aminotransferase • ( ALT ) 0-48units/L• Aspartate aminotransferase• ( AST ) 0-41units/L( S ) 0 u ts/• Alkaline phosphatase 30-117units/L• Serum amylase 25-125 units/L• Serum lipase 10-140

i /dLBy Dave Kotun for NSU Orlando 44

units/dL

Questions?Questions?


P A O 5600 Lecture 5 Liver Fx Tests (1hr) Dave

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Transcript of P A O 5600 Lecture 5 Liver Fx Tests (1hr) Dave