Your SlideShare is downloading. ×
0
LIVER FUNCTION TESTS

 CLINICAL LAB MEDICINE I
PAO 5600
The Liver
• Largest Gland
  – Weighs 1 5 Kg
             1.5
  – Inf edge is usually
    subcostal
  – Synthesizes and
   ...
OBJECTIVES
•  List the tests which aid in the assessment of the
   detoxification function of liver
•  List tests which ai...
LIVER FUNCTION TESTS
•       Tests which can assess the synthetic function of liver
    –      Prothrombin time
    –     ...
HEPATOBILIARY DISEASE
•       HEPATITIS
        •       Definition and important causes (viral; alcoholic; drug
          ...
HEPATOBILIARY DISEASE

• Hepatitis ( cont )
              cont.)
  – ALCOHOLIC HEPATITIS
        – Clinical presentation a...
HYPERBILIRUBINEMIA
•    Causes
    – Elevation of unconjugated bilirubin
    – Elevation of conjugated bilirubin
•    Lab ...
OVERVIEW OF LIVER
        ANATOMY
•       FUNCTIONAL UNIT: liver lobule
    –     Hexagonal structure with rows of liver c...
FUNCTIONS OF LIVER
•     Liver is the “major metabolic factory and disposal plant
      “
    –    PLASMA PROTEIN SYNTHESI...
FUNCTIONS OF LIVER
•       Why must unconjugated bilirubin be conjugated by liver and excreted
        from body:
    –   ...
FUNCTIONS OF LIVER

•       MAJOR SITE OF HORMONAL
        BREAKDOWN AND RECYCLYING
    –     Monitors plasma hormone leve...
LIVER FUNCTION TESTS
• INDICATORS OF HEPATIC SYNTHETIC FUNCTION
   – Prothrombin time ( nml: 10- 12.5sec)
     • Reflects ...
Cholesterol Biosynthesis




        By Dave Kotun for NSU Orlando   13
By Dave Kotun for NSU Orlando   14
Liver Function Tests
•   INDICATORS OF HEPATIC DETOXIFICATION FUNCTION
     – Ammonia Level
•   End product of protein met...
LIVER FUNCTION TESTS
•       INDICATORS OF HEPATIC DETOXIFICATION
        FUNCTION
    –     Bilirubin
        •    Total ...
LIVER FUNCTION TESTS
• TEST WHICH MAY REFLECT HEPATIC INJURY AND
  NECROSIS
   – Aminotransferases
     • Definition: enzy...
LIVER FUNCTION TESTS
•    TEST WHICH WHICH MAY REFLECT HEPATIC
     INJURY AND NECROSIS
    – ALKALINE PHOSPHATASE ( nml: ...
LIVER FUNCTION TESTS
•    USE OF LIVER FUNCTION TESTS TO
     DIAGNOSE HEPATOBILIARY DISEASE
    – HEPATITIS
      •      ...
LIVER FUNCTION TESTS
•    ACUTE VIRAL HEPATITIS
        •   Comprise 80-90% of cases of acute hepatitis
        •   Types:...
•       LABORATORY FINDINGS IN
        ACUTE VIRAL HEPATITIS
         C                  S
    –    AST (aspartate aminotr...
CHRONIC ACTIVE HEPATITIS
        (CAH)
•   HEPATITIS B ( HBV ): 5% patients develop CAH Criteria- if the
    following occ...
CHRONIC ACTIVE HEPATITIS
    (CAH)
–    MODE OF TRANSMISSON OF HEPATITIS ( for reference )
    •   Blood:
        IV drug ...
CHRONIC ACTIVE HEPATITIS
    (CAH)
–    ALCOHOLIC HEPATITIS
  excessive alcohol intake is the leading cause of liver disea...
Alcoholic Hepatitis

•    CLINICAL FEATURES OF ACUTE ALCOHOLIC
     HEPATITIS
    – Variable presentation: mild fatal hepa...
Alcoholic Hepatitis
•   LABORATORY FINDINGS IN ALCOHOLIC HEPATITIS
     – AST and ALT elevated up to 10 x ULN ( less than ...
DRUG INDUCED HEPATITIS
Drugs:
    g
   •   isoniazid ( anti-tuberculous drug ) – elevated
       aminotransferases in 10%;...
AUTOIMMUNE
HEPATITIS
•   Definition: chronic hepatocellular necrosis
    and inflammation usually with scarring which
    ...
Acute Fulmanant Hepatitis
        and Liver Failure Causes
•     Acetaminophen overdose (suicide; accidental in children)
...
Acute Fulmanant Hepatitis
       and Liver Failure
LAB FINDINGS
•    abrupt,
     abrupt extreme elevation of ALT and AST:...
Hyperbilirubinemia and
     Jaundice
     J   di
•   Jaundice, also known as icterus, is noted as
    yellowing of sclera ...
Hyperbilirubinemia and
        Jaundice
CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA
Unconjugated bilirubin is > 80-85% of to...
Hyperbilirubinemia and
Jaundice
J   di
CAUSES OF CONJUGATED ( DIRECT ) HYPERBILIRUBINEMIA
OBSTRUCTION TO FLOW OF BILE WITH...
Hyperbilirubinemia and
     Jaundice
LAB VALUES IN BILIARY TRACT
   OBSTRUCTION
• early, complete obstruction
  – increasi...
Hyperbilirubinemia and
     Jaundice
     J   di
•  Persistent ( chronic ), complete obstruction
  – ALP and GGT ( gamma-g...
Hyperbilirubinemia and
Jaundice
EXPLANATION OF LAB VALUES FOR CONJUGATED
HYPERBILIRUBINEMIA:
• Complete obstruction to bil...
Cirrhosis
DEFINITION: diffuse injury and scarring of liver tissue
     causing
           i
     total disruption of liver...
Cirrhosis
CONSEQUENCES OF CIRRHOSIS
•      PORTAL HYPERTENSION
   Definition: increased pressure in portal circulation due...
ASCITES
Definition: at least 500 ml of excess fluid in abdominal cavity
Causes:
•     Portal hypertension ( hydrostatic pr...
Coagulopathy
•   Definition - increased bleeding tendency
•   Causes:
    – Decreased ability of liver to make clotting
  ...
Hepatic Encephalopathy
•    Definition: complex neuropsychiatric syndrome with disturbances in
     consciousness, mood,
 ...
Hepatorenal Syndrome
• Definition: acute renal failure occurring in
  the setting of severe liver disease, in
  which ther...
Impaired Estrogen Metabolism
•       Symptoms
    –     In males: breast tissue development ( gynecomastia ),
          te...
NORMAL LAB VALUES:
• Serum albumin                                      3-5.5 gm/dL
• Prothrombin time                    ...
Questions?




        By Dave Kotun for NSU Orlando   45
Upcoming SlideShare
Loading in...5
×

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

4,159

Published on

Published in: Health & Medicine
1 Comment
3 Likes
Statistics
Notes
No Downloads
Views
Total Views
4,159
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
442
Comments
1
Likes
3
Embeds 0
No embeds

No notes for slide

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

  1. 1. LIVER FUNCTION TESTS CLINICAL LAB MEDICINE I PAO 5600
  2. 2. The Liver • Largest Gland – Weighs 1 5 Kg 1.5 – Inf edge is usually subcostal – Synthesizes and detoxifies By Dave Kotun for NSU Orlando 2
  3. 3. OBJECTIVES • List the tests which aid in the assessment of the detoxification function of liver • List tests which aid in the assessment of hepatic injury and necrosis • Explain why the gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase tests aid in the assessment of biliary tract obstruction y • Recall what effect the liver function has on the y the prothrombin time and serum albumin • Compare and contrast the lab findings in the hepatitises and what impact these conditions have on individual and community health • Trace the b ub pa ace e bilirubin pathway a d the lab findings in ay and e ab d gs bilirubin abnormalities and biliary tract obstruction. • Describe etiologies, lab findings, and complications associated with the effect of alcohol on the liver By Dave Kotun for NSU Orlando 3
  4. 4. LIVER FUNCTION TESTS • Tests which can assess the synthetic function of liver – Prothrombin time – Serum albumin – Cholesterol Ch l t l • 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 pathway – Serum ammonia • Tests which may be indicative of liver injury – Aminotransferases • Aspartate aminotransferase (AST) • Alanine aminotransferase (ALT) • Gamma- glutamyl-transpeptidase ( GGT ) • Tests which may be indicative of biliary tract obstruction – Alkaline h Alk li phosphatase (ALP) ht – Gamma- glutamyl-transpeptidase (GGT) By Dave Kotun for NSU Orlando 4
  5. 5. HEPATOBILIARY DISEASE • HEPATITIS • 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 • Clinical presentation – Why hepatitis C is of particular health concern in the US today By Dave Kotun for NSU Orlando 5
  6. 6. HEPATOBILIARY DISEASE • Hepatitis ( cont ) cont.) – ALCOHOLIC HEPATITIS – Clinical presentation and diagnostic findings p g g – DRUG-INDUCED HEPATITIS • Examples of drugs which may cause hepatitis – AUTOIMMUNE HEPATITIS – Definition – ACUTE FULMINANT HEPATITIS CU U S – Causes and diagnostic findings By Dave Kotun for NSU Orlando 6
  7. 7. HYPERBILIRUBINEMIA • Causes – Elevation of unconjugated bilirubin – Elevation of conjugated bilirubin • Lab findings associated with biliary tract obstruction – Complete: early and chronic findings – Partial or intrahepatic obstruction • CIRRHOSIS – Definition – Major causes • Lab findings • Complications » p portal hypertension (g yp (gastroesophageal varices etc.), pg ), ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, coagulopathy By Dave Kotun for NSU Orlando 7
  8. 8. 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 vein branch, bile duct) in each corner • CIRCULATION – hepatic artery brings blood rich in O2 to liver; blood flows from portal triad to central vein ein – portal vein drains GI tract and spleen and carries blood rich in nutrients to liver • 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 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 By Dave Kotun for NSU Orlando 8
  9. 9. FUNCTIONS OF LIVER • Liver is the “major metabolic factory and disposal plant “ – PLASMA PROTEIN SYNTHESIS • Albumin – major carrier of substances in blood – most abundant plasma protein so maintains plasma oncotic pressure • most clotting factors – BILIRUBIN METABOLISM ( figure 1 ) • Metabolic pathway of bilirubin: • RBC 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 reabsorbed and excreted in urine By Dave Kotun for NSU Orlando 9
  10. 10. 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 excreted can t – Conjugated bilirubin is water soluble and can be excreted in bile • BILE ACID PRODUCTION – Bile consists of : cholesterol, bile acids, conjugated bilirubin – Functions of bile: F ti f bil – 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 • CARBOHYDRATE METABOLISM – Synthesizes and stores glucose as glycogen – Releases glucose into blood upon appropriate neural and g p pp p hormonal stimulation By Dave Kotun for NSU Orlando 10
  11. 11. 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 ) By Dave Kotun for NSU Orlando 11
  12. 12. LIVER FUNCTION TESTS • INDICATORS OF HEPATIC SYNTHETIC FUNCTION – Prothrombin time ( nml: 10- 12.5sec) • 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 ) 3.0 5.5gm/dL • Indicative of chronic changes in synthetic function due to long half life •SSerum protein electrophoresis can b used t ti l t h i be d to evaluate albumin and other proteins made by the liver – Cholesterol synthesis – Gluconeogenesis By Dave Kotun for NSU Orlando 12
  13. 13. Cholesterol Biosynthesis By Dave Kotun for NSU Orlando 13
  14. 14. By Dave Kotun for NSU Orlando 14
  15. 15. Liver 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 • Most i M t is removed b th li ’ portal vein circulation and d by the liver’s t l i i l ti d 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 By Dave Kotun for NSU Orlando 15
  16. 16. LIVER 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/dL • Term “direct” refers to manner of measurement in lab – Gamma-glutamyl-transpeptidase (GGT ) • 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 injury • Can be used to monitor alcohol consumption in alcoholics because is located in microsomes, and alcohol activates microsomal enzymes • Males: 15-85 U/L; Dave Kotun for NSU OrlandoU/L females: 5-55 By 16
  17. 17. 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) – Aspartate aminotransferase (AST): 0-41 U/L nonspecific for liver: e.g. increased in MI • Significant increase in both AST and ALT (>10x) indicates severe hepatocyte damage By Dave Kotun for NSU Orlando 17
  18. 18. 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 ALP By Dave Kotun for NSU Orlando 18
  19. 19. LIVER FUNCTION TESTS • USE OF LIVER FUNCTION TESTS TO DIAGNOSE HEPATOBILIARY DISEASE – HEPATITIS • Definitions: – Hepatitis: i fl titi inflammation and necrosis of li ti d i f liver cells ll H resulting from different types of injury ( e.g. viruses; toxins ) – Antigen: biochemical component of a microbial pathogen or body tissue recognized as foreign by one’s immune system – Antibody: protein produced by plasma cells which forms complex with antigen to destroy microbial pathogens or body tissue – Autoimmunity: immune reaction to one’s own tissue one s and cells By Dave Kotun for NSU Orlando 19
  20. 20. LIVER FUNCTION TESTS • ACUTE VIRAL HEPATITIS • Comprise 80-90% of cases of acute hepatitis • Types: Hepatitis A, B, C, D E A B C D, • 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 throat – Clinical jaundice phase • occurs 1-2 weeks after onset of prodromal phase • serum blirubin > 2.5mg/dL to note signs of j g g jaundice • many patients do not develop jaundice ( anicteric hepatitis ) • liver enlarged and tender – Recovery phase: constitutional symptoms disappear but liver is till l i still enlarged, and some l b t t are still abnormal d d lab tests till b l (aminotransferases ) By Dave Kotun for NSU Orlando 20
  21. 21. • LABORATORY FINDINGS IN ACUTE VIRAL HEPATITIS C S – AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are increased 10 –100 100 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 y conjugate unconjugated bilirubin and excrete conjugated bilirubin ) – ALP (alkaline phosphatase): 2x upper limit normal (ULN) – GGT (gamma- glutamyl-transpeptidase): 5 x ULN – Prothrombin ti P th bi time: not t i ll elevated unless t typically l td l acute fulminant hepatitis NSU Orlando discussed) By Dave Kotun for (to be 21
  22. 22. CHRONIC ACTIVE HEPATITIS (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% patients develop CAH ): 60-80% ti t d l – 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 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 cost was approximately $5.46 billion By Dave Kotun for NSU Orlando 22
  23. 23. CHRONIC ACTIVE HEPATITIS (CAH) – MODE OF TRANSMISSON OF HEPATITIS ( for reference ) • Blood: 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 • Sharing Sh i razor or t th b h f tooth brush from an i f t d person infected – DETECTION ( for reference ) • often diagnosed incidentally on routine exam • 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: interferonDave Kotun for NSU Orlando By alpha and ribavirin ( for reference ) 23
  24. 24. CHRONIC ACTIVE HEPATITIS (CAH) – ALCOHOLIC HEPATITIS excessive alcohol intake is the leading cause of liver disease in most Western countries – some reasons why alcohol is hepatotoxic: ( for reference ) • alcohol d h d l h l dehydrogenase ( metabolizes alcohol ) causes f tt change t b li l hl fatty h which is initial pathologic change in alcoholic liver disease: fatty change alcoholic hepatitis ( continuous destruction with acute episodes of hepatic decompensation ) cirrhosis p 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 By Dave Kotun for NSU Orlando 24
  25. 25. Alcoholic Hepatitis • CLINICAL FEATURES OF ACUTE ALCOHOLIC HEPATITIS – Variable presentation: mild fatal hepatic p p decompensation – Clinical findings similar to viral hepatitis anorexia, anorexia weight loss abdominal pain nausea and loss, pain, 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 ) By Dave Kotun for NSU Orlando 25
  26. 26. Alcoholic 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 < 1 – GGT is increased – MCV > 100 fL • direct alcohol toxicity • megaloblastic anemia secondary to folate deficiency ( MCV > 110 fL in diagnostic range; macroovalocytes; hypersegmented neutrophils ) –HHyperbilirubinemia bili bi i By Dave Kotun for NSU Orlando 26
  27. 27. DRUG INDUCED HEPATITIS Drugs: g • isoniazid ( anti-tuberculous drug ) – elevated aminotransferases in 10%; illness like viral hepatitis i 1% with 10% f t lit rate h titi in ith fatality t • Methyldopa • “ 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 By Dave Kotun for NSU Orlando 27
  28. 28. AUTOIMMUNE HEPATITIS • Definition: chronic hepatocellular necrosis and inflammation usually with scarring which tends to progress to cirrhosis and liver failure ( i th in those who are untreated or unresponsive h t td i to therapy ) • Clinical presentation variable: may resemble acute viral hepatitis, but patients may be asymptomatic and diagnosed on routine exam • Diagnosis: a diagnosis of exclusion ( exclude other causes of hepatitis ) serologic p g testing helps make diagnosis: to be discussed in By Dave Kotun for NSU Orlando serology lecture 28
  29. 29. Acute Fulmanant Hepatitis and Liver Failure Causes • Acetaminophen overdose (suicide; accidental in children) • Viral h Vi l hepatitis ii • 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 cause lless severe abnormalities i li b liti in liver f function) ti ) • Some herbal meds – Chaparral: native to southwest US; thought to have broad anti- microbial 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 various medical conditions ( i di l diti (e.g. cough; b h bronchitis; j i t hiti joint symptoms) By Dave Kotun for NSU Orlando 29
  30. 30. Acute Fulmanant Hepatitis and Liver Failure LAB FINDINGS • abrupt, 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 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 HEPATITIS • FEATURE VIRAL ALCOHOLIC TOXIC/ISCHEMIC • AST/ALT RATIO <1 > 1 or 2 >1 • PEAK AST 10-100 1-10 > 100 ( x normal ) • nml or inc. usually > 15 sec PT normal By Dave Kotun for NSU Orlando 30
  31. 31. Hyperbilirubinemia and Jaundice J di • Jaundice, also known as icterus, is noted as yellowing of sclera and skin, due to increased serum bilirubin ( > 2.5 mg/dL ) By Dave Kotun for NSU Orlando 31
  32. 32. Hyperbilirubinemia and Jaundice CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA Unconjugated bilirubin is > 80-85% of total bilirubin U j d bili bi i 80 85% f l bili bi • BILIRUBIN OVER PRODUCTION – Hemolytic anemias ( e.g. sickle cell anemia ) – Hemolytic transfusion reaction – Resorption of major hemorrhages • DECREASED BILIRUBIN CONJUGATION – Gilbert s 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 ) • Significance of Gilbert’s syndrome: recognition avoids Si ifi f Gilb t’ d iti id expensive work-up and reassures patient – Physiologic neonatal jaundice: Liver too immature to conjugate bilirubin in neonatal period ( especially if neonate is premature ) By Dave Kotun for NSU Orlando 32
  33. 33. Hyperbilirubinemia and Jaundice J di CAUSES OF CONJUGATED ( DIRECT ) HYPERBILIRUBINEMIA OBSTRUCTION TO FLOW OF BILE WITHIN THE BILIARY TREE Conjugated ( direct ) bilirubin is > 50% of total bilirubin • GALLSTONES Cause > 95% biliary tract disease Types: – Cholesterol majority 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 Cancer of ampulla of V f ll f Vater – Cancer of bile duct • BILIARY ATRESIA – destruction or absence of all or part of extrahepatic biliary tree in infants – most common cause of death due to liver disease in early childhood By Dave Kotun for NSU Orlando 33
  34. 34. Hyperbilirubinemia and Jaundice LAB VALUES IN BILIARY TRACT OBSTRUCTION • early, complete obstruction – increasing conjugated bilirubin ( direct bilirubin ) – slow i l increase i ALP ( alkaline in lk li phosphatase ) over several days ( < 3-4 x U ULN ) – increase in AST ( aspartate aminotransferase ) and ALT – ( alanine aminotransferase ) By Dave Kotun for NSU Orlando 34
  35. 35. Hyperbilirubinemia and Jaundice J di • Persistent ( chronic ), complete obstruction – ALP and GGT ( gamma-glutamyl- transpeptidase) markedly increased: pp ) y often 10 –30x ULN – Progressive increase in total bilirubin g • Partial or intrahepatic obstruction – Progressive increase in ALP a d GG og ess e c ease and GGT: often 10-30x ULN – Minimal increase in direct bilirubin – Normal AST and ALT By Dave Kotun for NSU Orlando 35
  36. 36. Hyperbilirubinemia and Jaundice EXPLANATION OF LAB VALUES FOR CONJUGATED HYPERBILIRUBINEMIA: • Complete obstruction to bile flow results in the following: – Some bile which is not excreted diffuses back into the th 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 increase • Partial obstruction of biliary tract – Obstruction is enough to cause pressure in biliary tract and increase in enzymes ( ALP; GGT ) near small bile ducts d cts – Obstruction is NOT enough to cause significant By Dave Kotun for NSU Orlando 36 diffusion of bilirubin back into serum
  37. 37. Cirrhosis DEFINITION: diffuse injury and scarring of liver tissue causing i 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% – Primary hemochromatosis 5% – Remainder: 10-15% • Autoimmune h Ati hepatitis; alpha anti-trypsin titi lh ti t i deficiency; Wilson's disease; – Unknown cause – Look up the symptoms of Wilson’s disease By Dave Kotun for NSU Orlando 37
  38. 38. Cirrhosis CONSEQUENCES OF CIRRHOSIS • PORTAL HYPERTENSION Definition: increased pressure in portal circulation due to resistance to 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 • Periumbilical veins: “ caput medusae” – Congestive splenomegaly – Ascites By Dave Kotun for NSU Orlando 38
  39. 39. ASCITES Definition: at least 500 ml of excess fluid in abdominal cavity Causes: • 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 of Infection (bacteria can be grown from ascitic fluid ) By Dave Kotun for NSU Orlando 39
  40. 40. Coagulopathy • Definition - increased bleeding tendency • Causes: – Decreased ability of liver to make clotting factors – Decreased ability of liver to make bile acids y to absorb vitamin K from small intestine (vitamin K needed to make some clotting factors) – Decreased platelets because are sequestered in enlarged spleen ( q g p (due to portal hypertension) By Dave Kotun for NSU Orlando 40
  41. 41. Hepatic Encephalopathy • Definition: complex neuropsychiatric syndrome with disturbances in consciousness, mood, consciousness 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 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 ) – Electrolyte i b l El t l t imbalance – Infection – Surgery By Dave Kotun for NSU Orlando 41
  42. 42. Hepatorenal Syndrome • Definition: acute renal failure occurring in the setting of severe liver disease, in which there is no structural abnormality of y the 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 ) with diuretic agentsDave Kotun for NSU Orlando or paracentesis (fluid By 42 drainage)
  43. 43. 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 from scarring – AST and ALT nml or slightly elevated due to liver cell injury Not significantly elevated because significant acute liver cell necrosis is not occurring, and much liver tissue is already lost By Dave Kotun for NSU Orlando 43
  44. 44. NORMAL LAB VALUES: • Serum albumin 3-5.5 gm/dL • Prothrombin time 10 - 12.5sec • Total bilirubin 0.2- 1.2mg/dL 1 2mg/dL • Conjugated ( direct ) bilirubin 0.0-0.3 mg/dL • Serum ammonia 12- 47 umol/L • Alanine aminotransferase • ( ALT ) 0-48units/L • Aspartate aminotransferase • ( AST ) S 0 u ts/ 0-41units/L • Alkaline phosphatase 30-117units/L • Serum amylase 25-125 units/L • Serum lipase 10-140 units/dL i /dL By Dave Kotun for NSU Orlando 44
  45. 45. Questions? By Dave Kotun for NSU Orlando 45
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×