Transcript MLAB 2401: Clinical Chemistry Keri Brophy

MLAB 2401: Clinical Chemistry
Keri Brophy-Martinez
Alterations in Liver Function
Jaundice/Icterus
• Yellow discoloration of the skin, eyes and
mucous membranes
• Due to the presence of bilirubin
• Onset seen at bilirubin levels > 3.0 mg/dL
• Kernicterus
– Yellow staining of the meninges of the brain due
to bilirubin
– Found in newborns
– Causes brain damage
Classification of Jaundice
• Prehepatic
• Hepatic
• Posthepatic
Classifications of Jaundice
• Prehepatic
– Abnormality is outside the liver
– Liver function is normal
– Cause: too much bilirubin presented to liver
– Result
• Increase in unconjugated bilirubin
• Total bilirubin: increased or normal
• Increase in serum iron
– Examples: acute /chronic hemolytic anemias
Classifications of Jaundice
• Hepatic
– Intrinsic liver disease or defect
– Caused by
• Disorders of bilirubin conjugation
• Disorders of bilirubin transport
• Hepatocellular injury or destruction
– Cirrhosis
– Tumors
– Infection
– Toxins
– Intrahepatic obstructions
Inherited Hyperbilirubinemias
Liver
• Gilbert Syndrome
Reduction in the activity of UDP-glucoronyl transferase
• Crigler-Najjar syndrome
 Defective UDPG-transferase
• Dublin-Johnson disease
 Post-conjugation failure
Acquired Hyperbilirubinemias
• Neonatal jaundice
– Deficiency of glucuronyl transferase
– Causes an increase in unconjugated bilirubin
– Leads to kernicterus
– Treat by exposure to UV light or exchange
transfusion
Classifications of Jaundice
• Posthepatic
– Abnormality is outside the liver
– Liver function is normal
– Biliary obstruction due to gallstones, tumors, edema
– Stool turns clay-colored due to lack of bile
– Results:
• Increased: Conjugated bilirubin, urinary bilirubin, ALP,
GGT, total bilirubin, unconjugated bilirubin
• Decreased: Urine and fecal urobilinogen
Other Liver Dysfunctions
•
•
•
•
Reye’s Syndrome
Cirrhosis
Drug & Alcohol Disorders
Hepatitis
Reye Syndrome
• Group of disorders caused by infectious,
metabolic, toxic or drug-induced disease
found mostly in children
• Often preceded by viral syndrome
• Related to aspirin consumption during the
viral syndrome
• Symptoms
– Profuse vomiting
– Neurological impairment
Cirrhosis
• Scar tissue replaces normal healthy liver tissue
• As time moves forward, function deteriorates and signs
appear
– Fatigue, nausea, weight loss, jaundice, etc
• Common causes
– Chronic alcoholism
– Hepatitis
• Results:
– Increased: unconjugated and conjugated bilirubin, ALP,
GGT,AST, ALT
– Decreased: cholesterol, albumin
Drug and Alcohol Disorders
• Accounts for 1/3 to ½ of acute liver failure
since the liver plays a major role in drug
metabolism
• Drugs cause an immune mediated injury to
the hepatocytes, resulting in disease
• Ethanol is the most significant
• Acetaminophen also common
• Several stages of classification based on
disease severity
Alcoholic Liver Disease (ALD)
• Breakdown of alcohol leads to toxin formation
• Risk factors for ALD include:
– History and magnitude of alcohol consumption
– Hepatitis B or C infection
– Gender
– Genetic factors
– Nutritional status
Alcoholic Injury
• Stages
– Alcoholic Fatty Liver
• Mildest form
• Elevations of AST, ALT, GGT
• Complete recovery possible if drug removed
– Alcoholic hepatitis
• Moderate elevations of AST, ALT, GGT
• Bilirubin, ALP also elevated
• Albumin decreased
• PT prolonged
– Alcoholic cirrhosis
• Elevated AST, ALT, GGT, ALP, total bilirubin
• Albumin decreased
• PT prolonged
Hepatitis
• Inflammation of the liver
• Viral, bacterial, radiation, drugs, chemicals
and others can cause inflammation
• Viral infections account for the majority of
cases in the clinical lab
• Includes subtypes A, B,C, D, and E
• Clinical Symptoms
– Jaundice, dark urine, fatigue, nausea, abdominal
pain
Hepatitis Viruses
Virus
Incubation
Period
Mode of
transmission
Vaccine
Chronic
Infection
Hepatitis A
2-6 weeks
Fecal-oral
Yes
NO
Hepatitis B
8-26 weeks
Parenteral,
sexual
Yes
Yes
Hepatitis C
2-15 weeks
Parenteral,
sexual
No
Yes
Hepatitis D
21-90 days
Parenteral,
sexual
Yes
Yes
Hepatitis E
3-6 weeks
Fecal-oral
No
?
References
• Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry:
Techniques, principles, Correlations. Baltimore: Wolters
Kluwer Lippincott Williams & Wilkins.
• http://kidshealth.org/parent/pregnancy_center/newborn_car
e/jaundice.html
• Sunheimer, R., & Graves, L. (2010). Clinical Laboratory
Chemistry. Upper Saddle River: Pearson .