C - Chapter X: Liver Function Test Flashcards
Largest organ ([?] in adult)
~1.2 – 1.5 kg
Located in the
right upper quadrant of the abdomen
Dual Blood Supply:
a) Portal Vein
b) Hepatic Artery
– carries blood from alimentary tract
a) Portal Vein
– carries oxygenated blood to the liver
b) Hepatic Artery
Receives, processes & stores materials absorbed from the
digestive tract
Synthesis:
multiple plasma proteins
Main organ of
detoxification
Synthesis of bile acids from
cholesterol
Major site of
catabolism of hormones
– “Icterus”
JAUNDICE
– yellow discoloration of the plasma, skin, sclerae & mucous membranes caused by Bilirubin accumulation
JAUNDICE
PORTAL HYPERTENSION ( mmHg)
> 20
PORTAL HYPERTENSION
Increased:
sinusoidal infiltration, scarring or hepatic vein obstruction
PORTAL HYPERTENSION
Major Complications:
Hepatosplenomegaly, Ascites & Hepatorenal syndrome
Accumulation of substances that are normally metabolized by the liver
HEPATIC FAILURE & ENCEPHALOPATHY
Liver plays a major role in enzymatic transformation & disposition of drugs
ALTERED DRUG METABOLISM
Hormone imbalance
ENDOCRINE ABNORMALITIES
The liver efficiently sequesters dimeric IgA & secretes it into the bile
IMMUNOGLOBULIN ABNORMALITIES
Chronic liver disease produces alterations in Hemostasis and a generalized hemorrhagic tendenc
DISORDERED HEMOSTASIS
CLINICAL MANIFESTATIONS OF LIVER DISEASE
DAILY BILIRUBIN PRODUCTION
(average 250 – 300 mg)
: Derived from degradation heme from hemoglobin
85%
15%
FORMS OF BILIRUBIN
UNCONJUGATED
CONJUGATED
DELTA
– bound by albumin & transported to the liver
UNCONJUGATED
– formed from the reaction of UCB with glucuronic acid
CONJUGATED
– conjugated bilirubin bound to Albumin
DELTA
- Both have acceptable precision
Jendrassik-Grof & Evelyn-Malloy procedures
- Adapted by many automated instruments
Jendrassik-Grof & Evelyn-Malloy procedures
- Most frequently used methods to measure Bilirubin
Jendrassik-Grof & Evelyn-Malloy procedures
Occurs when the problem causing the jaundice occurs prior to liver metabolism
PRE-HEPATIC JAUNDICE
Caused by an increased amount of bilirubin being presented to the liver (e.g. Acute & Chronic Hemolytic Anemia)
PRE-HEPATIC JAUNDICE
Unconjugated hyperbilirubinemia
PRE-HEPATIC JAUNDICE
Primary problem causing the jaundice resides in the liver (intrinsic liver disease)
HEPATIC JAUNDICE
Disorders of Bilirubin Metabolism
Gilbert’s Syndrome
Crigler-Najjar Syndrome
– intermittent hyperbilirubinemia; cause by reduction in the expression of UGT1A1 gene (thereby reduced conjugating ability of the liver)
Gilbert’s Syndrome
Chronic unconjugated hyperbilirubinemia; rare & more severe disorder
Crigler-Najjar Syndrome
Molecular defect w/in the gene involved with bilirubin conjugation
Crigler-Najjar Syndrome
– complete absence of enzymatic bilirubin conjugation
Crigler-Najjar Syndrome Type I
– mutation causing a severe deficiency of the enzyme for conjugation
Crigler-Najjar Syndrome Type II
Disorders related to Transport (Transport Defects)
Dubin-Johnson Syndrome
Rotor Syndrome
Removal of conjugated bilirubin from the liver cell & the excretion into the bile are defective
Dubin-Johnson Syndrome
Caused by deficiency of the canalicular transporter protein (MDR2/cMOAT)
Dubin-Johnson Syndrome
Appearance of dark-stained granules on a liver biopsy
Dubin-Johnson Syndrome
Hypothesized to be due to a reduction in the concentration or activity of intracellular binding proteins (e.g. Ligandin)
Rotor Syndrome
Liver biopsy does NOT show dark pigmented granules
Rotor Syndrome
PHYSIOLOGIC JAUNDICE of the NEWBORN
Unconjugated [?]
hyperbilirubinemia
PHYSIOLOGIC JAUNDICE of the NEWBORN
Deficiency in the enzyme [?] (one of the last liver functions to be activated in prenatal life)
Glucuronyl transferase
– deposition of bilirubin in the nuclei of brain & nerve cells
Kernicterus
Usually results from biliary obstructive disease (e.g. gallstones, tumors)
POST-HEPATIC JAUNDICE
Prevents the flow of conjugated bilirubin into the bile canaliculi
POST-HEPATIC JAUNDICE
Clay-colored stool
POST-HEPATIC JAUNDICE
- results in cell damage & death in the newborn
Kernicterus
Usually results from biliary obstructive disease (e.g. gallstones, tumors)
POST-HEPATIC JAUNDICE
Prevents the flow of conjugated bilirubin into the bile canaliculi
POST-HEPATIC JAUNDICE
Clay-colored stool
POST-HEPATIC JAUNDICE
