Heme Degradation and Jaundice

Vocabulary practice flashcards covering the biochemical pathway of heme degradation, bilirubin metabolism, enterohepatic circulation, clinical types of jaundice, and diagnostic laboratory tests.

Reticuloendothelial System

The network of phagocytic cells, particularly located in the liver and spleen, responsible for degrading senescent red blood cells at the end of their approximately 120-day lifespan.

Sources of Degraded Heme

Approximately $85\%$ originates from senescent red blood cells that have reached the end of their life spans, while approximately $15\%$ comes from the turnover of immature red blood cells and cytochromes.

Heme Oxygenase

A macrophage enzyme that cleaves heme to form biliverdin, utilizing $O_2$ and $NADPH + H^+$ while releasing $Fe^{2+}$ and carbon monoxide ($CO$).

Biliverdin

A green pigment produced as the immediate product of heme cleavage by heme oxygenase in macrophages.

Biliverdin Reductase

The macrophage enzyme that catalyzes the reduction of biliverdin to bilirubin, consuming $NADPH + H^+$ to yield $NADP^+$.

Bilirubin

A yellow bile pigment produced from biliverdin that is not water soluble and must be transported bound noncovalently to albumin to reach the liver.

Bilirubin-Albumin Complex

The noncovalent plasma transport complex for unconjugated bilirubin in blood; certain anionic drugs can displace bilirubin from albumin, allowing it to enter the central nervous system and cause neural damage.

Bilirubin UDP-Glucuronosyltransferase

The hepatic enzyme that conjugates bilirubin by transferring glucuronic acid from two molecules of UDP-glucuronic acid to form water-soluble bilirubin diglucuronide.

Bilirubin Diglucuronide (Conjugated Bilirubin)

The water-soluble conjugated form of bilirubin that is actively secreted into bile; it is not normally found in blood unless there has been damage to hepatocytes.

Gilbert Syndrome

The most common inherited cause of unconjugated hyperbilirubinemia, transmitted as an autosomal recessive condition causing underactivity of hepatic bilirubin glucuronosyltransferase and intermittent jaundice without hemolysis or liver disease.

Precipitating Triggers of Gilbert Syndrome

Physiological stressors such as dehydration, fasting, menstrual periods, illness, or vigorous exercise that cause transient episodes of jaundice, general fatigue, and vague abdominal discomfort.

Urobilinogen

A colorless compound produced in the intestine when bacterial enzymes hydrolyze glucuronic acid off bilirubin diglucuronide and reduce the remaining bilirubin.

Enterohepatic Urobilinogen Cycle

The physiologic pathway in which a portion of intestinal urobilinogen is reabsorbed across the intestinal gut mucosa into portal blood and transported back to the liver.

Urobilin

A yellow compound produced by the kidneys from reabsorbed urobilinogen that is excreted into urine, providing its characteristic yellow color.

Stercobilin

A brown-colored pigment formed when unabsorbed intestinal urobilinogen is oxidized by bacterial flora, giving feces their characteristic brown color.

Jaundice

The yellow discoloration of the skin and sclerae caused by tissue deposition of bilirubin secondary to elevated bilirubin levels in the blood; it represents a sign of an underlying disorder rather than a distinct disease.

Hemolytic Jaundice

Prehepatic jaundice caused by massive RBC lysis exceeding the liver's conjugating capacity; characterized by elevated blood unconjugated bilirubin, dark yellow urine from increased urobilin, and elevated urinary urobilinogen.

Obstructive Jaundice (Cholestasis)

Jaundice caused by intrahepatic or extrahepatic bile duct blockage preventing bilirubin excretion into the intestine, leading to pale/clay-colored stools and dark red-orange urine.

Cholestatic Serum Markers

Serum elevations of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and 5'-nucleotidase (5'NT); concurrent elevations of ALP and GGT (or 5'NT) are specific for cholestasis.

Hepatocellular Jaundice

Jaundice resulting from damage or necrosis of liver cells, characterized early by marked elevations in serum AST (SGOT) and ALT (SGPT) along with high conjugated bilirubin (DBIL), followed later by impaired uptake and elevated unconjugated bilirubin.

Neonatal Jaundice

Transient hyperbilirubinemia occurring in newborns (especially premature infants) because hepatic bilirubin glucuronosyltransferase activity is low at birth, reaching adult levels by approximately 2 weeks of age.

Toxic Encephalopathy (Bilirubin Induced)

Neural damage resulting when elevated unconjugated bilirubin exceeds the binding capacity of serum albumin, allowing lipophilic bilirubin to cross the blood-brain barrier and diffuse into the basal ganglia.

Phototherapy

The clinical treatment for neonatal hyperbilirubinemia utilizing blue fluorescent light to convert bilirubin into water-soluble photo isomers that can be excreted in bile without glucuronide conjugation.

Direct Bilirubin (DBIL)

The laboratory measurement of water-soluble conjugated bilirubin in blood obtained via an aqueous van den Bergh colorimetric reaction; normally close to 0 and elevated during hepatocyte injury or biliary obstruction.

Total Bilirubin (TBIL)

The measurement of both conjugated and unconjugated bilirubin in blood determined when the van den Bergh colorimetric reaction is carried out in methanol.

Indirect Bilirubin (IBIL)

The calculated concentration of unconjugated bilirubin in the blood, obtained by subtracting Direct Bilirubin (DBIL) from Total Bilirubin (TBIL): $\text{IBIL} = \text{TBIL} - \text{DBIL}$.