Kernicterus

Not associated with increased morbidity REF: Nelson 17^1h edition page 687

KERNICTERUS OR BILIRUBIN ENCEPHALOPATHY:

• Kernicterus, or bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei.
• The greatest risk associated with hyperbilirubinemia is the development of kernicterus (bilirubin encephalopathy) at high indirect serum bilirubin levels.
• The level of serum bilirubin associated with kernicterus is dependent in part on the cause of the jaundice. Kernicterus has developed when bilirubin levels exceed 30 mg/dL, although the range is wide (21-50 mg/dL).
• Its onset is usually in the 1st wk of life, but it may_be delayed to the 2nd-3rd wk.
• Kernicterus develops at lower bilirubin levels in preterm infants and in the presence of asphyxia, intraventricular hemorrhage, hemolysis, or drugs that displace bilirubin from albumin. The exact serum bilirubin level that is harmful for VLBW infants is unclear. Kernicterus does occur in patients with breast milk jaundice but is very uncommon.
• The surface of the brain is usually pale yellow. On cutting, certain regions are characteristically stained yellow by unconjugated bilirubin
• Overt neurologic signs have a grave prognosis; 75% or more of such infants die, and 80% of affected survivors have bilateral choreoathetosis with involuntary muscle spasms. Mental retardation, deafness, and spastic quadriplegia are common. Infants at risk should have screening hearing tests.

Sulfasalazine is usaually absorbed from the small intestines. Only 10% of drug is absorbed remaining excreted unaltered in bowel. Hence, this drug acts locally in the intestine of patient with inflammatory bowel disease.

Ref: Paul Beringer (2006), Chapter 90, “Antiinfectives”, In the book, “Remington: The Science and Practice of Pharmacy”, Lippincott Williams and Wilkins, USA, Page 1631 ; KD Tripathi, 5th Edition, Pages 186, 643 ; Katzung 9th Edition, Page 591

Sulphonamides can precipitate kernicterus in the new born, especially if premature, by displacement of bilirubin from plasma protein binding sites and more permeable blood brain barrier.

Hence it may lead to unconjugated hyperbilirubinemia.

Free Bilirubin can become deposited in the basal ganglia and subthalamic nuclei of the brain, causing an encephalopathy called kernicterus.

Ref:D. A. Warrell, Timothy M. Cox, John D. Firth (2005), Chapter 7 “Infection”, In the book “Oxford Textbook of Medicine”, 4th Edition, New york, Volume 1, Page 737

Ans. is ‘a’ i.e., Hypotonia

Hypotonia is an early feature (in Phase I)

Clinical features

o Clinically, kernicterus is described in 3 phases, which may progress over 24 hours to 7 days :‑

1. Phase I —>           Poor suck, lethargy, hypotonia, depressed sensorium.

2. Phase II —>          Fever, hypertonia progressing to opisthotonus.

3. Phase III —>         High pitched cry, convulsions, death.

3 Long term survivors demonstrate choreoathetoid cerebral palsy, upward gaze palsy, sensorineural hearing loss and mental retardation.

Ans. is ‘d’ i.e., High level of serum albumin

o The toxic effects of elevated serum levels of unconjugated bilirubin are increased by following factors ‑

Hypoproteinemia (.1 albumin) —> Normally unconjugated bilirubin binds to albumin in circulation. If the level of albumin decreases, concentration of free unconjugated bilirubin will increase.

Ans. is ‘a’ i.e., Barbiturate

Treatment of hyperbilirubinemia

o The following are the treatment options for treatment of hyperbilirubinemia.

A)        Drugs (Pharmacological therapy)

B)        Phototherapy

C)        Exchange transfusion

Pharmacological therapy

Following drugs are used in hyperbilirubinemia ‑

1) Barbiturates (Phenobarbitone)

• It is effective only if given to mother before delivery.
• It acts by inducing the conjugation of bilirubin –> Phenobarbitone is an enzyme inducer.

2)       Metalloporphyrins (Tin-Sn & Zinc-Zn)

o These compounds decrease the formation of bilirubin by inhibiting heme oxygenase.

3)       Miscellaneous

o Frequent milk feeding Prevents reabsorption of unconjugated bilirubin from intestine by reducing enterohepatic circulation.

Charcol & agar —> These are bilirubin binding agents which prevent bilirubin reabsorption from gut.