Case 3 : Jaundice

By Group B3

A newborn boy develops was admitted to the hospital because of severe jaundice on day 2 of life and abdominal distension. The baby was born at term by spontaneous vaginal delivery to a 35 year old woman after uncomplicated pregnancy.

Difficult Terminology: severe jaundice

Key words:Newborn boySevere jaundice on day 2 of lifeAbdominal distensionTerm babySpontaneous vaginal deliveryUncomplicated pregnancy

Pre-hepatic Jaundice

• It occurs due to excessive destruction of red blood cells resulting in increased bilirubin formation.

• Jaundice may be due to the increased formation of in direct bilirubin than the normal liver can convert it into direct bilirubin and excrete.

• There is no hepatic damage.  

Hepatic Jaundice

• Hepatic jaundice results from failure in the function of hepatocytes to take up, metabolize or excrete bilirubin.

• Clinically, the jaundice tends to come on rapidly and is of an orange tint. Fatigue and malaise are common. Signs of hepatocellular failure may be evident.

• Serum transaminases are increased. Serum albumin is reduced in chronic disease. Prothrombin time is prolonged and does not fall in response to parenteral vitamin K.

Post Hepatic Jaundice:Bilirubin Metabolism & Elimination

Breakdown of senescent circulating erythrocytes

Extra hepatic bilirubin is bound to serum albumin

Glucoronidation in the ER generates bilirubin mono & diglucoronides

Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogen

Excreted in feces with some absorption & excretion into the urine

Physiological (normal) jaundice: occurring in most newborns, this mild jaundice is due to the immaturity of the baby's liver, which leads to a slow processing of bilirubin. It generally appears at 2 to 4 days of age and disappears by 1 to 2 weeks of age.

Jaundice of prematurity: occurs frequently in premature babies since they are even less ready to excrete bilirubin effectively. Jaundice in premature babies needs to be treated at a lower bilirubin level than in full term babies in order to avoid complications.

Breastfeeding jaundice: jaundice can occur when a breastfeeding baby is not getting enough breast milk because of difficulty with breastfeeding or because the mother's milk isn’t in yet. This is not caused by a problem with the breast milk itself, but by the baby not getting enough to drink.

Breast milk jaundice: in 1% to 2% of breastfed babies, jaundice may be caused by substances produced in their mother's breast milk that can cause the bilirubin level to rise. These can prevent the excretion of bilirubin through the intestines. It starts after the first 3 to 5 days and slowly improves over 3 to 12 weeks.

Physiological Jaundice

Phase 1

• Term infants - jaundice lasts for about 5 days with a rapid rise of serum bilirubin up to 12 mg/dL.

• Preterm infants: For preterm infants jaundice lasts for about a week, with a rapid rise of serum bilirubin up to 15 mg/dL

Phase 2 • bilirubin levels decline about 2 mg/dL for 2 weeks, eventually

mimicking adult values• Preterm infants - phase two can last more than 1 month

• in babies who receive exclusive breast feedings, phase two can last more than 1 month

CAUSES Increase bilirubin load on liver cells Increased red blood cell (RBC) volume Increased labeled bilirubin Increased circulation of bilirubin in the liver Decreased RBC survival Defective hepatic uptake of bilirubin from blood plasma Decreased ligadin (Y protein) Increased binding of Y proteins by other anions Decreased liver uptake especially in phase two Defective billirubin conjugation Decreased UDPG( uridine diphosphoglucuronic ) activity

THERE ARE 2 DIFFERENT FORMS OF BILIRUBIN

1. Unconjugated bilirubin- Insoluble in water (physiologic pH)- Tightly complexed to serum albumin- Cannot be excreted through urine

2. Conjugated bilirubin- Soluble in water- Nontoxic- Loosely bound to albumin

UNCONJUGATED BILIRUBINPresents as albumin free anion in plasma

Diffuse into tissue

- Exessive production of bilirubin- Reduced hepatocyte uptake- Impaired conjugation

CONJUGATED BILIRUBINProlonged conjugated hyperbilirubinemia

Circulating pigment covalently bound to albumin

- Decreased hepatocellular excretion- Impaired bile flow

Anatomy and physiology

Histological findings

Abdominal distension in newborn

Tympanitic abdominal distention may occur in healthy infants, in infants who have systemic conditions, and in newborns who have congenital causes of intestinal obstruction.

Some healthy infants experience mild distention because of air swallowing with crying or feeding. This distention is variable, greatest after feeding or fussing, and absent at other times. Vomiting is absent, and the stooling pattern and physical examination are normal. This transient generalized distention responds to changes in feeding technique and burping and in consoling techniques for the crying infant.

In the ill newborn, many systemic conditions cause a paralytic intestinal ileus characterized by quiet, nontender abdominal distention: sepsis, birth asphyxia, hypothyroidism, and electrolyte imbalance. Newborns who have pneumonia or respiratory distress may also develop distention from aerophagia

Viral infection

Induce immune response towards hepatocytes

Inflammation of hepatocyte

Swelling of hepatocyte

Hepatomegaly

Abdominal distention

cirrhosis, CHF,portal hypertension, peritonitis

CONGENITAL HYPERBILIRUBINAEMIA(non-haemolytic)

UNCONJUGATED• Gilbert’s Syndrome

– Hepatic glucuronidation is approximately 30% normal, resulting in an increased proportion of bilirubin monoglucuronide in bile.

– Most patients have reduced level of UDP-glucuronosyl transferase (UGT-1) activity (enzyme that conjugates bilirubin with glucuronic acid)

– Mutations occur in the gene (HUG-Br1) encoding this enzyme, with an expanded nucleotide repeat consisting of two extra bases in the upstream 5’ promoter element.

– This abnormality appears to be necessary for the syndrome, but not in itself sufficient for the phenotypic expression of the syndrome.

– Most common familial hyperbilirubinaemia– Asymptomatic, detected as incidental finding of a slightly raised bilirubin

on a routine check– Liver biochemistry normal; no sign of liver disease– Have family history of jaundice

Crigler-Najjar syndrome• Very rare

• Patients with type II (autosomal dominant) with a decrease rather than absence (type I – autosomal recessive) of UDP-glucuronosyl transferase can survive in adult life.

• Mutation of the HUG-Br1 gene for UDP-glucuronosyl transferase has been demonstrated in the coding region.

• Liver histology is normal.

• Transplantation is the only effective treatment

CONJUGATEDDubin-Johnson (autosomal recessive) & Rotor’s (possibly

autosomal dominant) syndromes • Defects in bilirubin handling in the liver.

• In the Dubin-Johnson syndrome, mutations in both MRP2 (multidrug-resistance protein 2) transporter genes. (Involved in Bile Secretion)

• Liver is black owing to melanin deposition

Acute Hepatitis

• Hepatocytes show degenarative changes (swelling, cytoplasmic granularity, vacuolation), undergo necrosis (becoming shrunken, eosinophilic Councilman bodies) and are rapidly removed.

• Necrosis maximal in zone 3.• Extent of damage is very variable between individuals affected by the

same agent; at one end of the spectrum, single and small groups of hepatocyte die(spotty or focal necrosis), while at the other end there is multiacinar necrosis involving a substansial part of the liver (massive hepatic necrosis), resulting in fulminant hepatic failure.

Questions

A1: why is the baby’s life span of RBC is shorter than the adults?(Shah)

A3: what is the relationship between jaundice and breast milk in the absence of breast milk?(Baim)

A4: Explain which nerve is innervated to hepar? (Adam)