Neonatal “Physiologic Jaundice”

 The unconjugated hyperbilirubinemia of neonatal “physiologic jaundice” results from accelerated hemolysis and an immature hepatic system for the uptake, conjugation, and secretion of bilirubin. In this transient condition, bilirubin glucuronosyltransferase activity, and probably also synthesis of UDP-glucuronate, are reduced. When the plasma concentration of unconjugated bilirubin exceeds that which can be tightly bound by albumin (20–25 mg/dL), bilirubin can penetrate the blood–brain barrier. If left untreated, the resulting hyperbilirubinemic toxic encephalopathy, or kernicterus, can result in mental retardation. Exposure of jaundiced neo nates to blue light (phototherapy) promotes hepatic excretion of unconjugated bilirubin by converting some to derivatives that are excreted in the bile, and phenobarbital, a promoter of bilirubin metabolism, may be administered.

Defects of Bilirubin UDP-Glucuronosyltransferase

 Glucuronosyltransferases (EC 2.4.1.17), a family of enzymes with differing substrate specificities, increase the polarity of various drugs and drug metabolites, thereby facilitating their excretion. Mutations in the gene that encodes bilirubin UDP glucuronosyltransferase can result in the encoded enzyme having reduced or absent activity. Syndromes whose clinical presentation reflects the severity of the impairment include Gilbert syndrome and two types of Crigler-Najjar syndrome.

Gilbert Syndrome

 Providing that about 30% of the bilirubin UDP-glucuronosyl transferase activity is retained in Gilbert syndrome, the condition is harmless.

Type I Crigler-Najjar Syndrome

 The severe congenital jaundice (over 20 mg bilirubin per dL serum) and accompanying brain damage of type I Crigler Najjar syndrome reflect the complete absence of hepatic UDP-glucuronosyltransferase activity. Phototherapy reduces plasma bilirubin levels somewhat, but phenobarbital has no beneficial effect. The disease is often fatal within the first 15 months of life.

Type II Crigler-Najjar Syndrome

 In type II Crigler-Najjar syndrome, some bilirubin UDP glucuronosyltransferase activity is retained. This condition thus is more benign than the type I syndrome. Serum bilirubin tends not to exceed 20 mg/dL of serum, and patients respond to treatment with large doses of phenobarbital.

Toxic Hyperbilirubinemia

 Unconjugated hyperbilirubinemia can result from toxin induced liver dysfunction caused by, for example, chloroform, arsphenamines, carbon tetrachloride, acetaminophen, hepatitis virus, cirrhosis, or Amanita mushroom poisoning. These acquired disorders involve hepatic parenchymal cell damage, which impairs bilirubin conjugation.

Obstruction in the Biliary Tree Is the Most Common Cause of Conjugated Hyperbilirubinemia

Conjugated hyperbilirubinemia commonly results from blockage of the hepatic or common bile ducts, most often due to a gallstone or to cancer of the head of the pancreas (Figure 1). Bilirubin diglucuronide that cannot be excreted regurgitates into the hepatic veins and lymphatics, conjugated bilirubin appears in the blood and urine (choluric jaundice), and the stools typically are a pale color.

Fig1. Major causes of jaundice. Prehepatic jaundice indicates events in the bloodstream, major causes being various hemolytic anemias. Hepatic jaundice arises from hepatitis or other liver diseases (eg, cancer). Posthepatic jaundice refers to events in the biliary tree, for which the major causes are obstruction of the common bile duct by a gallstone (biliary calculus) or by cancer of the head of the pancreas.

The term cholestatic jaundice includes both all cases of extrahepatic obstructive jaundice and also conjugated hyper bilirubinemia due to micro-obstruction of intrahepatic biliary ductules by damaged hepatocytes, such as may occur in infectious hepatitis.

Dubin-Johnson Syndrome

This benign autosomal recessive disorder consists of conjugated hyperbilirubinemia in childhood or during adult life. The hyperbilirubinemia is caused by mutations in the gene encoding the protein involved in the secretion of conjugated bilirubin into bile.

Some Conjugated Bilirubin Can Bind Covalently to Albumin

 When levels of conjugated bilirubin remain high in plasma, a fraction can bind covalently to albumin. This fraction, termed δ-bilirubin, has a longer half-life in plasma than does conventional conjugated bilirubin, and remains elevated during recovery from obstructive jaundice. Some patients therefore continue to appear jaundiced even after the circulating conjugated bilirubin level has returned to normal.

Urinary Urobilinogen & Bilirubin Are Clinical Indicators

 In complete obstruction of the bile duct, bilirubin has no access to the intestine for conversion to urobilinogen, so no urobilinogen is present in the urine. The presence of conjugated bilirubin in the urine without urobilinogen suggests intrahepatic or posthepatic obstructive jaundice.

In jaundice secondary to hemolysis, the increased pro duction of bilirubin leads to increased production of urobilinogen, which appears in the urine in large amounts. Bilirubin is not usually found in the urine in hemolytic jaundice, so the combination of increased urobilinogen and absence of bilirubin is suggestive of hemolytic jaundice. Increased blood destruction from any cause brings about an increase in urine urobilinogen.

Table 1 summarizes laboratory results obtained in patients with jaundice due to prehepatic, hepatic, or posthepatic causes: hemolytic anemia (prehepatic), hepatitis (hepatic), and obstruction of the common bile duct (posthepatic); see Figure1. Laboratory tests on blood (evaluation of the possibility of a hemolytic anemia and measurement of prothrombin time) and on serum (eg, electrophoresis of proteins; alkaline phosphatase and alanine aminotransferase and aspartate aminotransferase activities) also help to distinguish between prehepatic, hepatic, and posthepatic causes of jaundice.

Table1. Laboratory Results in Normal Patients and Patients With Three Different Causes of Jaundice

اخر الاخبار

اخبار العتبة العباسية المقدسة

مع وصول الزيارة ذروتها.. العتبة العباسية المقدسة تستنفر ملاكاتها لخدمة زائري مرقدي الإمامين العسكريين (عليهما السلام)

قسم الشؤون الطبية: الخطة الخدمية في سامراء تضمنت مشاركة نحو ٥٠ متطوعًا من ثلاث محافظات

عبر محطات الإجابة عن الاستفتاءات الشرعية مشروع التبليغ الحوزوي يقدّم خدماته لزائري مدينة سامراء

قسم حفظ النظام يشارك في تأمين زيارة الإمام الحسن العسكري (عليه السلام) بمدينة سامراء

المزيد

الآخبار الصحية

دون آثار جانبية.. زيت عشبة طبيعية قد يعالج القلق

"ليكانيماب".. علاج الزهايمر يطرح رسميا في السوق الألمانية

متى يجب تنظيف الأسنان في الصباح.. قبل أم بعد الإفطار؟

ارتفاع الوفيات.. منظمة الصحة تدق جرس الإنذار بشأن الكوليرا

المزيد

الآخبار التكنلوجية

أكبر مشروع طاقة رياح في نصف الكرة الجنوبي يحقق إنجازين جديدين

5 أمور لا تفعلها أثناء تشغيل مكيف سيارتك

ضوء إدارة المحرك: أسئلة مهمة لفهم عمله ومعانيه

"واتساب" يطلق خاصية جديدة لكتابة الرسائل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

The Deoxyribonucleosides of Uracil & Cytosine are Salvaged

Biosynthesis of Pyrimidine Nucleotides

Hepatic Purine Biosynthesis is Stringently Regulated

Inosine Monophosphate (IMP) is Synthesized From Amphibolic Intermediates

DNA & RNA are Polynucleotides

Synthetic Nucleotide Analogs are Used in Chemotherapy

Chemistry of Purines, Pyrimidines, Nucleosides, & Nucleotides

Catabolism of HEME Produces Bilirubin

Disorders of Heme Biosynthesis

Porphyrins are Colored & Fluoresce

Heme is Synthesized From Succinyl-CoA & Glycine

NON–α-AMINO ACIDS