neonatalcholistasis pptx - د.ضياء

Neonatal direct hyperbilirubinemia Neonatal cholestasis

• defined as prolonged elevation of conjugated bilirubin in neonatal period but usually beyond the 1st 14 days of life.
• caused by defect in bile formation & excretion due to hepatocyte dysfunction or From obstruction flow of bile through intrahepatic and extrahepatic biliary tree
• leading to accumulation of conjugated bilirubin, bile acids, and cholesterol in blood and extrahepatic tissues .

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Neonatal direct hyperbilirubinemia Neonatal cholestasis

so there will be retention of bilirubin & bile acid causing
malabsorption of fat & fat soluble vit (A,K,D.E )
xanthemas ( accumulation of cholesterol ) ,
itching also develop due to accumulation of bile acid .
pale acholic stool with dark color urin (usually +ve for bilirubin )
Progressive liver disease and biliary cirrhosis
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We regard the case as direct hyperB. when the direct B. is > 20% of total bilirubin .
It is not neurotoxic but it indicate serious disease

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Causes of neonatal Direct hyperbilirubinaemia (Cholestasis )

A – Infection : -
• Bacterial Sepsis , UTI .
• Viral Infections TORCH ,HIV ,Varicella Zoster ,Coxacki ,Hepatitis B C .
• TB , Syphilis .

B – Toxic : -

• Total Parenteral Nutrition , in neonatal care unit .
• Sepsis with endotoxaemia .
• Drug related .

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1 – Hepatocyte Injury :-

• C - Metabolic cause
• alpha1Antitrypsin deficiency ,
• Tyrosinaemia
• Galactossaemia,
• D – Idiopathic Neonatal Hepatitis :
is a disease of unknown cause

E – Miscellanouse :

• Hypopituitarism Hypothyroidism

Cystic Fibrosis

Chromosomal disorders
As 21 trisomies down syndrom

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Intrahepatic disease1 – Hepatocyte injury2 – Intrahepatic billiary dis or flow obst

intrahepatic billiary hypoplasia or paucity which may be isolated or syndromatic as Alagille syndrome and ‎progressive familial intrahepatic cholestasis

Caroli disease , autosomal dominant polycystic liver disease (cysts in liver only) , autosomal recessive polycystic kidney disease (cysts in liver and kidney )
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Extrahepatic bile flow obst. Biliary atresia ,

Choledochal cysts ,
Neonatal sclerosing cholangitis ,
Bile duct stenosis ,
Inspissated bile syndrom

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HISTORY

Certain aspects of the history may be helpful in narrowing the ‎differential diagnosis of neonatal cholestasis as
Consanguinity ‎ and family Hx ( inherted disease as metabolic disease or cystic fibrosis)
Hx of neonatal death
Ante natal fever , rash may suggest Congenital infections ( TORCH)
Neonatal infection, particularly urinary tract infection
failure to ‎thrive (neonatal hepatitis and metabolic disease)‎

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Stool color — persistent acholic (pale or clay colored) suggest billiary atresia , If patient has no pale acholic stool or has intermittent pale stool suggest viral , metabolic , hormonal disease.

Dark Urine suggests conjugated hyperbilirubinemia

Some time itching because of accumulation of bile acid & salt
Excessive bleeding — may indicate coagulopathy, vitamin K deficiency

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hypoglycemia , vomiting , lethargy , signs of metabolic disease , carbohydrate intolerance , galactosaemia

Stooling pattern —delay passage of meconium may occur in cystic fibrosis, ‎hypothyroidism; diarrhea may occur in infection, metabolic disease, ‎progressive familial intrahepatic cholestasis)‎

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examination
the jaundice of direct hyperB. is usually greenish yellowish in contrast to jaundice of indirect hyperB. which is usually orang-yellowish in colour .
dark color urin & light or acholic stool .
Also it may be associated with hepato-splenomegally with signs of chronic liver disease , bleeding , varices of portal hypertension , xanthemas , or associated with hepatic encephalopathy , ascites ,
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signs of fat soluble vitamin deficiency

Failure to thrive as metabolic disease or congenital infection
coarse features of hypothyroidism & Algille
Cataract , microcephally , Hx of infection in pregnancy as congenital infection TORCH .
Cardiac murmur or signs of heart failure (may be present in biliary atresia ‎or Alagille syndrome)‎
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Complication

Malnutrition resulting from malabsorption of dietary long-chain triglycerides
Fat-soluble vitamin malabsorption:
Micronutrient deficiency , Deficiency of water-soluble vitamins
Retention of biliary constituents such as bile acid , cholesterol causing itch or xanthomas
Progressive liver disease and biliary cirrhosis; portal hypertension (variceal bleeding, ascites, hypersplenism)
End-stage liver disease (liver failure)
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Lab. Investigation of patient with direct hyperbilirubinemia. : -
• include
• liver function test
• Radiological examination
• Specific test for Dx cause

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Lab. Investigation of patient with direct hyper B. : -

• liver function test
• TSB with direct & indirect , direct should be more than 2mg / dL or more than 20 % of total .
• Liver enz.
( ALT ) SGPT (liver specific )S. Glutamic Pyruvic Transaminase
( AST ) SGOT ; S.Glutamic Oxaloacetic acid Transaminase
increase these enz. indicate hepatocellular damage , the increase more marked in acute hepatic dis. than chr. liver dis. & intra or extra biliary obstruction .

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• (S. Albumin ) hypoalbuminaemia indicate severe liver dis.

• ( PT & PTT ) , prolonged PT & PTT because of
• deficiency of vit. K dependant factor ( 1972 )
• coagulation factor synthesized in liver so in severe liver dis. May not response to vit K .
• test for excretory function
• Alk. Phosphatase ( not specific to liver , also in bone) , also
• 5 nucleotidase and gamma glutamyl transpeptidase . They increase when there is defect in bile excretion as in biliary dis. or in hepatocellular dis.
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• test for synthetic function

• Cholesterol , increase in cholestasis & decrease in acute liver dis. as hepatitis
• serum ammonia, , serum glucose .
• Complete blood count
• Abdominal ultrasound
• size of liver ,texture , echogencity ( increase echogenicity in fatty liver ) , mass, stone , choledocal cyst , gall bladder size , biliary tract , ascitic fluid , portal hypertension , patency of portal vein , presence of collatral . presence of other anomalies specially renal .
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U / S

Findings in infants with biliary atresia

atretic gall bladder , or thin wall

absent common bile duct , dilatation of the intrahepatic bile duct

hepatic parenchyma is often inhomogeneous .

triangular cord sign cranial to portal vein bifurcation

choledochal cysts may be associated

other Congenital anomalies as polysplenia
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• Specific test for Dx cause

• Blood , urine & CSF analysis & culture for bact. , virus as HIV , Herpes , CMV .
• Serological exam. For TORCH , VDRL for syphilis
• Urine for B. , glucose , reducing substance as galactose , Red blood cell galactose-1-phosphate uridyl transferase.
• Serum & urine chromatography for a.a. dis. For tyrosinemia
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• Thyroxine , TSH .

• Sweat test for cystic fibrosis
• analysis for alpha 1 anti trypsin deficiency .
• Bone marrow examination and skin fibroblast culture for suspected storage disease
• Genetic testing for Alagille syndrome,
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Till now the Dx of most cases of direct hyperB is done with these Ix except some time we need to do more Ix to Dx & differntiate of idiopathic neonatal hepatitis , intrahepatic bile duct paucity , biliary atresia , so we need to do :-
Magnetic resonance cholangiography (MRC) ,
Liver scan
Duodenal intubation
Liver biopsy
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• Magnetic resonance cholangiography (MRC) , widely used to assess the biliary tract in all age groups
• Liver scan Tc 99m iminodiacetic acid dye with the use phenobarbitone 5mg/kg/day orally for 5 – 7 days to induce biliary excretion then we do the scan , In biliary atresia there is good uptake but no excretion , while in hepatitis uptake is sluggish with fair excretion .
• Duodenal intubation for measurement of B. in bile befor & after use of phenobarbitone where there is no B. in biliary atresia while there is good amount of B. in hepatitis .
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Biopsy :

• liver biopsy provide the most reliable discriminatory evidence & Dx .
• In biliary atresia there is bile ductular proliferation , bile plug ,portal or perilobular oedema & fibrosis , lobular achitecture is intact .
• In neonatal hepatitis , severe diffuse hepatocellular dis. , distortion of the lobular architecture , infl. Cell infilteration , focal hepatocellular necrosis , bile ductules show little alteration . Giant cell transformation present in both condition & have no dignostic specificity
• exploratory laporatomy some time may be needed

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Biliary atresia must be identified early and differentiated from other causes ‎of neonatal cholestasis because early surgical intervention (ie, before 2 ‎months of age) results in a better outcome.
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• if patient with cholestasis has persistent pale acholic Stool , sonar suggest billiary atresia then we do liver scan , MRC or biopsy that support diagnosis , so we take patient to surgery
• If patient with cholestasis has no pale acholic stool or has intermittent pale stool and sonar did not suggest billiary atresia so we viral , metabolic , hormonal study, liver scan and all investigation of intra hepatic disease and then we do biopsy

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Rx of direct hyperB. (cholestasis )

• include treatment of complication & original cause
• for complication with any cause of neonatal cholestasis, whether idiopathic neonatal hepatitis, intrahepatic cholestasis, or biliary atresia, affected patients are at increased risk for chronic complications. These are due to diminished bile flow.
• Give diet or formula with medium chain triglyceride , due to malabsorption of longchain triglyceride (there is fat malabsorption due to bile salt &acid retention ) ,
• give high dose fat soluble vit for the same reason .
• Give some micronutrient as Ca ,Ph ,zink.
• Give choleretics as ursodeoxycholic acid or bile acid binder as cholestyramine to decrease itching , xanthoma .

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Rx of direct hyperB. (cholestasis )
• develop progressive billiary cirrhosis ,portal hypertention , he may develop oesophageal varices so we do endoscopy for proper Rx .
• Oedema & ascites treated by salt restriction & diuretics as spironolactone alone or in combination with frussemide .
• End stage hepatic failure may need liver transplant .
• Rx of the cause of direct hyperB. as in Galactossaemia we give him lactose free formula , some infection may need Rx , surgery may be needed in biliary atresia or choledochal cyst .

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biliary atresia

The incidence is 1/10,000-15,000 live births , it is more in female , involve extrahepatic billiary duct , but in some cases there is intra & extrahepatic involvement
Etiology : It is unknown
So any patient with cholestatic jaundice especially if present at end of 1st month must be evaluated for biliary atresia because surgery most effective before 2 months , otherwise biliary cirrhosis & ascending cholangitis may occur .

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Clinical feature

Full term infants in whom J. develop during the 2nd – 3rd week of life , Acholic stool and Hepatomegally .
Other than these the infants appear healthy
But if patient not treated , later after 2nd month there is Splenomegally , progressive liver dis , cirrhosis & portal hypertesion.
A few infants have an increased incidence of other abnormalities, such as the polysplenia , malrotation , and intra-abdominal vascular anomalies.

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Lab investigation

• LFT It demonstyrate direct Hyperbilirubinaemia &may be highly elevated serum alkaline phosphatase , gamma glutamyl transpeptidase .
• U / S mention previously
• Liver scan following 5 days of phenibarbital , or MRC
• Percutaneous liver biopsy
• exploratory laporatomy some time may be needed , All patients suspected of having biliary atresia should undergo exploratory laparotomy and direct cholangiography to determine the presence and site of obstruction & ; if biliary atresia Kasai procedure (hepatoportoenterostomy )

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Treatment & prognosis

• A hepatoportoenterostomy, or Kasai operation is a surgical treatment to allow for bile drainage .
• the operation should be ( <2 m. of age ). Surgical success is judged by improvement in bile drainage ;
• Without surgery Kasai procedure , patient will die cirrhosis before 2 yr. of age
• 25 – 50 % of patients survive 5 yr. after a successful Kasai procedure , but complications of the procedure include progressive biliary cirrhosis & ascending cholangitis .
• Another Rx for most infants is liver transplant which has 80 – 90 % survival rate .
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Idiopathic neonatal hepatitis

• It is more in male , Familial incidence is 20 %.

• Also presnt with neonatal direct jaundice
• may be associated with growth retardation .
• cause unknown ,INH represents more than one dis. Resulting from infectiouse Or familial causes
• Normal color stool with transient acholic stool , little increase ALP or gamma glutamyl transferase ( GGT ).
• Biliary scan show the patency of the bile duct .
• Liver biopsy shows numerous giant cells ,lobular disorganisation , necrosis , & inflammation without the ductular proliferation & fibrosis characteristic of extrahepatic atresia .
• Prognosis is good & most patient recover within 6 - 8 month .

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It is either syndromic as Alagille syndrome, arteriohepatic dysplasia ,or non syndromic .
Infants with Alagille syn.present with sign & symptomes of direct hyperB.with
facial features , cardiac valvular or peripheral pulm. stenosis , butter fly vertebrae , dysplastic kidney , hypercholesterolaemia with cutaneous xanthomas , dis. is AD .

Intrahepatic bile duct paucity or hypoplasia

Differentiation of Idiopathic Neonatal Hepatitis & Biliary Atresia
I N H
 Familial incidence is 20 %.
 Usually no other abnormality

 More in premature & SGA infants.

 Normal color stool with transient acholic stool
 In duodenal intubation the fluid is bile stained .
 Liver size less common enlarge
 Hepatobiliary scintography there is sluggish uptake & fair excretion . en
 Liver biopsy . the most reliable discreminatory test larged

B A

 Unlikely to recur in same family .
 There is other abnormality as polysplenia , , malrotation , intra abdominal vascular abnormality
 No relation .
 Persistant acholic stool
 Persistant bile stained fluid after duodenal intubation against Dx of BA
 .Abnormal liver size & consistency
 There is good uptake but no excretion
Liver biopsy .
 exploratory laporatomy

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