Neonatal direct hyperbilirubinemia Neonatal cholestasis

Slides:



Advertisements
Similar presentations
OVERVIEW OF DISORDERS OF THE BILIARY TRACT IN CHILDREN
Advertisements

POST-OPERATIVE COMPLICATIONS
Clinical Course of Untreated BA Phoebe part. Clinical Course of Untreated BA Most present within four to six weeks of conjugated jaundice and acholic.
DIAGNOSTIC ANCILLARY PROCEDURES AND FINDINGS
Group D Florendo-Gaspar.  Tests based on detoxification and excretory functions  Tests that measure biosynthetic function  Coagulation factors  Other.
Neonatal Liver Biopsy Dr Claire Bowen Consultant Paediatric Pathologist.
Serina Farzin-Nasab, MD Emory University Family Medicine Residency Program.
Approach to a patient with jaundice
Case Report DISIDA Scan. Case I Name: 劉亦承 Age: 2 m/o Sex: Male.
Bilirubin Metabolism & Jaundice
Jaundice Encephalopathy (altered consciousness or behaviour)
RHY/CH00561 Biology of Disease CH0576 Hyperbilirubinaemia & Jaundice II.
Chapter 15 The Liver The liver lies in the upper right quadrant of the abdominal cavity and is the largest organ in the body. The functions of the liver.
Liver Function Tests (LFTs)
For final year medical students 2014 Dr Rosalind Pool GPST1
1 CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FOUR Dr. Essam H. Aljiffri.
1 CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE THREE Dr. Essam H. Aljiffri.
Cirrhosis Biol E-163 TA session 1/8/06. Cirrhosis Fibrosis (accumulation of connective tissue) that progresses to cirrhosis Replacement of liver tissue.
CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FIVE Dr. Essam H. Aljiffri.
This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration.
Dr Yasir M Khayyat,MBcHB,FRCPC,FACP 1 Khayyat Y. LFT WhyHowWhenWHO 600 ريال 2 Khayyat Y.
Chronic hepatitis in childhood Modes of presentation Acute onset jaundice and persisting Gradual development of signs of liver disease Asymptomatic finding.
NEONATAL CHOLESTASIS l Gregory J. Semancik, M.D. l Major, Medical Corps, U.S. Army l Fellow, Pediatric Gastroenterology and Nutrition l Walter Reed Army.
Sinusoids of liver are delicate structure and their walls are composed of endothelium. Sinusoids blockage can cause dilatation of these structures, liver.
By Dr. Abdelaty Shawky Assistant Professor of Pathology
MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Alterations in Liver Function.
This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration.
Hepatic And Post-hepatic Jaundice Sonal Pruthi Roll Number - 82.
Significance of Liver Function Tests
Hormones. Hormones: compounds which are synthesized and secreted from special secretory or endocrine glands.
Cholestatic Liver Disease Primary Biliary Cirrhosis.
Cholestatic liver diseases:
CHOLEDOCHAL CYSTS Aswad Habeeb Hameed Al-Obeidy FICMS GE & Hep.
Adult Medical- Surgical Nursing Gastro-intestinal Module: Liver Cirrhosis.
Clinical Approach to Neonatal Jaundice
Jaundice Dr. Gehan Mohamed Dr. Abdelaty Shawky.
Pathophysiology Complications Diagnosis Treatment
Liver Function Tests. Tests Based on Detoxification and Excretory Functions.
Evaluating the Patient With Abnormal Liver Tests-2 פרופ ' צבי אקרמן מבית חולים הדסה הר הצופים.
PED17.  Caroli disease and caroli syndrome are congenital disorders to the intarhepatic bile ducts. They are both characterized by dilatation of the.
Approach to a child with hepatomegaly Dr. Shreedhar Paudel May, 2009.
Blood Studies Liver function test (LFT) Group of biochemical tests Group of biochemical tests Uses of liver function test (LFTs) Differential diagnosis.
Adult Medical- Surgical Nursing Gastro-intestinal Module: Jaundice.
Hepatobiliary system Integrated practical
CIRRHOSIS.
Hepatitis. Hepatitis * Definition: Hepatitis is necro-inflammatory liver disease characterized by the presence of inflammatory cells in in the portal.
CIRRHOSISPathophysiology&Complications. Normal liver functions Carbohydrate Metabolism Hypo- or hyperglycemia Fatty Acids Metabolism Lipid Transport.
JAUNDICE Definition:- Jaundice refers to the yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentration.
Gilead -Topics in Human Pathophysiology Fall 2009 Drug Safety and Public Health.
Neonatal hepatitis syndrome
Liver function Tests What are liver tests? Liver tests (LTs) are blood tests used to assess the general state of the liver or biliary system. Few of these.
Lab # 2 Liver Function Tests (LFTs) ALT&AST T.A. Bahiya M. Osrah.
INTERPRETATION OF LABORATORY & DIAGNOSTIC TESTS GI SYSTEM Nora A.Kalagi, MSc. 326 PHCL April 2016.
1-urin and stool findings: hemolyticobstructivehepatocellular Urine bilinogenincreasedabsentMay increase or decrease Faeces stercobilinincreaseddecreasedDecreased.
Topic Review Biliary atresia Division of gastroenterology Department of pediatric YUMC R3 허윤정.
Laboratory tests in digestive systema Klinika Gastroenterologii Dr n. med. Małgorzata Pujanek.
LIVER FUNCTION TESTS
Liver Function Tests (LFTs)
Liver Function Tests (LFTs)
Interpretation of Liver Function Test
Lab (2): Liver Function profile (LFT)
INVESTIGATION OF HEPATOBILIARY DISEASE
Liver disorder in pregnancy
JAUNDICE.
Biliary Atresia Dr. Altan Alim
Liver “Function” Test 2013 Mini-Lecture
Gastroenterology & Nutrition Block Biochemistry Department
A Child with Jaundice M Rawashdeh, MD, MSc, FRCP, FRCPCH
Icterus differential diagnostics
Presentation transcript:

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 . 1/10/2011

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 1/10/2011

It is not neurotoxic but it indicate serious disease 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 1/10/2011

1/10/2011

Causes of neonatal Direct hyperbilirubinaemia (Cholestasis ) 1 – Hepatocyte Injury :- 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 . 1/10/2011

D – Idiopathic Neonatal Hepatitis : E – Miscellanouse : 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 1/10/2011

Intrahepatic disease 1 – Hepatocyte injury 2 – 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 ) 1/10/2011

Extrahepatic bile flow obst. Biliary atresia , Choledochal cysts , Neonatal sclerosing cholangitis , Bile duct stenosis , Inspissated bile syndrom 1/10/2011

Ante natal fever , rash may suggest Congenital infections ( TORCH) 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)‎ 1/10/2011

Dark Urine suggests conjugated hyperbilirubinemia 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 1/10/2011

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)‎ 1/10/2011

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 , 1/10/2011

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)‎ 1/10/2011

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) 1/10/2011

Lab. Investigation of patient with direct hyperbilirubinemia. : - include liver function test Radiological examination Specific test for Dx cause 1/10/2011

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 . 1/10/2011

test for synthetic function (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. 1/10/2011

Complete blood count Abdominal ultrasound 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 . 1/10/2011

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 1/10/2011

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 1/10/2011

Sweat test for cystic fibrosis 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, 1/10/2011

Magnetic resonance cholangiography (MRC) , Liver scan 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 1/10/2011

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 . 1/10/2011

Biopsy : exploratory laporatomy some time may be needed 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 1/10/2011

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. 1/10/2011

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 1/10/2011

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 . 1/10/2011

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 . 1/10/2011

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 . 1/10/2011

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. 1/10/2011

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 ) 1/10/2011

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 . 1/10/2011

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 . 1/10/2011

Intrahepatic bile duct paucity or hypoplasia 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 . 28/2/2005

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 1/10/2011