PATHOPHYSIOLOGYPATHOPHYSIOLOGY-The liver.-The liver.

Anne Aspin 2010Anne Aspin 2010

Bile.Bile.

Thick greenish yellow fluid secreted by Thick greenish yellow fluid secreted by liver cells.liver cells.

Alkaline.Alkaline. Emulsifies fats in the intestine.Emulsifies fats in the intestine. It stimulates peristalsis in the intestine, It stimulates peristalsis in the intestine,

acts as a natural aperient.acts as a natural aperient. Deodorant in faeces.Deodorant in faeces.

During fetal life, placenta is the principal During fetal life, placenta is the principal route to eliminate unconjugated bilirubin.route to eliminate unconjugated bilirubin.

In newborn infants hepatic cells excrete In newborn infants hepatic cells excrete conjugated water soluble bilirubin into conjugated water soluble bilirubin into biliary system and gastro intestinal tractbiliary system and gastro intestinal tract

A guide to the liver.A guide to the liver.

Located behind lower Located behind lower ribs on the right side ribs on the right side of the abdomen.of the abdomen.

An adult- size of a An adult- size of a rugby ball.rugby ball.

300 billion specialised 300 billion specialised cells- well organised cells- well organised intricate system of intricate system of bile ducts and blood bile ducts and blood vessels.vessels.

The little bile ducts drain every bile cell The little bile ducts drain every bile cell and join together like tributaries entering a and join together like tributaries entering a stream to form one main duct from each stream to form one main duct from each lobe.lobe.

The two ducts join to form the common The two ducts join to form the common hepatic duct, this joins the duct from the hepatic duct, this joins the duct from the gall bladder (cystic duct), to form the gall bladder (cystic duct), to form the common bile duct. This joins the small common bile duct. This joins the small intestine through the Ampulla of Vater.intestine through the Ampulla of Vater.

The gall bladder and its ducts.The gall bladder and its ducts.

Blood supply to and from the liver.Blood supply to and from the liver.

Hepatic artery- which divides into fine Hepatic artery- which divides into fine branches –to the fine bile ducts.branches –to the fine bile ducts.

Portal vein carries nutrients from the Portal vein carries nutrients from the stomach and intestine to the liver (also stomach and intestine to the liver (also from spleen).from spleen).

Portal vein divides into fine branches- into Portal vein divides into fine branches- into sinusoids.sinusoids.

Blood leaves sinusoids via hepatic vein to Blood leaves sinusoids via hepatic vein to heart.heart.

Functions of the liver.Functions of the liver.

Breaks down fat to produce energy.Breaks down fat to produce energy. Amino acids broken down to form urea.Amino acids broken down to form urea. Detoxicate drugs.Detoxicate drugs. Vit A synthesized to carotene.Vit A synthesized to carotene. Liver main heat producing organ.Liver main heat producing organ. Plasma proteins synthesized.Plasma proteins synthesized. Tissue cells broken down – uric acid and urea.Tissue cells broken down – uric acid and urea. Carbohydrate converted to fat for storage.Carbohydrate converted to fat for storage.

Functions (cont)Functions (cont)

Prothrombin and fibrinogen synthesized from Prothrombin and fibrinogen synthesized from amino acids.amino acids.

Antibodies and antitoxins are manufactured.Antibodies and antitoxins are manufactured. Heparin is manufactured.Heparin is manufactured. Stores: Vit A and D, anti anaemic factor, iron Stores: Vit A and D, anti anaemic factor, iron

from diet, glucose stored as glycogen and back from diet, glucose stored as glycogen and back to glucose in the presence of insulin.to glucose in the presence of insulin.

Bile is formed.Bile is formed.

Guess which one was on TPN?.Guess which one was on TPN?.

Extremely Low Birth Weight InfantExtremely Low Birth Weight Infant

Less than 1000g, less than 27/40Less than 1000g, less than 27/40 Susceptible to all complications of Susceptible to all complications of

prematurityprematurity

Thermoregulation – high surface area to Thermoregulation – high surface area to body weightbody weight

Hypoglycaemia – stress and low glycogen Hypoglycaemia – stress and low glycogen storesstores

ELBWELBW

Fluids and electrolytes – Fluids and electrolytes – PDA,IVH,CLD,BPDPDA,IVH,CLD,BPD

Compromised renal function Compromised renal function

– – decreased GFR decreased GFR

– – decreased ability to reabsorb bicarbonatedecreased ability to reabsorb bicarbonate

– – inability to concentrate urineinability to concentrate urine

NutritionNutrition

High energy requirements for growthHigh energy requirements for growth Heat loss raises energy needHeat loss raises energy need Trophic feeding stimulates gastro-Trophic feeding stimulates gastro-

intestinal tract and prevent mucosal intestinal tract and prevent mucosal atrophyatrophy

Prolonged TPN may result in cholestasis Prolonged TPN may result in cholestasis and elevated triglyceride levels.and elevated triglyceride levels.

Breast milkBreast milk

HyperbilirubinaemiaHyperbilirubinaemia

Increased production of bilirubin Increased production of bilirubin transfusion, infectiontransfusion, infection

Decreased activity of transferase enzyme Decreased activity of transferase enzyme due to hypoxia,infection,hypothermia or due to hypoxia,infection,hypothermia or thyroid deficiencythyroid deficiency

Hyperbilirubinaemia (cont)Hyperbilirubinaemia (cont)

Block of transferase enzymes (drugs)Block of transferase enzymes (drugs)

Decreased enzyme- prematurityDecreased enzyme- prematurity

Decreased bilirubin uptake by liver cellsDecreased bilirubin uptake by liver cells

KernicterusKernicterus

Occurs when unconjugated bili crosses Occurs when unconjugated bili crosses blood-brain barrier staining basal ganglia, blood-brain barrier staining basal ganglia, pons and cerebellumpons and cerebellum

Those who do not die with kernicterus are Those who do not die with kernicterus are deaf, mental retardation and cerebral deaf, mental retardation and cerebral palsypalsy

PhototherapyPhototherapy

Decreases unconjugated bilirubin levelsDecreases unconjugated bilirubin levels

Breaks down so water soluble, so can be Breaks down so water soluble, so can be easily excreted easily excreted

Hepatic complications in preterm Hepatic complications in preterm babies on TPNbabies on TPN

Cholestasis 7.4% - 84%Cholestasis 7.4% - 84%

11stst reported 1971 – baby 71days old, reported 1971 – baby 71days old, cholestasis, bile duct proliferation, early cholestasis, bile duct proliferation, early cirrhosiscirrhosis

Early feeding reduces aboveEarly feeding reduces above Increased biochemical test results of Increased biochemical test results of

damage, function and excretion damage, function and excretion

PreventionPrevention

Early enteral feedingEarly enteral feeding Prevention of sepsisPrevention of sepsis Cycling TPNCycling TPN Mucus fistula re-feedingMucus fistula re-feeding Ursodeoxycholic acidUrsodeoxycholic acid

Differential diagnosisDifferential diagnosis

Jaundice Jaundice birth-24hrsbirth-24hrs SepsisSepsis HaemorrhageHaemorrhage CytomegalovirusCytomegalovirus RubellaRubella Congenital toxoplasmosisCongenital toxoplasmosis

Jaundice day 2-3Jaundice day 2-3

Physiological jaundicePhysiological jaundice Criggler Najjar syndromeCriggler Najjar syndrome

Jaundice after day 3Jaundice after day 3

SepticaemiaSepticaemia SyphillisSyphillis ToxoplasmosisToxoplasmosis CytomegalovirusCytomegalovirus

Jaundice after one weekJaundice after one week

Breast milkBreast milk SepticaemiaSepticaemia Congenital atresia of ductsCongenital atresia of ducts HepatitisHepatitis RubellaRubella HerpesHerpes GalactosaemiaGalactosaemia HypothermiaHypothermia Haemolytic diseaseHaemolytic disease

Jaundice after one monthJaundice after one month

Inssipated bile syndromeInssipated bile syndrome TPN related cholestasisTPN related cholestasis CytomegalovirusCytomegalovirus SyphillisSyphillis ToxoplasmosisToxoplasmosis

Biliary atresia.Biliary atresia.

What is biliary atresia?.What is biliary atresia?.

Inflammation Inflammation develops within bile develops within bile ducts around time of ducts around time of birth, either within birth, either within ducts inside or ducts inside or outside of the liver.outside of the liver.

Bile ducts outside Bile ducts outside liver – irreversible liver – irreversible damage preventing damage preventing bile flow.bile flow.

Signs of biliary atresia.Signs of biliary atresia.

Seem well, but white of the eyes are Seem well, but white of the eyes are yellow, yellowing of the skin.yellow, yellowing of the skin.

Yellow coloured urine.Yellow coloured urine. Pale stools.Pale stools. Bleeding –prolonged.Bleeding –prolonged.

Investigations.Investigations.

Haematological and liver function tests.Haematological and liver function tests. Screening for infection and metabolic Screening for infection and metabolic

causes.causes. Ultrasound examination.Ultrasound examination. Radionuclide studies.Radionuclide studies. Percutaneous liver biopsy.Percutaneous liver biopsy.

Always look for yellow pooh!!!Always look for yellow pooh!!!

Treatment.Treatment.

Surgical operation Surgical operation called a Kasai called a Kasai procedure.procedure.

Major surgery, very Major surgery, very sick babies.sick babies.

Extrahepatic biliary atresia.Extrahepatic biliary atresia.

The blocked duct is The blocked duct is removed.removed.

A single open duct is A single open duct is then joined to a loop then joined to a loop of intestine.of intestine.

Hepaticojejunostomy.

Post operation.Post operation.

IV fluids.IV fluids. Pain relief.Pain relief. Antibiotics.Antibiotics. Parents.Parents. Medications regime.Medications regime.

Medications.Medications.

IV antibiotics –to reduce risk of cholangitis.IV antibiotics –to reduce risk of cholangitis. Vitamins A,D,E,K - due to poor bile flow Vitamins A,D,E,K - due to poor bile flow

which reduces absorption of dietary fat which reduces absorption of dietary fat soluble vits.soluble vits.

Phenobarbitone – given to increase bile Phenobarbitone – given to increase bile flow.flow.

Questran – improves liver function and Questran – improves liver function and removes substances which cause the skin removes substances which cause the skin to itch.to itch.

Medications (cont)Medications (cont)

Spironalactone – excretion of excess fluid Spironalactone – excretion of excess fluid which otherwise collects in the abdomen.which otherwise collects in the abdomen.

Ursodeoxycholic acid – promotes the flow Ursodeoxycholic acid – promotes the flow of bile.of bile.

Ranitidine – reduces stress induced Ranitidine – reduces stress induced stomach irritation.stomach irritation.

Some complications may occur.Some complications may occur.

Cholangitis Cholangitis AscitesAscites Low albuminsLow albumins Portal hypertensionPortal hypertension ItchingItching

Cholangitis.Cholangitis.

An infection of the bile ducts resulting in An infection of the bile ducts resulting in inflammation.inflammation.

PyrexiaPyrexia Increasing jaundiceIncreasing jaundice Further liver damageFurther liver damage IV antibiotics.IV antibiotics.

AscitesAscites

An abnormal collection of fluid in the abdomen An abnormal collection of fluid in the abdomen around the organs.around the organs.

May be associated with general oedema.May be associated with general oedema. Protruding abdomenProtruding abdomen Shiny, tenseShiny, tense Prominent veinsProminent veins Rapid weight gainRapid weight gain Shortness of breath Shortness of breath Reduced appetite.Reduced appetite.

Complications of ascitesComplications of ascites

Failure to thrive and vomitingFailure to thrive and vomiting InfectionInfection Restricted movementRestricted movement Breathing difficulties.Breathing difficulties.

Albumins.Albumins.

If ascites persists, disease process has If ascites persists, disease process has affected the livers ability to make albumin.affected the livers ability to make albumin.

Diet will be assessed to reduce fluid and Diet will be assessed to reduce fluid and salt intake.salt intake.

20% Albumin infusion. 20% Albumin infusion.

Portal hypertension.Portal hypertension.

High blood pressure in the portal vein, the High blood pressure in the portal vein, the main vein carrying blood from the gut to main vein carrying blood from the gut to the liver.the liver.

Occurs due to scarring in the liver which Occurs due to scarring in the liver which causes back pressure in the portal vein.causes back pressure in the portal vein.

This causes veins like varicose veins to This causes veins like varicose veins to develop in the lining of the oesophagus, develop in the lining of the oesophagus, stomach or intestine.stomach or intestine.

Portal hypertensionPortal hypertension

Blockage of portal Blockage of portal vein –thrombus.vein –thrombus.

Scarring in the liverScarring in the liver Increased resistance Increased resistance

to blood leaving the to blood leaving the liver, due to liver, due to obstruction or heart obstruction or heart disease.disease.

Portal hypertension (cont)Portal hypertension (cont)

Enlarged spleen – from back pressure, Enlarged spleen – from back pressure, effects breakdown of RBC as new are effects breakdown of RBC as new are made, when spleen enlarged it removes made, when spleen enlarged it removes more than it should – effects platelets more than it should – effects platelets needed for blood clotting.needed for blood clotting.

Ascites –from back pressure on blood Ascites –from back pressure on blood vessels –forces fluid to leak out to around vessels –forces fluid to leak out to around surrounding organs.surrounding organs.

Prominent veins over abdomen. Prominent veins over abdomen.

Portal hypertension (cont)Portal hypertension (cont)

Varices, also known as collaterals. Thin Varices, also known as collaterals. Thin walled and can bleed.walled and can bleed.

Bleeding causing tiredness, Bleeding causing tiredness, breathlessness, pale appearance. Present breathlessness, pale appearance. Present in vomit or stools.in vomit or stools.

Diarrhoea, poor weight gain –the blood Diarrhoea, poor weight gain –the blood vessels in the lining of the intestine swell vessels in the lining of the intestine swell as blood flows under pressure, reduces as blood flows under pressure, reduces absorption of digested food.absorption of digested food.

Pruritis/itching.Pruritis/itching.

Occurs with poor bile flow.Occurs with poor bile flow. Excessive amounts of bile acids.Excessive amounts of bile acids. From mild , intermittent or severe.From mild , intermittent or severe. Palms, soles of feet, extremeties and Palms, soles of feet, extremeties and

trunk.trunk. Medications for treatment.Medications for treatment.

Pruritis/itching (cont)Pruritis/itching (cont) Questran/ cholestyramine. Combines with bile Questran/ cholestyramine. Combines with bile

acids in the small intestine and reduces acids in the small intestine and reduces reabsorption.reabsorption.

Phenobarbitone –helps liver to excrete the Phenobarbitone –helps liver to excrete the substances thought to induce itching.substances thought to induce itching.

Rifampicin –significant relief from itching by Rifampicin –significant relief from itching by reducing harmful bile acids but increases the reducing harmful bile acids but increases the amount of protective acids.amount of protective acids.

Sedatives –Vallergan.Sedatives –Vallergan. Ursodeoxycholic acid –increases watery bile Ursodeoxycholic acid –increases watery bile

salts to aid secretion.salts to aid secretion.

Choledochal cyst.Choledochal cyst.

Chole – relating to bileChole – relating to bile Dochal – containing or receivingDochal – containing or receiving Cyst – fluid collectionCyst – fluid collection

Affects ducts outside liver. Bile collects Affects ducts outside liver. Bile collects inside dilated ducts – flow of bile impaired.inside dilated ducts – flow of bile impaired.

Caused by ?malformation of bile duct Caused by ?malformation of bile duct inutero.inutero.

Types of choledochal cyst.Types of choledochal cyst.

1:50,0001:50,000 3 x girls than boys3 x girls than boys These two types These two types

cause pancreatitis.cause pancreatitis.

Other types of choledochal cysts.Other types of choledochal cysts.

Signs and symptomsSigns and symptoms

Jaundice,Jaundice, Persistant or intermittent.Persistant or intermittent. Pale stools and dark urinePale stools and dark urine Intermittent abdominal pain.Intermittent abdominal pain. Cholangitis, causing rigors.Cholangitis, causing rigors. Peritonitis, if the cyst bursts or leaks.Peritonitis, if the cyst bursts or leaks. An abdominal swellingAn abdominal swelling

Roux loop.Roux loop.

ComplicationsComplications

BleedingBleeding InfectionInfection Leakage where ducts join to the bowel.Leakage where ducts join to the bowel. CholangitisCholangitis Pancreatitis.Pancreatitis. Cancer of bile ducts later in life –rare.Cancer of bile ducts later in life –rare.

Cystic fibrosis and liver disease.Cystic fibrosis and liver disease.

Liver disease more likely to develop with Liver disease more likely to develop with those babies who had meconium ileus as those babies who had meconium ileus as an infant.an infant.

Damage starts in the small bile ducts, bile Damage starts in the small bile ducts, bile stickier than normal –blockage of ducts.stickier than normal –blockage of ducts.

Surrounding tissue then becomes Surrounding tissue then becomes damaged and scarred –biliary fibrosis.damaged and scarred –biliary fibrosis.

Liver becomes hard and the blood flow Liver becomes hard and the blood flow through more difficult.through more difficult.

Physical examination – hepatomegaly, Physical examination – hepatomegaly, splenomegaly.splenomegaly.

Portal hypertensionPortal hypertension Liver function testsLiver function tests Abdominal ultrasoundAbdominal ultrasound

TreatmentsTreatments

MedicationsMedications NutritionNutrition Endoscopy for varicesEndoscopy for varices Sclerotherapy of oesophageal varicesSclerotherapy of oesophageal varices BandingBanding TIPS –radiological procedure which TIPS –radiological procedure which

reduces blood flow through varices reduces blood flow through varices directing it through a channel created in directing it through a channel created in the liver.the liver.

Alagille SyndromeAlagille Syndrome

Biliary hypoplasia in association with at Biliary hypoplasia in association with at least two other anomalies in the body.least two other anomalies in the body.

1:100,000, boys = to girls.1:100,000, boys = to girls. Severity differs with each babySeverity differs with each baby

Biliary hypoplasiaBiliary hypoplasia

Ducts not formed properly so the bile flow is Ducts not formed properly so the bile flow is poor causing liver dysfunction and sometimes poor causing liver dysfunction and sometimes jaundice.jaundice.

Typical facial features include prominent Typical facial features include prominent forehead, deep set eyes and a small chin.forehead, deep set eyes and a small chin.

Cardiovascular – pulmonary artery stenosis, Cardiovascular – pulmonary artery stenosis, from mild to severe symptoms.from mild to severe symptoms.

Posterior Embrytoxon –accumulation of a Posterior Embrytoxon –accumulation of a substance on inner aspect of cornea.substance on inner aspect of cornea.

Butterfly notches of the spine.Butterfly notches of the spine.

Autoimmune liver diseasesAutoimmune liver diseases

Caused by body’s defence mechanism, Caused by body’s defence mechanism, immune system malfunctioning and immune system malfunctioning and attacking part of itself.attacking part of itself.

Two types: autoimmune hepatitis and Two types: autoimmune hepatitis and autoimmune sclerosing cholangitis. autoimmune sclerosing cholangitis.

Continuous cell destruction results in Continuous cell destruction results in scarring of the liver leading to cirrhosis.scarring of the liver leading to cirrhosis.

SymptomsSymptoms

Tiredness, loss of appetite,spider-naevi, Tiredness, loss of appetite,spider-naevi, nausea and vomiting, weight loss, itching, nausea and vomiting, weight loss, itching, fever, nose bleeds, jaundice, abdominal fever, nose bleeds, jaundice, abdominal pain, ascites,lower limb oedema, pain, ascites,lower limb oedema, irritability.irritability.

Treatment with immunosuppresive drugs.Treatment with immunosuppresive drugs.

Gilbert’s disease.Gilbert’s disease.

A liver condition which is mild in nature.A liver condition which is mild in nature. Intermittent jaundice, no abnormality of Intermittent jaundice, no abnormality of

liver function.liver function. Males more than females.Males more than females. Abdominal discomfort, lethargy, malaise.Abdominal discomfort, lethargy, malaise. May be triggered by infection, overexertion May be triggered by infection, overexertion

and fasting.and fasting.

Feeding baby’s with liver disease.Feeding baby’s with liver disease.

NutritionNutrition

The liver plays an important role in good The liver plays an important role in good nutrition and growth.nutrition and growth.

It produces bile which helps to absorb fat It produces bile which helps to absorb fat in the dietin the diet

It converts the nutrients in the diet into It converts the nutrients in the diet into energy and substances needed for growth energy and substances needed for growth and normal body functions.and normal body functions.

Babies drink large quantities of milk, as Babies drink large quantities of milk, as they do not digest nutrients they still feel they do not digest nutrients they still feel hungry.hungry.

Poor nutrition leads to poor growth, lack of Poor nutrition leads to poor growth, lack of energy and increased risk of infection.energy and increased risk of infection.

Need to drink special formula. Not normal Need to drink special formula. Not normal formula which has long chained formula which has long chained triglycerides and needs a good bile flow for triglycerides and needs a good bile flow for absorption.absorption.

MilksMilks

Medium chain triglycerides found in Medium chain triglycerides found in Pregestimil, Peptijunior and Neocate.Pregestimil, Peptijunior and Neocate.

These milks can be taken and fully These milks can be taken and fully absorbed as they do not need bile for absorbed as they do not need bile for absorption of the fat.absorption of the fat.

Weaning between 4-6 months.Weaning between 4-6 months. Supplementary vitamins. Supplementary vitamins.

Tube feedingTube feeding

This is not unusual.This is not unusual. Pressure to get nutrition into a baby that Pressure to get nutrition into a baby that

will not feed.will not feed. Need to get full requirements as Need to get full requirements as

mentioned before.mentioned before. Continuous overnight feeding, small bolus’ Continuous overnight feeding, small bolus’

by dayby day Gastrostomy –only if absolutely Gastrostomy –only if absolutely

necessary.necessary.

Thank you Thank you

Time to go home.

ReferencesReferences Bassett M, Murray K (2008). Biliary atresia: recent progress. Bassett M, Murray K (2008). Biliary atresia: recent progress. Journal Journal

of Clinical Gastroenterology. of Clinical Gastroenterology. 42 (6) : 720 – 72942 (6) : 720 – 729

Cincinnati Childrens Hospital Medical Center (2009). Liver diseases Cincinnati Childrens Hospital Medical Center (2009). Liver diseases and treatments. Biliary atresia. and treatments. Biliary atresia. www.cincinnatichildrens.org/suc/alpha/1/liverwww.cincinnatichildrens.org/suc/alpha/1/liver

Manning D, Todd P, Maxwell M et al (2007). Prospective Manning D, Todd P, Maxwell M et al (2007). Prospective surveillance study of severe hyperbilirubinaemia in the newborn in surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. the UK and Ireland. Archives of Disease in Childhood. Fetal Archives of Disease in Childhood. Fetal Neonatal Edition. Neonatal Edition. 92 : F342 - F34692 : F342 - F346

Schwarz S (2009). Biliary atresia: eMedicine Pediatrics. Schwarz S (2009). Biliary atresia: eMedicine Pediatrics. Emedicine.medscape.comEmedicine.medscape.com

Smitherman H, Stark A, Bhutani V (2006). Early recognition of Smitherman H, Stark A, Bhutani V (2006). Early recognition of neonatal hyperbilirubinaemia and its emergent management. neonatal hyperbilirubinaemia and its emergent management. Seminars in Fetal Neonatal Medicine. Seminars in Fetal Neonatal Medicine. 11 : 214 - 22411 : 214 - 224