PATHOPHYSIOLOGY The liver'

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PATHOPHYSIOLOGY-The liver.

• Anne Aspin 2006

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Yellow additive
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Bile.

• Thick greenish yellow fluid secreted by liver
  cells.
• Alkaline.
• Emulsifies fats in the intestine.
• It stimulates peristalsis in the intestine, acts
  as a natural aperient.
• Deodorant in faeces.

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• During fetal life, placenta is the principal
  route to eliminate unconjugated bilirubin.
• In newborn infants hepatic cells excrete
  conjugated water soluble bilirubin into biliary
  system and gastro intestinal tract

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A guide to the liver.

• Located behind lower ribs on the right side of
  the abdomen.
• An adult- size of a rugby ball.
• 300 billion specialised cells- well organised
  intricate system of bile ducts and blood vessels.

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• The little bile ducts drain every bile cell and
  join together like tributaries entering a stream
  to form one main duct from each lobe.
• The two ducts join to form the common hepatic
  duct, this joins the duct from the gall bladder
  (cystic duct), to form the common bile duct. This
  joins the small intestine through the Ampulla of
  Vater.

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The gall bladder and its ducts.
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Blood supply to and from the liver.

• Hepatic artery- which divides into fine branches
  to the fine bile ducts.
• Portal vein carries nutrients from the stomach
  and intestine to the liver (also from spleen).
• Portal vein divides into fine branches- into
  sinusoids.
• Blood leaves sinusoids via hepatic vein to heart.

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Functions of the liver.

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

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Functions (cont)

• Prothrombin and fibrinogen synthesized from amino
  acids.
• Antibodies and antitoxins are manufactured.
• Heparin is manufactured.
• Stores Vit A and D, anti anaemic factor, iron
  from diet, glucose stored as glycogen and back to
  glucose in the presence of insulin.
• Bile is formed.

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Guess which one was on TPN?.
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Extremely Low Birth Weight Infant

• Less than 1000g, less than 27/40
• Susceptible to all complications of prematurity
• Thermoregulation high surface area to body
  weight
• Hypoglycaemia stress and low glycogen stores

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ELBW

• Fluids and electrolytes PDA,IVH,CLD,BPD
• Compromised renal function
• decreased GFR
• decreased ability to reabsorb bicarbonate
• inability to concentrate urine

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Nutrition

• High energy requirements for growth
• Heat loss raises energy need
• Trophic feeding stimulates gastro-intestinal
  tract and prevent mucosal atrophy
• Prolonged TPN may result in cholestasis and
  elevated triglyceride levels.
• Breast milk

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Hyperbilirubinaemia

• Increased production of bilirubin transfusion,
  infection
• Decreased activity of transferase enzyme due to
  hypoxia,infection,hypothermia or thyroid
  deficiency

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Hyperbilirubinaemia (cont)

• Block of transferase enzymes (drugs)
• Decreased enzyme- prematurity
• Decreased bilirubin uptake by liver cells

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Kernicterus

• Occurs when unconjugated bili crosses blood-brain
  barrier staining basal ganglia, pons and
  cerebellum
• Those who do not die with kernicterus are deaf,
  mental retardation and cerebral palsy

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Phototherapy

• Decreases unconjugated bilirubin levels
• Breaks down so water soluble, so can be easily
  excreted

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Hepatic complications in preterm babies on TPN

• Cholestasis 7.4 - 84
• 1st reported 1971 baby 71days old, cholestasis,
  bile duct proliferation, early cirrhosis
• Early feeding reduces above
• Increased biochemical test results of damage,
  function and excretion

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Prevention

• Early enteral feeding
• Prevention of sepsis
• Cycling TPN
• Mucus fistula re-feeding
• Ursodeoxycholic acid

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Differential diagnosis

• Jaundice birth-24hrs
• Sepsis
• Haemorrhage
• Cytomegalovirus
• Rubella
• Congenital toxoplasmosis

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Jaundice day 2-3

• Physiological jaundice
• Criggler Najjar syndrome

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Jaundice after day 3

• Septicaemia
• Syphillis
• Toxoplasmosis
• Cytomegalovirus

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Jaundice after one week

• Breast milk
• Septicaemia
• Congenital atresia of ducts
• Hepatitis
• Rubella
• Herpes
• Galactosaemia
• Hypothermia
• Haemolytic disease

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Jaundice after one month

• Inssipated bile syndrome
• TPN related cholestasis
• Cytomegalovirus
• Syphillis
• Toxoplasmosis

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Biliary atresia.
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What is biliary atresia?.

• Inflammation develops within bile ducts around
  time of birth, either within ducts inside or
  outside of the liver.
• Bile ducts outside liver irreversible damage
  preventing bile flow.

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Signs of biliary atresia.

• Seem well, but white of the eyes are yellow,
  yellowing of the skin.
• Yellow coloured urine.
• Pale stools.
• Bleeding prolonged.

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Investigations.

• Haematological and liver function tests.
• Screening for infection and metabolic causes.
• Ultrasound examination.
• Radionuclide studies.
• Percutaneous liver biopsy.

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Always look for yellow pooh!!!
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Treatment.

• Surgical operation called a Kasai procedure.
• Major surgery, very sick babies.

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Extrahepatic biliary atresia.

• The blocked duct is removed.
• A single open duct is then joined to a loop of
  intestine.

Hepaticojejunostomy.
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Post operation.

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

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Medications.

• IV antibiotics to reduce risk of cholangitis.
• Vitamins A,D,E,K - due to poor bile flow which
  reduces absorption of dietary fat soluble vits.
• Phenobarbitone given to increase bile flow.
• Questran improves liver function and removes
  substances which cause the skin to itch.

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Medications (cont)

• Spironalactone excretion of excess fluid which
  otherwise collects in the abdomen.
• Ursodeoxycholic acid promotes the flow of bile.
• Ranitidine reduces stress induced stomach
  irritation.

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Some complications may occur.

• Cholangitis
• Ascites
• Low albumins
• Portal hypertension
• Itching

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Cholangitis.

• An infection of the bile ducts resulting in
  inflammation.
• Pyrexia
• Increasing jaundice
• Further liver damage
• IV antibiotics.

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Ascites

• An abnormal collection of fluid in the abdomen
  around the organs.
• May be associated with general oedema.
• Protruding abdomen
• Shiny, tense
• Prominent veins
• Rapid weight gain
• Shortness of breath
• Reduced appetite.

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Complications of ascites

• Failure to thrive and vomiting
• Infection
• Restricted movement
• Breathing difficulties.

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Albumins.

• If ascites persists, disease process has affected
  the livers ability to make albumin.
• Diet will be assessed to reduce fluid and salt
  intake.
• 20 Albumin infusion.

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Portal hypertension.

• High blood pressure in the portal vein, the main
  vein carrying blood from the gut to the liver.
• Occurs due to scarring in the liver which causes
  back pressure in the portal vein.
• This causes veins like varicose veins to develop
  in the lining of the oesophagus, stomach or
  intestine.

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Portal hypertension

• Blockage of portal vein thrombus.
• Scarring in the liver
• Increased resistance to blood leaving the liver,
  due to obstruction or heart disease.

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Portal hypertension (cont)

• Enlarged spleen from back pressure, effects
  breakdown of RBC as new are made, when spleen
  enlarged it removes more than it should effects
  platelets needed for blood clotting.
• Ascites from back pressure on blood vessels
  forces fluid to leak out to around surrounding
  organs.
• Prominent veins over abdomen.

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Portal hypertension (cont)

• Varices, also known as collaterals. Thin walled
  and can bleed.
• Bleeding causing tiredness, breathlessness, pale
  appearance. Present in vomit or stools.
• Diarrhoea, poor weight gain the blood vessels in
  the lining of the intestine swell as blood flows
  under pressure, reduces absorption of digested
  food.

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Pruritis/itching.

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

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Pruritis/itching (cont)

• Questran/ cholestyramine. Combines with bile
  acids in the small intestine and reduces
  reabsorption.
• Phenobarbitone helps liver to excrete the
  substances thought to induce itching.
• Rifampicin significant relief from itching by
  reducing harmful bile acids but increases the
  amount of protective acids.
• Sedatives Vallergan.
• Ursodeoxycholic acid increases watery bile salts
  to aid secretion.

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Choledochal cyst.

• Chole relating to bile
• Dochal containing or receiving
• Cyst fluid collection
• Affects ducts outside liver. Bile collects inside
  dilated ducts flow of bile impaired.
• Caused by ?malformation of bile duct inutero.

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Types of choledochal cyst.

• 150,000
• 3 x girls than boys
• These two types cause pancreatitis.

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Other types of choledochal cysts.
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Signs and symptoms

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

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Roux loop.
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Complications

• Bleeding
• Infection
• Leakage where ducts join to the bowel.
• Cholangitis
• Pancreatitis.
• Cancer of bile ducts later in life rare.

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Cystic fibrosis and liver disease.

• Liver disease more likely to develop with those
  babies who had meconium ileus as an infant.
• Damage starts in the small bile ducts, bile
  stickier than normal blockage of ducts.
• Surrounding tissue then becomes damaged and
  scarred biliary fibrosis.
• Liver becomes hard and the blood flow through
  more difficult.

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• Physical examination hepatomegaly,
  splenomegaly.
• Portal hypertension
• Liver function tests
• Abdominal ultrasound

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Treatments

• Medications
• Nutrition
• Endoscopy for varices
• Sclerotherapy of oesophageal varices
• Banding
• TIPS radiological procedure which reduces blood
  flow through varices directing it through a
  channel created in the liver.

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Alagille Syndrome

• Biliary hypoplasia in association with at least
  two other anomalies in the body.
• 1100,000, boys to girls.
• Severity differs with each baby

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Biliary hypoplasia

• Ducts not formed properly so the bile flow is
  poor causing liver dysfunction and sometimes
  jaundice.
• Typical facial features include prominent
  forehead, deep set eyes and a small chin.
• Cardiovascular pulmonary artery stenosis, from
  mild to severe symptoms.
• Posterior Embrytoxon accumulation of a substance
  on inner aspect of cornea.
• Butterfly notches of the spine.

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Autoimmune liver diseases

• Caused by bodys defence mechanism, immune system
  malfunctioning and attacking part of itself.
• Two types autoimmune hepatitis and
  autoimmune sclerosing cholangitis.
• Continuous cell destruction results in scarring
  of the liver leading to cirrhosis.

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Symptoms

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

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Gilberts disease.

• A liver condition which is mild in nature.
• Intermittent jaundice, no abnormality of liver
  function.
• Males more than females.
• Abdominal discomfort, lethargy, malaise.
• May be triggered by infection, overexertion and
  fasting.

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Feeding babys with liver disease.
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Nutrition

• The liver plays an important role in good
  nutrition and growth.
• It produces bile which helps to absorb fat in the
  diet
• It converts the nutrients in the diet into energy
  and substances needed for growth and normal body
  functions.

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• Babies drink large quantities of milk, as they do
  not digest nutrients they still feel hungry.
• Poor nutrition leads to poor growth, lack of
  energy and increased risk of infection.
• Need to drink special formula. Not normal formula
  which has long chained triglycerides and needs a
  good bile flow for absorption.

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Milks

• Medium chain triglycerides found in Pregestimil,
  Peptijunior and Neocate.
• These milks can be taken and fully absorbed as
  they do not need bile for absorption of the fat.
• Weaning between 4-6 months.
• Supplementary vitamins.

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Tube feeding

• This is not unusual.
• Pressure to get nutrition into a baby that will
  not feed.
• Need to get full requirements as mentioned
  before.
• Continuous overnight feeding, small bolus by day
• Gastrostomy only if absolutely necessary.

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Thank you
Time to go home.