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Flashcards in Stomach, liver and pancreas Deck (72):

What is alagille syndrome?

Mutation in JAG1 gene
- 15% familial

Constellation of
- Chronic cholestais secondary to Intrahepatic bile duct paucity or arteriohepatic dysplasia
- Dysmorphic facial features including broad forehead and underdeveloped mandibles
- Occular abnormalities: posterior embyrotoxon seen on slit lamp in 70%
- Peripheral pulmonary stenosis
- Butterfly vertebrae in 50% (or other vertebral abnormalities)
- Tubulointestinal nephropathy


What is Schwachman-Diamond syndrome?

Autosomal recessive condition
- unifying cause not yet found...

Exocrine pancreatic insufficiency whereby acini are replaced by fat with little fibrosis (second most common cause of exocrine pancreatic dysfunction in childhood)

Recurrent pyogenic infections
- Common and frequent cause of death (AOM, pneumonia, osteomyelitis, dermatitis, sepsis)
- Seoncdary to neutropenia / neutrophil chemotaxis defect

Thrombocytopenia in 70%
Anaemia in 50%

Short stature
Metaphyseal dysostosis

Management: pancreatic replacement therapy
- 1/3 (predominantly boys), develop myeldysplastic syndrome
- 1/4 develop AML


What is the role of liver in CHO metabolism?

CHO metabolism
- store CHO as glycogen
- supply glucose by glycogenesis and glyconeongenesis
- in neonates, glycogen stores are maximal (2-3 of adults) then it gets used up postnatally until stores reaccumulate by wk 2-3


What is the significance of coagulopathy not reversible by vitamin K?

Suggests synthetic dysfunction (i.e can't produce clotting factor)

Malabsorption-related coagulopathy will response to vit K


What is achalasia?

Achalasia is a primary oesophageal motility disorder characterised by failure of a hypertensive LOS to relax, and the absence of oesophageal peristalsis. These abnormalities cause a functional obstruction at the gastro-oesophageal junction.


What is the role of the liver in protein metabolism?

Protein metabolism
- alpha-feto protein is the dominant early fatal protein
- albumin synthesis starts from 7 weeks gestation
- Other proteins: fibrinogen / clotting factors / transferrin / lipoproteins / caeruloplasmin and complement


What is the role of the liver in lipid metabolism?

Lipid metabolism
- Fatty acid oxidation --> major source of energy in early life
- neonatal intolerance of prolonged fasting is partly due to restricted capacity for ketogenesis


What is the role of the liver in biotransformation?

- oxidation / reduction / hydrolysis / conjugation
- CYP450


What is the role of the liver in bile acids synthesis / excretion?

Bile acids
- synthesized in the liver from cholesterol
- conjugated before excretion
- Enterohepatic circulation handles 90-95% of bile acids
- bile converted to bile acids by bacteria in colon --> reabsorbed


What does rise in ALT / AST suggest?

Intracellular damage
- ALT most liver specific
- AST also in RBC / muscle

If inc in AST > ALT then think extra hepatic causes like alcohol, echovirus and metabolic disease


What is the significance of raised GGT / ALP?

indicate cholestatic phenomenon
- found on cell membrane of bile duct annuli
- raised in cholestatic liver disease
- typically ALP rises then followed bbq rise in GGP once ALP improving.

Don't forget that GGT also inducible by phenytoin, morphine, alcohol
ALP also found in bone and placenta


What markers help assess synthetic function?

Albumin (prognostic factor) and protein
- however, can be low due to acute illness an poor nutritional state

- reflects factor V and vit K dep factors X, IV, VII II (1972)
- most reliable
- IV vit K reverses coagulopathy due to malabsorption from cholestasis but not if due to synthetic dysfunction

Persistently low factor VII is poor prognostic factor in fulminant liver disease


What information can liver biopsy give us?

Usually percutaneous and can do as young as 1 week

- histological diagnosis
- enzyme analysis for inborn errors of metabolism
- iron, copper and specific metabolites
- monitor therapy and assess severity


What's the difference between SBR in neonatal vs adult hepatitis?

Not uncommon to see conj SBR in neonatal hepatitis due to defect in transportation out of cell

In adult hepatitis, more likely to be unconjugated SBR due to inability to conjugate


What is the inheritance of alpha-1-antitrypsin?

Autosomal co-dominant
SERPINA1 - Found on chromosome 14
>20 different alleles but only a few associate with defective protease inhibitors


What is alpha-1-antitrypsin?

Glycoprotein produced by the liver and some macrophages.
Functions as a protease inhibitor and is one of the acute phase proteins.


How are diseased alleles of alpha-1-antitrypsin different from normal allele?

M --> normal
Disease alleles differs by single base pair substitution
E.g Substitution of glutamic acid with the amino acid lysine results in Z allele, whereas valine --> S allele

S --> slow --> SS 50% of normal alphaAT1 function
Z --> normal production but abnormal transport into circulation --> ZZ 10-20% (most common abnormality)
null --> null/null --> no production


What are the clinical implications of alphaAT1 deficiency?

Liver cirrhosis
- abnormal synthesis results in increase accumulation of product --> liver damage
- accumulation occurs in 100% ZZ phenotype
- 10-20% of ZZ develops neonatal cholestatic hepatitis (indistinguishable from other forms of neonatal hepatitis)
- 10-20% has liver cirrhosis
- null / null has no liver disease (no production)

Lung emphysema (panacinar)
- usually occurs in adulthood
- increased protease damage from dead bacterial or leucocyte
- 80% of ZZ adults develop COAD

Assoc with panniculitis
- inflammation of subcutaneous tissue


What are the investigations you would do for ? alphaAT1 deficiency?

Serum Alpha-1-antitrypsin
Trypsin inhibitory capacity (reduced because aAT1 usually inhibits trypsin)
Pi genotype
CXR in adults (looking for COAD)
Liver biopsy


What is the management of alpha-1-AT deficiency?

- Danazol: analogue testosterone which increases hepatic alphaAT1 production but can only be used in men and short term only

- purified blood derived A1A via IV, given in USA for ZZ / null null, costly!
- recombinant available
- intra-nasal spray also available
- liver transplant

- Bronchodilators
- Pneumococcal and flu vaccine
- Smoke-free
- prompt treatment of resp. infections

Screening for family members


What is autoimmune hepatitis?

Chronic hepatic inflammatory involving both hepatocytes and duct epithelium with incr serum transaminases and autoantibodies.

Highly variable clinical px of asymptomatic --> cirrhosis / LF
Mimics acute viral hepatitis

Px with insidious onset of malaise, anorexia before jaundice
Assoc with arthritis, vasculitis, nephritis, thyroiditis, coombs +ve anaemia, rash


What are the ix findings in autoimmune hepatitis?

Elevated transaminases 3-10x and SBR (mostly conjugated)
HypoAlb common

- titres as low as 1:40 may be significant but not that up to 20% of patients don't have detectable antibodies
- 'type 2' most common type in children: Anti liver-kidney-microsomal ab (LKM)
- 'type 1' usually found in young women with marked hypergammaglobulinaemia and lupoid features: ANA and antiSMA

- plasmolymphocytic infiltrate expanding portal tracts with variable bile duct injury
- piecemeal hepatic necrosis, riding necrosis


How do you treat autoimmune hepatitis?

+/- other immunosuppression e.g azathioprine
Ursa commonly used as cholerectic agent
Assess with biopsy prior to stopping tx in pt with biochemical remission


What are the causes of fatty liver?

obesity, insulin resistance, hyperlipidaemia, steroids, Tx, pregnancy, lipid metabolic disease, HIV, IBD

Manage by diet and weight reduction


What is haematochromatosis?

Excessive absorption and inappropriate storage of iron

- AR (HFE gene on chr 6)
- Increased intestinal iron absorption and deposition
- most common genetic disease almost Northern Eu descent people
- HLA A3, B7, B14
- A/N testing possible

- acquired due to a/n liver disease
- usually fatal w LF

Transfusion induced
- ie B thalaessaemia
- Prevent with Fe chelation (desferoxamine)


What is the presentation of haemachromatosis?

- hepatomegaly and splenomegaly
- skin bronzing
- dilated cardiomyopathy
- DM

- cirrhosis --> hepatocellular carcinoma
- arthropathy (second and third MCP, knees)
- testicular atrophy

Susceptible to
- sederophilic organisms like yersina, vibrio vulnificus septicaemia
- listeria


How do you ix for haemachromatosis?

- raised serum Fe / ferrite with low TIBC
- transferrin saturation elevated by 10yo, detected in adolescence, found in all homozygous individuals by age 40
- AbN LFTs
- Gene test (HFE gene, C282Y mutation)

- fasting BSL (DM)
- ECG (arrhythmias)
- Joint xrays


What's the tx for haemachromatosis?

Phlebotomy every 1-2 weeks until ferritin < 100 then titrate
avoid excess iron (supplements, vitamin C, red meat)
Vaccinate against HBV / HAV
Monitor w 2mly iron studies, Hb w venesection
Yearly AFP and USS if cirrhotic
Screen relatives


What is the Hep A virus?

non-enveloped ssRNA (picornavirus)


How is hep A transmitted?

Faecal-oral route
- person to person most common (last on hands few hours) - Contact with contaminated food / water

Incubation period 2-6 wks (15-50days)
- As viral excretion occurs late in incubation period, most infectious from latter 1/2 of incubation period until few days AFTER jaundice
- No increased risk of transmission to baby if maternal disease at time of delivery

As children have mild disease, they are considered as important reservoir of virus.


What's the clinical px of Hep A?

Asymptomatic - most common px in children, severity of illness increases with age

- 4-10 days of fever / malaise / nausea or vomiting / abode discomfort
- Tender RUQ +/- LUQ
- Dark urine followed by jaundice and pale faeces
- diarrhoea in children, constipation in adults
- All recover within 1 month but some relapsing course of several months

No chronic risks


What's the management of Hep A?

Mainly supportive
- notifiable disease
- exclusion from school / work until 1 wk after onset of jaundice / sx
- no sharing utensils when infectious


What is the Hep A vaccine?

Inactive vaccine
Given > 2yo

Indicated by
- travellers to endemic areas
- travellers to rural and remote indigenous communities
- child day care / pre-school staff and ID carers
- chronic liver disease of any cause

- after one dose - 95% protective level, lasting 1 year
- 100% after 2nd (booster dose), offers long lasting protection with no need to test immunity after vaccination


What's the use of HAV Ig G?

80-90% protective in preventing HAV
Lasts 2-3 months

- Pre-exposure in < 2y (can't be vaccinated) and trip to endemic area within 1 month
- Post exposure for close contacts

** do not give live vaccines or 3 months after dose of Ig G**


What is the hepatitis B virus?

DNA - hepadenavirdae family

Long incubation period of 50-180 days
- symptomatic 6-7 weeks after exposure and last for 6-8wks
- acute infection--> 1/3 symptomatic, 2/3 not

Virus replication predominates in liver (other places include lymphocytes, kidney, spleen and pancreas)


What is the risk of chronic Hep B infection?

Inversely related to age
- <10% HBV infectious are in kids but comprise of 20-30% chronic cases
- 90% of neonates develop lifeline infections
- 25% infants develop cirrhosis or HCC (as opposed to 15% adolescent / adult)
- 25-40% chronic HBV die of liver disease or HCC
- 1-4 % HCC


How is Hep B transmitted?

- blood tx, IVDU, sore->sore
Transplacental / exposure to amniotic fluid
- highest if mum is HBsAg positive
- increase risk if HBeAg + (80%) vs HBeAg - (10%)
Breast milk
- HBsAg inconsistency demonstrated in milk --> no increased risk of acquiring HBV

At risk groups
- babies of infected mothers
- sex worker
- Household contacts of HBsAg carriers

Period of infectivity present until HBsAg disappears
Infective several weeks before illness to end of symptomatic period


What are the markers of HBV?

HBsAg first to rise and closely associated with onset of sx
- peak during overt disease then disappears w/in 3m
- persistence of HBsAg --> chronic infection

HBeAg suggests active viral replication / infectious state
- always around with HBsAg in acute infection or chronic persistent / active hepatitis

- found when there is resolved viral replication
- present in chronic 'healthy' carriers

HBV DNA - marker of active viral replication

- Ig M most sensitive mark for active, recent infection (positive for 6 months post infection)
- Ig G shows past infection and persist for life

- Takes 3-6m to be positive after infection
- shows past infection and immunity to HBV
- passive Ab from HBV immunoglobulin
- only Ig G if had HBV vaccine


What's the cure rate of acute Hep B?

Causes injury by immune mediated processes
- the more complete the response the more likely viral clearance but more damage to hepatocytes

Cure 95%
Chronic infection 5-10% (as opposed to Hep C 85%)
Fulminant Hep B < 1%


What's are the types of chronic infection?

Asymptomatic chronic carrier
- HBs Ab present, HBeAg negative but HBeAb positive
- May lose HBsAb --> i.e cured in 2%
- 10% risk of having chronic Hep B

Both chronic infection has HBsAg and HBeAg positive with HBcIgM negative

Chronic active hepatits / clearance phase
- active hepatitis resulting in increased risk of cirrhosis and HCC if unable to clear

Chronic persistent hepatitis / immunotolerant phase
- no immune response despite active viral replication therefore benign self-limiting illness


What's the hepatitis B vaccine?

Not a live vaccine, grown in yeast and can be given to immunocompromised


What does a neonate need if mother is Hep B positive?

Ig G and vaccination
- Ig G given within 12 hours of birth is best, efficacy reduced if > 48 hours
- HBV vaccination must be given within 7 days
- Measure HBsAg and HBsAb at 9-15 months


What can circulating immune complexes containing HBsAg cause?

Membranous or membranoproliferazive glomerulonephritis
Guillaine barre
Polyarteritis nodosa


What is the Hep C virus?

ssRNA - flaviviridae family

Incubation period 6-7 week


How is Hep C transmitted?

Causes direct cytotoxicity to cells

Most commonly via blood
- 85% develop chronic infection with ALT fluctuating and slow progression to cirrhosis if received HCV positive blood

Via sex
- rare < 5% couples

Vertical transmission
- ~5% of infants born to HCV+ mothers
- test for anti HCV ab > 12m +/- 18m
- no conclusive evidence whether C/S is protective
- Ok to BF


What is the likely hood of getting Hep B / C / HIV via needle stick injury?

- Hep B 30%
- Hep C 3%
- HIV 0.3%

- Hep C 1%
- Hep B <1%
- HIV 0.1%


What are the clinical features of acute Hep C infection?

Usually asymptomatic in kids

- mild anorexia / nausea / abode pain
- rarely jaundiced
- increased incidence of symptomatic infection in immunocompromised patients
- fulminating hepatits rare


What are the clinical features of chronic Hep B infection?

Hep C is the most likely virus to cause chronic infection
- 50-90% persistent abnormal LFT (ALT tend to fluctuate)
- 40-60% HCV RNA positive long term
- majority of kids has clinically silent disease with slow progression or stable liver disease


What are the associated extra-hepatic features seen in Hep C?

- cutaneous vasculitis
- porphyria cutaenoius tardia
- type II cryoglobulinaemia

- Cerebritis
- Peripheral neuropathy

- Membranous GN


What ix are available for Hep C?

Antibody assays
- anti HCV is a marker of exposure
- does not confer immunity
- false positive rate as high as 50% in low risk population
- false neg in first 3m as ab take time to reappear

Acute infection
- HCV RNA +ve
- antiHCV neg for first 4-6wk
- normal LFT

Resolved infection (15%)
- HCV RNA negative on 2 occasions over 6-12m
- anti-HCV ab +ve
- normal LFT consistently

Chronic infection (85%
- HCV RNA +ve persistently
- Anti-HCV ab +ve
- +/- abnormal LFTs, abnormal liver biopsy


What treatments are available for Hep C?

Notifiable disease!
Consider acute / chronic carriers to be infectious
Immunise against HBV / HAV
Recommend no all

Little data on interferon tx on kids
- aim is to clear virus to reduce risk of cirrhosis and HCC
- indications include chronic liver disease, persistently abnormal ALT and HCV RNA positive
- ribacvarin (guanosine analogue) increases rate of sustained response with combined with interferon but SE is haemolytic anaemia and teratogenic


What does Hep D need to cause infection?

Hep B
- Hep D can't make its own coat protein


What is the incubation period of Hep D?

Super-infection (in someone with chronic HBV): 2-8wks
Co-infection with HBV: 50-180 days


What hep virus should you always consider in a child with fulminant liver failure?


- acute hepatitis more severe than HBV alone
- high risk for fulminant hepatitis
- low risk of chronic hep

- high risk to develop chronic hep
- high risk to develop fulminant hepatitis (more than co-infection .. ? cells already damaged)


How is Hep D spread?

Percutaneously ...

Unlike Hep B, not spread sexually nor vertically


What are some common causes of neonatal hepatitis?

Congenital infection
- a1AT deficiency
- CF
- CHO metabolism (galactossaemia, fructosemia, glycogen storage disease IV)
- Protein metabolism (tyrosinaemia)
- Lipd metabolism (Wolman disease)
- Storage disease (Gaucher, Neimann-Pick)
- Copper metabolism (Wilson)
- Neonatal haemachromatosis


What are basic ix of hepatitis?

Hepatitis serology (including CMV, EBV)
Other viruses to consider - HSV, VZV, HIV, rubella, adenovirus, enterovirus, parvovirus B19, arboviruses

- ANA, anti-smooth muscle Ab, anti-LKM ab, anti-mitochondrial Ab

alpha-1-antitrypsin phenotyping

Caeruloplasmin, 24 hour urinary copper excretion


What endocrine conditions can cause hepatomegaly?

Hypopituitarism and hypothyroidism


What autoimmune conditions can cause hepatomegaly?

Autoimmune hepatitis, JIA, SLE


What metabolic conditions can cause hepatomegaly?

A1AT deficiency


What are the types of biliary atresia?

- post natal form
- most common (65-90%)

Biliary atresia and congenital anomalies
- fetal / embryonic form
- 10-35% of cases
- a/w situs invertus, polyspenia / asplenia, other congenital anomaly


What are the long-term complications of biliary atresia?

Portal HTN - splenomegaly and ascites

Good outcome if kasai < 2 m, favourabe hepatic and bile duct histology at operation, absence of CLD, post-op clearing of jaundice.

Increased risk of HCC w early cirrhosis


What are the ix for biliary atresia?

SBR >20% conjugated
Must do a1AT phenotyping as biopsy pattern very similar

USS to excluded choleochal cyst

HIDA scan
- shows normal uptake but no excretion of bile
- reduced accuracy if v high SBR
- false neg in early stages

Intra-op cholangiogram
- gold standard


What's the management of biliary atresia?

- roux en Y
- small intestine transected with one end attaching directly to the liver, the other continuing on further down
- not worth doing after 12 wk

Operation --> horizontal scar

- BF encouraged: has lipase and bile ales
- if bottle fed use MCT formula
- fat soluble vitamins required

Most common cause of liver transplants in kids


What is the risk of having a choledochal cyst?

Congenital dilation of CBD
- can cause progressive obsbtuction
- a/w intrahepatic bile duct dilation

Usually presents as infant with conj. jaundice

Treat by excision
- any residual tissue has risk of cholangiocarcinoma


What's portal HTN?

When portal vein pressure > 10-12mmHg (normally 7mmHg)


What are the causes for portal HTN?

Pre hepatic
- portal vein thrombosis secondary to umb vein sepsis, intra-ado sepsis, neonatal dehydration, hypercoag
- portal vein obstruct: web / diaphragm, AV fistula,

- hepatitis, cirrhosis, congeilta hepatic fibrosis (ARPCK), idiopathic, drugs

- Budd Chiari syndrome (hep vein obstruction, usually idiopathic)
- Veno-occlusive disease post-transplant due to TBI +/- Cytotoxics


What are complications of portal HTN?

developmental of collateral circulations at
- gastro-oesophageal junction
- ano-rectal junction
- abN gastric submucosal AV connection

- oesophageal vatical bleeding
- ascites
- caput medusa
- splenomegaly / hypersplenism


What are the ix of choice for portal HTN?

US - demonstrate potency of portal vein and show varies
All should have endoscopy as size of varies correlates with likelihood of haemorrhage


What causes Reye syndrome?

High a/w aspirin ingestion in children w flu-like illness or varicella

Causes loss of mitochondrial function
- reduced hepatic intra-mitochondrial enzymes
- disturbs fatty acid and carnitine metabolism


What are the clinical features of Reye syndrome?

- Apparent recovery of febrile illness (URTI 90%, chicken pox 5-7%) then rotracted vomiting with encephalopathy, stupor, seizures
- examines with hepatomegaly w no jaundice

- raised transminaes, CK, LDH
- elevated prothrombin time, ammonia
- CSF normal

- phenobarb reduces cerebral metabolic demands
- reduce fluid intake
- mx coagulopathy and hypoglycaemia


What is the radiological finding of sclerosing cholangitis?

beading / irregularity of the intrahepatic and extra hepatic bile ducts