Hereditary and congenital liver diseases Flashcards Preview

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Flashcards in Hereditary and congenital liver diseases Deck (71):
1

What is the hallmark of hereditary haemochromatosis (HHC)

Systemic iron overload

2

What organs can be affected by iron overload

Liver
pancreas
heart
joints
pituitary

3

Mutations of what gene cause a defect in iron handling

The HHC gene (HFE)

4

Where is the class 1 protein, coded for by HFE expressed

Many cells including the duodenal crypts

5

What does the MHC protein interact with

The transferrin receptor to facilitate iron uptake into cells and defects in it alter this interaction

6

What type of condition is HHC

an autosomal dominant inherited condition

7

What type of condition is HHC

an autosomal dominant inherited condition

8

What is the prevalence of HHC in Caucasians

Between 1 in 300 to 1 in 400

9

What are the clinical features of HHC

Lethargy
Abdominal pain (episodic)
Hepatomegaly
Chronic liver disease if advanced
Diabetes

10

What coniditon is associated with iron overload and may occur in association with haemochromatosis

Porphyria cutanea tarda (PCT)

11

What are patients with iron overload at increased risk of

Yersinia enterocolitica infection

12

When might a false negative occur in blood tests for HHC

In menstruating women, ill patients, liver disease, hepatitis

13

What test has replaced liver biopsy in suspected iron overload

Genetic testing

14

What should be test for in genetic testing for HHC

C282Y and H63D

15

During screening of HHC, what should be acrried out

History and Examination
Transferrin saturation
Serum ferritin

16

What is the management of HHC

Venesection - at weekly intervals until the Hb concentration falls to normal.
Monitor the serum ferritin - keep value within the normal range

17

What is the prognosis of HHC like?

Dependent on the presence of cirrhosis or diabetes
Life expectancy is normal in the absence of this

18

What is Wilson's disease

An autosomal recessive disorder caused by a defect in hepatic copper excretion resulting in copper overlaod and copper deposition in various organs which results in many abnormalities

19

What is the prevalence of Wilson's disease

1 in 30000

20

How does copper accumulate in the liver in Wilson's disease

It is not incorporated into its carrier protein, caeruloplasmin within hepatocytes and therefore is not adequately excreted into bile and accumulates in the liver

21

The abnormal genee for Wilson's disease (ATP7B) is on which chromosome

Chromosome 13

22

How many copper binding sites are on the ATPase transporter

6

23

What might Wilson's disease present as

Acute hepatitis
Chronic liver disease
Fulminant liver disease
Progressive neurological disorder
Pschiatric illness

24

At what age do patients usually become symptomatic

between 6 and 45

25

All patients being tested for autoimmune hepatitis should also be tested for what

Wilson'd disease

26

What is the hallmark of Wilson disease

A low caeruloplasmni

27

What is the main management for Wilson disease

Chelation therapy
Penicillamine which increases urinary excretion of copper
Pyridoxine is given in conjunction iwth penicillamine

Second line: Trientine
zinc
reduction of dietary copper

28

What is alpha 1 antitrypsin

A protease inhibitor that control tissue degradation by inhibiting a large number of proteases including trypsin, plasmin etc.

29

Where is alpha 1 antitrypsin produced

The liver

30

Where is alpha 1 antitrypsin produced

The liver

31

How does liver disease occur in alpha 1 antitrypsin deficiency

The accumulation of aggregated alpha 1 antitrypsin within the hepatocyte endoplasmic reticulum

32

Lung injury in alpha 1 antitrypsin deficiency is a result of what

Loss of protease inhibition

33

What is also associated with alpha 1 antitrypsin deficiency

COPD

34

How is COPD related to alpha 1 antitrypsin deficiency

It is due to the loss of the normal antiproteolytic defences against elastase

35

alpha 1 antitrypsin is encoded for by what

By a single gene located on chromosome 14

36

What are the clinical features of alpha 1 antitrypsin deficiency in childhood

Pruritus
hepatomegaly
conjugated hyperbilirubinaemia
increased serum aminotransferase
cholestasis can be marked

37

What happens to liver disease in alpha 1 antitrypsin deficiency in childhood

It often resolves spontaneously after 6 months

38

In adults with alpha 1 antitrypsin deficiency, what is there a high risk of

cirrhosis and HCC

39

How can alpha 1 antitrypsin deficiency be diagnosed

By a marked reduction or absence of the alpha-1- globulin band in an agarose gel electrophoresis

40

What is the management for alpha 1 antitrypsin deficient patients

Regularly assessed with LFT
Monitor for renal disease and vasculitis
CXR and pulmonary function assessmet
Smoking cessation

41

What can be given to patients with progressive emphysema and vasculitis

Purified human alpha 1 antitrypsin

42

What condiiton is associated with iron overload and may occur in association with haemochromatosis

Porphyria cutanea tarda (PCT)

43

During screening of HHC, what should be carried out

History and Examination
Transferrin saturation
Serum ferritin

44

What is Wilson's disease

An autosomal recessive disorder caused by a defect in hepatic copper excretion resulting in copper overload and copper deposition in various organs which results in many abnormalities

45

All patients being tested for autoimmune hepatitis should also be tested for what

Wilson disease

46

What is the main management for Wilson disease

Chelation therapy
Penicillamine which increases urinary excretion of copper
Pyridoxine is given in conjunction with penicillamine

Second line: Trientine
zinc
reduction of dietary copper

47

What is the management for alpha 1 antitrypsin deficient patients

Regularly assessed with LFT
Monitor for renal disease and vasculitis
CXR and pulmonary function assessment
Smoking cessation

48

What can be given to patients with progressive emphysema and vasculitis

Purified human alpha 1 antitrypsin

49

What is Alagille's syndrome

An inherited autosomal dominant disease causing cholestasis in conjunction with cardiovascular, facial, ocular, skeletal and neurodevelopmental abnormalities

50

What is another name for Alagille's syndrome

Ateriohepatic dysplasia

51

What is the incidence of Alagille's syndrome in Caucasia populations

1 in 100000 live births with no gender differences

52

What are the clinical features of Alagille's syndrome

prolonged neonatal cholestasis
features of chronic liver disease, pruritus and xanthomata

53

What are some extrahepatic features of Alagille's syndrome

Triangular face, broad forehead, saddle shaped nose, widely spaced deep set eyes, pointed chin
butterfly vertebra
renal abnormalities
neurodevelopmental delay
malnutrition and failure tot thrive

54

What are the investigations to determine Alagille's syndrome

Liver biochemistry and bioosy \
cardiovascular testing
renal function
slit lamp eye examination
spinal X rays
serum bile acids
cholesterol and triglycerides
nutritional assessment

55

What is the management for patients with Alagille's syndrome

Careful provision of adequate calories, protein and fat soluble vitamins
Management of mineral deficiencies
severe hyperlipidaemia - cholestryamine and ursodeoxycholic acid
Antihistamines for pruritus

56

What is the prognosis of Alagille's sundrome

74% 10 year survival

57

What are the investigations to determine Alagille's syndrome

Liver biochemistry and biopsy
cardiovascular testing
renal function
slit lamp eye examination
spinal X rays
serum bile acids
cholesterol and triglycerides
nutritional assessment

58

What is the prognosis of Alagille's sundrome

74% 10 year survival

59

What are autoimmune polyglandular sundromes

Autoimmune syndromes with symptoms affecting gland-bearing tissues and as such, the gut s often involved

60

What is the diagnosis of autoimmune polyglandular syndromes based on

The pattern of glandular disease

61

What are the porphyrias

Rare disorders of haem biosynthesis, characterised as either hepatic or erythropoeitic

62

What are the common environmental factors for causing symptoms of porphyrias

Alcohol
iron excess
oestrogens
hep C infection

63

What are the clinical features of porphyrias

Usually after puberty...
Photosensitive skin: pain, erythema bullae, hyperpigmentation
Acute relapsing -remitting neurological features : abdo pain

64

What are three of the main investigations required for porphyrias

Blood, Urine and stool investigations

65

What is the management for porphyrias

Avoid skin exposure and trauma : barrier creams
Avoidance of triggers
IV glucose
Administration of haem

66

What is biliary atresia

A very rare congenital condition of unknown cause in which there is obliteration or discontinuity of the extrahepatic biliary system

67

In which population is biliary atresia highest

Asian

68

What are the clinical features of Biliary atresia

Jaundice
pale stools
dark urine
failure to thrive
splenomegaly
hepatomegaly

69

What are the 2 main groups of biliary atresia

Isolated biliary atresia (65-90%)
Associated situs inversus or polyspenia/aplenia with or without other congenital anomalies

70

What are the investigations involved for biliary atresia

Blood tests: Conjugater hyperbilirubinaemia
US to confirm diagnosis
Radioisotope scans of the liver
Liver biopsy

71

What is the management for Biliary atresia

Surgical reconstruction of the extrahepatic biliary tract is possible if the intrahepatic biliary tree is unaffected
If the atresia is complete - liver transplantation