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The Gastroenterology Training Handbook
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Alpha 1 Antitryspin Deficiency
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Written by Dr Sebastian Zeki
MCQs for this page
What the Curriculum Says
Knowledge
Recognises the importance of sepsis as a complication
Aware of the differential diagnosis and management of sepsis and its
possible sequelae
Knows the appropriate use of the appropriate antibiotics and their
complications Aware of prevention of nosocomial infection
Skills
Understands the principles and practice of diagnosis and treatment of
sepsis
Behaviours
Prepared to involve and liaise with specialist sepsis support
Also....
Knowledge
Knows the importance of clinical nutrition and its disturbances in
patients with acute and chronic liver disease
Appreciates indications for enteral or parenteral support and
understanding of limitations of these interventions
Skills
Shows ability to make careful nutritional assessment
Behaviours
Can liaise with nutritional support team where appropriate
Also...
Knowledge
Understands prognostic scoring systems including Child - Pugh
MELD UKELD Maddrey and disease-specific scoring systems where
they exist
Skills
Builds the use of accredited quantitative scoring systems into routine
clinical liver practice clinical colleagues and junior staff
Behaviours
Shows consistent application of evidence-based in the
evaluation of liver disease and the determination of prognosis
Alpha 1 Antitryspin Deficiency
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Prognosis
Depends on severity of underlying disease.
Do family screening - is only for prognosis.
Tests:
Alpha-1-antitrypsin levels.
PAS staining on hepatocytes.
Things that should arouse suspicion:
Emphysema FH/ in a young individual (ie, <45yr) / non or minimal smoker.
Emphysema characterized by predominant basilar changes on the chest
x-ray.
Unexplained cirrhosis or
hepatoma.
Clinical findings or history of
panniculitis
/ chronic liver disease.
Alpha 1 Antitrypsin Deficiency
Demographics
Implicated gene is on chromosome 14.
It affects 1 in 2000 people.
It results in decreased levels of alpha-1-
antitrypsin.
Pathogenesis of lung destruction in 1-antitrypsin
deficiency
.
1.Activation of airway neutrophils leads to...
2.The release of neutrophil elastase which remains active because
of a reduced inhibitory capacity as a direct consequence of
1-antitrypsin deficiency.
3. The elastase stimulates macrophages to release the chemoat
-
tractant leukotriene B4 (LTB4) which leads to further neutrophil
recruitment.
4. Recruitment of neutrophils through the interstitium causes
connective tissue destruction (particularly elastin) and the area of
destruction is enhanced again as a direct consequence of
1-antitrypsin deficiency.
5.The net result is perpetuation and amplification of the cycle of
events and tissue destruction.
Phenotype Emphysema Risk Plasma level, µmol/L Commercial plasma level, mg/dL
MM No increase 20-53 150-350
MZ Possible mild increase 12-35 90-210
SS No increase 15-33 100-140
SZ* Mild increase (20-50%) 8-19 75-120
ZZ High risk (80-100%) 2.5-7 20-45
Null High risk (100% by age 30) 0 0
Treatments:
-IV/ aerosolized augmentation therapy.
-Enhancement of endogenous alpha 1-antitrypsin production.
-Gene therapy.
-Liver transplant (phenotype becomes that of the new liver).
Macrophage
LRB4
Neutrophil recruitment
Elastase
Airway
neutrophil
Area of
destruction
Written by Dr Sebastian Zeki