Case studies of Alpha-1-antitrypsin deficiency

1. Selected for publication in student’s
corner
Biochemistry for Medics
www.namrata.co

2. Case studies of α -1
antitrypsin deficiency
Niveshnee D.
Kodai
Roll Num 39

3. • Introduction
• Functions
• Case study- Emphysema
• Diagnosis and treatment
• Case study- Juvenile
cirrhosis

4. Plasma
proteins
albumin globulin fibrinogen
α1 α2 β1 β2 γ
Acid
glycoprotein
Antitrypsin
Fetoprotein
Globulin

5. • Also known as α1-
antiproteinase.
• Single polypeptide chain
having 394 amino acids.
• Molecular weight of
450 000
• Isoelectric pH of 4
• Normal level = 75- 200
mg/dL

6. • Serine protease inhibitor.
• Inhibit the action of elastase,
trypsin and other proteases.
• Tumour marker of testis
and ovaries.
• Inhibits fibrinolysis.

7. • Increases during:
1) Inflammation- an acute phase
protein
2) Chronic hepatocellular diseases
3) Biliary tract obstruction
4) Pregnancy

8. • Decreases in
1) Nephrotic syndrome
2) Emphysema
3) Liver cirrhosis

9. A 42 year old woman presented with chronic
cough, excessive production of mucus and
shortness of breath.
Upon exercising, she started to hyperventilate
and her tolerance seemed to be decreasing. She
often suffered from dizziness and anxiety. There
was also an abnormal weight loss and her
fingers used to turn blue or grey. On examining
the blood sample, there was a low level of AAT.
What is the diagnosis?

10. About 5% of emphysema cases are due to α- 1
antitrypsin deficiency. Patients with zz genotype
having less protein are more susceptible to this
deficiency.
Any bacterial infection in lungs attracts
macrophages that release elastase.
In normal health, α- 1 antitrypsin protects the lung
tissues from injury by binding with the active
elastase, making it inactive.
However in α- 1 antitrypsin deficiency, there is
unopposed action of the active elastase leading to
serious lung tissue damage through proteolysis.
This condition whereby most of the elastin

11. Healthy
Unoppose
lungs
d action
of
No
Active elastase
tissue
elastase
damage
α1
More
antitrypsi
proteolysis
n def
No α1
proteolysis antitrypsi
n
More
Unhealthy tissue
Inactive lung damag
elastase e

13. • Spirometer Breath
Test: to know
the different stages
of emphysema
• AAT blood test
• Lung function test
• Chest x-ray

14.  Bronchodilators: relieve coughing
 Inhaled steroids
 Oxygen therapy
 Antibiotics- for respiratory
infections.
 Lung transplant-in severe cases
 Quit smoking

15.  Smoking is the most important risk factor for
emphysema. When a person inhales tobacco smoke, it
damages the air sacs in the lungs. Eventually, the lungs
lose their functions resulting in emphysema.
 Toxic substances are discharged from tobacco smoke
which enter the air sacs of the lungs. These toxic
substances damage the walls of the air sacs.
 People who smoke 20 or more cigarettes per day suffer
from emphysema.
 Smokers are 6 times more likely to develop emphysema
than non-smokers.
 Smoking causes 82% of emphysema among males and
76% among females.

16.  Smoking oxidises methionine to methionine
sulfoxide at 358 th position.
 Hence it deactivates AAT and causes tissue
damage, resulting in EMPHYSEMA.
 Damage from emphysema is irreversible.
Nevertheless giving up smoking is quite beneficial.

17. A 15 year-old female presented with itching,
weakness, fatigue, and loss of appetite. She was
found to be having a low serum albumin
concentration, together with a marked increase in
the concentration of Alanine amino Transferase
( ALT) and Aspartate Transferase (AST).
Serum total Bilirubin concentration was also found
to be higher, the patient apparently had
Jaundice.
What is the diagnosis?

18.  The patient is suffering from Juvenile hepatic
cirrhosis
 The piZ molecule accumulates in the cisternae of
endoplasmic reticulum of the hepatocytes.
 Thus they are unable to release AAT leading to
the cirrhosis of liver.

19. Imaging Tests
 Magnetic resonance imaging (MRI),
 computed tomography (CT), and ultrasound
liver biopsy

20. Treatment of cirrhosis includes
 1) preventing further damage to the liver,
 2) treating the complications of cirrhosis,
 3) preventing liver cancer or detecting it early
 4) liver transplantation.

21. α1 antitrypsin
Activity of
deficiency
elastase
Emphysema
Hepatic Smoking
cirrhosis

22. • Class notes
• Biochemistry for medics
• Internet

23. Thank
you…