Lecture 50 Flashcards
What causes Class II mutation in cystic fibrosis
3 base pair deletion = deletion of Phe amino acid on 508
Lung pathology of CF
Chronic sinopulmonary disease
Mucus is thickened which result in drier airways and inhibiting ciliary clearance. Thus leading to inflammation and infection, leading to destruction of lung,»_space; scarring of lung
- chronic cough, bronchitis, sputum production
- Airway obstruction
Pancreatic pathology of CF
Since mucus is too thick, pancreatic secretion cannot go through to reach duodenum. Thus obstruction happens, leading to destruction of tissue, being replaced with fibrotic tissue and fat.
Also, maldigestion happen due to absence of pancreatic enzymes and bicarbonate which foster optimum environment for other disgestive enzyme.
Fats are not absorbed leading to steatorrhea (fat in stool).
*Meconium ileus in newborns
Effect of CF mutation in male infertility
congenital bilateral absence of vas deferens»_space; infertility
What is sweat test in CF diagnosis
pilocarpine is placed on patients fore arm. Electric current force pilocarpine to enter skin to stimulate sweat gland, then sweat is collected using gauze. If chloride content «70mM, then CF is diagnosed.
Mutation causing sickle cell anemia
Change of 6th amino acid (Glu) to valine, causing protrusion of valine on beta globin.
Pathophysiology of sickle cell anemia
Protruding valine (mutated both oxy and deoxy) fits into a complementary site on Beta1 chain of another haemoglobin(normal) molecule in deoxy state, leading to sickled fibers (sickled shape)
* Only deoxy state has hydrophobic pocket (both normal and abnormal)
This increase leads to precipitation of deoxygenated state, leading to sickling crisis.
Clinical features of sickle cell anemia
- Sickled and distorted RBCs get trapped in splenic sinusoid and are removed by spleen, leading to hemolytic anemia.
Also, this leads to splenomegaly. - Also increase breakdown of RBC can result in jaundice (hyperbilirubinemia) due to overwork of liver.
- Vaso occlusive crisis
- obstruction of microcirculation by sickled RBCs causing ischaemia.
diagnostic testing of sickle cell anemia
- Non-denaturing protein electrophoresis
- based on charge. Valine has less negative charge than glutamate, so move slower to positive electrode. - RFLP analysis
- mutation result in loss of cleavage site, so mutated beta globin mRNA is longer than normal beta globin. - ASO
In what tissue, is dystrophin found?
in muscles and neurons
What happens in absence of dystrophin?
sarcolemma breaks down , becoming permeable ( hole formation), so calcium influxes, activating phospholipase and oxidative cellular injury, leading to muscle necrosis.
Type of mutation in DMD (duchenne)
frameshift mutation leading to immature stop codon
Type of mutation in BMD (Becker)
point mutation or in-frame deletion
Diagnosis of DMD
- High CK-MM (due to massive muscle tissue turnover)
- Multiple PCR analysis (PCR of all 9 exons)
