White Cool Lecture Oct 3 Flashcards
(36 cards)
Where are the RBC’s destroyed?
reticulo-endothelial system (liver and spleen)
What is hereditary spherocytosis in regards to the RBC’s?
The RBCs are spherical and fragile resulting in increased hemolysis
What are the clinical signs of HS?
hemolysis, anemia, and splenomegaly
Why is the cytoskeleton important in the RBC’s?
structure
flexibility while moving through the capillaries
strength
What is the structure and function of spectrin?
Spectrin provides the RBC with a resilient structure
alpha beta heterodimer with a head to head alignment
Describe the steps of the osmotic fragility test
- place the blood in a hypotonic solution (vary concentration of the solution)
- water will rush into the cell
- normal cells will swell and not break
- the HS cells will swell and lyse
Describe what the NAN mouse experiment aimed to test?
To see if there was another cytoskeleton molecule or other unassociated molecule that could be associated with the causation of HS
What was the finding in the NAN study in relation to the Fe and the Zn
Instead of having an Fe bound to the cell, the RBC had high levels of Zinc
What was the DNA binding protein that was found to have a mutation in the NAN experiment?
Kruppel Like factor 1 (KLF1)
Describe the actions of the KLF1
It binds to several promotor regions of ECM molecules
What is the binding motif that is highly conserved in DNA
RER
What are the various treatments for HS?
blood transfusions
splenectomy
increase the RBCs and Hb
Which muscular dystrophy is the most common fatal MD?
DMD
What are the treatments that can be provided for someone who has DMD?
glucocorticoids (prednisone)
and supportive measures
Describe the genetics of the DMD? What kind of inheritance pattern does it follow? What are the mutations that are involved?
X-linked recessive
frameshift mutation
What are the clinical factors of DMD?
dystrophic myopathy elevated CK levels that are 50-100 times more than normal slow walking and generalized weakness waddling problems with stairs tiptoe walking lordosis kyphosis scoliosis necrosis of the muscle fibers (increased tone) wheelchair by 13
What is the Gower man sign?
When a kid is on the floor and uses his hands to walk up his legs while standing
What is the average age for diagnosis of DMD?
4 years and 10 months
Define BMD
Becker Muscular Dystrophy
milder from of DMD
What are the cardiac issues that are commonly seen in BMD
increased workload on the left ventricle and the enlargement of the left ventricle
heart failure and death
Describe the genetics of BMD including the “odd” finding in regards to the genetics, mode of inheritance, and the type of mutations that are typical
- 1/3 of the cases are de novo, meaning that it was not directly inherited in the family
- X linked recessive
- inframe deletions
Describe why it was thought that growth factors would be a good treatment for DMD.
myostatin is a cell growth inhibitor, so it was thought that if you treated a pt with DMD with a myostatin inhibitor, it would promote muscle growth
What are the cons in using growth factor as a treatment for a pt with DMD?
It makes more defective muscle and is not useful
What are the two ways in which gene therapy can be used for someone with DMD?
- replace the dystrophin gene
2. use microdystrophins
