MS1 - Sickle cell (#6)

Sickle cell =

autosomal recessive disorder

SCD is characterized by

presence of an abnormal form of hemoglobin (Hb) in RBC

What is the specific form of SCD called ?

hemoglobin S (Hb S)

hemoglobin S (Hb S) is a result of a mutation in

β-Hb chain where amino acid glutamic acid at position 6 is substituted w/ valine

The presence of Hb S causes

RBCs to change to a crescent shape compared to a biconcave disk shape.

_______ O2 is normal

Transporting

When releasing O2 Hb changes its molecular arrangement into a long rigid rod that causes the

sickle shape

d/t negative charges changes from amino

Sickled RBCs are rigid and sticky, contributing to

vaso-occlusion (arteries, veins, capillaries)

Chronic hemolytic anemia = result of

constant sickling/unsickling leading to permanent damage and hemolysis.

Vasocclusion → ischemic injury due to

adhesion between sickle cells

Endothelial dysfunction =

increased activation of WBCs increasing adhesion to each other.

Chest syndrome involves

inflammation and blood vessels blockages in the lungs

SCD can be diagnosed through

1) Hemoglobin electrophoresis 2) Genetic testing 3) Newborn screening 4) Prenatal testing 5) Blood testing

Prenatal testing

chorionic villus sampling or amniocentesis

A haplotype is

DNA along a single chromosome from one parent

Having the inherited trait (sickle cell) without the illness leads to

more resistance against this form of malaria.

Events that occur physiologic stress such as

infection, hypoxia, dehydration, exposure to extreme temperatures, and fatigue may induce symptoms/episodes resulting in sickling of RBCs

Major complications of sickle cell include

acute chest syn, splenic sequestration with subsequent splenectomy, and dactylitis

dactylitis =

hand-foot syn in which the hands and/or feet swell and are very painful due to peripheral circulatory occlusion(

If SCD is identified prenatally, genetic counseling can lead to

significant decrease in affected children

Genetic counseling requires

1) the autotomy of an individual/couple 2) right to adequate and complete information 3) highest standards of confidentiality

The goal is to prevent further sickling of RBCs via

blood treatments, vaccines, gene therapies, and medications (Hydroxyurea)

What does medical treatment of sickle cell target and promote?

antipolymerization / NO (nitric oxide) production

Since many other body systems are affected then

rest, pain medication (opioid and nonopioid) oxygen, IV fluids, and antibiotics can be used to treat symp

Prophylactic transfusions will help

decrease risk of stroke and stenosis of arteries.

Medical advancement exist

gene editing therapy (CRISPR/Cas9 technology) for functional cures for SCD

Fear-avoidance for movement is

relatively common

Exercise intolerance:

consider low VO2 max, low anaerobic threshold, and low HR reserve.