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Flashcards in Hemoglobinopathies Deck (18)
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Why do fetuses not suffer from sickle cell disease if they have the gene?

The sickle cell gene mutation is found in the beta globulin region which does not begin to be transcribed until birth.. Gamma mutations may exist, and may cause some in-utero deaths, but little is known.


How might sickle cell trait actually lead to reproductive advantage?

Spermatogenesis occurs outside the body (testicles hanging outside) because it needs lower temps. Sickle cell trait interrupts the life cycle of malaria and lessens the severity of the disease, leading to lower fever temperatures. This lower body temp favors spermatogenesis.


What is required for the sickling of sickle cells?

The presence of the sickle cell trait and another abnormal beta globulin (Hb S, C, D, O, E, or even B-thalassemia underproducing normal Hb)


What is the normal progression of cells to sickle cells if they have HbS AND another abnormal beta globulin?

Typically normal shape while saturated with O2. O2 dissociation leads to polymerization of Hb, and the cell slowly loses its normal shape. Normal shape is mostly regained when it becomes saturated again in the lungs, so it depends on the time between dissociation and re-saturation. Once the cell is fully sicklated, it is irreversible and destroyed. Reversible stages of sickling still damage the RBC mmbr and make the cell "stickier".


Why do cells not sickle with HbS and Hbnormal?

The level of oxygen dissociation required for cells to sickle with only sickle cell trait is much more complete than occurs in human tissues, requiring fatally low levels of O2 pressure. However, regions of the body with very low O2 pressure (renal medulla, spleen) may trigger sickling at high altitudes in dehydrated white males (skiers).


How does sickle cell disease cause multi system effects?

The sickle cell RBCs, whether actually sickled or not, are abnormally sticky and display abnormal cellular adhesion to endothelium, esp. post capillary venuoles. This may lead to direct damage of the endothelium, up regulating adhesion molecules, repair mechanisms, and apoptosis. This all results in abnormal vasoregulation. This can occur in any location in the body.


Why is an elevated WBC assiciated with sickle cell disease?

The marrow is producing RBCs at an increased rate, and some of the stimulatory cytokines spill over into the WBC precursors, instigating increased WBC production.   WBC are also produced in reaction to organ and system damage caused by the sickle RBCs.


What is the process of events of RBCs sticking to endothelium?

The RBC sticks to the endothelial cells, loses all of its O2, sicklates and lyses, releasing heme and iron which are toxic, cellular damage attracts leukocytes.   Results in endothelial injury and potential for broader tissue injury and damage to an organ.   Also may block blood flow and cause infarction.  


How is sickle cell disease definitively diagnosed?

Protein (hemoglobin) electrophoresis.


What are the differences between normal RBCs and sickle cells?

Normal RBC: disk-shaped, pliable, easily flow through small blood vessels, live for 120 days.   Sickle Cells: sickle shaped, rigid, sticky in blood vessels, live for 20 days.   Short life span = increased erythropoiesis.


What are CBC and smear findings for Sickle cell?

Inc retic count, inc WBC, inc platelets, inc RDW, abnormal peripheral smear.   Also abnormal chemistries due to release from RBCs: AST, LDH, and unconjugated bilirubin.


What are some complications of chronic hemolysis (sickle cell disease)?

Predisposition to aplastic crisis.   Temporary interuptions in reticulocyte creation (caused by viral infection for example) have dramatic effects when retic counts are ~20%.   Increased incidence of gall stones (excess bilirubin).   Delayed growth/sexual maturation due to energy and nutritional use by erythropoiesis.


How do different HbS conditions present in terms of anemia, MCV, and target cells?


What conditions may sickle cell cause?

Stroke, Splenic infarction, sepsis (after splenectomy), large vessel occlusion - athersclerosis, sickle lung disease (pulmonary hypertension)


Which two organs do not experience much damage from sickle cells?

The heart and the liver.


What is the treatment for sickle cell pain?

Reverse any underlying pathophysiology.   Get endothelium "unsticky" (nitric oxide?).   Treat with antibiotics for fever, adequate pain control, adequate O2 and hydration.  


What is the treament for hemoglobinopathies?

Transfusion therapy - maintains hemoglobin, causes iron overload.  Induction of fetal hemoglobin with hydroxyurea  (Hb Gamma does not have sickle mutation).   Bone marrow translplant - actual cure.