Question about Sickle Cell Anemia

[fabiolablake]

Does anyone know the source of pain from sickle cell anemia? I have found that patients with SCA have significantly higher concentrations of hemoglobin than normal individuals and this decreases the concentration of nitric oxide in the blood. Nitric oxide is thought to play approximately 30% role in blood vessel diameter and in its absence, the sickle shaped RBCs get stuck in the smaller vessels resulting in ischemia and tissue necrosis. However, it doesn't seem that the acute pain would be a result in tissue necrosis. Does anybody have an explanation? I appreciate your help.

Blake

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[Goofyone]

Originally posted by fabiolablake
However, it doesn't seem that the acute pain would be a result in tissue necrosis.

Why not? I'm thinking MI or bowel infarct here, which are both very painful types of ischemic necrosis.

 

[BamaAlum]

The pain is probably due to microvascular occlusion which leads to ischemia as previously mentioned. Contrary to popular belief these occlusions are actually due to "normal" appearing erythrocytes which have greatly increased expression of adhesion molecules due to repeated sickling. Of course ischemia will ultimately lead to inflammation and release of nasty neutrophil oxidases, etc. which can cause pain. Not to mention the pain of ischemia itself.

 

[rbassdo]

Originally posted by BamaAlum
The pain is probably due to microvascular occlusion which leads to ischemia as previously mentioned. Contrary to popular belief these occlusions are actually due to "normal" appearing erythrocytes which have greatly increased expression of adhesion molecules due to repeated sickling. Of course ischemia will ultimately lead to inflammation and release of nasty neutrophil oxidases, etc. which can cause pain. Not to mention the pain of ischemia itself.

...which tend to occur at arterial bi-furcations...

 

[Idiopathic]

The pain is caused by infarcts in bone.

 

[DOnut]

The pain associated with sickle cell is due mostly to Ischemia and micro-infarcts. There are several different presentations of pain associated with sickle cell. The areas may differ, but the etiology is almost always some microvascular occlusion.

Vaso-occlusive crisis are the most common clinical syndrome of sickle cell disease. In vaso-occlusive crisis, you have infarctions of small bones (usually within the marrow cavity). Most of these infarctions are multifocal and lead to pain as well as edema. In infants, these crisis tend to occur in the hands and feet, where as in older children, these crisis can occur in the hip, chest, knee, and other joints.

Abdominal pain can look like typical peritoneal irritation, but unlike appendicitis, or cholecysititis there is NO rebound tenderness or murphy's sign (Atleast this is what I've read. As an aside, I have done quite a bit of research on sickle cell disease.)

When vascular occlusions occur in cerebral vessels, young children can present with symptoms of stroke. Sickle cell must always be ruled out in these situations. (I know that's not about pain, but hey)

This is what I know. Hope it helps. We do have a few people at NYCOM who know much more about sickle-cell than I do. Several of them post on SDN, so if you wish to have more info, I will have them post a reply. I hope this helps.

DOnut

PS- As an aside, to my knowledge, there is not an increase in hemoglobin. Sickle cell is caused by a genetic mutation leading to the formation of a type of hemoglobin that deforms under stress (hemoglobin S). This type of hemoglobin is unstable and has a much shorter life span (this is what leads to the aplastic anemia). Due to the mutation (Val for Glu), the addition of this nonpolar aminoacid weakens the structure of the hemoglobin preventing it from maintaining it proper conformation when deoxygenated.

 

[BamaAlum]

Total hemoglobin is not increased, but because of the fragility of the membrane the red cell loses electrolytes and water and becomes dehydrated. This raises the MCHC.

 

[Kalel]

hgb is low in sickle cell anemia (hence the "anemia"), but I think what the OP meant was that higher levels of hgb (and I assume lower levels of NO) are associated with more frequent painful vaso-oclusive episodes. Incidentally, very low levels of hgb are associated with an increase in mortality, so i guess you can't win. And although "typical sickle cell" deep-pain is associated with bony pain and arthritis, it's important to remember that sicklers can experience pain in any organ that they can cut off blood to and that have pain receptors (eg priapism, skin ulcers, mesenteric ischemia, myocardial infarction, etc). the bone pain is most common though.

 

[fabiolablake]

Originally posted by Kalel
hgb is low in sickle cell anemia (hence the "anemia"), but I think what the OP meant was that higher levels of hgb (and I assume lower levels of NO) are associated with more frequent painful vaso-oclusive episodes. Incidentally, very low levels of hgb are associated with an increase in mortality, so i guess you can't win. And although "typical sickle cell" deep-pain is associated with bony pain and arthritis, it's important to remember that sicklers can experience pain in any organ that they can cut off blood to and that have pain receptors (eg priapism, skin ulcers, mesenteric ischemia, myocardial infarction, etc). the bone pain is most common though.

I appreciate everyones' responses. I had found an article on the web (but I questioned its validity because I hadn't heard of the source before) and they said they had found increased levels of hemoglobin. Although this is an anemia, if the increased hgb is in fact true, there is less functional hgb. However, I would tend to take your word over the article because of the lack of credibility. Thanks again for all the responses, this is interesting.

Blake

 

[Kalel]

cite me the article. Is it on the internet? I may be able to look it up in ovid. I think that it's saying the same that I just said though (ie higher hgb but still anemic levels of sickle cell being associated with more pain).

 

[fabiolablake]

http://www.hon.ch/News/HSN/510192.html

 

[Kalel]

Originally posted by fabiolablake
http://www.hon.ch/News/HSN/510192.html

Oh! That makes sense. In the hospital, when people talk about hemoglobin levels, they are talking about total hemoglobin levels (ie there is no distinction between the hemoglobin in your RBC's vs the Hgb in your plasma, you are only given one total level). In sickle cell anemia, the avg Hgb level is somewhere around 7.5 mg/dl (with normal being somewhere between 12.5-14). The article is just saying that a larger proportion of the hgb in sickle cell patients resides outside of RBC's (since sickle cells are easily hemolyzed and subject to trauma and sequesteration) then in a normal person's plasma/blood. The scientists are proposing that the extra hemoglobin in the plasma is playing a role in the pathophysiology of vaso-oclusive events by degrading the nitric oxide that is also within the plasma (released by endothelial cells), causing vasoconstriction that probably exacerbates the occlusion or causes further occlusive events within presumably arterioles (since capillaries have no smooth muscle to constrict with). It's a theory, not a proven fact. Most still subscribe to the old fashion sickled cells getting clogged up in the arteries version of the story, but like most diseases, there are always a lot of contributing factors. Anyways, total hemoglobin levels are low in sickle cell anemia patients, but the hemoglobin level within the plasma is higher then patients without sickle cell secondary to all of that hemolysis. Thanks for finding the article!

 

[fabiolablake]

Thank you for the explanation. You'll be a good, knowledgeable doctor!

Blake