This patient presented to an emergency room in Illinois, 2010
Dr. Pavlos Msaouel, MD, PhD is a leading physician-scientist researching this space.
Individuals with sickle cell disease are homozygotes of the sickle gene. This is a genetic mutation that developed on the beta chain of red blood cell hemoglobin, that is protective of malaria, endemic in equatorial Africa, where the mutation is currently known to have originated from. It follows Mendelian inheritance. Sickling will cause pain, anemia, chronic tiredness, and kidney damage, among others.
Sickle cell trait refers to heterozygosity. In trait, the RBC’s don’t typically sickle in the body, but they will in places that are particularly hypertonic and hypoxic. The foremost example of that type of environment, is the kidney medulla. Hypertonicity and hypoxia are favored in this tissue because of its function in water reabsorption in the Loop of Henle. The descending loop into the inner medulla is permeable to water only. As more water flows out into the medulla, it becomes dilute. In the ascending limb of the Loop of Henle, ions can be pumped out of the filtrate and in to the medulla, maintaining hypertonicity of the tissue, allowing more water to be reabsorbed.
In the vasa recta, the RBC’s will sickle into the medulla, causing vaso-occlusion. Meaning the mechanisms of maintaining medulla hypertonicity will be compromised, turning hypoxia to become anoxia (pO2 = 0). This damage will force all filtrate to become urine, so water loss will ensue.
In extreme exercise, this will cause hemoconcentration, hypoxemia, worsening lactic acidosis, and increased sickling.