NSG 530 

Instructions

A 38-year-old African-American woman was admitted for arthroscopic knee surgery. Her hematocrit was 25%, blood pressure was 140/94 mm Hg, and pulse was 112 beats/minute. She had a history of joint and bone pain, jaundice, and abdominal pain.
Due to the presenting symptoms (joint and bone pain, abdominal pain, and jaundice) a diagnosis of Sickle Cell Disease was considered.

• Provide the pathophysiology of sickle cell disease.
• Discuss the clinical manifestations and etiology associated with these manifestations

Solution

In the provided scenario, a 38-year-old African American woman was admitted for arthroscopic knee surgery. He manifested a blood pressure of 140/94 mm Hg, 112 pulse bears/minute, and hematocrit of 25%. Further examination revealed that the patient was suffering from sickle cell disease. Based on the scenario, the week 9 discussion is about the pathophysiology of sickle cell disease including its clinical manifestation and etiology.

According to Sundd et al. (2019), sickle cell disease affects about 100,000 people in the United States and several millions, worldwide. In addition, more than 176,000 people die from sickle cell disease every year globally. Sickle cell disease is a genetic disorder caused by the inheritance of homozygous and compound heterozygous a mutation in the β-globin gene (Inusa et al., 2019).

A single base-pair point mutation (GAG to GTG) leads to the replacement of the amino acid ((hydrophilic) with Valine (hydrophobic) in position six on the β-chain of hemoglobin also called hemoglobin S (HbS). Sundd et al. (2019) state that Sickle cell disease (SCD) represents an umbrella term used for all mutations occurring in the β-globin gene. Homozygous inheritance of β-globin mutation leads to Sickle cell anemia that accounts for over 70% of sickle cell disease (Sundd et al., 2019). Heterozygous inheritance of β-globin caused other types of sickle cell disease, such as the co-inheritance of HbS and HbC (HbSC) and sickle β thalassemia genotype (HbS/βo or HbS/β+).

The symptoms of sickle cell disease are different for every individual and can range from mild to severe. Clinical manifestations include acute chest syndrome associated with chest pain, difficulty breathing, fever, and coughing (Inusa et al., 2019). Others include anemia, avascular necrosis, blood clots, and others.  According to Sundd et al. (2019), experts have identified three main pathways to SCD pathophysiology HbS polymerization, vaso-occlusion, and hemolysis-mediated endothelial dysfunction.

Red blood cells (RBCs) with HbS or a combination of HbS and other abnormal β alleles often undergo polymerization and become rigid when exposed to the deoxygenated environment (Inusa et al., 2019). The rigid RBCs may undergo hemolysis (which increases density) affecting blood flow and endothelial vessel wall integrity. The dense rigid red blood cells cause vaso-occlusion, infarction, ischemia, and hemolysis.

The effect of hemolysis is complex series of events, which in turn leads to complications such as stroke, leg ulceration, pulmonary hypertension, and priapism (Inusa et al., 2019). A normal red blood cell has a half-life of about 120 days while sickle RBC may survive just for 10 to 20 days due to increased hemolysis. . During acute sickling, intravascular hemolysis results in free hemoglobin in the serum, while RBCs are gaining Na+, Ca2+ with a corresponding loss of K+. The increasing concentration of calcium ions (Ca2+) leads to impairment in the calcium pump (Inusa et al., 2019). Furthermore, hypoxia also inhibits the production of nitric oxide, thereby causing the adhesion of sickle cells to the vascular endothelium.

References

Inusa, B. P., Hsu, L. L., Kohli, N., Patel, A., Ominu-Evbota, K., Anie, K. A., & Atoyebi, W. (2019). Sickle cell disease—genetics, pathophysiology, clinical presentation and treatment. International Journal of Neonatal Screening, 5(2), 20. https://doi.org/10.3390/ijns5020020

Sundd, P., Gladwin, M. T., & Novelli, E. M. (2019). Pathophysiology of Sickle Cell Disease. Annual review of pathology, 14, 263–292. https://doi.org/10.1146/annurev-pathmechdis-012418-012838