Pathomorphology and the Clinical Manifestation of Anemia

The pathologic changes from sickle cell anemia are primarily the result of

• Increased blood viscosity and
• Increased red blood cell destruction. The entanglement and enmeshing of rigid sickle-shaped cells with one another increases the internal friction to the suspension, thus increasing blood viscosity. The thickened blood slows the circulation, causing capillary stasis, obstruction by elongated and pointed erythrocytes, and thrombosis. Eventually, tissue ischemia and mecrosis result with pathologic changes in the following sites.

Spleen
Initially the spleen becomes enlarged from congestion and engorgement with sickled cells. Eventually the sinuses are compressed and infarctions result. The functioning ells are gradually replaced with fibrotic tissue. The functioning cells are gradually replaced with fibrotic tissue, until eventually severe stages of the disease the spleen is decreased in size and totally replaced by a fibrous mass.

As a result of splenic infarction, the spleen loses its ability to filter bacteria and to promote the release of large numbers of phagocytic cells. Consequently children with sickle cell anemia are much more susceptible to infection.

Liver
The Liver is also altered in form and function. Liver failure and necrosis are the result of severe impairment of hepatic blood flow from anemia and capillary obstruction. The liver is usually enlarged as focal necorsis and subsequent scarring, cirrhosis eventually occurs.

Kidney
Abnormalities are probably the result of the same cycle of congestion of glomerula capillaries and tubular arterioles with sickle cells and hemosiderin. Tissue necrosis, and eventual scarring. The principal results of kidney ischemia are hematuria, inability to concentrate urine, enuresis, and occasionally nephritic syndrome.

Bones
The hyperplasia and congestion of the bone marrow results in osteoporosis, widening of the medullary spaces, and thinning of the cortices. As a result of the weakening of bone, especially in the lumbar and thoracic region, skeletal deformities, occur. From chronic hypoxia, the bone becomes susceptible to osteomyelitis, frequently from salmonella, Aseptic necrosis of the femoral head from chronic ischemia is an occasional problem.

Vaso-occlusive crises can result in a variety of skeletal problems. One of the more frequent is the hand-foot syndrome, which is caused by infarction of short tubular bones. It is characterized by pain and swelling of the short tubular bones. It is characterized by pain and swelling of the soft tissue over the hands and feet. It usually resolves spontaneously within a couple of weeks. Localized swelling over joints with arthralgia can occur from erythrostasis with sickle cells. Many of the skeletal abnormalities that are seen in thalassemia are also present in sickle cell anemia but are seen in thalassemia are also present in sickle cell anemia but are usually less prominent.

Central nervous system
Changes in the central nervous system are primarily vascular from the same cyclic reaction of stasis, thrombosis, and ischemia. Stroke or cerebro-vascular accident is a major complication and can result in permanent paralysis or death. Any number of neurological symptoms can herald a minor cerebral insult, such as headache, aphasia, weakness, convulsions, or visual disturbances. Loss of vision is usually the result of progressive retinopathy and retinal detachment.

Heart
Cardiac problems are mainly attributable to the stress of chronic anemia, which can eventually result in decompensation and failure. Myocardial infarctions may also occur from stasis and thrombosis.

Blood
With the formation of sickled erythrocytes, mechanical fragility is increased, thereby decreasing the red blood cell’s life span. Hemolysis occurs both during intra-vascular circulation and as a result of stagnation of sickled cells in the congenital spleen. Although, the body attempts to compensate through stimulated erythropoietic activity, as evidenced by a hyperplasic bone marrow, the rate of destruction exceeds the rate of production. It results in a normocytic, normochromic anemia. With increased hemolysis, hemosiderosis (increased storage of iron) is present in the liver, spleen, bone marrow, kidneys and lymph nodes.

Other signs and symptoms
In addition to the effects of sickling on various organ structures, the child with sickle cell anemia may have a variety of complaints, such as weakness, anorexia, joint, back, and abdominal pain; fever; and vomiting. Chronic leg ulcers are common in adolescents and adults and are thought to be the result of thrombosis and decreased peripheral circulation. Other generalized effects include growth, decreased fertility. If the child reaches adulthood, sexual development and adult height are usually achieved.