Chapter 10, Problem 2LO

Summary Introduction

To describe: The pathophysiology, etiology, manifestations, diagnostic tests, and treatment for iron-deficiency, pernicious, aplastic, sickle cell, and thalassemia with their comparisons.

Concept introduction: Blood is a fluid connective tissue that carries oxygen, glucose, and nutrients throughout the body. Anemia is a condition in which the total number of red blood cells in the blood circulation is reduced, or there is a decrease in the quality or quantity of hemoglobin. Different types of anemia are different in their causes and treatments.

Explanation of Solution

Iron-deficiency anemia:

Pathophysiology: Iron-deficiency anemia (IDA) is the most common type of anemia that occurs due to lack of iron. Inadequate iron impairs the synthesis of hemoglobin and thus reduces the amount of oxygen transported through the blood. Due to depleted levels of hemoglobin, iron ions that are stored in the bone marrow are also used to maintain an adequate hemoglobin production, and fewer iron ions are recycled. A decreased hemoglobin production leads to insufficient iron supply and restricts the synthesis of hemoglobin. Thus, it causes iron-deficiency anemia.

Etiology: Deficit in iron can occur for several reasons as follows:

1. 1. Chronic blood loss within the body from a hiatal hernia, a peptic ulcer, or a colon polyp can cause IDA. Even a small amount of continuous blood loss can lead to IDA. This is because this condition can lead to a decrease in the number of red blood cells, which in turn depletes hemoglobin from the body.
2. 2. The acid-producing cells in the stomach called parietal cells release intrinsic factor (IF). IF binds to Vitamin B₁₂ and prevent the destruction of this vitamin from hydrochloric acid (secreted by the parietal cell). Vitamin B₁₂ is important for the production of red blood cells. A decrease in the number of red blood cells can lead to IDA.
3. 3. Inadequate iron intake can also cause IDA.
4. 4. Severe liver disease also affects the absorption and storage of iron.

Manifestations: The manifestations of IDA are as follows:

1. 1. Delayed healing
2. 2. Brittle hairs
3. 3. Concave and ridged nails
4. 4. Stomatitis and glossitis
5. 5. Heart palpitations
6. 6. Dyspnea
7. 7. Tachycardia
8. 8. Irritability
9. 9. Fatigue
10. 10. Cold intolerance
11. 11. Lethargy
12. 12. Shortness of breath
13. 13. Pale skin
14. 14. Menstrual irregularities

Diagnostic tests: Laboratory tests indicate low counts of hemoglobin and hematocrit. The microscopic examination shows that erythrocytes are appeared as hypochromic and macrocytic.

Treatment: The treatment of IDA depends on its cause. Iron-rich foods or iron supplements in the form of absorbable may be administered.

Pernicious anemia:

Pathophysiology: Pernicious anemia (PA) is the most common type of macrocytic anemia that is caused due to the deficit of Vitamin B₁₂ (cyanocobalamin). Pernicious means highly destructive or injurious. Vitamin B₁₂ plays an important role in the formation of red blood cells (RBC). This is because a deficit in this vitamin can inhibit the thymidylate and purine synthesis; impair the synthesis of deoxyribonucleic acid and apoptosis of erythroblast during the process of erythropoiesis. As red blood cells are the carriers of the hemoglobin (gives red color to the RBC and supply oxygen throughout the body), a decrease in the count of RBC also decreases the amount of hemoglobin.

Etiology:

1. 1. Malabsorption of Vitamin B₁₂ can cause pernicious anemia.
2. 2. It may develop from chronic gastric.

Manifestations: The manifestations of pernicious anemia are as follows:

1. 1. Enlarged tongue
2. 2. Nausea and vomiting
3. 3. Paresthesia
4. 4. Loss of muscle coordination
5. 5. Chest pain
6. 6. Weakness
7. 7. Headaches

Diagnostic tests: The microscopic observation shows macrocytic or megaloblatsic appearance of erythrocytes. The counts of erythrocytes are reduced in the peripheral blood. Serum Vitamin B₁₂ level is below normal. Granulocytes are hypersegmented with decreased number. The presence of gastric atrophy is confirmed by the presence of hypochlorhydria or achlorhydria.

Treatment: The treatments for the pernicious anemia are as follows:

1. 1. Oral supplements are recommended.
2. 2. Vitamin B₁₂ injection as well as replacement therapy is used to treat pernicious anemia.

Aplastic anemia:

Pathophysiology: Aplastic anemia is a condition that occurs due to damage of the bone marrow and results in the loss of stem cells and pancytopenia. This decreases the count of leukocytes, erythrocytes, and platelets in the blood, that is, all the cells differentiate from the bone marrow.

Etiology: Depending upon the cause, aplastic anemia may be permanent or temporary. The etiology of this condition is as follows:

1. 1. It may be caused by viruses, particularly by hepatitis C.
2. 2. Systemic lupus erythematosus (SLE) may affect the bone marrow.
3. 3. The bone may be affected by myelodysplastic syndrome.
4. 4. Exposure to toxic chemicals, such as insecticides, and pesticide and industrial chemicals, such as benzene may damage bone marrow and cause aplastic anemia.

Manifestations: The manifestations of aplastic anemia are as follows:

1. 1. Weakness
2. 2. Dyspnea
3. 3. Pale skin
4. 4. Skin rash
5. 5. Frequent infection
6. 6. Excessive bleeding
7. 7. Easy bruising
8. 8. Tachycardia
9. 9. Thrombocytopenia

Diagnostic tests: Red blood cells are normal in appearance. A bone marrow test is required to confirm. Blood counts indicate deficit of all three cellular components, such as red blood cells, white blood cells, and platelets.

Treatment: The treatments for the aplastic anemia are as follows:

1. 1. Bone transplantation is required to recover bone marrow.
2. 2. Blood transfusion may be required if levels of stem cells are very low.
3. 3. Chemotherapy and radiation are also used before the transplantations of bone marrow.
4. 4. Some medication, such as cyclosporine, and anti-theymocyte globulin are used to suppress the function of immune cells that damage the bone marrow.

Sickle-cell anemia:

Pathophysiology: Sickle cell anemia is a genetic condition of the red blood cells, wherein the shape of the red blood cells become sickle shaped. They cannot carry adequate oxygen to different parts of the body. It is caused due to the mutation in the gene, which is necessary for the production of hemoglobin. Sickle cell anemia leads to the formation of hemoglobin S (abnormal hemoglobin), wherein an amino acid in the pair of beta-globin chains changed into valine from the normal glutamic acid. This altered hemoglobin becomes deoxygenated, crystallizes, and changes the shape of red blood cells into sickle shape.

Etiology: Sickle cell anemia is caused by single point mutation in hemoglobin-beta gene (HBB) that is present in chromosome 11. The muted gene passes from one generation to next generation in a pattern of inheritance (autosomal recessive inheritance).

Manifestations: Sickle cell anemia shows signs from the early conditions that are as follows:

• Frequent infection
• Pain in chest, arms, or legs
• Jaundice
• Fussiness
• Fatigue
• Paleness
• Chest pain
• Rapid heart rate
• Splenomegaly
• Recurrent infection
• Vascular occlusion
• Congestive heart failure

Diagnostic tests: Hemoglobin electrophoresis helps to detect the carriers of the defective gene.

Treatment: The treatments for the sickle cell anemia are as follows:

Hydroxyurea is used to reduce the frequency of crisis and to prolong the life span.

Dietary supplements with folic acid are recommended.

Bone marrow transplantation is effective.

Thalassemia:

Pathophysiology: Thalassemia is an inherited blood disorder that is characterized by abnormal form of hemoglobin. These types of anemia result when one or more genes are variant or missing that are responsible for the synthesis of hemoglobin. Hemoglobin is normally made up of four globin chains, namely two α-chains and two β-chains. The abnormality in gene for hemoglobin interferes with the production of globin chains. As a result, the accumulation of other available chains damages the red blood cells and causes thalassemia.

Etiology: Thalassemia alpha is caused due to mutation in the α-chains and is more commonly found in those of Chinese, Indian, and southeast Asian descent. Thalassemia beta is caused due to mutation in the β-chains and is more commonly found in people from Mediterranean countries such as Italy and Greece.

Manifestations: The manifestations of thalassemia are as follows:

1. 1. Fatigue
2. 2. Weakness
3. 3. Pale skin
4. 4. Facial bone deformities
5. 5. Dark urine
6. 6. Abdominal swelling
7. 7. Slow growth and development
8. 8. Heart failure

Diagnostic tests: The blood tests indicate elevated levels of erythropoietin and low levels of hemoglobin (hypochromic). An iron overload often exists. Prenatal diagnosis can also be done by chorionic villus assay.

Treatment: The treatments for thalassemia are as follows:

1. 1. Blood transfusions are the only treatment to treat thalassemia.
2. 2. Folate acids administration is also recommended.
3. 3. In some children, bone marrow transplants have been used.

The pathophysiology, etiology, manifestations, diagnostic tests, and treatment for iron-deficiency, pernicious, aplastic, sickle cell, and thalassemia are compared in the table below:

Criteria	Iron-deficiency anemia	Pernicious anemia	Aplastic anemia	Sickle cell anemia	Thalassemia
Pathophysiology	A decreased hemoglobin production leads to insufficient iron supply and restricts the synthesis of hemoglobin.	A deficit in this vitamin can inhibit the formation of red blood cells.	It occurs due to damage of the bone marrow and results in loss of stem cells and pancytopenia that decrease the counts of blood cells.	The hemoglobin S becomes deoxygenated, crystallizes, and changes the shape of red blood cells into sickle shape.	It results when one or more genes are variant or missing that are responsible for the synthesis of hemoglobin.
Etiology	Inadequate iron intake Chronic blood loss Sever liver disease	Malabsorption of Vitamin B12 Chronic gastric	Myelodysplastic syndrome Systemic lupus erythematosus	Single point mutation in hemoglobin-beta gene (HBB) that present in chromosome 11.	Mutation in the α-chains and β-chain

Manifestations	Pale skin Delayed healing Tachycardia Dyspnea Shortness of breath Fatigue	Enlarged tongue Loss of muscle coordination Chest pain Weakness	Pale skin Excessive bleeding Tachycardia Dyspnea	Paleness Vascular occlusion Chest pain Fatigue	Pale skin Facial bone deformities Dark urine Heart failure fatigue
Diagnostic tests	Low counts of hemoglobin and hematocrit	Serum Vitamin B12 level is below normal	Blood counts indicate deficit of all three cellular components	Hemoglobin electrophoresis helps to detect the carriers of the defective gene	Elevated levels of erythropoietin and low levels of hemoglobin
Treatments	Iron-rich foods or iron supplements in the form of absorbable may be administered.	Vitamin B12 injection as well as replacement therapy is used to treat pernicious anemia.	Bone transplantation and blood transfusion	Dietary supplements with folic acid and bone marrow transplantation	Blood transformation and folate acids administration