Anemia Comes In All Sizes Quiz | Diseases of Specific Systems

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1. Anemia with the largest red cell size usually occurs when certain vitamin deficiencies affect the maturation of red blood cells in the bone marrow. A starving homeless person is brought to an emergency room in a weakened condition. His red blood count is moderately reduced and the size of his red blood cells greatly enlarged. Deficiency of which of the following B vitamins is a likely cause of this large-cell (macrocytic) anemia?

Answer: Folic acid

Folic acid deficiency can and generally does develop on a nutritional basis. Typically, a nutritionally replete individual has a store of body folic acid that will last for three months if they are deprived of the vitamin. In the United States (and I suspected in the rest of the developed world), the commonest setting in which folic acid deficiency develops is in alcoholics whose food intake is extremely low. In those patients, it may coexist with iron deficiency.

Deficiency of folic acid alone is one of the two vitamin deficiencies that produce monster red blood cells. (The other vitamin deficiency causing this will be presented in the next question). Arrested development of the nuclei of maturing red blood cells is the reason for this. A red cell begins in the bone marrow as pronormoblast: a cell with a large nucleus, scant cytoplasm and no oxygen carrying hemoglobin. As a cell develops, its nucleus gradually shrinks and is finally extruded from the cell resulting in the release of the cell into the blood stream. At the same time the nucleus is maturing, hemoglobin is being synthesized and the volume of cytoplasm is expanding. When a maturing red cell lacks folic acid or the other vitamin discussed in the next question, the shrinkage and extrusion of the nucleus is delayed, and the developing cell has more time to synthesize hemoglobin and increase in size. You can view a pictorial chart showing red cell maturation at www.irvingcrowley.com/cls/maturation.htm.

Normal red blood cells have an MCV of about 80-100. Any type of anemia producing abnormally large cells is called "macrocytic". It is not uncommon for the MCV to be above 140 when deficiency of folic acid or the other vitamin results in anemia.

2. One relatively common cause of very large-celled anemia tends to run in families and may manifest in a newborn before the mother herself is affected. A pregnant woman who is not anemic gives birth to an anemic child. She takes thyroid medication for low thyroid, has intermittent circular bald spots in her hair, and blotchy white areas on her fingers and hands where the pigment seems to have been lost. The child's blood count is barely half of normal and the red blood cells are extremely large. Which vitamin deficiency is the most likely cause of this anemia?

Answer: Vitamin B12

Anemia related to either vitamin B12 or folic acid deficiency is termed "megaloblastic anemia". The same defect in nuclear maturation of developing red blood cells produces both conditions. But it can take over three years to deplete a person's stored vitamin B12 on a nutritional basis. This is the likely reason that vitamin B12 deficiency is usually the result of a medical condition that prevents B12 absorption rather than developing on a purely nutritional basis. Vitamin B12 is absorbed very efficiently in the end portion of a person's small intestine (distal ileum) after it becomes bound to a molecule produced in the stomach (intrinsic factor).

Disorders that interfere with the production or effectiveness of intrinsic factor are usually the result of the production of abnormal antibodies. Patients with these antibodies may also produce antibodies that affect the skin or endocrine organs resulting in the loss of pigmentation termed "vitiligo" or patches of hair loss termed "alopecia areata". Antibodies affecting the function of other endocrine glands can produce thyroid deficiency, ovarian failure or adrenal gland insufficiency. The susceptibility to forming these antibodies can be genetic and occur in family clusters. The child described above had not yet begun to produce his own intrinsic factor and developed B12 deficiency in utero because his mother was developing a deficiency that reduced her ability to transfer B12 across the placenta. The mother developed her own B12 deficiency within several months. Unlike folic acid deficiency, B12 deficiency can result in dementia and/or damage to peripheral nerves.

If the terminal portion of the ileum is removed surgically or affected by disease, intrinsic factor assisted B12 absorption will be impaired. Such patients can also develop B12 deficiency.

Although vitamin B12 deficiency can be treated by injections of vitamin B12, injections are usually not needed. Vitamin B12 absorption is less efficient when the intrinsic factor mechanism is disrupted, and it is generally impossible to provide enough dietary vitamin B12. However, a small amount of vitamin B12 is still absorbed, and the body's requirement for B12 can usually be met with sufficient doses of oral vitamin B12.

3. A 37-year-old well-nourished, heavily drinking man is found to have a very mild anemia with a mild increase in cell size. The laboratory reports that a blood smear has many red cells that look like targets. Liver function tests are moderately elevated. Which of the following is the most likely cause of this man's anemia?

Answer: Alcoholic liver disease

Alcoholic cirrhosis can be associated with a slightly large-celled (macrocytic) anemia with cells that look like targets (not surprisingly called "target cells"). Alcoholics are also subject to iron and folic acid deficiency. However, iron deficiency is characterized by a different cell size.

The mechanism that produces the macrocytosis is different for this disorder than for folic acid and B12 deficiency. In this case, cell membranes have grown too large for the cellular contents resulting in folding of the cell membranes producing a target appearance on stained blood smears.

4. A 23-year-old woman suffers from active systemic lupus erythematosis. She has a moderate anemia. Immune mediated breakdown of red blood cells within the circulatory system is suspected to be the cause. What is likely to be the result of a measurement of cell size?

Answer: Slightly elevated or normal

Breakdown of red cells is termed "hemolysis", and the corresponding anemia, hemolytic anemia. Young red blood cells are a bit larger than cells that have spend time in circulation. (Normal red blood cells survive more than 3 months.) Because the older blood cells are preferentially destroyed (hemolyzed) and new blood cells are being created at a higher rate, there are more young blood cells in patients with hemolytic anemia. This leads to a mild increase in the average cell size. However, this mild increase is not always large enough to increase the cell size to above the normal limit. The young blood cells can be recognized utilizing a special stain. From this it can be documented that the proportion of young red blood cells, called reticulocytes, is greater than normal. The reticulocyte count is both a more specific and a more sensitive indicator of an increased proportion of young red cells.

In systemic lupus, antibodies against a patient's own red blood cells attach to them and "sensitize" them to removal. This type of "autoimmune" anemia occurs in many other medical conditions, can be induced by medication or can occur as an isolated disease. Often in such patients, transfused blood cells will be destroyed as readily as the patient's own blood.

5. A physician has become aware that the gatekeeper of the doctor's parking lot has developed a husky voice and has been dressing warmer. He persuades the gatekeeper to obtain blood tests. The results of the blood count return first, and the gatekeeper is mildly anemic. The red blood cell size is slightly higher than normal. Which endocrine abnormality are additional tests likely to show?

Answer: Low thyroid

Low thyroid levels or hypothyroidism are likely to be discovered at an early stage of disease in the 21st century. Thyroid blood tests obtained because of mild anemia and elevated blood cell size (an elevated MCV) may still lead to the diagnosis in a patient with few symptoms.

However, there is a story of a gatekeeper from a San Francisco hospital in the mid 20th century developing a deepening voice, moving slower and dressing warmer over a period of years - all these being typical signs of hypothyroidism. According to the story, many years passed before these changes prompted a passing physician to advise thyroid testing for the gatekeeper.

6. A 23-year-old woman with heavy periods is found to have a mild anemia with moderate reduction of red cell size. What is the most likely cause of the woman's anemia?

Answer: Iron deficiency

Iron deficiency is the most common cause of a small-celled (microcytic) anemia. As was mentioned in the information section of question #1, developing red blood cells begin in the bone marrow with scant cytoplasm and contain no hemoglobin. As the cell develops, the cell nucleus shrinks and is extruded from the cell.

The non-nucleated cell is released from the bone marrow into the circulation. While this is happening, the volume of cytoplasm expands and hemoglobin is synthesized. When adequate iron is unavailable, the nucleus matures and is extruded leading to release of the blood cell into the circulation and the cessation of hemoglobin synthesis before there is adequate hemoglobin or the usual volume of cytoplasm. Because of this, the cells are much smaller than normal.

Other processes that interfere with adequate hemoglobin synthesis can produce microcytic anemia.

7. A 56-year-old man comes to his physician reporting fatigue, belly pain and headaches. The patient reports exposure to lead based paint. The patient's wife seems peculiarly unsympathetic to her husband's illness. The patient is found to have a small-celled (microcytic) anemia. A microscopic examination of the blood cells showed the red cells were stippled with tiny purple deposits. Iron levels were found to be normal. Which of the following are reasonable suspicions?

Answer: Both

Lead and arsenic poisoning can be considered in non-iron deficient microcytic anemia patients with a history of exposure. Purple stippling of red cells (basophilic stippling) may or may not be present.

8. An 18-year-old Asian woman is found to be mildly anemic with very small red blood cell size on a routine examination. The total number of red cells (RBC count) is normal despite a reduced hemoglobin level. Which of the following most commonly produces this situation?

Answer: Beta thalassemia trait

One of the most common genetic disorders worldwide, thalassemia is particularly common in Africa, Southern Asia and Southern Europe. The diagnosis can be suspected when the MCV (red cell size) divided by the RBC is unexpectedly low. It is confirmed with a test called hemoglobin electrophoresis. Genetic counseling is generally indicated for thalassemia patients.

9. A Laotian man has been told that he has an inherited form of anemia that causes very small blood cells and very mild anemia. He remembers that it is caused by a hemoglobin variant named with a single letter but does not remember the letter. Which of the following is most likely?

Answer: Hemoglobin E

Although seldom seen in the United States, worldwide, hemoglobin E is the second most common mutation of the beta chain of hemoglobin. Even people with two hemoglobin E genes have only a mild anemia. Unfortunately, a patient having one hemoglobin E and one thalassemia gene has a very severe anemia.

As is the case with thalassemia, patients have a very high red blood cell count relative to the degree of anemia present.

10. A trauma patient has suffered serious blood loss two hours before a blood count is obtained. What would one expect the size of the patient's blood cells to be?

Answer: Normal

If hemorrhage is acute, no change in cell size will have occurred. In fact, a specimen obtained soon enough after traumatic blood loss will still show normal blood counts. The drop in blood count occurs because blood volume is reconstituted with interstitial body fluids that contain no blood cells thus diluting the blood count.

Source: Author uglybird

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Anemia Comes In All Sizes Trivia Quiz

Anemia is often categorized by red cell size to assist in identification of the cause. See if you can determine the cause of anemia in the following examples.

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