Lecture #10: Friday, February 6, 1998


Textbook Assignment: Read "Erythrocyte Disorders" pp170-178 and "Leukocyte Disorders" pp178-183.



Normal Erythropoiesis in bone marrow enter blood by marrow sinusoids.
Mature red blood cell maintains its membrane, its hemoglobin structure and anaerobic energy metabolism.
Erythrocytes last about 120 days in bloodstream--removed by macrophages in spleen, liver and marrow (about 1% per day) (lose about 173 million per minute).
RBC is about 5 billion per milliliter.
The production-destruction balance so that the adult maintains about 5 liters of blood.
The hematocrit is typically about 42-45%



Anemia (an: without, negative; haima: blood) is a hemoglobin level below its normal range of 14-18 g/dl for males and 12-16 g/dl for females. CBI#10-2

Symptoms include pallor (paleness), weakness, lethargy and exercise intolerance.
Other tests to help classify anemia:
Red blood cell count (RBC).
Mean corpuscular volume (MCV): normocytic, macrocytic, and microcytic.
Mean corpuscular hemoglobin concentration (MCHC): normochromic, hyperchromic and hypochromic.
Reticulocyte count (1:100), helps assess erythropoiesis rate/bone marrow adequacy (need about 3 days for maturity).


Anemia Based Upon Reduced Production Rate

APLASTIC ANEMIA Pancytopenia: all formed elements are deficient. Occurs with marrow suppressants such as used in chemotherapy, radiation or drug reactions. All normal formed element precursors are greatly reduced. CBI#10-3

IRON DEFICIENCY ANEMIA Most iron is recycled although about 1-2 mg are lost daily in the urine, faces, and skin (perspiration, sloughing); menstrual blood iron loss amounts to another 1 mg/day. Iron from animal products (meat, liver, eggs) is more likely in the "heme" form, a more easily absorbed form. First absorbed iron is stored in the intestinal epithelium, liver and in macrophages widely dispersed throughout the body. Often the blood loss component of iron deficiency anemia is from GI bleeding. Erythrocytes are microcytic and hypochromic. Do you see how the red blood cell count may be "normal" and yet there is anemia? CBI#10-4

VITAMIN B12 DEFICIENCY ANEMIA We need 1 microgram daily and the body normally stores 2-5 mg. Vitamin B12 is also known as cobalamin and is required for normal DNA synthesis; when lacking, pancytopenia results. But with no impairment of RNA or protein synthesis, growth proceeds causing megaloblastic anemia or more commonly pernicious anemia. These abnormally large erythrocytes (macrocytic cells) are removed more rapidly from circulation than normocytic cells. Most frequently, absorption is inadequate because intrinsic factor, a glycoprotein normally produced by parietal cells of the gastric mucosa, is insufficient. The ileum absorbing epithelial cells contain receptors, not for cobalamin alone but the combined cobalamin-intrinsic factor. It is transported in the blood to the bone marrow as trans-cobalamin. Thus, the basis is often atrophic gastritis, an autoimmune attack on both the parietal cells and intrinsic factor. This vitamin is also needed for normal myelin formation and so pernicious anemia is often associated with neuropathy as well. CBI#10-5

FOLIC ACID DEFICIENCY ANEMIA Usually associated with poor diets so is more common in poor, elderly, alcoholics and in cancer patients. It is a megaloblastic anemia. Many forms of chemotherapy produce a folic acid deficiency. CBI#10-6

CHRONIC DISEASE-BASED ANEMIAS Often associated with long term infections and chronic inflammations. More erythrocytes may be produced so reticulocyte count often rises. Also, erythropoietin may be not be produced in sufficient quantities to maintain equilibrium.


Anemia Based Upon Excessive Blood Loss Rate

Intrinsic Forms of Hemolytic Anemia

Produced by excessive loss of erythrocytes, hemolysis.

SICKLE CELL ANEMIA The erythrocytes contain abnormal hemoglobin (HbS rather than the normal HbA) which polymerizes when hypoxic. This changes the shape of the erythrocyte to a crescent shape which aggregates with other erythrocytes. They have to be removed by macrophages and the normal life span is 20 rather than 120 days. There is an increased reticulocyte count. Individuals with the sickle cell trait are generally unaffected except in extreme hypoxia. Blacks of African origin are the population most affected. Sickle cell anemia is caused by an autosomal recessive trait. Symptoms include splenomegaly, leg ulcers, and abdominal pain. CBI#10-7

THALASSEMIAS are a group of genetic disorders that involve hemoglobin. The most common is beta-thalassemia due to a defect in the production of beta-globin. The membrane is also defective causing an abnormally rapid removal rate. The thalassemias are more common in individuals who are of Mediterranean origin. CBI#10-8


Intrinsic Forms of Hemolytic Anemia CBI#10-9

TOXIC FORMS include plumbism. Here, lead salts attach to erythrocyte membranes making it more vulnerable to lysis or removal from circulation. Often we see a gingival "lead line" in plumbism.

BLOOD INCOMPATIBILITIES These forms include immune hemolysis such as from D or Rh antigens (maternal-fetal incompatibilities) or the ABO antigens (transfusion-related incompatibilities).

AUTOIMMUNE HEMOLYTIC ANEMIAS may be associated with tumors, infections and inflammatory conditions.

MECHANICAL HEMOLYSIS may be associated with artificial cardiac valves.


Polycythemia CBI#10-10

Polycythemia is an over-production of erythrocytes and blood plethora (may be 2-3X; RBC 6-10 million/mm3). Often characterized by liver enlargement and excessive thrombosis (elevated platelet levels). Also presents general circulation problems.

Secondary polycythemia such as from excessive erythropoietin, or subsequent to high-altitude training or to carbon monoxide poisoning.

Primary polycythemia (polycythemia vera) may be due to a benign tumor of the bone marrow.



Normal leukocyte count is around 10,000/mm3 with normal neutrophil count 1800-7200/mm3.

Leukopenia or leukocytosis (if not neoplastic) and leukemia (if neoplastic). Also consider lymphoma.


Leukopenia CBI#10-12

There are frequent infections when below 500/mm3). Usually neutropenia (below 1800mm3) but other leukocytes may also be affected. Extreme neutropenia is called agranulocytosis (e.g., 200-300/mm3). Most neutropenia is subsequent to antitumor therapy (chemotherapy or radiation therapy). Other causes may be specific infections, folic acid or vitamin B12 deficiencies, or genetic defects.


Leukocytosis CBI#10-13

POLYMORPHONUCLEAR LEUKOCYTOSIS (neutrophilia) may be subsequent to acute inflammations.

BASOPHILIC LEUKOCYTOSIS may be due to myeloproliferative disorders or lung tumors.

EOSINOPHILIA may be due to allergic disorders such as hay fever, asthma, or drug reactions. It may also be due to parasitic and fungal infections.

MONOCYTOSIS may be due to collagen vascular diseases such as systemic lupus erythematosus and rheumatoid arthritis. It may also be due to intestinal inflammations such as in Crohn's disease or ulcerative colitis. Or it may be due to chronic infections such as tuberculosis.

LYMPHOCYTOSIS may be due to acute viral infections or even to chronic infections such as tuberculosis.



Basis is primary lymphatic tumors in the bone marrow; excessive proliferation in the bone marrow. Leukocytes in the blood show varying degrees of differentiation. Cells lose their ability to mature while maintaining their ability to divide. The bone marrow often fills with these cells crowding out other cell lines, e.g., erythropoiesis. CBI#10-14

The growing tumor may invade the bone that houses it resulting in extreme bone pain. Metastasis to the spleen, liver, meninges and lymph nodes often occurs. Here, secondary growth, may cause splenomegaly, hepatomegaly, meningeal disorders and lymphadenopathy, respectively. The various leukemias are classified according to their pattern of development: acute and chronic and also myeloblastic (granulocytic) or lymphoblastic (lymphocytic) forms. CBI#10-15


Acute Forms of Leukemia CBI#10-16

ACUTE LYMPHOCYTIC LEUKEMIA is most common in children and adolescents; the most common malignancy affecting children. Anemia is common as are reduced ability to clot blood (thrombocytopenia). These children are susceptible to infection and often have cervical lymphadenopathy. Treatment is usually aggressive chemotherapy and bone marrow transplants.

ACUTE MYELOBLASTIC LEUKEMIA also affects adolescents and young adults with less successful treatments available.


Chronic Forms of Leukemia CBI#10-17

CHRONIC LYMPHOCYTIC LEUKEMIA (B-cells) is the most common form of leukemia and is typically seen in older adults (over 50). Onset is gradual and symptoms are fatigue, weight loss, and anorexia. Lymphocyte counts may be as high as 200K/mm3.

CHRONIC MYELOBLASTIC LEUKEMIA manifest as granulocytosis. Liver and spleen infiltration is common with subsequent hepatomegaly and splenomegaly. Many of these patients have Philadelphia chromosome, damaged chromosome #22.



These are solid malignant tumors arising in cells of lymphoid tissue, lymphocytes and their precursors. They invade or compress normal tissues/organs. Often begin with painless enlargement of lymph nodes followed by hepatomegaly or splenomegaly There is a generalized loss of lymphoid function due to lack of differentiation. Symptoms are anemia and lymphadenopathy.

BURKITT'S LYMPHOMA (Denis Burkitt: English surgeon in Uganda) more common in Central Africa. Manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Caused by the Epstein-Barr virus, a herpesvirus. The affected lymphocytes are small non-cleaved cells. CBI#10-18

HODGKIN'S LYMPHOMA (Hodgkin's Disease) occurs in young adults. Often manifest as a single, painless, cervical lymph node followed by spread to adjacent nodes until it becomes widely disbursed. One subtype of based upon the abnormal proliferation of cells called Reed-Sternberg cells. These are large multinucleated cells. CBI#10-19

What You Need to Understand for Exam II