Mike Clark, M.D.
Anemia is a decrease in the normal number of
red blood cells (RBCs) or less than the normal
quantity of hemoglobin in the blood. However, it
can include decreased oxygen-binding ability of
each hemoglobin molecule due to deformity or
lack in numerical development as in some other
types of hemoglobin deficiency.
Because anemia has multiple causes (etiologies) a
work-up must be performed to identify the
specific cause or in some cases causes.
Most commonly, people with anemia report nonspecific symptoms of a feeling of weakness, or
fatigue, general malaise and sometimes poor
concentration. They may also report shortness of
breath, dyspnea, on exertion. In very severe
anemia, the body may compensate for the lack of
oxygen carrying capability of the blood by
increasing cardiac output. The patient may have
symptoms related to this, such as palpitations,
angina (if preexisting heart disease is present),
intermittent claudication of the legs, and
symptoms of heart failure
• On examination, the signs exhibited may
include pallor (pale skin, mucosal linings and
nail beds) but this is not a reliable sign. There
may be signs of specific causes of anemia, e.g.,
koilonychia (in iron deficiency), jaundice
(when anemia results from abnormal break
down of red blood cells — in hemolytic
anemia), bone deformities (found in
thalassemia major) or leg ulcers (seen in sickle
cell disease).
History and Physical
• As a result of the non-specific signs and
symptoms a history and physical examination
is performed.
Two main causes of anemia
• Decreased Production of red blood cells
and/or hemoglobin
• Increased destruction of red blood cells
and/or hemoglobin
• Main test to distinguish the difference is the
reticulocyte count. Normal count is .5 – 2%
• Generally a low normal to low reticulocyte
count is caused by decreased production and
high one is caused by increased destruction
Decreased Production Causes
• Reduction in red blood cells or subnormal level of
• Inadequate production of red cells
• Insufficient raw materials
– Iron deficiency
– Vitamin B12 deficiency
– Folic acid deficiency
• Inability to deliver adequate red cells into circulation
due to marrow damage or destruction (aplastic
anemia), replacement of marrow by foreign or
abnormal cells
Increased Destruction Causes
• Excessive loss of red cells
– External blood loss (hemorrhage)
– Shortened survival of red cells in circulation
– Defective red cells: hereditary hemolytic
– Accelerated destruction of cells from
antibodies to red blood cell or by mechanical
trauma to circulating red cells
Diagnostic Evaluation of Anemia
• 1. History and physical examination
• 2. Complete blood count: to assess degree of anemia,
leukopenia, and thrombocytopenia
• 3. Blood smear: determine if normocytic, macrocytic,
or hypochromic microcytic
• 4. Reticulocyte count: assess rate of production of new
red cells
• 5. Lab tests: determine iron, B12, folic acid
• 6. Bone marrow study: study characteristic
abnormalities in marrow cells
• 7. Evaluation of blood loss from gastrointestinal tract to
localize site of bleeding
CBC indices regarding red blood cells
• Red Blood Cell Count - 4.8 – 5.4 million per microliter
• Hematocrit ( 30 – 60) generally 45% to 52% for men and
37% to 48% for women
• Hemoglobin ( 13 to 18 grams per deciliter for men and 12 to
16 for women)
• MCV (Mean Corpuscular Volume) - 80 to 100
• MCH (Mean Corpuscular Hemoglobin) –this is the average
amount of Hgb. in a the typical red blood cell. 27 to 32
• MCHC (Mean Corpuscular Hemoglobin Conc.) - the average
concentration of hemoglobin in a given volume of red cells
(32 – 36%)
• RDW – (Red Cell Distribution Width) – a measurement of
the variability of red cell size and shape. Higher numbers
indicate greater variation in size 11 - 15
Peripheral Smear
Look at size – 6 – 9 micromillimeters
Too small – microcytic
Too big – macrocytic
Normal size – normocytic
Look at color
Too pale – hypochromic
Too dark – hyperchromic
Normal color - normochromic
Anemia: Morphologic Classification
• Classification based on red cell appearance suggests the
etiology of the anemia:
– Normocytic anemia: normal size and appearance
– Macrocytic anemia: cells larger than normal
• Folic acid deficiency
• Vitamin B12 deficiency
– Microcytic anemia: cells smaller than normal
Anemia: Morphologic Classification
• Hypochromic anemia: reduced hemoglobin
• Hypochromic microcytic anemia: smaller than
normal and reduced hemoglobin content
Increased Destruction (Peripheral)
• Too extensive destruction after cells have
been formed and released from bone marrow
• Generally find a high reticulocyte count –
because more and more immature red blood
cells are being released from bone marrow to
compensate for the shortage in the peripheral
Possible Causes of Increased Destruction
• Acquired hemolytic anemia
– Normal red cells but unable to survive due to a
“hostile environment”
– Attacked and destroyed by antibodies
– Destruction of red cells by mechanical trauma
– Passing through enlarged spleen (splenomegaly)
– In contact with some part of artificial heart valve
Possible Causes of Increased Destruction
Hemolytic Anemia (Genetic)
• Hereditary hemolytic anemia
– Genetic abnormality prevent normal survival
• 1. Abnormal shape: hereditary spherocytosis
• 2. Abnormal hemoglobin: hemoglobin S (sickle
hemoglobin); hemoglobin C; both found predominantly
in persons of African descent
• 3. Defective hemoglobin synthesis: thalassemia minor
and major; globin chains are normal but synthesis is
defective (Greek and Italian ancestry)
• 4. Enzyme defects: glucose-6-phosphatase
dehydrogenase deficiency predisposes to episodes of
acute hemolysis
Distortion of red cells containing sickle hemoglobin when
incubated under reduced oxygen tension.
Distortion of red calls containing sickle hemoglobin when
incubated under reduced oxygen tension. Higher
magnification view.
Decreased Production
• Something is causing red blood cells not to be
produced fast enough
• Generally the reticulocyte count is low or low
normal. The reason is that if production is bad
–reticulocytes (immature red blood cells) also
cannot be produced adequately.
Classification of anemia based on the
“bone marrow factory” concept
Iron-Deficiency Anemia
• Characteristic laboratory profile
– Low serum ferritin and serum iron
– Higher than normal serum iron-binding protein
– Lower than normal percent iron saturation
• Treatment
– Primary focus: learn cause of anemia
– Direct treatment towards cause than symptoms
– Administer supplementary iron
• Examples
– Infant with a history of poor diet
– Adults: common cause is chronic blood loss from GIT (bleeding
ulcer or ulcerated colon carcinoma)
– Women: excessive menstrual blood loss
– Too-frequent blood donations
Normal red cells
Cells of hypochromic microcytic anemia
Vitamin B12 Deficiency Anemia
• Vitamin B12: meat, liver, and foods rich in animal protein
• Folic acid: green leafy vegetables and animal protein
– Both required for normal hematopoiesis and normal
maturation of many other types of cells
– Vitamin B12: for structural and functional integrity of nervous
system; deficiency may lead to neurologic disturbances
Vitamin B12 Deficiency Anemia
• Absence or deficiency of vitamin B12 or folic acid
– Abnormal red cell maturation or megaloblastic
erythropoiesis with formation of large cells called
– Mature red cells formed are larger than normal or
macrocytes; corresponding anemia is called macrocytic
– Abnormal development of white cell precursors and
megakaryocytes: leukopenia, thrombocytopenia
Most vitamin B12 deficiency symptoms are
actually folate deficiency symptoms, since
they include all the effects of pernicious
anemia and megaloblastosis, which are due to
poor synthesis of DNA when the body does
not have a proper supply of folic acid for the
production of thymine. When sufficient folic
acid is available, all known B12 related
deficiency syndromes normalize, save those
narrowly connected with the vitamin B12dependent enzymes
The total amount of vitamin B12 stored in body is
about 2–5 mg in adults. Around 50% of this is
stored in the liver. Approximately 0.1% of this
is lost per day by secretions into the gut as not
all these secretions are reabsorbed. Bile is the
main form of B12 excretion, however, most of
the B12 that is secreted in the bile is recycled
via enterohepatic circulation
Macrocytic Cells
Pernicious Anemia
• Lack of intrinsic factor results in macrocytic anemia
– Vitamin B12 in food combines with intrinsic factor in gastric
– Vitamin B12 intrinsic factor complex absorbed in ileum
• Causes
– Gastric mucosal atrophy; also causes lack of secretion of acid
and digestive enzymes
– Gastric resection and bypass: vitamin B12 not absorbed
– Distal bowel resection or disease: impaired absorption of
vitamin B12 intrinsic factor complex
– May develop among middle-aged and elderly
– Associated with autoantibodies against gastric mucosal cells
and intrinsic factor
• Longitudinal layer
• Circular layer
• Oblique layer
Rugae of
Pyloric sphincter
(valve) at pylorus
Figure 23.14a
Gastric pits
Surface epithelium
(mucous cells)
Mucous neck cells
Parietal cell
Chief cell
Enteroendocrine cell
(b) Enlarged view of gastric pits and gastric glands
Figure 23.15b
Folic Acid Deficiency Anemia
• Relatively common
• The body has very limited stores, which rapidly
become depleted if not replenished continually
• Pathogenesis
– Inadequate diet: encountered frequently in chronic
– Poor absorption caused by intestinal disease
– Occasionally occurs in pregnancy with increased demand
for folic acid
• Secondary polycythemia
– Reduced arterial O2 saturation leads to compensatory
increase in red blood cells (increased erythropoietin
– Emphysema, pulmonary fibrosis, congenital heart disease;
increased erythropoietin production by renal tumor
• Primary/Polycythemia vera
– Manifestation of diffuse marrow hyperplasia of unknown
– Overproduction of red cells, white cells, and platelets
– Some cases evolve into granulocytic leukemia
• Complications
– Clot formation due to increased blood viscosity and platelet
• Treatment
– Primary polycythemia: treated by drugs that suppress
marrow function
– Secondary polycythemia: periodic removal of excess blood
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