NSC 834 – Advanced Pathophysiology
Mary DeLetter, PhD, RN
Associate Professor
Dept. of Baccalaureate and Graduate Nursing
Eastern Kentucky University
Hematology Disorders:
Altered Erythrocyte Function - Macrocytic or Microcytic Anemias
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This is Dr. Mary DeLetter. In this presentation, I will discuss Erythrocytic Hematologic
Alterations producing macrocytic or microcytic anemias.
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Anemia is defined as a decrease in the total number of circulating erythrocytes or a
decrease in quality or quantity of hemoglobin. It is generally caused by one of three
conditions, which can occur individually or in combination. These include
 Impaired erythrocyte production
 Increased erythrocyte destruction, or
 Blood loss
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Anemias are classified either by their causes or by changes in the size and shape of the
RBC or the hemoglobin content.
Descriptive terms that end in the suffix “–cytic” refer to changes in cell size; terms that
end in “-chromic” refer to changes in hemoglobin content.
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This table, also found in your textbook, summarizes the terminologies of common
anemias according to cell size and hemoglobin content.
This diagram is a classification of anemia according to the cause. Some of these will be
reviewed in this presentation. The diagram may be a helpful referral source as I present
different types of anemias, or may be helpful to you later in nurse practitioner courses or
your practice.
Hematology Disorders: Altered Erythrocyte Function
Macrocytic or Microcytic Anemias
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The overall effect of anemia is a reduction in the oxygen carrying capacity of the blood,
producing hypoxia. In the hypoxic state, the oxygen level reaching the cells is
insufficient, resulting in tissue injury.
In a relatively healthy individual, the body is able to compensate for the reduced number
of RBC or the decreased quality or quantity of hemoglobin. These compensatory
mechanisms include:
 Increased preload (LVEDV) (volume of blood in the ventricle just prior to
systole)
 Increased heartrate
 Increased stroke volume
 Decreased afterload (mean arterial pressure) (the pressure against which the
ventricle ejects blood)
All four of these compensatory mechanisms will increase cardiac output, thus allowing the
body to maintain adequate tissue oxygenation and avoid the hypoxic state.
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In this diagram, you can see the physiologic path that results when there is a loss of red
blood cells from the body.
The anemic condition causes hypoxemia, or a reduced oxygen carrying capacity of the
blood. This produces tissue hypoxia, affecting the muscles, general energy levels, skin,
breathing capacity, CNS, liver, heart, and kidneys.
The body responds to the hypoxemia and hypoxia with a cardiovascular compensation. In
addition, renal and other metabolic compensation also help to maintain sufficient tissue
oxygenation.
When the compensatory mechanisms are insufficient or fail, the result is tissue ischemia
and cardiac dysfunction.
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Clinical manifestations of anemia are evident in multiple body systems. Most
concerning are the changes in vital organs. Patients also have peripheral changes to their
musculoskeletal and integumentary systems.
Patients with anemia often complain of being lethargic, cold and may have weight loss.
Macrocytic, or Megaloblastic anemias are a group of anemias of varying etiologies,
marked by larger than normal red cells.
Macrocytic anemias are usually caused by vitamin deficiencies, such as vitamin B-12 or
Folate. These deficiencies result in a defective erythrocyte precursor DNA synthesis that
causes unusually large stem cells in the bone marrow.
The large stem cells produce large erythrocytes that are missing the normally pale center.
The patient is normochromic, or has normal hemoglobin.
Hematology Disorders: Altered Erythrocyte Function
Macrocytic or Microcytic Anemias
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Pernicious anemia is the most common megaloblastic anemia and results from a B12
deficiency. Vit B12 cannot be manufactured in the body, so must be ingested in the diet.
Pernicious anemia is common in persons over 50;
The pathophysiology of pernicious anemia is the absence of Intrinsic Factor, normally
found in the gastric parietal cells, and responsible for transporting dietary B12 across the
gastric mucosa.
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When the IF is lacking, there is nothing to which the B12 can bind, and there is a decrease
in absorption of B12 from the small intestine. The lack of B12 causes a defective DNA
synthesis in the erythrocytes, producing the oversized red blood cells.
There are four common causes of pernicious anemia, all related to integrity of the
gastric mucosa.
Chronic atrophic gastritis is a Type A autoimmune condition which causes chronic
inflammation of the gastric mucosa. It can be genetic or occur as a co-morbid condition
with other endocrine autoimmune disorders.
Any habit which damages the gastric mucosa can also produce pernicious anemia,
including alcohol and caffeine ingestion, and smoking.
Loss of the gastric lining, such as a partial or full Gastrectomy, or gastritis from the Hpylori bacteria can also decrease the number and quality of available parietal cells in the
gastric mucosa.
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Vit B12 is stored and slowly released from the liver, so the onset of pernicious anemia is
often insidious. Is may be so insidious that patients are quite severe at the time of their
diagnosis.
The pathophysiology of a Folate-deficient anemia is a decrease in RBC production and
maturation that occurs from the altered DNA synthesis found in megaloblastic cells with
clumped nuclear chromatin (color) and apoptosis of erthryrocytes during the late stage of
erythropoesis.
Folate deficiency in a childbearing age or pregnant females can lead to neural tube
defects. In the general population, Folate deficiency increases the amount of circulating
homocysteine, a theorized, but not well established cause of atherosclerosis, and may lead
to colorectal cancers.
One of the unique consequences of Folate deficiency, and consequently a common feature
of Folate-deficiency anemia, of is ulcerations of mouth, lips, and buccal mucosa.
Microcytic anemias are characterized by small erythrocytes, and reduce the hemoglobin.
Microcytic anemias are caused by disorders of iron metabolism (causing iron-deficiency
anemia) or disorders affecting the synthesis of hemoglobin components. These include
the heme, or pigment component, is a member of the organic compound group called
porphyrins. The globin is the protein component of hemoglobin.
Hematology Disorders: Altered Erythrocyte Function
Macrocytic or Microcytic Anemias
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Iron-deficiency anemia is the most common anemia world-wide.
Iron is not excreted from the body, so the only methods of iron depletion are dietary
deficiency, blood loss or impaired absorption from the duodenum or upper jejunum.

Inadequate dietary intake of iron may occur in those who have increased iron
requirements for growth, such as infants, small children, adolescents, or pregnant
women

In chronic bleeding, iron is contained in the hemoglobin that is lost. Common
situations include
o GI bleeding that is either pathologic or medication-induced from chronic
use of ASA products or NSAIDS.
o Menorrhagia, which is heavy menstrual bleeding

GI absorption of iron is inhibited by conditions which result in a reduction of
gastric acid, such as long-term use of proton pump inhibitors, like Omeprazole or
the OTC Prilosec. These drugs block the production of gastric acid, which is
necessary for iron availability and uptake in the GI tract.
Since lead competes with iron in the heme, lead poisoning will often by accompanied
severely depleted iron levels.
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Iron-deficiency anemia is develops from one of two pathophysiologic conditions. The
first is depletion of iron stores, which occurs from either inadequate dietary iron intake or
from excessive chronic blood loss. The result is decreased iron availability in the bone
marrow and deceased hemoglobin synthesis.
The second cause is any type of metabolic dysfunction that results in insufficient iron
delivery to the bone marrow or impaired use of iron by the bone marrow, both of which
can decrease hemoglobin synthesis.
Hematology Disorders: Altered Erythrocyte Function
Macrocytic or Microcytic Anemias
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Quite simply, iron-deficiency anemia occurs when the body’s need for iron exceeds the
amount of available iron. This is an insidious process, and occurs in three overlapping
stages.
In Stage 1, iron stored in the tissues, called ferritin, is being used in place of circulating
iron. There is a drop in the serum ferritin level, which is the measure of stored iron. At this
early stage, erythropoeisis, or the production of red blood cells in the red bone marrow, is
normal. The newly released ferritin is incorporated into the red blood cells. Hemoglobin
production, which is the coordinated production of both the heme and the globin protein,
remains normal.
In Stage 2, ferritin is depleted, reducing the amount of iron that is being transported to the
bone marrow. With the depletion of both iron and ferritin, there is no circulating iron, so
both the serum ferritin level and serum iron level will be low. Erythropoeisis continues,
but the RBCs that are being produced are iron-deficient. In this stage, there is an initial
decrease in hemoglobin production.
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In Stage 3, many iron-deficient red blood cells are released from the bone marrow to
replace mature erythrocytes in the circulation. The iron-deficient RBCs outnumber the
iron-rich RBCs, while both ferritin and circulating iron are severely depleted. The
erythrocytes being produced in the red bone marrow are hypochromic (low in pigment)
and small (microcytic). The poor quality heme does not bind as well with the protein
globin, so hemoglobin production is more significantly reduced. Patients begin to show
signs of the iron-deficiency anemia.
Early signs and symptoms of iron-deficient anemia are similar to other anemias and
include fatigue, weakness, and shortness of breath.
Progressive signs that are unique to the iron deficiency include epithelial tissue changes,
such as brittle nails, Glossitis, and dysphagia secondary to hyposalivation and the
development of a thin membrane across the esophageal lumen, called an esophageal web.
This concludes the presentation on Erythrocytic Hematologic Alterations producing
macrocytic or microcytic anemias.