Anemia – Pathophysiologic Consequences and Clinical Investigation

Definition of Anemia

• any condition resulting from a significant decrease in the total body erythrocyte mass
• working definition – hemoglobin < 12 g/dL or hematocrit < 37 cL/L
• usually results from the body’s compensation to maintain blood volume in the response to rbc loss.

Physiologic Compensation for the decreased RBC mass

• Remember that the tissue requirement for O₂ cannot decrease to compensate for the decreased O₂ capacity (anemia)
• The overall body oxidative metabolism increases in response to anemia because of the energy requirement of the compensatory activities

The Blood

• In average 70L human – 5L of blood (7% by volume)
• Of this 5L of blood

Ø  45% cells (erythrocytes, Leukocytes/WBCs, Platelets)

-        98.1% erythrocytes

-        1.6% leukocytes

¨      of these leukocytes,

q  40-70% PMNs

q  20-40% lymphocytes

q  2-10% monocytes

q  1-6% eosinophils

q  <1% Basophils

-        0.3% platelets

Ø  55% plasma

-        91.5% H₂O

-        7% solids (majority of which is Albumin)

-        1.5% salts, lipids, enzymes, vitamins

Decreased Hemoglobin O₂ affinity

• the tissues strip the O₂ off of the anemic blood which produces an increased amount of deoxyhemoglobin in the rbc
• this stimulates the production of 2,3-DPG which shifts the hemoglobin-O₂ dissociation curve to the right which allows the tissues to take the O₂ more easily.

Redistribution of blood flow

• selective vasoconstriction of BVs in non-vital areas allows for more flow into critical areas
• Main donors – skin and kidneys
• Remember pallor is a cardinal sign of anemia.

Increased CO

• the Cardiac output can rise w/o a rise in BP because there is decreased peripheral vascular resistance and decreased blood viscosity.
• Generally, anemia has to be severe (hemoglobin < 7 g/dL) before CO rises

Clinical signs and symptoms of anemia

• The severity of the clinical symptoms bears less relationship to the severity of the anemia than to the length of time over which the condition develops.
• Symptoms – generally what is expected when the tissues have a lack of O₂

Ø  dyspnea on exertion

Ø  easy fatigability

Ø  fainting

Ø  lightheadedness

Ø  tinnitus

Ø  headache

• Pre-existing CV pathologic conditions are exacerbated by the anemia

Ø  angina pectoris

Ø  intermittent claudication

Ø  night muscle cramps

• Clinical signs of a slowly developed anemia

Ø  pallor

Ø  tachycardia

Ø  systolic ejection murmur

• Rapidly developing anemia (above +…)

Ø  syncope

Ø  orthostatic hypotension

Ø  orthostatic tachycardia

Ø  Remember that the hematocrit and hemoglobin can be normal in rapid bleeding because the rbcs and plasma are lost in proportion

Classification of Anemias

• can be classified by cytometric, erythrokinetic, and biochemical/molecular schemes

Cytometric Anemia classifications

Normochromic, normocytic (normal MCHC, normal MCV)

-        anemias of chronic disease

-        hemolytic anemias

-        anemia of acute hemorrhage

-        aplastic anemias

Hypochromic, microcytic (low MCHC, low MCV)

-        iron deficiency anemia

-        thalassemias

-        anemia of chronic disease (rare cases

-        sideroblastic anemias

Normochromic, macrocytic (normal MCHC, high MCV)

-        vit B₁₂ deficiency

-        folate deficiency

Erythrokinetic Anemia Classifications

• look at rate of rbc turnover

Ø  if high

-        normoregenerative anemia exists

-        hemolysis or hemorrhage

Ø  if low

-        hyporegenerative anemia exists

-        marrow functioning too slow

• lab tests to figure Erythrokinetically

I.                 Reticulocyte count

• an increased # of reticulocytes is seen when the marrow is churning out RBCs at high speed
• lab sends the reticulocyte count in percent of all RBCs counted; this is misleading
• to correct this misleading evidence, a fudge factor system is in place to prevent misdiagnoses.
• Two ways

1.     absolute reticulocyte count     (rbc count) x (relative reticulocyte count(in %))

2.     reticulocyte production index

-         RPI (%) =   relative reticulocyte count (%)     x        (hematocrit cL/L) /45

Fudge factor

II.               Serum unconjugated bilirubin and urine urobilinogen concentration

• in cases of accelerated RBC destruction, the capacity of the liver to capture the bilirubin is saturated, and the conc. of unconjugated bilirubin in the serum increases, sometime producing clinical jaundice.

III.              Serum Haptoglobin Concentration

• when the RBC is destroyed the hemoglobin binds mole-for-mole with the serum protein haptoglobin.
• This cause the serum haptoglobin concentration to decrease
• In cases of intravascular hemolysis, that hemoglobin in excess of the haptoglobin binding capacity is rapidly filtered in the urine. That which remains in the plasma degrades into metheme and globin. Some of the metheme binds to albumin and can be measured as methemalbumin, while the other binds to hemopexin.

Bone Marrow Biopsy

• can directly observe any accelerated production of the RBCs
• the ratio of myeloid to erythroid precursors (M:E ratio) decreases in high production states
• marrow becomes hypercellular

Biochemical Anemia Classification

• to determine the etiology of the anemia as specifically as possible
• Generally the biochemical tests are aimed at identifying a depleted cofactor necessary for normal hematopoiesis (iron, ferritin, folate, B₁₂), a depleted or abnormally functioning enzyme (G-6-P dehydrogenase, pyruvate kinase), or abnormal function of the immune system

Erythrocytes

• basic function = creation and maintenance of an environment salutary to the physical integrity and functionality of hemoglobin
• Normally produced only in skeleton (adults-axial skeleton)
• In pathologic states – almost any organ can become the site for erythropoiesis
• They are released in the blood as reticulocytes and after one day become erythrocytes.
• Life span of normal adult rbc = 120 days
• Clinical Lab tests

Ø  reflect rbc structure and function.

Ø  Used to evaluate O₂ delivery to tissues and to detect abnormalities in rbc shape and size

Ø  Different tests…

q  Hemoglobin concentration in blood

¨      First the erythrocytes are lysed to produce an evenly distributed sample of hemoglobin in the sample

¨      Then the hemoglobin is chemically converted to the more stable cyanmethoglobin which can be measured colorimetrically using Beer’s law.

¨      Values are highly age and sex dependent (neonates>adult males>adult females>children)

q  Erythrocyte count

¨      Number of RBCs per unit volume of whole blood

¨      Males>females

q  Hematocrit

¨      Also called the packed cell volume or PCV

¨      Measure of the total volume of the erythrocytes relative to the total volume of whole blood in a sample.

¨      Old style – centrifuge

¨      New style – fancy measuring devices

¨      Normal range =           females-0.37-0.47 L/L             males-0.42-0.52 L/L

q  Erythrocyte indices (MCV, MCH, MCHC)

¨      Uses the above values (Hematocrit, Erythrocyte count, and Hemoglobin) to calculate the MCV, MCH, and MCHC

¨      MCV – Mean corpuscular volume

§  Mean volume of all the erythrocytes counted in the sample

§  MCV = (hematocrit)/rbc count

§  Fudge factors required for unit conversion

MCV = (Hematocrit (in L/L) x 1000) / (rbc count (in millions/mL))

When MCV is …         then…

Low                             microcytic

High                             macrocytic

Normal                        normocytic

§  Remember that there can still be an abnormality if the sample is normocytic because the rbcs can vary so much from in volume from one sample to the next.  This is called anisocytosis.

§  To determine if there is anisocytosis involved, use the red cell distribution width (RDW).  This is an expression for the dispersion of a population about a mean.

¨      MCH – Mean corpuscular hemoglobin

§  Represents the mass mean of hemoglobin in the RBC

§  MCH = (hemoglobin (in g/dL) x 10) / rbc count (in millions/mL)

§  Variation in the MCH tends to follow the MCV because small cells have less hemoglobin than larger ones.

§  Minor leaguer among the indices

¨      MCHC – Mean corpuscular hemoglobin concentration

§  Mean concentration of hemoglobin in the red cell

§  Remember that whole blood is about 45% cell by volume (roughly ½).  So therefore you would expect the value for MCHC to be roughly 2X the value for hemoglobin in whole blood.

§  MCHC = hemoglobin (in g/dL) / hematocrit (in L/L)

When MCHC is…

Normal            then… normochromic

High                             hyperchromic

Low                             hypochromic

Leukocytes and the leukocyte differential count

Neutrophils

• most populous and most short lived
• 40-75% of the total WBCs
• capable of phagocytosis
• HISTO: multilobed nucleus. Large spherical azurophilic 1^o granules
• produced as a response to acute body stress (infection, infarction, trauma, emotional distress, or other noxious stimuli)
• Normally the neutrophil series consists of band neutrophils and segmented neutrophils.
• In stress situations the earlier forms (usu. No earlier than the myelocytes) can be seen.
• Other morphologic clues to acute stress

Ø  neutrophil forms develop deep blue cytoplasmic granules, vacuoles, and vague cytoplasmic inclusions (Dohle bodies)

• lower count of neutrophils is common in African Americans
• Obesity and smoking tend to increase neutrophil count

Monocytes

• Monocytes and neutrophils share the same stem cell.
• 2-10% of leukocytes
• HISTO: Large Kidney shaped nucleus, “frosted glass cytoplasm”
• Once the monocytes enter the tissues, they become histiocytes (macrophages)

Eosinophils

• Traditionally grouped with the neutrophils and basophils as “granulocytes” although this connection is not quite right.
• 1-6% of all leukocytes
• HISTO: bilobate nucleus. Large eosinophilic granules of uniform size
• Capable of ameboid motion and phagocytosis
• Seen in: parasitic infections, allergic conditions
• Causes of eosinophilia = NAACP (Neoplastic, Asthma, Allergic processes, Collagen vascular diseases, Parasites)

Basophils

• least numerous
• connected to mast cells in the tissues.
• <1% of all leukocytes
• HISTO: bilobate nucleus, densely basophilic granules
• Mediates allergic reaction

Lymphocytes

• B lymphocytes – humoral immunity
• T lymphocytes – cellular immunity
• Can move back and forth from the vessels to the tissues
• Can revert to blast-like cells
• Can multiply if needed (immune response)
• HISTO: small round sensely staining nucleus

Platelets

• LOOK FOR THEM 1^st!
• Probably the most inaccurate of all the parameters
• Abnormal bleeding usually does not occur unless the platelet count in < 30000/mL

Other cells in peripheral blood

• Plasma cells
• Endothelial cells – from phlebotomy needle contamination
• Histiocytes – seen in states of extreme reactivity (ex. Septic neonates)
• Nucleated red cells – always abnormal in an adult
• Myeloblasts – always abnormal and usu indicate leukemia or some other neoplastic disease.

Tags: asophils, Dyspnea, Eosinophils, erythrocytes, Hypochromic, leukocytes, Lymphocytes, microcytic, Monocytes, Myeloblasts, Neutrophils, Normochromic, normocytic, Reticulocyte count, Serum unconjugated bilirubin, Tachycardia, urine urobilinogen concentration

This entry was posted on Saturday, July 4th, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.