Impaired RBC production can occur secondary to problems with RBC synthesis or maturation. Pure red cell aplasia is a type of anemia that results from decreased production of RBCs, but not white blood cells (WBCs), by bone marrow. Causes include autoimmune disease, viral infections, drug reactions, congenital defects or idiopathic etiologies. In aplastic anemia, both RBCs and WBCs are affected. RBC maturation can be affected by deficiencies of nutrients such as vitamin B12 (pernicious anemia), folate or iron. Renal failure can cause anemia due to decreased EPO production. Thalassemia is an autosomal recessive blood disease that results in the formation of abnormal hemoglobin molecules and decreased oxygen-carrying capacity of the affected RBCs.
Anemia during pregnancy occurs when the normal increase of a pregnant female’s blood volume has a dilutive effect on the RBCs. Iron deficiency during pregnancy is not uncommon, further contributing to anemia. In non-pregnant individuals, increased sodium or fluid intake can also result in increased fluid volume and a dilutive effect, as will any mechanism that results in an intravascular shift of fluid from the interstitial or intracellular spaces.
Blood loss resulting in anemia can be classified as acute or chronic. Acute etiologies include trauma or surgery that results in the loss of large volumes of blood. Anemia of prematurity occurs in premature newborns that tend to have insufficient RBC production and are subjected to frequent blood draws from laboratory tests. The frequent small-volume blood draws can be sufficient to remove a substantial portion of the newborn’s total blood volume. Chronic blood loss from gastrointestinal hemorrhage or excessive menstrual bleeding can also result in anemia.
Physiologic Response to Anemia
The body will respond to anemia in several ways to compensate for the reduction in oxygen-carrying capacity of the blood. The specific compensatory mechanism depends on the acuity of onset, etiology of the insult and underlying health of the patient. For example, to compensate for the hypoxia and hypotension that occur in acute anemia secondary to blood loss, the body will mount a sympathetic response that results in increased heart rate (HR), cardiac output (CO) and systemic vascular resistance (SVR), which preserves perfusion of the vital organs. If the sympathetic stimulation is unsuccessful at correcting tissue hypoxia, peripheral vasodilation will occur and hypotension (and decompensated shock) will result.
Within the kidney, juxtaglomerular cells and peritubular capillary cells release renin and EPO, respectively, in response to decreased renal perfusion or sympathetic stimulation. Release of EPO stimulates the red bone marrow to produce red blood cells. After entering the bloodstream, renin starts an enzymatic cascade known as the renin-angiotensin system. Renin first converts angiotensinogen, a plasma protein synthesized by the liver, to angiotensin I. In the lungs, angiotensin I is converted to angiotensin II, which causes vasoconstriction to arterial smooth muscle, resulting in increased SVR and blood pressure. In addition, angiotensin II stimulates the release of antidiuretic hormone (ADH) by the pituitary gland and aldosterone by the adrenal cortex. ADH increases water reabsorption in the distal collecting tubules of the kidneys, reducing water loss in urine and restoring intravascular volume. Aldosterone also results in reabsorption of water in the kidney via reabsorption of sodium, further increasing intravascular volume. The end result of all of these systems acting together is an increase in HR, CO and SVR, which increases blood pressure and perfusion of peripheral tissues. In addition, intravascular fluid volume is replaced and RBCs are produced to increase the oxygen-carrying capacity of the blood. Oxygen delivery is enhanced with the improved perfusion, resulting in correction of the underlying hypoxia.
For anemia with an etiology other than hypovolemia secondary to blood loss, the normal compensatory mechanisms may be interrupted by the underlying etiology, the patient’s health, or even by medications. For example, a patient with pure red cell aplasia or aplastic anemia will not be able to effectively produce RBCs to increase oxygen-carrying capacity. A patient with anemia secondary to kidney failure may not be able to effectively synthesize and secrete renin or EPO. Medications like beta blockers and angiotensin-converting enzyme (ACE) inhibitors may interfere with an increase in HR or peripheral vasoconstriction, respectively.