• Anemia means a deficiency of hemoglobin in the blood.
• Anemia can occur because:
  • There are too few RBCs.
  • The RBCs contain too little hemoglobin.
• Different types of anemia have different physiological causes.
• Blood Loss Anemia
  • After a rapid hemorrhage, the body replaces the fluid portion of the plasma within 1–3 days.
  • This causes the concentration of RBCs in the blood to become low.
• If no second hemorrhage occurs:
  • The RBC concentration usually returns to normal within 3–6 weeks.
• During chronic blood loss:
  • The body often cannot absorb enough iron from the intestines.
  • As a result, hemoglobin cannot be produced as rapidly as it is lost.
• Consequently:
  • RBCs become much smaller than normal.
  • RBCs contain too little hemoglobin.
• This condition produces microcytic hypochromic anemia.
• Figure 33.3 shows microcytic hypochromic anemia.

KEY CONCEPT

• Anemia is a deficiency of hemoglobin in the blood.
• It results from:
  • Too few RBCs, or
  • Too little hemoglobin in RBCs.
• After acute hemorrhage, plasma volume is restored in 1–3 days, while RBC concentration returns to normal in 3–6 weeks if no further bleeding occurs.
• Chronic blood loss causes iron deficiency, reducing hemoglobin production.
• This leads to microcytic hypochromic anemia, in which RBCs are small and contain less hemoglobin.
• Figure 33.3 illustrates microcytic hypochromic anemia.

ANEMIAS

• Aplastic anemia is caused by bone marrow dysfunction.
• Bone marrow aplasia means lack of functioning bone marrow.
• Exposure to high-dose radiation can damage bone marrow stem cells.
• Chemotherapy for cancer treatment can also damage bone marrow stem cells.
• A few weeks after stem cell damage, anemia develops.
• High doses of certain toxic chemicals can also damage the bone marrow.
• Examples include:
  • Insecticides
  • Benzene in gasoline
• These toxic chemicals can produce the same effect as radiation and chemotherapy.
• In autoimmune disorders, the immune system attacks healthy cells.
• In lupus erythematosus, the immune system may attack bone marrow stem cells.
• This can lead to aplastic anemia.
• In about half of all aplastic anemia cases, the cause is unknown.
• This condition is called idiopathic aplastic anemia.
• People with severe aplastic anemia usually die if they are not treated.
• Blood transfusions can temporarily increase the number of RBCs.
• Bone marrow transplantation is another treatment option.

KEY CONCEPT

• Aplastic anemia results from bone marrow dysfunction.
• Bone marrow aplasia means non-functioning bone marrow.
• Causes include:
  • High-dose radiation
  • Chemotherapy
  • Toxic chemicals (insecticides, benzene)
  • Autoimmune disorders such as lupus erythematosus
• About 50% of cases are idiopathic (cause unknown).
• Severe aplastic anemia requires treatment with blood transfusions or bone marrow transplantation.

ANEMIAS

• Megaloblastic anemia is characterized by abnormally large, poorly developed RBCs.
• Deficiency of any of the following can slow the reproduction of erythroblasts in the bone marrow:
  • Vitamin B12
  • Folic acid
  • Intrinsic factor
• As a result, RBCs grow too large.
• These abnormally large RBCs have irregular (odd) shapes.
• These cells are called megaloblasts.
• Atrophy of the stomach mucosa, as seen in pernicious anemia, can cause megaloblastic anemia.
• Total gastrectomy (complete surgical removal of the stomach) can also lead to megaloblastic anemia.
• Megaloblastic anemia also commonly develops in patients with intestinal sprue.
• In intestinal sprue, absorption of the following is poor:
  • Folic acid
  • Vitamin B12
  • Other vitamin B compounds
• Because erythroblasts cannot proliferate rapidly enough, they cannot produce a normal number of RBCs.
• The RBCs that are produced are:
  • Mostly oversized
  • Bizarre in shape
  • Have fragile membranes
• These abnormal RBCs rupture easily.
• As a result, the person develops a severe shortage of adequate RBCs.

KEY CONCEPT

• Megaloblastic anemia is caused by abnormally large, poorly developed RBCs.
• Deficiency of vitamin B12, folic acid, or intrinsic factor slows erythroblast reproduction.
• Slow cell division produces large abnormal RBCs (megaloblasts).
• Causes include:
  • Pernicious anemia (atrophy of the stomach mucosa)
  • Total gastrectomy
  • Intestinal sprue with poor absorption of folic acid, vitamin B12, and other vitamin B compounds
• The resulting RBCs are oversized, irregularly shaped, and have fragile membranes.
• These fragile cells rupture easily, leading to anemia.

ANEMIAS

• Hemolytic anemia occurs when RBCs are destroyed faster than they can be replaced.
• Different abnormalities of RBCs, many of them inherited, make the cells fragile.
• These fragile RBCs rupture easily while passing through capillaries, especially in the spleen.
• In some hemolytic diseases, RBC production may be normal or even increased.
• However, the lifespan of the fragile RBCs is very short.
• Therefore, RBC destruction occurs faster than RBC production.
• This results in serious anemia.
• Hereditary spherocytosis
  • RBCs are small and spherical instead of normal biconcave discs.
  • These RBCs lack the normal loose, bag-like membrane.
  • Therefore, they cannot tolerate compression.
  • While passing through the splenic pulp and other narrow blood vessels, they rupture easily with even slight compression.
• Sickle cell anemia
  • RBCs contain an abnormal hemoglobin called hemoglobin S.
  • Hemoglobin S contains abnormal beta (β) chains.
  • When exposed to low oxygen concentration, hemoglobin S forms long crystals inside the RBC.
  • These crystals elongate the RBC.
  • The RBC becomes sickle-shaped instead of a biconcave disc.
  • The crystals also damage the RBC membrane.
  • As a result, the RBCs become highly fragile.
  • This leads to serious anemia.
• Sickle cell disease crisis
  • Low tissue oxygen tension causes RBC sickling.
  • Sickled RBCs rupture.
  • RBC destruction further decreases oxygen tension.
  • Lower oxygen tension causes even more sickling.
  • This creates a vicious cycle of sickling and RBC destruction.
• An important clinical feature of sickle cell crisis is acute pain.
• Acute pain occurs because sickled RBCs block small blood vessels.
• Once sickle cell crisis begins, it may progress rapidly.
• Within a few hours, there may be a severe decrease in RBCs.
• In some cases, sickle cell crisis may cause:
  • Target organ injury
  • Death
• Erythroblastosis fetalis
  • In this condition, Rh-positive fetal RBCs are attacked by antibodies from an Rh-negative mother.
  • These antibodies make the fetal RBCs fragile.
  • Fragile RBCs rupture rapidly.
  • As a result, the baby is born with severe anemia.
• Because RBC destruction is very rapid in erythroblastosis fetalis:
  • The bone marrow rapidly increases RBC production.
  • Many early blast forms of RBCs are released into the bloodstream.

KEY CONCEPT

• Hemolytic anemia results from premature destruction of RBCs.
• Fragile RBCs are destroyed faster than they are produced, causing anemia.
• Hereditary spherocytosis:
  • Small, spherical RBCs
  • Easily rupture during passage through the spleen.
• Sickle cell anemia:
  • Hemoglobin S contains abnormal β chains.
  • Low oxygen causes crystal formation, sickling, membrane damage, and RBC destruction.
• Sickle cell crisis:
  • Low oxygen → Sickling → RBC destruction → Further low oxygen → More sickling.
  • Causes acute pain due to vascular occlusion and may lead to organ injury or death.
• Erythroblastosis fetalis:
  • Maternal antibodies destroy Rh-positive fetal RBCs.
  • Rapid RBC destruction causes severe anemia.
  • Bone marrow releases many immature blast forms of RBCs into the blood.

Effects of Anemia on Circulatory System Function

• Blood viscosity depends mainly on the concentration of RBCs.
• In people with severe anemia, blood viscosity may decrease to about 1.5 times the viscosity of water.
• Normally, blood viscosity is about 3 times the viscosity of water.
• Lower blood viscosity decreases the resistance to blood flow in the peripheral blood vessels.
• As a result, much larger amounts of blood flow through the tissues.
• More blood also returns to the heart.
• This greatly increases cardiac output.
• Reduced oxygen transport in anemia causes hypoxia.
• Hypoxia causes the peripheral blood vessels to dilate.
• Vasodilation allows even more blood to return to the heart.
• This further increases cardiac output.
• Cardiac output may increase to 3–4 times the normal value.
• Therefore, one of the major effects of anemia is a marked increase in cardiac output.
• The increased cardiac output also increases the pumping workload of the heart.
• The increased cardiac output partly compensates for the reduced oxygen-carrying capacity of the blood.
• Although each unit of blood carries less oxygen, the higher blood flow helps deliver almost normal amounts of oxygen to the tissues.
• During exercise, tissue oxygen demand increases greatly.
• In a person with anemia, the heart is already pumping at a high rate.
• Therefore, the heart cannot increase cardiac output much further during exercise.
• As a result, severe tissue hypoxia develops during exercise.
• Severe tissue hypoxia may lead to acute cardiac failure.

KEY CONCEPT

• Blood viscosity depends mainly on the RBC concentration.
• In severe anemia:
  • Blood viscosity falls from about 3 to 1.5 times the viscosity of water.
  • Peripheral vascular resistance decreases.
  • Blood flow to tissues and venous return increase.
• Hypoxia causes peripheral vasodilation, further increasing venous return and cardiac output.
• Cardiac output may rise to 3–4 times normal.
• Increased cardiac output partially compensates for reduced oxygen-carrying capacity.
• During exercise, the heart cannot increase output much further, leading to severe tissue hypoxia and possible acute cardiac failure.

POLYCYTHEMIA

• Secondary polycythemia occurs when the tissues become hypoxic.
• Tissue hypoxia may occur because:
  • Too little oxygen is present in the inspired air, such as at high altitudes.
  • Oxygen delivery to the tissues is reduced, such as in cardiac failure.
• In response to hypoxia, the blood-forming organs automatically produce large numbers of additional RBCs.
• This increase in RBC production is called secondary polycythemia.
• In secondary polycythemia, the RBC count commonly increases to 6–7 million/mm³.
• This is about 30% above the normal RBC count.
• A common type of secondary polycythemia is physiological polycythemia.
• Physiological polycythemia occurs in people living at 14,000–17,000 feet above sea level.
• At these high altitudes, the atmospheric oxygen level is very low.
• The RBC count in these people is generally 6–7 million/mm³.
• This increased RBC count allows them to perform reasonably high levels of continuous work.
• They are able to do this even in a rarefied (low-oxygen) atmosphere.

KEY CONCEPT

• Secondary polycythemia develops due to tissue hypoxia.
• Causes of hypoxia include:
  • High altitude
  • Cardiac failure
• Hypoxia stimulates the blood-forming organs to produce more RBCs.
• The RBC count commonly rises to 6–7 million/mm³, about 30% above normal.
• Physiological polycythemia occurs in people living at 14,000–17,000 feet, where atmospheric oxygen is low.
• The increased RBC count helps maintain work capacity in a low-oxygen (rarefied) environment.

POLYCYTHEMIA

• Polycythemia vera (erythremia) is a pathological type of polycythemia.
• It is caused by a genetic abnormality (aberration) in the hemocytoblastic cells that produce blood cells.
• Because of this abnormality, the blast cells continue producing RBCs even when too many RBCs are already present.
• In polycythemia vera, the RBC count may increase to 7–8 million/mm³.
• The hematocrit may increase to 60%–70%.
• The normal hematocrit is 40%–45%.
• In this disorder, the production of:
  • White blood cells (WBCs)
  • Platelets
  is also usually increased.
• In polycythemia vera, not only does the hematocrit increase, but the total blood volume also increases.
• The total blood volume may become almost twice the normal value.
• As a result, the entire vascular system becomes intensely engorged.
• The blood becomes highly viscous (thick).
• Many blood capillaries become plugged by the viscous blood.
• Normally, blood viscosity is about 3 times the viscosity of water.
• In polycythemia vera, blood viscosity may increase to about 10 times the viscosity of water.

KEY CONCEPT

• Polycythemia vera (erythremia) is a pathological polycythemia caused by a genetic abnormality of hemocytoblastic cells.
• Blast cells continue producing RBCs despite an already increased RBC count.
• RBC count: 7–8 million/mm³
• Hematocrit: 60%–70% (Normal: 40%–45%)
• WBC and platelet production are also increased.
• Total blood volume may increase to almost twice normal.
• The vascular system becomes engorged.
• Blood viscosity increases from about 3 to 10 times the viscosity of water, which may plug small capillaries.

Effect of Polycythemia on Function of the Circulatory System

• In polycythemia, blood viscosity is greatly increased.
• Because the blood is more viscous, blood flow through the peripheral blood vessels becomes very sluggish.
• Increased blood viscosity decreases tissue blood flow.
• Reduced tissue blood flow decreases venous return.
• Reduced venous return decreases cardiac output.
• However, in polycythemia, the total blood volume is greatly increased.
• The increased blood volume increases venous return.
• The increased blood volume also increases cardiac output.
• Therefore, in polycythemia:
  • Increased blood viscosity tends to decrease cardiac output.
  • Increased blood volume tends to increase cardiac output.
• These two effects largely neutralize each other.
• As a result, cardiac output remains close to normal.
• In most people with polycythemia, arterial blood pressure remains normal.
• However, about one-third of people with polycythemia have elevated arterial pressure.
• This indicates that the body’s blood pressure regulatory mechanisms usually compensate for the increased blood viscosity.
• These mechanisms prevent increased peripheral resistance from causing hypertension.
• However, when these compensatory mechanisms are exceeded, hypertension develops.
• The color of the skin depends largely on the amount of blood present in the subpapillary venous plexus.
• In polycythemia vera, the amount of blood in the subpapillary venous plexus is greatly increased.
• Blood flows slowly through the skin capillaries before entering the venous plexus.
• Because blood flow is slow, more hemoglobin becomes deoxygenated.
• The blue color of the deoxygenated hemoglobin partially masks the red color of oxygenated hemoglobin.
• Therefore, people with polycythemia vera usually have:
  • A ruddy (reddish) complexion
  • A bluish (cyanotic) tint to the skin

KEY CONCEPT

• Increased blood viscosity in polycythemia causes sluggish blood flow.
• High blood viscosity:
  • Decreases tissue blood flow
  • Decreases venous return
  • Decreases cardiac output
• Increased blood volume:
  • Increases venous return
  • Increases cardiac output
• These opposite effects keep cardiac output near normal.
• Arterial pressure is usually normal, but about one-third of patients develop hypertension when compensatory mechanisms fail.
• In polycythemia vera, increased blood in the subpapillary venous plexus and increased deoxygenated hemoglobin produce a ruddy complexion with a bluish (cyanotic) tint.