Altered Hematologic Altered Hematologic Function:Function:ErythrocytesErythrocytes

Physical Characteristics Physical Characteristics of Bloodof Blood

Heavier, thicker, and 3-4 X more Heavier, thicker, and 3-4 X more viscous than waterviscous than water

3838oo C (100.4 C (100.4ooF)F) pH : 7.35 – 7.45pH : 7.35 – 7.45 4-6 liters in an adult4-6 liters in an adult Varies with electrolyte concentration Varies with electrolyte concentration

and amount of adipose tissueand amount of adipose tissue

Blood VolumeBlood Volume

Blood volume is about 8% of body Blood volume is about 8% of body weight.weight.

1 kg of blood 1 kg of blood ≈ ≈ 1 L of blood 1 L of blood 70 kg X 0.08 = 5.6 Kg = 5.6 L70 kg X 0.08 = 5.6 Kg = 5.6 L 45 % is formed elements45 % is formed elements 55% plasma55% plasma

PlasmaPlasma 92 % Water92 % Water 8% Solutes – organic and inorganic8% Solutes – organic and inorganic

– Plasma proteins – largest proportion of solutesPlasma proteins – largest proportion of solutes Albumins – 58 % of the proteins – maintain Albumins – 58 % of the proteins – maintain

osmotic (oncotic) pressure – hold water in osmotic (oncotic) pressure – hold water in the bloodthe blood

Globulins – 38 % - antibodies synthesized by Globulins – 38 % - antibodies synthesized by plasma cellsplasma cells

Clotting factors – fibrinogen – 4 % (Serum Clotting factors – fibrinogen – 4 % (Serum without)without)

Other components of Other components of plasmaplasma NutrientsNutrients HormonesHormones ElectrolytesElectrolytes Waste productsWaste products Dissolved gasesDissolved gases

Formed elementsFormed elements Three types:Three types:

Erythrocytes – red blood cells- RBC’sErythrocytes – red blood cells- RBC’s

Leukocytes – white blood cells – WBC’sLeukocytes – white blood cells – WBC’s

Thrombocytes – platelets – cell fragmentsThrombocytes – platelets – cell fragments

Hemopoiesis Hemopoiesis (Hematopoiesis)(Hematopoiesis)

All blood cells common from a All blood cells common from a common stem cell – Hemocytoblastcommon stem cell – Hemocytoblast

These are in the bone marrow (red) These are in the bone marrow (red) and develop into blood cells as and develop into blood cells as needed by the bodyneeded by the body

Mitosis is signaled by biochemicals Mitosis is signaled by biochemicals released from the body released from the body →→

Stem cell is signaled to differentiate Stem cell is signaled to differentiate into the needed type of blood cellinto the needed type of blood cell

Hematopoiesis / cell breakdown Hematopoiesis / cell breakdown continue through life.continue through life.

Erythrocytes (RBC’s)Erythrocytes (RBC’s) Most abundant blood cell typeMost abundant blood cell type Transport gasesTransport gases Shape is important Shape is important

– Large surface to volume ratioLarge surface to volume ratio– Reversible deformability – can change Reversible deformability – can change

shapeshape Development is called erythopoiesisDevelopment is called erythopoiesis

– Erythropoietin is a hormone produced Erythropoietin is a hormone produced by the by the kidneyskidneys in response to low in response to low blood oxygen levels; signals bone blood oxygen levels; signals bone marrow to increase RBC productionmarrow to increase RBC production

Cytoplasm is mostly hemoglobin Cytoplasm is mostly hemoglobin (lacks organelles, no nucleus)(lacks organelles, no nucleus)

Made up of 4 peptide chains that form Made up of 4 peptide chains that form the globin portion and four molecules the globin portion and four molecules of the pigment heme which contains of the pigment heme which contains an atom of ironan atom of iron– Oxygen binds to iron in heme (also CO)Oxygen binds to iron in heme (also CO)

– 23 % of CO23 % of CO22 is bound to globin portion is bound to globin portion

If there is a problem with any part of If there is a problem with any part of the molecule it may not be functional.the molecule it may not be functional.

RBC breakdownRBC breakdown

Healthy RBC’s live about 120 days; we Healthy RBC’s live about 120 days; we break down about 174 million per minutebreak down about 174 million per minute

RBC’s are removed from circulation by RBC’s are removed from circulation by the liver and spleenthe liver and spleen

Broken down into heme and globin Broken down into heme and globin portionsportions

Globin is broken down into amino acids Globin is broken down into amino acids Iron is removed from heme and stored or Iron is removed from heme and stored or

recycledrecycled Heme is broken down into biliverdin and Heme is broken down into biliverdin and

then into bilirubinthen into bilirubin

Usually eliminated in bile.Usually eliminated in bile. If liver insufficiency, bilirubin If liver insufficiency, bilirubin

accumulates in blood accumulates in blood Jaundice Jaundice too much too much kernicteruskernicterus

To produce more RBC’s, the body To produce more RBC’s, the body needs sufficient iron and amino needs sufficient iron and amino acids as well as the vitamins folate acids as well as the vitamins folate (folic acid) and vitamin B(folic acid) and vitamin B1212

Abnormalities AnemiasAbnormalities Anemias

Anemia Anemia is the inability of the is the inability of the blood to carry sufficient oxygen blood to carry sufficient oxygen to the body.to the body.

low #’s of RBCslow #’s of RBCs lack of hemoglobinlack of hemoglobin

Clinical ManifestationsClinical Manifestations PallorPallor FatigueFatigue Weakness; exercise intoleranceWeakness; exercise intolerance DyspneaDyspnea Syncope (fainting) and dizzinessSyncope (fainting) and dizziness Angina Angina Tachycardia (increased heart rate)Tachycardia (increased heart rate) Organ dysfunctionsOrgan dysfunctions

Classification of AnemiasClassification of Anemias Identified by their causes or by the Identified by their causes or by the

changes that affect the size, shape changes that affect the size, shape or substance of the erythrocyteor substance of the erythrocyte

Terms that end with –cytic refer to Terms that end with –cytic refer to cell size, and those that end in –cell size, and those that end in –chromic refer to hemoglobin chromic refer to hemoglobin content.content.

Macrocytic / Macrocytic / Megaloblastic AnemiaMegaloblastic Anemia

Characterized by abnormally large Characterized by abnormally large stem cells (megaloblasts) in the stem cells (megaloblasts) in the marrow that mature into marrow that mature into erythrocytes that are unusually large erythrocytes that are unusually large in size, thickness and volume. The in size, thickness and volume. The hemoglobin content is normal, so hemoglobin content is normal, so these are these are normochromicnormochromic anemias. anemias.

These anemias are the result of:These anemias are the result of:– Ineffective DNA synthesisIneffective DNA synthesis

Commonly due to folate and BCommonly due to folate and B1212 (cobalamin) deficiencies – mal-(cobalamin) deficiencies – mal-absorption or malnutritionabsorption or malnutrition

These cells die prematurely, These cells die prematurely, decreasing the numbers of RBC’s in decreasing the numbers of RBC’s in circulationcirculation

Pernicious AnemiaPernicious Anemia

Common megaloblastic anemiaCommon megaloblastic anemia Caused by a Vitamin BCaused by a Vitamin B1212 deficiency deficiency Pernicious means highly injurious or Pernicious means highly injurious or

destructive – this condition was once destructive – this condition was once fatalfatal

Can be congenital – baby born with a Can be congenital – baby born with a deficiency in a protein , deficiency in a protein , intrinsic intrinsic factorfactor, necessary to absorb B, necessary to absorb B1212 from from the stomachthe stomach

Adult onset – one example is an Adult onset – one example is an autoimmune dysfunction - type A autoimmune dysfunction - type A chronic atrophic gastritis – where there chronic atrophic gastritis – where there is destruction of the gastric mucosais destruction of the gastric mucosa

Most commonly affects people over 30Most commonly affects people over 30 Females are more prone to pernicious Females are more prone to pernicious

anemia , and black females have an anemia , and black females have an earlier onset.earlier onset.

Pernicious Anemia is also associated Pernicious Anemia is also associated with:with:

Heavy alcohol consumptionHeavy alcohol consumption

Hot teaHot tea

Cigarette smokingCigarette smoking

Other autoimmune conditionsOther autoimmune conditions

Complete or partial removal of the Complete or partial removal of the stomach can cause intrinsic factor stomach can cause intrinsic factor deficiencydeficiency

Develops slowly – over 20 - 30 years Develops slowly – over 20 - 30 years Usually severe by the time individual Usually severe by the time individual

seeks treatmentseeks treatment Early symptoms ignored because they Early symptoms ignored because they

are nonspecific and vague- infections, are nonspecific and vague- infections, mood swings, and gastrointestinal, mood swings, and gastrointestinal, cardiac or kidney ailments.cardiac or kidney ailments.

Usually a degree of neuropathy occursUsually a degree of neuropathy occurs Untreated, it is fatal, Untreated, it is fatal, due to heart due to heart

failurefailure

Folate deficiency Folate deficiency anemiaanemia

Folic acid also needed for DNA Folic acid also needed for DNA synthesissynthesis

Demands are increased in pregnant Demands are increased in pregnant and lactating femalesand lactating females

Absorbed from small intestine and Absorbed from small intestine and does not require any other elements does not require any other elements for absorption.for absorption.

Folate deficiency is more common Folate deficiency is more common than Bthan B1212 deficiency deficiency

Folate deficiency is more common than Folate deficiency is more common than BB1212 deficiency , esp. in alcoholics and deficiency , esp. in alcoholics and those who are malnourished because those who are malnourished because of fat diets or diets low in vegetables.of fat diets or diets low in vegetables.

Estimated that 10 % of North Estimated that 10 % of North Americans are folate deficient.Americans are folate deficient.

Specific manifestations include Specific manifestations include cheilosis, (scales and fissures of the cheilosis, (scales and fissures of the mouth), inflammation of the mouth, mouth), inflammation of the mouth, and ulceration of the buccal mucosa and ulceration of the buccal mucosa and tongue.and tongue.

Microcytic – Hypochromic AnemiasMicrocytic – Hypochromic Anemias

Characterized by abnormally small Characterized by abnormally small RBC’s that contain reduced amounts RBC’s that contain reduced amounts of hemoglobin.of hemoglobin.

Possible causes:Possible causes:– Disorders of iron metabolismDisorders of iron metabolism– Disorders of porphyrin and heme Disorders of porphyrin and heme

synthesissynthesis– Disorders of globin synthesisDisorders of globin synthesis

Iron Deficiency AnemiaIron Deficiency Anemia Most common type of anemia Most common type of anemia

throughout the world.throughout the world. High risk:High risk:

– Individuals living in povertyIndividuals living in poverty– Females of childbearing ageFemales of childbearing age– ChildrenChildren

Common causesCommon causes– Insufficient iron intake Insufficient iron intake – Chronic blood loss – even 2- 4 ml/ dayChronic blood loss – even 2- 4 ml/ day– In men –gastrointestinal bleedingIn men –gastrointestinal bleeding– In women – profuse menstruation, pregnancyIn women – profuse menstruation, pregnancy

Other causes:Other causes:– Use of medications that cause GI Use of medications that cause GI

bleedingbleeding– Surgical procedures that decrease Surgical procedures that decrease

stomach acidity, intestinal transit time, stomach acidity, intestinal transit time, and absorptionand absorption

– Eating disorders such as picaEating disorders such as pica

Clinical Clinical manifestations:manifestations:

Early symptoms are nonspecificEarly symptoms are nonspecific Later - changes in epithelial tissue: Later - changes in epithelial tissue:

– Fingernails become brittle and concave Fingernails become brittle and concave (koilonychia)(koilonychia)

– Tongue papillae atrophy and cause Tongue papillae atrophy and cause soreness, redness and burningsoreness, redness and burning

– Corners of mouth become dry and soreCorners of mouth become dry and sore– Difficulty in swallowing due to web of Difficulty in swallowing due to web of

mucus and inflammatory cells at mucus and inflammatory cells at opening of esophagusopening of esophagus

TreatmentTreatment

Stop blood lossStop blood loss Iron replacement therapyIron replacement therapy

Normocytic –Normocytic –Normochromic Normochromic AnemiasAnemias RBC’s are normal in size and RBC’s are normal in size and

hemoglobin content, but are too hemoglobin content, but are too few in number.few in number.

Less common than the Less common than the macrocytic and microcytic macrocytic and microcytic anemias anemias

Several types that do not have Several types that do not have anything else in common:anything else in common:– AplasticAplastic– PosthemorrhagicPosthemorrhagic– Hemolytic Hemolytic – Sickle cell Sickle cell – Anemia of chronic inflammationAnemia of chronic inflammation

Aplastic anemiaAplastic anemia Fortunately, this condition is rare; it means Fortunately, this condition is rare; it means

the RBC’s are not being produced. Bone the RBC’s are not being produced. Bone marrow stem cells are not functioning.marrow stem cells are not functioning.

Can result from disorders of the bone Can result from disorders of the bone marrow, such as cancer; autoimmune marrow, such as cancer; autoimmune diseases; renal failure due to lack of diseases; renal failure due to lack of erythropoietin; Berythropoietin; B1212 or folate deficiency; or folate deficiency; congenital problems; or it may be induced congenital problems; or it may be induced by radiation, toxins or the use of some by radiation, toxins or the use of some drugs, such as chloramphenicol.drugs, such as chloramphenicol.

Treatment – treat the underlying disorder, Treatment – treat the underlying disorder, blood transfusions, and possibly bone blood transfusions, and possibly bone marrow transplantmarrow transplant

PosthemorrhagicPosthemorrhagic

Caused by sudden loss of blood.Caused by sudden loss of blood. Can be fatal if loss exceeds 40- Can be fatal if loss exceeds 40-

50 % of plasma volume.50 % of plasma volume. Treatment is to restore blood Treatment is to restore blood

volume by intravenous volume by intravenous administration of saline, dextran, administration of saline, dextran, albumin, plasma or whole blood.albumin, plasma or whole blood.

Hemolytic AnemiaHemolytic Anemia Red blood cells are formed, but are Red blood cells are formed, but are

broken down. broken down. May be acquired or hereditary.May be acquired or hereditary. Acquired hemolytic anemia is Acquired hemolytic anemia is

extrinsic, due to factors outside the extrinsic, due to factors outside the red blood cell, such as an abnormal red blood cell, such as an abnormal autoimmune response that targets autoimmune response that targets red cells, or by improper matches red cells, or by improper matches during transfusions; or due to during transfusions; or due to infection, systemic diseases, or infection, systemic diseases, or drugs or toxins.drugs or toxins.

Hereditary or intrinsic hemolytic Hereditary or intrinsic hemolytic anemias:anemias:

Sickle cell anemia –Sickle cell anemia – due to a change due to a change in one amino acid in each of the beta-in one amino acid in each of the beta-chains in the globin, under conditions of chains in the globin, under conditions of low oxygen the hemoglobin forms low oxygen the hemoglobin forms insoluble threads that change the shape insoluble threads that change the shape of the erythrocyte into a crescent. This of the erythrocyte into a crescent. This shape is not as flexible and tend to be shape is not as flexible and tend to be trapped in the capillaries, where they trapped in the capillaries, where they obstruct blood flow and cause ischemic obstruct blood flow and cause ischemic injury.injury.

The life span of a sickled cell is only The life span of a sickled cell is only 20 days rather than 120, and is 20 days rather than 120, and is removed from circulation by the removed from circulation by the spleen. spleen.

Either mechanism causes a chronic Either mechanism causes a chronic anemia.anemia.

Sickle crisisSickle crisis: episodes of acute : episodes of acute sickling that block blood flow, posing sickling that block blood flow, posing the threat of widespread and the threat of widespread and possibly life-threatening ischemic possibly life-threatening ischemic organ damage.organ damage.

This is an inheritable condition.This is an inheritable condition. If a person has only one defective gene, it If a person has only one defective gene, it

is called sickle cell trait, and the person is is called sickle cell trait, and the person is essentially normal. This condition tends essentially normal. This condition tends to persist because it protects against to persist because it protects against malaria. When a cell becomes infected by malaria. When a cell becomes infected by the parasite, the cell sickles and is the parasite, the cell sickles and is removed from circulation, preventing removed from circulation, preventing reproduction of the parasite.reproduction of the parasite.

Only when a person inherits two defective Only when a person inherits two defective genes does sickle cell anemia occur.genes does sickle cell anemia occur.

Thalassemia Thalassemia is another hemolytic is another hemolytic disorder where the alpha or beta chains disorder where the alpha or beta chains of the globin are defective, or the beta of the globin are defective, or the beta chain is not produced. When the beta chain is not produced. When the beta protein is lacking, the alpha protein protein is lacking, the alpha protein accumulates and causes destructive accumulates and causes destructive membrane effects, causing these cells to membrane effects, causing these cells to be rapidly removed from the circulation.be rapidly removed from the circulation.

Highest incidence in populations around Highest incidence in populations around the Mediterranean and Southeast Asia.the Mediterranean and Southeast Asia.

Problem occurs when two defective genes Problem occurs when two defective genes are inherited; heterozygotes are are inherited; heterozygotes are essentially normal.essentially normal.

Thalassemia major is an inherited form Thalassemia major is an inherited form of hemolytic anemia, characterized by of hemolytic anemia, characterized by red blood cell (hemoglobin) production red blood cell (hemoglobin) production abnormalities. This is the most severe abnormalities. This is the most severe form of anemia, and the oxygen form of anemia, and the oxygen depletion in the body becomes depletion in the body becomes apparent within the first 6 months of apparent within the first 6 months of life. If left untreated, death usually life. If left untreated, death usually results within a few years. Note the results within a few years. Note the small, pale (hypochromic), abnormally-small, pale (hypochromic), abnormally-shaped red blood cells associated with shaped red blood cells associated with thalassemia major. thalassemia major.

Myeloproliferative Myeloproliferative DisordersDisorders

The opposite of anemias – here we have The opposite of anemias – here we have too many RBC’s.too many RBC’s.

Polycythemia – excessive production of Polycythemia – excessive production of RBC’sRBC’s– Primary polycythemia – cause is Primary polycythemia – cause is

unknown, but is in effect, a benign unknown, but is in effect, a benign tumor of the marrow, leading to tumor of the marrow, leading to increased numbers of stem cells and increased numbers of stem cells and therefore RBC’s, and splenomegally.therefore RBC’s, and splenomegally.

– Polycythemia veraPolycythemia vera – rare, mostly – rare, mostly Northern European Jewish males Northern European Jewish males between 60 – 80 yrs.between 60 – 80 yrs.

Secondary PolycythemiaSecondary Polycythemia

Due to the overproduction of Due to the overproduction of erythropoietin caused by hypoxia. erythropoietin caused by hypoxia. This is more common.This is more common.

Seen in:Seen in:– Persons living at high altitudesPersons living at high altitudes– SmokersSmokers– COPD patientsCOPD patients– Congestive heart failure patientsCongestive heart failure patients

Polcythemia leads to :Polcythemia leads to :– Increased blood volume and viscosityIncreased blood volume and viscosity– Congestion of liver and spleenCongestion of liver and spleen– ClottingClotting– Thrombus formationThrombus formation– (last two may be due increased numbers (last two may be due increased numbers

of platelets along with the increase in of platelets along with the increase in RBC’s due to bone marrow dysfunction.)RBC’s due to bone marrow dysfunction.)

Clinical manifestation Clinical manifestation of Polycythemiaof Polycythemia HeadacheHeadache DizzinessDizziness Weakness Weakness Increased blood pressureIncreased blood pressure Itching / sweatingItching / sweating

Treatment of Treatment of polycythemiapolycythemia Reduce blood volume by phlebotomy Reduce blood volume by phlebotomy

– 300-500 ml. – 300-500 ml. Treat underlying condition - Stop Treat underlying condition - Stop

smokingsmoking Radioactive phosphorus injectionsRadioactive phosphorus injections Prevent thrombosisPrevent thrombosis