BloodBlood

HematologyHematology

BLOOD: BLOOD: actually is a specialized CT with actually is a specialized CT with intercellular material comprised entirely of intercellular material comprised entirely of fluid.fluid.

formed from undifferentiated mesenchyme formed from undifferentiated mesenchyme of embryos (similar to other CT)of embryos (similar to other CT)- contains formed elements (blood cells) and - contains formed elements (blood cells) and plasmaplasma

1. In average human blood formed elements 1. In average human blood formed elements comprise 46% of blood volume, plasma 54% comprise 46% of blood volume, plasma 54% (hematocrit or pcv- packed cell volume)(hematocrit or pcv- packed cell volume)

Men: 40-50% (5-6 million RBC's/mm3)Men: 40-50% (5-6 million RBC's/mm3) Women: 35-45% (4-5 million RBC's/mm3)Women: 35-45% (4-5 million RBC's/mm3)

2. Blood volume in average human about 5 L 2. Blood volume in average human about 5 L (8% of body weight)(8% of body weight)

3. Formed elements include: erythrocytes 3. Formed elements include: erythrocytes (RBC), leukocytes (WBC), platelets (RBC), leukocytes (WBC), platelets (thrombocytes which are cell fragments (thrombocytes which are cell fragments from megakaryocyte).from megakaryocyte).

Origin of bloodOrigin of blood:: Blood cells originate in red bone marrowBlood cells originate in red bone marrowfrom hematopoietic stem cells (pluripotent from hematopoietic stem cells (pluripotent

or hematocytoblasts). These in turn will or hematocytoblasts). These in turn will differentiate (progenitor cells) into the differentiate (progenitor cells) into the specialized blood cells.specialized blood cells.

Erythropoietin (EPO): Hormone Erythropoietin (EPO): Hormone produced in the kidneys used to produced in the kidneys used to stimulate erythropoiesis in the bone stimulate erythropoiesis in the bone marrow.marrow.

EPO is produced in response to:EPO is produced in response to:

- hypoxia- hypoxia

- decrease in rbc count - decrease in rbc count

- decrease in hemoglobin conc. - decrease in hemoglobin conc. AnemiaAnemia

Refer to handout on common anemia'sRefer to handout on common anemia's

Blood:Blood:

pH- 7.35-7.45 (arterial blood)pH- 7.35-7.45 (arterial blood)

- slightly alkaline- slightly alkaline

4-5x more viscous than water4-5x more viscous than water

Blood temp. approx. 100F.Blood temp. approx. 100F.

Salt conc. .85-.90% (Saline?)Salt conc. .85-.90% (Saline?)

Erythrocytes (RBC’s)Erythrocytes (RBC’s)- Erythropoiesis: begin as immatureErythropoiesis: begin as immature

proerythroblasts which in turn proerythroblasts which in turn mature to a reticulocytes and mature to a reticulocytes and ultimately an erythryocyte.ultimately an erythryocyte.

- Adult RBC production is Adult RBC production is approximately 200 billion RBC's approximately 200 billion RBC's /day.  This means that RBC's are /day.  This means that RBC's are produced at the astonishing rate of 2 produced at the astonishing rate of 2 million/sec in healthy adults.million/sec in healthy adults.

RBC's outnumber WBC's about 800 to 1RBC's outnumber WBC's about 800 to 1Female: RBC count is 4-5 million/mm3Female: RBC count is 4-5 million/mm3Male: RBC count is about 5-6 million/mm3Male: RBC count is about 5-6 million/mm3

Characteristics:Characteristics: - anucleated - anucleated - 7.5 micrometers in diameter- 7.5 micrometers in diameter

- lacks other subcellular organelles as well - lacks other subcellular organelles as well - biconcave shaped (allows a 20-30% - biconcave shaped (allows a 20-30% increase increase in surface area which in surface area which increases increases efficiency of O2 and efficiency of O2 and CO2 transport)CO2 transport) - life span of 120 days- life span of 120 days

- The protein The protein spectrinspectrin allows cell to flex allows cell to flex and change shape to squeeze through and change shape to squeeze through capillaries.capillaries.

- Ability to carry O2 and CO2- hemoglobinAbility to carry O2 and CO2- hemoglobin

Hemoglobin (Hb):Hemoglobin (Hb):- Protein found in rbc’s that bind O2. Protein found in rbc’s that bind O2. - Imparts reddish color to rbc.Imparts reddish color to rbc.- Hemoglobin (Hb) in g/100 mL of blood Hemoglobin (Hb) in g/100 mL of blood 13-18 g of hemoglobin/100 mL of blood in 13-18 g of hemoglobin/100 mL of blood in

adult malesadult males 12-16 g of hemoglobin/100 mL of blood in 12-16 g of hemoglobin/100 mL of blood in

adult femalesadult females

- Hb contains a structure called the porphyrin - Hb contains a structure called the porphyrin ring (also called heme) that is bound to a ring (also called heme) that is bound to a centrally located Fe molecule.centrally located Fe molecule.

- Each Hb can carry 4 O2's.  One RBC contains - Each Hb can carry 4 O2's.  One RBC contains 250 million Hb molecules (ie. 1 RBC can 250 million Hb molecules (ie. 1 RBC can carry as many as 1 billion molecules of O2). carry as many as 1 billion molecules of O2).

- O2 is picked up in the lungs and binds to Hb - O2 is picked up in the lungs and binds to Hb along with Halong with H++. Hb is now called . Hb is now called oxyhemoglobinoxyhemoglobin (bright red arterial blood). (bright red arterial blood).

- When O2 is dumped off in the tissues it is - When O2 is dumped off in the tissues it is called called deoxyhemoglobindeoxyhemoglobin..

- When Hb picks up CO2 from tissues it binds - When Hb picks up CO2 from tissues it binds to the protein portions of the Hb. Hb to the protein portions of the Hb. Hb carrying CO2 is called carrying CO2 is called carbaminohemoglobin.carbaminohemoglobin. This gives venous This gives venous blood its bluish color. Venous blood is not blood its bluish color. Venous blood is not blue due to the decrease in O2 in the blood.blue due to the decrease in O2 in the blood.

Life cycle of an RBCLife cycle of an RBC1- Nutrients (folic acid, Fe and Vit. B-12) are 1- Nutrients (folic acid, Fe and Vit. B-12) are

absorbed in the small intestine.absorbed in the small intestine.2- Nutrients go to red bone marrow2- Nutrients go to red bone marrow3- RBC’s develop from progenitor cells3- RBC’s develop from progenitor cells4- RBC’s released in bloodstream and 4- RBC’s released in bloodstream and

circulate for approx. 120 dayscirculate for approx. 120 days5- After 120 days, RBC’s are broken down by 5- After 120 days, RBC’s are broken down by

macrophages in the liver and spleenmacrophages in the liver and spleen6- Hb is broken down into heme and globin6- Hb is broken down into heme and globin7- Heme decomposes into Fe and a greenish 7- Heme decomposes into Fe and a greenish

substance called biliverdinsubstance called biliverdin

8- Iron binds to a protein called transferrin 8- Iron binds to a protein called transferrin which ultimately travels to the red bone which ultimately travels to the red bone marrow to be recycled. (80% of Fe in marrow to be recycled. (80% of Fe in the body is stored in the liver as ferritin)the body is stored in the liver as ferritin)

9- Some biliverdin is converted to 9- Some biliverdin is converted to bilirubin, as yellowish/orange pigment bilirubin, as yellowish/orange pigment found in bile –gallbladder.found in bile –gallbladder.

10- Bilirubin travels into small intestine 10- Bilirubin travels into small intestine and 10 % is metabolized to urobilinogen and 10 % is metabolized to urobilinogen (urochromes filtered in the liver)(urochromes filtered in the liver)

11- 90% of bilirubin exits in the feces 11- 90% of bilirubin exits in the feces giving fecal matter its brown color giving fecal matter its brown color (stercobilin)(stercobilin)

- RBC’s do not have mitochondria so RBC’s do not have mitochondria so they obtain their energy from they obtain their energy from anaerobic glycloysis (produce ATP)anaerobic glycloysis (produce ATP)

- primary component in this pathway - primary component in this pathway isis

2,3 diphosphoglycerate (2,3 DPG)2,3 diphosphoglycerate (2,3 DPG)

- assists in unloading O2 in the - assists in unloading O2 in the tissues tissues from the Hg in the RBCfrom the Hg in the RBC

Leukocytes (WBC’):Leukocytes (WBC’):- Contain a nucleus plus all common organellesContain a nucleus plus all common organelles- 5,000-10,000/mm5,000-10,000/mm3 3 lab valueslab values- Have the ability to move once outside the Have the ability to move once outside the

blood (diapedesis) through fenestrations blood (diapedesis) through fenestrations (holes) in the capillaries(holes) in the capillaries

- Ability to be attracted to chemicals Ability to be attracted to chemicals (chemotaxis)(chemotaxis)

- Grouped according to the presence of Grouped according to the presence of granules in their cytoplasm (granules in their cytoplasm (Chasing bacteria)

Granular leukocytes/ granulocytes/ myeloblast Granular leukocytes/ granulocytes/ myeloblast series cells/ polymorphonuclear cells (PMN’s)series cells/ polymorphonuclear cells (PMN’s)

- NeutrophilsNeutrophils- BasophilsBasophils- EosinophilsEosinophils

Agranular leukocytes (agranulocytes):Agranular leukocytes (agranulocytes):- MonocytesMonocytes- LymphocytesLymphocytesWBC’s are involved in immune WBC’s are involved in immune

functions and are primarily active functions and are primarily active outside the blood stream.outside the blood stream.

To remember granulocytic and To remember granulocytic and agranulocyticagranulocytic““Every Boy Needs Mommies Love”Every Boy Needs Mommies Love”

To remember percentage of proportionTo remember percentage of proportion““Never Let Monkeys Eat Bananas”Never Let Monkeys Eat Bananas”

NEVER: neutrophils (60%)NEVER: neutrophils (60%)

LET: lymphocytes (30%) LET: lymphocytes (30%)

MY: monocytes (5%) MY: monocytes (5%)

ENGINE: eosinophils (4%)ENGINE: eosinophils (4%)

BLOW: basophils (0-1%) BLOW: basophils (0-1%)

Neutrophil (lobed)Neutrophil (lobed)

Neutrophils:Neutrophils:

2-5 lobes that are interconnected by fine 2-5 lobes that are interconnected by fine strands (sometimes called “segs”)strands (sometimes called “segs”)

- acute inflammatory response and - acute inflammatory response and phagocytize bacteria, fungi and some phagocytize bacteria, fungi and some virusesviruses

- circulate in blood for short period of time - circulate in blood for short period of time (10 hrs.) before migrating into tissues (5 (10 hrs.) before migrating into tissues (5 days).days).

- first white cell on the scene of an infection- first white cell on the scene of an infection Neutropenia: too few neutrophilsNeutropenia: too few neutrophils Neutrophilia: too many neutrophilsNeutrophilia: too many neutrophils

BasophilBasophil

Basophils:Basophils:- Nucleus is typically bilobedNucleus is typically bilobed- Granules contain histamine and heparinGranules contain histamine and heparin- Little ameboid and no phagocytic activityLittle ameboid and no phagocytic activity- when basophil stimulated by an antigen or when basophil stimulated by an antigen or

by tissue injury, responds byby tissue injury, responds bybreaking open granulations causing breaking open granulations causing histamine release. Histamine release histamine release. Histamine release initiates inflammatoryinitiates inflammatoryreaction causing vasodilation and reaction causing vasodilation and increasing permeability of blood vessels.increasing permeability of blood vessels.

- erythema- erythema- heat- heat- plasma release- plasma release

EosinophilEosinophil

EosinophilEosinophil- nucleus usually bilobed nucleus usually bilobed - High number present in an allergic High number present in an allergic

reaction.reaction.- Phagocytize and kill larval stage of Phagocytize and kill larval stage of

parasitic worms.parasitic worms.- Phagocytosis of the Ab/Ag complex Phagocytosis of the Ab/Ag complex

found in an immune responsefound in an immune response

Lymphocytes:Lymphocytes:- 30% of WBC population30% of WBC population- Large dark purple nucleusLarge dark purple nucleus- Small, medium and largeSmall, medium and large- Majority are not found in circulating blood Majority are not found in circulating blood

but in lymphoid tissue (nodes, spleen, but in lymphoid tissue (nodes, spleen, marrow etc..)marrow etc..)

- Smallest WBC slightly larger than RBCSmallest WBC slightly larger than RBC- T- lymphocytes (immune response)T- lymphocytes (immune response)- B- lymphocytes (antibodies-immunoglobins)B- lymphocytes (antibodies-immunoglobins)

We will cover these two lymphocytes in much We will cover these two lymphocytes in much detail under immunologydetail under immunology

LymphocyteLymphocyte

Monocytes:Monocytes:- Largest of the WBC’sLargest of the WBC’s- Nucleus is indentedNucleus is indented- monocytes are phagocyticmonocytes are phagocytic- when monocytes leave bloodstream they when monocytes leave bloodstream they

rapidlyrapidlytransform to macrophages that are very active transform to macrophages that are very active in ingesting bacteria, deadin ingesting bacteria, deadcells, tissue debris (“wandering cells, tissue debris (“wandering macrophages”)macrophages”)

- Uses filopodia to search for things to eatUses filopodia to search for things to eat- cytoplasmic extensions- cytoplasmic extensions

- stimulate antibody production by lymphocytes.stimulate antibody production by lymphocytes.

MonocyteMonocyte

Platelets:Platelets:- Not cells but cell fragmentsNot cells but cell fragments- Hemocytoblast Megakaryoblast Hemocytoblast Megakaryoblast

MegakaryocyteMegakaryocyte- 150,000 to 400,000/mm3 150,000 to 400,000/mm3 - AnucleatedAnucleated- Aid in blood clottingAid in blood clotting- Arise from megakaryocytes in red bone Arise from megakaryocytes in red bone

marrowmarrow- granulated: granules contain serotonin that granulated: granules contain serotonin that

aid in vasoconstrictionaid in vasoconstriction- Form a temporary plug when vessel is Form a temporary plug when vessel is

damaged.damaged.- Formation is regulated by a hormone called Formation is regulated by a hormone called

thrombopoietinthrombopoietin

Platelets Platelets

Plasma vs. serum:Plasma vs. serum:Plasma Plasma is an aqueous (92% water), straw is an aqueous (92% water), straw

colored solution containing proteins, lipids colored solution containing proteins, lipids (digested nutrient), blood gases (O(digested nutrient), blood gases (O22, CO, CO22 and Nand N22), amino-acids, vitamins, hormones, ), amino-acids, vitamins, hormones, and electrolytes (i.e. Na and Cl). and electrolytes (i.e. Na and Cl). The main plasma proteins are: The main plasma proteins are: 1- gamma globulins (immunoglobulins or 1- gamma globulins (immunoglobulins or

antibodies)- lymphoid tissueantibodies)- lymphoid tissue2- albumins (maintains osmotic pressure 2- albumins (maintains osmotic pressure of blood) - liverof blood) - liver3- fibrinogen (clotting agent)- liver3- fibrinogen (clotting agent)- liver

To obtain plasma, blood sample is spun To obtain plasma, blood sample is spun down with an anticoagulant in the tubedown with an anticoagulant in the tube

Serum:Serum:

If blood is allowed to clot, the clear If blood is allowed to clot, the clear yellow liquid that separates out is yellow liquid that separates out is called serum. Serum is similar to called serum. Serum is similar to plasma but lacks fibrinogen and plasma but lacks fibrinogen and other clotting agents.other clotting agents.

To obtain serum, blood sample is spun To obtain serum, blood sample is spun down with down with nono anticoagulant in the anticoagulant in the tube.tube.

Normal lab values of common Normal lab values of common substances dissolved in blood substances dissolved in blood plasma/serum.plasma/serum.

Glucose: 70-110 mg/dl (fasting)Glucose: 70-110 mg/dl (fasting)

Sodium (Na): 135 - 145 mEq/L Sodium (Na): 135 - 145 mEq/L

Calcium (Ca): 8.5- 10.5 mEq/L Calcium (Ca): 8.5- 10.5 mEq/L

Chloride (Cl): 98-106 mEq/LChloride (Cl): 98-106 mEq/L

Potassium (K): 3.5 - 5.0 mEq/L Potassium (K): 3.5 - 5.0 mEq/L

Bicarbonate (HCO3): 18-23 mEq/LBicarbonate (HCO3): 18-23 mEq/L

Hemostasis- blood stoppageHemostasis- blood stoppageInitial goal is to turn liquid (blood) into Initial goal is to turn liquid (blood) into

gel (coagulation).gel (coagulation).Steps:Steps:1- smooth muscle in blood vessel wall 1- smooth muscle in blood vessel wall

contracts when vessel is damaged contracts when vessel is damaged (vasospasm) (vasospasm)

-decrease blood loss, may seal -decrease blood loss, may seal off off opening opening

- slower flow of blood also helps - slower flow of blood also helps platelets & coagulation. platelets & coagulation.

2- attracted & stick to damaged vessel walls 2- attracted & stick to damaged vessel walls & to other sticky platelets & to other sticky platelets

-platelets release attractant -platelets release attractant chemicals that attracts other platelets chemicals that attracts other platelets

-platelets release thrombospondins -platelets release thrombospondins that that aid platelet adhesion aid platelet adhesion

- platelet plug- platelet plug

3- Blood coagulation: Cascade of blood 3- Blood coagulation: Cascade of blood clotting chemicals.clotting chemicals.

To form a blood clot a soluble plasma To form a blood clot a soluble plasma protein, fibrinogen (factor I), must be protein, fibrinogen (factor I), must be converted to insoluble threads called fibrin.converted to insoluble threads called fibrin.

Prothrombin (factor II) is a protein made in the Prothrombin (factor II) is a protein made in the liver and is a normal part of blood plasma. liver and is a normal part of blood plasma.

a. Prothrombin is converted to thrombin (factor a. Prothrombin is converted to thrombin (factor II a).II a).

b. Thrombin fragments fibrinogen.b. Thrombin fragments fibrinogen.

c. Fibrinogen joins to form long slender threads c. Fibrinogen joins to form long slender threads of fibrin.of fibrin.

d. Fibrin threads attach to the damaged blood d. Fibrin threads attach to the damaged blood vessels and more blood cells and platelets vessels and more blood cells and platelets will stick. This mesh will form a blood clot.will stick. This mesh will form a blood clot.

Under normal conditions clotting of blood in Under normal conditions clotting of blood in the body should only occur if blood remains the body should only occur if blood remains stationary. Embolus vs. thrombusstationary. Embolus vs. thrombus

Blood typing (ABO):Blood typing (ABO):- Discovered in 1900 by Dr. Karl Discovered in 1900 by Dr. Karl

LandsteinerLandsteiner

A – antigen A (40%)A – antigen A (40%)

B – antigen B (10%)B – antigen B (10%)

AB – antigen A & B (universal recipient AB – antigen A & B (universal recipient 5%) 5%)

O – no antigens (universal donor O – no antigens (universal donor 45%)45%)

In the plasma:In the plasma:

A: Antigen A in RBCA: Antigen A in RBC

Plasma: anti-B type antibodies Plasma: anti-B type antibodies

B: Antigen B B: Antigen B

Plasma: anti-A type antibodiesPlasma: anti-A type antibodies

AB: antigen A&BAB: antigen A&B

Plasma: no anti-A or anti-B antibodiesPlasma: no anti-A or anti-B antibodies

O: no antigens O: no antigens

Plasma: both anti-A and anti-B Plasma: both anti-A and anti-B antibodiesantibodies

Blood Blood TypeType

Type of Type of Antigen?Antigen?

Type of Type of Antibody?Antibody?

Receive?Receive?

AA A antigenA antigen Anti-BAnti-B A, OA, O

BB B antigenB antigen Anti-AAnti-A B, OB, O

ABAB Both A and Both A and B antigensB antigens

NoneNone A, B, AB, A, B, AB, OO

OO NoneNone Both Anti-A Both Anti-A and Anti-Band Anti-B

O onlyO only

Type O 45%

Type A 42%

Type B 10%

Type AB 3%

Rh factor (Antigen D)Rh factor (Antigen D)

Rh + = Rh factor antigen (marker) on RBC Rh + = Rh factor antigen (marker) on RBC (85%)(85%)

Rh - = no Rh antigenRh - = no Rh antigen

Rh- mother and Rh+ father: If baby inherits Rh- mother and Rh+ father: If baby inherits Rh+ from dad, mom’s blood will recognize Rh+ from dad, mom’s blood will recognize baby’s blood as foreign and will attack it.baby’s blood as foreign and will attack it.

- Erythroblastosis fetalis- Erythroblastosis fetalisBlood typing

Blood Blood TypeType

Presence Presence of D of D Antigen?Antigen?

Type of Type of AntibodyAntibody??

ReceiveReceive??

Rh PositiveRh Positive

YesYes NoneNone + and -+ and -

Rh Rh NegativeNegative NoNo Anti-DAnti-D - only- only