Biology 2402 AP

Biology 2402 AP II     Lecture Notes
Blood
Dr. Weis

BLOOD
Part of the cardiovascular system.
Considered ECF located in Blood Vessels
Study of Blood :: Hematology
Hemogram for clinical diagnostics = Erythron, Leukon, Thrombon, Total Protein

Connective tissue :

~ 45% formed elements : RBC, WBC, Platelets

~ 55% fluid and ground substance.......Plasma

Of the 45% Connective Tissue formed element portion

(Hematocrit which is the actual test

or PCV which is calculated, both are expressed as %)

I. Cellular Components :

A. Red Blood Cells :: RBC formation......called Erythropoiesis.......takes approx 1 wk

PHSC --> myeloid committed stem cell --> proerythroblast line [rubriblast --> prorubriblast --> rubricyte --> (starts loosing ribosomes, synth. hemoglobin) --> metarubricyte (nucleus ejected)] ---> reticulocyte (ribosome remnants clumped) -->erythrocyte

Red Blood Cells (RBC)or Erythrocytes = make up most of the formed element % of blood

1) Characteristics....

2) Primary Function....

* ENCLOSE hemoglobin within membrane for :: reversible binding of oxygen and TRANSPORT to tissues

Note: The lack of mitochondria, means no Oxygen usage & therefore provides good mechanism for transport

Most common form of human adult hemoglobin is called Hemoglobin A and consists of a protein globulin made up of 4 polypeptide chains (two alpha and two beta) that combine with four groups of a red pigment Heme that contains ferrous iron (Fe++) in the center of each group.

In RBC's, there are millions of hemoglobin molecules that make up 95% of the proteins in RBCs

there will be 15 grams of Hemoglobin per deciliter (dl) of whole blood, written as 15g/dl.

Overall, in the body fluids, the hemoglobin % will be approximately 34%, (34g/dl)

The oxygen can reversibly bind to the ferrous iron so hemoglobin can transport up to 4 oxygen molecules:

Hormonal control ........

by a glycoprotein from the Kidneys (90%) & liver (10%) : Erythropoietin
secreted in response to low oxygen tissue levels to cause an increased stem cell production of the proerythroblast stem cell series and cause more rapid maturation.

Additonal hormones such as T4, GH, and androgens also influence erythropoiesis

Requirements for RBC formation ::

iron.............stored in the body, primarily in the liver,
bound to protein for transport as transferrin and storage as ferritin.

B-complex vitamins.....B-12, B-6, and folic acid

B-12 needed for DNA synthesis and maturation.
(B-12 absorption from the digestive track requires
intrinsic factor that is produced in the stomach).

Folic acid needed for DNA and RNA

Life span of RBC............100-120 days

degenerate..........trapped primarily in spleen, but can be phagocytized in the liver and bone marrow

therefore the possible major blood groups of concern are: A, B, AB, and O

In Plasma : preformed antibodies --> agglutinins (IgM or IgG gamma globulins) occur after birth, due to exposure of A or B antigens in food. If Antibodies react with the RBC surface antigen receptor, it can cause a clumping {agglutination} of the cells and mark them for destruction by the immune system. Also, bacteria can attach to 2 or more RBC due to bivalent/polyvalent structure cause cells to adhere and clump.

Therefore to create a chart we have :

Genotype	Phenotype	Blood Group RBC antigen called an agglutinogen	Plasma antibodies called agglutinins	Blood received
IA IB	AB	A & B	none	A,B,AB,O
IBi, IBIB	BO, BB	B	anti-A	B,O
IAi, IAIA	AO, AA	A	anti-B	A,O
ii	OO	none	anti-A & anti-B	O

Population in Percentage for each major blood type:
47% O
40% A (80% are A1 and 20% are A2)
10% B
3% AB

Percentage of each ABO Blood Type by Country
Country	U.S.	G.B.	Germany	Japan	China
ABO Type	%	%	%	%	%
O	46	47	41	30	35
A	40	42	45	38	27
B	10	8	10	22	26
AB	4	3	4	10	12

Remember the genotype is a co-dominant pattern of inheritance I¨ I¨

Blood typing ...use recipient RBC, and anti-Sera

RBC membrane	Serum immune proteins
	anti-A	anti-B
O	(+)	(+)
A (subtypes 1 and 2)	(-)	(+)
B	(+)	(-)
AB	(-)	(-)

For more information about Blood Groups and Subtypes use the following links:

http://www.owenfoundation.com/Health_Science/ABO_Blood_Cells.html

http://www.owenfoundation.com/Health_Science/Blood_Group_A_Subtypes.html

Transfusion Reactions ::

DONOR RBC are attacked by RECIPIENT'S plasma agglutinins causing : clumping, lysis, release of hemoglobin

sequela : acute renal failure : due to circulatory shock, vasoconstriction, and blocking of renal tubules

i.e..........

Transfusion reactions cause agglutination (clumping) and the phagocytic process (hrs - days) by the reticuloendothelial system will destroy the agglutinated cells, releasing hemoglobin.

Acute renal failure (kidney shutdown) can occur due to :

each person will have one of each of the three Rh antigens:

for instance :: for the C antigen: If the person has a C, cannot have c, if no C, then must have the c

Rh+.....RBC carry Rh antigen D, majority of the population are Rh+ (85-95%)

Rh- means negative for D & will have d. (remember, everyone has Rh agglutinogens)

In plasma, anti-Rh antibodies develop if individual is sensitized (Rh+ mixed with Rh-) problems seen

* delayed transfusion reactions

* severe reactions in future transfusions

* pregnancy

Rh- mother with second Rh+ fetus:: If mother was previously sensitized by first Rh+ fetus, her anti Rh antibodies can diffuse across the placenta and cause agglutination (clumping) of the fetus' blood. A condition called: Erythroblastosis fetalis
The baby will be jaundiced and ANEMIC with an enlarged liver & spleen.
Death is due to the severe anemia and treatment involves multiple transfusions

II. WHITE BLOOD CELLS :: Leukocytes

Production of WBC : Leukopoiesis

stimulated by hormones collectively called ->Colony Stimulating factors (C-SF)

Pathway :

Hematocytoblast (stem cell) ----------> undergoes Leukopoiesis

myeloid stem cell lymphoid stem cell

| | |

myeloblast monoblast lymphoblast

| | |

promyelocyte promonocyte prolymphocyte

| | |

myelocyte monocyte lymphocyte

| | |

metamyelocyte macrophage T, B, NK

| |

band plasma cells

| from B cells

granular WBC [PMN, Eos, Baso]

WBC Numbers : 7000 per microliter of blood

Function : defense. Mobile cells that will travel through blood stream and go to tissues by diapedesis: a movement type of attraction caused by the release of inflammatory chemicals in the tissues.

Two Categories : Granulocytes and Agranulocytes

Can identify different WBC on blood smear :

Differential white cell count, also known as a WBC differential

A. Granulocytes : From myelocytic stem cell line

1) Neutrophils : ("polymorphs" or "segs" or "PNMs")

40-70 % of WBC number

2x RBC size

granules take up both stains == Neutral

lobed nuclei : 3-6 lobes

respond to damaged tissue, phagocytize bacteria and destroy pathogens using various chemicals and enzymes
release several chemical mediators to signal other leukocytes to aid in defense response

1 week formation, 1 day (12-24 hour) lifespan

2) Eosinophils

1-4 % of WBC number

nucleus 2 lobes

granules are large and pink staining lysozomes

function : respond and digest antigen-antibody complexes usualy caused by allergic reactions (lungs of asthmatics, skin)

parasitic infection (schistosomiasis, trichinosis)

3) Basophils

0-3% of WBC number

nucleus is U shaped or bilobed

granules contain histamine, bradykinin, serotonin and will stain blue

function : some allergic reactions involving IgE

some parasitic diseases in animals (heartworm disease)

possibly related to mast cells (as a tissue form of the cell)

B. Agranulocytes

lack granules, nuclei round to kidney shaped

1) Lymphocytes : from Lymphocytic stem cell line

Intensity of inflammation is usually proportional to the degree of tissue injury.

Results :: wall off area of injury by swelling & clotting to delay spread of bacteria or toxic substances

Local macrophages in the injured tissue are the first to respond within the 1st hour.

Neutrophils arrive within hours by chemotaxis and diapedisis. Other monocytes and macrophages arrive over the next few days to weeks to help with the clean-up

Bone Marrow is stimulated to produce more WBCs over the next week and months if necessary.

WBC Disorders :

Leukocytosis : high WBC count

Leukopenia : low WBC count

Leukemias : abnormal, undifferentiated WBC = cancer

Mononucleosis : increase in monocytes, viral induced

Individual cell increases or decreases :

Neutrophilia, lymphopenia, eosinophilia etc., based on differential white cell count

III. Platelets

Size : 2 - 4 micrometers, fragments of megakaryocyte, enzyme bags

Function : clotting process --> enzymes, plug, contract

Formation....:: Thrombopoeisis via enzyme thrombopoietin

Hemocytoblast --> megakaryoblast --> promegakaryocyte -->
megakaryocyte --> cytoplasmic fragments called thrombocytes or platelets

Platelets have many functional characteristics of whole cells:

Platelet formation in the red bone marrow is regulated by hormone : Thrombopoietin [TPO] from the kidneys as well as Interleukin 6 (Il-6) and Multi-CSF

Life span : approx. 10 days (8-12 days) and are removed by the macrophages (spleen)

Number : 150,000-300,000 per microliter

Low number of platelets : thrombocytopenia, results in bleeding disorders {pettechia, ecchymosis}

Excess number of platelets : thrombocytosis, results in thrombus formation

IV. Plasma ~ 55% of blood volume (46-63%)

92% water

remaining : Plasma Proteins.....90% of which are synthesized in the liver

NOTE: serum Vs. plasma.........no clotting factors in serum

Blood Tests :

CBC : Complete blood count

RBC.....#, size, hemoglobin content

WBC.....differential count

platelet count

HCT (hematocrit) or PCV (packed cell volume)

Clot times

Chemistries

a) vascular spasm.......vasoconstriction due to local pain

receptors, smooth muscle contraction will decrease diameter of vessel

In smaller vessels, platelets release thromboxane A2 to cause vasoconstriction.

b) platelet plug...... seal break in vessel wall by attatching to damaged tissue.
Platelets become sticky, swell, take on irregular form and make processes

thromboxane A2 causes platelet granules to release chemicals to activate more platelets,
as well as vasoconstriction
Other chemicals are released such as ADP, serotonin, Ca++, and PDGF {platelet derived growth factor}

c) coagulation (blood clotting to prevent blood loss)

two pathways (extrinsic and intrinsic) cascade into one common pathway

Events of the common pathway

Whether or not the blood will coagulate depends on the balance between the two groups of substances above.

Coagulation Cascade : Two Pathways --> Extrinsic, and Intrinsic

both pathways require calcium ion (Factor IV)

both sequence forward toward Factor X,
then use the same pathway (common pathway) toward forming prothrombin activator (PTA)

extrinsic pathway --> shortcut, clot can start within 15 seconds, begins at vessel wall

intrinsic pathway --> clotting 3-6 min, begins in the bloodstream

remember...prothrombin and fibrinogen are plasma proteins formed in the liver.

Vit K is needed for prothrombin formation.

Extrinsic Pathway :

trauma to tissue releases tissue thromboplastin (Factor III) and reacts with Factor VII and Ca++ to activate ---> X

X ------------> active X

PT (Factor II) -----------------à thrombin (IIa)

fibrinogen (Factor I) --------------------à fibrin, stabilized with XIIIa to help crosslinking

INTRINSIC PATHWAY : trauma to blood or exposure to collagen will activate proenzymes and cause platelets to release other chemicals to cause::

XII à XII active

XI -------à XI active

| VIIa, Ca++

IX ---------à IX active

PT (Factor II) ------------------------à thrombin (IIa)

fibrinogen (Factor I) ----------------------à fibrin

Both are positive feed back mechanisms.

Factor Xa levels for Extrinsic and Factor VIII levels for intrinsic pathways can be measured.

More common measurements are done using Factor X, PTA, thrombin and fibrinogen.

Clot retraction :

platelets contract to compress the clot, causing the edges of tissues to be pulled together for tissue repair and unneeded clots are removed by fibrinolysis involving the enzyme plasmin, the activated form of plasminogen.

Clot growth or formation is limited by :

Hemostatic Disorders :Thromboembolic and Bleeding

A. Thromboembolic

thrombus --> blood clot along a vessel wall causes blockage (occulusion)

embolus --> free floating thrombus, can become trapped in smaller vasculature

causes : roughing of vessel wall (endothelium)to slow, flowing blood = stasis

treatment : drugs --> Aspirin affects platelets adherence

Heparin affects thrombin, Cumarin

dissolve clots --> streptokinase

B. Bleeding disorders :

1) thrombocytopenia : decreased # of platelets spontaneous bleeding in small vessels

causes : suppression / destruction of myeloid tissue due to radiation, drugs, autoimmune

2) Liver disease: decreasedsynthesis of procoagulants

prothrombin in Vit K deficiency (fat soluble vitamin); needs bile to absorb fat

factors : VII, IX, X, and fibrinogen (Factor 1)