BLOOD

BLOOD FUNCTIONS
• Transport
• Immunity (later in semester )
• Hemostasis
• Homeostasis

BLOOD:
• Volume (in L) = approx. 6 - 8 % OF BODY WEIGHT (in Kg)

• 4.5 - 6.0 L

BLOOD COMPONENTS
• Plasma (Vs. Serum)
        – Proteins
        – Lipids
        – Carbohydrates
        – Ions
        – Water
• Cellular

Leukocytes
• Polymorphonuclear or granulocytes
        • Neutrophil
        • Basophil
        • Eosinophil
• Monomorphonuclear or agranulocytes
        • Monocytes (m??
        • Lymphocytes

ERYTHROCYTES

• MEN:  4.5 - 6.5 x 10⁶ cells/µl
• WOMEN:  3.8 - 5.8 x 10⁶ cells/µl

HEMATOCRIT

Blood Properties
• Hematocrit (42±5% & 47±5%)
• Density or specific gravity 1.050 g/ml
• Viscosity (3.5 - 5.5 x H₂O)
• Erythrocyte sedimentation rate (2-8 mm/hr)

HEMOGLOBIN
• 2 - 3 X108 molecules/RBC

• 12 - 16 gms/100 mls of BLOOD

Fig. 13.2
 
 

[O2] + [Hb] --> [Hb(O₂)₄]
• 98% of O₂ in blood is bound to Hb
• 1.34 mls O₂/gm of Hb
• 20.1 mls of O₂ carried/100 mls blood

ADULT HEMOGLOBIN (HbA)  Fig 13.2
• MW = 64,458
• 4 polypeptide chains - 2 pairs
        – 2  - 141 amino acids
        – 2  - 146 amino acids
• 4 heme groups
        – Porphyrin
        – Iron

OTHER TYPES OF Hb
• HbF - Fetal Hemoglobin
        – 2   &  either  (2OR  2CHAINS)
        -- High affinity for oxygen
• HbS
        – Replace #6 amino acid glutamic acid with valine in  chain
 

See Figures 16.8 – 16.10 !!!!

P₅₀

P₅₀ = [O₂] in mm Hg that yields 50%  saturation of Hb with O₂

INCREASE P₅₀ OR  DECREASE Hb  AFFINITY FOR O₂
• DECREASE pH
• INCREASE TEMPERTATURE
    (Hb UNLOADS MORE O₂
           @ GIVEN PO₂)

 
 

BLOOD TYPES
• See page 730 in the text !!!!
• Web sites to visit:
       – http://opbs.okstate.edu/~melcher/MG/MGW1/MG11121.html
        – http://ftp.bbc.co.uk/tw/9798/9801blood.shtml

ABO Blood types

 
 

Blood Type	Antigen	Antibodies
O	NONE	ANTI  A ANTI  B
A	A	ANTI  B
B	B	ANTI   A
AB	A  &  B	NONE

Rh FACTOR
1.  MAKE ANTI-RHESIS  MONKEY RED CELL ANTIBODIES IN RABBIT
2.  IF ANTI-Rh REACTS WITH HUMAN RBC --> Rh+
3.  IF ANTI-Rh DOES NOT REACT WITH HUMAN RBC ---> Rh -
                                                                        Rh FACTOR PROBLEMS
• Rh -  MOTHER CONCEIVES Rh + FETUS
• FETAL RBCs LEAK INTO MATERNAL CIRCULATION
• MOTHER PRODUCES ANTI Rh ANTIBODIES  (IgG)
• SECOND Rh +  CHILD:  FETAL RBCs ATTACKED BY MATERNAL IgG

SECOND Rh +  CHILD:  FETAL RBCs ATTACKED BY MATERNAL IgG

ERYTHROBLASTOSIS FETALIS

Rh TREATMENTS
RHOGAM:  ANTI - Rh TO MOTHER AFTER BIRTH OF FIRST CHILD.
TRANSFUSION OF SECOND CHILD

QUESTION:
WHY DOES Rh FACTOR POSE A PROBLEM WHILE ABO BLOOD TYPES DO NOT???

Erythropoietin:
• Stimulus?
     Tissue Hypoxia

STEM CELL   +  ERYTHROPOETIN ---->
     ERYTHROBLAST  ---->
       NORMOBLAST  ---->
          RETICULOCYTE ---->
             MATURE RBC
(MAKE ABOUT 2.3 X 10⁸/DAY)

ANEMIA
• Hemorrhagic - blood loss
• Aplastic - marrow damage
        – certain organics, x-rays, etc.
• Hemolytic
        – Sickle Cell & Snake Venoms
• Pernicious ( vitamin B₁₂ deficit)
        – Intrinsic & Extrinsic Factors
• Fe³⁺ deficiency

Destruction of hemoglobin
• Polypeptide chains ------> amino acids
• Iron (Fe³⁺)
        – released from  m
        – transferrin in plasma
        – ferritin in cells, esp. liver
 

Heme group ---->  BILIRUBIN
• Jaundice
• Elevated Free ---> Liver Problems
• Elevated Conjugated ---> Kidney Malfunction
• Problem For Some New Borns (Use UV Light)

HEMOSTASIS:  CLOTTING
• VASCULAR SPASM PAIN --->SYMPATHETIC RESPONSE
• PLATELET PLUG
• CLOT FORMATION

PLATELET PLUG
Fig 13.4
• PLATELETS (2 - 4 µM DIAMETER)
• ADHERE TO - CHARGED SURFACE, e.g., COLLAGEN IN CUT BVs
• DEGRANULATION (SEROTONIN, ADP, PROSTAGLANDINS, etc.)

PLATELETS
• 140,000 - 300,000 / mm³
• TOO FEW ---> THROMBOCYTOPENIA PURPURA
• NOTE: ASPIRIN, etc. AS ‘BLOOD THINNERS’

Platelet Plug
• von Willebrand Factor (vWf)
• From megakaryocytes, platelets & endothelial cells of blood vessels
• Serotonin & epinephrine
• Local vasoconstriction
• ADP - causes adhesiveness and aggregation
• Thromboxane A₂  (TXA₂)
• From arachidonic acid
• Aggregation, ADP release & vasoconstriction

Prevention of Platelet Plug
• Prostacyclin (PGI₂)
• Nitric Oxide
• Both released by healthy, intact endothelial cells

CLOT FORMATION
• FIBRINOGEN (340,000) ---> FIBRIN (LOOSE CLOT)
• FSF COVALENTLY LINKS FIBRIN THREADS (TIGHT CLOT)
• See Figs 13.5 - 7

• FIBRININOGEN ---> FIBRIN
• PROTHROMBIN ---> THROMBIN (ACTIVE ENZYME)
• FACTOR X_inactive --->
                         FACTOR X _active

ACTIVATE FACTOR X
• Extrinsic mechanism: tissue thromboplastin + lipids
• Intrinsic mechanism:  IX via XI via XII activated by collagen or negatively charged surface

ANTI-COAGULANTS
• Ca⁺⁺ Chelators + siliconized glass
• Heparin from mast cells and basophils
• Coumarin derivatives (vitamin k analogs; Dicoumarol; Warfarin)

Coumarin
• Analog of Vitamin K
• Vitamin K is required for addition of carboxyl group to glutamic acid residues of clotting factors
• This addition bestows Ca⁺⁺ binding site and function to clotting factor
• Vit K inhibits this addition, rendering clotting factors inactive

CLOT RETRACTION
• Profibrinolysin --->Fibrinolysin
                    or
• Plasminogen ---> Plasmin
• Activated By Thrombin, Factor XII, Tissue Enzymes
 

Blood vessels:  Structures and Functions
• Figs 13.8 & 12 and pages 411 - 417
Artery --> arteriole  -->  capillary  -->
  venule -->  veins

Starling’s Capillary Hypothesis
• Hydrostatic Pressure

• Plasma Osmotic or Oncotic Pressure
–  (pi)

= RT C
•= osmotic pressure
• R = Gas constant
• T = temperature, oK
• C = difference in concentration of impermeant solute molecules
        – Across capillaries, the solutes are plasma proteins

 
 

Capillary barrier is selectively permeable to solutes > 69,000 mw

Lymphatic system drains the interstitial space of proteins and water

FILTRATION = REABSORPTION

Edema:
        Filtration > Reabsorption

Tissue  Dehydration:
           Filtration < Reabsorption

Factors influencing movement of water across capillaries
• BP
• Dehydration
• Hydration
• Add Osmotic Solute
• Capillary Damage
• Lymphatic Blockage