BLOOD

Liquid connective tissue (20% of extracellular fluid)

T = 38C, pH 7.35-7.45
Color depends on O2 content: bright red (hi), dark red (lo)
Volume ~5-6 l (adult male), ~4-5 l (adult female)
Venipuncture = withdrawal of blood from the vein (usually median cubital vein anterior to the elbow)
using a needle & collection tube containing additives

Function
1) Transportation- Gases, nutrients, hormones, heat, waste products
2) Regulation- pH, body temperature, osmotic pressure
3) Protection- Clotting, white blood cells, proteins

Components
1) Blood plasma- water liquid extracellular matrix
91.5% water, 8.5% solutes (primarily proteins)
Hepatocytes(liver cells) synthesize most plasma proteins:
Albumins maintains osmotic pressure. Fibrinogen for clotting. Antibodies
- Other solutes include electrolytes, nutrients, enzymes, hormones, gases and waste products
2) Formed elements cells and cell fragments
Red blood cells (RBCs), White blood cells (WBCs), Platelets

Formation of Blood Cells

Negative feedback systems regulate the total number of RBCs and platelets in circulation
Abundance of WBC types based on response to invading pathogens or foreign antigens
Hemopoiesis or hematopoiesis: formed elements of blood develop
- Red bone marrow primary site (spaces btw trabeculae of spongy bone tissue)
- Stem cells in bone marrow: Reproduce themselves. Proliferate and differentiate
Cells enter blood stream through sinusoids
Formed elements do not divide once they leave red bone marrow. Exception is lymphocytes
Pluripotent stem cells have the ability to develop into many different types of cells
1) Myeloid stem cells
Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils
2) Lymphoid stem cells
give rise to Lymphocytes
Hemopoietic growth factors regulate differentiation and proliferation
- Erythropoietin RBCs
- Thrombopoietin platelets
- Colony-stimulating factors (CSFs) and interleukins WBCs

Red Blood Cells (Erythrocytes)

Contain oxygen-carrying protein hemoglobin
Production = destruction with at least 2 million new RBCs per second
Biconcave disc increases surface area
Strong, flexible plasma membrane (can deform without rupturing as they squeeze through narrow capillaries)
Glycolipids in plasma membrane responsible for ABO and Rh blood groups
Lack nucleus and other organelles. No mitochondria doesnt use oxygen
Haemoglobin
Globin 4 polypeptide chains
Heme (non- protein) in each of 4 chains
Iron ion (center of each heme group) can combine reversibly with one oxygen molecule
Also transports 23% of total carbon dioxide. Combines with amino acids of globin
Nitric oxide (NO) binds to hemoglobin. Releases NO causing vasodilation to improve blood flow and oxygen
delivery

RBC Life Cycle

Live only about 120 days
Cannot synthesize new components no nucleus
Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen
and liver
Breakdown products recycled
Globins amino acids reused
Iron reused
Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces
Erythropoiesis- production of RBC
Hypoxia (low O2) stimulates release of erythropoietin into blood
proerythroblast in red bone marrow mature more quickly into reticulocytes
cells become reticulocyte after ejecting nucleus at end of development of cell
develop into mature RBC within 1-2 days
negative feedback balances production with destruction
controlled condition is amount of oxygen delivery to tissues

White Blood Cells

got nuclei. No haemoglobin

Granular leukocytes: Neutrophils, eosinophils, basophils
Agranular leukocytes: Lymphocytes and monocytes
Lifespan: few days except lymphocytes- months/years
Leukocytosis (raised in WBC counts above normal range) is a normal protective response to invaders,
strenuous exercise, anesthesia and surgery
Leukopenia (decrease in the number of WBC) is never beneficial
General function: to combat invaders by phagocytosis or immune responses

Emigration (diapedesis)of WBC

WBC leaves the bloodstream
roll along endothelium
stick to it and then squeeze between endothelial cells
precise signals vary for different types of WBCs
endothelial cells display adhesion molecules called selectins in response to nearby injury and inflammation.
Selectins stick to carbohydrates on the surface of neutrophils, causing them to slow down and roll along the
endothelial surface. On the neutrophil surface are other adhesion molecules called integrins, which tether
neutrophils to the endothelium and assist their movement through the blood vessel wall and into the interstitial
fluid of the injured tissue
Types + Functions of WBCs
Neutrophils and macrophages are active phagocytes. Attracted by chemotaxis
1) Neutrophils
respond most quickly to tissue damage by bacteria
uses lysozymes, strong oxidants, defensins
bacterial infection, burns, stress, inflammation.
2) Monocytes
take longer to arrive but arrive in larger numbers and destroy more microbes
Enlarge and differentiate into macrophages
Viral or fungal infections, tuberculosis, some leukemias, other chronic diseases
3) Basophils
leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation
Intensify inflammatory reaction
Involved in hypersensitivity reactions (allergies)
- Antihistamine, prescribed for the relief of allergies, works by preventing the action of histamine (how?)
Allergic reactions, leukemias, cancers, hypothyroidism.
4) Eosinophils
leave capillaries and enter tissue fluid
Release histaminase, phagocytize antigen-antibody complexes and effective against certain parasitic worms
Allergic reactions, parasitic infections, autoimmune diseases

5) Lymphocytes are the major soldiers of the immune system

B cells destroying bacteria and inactivating their toxins
T cells attack viruses, fungi, transplanted cells, cancer cells and some bacteria
Natural Killer (NK) cells attack a wide variety of infectious microbes and certain tumor cells

Platelets (Thrombocytes)
Myeloid stem cells develop eventually into a megakaryocyte
Splinters into 2000-3000 fragments. Each fragment enclosed in a piece of plasma membrane
Disc-shaped with many vesicles but no nucleus
Help stop blood loss by forming platelet plug. Granules contain blood clot promoting chemicals
Short life span 5-9 days
Hemostasis
- Sequence of responses that stops bleeding
- Successful hemostasis prevents hemorrhage (the loss of large amount of blood from the vessels)
3 mechanisms to reduce blood loss:
1. Vascular spasm- Smooth muscle in artery or arteriole walls contracts
2. Platelet plug formation
Platelets stick to parts of damaged blood vessel, become activated and accumulate large numbers
Platelet activation majority by ADP & thromboxane A2.
Serotonin & thromboxane A2 cause vasoconstriction decreased blood flow to injury site
ADP release makes platelet sticky and adhere to previously activated ones (positive feedback)
3. Blood clotting (coagulation)
Serum is blood plasma minus clotting proteins
Clotting series of chemical reactions culminating in formation of fibrin threads
Clotting (coagulation) factors Ca2+, several inactive enzymes, various molecules associated with platelets
or released by damaged tissues
3 stages of clotting:
1. Extrinsic or intrinsic pathways lead to formation of prothrombinase
2. Prothrombinase converts prothrombin into thrombin
3. Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot
3 Pathways:
1) Extrinsic
Fewer steps then intrinsic and occurs rapidly (seconds)
Tissue factor (TF) or thromboplastin leaks into the blood from cells outside (extrinsic to) blood vessels and
initiates formation of prothrombinase
2) Intrinsic
More complex and slower than extrinsic (minutes)
Activators are either in direct contact with blood or contained within (intrinsic to) the blood
Outside tissue damage not needed
Also forms prothrombinase
3) Common
Marked by formation of prothrombinase
Prothrombinase with Ca2+ catalyzes conversion of prothrombin to thrombin
Thrombin with Ca2+ converts soluble fibrinogen into insoluble fibrin
Thrombin has 2 positive feedback effects
- Accelerates formation of prothrombinase
- Thrombin activates platelets
Clot formation remains localized because fibrin absorbs thrombin and clotting factor concentrations are low;
dry clot forms scab

Haemophilia- Inherited deficiency of clotting factors

bleeding spontaneously or after minor trauma
subcutaneous & intramuscular hemorrhaging

nosebleeds, blood in urine, articular bleeding & pain

Haemophilia A: deficiency of factor VIII (males only) most common
Haemophilia B: deficiency of factor IX (males only)
Haemophilia C: deficiency of factor XI (males & females) less severe because alternate clotting activator
(factor VII) exists
Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor

Blood Groups and Blood Types

Agglutinogens surface of RBCs contain genetically determined assortment of antigens
Blood group based on presence or absence of various antigens
Type A blood has only antigen A (phenotype). Anti- B antibody.
Type B blood has only antigen B. Anti- A antibody
Type AB blood has antigens A and B Universal recipients neither anti-A or anti-B antibodies
Type O blood has neither antigen. Both anti- A and anti- B antibodies. Universal donor
Rh Blood Group
People whose RBCs have the Rh antigen are Rh+
People who lack the Rh antigen are Rh Normally, blood plasma does not contain anti-RH antibodies
Hemolytic disease of the newborn (HDN) if blood from Rh+ fetus contacts Rh-mother during birth, antiRh antibodies made. Affect is on second Rh+ baby

Complete Blood Count (CBC)

Screen for anemia and various infections

Includes:
RBC, WBC, platelets per l of whole blood
Hematocrit
Differential WBC count
Amount of hemoglobin
- Infant: 14-20g/100ml blood. Adult female: 12-16g/100ml blood. Adult male: 13.5-18g/100ml blood

Stem cell transplants

1) Bone marrow transplant
Recipient's red bone marrow replaced entirely by healthy, noncancerous cells to establish normal blood cell
counts
Takes 2-3 weeks to begin producing enough WBCs to fight off infections
Graft-versus-host-disease transplanted red bone marrow may produce T cells that attack host tissues
2) Cord-blood transplant
Stem cells obtained from umbilical cord shortly before birth
antigens on these cells not yet developed, minimize rejection
Easily collected and can be stored indefinitely
Less likely to cause graft-versus-host-disease