I. Composition/function.

A. Introduction.

- 8% body volume; specialized connective tissue where cells are formed elements and plasma is extracellular matrix (ECM); the two ECM components are ground substance (serum) and fibers (soluble fibrinogen)

B. Composition.

1. Formed elements (42% in females, 45% in males)

a. RBC - 99.9% of formed elements

b. WBC

c. platelets

2. Plasma (58% for women, 55% for men)

a. water

b. plasma proteins

c. other solutes

C. Functions of blood

• Distribution of gases, nutrients , removal of waste products, hormone transport
• Regulation of body temp, pH, fluid volume
• Protection: clotting, prevention of infection

II. Blood plasma.

A. Composition.

1. Water: 90-92%.

2. Solutes.

a. Proteins 7-8%

(i) albumins (60%):  allow fluid to be retained in circulatory system

(ii) globulins (36%)

- antibodies

(iii) clotting proteins (4%)

(iv) other plasma proteins: hormones, enzymes

b. "other solutes"

- nutrients

- ions

- respiratory gases

III. Formed elements: erythrocytes, leukocytes, platelets

- all produced in bone marrow in adult from a pluripotent stem cell (PPSC); PPSC gives rise to myeloid stem cells (MSC) or lymphoid stem cells (LSC); MSC will give rise to RBC, WBC, platelets; LSC gives rise to lymphocytes

A. Erythrocytes: have biconcave shape which gives them a huge surface area relative to volume; lack nucleus, organelles, contain predominantly hemoglobin

1. Function of gas transport

- a function of hemoglobin which binds easily to oxygen

a. Structure of hemoglobin

(i) globin is protein unit: four polypeptide chains, each bound to heme group

(ii) heme is a complex ring structure which has atom of iron in its center; iron binds reversibly to oxygen

b. Oxygen transport

- a hemoglobin molecule can transport 4 molecules of oxygen; most of oxygen in blood is bound to hemoglobin

c. has a role in carbon dioxide transport

2. Production of erythrocytes (erythropoiesis)

- occurs in bone marrow

-  stem cell becomes committed to becoming RBC by environmental signal -- begins producing and storing large amount s of hemoglobin

3. Erythropoiesis.

a. Hormonal control.

- occurs by differential release of erythropoietin (EPO) by kidneys in response to changing levels of O₂ in blood

-  EPO release stimulated by low O₂ levels in blood

4. Destruction of erythrocytes

- usually occurs in large circulatory channels (spleen, liver)

- as cells age, they become abnormally shaped, fragment engulfed by macrophages; iron and amino acids are recycled, heme used for synthesis of bile by liver

5. Erythrocyte disorders - anemias: conditions in which blood has abnormally low O2 carrying capacity; a symptom of a disorder, can have several causes

a. Insufficient number of RBC

• hemorrhagic anemias
• hemolytic anemias

b. Decreases in Hb content

• iron-deficiency anemia
• pernicious anemia

c. Abnormal hemoglobin

• thalassemias
• sickle cell anemia

6. Erythrocyte disorders - polycythemias: abnormal excess of erythrocytes, increased blood viscosity

• polycythemia vera
• secondary polycythemias

B. Leukocytes: true cells, granulocytes and agranulocytes

- function in body defense against pathogens

- characteristics:

• amoeboid movement
• positive chemotaxis
• phagocytosis

1. Granulocytes: contain specialized membrane-bound granules, lobed nuclei; all originate from MSC

a. Neutrophils: most common WBC, have a mix of basophilic and acidophilic granules

- first WBC to arrive at site of infection, very mobile; engulfs pathogen

-  very effective against bacteria

b. Eosinophils: have acidophilic granules

- granules have a special variety of digestive enzymes lacking those that can digest bacteria

- primary mode of attack involves exocytosis of toxic compounds onto target surface (multicellular organism too large to be phagocytosed, parasitic worms.

c. Basophils: rarest WBC.

- cytoplasm contains histamine 

- migrate to site of injury, cross capillary endothelium, discharge granules - histamine release.

2. Agranulocytes: lack obvious granules, have kidney-shaped or round nuclei.

a. Lymphocytes: have very large spherical nuclei with small rim of cytoplasm.

- most found in lymph nodes, spleen, marrow.

- participate in immune response, T-lymphocytes in cell-mediated immunity, B-lymphocytes in humoral immunity.

b. Monocytes: the largest WBC, large nucleus, kidney-shaped.

- only remain in circulation for 24 hours, enter peripheral tissues where they mature into macrophages. the body's greatest scavengers; very aggressive phagocytic cells.

- when encounter invader release many chemotaxic and growth factors that attract other WBCs and stimulate tissue repair.

- important participants of immune response.

3. Production of leukocytes (leukopoiesis).

- hormonally stimulated.

-  body's internal environment dictates relative numbers of WBC produced at a given point

4. Leukocyte disorders.

-  Leukemia: excessive production of abnormal leukocytes

- renegade leukocytes member of one clone, remain unspecialized, mitotic, suppress and impair marrow function.

- named according to abnormal cell type primarily involved; myelocytic leukemia, lymphocytic leukemia.

- acute leukemia: (quick advancing), derived from blast-type cells like lymphoblast; usually affects children.

- chronic leukemia: (slow advancing), involves proliferation of later cell stages, more common in elderly people.

5. Platelets.

- not cells in the strict sense, cytoplasmic fragments of extremely large cells called megakaryocytes.

- contains many substances that aid in clotting processes such as calcium ions, serotonin, a variety of enzymes, ADP

- are essential for clotting when blood vessels are ruptured or the lining is injured.

A. Hemostasis:

- prevents blood loss through walls of damages vessels, establishes a framework for tissue repair.

1. Vascular spasms: damage to the blood vessel walls causes constriction of vessel walls

-  due to damage vessel wall becomes sticky

-  platelets attach, adhere

2. Platelet plug formation:

- platelets begin to attach -- platelet adhesion.

- as platelets adhere they become activated, more platelets attach, platelet aggregation.

- how does platelet activation lead to platelet aggregation?

- activated platelets begin synthesizing and releasing many substances that further attract other platelets

• ADP
• serotonin

3. Coagulation: blood clotting.

- complex series of steps involving many factors that lead to the conversion of circulating soluble clotting proteins (fibrinogen) into insoluble protein fibrin

-  fibrin covers the surface of platelet plug and forms a blood clot

PHASE 1: (2 pathways)

- intrinsic pathway: activated platelets produce factors that lead to production of prothrombin activator

- extrinsic pathway: injured tissue produces factors that lead to production of prothrombin activator

PHASE 2: common; prothrombin --> thrombin catalyzed by prothrombin activator.

PHASE 3: fibrinogen --> fibrin

B. Clot retraction & repair

- within 30-60 minutes, a clot is stabilized further by the platelet induced process of clot retraction.

- effects of clot retraction: pulls the edges of the vessel together, lowers the residual bleeding, and stabilizes the injury site; also reduces the size of the damaged area.

C. Fibrinolysis.

- a process that removes unneeded clots when permanent healing has occurred

- clot "buster" is a fibrin-digesting enzyme, plasmin; produced by activation of a proenzyme plasminogen that was incorporated in large amounts into a forming clot, remains inactive until the appropriate signals reach it.

- the presence of clots in/around blood vessels are detected by surrounding cells lining blood vessel that release tissue plasminogen activator (t-PA)

- plasmin digests fibrin strands