Blood Physiology

Carolina C. Jerez, MDDept. of Physiology

Stages in Hematopoiesis

Mesoblastic phaseYolk sacBlood islands near the aorta

Hematopoiesis

Hepatic stage : continue untll birth ; by the third month the peak for both eryhropoiesis and granulopoiesis will be reached

Splenic activity also starts here The thymus is the first organ of the

lymphatic system to develop fully in the fetus; continue to enlarge until childhood

The medullary phase

Medullary production starts with the ossification and development of the marrow within the core of the bone

Clavicle first to demonstrate marrow hematopoietic activity

By the 6th month the marrow become the primary site of hematopoiesis

Measurable products : various stages of maturation of all cell lines;EPO; fetal Hgb ;adult Hgb

The hematopoietic microenvironment

A carbon dioxide atmosphere Wet sticky surface where the cells

anchor Normal population of red marrow cells

necessary for interaction Provides the growth factors, cytokines

and extracellular matrix which helpregulate hematopoiesis

The Liver

Synthesizing and providing transport proteins;storing essential minerals and vitamins utilized in DNA and RNA synthesis, conjugating bilirubin from hemoglobin degradation, transporting the bilirubin to the small intestine

The SPLEEN

The largest lymphoid organ in the bodyIt is vital but not essential for lifeThere are three zones The white pulp > the red pulp The marginal zone Splenomegaly is observed in various diseases

like ; chronic leukemias, genetically defective RBC, HGB, thalassemias, malaria

Lymph Nodes

Formation of new lymphocytes from the germinal centers

Processing of specific immunoglobulin Filtration of particulate matter, debris,

bacteria entering the lymph nodes

The Thymus

Has 2 portions > the cortex; waiting zone; densely

populated by lymphocytes from the bone marrow with no surface markers

The medulla : holding zone; contains 5% mature T lymphocytes,

The stem cell theory

@ types of Stem cells : > undifferentiated or pluripotent or

totipotent cells : capable of self renewal, and differentiation to progenitor cells committed to either lymphoid or myeloid lineage

> progenitor cells : give rise to recognizable lineage –specific recursor cells; called CFU1 or CFU-GEMM

Cytokines

Diverse group of soluble proteins which modulates the functional activities of the cell

Most are glycoproteins and include the interleukins, lymphokines, monokines, interferrons, chemokines, CSF,

Responsible for trafficking of mature blood cells( stimulation, inhibition, production, differentiation )

> prevents apoptosis

Erythrocyte production and destruction

Erythron : all stages of the red cell in designated areas of the body( bone marrow, circulating red cells, vascular spaces within the specific organs

Erythropoietin : thermostable, nondialyzable glycoprotein which has

A. CHO unit which conveys specificity B. terminal sialic acid for its biologic

activity in vivo

Functions of erythropoietin

Regulates the 3 reduction division of normoblastic production

Shortens the time of division maturation process

Increases the rate of the pentose phosphate shunt

Assists in the egression of the mature red cell Stimulates the early release of shift reticulocyte Increases the rate of hemoglobin syntheis

Factors stimulating EPO release

Hypoxia or decrease in oxygen tension Testosterone

EPO can be measured by immunoassay Plasma values : 3-8 mU /ml to maintain steady

erythropoiesis 2000-3000 mU/ml is necessary to compensate

a severe hemolytic process or blood loss

Anti=erythropoietin antibodiess

Type 1 : neutralizes the biological activity of EPO

Type !! Causes hemagglutination

The mature red cell

7-8 micro m in diameter ; 1.5-2,5 micro m thick Cell membrane functions Maintain cell shape deformability Suppporting skeletal system for surface antigen Transports essential ions and gases

The membrane proteins Integral Peripheral : spectrin, actin, ankyrin, G3PD

Blood Groups

ABO Rh Other minor blood groups Proper blood typing and cross matching Major X match: Donor red cell x recipient

serum Minor X matching Donor serum X

recipients red cell

Case:” Nanlalata”

A 45 year old female called her physician complaining of fatigue, shortness of breath on exertion, and general malaise. She requested some B12 shots to make her feel better’ the physician asked for an appointement to determine what was really wrong with her.

Anemia

A reduction of more than 10% from the normal value for the total nuimber of RBC , amount of hemoglobin and RBC mass of a particular patient

Good history : diet, drug ingestion, exposurre to chemicals, occupation, hobbies, travel, bleeding history, ethnic groups, family history of disease, jaundice

Good physical examination

Laboratory tests

Complete blood count with cell indices Rbc count MCV MCH MCHC RDW Reticulocyte count Bone marrow examination

Mechanisms of Anemia

Ineffective erythropoiesis : production of progenitor cells that are defective and are destroyed prior to or shortly after leaving the bone marrow

Insufficient erythropoiesis: quantitative lack of erythroid precursors in the marrow (aplastic anemia)

Physiologic adaptation to the Anemias

Rapid delivery of oxygen to the tissues by :

> increased in heart rate > increased respiratory rate Increased cardiac output Increased in 2,3 BPG

Polycythemia

Neoplastic clonal MPD that expresses with panmyelosis in the bone marrow and increases RBC, WBC and platelets in the peripheral blood

Splenomegaly is common Neoplastic clonal stem cells are sensitive

to the presence of EPO

Ode to a red cell

Erythrocyte, erythrocyte, Thou General Physiologists’ delight! Thy gently rounded biconcavity Arouses wonder, not depravity. Thy subtle shape proclaims an adaptation To Dr. Roughton’s diffusional equation. And Biochemists still persist in hopin’ You’re more than just a bag of hemoglobin. When comes Hemolysis; as come it must to most; You’ll make a very pretty red cell ghost!

- Alan C. Burton

Thank you!

Mwaauh..