071709 blood physiology
TRANSCRIPT
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..