The Cardiovascular System:

Hemopoietic Growth Factors:

• Regulate differentiation and proliferation 

• Erythropoietin (EPO) 

  • Produced by the kidneys increase RBC precursors 

  • A hormone 

  • Stimulates the production of Red Blood Cell production to makes the cells make more energy 

• Thrombopoietin (TPO) 

  • Hormone from liver stimulates platelet formation 

• Cytokines are local hormones of bone marrow 

  • Stimulate White Blood Cell (WBC) production

  • Leukopoietin helps stimulate WBC and comes from a group of stem cells called pluripotent stem cells (another name Hemocytoblast) 

Red Blood Cells

• Another name is Erythrocytes 

• Contain oxygen-carrying protein hemoglobin that gives blood its red color 

• A mature red blood cell does not contain nucleus 

• Biconcave Disk 

  • Increased surface area/volume ratio 

  • Flexible shape for narrow passages 

  • No nucleus or other organelles 

    • No cell division or mitochondrial ATP formation

Hemoglobin

• Globin protein consists of 4 polypeptide chains 

• It is the “Hem” part of the Hemoglobin molecule that contains iron 

Function of Red Blood Cells

• Transport of O2 (oxygen) ,CO2 (carbon dioxide), and Nitric Oxide 

• How it transport oxygen: 

  • Hb + O2 (Pale red) to HbO2 (Oxyhemoglobin (scarlet) = Carboaminohemoglobin

• Each hemoglobin molecule can carry 4 oxygen molecules from lungs to tissue cells 

• Hemoglobin transports 23% of total CO2 waste from tissue cells to lungs for release

  • Combines with amino acids in globin portion of Hb 

• Hemoglobin transports nitric oxide helping to regulate BP 

Red Blood Cell Life Cycle

• RBC’s live only 120 days 

• Wear out from bending to fit through capillaries 

• No repair possible due to lack of organelles

• Worn out cells removed by fixed macrophages in spell and liver 

• Breakdown products are recycled 

• Unused parts that are not recycled are rid of - color of feces and urine are a result of breakdown products of red blood cells ( bilirubin and biliverdin)

• “Globin” contains amino acids (Protein)

• The amino acid part of the hemoglobin is removed and reused for Protein Synthesis

• The Iron is removed from the “hem” part and sent to the liver and then gets to the blood system where the blood transports it the the red bone marrow

• Bilirubin is sent to the small intestine to form urobilinogen and then turned into feces

• Some of the blood changes to the urobilin and goes to the kidney to where the Urin gets its color

• The process by which red blood cells are produced is Erythropoiesis

Fate of Components of Heme

• Iron (Fe+3) 

  • Transported in the blood 

  • Stored in liver, muscle, or spleen 

  • Is in bone marrow to be used for hemoglobin synthesis 

• Biliverdin (green) converted to bilirubin (yellow) 

  • Hemocytoblast 

  • Pluripotent Stem Cell - Myeloid - lymphoid ( T-lymphoblast (T cell name) and B-lymphoblast ( B Cell name)) 

  • T Cell matures in the thymus gland 

  • B cell matures in the bone marrow 

  • B lymphoblast - can develop special proteins into special cells called plasma cells 

  • Lymphocytes are important because they have to fight viral infections in the body 

  • Neutrophil are the most abundant of the white blood cells - approximately 70 to 72% of white cells in our body - also the first line of defense in our body (phagocytic in nature) 

  • Bilirubin secreted by liver into bile 

    • Converted to other chemicals (brown pigment in feces) by bacteria of large intestine 

    • If absorbed from intestine into blood is converted to yellow pigment, and excreted in urine

Leukocytes

• Leukocytes or white blood cells (WBCs) - larger than erythrocytes with a prominent nucleus; use blood-stream as transportation; generally don’t perform their functions within blood 

  • Adhere to walls of blood vessels then squeeze between endothelial cells to enter surrounding tissue 

  • Leukocytes are divided into two basic categories Granulocytes contain cytoplasmic granules that are released when activated while agranulocytes lack visible granules 

Granulocytes

• Are distinguished by their unusual nuclei; single nucleus composed of multiple connected lobes 

  • All cells in this group contain general lysosomal granules as well as granules unique to each type of granulocyte 

  • Divided into following three categories based on color that granules appear, either light lilac, dark purple, or red respectively, whens stained with basic (methylene blue) or acidic (eosin) dye 

• Neutrophils - most common leukocyte; have cytoplasmic granules that absorb both dyes; stains their cytoplasm a light lilac color 

  • Active phagocytes that ingest and destroy bacterial cells 

  • Also called polymorphonucleocytes (polys or PMNs); uniquely shaped nucleus composed of three or five lobes 

  • Injured cells release chemicals that attract neutrophils; process called chemotaxis, in which neutrophils exit bloodstream and release granules in damaged tissue 

  • Granule contents directly kill bacterial cells, attract more neutrophils and leukocytes to region, and enhance inflammation 

  • Attracted to the chemicals by injured cells and that makes phagocytes 

• Eosinophils - have a b

• Basophils - least common leukocyte 

  • Have an s shaped nucleus and appear dark purple due to uptake of methylene blue dye 

  • Chemicals in granules mediate inflammation 

Erythrocyte

Reticulocyte

• Immature RBC that has a nucleus - once it starts to become mature it loses the nucleus

Lymphocytes

White Blood Cell Anatomy and Types

• All WBCs’s (leukocytes) have a nucleus and no hemoglobin 

• Granular or agranular classification based on presence of cytoplasmic granules 

White Blood Cell Physiology

• Less numerous than RBC’s 

  • 1 WBC for every 700 RBC 

• Leukocytosis is a high white blood cell count 

  • microbes , strenuous exercise, anesthesia or surgery 

• Leukopenia is low white blood cell count 

  • Radiation, shock or chemotherapy 

• Only 2% of total WBC population is in circulating blood at any given time 

  • Rest is in lymphatic fluid, skin, lungs, lymph nodes and spleen 

Emigration and Phagocytosis

• WBC’s roll along endothelium, stick to it and squeeze between cells 

• Neutrophils and macrophages phagocytose bacteria and debris 

  • Chemotaxis of both 

  • Chemicals from injury site and toxins 

Neutrophil Function

• Fastest response of all WBC to bacteria 

• Direct actions against bacteria 

  • Release chemicals which destroy/digest bacteria 

Monocyte Function

• Takes longer to get to site of infection, but arrive in larger numbers 

• Become wandering macrophages, once they leave the capillaries 

• Destroy microbes  and clean up dead tissue following an infection

Platelet (Thrombocyte) Anatomy

• Disc-shaped, tiny cell fragment with no nucleus 

• Normal platelet count is 150,000 - 400,000/drop of blood 

• Other blood cell counts 

  • 5 million red and 5-10,000 white blood cells 

Platelets - Life History

• Platelets form in bone marrow by following steps: 

  • Myeloid stem cells to megakaryocyte - colony forming cells to megakaryoblast to megakaryocytes whose cell fragments form platelets 

• Short life span (5 to 9 days in bloodstream) 

  • Formed in bone marrow 

  • Few days in circulating blood 

  • Aged ones removed by fixed macrophages in liver and spleen 

What do Platelets do?

• Platelet prevents blood loss

Hemostasis

• Stoppage of bleeding ina quick localised fashion when blood vessels are damages 

• Prevents hemorrhage (loos of a large amount of blood) 

• Methods utilized

  • Vascular system 

  • Platelet plug formation 

  • Blood clotting (coagulation = formation of fibrin threads) 

Vascular Spasm

• Damage to blood vessel stimulates pain receptors 

• Contraction of smooth muscle of small blood vessels 

• Can reduce blood loss for several hours until other mechanism can take over 

• Only for small blood vessels or arteriole 

Platelet Plug Formation

• Platelets store a lot of chemicals in granules needed for platelet plug information 

• Steps in the process 

  • 1) platelet adhesion

  • 2) platelet release reaction

  • 3) platelet aggregation 

Platelet Adhesion

• Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall 

Platelet Release Reaction

• Platelets activated by adhesion 

• Make contact with each other 

• Release chemicals activating other platelets 

• Spoke chemicals are vasoconstrictors decreasing blood flow through the injured vessel 

Platelet Aggregation

• Activated platelets stick together and activate new platelets to form a mass called a platelet plug 

• Plug reinforced by fibrin threads formed during clotting process 

Overview of the Clotting Cascade

• Prothrombinase is formed by either the intrinsic or extrinsic pathway 

• Final common pathway produces fibrin threads 

Common Pathway

• Prothrombin to thrombin - called the prothrombinase 

• Prothrombin to thrombin - called the prothrombinase 

Agglutinins

• Substances that cause particles, like cells or bacteria, to clump together. They can be antibodies that bind to antigens 

Agglutinogen 

• protein on a foreign cell that triggers an immune response in the body. Agglutinogens are also known as antigens. 

• An antigen that causes the formation o agglutinins in the body and leads to agglutinogen, such as hema, which involved red blood cells  - Found in the surface of RBC

  

Blood Groups and Blood Types

• RBC surfaces are marked by genetically determined glycoproteins and glycolipids 

  • Agglutinogens or isoantigens 

  • Distinguishes at least 24 different blood groups 

    • ABO, Rh, Lewis, Kell, Kidd, and Duffy 

ABO Blood Groups

• Based on 2 glycolipid isoantigens called A and B found on the surface of RBC’s 

  • Display only antigen A – blood type A 

  • Display only antigen B – blood type B 

  • Display both antigens A&B – blood type AB

  • Display neither antigen – blood type O 

• Plasma contains isoanti

RH Blood Groups

• People with Rh agglutinogens on the RBC surface are Rh+. Normal plasma contains no anti- Rh antibodies 

• Antibodies develop only in Rh- blood type and only with exposure to the antigen 

  • Transfusion of positive blood 

  • During a pregnancy with a positive blood type fetus 

• Transfusion reaction upon 2nd exposure to the antigen results in hemolysis of the RBCs in the donated blood 

Type AB is called the universal recipient - can receive blood from any type

Type O is called the universal donor - any type can recieve Type O blood

Vitamin K

• Vitamin k is used by the liver to make the protein that is required for hemostasis 

• Without vitamin K the blood will not clot 

• Hemophilia - absence of clotting factors - is genetic 

• Anemia - inadequate RBC or hemoglobin

• Polycythemia- high red blood cell reduction - more than what is required

• Hematocrit - percentage of red blood cells in the fix volume of blood - 

• Thrombus - is a stationary blood clot - most common is called DVT ( Deep Vein Thrombosis) - can break off from the vein and float 

• Embocus - a floating blood clot - can result in death

Tissue Deprivation of Oxygen

• Because of hemostasis kidneys are messaged to produced Erythropoiesis makes RBC to then make oxygen for the tissue 

• Hypoxia is the end product of this 

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