Blood, Hemostasis and Lymphatics

Structure of Erythrocytes

• Shaped like a biconcave disc which is the greatest surface area to volume ratio which allows RBCs to transport the most oxygen while having the fewest metabolic needs

• Contain a strong flexible membrane that won't rupture when deformed (helps them fold like a taco)

• Lack a nucleus and contain no organelles. This makes them die pretty fast

• Generate ATP to maintain fluid volume anaerobically

• Only job in life is oxygen transport. Contains hemoglobin which is an oxygen binding protein

Structure of Hemoglobin

• Consists of a protein called globin which is composed of 4 polypeptide chains (2 alpha 2 beta). 

• At the center of each chain is a nonprotein pigment called heme. Heme contains an iron in the center which can bind reversibly to oxygen.

• One hemoglobin can bind to 4 oxygens

• Hemoglobin also transports CO2. The CO2 binds to the polypeptide chains.

Erythopoeisis

• Hematopoiesis is the process by which all formed elements of the blood develop

• Erythropoiesis refers specifically to the development and formation of RBCs

• Erythropoiesis begins in the bone marrow under the influence of the hormone erythropoietin

• Erythropoietin causes pluripotent stem cells in the bone marrow to develop into reticulocytes that eventually lose their nucleus and leave the bone marrow and become RBCs

• The kidney releases erythropoietin through negative feedback. Low oxygen means making more blood cells and vice versa.

Lifespand of an RBC

• RBC's typically last 120 days in circulation

• Damaged or worn RBCs are removed from circulation by the liver and spleen

• They get phagocytosed by macrophages

• Globin and iron from hemoglobin are recycled to make new RBC and heme (which is toxic) is excreted from the body through the bile in the liver from bilirubin

• RBC production and destruction occur at the same pace

Antigen vs Antibody

• Antigen: An antigen is any substance that causes an antibody response to be generated

• Antibody: Circulate around your blood and contain info on how to identify and destroy certain antigens

Blood Types and Compatibility

• A Type Blood: Contains anti-B antibodies in their PLASMA and A type antigens

• B Type Blood: Contains anti-A antibodies in their PLASMA and B type antigens

• AB Type Blood: Contains no antibodies and A and B type antigens

• O type blood: Contains both anti A and anti B antibodies in it’s plasma but contains no antigens on it’s RBC

• Therefore, AB blood is the universal receiver because if you put any other blood in them, there are no antibodies in their plasma to attack the oncoming blood. O type blood is the universal donor because no matter what antibodies are in your plasma, O type blood has no antigens to be attacked.

• Blood donations are usually RBCs which is why this type of compatibility works. Whole blood transfusions would need an exact match.

RH Blood Group and hemolytic disease of the fetus

• RH is an antigen that is commonly found on the RBC

• Most people have RH (RH+) but very rarely some people don't (RH-). If you don't have RH, your body doesn't randomly create anti-RH antibodies like it does with A and B antigens. 

• However, if an anti RH person gets exposed to RH blood they will develop those antibodies

• This means RH negative mothers whose first child is RH positive will develop antigens that will kill the next RH positive child they have. This can be prevented with a treatment against RH antibodies

Platlet Formation

• Pluripotent stem cells are stimulated by thrombopoeioten and form megakaryoccytes which are large cells

• These large cells break into fragments called platelets.

Vasospasm

works in small vessels (arterioles). Damage to these vessels results in intense vascular constriction that can reduce blood loss for minutes to hours

3 Steps of Platleg Plug Formation

• Adhesion: Damaged endothelium exposes collagen fibers which platelets adhere to

• Release Reaction: Platelets release ADP (brings more platelets over), serotonin (vasoconstrictor) and thromboxane A2 (does both).

• Aggregation: All these activated platelets adhere to one another and form the platelet plug and then the positive feedback loop ends

3 Steps of Coagulation

1. Prothrombinase formation: Damage outside the blood vessel releases tissue factor while damage inside releases factor XII. These factors come together with activated factor X, V and calcium and form PROTHROMBINASE

2. Thrombin formation: Prothrombinase converts prothrombin to active thrombin with the help of calcium. 

3. Fibrin Formation: Activated thrombin converts fibrinogen to fibrin with the help of calcium. Fibrin is strengthened with factor XII.

Clot Retraction

• Platlets from the blood clot pull on the fibrin threads causing clot retraction and pulling the edges of the BV closer together. 

• Fibroblasts and endothelial cells help repair the BV wall

• A thrombus is a clot in a BV

• A thromboembolism is a clot that travels to a distant site through the blood stream

Clot Lysis

• As soon as the clot begins to form, a blood plasma enzyme called plasminogen gets incorporated into the clot

• Many substances in the blood convert plasminogen into active plasmin (fibronlysin) which slowly eats at the fibrin in the clot.

4 Components of the lymphatic system

• Lymph Fluid

• Lymphatic Vessels (Begin in tissues as capillaries)

• Structures/Organs containing lymphatic tissue

• Red Bone Marrow

3 Functions of Lymph

• Return tissue fluids

• Carry out immune functions (adaptive)

• Transport of dietary fats (more detail provided later in the GI lectures)

Structure of Lymph Capillaries

• Begin as capillaries in the tissue held in place by anchoring filaments

• They drain excess fluid and return it to venous circulation (right of left subclavian vein)

Difference Between Primary and Secondary Lymphoid Tissue

• Primary Lymphoid Tissues: Production and education of immune cells (Red bone marrow, thymus)

• Secondary Lymphoid Tissues: Where most immune responses are initiated/occur (lymph nodes, lymph nodules, spleen)