Lecture 15 Blood and Hemostasis Flashcards
What % of the body’s total weight is blood?
8%f
What is the pH range of blood?
7.35 to 7.45
Plasma
Blood minus the formed elements
Serum
Plasma without the blood-clotting proteins
Name the three layers in heparinized and centrifuged blood
Supernatant (plasma)
Buffy coat (leukocytes and platelets)
Precipitate (sedimented red blood cells)
Hematocrit
Measure of what fraction of blood is made up of RBCs
Compare Male and Female Blood
Volume
Formed Elements
Hematocrit
F vs. M
4-5 L —– 5-6 L
38-48% —— 44-54% Formed elements
42% —– 47% Hematocrit
Name the three blood proteins
Fibrinogens
Albumins
Globulins - Immunoglobulins
What blood proteins are made in the liver?
Fibrinogens and Albumins
What is the function of Fibrinogen?
Function in blood clotting
What is the function of Albumin?
Exert major osmotic pressure on blood vessel walls
Which blood protein is targeted by thrombin?
Fibrinogen
Erythropoietin increases the number of what?
Erythrocytes
What produces erythropoietin?
The Kidney
Describe an erythrocyte and name is major contents
Devoid of granules and organelles
Major contents: Lipids, ATP, Carbonic anhydrase, Hemoglobin
Describe the proteins of an erythrocyte
50% = integral membrane proteins
Peripheral proteins: Spectrin and Actin (bond via ankyrin)
Hereditary Spherocytosis
Red blood cells are spheroidal, less rigid, and subject to destruction in the spleen.
Caused by cytoskeletal abnormalities involving sites of interactions between spectrin alpha & beta and protein4.1
Why are erythrocytes useful in studies of the cortical cytoskeleton?
No nucleus or organelles, so plasma membrane & associated proteins are easily isolated
Also lacks other cytoskeletal components, so cortical cytoskeleton is principal determinant of cell shape
What is the major structural protein of erythrocytes?
Spectrin
What family does Spectrin belong to?
Member of the calponin family of actin-binding proteins
Describe Spectrin and the network it forms
Spectrin is a tetramer of 2 polypeptide chains (a and b)
The end of the spectrin tetramers associate with short actin filaments resulting in the spectrin-actin network
What does Ankyrin do?
Links the specrtin-actin network and the plasma membrane by binding to spectrin and a transmembrane protein (band 3)
What does Protein 4.1 do?
Another link that binds spectrin-actin junctions and the transmembrane protein glycophorin
What is another name for a Neutrophil?
Polymorphonuclear leukocyte
Name the characteristics of a neutrophil
3-5 nuclear lobes Active amoeboid phagocytes Small, numerous specific granules Larger, less numerous azurophilic granules Remain in circulation for 10-12 hours Live 1-2 days after leaving circulation Secrete a class of enzymes
What type of enzymes do neutrophils secrete?
Enzymes capable of destroying certain bacteria by formation of free radicals (superoxide) as well as the release of lysozyme and lactoferrin which destroy bacterial walls
Name the characteristics of a Basophil
Lobulated nucleus (bilobed) Large, membrane bound basophilic granules
What do the large, membrane bound basophilic granules of a basophil contain?
Contain Vasoactive substances: Serotonin, Heparin, and Kallikrein
Can produce leukotrienes
What is heparin?
Anticoagulant
What does Kallikrein do?
Attracts eosinophils
What do leukotrienes do?
Increase vascular permeability
Slow contraction of smooth muscle
Name the characteristics of Eosinophils
Bilobed nucleus
Specific granules
Respond in allergic diseases and parasitic infections
Phagocytize antibody-antigen complexes and parasites
What are the specific granules of a eosinophil?
Major basic protein (MBP)
Peroxidase
Cationic protein
What does Major Basic Protein (MBP) do?
Disrupts parasite membranes
Causes basophils to release histamine
What does Cationic Protein do?
Neutralizes heparin and is anti-parasitic
What does Eosinophil Peroxidase do?
Binds to microorganisms and facilitates their killing by macrophages
Name the characteristics of Lymphocytes
Large round, sometimes slightly indented nucleus; fills most of the cell
Variable in size
B lymphocytes and T lymphocytes
What are B lymphocytes?
Precursors of plasma cells
What are T lymphocytes?
Precursors of T lymphocytes
Name the characteristics of a Monocyte
Largest leukocyte
Eccentrically located, kidney-shaped nucleus
Granular cytoplasm due to small lysosomes
Precursor of macrophages and osteoclasts
What are Platelets derived from?
Megakaryocytes
What are the functions of platelets?
Enhance aggregation by release of factors, and promote clot formation, retraction, and dissolution
Repair damage to endothelium by forming platelet plug
The adhesion of platelets involves what?
Integrins
Platelets release ______ which increases platelet aggregation
Thromboxane
Endothelial cells release ______ which decreases platelet aggregation
Prostacyclin
Define Hemostasis
The elimination of bleeding
Define Hematoma
Accumulation of blood in tissues
Hemostatic sequence of events (in small vessels):
Constriction of smooth muscle around vessels Constriction of vessels Slowing of blood Formation of platelet plug Blood clotting (coagulation)
Review formation of platelet plug
Slides 37-38
Review blood clotting
Slides 39-43
What are the two different cascade sequences that lead to the common pathway?
Intrinsic and Extrinsic
Briefly summarize the difference between intrinsic and extrinsic pathways
In the intrinsic pathway, everything necessary for it to occur is already within the blood.
In the extrinsic pathway, the formation of a tissue factor (thromboplastin) is necessary
Draw out the intrinsic pathway
Picture will be added soon
See slide 50
Draw out the extrinsic pathway
Picture will be added soon
See slide 52
Draw out the common pathway
Picture will be added soon
See slide 54
Where are most of the clotting factors synthesized?
The liver
What vitamin is necessary for the synthesis of factors VII, IX, and X?
Vitamin K
What activates the homing mechanism?
Cytokines released by mast cells, platelets, and damaged tissue cells
What is released by endothelial cells and responsible for increasing vascular permeability?
Nitric oxide (NO)
What are the two phases involving cellular adhesion molecules?
Selectin Phase
Integrin Phase
What are Sialyl Lewis-x antigens?
Oligosaccharide ligands for P-selectin binding found on leukocyte membranes
Summarize the Selectin Phase
P-selectins appear on cell surface when endothelial cells are activated by inflammatory signaling
Oligosaccharide ligands on leukocytes bind to carb. recognition domains (CDRs) on the P-selectins
Binding of ligands to P-selectins causes leukocytes to roll along endothelium
Where are P-selectins from?
Weibel-Palade bodies
Summarize the Integrin Phase
Integrin receptors activated on leukocyte membrane (bind to ICAM-1 & ICAM-2 on endothelial cells)
Integrins B1 & B2 activated on leukocyte membrane & bind VCAM & ICAM on endothelial cell membranes
Integrins interacting w/ endothelial ligands promote transendothelial migration of leukocytes
What is Erythroblastosis Fetalis?
Antibody-induced hemolytic disease in the newborn that is caused by blood group incompatibility between mother and fetus
What are the particular blood group antigens of interest in Erythroblastosis Fetalis?
ABO and Rh blood group antigens
What antigen is the major cause of Rh incompatibility?
D antigen
Why is the first Rh positive pregnancy not affected?
Because IgM is produced and IgM is too large to cross the placental barrier. With the later pregnancies, IgG is produced and IgG can cross the placenta