Blood Flashcards
Blood
- ## a connective tissue composed of cellular elements suspended in an extensive fluid matrix that circulates in the CV system
Composition of Blood
- plasma
Composition of Plasma
- water (92%)
- ion
- organic molecules
- trace elements and vitamins
- gases
Composition of Organic Molecules
- amino acids
- proteins (7%)
- glucose
- lipids
- nitrogenous waste
Gases in Blood
- CO2 and O2
Plasma Proteins
- primary difference between plasma and the interstitial fluid
- Albumins
- Globulins
- Fibrinogen
- Transferrin
Albumins
- multiple types
- source = liver
- major contributors to colloid osmotic pressure of plasma
- carriers for various substances
Globulins
- multiple types
- source = liver and lymphoid tissue
- clotting factors, enzymes, antibodies, carriers for various substances
Fibrinogen
- source = liver
- forms fibrin threads essential to blood clotting
Transferrin
- source = liver and other tissues
- iron transport
Cellular Elements
- Erythrocyte
- Leukocytes
- Thrombocytes
Leukocytes
- white blood cells Types 1. lymphocytes 2. monocytes (macrophage) 3. neutrophils 4. eosinophils 5. basophils (mast cell)
Hematocrit
- 40-45%
- the fraction of the total column occupied by RBC’s
Buffy Coat
- is WBC’s and platelets
- 1%
Plasma
- 55-60%
- pale white solution of electrolytes, plasma proteins, carbohydrates and lipids
Hematopoiesis
- production of blood cells
- lineage development guided by cytokines (cell signalling molecules)
- begins with pluripotent hematopoietic stem cell
- bone marrow
- in adults: pelvis, spine, ribs, cranium and proximal ends of long bones
Bone Marrow
- hidden within the bones of the skeleton
- consists of blood cells in different stages of development and supporting tissue known as stroma (mattress)
Cytokines
- proteins or peptides released from one cell that affect growth of activity in another cell
- cytokines involved in Hematopoiesis
1. Erythropoietin (EPO)
2. Thrombopoietin (TPO)
3. Leukopoiesis
4. Colony-stimulating factors (CSF), interleukins, stem cell factor
Erythropoietin (EPO)
- RBC production
- sites of production in kidney cells primarily
- stimulated by low O2
Thrombopoietin (TPO)
- produced in liver primarily
- influences growth or differentiation of megakaryocytic (platelets)
- thrombocyte (platelet) production (TPO)
Leukopoiesis
- Leukocyte (WBC) production (CSF’s)
Colony-Stimulating Factors (CSF)
- produced in endothelium and fibroblasts of bone marrow, leukocytes
- influences growth or differentiation of all types of blood cells; mobilizes hematopoietic stem cells
RBC’s Erythrocytes
- non-nucleated biconcave cells with diameter ~7.5um
- distinctive shape increases surface to volume ratio
- most abundant cell type in blood
Tasks of RBC’s
- carrying O2 from the lungs to the systemic tissue
- carrying CO2 from the tissues to the lungs
- assisting in the buffering of acids and bases
Shape of RBC’s
- allows them to squeeze through capillaries
- respond to osmotic changes
- provide evidence of disease
RBC’s in Hypertonic Solution
- cell shrink, but rigid cytoskeleton remains intact
- spiky surface
- cells are crenated
RBC’s in Hypotonic Solution
- cell swells and lose their characteristic biconcave disk shape
Hemoglobin
- RBC’s mainly consist of hemoglobin
- the O2 transport protein
- each are composed of 4 protein global chains
- each entered around a heme group
- 2 alpha and 2 beta chains
Globin Proteins
- alpha, beta, gamma, delta
Heme Group
- each group consists of a porphyrin ring with an iron atom in the centre
- each group can bind one O2 molecule
- 70% of iron in body found here
Hemoglobin and Iron Process
- Fe ingested from diet
- Fe absorbed by active transport
- transferrin protein transports Fe in plasma
- bone marrow uses Fe to make Hb as part of RBC synthesis
- RBCs live about 120 days in the blood
- spleen destroys old RBCs and converts Hb to bilirubin
- bilirubin and metabolites are excreted in urine and feces
- liver metabolizes bilirubin and excretes it in bile
- livers stores excess Fe as ferritin
Hemoglobin Synthesis
requires iron
WBC’s (Leukocytes)
- defend against infection
- grouped into two major groups
1. Granulocytes
2. Non-granule containing lymphocytes and monocytes
Granulocytes
- contain cytoplasmic granules visualized under microscope
- brief lifespan in the blood <12 hours, but if activated can migrate into tissues for longer time
- types: neutrophil, eosinophil, basophil
Neutrophil
- most abundant leukocyte, contain granules with lysosomal enzymes capable of digesting foreign material (phagocytosis)
Eosinophil
- granules contain Major Basic Protein (MBP) which is toxic to parasites and other enzymes
- important in response to virus’ and in allergic reactions
Basophil
- least common granulocyte, granules contain histamine, heparin and peroxidase and play a role in allergic reactions
Non-Granule
- Lymphocytes
- Monocytes
Lymphocytes
- two types
1. T-lymphocytes (T-cells)
2. B-lymphocytes (B-cells)
T-Cells
- 70-80% of all lymphocytes
- responsible for cell mediated immunity
- doesn’t involve antibodies
- Tmem, Treg, Thelp, Tnk…
B-Cells
- responsible for humoral immunity, make antibodies to antigens
- Bmem, Breg…
Monocytes
- spend life in peripheral tissues developing into macrophages
- purposes of macrophages
1. phagocytosis of pathogens or cellular debris
2. present antigens to lymphocytes
Platelets (Thrombocytes)
- nucleus-free fragments
- 2-3um in diameter in their inactive state
- a single megakaryocytic can produce 1000s of platelets
- 140-400000 platelets per 1ul of blood
- contain two special types of granules (dense core granules and alpha-granules)
- essential for hemostasis
Dense Core Granules
- contain ATP, ADP, serotonin, and Ca2+
Alpha-Granules
- store von Willebrand factor, platelet firbrinogen, and clotting factor V
Megakaryocytes
- giant cells with multiple copies of DNA in the nucleus
Platelets Formation
- edge of megakaryocyte break off to form cell fragments (platelets)
Hemostasis
- the prevention of hemorrhage (bleeding) is achieved through a 3 step process
Hemostasis Process
- Vasoconstriction
- Platelets Plus Formation
- Coagulation
Vasoconstriction
- contributes to hemostasis by closing the vessel and preventing blood flow to the damaged region
- can be triggered by direct injury to vascular smooth muscle, the release of paracrine signals from damaged endothelial cells (edothelin) or platelets (serotonin, thromboxane A2)
- bring down pressure in vessel so secure mechanical seal can be applied in form of clot
Platelet Plug Formation
- inactivated platelets do not adhere to themselves or to the intact endothelium cells that line the vessel (both: neg. charge)
- platelets contain cell surface receptors (integrins)
- damage triggers platelet formation where collagen is exposed
Platelet Plug Formation Process
- Exposed collagen binds and activates platelets
- Release of platelet factors
- Factors attract more platelets
- Platelets aggregate into platelet plug
What causes platelets to bind?
- a breach of the endothelium
- it exposes interns to collagen, fibronectin and laminin
Subendothelial Layer
- collagen, fibronectin and laminin
What does the binding of interns cause?
- activation of an intracellular signalling pathway in platelets
- causes them to release the contents of their granules
What is contained in Granules
- serotonin (vasoconstrictor)
- ADP
- Platelet-activating factor (PAF activates more platelets
PAF signals platelets to…
release thromboxane A2 (vasoconstrictor)
Intact Endothelial Cells
- release substances to prevent activated platelets from binding
What causes platelets to recruit to site and aggregate?
- ADP, serotonin, thromboxane A2
Von Willebrand Factors
- causes platelets to form molecular bridges between one another
Coagulation (Coagulation Cascade)
- a fibrin protein mesh stabilizes the platelets plug into a clot
- clot is a semisolid mass of platelets and fibrin with RBC’s, WBC’s and serum entrapped within
- being with 2 pathways of activation that converge
Intrinsic Pathway
- surface contact pathway
- factor XII is activated when contacting exposed collagen, activated platelets
- final product = factor Xa
Proteolysis
- breakdown of proteins into smaller polypeptides or amino acids
Extrinsic Pathway
- cell injury pathway
- factor VII (tissue factor) leaves vessel binds to tissue factor receptor and becomes factor VIIa
- final product = factor Xa
Common Pathway
- factor Xa from intrinsic and extrinsic is used to create thrombin which ultimately converts fibrinogen to a stable fibrin clot
Hemophilia
- where one of the factors in the coagulation cascade is defective or lacking
- bruise easily, spontaneous bleeding
- bleeding in joints and muscles can be painful and disabling
- can be fatal
- treated with synthetic factors
- AAV treatment
Hemophilia A
- factor VII deficiency
- most common
Hemophilia B
- factor IX deficiency
Why is too much coagulation bad?
- can because a stroke, heart attack, pulmonary embolism
Anticoagulant Factors
- produced by healthy endothelial cells
- interfere with the clotting cascade
- Prostacyclin and NO: prevent platelet binding
- TFPI
- Antithrombin III
- Thrombomodulin
- Protein S and C
Fibrinolysis
- breakdown of blood clots
Fibrinolysis Process
- conversion of plasminogen to plasmin (proteolysis)
- endothelial cells produce tissue plasminogen activator (t-PA) that cause this conversion
- plasmin is capable of breaking down both stable fibrin and fibrinogen