Blood Physiology Flashcards
Function of Blood
- Transport of substances in blood
- Regulation of ion and pH balance
- Defense and Immune protection
- Hemostasis
Centrifugation
Separation of blood
- upper layer = plasma
- middle layer = buffy coat (white blood cells and platelets)
- bottom layer = red blood cells
Hematocrit
% of total blood volume occupied by red blood cells
Clinical significance of Hematocrit
Indicates anemia or polycythemia
Fluid Compartments
Intracellular = fluid inside of cells Extracellular = fluid outside of cells
Plasma
Liquid portion of blood containing water, electrolytes, organic molecules, trace elements, gases
Albumin
Contribute to colloid osmotic pressure of plasma, carry/transport substances in plasma
Globulin
clotting factors, enzymes, antibodies, carriers for various substances in blood
Fibrinogen
Forms fibrinogen threads for blood clotting
Transferrin
Transport of Iron
Red Blood Cells
Transport of oxygen and carbon dioxide
Biconcave
No nucleus
Contain hemoglobin
Neutrophils
Phagocytes
Eosinophils
Defence against parasites
Basophils
Inflammation, allergies
Monocytes
Phagocytes and immune defence
Lymphocytes
B-Cell = antibody production and humoral immunity T-Cell = cellular immunity
Hematopoiesis
Process of formation of blood cells
Before birth - yolk sac, liver, spleen
After birth - bone marrow
Stem Cell
undifferentiated cell capable of giving rise to any type of blood cell
Factors Affecting Hematopoiesis
Cytokines = small secreted proteins that are released into the blood and act on receptors on target cells
Erythropoietin
Regulates production of red blood cells
Thrombopoietin
Regulates production of platelets
Hemoglobin
Composed of heme (non-protein) and globin (protein)
Hemoglobin A is composed of 4 globin chains (2 alpha and 2 beta) and 4 ferrous ions
Each iron can bind 1 oxygen
Hemoglobin and O2 Transport
Oxygen is transported in red blood cells bound to hemoglobin
Hemoglobin binds oxygen in a loose and reversible manner
Factors Affecting RBC Production
Cytokines = EPO
Dietary Factors = iron needed for Hb, folic acid, vitamin B12
Intrinsic Factor = made by cell in the stomach and needed for absorption of vitamin B12
Regulation of RBC Production via EPO
- Decrease in tissue oxygenation
- Stimulates the release of erythropoietin from kidneys
- Increases production of RBC in bone marrow
- Increases oxygen-carrying capacity of the blood
- Increased oxygenation of tissues
Hypoxia + Causes
Low oxygen concentration in blood Caused by: -low blood volume -anemia -low hemoglobin -poor blood flow -pulmonary disease
Uptake of Iron
Obtained from diet and absorbed into blood in intestine
Transported in blood via transferrin
Body Iron reserve: 50% in dying RBC’s, 25% in iron-containing proteins, 25% stored in liver
Recycling of Iron
Hemoglobin broken into heme and globin
globin broken into amino acids
heme broken into iron and bilverdin
Anemia
Decreased oxygen-carrying capacity of blood due to a deficiency of red blood cells and/or hemoglobin
Factoring Causing Anemia
- Lack of iron
- Pernicious anemia - lack of vitamin B12
- Aplastic anemia - damage to the bone marrow
- Kidney Disease - low EPO
- Hemolytic anemia - destruction of RBCs
- Hemorrhagic anemia - blood loss
- Abnormal structure of hemoglobin
Sickle Cell Disease
Have abnormal Hb called Hbs
A sickle-shaped cell that is hard and non-flexible
Hemolytic anemia
Immunity
Process where our body defends against anything foreign - protects our “self” from our “non-self”
Innate/Natural Immunity
Nonspecific immunity that we are born with
No memory involved
Involves neutrophils, macrophages, and the complement system
Acquired Immunity
Specific immunity that is acquired over time and upon exposure to pathogens
Has memory
Involves lymphocytes, antibodies, and cytotoxic molecules
Appropriate/Inappropriate immune responses
Appropriate = defence, removal of abnormal cells Inappropriate = allergies, autoimmune response
Inflammation
Non-specific innate immune response to tissue damage
Purpose of Inflammation
To heal
To destroy non-self agents
Fibrosis
Physical Characteristics of Inflammation
Redness Swelling Heat Pain Loss of function
Vascular Events - Inflammation
Involves blood vessels
- Histamine causes vasodilation of blood cells, increasing blood flow causing redness and heat and it also causes leaky cells with increased permeability, causing a buildup of fluid which causes swelling
- Inflammatory mediators are released
Cellular Events - Inflammation
Involves cells
- macrophages kill pathogens
- increased movement of white blood cells into the affected area
- phagocytosis and destruction of the foreign agent
Sequence of Cellular Events - Inflammation
- Margination of WBCs - move to edge of blood vessels
- Tethering + rolling of WBCs - attaching of WBC to endothelial cells of blood vessels + slow rolling along the vessel
- Activation of WBC - involves protein expression
- Arrest/Firm Attachment - neutrophils bind to complementary proteins
Emigration/Diapedesis - Chemotaxis
- Recognition of non-self by WBC at the site of infection
- Phagocytosis of non-self agents
Diapedesis
White blood cells squeeze in between adjacent endothelial cells to exit out of the blood vessel and move into tissue spaces
Chemotaxis
Ability of WBCs to move against a concentration gradient
Chemotactic factors attract WBCs to site of infection
Phagocytes
A cell that can eat other non-self pathogens or dying cells by engulfing them with pseudopodia
eg. monocytes, macrophages, neutrophils
Steps of Phagocytosis
- Recognition of substance to be ingested
- Attachment of phagocytes to the substance to be ingested
- Pseudopdia reach around substance and come together to form a phagosome inside of the phagocytic cell
- Fusion of the phagosome to a lysosome to form a phagolysosome
- Destruction of ingested substance by lysosomal enzymes
- Release of end products into the cell or out of the cell by exocytosis
How do Phagocytes Recognize Bacteria?
They have receptors called pattern recognition receptors that recognize a specific pattern of molecules expression on bacteria - do not recognize specific bacteria necessarily
Opsonins
Molecules added to the surface of bacteria to help in speeding up the rate of phagocytosis
Opsonization
Coating of bacteria with opsonins facilitates the attachment and phagocytosis of the bacteria by the phagocytic cell
Killing by Neutrophils
Oxygen-dependent = corrosive oxygen-free radicals products are synthesized to destroy the foreign body
Oxygen-independent = use bactericidal enzymes
-lysosomes
-lactoferrin
-defensins
Complement Proteins
Found inactive in plasma and are activated by a cascade that amplifies the signal
Innate immune response
3 pathways activate complement proteins
Function of Complement Proteins
OIL
Opsonization = activated complement proteins act as opsonins
Inflammation mediator = activated complement proteins attract other immune cells to site of infection
Lysis = complement proteins cause lysis of bacteria
Characteristics of Acquired Immunity
Recognize a specific foreign antigen or agent
Respond to then antigen by mounting an immune response to bring about their destruction
Remember the first encounter with the antigen
Role of B Cells
Humoral component of acquired immunity
B cells binds a complementary antigen and undergoes clonal expansion where 2 types of B cells are formed:
- Plasma cells synthesize antibodies specific to the antigen. Freely circulates (humoral immunity)
- Memory cells are long-lived cells that remember the first exposure
Humoral Immunity
Free circulating antibody molecules bing specific foreign antigens to form antigen-antibody or immune complexes
Neutralizes toxic materials produced by bacteria
Cellular Immunity
immune response that does not involve antibodies but rather phagocytes and T-cells
Types of T-cells
cytotoxic T-cells, helper T-cells, memory T-cells
Function of T-cells
Recognize a foreign antigen
Respond to the foreign antigen by generating a cellular immune response
Remember the first encounter with a foreign antigen
Major Histocompatibility Complex
Used for antigen presentation for T cells for antigen memory
MHC 1 = found in nucleated cells
MHC 2 = found specifically in antigen-presenting cells like macrophages and dendritic cells
Immunological Memory
First/primary immune response = slow to develop and not a lot of antibodies is generated
Secondary immune response = magnitude of response is very quick because cells recognize the antigen
Practical for active immunity via vaccination and passive immunity via antibodies transferred from mother to fetus
Hemostasis
Preventation of blood loss
Platelets are important in hemostasis
Why is hemostasis necessary?
Body wants to maintain a state where blood can circulate smoothly with no unnecessary blood clots
Pro-hemostatic factor
factors prevent blood loss
Anti-hemostatic factor
factors that keep blood fluid
Steps of Hemostasis
- Vasoconstriction (vascular spasm) - ruptured blood vessel contracts to minimize blood loss at site of cut
- Primary hemostasis/platelet plug formation - platelets aggregate to form a platelet plug (white thrombus)
- Secondary hemostasis/coagulation - blood clotting enzymes are activated to form a stronger, gel-like red thrombus
Where do platelets come from?
originate from stem cells of bone marrow that become megakaryocytes. platelets are pinched off from the cytoplasmic part of megakaryocytes
Structure of Platelets
Contain organelles but have no nucleus
Contain glycogen for energy
Contain actin and myosin
Contain surface glycoproteins which act as receptors
Platelet granules
Alpha granules = contain large molecules like adhesive protein von Willebrand factor, growth factors, blood clotting factors
Dense granules = contain small molecules like ADP and ATP, calcium
Platelet Plug Formation
- Platelets adhere to collagen using von Willebrand factor (factor forms a bridge between damaged vessel wall and the platelets)
- Activation of platelets - change shape, express various receptors, and secrete various substances
- Aggregation of platelets - they stick to each other to form a plug
After the plug is formed, myosin and actin contract to tighten and seal the plug
Role of Activated Platelets
Activated platelets secrete:
- serotonin + ADP which acts as a vasoconstrictor and ADP further aggregates platelets
- thromboxane A2 which promotes further aggregation and vasoconstriction
Why does Platelet Plug not Continuously Expand?
Adjacent undamaged endothelial cells synthesize and release prostacyclin and nitric oxide which inhibit the spread of the platelet plug along undamaged endothelium
Lipoxygenase Pathway
Arachidonic Acid is converted to leukotrienes by lipoxygenase which initiates swelling - inflammation
Cyclooxygenase Pathway
Arachidonic acid is converted to prostaglandin by cyclooxygenase. Hemostatic responses vary - hemostasis
COX 1
causes vasoconstriction - pro-hemostatic effect
COX 2
causes vasodilation - anti-hemostatic effect
Effect of Aspirin on Hemostasis
Aspirin blocks COX 1 and COX 2. COX 2 can overcome the inhibitory effects to continue producing prostaglandins to keep blood vessels open
Secondary Hemostasis
Occurs following a platelet plug formation
Involves a cascade of enzyme activation
Activation of enzymes occurs by proteolytic cleavage
Formation of gel-like fibrin clot
Factors in Blood Clotting
Synthesized in liver Factor 1 = fibrinogen Factor 2 = prothrombin Factor 3 = tissue thromboplastin Factor 4 = calcium
Key Step in Blood Clotting
Generation of the active thrombin enzyme
- Inactive enzyme prothrombin is converted to thrombin
- thrombin converted fibrinogen to fibrin
Pathways and Common Activation Factor
Intrinsic pathway = inside blood vessel
Extrinsic pathway = outside blood vessel
Both meet the common activation factor “Xa”
Factor Deficiencies
VII - severe bleeding
VIII - severe bleeding (hemophilia)
XI - moderate bleeding
XII - no bleeding in vivo, failure to clot in vitro
Thrombin as an anti-coagulant
Thrombomodulin binds to thrombin and activates protein C
Activated protein C inhibits factors VIIIa and Va
How does a clot not spread to where it isn’t needed?
Anticoagulants prevent clot formation
Fibrinolysis
The breakdown of fibrin in a clot
Plasminogen Activators
break down a clot
tPA converts inactive plasminogen to the active enzyme plasmin that breaks down the insoluble fibrin strands into soluble fibrin that can be dissolved
Factors Leading to Abnormal Hemostasis
When pro-hemostatic factors fail
-problems with platelets
-problems with clotting factors
When anti-hemostatic factors fail
-deficiencies of natural anticoagulants and fibrinolytic factors may cause thrombosis
-acquired disorders may lead to formation of blood clots
Blood types
A, B, AB, O
Antigens found on surface of red blood cells, antibodies found in blood
Determination of blood types
Determined by which antigens are present
A mixture of a blood sample with anti-A or anti-B antibodies are tested for agglutination
Agglutination
A process in which surface antigens on RBCs are bound to antibodies to form a clot following hemolysis
Blood Donor Selection
a donors red blood cell antigens are matched with the recipient’s plasma antibodies
Universal Donor
Type O
Universal Recipient
Type AB
