Blood Physiology Flashcards
Functions of blood
- transport of substances in blood
- regulation of ion and pH balance
- defense and immune protection
- hemostasis or prevention of blood loss
Blood centrifugation
upper layer: plasma 55%
middle layer: buffy coat - white blood cells and platelets <1%
bottom layer: red blood cells 42% females, 47% males
Composition of plasma
- water, electrolytes, organic molecules, trace elements, gases
Functions of plasma proteins
Albumins: colloid osmotic pressure of plasma, transport substances in plasma
Globulins: clotting factors, enzymes, antibodies
Fibrinogen: forms fibrinogen threads to blood clotting
Transferrin: transport of iron
Made in liver
3 types of blood cells
Red blood cells (erythrocytes): transport of oxygen and carbon dioxide
White blood cells (leukocytes):
Platelets (thrombocytes):
Different types of white blood cells
Neutrophils, eosinophils, basophils, monocytes, lymphocytes
neutrophils
phagocytes
Eosinophils
defense against parasites
Basophils
inflammation
Monocytes
phagocytes and immune defense, leave blood stream and transformed into macrophages
Lymphocytes
B-cell: antibody production and humoral immunity
T-cell: cellular immunity
Hematopoiesis
formation of blood cells
before birth - yolk sac, liver, spleen
after birth - bone marrow
all originate from a pluripotent hematopoietic stem cell
Cytokines
protein that regulates hematopoiesis
released into blood and act on receptors of cells
erythropoietin - production of RBC
thrombopoietin - production of platelets
Structure of hemoglobin
single hemoglobin molecule has 4 globin protein chains (2 alpha and 2 beta chains), 4 heme groups, 4 iron atoms (each hemoglobin can find 4 oxygen)
Manner of oxygen binding
relaxed manner means successive oxygen facilitates finding of next oxygen
oxyhemoglobin is hemoglobin bound to oxygen
deoxyhemoglobin has tight binding structure and has given up oxygen
CO inhalation
Hb has higher affinity for carbon monoxide so it binds very tightly and cannot bind oxygen and deliver it to body
3 factors needed for RBC production
Cytokines: erythropoietin (EPO) stimulates RBC production
Dietary factors: iron needed in Hb, folic acid, vitamin B2
Intrinsic factors: made by cells in stomach to absorb vit B12
EPO RBC production
stimulus for EPO secretion comes from low oxygen in kidneys
EPO acts on bone marrow to turn stem cells to RBC
Increases oxygen carrying capacity of blood
Hypoxia
low oxygen concentration in blood
Transferrin
iron transport protein in blood
Ferritin
protein that stores iron in liver
Recycling hemoglobin
Heme - iron (absorbed in blood or ferritin), biliverdin (bilirubin secreted into bile and enters small intestine)
Globin: broken down into amino acids
Pernicious anemia
lack of intrinsic factor or vit B12
Aplastic anemia
damage of bone marrow due to radiation/drugs
Kidney disease
reduced level of EPO
Hemolytic anemia
increased breakdown due to abnormal shape of RBC
Hemorrhagic anemia
blood loss due to injury, ulcers, chronic menstruation
Sick cell disease
abnormal Hb called HbS, nonflexible membrane and sickle shaped, recessive disease
2 types of immunity
Innate/natural: born with, non-specific defenses, physical or chemical barriers on body, no memory, fast, phagocytes (neutrophils and macrophages)
Acquired/adaptive: acquired over time upon exposure to foreign pathogens (antibodies), has memory, slow, lymphocytes (B and T cells)
Inflammation
innate immune response to tissue injury
cause healing, destruction of non-self, formation of scar tissue (fibrosis)
Histamine
causes vasodilation which increases blood flow causing redness and heat
causes blood vessels to become leaky and permeable allowing protein and fluid to move to extracellular space causing swelling
Cellular events of inflammation
WATCH VIDEO
- WBC move to edge of blood vessels
- WBC attach to endothelial cells and slow rolling along vessel
- WBC activated - expression of proteins on surface of neutrophils and endothelial cells
- Neutrophils bind to complementary proteins on endothelial cells and stop rolling
- WBC squeeze between cells to exit out of blood vessel into tissue spaces
- WBC move to site of inflammation by chemotaxis
- Recognition of foreign agents
- Phagocytosis of foreign agents
Chemotaxis
WBC move against concentration gradient in response to their attraction to chemical factors
Phagocyte
cell that can eat non self pathogen by gulfing with temporary cytoplasm extension called pseudopodia
monocytes, macrophages, neutrophils
Opsonization
coating of bacteria with opsonins (either antibodies or complement type proteins produced by host body which then speeds up attachment and phagocytosis of bacteria
Neutrophils - oxygen dependent killing
corrosive free radical products are synthesized by body to destroy foreign body
Neutrophils - oxygen independent killing
use bactericidal enzymes
lysozymes - degrade entire bacteria by proteolytic breakdown
lactoferrin - binds to iron and reduced iron in environment to bacteria cannot grow
defensins - drill holes in bacteria surface
Complement proteins (OIL)
Opsonization - opsonins
Inflammation mediatory - chemoattractant that attract immune cells to site of inflammation, increasing histamine
Lysis - lysis of bacteria
MAC attack
kill pathogen by forming a membrane attack complex
form a pore on bacteria surface
innate immune response
B cell production
primary: develop in bone marrow, move to blood
secondary: move to lymphoid tissue or nodes
T cell production
primary: start in bone marrow and develop in thymus gland, move to blood
secondary: move to lymphoid tissue or nodes
3 R’s of Acquired immunity in B and T cells
Recognize, Respond, Remember
Antigens
specifically recognized by antibody to form antibody-antigen complex
immunogen - activated immune response
Antibody
globulin class of plasma proteins
Y shaped molecule with two heavy chains and two light chains connected by disulfide bridge
Humoral immunity
naive B cells in lymph nodes are exposed to foreign antigens
B cell will bind and undergoes mitosis
One group plasma cells - synthesize antibodies specific to antigens and will freely circulate
One group memory cells - retain memory of first exposure for long time
Cellular immunity
involves T cells: cytotoxic T cells, helper T cells, memory T cells
Antigen presentation
macrophage engulfs foreign antigen, breaks into smaller pieces, and presents it to T cell in a protein called MHC
T cells will produce cytokines which interact with B cells
MHC proteins
MHC I: all nucleated cells
MHC II: antigen presenting cells like macrophages
Active immunity
direct exposure to antigen or exposure by vaccination
antibodies are self generated
not immediate and long term immunity
Passive immunity
preformed antibodies are transferred from mother to fetus during pregnancy or nursing
immediate and short term immunity
Hemostasis
prevention of blood loss - platelets
pro-hemostatic factors - prevent blood loss
anti-hemostatic factors - keep blood fluid
Steps of hemostasis
- Vasoconstriction - through pain receptors, smooth muscle injury, serotonin
- Primary - Platelet plug formation - white thrombus
- Secondary - Blood clotting/coagulation - red thrombus
Structure of platelets
Contain vesicles called alpha granules (von Willebrand factor) or dense granules (ATP, serotonin, calcium), glycogen, contractile proteins actin and myosin, glycoproteins
Do not contain nucleus
Primary hemostasis - platelet plug formation
- Adhesion - platelets stick to collagen tissue using von Willebrand factor and form a bridge
- Activation of platelets - binding triggers release of ADP and serotonin, express fibrinogen receptor to form lattice like structure, prothrombin converts to thrombin
- Aggregation of platelets - new platelets adhere to old ones positive feedback which rapidly form plug, actin and myosin tighten plug and seal cut site
Inhibits Platelet Plug
adjacent undamaged endothelial cells release prostacyclin, nitric oxide which inhibit spread of plug
Arachidonic Acid Metabolites
Lipoxygenase pathway - arachidonic acid is converted to leukotrienes by enzymes lipoxygenase which initiate swelling
Cyclooxygenase pathway - converted to cyclooxygenase enzyme which prevent blood loss
COX 2 produces prostacyclin
COX 1 produces thromboxane A2
Aspirin
prevent clot formation during heart attacks
inhibit COX 1
initially inhibit COX 2 (cyclooxygenase) but will overcome it
Secondary hemostasis - formation of blood clot
cascade of clotting factor enzymes
activation occurs by proteolytic cleavage
formation of gel-like fibrin clot where RBC cells become trapped in red thrombus
Factors involved in blood clotting
13 factors, all present in inactive plasma proteins in blood, synthesized in liver
Factor I
Fibrinogen
Factor II
Prothrombin
Factor III
Tissue thromboplastin, tissue factor
Factor IV
Calcium
Factor Xa
formation of active thrombin by prothrombin which will turn fibrinogen to fibrin
Intrinsic pathway for blood clotting
Activation of factor XIII when contacted with damaged blood vessel wall, triggers clotting
Extrinsic pathway for blood clotting
Activation of factor VII when contacted with tissue factors outside blood vessel. Factor VIIa activates X to facilitate fibrin formation by thrombin production
Deficiency of factor VII and VIII
serious bleeding
Deficiency of factor XI
moderate bleeding
Deficiency of factor XII
no bleeding problem, but won’t clot in vitro
Roles of Thrombin
activation of platelets
converts soluble fibrinogen into insoluble fibrin
activates several other clotting factors
plays a role in anti clotting pathways
Regulation of blood clotting
Anticoagulants - prevent clot formation
Fibrinolysis - enzymatic breakdown of fibrin in blood clots
Natural anticoagulants
Tissue factory pathway inhibitor (TFPI) - inhibit factor III tissue factor
Antithrombin 3 - inhibits thrombin
Thrombomodulin - binds to thrombin to prevent clot, expressed on healthy endothelial cells, activates protein C
Clinical anticoagulants
Calcium chelators - remove free ionized calcium
Heparin - increases antithrombin 3
Vitamin K - inhibit clotting factors
Fibrinolysis
breakdown of fibrin in a clot
tPA tissue plasminogen activator
converts inactive plasminogen to active enzyme plasmin which breaks down fibrin strands
ABO Blood Type
A, B, AB, O
surface carbohydrate antigens
Blood group A - antigen A, B antibodies
Blood group B - antigen B, A antibodies
Blood group AB - antigen A and B, no antibodies
Blood group O - no antigens, A and B antibodies
Dominant is A and B antigen
ABO gene code
DNA will code for enzyme protein that attaches specific carbohydrate molecule to surface proteins of RBC
Agglutination
surface antigens on RBC are bound to antibodies to form a clump followed by hemolysis or RBC, blood is not matched
Major cross-match
donors RBC antigens are matched with recipient plasma antibodies
Minor cross-match
whole blood is transfused where RBC are not separated from plasma which contains antibodies
Universal donor
Type O
Universal recipients
Type AB
Rhesus blood type
protein antigen
Rh positive - presence of D antigen, no D antibodies
Rh negative - absence of D antigen, no D antibodies
dominant is D antigen
anti-D antibodies are immunoglobin G class
Mismatched blood transfusion in Rh system
Rh- with no D antibodies is exposed to Rh+ and develops D antibodies. Then same Rh- person exposed mistakenly to another Rh+ which leads to clumping
Rhesus mismatch between mother and child
Rh- woman conceives with Rh+ man, baby will be Rh+
First delivery - fetal Rh+ RBC enters maternal blood through placental rupture
Mom produces D antigens
Second delivery - mom’s D antigens will enter baby’s body and bind to baby RBC and hemolysis
Hemolytic disease of the newborn - enlarged spleen and jaundice
Treatment: after first delivery mom is treated with D antigens that will bind with new Rh+ blood and will be blocked
