ME01 - Hematology 1,2,3 Flashcards
What is the composition of Blood
PLASMA (5% of TBW) - fluid medium of blood; where cells are suspended; yellow colored contains proteins, nutrients and wastes
SERUM - Plasma minus clotting factors
- closest to distilled water
Essential Component of Clotting System
Blood Coagulation Proteins
Major contributors to Osmotic Pressure of Plasma
Albumin
Types of Globulins present in Plasma
Alpha - Proteases, antiproteases, transport proteins
Beta - Transferrin, other transport proteins
Gamma - Immunoglobulins
Other products involved in the plasma
Electrolytes - Major ECF Cation: Na+
Organic Nutrients - Lipids, CHO, Amino Acids
Organic Wastes - Carried to the sites of breakdown or excretion (urea, uric acid, bilirubin, ammonium ions)
Plasma collectively exert __________ within the circulatory system
Colloidal osmotic Pressure
Plasma proteins are derived from
*Primary source of plasma proteins
Liver
except Immunoglobulins which are derived from plasma cells
How can liver disorders and clotting factors relate
Liver disorders can alter the composition and functional properties of blood
Liver disease can lead to uncontrolled bleeding due to inadequate synthesis of proteins involved in clotting
Formed elements are made in the ________ via the process called ___________
Bone Marrow
Hematopoiesis
1st site of blood cell production during 3rd week of fetal embryologic development
Yolk Sac/Aorta Gonad Mesonephros (AGM) Region
Chief site of blood cell formation shortly after birth
Liver
Site of Hematopoiesis that begins during the 3rd month of embryogenesis
Liver
Organs that gives minor contribution in Hematopoiesis during Liver Stage
Spleen and Lymph nodes
Only source of hematopoiesis “post-natally”
Bone Marrow
During when does hematopoiesis in the bone marrow begin
4th month of development
Hematopoiesis in relation to age
Birth to Puberty - marrow throughout the skeleton remains red and hematopoietically active
Age 20 and above - only vertebrae, ribs, sternum, skull, pelvis & proximal epiphyseal region of humerus retain red marrow. Remaining marrow becomes yellow, fatty and inactive
Hematopoiesis Organs in Order
Yolk Sac»_space; Liver, Spleen»_space; Bone Marrow
Chief site of blood formation PRE-NATALLY
Liver
Chief site of blood formation POST NATALLY
Bone Marrow
Post embryonic extramedullary hematopoiesis is ________ in a full term infant
Abnormal
What causes extramedullary hematopoiesis in adults
In conditions such as Hemolytic Anemia, it maxes out bone marrow compensatory mechanism thus “asking help” from spleen, liver and lymph node
Difference of Progenitors (Committed Cell Types) from Hsc (Parent Cell)
Loss of Pluripotency
Lack of Capacity for Self-renewal
Higher fraction of cells traversing the cell cycle
Reduced ability to efflux foreign substances
Change in their surface protein profile
Genetic Basis for Transition of Hsc to Committed Progenitors
Marked downregulaion of large number of hsc-associated genes
Progressive upregulation of limited number of lineage-specific genes
Cytokine that induces production of other cytokines from many cells
Works in synergy with other cytokines on primitive hematopoietic cells
IL-1
Cytokine for T-cell growth factor
IL-2
Cytokine that stimulates the growth of multiple myeloid cell types, involved in delayed type hypersensitivity
IL-3
Cytokine for Eosinophil growth factor and affects mature cell function
IL-5
Cytokine that stimulates B lymphocyte growth:
Works in synergy with other cytokines on megakaryocytic progenitors
IL-6
Principal regulator of early lymphocyte growth
IL-9
Cytokine that stimulates growth of multiple lymphoid and myeloid cells
IL-11
Cytokine that modulates T-lymphocyte activity and stimulates natural killer cell proliferation
IL-15
Cytokine that affects growth and maturation of B, T and natural killer cells
IL-21
Cytokine that induces production of other cytokines from many cells
SCF
Stimulates proliferation of erythroid progenitors
EPO
Promotes proliferation of monocytic progenitors
M-CSF
Stimulates proliferation of neutrophilic progenitors
Acts in synergy with IL-3 on primitive myeloid cells and activates mature neutrophils
G-CSF
Cytokine that affects granulocyte and macrophage progenitors and activates macrophage
GM-CSF
Cytokine that affects hematopoietic stem cells and megakaryocytic progenitors
TPO
Gives the whole blood its characteristics
RBC
Function of RBC
Transports hemoglobin (carries oxygen) from lungs to tissues
Transports CO2 from tissues to lungs for expulsion
Acts as acid-base buffer for whole blood
What enzyme is involved in catalyzing reaction between CO2 and H2O to form carbonic acid or H2CO3
Carbonic Anhydrase
Normal resting shape of RBC
Biconcave disc
Central 1/3 appears pale compared to its periphery
Implications of RBC Structure
Large ratio of SA to volume
Enable RBCs to for stacks for smoother blood flo
Allows large reversible elastic deformation as it passes through microcirculation
Hgb vs Hct
HGB - protein inside RBC that binds with oxygen
HCT - % of whole blood occupied by cellular elements
Normal values for Hgb and Hct
Hgb Male - 14-18g/dL Female 12-18g/dL
Hct Mlale - 46(40-54) Female 42 (37-47)
Structure of adult hemoglobin (HbA)
2 alpha units and 2 beta units
Formation of Hgb
2succinyl CoA + 2 glyine 4 pyrrole >> protoporphyrin IX Protoporphyrin IX + Fe++ >> Heme Heme + Polypeptide >> Hemoglobin chain (a or B) 2 a chains + 2 B chains >> HbA
How many oxygen molecules can 1 hemoglobin molecule bind
4 oxygen molecules
How many oxygen molecules can 1 myoglobin molecule bind
1 oxygen molecule
Structure of HbF
2 a and 2 gamma chains
Has higher affinity to oxgen
HbF because it binds less to 2-3 BPG
Enzyme that causes shift to the right of the O2-Hgb Dissociation curve or increase unloading of O2
2,3 BPG
Essential metallic component of Heme
Iron
Total iron in the body
4-5 g
Primary storage protein for iron found in the liver
Ferritin
Storage of iron outside the liver
Hemosiderin
Transport of iron in the blood
Transferrin
Hormone responsible for RBC Production
Erythropoietin
Stimulus for EPO production
Hypoxia
Formation of Erthrocytes/RBC
Proerythroblast Basophil erythroblast Polychromatophilic erythroblast Orthochromic erythroblast Reticulocyte Erythrocyte
(+) Nucleus, ER absorbed
Orthochromatic Erythroblast
No nucleus
(+) remnants of Golgi Apparatus, mitochondria and other organelles
Reticulocytes
Average life span of RBC
Adult - 120 days
Fetal - 90 days
RBC Destruction (Intravascular)
RBC membrane breeched»_space; becomes fragile» self destruct in RED PULP OF SPLEEN
RBC is destroyed» Hgb that escapes is bound to “Haptoglobin”»_space; Hgb-Haptoglobin complex goes to the liver
RBC Destruction (extravascular)
Ingestion by a macrophage (Kuppfer cells of liver/macrophages in spleen and blood)»_space; degraded within lysosomes»_space; lipid, protein and heme
2 signals that differentiate young from OLD RBC
- Decreased deformability
2. Altered surface properties
Heme (in hemoglobin) is converted to iron and BILIVERDIN by “heme oxygenase”»_space; Biliverdin is converted to _____ (final product of Hgb Metabolism)»_space; Excreted into bile in GIT
Bilirubin
Conjugated Bilirubin excreted in the urine
Urobilin
Conjugated Bilirubin excreted in feces
Stercobilin
Role of Vitamin B12 and Folic Acid in RBC Formation
essential for synthesis of DNA
Formation of thymidine triphosphate, building block of DNA
Vitamin B12/Folic Acid Deficiency can cause what time of Anemia
Megaloblastic Anemia (macrocytes with flimsy membranes that are oval in shape and irregular)
Neural Deficits are caused by what deficiency
Vitamin B12 Deficiency
Neural Tube Defects are caused by what deficiency
Folic Acid Deficiency
Capability of the body to resist almost all types of organisms or toxins that tend to damage tissues and organs
Immunity
2 types of Immunity
Innate Immunity
Acquired Immunity
Innate Immunity vs Acquired Immunity
INNATE ACQUIRED
Pre-existing Antibody-mediated
(skin, mucous membranes, lymphoid cells
complement system)
Not acquired through contact Occurs after exposure to antigen
with non self (antigen)
Non specific Specific Quick Delayed Response
Granulocytes/PML/Myeloid Cells
Basophils, Eosinophils, Neutrophils
Agranulocytes
Monocytes, Lymphocytes
Site of production of lymphocytes, Plasma cells
LN, Spleen, Thymus, Peyer’s patches
Site of production of granulocytes, monocytes
Bone Marrow
Lifespan of Monocytes
10-20 hours in the blood, for several months in the tissues
Lifespan of Granulocytes
4-8 hours in the blood, 4-5 days in the tissues
shortened during infection
Lifespan of Lymphocytes
Weeks to months
Arrange WBC according to number
Neutrophil Lymphocytes Monocytes Eosinophils Basophils
Appearance of Macrophage indicates
Inflammation
Functions of WBC
Neutrophils - acute inflammatory response to tissue injury
Eosinophils - allergic reactions and parasitic infection
Basophil - allergic reaction
Monocytes -
Platelets - Hemostasis
Prominent feature is the highly lobulated nucleus
Neutrophills
Prominent feature is bilobed nucleus, stain bright red with eosin dye
Eosinophil
Weak phagocyte
Eosinophil
Share functional similarities with Mast Cells
Basophils
Basophils produces _______
Histamine, Heparin, Bradykinin, Serotonin
Prominent feature is bilobed/trilobed, largely densely basophilic (blue) granules
Basophils
Resident phagocyte
Monocyte
Prominent feature is eccentrically placed nucleus
Monocyte
Small, non-nucleated cells from Megakaryocytes
Platelets
Life span of platelets
7-10 days
Prominent feature is round, densely stained nucleus with a pale basophilic, non-granular cytoplasm
Lymphocytes
Cells of the adaptive immunity
Lymphocytes
What is the largest WBC
Monocyte
What is most numerous, least numerous WBC
Most numerous: Neutrophils
Least Numerous: Basophils
Cells involved in adaptive immunity and parasitic infection
Adaptive immunity : Lymphocytes
Parasitic Infection: Eosinophils
Differences of Neutrophils and Macrophages
NEUTROPHILS MACROPHAGES
Released as mature cells Released as immature cells
Phagocytize 3-20 bacteria Phagocytize 100 bacteria
Similarities of Neutrophils and Macrophages
Chemotaxis - method by which they are attracted to the site of injury
Diapedesis - Entering the tissue
Ameboid Movement - movement through the tissue
Lysosomes present: Proteases, hypochlorite, Lipases
Peroxisomes: Free radicals like superoxide, hydrogen peroxide
Movement out of the circulatory system and into the site of injury
Diapedesis
Movement of neutrophils and macrophages towards a chemical signal
Chemotaxis
Mast cells release _______ to cause vasodilation and increased vascular permeability
Histamine
1st line of defense
Present within minutes
Identifies pathogen»_space; phagocytosis
Tissue macrophage
2nd line of defense Blood monocytes (inactive) are converted to tissues: macrophage (active) Response takes time (up to 8 hours)
Monocytes
4th line of defense
takes 3-4 days
Inc Monocytes & Granulocyte production by BM
Monocytes and Granulocytes are mediated by
TNF, IL-1, GM-CSF, M-CSF
The battlefield of dead cells and pathogens
PUS
caused by special immune system that forms antibodies and/or activated lymphocytes that attack and destroy the specific invading organism or toxin
Adaptive Immunity
antibodies are gamma globulins called
immunoglobulins
Portions of Antibodies
Variable Portion: determines specificity to antigen
Constant Portion: determines other properties of antibodies
Different functions of Immunoglobulins IgG IgM IgA IgE IgD
IgG - most abundant, secondary response, smallest, to cross placenta
IgM - primary immune response, largest
IgA - main in secretions (milk, saliva, tears)
IgE - allergies and hypersensitivity
IgD - antigen receptor present on surface of B lymphocytes
DIRECT ACTION of Antibodies
Agglutination - clumping
Precipitation - insoluble Ag-Ab complex
Neutralization - AB covers the toxic sites of the antigenic agent
Lysis - rupture of the agent
INDIRECT ACTION of Antibodies
via the Complement System
Part of innate and adaptive immunity
Complement proteins are soluble proteins in the blood stream
Complement System
3 important processes involved in Complement System
Opsonization - marker that makes easier to phagocytize foreign bodies
Membrane Attack Complex (MAC) - perforate foreign organisms
Stimulate Inflammation
Complement responsible for Opsonization
C3b
Complement is an anaphylatoxin (induces inflammation)
C3a, C4a, C5a
Which complement is chemotactic to WBCs
C5
Which complement is part of the Membrane Attack Complex (MAC)
C5-C9
Types of T cells
T-helper cells (CD4, MHCII)
Cytotoxic T cells (CD8, MHCI)
Suppressor T cells
Cancer cells
Virally infected cells
Transplanted/Grafted cells
CD8
Most numerous of T cell
Various “helper” function
Helper T cell
“Helper function” of T cells
Regulatory function of lymphokines
Stimulation of growth and proliferation of Cytotoxic T cells & Suppressor T cells
Stimulation of growth and differentiation of B-cell and antibody formation
Activation of macrophage system
Direct attack cell capable of killing microorganisms
Creates “holes” (perforins)
Targets virally infected cells, cancer cells and transplanted cells
Cytotoxic T cell
Suppressing action of Helper T cell and Cytotoxic T cells
Important role in limiting the ability of the immune system to attack a person’s own body tissue
Suppressor T cell
Could either be passive or active immunity
Artificial Immunity
Disadvantage of artificial immunity
Short life span of antibodies, hypersensitivity reaction
Type of immunity that is has developed antigen in the body
Active immunity
Type of immunity that you administer the antibody
Passive immunity
Induced after contact with foreign antigen (usually killed or live attenuated infectious agents)
ACTIVE IMMUNITY
Advantage: long term protection
Disadvantage: slow onset of action
Administration of antibody (in antisera) in a vaccine
PASSIVE IMMUNITY
Advantage: prompt availability of large amount of antibodies
Disadvantage: short life span of antibodies, hypersensitivity reaction
Blood groups is based on _________
Carbohydrate antigens (A and B) present on RBC membrane either as glycoprotein/glycospingolipids
What determines the O-A-B Blood type
Two genes, one one each of two paired chromosomes
Universal Donor
Type O
Universal Recipient
Type AB
Why are agglutinins produced in people who do not have the respecive agglutinogens in their red blood cells?
Small amounts of type A and B antigens enter the body in food, in bacteria and in other ways, substances initiate dev’t of anti A and anti B agglutinins
ABO System Blood Group Genotypes Blood Types Agglutinogen Agglutinins OO OA or AA OB or BB AB
Genotypes Blood Types Agglutinogen Agglutinins
OO O - Anti A and Anti B
OA or AA A A Anti B
OB or BB B B Anti A
AB AB A and B No antibodies
Rh Blood Group
Blood group with 6 Antigens – C, D, E, c, d, e
Blood group that is supposed to be exposed to blood products to develop antibodies
Rh Blood Group
Agglutinins are produced after massive exposure to the Rh agglutinogens
Most widely prevalent antigen
D
If you have D antigen - Rh+
If you do not have D antigen - Rh- (No exposure to blood group does not develop antibodies for D antigen)
Complication that manifest in second Rh+ baby
Hemolytic Disease of the Newborn
Implications and Treatment of HDN
Erythroblastosis Fetalis , where the antibodies developed by the mom attacks the fetus RBC resulting to (+) hemolysis
Treatment - Rhogam
Rhogam destroys anti D antibodies to prevent hemolysis of the 2nd baby
IDENTIFYING BLOOD TYPE
Forward
Reverse
Pretesting of blood
Forward - identify antigen by antisera
Reverse - identify isoagglutinin in serum
Matches donor blood unit to recipient’s blood
Cross Matching
Serum used for Rh typing
Anti-D serum
Transfusion Agglutination Reactions in ABO Blood Group
Delayed hemolysis - AgAb complex cause agglnt
Immediate hemolysis - Ab meet Ag donor RBCs
BLOOD TRANSFUSION PRODUCTS Whole Blood Packed RBCs Platelet concentrates Fresh Frozen Plasma Cryoprecipitate Cryosupernate
Whole Blood - Cases of Acute Hemorrhage
Packed RBCs - Anemia and symptoms of Dizziness, Inc HR
Platelet concentrates - Mucosal bleeding, Px with fever or infection
Fresh Frozen Plasma - Thrombocytic Thrombocytopenic purpura
Cryoprecipitate - More spec. clotting factor fibrinogen, F8, vWF
Cryosupernate - Contains factor IX (hemophilia B)
Prevention of blood loss
Hemostasis
Stages of Hemostasis
Vasoconstriction - Use of Endothelin 1
Primary Hemostasis - Formation of initial platelet plug
Secondary Hemostasis - Coagulation cascade
Clot Retraction - Dissolved blood clot
Mechanism in Vasoconstriction
Local myogenic spasm - strongest contributor
Autocoid factors such as thromboxane A2, Endothelin
Nervous reflexes
Thrombocytes
Originate from megakaryocyte
Eventually cleared by macrophages in the blood and in the spleen
Platelets
Stages in Formation of Platelet Plug
Platelet adhesion - Plt secrete glycoprotein Ib bind to vWF
Platelet activation - thromboxane A2 activates other platelets
Platelet aggregation - fibrinogen in blood bind to GpIIbIIIa
Formation of thombin
Stabilizes thrombin _______
Dissolves Fibrin __________
Fibrin
Plasmin
Platelet count
Formation of fibrin through the coagulation cascade
Secondary Hemostasis
- Extrinsic Pathway
- Intrinsic Pathway
Important clotting factors
Tissue Factor - Factor III - triggers Extrinsic Pathway
Hageman factor - Factor XII - trigger Intrinsic Pathway
Extrinsic vs Intrinsic Pathway
Extrinsic Pathway – BLOOD
- initiates coagulation cascade
- can be explosive
- limited quantities of traumatized tissue, Factor X, VII and V
- clotting occur in 15 sec
Intrinsic Pathway – TISSUES
- Amplifies the cascade
- slower, clotting in 1 to 6 minutes
Which part of Coagulation Cascade does extrinsic and intrinsic pathways converge
Factor Xa - mediated generation of thrombin to form prothrombin
What other factors are involved in the coagulation cascade
Calcium, - involved in all steps except the first 2 steps
Vitamin K - required to produce prothrombin and other clotting factors
Anticoagulant mechanism
Smooth endothelium
Glycocalyx layer repels platelets ad clooting factors
Endothelium
Secreted by endotheliu, that binds thrombin thereby reducing free thrombin
Activates Protein C which inactivates Factor V and VIII
Thrombomodulin
What are intravascular anticoagulants
Antithrombin III - inactivates thrombin
HEPARIN - increases activity of antithrombin III
Lysis of blood clot
Injured vascular endothelial cells»_space; plasminogen activators»_space; plasminogen»_space; plasmin»_space; helps degradation of fibrin to fibrin degradation products
ABNORMALITIES IN COAGULATION Severe Bleeding Liver Diseases Vit K Deficiency Hemophilia A Hemophilia B
Excess Coagulation
Severe Bleeding
Liver Diseases - Liver produce clotting factors (neonates supplemental)
Vit K Deficiency - Vit K dependent factors
Hemophilia A - Factor 8 deficiency
Hemophilia B - Factor 9 deficiency
Excess Coagulation
Protein C and Protein S (cofactor of Protein C)
DIC
General Functions of Blood
Vehicle of Transport
Regulation of pH and ion composition
Defense against toxins and pathogens via WBC lymphocytes
Stabilization of body temperature