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(2) Blood (Blood Groups
2 genes determine (Isoforms (Rh+ / Rh-) (Rh +
…
(2) Blood
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Mismatched Blood
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Result
- Agglutination
- Hemolysis
- Diminished O2 carrying capacity
- Released Hb cause renal failure
Antigens / Agglutinogens
- Glyoprotein
- Surface of RBC
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Isoforms (Rh+ / Rh-)
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Rh -
- Absence of Factor D
- Receives Rh + Blood
- Develop anti-Rh antibodies
Example
- Mother Rh -
- Second birth of Rh +
- Anti-Rh antibodies cross into fetus
- Fetus RBC lyse and agglutinate
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Clinical Implications
Normocytic Anemia
- Normally acute
- Bone marrow yet to respond
- eg. Blood loss / Hemolysis
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Causes
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Overdestruction
Intrinsic
- Hb Defect (Sickle Cell)
- Membrane Defect (Spherocytosis
- Enzyme Defect (Pyruvate Kinase / G6PD)
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Microcytic Anemia
Diagnosis
Decreased
- Mean MCV (Avr RBC Vol)
- Hematocrit / RBC
- Hb
Intrinsic
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Primary
- Tumor like condition in bone marrow
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Blood Clotting Problems
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Liver Disease
1) Cannot synthesize clotting factors
2) Lack Vitamin K
- No bile
- Cannot absorb fats
- Cannot produce clotting factors (2, 7, 9, 10)
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Thrombocytopenia
- Circulating platelets are too low
- Widespread hemorrhage
- Destruction of bone marrow
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Leuko-penia (Deficiency)
- Too few leukcytes
- Radiation/Chemo/Viral
Leukocytosis
- WBC Count > 1.1 x 10^7/ml
- Normal response to bacterial / viral invasion
- Can indicate cancer
Leukemia: Cancer of blood
Lymphoma: Cancer of lymphatic system
- Immune deficiency
- Not functional
- Irradiation/Chemotherapy/Bone Marrow Transplant
Composition
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Urobilinogen
- Urine; Colourless
Urobilin
- Urine; Yellow
Important Facts
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Pathology
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Anemia Leading to Hypoxia
- Less viscous
- Reduced gas exchange time
- Less supply of oxygen
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Anemia: Deficiency
- Red Blood Cells
- Hemoglobin
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Hemostasis
Phases
Vasoconstriction
- Immediate
- Veins & Arteries
- Not Capillaries
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Process
- Platelets adhere / activate
- Clotting / PF3 released
- Attract more platelets
- Receives help from Factor 8
- Receives help from Von Willebrand’s
- Positive Feedback
Trigger
- Damaged endothelium (TF3)
- Exposed collagen
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Coagulation / Fibrin Clot
Process
- Thromboxane A vascular spasm
- Seratonin vascular spasm
Clot Retraction & Repair
- Squeezing serum from fibrin clot
- Platelet-derive growth factor (PDGR): Vessel wall growth
- Vascular endothelial growth factor (VEGF): Endothelial growth
Acronym: Degranulated platelets secrete:
- Thromboxane A
- VEGF
- Seratonin
- ADP
- PDGF
- Calcium
- PF3
- Factor 13
TV SAP CPF
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Coagulation Cascade
Intrinsic
- Initiation:
- Collagen (Activate Factor 12)
- Platelet Factor 3
- Thrombin (Clotting Factor 2)
- Exposed Endothelium
- Time: Minutes
- Amplified
Process
12 (Release Brandykinin), 11, 9 + 8, 10 + 5
2
1
13
Extrinsic (Usually happens first)
- Intiation:
- Time: Seconds
- Not amplified
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Regulation
Positive
Clotting Factor 2: Thrombin
5, 7, 8, 11, 13
Negative
Fibrinolysis
(1) Clotting Factor 2: Thrombin
(2) Plasminogen to Plasmin (Found in clot)
Equilibrium
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Cellular Components
Leukocytes
- Remove toxins, waste, cancer
Common Myeloid Progenitor
Monocytes (2-8%)
- Differentiated in tissues to macrophages
- Kupffer cells / Osteoclasts / Microglia
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Macrophages
- APC
- Phagocyte
- Same contents as neutrophils but more effective
- Can use multiple times
- Remove dead / dying cells (prevent disease/cancer)
Metamyelocyte
Eosinophils (2-4%)
- Filled with toxic compounds (Lipase/RNAase/DNAse)
- Defense against multicellular parasites (worms)
- Attach and release contents into parasites
- Major role in asthma & allergic diseases
Basophils (<1%)
- Contain inflammatory mediators (Histamine / Leukotrienes)
- Allergic manisfestation
- Similar to mast cells
- Regulate inflammation
Neutrophils (50-70%)
- Lysozymes
- Attack bacteria
- First to arrive at inflammation site
- Phagocytose - Die - Pus
Megakaryocytes
- Reside in Bone Marrow only
- Produce platelets
Mast Cell
- Similiar to Basophils
- Inflammation
Common Lymphoid Progenitor
- Produced in lymphoid tissue
Lymphoytes (20-30%)
T-Cells (Antigen-specific)
Helper T-Cells
- Activated by presented antigen
- Release cytokine to activate B-Cells
Cytotoxic T-Cells
- Kill virus-infected / cancer cells (Th - Immune, Tc - Cancerous)
- Secretion of perforin
- Analogous to Natural Killer Cells
Suppressor T-Cells
- Prevent immune response to normal things
B-Cells (Antigen-specific)
- Antigen presenting
- Secrete antibodies (Bind to virus prevent entry / Facilitate phagocytosis)
- Humoral (Adaptive)
Natural Killer Cells
- Not antigen specific
- Kill abnormal cells
- Analogous to Cytotoxic T
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Erythrocytes
(45% vol)
Process
- Rupture in tiny vessels of spleen (3um)
- Macrophages take up dying RBC
- Iron
- Reuse bone marrow
- Stored in liver
- Globin
- Heme
Causes
- 100-120 days
- Lack of protein synthesis
- Fragile
Erythropoietin
- Growth factor
- Stimulate proliferation of stem cells
- Stimulate Hb synthesis
Regulation
Artifical: Epogen - human erythropoietin recombinant tech
- Uses:
- Surgery
- Chemotherapy
- Dialysis (CHF: Reduc EPO)
- Doping
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Physiological Response
- Produce Erythropoietin (Stimulates marrow)
- Requires intrinsic factors
- Iron
- Folic Acid
- Vitamin B12
Location
- Fetus: Yolk sac, Liver, Spleen, Lymph node
- <5 years: Bone marrow (All)
- 5-20 years: Bone marrow (RIbs, Sternum, Vertebrae, Long bones)
- 20 years: Bone marrow (RIbs, Sternum, Vertebrae)
Binding:
- Oxyhemoglobin (Bright red)
- Deoxyhemoglobain (Dark red)
- Carbaminohemoglobin (Bound to CO2)
Heme (Red Pigment):
- 1 Fe
- 1 molecule carries 4 O2
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No Organelles
Disadvantages:
- Glucose only
- Anaerobic metabolism
- Short lifespan (No proteins synthesis or repair)
- Require replacements
Advantages:
- No O2 consumption
- More capacity
- Less heart work
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Properties
- No organelles
- Biconcave disc
- SA/Volume ratio
- Determines viscosity
- Life span: 100-120 days
- Transports 10^9 O2 molecules
Platelets
Organelles
- Mitochondria
- Golgi / ER (Store Ca, Synthesize enzymes)
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Properties
- Only found in mammals
- Lifespan: 8 - 9 days
Creation
- Fragment of megakaryocytes
- (Marrow bound leukocytes)
Regulation of Clotting
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Anticoagulants
Artifical
Chelators
- Chelate Ca2+ (Factor 4)
- Blood bank use for donated blood
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Warfarin
- Prevents reactivation of Vitamin K1
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Endogenous
Smooth Endothelium
- Most important
- GAGSs are repulsive
- Prevent adhesion of platelets
Antithrombin III (Intrinsic)
- Competitive Inhibitor
- Activated/Enhanced by Herapin
- Inactives Factor 2 (Thrombin), 9, 10, 11
Herapin
- GAG
- Enhances Antithrombin III
- Neutralized by Protamine Sulfate (Overdose)
Thrombomodulin (Intrinsic)
- Endothelial cells
- Binds to Factor 2 (Thrombin)
- Inactivates Factor 5 & 8
Tissue Plasminogen Activator (tPA)
- Equilibrium between thrombin
- Plasminogen trapped in clot
- tPA released by tissues to activate plasminogen
- Fibrinolysis
Tissue Factor Pathway (TF3) Inhibitor (TFPI) (Extrinsic)
- Produced by Mesengial cells
- Inhibits extrinsic pathway
- Inhibits Factor 10
Anti-thrombotic
Aspirin
- Not an anti-coagulant
- Prevent thrombosis
- Blocks platelet activities
Blood Coagulation Tests
Partial Thromboplastin Time (PTT) / Active PTT (aPTT)
- Measures efficacy of Intrinsic
- 12, 11, 9 + 8, 10 + 5, 2, 1
- Used to monitor Heparin Therapy (Antithrombin III)
Prothrombin (PT)
- Measures efficacy of Extrinsic & Common Pathway
- Used to monitor Warfarin Therapy (Vitamin K antagonist)
- Treatment for Vitamin K antagonist overdose Frozen Plamsa
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