Molecular Physiology of Blood and Body Defense Mechanisms.

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Molecular Physiology of Blood and Body Defense
Mechanisms.     1. Introduction scientific and
socio-economic significance of haematology.
Composition of Blood, Haematocrit ESR. The
normal complete blood count and common
abnormalities.     2. Plasma Proteins in Health
and Disease. Serum Protein Electrophoresis.
Viscosity and Flow non-newtonian
properties     3. Haematopoiesis Pluripotent
(Trilinear) stem cells and lineage committed
precursors. Haematopoietins, signalling
apoptosis in haematopoietic differentiation.
Molecular Pathology of leukaemia     4. Erythrocye
s, erythropoiesis and erythropoietin.
Anaemia erythrocytosis.     5. Haemoglobin
structure and function developmental biology.
Abnormal haemoglobins and thalassaemia.     6. Ery
throcytes metabolism storage lesion membrane,
blood groups transfusion serology, electrolyte
shifts   7.    Nutrition and Haematopoiesis
vitamins B Folate iron-haem-bilirubin
hyperbilirubinaemia, porphyria.
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  8. Inflammation and repair
Polymorphonuclear leukocytes - Granulocytes
reactive leukocytosis Oxygen dependent and
independent killing NADPH Oxidase
Myeloperoxidase     9. Leukocyte
migration and the extracellular matrix selectins
and integrins chemokines cytokines
pyrogens.   10. Mononuclear leukocytes
phagocytosis, dendritic cells and antigen
presentation lymphocytes subsets and
interactions in cellular immunity.     11.
Proteins of innate and acquired immunity
Immunoglobulin diversity.     12. Immune
reactions primary secondary responses memory
cells allergy hypersensitivity, atopy.
autoimmunity, clonal deletion / anergy
superantigens toxic shock     13.
Hemostasis the endothelium , atherosclerosis
thrombosis coagulation factors in
surface mediated complexes     14. Platelets,
thrombosis, thrombophilia anti-coagulants
fibrinolysis
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TEXTS IN HAEMATOLOGY.   MOST PHYSIOLOGY TEXTS
HAVE BARE MINIMUM MUST KNOW.   SOME OVERLAP
WITH BIOCHEMISTRY TEXTS (SIGNALLING, HAEMOGLOBIN,
IMMUNOLOGY ETC.)   ISRAELS AND ISRAELS (CORE)
MECHANISMS IN HEMATOLOGY. SIMPLE STYLE,
ATTRACTIVE, CD   HOFBRAND PETTIT (MOSBY)
CD CLINICAL HAEMATOLOGY.   REFERENCE /SPECIAL
TOPICS IN WINTROBE CLINICAL HAEMATOLOGY. NATHAN,
OSKI, ORKIN HEMATOLOGY 0 F INFANCY AND
CHILDHOOD. STAMATOYANNOPOULOS ET THE MOLECULAR
BASIS OF BLOOD DISEASES. SCRIVER ET THE
METABOLIC AND MOLECULAR BASIS OF INHERITED
DISEASE.   REVIEWS I N "BLOOD" (ASH) AND
BRITISH J. HAEMATOLOGY (ESH)   ONLINE SOURCE
(WITHOUT CHARGES) http//www.cjp.com/blood/
MYNOTES / MYCHARTS
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Lyonel G. Israels Distinguished Professor
University of Manitoba Senior Scientist, Manitoba
Cancer Treatment and Research Foundation   Esther
D. Israels Associate Professor, Department of
Pediatrics, University of Manitoba Published
by Core Health services Inc. 1800 Steeles Avenue
West, Concord, Ontario, Canada L4K 2P3 E-mail
coremail _at_direct.com
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SCIENTIFIC AND SOCIO-ECONOMIC CONTEXT OF
HAEMATOLOGY. UNDERSTANDING CELLULAR AND
MOLECULAR CONTROL OF BLOOD CELL DIFFERENTIATION -
HAEMATOPOIESIS HAEMATOPOIETINS GLOBIN GENE
CONTROL IMMUNOLOGY INFECTIONS IRON
METABOLISM  HAEMATOLOGICAL DISORDERS HEREDITARY
AND ACQUIRED ANAEMIAS LEUKAEMIA AND LEUKOPOENIA /
CANCER CHEMOTHERAPY IMMUNODEFICIENCY
AUTO-IMMUNITY. COAGULATION DISORDERS BLOOD
TRANSFUSION MEDICINE COMPONENT THERAPY BLOOD
PRODUCTS RECOMBINANT PROTEINS /
PLASMA FRACTIONATION  BONE MARROW TRANSPLANTATION
STEM CELL HARVESTING, CELLULAR ENGINEERING / GENE
THERAPY .  BLOOD BIOTECHNOLOGY RECOMBINANT
HAEMATOPOIETINS / COAGULATION FACTORS. BLOOD
SUBSTITUTES  LABORATORY MEDICINE BLOOD TESTS -
CBC PICTURE / DIFFERENTIAL W BC MANY ANALYTES
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BLOOD IS A GIGANTIC FLUID AND CIRCULATING ORGAN
COMPOSED OF SUSPENSION OF CELLS IN A SOLUTION OF
PLASMA PROTEINS AND WHICH IS PHYSIOLOGICALLY AND
ANATOMICALLY CLOSELY RELATED TO THE VASCULAR
SYSTEMS ESPECIALLY IN THE MICRO-VASCULATURE   "FU
NCTIONAL VESSEL-BLOOD UNIT"   THE FORMATION OF
MICRO-CAPILLARY NETS WITH DIAMETERS OFTEN SMALLER
THAN THOSE OF BLOOD CELLS IN THE INTERSTITIAL
SPACES ENHANCE BLOOD FUNCTION BUT DEPEND ON
PECULIAR PHYSICAL PROPERTIES WHICH MAINTAIN FLOW
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Hematopoietic site and development of different
globin chains during fetal life and early
infancy, (After Knoll, W. and Pingel, E. Acta
Haematol. 2369 1949 and Huehns, E. R., Dance
N., et al. Scinece 175  134, 1972
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FUNCTIONS OF BLOOD  DEPEND ON PHYSICAL PROPERTIES
THAT DETERMINE FLOW   1. TRANSPORT OF RESPIRATORY
GASSES - FLUIDITY AND FLOW RATE. - N
ERYTHROCYTES / RBC MASS. - HAEMOGLOBIN
ALLOSTERIC EFFECTORS.   2. TRANSPORT OF NUTRIENTS
METABOLIC ENDPRODUCTS, AND OF BIOCHEMICAL
SIGNALS   3. MAINTENANCE OF BIOCHEMICAL
ENVIRONMENT PLASMA PROTEIN ONCOTIC PRESSURE   4.
HOST DEFENCE MECHANISMS. GRANULOCYES AND
MONONUCLEAR CELLS IMMUNOGLOBULINS AND
COMPLEMENT   5. HEMOSTASIS PLATELETS COAGULATION
AND FIBRINOLYTIC FACTORS 6. TEMPERATURE
REGULATION AND DISSIPATION . 1 Structal e.g.
penile erection, Osmotic ? hyperviscosity
syndrome, Innate/ acquired immunity,
Hemostasis endothelium/ platelet interaction ?
risk for vascular disease
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COMPOSITION OF BLOOD   THE STEADY STATE
COMPOSITION RESULTS FROM DYNAMIC EQUILIBRIUM
BETWEEN PRODUCTION AND DESTRUCTION
Proteins
Plasma
Water
Albumin
Red cells
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THE BLOOD VOLUME   5.5 L IN NORMAL ADULT
MALE   MEASURED WITH DILUTION TECHNIQUES   IT IS
FLUID AS LONG AS IT IS WITHIN THE BLOOD VESSELS
THE VASCULAR ENDOTHELIUM IS INTACT / UNDAMAGED.
OTHERWISE BLOOD FORMS A CLOT   BLEEDING
TIME CLOTTING TIME COLLECTION   WITH/WITHOUT
ANTICOAGULANTS/ METABOLIC SOLUTIONS   APROX 45
IS CELLS  
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HAEMATOCRIT / PACKED CELL VOLUME (PCV 45)   X
CENTRIFUGATION (MICROHAEMATOCRIT)   OR BY
CALCULATION WITH HAEMATOLOGY AUTO-ANALYSERS   PCV
NUMBER RBC X MEAN CORPUSCULAR VOLUME   DEPEND
ON ANATOMICAL SOURCE, HEALTH, DEVELOPMENT   USE
OF VISCOUS SOLUTIONS TO SEPARATE
CELLS DIFFERENTIAL CENTRIFUGATION TO HARVEST
STEM CELLS / OTHER CELLULAR COMPONENTS   ERYTHROC
YTE SEDIMENTATION RATE (ESR NV lt 1 8)   AT UNIT
GRAVITY - RBC MASS/ RIGIDITY - PLASMA PROTEIN
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INTERPRETATION OF THE COMPLETE BLOOD
COUNT   WBC lt 4 K / uL LEUKOPOENIA (SI X
109/L) gt 11 K / uL LEUKOCYTOSIS   HB lt 16
g/dL (NEONATE) ANAEMIA NORMAL NEONATE 16 - 24
g/dL lt 14 g/dL (ADULT MALE)
ANAEMIA lt 13 g/dL (ADULT FEMALE) ANAEMIA lt
12 g/dL (PREGNANT FEMALE) ANAEMIA
gt 16 g/dL(ADULT) ERYTHROCYTOSIS   MCV 80
- 100 fL NORMOCYTIC lt 80 fL MICROCYTIC gt
100 fL MACROCYTIC   MCH 26 - 34 pg
NORMOCHROMIC lt 26 pg HYPOCHROMIC PLATELETS
gt 400 K/uL THROMBOCYTOSIS (SI X 109/L)
lt 150 K/uL THROMBOCYTOPOENIA.
RETICULOCYTES NORMAL VALUE lt
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Cont
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DIFFERENTIAL WBC (NORMAL ADULT)   NEUTROPHILS
(45 - 70) BASOPHILS (0 - 2) EOSINOPHILS (0
- 3) LYMPHOCYTES (20 - 45) MONOCYTES (0 -
8) PLASMA CELLS (0 - 2)   MINUTE NUMBERS OF
OTHERS INCLUDING STEM CELLS DENDRITIC OR
ANTIGEN PRESENTING CELLS.  
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THE COMPLETE BLOOD COUNT METHODS  
MANUAL HAEMOGLOBIN CONCENTRATION BY
PHOTOMETRY PCV
CENTRIFUGATION OF MICROCAPILLARIES
NUMBERS OF CELLS WITH COUNTING CHAMBERS
DIFFERENTIAL WBC RETIC. X
MICROSCOPY DERIVED INDICES
MCV MEAN CORPUSCULAR VOLUME MCH MEAN
CORPUSCULAR HAEMOGLOBIN MCHC MEAN CORPUSCULAR
HAEMOGLOBIN CONCENTRATION  
HAEMATOLOGY
AUTO-ANALYSERS   ELECTRONIC
(COULTER PRINCIPLE)
OPTICAL PRIMARY VALUES   NUMBER
OF WBC DIFFERENTIAL,
HAEMOGLOBIN CONCENTRATION NUMBER
OF R B C ,
MCV DISTRIBUTION (RDW)
PLATELET .COUNT, VOLUME
DISTRIBUTION   CALCULATED VALUES ARE THE HCT, MCH
MCHC DIRECT DETERMINATION OF THE MCHC AND THE
RETICULOCYTE COUNT POSSIBLE WITH THE FLOW
CYTOMETER. QUANTIFICATION OF SOLUBLE TRANSFERRIN
RECEPTOR MAY REPLACE RETICULOCYTE COUNTS.
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Prime time for primates? Baseline white blood
cell counts (mean SElV) for monogamous primates
(A) the Bolivian gray titi (Callicebus
donacophilus) and (B) the white-handed gibbon
(Hylobates lar) and for their promiscuous
relatives (C) the chimpanzee (Pan troglodytes)
and (D) the yellow baboon (Papio cynocephalus).
Numbers in parentheses refer to the number of
blood samples contributing to the estimates.
Data from (3)
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Figure 2   Microlaser cytometer diagnoses blood
disorders. (a) A schematic of flow chamber and
top view of flowing red blood cells (RBCs)
recorded by high-speed video microscopy. (b) A
laser scanning confocal micrograph showing RBCs
surrounding a white blood cell. Scale bar 5 wm.
(c) A portable spectrometer for reading the
microlaser cytometer. (d) The measurements of
hemoglobin in normal (top) and anemic (bottom)
blood cells.
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Figure 2-7. Hemoglobin concentration in infants
of different degree of maturation at birth. ?
full-term infants ? premature infants with
birth weights of 1200 - 2350 g, ? premature
with weights less than 1200g