Upload
christina101
View
909
Download
29
Tags:
Embed Size (px)
Citation preview
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. Erythrocyes, erythropoiesis and erythropoietin. Anaemia & erythrocytosis. 5. Haemoglobin; structure and function; developmental biology. Abnormal haemoglobins and thalassaemia. 6. Erythrocytes: metabolism & storage lesion; membrane, blood groups & transfusion serology, electrolyte shifts 7. Nutrition and Haematopoiesis; vitamins B & Folate; iron- haem-bilirubin; hyperbilirubinaemia, porphyria.
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. ; auto immunity, 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
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
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 @direct.com
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
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 "FUNCTIONAL 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
Hematopoietic site and development of different globin chains during fetal life and early infancy, (After Knoll, W. and Pingel, E. Acta Haematol. 2:369 1949; and Huehns, E. R., Dance N., et al. Scinece 175 : 134, 1972
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
COMPOSITION OF BLOOD THE STEADY STATE COMPOSITION RESULTS FROM DYNAMIC EQUILIBRIUM BETWEEN PRODUCTION AND DESTRUCTION
Red cells
Plasma
Water
Proteins
Albumin
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 TIMECLOTTING TIME
COLLECTION WITH/WITHOUT ANTICOAGULANTS/ METABOLIC SOLUTIONS APROX 45 % IS CELLS;
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
ERYTHROCYTE SEDIMENTATION RATE (ESR NV: < 1 8) AT UNIT GRAVITY‑ RBC MASS/ RIGIDITY‑ PLASMA PROTEIN
INTERPRETATION OF THE COMPLETE BLOOD COUNT WBC; < 4 K / uL = LEUKOPOENIA (SI: X 109/L)
> 11 K / uL = LEUKOCYTOSIS HB; < 16 g/dL (NEONATE) = ANAEMIA
NORMAL NEONATE: 16 ‑ 24 g/dL
< 14 g/dL (ADULT MALE) = ANAEMIA< 13 g/dL (ADULT FEMALE) = ANAEMIA< 12 g/dL (PREGNANT FEMALE) = ANAEMIA
> 16 g/dL(ADULT) = ERYTHROCYTOSIS MCV; 80 ‑ 100 fL = NORMOCYTIC
< 80 fL = MICROCYTIC> 100 fL = MACROCYTIC
MCH 26 ‑ 34 pg = NORMOCHROMIC
< 26 pg = HYPOCHROMIC
PLATELETS; > 400 K/uL = THROMBOCYTOSIS (SI: X 109/L) < 150 K/uL = THROMBOCYTOPOENIA. RETICULOCYTES; NORMAL VALUE < 2:0%
Cont…
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.
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.
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)]
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.
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