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