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Basic	
  Hematology	
  	
  
(Biology	
  and	
  Physiology	
  of	
  Blood)	
  
Fadel	
  Muhammad	
  Garishah	
  
Diponegoro	
  University	
  School	
  of	
  Medicine	
  
In	
  affilia:on	
  Dr.	
  Kariadi	
  General	
  Hospital	
  
Semarang,	
  CJ,	
  Republic	
  of	
  Indonesia	
  
Component	
  of	
  blood	
  
Blood	
  is	
  the	
  term	
  for	
  the	
  liquid	
  substance	
  within	
  vascular	
  system.	
  It	
  consisted	
  of	
  plasma	
  
(55%),	
  leukocytes	
  and	
  platelet	
  (<1%)	
  and	
  red	
  blood	
  cells	
  (45%).	
  
	
  	
  
Cellular	
  basis	
  of	
  red	
  blood	
  cells	
  
Hemoglobin	
  structure	
  
erythropoiesis	
  
Erythropoiesis	
   is	
   a	
   sequence	
   involving	
   proliferaFon	
   and	
  
differenFaFon	
   of	
   commiHed	
   red	
   marrow	
   cells	
   through	
   the	
  
erythroblast	
   and	
   normoblast	
   stages	
   to	
   the	
   reFculocytes	
   that	
   are	
  
released	
  into	
  the	
  bloodstream,	
  and	
  finally	
  become	
  erythrocytes.	
  
RegulaFon	
  of	
  erythrocyte	
  
PO2
PO2
PO2
“Still
Hemolysis
Erythropoietin
Kidney
Bone marrow
High altitude, etc.
2 Hemolysis
1 Hypoxia
Spleen
Blood
Bone marrow
RBC formation
Life span:
120 days
Erythrocytes
Break-
down
B. Life cycle of red blood cellsA. Regulation of RBC production
PO2
PO2
Erythropoietin
Hemolysis
Bone marrow
2 Hemolysis
C. Erythrocyte parameters MCH, M
Life	
  cycle	
  	
  
of	
  erythrocytes	
  
Plate4.1CompositionandFunctionofBlood
“Still good”
Bone marrow
Lymph nodes
Spleen
Liver, etc.
Spleen
Blood
Bone marrow
Test
RBC formation
Phagocytosis
by
macrophages in:
Sinus
“Too old”
Pulpal
arteriole
Life span:
120 days
es
Spenic
pulp
Break-
down
Clinically	
  related	
  erythrocytes	
  
parameter	
  
89
b
a
MCHC (mean Hb conc. in RBCs)
Hb conc.
= (g/LRBC)
Hct
MCV (mean volume of one RBC)
Hct
= (L/RBC)
red cell count
MCH (mean Hb mass/RBC)
Hb conc.
= (g/RBC)
red cell count
Normal:
320–360g/L
Normal:
80–100fl
Normal:
27–32pg
Centrifugation
Hemoglobin concentration
(g/LBLOOD)
Erythropoietin
Bone marrow
Lymph nodes
Spleen
Liver, etc.
Sinus
arteriole
Red cell count (RCC)
(quantity/LBLOOD)
Hematocrit (Hct)=b/a
(LRBC/LBlood)
Blood sample
C. Erythrocyte parameters MCH, MCV and MCHC
Iron	
  intake	
  and	
  metabolism	
  
HCI
Fe
Fe
Fe
FeIII
FeIII
FeIII
Fe2+
FeIII
Fe2+
H
+
Stomach
Liver
Fe absorption:
3–15% of
Fe intake
Normal Fe intake:
10–20 mg/day
5–10 mg/day
Lumen
Ferritin
Blood
Lyso-
some
Cell
turnover
Mucosal
transferrin
Apo-
transferrin
Heme-
FeII
Mucosal cells
(duodenum)
Trans-
ferrin
Non-absorbed Fe in feces:
Normally 85–97% of intake
Heme
FR
FeIII
2 Fe absorption1 Iron intake
A. Iron intake and metabolism
Iron	
  storage	
  and	
  recycling	
  
Fe
FeFe
Fe stores
Systemic
blood
Liver
Bone
marrow
Hemo-
siderin
FerritinHeme
Hb
Erythrocytes
Hemo-
pexin
Hapto-
globin
Ferritin
Hemo-
siderin
Transferrin
Macrophages
in spleen, liver and
bone marrow (extravascular)
Already in bone marrow
Vitamin B12
Folic acid
0.05mg/day
Other organs
NADP NADPH +H+
Dihydrofolate
reductase
Non-absorbed Fe in feces:
Normally 85–97% of intake
FeIII
3 Fe storage and Fe recycling
B. Folic acid and vitamin B12 (cobalamins)
Folic	
  acid	
  and	
  Cobalamin	
  (B12)	
  
metabolism	
  
7mg
1 mg
Fe stores
siderinHb
Erythrocytes
globin
Macrophages
in spleen, liver and
bone marrow (extravascular)
Already in bone marrow
Liver
Ileum
Vitamin B12
0.001mg/day
Folic acid
0.05mg/day
Other organs
Stores
Bone marrow
NADP NADPH +H+
Dihydrofolate
reductase
Folate
regeneration
Thymidylate
synthase
7,8-
dihydro-
folate
Tetrahydro-
folate
N5
-tetra-
hydrofolate
Deoxy-
uridylate
Deoxy-
thymidylate
Erythroblast
DNA synthesis
Erythropoiesis
Stomach
Erythrocytes
Intrinsic
factor
Methyl-
cobalamin
B. Folic acid and vitamin B12 (cobalamins)
Despopoulos, Color Atlas of Physiology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
The	
  blood	
  groups	
  
O
A
B
AB
O A B AB
5 10 15 20
2
(After Kownatzki)
Days after first antigen exposure
Compatible
Incompatible
(agglutination)
Anti-A
Anti-B
Antigenonredbloodcells
otrienes
tors
Antibody in serum
ity
Biology	
  of	
  Rhesus	
  
101
Pla
+
=
A
B
AB
Rh+
Rh+
Rh+ Rh+
Rh–
Rh–
Rh–
Rh–
Rh+
Incompatible
(agglutination)
Anti-A
Anti-B
Antigenonredbl
Agglutination
Hemolysis
Severe hemolysis
in fetus
Father Mother
Subsequent Rh+
childrenFirst Rh+
child
Subsequent mismatched Rh+
transfusion
Rh+
red cells
High
anti-Rh+
titer
Damage
Rh+
red cells
Anti-Rh+
High
anti-Rh+
titer
Damage
Anti-Rh+
antibodyBlood
First mismatched Rh+
transfusion
D. Rh sensitization of mother by child or by Rh-mismatched transfusion
Plasmaproteins	
  
wPropertiesofBlood
60% 4% 8% 12% 16%
α1 α2 β γ
0 100 500 1000
Plasma
Albumin Globulins
Electrophoretic protein fractions
65–80g/L
Proteins(100%)
e diameter (µm)
Blood
Plasma
Water
ist effect B. Plasmaproteins
of body fluids
Ion	
  composiFon	
  of	
  body	
  fluids	
  
Plate4.3FlowPropertiesofBlood
2
1
0
1 5 10 50 100 500 1000
Na+
K+
142
4.3
2.6 (1.3*)
1.0 (0.5**)
153
4.6
2.8 (1.3)
1.0 (0.5)
145
4.4
2.5 (1.5)
0.9 (0.45)
ca. 12
ca. 140
<0,001
1.6
150 162 153 ca. 152
Cl–
HCO3
–
*) Total plasma Ca: 2.5mmol/L; **) Total plasma Mg: 0.9mmol/L
Na+
Ca
2+
,Mg2+
Cl–
HCO3
–
HCO3
–
K+
Ca2+
,Mg2+
Na+K+
mval/L (mmol/L)
104
24
2
14
5.9
112
36
2.2
15
6.3
117
27
2.3
0.4
6.2
ca. 3
10
ca. 30
ca. 54
ca. 54
150 162 153 ca. 152
Electrophoretic protein fractions
65–80
Proteins(1
Cations
Plasma Interstitium CytosolSerumIon
Anions
Proteins
Misc.
Sum
Sum
Proteins,phosphates,
etc.
Proteins–
Interstitium Cytosol
Cations Anions Cations Anions
Viscosity
Vessel inside diameter (µm)
Plasma
Water
Free Ca2+
Inorganic phosphate
Inorganic
phosphate
Misc.
Free Mg
2+
C. Ion composition of body fluids
The	
  immunoglobulin	
  in	
  serum	
  
IgA 2.25
IgM 1.15
IgD 0.03
IgE 0.0002
IgG 11.0
g/L
100
50
–3 181512963
IgM
IgG
IgA
IgD
IgE
*) Total plasma Ca: 2.5mmol/L; **) Total plasma Mg: 0.9mmol/L
2
14
5.9
2.2
15
6.3
2.3
0.4
6.2
ca. 30
ca. 54
ca. 54
150 162 153 ca. 152
Birth Age (months)
From Mother
(After Hobbs)
Anion
Proteins
Misc.
Sum
Inorganic phosphate
%ofrespective
serumconcentration
inadult
D. Concentrations of immunglobulins in serum
Despopoulos, Color Atlas of Physiology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
White	
  blood	
  cells	
  (Leukocytes)	
  
The	
  leukocytes	
  
Leukocytes.	
  	
  (a)	
  Neutrophil.	
  (b)	
  Eosinophil.	
  (c)	
  Basophil.	
  (d)	
  Small	
  lymphocyte.	
  (e)	
  
Monocyte.	
  In	
  each	
  case	
  the	
  leukocytes	
  are	
  surrounded	
  by	
  erythrocytes.	
  Note	
  also	
  the	
  
three	
  platelets	
  above	
  the	
  lymphocyte	
  in	
  (d).	
  (All	
  1600×) 	
  	
  
The	
  	
  
Leukopoiesis	
  
Leukocyte	
  formaFon.	
  	
  
Leukocytes	
  arise	
  from	
  
ancestral	
  stem	
  cells	
  called	
  
hemocytoblasts.	
  (a–c)	
  Granular	
  
leukocytes	
  develop	
  via	
  a	
  
sequence	
  involving	
  
myeloblasts.	
  (d–e)	
  Monocytes,	
  
like	
  granular	
  leukocytes,	
  are	
  
progeny	
  of	
  the	
  myeloid	
  stem	
  
cell	
  and	
  diverge	
  from	
  a	
  
myeloblast	
  that	
  can	
  become	
  
either	
  a	
  neutrophil	
  or	
  a	
  
monocyte.	
  Only	
  lymphocytes	
  
arise	
  via	
  the	
  lymphoid	
  stem	
  cell	
  
line.	
  	
  
The	
  Thrombopoiesis	
  
The	
  hemocytoblast	
  gives	
  rise	
  to	
  cells	
  that	
  undergo	
  several	
  mitoFc	
  divisions	
  
unaccompanied	
  by	
  cytoplasmic	
  division	
  to	
  produce	
  megakaryocytes.	
  The	
  cytoplasm	
  of	
  the	
  
megakaryocyte	
  becomes	
  compartmentalized	
  by	
  membranes,	
  and	
  the	
  plasma	
  membrane	
  
then	
  fragments,	
  liberaFng	
  the	
  platelets.	
  (Intermediate	
  stages	
  between	
  the	
  hemocytoblast	
  
and	
  megakaryoblast	
  are	
  not	
  illustrated.)	
  
Clo]ng	
  factors	
  
stops bleeding. Throm-
ulation (or clotting) fac-
l walls interact to seal
The damaged vessel
dothelin), and platelets
puncture (and attract
the leak by a platelet
for sealing (ca. 2 to 4
ng time. Subsequently,
m produces a fibrin
ent cross-linking of fi-
ot or thrombus that re-
reinforcing the seal.
f the vessel can be
103
per µL of blood;
small non-nucleated
d off from megakaryo-
I Fibrinogen Half-life (h): 96
II K
Prothrombin 72
III Tissue thromboplastin
IV Ionized calcium (Ca2+
)
V Proaccelerin 20
VII K
Proconvertin 5
VIII Antihemophilic factor A 12
IX K
Antihemophilic factor B; plasma
thromboplastin component (PTC);
Christmas factor 24
X K
Stuart–Prower factor 30
XI Plasma thromboplastin antecedent
(PTA) 48
XII Hageman factor 50
XIII Fibrin-stabilizing factor (FSF) 250
– Prekallikrein (PKK); Fletcher factor
– High-molecular-weight kininogen
(HMK); Fitzgerald factor
Platelet	
  Mediated	
  Hemostasis	
  
Plate4.8Hemostasis
vWF
Kollagen
Endothelial
damage
Blood
Change in shape
Vasoconstriction
Slowing of
blood flow
1
2
3
5
PLT aggregation:
Clot formation
4
PLT adhesion
Platelet (PLT)
PLT activation
Fibrinogen
Secretion
ADP,
PAF
TXA2Serotonin,
PDGF
vWF
A. Platelet-mediated hemostasis
B. Blood clotting

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Basic Hematology

  • 1. Basic  Hematology     (Biology  and  Physiology  of  Blood)   Fadel  Muhammad  Garishah   Diponegoro  University  School  of  Medicine   In  affilia:on  Dr.  Kariadi  General  Hospital   Semarang,  CJ,  Republic  of  Indonesia  
  • 2. Component  of  blood   Blood  is  the  term  for  the  liquid  substance  within  vascular  system.  It  consisted  of  plasma   (55%),  leukocytes  and  platelet  (<1%)  and  red  blood  cells  (45%).      
  • 3.
  • 4.
  • 5. Cellular  basis  of  red  blood  cells  
  • 7. erythropoiesis   Erythropoiesis   is   a   sequence   involving   proliferaFon   and   differenFaFon   of   commiHed   red   marrow   cells   through   the   erythroblast   and   normoblast   stages   to   the   reFculocytes   that   are   released  into  the  bloodstream,  and  finally  become  erythrocytes.  
  • 8. RegulaFon  of  erythrocyte   PO2 PO2 PO2 “Still Hemolysis Erythropoietin Kidney Bone marrow High altitude, etc. 2 Hemolysis 1 Hypoxia Spleen Blood Bone marrow RBC formation Life span: 120 days Erythrocytes Break- down B. Life cycle of red blood cellsA. Regulation of RBC production PO2 PO2 Erythropoietin Hemolysis Bone marrow 2 Hemolysis C. Erythrocyte parameters MCH, M
  • 9. Life  cycle     of  erythrocytes   Plate4.1CompositionandFunctionofBlood “Still good” Bone marrow Lymph nodes Spleen Liver, etc. Spleen Blood Bone marrow Test RBC formation Phagocytosis by macrophages in: Sinus “Too old” Pulpal arteriole Life span: 120 days es Spenic pulp Break- down
  • 10. Clinically  related  erythrocytes   parameter   89 b a MCHC (mean Hb conc. in RBCs) Hb conc. = (g/LRBC) Hct MCV (mean volume of one RBC) Hct = (L/RBC) red cell count MCH (mean Hb mass/RBC) Hb conc. = (g/RBC) red cell count Normal: 320–360g/L Normal: 80–100fl Normal: 27–32pg Centrifugation Hemoglobin concentration (g/LBLOOD) Erythropoietin Bone marrow Lymph nodes Spleen Liver, etc. Sinus arteriole Red cell count (RCC) (quantity/LBLOOD) Hematocrit (Hct)=b/a (LRBC/LBlood) Blood sample C. Erythrocyte parameters MCH, MCV and MCHC
  • 11. Iron  intake  and  metabolism   HCI Fe Fe Fe FeIII FeIII FeIII Fe2+ FeIII Fe2+ H + Stomach Liver Fe absorption: 3–15% of Fe intake Normal Fe intake: 10–20 mg/day 5–10 mg/day Lumen Ferritin Blood Lyso- some Cell turnover Mucosal transferrin Apo- transferrin Heme- FeII Mucosal cells (duodenum) Trans- ferrin Non-absorbed Fe in feces: Normally 85–97% of intake Heme FR FeIII 2 Fe absorption1 Iron intake A. Iron intake and metabolism
  • 12. Iron  storage  and  recycling   Fe FeFe Fe stores Systemic blood Liver Bone marrow Hemo- siderin FerritinHeme Hb Erythrocytes Hemo- pexin Hapto- globin Ferritin Hemo- siderin Transferrin Macrophages in spleen, liver and bone marrow (extravascular) Already in bone marrow Vitamin B12 Folic acid 0.05mg/day Other organs NADP NADPH +H+ Dihydrofolate reductase Non-absorbed Fe in feces: Normally 85–97% of intake FeIII 3 Fe storage and Fe recycling B. Folic acid and vitamin B12 (cobalamins)
  • 13. Folic  acid  and  Cobalamin  (B12)   metabolism   7mg 1 mg Fe stores siderinHb Erythrocytes globin Macrophages in spleen, liver and bone marrow (extravascular) Already in bone marrow Liver Ileum Vitamin B12 0.001mg/day Folic acid 0.05mg/day Other organs Stores Bone marrow NADP NADPH +H+ Dihydrofolate reductase Folate regeneration Thymidylate synthase 7,8- dihydro- folate Tetrahydro- folate N5 -tetra- hydrofolate Deoxy- uridylate Deoxy- thymidylate Erythroblast DNA synthesis Erythropoiesis Stomach Erythrocytes Intrinsic factor Methyl- cobalamin B. Folic acid and vitamin B12 (cobalamins) Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Usage subject to terms and conditions of license.
  • 14. The  blood  groups   O A B AB O A B AB 5 10 15 20 2 (After Kownatzki) Days after first antigen exposure Compatible Incompatible (agglutination) Anti-A Anti-B Antigenonredbloodcells otrienes tors Antibody in serum ity
  • 15. Biology  of  Rhesus   101 Pla + = A B AB Rh+ Rh+ Rh+ Rh+ Rh– Rh– Rh– Rh– Rh+ Incompatible (agglutination) Anti-A Anti-B Antigenonredbl Agglutination Hemolysis Severe hemolysis in fetus Father Mother Subsequent Rh+ childrenFirst Rh+ child Subsequent mismatched Rh+ transfusion Rh+ red cells High anti-Rh+ titer Damage Rh+ red cells Anti-Rh+ High anti-Rh+ titer Damage Anti-Rh+ antibodyBlood First mismatched Rh+ transfusion D. Rh sensitization of mother by child or by Rh-mismatched transfusion
  • 16. Plasmaproteins   wPropertiesofBlood 60% 4% 8% 12% 16% α1 α2 β γ 0 100 500 1000 Plasma Albumin Globulins Electrophoretic protein fractions 65–80g/L Proteins(100%) e diameter (µm) Blood Plasma Water ist effect B. Plasmaproteins of body fluids
  • 17. Ion  composiFon  of  body  fluids   Plate4.3FlowPropertiesofBlood 2 1 0 1 5 10 50 100 500 1000 Na+ K+ 142 4.3 2.6 (1.3*) 1.0 (0.5**) 153 4.6 2.8 (1.3) 1.0 (0.5) 145 4.4 2.5 (1.5) 0.9 (0.45) ca. 12 ca. 140 <0,001 1.6 150 162 153 ca. 152 Cl– HCO3 – *) Total plasma Ca: 2.5mmol/L; **) Total plasma Mg: 0.9mmol/L Na+ Ca 2+ ,Mg2+ Cl– HCO3 – HCO3 – K+ Ca2+ ,Mg2+ Na+K+ mval/L (mmol/L) 104 24 2 14 5.9 112 36 2.2 15 6.3 117 27 2.3 0.4 6.2 ca. 3 10 ca. 30 ca. 54 ca. 54 150 162 153 ca. 152 Electrophoretic protein fractions 65–80 Proteins(1 Cations Plasma Interstitium CytosolSerumIon Anions Proteins Misc. Sum Sum Proteins,phosphates, etc. Proteins– Interstitium Cytosol Cations Anions Cations Anions Viscosity Vessel inside diameter (µm) Plasma Water Free Ca2+ Inorganic phosphate Inorganic phosphate Misc. Free Mg 2+ C. Ion composition of body fluids
  • 18. The  immunoglobulin  in  serum   IgA 2.25 IgM 1.15 IgD 0.03 IgE 0.0002 IgG 11.0 g/L 100 50 –3 181512963 IgM IgG IgA IgD IgE *) Total plasma Ca: 2.5mmol/L; **) Total plasma Mg: 0.9mmol/L 2 14 5.9 2.2 15 6.3 2.3 0.4 6.2 ca. 30 ca. 54 ca. 54 150 162 153 ca. 152 Birth Age (months) From Mother (After Hobbs) Anion Proteins Misc. Sum Inorganic phosphate %ofrespective serumconcentration inadult D. Concentrations of immunglobulins in serum Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Usage subject to terms and conditions of license.
  • 19. White  blood  cells  (Leukocytes)  
  • 20. The  leukocytes   Leukocytes.    (a)  Neutrophil.  (b)  Eosinophil.  (c)  Basophil.  (d)  Small  lymphocyte.  (e)   Monocyte.  In  each  case  the  leukocytes  are  surrounded  by  erythrocytes.  Note  also  the   three  platelets  above  the  lymphocyte  in  (d).  (All  1600×)    
  • 21. The     Leukopoiesis   Leukocyte  formaFon.     Leukocytes  arise  from   ancestral  stem  cells  called   hemocytoblasts.  (a–c)  Granular   leukocytes  develop  via  a   sequence  involving   myeloblasts.  (d–e)  Monocytes,   like  granular  leukocytes,  are   progeny  of  the  myeloid  stem   cell  and  diverge  from  a   myeloblast  that  can  become   either  a  neutrophil  or  a   monocyte.  Only  lymphocytes   arise  via  the  lymphoid  stem  cell   line.    
  • 22. The  Thrombopoiesis   The  hemocytoblast  gives  rise  to  cells  that  undergo  several  mitoFc  divisions   unaccompanied  by  cytoplasmic  division  to  produce  megakaryocytes.  The  cytoplasm  of  the   megakaryocyte  becomes  compartmentalized  by  membranes,  and  the  plasma  membrane   then  fragments,  liberaFng  the  platelets.  (Intermediate  stages  between  the  hemocytoblast   and  megakaryoblast  are  not  illustrated.)  
  • 23. Clo]ng  factors   stops bleeding. Throm- ulation (or clotting) fac- l walls interact to seal The damaged vessel dothelin), and platelets puncture (and attract the leak by a platelet for sealing (ca. 2 to 4 ng time. Subsequently, m produces a fibrin ent cross-linking of fi- ot or thrombus that re- reinforcing the seal. f the vessel can be 103 per µL of blood; small non-nucleated d off from megakaryo- I Fibrinogen Half-life (h): 96 II K Prothrombin 72 III Tissue thromboplastin IV Ionized calcium (Ca2+ ) V Proaccelerin 20 VII K Proconvertin 5 VIII Antihemophilic factor A 12 IX K Antihemophilic factor B; plasma thromboplastin component (PTC); Christmas factor 24 X K Stuart–Prower factor 30 XI Plasma thromboplastin antecedent (PTA) 48 XII Hageman factor 50 XIII Fibrin-stabilizing factor (FSF) 250 – Prekallikrein (PKK); Fletcher factor – High-molecular-weight kininogen (HMK); Fitzgerald factor
  • 24. Platelet  Mediated  Hemostasis   Plate4.8Hemostasis vWF Kollagen Endothelial damage Blood Change in shape Vasoconstriction Slowing of blood flow 1 2 3 5 PLT aggregation: Clot formation 4 PLT adhesion Platelet (PLT) PLT activation Fibrinogen Secretion ADP, PAF TXA2Serotonin, PDGF vWF A. Platelet-mediated hemostasis B. Blood clotting