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BLOED 1Inhoud
1 De bloedcellen en de organisatie van hematopoiese ..................................................................................... 1
1.1 De bloedcellen ....................................................................................................................................... 1
1.1.1 Algemeen .......................................................................................................................................... 1
1.1.2 Rode bloedcellen/erythocyten .......................................................................................................... 1
1.1.3 Witte bloedcellen/leukocyten ........................................................................................................... 2
1.1.4 Trombocyten/bloedplaatjes .............................................................................................................. 5
1.1.5 Aanmaak en levensduur .................................................................................................................... 5
1.2 Organisatie van de hematopoiese: hematopoietische stamcellen en progenitoren............................. 5
1.2.1 Algemeen .......................................................................................................................................... 5
1.2.2 Hematopoietische stamcellen geven aanleiding tot meer gespecialiseerde progenitoren .............. 6
1.2.3 Progenitoren geven aanleiding tot precursoren ............................................................................... 7
1.3 Hematopoietische groeifactoren ........................................................................................................... 8
1.3.1 Algemeen .......................................................................................................................................... 8
1.3.2 Eigenschappen van hematopoietische groeifactoren ....................................................................... 8
1.3.3 Verschillende hematopoietische groeifactoren geïsoleerd en gekarakteriseerd.............................. 8
1.3.4 Hiërarchie in de werking van de verschillende hematopoietische groeifactoren ............................. 9
1.3.5 Aspecten van bloedvorming ............................................................................................................ 10
1.4 Piramidesysteem hemotopoiese ......................................................................................................... 11
2 Biochemie van zuurstof- en koolstofdioxidetransport en van de bloedgroepen .......................................... 12
2.1 Inleiding van hemoglobine .................................................................................................................. 12
2.2 Structuur en functie van hemoglobine ................................................................................................ 12
2.2.1 Bouw................................................................................................................................................ 12
2.2.2 Functie ............................................................................................................................................. 13
2.2.3 Types ............................................................................................................................................... 13
2.2.4 Structuur.......................................................................................................................................... 13
2.3 Werking van hemoglobine ................................................................................................................... 14
2.4 Aanmaak van haem en hemoglobine .................................................................................................. 15
2.4.1 Structuur en locatie haem ............................................................................................................... 15
2.4.2 Heemsynthese ................................................................................................................................. 16
2.4.3 Globinesynthese .............................................................................................................................. 17
2.5 Heemdegradatie en bilirubinemetabolisme ........................................................................................ 17
2.6 Normale hemoglobines ....................................................................................................................... 18
2.6.1 Algemeen ........................................................................................................................................ 18
2.6.2 Hemoglobine A2 (HbA2) .................................................................................................................. 18
2.6.3 Hemoglobine F (HbF) ....................................................................................................................... 18
, 2.7 Intoxicaties mbt de werking van hemoglobine .................................................................................... 18
2.7.1 Koolstofmonoxidevergifitiging ........................................................................................................ 18
2.7.2 Loodintoxicatie ................................................................................................................................ 19
2.8 Inleiding van bloedgroepen met enkele definities .............................................................................. 19
2.8.1 Wat verstaat men onder bloedgroep? ............................................................................................ 19
2.8.2 Wat is een bloedgroepsysteem? ..................................................................................................... 20
2.8.3 Wat is de rol van bloedgroepantigenen? ........................................................................................ 20
2.9 ABO bloedgroepsysteem of ABH bloedgroepsysteem ........................................................................ 20
2.9.1 Algemeen ........................................................................................................................................ 20
2.9.2 Antigenen ........................................................................................................................................ 21
2.9.3 Antistoffen....................................................................................................................................... 21
2.9.4 Bloedgroepbepaling ........................................................................................................................ 21
2.9.5 Transfusie in praktijk ....................................................................................................................... 22
2.9.6 ABO compatibiliteitsregels .............................................................................................................. 22
2.10 Rhesus bloedgroepsysteem ................................................................................................................. 22
2.10.1 Rhesus historiek .......................................................................................................................... 22
2.10.2 Antigenen .................................................................................................................................... 22
2.10.3 Genen .......................................................................................................................................... 22
2.10.4 Antistoffen .................................................................................................................................. 22
2.10.5 Transfusie in praktijk ................................................................................................................... 23
3 De hematologische diagnostiek .................................................................................................................... 23
3.1 Symtomen............................................................................................................................................ 23
3.2 Klinische tekens bij fysisch onderzoek ................................................................................................. 23
3.3 Etiologie van lymfadenopathie ............................................................................................................ 24
3.4 De hematologische diagnostiek ........................................................................................................... 24
4 Het oppuntstellen van een anemie ............................................................................................................... 25
4.1 Algemeen ............................................................................................................................................. 25
4.2 Hypochrome microcytaire anemie ...................................................................................................... 26
4.3 Normochrome normocytaire anemie .................................................................................................. 26
4.4 Macrocytaire anemie ........................................................................................................................... 27
4.5 Vergelijking tussen de verschillende anemieën ................................................................................... 28
4.6 Morfologie rode bloecel ...................................................................................................................... 28
5 Microcytaire anemie ..................................................................................................................................... 28
5.1 Het ijzermetabolisme........................................................................................................................... 28
5.1.1 IJzer in heem.................................................................................................................................... 29
5.1.2 IJzervoorraden in macrofagen en leverparenchymcellen ............................................................... 29
5.1.3 Circulerend ijzer .............................................................................................................................. 29
5.1.4 IJzerabsorptie, transport en verlies ................................................................................................. 30
, 5.2 Ferriprieve of ijzerdeficiëntie-anemie ................................................................................................. 30
5.2.1 Algemeen ........................................................................................................................................ 30
5.2.2 Klinische verschijnselen ................................................................................................................... 30
5.2.3 Algemene oorzaken ......................................................................................................................... 31
5.2.4 Etiologie ........................................................................................................................................... 31
5.2.5 Diagnose .......................................................................................................................................... 32
5.3 Anemie van chronische ziekten ........................................................................................................... 32
5.3.1 Algemeen ........................................................................................................................................ 32
5.3.2 Diagnose .......................................................................................................................................... 33
5.4 Sideroblastische anemie ...................................................................................................................... 33
5.4.1 Algemeen ........................................................................................................................................ 33
5.4.2 Etiologie ........................................................................................................................................... 33
5.4.3 Diagnose .......................................................................................................................................... 33
5.5 Thalassemie ......................................................................................................................................... 34
5.5.1 Algemeen ........................................................................................................................................ 34
5.5.2 Genetisch voorkomen ..................................................................................................................... 34
5.5.3 Klinische classificatie ....................................................................................................................... 34
6 Macrocytaire anemie .................................................................................................................................... 35
6.1 Etiologie van macrocytaire anemie ..................................................................................................... 36
6.2 Fysiopathologie van megaloblastische anemie ................................................................................... 36
6.3 Klinische manifestaties van megaloblastische anemie ........................................................................ 37
6.3.1 Hematologische afwijkingen ........................................................................................................... 37
6.3.2 Gastro-intestinale afwijkingen ........................................................................................................ 38
6.3.3 Subacute gecombineerde degeneratie van zenuwstelsel ............................................................... 38
6.4 Belangrijkste oorzaken van megaloblastische anemie ........................................................................ 38
6.4.1 Megaloblastische anemie tengevolge van vitamine B12-deficiëntie .............................................. 38
6.4.2 Megaloblastische anemie tengevolge van folaatdeficiëntie ........................................................... 39
6.5 Diagnosestelling van megaloblastische anemie .................................................................................. 39
6.6 Macrocytaire anemie met normoblastisch beenmerg ........................................................................ 40
7 Hemolytische anemieën ................................................................................................................................ 40
7.1 Definitie en classificatie van hemolytische anemieën ......................................................................... 40
7.1.1 Hemolyse ......................................................................................................................................... 40
7.1.2 Voorbeelden van oorzaken van hemolytische anemie ................................................................... 42
7.2 Hereditaire sferocytose ....................................................................................................................... 43
7.2.1 Algemeen ........................................................................................................................................ 43
7.2.2 Achtergrond: het RBC membraan ................................................................................................... 44
7.2.3 Klinische verschijnselen ................................................................................................................... 44
7.2.4 Diagnose .......................................................................................................................................... 44
, 7.3 Glucose-6-fosfaat-dehydrogenase deficiëntie ..................................................................................... 44
7.3.1 Algemeen ........................................................................................................................................ 44
7.3.2 Biochemische achtergrond .............................................................................................................. 44
7.3.3 Klinische verschijnselen ................................................................................................................... 45
7.3.4 Diagnose .......................................................................................................................................... 45
7.4 Pyruvaat kinase deficiëntie .................................................................................................................. 46
7.4.1 Algemeen ........................................................................................................................................ 46
7.4.2 Klinische verschijnselen ................................................................................................................... 46
7.4.3 Diagnose .......................................................................................................................................... 46
7.5 Sikkelcelanemie ................................................................................................................................... 46
7.5.1 Algemeen ........................................................................................................................................ 46
7.5.2 Belangrijkste klinische verschijnselen ............................................................................................. 46
7.5.3 Diagnose .......................................................................................................................................... 47
7.6 Immune hemolytische anemieën ........................................................................................................ 47
7.6.1 Algemeen ........................................................................................................................................ 47
7.6.2 Antiglobulinetesten (Coombstesten) .............................................................................................. 47
7.6.3 Allo-of iso-immune hemolytische anemie....................................................................................... 48
7.6.4 Auto-immune hemolytische anemie ............................................................................................... 49
7.7 Bloedgroepantigenen en bloedtransfusie ........................................................................................... 50
7.7.1 Algemeen ........................................................................................................................................ 50
7.7.2 Procedures bij een transfusie met RBC ........................................................................................... 51
8 Inleiding tot kwaadaardige hematologische aandoeningen ......................................................................... 53
8.1 Definities en gemeenschappelijke biologische eigenschappen ........................................................... 53
8.2 Pathogenese van de belangrijkste klinische manifestaties van hematologische maligniteiten .......... 53
8.3 Het verschil tussen acute en chronische leukemie en de verschillende vormen van leukemie .......... 54
9 Leukocytose, leukopenie, polycytemie en trombocytose ............................................................................. 54
9.1 Leukocytose en leukopenie ................................................................................................................. 54
9.2 Neutrofilie ............................................................................................................................................ 55
9.2.1 Algemeen ........................................................................................................................................ 55
9.2.2 Voorbeelden van oorzaken neutrofiele leukocytose ...................................................................... 55
9.2.3 Mogelijke eigenschappen van de granulocyten .............................................................................. 55
9.3 Lymfocytose ......................................................................................................................................... 55
9.3.1 Algemeen ........................................................................................................................................ 55
9.3.2 Voorbeelden van oorzaken ............................................................................................................. 56
, 9.4 Neutropenie......................................................................................................................................... 56
9.4.1 Algemeen ........................................................................................................................................ 56
9.4.2 Eigenschappen ................................................................................................................................ 56
9.4.3 Voorbeelden van oorzaken ............................................................................................................. 56
9.4.4 Klinische verschijnselen ................................................................................................................... 56
9.4.5 Diagnose .......................................................................................................................................... 57
9.4.6 Verloop ............................................................................................................................................ 57
9.5 Polycytemie ......................................................................................................................................... 57
9.5.1 Algemeen ........................................................................................................................................ 57
9.5.2 Voorbeelden van oorzaken ............................................................................................................. 57
9.6 Trombocytose ...................................................................................................................................... 58
9.6.1 Algemeen ........................................................................................................................................ 58
9.6.2 Voorbeelden van oorzaken ............................................................................................................. 58
10 Pancytopenie ........................................................................................................................................... 58
10.1 Definitie en etiologie ........................................................................................................................... 58
10.1.1 Algemeen .................................................................................................................................... 58
10.1.2 Voorbeelden van oorzaken ......................................................................................................... 59
10.2 Aplastische anemie (beenmergaplasie) ............................................................................................... 59
10.2.1 Algemeen .................................................................................................................................... 59
10.2.2 Voorbeelden van oorzaken ......................................................................................................... 59
10.2.3 Klinische verschijnselen .............................................................................................................. 59
10.2.4 Diagnose...................................................................................................................................... 59
11 Hemostase en fibrinolyse ......................................................................................................................... 60
11.1 Fysiologie van normale hemostase en fibrinolyse ............................................................................... 60
11.1.1 Hemostase .................................................................................................................................. 60
11.1.2 Testen voor de bloedstolling....................................................................................................... 66
11.2 Pathofysiologie van de bloedstolling ................................................................................................... 69
11.2.1 Primaire hemostase en het begrip purpura ................................................................................ 69
11.2.2 Afwijkingen van plasmatische stolling ........................................................................................ 73
12 Trombose ................................................................................................................................................. 78
12.1 Trombose ............................................................................................................................................. 78
12.2 Erfelijke en verworven trombofilie ...................................................................................................... 80
12.2.1 Algemeen .................................................................................................................................... 80
12.2.2 Erfelijke varianten ....................................................................................................................... 80
12.2.3 Lupus anticoagulans (LAC) .......................................................................................................... 82
,13 Practicum: Leukocyten formule ............................................................................................................... 82
13.1 Normale witte bloedcel differentiatie ................................................................................................. 82
13.1.1 Cellen perifeer bloed................................................................................................................... 83
13.1.2 Leukocyten: uitzicht .................................................................................................................... 83
13.1.3 Leukocyten: voorkomen in perifeer bloed .................................................................................. 84
13.1.4 Normale hematopoiese .............................................................................................................. 84
13.1.5 Varia cellen in perifeer bloed ...................................................................................................... 85
13.2 Reactieve en pathologische morfologie .............................................................................................. 85
13.2.1 Granulocyten............................................................................................................................... 85
13.2.2 Lymfocyten.................................................................................................................................. 86
13.2.3 Inclusies....................................................................................................................................... 86
13.3 Celtelling in routine klinisch laboratorium........................................................................................... 86
13.3.1 Inleiding....................................................................................................................................... 86
13.3.2 Pitfalls.......................................................................................................................................... 87
13.3.3 Preparaat .................................................................................................................................... 88
13.4 Normaalwaarden ................................................................................................................................. 88
13.5 Beelden ................................................................................................................................................ 88
13.5.1 Neutrofiel .................................................................................................................................... 88
13.5.2 Lymfocyt...................................................................................................................................... 89
13.5.3 Monocyt ...................................................................................................................................... 89
13.5.4 Eosinofiel ..................................................................................................................................... 89
13.5.5 Basofiel........................................................................................................................................ 89
13.5.6 Bloedbeelden .............................................................................................................................. 89
,1 De bloedcellen en de organisatie van hematopoiese
1.1 De bloedcellen
1.1.1 Algemeen
- plasma
~ Bevat
Bloedcellen
Eiwitten
§ Stollingsfactoren: nodig voor de hemostase
¨ Dit kan je onderzoeken door plasma te testen
§ Immunoglobinen: nodig voor humorale afweer
¨ Dit kan je onderzoeken door serum te testen
§ Complement: speelt een rol in de lyse van cellen en micro-organismen waarop antilichamen
of antistoffen (= immunoglobulinen) zich vooraf gebonden hebben
¨ Dit je kan je onderzoeken door serum te testen
~ Onderzoeken van bloedcellen en/of plasma
~ Proefbuis met anticoagulens
EDTA (= ethyleendiamine tetraacetaat) voor bloedcellen
Natriumcitraat voor plasmastolling
- Serum
~ Bloed laten centrifugeren
bovenste vloeistof = serum
onderste = bloedklonter
~ bevat geen stollingsfactoren
- Bloedcellen
~ Zijn gedifferentieerd
~ Functie
cardiovasculair-pulmonair systeem (vervoer zuurstof)
in de afweer
in de hemostase (bloedstelping)
1.1.2 Rode bloedcellen/erythocyten
- Functie: belangrijke rol in zuurstof- en CO2 transport.
~ D.m.v. hemoglobine
Zorgt voor de kleur van de RBC
- Hebben geen kern meer
- Vertegenwoordigen 1/3e van alle cellen in het menselijk lichaam
~ compatibel met hun belangrijke rol in het onderhoud van weefsels van het lichaam
RBC en trombocyten
1
, 1.1.3 Witte bloedcellen/leukocyten
(a) Fagocyten
- gespecialiseerd in het fagocyteren van partikels en micro-organismen
- soorten
~ granulocyten
neutrofiele granulocyten
eosinofiele granulocyten
basofiele granulocyten
~ monocyten
~ dendritische cellen
Granulocyten
- WBC die granules vertonen.
~ Indeling o.b.v. aankleuring van de granules in een May-Grünwald-Giemsakleuring:
- Neutrofiele granulocyten
~ Kleur granules: blauw-roos of blauw-grijs
~ Kern:
Staafkernige neutrofiel/granulocyt: staafkernig gebogen (links)
Segmentkernige granulocyt: bestaat uit 2 – 5 met elkaar verbonden
gecondenseerde kwabben (rechts)
~ Functie: fagocyteren en doden van bacteriën
Vormen de eerste verdedigingslijn van de huid- en mucosabarrière
~ Granules
Vertegenwoordigen lysosomen
Primaire granules
§ Beginnen vanaf stadium van de promyelocyt in beenmerg
§ bevatten o.a. myeloperoxidase
Secundaire granules
§ Verschijnen vanaf het niveau van de myelocyt in het beenmerg
§ Vormen grootste deel van de lysosomen in rijpe granulocyt vormen
§ bevatten o.a. collagenase
- Eosinofiele granulocyten
~ Kleur granules: oranje-rood
Zijn groot
Secundaire granules
~ Kern: 2 – 3 kwabben
~ Functie: rol in de bestrijding van worminfecties en allergische aandoeningen.
- Basofiele granulocyten
~ Kleur granules: donkerblauw
Grof
gelegen boven de kern
secundaire granules
§ bevatten heparine en histamine
§ Functie histamine: bevordert vasodilatatie waardoor witte
bloedcelbevoorrading wordt bevorderd aan een site van inflammatie.
~ Functie:
Rol in de bestrijding van parasieten
Rol in de chemotaxis van eosinofiele granulocyten
Rol in bestrijding van allergische aandoeningen
2
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