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Samenvatting - Shock en orgaanfalen
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Samenvatting van het vak 'Shock & Orgaanfalen' gegeven door prof. Jorens in de 2e Bachelor Geneeskunde aan de UA. Samenvatting van slides én lesnotities.
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InhoudstafelZuurstofradicalen...........................................................................................................................................8
Reactive Oxygen Species (ROS)...............................................................................................................8
Stikstofoxide (NO)...................................................................................................................................... 9
Ischemie-reperfusie..................................................................................................................................10
Eliminatie van ROS.................................................................................................................................. 10
Necrose vs. apoptose.................................................................................................................................. 11
Necrose.................................................................................................................................................... 11
Apoptose.................................................................................................................................................. 12
Necrose vs. apoptose.............................................................................................................................. 12
Inflammatie................................................................................................................................................... 13
Acute inflammatie.....................................................................................................................................13
LPS / superantigen...................................................................................................................................13
Mediatoren van sepsis............................................................................................................................. 14
Acute fase respons.................................................................................................................................. 15
Werking van NO....................................................................................................................................... 16
Prostaglandines....................................................................................................................................... 17
Ischemie reperfusie..................................................................................................................................... 17
Stikstofmonoxide (NO)............................................................................................................................. 18
Endotheline.............................................................................................................................................. 18
Eicosanoïden........................................................................................................................................... 19
Cytokines – chemokines.......................................................................................................................... 19
Reperfusieschade.................................................................................................................................... 19
Biochemische aspecten.............................................................................................................................. 19
Celbeschadiging.......................................................................................................................................19
Lactaatvorming.........................................................................................................................................20
Metabole respons bij shock......................................................................................................................20
Zuur-base......................................................................................................................................................21
Bufferes.................................................................................................................................................... 21
Anion gap................................................................................................................................................. 22
H+ excretie............................................................................................................................................... 22
Beoordeling van zuur-base status............................................................................................................22
Bloedstolling................................................................................................................................................ 23
Bloedstolling.............................................................................................................................................23
Stollingscascade...................................................................................................................................... 23
Disseminated intravascular coagulation (DIC)......................................................................................... 24
Hemoglobine en zuurstoftransport............................................................................................................ 24
Gastransport............................................................................................................................................ 24
Zuurstofdissociatiecurve.......................................................................................................................... 25
Cellulaire hypoxie en weefselhypoxie........................................................................................................27
Celdood....................................................................................................................................................27
Hypoxie.................................................................................................................................................... 27
Zuurstoftransport......................................................................................................................................28
Zuurstofaanbod........................................................................................................................................ 28
Zuurstofverbruik....................................................................................................................................... 28
Zuurstofextractie...................................................................................................................................... 28
Weefselhypoxie........................................................................................................................................ 28
, Arteriële hypoxie...................................................................................................................................... 29
Anemische hypoxie.................................................................................................................................. 29
Hypokinetische hypoxie........................................................................................................................... 29
Oorzaken van weefselhypoxie................................................................................................................. 29
Gevolgen..................................................................................................................................................30
Autonoom zenuwstelsel.............................................................................................................................. 30
Neurotransmissie..................................................................................................................................... 30
Sympathisch zenuwstelsel....................................................................................................................... 30
Adrenerge receptoren.............................................................................................................................. 31
Parasympathisch zenuwstelsel................................................................................................................ 31
Neurotransmitters.....................................................................................................................................31
Circulatie.......................................................................................................................................................32
Nerveuze controle van de circulatie......................................................................................................... 32
Hartdebiet.................................................................................................................................................32
Shock............................................................................................................................................................ 33
Klinische vormen......................................................................................................................................... 33
Multiple Orgaan Falen (MOF) = Multiple Organ Disfunction Syndrome (MODS).....................................33
Stadia van shock......................................................................................................................................34
Algemene symptomatologie....................................................................................................................... 34
Cyanose................................................................................................................................................... 34
Diagnose, labo, hemodynamisch profiel................................................................................................... 35
Arteriële bloeddruk................................................................................................................................... 35
Afwijkende polsdrukken........................................................................................................................... 35
Centraal veneuze druk............................................................................................................................. 36
Capillaire refill...........................................................................................................................................36
Cardiac output..........................................................................................................................................36
Swan-Ganz katheterisatie........................................................................................................................ 37
Tekens van cellulaire schade................................................................................................................... 37
Labo......................................................................................................................................................... 37
Weefselhypoxie meten............................................................................................................................. 38
Lactaat..................................................................................................................................................... 38
Gemengd veneuze zuurstofsaturatie....................................................................................................... 38
Toekomst.................................................................................................................................................. 39
Conclusie................................................................................................................................................. 39
Cardiogene shock........................................................................................................................................ 39
Fysiopathologie........................................................................................................................................ 40
Risicofactoren.......................................................................................................................................... 40
Klinische presentatie................................................................................................................................ 40
Dyspnoe................................................................................................................................................... 41
Oedeem................................................................................................................................................... 41
Hemodynamische parameters................................................................................................................. 41
Hemodynamische subsets....................................................................................................................... 42
Hemodynamische profielen......................................................................................................................42
Hypovolemische shock............................................................................................................................... 43
Stadia van shock......................................................................................................................................43
Hemodynamische profielen......................................................................................................................43
Oorzaken..................................................................................................................................................43
Klinische presentatie................................................................................................................................ 44
1
,Septische shock...........................................................................................................................................44
Systemic inflammatory response syndrome (SIRS).................................................................................44
Sepsis...................................................................................................................................................... 44
Ernstige sepsis.........................................................................................................................................45
Septische shock....................................................................................................................................... 45
Definities.................................................................................................................................................. 45
Verband tussen zuurstofaanbod en zuurstofverbruik...............................................................................45
Lactaat..................................................................................................................................................... 46
Klinische presentatie................................................................................................................................ 46
Sequentie van pathogenetische stappen................................................................................................. 46
Verstoring van bloedstolling..................................................................................................................... 47
Hemodynamische veranderingen............................................................................................................ 47
Tekens ter hoogte van de huid................................................................................................................... 48
Darmen..........................................................................................................................................................48
Anatomie.................................................................................................................................................. 48
Fysiologie................................................................................................................................................. 49
Splanchnische circulatie...........................................................................................................................49
Oxygen countercurrent exchange............................................................................................................ 50
Pathofysiologie van ischemische enteritis................................................................................................50
Hypoperfusie van de darm....................................................................................................................... 51
Hypovolemische shock............................................................................................................................ 51
ischemie en infarct................................................................................................................................... 51
necrose en sepsis.................................................................................................................................... 52
Klinisch beeld - dikke darm...................................................................................................................... 52
Diagnose.................................................................................................................................................. 52
Klinisch beeld - dunne darm.....................................................................................................................53
Bacteriële translocatie..............................................................................................................................53
Behandeling............................................................................................................................................. 53
Bij acute intestinale ischemie................................................................................................................... 54
Lever..............................................................................................................................................................54
Anatomie.................................................................................................................................................. 54
Ischemische hepatitis (levershock).......................................................................................................... 54
Evolutie naar acuut leverfalen..................................................................................................................55
Behandeling............................................................................................................................................. 55
Onthouden.................................................................................................................................................... 55
Shock............................................................................................................................................................ 55
Regulatie van bloeddruk bij shock.............................................................................................................56
Acute regulatie van arteriële druk............................................................................................................ 56
Baroreceptorreflex....................................................................................................................................56
Chemoreceptorreflex................................................................................................................................57
CZS ischemische respons....................................................................................................................... 57
Verloop van reflexmechanismen.............................................................................................................. 57
Renine-angiotensine vasoconstrictor mechanisme..................................................................................58
Vloeistofshift doorheen de capillaire wand...............................................................................................58
Conclusie................................................................................................................................................. 59
Effecten van shock op het cardiovasculair systeem................................................................................59
Sepsis-geïnduceerde cardiomyopathie....................................................................................................59
Microcirculatoire disfunctie.......................................................................................................................59
2
,Cardiogene shock........................................................................................................................................ 60
Oorzaken..................................................................................................................................................60
Ruptuur van papillairspiertjes...................................................................................................................60
Ventriculair septum ruptuur...................................................................................................................... 61
Vrije wand ruptuur.................................................................................................................................... 61
Mechanische complicaties....................................................................................................................... 61
Behandeling............................................................................................................................................. 61
Intra-aortic balloon pump (IABP)..............................................................................................................62
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO).......................................................... 62
ARDS............................................................................................................................................................. 63
ARDS vs. acute longbeschadiging...........................................................................................................63
Risicofactoren.......................................................................................................................................... 63
De spelers................................................................................................................................................ 64
Verschillende stappen.............................................................................................................................. 64
3 stadia.....................................................................................................................................................64
Fysiopathogenese: 4 basisconcepten......................................................................................................64
Radiografie...............................................................................................................................................65
Verwikkelingen......................................................................................................................................... 65
Fysiologische principes.............................................................................................................................. 66
Cerebrale bloedflow (CBF).......................................................................................................................66
Cerebrale perfusiedruk (CPP)..................................................................................................................66
Cerebrale autoregulatie............................................................................................................................66
Monroe-Kelly principe.............................................................................................................................. 67
Cerebrale bloedvolume............................................................................................................................ 68
Effect van PCO2.......................................................................................................................................68
Bloed-hersenbarrière............................................................................................................................... 68
Encephalopathie.......................................................................................................................................... 68
Septische encephalopathie...................................................................................................................... 69
Rol van endotheel bij pathogenese
NIET......................................................................................................................................................... 70
Rol van astrocyten bij pathogenese
NIET......................................................................................................................................................... 70
Rol van neuronen bij pathogenese
NIET......................................................................................................................................................... 70
Cushing-respons...................................................................................................................................... 70
Neurogeen longoedeem...........................................................................................................................70
Invloed van hersenpatholgoie op de hemodynamiek...............................................................................71
Shock............................................................................................................................................................ 71
Acute Kidney Injury (AKI)............................................................................................................................71
Diagnose.................................................................................................................................................. 71
AKI + shock vs. AKI - shock..................................................................................................................... 72
Pathofysiologie: AKI etiologische diagnose............................................................................................ 72
Renale hypoperfusie................................................................................................................................ 73
Renale veneuze congestie.......................................................................................................................73
Microcirculatoire disfunctie.......................................................................................................................73
Endotheliale disfunctie............................................................................................................................. 74
Microvasculaire trombose........................................................................................................................ 74
Inflammatie...............................................................................................................................................74
3
, Tubulaire obstructie..................................................................................................................................74
Algemeen verloop.................................................................................................................................... 75
AKI-fenotypes...........................................................................................................................................75
Crosstalk met andere organen.................................................................................................................75
Behandeling van AKI................................................................................................................................... 75
Hemodynamische behandeling................................................................................................................76
Anti-inflammatoire behandeling................................................................................................................76
Supportieve behandeling......................................................................................................................... 76
Vermijden van nefrotoxische agentia....................................................................................................... 76
Nierfunctievervangende therapie (RRT)...................................................................................................76
CRRT bij intracraniële hypertensie...........................................................................................................77
Chronische kidney disease (CKD)..............................................................................................................77
Prognose.......................................................................................................................................................78
Conclusie...................................................................................................................................................... 78
Hypovolemie.................................................................................................................................................78
Algemene principes van behandeling van shock..................................................................................... 78
VIP-benadering........................................................................................................................................ 79
Behandelingsprincipes............................................................................................................................. 79
Vocht............................................................................................................................................................. 79
Ionen........................................................................................................................................................ 80
Eiwitten.....................................................................................................................................................80
Vochtverlies..............................................................................................................................................80
Colloïdale oplossingen................................................................................................................................80
Natuurlijke colloïden.................................................................................................................................81
Albumine.................................................................................................................................................. 81
Fresh Frozen Plasma (FFP).....................................................................................................................81
Synthetische colloïden............................................................................................................................. 81
Hydroxyethyl-zetmeel (HES).................................................................................................................... 81
Dextranen.................................................................................................................................................82
Gelatines.................................................................................................................................................. 82
Hypertoon zout.............................................................................................................................................82
Studies.......................................................................................................................................................... 82
Albumine vs. saline (NaCl).......................................................................................................................82
Hydroxyethyl-zetmeel vs. zout................................................................................................................. 83
Toekomst.................................................................................................................................................. 83
Conclusie................................................................................................................................................. 83
Overzicht.......................................................................................................................................................83
Adequaat transfusiebeleid.......................................................................................................................... 84
Rode bloedcellen..................................................................................................................................... 85
Wanneer transfusie.................................................................................................................................. 85
Vormen van RBC..................................................................................................................................... 85
Trombocytenconcentraat..........................................................................................................................86
Plasmaderivaten...................................................................................................................................... 86
Complicaties van transfusies................................................................................................................... 86
Orthosympathicus....................................................................................................................................... 87
Receptoren...............................................................................................................................................87
Inotropie................................................................................................................................................... 87
Shock............................................................................................................................................................ 87
4
,Farmaca bij kritisch hemodynamische toestanden (orthosympathicus)............................................... 88
Sympatho-adrenerge farmaca................................................................................................................. 88
Dominerende -receptor agonisten: dopamine..........................................................................................89
Dominerende -receptor agonisten: dobutamine.......................................................................................89
Dominerende -receptor agonisten: adrenaline.........................................................................................89
Dominerende -receptor agonisten: noradrenaline....................................................................................89
Digitalis.....................................................................................................................................................89
Fosfodiesterase inhibitoren...................................................................................................................... 89
Verbetering van systolische functie..........................................................................................................90
Glucocorticoïden..........................................................................................................................................90
Cortisol..................................................................................................................................................... 90
Catecholamines....................................................................................................................................... 91
Anti-oxidantia............................................................................................................................................... 91
NO-blokkers..................................................................................................................................................91
Plasmaferese................................................................................................................................................ 91
Activated proteine C.................................................................................................................................... 91
Weefselhypoxie............................................................................................................................................ 91
Septische shock (distributieve shock).......................................................................................................93
Klinisch onderzoek................................................................................................................................... 93
Infectieuze focus...................................................................................................................................... 94
Bepalende factoren.................................................................................................................................. 94
Orgaanfalen............................................................................................................................................. 94
Gastheerfactoren..................................................................................................................................... 94
Pathogeen/kiem....................................................................................................................................... 94
Principes van behandeling....................................................................................................................... 95
Hemodynamiek: hypotensie.....................................................................................................................95
Antibiotica.................................................................................................................................................95
Source control.......................................................................................................................................... 95
Orgaan ondersteunende therapie............................................................................................................ 96
Andere: immunotherapie/anticoagulerende therapie............................................................................... 96
Surviving sepsis campaign.......................................................................................................................96
Cardiogene shock........................................................................................................................................ 96
Swan-Ganz katheter................................................................................................................................ 97
Behandeling............................................................................................................................................. 97
Inotropica en vasopressoren....................................................................................................................97
Kunstmatige ventilatie en sedatie............................................................................................................ 98
Intra-aortische ballonpomp.......................................................................................................................98
Therapieresistentie...................................................................................................................................98
Coronaire arteriële bypass grafting (CABG)............................................................................................ 98
Biventricular assist device (BiVAD).......................................................................................................... 99
Hypovolemische shock............................................................................................................................... 99
Obstructieve shock....................................................................................................................................100
Spanningspneumothorax (klaplong)...................................................................................................... 100
Harttamponade...................................................................................................................................... 101
Constrictieve pericarditis........................................................................................................................ 102
Volume/druk relatie................................................................................................................................ 102
Pulsus paradoxus...................................................................................................................................102
Pericardpunctie...................................................................................................................................... 103
5
, Longembolen......................................................................................................................................... 103
Beroepsgeheim.......................................................................................................................................... 105
Gedeeld en gezamenlijk beroepsgeheim...............................................................................................105
Informatie geven aan familie.....................................................................................................................106
Wie is familie.............................................................................................................................................. 0
Informatie geven aan derden.................................................................................................................... 107
Informatie over kinderen doorgeven aan ouders....................................................................................107
Slecht nieuws gesprek en orgaandonatie............................................................................................... 107
Inleiding...................................................................................................................................................... 108
Historisch............................................................................................................................................... 108
Wetgeving.............................................................................................................................................. 108
Opting-out – registratie...........................................................................................................................109
Mogelijke attesten.................................................................................................................................. 109
Orgaan acceptor.................................................................................................................................... 109
Soorten donoren.....................................................................................................................................110
Heart beating donor (HBD)........................................................................................................................ 110
Areactief irreversiebele coma................................................................................................................. 111
Afwezigheid van hersenstamreflexen..................................................................................................... 111
Pupilreflex............................................................................................................................................... 111
Corneareflex........................................................................................................................................... 111
Vestibulo-oculaire reflex..........................................................................................................................111
Faryngeale en tracheale reflex............................................................................................................... 111
Bijzondere reflexen.................................................................................................................................112
Afwezigheid van spontane ademhaling.................................................................................................. 112
Apneutest............................................................................................................................................... 112
Donormanagement.................................................................................................................................112
Non heart beating donation (NHBD).........................................................................................................113
Wie......................................................................................................................................................... 113
Potentiële donoren................................................................................................................................. 113
Categorie 3: awaiting cardiac death....................................................................................................... 114
Criteria voor cardiocirculatoir overlijden................................................................................................. 114
No touch period...................................................................................................................................... 114
Hoe......................................................................................................................................................... 114
Het hart...................................................................................................................................................115
Cijfers.......................................................................................................................................................... 115
Organisatie: Eurotransplant......................................................................................................................115
● Je kan de principes van diagnose, labo, monitoring, ondersteuning van falende organenstelsels
opnoemen, definiëren en onderscheiden
● Je kan de kennis die eerder werd behandeld toepassen op concrete situaties van shock
● Je kan aan de hand van klinische casussen begrijpen en uitleggen wat het ontstaansmechanisme
is, wat de klinische kenmerken zijn en wat de principes zijn van diagnose en behandeling
● Je neemt kennis van de verschillende niveaus van zorg
● Je kan omgaan met hersendood in de optiek van orgaandonatie en transplantatie
● Je kan omgaan met begeleiding van levenseinde met inbegrip van slechtnieuwsgesprek en het
rouwproces
● Je kan omgaan met crisissituaties
6
,Fysiopathologie van shock
11 belangrijke factoren
● zuurstofradicalen
● inflammatie
● ischemie reperfusie
● biochemische aspecten
● zuur-base
● bloedstolling
● hemoglobine en zuurstoftransport
● cellulaire- en weefselhypoxie
● autonoom zenuwstelsel
● circulatie
Zuurstofradicalen
→ welke zuurstofradicalen, wat ze beschadiging, xanthine oxidase & hypoxanthine, anti-oxidanten
= reactive oxygen species = onvoldoende gereduceerde vormen van O2
vicieuze cirkel (bv. reperfusie)
1. vorming van vrije radicalen door ziekteproces, medicatie of toxines
● bv. farmaca, toxische omstandigheden (shock)
2. membraan lipide peroxidatie = aantasting van lipiden die essentiële
rol spelen in de celwand
3. cel- en weefselschade
4. meer vrijzetting van vrije radicalen
⇒ vrije radicalen zorgen voor lipide peroxidatie, waarbij lipiden worden beschadigd die een essentiële rol
spelen in de celwand (cel- en weefselschade)
Reactive Oxygen Species (ROS)
elektronen worden continu gecapteerd en toegevoegd aan zuurstof, met uiteindelijk vorming van water:
O2 → O2- (superoxide anion, radicaal) → H2O2 (waterstofperoxide) → OH- (hydroxyl radicaal) → H2O
● H2O2: wordt gebruikt als desinfectans in de kliniek, valt bacteriën aan door zijn radicale eigenschap
● detoxificatie: ROS geven elektronen af of nemen elektronen op om een stabielere species (H2O) te
vormen
vorming van vrije zuurstofradicalen in de cel: ter hoogte van lysosoom, cytoplasma, transportsysteem van
mitochondriën …
Detoxificatie van ROS
→ ROS geven elektronen af of nemen elektronen op om een stabielere species te vormen
1. ziekteproces, medicatie of toxines: O2 → O2-
● onder invloed van NAD(P)H oxidase
7
,2. enzymen in het lichaam zorgen ervoor dat O2-radicalen van de instabiele vorm worden weggewerkt
● O2- → H2O2 onder invloed van superoxide dismutase (SOD)
● H2O2 → HOCl (hypochlorus acid) onder invloed van myeloperoxidase (MPO)
● H2O2 → H2O onder invloed van catalase
- -
● O2 + NO → OONO (peroxynitrite anion) met NO uit het endotheel (vasodilatatie)
Beschadiging door ROS
→ ROS beschadigen de belangrijkste klassen van macromoleculen
● lipide peroxidatie (door OH-)
○ het celmembraan wordt minder vloeibaar → verlies aan selectieve permeabiliteit
○ lekt en verstoring van het membraan
■ gevolg: water, elektrolyten … kunnen over het membraan uitgewisseld worden
● proteïne beschadiging (O2-, H2O2, OH-)
○ verstoring van cellulaire enzymen vanwege fragmentatie → metabole activiteit is verstoord
● DNA-beschadiging (door OH-)
○ breken van single strands → verstoring van het verouderingsproces
O2- (superoxide anion) H2O2 (waterstofperoxide) OH- (hydroxylradicaal)
nucleïnezuren basemodificatie
(105 / cel /dag)
proteïnen beschadiging van Fe-S oxideren SH-groep van proteïnen tot aminozuur modificatie
→ DNA proteïnen disulfide (S2)
X-linking
lipiden lipide peroxides
→ celwand
Stikstofoxide (NO)
functie
● endogene vasodilatator
● neurotransmitter in CZS
● inhibitie van plaatjesaggregatie, gladde spiercel proliferatie
● anti-bacterieel (bactericide)
O2- + NO → OONO- (peroxynitrite anion) + tyrosine → nitrotyrosine
1. NO bindt met radicalen (O2-) met vorming van peroxynitriet
2. peroxynitriet bindt met tyrosine met vorming van nitrotyrosine
3. nitrotyrosine residu’s zijn een indirecte marker van ROS/RNS schade
8
, Ischemie-reperfusie
ischemie = verminderde doorbloeding van organen en weefsels
● geeft afbraak van ATP tot hypoxanthine
● gevolg: weefselschade
reperfusie = herstel van de bloedstroom naar weefsels in het lichaam, wanneer de bloedstroom eerst
verminderd/afwezig was
hypoxanthine → xanthine + urinezuur (uraat) onder invloed van xanthine oxidase (O-vorm)
1. hypoxanthine: afbraakproduct van ATP, AMP … (purines) dat wordt opgestapeld bij ischemie
2. normaal: xanthine dehydrogenase (XD) zet xanthine om tot NADH en urinezuur
3. bij lange hypoxie: hypoxische cytokines activeren xanthine dehydrogenase (XD) dat wordt omgezet
naar xanthine oxidase (heeft zuurstof nodig !)
4. bij reperfusie: xanthine oxidase (XO) zet xanthine om naar zuurstofradicalen (O2-) en urinezuur, dat
zich opstapelt bij weefselschade
Voorbeeld: acuut myocard infarct
ischemie
1. ATP ↓, ADP ↑, AMP ↑
2. degradatie van AMP tot hypoxanthine ↑: accumulatie want xanthine oxidase (enzym) dat O2 vereist
3. xanthine en urinezuur ↓
reperfusie: O2 toevoer en hoge [hypoxanthine] → hoge snelheid van omzetting naar urinezuur waardoor
O2- en H2O2 ontstaat
⇒ reperfusie beschadiging treedt op wanneer reoxygenatie van ischemisch weefsel ervoor zorgt dat ROS
worden gevormd
Eliminatie van ROS
natuurlijke beschermingsmechanismen om ROS om te zetten naar stabiele vorm
● anti-oxidantia
9
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