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Volledige samenvatting ziektemechanismen Vangoitsenhoven
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volledige samenvatting pathofysiologie ziektemechanismen gegeven door professor Vangoitsenhoven met notities uit de les
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ZIEKTEMECHANISMEN –VANGOITSHOVEN
H1: Inleiding ................................................................................................................................................... 4
Definities ............................................................................................................................................................. 4
Huidige doodsoorzaken....................................................................................................................................... 4
Veroudering ........................................................................................................................................................ 4
Cellulaire en moleculaire oorzaken van veroudering ..................................................................................... 4
Schade aan macromoleculen ..................................................................................................................... 4
Inadequaat herstel van schade .................................................................................................................. 5
Ontregeling van de homeostase van celaantal .......................................................................................... 7
Kan men veroudering vertragen? ....................................................................................................................... 7
H2: Inflammatie .............................................................................................................................................. 8
Inleiding .............................................................................................................................................................. 8
Pathofysiologie van de acute ontstekingsreactie ................................................................................................ 8
Vasculaire elementen van de ontstekingsreactie ................................................................................................ 8
Pathofysiologie ............................................................................................................................................... 8
Hyperemie .................................................................................................................................................. 8
Marginatie en diapedese............................................................................................................................ 8
Vorming van een vochtexsudaat ................................................................................................................ 9
Biochemische mediatoren .............................................................................................................................. 9
Histamine ................................................................................................................................................... 9
De kinines ................................................................................................................................................. 10
Het complementsysteem ......................................................................................................................... 10
Lipide-mediatoren .................................................................................................................................... 11
Cellulaire elementen van de ontstekingsreactie ............................................................................................... 11
Pathofysiologie ............................................................................................................................................. 11
Biochemische aspecten ................................................................................................................................ 12
Motiliteit en chemotaxis .......................................................................................................................... 12
Fagocytose ............................................................................................................................................... 12
Algemene weerslag van de acute ontstekingsreactie ....................................................................................... 12
H3: Thermoregulatie ..................................................................................................................................... 13
Inleiding ............................................................................................................................................................ 13
Fysiologie van de thermoregulatie .................................................................................................................... 13
Effector-apparaat ......................................................................................................................................... 13
Warmteproductie en aanpassingsmechanismen ..................................................................................... 13
Warmte-afgave en aanpassingsmechanismen ......................................................................................... 13
Sensor-apparaat ........................................................................................................................................... 14
Set-Point ....................................................................................................................................................... 14
Fysiopathologie van de thermoregulatie .......................................................................................................... 15
, Koorts ........................................................................................................................................................... 15
Hyperthermie ............................................................................................................................................... 16
Hypothermie ................................................................................................................................................. 16
H4: Voeding en metabolisme ........................................................................................................................ 17
Normale voedingsbehoeften van de mens ........................................................................................................ 17
Essentiele nutritionele behoeften ................................................................................................................ 17
Energie ..................................................................................................................................................... 17
Eiwit.......................................................................................................................................................... 17
Lipiden ...................................................................................................................................................... 18
Koolhydraten ............................................................................................................................................ 18
Vitaalstoffen ............................................................................................................................................. 18
Water en elektrolyten .............................................................................................................................. 18
Aanbevolen hoeveelheden ........................................................................................................................... 18
Factoren die de behoefte aan nutriënten beïnvloeden................................................................................ 18
Malnutritie ........................................................................................................................................................ 19
Eiwit-energie malnutritie .............................................................................................................................. 19
Marasmus-like .......................................................................................................................................... 19
Kwashiorkor-like ....................................................................................................................................... 19
Hypometabole en hypermetabole toestanden ............................................................................................ 19
Hormonen ................................................................................................................................................ 19
Metabolisme ............................................................................................................................................ 21
Eiwitkatabolisme ...................................................................................................................................... 21
Gluconeogenese ....................................................................................................................................... 21
Kanker cachexie ............................................................................................................................................ 21
Regeling van de energiebalans en obesitas ...................................................................................................... 21
Regeling van de energiebalans ..................................................................................................................... 21
Appetijt..................................................................................................................................................... 21
Energieverbruik ........................................................................................................................................ 22
Obesitas ........................................................................................................................................................ 22
Definitie en maatstaven ........................................................................................................................... 22
Etiologie van obesitas............................................................................................................................... 22
Pathogenese van obesitas ........................................................................................................................ 23
H5: Calcium................................................................................................................................................... 24
Fysiologische aspecten ...................................................................................................................................... 24
Homeostase van het serum calcium............................................................................................................. 24
Vorming en turn-over van het bot ................................................................................................................ 25
Hormonale controle van de calciumhomeostase ......................................................................................... 25
Parathyroidhormoon of parathormoon ................................................................................................... 25
Vitamine D ................................................................................................................................................ 26
Pathofysiologie van de calciumhomeostase ..................................................................................................... 26
Hypocalcimie ................................................................................................................................................ 26
Definitie .................................................................................................................................................... 26
Oorzaken .................................................................................................................................................. 26
Symptomen .............................................................................................................................................. 27
Behandeling.............................................................................................................................................. 27
Hypercalcimie ............................................................................................................................................... 27
Definitie .................................................................................................................................................... 27
Oorzaken .................................................................................................................................................. 27
Symptomen .............................................................................................................................................. 28
Behandeling.............................................................................................................................................. 28
,H6: Ademhaling ............................................................................................................................................ 30
Inleiding ............................................................................................................................................................ 30
Pathofysiologie van hypoxie en hypercapnie .................................................................................................... 30
Hypoxie ......................................................................................................................................................... 30
Oorzaken .................................................................................................................................................. 30
Symptomen en begeleidende verschijnselen........................................................................................... 30
Hypercapnie.................................................................................................................................................. 31
Oorzaken .................................................................................................................................................. 31
Symptomen en begeleidende verschijnselen........................................................................................... 31
Belangrijkste vormen van longpathologie ........................................................................................................ 32
Obstructieve aandoeningen ......................................................................................................................... 32
Astma ....................................................................................................................................................... 32
Chronisch obstructief longlijden (COPD) .................................................................................................. 33
Restrictieve aandoeningen ........................................................................................................................... 34
Interstitieel longlijden .............................................................................................................................. 35
Pneumonie ............................................................................................................................................... 35
Vasculaire aandoeningen ............................................................................................................................. 35
Pulmonale hypertensie ............................................................................................................................ 35
LOngstuwing en longoedeem................................................................................................................... 36
Longembool.............................................................................................................................................. 36
Diagnose: longfunctieproeven .......................................................................................................................... 37
Metingen van de statische longvolumes ...................................................................................................... 37
Metingen van de dynamische longvolumes (ventilatie) ............................................................................... 37
H7: Cardiovasulair......................................................................................................................................... 38
Syncope ............................................................................................................................................................. 38
Circulatoire oorzaken ................................................................................................................................... 38
Syncope door arteriolaire vasodilatatie ................................................................................................... 38
Cardiale vormen van syncope .................................................................................................................. 40
Andere circulatoire oorzaken van syncope .............................................................................................. 40
Niet-circulatoire oorzaken ............................................................................................................................ 40
Hartfalen ........................................................................................................................................................... 40
Definitie ........................................................................................................................................................ 41
Symptomen .................................................................................................................................................. 41
Pathofysiologie ............................................................................................................................................. 41
Hartfalen met een gedaalde ejectiefractie .............................................................................................. 41
Hartfalen met een bewaarde ejectiefractie ............................................................................................. 41
Compensatoire mechanismen ................................................................................................................. 42
Behandeling .................................................................................................................................................. 42
Shock ................................................................................................................................................................. 42
Indeling op basis van pathogenese............................................................................................................... 42
Shock door relatieve hypovolemie ........................................................................................................... 42
Cardiogene shock ..................................................................................................................................... 43
Algemene fysiopathologie van shock ........................................................................................................... 43
Symptomen .................................................................................................................................................. 44
, H1: INLEIDING
DEFINITIES
Het begrip ‘Activiteit’
• Evolutie van een ziekte: schadelijk agens + terrein (omgevingsfactoren + genetisch)
• Normale O2 spanning
o 100 mmHg
o 85-jarige: 60 mmHg is normaal, wat niet normaal is bij 20-jarige
HUIDIGE DOODSOORZAKEN
1. Kanker
2. Hart- en vaatziekten
VEROUDERING
= progressieve, algemene afname eerst in functionele reserves en nadien in de functie van een
organisme
= geen ziekte, maar risico om ziekte te ontwikkelen is toegenomen
CELLULAIRE EN MOLECULAIRE OORZAKEN VAN VEROUDERING
• Omgevingsfactoren en gedrag + genetische factoren -> bepalen levensduur
• Vroegtijdige veroudering (progeria)
• 3 processen van veroudering
o Schade door oxidatieve stress (of andere factoren)
o Inadequaat herstel van schade
o Ontregeling van de homeostase van celaantal
SCHADE AAN MACROMOLECULEN
Oxidatieve stress
• ROS (reactieve oxygen species): waterstofperoxide, hydoxylradicaal, superoxide radicaal
o Onstabiel -> schade aan belangrijke biologische moleculen
o Fysiologische processen
o Ontstaat bij verbruik van O2 in de mitochondriën -> inherent aan normaal
metabolisme
o Bescherming
§ Antioxidatieve enzymes: superoxide dismutase (SOD), catalase, glutathione
peroxidase
§ Antioxidantia: vitamine C en E
,Glycatie en glycoxidatie
• = niet-enzymatische reacties tussen suiker en macromolecule waarbij ‘advanced glycation end
products (AGEs)’ gevormd worden
• AGEs veranderen structuur en functie van langlevende eiwitten, vb vertroebeling ooglens
Mitochondriale schade
• Mitochondria = belangrijkste bron van ROS -> daar meeste schade
• MtDNA: niet beschermd door histonen -> toenemende schade met leeftijd -> kunnen minder
ATP genereren -> celfunctie daalt
Somatische mutaties
• Door omgevingsfactoren en oxidatieve stress
• Beperkte herstelmechanismen
INADEQUAAT HERSTEL VAN SCHADE
DNA herstel
• Herstelmechanismen minder efficiënt met leeftijd ->
meer schade
• Genetische defecten van herstelmechanismen ->
premature veroudering = progeria
Turnover van eiwitten
• Beschadigde eiwitten -> proteolyse -> vervangen
door nieuw eiwit
• Ombouw van eiwitten vermindert met de leeftijd ->
vooral effect op langlevende eiwitten
,
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