Samenvatting van het vak "Stowisseling & Hormonen 1" gegeven door prof. De Block in de 2e Bachelor Geneeskunde aan de UA. Volledige samenvatting gebaseerd op slides én lesnotities.
Bevat onder andere duidelijke overzichten van de hypothalamo-hypofysaire assen.
Fysiologie van het groeihormoon.............................................................................................................. 40
Synthese en secretie..........................................................................................................................40
Hypothalamo-hypofysaire-groeihormoon as...........................................................................40
Controle van GH-secretie....................................................................................................... 41
Werking van GH................................................................................................................................. 42
Fysiologische effecten............................................................................................................ 42
Pathologie.......................................................................................................................................... 43
GH-deficiëntie.........................................................................................................................43
GH-excess..............................................................................................................................43
Fysiologie van de hypothalame-hypofysaire gonadale as bij de man....................................................44
Anatomie............................................................................................................................................ 44
Hormonaal systeem........................................................................................................................... 45
GnRH en LH/FSH synthese................................................................................................... 45
Testes als eindorgaan.............................................................................................................46
Testosteron.........................................................................................................................................47
Biologische effecten van testosteron en dihydrotestosteron.................................................. 48
Fysiologie van de bijnier............................................................................................................................. 50
Morfologie...........................................................................................................................................50
Histologie................................................................................................................................50
Synthese van bijnierschorshormonen................................................................................................ 50
Synthese van cortisol............................................................................................................. 51
Synthese van aldosteron........................................................................................................ 52
Synthese van androgenen......................................................................................................52
Pathofysiologie....................................................................................................................... 52
Glucocorticoïden - cortisol..................................................................................................................53
Hypothalamo-hypofysaire-bijnier as....................................................................................... 53
Adrenocorticotroop hormoon (ACTH).....................................................................................54
Werking van glucocorticoïden................................................................................................ 54
Mineralocorticoïden - aldosteron........................................................................................................ 56
Controle van aldosteron......................................................................................................... 56
Werking van aldosteron.......................................................................................................... 56
Androgenen........................................................................................................................................56
Synthese van bijniermerghormonen...................................................................................................57
Biosynthese van catecholamines........................................................................................... 57
Werking van catecholamines..................................................................................................57
Metabolisatie van catecholamines..........................................................................................58
Pathofysiologie: hyperfunctie............................................................................................................. 58
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Fysiologie van de schildklier...................................................................................................................... 62
Anatomie en histologie....................................................................................................................... 62
Synthese van iodothyronines............................................................................................................. 62
Biosynthese van iodothyronines.............................................................................................62
Transport van iodothyronines................................................................................................. 64
Transformatie van iodothyronines.......................................................................................... 64
Schildklierwerking...............................................................................................................................65
Hypothalamo-hypofysaire-schildklier as................................................................................. 65
Metabole activiteit van schildklierhormonen........................................................................... 66
Schildklierfunctie testen......................................................................................................................67
Pathologie: hyperthyroïdie..................................................................................................................67
Graves-Basedow.................................................................................................................... 68
Toxisch adenoom....................................................................................................................68
Toxische multinodulaire goiter................................................................................................ 68
Jodium-geïnduceerde hyperthyroïdie..................................................................................... 69
Thyroïditis............................................................................................................................... 69
Kliniek van hyperthyroïdie...................................................................................................... 70
Pathologie: hypothyroïdie...................................................................................................................70
Etiologie..................................................................................................................................71
Hashimoto = chronisch autoimmune thyroïditis......................................................................71
Kliniek van hypothyroïdie........................................................................................................72
Fysiologie van de bijschildklier.................................................................................................................. 73
Anatomie en histologie....................................................................................................................... 73
Synthese van parathyroïdhormoon (PTH)..........................................................................................73
Controle van PTH................................................................................................................... 73
Werking van parathyroïdhormoon (PTH)........................................................................................... 75
Werking van PTH in nieren.....................................................................................................75
Werking van PTH in bot..........................................................................................................76
Werking van PTH in darmen.................................................................................................. 77
Calcium metabolisme......................................................................................................................... 77
Calcium homeostase.............................................................................................................. 78
Fosfaat homeostase............................................................................................................... 79
1,25-dihydroxy-vitamine D3....................................................................................................79
Calcitonine..............................................................................................................................80
Fysiologie van het lipidenmetabolisme..................................................................................................... 81
Lipiden................................................................................................................................................81
Cholesterolmetabolisme......................................................................................................... 81
Lipoproteïnen..................................................................................................................................... 83
Lipoproteïnen..........................................................................................................................83
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, Apolipoproteïnen.................................................................................................................... 83
Exogene en endogene pathway.........................................................................................................84
Exogene cholesterolpathway..................................................................................................85
Endogene cholesterolpathway............................................................................................... 85
Regulatie van LPL.................................................................................................................. 86
Regulatie van LDL-receptor....................................................................................................86
Implicaties voor de kliniek.................................................................................................................. 87
Bepaling van bloedlipiden.......................................................................................................87
Hyperlipidemie........................................................................................................................88
Werkingsmechanismen van lipiden-verlagende medicatie................................................................ 89
Cholesterolverlagende medicatie........................................................................................... 89
Triglyceriden verlagende medicatie........................................................................................ 91
Effecten van lipidenverlagende medicatie.............................................................................. 92
Gewichtshomeostase.................................................................................................................................. 93
Lichaamssamenstelling en metabolisme............................................................................................93
Antropometrische metingen....................................................................................................93
Metabolisme........................................................................................................................... 94
Centraal zenuwstelsel........................................................................................................................ 94
Hypothalamus.........................................................................................................................94
Melanocortine systeem...........................................................................................................95
Autonoom (perifeer) zenuwstelsel......................................................................................................95
Communicatie tussen vetcellen en hersenen.....................................................................................95
Leptine....................................................................................................................................95
Adiponectine...........................................................................................................................96
Communicatie tussen gastro-intestinaal stelsel en hersenen............................................................ 97
Ghreline.................................................................................................................................. 97
Glucagon-like peptide-1 (GLP-1)............................................................................................98
Oxyntomoduline......................................................................................................................99
Communicatie tussen pancreas en hersenen.................................................................................... 99
Insuline................................................................................................................................... 99
Amyline.................................................................................................................................100
Communicatie tussen smaakpapillen en hersenen..........................................................................100
Communicatie tussen lever en hersenen......................................................................................... 100
FGF-21................................................................................................................................. 100
Communicatie binnen de hersenen..................................................................................................101
Circadiaans ritme..................................................................................................................101
,Fysiologie van de endocriene pancreas
Pancreas
● exocrien deel
○ secretie van spijsverteringsenzymen en HCO3- in de GI-tractus
● endocrien deel
○ eilandjes van Langerhans
Eilandjes van Langerhans
● +/- 1-1.5 miljoen eilandjes = 1-1.5% van de pancreasmassa
● elk eilandje bevat 2500 cellen, bestaande uit 4 types
○ 60-75% β-cellen: insuline en amyline
○ 20-25% α-cellen: glucagon
○ 4% δ-cellen: somatostatine
○ 2% PP-cellen = F-cellen: pancreatic polypeptide
communicatie
● humoraal: via bloedvoorziening (van centraal → perifeer)
○ hormonale secreties van cellen in het centrum
beïnvloeden hormonale vrijstelling van cellen in de
periferie
○ insuline (β-cellen) remt vrijstelling van glucagon (α-cellen)
● neuraal: OS en PS van het autonoom zenuwstelsel
○ cholinerge stimulatie van insuline
● cel-tot-cel
○ via gap junctions en tight junctions
distributie van cellen in eilandjes van Langerhans
● β-cellen: centraal
● de rest: perifeer
hormoondistributie in de pancreas
● insuline: gelijkmatige verdeling
● pancreatic polypeptide: vooral in processus uncinatus en hoofd
● glucagon: vooral in de staart
type 1 diabetes: afwezige insulineproductie
● invaliderende langetermijncomplicaties: oogaantasting, nierbelasting
● behandeling: β-cel transplantatie → β-cellen (van donoren) in v. portae inspuiten om
insulineproductie te normaliseren
○ nadeel: 5-6 pancreassen nodig voordat voldoende grote hoeveelheid β-cellen is verzameld +
slechts 2 weken op celcultuur bewaren
Insuline
Biosynthese
1. transcriptie van het gen op chromosoom 11 (DNA) resulteert in productie van mRNA dat codeert
voor pre-proinsuline
6
, 2. vorming van proinsuline door translatie thv het endoplasmatisch reticulum (ribosomen)
3. verpakking van proinsuline in secretoire granules thv het golgi-apparaat
4. splitsing van proinsuline door protease, waardoor C-peptide (connecting peptide) wordt afgesplitst
van de α- en β-keten die aan elkaar gebonden zijn door disulfidebruggen (insuline)
5. secretie van insuline in de portale circulatie, waarvan 60% wordt geëlimineerd door de lever tijdens
first pass effect
6. excretie van C-peptide door de nieren (niet geëlimineerd door de lever)
C-peptide
● gebruikt als merker voor endogene insulinesecretie
● bv. patiënt met familiale diabetes die behandeld wordt met
insuline
○ insuline-meting geeft ook het ingespoten insuline weer
○ endogene en exogene insuline onderscheiden dankzij
C-peptide
● type 1 diabetes: afwezig insulineproductie
○ geen C-peptide
● type 2 diabetes: relatief insulinetekort
○ aanwezig C-peptide
insuline: α-keten (21 AZ) en β-keten (30 AZ), verbonden door disulfidebruggen
● wijziging in AZ-sequentie en replacement van AZ → farmacokinetisch en farmacodynamisch profiel
wijzigen
● gevolg: ultra-traag vs. ultra-snelwerkende insulines
Insulinesecretie ⭐⭐⭐
maaltijd: insulineconcentratie stijgt door glucose, neurale en incretine-gemedieerde stimulatie van β-cellen
stimulatie: glucose
1. β-cel neemt glucose op via GLUT2-transporters (gefaciliteerde diffusie)
2. glucose wordt oiv glucokinase omgezet tot glucose-6-fosfaat, en ondergaat verdere glycolyse tot
pyruvaat
3. pyruvaat ondergaat oiv pyruvaat dehydrogenase de oxidatieve decarboxylatie in het mitochondriën,
met vorming van acetyl-CoA
4. acetyl-CoA wordt verder gemetaboliseerd in de krebscyclus met productie van ATP dankzij de
protonengradiënt en oxidatieve fosforylatie
5. toegenomen intracellulaire ATP-concentratie zorgt voor sluiten van KATP-gevoelige K+-kanalen
6. verminderde K+-geleiding veroorzaakt depolarisatie van het celmembraan
7. membraandepolarisatie opent de voltage-gated Ca2+-kanalen
8. verhoogde Ca2+-influx resulteert in toegenomen intracellulaire vrije Ca2+-concentratie
9. dit lokt een additionele Ca2+-geïnduceerde Ca2+-release uit thv het endoplasmatisch reticulum
10. exocytose en vrijstelling van insuline in 2 fases
● acute first-phase insuline response (FPIR): reeds gevormde en opgeslagen insuline
vrijstellen uit de secretoire granules
● second-phase insuline response: zowel reeds gesynthetiseerd als nieuw gevormd insuline
vrijstellen
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