MG: endocrine system + DT/RT L4

Reflux-esophagitis

Inflammation of lower part esophagus due to reflux of stomach acid. Due to dysfunctional lower esophageal sphincter or inadequeate peristalis or insufficient salvia alkaline.

It is promoted by obesity, pregnancy applying pressure on stomach and certain foods that can intervere with the neuronal network. Drugs that relax the sphincter muscle can also promote this so be aware of anticholinergics, theophyline, calcium antagonists and progesterone.

Treatment reflux esophagitis

Adjustment life style

Prokinetic drugs

H2 inhibitors and proton pump inhibitors

antacids but not for the long run

Prokinetic drugs + mode of action

Domperidone and metoclopramide help with reflux disease. D2 receptor blockers only in the periphery. The D2 receptor normally blocks AcH from being released and contracting SMC. So when inhibited = more Ach = more contraction.

Metoclopramide also activates the 5HT4 receptor increasing even more AcH release.

Dyspepsia treatment

Stomach complaints with unkown reason:

-Ulcus-like: H2 antagonist or proton pump inhibitor

-Feeling full: prokinetic drugs

Emesis neuronal control

vomitting reflex.

input: Ear, Gut (5HT3/4 and D2), brain stem (D2)

output: naussea, vassopressin (pale), motor outputs to diaphragm and abdominal muscle and also to autnomic for cold sweating etc.

Treatment emesis

-antihistamines first gen

-D2 antagonsits on the chemo trigger zone in the brain,domperidone, metoclopramide. also in GI tract.

alternatives:

-5HT antagonist GI and chemo trigger zone

-anticholinergics will open the sphincter so not ideal

Gut role of CFTR

Cystic fibrosis conductance regulator. Certain toxins can interact with them (cholera) resulting in diarhea. These toxins activate Gs consistently because they bound very thightly, resulting in cAMP which will persistently activate CFTR which will pass cl- and therefore water will folow.

cAMP also relaxes smooth muscle cells.

Diarhea types

Osmotic diarhea(exess water into lumen), secretory diarhea(eg toxin), Motor dysfunction (exessive motillity), exudative (inflammation, ulcers). Treat underlying problem.

Acute + chronic diarhea causes.

Acute: infections/toxins, drugs or stress.

Chronic: Underlying disease, like allergies, tumors, mal absorptions.

Treatment options diarhea

-antimicrobial: when bacterial infection

-opioids or anticholinergics: problem with motility

-ORS (rehydration): Salt plus glucose. helps reabsorption in kidney.

-Absorbent drugs

opiods mode of action in diarhea and which drugs

Codeine(CNS side effects) use:

difenoxylate, loperamide. Only use with motility problems. When they activate opiod receptor the sphincter will relax more. But if there is an infection this will only make it worse.

Often used in combination with anticholinergics. Atropine and hyoscine.

Cystic fibrosis (taaislijm)

Often symptomps in lung but also in liver and gut possible. CFTR malfunctioning. abnormally thick mucus in bronchi and gut. Dehydration due to sweat.

Treatment CF

-ivacaftor: Can improve defective CFTR function. Can open closed channels. But expensive and only usefull for a few people. When there is no channel at all at the membrane not usefull.

-organoids: small organ like structures could be the solution.

Inflammatory bowel disease (IBD) 2 catagories

-Crohn’s disease: whole GI tract. Problem with absorption resulitng in weight loss. Thickening of the gut wall.

-Ulcerative colitis: colon primarily. problem with absorption is less. painfull and diarhea.

IBD mode of action

Hyperrespnsive cytotoxic T cell response to compound present in foods. Cytotoxic T cells release cytkines like TNFalpha which will disrupt the epithelium making it even more exessable to food antigens.

IBD treatment

-Aminosalicylates: suppresses AA to produce less PGs and LTs. broad spectrum. Sulfasalazine is broken down in the colon into mesalazine.

-glucocorticosteroids

-Immunosupressive: Methotrexate: suppresses immune response

If not enough:

-Anti-TNF alpha to stop epithelium break down

If still not enough: Anti-IL23 and 12, JAk inhibitors, etc.

Celiac disease + treatment if diet is not enough

Gluten intolerance.

-Glucocorticosteroids, immunosuppresive agents. anti-TNF alpha.

IBS + main mechanism

Irritable bowel syndrome.

IBS-C: Constipatation. Laxatives

IBS-D: Diarhea

IBS-M: Mixed

Treatment constipation

Osmotic laxatives: Mg2+ salt to draw water into lumen.

Bulk laxatives: Swell up the colon so mechanoreceptors send signals to speed up

If severe:

Fecal softeners: detergent for sticky feces

Stimulant laxatives: stimulates ENS both motility and secretoy effects

Treatment of severe IBS

Secretgogues. Enhance secretion.

5HT receptor with diarhea and constipation:

serotonin promotes secretion and motility

5HT agonist with constipation

5HT antagonist with diarhea

Main function skin

Barrier, Vitamine D synthesis, sensory and thermoregulation.

Acne

hormones allow more production of tallow. Tallow in hairsacs can be infected = acne. Or dead skin cells can also obstruct those hair sacs.

Treatment:

-Benzolyperoxide: Kills bacteria and skin cells. Also inactivates tretonine.

-Tretonine: cleans skin.

Rosacea

Local vasodilation. dry and painfull skin. Antibiotics or alpha 2 agonist to stop vasodilation.

Baldness

Caused by DHT made from androgen. Small blood vessels will narrow due to DHT. Stem cells die of therefore irreversible.

Treatment prevention:

-Minoxidil: Local vasodilator opening potassium channels

-caffeine shampoo: dilator due to PDE inhibition, so cAMP can deactivate DHT formation.

-Finasteride: Inhibits testosterone into DHT conversion.

Eczema

Contact eczema: direct exposure to skin Tct response. Allergic eczema: IgE mediated.

Treatment:

-topical corticosteroids: stop both kinds, because blocks all kinds of T cells.

-calcineurin inhibitors: Suppress Tct and Th2 cells by inhibiting the CNA, the transducting protein between recepto and gene.

Urticaria

Same as eczema but signal comes from inside. antihistamines or corticosteroids.

psoriasis

almost same as contact eczema. Treat with anti-TNFalpha, Antti-IL17, calcineurin inhibitors or methotrexate.