gi involvement in systemic diseases
DESCRIPTION
GI involvement in systemic diseases. Dr. Eran Israeli. General principles. Common!! The GI manifestation is due to the same mechanism (e.g. neuropathy, infiltration of mucosa). General principles -2. The GI tract can be the first manifestation of many systemic disorders - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/1.jpg)
GI involvement in systemic diseases
Dr. Eran IsraeliDr. Eran Israeli
![Page 2: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/2.jpg)
General principles Common!!
The GI manifestation is due to the same
mechanism (e.g. neuropathy, infiltration of
mucosa)
![Page 3: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/3.jpg)
General principles -2
The GI tract can be the first manifestation of
many systemic disorders - Dysphagia in CREST syndrome - Constipation in hyperparathyroidism
The GI manifestations are a complication of the disease
- amyloidosis in FMF
![Page 4: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/4.jpg)
GI manifestation is an adverse effect of the treatment of the disease
- Chemotherapy - Metformin/ Colchicine / antibiotic-associated diarrhea - NSAIDS It is better to consider first an uncommon manifestation of a common disease rather than a common manifestation of a rare disease - 70 yrs old male with new onset dyspepsia- gastric adenocarcinoma vs. gastrinoma (Z-E syndrome)
General principles -3
![Page 5: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/5.jpg)
Different mechanisms of disease may only cause a limited “repertoire” of symptoms:
Dysphagia:Dysphagia: Upper vs. lower / Dysmotility vs. obstructive:
- Diabetic autonomic neuropathy - Achalasia- nonprogressive pressure waves, increased LES pressure - Pseudoachalasia- infiltration of a tumor, but also may be a paraneoplastic (autoimmune) phenomenon
General principles -4
![Page 6: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/6.jpg)
Globally, as of 2010, an estimated 285 million people had diabetes, with type 2 making up about 90% of the cases. Its incidence is increasing rapidly, and by 2030, this number is estimated to almost double.
Recent work has shown that the gut microbiome may play an important role in obesity and evolution of DM:
- modulation of energy harvesting capacity by the host - low-grade inflammation and the corresponding immune
response on adipose tissue plasticity, hepatic steatosis, insulin resistance
GI Involvement in Diabetes MellitusGI Involvement in Diabetes Mellitus
![Page 7: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/7.jpg)
GI Manifestations in DMGI Manifestations in DM
A population based survey of 8567 subjects from Sydney, Australia (423 with diabetes), showed that upper GI as well as lower GI symptoms were significantly more prevalent among diabetics than among controls:
adjusted odd ratio: 1.4 - 2.1 for the different GI symptoms
Bytzer, Arch Intern Med 2001;161:1989
![Page 8: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/8.jpg)
Diabetes MellitusDiabetes Mellitus 75% of pts. have GI manifestations: Constipation Diarrhea Dysphagia Nausea Vomiting
![Page 9: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/9.jpg)
Pathogenesis
Autonomic Neuropathy Hyperglycemia
Dysbalance of the autonomicnervous system:
Disordered motor function of the GI tract .
![Page 10: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/10.jpg)
In IDDM autonomic neuropathy : 20-40%
Most commonly affects sympathetic nervous system
Cholinergic denervation causes relaxation
No response to a2+ (usually increases absorption): malabsorption
![Page 11: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/11.jpg)
Pathogenesis-other factors
Enteric myopathy (d/t autoimmune and metabolic insults)
Loss of Interstital cells of Cajal (ICC)- serve as pacemaker cells that are responsible for initiating and organizing phasic contractions, and also for propagation of electrical activity in smooth muscles- decrease of trophic factors for ICC’s in DM
Ischemia and hypoxia from microvascular disease of the GIT
Mitochondrial dysfunction Formation of irreversible advanced glycation end products
![Page 12: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/12.jpg)
Diabetes Mellitus-2Diabetes Mellitus-2 Esophagus: low LES pressure Decreased peristalsis Esophagitis, candidiasis, dysphagia Stomach: Low peristalsis, gastroparesis, pylorospasm,
nausea, vomiting, bezoars
![Page 13: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/13.jpg)
Diabetes Mellitus -3Diabetes Mellitus -3 Small bowel: Sympathetic denervation: malabsorption,
diarrhea, bacterial overgrowth Colon: Constipation or diarrhea Rectum: Low pressure of internal sphincter, incontinence
![Page 14: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/14.jpg)
Diabetes Mellitus-4Diabetes Mellitus-4
Radiculopathy – upper abdominal pain
Stomach - gastric atrophy, macrocytic anemia
(IF deficiency), hypochlorydria
Gallbladder - Cholelithiasis
Liver - steatosis, hepatomegaly,
steatonecrosis
![Page 15: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/15.jpg)
Mechanisms of treatment of hypomotility disorders – GI tract Diabetes mellitus: control of hyperglycemia Metoclopramide (Pramin):Metoclopramide (Pramin):
- antidopaminergic, increases acetyl-choline in myenteric plexus
- central effect on vomiting center
- vagus excitation
- increases gastric contractions
- pyloric relaxation Side effectsSide effects: CNS, increased prolactin
![Page 16: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/16.jpg)
Domperidone (Motilium):Domperidone (Motilium): - anti-dopaminergic, increases acetyl-choline in myenteric plexus - increases gastric contractions - does not cross into CNS Cisapride (Prepulsid): Cisapride (Prepulsid): - increases release of acetylcholine from post-
ganglionic neurons - increase motility in the stomach and small bowel
Mechanisms of treatment of hypomotility disorders – GI tract (2)
![Page 17: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/17.jpg)
Mechanisms of treatment of hypomotility disorders – GI tract (3) Erythromycin:Erythromycin:
- Motilin receptor +
Clonidine Clonidine 22++
- increase absorption of water and electrolytes SomatostatinSomatostatin:
- Increases transit time FibersFibers
![Page 18: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/18.jpg)
GI Manifestations in SclerodermaGI Manifestations in Scleroderma
Systemic sclerosis (SSc) and CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal disease, sclerodactyly and telangectasia) - multisystem diseases
Affecting women 3 to 4 times more commonly than men, with symptoms occurring in their 20 to 40s.
A relatively rare disease with 10 new cases per 1 million adults per year.
Characterized by vasculitis of the small arteries and fibrosis of the skin and other organs.
![Page 19: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/19.jpg)
Sclerodactyly
Calcinosis
Telangectasia
Raynaud’s syndrome
![Page 20: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/20.jpg)
Scleroderma-pathogenesis
Primarily, an early vascular lesion that manifests as mild changes in intestinal permeability, transport and absorption.
The second stage is neural dysfunction when early symptoms begin.
The third stage is smooth muscle atrophy, The end stage lesion is muscle fibrosis, at which point
pharmacologic restoration of function is no longer possible
A recent detection of circulating auto-antibodies to myenteric neurons and anti-muscarinic-3-acetylcholine receptors (M3R) suggests an autoimmune neuropathic etiology for scleroderma.
![Page 21: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/21.jpg)
Scleroderma-GI Manifestations
Altered peristaltic activity with multiple secondary problems, including esophageal reflux, early satiety, nausea, vomiting, pseudo-obstruction, small intestinal bacterial overgrowth, malabsorption and ultimately malnutrition
The esophagus is the most commonly affected organ, between 70% and 90%
Smooth muscle atrophy leads to absent or low-amplitude esophageal contractions and weakening of the lower esophageal sphincter:
- reflux of acid and retarded clearance of the refluxed material. - gastric emptying is commonly delayed, further increasing acid reflux
The result is severe symptomatic reflux and erosive esophagitis
![Page 22: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/22.jpg)
Scleroderma-GI Manifestations
Dysphagia - secondary to dysmotility and reflux
- less commonly due to stricture formation (occurring in 17% to 29% of patients) - Candida esophagitis
Due to the high risk of developing strictures, patients should be maintained on a proton pump inhibitor at a dose sufficient to suppress heartburn.
Gastro-esophageal reflux (GER) may contribute to pulmonary disease by microaspiration of acid and by vagal stimulation of esophageal acid causing bronchoconstriction
![Page 23: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/23.jpg)
Scleroderma-GI Manifestations
Stomach:
- delayed gastric emptying, which contributes to GER and subsequently to malnutrition.
- iron deficiency anemia or severe bleeding secondary to telangectasia, including gastric antral vascular ectasia (GAVE)/watermelon stomach
![Page 24: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/24.jpg)
Scleroderma-GI Manifestations
Malnutrition:
- Malabsorption related to small intestine bacterial overgrowth (SIBO), and to motility disorders of the gastrointestinal tract that may lead to early satiety and persistent nausea and vomiting.
- If SIBO is suspected cycled antibiotics should be tried
- In cases with refractory small bowel symptoms therapy with octreotide 50 to 100 mg subcutaneously at bedtime, should be considered
- enteral nutrition via jejunostomy or home parenteral nutrition.
![Page 25: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/25.jpg)
Rheumatoid arthritis
Typical signs and symptoms include
- morning stiffness
- symmetrical polyarthritis
- rheumatoid nodules
- Rheumatoid Factor
- radiographic erosions in hands and/or wrists
![Page 26: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/26.jpg)
Rheumatoid arthritis
- Felty’s syndrome: Hepatomegaly, abnormalities in liver function tests, and evidence of portal fibrosis causing portal hypertension
- Vasculitis (less common than in other rheumatic diseases).
- Necrotizing vasculitis of the mesenteric vessels may result in intestinal ischemia and perforation.
Cholecystitis, appendicitis, and splenic infarctions have also been described
![Page 27: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/27.jpg)
Rheumatoid arthritis- Treatment complications Chronic administration of salicylates or NSAIDS
![Page 28: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/28.jpg)
Am J Gastroenterol 2009; 104:728 – 738
![Page 29: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/29.jpg)
Rheumatoid arthritis, FMF, IBD In the past: chronic TB, osteomyelitis,
Bronchiectasis Infiltration of bowel wall / hypomotility
AmyloidosisAmyloidosis
![Page 30: GI involvement in systemic diseases](https://reader035.vdocuments.net/reader035/viewer/2022062221/56812ce2550346895d91a732/html5/thumbnails/30.jpg)
Cancer / GVHD Metastasis to GI: - Breast, lung, ovary, melanoma Sx: Bowel obstruction, bleeding LeukemiaLeukemia: 10% severe GI complications direct involvement: bowel infiltration,
chemotherapy related, immune deficiency - Leukemic typhlitis: neutropenic pts., post chemotherapy/antibiotics