1. Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits without detectable structural abnormalities.
2. IBS is caused by abnormalities in gastrointestinal motility, visceral hypersensitivity, central neural processing, the gut microbiome, and serotonin signaling.
3. Treatment involves managing symptoms through diet, stress reduction, antispasmodics, antidepressants, and antibiotics in some cases. Thorough evaluation is needed to rule out other causes for symptoms.
Irritable Bowel Syndrome: An Update in Pathophysiology and Management Monkez M Yousif
Irritable bowel syndrome is the commonest health problem in hospital outpatient clinics and in private health care facilities and represents a big challenge for patients and physicians. This presentation discusses a different aspect of the disease from pathophysiology, clinical presentation and management
Irritable Bowel Syndrome: An Update in Pathophysiology and Management Monkez M Yousif
Irritable bowel syndrome is the commonest health problem in hospital outpatient clinics and in private health care facilities and represents a big challenge for patients and physicians. This presentation discusses a different aspect of the disease from pathophysiology, clinical presentation and management
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation. Severe constipation includes obstipation (failure to pass stools or gas) and fecal impaction, which can progress to bowel obstruction and become life-threatening.
Constipation is a symptom with many causes. These causes are of two types: obstructed defecation and colonic slow transit (or hypo mobility). About 50 percent of people evaluated for constipation at tertiary referral hospitals have obstructed defecation. This type of constipation has mechanical and functional causes. Causes of colonic slow transit constipation include diet, hormonal disorders such as hypothyroidism, side effects of medications, and rarely heavy metal toxicity. Because constipation is a symptom, not a disease, effective treatment of constipation may require first determining the cause. Treatments include changes in dietary habits, laxatives, enemas, biofeedback, and in particular situations surgery may be required.
Constipation is common; in the general population rates of constipation varies from 2–30 percent. In elderly people living in care homes the rate of constipation is 50–75 percent.[4] In the United States expenditures on medications for constipation are greater than US$250 million per year.
The definition of constipation includes the following:
infrequent bowel movements (typically three times or fewer per week)
difficulty during defecation (straining during more than 25% of bowel movements or a subjective sensation of hard stools; straining in this context is a strong effort to push out stool often by holding one's breath and by pushing the respective muscles in the abdominal area hard), or
the sensation of incomplete bowel evacuation.
The Rome III criteria are widely used to diagnose chronic constipation, and are helpful in separating cases of chronic functional constipation from less-serious instances.
Another definition states that less than three bowel movements per week and straining on more than 75% of occasions represents constipation in clinical surveys.
UC is an idiopathic IBD that affects the colonic mucosa.
Hallmark of UC is bloody diarrhea often with prominent symptoms of rectal urgency and tenesmus.
The clinical course is marked by exacerbations and remissions.
The diagnosis of UC is suspected on clinical grounds and supported by the appropriate findings on
Proctosigmoidoscopy or colonoscopy
Biopsy
By negative stool examination for infectious causes
Gastro esophageal Reflux Disease (GERD) and its managementDr. Ankit Gaur
In this presentation I have tried to explain in brief about gastro esophageal Reflux Disease (GERD), its etiology, risk factors, diagnosis, and its management via pharmacotherapy.
an over view of IBS in the general population, talks about aetiology pathology clinical features and diagnosis with special reference to the ROME criteria and the differences between ROME II and III.
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation. Severe constipation includes obstipation (failure to pass stools or gas) and fecal impaction, which can progress to bowel obstruction and become life-threatening.
Constipation is a symptom with many causes. These causes are of two types: obstructed defecation and colonic slow transit (or hypo mobility). About 50 percent of people evaluated for constipation at tertiary referral hospitals have obstructed defecation. This type of constipation has mechanical and functional causes. Causes of colonic slow transit constipation include diet, hormonal disorders such as hypothyroidism, side effects of medications, and rarely heavy metal toxicity. Because constipation is a symptom, not a disease, effective treatment of constipation may require first determining the cause. Treatments include changes in dietary habits, laxatives, enemas, biofeedback, and in particular situations surgery may be required.
Constipation is common; in the general population rates of constipation varies from 2–30 percent. In elderly people living in care homes the rate of constipation is 50–75 percent.[4] In the United States expenditures on medications for constipation are greater than US$250 million per year.
The definition of constipation includes the following:
infrequent bowel movements (typically three times or fewer per week)
difficulty during defecation (straining during more than 25% of bowel movements or a subjective sensation of hard stools; straining in this context is a strong effort to push out stool often by holding one's breath and by pushing the respective muscles in the abdominal area hard), or
the sensation of incomplete bowel evacuation.
The Rome III criteria are widely used to diagnose chronic constipation, and are helpful in separating cases of chronic functional constipation from less-serious instances.
Another definition states that less than three bowel movements per week and straining on more than 75% of occasions represents constipation in clinical surveys.
UC is an idiopathic IBD that affects the colonic mucosa.
Hallmark of UC is bloody diarrhea often with prominent symptoms of rectal urgency and tenesmus.
The clinical course is marked by exacerbations and remissions.
The diagnosis of UC is suspected on clinical grounds and supported by the appropriate findings on
Proctosigmoidoscopy or colonoscopy
Biopsy
By negative stool examination for infectious causes
Gastro esophageal Reflux Disease (GERD) and its managementDr. Ankit Gaur
In this presentation I have tried to explain in brief about gastro esophageal Reflux Disease (GERD), its etiology, risk factors, diagnosis, and its management via pharmacotherapy.
an over view of IBS in the general population, talks about aetiology pathology clinical features and diagnosis with special reference to the ROME criteria and the differences between ROME II and III.
Irritable Bowel Syndrome Part 1 - Dr Vivek BaligaDr Vivek Baliga
In this presentation, Dr Vivek Baliga discusses the important aspects of irritable bowel syndrome - a common medical problem in clinical practice. For more articles, visit http://baligadiagnostics.com/author/drbvb/
IRRITABLE BOWEL SYNDROME
The term irritable bowel syndrome is used to describe a functional gastrointestinal disorder characterized by a variable combination of chronic and recurrent intestinal symptoms not explained by structural or biochemical abnormalities.
Local Council for Public Safety, April 2014 - Kosovo Flamur Kastrati
Këshilli lokal për siguri publike -
KLSP-ja, themelimi, funksionimi, projektet e realizuara
Negocimi –shkathësitë e negocimit, përgatitja për negociata, efikasiteti dhe fuqia në negocim, etapat e negocimit të sukseshëm negociatori i suksesshëm
- Negocimi në praktikë (raste te inskenuara)
- Avokimi- ç`është avokimi, parimet e mbështetjes së avokimit, çfarë duhet të bëjë një ofrues i avokimit dhe çfarë nuk duhet të bëjë, pse fëmijëve u nevojitet avokimi etj,
Evaluation and management of patients with Dyspepsia.pptxgarvitnanecha
Evaluation and management of patients with Dyspepsia.
Dyspeptic symptoms.
Causes of dyspepsia
Approach to adult with Dyspepsia.
Newer advancement about diagnosing dyspepsia causes.
GERD and peptic ulcer and many more organic diseases.
Functional Dyspepsia and organic dyspepsia
IBS(Irritable Bowel Syndrome) Management Update-2021Pritom Das
Some slides are taken from different textbooks of medicine like Davidson, Kumar and Clark and Oxford, and some from other presentations made by respected tutors. I'm barely responsible for compilation of various resources per my interest. These resources are free for use, and I do not claim any copyright. Hoping knowledge remains free for all, forever.
gutCARE IBS Talk on 20/5/2020.
In this talk, we update Singapore local epidemiology about increasing trend of IBS locally since 1998. There is also challenges in diagnosing IBS confidently in primary care due to patient presentation and symptoms.
We also update audience about latest diagnostic criteria for IBS.
New treatment for IBS, relationship between Small intestine bacterial overgrowth and IBS and the role of hydrogen breath testing in managing IBS.
We hope you enjoy the slides.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. Inflammatory Bowel Disease
• Immune-mediated chronic intestinal condition
• 2 major types: Ulcerative colitis (UC) and Crohn’s
disease (CD)
• Highest incidence in Europe, the United
Kingdom, and North America
• Urban areas have a higher prevalence of IBD
than rural areas, and high socioeconomic classes
have a higher prevalence than lower
socioeconomic classes
5. Etiology and Pathogenesis
In genetically predisposed individuals,
exogenous factors (e.g., composition of normal intestinal
microbiota)
+
endogenous host factors (e.g., intestinal epithelial cell barrier
function, innate and adaptive immune function)
chronic state of dysregulated mucosal immune function that is
further modified by specific environmental factors (e.g.,
smoking, enteropathogens)
6. Genetic Considerations
• The diseases and the genetic risk factors that are
shared with IBD include rheumatoid arthritis
(TNFAIP3), psoriasis (IL23R,IL12B), ankylosing
spondylitis (IL23R), type 1 diabetes mellitus
(IL10,PTPN2), asthma (ORMDL3), and systemic
lupus erythematosus (TNFAIP3,IL10)
7. Genetic Considerations
• Defective Immune regulation
• Suppression of inflammation is altered
uncontrolled inflammation
• Inflammatory cascade
• Cytokine activity not regulated imbalance
between proinflammatory and anti-
inflammatory mediators
• Exogenous factors
• Normal microbiota is perceived inappropriately
as if it were a pathogen
24. Treatment
• 5-ASA Agents
• Mainstay of therapy for mild to moderate UC
is Sulfasalazine and other 5-ASA agents.
Limited role in inducing remission in CD.
25. Treatment
• Glucocorticoids
• For moderate to severe UC and CD
• Prednisone 40–60 mg/d for active UC that is
unresponsive to 5-ASA therapy.
• Parenteral: hydrocortisone, 300 mg/d, or
methylprednisolone, 40–60 mg/d.
• No role in maintenance therapy for both UC
and CD
26. Treatment
• Antibiotics
• Pouchitis in 1/3 of UC patients post colectomy =
responsive to metronidazole and/or ciprofloxacin
• Metronidazole
• Effective in active inflammatory, fistulous, and
perianal CD and may prevent recurrence after
ileal resection.
• The most effective dose is 15–20 mg/kg per
day in three divided doses; it is usually
continued for several months.
32. Irritable Bowel Syndrome
• A functional bowel disorder characterized by
abdominal pain or discomfort and altered bowel
habits in the absence of detectable structural
abnormalities
• 10-20% of adults and adolescents have
symptoms c/w IBS, with FEMALE predominance
(2-3x as often as men)
• Commonly first symptoms occur before age 45
34. Clinical Features
• Abdominal pain/discomfort
• Prerequisite clinical feature of IBS
• Variable in intensity and location
• Exacerbated by eating or emotional stress and
improved by passage of flatus or stools
• Altered bowel habits
• Most consistent clinical feature in IBS
• Constipation alternating with diarrhea,
usually with one symptom predominating
35. Clinical Features
• Gas and flatulence
• Impaired transit and tolerance of intestinal
gas loads
• Reflux gas from distal to proximal intestine -
flatulence
• Upper GI symptoms
• 25-50% of patients complain of dyspepsia,
heartburn, nausea or vomiting
36. Pathophysiology
1. Gastrointestinal motor abnormalities
• Increased rectosigmoid motor activity for up
to 3 hours after eating
• Recordings from the transverse, descending
and sigmoid colon showed that the motility
index and peak amplitude of high-amplitude
propagating contractions (HAPCs) in IBS-D
were increased
38. Pathophysiology
3. Central Neural Dysregulation
• Clinical association of emotional disorders and
stress with symptom exacerbation and the
therapeutic response
• In response to distal colonic stimulation, the
mid-cingulate cortex shows greater activation
in IBS patients
• Preferential activation of the prefrontal lobe
increased perception of visceral pain
39. Pathophysiology
4. Abnormal Psychological Features
• Abnormal psychiatric features are present in
up to 80% of IBS patients
• An association between prior sexual or
physical abuse and development of IBS has
been reported
• Increased motor reactivity of the colon and
small bowel to a variety of stimuli and altered
visceral sensation associated with lowered
sensation thresholds
41. Pathophysiology
5. Post-Infectious IBS
• Occurs more commonly in females and affects
younger rather than older patients
• Risk factors: prolonged duration of initial
illness, toxicity of bacterial strain, smoking,
mucosal markers of inflammation, female
gender, depression, hypochondriasis, and
adverse-life events in the preceding 3 months
• Campylobacter, Salmonella and Shigella
42. Pathophysiology
6. Immune Activation and Mucosal Inflammation
• Activated lymphocytes, mast cells, and
enhanced expression of proinflammatory
cytokines abnormal epithelial secretion
and visceral hypersensitivity
• Psychological stress release of
proinflammatory cytokine alter intestinal
permeability
43. Pathophysiology
7. Altered Gut Flora
• High prevalence of small intestinal bacterial
overgrowth in IBS patients (positive lactulose
hydrogen breath test)
• Bacterial genera with Lactobacillus sequence
appear to be absent from IBS, and Collinsella
sequences were reduced
44. Pathophysiology
8. Abnormal Serotonin Pathways
• Serotonin (5HT)-containing enterochromaffin
cells in the colon are increased in a subset of
IBS-D patients compared to healthy
individuals or patients with ulcerative colitis
• Increased release of serotonin may contribute
to postprandial symptoms and provides a
rationale for the use of serotonin antagonists
in the treatment of IBS
45. Approach to the Patient with IBS
IBS NOT IBS
• recurrence of lower • appearance of the disorder
abdominal pain with for the first time in old age
altered bowel habits over a • progressive course from time
period of time without of onset, persistent diarrhea
progressive deterioration after a 48-h fast
• onset of symptoms during • presence of nocturnal
periods of stress diarrhea or steatorrheal
• absence of other systemic stools
symptoms such as fever and
weight loss
• small-volume stool without
any evidence of blood
46. Differentials
• Lactase deficiency • Diverticular disease of
• Celiac sprue the colon,
• Side-effects from inflammatory bowel
anticholinergic, disease
antihypertensive, and • Giardia
antidepressant meds • Laxative abuse
• Biliary tract disease, • Hyperthyroidism
intestinal ischemia,
peptic ulcer disorders,
and carcinoma of the
stomach and pancreas
47. Approach to the Patient with IBS
• Young pxs with mild symptoms require minimal
diagnostic evaluation, while older pxs or those
with rapidly progressive symptoms should
undergo a more thorough one
• CBC and sigmoidoscopic examination, stool
exam
• In pxs with persistent diarrhea not responding to
anti-diarrhea agents, a sigmoid colon biopsy
should be performed to rule out microscopic
colitis
48. Approach to the Patient with IBS
• In those aged >40 years, an air-contrast barium
enema or colonoscopy should also be performed
• If the main symptoms are diarrhea and
increased gas, the possibility of lactase deficiency
should be ruled out with a hydrogen breath test
or with evaluation after a 3-week lactose-free
diet
• Lab features that argue against IBS include
anemia, elevated ESR, presence of leukocytes or
blood in stool, and stool volume >200–300 mL/d
49. Treatment
• High-fiber diet
• Anticholinergic drugs inhibit gastrocolic reflex
(ipratropium bromide)
• Anti-diarrheals (loperamide)
• Anti-depressants – TCAs and SSRIs (fluoxetine)
• Activated charcoal as part of anti-flatulence
therapy
• Serotonin Receptor Agonist and Antagonists –
alosetron, tegaserod
• Chloride Channel Activators – lubiprostone
Oral contraceptives are also linked to CD; the odds ratio of CD for oral contraceptive users is about 1.4.
Additional evidence for genetic predisposition to IBD comes from its association with certain genetic syndromes.
IBD is currently considered an inappropriate immune response to the endogenous commensal microbiota within the intestines, with or without some component of autoimmunity.During the course of infections in the normal host, full activation of the gut-associated lymphoid tissues occurs but is rapidly superseded by dampening of the immune response and tissue repair. In IBD this process may not be regulated normally.
IBD is a polygenic disorder that gives rise to multiple clinical subgroups within UC and CD. A variety of genetic approaches including candidate gene studies, linkage analysis and genome-wide association studies that focus on the identification of disease-associated, single-nucleotide polymorphisms (SNP) within the human genome have identified approximately 100 disease-associated loci on many different chromosomes.
The mucosal immune system is normally unreactive to luminal contents due to oral (mucosal) tolerance. Oral tolerance may be responsible for the lack of immune responsiveness to dietary antigens and the commensal microbiota in the intestinal lumen. In IBD this suppression of inflammation is altered, leading to uncontrolled inflammation.These cytokines are normally produced in response to infection but are usually turned off or inhibited at the appropriate time to limit tissue damage. In IBD their activity is not regulated, resulting in an imbalance between the proinflammatory and anti-inflammatory mediators. Observational studies suggest that multiple pathogens (e.g., Salmonella, Shigella, Campylobacter, Clostridium difficile spp.) may initiate IBD by triggering an inflammatory response that the mucosal immune system may fail to control. However, in an IBD patient, the normal microbiota is likely perceived inappropriately as if it were a pathogen.
UC is a mucosal disease that usually involves the rectUmand extends proximally to involve all or part of the colon. About 40–50% of patients have disease limited to the rectum and rectosigmoid, 30–40% have disease extending beyond the sigmoid but not involving the whole colon, and 20% have a total colitis.With mild inflammation, the mucosa is erythematous and has a fine granular surface that resembles sandpaper. In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated (Fig. 295-1) In long-standing disease, inflammatory polyps (pseudopolyps) may be present as a result of epithelial regeneration. The mucosa may appear normal in remission, but in patients with many years of disease it appears atrophic and featureless, and the entire colon becomes narrowed and shortened. Patients with fulminant disease can develop a toxic colitis or megacolon where the bowel wall thins and the mucosa is severely ulcerated; this may lead to perforation.
CD can affect any part of the GI tract from the mouth to the anus. Some 30–40% of patients have small bowel disease alone, 40–55% have disease involving both the small and large intestines, and 15–25% have colitis alone. In the 75% of patients with small intestinal disease, the terminal ileum is involved in 90%. Unlike UC, which almost always involves the rectum, the rectum is often spared in CD. CD is segmental with skip areas in the midst of diseased intestine.Perirectal fistulas, fissures, abscesses, and anal stenosis are present in one-third of patients with CD, particularly those with colonic involvement. Rarely, CD may also involve the liver and the pancreas.Unlike UC, CD is a transmural process. Endoscopically, aphthous or small superficial ulcerations characterize mild disease; in more active disease, stellate ulcerations fuse longitudinally and transversely to demarcate islands of mucosa that frequently are histologically normal. This "cobblestone" appearance is characteristic of CD, both endoscopically and by barium radiography. As in UC, pseudopolyps can form in CD.Active CD is characterized by focal inflammation and formation of fistula tracts, which resolve by fibrosis and stricturing of the bowel. The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstructions. Projections of thickened mesentery encase the bowel ("creeping fat"), and serosal and mesenteric inflammation promotes adhesions and fistula formation.
The process is limited to the mucosa and superficial submucosaTwo major histologic features suggest chronicity and help distinguish it from infectious or acute self-limited colitis. First, the crypt architecture of the colon is distorted; crypts may be bifid and reduced in number, often with a gap between the crypt bases and the muscularis mucosae. Second, some patients have basal plasma cells and multiple basal lymphoid aggregates. Mucosal vascular congestion, with edema and focal hemorrhage, and an inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells, and macrophages may be present. The neutrophils invade the epithelium, usually in the crypts, giving rise to cryptitis and, ultimately, to crypt abscesses
The earliest lesions are aphthoid ulcerations and focal crypt abscesses with loose aggregations of macrophages, which form noncaseating granulomas in all layers of the bowel wall. Granulomas can be seen in lymph nodes, mesentery, peritoneum, liver, and pancreas. Although granulomas are a pathognomonic feature of CD, they are rarely found on mucosal biopsies. Surgical resection reveals granulomas in about one-half of cases. Other histologic features of CD include submucosal or subserosal lymphoid aggregates, particularly away from areas of ulceration, gross and microscopic skip areas, and transmural inflammation that is accompanied by fissures that penetrate deeply into the bowel wall and sometimes form fistulous tracts or local abscesses.
Sigmoidoscopy is used to assess disease activity and is usually performed before treatment. If the patient is not having an acute flare, colonoscopy is used to assess disease extent and activity.Endoscopically mild disease is characterized by erythema, decreased vascular pattern, and mild friability. Moderate disease is characterized by marked erythema, absent vascular pattern, friability and erosions, and severe disease by spontaneous bleeding and ulcerations.
The earliest radiologic change of UC seen on single-contrast barium enema is a fine mucosal granularity. With increasing severity, the mucosa becomes thickened, and superficial ulcers are seen. Deep ulcerations can appear as "collar-button" ulcers, which indicate that the ulceration has penetrated the mucosa. Haustral folds may be normal in mild disease, but as activity progresses they become edematous and thickened. Loss of haustration can occur, especially in patients with long-standing disease. In addition, the colon becomes shortened and narrowed. Polyps in the colon may be postinflammatory polyps or pseudopolyps, adenomatous polyps, or carcinoma.
Once a diagnosis of IBD is made, distinguishing between UC and CD is impossible initially in up to 15% of cases. These are termed indeterminate colitis. Fortunately, in most cases, the true nature of the underlying colitis becomes evident later in the course of the patient's disease. Approximately 5% (range 1–20%) of colon resection specimens are difficult to classify as either UC or CD because they exhibit overlapping histologic features.The other differentials would include the ff:
Up to one-third of IBD patients have at least one extraintestinal disease manifestation.
Once a diagnosis of IBD is made, distinguishing between UC and CD is impossible initially in up to 15% of cases. These are termed indeterminate colitis. Fortunately, in most cases, the true nature of the underlying colitis becomes evident later in the course of the patient's disease. Approximately 5% (range 1–20%) of colon resection specimens are difficult to classify as either UC or CD because they exhibit overlapping histologic features.The other differentials would include the ff:
The majority of patients with moderate-to-severe UC benefit from oral or parenteral glucocorticoids.Prednisone is usually started at doses of 40–60 mg/d for active UC that is unresponsive to 5-ASA therapy. Parenteral glucocorticoids may be administered as hydrocortisone, 300 mg/d, or methylprednisolone, 40–60 mg/d.
Antibiotics have no role in the treatment of active or quiescent UC however.Metronidazole is effective in active inflammatory, fistulous, and perianal CD and may prevent recurrence after ileal resection. The most effective dose is 15–20 mg/kg per day in three divided doses; it is usually continued for several months.
Nearly one-half of patients with extensive chronic UC undergo surgery within the first 10 years of their illness. The indications for surgery are listed in Table 295-8.Morbidity is about 20% in elective, 30% for urgent, and 40% for emergency proctocolectomy. The risks are primarily hemorrhage, contamination and sepsis, and neural injury. The operation of choice is an IPAA.
No clear diagnostic markers exist for IBS, thus the diagnosis of the disorder is based on clinical presentation.
Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
IBS-C (constipation), IBS-D, IBS-M
Prevalence of IBS is 31.7% higher among patients with dyspepsia. Conversely among patients with IBS, 55.6% of patients report symptoms of dyspepsia.
It has been proposed that these exaggerated responses may be due to (1) increased end-organ sensitivity with recruitment of "silent" nociceptors; (2) spinal hyperexcitability with activation of nitric oxide and possibly other neurotransmitters; (3) endogenous (cortical and brainstem) modulation of caudad nociceptive transmission; and (4) over time, the possible development of long-term hyperalgesia due to development of neuroplasticity, resulting in permanent or semipermanent changes in neural responses to chronic or recurrent visceral stimulation.
In addition, IBS patients also show preferential activation of the prefrontal lobe, which contains a vigilance network within the brain that increases alertness. These may represent a form of cerebral dysfunction leading to the increased perception of visceral pain.
Brain functional MRI studies show greater activation of the posterior and middle dorsal cingulate cortex, which is implicated in affect processing in IBS patients with a past history of sexual abuse.Patients with IBS frequently demonstrate increased motor reactivity of the colon and small bowel to a variety of stimuli and altered visceral sensation associated with lowered sensation thresholds. These may result from CNS—enteric nervous system dysregulation.
These may result from CNS—enteric nervous system dysregulation.Patients with mild to moderate symptoms usually have intermittent symptoms that correlate with altered gut physiology. Treatments include gut-acting pharmacologic agents such as antispasmodics, antidiarrheals, fiber supplements, and gut serotonin modulators. Patients who have severe symptoms usually have constant pain and psychosocial difficulties. This group of patients is best managed with antidepressants and other psychosocial treatments. CNS, central nervous system; ENS, enteric nervous system.
IBS may be induced by GI infection. This group of "postinfective" IBS occurs more commonly in females and affects younger rather than older patients. Risk factors for developing post-infectious IBS include, in order of importance, prolonged duration of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse-life events in the preceding 3 months. Age older than 60 years might protect against post-infectious IBS, whereas treatment with antibiotics has been associated with increased risk. The microbes involved in the initial infection are Campylobacter, Salmonella, and Shigella. Those patients with Campylobacter infection who are toxin-positive are more likely to develop postinfective IBS. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability are acute changes following Campylobacter enteritis that could persist for more than a year and may contribute to postinfective IBS.
Some patients with IBS display persistent signs of low-grade mucosal inflammation with activated lymphocytes, mast cells, and enhanced expression of proinflammatory cytokines. These abnormalities may contribute to abnormal epithelial secretion and visceral hypersensitivity. Interestingly, clinical studies have shown increased intestinal permeability in patients with IBS-D. Psychological stress and anxiety can increase the release of proinflammatory cytokine and this in turn may alter intestinal permeability. This provides a functional link between psychological stress, immune activation, and symptom generation in patients with IBS.
A high prevalence of small intestinal bacterial overgrowth in IBS patients has been noted based on positive lactulose hydrogen breath test. A number of studies found significant differences between the molecular profile of the fecal microbiota of IBS patients compared with that of healthy subjects. Several bacterial genera with Lactobacillus sequence appear to be absent from IBS, and Collinsella sequences were greatly reduced in this group of patients. It is unclear whether such changes are causal, consequential, or merely the result of constipation and diarrhea.
The serotonin (5HT)-containing enterochromaffin cells in the colon are increased in a subset of IBS-D patients compared to healthy individuals or patients with ulcerative colitis. Furthermore, postprandial plasma 5HT levels were significantly higher in this group of patients compared to healthy controls. Since serotonin plays an important role in the regulation of GI motility and visceral perception, the increased release of serotonin may contribute to the postprandial symptoms of these patients and provides a rationale for the use of serotonin antagonists in the treatment of this disorder.
Clinical features suggestive of IBS include the following: recurrence of lower abdominal pain with altered bowel habits over a period of time without progressive deterioration, onset of symptoms during periods of stress or emotional upset, absence of other systemic symptoms such as fever and weight loss, and small-volume stool without any evidence of blood.On the other hand, the appearance of the disorder for the first time in old age, progressive course from time of onset, persistent diarrhea after a 48-h fast, and presence of nocturnal diarrhea or steatorrheal stools argue against the diagnosis of IBS.
a younger individual with mild symptoms requires a minimal diagnostic evaluation, while an older person or an individual with rapidly progressive symptoms should undergo a more thorough exclusion of organic disease. Most patients should have a complete blood count and sigmoidoscopic examination; in addition, stool specimens should be examined for ova and parasites in those who have diarrhea. In patients with persistent diarrhea not responding to simple anti-diarrhea agents, a sigmoid colon biopsy should be performed to rule out microscopic colitis.
a younger individual with mild symptoms requires a minimal diagnostic evaluation, while an older person or an individual with rapidly progressive symptoms should undergo a more thorough exclusion of organic disease. Most patients should have a complete blood count and sigmoidoscopic examination; in addition, stool specimens should be examined for ova and parasites in those who have diarrhea. In patients with persistent diarrhea not responding to simple anti-diarrhea agents, a sigmoid colon biopsy should be performed to rule out microscopic colitis. In those aged >40 years, an air-contrast barium enema or colonoscopy should also be performed. If the main symptoms are diarrhea and increased gas, the possibility of lactase deficiency should be ruled out with a hydrogen breath test or with evaluation after a 3-week lactose-free diet
A prospective study has shown marked symptomatic improvement in stool frequency, consistency, pain scores, and quality of life following 4 weeks of a very-low-carbohydrate (CHO) diet (20 g CHO/day).