Diarrhoea and IBS Flashcards
Diarrhoea
a condition of excessively frequent and loose bowel movements
(>300g/24 hours)
Malabsorption
imperfect absorption of food material by the small intestine
What activates pancreatic proteolytic enzymes?
Trypsinogen
Stomach secretions
HCl, intrinsic factor, pepsinogen, gastrin
Gallbladder secretions
Bile (almost a litre)
Pancreatic secretions
HCO3, amylase, lipase, trypsinogen, CCK (Cholecystokinin)
Small intestine secretions
disaccharidases, peptidases
somatostatin
Anus secretions
Stool ~200g
Where do we start to absorb vitamins and nutrients?
Duodenum
What is absorbed in the duodenum?
Water soluble vitamins (active absorption)
Fat soluble (passive absorption)
Ca, Fe, An (increase by ascorbic acid, decrease with phytates)
Polysaccharides, proteins and fats
What is absorbed in jejunum?
Magnesium
What is absorbed in the ileum?
2ndary Bile acids, vit B12
What is absorbed in the large colon?
Na, Cl, water, SCFAs
What are the causes of diarrhoea?
Osmotic (non-absorbable solute)
Secretory (impaired electrolyte transport)
Exudative (intestinal mucosal damage)
Motility (increased transit)
Where are most sugars, proteins and fats absorbed?
Most polysaccharides, proteins and fats are digested and absorbed within the upper 200cm of the small intestine. Site of absorption depends on meal composition. Meat and salad absorbed high in the jejunum, while milk and doughuts are absorbed more distally, after a large amount of water has been secreted.
What are osmotic causes of diarrhoea?
Deficiency in digestive enzymes
Lactulose
Magnesium salts
Sorbitol
What are secretory causes of diarrhoea?
Bacterial endotoxins
Bile salts
Laxatives
Hormone producing tumours
What are exudative causes of diarrhoea?
Infections IBD Coeliac diseaase Irradiation Ischaemia Colon cancer
What are motility causes of diarrhoea?
Irritable bowel syndrome
Thyrotoxicosis
Autonomic neuropathy (DM)
Drugs
What do you want to find out from a patient’s history when diagnosing diarrhoea?
HISTORY OF PRESENTING COMPLAINT
Time course and severity Impact of fasting on symptoms Volume and consistency of stools Floating stools Bloody stools Nocturnal symptoms
Constitutional symptoms
- Anorexia/weight loss
- Fever
- vomiting
What could we find from past medical history, social and family history that could help in diagnosing diarrhoea?
PMH:
childhood diseases
IBD
previous GI surgery
SH/FH: foreign travel contacts w similar symptoms dietary factors (milk intolerance?) ethnicity
Causes of diarrhoea: clues on examination
General - ?ill, shock, dehydration, pyrexia, anaemia, weight loss
hands, eyes, mouth, skin, joints, lymph nodes, oedema
CVS/RS - pulse, BP, etc.
Abdomen - distension, scars
tenderness, rebound, guarding
inflammatory masses, bowel sounds
PR/Epsilon - anus, anal canal, rectal mucosa, ?blood/pus, stool
rectal biopsy
Investigations of diarrhoea
Blood tests: FBC, ESR U&E, LFT, CRP Vit B12 and folate Iron studies TFT Coeliac serology
Stool tests:
M,C and S
Elastase
Calprotectin
Functional tests:
Hydrogen breath tests
Schilling test
Imaging:
Barium studies/USS
CT/MRI
Endoscopy:
OGD with D2 biopsies
Colonoscopy
Capsule endoscopy/SBE
Gut hormone profile
Urinary catecholamines
Irritable bowel syndrome
IBS is defined as a “Functional” GI disorder, i.e. a disorder of gut–brain interaction.
These disorders are classified by GI symptoms related to any combination of the following:
motility disturbance
visceral hypersensitivity
altered mucosal and immune function
altered gut microbiota
altered central nervous system processing.
About 20% of adolescent/adult Westerners have symptoms consistent with IBS
Rome IV Criteria for IBS diagnosis
Recurrent abdominal pain, on average, at least 1 day/week in the last 3 months, associated with two or more of the following criteria:
- Related to defecation
- Associated with a change in frequency of stool
- Associated with a change in form (appearance) of stool.
Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.
IBS management
- investigations + reassurance
- diet
- lifestyle advice
- medication for symptom relief:
- anti-spasmodics
- -mebeverine
- -peppermint oil - drugs to alter intestinal transit
- opiates/loperamide
- Laxatives - probiotics
- anti-depressants
Coeliac disease
‘an inflammatory condition of the small intestinal mucosa, that is most marked proximally, and which improves morphologically when gluten is removed from the diet’
Inherited auto-immune condition
CD strongly associated with HLA-DQ2 genotype (95%)
likelihood of 1st degree relative having CD 10-15%
Gluten
Gluten is a general name for the proteins found in wheat (wheatberries, durum, emmer, semolina, spelt, farina, farro, graham, KAMUT® khorasan wheat and einkorn), rye, barley and triticale – a cross between wheat and rye. Gluten helps foods maintain their shape, acting as a glue that holds food together.
Coeliac disease autoantibodies
- anti-gliadin
- anti-reticulin
- anti-endomysial
Coeliac disease UK prevalence
Prevalence probably M=F. but incidence higher (x2) in F (present during pregnancy and childbirth/feeding and because of fertility or menstrual problems).
GP study in Oxfordshire, screening of patients with anaemia (30 new CD patients identified (previously 8 on books)
Previously thought of as childhood disease, but now incidence increasing in adults and decreasing in children (better weaning and many commersial baby foods and milk gluten-free)
Adults usually diagnosed between 30 and 40, but increasingly now between 50 and 60.
Increased incidence almost certainly due to diagnostic phenomena
~150 patients at any one time in an average DGH
Histology for symptomatic, asymptomatic and latent coeliac disease
Symptomatic CD (positive histology)
Asymptomatic CD (positive histology)
Latent CD (negative histology)
Coeliac disease presentation: childhood vs adult
Childhood: Failure to thrive/short stature Diarrhoea/steatorrhoea Vomiting (50%) Abdominal pain/distension
Adult: Adults Fatigue (80-90%) Anaemia (85%) Microcytic Macrocytic Diarrhoea/steatorrhoea (75-80%) Weight loss Mouth ulcers infertility
Coeliac disease diagnostic criteria for adults
4 intestinal biopsies
abnormal mucosa on gluten*
b) improvement on GFD ( 3 - 6 months) #
* Histological abnormality may be minimal (eg increased IEL only).
# Mucosal healing may take 2 years - or remain incomplete.
What happens to villi in CD?
In untreated coeliac disease, villi become inflamed and flattened. In some cases, they can even disappear. This is called villous atrophy. When the gut is damaged in this way, it means the body can’t absorb all the nutrients from food properly.
Diseases associated w CD in adults
Dermatitis herpetiformis
Itchy blistering skin eruption which affects knees, elbows, buttocks and back
Complicates 2-5% of CD prevalence 1:20,000 in UK onset age 15-40 years M>F improved by GFD diagnosis confirmed by granular IgA at dermo-epidermal junction of un-involved skin
Coeliac disease treatment
Gluten exclusion
-no food containing wheat, rye barley or ?oats
dietary supplements
-iron, folic acid, Ca, vitamin B12
bone abnormalities
hyposplenism
information and support
Why CD patients need a gluten free diet?
- Amelioration of symptoms
- reduction in risk of osteoporosis
- reduction in risk of associated malignancies
- reduction in risk of associated autoimmune diseases
Coeliac disease follow up
6 monthly OPA
- (repeat small intestinal biopsy after 1st 6 months)
- blood tests
- symptomatic assessment
- nutritional assessment
- dietary compliance
close monitoring during pregnancy
Management of poor response/relapse CD
Important to check
- dietary compliance
- is the diagnosis correct?
-other co-incident disease eg: ulcerative jejuno-ileitis microscopic colitis malignancy lymphoma SB carcinoma oesophageal/colonic carcinoma
What is IBS?
chronic, relapsing, immunologically mediated
disorders (ulcerative colitis and Crohns) that are collectively referred to as
inflammatory bowel diseases (IBD)
Which two conditions genetically overlap with many loci in common with IBS?
Crohn’s disease
Ulcerative colitis
Ulcerative colitis
Chronic inflammatory disease of unknown aetiology, only affects colon
Presents with: Diarrhoea with blood and mucus
Systemic (extra intestinal) features if extensive and/or severe
Exacerbations and remissions
15-20% of attacks are ‘severe’
Types of ulcerative colitis
Proctitis and distal colitis - only affects rectum
Left sided colitis - left side of colon
Pancolitis - affects all of large intestine
What is the treatment for the different types of UC?
Proctitis: 5-ASA suppositories
Distal colitis: 5-ASA foam enema
L sided colitis: 5-ASA liquid enema
Extensive/pancolitis: topical Rx PLUS oral Rx
Crohns disease
Chronic granulomatous inflammatory disease
Affects any part of the GI tract from mouth to anus
Commonest site ileo-colonic
Crohn’s colitis behaves similarly to ulcerative colitis
Minority of colitis cases indeterminate
Protective and causative differences between UC and Crohn’s?
UC: smoking preventative appendicectomy protective 8% concordance monozygotic twins pANCA +ve 75%
Crohns: smoking causative appendicectomy NOT protective 67% concordance pANCA negative, ASCA positive 86%
UC vs Crohn’s presentation
UC: Bloody diarrhoea Mucus Mucosal and submucosal Continuous disease Association with PSC
Crohns: Bloody diarrhoea Mucus Mucosal and submucosal Continuous disease Association with PSC
UC vs Crohn’s pathophysiology
UC: Granular, friable mucosa Pseudopolyps Acute and chronic inflammation Muscularis and serosa normal Reduction in goblet cells, many crypt abscesses
Crohns: Transmural Submucosal oedema Lymphoid aggregation and fibrosis Apthous ulceration Granulomas (eg sarcoid/TB)
UC microscopic features
Architectural:
Crypt distortion
Decreased crypt density
Villous surface
Inflammatory: Heavy diffuse transmucosal lamina propria cell increase Diffuse basal Mucin depletion Paneth cell metaplasia
Crohn’s microscopic features
Architecture
Normal/irregular/villous
Crypt atrophy
Distorted,dilated, branching crypts
Inflammatory:
Basal plasmacytosis
Increase cells in basal third LP (round cells.
Specific:
Epitheliod granuloma
Basal giant cells
XS histiocytes in LP
Problems UC and Crohn’s can cause in other parts of the body
How is musculoskeletal affected by UC and Crohn’s?
Affects up to half of UC/Crohn’s patients
Arthritis - sero-negative spondylo-arthropathies
More common in colonic than small bowel dis
More common in Crohn’s colitis than UC
More common in pan-UC than left sided
Type 1 – pauciarticular- (less than 5 joints affected) – associated with disease activity
Type 2 – polyarticular, independent of disease activity
Treatment – NSAIDs/sulphasalazine
Osteoporisis risk
Common in patients with IBD Corticosteroid use Reduced physical activity Inflamatory-mediated bone-resorption Ca/vit D malabsorption Poor intake (lactose intolerance) Fracture risk 40% higher than general population
Dermatological impact of UC/Crohn’s
2-34% of IBD pts
EN and PG most common
Psoriasis, apthous stomatitis, Sweet syndrome
EN – painful palpable nodules (F>M, CD>UC), mirrors disease activity
PG – usually shins , adjacent to stoma, pathergy
1-10.5% UC pts, 0.5-20% CD
Hepatobiliary and pancreas (HPB) impact of UC/Crohn’s
PSC (primary sclerosing cholangitis) Cholelithiasis Portal vein thrombosis Drug-induced hepatotoxicity Drug-induced pancreatitis
PSC (primary sclerosing cholangitis)
Inflammation, stricturing and fibrosis intra and extra-hepatic bile ducts 75% have coexisting UC (5% of UC) 5-10% have CD (2% of CD) Pancolitis>left sided UC 30-59yrs M:F 2:1 Think – raised ALP 33% raised ANA 80% raised ANCA
PSC RF for cholangiocarcinoma
12-15% of pts undergoing liver transplantation for PSC
Increased colorectal cancer risk
Cholelithiasis
Crohn’s with ileal disease
Interruption of EHC of bile acids
Bile acid malabsorption
Pancreatitis in IBD
Common side effect of azathiopurine and 6-mercaptopurine
Ocular manifestations of IBD
0.3-5%
Less common in isloated small bowel disease
Episcleritis – can parallel intestinal activity – treat bowel disease- may need topical steroids
Scleritis – can impair vision – more severe – may require systemic steroids/immunosuppresion
Uveitis – assoc with joint/derm manifestation
F:M 4:1
Renal/pulmonary manifestations of IBD
Nephrolithiasis
obstructive uropathy
Fistulisation
6-23%
Sulphasalazine – ILD
Pulmonary Embolus
Acute colitis
Symptoms of colonic inflammation irrespective of cause of inflammation:
- bloody diarrhoea
Assessment of colitis
History
Features of toxicity: patient wellbeing, pulse rate, temperature, abdominal tenderness, abdominal distension,
Blood investigations ESR and CRP, Hb, white cell count,platelet count, albumin
Abdominal X ray
Pharmacological treatment of ulcerative colitis
5-Amino-salicylates (5-ASAs) Azathioprine Oral steroids Intravenous hydrocortisone Ciclosporin Infliximab
Severe colitis (Truelove and Witts criteria)
Truelove and Witts criteria:
6 bloody stools daily+ one or more of: temp >37.8 C pulse >90 per minute Haemoglobin <10.5 g/dL ESR >30 mm/h
Diagnosing acute severe colitis
CASE:
18 year old boy
Admission to hospital with 3 weeks of bloody diarrhoea
Tired, lethargic
Bowel frequency 15/day, getting up at night time
Overweight, but losing weight
What do you do?
DDx: I.B.D. Ischaemic colitis BehÇet’s Drug related exacerbations of UC: NSAID’s cocaine, amphetamines Drugs: nicorandil
Bacterial infection? (Salmonella, CMV colitis, Clostridium difficile, Ecoli?)
Day 1: Bloods (FBC, U/Es, CRP, LFTS, CRP/ESR, also Mg + lipid profile), AXR, Stool cultures, Stool O.C.P., C difficile toxin, Sigmoidoscopy and biopsy REFER TO GASTROENTEROLOGIST
Blds – Hb 90g/dl, ESR 75, K 3.0, Alb 28, plts 540
HR 90, BP 95/40 temp 37.5
Now initiate treatment: i.v. Hydrocortisone 100mg q.d.s. Correct electrolytes DVT prophylaxis Can eat and drink normally Avoid opiates
Truelove and Witt’s classification
Management for acute severe colitis
Daily bloods (correct electrolyte imbalance) Stool chart LMW heparin (VTE prophylaxis) Avoid - opiate analgesia NSAID’s Anti-cholinergics I.V. Hydrocortisone No role for bowel rest No role for antibiotics in uncomplicated disease
Factors predicting outcome in severe UC
By day 3 of managing acute severe colitis you must have:
Stool culture results
Corrected electrolytes (especially Mg)
Colonic biopsy results
Gastroenterologists ready to decide on treatment escalation
Toxic megacolon
Daily abdominal x-ray Toxic megacolon (megacolon toxicum) is an acute form of colonic distension - characterized by a very dilated colon - accompanied by abdominal distension, and often fever, abdominal pain and shock
Very bad sign – call the surgeons
What does severe colitis treatment escalation depend on? What are your options?
Depends on: Age, severity, “colitis history”, pre-flare up therapy, patients wishes
Options: cyclosporin, infliximab, surgery
Cyclosporin
Calcineurin inhibitor
Blocks activation of pro-inflammatory mediators
Rapid onset with i.v. dosing
High oral bioavailability
Effectiveness:
Response rate 80-90%
30-47% colectomy rate at 6-39 months in responders
Avoidance of colectomy at 5 years in 55-70%
Infliximab
Anti TNF biologic drug
Main use is in Crohn’s disease
Increasing evidence of use in UC
Clostridium difficile
C difficile + IBD –> Colectomy rate 20%
C diff can mimic and precipitate IBD flares
IBD treatment may precipitate deterioration of C diff colitis
C diff enteritis more problematic in IBD patients
When would you use surgery in IBD patient and what surgical interventions would you do?
When patient is no longer responding to medications, perforations or severe bleeding
Options:
Colectomy and ileostomy (ilium taken out and temporary stoma bag)
Then second procedure to restore continuity of intestines with anus
Main causes of diarrhoea: Inflammation
INFLAMMATION:
1. Infective causes: gastro-enteritis / enterocolitis
- bacterial – eg Shigella, Salmonella, viral – eg enteroviruses such as rotavirus, Tuberculosis
- protozoal – eg giardiasis, amoebiasis).
atypical infective agents can affect the bowel and cause diarrhoea but are more usual in immunosuppressed people (eg renal transplant recipients, HIV/AIDS)
- Pseudomembranous colitis (usually post-antibiotic therapy and characterised by C.difficile toxin secretion)
- Coeliac disease (gluten induced enteropathy): often designated an autoimmune disease but is reversible if gluten is avoided
- IBD: Crohn’s disease, ulcerative colitis (together called ‘chronic idiopathic inflammatory bowel disease, CIBD or IBD)
Main causes of diarrhoea: Vascular disease
Vascular disease:
vasculitis, ischaemic enteritis/colitis, radiation enteritis/colitis
(damages small blood vessels)
Main causes of diarrhoea: Neoplasia
Neoplasia:
- lymphoma (particularly small bowel) may cause malabsorption,
- overflow diarrhoea (may complicate carcinoma of distal colon),
- neuroendocrine tumour (old term ‘carcinoid’ secretes peptides eg 5-HT, which may cause episodic palpitations, flushing and diarrhoea)
Gross and microscopical features distinguishing between UC and Crohn’s (revision slide)
Pattern difference between Crohns and UC
Crohns:
- transdural inflammation (goes through mucosa, submucosa and muscle, fistula formations w other organs)
- skip lesions - patchy
UC:
- pseudopolyp
- superficial ulceration (active disease) or atrophy (inactive disease)
Proctitis Proctosigmoiditis Distal colitis Pancolitis Backwash ileutis
Proctitis- only rectum Proctosigmoiditis- rectum and sigmoid colon Distal colitis- only left side of colon Pancolitis- entire colon Backwash ileitis- distal ileum
Clinical features of UC and Crohns revision slide
Which one is normal and which one is UC?
What is cobblestone appearance?
Irregular nodular appearance of mucosal surface with hyperaemia and focal superficial ulceration
In Crohn’s (small bowel)
Faecal calprotectin
Calprotectin is a stool (faecal) test that is used to detect inflammation in the intestines. Intestinal inflammation is associated with, for example, some bacterial infections and, in people with inflammatory bowel disease (IBD), it is associated with disease activity and severity.
Endoscopy differences between UC and Crohns
Crphns:
rectal sparing
cobblestoning
skip areas
UC:
rectum always involved
granularities
inflamed mucosa
In what disease is ileal involvement common?
Ulcerative colitis
In what disease are gripped abscesses more common?
Ulcerative colitis
Anatomical involvement in Crohns vs UC
Crohns vs UC macroscopic
Crohns vs UC macroscopic
UC vs Crohns disease histology
What genes is UC more common in?
DR2-related genes
What genes is UC more common in?
DR2-related genes
What genes is Crohn’s more common in?
DR5 DQ1 alleles
Colonic complications in ulcerative colitis
Perforation
Bleeding
Cancer
Stricture
Crohn’s disease intestinal complications
Perforation Cancer Fistula Abscess Stricture
Other forms of IBD
Collagenous colitis/lymphocytic colitis
Ischaemic colitis
Infective colitis
Intermediate colitis - never to be useddd
