Block 2, Case 2Ben BROWN

Abdominal Pain and altered bowel habits.

BY SURAG KHADKA AND Issylikesitjizzy

Session 1

Presentation

29 year old White British male presents to GP with “diarrhoea

and crampy stomach pain”.

Some bright red blood mixed with stools.

Accompanied by his wife- confidentiality issue?

Has had diarrhea for longer than two days and has opened

bowels 5 times in past 24 hours.

Has been taking Loperamide (Imodium®).

Works as a primary school teacher.

Session 1: Learning Outcomes

Pain referral to umbilical region

Physiology of the large and small intestine.

Loperamide: mechanism of action

Patient Confidentiality

Differential diagnoses:

Crohn’s Disease

Ulcerative Colitis

Diverticula

Gastroenteritis

Haemorrhoids

*See Anne Green’s lecture: “Physiology

of the Small Intestine”

Pain referral to the umbilical region

The mechanism of referred pain is still not fully understood, but it is believed to occur because somatic nerve fibres from the skin and visceral nerve fibres from internal organs converge at the same level of the spinal chord, thus resulting in visceral organ pain being perceived as pain from the corresponding area of skin (dermatome).

ORGAN SPINAL LEVEL SITE OF REFERRED PAIN ORGAN

STOMACH T5-T9 EPIGASTRIC/LEFT HYPOCHONDRIUM

STOMACH

DUODENUM T5-T8 EPIGASTRIC/RIGHT HYPOCHONDRIUM

DUODENUM

JEJUNUM T6-T10 UMBILICAL JEJUNUM

ILEUM T7-T10 UMBILICAL ILEUM

CAECUM T10-T11 UMBILICAL/RLQ CAECUM

APPENDIX T10-T11 UMBILICAL THEN RIGHT ILEAC FOSSA

APPENDIX

ASCENDING COLON T10-T12 UMBILICAL/RIGHT LUMBAR ASCENDING COLON

SIGMOID COLON L1-L2 LLQ SIGMOID COLON

SPLEEN T6-T8 LEFT HYPOCHONDRIUM SPLEEN

LIVER/GALLBLADDER T6-T9 EPIGASTRIC THEN RIGHT HYPOCHONDRIUM

LIVER/GALLBLADDER

PANCREAS T7-T9 INFERIOR EPIGASTRIUM PANCREAS

KIDNEY T10-L1 SMALL OF BACK/FLANK KIDNEY

Loperamide: mechanism of action

Loperamide (Imodium) is a spasmolytic agent which reduces smooth muscle activity in

the GI tract to decrease the passage of faeces.

It is an opioid receptor agonist and exerts its effects on the -opioid receptors of the

myenteric plexus of the large intestine.

It cannot cross the blood-brain barrier and therefore has no effect on the CNS.

The serosal strain gauge recording below shows the effects of Loperamide on colonic

activity. In the Proximal colon Loperamide increases the tone and you see an increase in

haustral (mixing) contractions, however towards the distal colon there is inhibition of

propulsive mass movements; overall you get a reduction in force and speed of colonic

movement.

Side effects: constipation, abdominal cramps and dizziness.

Patient Confidentiality

GMC Guidelines state: Confidentiality is an important duty, but it is not absolute. You can

disclose personal information if: It is required by law. The patient consents – either implicitly for the sake of their own or

expressly for other purposes. It is justified in the public interest

The GMC state that a doctor must establish with a patient what information they wish to share, who with and under what circumstances. This is particularly important if they are likely to lose capacity (even if only temporarily).

If anyone close to the patient (e.g. a wife) wishes to discuss a patient’s health the doctor must make it clear that while it is not a breach of confidentiality to listen to a spouse’s concerns you cannot guarantee that you will not tell the patient about the conversation, as you might need to share with them any information that influences assessment or treatment.

Diverticula

Diverticula are small bulges of the intestinal mucosa through

surrounding muscle in a hollow organ. They can become inflamed

or infected. They occur more often in the sigmoid colon due to

high peristaltic pressures and the increasing hardness of faeces.

Diverticular Disease is presence of diverticula in the bowel. It is not always symptomatic, can be

noticed post-mortem.

Diverticulosis is symptomatic diverticular disease, with abdominal pain (in left iliac fossa).

Diverticulitis is infection of diverticula by trapped faeces. Symptoms include pain and bleeding (as

blood vessels of diverticula burst).

Gastroenteritis

Gastroenteritis a general term for inflammation of the stomach and intestines, usually in response to infection.

Inflammation impairs water reabsorption from the GI tract, leading to the production of watery diarrhoea.

Very common

Symptoms include: loss of appetite

Nausea/vomiting

Stomach pain

Diarrhea.

Mild attacks are often self-limiting and last for around two to three days without the need for any specific treatment, other than rehydration therapy to replace lost fluids and minerals.

Severe attacks may require hospitalisation for antibiotic treatment and IV fluids.

Haemorrhoids Haemorrhoids are enlargements of the spongy

blood-filled cushions in the wall of the anus. Usually a consequence of prolonged constipation or less commonly diarrhoea.

Symptoms include: bright red blood in stools and itchiness around the anus.

Internal haemorrhoids are covered by mucosa and do not have sensory innervations. This is where classic haemorrhoids prolapse.

External haemorrhoids are covered by squamous epithelium and have sensory innervation. They can palpate through the skin and look and feel like blackberries.

Internal venous plexusHaemorrhoids

External venous plexusExternal haemorrhoids

Inflammatory Bowel Disease

Inflammatory Bowel Disease is inflammation of the GI tract.

It normally refers to Ulcerative Colitis or Crohn’s disease.

Other rarer forms of IBD are termed microscopic colitis which is divided into collagenous and lymphocytic colitis.

Lymphocytic colitis is characteried by an increase in the presence of inflammatory cells.

Collagenous colitis is characterised by an increase in inflammatory cells and the presence of a thick collagen layer under the epithelium, as a result of inflammation.

NB. It is possible that collagenous and lymphocytic collitis may be different stages of the same disease.

Crohn’s DiseaseDefinition

A disorder characterised by the involvement of all bowel wall layers in a chronic inflammatory process, with non caseating granulomas (non-necrozing). This granulomatous inflammation most frequently affects the terminal ileum but it may affect any part of the gastrointestinal tract.

Aetiology

Unknown, although several factors suggested :

Genetic: 3 in 20 people with the condition have a close relative who also suffers (mother, father, sibling)

Smoking

Infective Organism: Mycobacterium paratuberculosis causes a granulomatous inflammation in the small intestine of cattle. Persistence of measles virus; those born at the time of measles epidemics seem to be at higher risk

Diet: low intake of fiber from fruit and vegetables has been associated with the development of Crohn’s.

Immune mechanism : may be a down-regulation of the normal mucosal immune response in Crohn’s. e.g. Defects in regulatory T Cells

Clinical Features

This is a chronic, relapsing and remitting disease that has symptomsy dependent on the site of involvement of the GI tract. The commonest site at presentation is the terminal ileum and proximal colon.

Various symptoms occur in most patients:

Abdominal pain

Weight loss

Diarrhoea

Histopathology of Crohn’s Disease Macroscopic Findings

In Crohn's disease there may be a swollen, reddened and rubbery bowel with:

Skip lesions - discontinuous sites of pathology along the gastrointestinal tract

Cobblestone ulceration; which results from a repeated ulceration and the formation of nodules/small swellings.

Lead pipe thickening - thickened, stiff bowel Narrowed lumen Strictures (scarring occurs due to chronic inflammation and this can

lead to segments of the bowel becoming narrowed, in what is known as a stricture.

Fistulae, often between adherent bowel and/or bladder, vagina, other abdominal organs or the abdominal wall

 

Microscopic Findings

Transmural inflammation, which means that the inflammation spans the entire depth of the intestinal wall.

Lymphocyte infiltration

  Crohn's disease may involve any part of the bowel

from the mouth to the anus.

Ulcerative ColitisDefinition

In idiopathic (unknown cause) chronic inflammatory disease of the colon, which follows a course of relapse and remission. Colitis refers to chronic inflammation of the colon. Ulcerative refers to the presence of ulcers, typically at sites of inflammation.

Epidemiology

Approximately 1 in 500 will develop UC, typically between the ages of 10 and 40.

The disease occurs in men and women at equal rates.

Aetiology

Unknown. It is probably an autoimmune disease triggered by colonic bacteria causing inflammatin of the GI tract.

There is a familial link: 1 in 5 with UC have a close relative with the condition.

Non-smokers appear more likely to develop UC than smokers.

Clinical Features

Haematochesia (bloody diarrhoea)

Colicky abdominal pain

May be systemic symptoms such as weight loss, malaise, fever and pain/swelling in joints 

Rectal urgency

Tenesmus (feeling of constantly needing to pass stools, despite an empty colon)

Anaemia (shortness of breath, irregular heartbeat, tiredness and pale skin)

UC almost always involves inflammation of the rectum (proctitis).

Dehydration

Erythema Nodosum (tender red nodules which appear over shins or ankles and sometimes on arms)

Nb. Symptoms can mimic gastroenteritis, therefore history should explore other possible causes of gastrointestinal upset.

Pathogenesis of Ulcerative Colitis

Pathogenesis

It is believed that in UC normal gut microflora can trigger an excessive inflammatory response due to dysregulation of the mucosal immune system.

In 95% of cases this response extends proximally from the rectum in an uninterrupted pattern involving part or all of the colon.

Chronic inflammation causes the intestinal crypts of Lieberkuhn to become branched and abscessed. Villi shorten due to this atrophy, resulting in a reduced surface area for absorption.

The number of goblet cells is also reduced, leading to less production of protective mucus, which furthers damage.

Parts of the colonic epithelium undergo apoptosis and ulcerative lesions form, which bleed and pus.

An excess of granulation tissue leads to formation of inflammatory polyps (benign growths of the mucous membrane).

These pathological changes prevent the intestinal mucosa from acting as an effective barrier and it becomes increasingly permeable.

The colon responds by emptying frequently, leading to diarrhoea.

Session 2

History

Patient noticed looser stools ~5/6 weeks ago.

Most stools in past week bloody with mucus

No blood in pan or on wiping (indicates bleeding occurring further up inside bowel).

Some tenesmus and urgency

Crampy, intermittant abdominal pain around umbilicus and in left iliac fossa.

Tiredness

No foreign travel or contact with anyone with similar symptoms (rules out gastroenteritis).

Skin lesions noted to both lower legs over last 1-2 weeks.

Non-smoker

No family history of bowel disease

Patient’s ICE: Ideas: Thinks diarrhea is due to stress.

Concerns: Concerned that it has gotten worse and thinks he has a “bad infection”.

Expectations: He is expecting to be reassured and have some tests.

Examination

Looks pale, but conjunctivae are not pale (therefore not anemic)

Redness seen on inspection of anus and peri-anal region; no anal fissure, tags or haemorrhoids.

Rectum empty and no masses felt.

No stool or blood on the glove.

Erythema nodosum seen on legs, especially shins. (Erythema nodosum is common in ulcerative colitis, but can also occur with Crohn’s disease of the colon).

Test Results

Haematology

Hb: 131 g/l [normal 130-175 for a male] at lower end of normal (probably due to rectal bleeding)

WBCs: 9.9 (109/L) [normal 3.0-10.0] at higher end of normal

Biochemistry

Sodium: 131 mmol/l [normal 135-146] loss of salt due to diarrhea.

CRP*: 151 mg/l [normal <5]

Thyroid hormone levels are normal (Diarrhea can be a symptom of thyroidtoxicosis, therefore rules out hyperthyroidism)

Microbiology

No bacterial pathogens isolated from stool sample. Clinical details provided were: “abdominal pain and diarrhoea”.

Sample tested for presence of Salmonella, Shigella, E.coli 0157 and campylobacter.

*CRP= C-reactive protein; a marker of inflammation (see later for more information).

Initial Diagnosis

The GP thinks Ben’s likely diagnosis is inflammatory bowel disease (IBD). A history of bloody diarrhea with mucus and abdominal pain over a number of weeks in a young adult with a negative stool culture points to this diagnosis.

Session 2: Learning Outcomes

What is the difference between a fissure and a fistula?

What is C-Reactive protein?

Investigations for detecting Crohn’s disease and ulcerative colitis.

How to distinguish between Crohn’s disease and Ulcerative Colitis.

Treatment and management of Crohn’s disease and ulcerative colitis.

Endoscopy and a colonscopy procedures.

What is the difference between a fissure and a fistula?

Fistula

An anal fistula is a small channel that develops between the anal canal and the skin near the anus. Some types of fistula have one channel, whereas others branch out into more than one opening. Fistula ends can appear as holes on the surface of the skin around the anus. Anal fistulas usually occur when an anal abscess bursts, but they may also be caused by conditions such as Crohn’s disease or ulcerative colitis.

Fissure

A fissure is a cut or tear which develops in the lining of the anal canal. Normally fissures heal within 2 weeks (acute fissure), however a chronic fissure can persist for over 6 weeks. most fissures occur when passing particularly hard stools although they can also occur during childbirth, following persistent diarrhoea and as a result of IBD.

An anal fistula is painful and can cause bleeding when you go to the toilet.

C-Reactive protein

C-reactive protein is an acute-phase protein produced by the liver.

Inflammatory cytokines (e.g. IL-6) stimulate the liver to produce CRP, therefore CRP levels rise during inflammation.

Its physiological role is to bind to phosphocholine (expressed on the surface of dead or dying cells and some types of bacteria) in order to activate the complement system via the C1Q complex and facilitate the clearance of apoptotic and necrotic cells.

Normally CRP levels should be below 10mg/l.

A positive CRP test shows inflammation is occurring somewhere in the body.

High levels of CRP are caused by infections and many long-term diseases, however a CRP test cannot show where the inflammation is located or what is causing it.

Distinguishing between UC and Crohn’s

Blood Tests:

Vitamin B-12, may be low if the small intestine isn't properly absorbing nutrients due to Crohn's disease.

Antibody Blood Tests: pANCA (perinuclear anti-neutrophil antibodies) and ASCA (anti-saccharomyces cerevisiae antibody). Many patients with ulcerative colitis have the pANCA antibody in their blood; patients with Crohn’s disease are more likely to have ASCA in their blood. However, these antibody tests are not foolproof. In some cases, patients have neither antibody, while others who carry one type may actually have the opposite or neither disease.

 Further information about symptoms:

With ulcerative colitis, bleeding from the rectum during bowel movements is very common, and bleeding is much less common in patients with Crohn's disease.

Distinguishing between UC and Crohn’s

Treatment and management of Crohn’s disease & Ulcerative Colitis

Symptomatic Treatments include anti-diarrhoeal medication and vitamin supplementation.

Stopping smoking can also ease symptoms.

Glucocorticoids and immunosuppressant’s such as azathiprine can be used to induce remission.

In order to maintain remission it may be necessary to continue giving immunosuppressants or anti-inflammatoriy drugs such as aminosalicylates.

If patient is resistant to glucocorticoids a dose of a stronger immunosuppressant such as methotrexate or cyclosporine can be given to induce leucopenia.

Surgical interventions can also be used, although resections are avoided wherever possible.

Endoscopy & Colonoscopy

EGD: (Esophagogastroduodenoscopy) examines the lining of the esophagus, stomach, and duodenum (first part of the small intestine). Crohn’s disease can affect these areas.

Colonoscopy: examines the lining of the entire large intestine and can also be used to look into the very end of the small intestine (ileum). This exam can help determine the severity of ulcerative colitis and Crohn’s disease as well as distinguish between the two diseases or other types of intestinal conditions.

Session 3

Management

The GP rang the gastroenterology registrar on call for advice on how best to manage Ben. He arranged for an urgent clinic appointment and colonoscopy. At the clinic Ben is provided with a patient information sheet about his colonoscopy. Consent for the procedure is given prior to the colonoscopy. Following the colonoscopy, Ben was commenced on oral and per rectum mesalazine (an amino-salicylate). Steroids are a second line treatment if the mesalazine does not work.

Key Findings from Colonoscopy Report

Mucosa showed extensive severe congestion with patchy moderate mucopurulent exudate (contains both mucus and pus).

Multiple small and large ulcers were seen.

Ulceration was confluent (continuous).

Histopathology Report Biopsies taken during colonoscopy.

Samples taken from rectum, sigmoid colon, ascending colon and transverse colon.

All four specimens showed similar morphological changes and were composed of necro-inflammatory ulcer slough overlying ulcer base formed by granulation tissue.

Scattered erosion was seen. (Erosion= the superficial destruction of a surface area of a tissue by inflammation, ulceration or trauma).

The epithelium showed marked regenerative changes and evidence of goblet cell depletion.

There is a diffuse increase in inflammatory cells and the increase is composed of lymphocytes and plasma cells (both found in chronic inflammation), however the biopsies were scattered with neutrophils within the epithelium and lumen of the crypts, indicating cryptitis and crypt abscess formation (neutrophils tend to be found in acute inflammation).

No submucosal granulomata are seen (Crohn’s disease affects all wall layers!)

No evidence of paneth cell metaplasia, dysplasia or malignancy.Summary:Diffuse active- chronic inflammationUlcerationNegative for dysplasia or malignancy

Prognosis

Most patients with UC have mild disease at presentation .

A large proportion continue to have mild disease or remission.

20% of patients have continuous symptoms and more extensive disease (affecting more of the colon).

Up to one third will undergo colectomy at some point in their lifetime.

The outlook of Crohn’s disease is worse than in ulcerative colitis, with only 10% of patients having prolonged remission.

Patients with UC have an increased risk of developing colorectal cancer and the risk of malignancy is related to the duration of symptoms.

Patients with continuous UC must have regular colonoscopies with biopsies to look for dysplasia or they may opt for a total prophylactic colectomy.

Frequency of follow-up depends on the nature of the disease and patients should be educated as to the signs and symptoms to look out for,

Tiny doctor says you will all be fine….<3