• highly innervated and integrated

• feedback system to ensure balance

1. Digestion

   Nutrient absorption begins with the process of digestion, which involves breaking down complex food molecules into smaller, absorbable units. Digestion primarily occurs in the lumen of the small intestine and is facilitated by various enzymes secreted by the pancreas, liver (via bile), and intestinal mucosa.

2. Transport

From lumen into epithelium.

3. Assimilation

   Once inside the epithelial cells, absorbed nutrients undergo assimilation, where they are either utilized for energy production, stored, or used for various metabolic processes.

   • Glucose, amino acids, and short-chain fatty acids are absorbed into the bloodstream and transported to various tissues for energy production or storage.

   • Some nutrients, like vitamins and minerals, are directly utilized by the epithelial cells or transported to other tissues for specific functions.

4. Transport in blood or lymph

   After assimilation, nutrients are transported away from the small intestine to other tissues and organs through either the bloodstream or the lymphatic system.

   • Water-soluble nutrients, such as glucose and amino acids, are primarily transported via the bloodstream (systemic circulation) to the liver and then distributed to other tissues.

   • Lipids, including long-chain fatty acids and fat-soluble vitamins, are absorbed into the lymphatic system (lacteals) as chylomicrons, which are large lipid particles, and then transported via the lymphatic vessels to the bloodstream (thoracic duct), eventually reaching the liver and peripheral tissues.

• villi (finger-like surfaces) - increase surface area for absorption

• enterocytes have microvilli to further increase surface area

a) Lamina propria

b) Muscularis mucosae

2. Submucosa

• contains large blood and lymph vessels

• nervous system is integrated

a) Submucosal plexsus

3. Muscularis externa

a) circular muscles

• thicker

b) longitudinal muscles

• thinner

• outer layer

4. Serosa

• connective tissue

1. Starch broken down to oligo, di and mono- triglycerades, first by salivary amalyse, and then finally by pancreatic amylase

2. Absorbed through SGLT (sodium-dependent-glucose transporter)

Proteins

1. Digestion Begins: Protein digestion begins in the stomach with the action of pepsin, which breaks down proteins into smaller polypeptides and some amino acids.

2. Continued Breakdown: In the small intestine, pancreatic proteases (trypsin, chymotrypsin, and carboxypeptidase) further hydrolyze polypeptides into smaller peptides and free amino acids.

3. Final Digestion: Brush border enzymes like aminopeptidase and dipeptidase on the surface of enterocytes complete protein digestion by breaking down dipeptides and tripeptides into amino acids for absorption.

4. Absorption: Amino acids and small peptides are absorbed into enterocytes via specific transporters, then transported into the bloodstream for utilization by the body.

Fats (lipids)

DEMI

1. Emulsification by bile

2. Digestion by pancreatic lipase (hydrolysis to triglyceride and fatty acids)

3. Absorption of products of fat digestion depends on size

Water and electrolytes

1. small intestines absorb 8-9L water per day along with electrolytes

2. large intestines absorb

a) Myenteric plexus - responsible for motility

b) Submucosal plexus - responsible for secretion of hormones

Motility: contraction of smooth muscles of GIT

1. move food from mouth to anus

2. mechanically mixing food to break into small particles

Types of contractions (peristalsis)

1. Circular

2. Segmental

Fasting

Phase 1: period of motor inactivity - 90 min

Phase 2: irregular contractible activity - 90 min

Phase 3: regular phasic contractions - 5-10 bursts, 90 min

During eating these phases are disrupted

After a meal = MMC pattern is disrupted → now irregular contractions (lasts 2-5 hours after meal)

Late gastric emptying (Demi) - progesteron slows digestion

Elevated levels of hormones, such as progesterone, contribute to delayed gastric emptying. Gastric acidity is increased because of the higher production of gastrin by the placenta

Higher gastric acidity - due to higher production gastrin

• chronic fatigue syndrome

• fibromyalgia

• temporomandibular joint dysfunction

2nd: lab tests to exclude other causes of symptoms

3rd: apply ROME-IV criteria

Rome IV 2016

In preceding 3 months, at least 1 day per week in last 3 months of recurrent abdominal pain

and 2(+):

1. related to defacation

2. onset associated with change in frequency of stool

3. onset associated with change in form (appearance) of stool

Lifestyle and dietary modifications

• in case of mild-moderate symptoms

• Low FODMAP

• Consume soluble fiber

  
  

Peppermint oil

• relaxes smooth muscle, targeting spasms

Pharmacological therapy

• for those who fail to respond or have more severe symptoms

• tricyclic anti-depressants

Gut-directed psychotherapy

1. Crohn's Disease (CD) - affects any part of GIT

2. Ulcerative Colitis (UC) - affects colon

Other types

3. Colitis undetermined (indeterminate colitis)

• 10% of cases of IBD

• when definitive diagnosis is not possible due to overlap

4. Microscopic colitis

• absence of macroscopic evidence of inflammaiton

  a) lymphocytic type

  b) collagenous type

• genetic component

• environmental component - can trigger onset of inflammation

Target of treatment - immune system

• varies from country to coutnry

• 4-10 per 100 000 annually

Prevalence

• 25-100 per 100 000 annually

• 
  

• NOD1 (CARD 15) gene - expressed in epithelial cells, macrophages and endothelial cells

• autophagy genes

• Th17 pathway (IL-13 type 17 helper T cells)

• chronic inflammatory condition

• may affect any part of GIT (mouth - anus)

• particular tendency to affect terminal ileum and ascending colon (ileocolonic disease)

• can involve

  • 1 small area

  • multiple areas with normal bowel in between (= skip lesions)

  • whole colon (= total colitis)

  • cobblestone appearance

• sometimes w/o macroscopic small bowel involvement

Biopsy: transmural damage - associated with development of perianal fistulae and fissures

Microscopic

• inflammation extend through all layers (= transmural) of bowel

• increase in chronic inflammatory cell epithelioid hyperplasia

• 50-60% - granulomas - non-caveating epithelioid cell aggregates with Langhans’ giant cells

Diarrhoea

• 80%

• usually contains blood (therefore difficult to differentiate from UC)

• steatorrhoea (small bowel disease) - fatty poop

• due to bile acid malabsorption - as a consequence of ileal resection of ileal disease

Abdominal pain

• colicky (indicates obstruction)

Weight loss

Constitutional symptoms of malaise (in 15% of patients)

• lethargy

• anorexia

• nausea

• vomitting

• low-grade fever

• NO GI SYMPTOMS

Children

• reduced growth velocity

• delayed puberty

• weight loss

• signs of malnutrition

• aphthous ulceration of mouth

• occasional tenderness or right iliac fossa mass on abdominal examination

• anus: oedematous anal tags, fissures or perianal abscesses

• extra-intestinal features

Anaemia

• common

• may be normocytic, normochromic or chronic disease

• deficiency of iron/folate or vitamin B12 (unusual)

• serum B12 may be low

Raised ESR and CRP

• and raised white cell and platelet counts

Hypoalbuminaemia

• present in severe disease as part of acute phase response to inflammation associated with raised CRP

Abnormal liver chemistry

Blood cultures

• required if septicaemia suspected

Serological tests

• ANCA (-)

• ASCA (+)

  
  

2. Stool test

• C. difficile toxin assay - if diarrhoea is present

• microscopy for parasites - relevant travel history

• raised faecal calprotectin and lactoferrin in active intestinal disease

• calprotectin is useful in monitoring IBD

3. Colonoscopy

• if colonic involvement is suspected - except in patients with severe diseases (-> limited unprepared sigmoidoscope)

• Endoscopic assessment of terminal ileum if CD is suspected

• 2 biopsies in 5 areas (including rectum and terminal ileum)

Findings

• mild, patchy. superficial (apthoid) ulceration

• more widespread, larger and deeper ulcers producing cobblestone appearance

  
  

4. Upper gastrointestinal endoscopy

• required to exclude oesophageal and gastroduodenal disease in patients with relevant symptoms

• increasingly performed in all patients to define extent of disease as guide for prognosis

5. Small bowel imaging

• mandatory in patients with suspected CD

• depends on availability and local expertise

a) barium swallow-through

b) CT scan with oral contrast

c) small bowel ultrasound

d) MRI enteroclysis

e) axial imaging (preferred in acute situations)

Findings

• symmetrical alternation of mucosal pattern with deep ulceration

• areas of narrowing or stricturing

• skips lesions between normal and affected bowel sites

6. Ultrasound scanning

• provides convenient radiation-free method for assessing disease activity in ileum and colon

• can be performed at bedsite

7. Perianal MRI or endoanal ultrasound

• evaluate perianal disease

8. Capsule endoscopy

• CD patients - when radiological examination is normal

• often 1st performed to exclude strictures of small bowel that would constitute a contraindication to subsequent capsule endoscopy

9. Radionuclide scans - with indium- or technetium-labelled leucocytes

• used in some centres to identify small intestinal and colonic disease inflammation

• to localise extra-intestinal abscesses

• most effective

• quick response

• moderate-severe attacks

2. Aminosalicylates

• not very effective against Crohn's

• more effective in UC

3. Antibiotics

4. Exclusive enteral nutrition

5. Refractory of fulminant disease

6. Surgery

• cannot always be cured because of inflammation

• stable

• 6-15 per 100 000 annually

Prevalence

• 80-150 per 100 000 annually

  
  

• mutations in genes associated with mucosal barrier

• can affect

  • rectum (= proctitis)

  • extend proximally from anus to involve sigmoid and descending colon (= left-sided colitis)

  • whole colon (= extensive colitis)

Microscopic

• superficial inflammation limited to mucosa

• chronic inflammatory cell infiltrate in lamina propria

• crypt abscesses and goblet cell depletion

• most patients have a course of remissions and exacerbations

General features (not as severe as CD)

• diarrhoea with blood and mucus, sometimes with lower abdominal discomfort

• malaise

• lethargy

• anorexia with weight loss

• aphthous ulceration in mouth

Proctitis

• limited to rectum

• frequent passage

• urgency

• tenesmus

• normally few constitutional symptoms

• stool may be solid (when passed)

• great inconvenience by frequency of defecation

Acute attack of left-sided or extensive UC

• bloody diarrhoea

• passing up to 10-20 liquid stools per day

• diarrhoea at night

• severely disabling urgency and incontinence

• require urgent admission for intensive therapy

Toxic megacolon

• serious complication associated with acute severe colitis

• plain abdominal X-ray:

  • dilated, thin-walled colon

  • diameter +6 cm

  • gas-filled

  • contains mucosal islands

• dangerous stage of advanced disease

• impending perforation

• high mortality (15-25%)

• urgent surgery -> toxic dilation not resolved in 48 hrs with intensive therapy

White cell and platelet counts

• raised in moderate-severe attacks

• iron deficiency anaemia is present

ESR and CRP

• often raised

• liver biochemistry may be abnormal with hypoalbuminaemia occurring in severe disease

pANCA

• may be positive

• contrary to CD (pANCA is usually negative)

2. Stool test

• always performed to exclude infective causes of colitis

• microscopy to exclude amoebiasis in patients with a relevant travel history

• faecal calprotectin/lactoferrin elevated

3. Colonoscopy

• endoscopy with mucosal biopsy (GOLD STANDARD)

• allows assessment of disease activity and extent

• long-term colitis -> chromoendoscopy - diagnose dysplasia

• don't perform in severe attacks of disease for fear of perforation -> limited unprepared flexible sigmoidoscopy to confirm diagnosis

Chromoendoscopy

4. Imaging

Plain abdominal X-ray

• patients suffering acute severe attacks to exclude colonic dilation

• extent of disease is not reliably assessed

Other imaging modalities are rarely used

Ultrasound

• inflammation of colonic wall

• presence of free fluid within abdominal cavity

1. Aminosalicylate

2. Proctitis

• rectal 5-ASA suppositories: 1st line treatment

• oral 5-ASA can be added to increase remission rates

  
  

3. Left-sided colitis

• topical 5-ASA enemas: 1st line treatment

• addition of oral 5-ASA will increase remission rates

• do not respond: oral prednisolone

  
  

4. Extensive colitis

• oral 5-ASA

• addition of 5-ASA enema increases remission rates

Type 1 (pauciarticular) - acute attack and self-limiting (less than 10 weeks)

Type 2 (polyarticular) - last longer and is independent of IBD

Seeking help depends on

• illness attitude scores

• anxiety and depression scores

• amount and severity of symptoms

• infectious diarrhoea precedes onset of symptoms in 7-30% of patients

• stress or adverse life events often precede onset of IBS

Risk factors

• female

• severity and duration of diarrhoea

• pre-existing adverse life events

• high hypochondriacal anxiety and neurotic scores at time of initial illness

IBS-C

• mostly constipation

• less than 25% loose and watery stool

IBS-D

• mostly diarrhoea

IBS-M

• more than 25% lumpy and more than 25% watery stool

Unsubtyped IBS

• insufficient abnormalities of stool deficiencies

Thorough investigation is required if patients meets criteria + one of:

• rectal bleeding (hematochezia)

• nocturnal pain

• fever

• weight loss

• clinical suspicion of organic diarrhoea

• raised calprotectin or lactoferrin (indicates inflammation)

• family history colon cancer

Symptoms

• pain and bloating w/o altered defecation

• postprandial fullness

• nausea

• anorexia and weight loss

Management

• not easy as it can be chronic and severe

1. Avoid narcotics

2. Combine central and end-organ-targeted treatment

3. Non-absorbed antibiotics (rifaximin)

4. FODMAP (fermentable oligo-di and monosaccharides and polyols)

   • alter fermentable components of diet by excluding certain food types (e.g. garlic, onion, wheat-containing products, etc.)

5. Probiotics

   • no clear efficacy

   • might help reduce pain, bloating and flatulence

• passage of several stools in rapid succession, 1st thing in the morning and no further bowel action later that day OR defecation only after meals

• 1st stool is formed, after that mushy, looser or watery

• urgency for defecation

• anxiety and uncertainty about bowel function and restriction of movement

• exhaustion after defecation

Treat

• loperamide combined with tricyclic antidepressants prescribed at night

• most commonly in females who surreptitiously take high-dose purgatives and are often extensively investigated for chronic diarrhoea

• lower serum potassium

• often occurs in association with eating disorders

• patients might need psychiatric help

Diagnosis

• biochemical analysis of stool

Environmental factors

Smoking

• CD: exacerbates and shows increased risk of recurrence after surgery

• UC: increased risk in non-/ex-smokers

• UC: nicotine can be effective treatment

NSAIDS

• trigger onset of IBD

• can cause flares of disease in established diagnoses

Hygiene (you might die before x_x)

• poor and large families living in crowded conditions have lower risk of CD

• clean environment - intestinal immune system gets no exposure to pathogenic or non-pathogenic microorganisms which alters balance between effector and regulatory immune responses

Nutritional factors

• many food (components) are suggested as playing a role in aetiopathogenesis (e.g. high sugar and fat intake)

• breast-feeding may provide protection against development of IBD (CD) in offspring

Psychological factors

• chronic stress and depression increase relapse in patients with quiescent disease

Appendicectomy (UC)

• protective against development of UC - particularly if performed for appendicitis or mesenteric lymphadenitis before 20 y/o

• influences the clinical course of UC

  • lower incidence of colectomy

  • reduced need for immunosuppressive therapy

Symptoms persisting beyond 5 days - unlikely caused by infective gastroenteritis

Relevant travel history - stool microscopy for parasitic diseases (amoebiasis)

Vitamin malabsorption or malnourishment - consider CD

Children with reduced growth velocity - consider CD

Illeocolonic tuberculosis

• common in developing countries (India)

• make diagnosis CD difficult

• microscopy and culture for TB of any available tissue

• therapeutic trial anti-TB therapy may be required

Lymphomas

• can occasionally involve ileum and caecum (rare)

• is not curing in CD

• can cure in UC - but weigh benefits

• used for absorption

  
  

Goblet cells

• mucus production

Paneth cells

• host defence and immunity

• secrete anti-microbial peptides and other molecules to protect host against infection

Tuft cells

• produce IL-25

ISC (intestinal stem cells)

• regenerates every 48 hrs

Enteroendocrine cells

• produce hormones

  • somatostatin

  • CCK

  
  

CCK - promotes food delivery from stomach into small intestine

Serotonin - regulation and secretion in digestion process of GI

• more goblet cells

• less enterocytes (most food has been absorbed)

• thicker muscle layer (needs more contraction)

• absorption water and electrolytes

Small intestine

• absorption of nutrients and water (80%?)

• production hormones

• 40% of women with IBS report influence of the menstrual cycle on their symptoms

• high ovarian hormones levels → in rodents = reduce somatic and visceral pain sensitivity

• hyperestrogenemia and hyperprogesteronemia a prolonged GI transit is also observed

• chronic pain syndromes frequently associated with IBS, like migraine headache for example, are alleviated during the time of pregnancy

• Variations in ovarian hormones modulate visceral pain perception. It also modulates susceptibility to stress, a pivotal factor in IBS occurrence and symptom severity. Hyperresponsiveness to stress promotes immune activation and impairs gut barrier function. 

Disorder: set condition, known cause and pathogenesis

• ulceration

Inactive

• atrophy