3+4 - GASTROINTESTINAL TRACT DISORDERS AND DIAGNOSIS Flashcards
What makes up gastrointestinal tract?
mouth pharynx oesophagus stomach pancreas small intestine large intestine
Structure of the stomach
fundus cardia body rugae (folds) pylorus duodenum
Structure of the stomach wall
mucosa
submucosa
muscularis
serosa
MUCOSA
consists of simple columnar epithelial cells called surface mucous cells, which secrete mucus
SUBMUCOSA
areolar connective tissue
MUSCULARIS
3 layers of smooth muscle
SEROSA
simple squamous epithelium and areolar connective tissue
GASTRIC PIT
gastric glands are the columns of various secretory cells (e.g. parietal cell, chief cell) lining the gastric pit.
To form a gastric pit, the surface epithelial cells extend into the lamina propria. (The lamina propria consists of areolar connective tissue.)
Chief cells
these produce PEPSINOGEN (protease) which gets converted to the active PEPSIN at low pH, and gastric lipase.
G cells
- within the gastric gland
- enteroendocrine cells -they secrete the hormone gastrin into the blood. (This facilitates production of gastric juice when there is food in the stomach.)
chyme
gastric juices mixed with food, secreted into duodenum
SECRETION OF HYDROCHLORIC ACID BY GASTRIC PARIETAL CELLS
- ATP powers PROTON PUMPS in the parietal cell membrane, which enables H+ to be secreted into the gastric pit.
- Cl- diffuses into the stomach via the Cl- channels in the cell.
- Parietal cells contain the enzyme CARBONIC ANHYDRASE which converts carbon dioxide and water to carbonic acid.
- This dissociates into H+ (actively transported out of cell into chyme by exchange with K+) and bicarbonate ions.
- The bicarbonate ions leave the cell into the bloodstream in exchange for chloride ions.
- H+ and Cl- combine in chyme
The small intestine
Most digestion and absorption of nutrients occurs in the small intestine (by virtue of its long length, and large surface area.
What does the small intestine consist of ?
duodenum, jejunum and ileum.
Layers of the small intestine wall
mucosa, submucosa, muscularis and serosa
mucosa in small intestine
contains crevices called INTESTINAL GLANDS (CRYPTS OF LIBERKUHN) – these secrete INTESTINAL JUICE
Within the intestinal glands there are also enteroendocrine cells which secrete hormones such as secretin and cholecystokinin and paneth cells which secrete lysozyme – (this kills bacteria)
submucosa in duodenum
duodenal glands secrete alkaline mucus.
MICROVILLI
projections of the apical surface of the epithelial cells.
These form a ‘BRUSH BORDER’.
enzymes in brush border
for final digestion
- lactase, sucrase, peptidase, nuclease, phosphatase
pancreas
secrete main digestive enzymes for larger molecules (lipase).
Secreted as zymogens, activated when mixed with chyme
haematoxylin
basic dye, stains acidic structure blue
- nuclei as DNA content (- charge)
eosin
acidic dye, stains basic structures pink
- cytoplasmic proteins (+ charged amino acids)
Eosin Y
acidic and binds to basic components of the cell to produce a red colouration
What is helicobacter pylori?
gram-negative, motile bacteria that grows in the digestive tract and has a tendency to attack the stomach lining.
What does Helicobacter pylori cause?
GASTRITIS (stomach inflammation)
STOMACH ULCERATION (gastric ulcer)
DUODENAL ULCERATION
What is an ulcer?
- Break in the lining of the gut which fails to heal
* Often inflamed which causes more acid secretion
What percent of stomach ulcers (gastric and duodenal) are caused by H. pylori?
•80% gastric and 95% duodenal ulcers caused by H. pylori
H.pylori symptoms (ulcers)
upper abdominal pain, nausea
H.pylori treatment (ulcers)
antibiotics and proton-pump inhibitors (pump in parietal cells stops HCl production in stomach)
H.pylori form ulcers
•Motile – swim into the mucus layer
•H. pylori produces enzyme UREASE
Urease catalyses the breakdown of urea into ammonia and CO2 ~ These further react to form NH3 and HCO3- which both neutralise stomach acid
Urea breath test
Give 13C labelled urea to patient orally (14C produced naturally). Bacteria in stomach contains urease that convert urea to ammonia and 13CO2.
Diffuses into blood and can be exhaled.
Breath sample ran on mass spec, peak at 45.
COELIAC DISEASE
Sensitivity to GLIADIN –
component of GLUTEN in wheat, barley, rye
Autoimmune disease
Reversible
Symptoms of coeliac disease
Diarrhoea, weight loss
Diagnosis of coeliac
by biopsy of small intestine mucosa and ELISA
coeliac treatment
gluten-free diet
Coeliac histology
- flattening of the surface of the jejunum, expansion of the lamina propria and lymphocytic infiltration of the mucosa.
This lymphocytic infiltration occurs as part of the inflammatory response.
Coeliac cause
- Tissue Transglutaminase (TTGA) attaches to gliadin peptides followed by phagocytosis
- Activation of T and B cells
- AutoAntibodies produced against TTGA
- Immune destruction of intestinal mucosa
Coeliac ELISA
• Identify anti-TTGA in patient’s serum. Antigen = TTGA. Add serum. Add anti-human labelled antibody. Detect by fluorescent label on antibody
CROHN’S DISEASE
• Chronic inflammatory disease affecting small intestine (sometimes large
intestine).
• Submucosa thickened – oedema and inflammation
• Patchy distribution – normal GI tract wall in between (skip lesions)
Chron’s disease cause
unknown
Chron’s disease symptoms
•diarrhoea (may contain blood), abdominal pain, tiredness, weight loss.
Chron’s disease diagnosis
intestinal biopsy, fecal tests, barium meal, CT/MRI scan.
Chron’s disease treatment
surgery, corticosteroids, antibiotics, but no cure.
What causes cystic fibrosis?
Mutation in Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR)
Chloride ion channel
- Important in sweat production
* Important in intestinal chloride ion secretion
How does the Mutation in Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) affect the cells
Less Cl- released
Less H2O release
THICK mucus
CFTR PROTEIN ACTION
cAMP increase in cell Protein kinase A activated CFTR phosphorylated – channel opens Secretion of chloride, sodium and water follow Mucus liquefied = normal
effects of cystic fibrosis on lungs
Viscous mucus accumulates - chest infections, inflammation, structural change.
effects of CF on GI tract
Viscous mucus accumulates -exocrine ducts in pancreas blocked.
malabsorption
SWEAT GLANDS IN CYSTIC FIBROSIS
- Sodium and chloride content of sweat is increased in Cystic Fibrosis
- In normal sweat glands, CFTR facilitates movement of Cl- FROM the sweat to the cytoplasm of the cell.
- CFTR not working in cystic fibrosis, so Cl- stays on surface of skin, combines with Na+ to give NaCl
PILOCARPINE IONTOPHORESIS SWEAT TEST
Pilocarpine stimulates localised sweating
Iontophoresis = electric charge used for drug delivery via skin
Collection of sweat using filter paper or microtubing
High chloride/sodium indicates positive for Cystic Fibrosis
Detection of Cystic Fibrosis gene mutations
Over 1300 CF mutations known, Commonest DF508 (phenylalanine deletion position 508).
So
Amplify the section of the patient’s genome by PCR with specific primers to detect mutation.
Or
When voltage applied small DNA molecules move faster than large ones
Stain gel to visualise DNA
Lactose intolerance (Lactase deficiency)
Insufficient lactase made in small intestine
Undigested lactose causes fluid retention in faeces (symptom: diarrhoea)
Lactose intolerance (Lactase deficiency) detection
Bacterial fermentation of lactose produces H2 in breath (detect via mass spec)
Lactose meal diagnostic test – 50g lactose given then determine blood glucose levels over 3 hours. <1mmol/l over 3h = lactose intolerant
