ILO WEEK 1 Flashcards
Recognise stomach, gallbladder, small intestine, large intestine, greater momentum, lesser momentum and epiploic foramen
See picture
Distinguish jejenum, ileum, caecum, appendix and regions of colon
( ascending, transverse, descending, sigmoid)
See picture of intestines
Draw outline of the stomach and oesophagus; relate features to organ function
See picture; Actually DRAW IT
Relate histological features to organ function (stomach and oesophagus)
- Oesophagus: passing food down; tube; stratified squamous; needs protection from friction
- Stomach; mixing and storage, partial digestion; columnar; need protection from acid
Blood supply; lymphatic drainage (stomach and oesophagus)
Arteries: STOMACH
- greater curvature-> left gastroepiploic artery & right gastroepiploic artery
- fundus and upper part-> short gastric artery (from splanchnic artery)
- pyloric end + lesser curvature-> right gastric artery anastomosing with left gastric artery
Veins: STOMACH
- same! gastric, gastroepiploic, short
Lymph: STOMACH
Celiac lymph nodes
Arteries: OESOPHAGUS
-abdominal-> left gastric artery; left inferior phrenic artery
Veins: OESOPHAGUS
- to portal circulation-> left gastric vein
- to systemic circulation-> azygous vein
Lymph:OESOPHAGUS
- deep cervical lymph nodes
- superior and posterior mediastinal nodes
- left gastric and celiac nodes
Describe the regulation of gastric secretions
!!!Put picture here!!!
- gastrin
- ACh
- Histamine
- Somatostatin
- HCl
Gastrin Released by G-cells in pyloric gland area (PGA) in response to Vagal (Ach) stimulation and Protein in stomach
Vagal stimulation and Gastrin causes Parietal cells to secrete HCL
Gastrin acts on Enterochromaffin like cells which secrete histamine (which then in turn causes on parietal cells to secrete more acid)
Vagal stimulation and Gastrin Acts on Chief cells to promote secretion of Pepsinogen which is converted to Pepsin by presence of acid (Autocatalysis).
Pepsin digests protein (hence stored in inactive form) + protected from high pH
Increased acid (pH 2-3) causes Somatostatin release form D cells which inhibit Gastrin (blocks action of histamine)
Duodenal factors (to come)
Intrinsic factor released binds with B12
3 phases:
Cephalic Phase (35-40%)
• stimulated by Sight, Smell and Taste of food.
• 30% of acid secretion occurs before food enters the stomach.
• Sensory Stimuli from food activates Dorsal Motor Neurones of the
Vagus Nerve, resulting in:
• In the body of the stomach, the vagal postganglionic muscarinic
nerves release Acetylcholine, which stimulates parietal cells to
release H+.
• Release of Gastrin from G cells in the astral glands. Gastrin
reaches the gastric glands by the bloodstream.
• Both vagal activity and gastrin stimulate the release of Histamine
from mast cells/ECL cells (enterochromaffin-like cells)
• Histamine acts on H2 receptors on parietal cells to stimulate H+
secretion.
• Thus, ACh, Gastrin and Histamine all enhance the secretion of gastric
juice.
Gastric Phase (60%)
• 50 – 60% of total Gastric Acid secretion occurs during this phase. It is the period in which swallowed food and semi-digested protein activate Gastric Activity.
• Food causes distension of the stomach, which activates vago- vagal reflexes and short-loop myenteric reflexes. These both lead to the secretion of ACh which stimulates gastric secretions.
• Vagal stimulation also stimulates G cells to produce gastrin. Also certain proteins that are digested into specific amino acids and peptides directly stimulate G cells to secret more gastrin.
• Gastrin secretion is inhibited when the pH falls below 2 or 3.
• Somatostatin produced from D cells inhibits gastrin release
from G cells, which in turn reduce acid secretion.
Intestinal Phase (5-10%)
• Short lived gastrin release from duodenal G cells, as partially digested food starts to enter the duodenum.
• However as the chyme distends the duodenum, it triggers an enterogastric reflex, whereby gastric secretory activity is suppressed. This is due to:
• Secretin is released by S cells of the duodenal mucosa in response to acid. Secretin reaches the stomach via the bloodstream to inhibit Gastrin release, and reduces the affinity of parietal cells to gastrin.
• Cholecystokinin (CCK) and Gastric Inhibitory Peptide (GIP) are released in the presence of lipids and carbohydrates. Both inhibit gastrin release.
Discuss the pathophysiology of peptic ulcer disease and role of H. pylori
A peptic ulcer consists of a break in the superficial epithelial cells penetrating down to the muscularis mucosa of either the stomach or the duodenum. There is a fibrous base and an increase in inflammatory cells.
Too much attack:
- Zollinger Ellison Syndrome
(Gastrin producing tumour)
- Helicobacter pylori antral gastritis
Weakened defence:
- Non steroidal anti-inflammatory drugs - “Stress” ulceration - Helicobacter pylori corpus/pan gastritis
Imbalance between factors promoting mucosal damage & gastroduodenal defence
H. pylori infection
- Duodenal ulcers are mostly the result of gastric acid hypersecretion caused by H. pylori infection. In gastric ulcers gastric acid secretion is normal or low.
- In duodenal ulcers, chronic H pylori infection confined mainly to the gastric antrum leads to impaired secretion of somatostatin & consequently increased gastrin release resulting in gastric acid hypersecretion.
- In gastric ulcers, there is chronic H pylori throughout the stomach accompanied by severe inflammation results in gastric mucus degradation, disruption of tight junctions between gastric epithelial cells & induction of gastric epithelial cell death.
- (NH2)2CO + H2O → CO2 + 2NH3 increase pH and thus increase gastric acid secretion
Discuss the pharmacological basis of the treatment of peptic ulcer and H.pylori
Treatment:
- H. pylori
- Symptom relief
- Healing ulcer crater
- proton pump inhibitors (PPI)
- H2 receptor antagonist
- Antibiotics
- H2 receptor antagonist
e. g. cimetidine, famotidine, nizatidine, ranitidine
competitive reversible binding
decreases gastric acid secretion ~60%; works on parietal cell; work less if used long-term
- Protein pump inhibitors (PPI)
e. g. omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
inhibit parietal cell H+,K+-ATPase; irreversible; weak base
decrease gastric acid secretion 95% (basal, nocturnal and food-stimulated)
drug only active in highly acidic conditions in parietal cell, protonated and converted, stay in parietal cell; react covalently with cysteine residues in the enzyme (H+,K+-ATPase) ; prevents transport of H+ into the stomach; cause denaturation of the pump
best when taken 0.5-1hour before eating; works only on active parietal cells
work for 24-48 hours
Antacids
e.g. pepto-bismol; gaviscon; alternagel
weak bases, don’t decrease acid secretion; Na+, Ca2+, Mg2+, Al3+ -> soluble chloride salts, form poorly soluble bicarbonates and carbonates; excreted in feces
inhibits pepsin activity; binds bile salts
Triple Therapy:
Needed for eradication of H. Pylori; 2 antibiotics (clarithromycin, amoxicillin, metronidazole) and an antisecretory drug (PPI)
Discuss the epidemiology of peptic ulcer disease
Common 1-5% population Chronic disabiling More in males More in smokers Stress considered important Associated with increased acid Maximal acid 50% higher in DU Basal acid also higher
In Adult General Population
1. H. pylori infection is associated with reduced intragastric acidity.
2. H. pylori positives have reduced parietal and Chief cell densities
This likely represents the H. pylori gastritis producing atrophy of gastric mucosa.
May explain the negative association between H.pylori and Reflux Disease
Describe the anatomy of the biliary tract
BILIARY TREE
- Biliary canaliculi
- Interlobular bile ducts
- Septal bile ducts
- Intrahepatic ducts
- R/L hepatic duct
- Common hepatic duct
- Common bile duct
Common bile duct passes :
-BEHIND duodenum
THROUGH the head of the pancreas
joins with main pancreatic duct
opens in to 2nd part of duodenum (Ampulla of Vater)
flow of bile regulated by Sphincter of Oddi (smooth muscle)
Liver constantly makes bile
Around 600 ml of bile produced per day
Gallbladder is reservoir for bile - 30-50ml capacity
Columnar epithelial lining
Concentrates bile (H2O and salts reabsorbed)
Lies in GB fossa on inferior surface R lobe liver
3 anatomically defined regions
Connected to CHD/CBD by Cystic duct - ~ 2.5cm length
Most anterior of visceral organs
GB fundus may be palpated between lateral border of rectus abdominus muscles and costal margin (9th costal cartilage)
Describe the composition and formation of bile including the enterohepatic circulation
Components of bile:
- Conjugated bilirubin
- Bile acids
- Cholesterol
- Water
- Electrolytes
- Phospholipids
•
Bile salts are the bile acids which act as
emulsifiers
, to allow lipids to be absorbed into the bloodstream.
•
Emulsification
is the breakdown of large lipid droplets into small uniformly distributed droplets.
•
The hydrophobic portion binds to and disperses large triglyceride lipids droplets and prevents large
droplets from reforming. It increases the surface area on which triglyceride lipase can act.
•
Bile salts are synthesised from
cholesterol
in a multistep process in
hepatocytes.
•
Cholic acid and Chenodeoxycholic acid are the main “primary” bile acids.
•
An amino acid group (either taurine or glycine) is conjugated to the bile salt
before active export from the hepatocyte.
Example:
Cholic Acid
(cholesterol derivative).
•
Taurocholic Acid
•
Glycholic Acid
Recycling of Bile - Enterohepatic Circulation • Bile salts present in the body are not enough to fully process the fats in a typical meal. • Thus they need to be recycled by the ‘ enterohepatic circulation ’ • Transporters move bile salts from the digestive tract to the intestinal capillaries at the terminal ileum . • They are then transported to the liver via the hepatic portal vein • Hepatocytes take up bile salts from the blood and increase bile salt secretion into bile canaliculi • 95% of released bile salts recycled via the enterohepatic circulation, 5% lost in faece s • The total pool of bile salts roughly circulates around this cycle 6-8 times a day
95% of bile acids recirculate via enterohepatic circulation
Total pool of bile acids circulates 6-8x/day
Reabsorption mainly in ileum/terminal ileum by active transport into portal circulation
Synthesis of new bile acids in the liver compensates for faecal loss
Unconjugated bilirubin is conjugated through a 2 step process involving Uridine diphosphate glucoronsyltransferase (UGT) enzyme.
Gilbert’s syndrome is a genetic defect on chromosome 2 for the locus coding for the UGT-1A1 protein.
Around 5% of you will have this genetic defect and therefore may develop jaundice in times of fasting or stress
Cholesterol derivatives are conjugated with the amino acids glycine and taurine to form primary bile acids
Bacterial action in the gut convert primary bile acids to secondary bile acids
Bile acids are amphipathic ie they have both hydrophillic and lipophillic moieties
3 SLIDES I DONT UNDERSTAND
Outline the regulation of gallbladder contraction
Between meals (the interdigestive period), the sphincter of Oddi is contracted, meaning the bile cannot enter the duodenum. Pressure increases in the common bile duct and bile flows into the gallbladder.
Epithelial cells reabsorb water and electrolytes, thus concentrating the bile.
• Once fatty acids & amino acids
enter the duodenum, they stimulate endocrine cells to release cholecystokinin
(CCK). This stimulates (via vagus nerve) contraction of the gallbladder smooth muscle
and relaxes the sphincter of Oddi, ultimately resulting in bile release.
Acidic chyme in the duodenum stimulates other endocrine cells to release
secretin
. Secretin stimulates duct cells in the liver to release bicarbonate into the bile and stimulates bile production
Vagal stimulation promotes GB contraction
Cholecystokinin (CCK) released from duodenum in response to presence of luminal fat
CCK mediated GB contraction and relaxation of sphincter of Oddi (SO) promoting release of bile juice in to duodenum
GB relaxation and closure of SO mediated by sympathetic nerves, and gut hormones vasoactive intestinal polypeptide (VIP) and somatostatin
Discuss the emulsification of lipids by bile
Emulsification of lipid aggregates:
Bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.
Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and are able to solubilize many lipids by forming micelles - aggregates of lipids such as fatty acids, cholesterol and monoglycerides - that remain suspended in water. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.
Outline the causes of peptic ulcer disease
- H. Pylori infection (hyper acid)
- NSAIDs ( not enough mucus; COX 1 inhibition; prostaglandins)
- Zollinger Ellison Syndrome (Gastrin producing tumour)( too much acid)
External Oblique and Aponeurosis (n.b. linea alba)
Origin: Ribs 5 – 12
• Insertion: Xiphoid process,
aponeurosis to line alba
• Nerve supply: Thoracoabdominal (T7-11) and Subcostal nerves (T12)
• Action: Flexion of torso; contralateral rotation of torso
