GastroIntestinal Flashcards
LO 1.1 Describe the overall processes of the GI tract
Metabolic processes need a specific range of small molecules. Food has a wide range of mostly large molecules locked into complex structures. It may also be contaminated with pathogens.
Digestion makes food into a sterile, neutral, and isotonic solution of small sugars, amino acids and small peptides, small particles of lipids and other small molecules. This is now ready for absorption and excretion.
LO 1.4 Describe regional variation in macro and microstructure of each of the major divisions of the alimentary canal that relate to functional adaptations for transport, storage, digestion and absorption
From the oral cavity to the anus the alimentary canal consists of four layers:
Mucosa - Epithelial lining and thin layer of smooth muscle
Submucosa - Fibroelastic tissue with vessels, nerves, leucocytes and fat cells
Muscularis Externa - Inner circular and outer longitudinal layer of smooth muscle with the myenteric plexus lying in between the layers.
Serosa/Adventitia - Thin outer covering of connective tissue
A variation in the cellular composition of these layers provides adaptations for specific functions whilst remaining a continuous hollow tube of variable diameter and shape.
LO 1.5 Describe the fluid balance of the gut
Each day we ingest about 1kg of food and about a litre of liquids. The food is mixed with 1.5L of Saliva and about 2.5L of gastric secretions to form chyme. Chyme is very hypertonic (has a high osmotic strength) and is very acidic. When chyme is slowly released from the stomach, around 9L of water (and alkali) moves into it from the ECF via osmosis.
The small intestine then absorbs about 12.5L of the fluid, and the large intestine absorbs about 1.35L.
LO 1.6 Describe the properties of the enteric nervous system and its relationship to the autonomic nervous system
The enteric nervous system is a subdivision of the autonomic nervous system that directly controls the GI system. It is made up of two nerve plexuses in the wall of the gut that may act independently of the CNS (short reflex pathway). This activity may be modified by both branches of the ANS (long reflex pathway). Parasympathetic control however is the most significant. It coordinates both secretion and motility using a range of neurotransmitters
LO 1.7 Describe the role of hormones and other peptides which affect the motility and secretion in the gut
Endocrine cells in the walls of the gut release a dozen or more peptide hormones. These include both hormones with endocrine action and paracrine action. The hormones comprise two structurally related groups – the Gastrin group and the Secretin group. These hormones are released from one part of the gut to affect the secretions or the motility of other parts.
LO 2.1 Briefly describe the anatomy of the oral cavity and its contents and relate these to their function
The mouth is the entrance to the GI tract. It serves to disrupt foodstuffs and mix them with saliva to form boluses to be swallowed.
Teeth
The teeth cut (incisors), crush (molars) and mix food with saliva. The powerful muscles of mastication, the Masseter, generate the force behind teeth. A branch of the trigeminal nerve innervates the Masseter.
Tongue
The tongue is a collection of 8 muscles that work to manipulate food for mastication and form it into a bolus. It also aids in swallowing by pushing the bolus to the back of the mouth.
LO 2.2 Describe the structure of the oropharynx and oesophagus and outline their respective functions
The oropharynx lies behind the oral cavity, and forms the portion of the pharynx below the nasopharynx but above the laryngopharynx.
It extends from the uvula, which is the end of the palate, to the level of the hyoid bone. Because both food and air pass through the oropharynx, a flap of tissue called the epiglottis closes over the glottis to prevent aspiration.
The oesophagus is a muscular tube that passes food from the pharynx to the stomach. It is continuous with the lower part of the laryngopharynx. The oesophagus has several layers, from inside to out:
Mucosa composed of non-keratinized stratified squamous epithelium, lamina propria and a layer of smooth muscle (Muscularis Mucosa)
Submucosa containing the mucous secreting glands
Mucularis externa. Upper third of oesophagus is striated, skeletal muscle under conscious control for swallowing. The lower two thirds are smooth muscle under autonomic control (peristalsis).
LO 2.3 Describe the functions of saliva and define zerostomia
1.5 litres of saliva is produced each day. It has several functions:
Lubricates and wets food
Starts the digestion of carbohydrates (Amylase)
Protects oral environment
o Keeps mucosa moist
o Washes teeth
o Maintains alkaline environment - Neutralises acid produced by bacteria
o High Ca2+ concentration
Zerostomia
Insufficient Saliva production. You are still able to eat provided food is moist, but teeth and mucosa degrade very quickly.
LO 2.4 List the components of saliva secreted by each pair of salivary glands
Constituents of Saliva
Water
Electrolytes Na+, Cl- (lower conc than plasma), Ca2+, K+, I- (higher concentration than plasma)
Alkali - HCO3- at a higher concentration than plasma
Bacteriostats
Mucus - (Mixture of mucopolysaccharides)
Enzymes - Salivary amylase (can live without it, relatively minor)
Salivary Glands
There are three paired salivary glands. They are all ducted, exocrine glands, but do not all excrete the same thing.
Exocrine glands are made up of blind-ended tubes (Acini), lined with acinar cells. The acini are connected via a system of ducts to a single outlet, lined by duct cells. Acinar cells and duct cells have different functions.
Parotid Glands
Watery secretion, rich in enzymes but little mucus
Serous saliva
25% of volume secreted
Sub-lingual glands
Viscous secretion, no enzymes but lots of mucus
Mucus saliva
5% of volume secreted
Sub-maxillary glands
All components of saliva (mixed serous and mucus)
Mixture of serous and mucus acini leading to a common duct
70% of volume secreted
LO 2.5 Explain the mechanisms of secretion of serous saliva
Saliva is a hypotonic solution, but there is no cellular mechanism to secrete water. Therefore more concentrated solution is secreted, and solute is then reabsorbed from it to leave the final hypotonic solution.
Acinar Cells secrete an isotonic fluid containing enzymes. Duct Cells then remove Na+ and Cl- and add HCO3-. The gaps between duct cells are tight, so water does not follow the resulting osmotic gradient and so saliva remains hypotonic.
At a low flow rate, the duct cells have the opportunity to remove most Na+, so saliva is very hypotonic. However, the rate at which duct cells can modify saliva is limited, so at a high flow rate a smaller fraction is removed and the saliva becomes less hypotonic. However, the stimulus for secretion (see below) promotes HCO3- secretion, so saliva becomes more alkaline.
Mechanisms of Acinar Secretion
Cl- ions are actively secreted from Acinar cells into the lumen of the duct. Water and other ions (Na+) will then follow passively.
Mechanisms of Ductal Modification
The action of the Na/K-ATPase Antiporter in the Basolateral membrane of duct cells lowers the [Na+] inside the cell. This means there is a concentration gradient, where [Na+] is high in the duct lumen and low in the duct cells. Na+ diffuses passively back into the Duct cells.
The action of the Na/K-ATPase Antiporter also increases the [K+] concentration in side the cell. The resulting concentration gradient drives the expulsion of Cl- from the duct cells into the ECF. Again, a concentration gradient is set up between the duct lumen and cells, with [Cl-] low inside and [Cl-] high outside. This gradient drives the expulsion of HCO3- into the duct lumen.
LO 2.6 Describe the control of salivary secretion
Salivary secretion is mostly controlled by the autonomic nervous system.
Parasympathetic
Parasympathetic stimulation increases the production of primary secretion (Acinar cells) and increases the addition of HCO3- (Duct cells)
o Glossopharyngeal (9th cranial nerve)
o Otic ganglion
o Muscarinic receptors - Blocked by atropine like drugs
o Co-transmitters stimulate extra blood flow
Outflow is mediated by: o Centres in the medulla o Afferent information from: Mouth and tongue o Taste receptors, especially acid Nose Conditioned reflexes o Pavlov’s dogs
Sympathetic
Sympathetic stimulation reduces the blood flow to the salivary glands, limiting salivary flow and producing the typical dry mouth of anxiety.
o Superior cervical ganglion
The rate of ductal recovery of Na+ is also increased by the release of aldosterone from the adrenal cortex.
LO 2.7 Describe the process of swallowing
Once food has been masticated and mixed with saliva to form a bolus, it must be swallowed. Swallowing is in three phases:
1.Voluntary Phase
Tongue moves the bolus back onto the pharynx
2.Pharyngeal Phase
Afferent information from pressure receptors in the palate and anterior pharynx reaches the swallowing centre in the brain stem.
A set of movements is triggered
Inhibition of breathing
Raising of the larynx
Closure of the glottis
Opening of the upper oesophageal ‘sphincter’
3.Oesophageal Phase
The muscle in the upper third of the oesophagus is voluntary striated muscle under somatic control
The muscle of the lower two thirds is smooth muscle under control of the parasympathetic nervous system.
A wave of peristalsis sweeps down the oesophagus, propelling the bolus to the stomach in ~9 seconds.
Coordinated by extrinsic nerves from the swallowing centre of the brain
Lower oesophageal ‘sphincter’ opens
LO 2.8 Outline the anatomical relationships of the oesophagus and how disordered swallowing may occur as a consequence of a primary oesophageal disorder or a condition in a closely related structure
Dysphagia – The symptom of difficulty in swallowing
Odynophagia – The symptom of pain whilst swallowing
Dysphagia may result as a consequence of a primary oesophageal disorder, for example motility problems of the smooth muscle preventing peristalsis. The name for this condition is achalasia.
Dysphagia may also result as a secondary consequence of another issue, E.g. obstruction or compression of the oesophagus due to a tumour.
LO 2.9 Categorise different types of dysphagia based on the underlying pathology
Broadly speaking, dysphagia can be split into two categories
Dysphagia for Solids
Oesophageal Dysphagia
Investigate with a barium swallow/endoscopy
Dysphagia for liquids
Oropharyngeal Dysphagia
Investigate with a flexible endoscopy evaluation of swallowing. This will allow you to view the entire trachea/oesophagus
LO 2.10 Describe the anatomical mechanisms that prevent gastro-oesophageal reflux and outline some of the clinical consequences of free gastro-oesophageal reflux
The stomach produces strong acids (HCl) and enzymes (pepsin) to aid in the digestion of food. The mucosa of the stomach provides protection from it’s harmful content, but the mucosa of the oesophagus does not have this protection.
The oesophagus is protected from these acids by a one way valve mechanism at it’s junction with the stomach. This one way valve is called the lower oesophageal sphincter. This coupled with the angle of His that is formed at this point prevents the contents of the stomach refluxing back into the oesophagus. The crus of the diaphragm helps with the sphincteric action.
Consequences of Free Gastro-Oesophageal Reflux
Barrett’s Oesophagus
An abnormal change of the epithelial cells of the oesophagus. This is a metaplasia from non-keratinised stratified squamous epithelia to columnar epithelium and goblet cells. This is in an attempt to better resist the harmful contents of the stomach. Barrett’s oesophagus is strongly associated with adenocarcinoma, a particularly lethal cancer.
Gastro-oesophageal Reflux Disease (GERD)
The reflux of the stomach’s contents into the oesophagus and pharynx causes several symptoms, including a cough, hoarseness and asthma. All of the symptoms result from the acidic contents of the stomach refluxing back out.
LO 3.15 Describe areas of potential weakness in the abdominal wall
The chief sites of hernia are inguinal, femoral and umbilical.
The potential areas of weakness for these hernias are the inguinal canal, femoral ring and umbilicus respectively.
LO 3.16 Describe the structure of the inguinal canal
The inguinal canal is an oblique passage that extends in a downward and medial direction. It begins at the deep (internal) inguinal ring and continues for approximately 4cm, ending at the superficial (external) inguinal ring. The canal lies in between the muscles of the anterior abdominal wall and runs parallel and superior to the medial half of the inguinal ligament (the inguinal ligament is the inferior border of the aponeurosis of the external oblique muscle, attached between the ASIS and the pubic tubercle).
The spermatic cord in men and the round ligament of the uterus in women passes through the canal. Additionally, in both sexes the ilioinguinal nerve passes through part of the canal.
LO 3.17 Distinguish direct and indirect inguinal hernias
An inguinal hernia is a protrusion of the abdominal cavity contents through the inguinal canal. They are very common (Lifetime risk 27% for men, 3% for women).
Direct Inguinal Hernia
Protrudes into the inguinal canal through a weakened area in the transversalis fascia near the medial inguinal fossa within an anatomical region known as the Inguinal / Hesselbach’s triangle. The borders of Hesselbach’s triangle are:
o Inferiorly – Medial half of the inguinal ligament
o Medially – Lower lateral border of rectus abdominis
o Laterally – Inferior epigastric artery
Indirect Inguinal Hernia
Protrudes through the deep inguinal ring, within the diverging arms of the transversalis fascial sling. Most indirect inguinal hernias are the result of the failure of embryonic closure of the deep inguinal ring after the testicle has passed through it.
LO 3.18 Describe epigastric, umbilical and femoral hernias in relation to their relevant anatomy
Epigastric Hernias
Epigastric Hernias occur in the epigastric region, in the midline between the xiphoid process and the umbilicus, through the linea alba.
The primary risk factors are obesity and pregnancy.
Umbilical Hernias
Umbilical Hernias occur through the umbilical ring. They are usually small and result from increased intra-abdominal pressure in the presence of weakness and incomplete closure of the anterior abdominal wall after ligation of the umbilical cord at birth. Acquired umbilical hernias occur in adults, most commonly in women and obese people.
Femoral Hernias
Femoral Hernias are a protrusion of abdominal viscera into the femoral canal, occurring through the femoral ring. A femoral hernia appears as a mass, often tender, in the femoral triangle. Femoral Hernias are bounded by the femoral vein laterally and the lacunar ligament medially. The hernia compresses the contents of the femoral canal (loose connective tissue, fat and lymphatics) and distends the wall of the canal. Initially femoral hernias are small, as they are contained within the canal, but they can enlarge by passing inferiorly through the saphenous opening into the subcutaneous tissue of the thigh. Femoral Hernias are more common in females as they have wider pelves.
Strangulation of femoral hernias may occur because of the sharp, rigid boundaries of the femoral ring.
Hernia Complications
Strangulation – The constriction of blood vessels, preventing the flow of blood to tissue
Incarceration – Hernia cannot be reduced, or pushed back into place, at least not without very much external effort.
LO 4.1 Describe the functions of the stomach
Stores Food
Disinfects Food
Breaks food down into Chyme oChemical disruption (Acid and enzymes) oPhysical disruption (Motility)
LO 4.2 Describe the components of gastric secretion and their cellular origins
Stomach secretions come from Gastric Pits, indentations in the stomach mucosa that are the openings to gastric glands.
Gastric pits contain Neck Cells, and gastric glands contain Parietal, Chief and G-Cells, along with smooth muscle cells.
Hydrochloric acid
Parietal cells
Acid keeps lumen pH low
Proteolytic Enzymes
Chief cells
Break down proteins to peptides
Mucus
Neck Cells
Sticky, lines stomach lining and basic due to amine groups on proteins
HCO3-
Neck cells
Buffer H+ ions
Gastrin
G-Cells
Binds to surface receptor on parietal cells stimulating acid and intrinsic factor
LO 4.3 Explain the mechanism of secretion of stomach acid
Most body fluids are slightly alkaline, so to secrete H+ ions they need to be created in large quantities. This takes place in the mitochondria of parietal cells by splitting water into H+ and OH- ions.
The generated OH- ions combine with CO2 from metabolism to form HCO3-, which is exported to the blood.
For every mol of H+ secreted into the stomach, 1 mol of HCO3- enters the blood.
Parietal Cells
Parietal cells have lots of mitochondria, allowing them to produce H+ at a high rate. However, these produced ions cannot accumulate in cells. To overcome this problem, parietal cells have invaginations in their cells walls called canaliculi.
Canaliculi have proton pumps, which expel H+ from parietal cells up a high concentration gradient. As the concentration gradient is high, this is a very energy intensive process.
The proton pumps in canaliculi are a key target for drug action, as if inhibited they will reduce the amount of acid in the stomach.
LO 4.4 Explain the control of gastric acid secretion
A complex of neural and endocrine systems controls acid secretion. Parietal cells are stimulated by Acetylcholine, Gastrin and Histamine, which act via separate receptors to promote acid secretion.
Acetylcholine
Ach is released from postganglionic parasympathetic neurones, stimulated by gastric distension as food arrives. It acts on muscarinic receptors on parietal cells.
Gastrin
Gastrin is released from endocrine cells in the stomach, G-Cells. It is a 17-amino acid polypeptide, which binds to surface receptors on parietal cells.
Gastrin secretion is stimulated by the presence of peptides and Ach from intrinsic neurones. It is inhibited by low pH in the stomach, which acts as a ‘feedback’ control.
Histamine
Histamine is released from Mast Cells and diffuses locally to bind H2 surface receptors on parietal cells. Acid secretion is then stimulated via c-amp.
Gastrin and Ach stimulate mast cells, so Histamine works as an amplifier.
Phases of Control
There are three phases of gastric secretion.
Cephalic Phase
The ‘brain led’ phase. The sight and smell of food, and the act of swallowing, activates the parasympathetic nervous system, which stimulates the release of Ach. This stimulates parietal cells directly and via histamine (Increases Acid).
Gastric Phase
Once food reaches the stomach, it causes distension, further stimulating Ach release, and subsequently parietal cells (Increasing Acid).
The arrival of food will also buffer the small amount of stomach acid in the stomach in between meals, causing luminal pH to rise. This disinhibits Gastrin ( Acid).
Acid and enzymes will then act on proteins to produce peptides, further stimulating Gastrin release as the pH falls and the initial disinhibition is removed ( Acid).
Intestinal Phase
Once chyme leaves the stomach in significant quantities, it stimulates the release of the hormones Cholecystokinin and Gastric Inhibitory Polypeptide from the intestines that antagonise Gastrin ( Acid). Coupled with this, the small amount of acid left in the stomach is no longer being buffered by food, and the low pH inhibits Gastrin ( Acid).
The low pH of the stomach between meals can aggravate ulcers. Because of this, pain from ulcers is particularly bad at night.
LO 4.5 Outline the ways in which gastric acid secretion may be reduced by drugs
Acid secretion may be reduced by inhibition of:
o Histamine at H2 Receptors
o E.g. Cimetidine
o Removes the amplification of Gastrin/Ach signal
Proton Pump Inhibitors (PPIs)
o E.g. Omeprazole
o Prevents H+ ions being pumped into parietal cell canaliculi
LO 4.6 Describe the function of the stomach defences
The luminal pH of the stomach is usually below 2. Without any protection, this would dissolve mucosa. Neck cells secrete mucus to protect the mucosa.
Mucus
Mucus is Sticky, so is not easily removed from the stomach lining. It is also Basic, due to Amine groups on the proteins.
The mucus forms a ‘unstirred layer’ that ions cannot move through easily.
H+ ions slowly diffuse in and react with the basic groups on mucus and with HCO3- that is secreted by surface epithelial cells.
Because of the unstirred layer, HCO3- stays close to the surface cells. This means the pH at the surface cells is well above 6.
Mucus and HCO3- secretion from neck cells and surface cells respectively is stimulated by prostaglandins, which are promoted by most factors that stimulate acid secretion.
Breaching the Stomach’s Defences
o Alcohol
Dissolves the mucus, allowing the acid to attack the stomach
o H. Pylori
Surface cells become infected, inhibiting mucus/HCO3- production
o NSAIDS
Inhibit prostaglandins, therefore reducing defences
Some, like aspirin are converted to a non-ionised form by stomach acid, allowing them to pass through the mucus layer into cells before they re-ionise.
If the stomach’s defences are breached it results in peptic ulcers.
Treatment involves reducing acid secretion (see above) and, if present, eliminating H. Pylori with antibiotics.
LO 4.7 Describe the patterns of motility of the stomach, including receptive relaxation and peristalsis
Receptive Relaxation
As food travels down the oesophagus, a neural reflex carried out by the vagus nerve triggers the relaxation of the muscle in the stomach’s wall, so pressure does not increase. This means that pressure in the stomach does not increase as it fills limiting reflux and allowing us to consume large meals (but not if there is damage to the vagus nerve).
Rhythmic Contractions
The stomach has longitudinal and circular muscle that is driven by a pacemaker in the cardiac region. The pacemaker fires ~3 times a minute, causing regular, accelerating peristaltic contractions from the Cardia Pylorus.
This, combined with the stomach’s funnel shape both mixes the contents of the stomach and moves liquid chyme into the pyloric region. This occurs as the accelerating peristaltic wave overtakes larger lumps, driving them back into the fundus. Chyme however is decanted into the pyloric region.
LO 4.8 Describe the process of gastric emptying and its control
The accelerating, rhythmic, peristaltic contraction moves solid lumps backwards into the fundus of the stomach whilst letting liquid chyme move forwards.
As the chyme enters the pyloric region, a small squirt is ejected before the peristaltic wave reaches the pylorus and shuts it, so the rest of the chyme returns to the stomach.
Control of Gastric Emptying
o Three peristaltic waves three ejected squirts of chyme a minute.
o Squirt volume affected by the rate of acceleration of peristaltic wave and hormones from the intestine.
o Gastric Emptying is slowed by fat, low pH and Hypertonicity in the duodenum.
LO 5.2 Describe the presentation, investigation and outline the management of common Gastric disorders
Gastro-oesophageal reflux disease (GORD):
There are anti-reflux mechanisms that prevent reflux of gastric into the lower oesophagus:
o Lower oesophageal sphincter – which is usually closed and transiently relaxes as part of physiology of swallowing to allow bolus to move into stomach
o Oesophagus enters stomach in abdominal cavity
o Pressure in abdominal cavity is higher than that of thoracic
o Right crus of diaphragm acts as sling around the lower oesophagus
Some acid reflux is normal and this is normally dealt with by secondary peristaltic waves, gravity and salivary bicarbonate.
Clinical features of GORD occur when antireflux mechanisms fail and there is prolonged contact of gastric juices with lower oesophageal mucosa.
Clinical features
o Dyspepsia (heartburn)
Worse on lying down, bending over and drinking hot drinks.
Investigations and diagnosis
o Usually clinical diagnosis made without investigation on symptoms alone, no need to investigate unless alarming symptoms (such as dysphagia) or hiatus hernia is suspected (which would be investigated by endoscopy)
Management
o Lifestyle
Lose weight, stop smoking, reduce alcohol consumption, reduce consumption of food groups known to aggravate (e.g. chocolate, fatty foods)
o Medication
Simple antacids – e.g. calcium carbonate (neutralisies acid)
Raft antacids (alginates) – e.g. Gaviscon liquid, taken after eating which creates protective raft that sits on top of stomach contents to prevent reflux
PPIs – e.g. omeprazole – reduction in acid secretion by parietal cells
H2 antagonists – e.g. ranitidine – blocks H2 receptors which reduced acid secretion
Complications
Continual contact of gastric juices with oesophageal mucosa can lead to metaplastic change Barrett’s oesophagus
LO 5.3 Describe the clinical features and natural history of ulcer disease
Peptic ulcer disease (PUD):
Peptic ulcer is break in superficial epithelial cells penetrating down into Muscularis mucosa of either stomach (GU) or duodenum (DU). Most DUs are found in duodenal cap and GUs are most commonly seen in lesser curvature of stomach
Causes
Leading cause in developed world is use of NSAIDs, which inhibit production of prostaglandins, prevents production of protective unstirred layer (innate protection against gastric acid). 50% of patients taking long term NSAIDs have mucosal damage and 30% when endoscoped have peptic ulceration but only 5% will be symptomatic and only 1-2% will have complication such as GI bleed.
Epidemiology
Duodenal Ulcers found in ~10% adult population and are 2-3 times more common than GUs. Prevalence is falling for younger people (especially men) and increasing in older people (especially older women). In developed countries increased prevalence of NSAID-associated DUs and decreasing prevalence of H pylori associated ulceration
Clinical features
o Recurrent, burning epigastric pain (pain is often worse at night and when hungry with Duodenal Ulcers and relieved when eating). Pain may subside with antacids
Persistent, severe pain suggest penetration of ulcer into other organs
Back pain suggest penetrating posterior ulcer
o Can also get nausea, vomiting (though less common)
o With GUs can get weight loss and anorexia
o May be asymptomatic and present for first time with hematemesis when ulcer has perforated blood vessel(s)
Investigations
o Investigate H pylori infection
o In older patients (over 55y/o) or with other alarming symptoms endoscopy to exclude cancer
Management
o If due to H pylori infection Triple Therapy
Proton Pump Inhibitor – Omeprazole
Antibiotics – Clarithromycin / Amoxicillin
H2 Antagonist – Cimetidine
o If taking NSAIDs – stop or review – use alternatives (NSAIDs with lower risk of causing PUD), or use prophylactic PPI as well as NSAID
PPI – e.g. omeprazole
Complications of PUD
o Haemorrhage of blood vessel which ulcer has eroded presents with hematemesis and melena
o Perforation of the ulcer – more common in DUs than GUs – usually perforate into peritoneal cavity
o Gastric outlet obstruction can be pre-pyloric, pyloric or duodenal. Occurs either because of active ulcer with oedema or due to healing of an ulcer with associated fibrosis (scarring). Gastric outlet obstruction normally presents as vomiting without pain.
LO 5.4 Explain the importance of Helicobacter Pylori in causing chronic gastritis
Helicobacter pylori infection
o H pylori is a gram negative, aerobic, helical, urease producing bacterium that resides in the stomach of infected individuals.
o Production of urease produces ammonia, which neutralises acidic environment, which allows bacterium to survive.
o It colonises gastric epithelium – in mucous layer or just beneath. Damage to epithelia occurs through enzymes released and through induction of apoptosis. Damage also occurs due to the inflammatory response to the infection (inflammatory cells and mediators)
Diagnosis
o IgG detected in serum (relatively good sensitivity and specificity)
o 13C-urea breath test (13C-urea ingested – if H pylori present the urease produced will break down 13C-urea to NH3 and CO2 – CO2 (where the carbon is 13C) will be exhaled on breath and detected).
o Can also take gastric sample by endoscopy and detect by histology and culture
Treatment
o Triple therapy.
Proton Pump Inhibitor – Omeprazole
Two Antibiotics – Clarithromycin / Amoxicillin
H2 Antagonist (if severe)
o This standard eradication therapy, depending on local resistance, is successful at eradicating infection in 90% of patients.
7-14 day treatment – 14 days more effective but side-effects of treatment may put patients off finishing two week course
H pylori causing gastric disease:
o Gastritis
Usual effect of infection, which is usually asymptomatic.
Chronic gastritis causes hypergastrinaemia due to gastrin release from astral G cells this increased acid production is usually asymptomatic but can lead to duodenal ulceration (which will eventually produce symptoms)
o Peptic ulcer disease
Duodenal ulcers (DUs) prevalence of DU due to H pylori is falling due to decreased prevalence of H pylori infection. If ulcers due to H pylori infection, eradication of infection relieves symptoms and decreases chances of recurrence. The precise mechanism of ulceration is unclear (only occurs in 15% of infected people) factors implicated though are genetic predispositions, bacterial virulence, increased gastrin secretion and smoking
Gastric ulcers (GUs) associated with gastritis affecting the body as well as antrum, which can cause parietal cell loss reduction in acid production. Ulceration thought to occur due to reduction in gastric mucosal resistance due to cytokine production as a result of infection
o Gastric cancer
LO 5.5 Outline the principles of modern ulcer treatment
If due to H pylori infection Triple Therapy
Proton Pump Inhibitor – Omeprazole
Two Antibiotics – Clarithromycin / Amoxicillin
H2 Antagonist (if severe)
If taking NSAIDs – stop or review – use alternatives (NSAIDs with lower risk of causing PUD), or use prophylactic PPI as well as NSAID
PPI – e.g. omeprazole
LO 5.6 Outline the ways in which gastric acid secretion may be reduced by drugs
Acid secretion may be reduced by inhibition of:
Histamine at H2 Receptors
o E.g. Cimetidine
o Removes the amplification of Gastrin/Ach signal
Proton Pump Inhibitors (PPIs)
o E.g. Omeprazole
o Prevents H+ ions being pumped into parietal cell canaliculi
LO 6.1 Describe the key properties of chyme leaving the stomach
Chyme – The stomach empties chyme into the duodenum that is:
o Acidic
Corrected by HCO3- secreted from the pancreas, liver and duodenal mucosa
HCO3- produced during the production of Gastric Acid
o Hypertonic
Corrected by the osmotic movement of water into the duodenum across its wall
o Partly digested
Digestion completed by enzymes from the pancreas and duodenal mucosa, with bile acids from the liver.
LO 6.2 Describe the digestive functions of the liver and the components of bile
Bile – Made up of two components, Bile Acid Dependent and Bile Acid Independent.
Bile Acid Dependent Secreted by cells lining the canaliculi Bile acids (salts) Cholic Acid/Chenodeoxycholic Acid Bile salts are conjugated to Amino Acids, travelling as micelles in bile. They play a major role in the digestion and absorption of fat. Cholesterol Bile pigments (majority is Bilirubin)
Bile Acid Independent Secreted by cells lining the intra-hepatic bile ducts Alkaline juice (HCO3-) like that from pancreatic duct cells
LO 6.3 Describe how the microscopic structure of the Liver relates to its functions
The microscopic structure of the liver supports its function. The basic functional unit is a lobule surrounding a central vein, which drains blood from the liver to the systemic veins. Blood from the hepatic portal vein and hepatic arteries enters vessels at the periphery of the lobule, and flows through sinusoids lined by hepatocytes to the central vein.
Hepatocytes are very complex cells that support most of liver functions.
Bile is formed in canaliculi, and flows towards the periphery into bile ducts.
LO 6.4 Describe the secretion and the entero-hepatic circulation of bile acids
In response to Gastric emptying, the duodenum secretes Cholecystokinin (CCK). This stimulates the contraction of the Gall Bladder, ejecting concentrated bile acids together with enzymes from the pancreas.
Alkali from the Pancreas and Liver is also released in response to Secretin.
Bile acids are released through the Ampulla of Vater, and aid with the digestion and absorption of fats. They continue to the terminal ileum, where they are actively absorbed by the epithelium.
The venous return from the gut enters the hepatic portal blood, where hepatocytes actively take up Bile Acids and re-secrete them into Canaliculi.
Most bile acids are recovered, but some are unconjugated by the action of gut bacteria and are lost. Hepatocytes subsequently replace it.
LO 6.5 Describe the function of the gall bladder and the relationship to the formation of gallstones
Bile acids return to the liver in between meals and are secreted by canaliculi cell walls a long time before they are next needed. Until they are needed, they are stored in the gall bladder.
To reduce the volume that needs to be stored, bile acids are concentrated by the transport of salt and water across the gall bladder epithelium. However, the concentration process increases the risks of precipitation, leading to Gall Stones.
Gallstones are often asymptomatic, but they can move into the neck of the gall bladder or biliary tree, causing very painful biliary colic or even obstruction. This is often followed by inflammation (Cholecystitis) and infection of the Gall Bladder.
Pain from Gallstones can be worse after eating, as the secretion of Cholecystokinin (CCK) will cause the gall bladder to contract.
LO 6.6 List the secretions of the exocrine pancreas
The exocrine pancreas secretes alkaline juice (HCO3-) and enzymes: o Proteases Trypsin (ogen) Chymotrypsin Elastase Carboxypeptidase o Amylases o Lipases
LO 6.7 Relate the structure of the exocrine pancreas to its secretions
The exocrine pancreas is a gland with Acini and Ducts.
o Acini
Secrete Enzymes, mostly as inactive precursors
Packaged into condensing vacuoles, forming Zymogen granules
Zymogen granule secreted by exocytosis
Activated in the intestine by enzymatic cleavage
o Ducts
Secrete Alkaline Juice (HCO3-)
LO 6.8 Describe the mechanism of secretion of alkaline juice (Ductal Secretion)
HCO3- is present in the blood at elevated concentrations due to gastric acid secretion. The pancreatic duct cells secrete the HCO3- using the same cellular mechanism as other HCO3- secreting cells:
o Na-K-ATPase sets up a Na+ concentration gradient
o Hydrogen ions are exported from the duct cell into ECF using the Na+ concentration gradient
o H+ ions combine with HCO3- to form H2O and CO2, which are taken up into the cell
o H2O and CO2 reform H+ and HCO3- inside the cell
o HCO3- is exported into the duct lumen
o H+ ion is recycled, ‘going around in a circle’ to carry more HCO3- from the ECF to the Lumen
Duct secretion is stimulated by Secretin, which is released from Jejunal cells in response to low pH. Cholecystokinin (CCK) facilitates secretin’s action.
LO 6.9 Describe the control of pancreatic and biliary secretion
Pancreatic Secretions o Acinar Stimulated by Cholecystokinin (CCK) Released from duodenal APUD cells Stimulated by Hypertonicity and Fats o Duct Stimulated from Secretin Released from jejunal cells Stimulated in response to low pH
Biliary Secretion
o Cholecystokinin secreted by the duodenum in response to gastric emptying
o Stimulates contraction of gall bladder muscle
LO 6.10 Describe the mechanisms of digestion of fats
Fats are relatively insoluble in water, making them tend to aggregate into large globules, preventing the effective action of digestive enzymes. Acid in the stomach exacerbates this.
In the duodenum, bile acids enable fats to be incorporated into small (4-6nm) micelles, with fats in the middle and the polar components of bile acids on the outside. These micelles generate a high surface area for the action of lipases, which cleave the fatty acids from glycerol. The micelles also carry these products into the ‘unstirred layer’ immediately next to the mucosa, where fatty acids can be released to slowly diffuse into the epithelial cells.
Once inside the epithelial cells they are reconstituted into triacylglycerols and re-expelled as chylomicrons, structured small particles made up of lipids covered in phospholipids, which facilitate the transport of fat in the lymphatic system from the gut to systemic veins.
Steatorrhoea
If bile acids or pancreatic enzymes are not secreted in adequate amounts, fat appears in faeces. This makes them pale, float and smell foul. This is relatively common, and is called Steatorrhoea, or ‘Fatty Faeces’.
Jaundice
Bile pigments are excretory products. The most common bile pigment is Bilirubin, produced as a product of haemoglobin breakdown.
Bilirubin is conjugated in the liver and secreted in the bile to be excreted in faces.
If it cannot be excreted it accumulates in the blood, giving the condition known as Jaundice.
LO 7.1 Describe the range of toxins that the GI tract and liver may be exposed to
Inevitably, when we ingest food and water we also risk ingesting toxins. These include: o Chemical o Bacteria o Viruses o Protozoa o Nematodes (Roundworms) o Cestodes (Tapeworms) o Trematodes (Flukes)
LO 7.2 Describe the defence mechanisms present in the GI tract to deal with such toxins
Defences can be split into two categories, Innate (Physical and cellular) and Adaptive.
Physical Innate Defences
o Sight / Smell
If food looks or smells bad you don’t eat it
o Memory
If food tastes bad, you don’t eat it next time
o Saliva
pH 7.0
Contains lysozyme, lactoperoxidase, complement, IgA and polymorphs
Washes toxins down into the stomach
o Stomach Acid
Low pH kills the majority of bacteria and viruses
o Small Intestine Secretions
Bile
Proteolytic enzymes
Lack of nutrients
Shedding of epithelial cells
o Colonic mucus
Protects the colonic epithelium from it’s contents
o Anaerobic environment (Small bowel, colon)
o Peristalsis/Segmentation
Normal intestinal transit time is 12 – 18hrs. If peristalsis is slowed, gut infections are prolonged. E.g. shigellosis.
Cellular Innate Defences o Neutrophils o Macrophages Kupffer cells in the Liver o Natural Killer cells (Kill virus infected cells) o Tissue Mast Cells o Eosinophils Parasitic infections
Hepatic Portal System
o All venous blood from the GI tract passes through the liver before returning to systemic circulation
o Kupffer cells are specialised macrophages in the liver
Adaptive Defences (Cellular)
o B Lymphocytes
o Produce antibodies including IgA and IgE that are particularly effective against extracellular microbes
o T Lymphocytes
o Directed against intracellular organisms
o Lymphatic Tissues
o Mucosal Associated Lymphoid Tissue (MALT) in the GI tract is called Gut Associated Lymphoid Tissue (GALT)
o GALT is diffusely distributed by also nodular in three locations:
Tonsils
Peyer’s patches
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