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Flashcards in GastroIntestinal Deck (111):
1

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.

2

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.

3

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.

4

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

5

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.

6

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.

7

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).

8

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.

9

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

10

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.

11

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.

12

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

13

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.

14

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

15

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.

16

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.

17

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.

18

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.

19

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.

20

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)

21

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

22

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.

23

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.

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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

25

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.

26

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.

27

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.

28

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

29

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.

30

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

31

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

32

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

33

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.

34

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

35

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.

36

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.

37

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.

38

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

39

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-)

40

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.

41

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

42

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.

43

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)

44

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
 Appendix

45

LO 7.3 Describe the consequences of failure of these defence mechanisms

Saliva
Severe illness and/or dehydration results in reduced salivary flow (Xerostomia), which then leads to microbial overgrowth in the mouth and dental caries. This can lead to parotitis (salivery gland infections) caused by Staphylococcus aureus.

Gastric Acid
Reduced/Absent Production
Patients who have absent or low Gastric Acid production (Achlorhydria), e.g. pernicious anaemia, drugs such as H2 Antagonists, PPIs) are more susceptible to Shigellosis, Cholera and Salmonella infections.
In a hospital environment, patients taking protein pump inhibitors are at increased risk of acquiring Clostridium difficile.

Resistant Organisms
o Mycobacterium Tuberculosis is resistant to gastric acid (Acid and Alcohol fast bacterium)
o Enteroviruses, such as Hepatitis A, Polio and Coxsackie are resistant to gastric acid
o Helicobacter Pylori produces urease, which acts on urea to produce a protective cloud of ammonia

Mast Cells
o Mast cell granules contain Histamine
o Gut infections which activate complement recruit mast cells, which then release histamine
o This causes vasodilation and increased capillary permeability
 Can get massive fluid loss
o In cholera, may get losses of 1 Litre/hr
 60% Mortality if untreated
Gut Associated Lymphoid Tissue (GALT)
o Tonsillitis
o Ileocaecal lymphatic tissue
o Mesenteric adenitis is a common cause of right iliac fossa pain in children, and can easily be mistaken for appendicitis
o Caused mostly by adenovirus/coxsackie virus
o Typhoid fever causes inflamed Peyer’s patches in terminal ileum, which can perforated and kill patients
o Appendicitis
 Many cases arise from lymphoid hyperplasia at the appendix base leading to an obstructed outflow
o Stasis  Infection
 Purulent appendicitis is commoner during epidemics of chickenpox in children
 Appendix may be obstructed by a faecolith
o Calcified faecal matter, visible on an X-ray
 Appendix may be obstructed by a worm

Gut Ischaemia
The GI tract’s defence mechanisms require the GI tract itself to have an intact blood supply.
Intestinal/hepatic ischaemia due to arterial disease, systemic hypotension, or intestinal venous thrombosis can (frequently does) lead to overwhelming sepsis and rapid death (within hours)

Liver Failure
Liver failure gives an increased susceptibility to infections, toxins, drugs and hormones. There is also increased blood ammonia due to the failure of the urea cycle. Ammonia is produced by colonic bacteria and the deamination of amino acids, and can cause hepatic encephalopathy.

Causes of Liver Failure:
o Viral hepatitis
 Main cause worldwide
o Alcohol
 Main cause in the UK
o Drugs
 Paracetamol, halothane
o Industrial solvents
o Mushroom poisoning

Cirrhosis (Hepatic Fibrosis)
Hepatic fibrosis leads to portal venous hypertension, leading to porosytemic shunting and therefore toxin shunting.
Portosystemic shunting leads to oesophageal varices, haemorrhoids and caput medusa.

46

LO 7.4 Describe the role of the liver in the handling of bile pigments, hormones, drugs and toxins, including alcohol

Bile Pigments
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.

Hormones
The liver breaks down many hormones, notably insulin.

47

LO 7.5 Describe the functions of the Liver in relation to blood proteins


Albumin
Albumin is the most abundant plasma protein. Albumin is essential in maintaining the oncotic pressure needed for proper distribution of body fluids.

Coagulation Factors
The liver produces several coagulation factors:
o I – Fibrinogen
o II – Prothrombin
o V
o VII
o IX
o X
o XI
As well as Protein C, Protein S and Antithrombin.

Thombopoietin
A glycoprotein hormone that regulates the production of platelets by bone marrow.

Amino Acid Synthesis
o Transamination

48

LO 7.6 Interpret basic Liver function tests

Hepatocellular Damage
If hepatocytes are damaged, their ruptured membranes will allow Aminotransferases into the blood stream. Their presence there is indicative of liver damage (ALT/AST).

Cholestasis (Bile ducts)
Bilirubin – Unable to excrete bilirubin, plasma concentration rises
Alkaline Phosphatase – Enzyme in cells lining the liver’s biliary ducts. Plasma levels rise with an obstruction.

Synthetic function
Albumin – Levels reduced in chronic liver disease
Prothrombin time (Clotting) – Measures the clotting tendency of blood

49

LO 7.7 Describe the causes of and effects of jaundice

Damaged hepatocytes have a reduced capacity to excrete bilirubin. This leads to bilirubin accumulating in the blood, giving Jaundice.

The increased levels of bilirubin (Hyperbilirubinaemia) results in a yellowish pigmentation of the skin, conjunctival membranes over the scleae and other mucus membranes.

Jaundice is clinically detectable at >40umol/L (Normal range <22umol/L)

50

LO 7.8 Distinguish pre-hepatic, hepatic and post-hepatic jaundice

Pre-Hepatic Jaundice
Excessive Bilirubin Production, usually due to an increased breakdown of red blood cells (haemolysis)
o Liver unable to cope with excess bilirubin

Lab Findings:
o Unconjugated hyperbilirubinaemia
o Reticulocytosis
o Anaemia
o  LDH
o  Haptoglobin

Causes:
o Inherited
 Red Cell Membrane defects
 Haemoglobin abnormalities
 Metabolic defects
o Congenital Hyperbilirubinaemias
 Gilbert’s syndrome  10% of the population
 Crigler-Najjar syndrome  Rare
 Dublin-Johnson syndrome  Rare
o Acquired
 Immune
 Mechanical  E.g. RBC’s running across metal heart valves
 Acquired membrane defects
 Infections
 Drugs
 Burns








Hepatic Jaundice
Reduced capacity of liver cells to secrete conjugated bilirubin into the blood

Lab Findings:
o Mixed unconjugated and conjugated hyperbilirubinaemia
o  Liver enzymes (ALT/AST)
o Abnormal Clotting

Causes
o Congenital
 Gilbert’s Syndrome
 Crigler-Najjar syndrome
o Hepatic Inflammation
 Viral (Hepatitis A, B, C and E, Epstein Barr Virus (EBV))
 Autoimune hepatitis
 Alcohol
 Haemochromotosis
 Wilson’s disease
o Drugs
 Paracetamol
o Cirrhosis
 Alocohol
 Chronic hepatitis
 Metabolic disorders
o Hepatic tumours
 Hepatocellular carcinoma
 Metastases

Post-Hepatic Jaundice
Obstruction to drainage of bile, causing a back up of bile acids into the liver. Can be intrahepatic or extrahepatic. The passage of conjugated bilirubin is blocked.

Lab Findings
o Conjugated hyperbilirubinaemia
o Bilirubin in urine (dark)
o  Canalicular enzymes (ALP)
o -/ liver enzymes (ALT/AST)

Causes
o Intrahepatic
 Hepatitis
 Drugs
 Cirrhosis
 Primary biliary colic
o Extrahepatic
 Gallstones/Biliary stricture
 Carcinoma
o Head of pancreas
o Ampulla
o Bile duct
o Porta hepatis lymph nodes
o Liver metastases
 Pancreatitis
 Sclerosing cholangitis

51

LO 7.9 Describe the effects of excessive alcohol consumption on the liver, and the key features of alcoholic liver disease

Pathology
Fatty liver
o Alcohol metabolism generates NADH from NAD+
  NADH induces fatty acid synthesis
  NAD+ results in decrease fatty acid oxidation
o Accumulation of fatty acids in the liver
 Glycerol  TAGs
o TAGs accumulate, giving fatty liver
Alcoholic Hepatitis
o Inflammation of hepatocytes
Cirrhosis
Liver cell necrosis followed by nodular regeneration and fibrosis, resulting in increased resistance to blood flow and deranged liver function.

Complications
o Hepatocellular carcinoma
o Liver failure
o Wernicke-Korsakoff syndrome
o Encephalopathy
o Dementia
o Epilepsy

52

LO 7.10 Describe the consequences of cirrhosis of the liver

Causes
o Alcohol
o Wilson’s Disease
o 1-antitrypsin deficiency
o Biliary cirrhosis
o Haemochromotosis
o Hepatitis B or C
o Autoimmune hepatitis

Clinical Features
o Liver dysfunction
o Jaundice
o Anaemia
o Bruising
o Palmar erythema
o Dupuytren’s contracture


Investigations
o - /  ALT/AST
o  ALP
o  Bilirubin
o  Albumin
o Deranged clotting

The management of Cirrhosis includes stopping drinking, treating complications and transplantation.

53

LO 7.11 Outline how liver diseases may lead to portal hypertension and appreciate the associated pathology these may lead to

Portal hypertension is defined as portal venous pressure > 20mmHg. It can be caused by
o Obstruction of the portal vein
 Congenital, thrombosis or extrinsic compression
o Obstruction of flow within the liver
 Cirrhosis, hepatoportal sclerosis, Schistosomiasis, sarcoidosis)
Portal hypertension may lead to:

Ascites
The high pressure in the portal venous system means blood is backed up into the abdomen. The increase in hydrostatic pressure in the abdomen means less fluid is reabsorbed into blood vessels at the end of capillary beds.
If the liver is damaged, reduced oncotic pressure inside the vessels, due to lack of plasma proteins, may also contribute.

Splenomegaly – Due to subsequent increased B.P. in the spleen

Porto-Systemic Anastomoses
There are several anastomoses between the hepatic portal and systemic veins. As such, when the pressure is increased in the portal venous system, blood is backed up through these anastomoses. The increased blood pressure causes the vessels to dilate, protrude into the lumen, rupture/ulcerate and haemorrhage.
o Oesophageal varices
o Rectal varices
o Caput Medusae

Portal  Systemic

A. Left Gastric  Azygous/Oesophageal
Oesophageal Varices
B. Superior rectal  Inferior rectal
Rectal Varices
C. Paraumbilical  Small epigastric of abdominal wall
Caput Medusae
D. Colic/Splenic/Portal  Retroperitoneal veins of posterior abdominal wall or diaphragm
Portal veins here are on the posterior aspects (bare areas) of secondarily retroperitoneal viscera or the liver.

54

LO 7.12 Describe the causes and consequences 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.

55

LO 7.13 Describe the causes and consequences of acute pancreatitis

Pancreatitis is an inflammatory process, caused by the effects of enzymes released from pancreatic Acini.

Acute
o Oedema, Haemorrhage, Necrosis
o Severe pain, vomiting, dehydration, Shock
o  Amylase, Glycaemia, ALP/Bilirubin
o  Ca2+
Chronic
o Fibrosis, Calcification
o Pain, Malabsorption (Steatorrhoea,  albumin, weight loss)
o Jaundice

Causes of Pacreatitis – GET SMASHED
o Gallstones (Block Pancreatic duct/Amuplla of Vater)
o Ethanol (Hyper-stimulation of pancreatic secretions)
o Trauma
o Steroids
o Mumps
o Autoimmune
o Scorpion bite
o Hyperlipidaemia
o ERCP/Iatrogenic
o Drugs

56

LO 7.14 Describe the presentation of carcinoma of the pancreas

90% of pancreatic carcinomas are Ductal Adenocarcinomas, and they account for ~5% of cancer deaths.

Clinical Presentation:
Initially symptomless, but then lots of symptoms all at the same time:
o Obstructive jaundice, pain, vomiting, Malabsorption, diabetes

57

LO 9.1 Describe the role bacteria play in supporting the normal function of the GI tract

There are approximately 1014 bacteria in the GI Tract, the majority of which are in the colon. This normal flora and has several beneficial roles:
o Synthesise and excrete vitamins
 Vitamin K, Vitamin B12, Thiamine
o Prevent colonisation by pathogens
 Space, Bacteriosides
o Kill non-indigenous bacteria
 Bacteriosides
o Stimulate the development of GALT
o Stimulate production of natural antibodies

58

LO 9.2 Describe the broad categorisation of bacteria present in the GI tract

o Cocci/Bacilli
o Gram Positive/Gram Negative
o Aerobic/Anaerobic (Obligate or facultative)
o Some bacteria form protective endospores
o Bacillus Anthrax
o Clostridium Tetani
o Bacteria can stick to surfaces using pili and/or slime

Anaerobes versus Aerobes

Obligate Aerobes must have oxygen. E.g. Pseudomonas and Mycobacterium TB

Obligate Anaerobes die in the presence of oxygen. Bacteroides fragilis / Clostridial organisms. But Clostridia form protective spores

Facultative Anaerobes prefer oxygen but can live without it. E.g. Gram –‘ve enteric bacteria such as E. coli and Gram +’ve skin-dwellers such as Staphylococcus.

Anaerobic Zones in the GI Tract
o Parts of the mouth
o Tongue, deep in taste buds, biofilm between teeth, gingival crevice areas
o Small Bowel
o Colon

Mouth Bacteria
The mouth has many Anaerobic bacteria, therefore can cause very nasty/fatal infections
o Streptococci
 Streptococcus mutans cause dental caries/gingivitis (dental plaque)
o Staphylococci
 Staphylococcus aureus can cause Parotitis
o Candida
 Oral Thrush, caused by Candida Albicans
o Lactobacillus
o Enterococcus
In a malnourished, dehydrated, immunocompromised or systemically unwell patient, these bacteria can cause tissue destruction, known as Noma / Cancrum Oris.


Nose Bacteria
The nose has Staphylococcus and Streptococcus amongst many others. The nose is one of three sites for MRSA screening swabs (Nose, Throat, Perineum), as these are the three sites where Staphylococci are normally found.


Throat Bacteria / Fungi
o Strep. Viridans
 100% of people
 Non-pathogenic throat commensal
 During teeth brushing, dental procedures and general anaesthesia may enter the blood stream (Bacteraemia)
o Strep. Pyogenes
 Tonsillitis (30%, 70% is viral)
o Strep. Pneumoniae
 Community acquired pneumonia (30%)
o Staphylococci
 100% of people
o Neisseria Meningitidis
 100% of people
o Haemophilus Influenzea
 Community acquired pneumonia (13%)
o Lactobacilli
 Makes vagina acidic, so Candida Albicans can’t grow (Thrush)
o Corynebacterium Diptheriae
o Candida Albicans
 Oral/vagina thrush

Tonsillitis
o 70% Viral
 Adenovirus, Rhinovirus, Epstein-Barr Virus (EBV)
o 30% Bacterial
 Step. Pyogenes

Stomach
o Helicobacter Pylori
 At least 50% of the worlds population is infected
 Only 10-20% infected develop gastric/duodenal ulcers
 Associated with 90% of Duodenal and 70% of Gastric ulcers
Colonic
More than 100 species regularly exist in the colon of humans, 95-99% of which are anaerobes, particularly Bacteroides and Clostridial species.
o Always present in the colon
 Bacteroides fragillis
 Bacteroides oralis
 Bacteroides melaninogenicus
 E. Coli – Most common cause of UTI
 Enterococcus faecalis – Second most common cause of UTI
o Other Colonic Bacilli (Gram –‘ve Enteric Bacilli)
 Pseudomonas
 Proteus
 Klebsiella
 Salmonella
 Shigella
 Vibrio cholera
 Campylobacter

Although it is only the colon that normally contains large numbers of bacteria, if we are operating on the small bowel it will be abnormal. This all gut surgery is viewed as ‘dirty surgery’ with a high risk of wound infection.
To reduce surgical wound infection, antibiotics are given prophylactically. They need to be able to cover Anaerobes, Gram –‘ve Bacilli and Gram +’ve Bacilli.

Metronidazole kills anaerobes, so it is given with a broad-spectrum antibiotic such as Gentamicin or Cephalosporin.

Faecal Peritonitis
Has a high mortality rate, even in young fit people, due to the huge numbers of bacteria floating free in the peritoneum.

Perianal Abscess
Glands in the anal canal produce mucus for lubrication to aid with passing faeces. Infection of them leads to abscess around the anus – perianal abscess.


Vaginal Flora
Lactobacillus (Gram +’ve Bacilli) is a normal vaginal flora organism. It converts glycogen into lactic acid, providing an acidic environment to prevent other bacteria and candida albicans from growing (Thrush).

Perineal Skin
o Bacteroides  Cannot survive O2  Not present
o E. Coli  Can survive O2  Present
o Enterococcus faecalis  Can survive O2  Present
o Lactobacillus  Can survive O2  Present


Urinary Tract Infections
90% of UTIs occur in women, as there is a much shorter distance from the anus to the urethra.
The commonest causative organism is E. coli, followed by Enterococcus faecalis and thereafter various Gram –‘ve enteric bacilli (Klebsiella, Proteus, Pseudomonas).

Clostridia
Tetani – Tetanus
o Neonatal tetanus kills 60,000 a year
Difficile – Pseuomembranous colitis
o Severe inflammation of the colon
o Often arises after antibiotic treatment
o Produces spores, which are present in hospitals
Perfringens – Gas/wet gangrene
o Anaerobic digestion of glucose leads to ethanol + CO2 (Fluid plus gas), thus wet or gas gangrene

59

LO 9.3 Describe the common causes for a range of gastrointestinal infections

The ecology of the normal gut flora is easily disrupted, leading to gastrointestinal disturbances such as diarrhoea, as often happens after treatment with antibiotics.
Patients may also be infected with a variety of pathogens (some above).

Noro-virus
Every year there are epidemics of viral infections, often noro-viruses that produce a short period of vomiting and diarrhoea.

Gastroenteritis (Food Poisoning)
Gastroenteritis may follow consumption of food or drink contaminated with organisms or toxins, often of bacterial origin but already present in food.
In both cases there is vomiting and diarrhoea. Onset is very rapid if toxins are ingested, within a very small number of hours, but may take up to 48 hours if caused by organisms.
The most common organisms are strains of Salmonella, Campylobacter and Listeria. Toxins may come from Staphylococcus and Clostridium.

Cholera
Cholera is a severe acute infection, which is endemic in many parts of the world and periodically occurs in epidemics that are a real risk after natural disasters.
The organism responsible, Vibrio Cholerae survives in water supplies and has a very specific effect on the ileum, leading to massive movement of water and salt into the lumen by active secretion.
This leads to very serious diarrhoea, which after initial evacuation has a characteristic ‘rice-water’ appearance made up of intestinal secretions plus mucus.
Rapid, severe dehydration follows, which is severely life threatening. Management must replace lost water and electrolytes with appropriate replacement fluids.

Intestinal Parasites
Intestinal parasites are common around the world and can cause a variety of effects. Some protozoans such as Giardia and Cryptosporidium cause Gastroenteritis. Other Helminth infestations may lead to Malabsorption amongst other effects.


Bacteraemia vs. Septicaemia
In Bacteraemia, the bacteria are rapidly cleared from the bloodstream (by liver/spleen macrophages). No symptoms are produced.

In Septicaemia, bacteria are not cleared and multiply in the blood stream. Sepsis symptoms develop.

60

LO 9.4 Discuss the common causes of ‘Traveller’s diarrhoea’

Enterotoxinogenic E. Coli (ETEC) is a major cause of Travellers’ diarrhoea in developing countries, caused by heat stable or labile toxins produced from this serotype, which results in severe, cholera-like watery diarrhoea.
There is no inflammation and the condition is usually self-limiting.

61

LO 9.5 Describe the causes of intestinal inflammation and infection

Inflammatory Bowel Disease
o Ulcerative Colitis
o Crohn’s Disease
o Diversion Colitis
o Diverticular colitis
o Radiation, Drug, Infectious, Ischaemic Colitis

Infection
Infection with pathogen or toxin (Normal gut flora disturbed, immunosuppressed etc)

62

LO 8.1 Describe the gross and microscopic anatomy of the small and large intestine and relate these to their function

Small Intestines

Chyme
The stomach empties chyme into the duodenum, where it is conditioned:
1. Acidic
1. Corrected by HCO3- secreted from the pancreas, liver and Duodenal mucosa
2. HCO3- produced during the production of Gastric Acid
2. Hypertonic
1. Corrected by the osmotic movement of water into the duodenum across its wall
3. Partly digested
1. Digestion completed by enzymes from the pancreas and Duodenal mucosa, with bile acids from the liver.

Absorption
Absorption requires a large surface area, to which the luminal contents of the small intestine need to be exposed to through gentle agitation for hours.

The small intestine is very long and the surface area for absorption is increased by millions of villi projecting into the lumen.

Epithelial cells (enterocytes) arise by rapid division in the crypts between the villi, and migrate towards the tips, from which they are shed. They mature as they migrate and their luminal surface is covered with millions of micro villi, further increasing the surface area and forming the brush border.

The brush border forms an ‘unstirred layer’ where nutrients meet and react with enzymes secreted by the enterocytes, completing digestion prior to absorption.

Large Intestines

The large intestines absorb water from the indigestible residues of chyme, converting it into semi-solid stool or faeces that is stored temporarily and allowed to accumulate until defecation occurs.

The large intestines have teniae coli (thickened bands of smooth muscle, representing most of the longitudinal coat). They run the length of the large intestine, and because their tonic contraction shortens the part of the wall with which they are associated, the colon becomes sacculated or ‘baggy’ between the teniae, forming Haustra.

63

LO 8.2 Outline the functions of the different parts of the bowel

Small Intestine
All sections:
4. Secrete protease / carbohydrase enzymes to complete digestion
5. Secrete Hormones
1. Secretin
2. Gastrin
3. Cholecystokinin

Duodenum
6. Bile and Pancreatic Secretions added
1. Ampulla of Vater
7. Secretes HCO3- to neutralise Chyme
8. Osmotic movement of water into the Duodenum, making Chyme more hypotonic
9. Absorption
1. Iron

Jejunum
1. Absorption
1. Carbohydrates
2. Amino Acids
3. Small enough to soak through the villi
4. Fatty acids
5. Vitamins
6. Minerals
7. Electrolytes
8. Water

Ileum
1. Absorption
1. Vitamin B12
2. Bile
3. Anything not absorbed by the jejunum


Large Intestine
Takes about 16 hours to finish the digestion of food.
1. Absorption
1. Water
1. Any remaining absorbable nutrients
2. Vitamins created by colonic bacteria
1. Vitamin K, B12, Thiamine, riboflavin
2. Sends indigestible matter to the rectum

Rectum
3. Faeces
1. Stores and compacts faecal matter

64

LO 8.3 Describe the mechanisms of absorption in the following groups of nutrients in the small intestine: Sugars, Amino Acids, Fats, Salts and Water

Sugars
Carbohydrates are ingested in the form of amyloses, amylopectins or disaccharides such as sucrose.
1. Amylose – Straight chain -1,4 bonds
2. Amylopectin – Branched with -1,6 bonds at branches

-Amylases act on -1,4 bonds, and are secreted in saliva and by the pancreas. They yield glucose and maltose from amyloses, and -limit dextrins from amylopectins.

Brush Border Enzymes (see above) complete breakdown to glucose.
1. Isomaltase
1. Breaks down branched molecules at -1,6 bonds
2. Maltase
1. Maltose  Glucose
3. Sucrase
1. Sucrose  Glucose/Fructose diamer
4. Lactase
1. Lactose  Glucose/Galactose diamer

Glucose is absorbed actively using the energy from a Na+ gradient set up by Na/K/ATPase in the basolateral membrane.
Glucose enters the epithelial cell across its apical membrane via a Na+/Glucose Symporter, SGLT1. This transporter also transports Galactose.

Glucose then leaves the epithelia cell into the bloodstream across its basolateral membrane via facilitated diffusion through the GLUT2 transporter.
Fructose enters the cell from the lumen via facilitated diffusion

Amino Acids
Proteins are digested to short peptides, 10-20 AA’s long (oligopeptides) in the stomach by Pepsin secreted from chief cells.
In the Duodenum, Peptidases are secreted from the pancreas.
Different enzymes ‘prefer’ breaking different bonds:
1. Pepsin
1. Bonds near aromatic AA side chains
2. Trypsin
1. Bonds near basic AA side chains
3. Chymotrypsin
1. Bonds near aromatic AA side chains
4. Carboxypeptidase
1. C-terminal AA’s with basic side chains


Both amino acids and small peptides (2/3 AA’s) are absorbed. Further to this, in neonates our guts are ‘open’, so they are able to pick up whole proteins. This allows breast milk to confer passive immunity on babies via IgA absorption.

Active Uptake of Amino Acids
There are at least five Na+/Amino acid Co-transporters (below), which work in a similar way to the uptake of glucose by using the Na+ gradient set up by Na-K-ATPase.
1. Small, neutral AA’s
2. Neutral AA’s, Basic AA’s and Cystine
3. Acidic AA’s
4. Imuno-AA’s
5.  AA’s (Mainly Taurine)

Some AA uptake is by facilitated passive diffusion.

Dipeptides and tripeptides are taken up by an active mechanisms associated with pumping H+ into the lumen, which then returns by co-transport with the peptide.
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.


Salts and Water
Sodium is taken up via diffusion into the cell, and actively transported across the basolateral membrane by Na-K-ATPase. This provides the driving force for the majority of absorption (see above).
Chloride follows the movement of Na+.
The movement of the two ions, coupled with all of the absorption, gives an Osmotic Gradient leading to the uptake of water.


Minerals

Calcium
1. 700mg/day absorbed out of 6g consumed (Just > 10%)
2. Enters the cell by facilitated diffusion
1. Low Intracellular concentration
3. Pumped out of basolateral membrane by Ca2+-ATPase
4. Both processes require Vitamin D
5. Stimulated by Parathyroid Hormone (PTH)

Iron
1. 20mg a day of Iron is consumed
1. Mostly haem
2. Iron can only be absorbed in it’s ferrous form (Fe2+)
1. Gastric acid solubises iron complexes (Makes it ferrous)
2. Stomach also secretes Gastroferrin (Binds iron and keeps it ferrous)

Intestinal mucosal cells secrete transferrin, which finds to ferrous iron (Fe2+) in the lumen. The complex is taken into cells by endocytosis, split and the iron is exported to the blood, where it binds again to transferrin.

Vitamins
1. Water-soluble vitamins are absorbed via passive diffusion
1. Vitamin C, B vitamins
2. Vitamin B12 is absorbed with a co-factor in the terminal ileum only
1. Intrinsic Factor – Binds to B12 in the stomach to keep it soluble
2. Secreted by the stomach mucosa
Pernicious anaemia occurs with Vitamin B12 deficiency. It occurs when there is damage to the stomach, preventing it from secreting intrinsic factor, or the terminal ileum has been damaged (e.g. Crohn’s) or removed.

65

LO 8.4 Describe the basis of oral rehydration therapy

1. The uptake of Na+ generates an osmotic gradient, which water follows.
2. Glucose uptake stimulates Na+ uptake, plus generates its own osmotic gradient

So a mixture of glucose and NaCl will stimulate maximum water uptake.
This is known as Oral Rehydration Fluid.

66

LO 8.5 Describe the patterns of motility of the small intestine

Intestinal contents must move very slowly (transit time in hours), whilst being gently agitated for effective absorption.
This is achieved by a pattern of motility called Segmenting, which is very different to peristalsis.

The small intestine is divided into sections, each with a pacemaker. The frequency of the pacemaker gets less from the duodenum to the terminal ileum (12 times a minute  8), a phenomenon known as the intestinal gradient.
Each pacemaker drives a small section of intestine, causing intermitted contraction of smooth muscle along its length.
These contractions separate the intestine into segments where the muscle is not contracted, whose contents are effectively mixed by movement from the portions that do contract. After a few seconds he contractions relax, and at the next pacemaker firing different areas contract.

Segmenting itself does not propel contents along the intestine, merely mixes the contents. The intestinal gradient however means that there is a net movement, albeit slow, in a caudal direction.

67

LO 8.7 Describe the motility of the colon and rectum

Haustral Shuffling
The large intestine is divided naturally into segments known as Haustra, as the circular muscles are more complete than the longitudinal, which have been reduced to taenia coli (thick circular muscle, thin longitudinal – only 3 layers).
Contraction of the smooth muscle in the walls of the Haustra shuffles the contents back and forth, as the slow absorption of remaining water and salts forms faeces. The contents slowly progresses towards the sigmoid colon, with control like segmenting.

Mass Movement
Infrequently (once or twice a day), there is a Peristaltic, propelling pattern from the transverse through to the descending colon. This forces faeces rapidly into the rectum, which is normally empty, inducing the urge to defecate.
Mass movement is often triggered by eating, the Gastro-colic reflex. They often also happen at certain times of the day, as “people like to be regular”.

68

LO 8.8 Describe the mechanism of defecation

Once mass movement has filled the rectum, the urge to defecate arises due to pressure receptors. Waves of contraction in the rectal muscle then force faeces towards the anus.

Anal Sphincters

Internal
1. Smooth Muscle
2. Parasympathetic control
1. Relaxes

External
1. Voluntary Striated Muscle
2. Voluntary (normally) control
1. Relaxes

Once both sphincters are relaxes, intra-abdominal pressure is increased (forces expiration) and there is an expulsion of faeces.
The voluntary control of the external sphincter is overridden if rectal pressure becomes too high.

69

LO 8.10 Describe the causes of intestinal inflammation and infection

Inflammatory Bowel Disease
1. Ulcerative Colitis
2. Crohn’s Disease
3. Diversion Colitis
4. Diverticular colitis
5. Radiation, Drug, Infectious, Ischaemic Colitis

70

LO 8.11 Describe the clinical presentations associated with common inflammatory bowel disease and the variety of symptoms the separate pathological conditions may cause

Ulcerative Colitis
Ulcerative Colitis (UC) is an inflammatory disorder that affects the rectum and extends proximally, IN CONTINUITY (no breaks in inflammation) to affect a variable extent of the colon.
There is a high incidence in the US, UK and northern Europe and it presents in young adults, more commonly in females.

The mucosa of UC patients is dominated by Th2 (T-helper) cells, which produce Transforming Growth Factor (TGF) and IL-5.

Ulcerative colitis presents with Rectal Bleeding, Diarrhoea and Abdominal Pain
Crohn’s Disease
Crohn's Disease (CD) is a condition of chronic inflammation, potentially involving any location of the GI tract from mouth to anus.

There are two peaks in the incidence of CD, 1st at 15-30 years and 2nd at 60 years.

The mucosa of CD patients is dominated by Th1 (T-helper) cells, which produce Interferon Gamma (IFN-) and IL-2.

The presentation of Crohn’s disease depends on the disease’s location
1. Upper GI involvement
1. Nausea and vomiting
2. Dyspepsia
3. Small bowel obstruction
4. Anorexia, weight loss
5. Loose stools
6. Colonic Disease
7. Diarrhoea
8. Passage of obvious blood

If the terminal ilium is involved, there may be anaemia due to poor absorption of Vitamin B12



Patients may have a Genetic Predisposition, and Environmental Factors may also play a role in developing Inflammatory Bowel Disease.
1. Genetic Predisposition
1. IBD1
2. NOD2/CARD15
3. Having one copy of a risk allele confers 2-4 fold risk for Crohn’s
4. Two couples of risk allele confers 20-40 fold risk for Crohn’s
1. Environmental Factors
1. NSAIDs
1. Altered intestinal barrier (?)
2. Early Appendectomy
1. Increased UC incidence
3. Smoking
1. Protects against UC
2. Increases risk of CD


Triggers of Inflammatory Bowel Disease include:
1. Antibiotics
1. Gets rid of normal flora
2. Diet
3. Acute infections
4. NSAIDs
5. Smoking
1. Increase’s risk of Crohn’s
6. Stress

71

LO 8.12 Describe the common methods used for investigating inflammatory bowel disease

atory bowel disease

1. Colonoscopy
1. Biopsies of involved mucosa
2. Ulceration
3. Stool analysis
1. Parasites
2. Clostridium difficile toxin
3. Culture
4. Barium radiographs
5. CT scan
6. Capsule endoscopy
7. Plain X-Ray if bowel obstruction or perforation suspected

72

LO 8.13 Recognise some of the gross and microscopic changes induced by CD/UC

Macroscopic Changes

Crohn's
The involved bowel is usually thickened and is often narrowed. Deep ulcers and fissures in the mucosa may produce a Cobblestone appearance. Fistulae and abscesses may be seen, which reflect penetrating disease.

Ulcerative Colitis
The mucosa looks reddened, inflamed and bleeds easily. In severe disease there is extensive ulceration with the adjacent mucosa appearing as inflammatory (pseudo) polyps.



Microscopic Changes

Crohn's
1. Inflammation through all layers of the bowel (Transmural)
2. Increase in chronic inflammatory cells
3. Lymphoid hyperplasia
4. Granulomas (TH1 Response)

Ulcerative Colitis
1. Superficial inflammation
2. Chronic inflammatory cell infiltrate in the lamina propria
3. Crypt abscesses
4. Goblet cell depletion

73

LO 8.14 Explain some of the diagnostic difficulties in separating CD/UC

The differentiation between these two diseases can usually be made not only on the basis of clinical and radiological data, but also on the histological differences seen in the rectal and colonic mucosa obtained by biopsy.
It is occasionally not possible to distinguish between the two disorders, particularly if biopsies are obtained in the acute phase. Such patients are considered to have Colitis of Undetermined Type and aEtiology (CUTE).
Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) in UC and anti-Saccharomyces cervisiae antibodies (ASCA) in CD may be of value in differentiating the two conditions.

Sometimes, an exact diagnosis can only be made after examining a surgical colectomy specimen.

74

LO 8.15 Describe some of the commoner endoscopic and radiological abnormalities in IBD

Crohn’s
1. Colonoscopy
1. Performed if colonic involvement is suspected
2. Mild, patchy surface ulceration  Cobblestoning
3. Upper GI Endoscopy
4. Required to exclude oesophageal and Gastroduodenal disease in patients with relevant symptoms
5. Small Bowel Imaging
6. Mandatory in patients with suspected Crohn’s
7. Barium follow through
8. CT scan with oral contrast
9. Small bowel ultrasound
10. MRI
11. Asymmetrical alteration in the mucosal pattern with deep ulceration, and areas of narrowing or structuring
12. String sign of Kantor
13. Perianal MRI or Endoanal Ultrasound
14. Used to evaluate perianal disease
15. Capsule Endoscopy
16. Used in Crohn's disease patients who have a normal radiological examination
Ulcerative Colitis
1. Colonoscopy
1. Biopsy is the ‘gold standard’ investigation for the diagnosis of UC
2. Assess disease activity and extent
2. Imaging
1. Plain Abdominal X-Ray to exclude colonic dilation
2. Other imaging techniques rarely used as endoscopy is preferred
3. Collar Button Ulcers
1. Ulcer through the bowel mucosa to the muscle, then up and down in a ‘T’ shape

75

LO 8.16 Describe some of the common treatment options that are available for IBD

Crohn’s Disease
Induction of Remission
Oral or IV Glucocorticosteroid
Enteral Nutrition
Anti-TNF antibodies (Infliximab)
Maintenance of Remission
Methotrexate, Azathioprine
Anti-TNF antibodies (Infliximab)
Perianal Disease
Ciprofloxacin and Metrronidazole
Azathioprine
Anti-TNF Antibodies (Infliximab), bind to membrane bound TNF-α and induce immune cell apoptosis.
Surgical Management
Failure of therapy with acute or chronic symptoms
Complications, e.g. dilation, obstruction, perforation, abscesses
Failure to grow in children despite treatment
Colectomy and ileorectal anastomosis may be performed.


Ulcerative Colitis
Distal Disease (Proctitis)
Topical or suppository corticosteroidLeft Sided Colitis
Topical corticosteroid enema
Extensive Colitis
Oral corticosteroids
Infliximab
Surgical Management
Patients with complications / Corticosteroids dependence
In acute disease, subtotal colectomy with end ileostomy and preservation of the rectum is the operation of choice.

76

LO 10.5 Describe the imagining investigations available to investigate the GI tract and abdominal viscera, including: Plain X-Rays, Contrast X-rays, including Barium swallow and enema, Ultrasound, Cross-sectional imaging and Angiography

Types of Imaging used to investigate the GI tract
All these investigations below are used to investigate the abdomen.
o Plain X-rays
 Abdominal x-ray (AXR)
 Erect chest x-ray (CXR)
o Contrast studies
 Barium swallow
 Barium enema
 Barium meal/follow through
 Water soluble contrast studies
o Ultrasound
o Cross-sectional imaging
 Computed Tomography (CT)
 Magnetic Resonance Imaging (MRI)
o Angiography

The dose of radiation that these modalities give the patient, vary considerably. Ultrasound and MRI don’t use radiation while a CT scan can deliver a high dose of radiation (up to 15x the dose of an abdominal X-ray)
Risks of radiation include;
o Carcinogenesis
o Genetic
o Developmental risk to foetus

Contrast Studies
Contrast is used to define hollow viscera. Examples of contrast that is used include Barium and water soluble contrast (typically using iodine).
Common GI contrast studies
o Swallow
o Meal
o Follow through
o Enema

A Barium Enema is a Barium study where the contrast medium is inserted rectally. This study enables the colon to be visualized.

Ultrasound
o Use of sound waves to generate image
 Frequency above audible range of human hearing (20 KHz)
 Usually 2-18 MHz
o Cheap compared to CT and MRI
o Portable
o Highly user dependent

Can be used to determine if a patient has Gallstones, or to see if the common bile duct is dilated (an indicator that there is an impacted gallstone in the duct).

Abdominal ultrasound scan can also view the Liver and portal vein, even the Appendix.
These scans are often difficult to interpret and the usefulness of a scan is often down to who is doing and interpreting the scan.

GI angiography
For both bleeding and ischaemia, being able to visualise the Blood supply to the GI tract is very useful.

This is done by injecting a radio-opaque contrast agent intravenously and then using various modalities to capture the images.

Here you can see the Aorta with the Coeliac trunk and the Superior Mesenteric arteries (and branches) very obviously shown. The Inferior Mesenteric artery and it’s branches are harder to see.

77

LO 10.6 Recognise the key structures in cross-sectional images of the abdomen

Abdominal X-ray
Some structures that are potentially visible are shown to the right

Features of an AXR
o Stomach
o Small and Large Bowel
o Soft Tissues
o Liver, spleen, kidneys, psoas muscles, bladder, lung bases
o Bones

Any part of a hollow tube is visible on an X-ray if it is filled with gas (Low density gas acts as a contrast).
Fully fluid filled lumens are not visible.
You can visualise the stomach (if gas filled) but more commonly we use this to visualise the small bowel.

78

LO 10.7 List the common reasons for requesting a plain abdominal radiograph

Common Reasons for Requesting a Plain Abdominal X-ray
o Acute abdominal pain
o Small or large bowel obstruction
o Acute exacerbation of IBD
o Renal colic

79

LO 10.8 Compare and contrast the appearance of small and large bowel on an abdominal radiograph and describe the classical images of bowel obstruction

The small bowel
Usually occupies a central position on the Abdominal X-ray and can display its ‘circular folds’ or Valvulae conniventes, which appear as lines that appear to cross the whole of the bowel lumen


Large bowel
In contrast to the small bowel, this usually occupies a more peripheral position on the abdominal X-ray.

It is often possible to see the Haustra on the X-ray, which appear as incomplete lines going across the lumen.

Faeces can also appear on the X-ray and this can look like clouds in the lumen.


Abnormal Gas Patterns on Abdominal X-ray
Small and large bowel obstruction can be noted and follow the rule of 3/6/9.
o The small bowel is said to be dilated when it is greater than 3cm diameter.
o The large bowel when it is greater than 6cm
o The Caecum (when the ileocaecal valve is working) is said to be dilated when it is greater than 9cm
o This only applies when the X-ray shown is to scale. You can’t tell on these pictures!
Small Bowel Obstruction
This is small bowel. See its central position and lines going across the lumen (Valvulae conniventes)

Small bowel usually presents with vomiting (early) and mild distension. Absolute constipation (not passing anything per rectum, even flatus) is a late feature.
You vomit early simply because the obstruction is nearer the mouth than a large bowel obstruction. For the same reason constipation is a late feature in small bowel obstruction.

There will be colicky pain that presents every 2-3 minutes.

Causes of small bowel obstruction
o Adhesions
o Hernias
 Inguinal, Femoral, Incisional
o Tumours
o Inflammation


Large bowel obstruction
The large bowel is seen more at the periphery of the X-ray and the lines going across the lumen are incomplete (Haustra).

This presents with abdominal pain and distension with constipation as an early feature (nothing can pass into the rectum and out).
The pain is also colicky but not as frequent as small bowel obstruction (every 10-15 minutes).

Vomiting is a late feature of large bowel obstruction (it has further to travel to the mouth) and can be faeculant.

Causes of large bowel obstruction
o Colorectal carcinoma
o Diverticular stricture
o Hernia
o Volvulus
o Pseudo-obstruction

Volvulus
This is when a viscera twists around itself or more commonly when it twists around its mesentery. Most common is a Sigmoid volvulus or more rarely Caecal volvulus.
When this twisting occurs the enclosed loop of bowel dilates and is at risk of perforating or cutting of its blood supply (which runs in the mesentery).

At this stage we would not expect you to be comfortable interpreting a volvulus on an abdominal X-ray. I would like you to be aware that it can happen though and what it means (basic clinical consequences).
Other Abnormalities that can be visualized on an abdominal X-ray:
o Pancreatitis (chronic)
o Aneurysms with calcification
o Nodes
o Bones
o Artifact
o Foreign body
o Kidney Stones

80

LO 10.9 Explain the role of the erect chest radiograph in assessment of the patient with acute abdominal pain

Perforation
An Erect Chest X-ray can be useful in diagnosing perforated bowel.
This can be caused by:
o Peptic ulcer
o Diverticular disease
o Tumor
o Obstruction
o Trauma
o Iatrogenic

The CXR needs to be erect because you are looking for the diaphragm to be elevated away from any other viscera (the Liver on the right) by the presence of air/gas in the peritoneal cavity.

The air/gas will rise to the top of the cavity and so the patient needs to be sat up for 10 minutes prior to the X-ray to ensure this happens.

The peritoneal cavity only normally contains a small amount of fluid, so the presence of air/gas is abnormal and could be the result of perforated bowel.

81

LO 10.10 Recognise the use of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans in investigation of the abdomen, and identify key anatomical structures

Abdominal CT
o High dose radiation
o Good spatial resolution (poor contrast resolution vs MRI)
o Use of IV or oral/rectal contrast

Can be done in a variety of anatomical planes

Magnetic resonance imaging (MRI)
o Magnetic resonance imaging
o First human MRI scan 1977 (in the US)
 However developed by Sir Peter Mansfield (University of Nottingham)
o No radiation
o Good spatial and contrast resolution
o Time consuming

Magnetic resonance cholangio-pancreatogram (MRCP) is an MRI scan that can visualize the Gallbladder and biliary tree.

82

Common Presentations – Dyspepsia, Abdominal Pain, Constipation/Diahorrea, Dysphagia

Dyspepsia
o Upper abdominal pain/Bloating
o Chronic or recurrent pain or discomfort in the Upper abdomen
Causes- There is some debate.
o Chronic peptic ulcer disease
o GORD
o Malignancy
o Functional/non ulcer
 60% of dyspepsia.
 No functional problem found to account for symptoms
 Functional dyspepsia- 3 months of dyspepsia with no structural causes found
What do you do?
o Empirical acid suppression
o Non invasive H-pylori testing/eradication
o Early endoscopy

Abdominal pain
o Very common presentation (2% of all hospital admissions)
o Multiple causes
o Can be misleading- we need a sensible approach

E.g Small bowel
o Is it intra-peritoneal/extra-peritoneal?  Intra-Peritoneal
o What embryological division does it belong to?
o Intra-peritoneal structures refer pain to shared areas of the abdominal wall
 Foregut – Up to 2nd part of Duodenum - Epigastric area
 Midgut – Up until the distal third of the transverse colon - Peri-umbilical
 Hindgut – Supra-pubic

Foregut Pain Examples
o Ulcers-epigastric pain
 Commonly in the first part of the duodenum / lesser curve of the stomach
o Pancreatits – Epigastric pain, back pain (retroperitoneal structure)
o Gallstones – Epigastric pain, can also get Right Upper Quadrant (RUQ) pain. Often refered to as colicky pain (slight misnomer as the pain fairly constant).
Midgut Pain Examples
‘Real’ colicky pain
o Small bowel – Every 2-3 minutes
o Large bowel – Every 10-15 mins

Small bowel obstruction
o Vomiting (fairly early feature)
o Abdominal distension
o Xray may show
 central abdominal distended loops
 Circular folds (extending the full width of the bowel lumen)

Classic midgut scenario- Appendicitis! (Why epigastric  Localised pain)
This should help you understand the difference between Visceral and Parietal pain

Hindgut Pain Examples
Sigmoid volvulus (Responsible for 8% of intestinal obstruction)
o Twists on itself or its mesentery
o Bowel obstruction- Absolute constipation
o Blood supply interrupted- tissue death


Anorexia- Loss of appetite
o Subjectively unpleasant food or surroundings
o Anxiety
o Anger/fear
o Symptom of a physical disorder
 Cancer (in particular GI tract)
 Chemotherapy/certain Antibiotics
 Pregnancy
 Depression
 Endocrine disorders
o Symptom of a psychological disorder

Weight loss
o Massive topic
o Intentional/unintentional?
o More than a 5% unintentional weight loss should be investigated
Nausea
o Subjective sensation of the need to vomit
o Most people hate nausea more than vomiting!

Food Poisoning
Common causes
o Food poisoning (Staphlococcal, salmonella, E-coli)
o Gastroenteritis (viral- Norwalk)
o Cholecystitis
o Appendicitis
o Viral hepatitis
o Pancreatitis
o Intestinal blockage
o Pain

Constipation
o Classified if less than 3 times a week (varies)
o Change in bowel habit more important
Causes
o Diet
o Medication (opiod analgesics, tricyclics)
o Dehydration
o Immobility
o Disease-neurological (Stroke)
 Diabetes
 Colorectal Stricture
o Functional
 No reason for constipation
 Possibly pain – Paediatrics

Diarrhoea
o Different for individuals (good history necessary)
o More stools or change in consistancy
Categories
o Secretory (Infection)
o Osmotic (Lactose intolerance)
o Abnormal Intestinal Motility (Thyrotoxicosis, IBS)
o Exudative (Colitis, Cancer)
o Malabsorption (Pancreatic enzyme/Bile Salt Deficiency)

Dysphagia
o Difficulty swallowing (solids and liquids)
o Differentiate from painful swallowing (Odynophagia)
Broad categories
o Difficulty initiating swallow
 Neurological causes
o Food sticking in oesophagus
 Anatomical problems

Bleeding
From the top
o Haematemesis
o Acute/chronic peptic ulcer
o Mallory-Weiss tear
 Tear in oesophagus from repetitive retching
o Oesophageal/Gastric Varices
o Erosive Oesophagitis
o Gastric/Oesophageal cancer


From the bottom
o Angiodysplasia
 Vascular malformation of the gut blood vessels
o Diverticular disease
o Colonic carcinoma
o Haemorrhoids/Anal fissure
o Inflammatory Bowel Disease
o Massive upper GI bleed
 Malaena

Abdominal distension
o Fat
o Fluid
o Faeces
o Flatus
o Foetus
Fluid-Ascites
o Abnormal amounts of fluid collecting in the Peritoneal cavity
 Liver failure
 Portal hypertension
 Cancer
Flatus
o Aerophagia- Air swallowing
o Gas production in gut (especially if digestion has been incomplete)

During practical
o Hand signs
o Jaundice
o Spider naevi
o Organomegaly

83

LO 1.2 Outline the broad functions of the Mouth and Oesophagus

Mastication
Saliva - Protects mouth
Wets / Bacteriostatic / Alkaline / High Ca2+
Lubricates food for mastication and swallowing -Wet / Mucus
Starts digestion -Sugars
Swallowing
Formation of bolus
Rapid oesophageal transport

84

LO 1.2 Outline the broad functions of the Stomach

Storage
Relaxes to accommodate food
Initial disruption
Contracts rhythmically to mix and disrupt
Secretes acid and Proteolytic enzymes to break down tissues and disinfect
Now known as Chyme
Delivers Chyme slowly into the Duodenum

85

LO 1.2 Outline the broad functions of the Duodenum

Dilution and neutralisation of Chyme
Water drawn in from ECF. Stomach impermeable, Duodenum permeable.
Alkali (bile) added from Liver and Pancreas
Enzymes added from pancreas and intestine

86

LO 1.2 Outline the broad functions of the Small Intestine

Absorption of nutrients and electrolytes
Fluid passes very slowly through the small intestine
Large surface area
Epithelial cells absorb molecules, some actively some passive -Often coupled to Na+ absorption
Pass into hepatic portal circulation (First pass…)
Absorbs the majority of water (1.5L vs. 0.15L large intestine)

87

LO 1.2 Outline the broad functions of the Large Intestine

Final absorption of water (0.15)
Very slow transit
Faeces form and accumulate in the descending and sigmoid colon

88

LO 1.2 Outline the broad functions of the Rectum

Faeces propelled periodically into rectum
Urge to defecate
Controlled relaxation of sphincters and expulsion of faeces

89

LO 1.8 Identify the common disease processes affecting each part of the gut - Dysphagia

Difficultly swallowing. May be caused by problems with the oesophagus, e.g. musculature, obstruction by tumour or neurological, e.g. a stroke. Tumours of the oesophagus, high up are Squamous Cell Carcinoma, lower down are Adenocarcinomas.

90

LO 1.8 Identify the common disease processes affecting each part of the gut - Acid Reflux

Sphincter between the oesophagus and the stomach is weak, acid refluxes into the oesophagus and causes irritation and pain (heartburn).

91

LO 1.8 Identify the common disease processes affecting each part of the gut - Barrett’s Oesophagus

Metaplasia of the lower oesophageal squamous epithelium to gastric columnar. This is to protect against acid reflux.

92

LO 1.8 Identify the common disease processes affecting each part of the gut - Oesophageal Varices

Portal venous system is overloaded due to cirrhosis, blood is diverted to the oesophagus through connecting vessels. This leads to the dilation of sub mucosal veins in the lower part of the oesophagus.

93

LO 1.8 Identify the common disease processes affecting each part of the gut - Peptic Ulceration

Area of damage to the inner mucosa of the stomach or duodenum, usually due to irritation from gastric acid.

94

LO 1.8 Identify the common disease processes affecting each part of the gut - Pancreatitis

Inflamed pancreas, causes considerable pain. Characterised by the release of amylases into the blood stream.

95

LO 1.8 Identify the common disease processes affecting each part of the gut - Jaundice

Liver cannot excrete bilirubin, which accumulates in the blood. If build up of bilirubin is due to excess haemoglobin breakdown it is Pre-hepatic Jaundice. If build up of bilirubin is due to bile duct obstruction and back up of bile causing liver damage it is Post-hepatic or Obstructive Jaundice

96

LO 1.8 Identify the common disease processes affecting each part of the gut - Gallstones

Precipitation of bile acids and cholesterol in the bladder forms gall stones. Often asymptomatic, but may move within the gall bladder causing painful Biliary Colic, or move to obstruct biliary outflow. Tumours of the pancreas may also obstruct outflow.

97

LO 1.8 Identify the common disease processes affecting each part of the gut - Appendicitis

Inflammation of the appendix, presents as a sharp pain in the side at the same level as T10, which then localises to the right lower quadrant.

98

LO 1.8 Identify the common disease processes affecting each part of the gut - Peritonitis

Inflammation of the peritoneum.

99

LO 1.8 Identify the common disease processes affecting each part of the gut - Acute blockage of small intestines

Present with Pain (in their back), vomiting and bloating.

100

LO 1.8 Identify the common disease processes affecting each part of the gut - Haemorrhoids

Vascular structures in the anal canal that aid with stool control. When they become swollen and inflamed they are painful, itchy and blood may be present in stool.

101

LO 1.8 Identify the common disease processes affecting each part of the gut - Prolapse

Literally means ‘to fall out of place’. Prolapse is a condition where organs fall down or slip out of place. E.g. the rectum can prolapse.

102

LO 1.8 Identify the common disease processes affecting each part of the gut - Diverticula

Pressure is too high in the colon, producing an abnormal ‘outpouching’ to form a hollow. The sigmoid colon is the area most prone as the blood supply causes an area of weakness (?)

103

LO 1.8 Identify the common disease processes affecting each part of the gut - Meckels’ Diverticulum

A pouch in the lower part of the small intestine, a vestigial remnant of the yolk sac. It can produce ectopic gastric mucosa that may then produce gastric acid, causing irritation.

104

LO 1.8 Identify the common disease processes affecting each part of the gut - Colo-Rectal Cancer

The large intestine is a common site of malignancies, and colo-rectal cancer is a major cause of mortality.

105

LO 10.1 Describe common GI cancers and their clinical presentations - Oesophageal Carcinoma

Epidemiology
Wide Geographical variation
Incidence low in USA, and high around Caspian sea and parts of China
2% of malignancies in the UK
Males > Females

Clinical Features
Dysphagia
Progressively worsening as tumour grows and occludes lumen
Weight loss

Investigation
Endoscopy, Biopsy, Barium

Pathological Features
Squamous cell carcinoma
Commonest type
May occur at any level
Adenocarcinoma
Uncommon
Lower third
Association with Barrett’s oesophagus

Prognosis
Advances disease at presentation in most cases
Direct spread through the oesophageal wall
Only 40% resectable
5% five year survival

106

LO 10.1 Describe common GI cancers and their clinical presentations - Gastric Cancer

Gastric cancer is the second most common GI malignancy, with approximately 11,000 new cases in England and Wales each year.

Epidemiology
Common
15% of Cancer deaths worldwide
Men > Women
Geographical variation
Common in Japan, Columbia, Finland
Associated with Gastritis
Commoner in Blood Group A

Clinical Features
Symptoms often vague
Epigastric pain, vomiting, weight loss

Investigations
Endoscopy, Biopsy, Barium

Macroscopic Features
Fungating
Ulverating
Infiltrative
Linitis plastica

Microscopic Features
Intestinal
Variable degree of gland formation
Diffuse
Single cells and small groups, signet ring cells

Prognosis
Early Gastric Cancer
Confined to mucosa/sub-mucosa
Good Prognosis
Advanced Gastric Cancer
Further spread
Common in the UK
~10% 5 year survival
Spread
Direct
Through gastric wall into duodenum, transverse colon, pancreas
Lymph nodes
Liver
Trans-Coelomic
Peritoneum
Ovaries


H. Pylori and Gastric Cancer
There is a general association of chronic inflammation with cancer. Gastric cancer is common in countries with high H. Pylori prevalence, e.g. Columbia. The association is supported by serological and epidemiological evidence.


Gastric Lymphoma
The commonest GI Lymphoma
Starts as a low-grade lesion
Strong association with H. Pylori
Eradication of H. Pylori may lead to regression of tumour
Prognosis much better than gastric cancer

Gastrointestinal Stromal Tumours
Uncommon
Derived from interstitial cells of Cajal
The causative mutation, C-kit (CD117) makes it vulnerable to targeted treatment
Unpredictable behaviour
Pleomorphism
Mitoses
Necrosis

107

LO 10.1 Describe common GI cancers and their clinical presentations - Tumours of the Large Intestine

Adenomas
Benign, neoplastic lesions in the large bowel (Dysplasia)
Familial Adenomatous Polyposis (FAP)
Gardner’s Syndrome
Adenocarcinomas
Polyps
Anal Carcinoma

Large Intestinal Adenomas
Benign, neoplastic lesions in the large bowel (Dysplasia)
Macroscopic
Sessile or pedunculated
Microscopic
Variable degree of dysplasia
Malignant Potential
Incidence increases with age in western population
Genetic Syndromes

Familial Adenomatous Polyposis (FAP)
FAP An autosomal dominant condition on Chromosome 5. By the time the patient is 20 there are thousands of adenomas in the large intestine, giving a high risk of cancer.

Gardner’s Syndrome
Gardner’s is similar to FAP, with bone and soft tissue tumours.

108

LO 10.1 Describe common GI cancers and their clinical presentations - Colorectal Adenocarcinoma

Colorectal cancer is the commonest GI malignancy, with ~25,000 new cases reported each year in England and Wales.

Macroscopic
60-70% rectosigmoid fungating/stenotic
Microscopic
Moderately different adenocarcinomas
Mucinous
Signet ring cell type

Spread
Direct through bowel wall to adjacent organs (e.g. bladder)
Via lymphatics to mesenteric lymph nodes
Via portal venous system to liver

Staging
Duke’s
A – Confined to Bowel Wall
B – Through wall, lymph nodes clear
C – Lymph node involvement
C1/C2 – Highest node clear/involved
TMN
Mutations
FAP – Chromosome 5
Ras mutations
p53 loss/inactivation

Incidence
Peak at 60-70
High in UK/USA, low in Japan
Polyposis syndromes
UC and Crohn’s

Aetiology
Low residue diet, slow transit time, high fat intake, genetic predisposition.
Outcome
The survival time reduces with increasing Duke’s staging, and metastases to the liver are common in advanced disease.

Other Large Intestine Tumours
Carcinoid Tumour
Rare and unpredictable neuro-endocrine tumour
Lymphoma
Rare, may be primary or spread from elsewhere
Smooth muscle/stromal tumours
Rare and unpredictable

109

LO 10.1 Describe common GI cancers and their clinical presentations -

Carcinoma of the Pancreas
Morphology
2/3 in the head
Firm pale mass with a necrotic centre
May infiltrate adjacent structures, e.g. the spleen

Histology
80% are ductal adenocarcinomas
Well formed glands
Some acinar tumours contain zymogen granules
All types have poor prognosis

110

LO 10.1 Describe common GI cancers and their clinical presentations -

Carcinoma of the Ampulla of Vater
The bile duct is blocked with only a small tumour, leading to jaundice and early presentation when the tumour is still treatable.

Islet Cell Tumours
Rare
Insulinoma
Hypoglycaemia
Glycagonoma
Characteristic skin rash
Vasoactive Intestinal Peptideoma (VIPoma)
Werner Morrison syndrome
Gastrinoma
Zollinger-Ellison syndrome

111

LO 10.1 Describe common GI cancers and their clinical presentations -

Tumours of the Liver

Benign tumours are fairly rare
Hepatic adenoma
Bile duct adenoma/hamartoma
Haemangioma

Malignant
Hepatocellular carcinoma
Cholangiocarcinoma
Hepatoblastoma
Common -> Rare (New cases per year in England and Wales)

Colorectal (25,000)  Stomach (11,000)  Pancreas (5,500)  Oesophagus