GI Flashcards
(228 cards)
1
Q
Describe the overall processes of the GI tract
A
Initial physical disruption → Ingestion and transport to storage → Initial chemic disruption and creation of suspension (chyme) → Disinfection → Controlled release of Chyme → Dilution and neutralisation → Completion of chemical breakdown → Absorption of nutrients and electrolytes → Final absorption of water and electrolytes → Producing faeces for controlled excretion.
2
Q
What are the basic functions of the Mouth and oesophagus?
A
o Mastication
o Saliva - protects mouth
lubricates food
starts digestion of sugars
o Swallowing
o Formation of bolus
o Rapid oesophageal transport
3
Q
What are the basic functions of the stomach?
A
o Storage - Relaxes to accommodate food
o Initial disruption - contract rhythmically to mix and disrupt. Secretes acid and proteolytic enzymes
o Delivers Chyme slowly into the Duodenum
4
Q
What are the basic functions of the duodenum?
A
Dilution and neutralisation of Chyme o Water drawn in from ECF. Stomach impermeable, Duodenum permeable. o Alkali (bile) added from Liver and Pancreas o Enzymes added from pancreas and intestine
5
Q
What are the basic functions of the small intestines?
A
Absorption of nutrients and electrolytes
o Fluid passes very slowly through the small intestine
o Large surface area
o Epithelial cells absorb molecules, some actively some passive - Often coupled to Na+ absorption
o Pass into hepatic portal circulation
Absorbs the majority of water (1.5L vs. 0.15L large intestine)
6
Q
What are the basic functions of the large intestines?
A
o Final absorption of water (0.15)
o Very slow transit
o Faeces form and accumulate in the descending and sigmoid colon
7
Q
What are the basic functions of the rectum?
A
o Faeces propelled periodically into rectum
o Urge to defecate
o Controlled relaxation of sphincters and expulsion of faeces
8
Q
What are the 4 layers of tissue of the GI tract?
A
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
9
Q
Describe the fluid balance of the gut
A
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.
The small intestine then absorbs about 12.5L of the fluid, and the large intestine absorbs about 1.35L.
10
Q
What is the enteric nervous system?
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, not just Ach as you may expect (parasympathetic).
11
Q
Describe the role of hormones and other peptides which affect the motility and secretion in the gut
A
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.
12
Q
Define Dysphagia
A
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.
13
Q
Define Acid Reflux
A
Sphincter between the oesophagus and the stomach is weak, acid refluxes into the oesophagus and causes irritation and pain (heartburn).
14
Q
Define Barrett’s Oesophagus
A
Metaplasia of the lower oesophageal squamous epithelium to gastric columnar. This is to protect against acid reflux.
15
Q
Define Oesophageal Varices
A
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.
16
Q
Define Peptic Ulceration
A
Area of damage to the inner mucosa of the stomach or duodenum, usually due to irritation from gastric acid.
17
Q
Define Pancreatitis
A
Inflamed pancreas, causes considerable pain. Characterised by the release of amylases into the blood stream.
18
Q
Define Jaundice
A
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
19
Q
Define Gallstones
A
Precipitation of bile acids and cholesterol in the gallbladder 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.
20
Q
Define Malabsorption
A
conditions that affect how well the intestines can absorb things.
21
Q
Define Appendicitis
A
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.
22
Q
Define Peritonitis
A
Inflammation of the peritoneum.
23
Q
Define Inflammatory Bowel Disease
A
Group of inflammatory conditions of the colon and small intestines
Ulceritive colitis and Crohn’s disease
24
Q
Define Acute blockage of small intestines
A
Present with Pain (in their back), vomiting and bloating.
25
Define 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.
26
Define 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.
27
Define 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 (?)
28
Define 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.
29
Define Colo-Rectal Cancer
The large intestine is a common site of malignancies, and colo-rectal cancer is a major cause of mortality.
30
Describe the anatomy of the oral cavity, its content and their functions
The mouth is the entrance of the GI tract. Disrupts foodstuff and mix them with saliva to form boluses
Teeth - incisors (cut) and molars (crush) using force created by masseters (supplied by branch of trigeminal nerve)
Tongue - Collection of 8 muscles that work to manipulate food for mastication and form it into a bolus. Aids in swallowing by pushing bolus to the back of the mouth.
31
Describe structure of oropharynx and its function
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.
32
Describe the structure and function of the oesophagus
Muscular tube
Passes food from the pharynx to the stomach. Continuous with the lower part of the laryngopharynx.
Layers, from inside to out are:
◦ 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).
33
What is the function of saliva?
1.Lubricates and wets food
2.Starts the digestion of carbohydrates (Amylase)
3.Protects oral environment
◦Keeps mucosa moist
◦Washes teeth
◦Maintains alkaline environment - neutralise acid produced by bacteria
◦High Ca2+ concentration
34
How much saliva is produced everyday?
1.5L
35
What is the name given when not enough saliva is produced?
Zerostomia
Still able to eat provided food is moist, but teeth and mucosa degrade very quickly.
36
What are the components of saliva?
◦Water - Hypotonic solution
◦Electrolytes - Na+, Cl-, usually at a lower concentration than plasma. Ca2+, K+, I- (iodide) usually at a higher concentration than plasma
◦Alkali - HCO3- at a higher concentration than plasma
◦Bacteriostats
◦Mucus - (Mixture of mucopolysaccharides)
◦Enzymes - Salivary amylase
37
What are the 3 types of salivary glands?
◦Parotid Glands
◦Sub-lingual glands
◦Sub-mandibular glands
38
Describe the parotid gland secretion
◾Watery secretion, rich in enzymes but little mucus
◾Serous saliva
◾25% of volume secreted
39
Describe the sub-lingual gland secretion
◾Viscous secretion, no enzymes but lots of mucus
◾Mucus saliva
◾5% of volume secreted
40
Describe the sub-mandibular gland secretions
◾All components of saliva (mixed serous and mucus)
◾Mixture of serous and mucus acini leading to a common duct
◾70% of volume secreted
41
Explain the mechanism of serous saliva secretion
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.
42
Explain the mechanism 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.
43
Explain the mechanism 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 inside 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.
44
Which part of the nervous system controls saliva secretion?
Autonomic nervous system
45
How does the parasympathetic nervous system control saliva secretion?
Parasympathetic stimulation increases the production of primary secretion (Acinar cells) and increases the addition of HCO3- (Duct cells)
◦Parotid Gland
◾Glossopharyngeal Nerve (9th cranial nerve)
◾ Otic ganglion
◦Submandibular and Sublingual Glands
◾ Facial Nerve (7th cranial nerve)
◾Submandibular ganglion
◦Muscarinic receptors
◾Blocked by atropine like drugs
◦Co-transmitters stimulate extra blood flow
```
Outflow is mediated by:
◦From centres in the medulla
◦Afferent information from:
◾Mouth and tongue - Taste receptors, especially acid
◾Nose
◾Conditioned reflexes - Pavlov's dogs
```
46
How does the sympathetic nervous system control saliva secretion?
Sympathetic stimulation reduces the blood flow to the salivary glands, limiting salivary flow and producing the typical dry mouth of anxiety.
◦Superior cervical ganglion
The rate of ductal recovery of Na+ is also increased by the release of aldosterone from the adrenal cortex. (increase ENaC, increase Na/K/ATPase), making saliva even more hypotonic.
47
What are the 3 phases of swallowing?
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.
◦Peristaltic waves sweep down the oesophagus, propelling the bolus to the stomach in ~9 seconds, coordinated by extrinsic nerves from swallowing centre of brain.
◦Lower oesophageal ‘sphincter’ opens and bolus enters stomach
48
Define Odynophagia
The symptom of pain whilst swallowing
49
Define Achalasia
Dysphagia may result as a consequence of a primary oesophageal disorder, for example motility problems of the smooth muscle preventing peristalsis
50
What can be the causes for dysphagia?
Consequence of a primary oesophageal disorder, for example motility problems of the smooth muscle preventing peristalsis.
Dysphagia may also result as a secondary consequence of another issue, E.g. obstruction or compression of the oesophagus due to a tumour.
51
What are the two types of dysphagia?
◦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.
◾Most commonly due to a stroke
52
Describe the anatomical mechanisms that prevent gastro-oesophageal reflux
Lower oesophageal sphincter (one way valve)
This coupled with the angle of His
The crus of the diaphragm helps with the sphincteric action.
53
Outline some of the clinical consequences of free gastro-oesophageal reflux
Barrett’s Oesophagus - 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 (GORD)
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.
54
Describe areas of potential weakness in the abdominal wall
inguinal canal, femoral ring and umbilicus
Can lead to inguinal, femoral and umbilical hernias respectively
55
Describe the structure of the inguinal canal
Oblique passage that extends in a downward and medial direction.
Begins at the deep (internal) inguinal ring and continues for approximately 4cm, ending at the superficial (external) inguinal ring.
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).
56
What passes through the inguinal canal?
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.
57
What are potential hernia complications?
Strangulation
| Incarceration
58
What is Strangulation of a hernia?
Constriction of blood vessels, preventing the flow of blood to tissue
59
What is incarceration of a hernia?
Hernia cannot be reduced, or pushed back into place, at least not without very much external effort.
60
What is an inguinal hernia?
Protrusion of the abdominal cavity contents through the inguinal canal.
61
What are the borders of Hesselbach's triangle?
◦Inferiorly – Medial half of the inguinal ligament
◦Medially – Lower lateral border of rectus abdominis
◦Laterally – Inferior epigastric artery
62
Describe a 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
63
Describe an 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.
64
Describe an epigastric hernia
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.
65
Describe an umbilical hernia
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.
66
Describe femoral hernias
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.
67
In which sex are femoral hernias more common and why
more common in females as they have wider pelvis.
68
What can lead to strangulation of femoral hernias?
Strangulation of femoral hernias may occur because of the sharp, rigid boundaries of the femoral ring.
69
Describe the functions of the stomach
◦Stores Food
◦Disinfects Food
◦Breaks food down into Chyme - chemical and physical disruption
70
What are the components of gastric secretions?
```
Hydrochloric Acid (HCl)
Proteolytic Enzymes (Pepsin)
Mucus
HCO3-
Gastrin
```
71
Where does HCl get released from and what is its function?
Parietal (Oxyntic) Cells
Acid keeps luminal pH
72
Where does pepsin get released from and what is its function?
Chief Cells
Non-specifically breaks down proteins into peptides
73
Where does mucus get released from and what is its function?
Neck Cells (Surface cells)
Sticky, so is not removed easily from the stomach lining and basic, due to amine groups on proteins
74
Where does HCO3 get released from and what is its function?
Neck Cells (Surface cells)
Secreted by surface cells into the mucus, provides a buffer for H+ ions
75
Where does gastrin get released from and what is its function?
G-Cells
Binds to surface receptor on parietal cell, stimulating acid and intrinsic factor
76
What are gastric pits and what do they contain?
Indentations in the stomach mucosa that are the openings to gastric glands.
Neck cells
77
What do gastric glands contain?
Parietal
Chief
G-Cells
smooth muscle cells
78
Explain the mechanism of stomach secretion
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 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.
79
Explain the control of gastric acid secretion
Parietal cells are stimulated by Acetylcholine, Gastrin and Histamine.
Acetylcholine - Ach is released from postganglionic parasympathetic neurones, stimulated by gastric distension as food arrives. It acts on muscarinic receptors on parietal cells.
Gastrin is released from endocrine cells in the stomach, G-Cells. It 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.
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.
80
Explain the 3 phases of gastric secretion
Cephalic Phase
Gastric Phase
Intestinal Phase
81
Explain the cephalic 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 ( increase Acid).
82
Explain the gastric phase
Once food reaches the stomach, it causes distension, further stimulating Ach release, and subsequently parietal cells (increase Acid).
The arrival of food will buffer the small amount of stomach acid in the stomach in between meals, causing luminal pH to rise. This disinhibits Gastrin (increase 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 (increase Acid).
83
Explain the 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 (decrease Acid). The small amount of acid left in the stomach is no longer being buffered by food, and the low pH inhibits Gastrin (decrease Acid).
84
Why are pain from ulcers worse at night?
The low pH of the stomach between meals can aggravate ulcers. Because of this, pain from ulcers is particularly bad at night.
85
How can gastric acid secretion be reduced by drugs?
Reduced by inhibition of:
◦Histamine at H2 Receptors - E.g. Cimetidine
Removes the amplification of Gastrin/Ach signal
◦Proton Pump Inhibitors (PPIs) - E.g. Omeprazole
Prevents H+ ions being pumped into parietal cell canaliculi
86
Describe the function of the stomach defences
Protect against stomach acids
Neck cells secrete mucus to protect the mucosa.
Mucus is Sticky, so is not easily removed from the stomach lining. It is also Basic, due to Amine groups on the proteins.
H+ ions slowly diffuse in and react with the basic groups on mucus and with HCO3- that is secreted by surface epithelial cells.
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.
87
What substances are able to breach the stomach lining?
◦Alcohol - Dissolves the mucus, allowing the acid to attack the stomach
◦H. Pylori - Surface cells become infected, inhibiting mucus/HCO3- production
◦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.
88
What happens stomach defences are breached?
Results in peptic ulcers
89
What are the two types of motility in the stomach?
Receptive Relaxation
| Rhythmic Contractions
90
What happens during receptive relaxation?
As food travels down the oesophagus, a neural reflex carried out by the vagus nerve triggers 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
91
What happens during 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 to the Pylorus.
92
Describe the process of gastric emptying
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.
93
Describe the control of gastric emptying
◦Three peristaltic waves lead to three ejected squirts of chyme a minute.
◦Squirt volume affected by the rate of acceleration of peristaltic wave and hormones from the intestine.
94
What slows down gastric emptying?
Fat
low pH
Hypertonicity in the duodenum
95
What is the usual mechanism which prevents gastric reflux
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.
96
What are the clinical features of GORD?
Dyspepsia (heartburn)
| • Worse on lying down, bending over and drinking hot drinks.
97
What are the investigations and diagnosis for GORD?
Usually 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)
98
What are the managements for GORD?
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
99
What are complications of GORD?
Continual contact of gastric juices with oesophageal mucosa can lead to metaplastic change → Barrett’s oesophagus
100
What is Peptic ulcer disease (PUD)?
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
101
What are the causes of PUD?
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.
102
What are the clinical features of PUD?
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)
103
What are the investigations for PUD?
o Investigate H pylori infection
| o In older patients (over 55y/o) or with other alarming symptoms → endoscopy to exclude cancer
104
What is the management of PUD?
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
105
What are the 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.
106
Explain how helicobacter pylori causes infection
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)
107
How is H.pylori infections diagnosed?
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
108
How are H.pylori infections treated?
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
109
What gastric conditions are caused by H.pylori?
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
110
What are the modern ulcer treatments?
o If due to H pylori infection → Triple Therapy
• Proton Pump Inhibitor – Omeprazole
• Two Antibiotics – Clarithromycin / Amoxicillin
• H2 Antagonist (if severe)
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
111
What are the properties of chyme?
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.
112
What is bile made up of?
Bile Acid Dependent
| Bile Acid Independent
113
What are the components of bile acid dependant?
o Secreted by cells lining the canaliculi
o 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.
o Cholesterol
o Bile pigments (majority is Bilirubin)
114
What are the components of bile acid independant?
o Secreted by cells lining the intra-hepatic bile ducts
| o Alkaline juice (HCO3-) like that from pancreatic duct cells
115
How does the structure of the liver relate to its function?
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.
116
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.
117
Describe the function of the gall bladder
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.
118
Describe the relationship between the gallbladder and gallstones
The concentrated bile 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.
119
List the secretions of the exocrine pancreas
```
o Proteases
• Trypsin (ogen)
• Chymotrypsin
• Elastase
• Carboxypeptidase
o Amylases
o Lipases
```
120
Relate the structure of the exocrine pancreas to its secretions
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-)
121
Describe the mechanism of secretion of alkaline juice
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.
122
Describe the control of 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
```
123
Describe the control of bile secretions
o Cholecystokinin secreted by the duodenum in response to gastric emptying
o Stimulates contraction of gall bladder muscle
124
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.
125
Describe the term 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.
126
Describe the term 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
127
Describe the range of toxins that the GI tract and liver may be exposed to
```
o Chemical
o Bacteria
o Viruses
o Protozoa
o Nematodes (Roundworms)
o Cestodes (Tapeworms)
o Trematodes (Flukes)
```
128
What are the two types of defence mechanisms present in the GI tract to deal with such toxins
Split into two categories, Innate (Physical and cellular) and Adaptive.
129
Describe the innate defences present in the GI tract to deal with such toxins
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
130
Describe the adaptive defences present in the GI tract to deal with such toxins
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 but also nodular in three locations:
• Tonsils
• Peyer’s patches
• Appendix
131
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 (salivary 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, leading to 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
Mesenteric adenitis is a common cause of right iliac fossa pain in children, and can easily be mistaken for appendicitis
Caused mostly by adenovirus/coxsackie virus
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.
132
Describe the role of the liver in the handling of bile pigments, hormones, drugs and toxins, including alcohol
Bile Pigments - 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.
Drugs, Toxins and Alcohol
133
Describe the functions of the Liver in relation to blood proteins
Albumin - most abundant plasma protein. 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 - glycoprotein hormone that regulates the production of platelets by bone marrow.
Amino Acid Synthesis
o Transamination
134
Interpret basic Liver function tests
Hepatocellular Damage - If hepatocytes damaged, 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
```
135
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 >40μmol/L (Normal range
136
Lab findings and causes of 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 increase LDH
o decrease 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
```
137
Lab findings and causes of hepatic jaundice
Reduced capacity of liver cells to secrete conjugated bilirubin into the blood
Lab Findings:
o Mixed unconjugated and conjugated hyperbilirubinaemia
o increase 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))
• Autoimmune hepatitis
• Alcohol
• Haemochromotosis
• Wilson’s disease
o Drugs
• Paracetamol
o Cirrhosis
• Alcohol
• Chronic hepatitis
• Metabolic disorders
o Hepatic tumours
• Hepatocellular carcinoma
• Metastases
```
138
Lab findings and causes of 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 increase Canalicular enzymes (ALP)
o -/increase 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 Portal hepatic lymph nodes
o Liver metastases
• Pancreatitis
• Sclerosing cholangitis
```
139
Describe the effects of excessive alcohol consumption on the liver, and the key features of alcoholic liver disease
Fatty liver
o Alcohol metabolism generates NADH from NAD+
• increase NADH induces fatty acid synthesis
• decrease 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
```
140
Describe the causes, consequences, investigations and management of cirrhosis of the liver
```
Causes
o Alcohol
o Wilson’s Disease
o α1-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 - / increase ALT/AST
o increase ALP
o increase Bilirubin
o decrease Albumin
o Deranged clotting
```
The management of Cirrhosis includes stopping drinking, treating complications and transplantation.
141
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
Several anastomoses between the hepatic portal and systemic veins. As such, when pressure is increased in the portal venous system, blood is backed up through these anastomoses. The increased blood pressure causes 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.
142
Describe the causes and consequences of gallstones
Bile acids return to liver in between meals and are secreted by canaliculi cell walls a long time before next needed. Until needed, they are stored in the gall bladder.
To reduce 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.
143
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 increase Amylase, Glycaemia, ALP/Bilirubin
o decrease Ca2+
Chronic
o Fibrosis, Calcification
o Pain, Malabsorption (Steatorrhoea, decrease 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
```
144
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
145
What are the characteristics of chyme?
The stomach empties chyme into the duodenum, where it is conditioned:
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.
146
Describe absorption in the small intestines
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.
147
What is the function of the large intestine?
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.
148
Describe the structure of the large intestines
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.
149
Outline the functions of the different parts of the small intestines
```
All sections:
o Secrete protease / carbohydrase enzymes to complete digestion
o Secrete Hormones
• Secretin
• Gastrin
• Cholecystokinin
```
```
Duodenum
o Bile and Pancreatic Secretions added
• Ampulla of Vater
o Secretes HCO3- to neutralise Chyme
o Osmotic movement of water into the Duodenum, making Chyme more hypotonic
o Absorption
• Iron
```
```
Jejunum
o Absorption
• Carbohydrates
• Amino Acids
o Small enough to soak through the villi
• Fatty acids
• Vitamins
• Minerals
• Electrolytes
• Water
```
```
Ileum
o Absorption
• Vitamin B12
• Bile
• Anything not absorbed by the jejunum
```
150
Outline the functions of the different parts of the large intestines
Takes about 16 hours to finish the digestion of food.
o Absorption
• Water
• Any remaining absorbable nutrients
• Vitamins created by colonic bacteria
o Vitamin K, B12, Thiamine, riboflavin
o Sends indigestible matter to the rectum
Rectum
o Faeces
• Stores and compacts faecal matter
151
Describe sugar absorption in the small intestines
Carbohydrates are ingested in the form of amyloses, amylopectins or disaccharides such as sucrose.
o Amylose – Straight chain α-1,4 bonds
o Amylopectin – Branched with α-1,6 bonds at branches
α-Amylases act on α-1,4 bonds, and are secreted in saliva and by the pancreas. They yield glucose and maltose from amyloses, and α-limit dextrins from amylopectins.
Brush Border Enzymes (see above) complete breakdown to glucose.
o Isomaltase
• Breaks down branched molecules at α-1,6 bonds
o Maltase
• Maltose → Glucose
o Sucrase
• Sucrose → Glucose/Fructose diamer
o Lactase
• 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
152
Describe amino acid absorption in the small intestines
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:
o Pepsin
• Bonds near aromatic AA side chains
o Trypsin
• Bonds near basic AA side chains
o Chymotrypsin
• Bonds near aromatic AA side chains
o Carboxypeptidase
• 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, which work in a similar way to the uptake of glucose by using the Na+ gradient set up by Na-K-ATPase.
o Small, neutral AA’s
o Neutral AA’s, Basic AA’s and Cystine
o Acidic AA’s
o Imuno-AA’s
o β 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.
153
Describe fat absorption in the small intestines
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.
154
Describe salt and water absorption in the small intestines
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.
155
Describe mineral absorption in the small intestines
Calcium
o 700mg/day absorbed out of 6g consumed (Just > 10%)
o Enters the cell by facilitated diffusion
• Low Intracellular concentration
o Pumped out of basolateral membrane by Ca2+-ATPase
o Both processes require Vitamin D
o Stimulated by Parathyroid Hormone (PTH)
Iron
o 20mg a day of Iron is consumed
• Mostly haem
o Iron can only be absorbed in it’s ferrous form (Fe2+)
• Gastric acid solubises iron complexes
• 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.
156
Describe vitamin absorption in the small intestines
Vitamins
o Water-soluble vitamins are absorbed via passive diffusion
• Vitamin C, B vitamins
o Vitamin B12 is absorbed with a co-factor in the terminal ileum only
• Intrinsic Factor – Binds to B12 in the stomach to keep it soluble
• 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.
157
Describe the basis of oral rehydration therapy
o The uptake of Na+ generates an osmotic gradient, which water follows.
o 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.
158
Describe the patterns of motility of the small intestine
Contents must move very slowly, whilst being gently agitated for effective absorption.
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 muscle is not contracted, whose contents are effectively mixed by movement from the portions that do contract. After a few seconds the 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.
159
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”.
160
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
o Smooth Muscle
o Parasympathetic control
• Relaxes
External
o Voluntary Striated Muscle
o Voluntary (normally) control
• 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.
161
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
```
162
What is 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.
163
What happens during ulcerative colitis?
The mucosa of UC patients is dominated by Th2 (T-helper) cells, which produce Transforming Growth Factor (TGF) and IL-5.
164
How does UC present?
Rectal Bleeding, Diarrhoea and Abdominal Pain
165
What is 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.
166
What happens during Crohn's disease?
The mucosa of CD patients is dominated by Th1 (T-helper) cells, which produce Interferon Gamma (IFN-γ) and IL-2.
167
How does a patient with Crohn's disease present?
```
o Upper GI involvement
• Nausea and vomiting
• Dyspepsia
• Small bowel obstruction
• Anorexia, weight loss
• Loose stools
o Colonic Disease
• Diarrhoea
• Passage of obvious blood
```
168
Why could a person with Crohn's disease develop anaemia?
If the terminal ilium is involved, there may be anaemia due to poor absorption of Vitamin B12
169
What are genetic predisposition for inflammatory bowel diseases?
* IBD1
* NOD2/CARD15
* Having one copy of a risk allele confers 2-4 fold risk for Crohn’s
* Two couples of risk allele confers 20-40 fold risk for Crohn’s
170
What are environmental factors for inflammatory bowel diseases?
```
• NSAIDs
• Early Appendectomy
o Increased UC incidence
• Smoking
o Protects against UC
o Increases risk of CD
```
171
What are triggers for inflammatory bowel disease?
```
o Antibiotics
• Gets rid of normal flora
o Diet
o Acute infections
o NSAIDs
o Smoking
• Increase’s risk of Crohn’s
o Stress
```
172
Describe the common methods used for investigating inflammatory bowel disease
```
o Colonoscopy
• Biopsies of involved mucosa
• Ulceration
o Stool analysis
• Parasites
• Clostridium difficile toxin
• Culture
o Barium radiographs
o CT scan
o Capsule endoscopy
o Plain X-Ray if bowel obstruction or perforation suspected
```
173
Recognise some of the microscopic changes induced by CD/UC
```
Crohn's
o Inflammation through all layers of the bowel (Transmural)
o Increase in chronic inflammatory cells
o Lymphoid hyperplasia
o Granulomas (TH1 Response)
```
```
Ulcerative Colitis
o Superficial inflammation
o Chronic inflammatory cell infiltrate in the lamina propria
o Crypt abscesses
o Goblet cell depletion
```
174
Recognise some of the macroscopic changes induced by CD/UC
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.
175
Explain some of the diagnostic difficulties in separating CD/UC
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.
176
Describe some of the commoner endoscopic and radiological abnormalities in Crohn's disease
Colonoscopy
• Performed if colonic involvement is suspected
• Mild, patchy surface ulceration → Cobblestoning
Upper GI Endoscopy
• Required to exclude oesophageal and Gastroduodenal disease in patients with relevant symptoms
```
Small Bowel Imaging
• Mandatory in patients with suspected Crohn’s
• Barium follow through
• CT scan with oral contrast
• Small bowel ultrasound
• MRI
• Asymmetrical alteration in the mucosal pattern with deep ulceration, and areas of narrowing or structuring
• String sign of Kantor
```
Perianal MRI or Endoanal Ultrasound
• Used to evaluate perianal disease
Capsule Endoscopy
• Used in Crohn's disease patients who have a normal radiological examination
177
Describe some of the commoner endoscopic and radiological abnormalities in Ulcerative collitis
Colonoscopy
• Biopsy is the ‘gold standard’ investigation for the diagnosis of UC
• Assess disease activity and extent
Imaging
• Plain Abdominal X-Ray to exclude colonic dilation
• Other imaging techniques rarely used as endoscopy is preferred
• Collar Button Ulcers
o Ulcer through the bowel mucosa to the muscle, then up and down in a ‘T’ shape
178
Describe some of the common treatment options that are available for Crohn's
o Induction of Remission
• Oral or IV Glucocorticosteroids
• Enteral Nutrition
• Anti-TNF antibodies (Infliximab)
o Maintenance of Remission
• Methotrexate, Azathioprine
• Anti-TNF antibodies (Infliximab)
o Perianal Disease
• Ciprofloxacin and Metrronidazole
• Azathioprine
• Anti-TNF antibodies (Infliximab)
Anti-TNF Antibodies (Infliximab), bind to membrane bound TNF-α and induce immune cell apoptosis.
o Surgical Management
• Failure of therapy with acute/chronic symptoms
• Complications, e.g. dilation, obstruction, perforation, abscesses
• Failure to grow in children despite treatment
• Colectomy and ileorectal anastomosis may be performed.
179
Describe some of the common treatment options that are available for UC
```
Distal Disease (Proctitis)
• Topical or suppository corticosteroids
```
Left 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.
180
Describe the role bacteria play in supporting the normal function of the GI tract
```
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
```
181
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
182
What are obligate aerobes?
Obligate Aerobes must have oxygen. E.g. Pseudomonas and Mycobacterium TB
183
What are obligate anaerobes?
Obligate Anaerobes die in the presence of oxygen. Bacteroides fragilis / Clostridial organisms. But Clostridia form protective spores
184
What are faculative anaerobes?
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.
185
What are the 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
186
What type of bacteria is present in the mouth?
The mouth has many Anaerobic bacteria, therefore can cause very nasty/fatal infections
o Streptococci - 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.
187
What are the bacteria in your nose?
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.
188
What are the bacteria and fungi found in the throat?
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
189
Bacteria and Viruses causing tonsillitis?
o 70% Viral
• Adenovirus, Rhinovirus, Epstein-Barr Virus (EBV)
o 30% Bacterial
• Step. Pyogenes
190
Bacteria in the stomach?
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
191
Bacteria in the colon?
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.
192
What is the 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).
193
What is found on 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
194
What are the commonest causes for UTIs?
The commonest causative organism is E. coli, followed by Enterococcus faecalis and thereafter various Gram –‘ve enteric bacilli (Klebsiella, Proteus, Pseudomonas).
195
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.
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.
196
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.
197
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)
198
Explain oesophageal carcinoma
```
Epidemiology
o Wide Geographical variation
• Incidence low in USA, and high around Caspian sea and parts of China
o 2% of malignancies in the UK
• Males > Females
Clinical Features
o Dysphagia
• Progressively worsening as tumour grows and occludes lumen
o Weight loss
Investigation
o Endoscopy, Biopsy, Barium
Pathological Features
o Squamous cell carcinoma
• Commonest type
• May occur at any level
o Adenocarcinoma
• Uncommon
• Lower third
• Association with Barrett’s oesophagus
Prognosis
o Advances disease at presentation in most cases
o Direct spread through the oesophageal wall
o Only 40% resectable
o 5% five year survival
```
199
Explain gastric cancer
Gastric cancer is the second most common GI malignancy, with approximately 11,000 new cases in England and Wales each year.
```
Epidemiology
o Common
• 15% of Cancer deaths worldwide
o Men > Women
o Geographical variation
• Common in Japan, Columbia, Finland
o Associated with Gastritis
o Commoner in Blood Group A
```
Clinical Features
o Symptoms often vague
• Epigastric pain, vomiting, weight loss
Investigations
o Endoscopy, Biopsy, Barium
```
Macroscopic Features
o Fungating
o Ulverating
o Infiltrative
• Linitis plastica
```
```
Microscopic Features
o Intestinal
• Variable degree of gland formation
o Diffuse
• Single cells and small groups, signet ring cells
```
Early Gastric Cancer
o Confined to mucosa/sub-mucosa
o Good Prognosis
Advanced Gastric Cancer
o Further spread
o Common in the UK
o ~10% 5 year survival
```
Spread
o Direct
• Through gastric wall into duodenum, transverse colon, pancreas
o Lymph nodes
o Liver
o Trans-Coelomic
• Peritoneum
• Ovaries
```
200
What is the association between 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.
201
Explain gastric lymphoma
o The commonest GI Lymphoma
o Starts as a low-grade lesion
o Strong association with H. Pylori
o Eradication of H. Pylori may lead to regression of tumour
o Prognosis much better than gastric cancer
202
Explain Gastrointestinal Stromal Tumours
o Uncommon
o Derived from interstitial cells of Cajal
o The causative mutation, C-kit (CD117) makes it vulnerable to targeted treatment
o Unpredictable behaviour
• Pleomorphism
• Mitoses
• Necrosis
203
Name Tumours of the Large Intestine
```
o Adenomas
• Benign, neoplastic lesions in the large bowel (Dysplasia)
• Familial Adenomatous Polyposis (FAP)
• Gardner’s Syndrome
o Adenocarcinomas
o Polyps
o Anal Carcinoma
```
Carcinoid Tumour
o Rare and unpredictable neuro-endocrine tumour
Lymphoma
o Rare, may be primary or spread from elsewhere
Smooth muscle/stromal tumours
o Rare and unpredictable
204
What are Large Intestinal Adenomas?
```
Benign, neoplastic lesions in the large bowel (Dysplasia)
o Macroscopic
• Sessile or pedunculated
o Microscopic
• Variable degree of dysplasia
o Malignant Potential
o Incidence increases with age in western population
o Genetic Syndromes
```
205
What are 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
206
What is Gardener's syndrome?
Gardner’s is similar to FAP, with bone and soft tissue tumours.
207
Explain colorectal adenocarcinoma
```
Colorectal cancer is the commonest GI malignancy, with ~25,000 new cases reported each year in England and Wales.
Macroscopic
o 60-70% rectosigmoid fungating/stenotic
Microscopic
o 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
o Duke’s
• A – Confined to Bowel Wall
• B – Through wall, lymph nodes clear
• C – Lymph node involvement
• C1/C2 – Highest node clear/involved
o TMN
Mutations
o FAP – Chromosome 5
o Ras mutations
o p53 loss/inactivation
Incidence
o Peak at 60-70
o High in UK/USA, low in Japan
o Polyposis syndromes
o 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.
```
208
Explain carcinoma of the pancreas
```
Morphology
o 2/3 in the head
o Firm pale mass with a necrotic centre
o May infiltrate adjacent structures, e.g. the spleen
Histology
o 80% are ductal adenocarcinomas
o Well formed glands
o Some acinar tumours contain zymogen granules
o All types have poor prognosis
```
209
What happens during 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.
210
Name some Islet cell tumours
```
o Rare
o Insulinoma
o Hypoglycaemia
o Glycagonoma
o Characteristic skin rash
o Vasoactive Intestinal Peptideoma (VIPoma)
o Werner Morrison syndrome
o Gastrinoma
o Zollinger-Ellison syndrome
```
211
What are tumours of the liver?
```
Benign tumours are fairly rare
o Hepatic adenoma
o Bile duct adenoma/hamartoma
o Haemangioma
Malignant
o Hepatocellular carcinoma
o Cholangiocarcinoma
o Hepatoblastoma
Common → Rare (New cases per year in England and Wales)
```
Colorectal (25,000) → Stomach (11,000) → Pancreas (5,500) → Oesophagus
212
What are the 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
```
213
Explain 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.
214
Explain 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.
215
Explain 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.
216
What are 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.
217
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
```
218
What is the appearance of small bowel on an abdominal radiograph?
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
219
What is the appearance of large bowel on an abdominal radiograph?
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.
220
What are 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!
221
What do you see on an Xray for small bowel obstructions?
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.
222
What are causes of small bowel obstructions?
```
o Adhesions
o Hernias
• Inguinal, Femoral, Incisional
o Tumours
o Inflammation
```
223
What do you see on an Xray for large bowel obstructions?
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.
224
What are causes of large bowel obstructions?
```
o Colorectal carcinoma
o Diverticular stricture
o Hernia
o Volvulus
o Pseudo-obstruction
```
225
What is a 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).
226
What are 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
```
227
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.
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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
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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
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Magnetic resonance cholangio-pancreatogram (MRCP) is
