2. What is it all about?
The gastrointestinal (GI) system encompasses anatomy, embryology, physiology, pharmacology,
biochemistry, immunology and pathology. We learn about what goes into the gut, how it is moved
along the gut, how it is broken down, what it gets turned into, where the products go and how we
get rid of the unwanted stuff. Understanding the basic science of normal gut behavior makes
learning about the diseases a lot easier.
Where does it happen?
We all know that the gut begins at the mouth and ends at the anus. But the GI system isn’t just
the esophagus, stomach and intestines; it also includes the liver, biliary tract, pancreas and
gallbladder.
At the cellular level, a vast array of different cell types and functions interrelate to produce the
puzzle that is the working GI system. From hydrochloric acid (HCl) secretion by the oxyntic cells
in the stomach to phagocytic Kupffer cells in the liver, the GI system does a lot more than just
break down food for us.
It is important to learn some specifics about motility, and also about the mucosal surfaces, if we
are going to understand disorders such as achalasia or ulcerative colitis. Things going wrong in
the gut can have a knock-on effect throughout the body. For example, liver damage leading to
reduced drug metabolism can result in toxic metabolites entering the systemic circulation.
100 high-return facts to get you started
General principles
• The gut is composed of a basic structure throughout its length: mucosa, submucosa,
muscular layer and adventitia (or serosa).
• It is innervated through intrinsic submucosal and mucosal nerve plexuses (Meissner’s
and Auerbach’s plexuses). This activity is moderated by extrinsic innervation.
• Food is moved through the tract by gravity and peristalsis, which is a wavelike movement
involving coordinated contraction of muscle in one area and relaxation of muscle in the
next.
• The major functions of the gut are: ingestion, breakdown and digestion of food; storage of
waste; secretion of exocrine, endocrine and paracrine substances; and excretion of
waste products.
• The gut defense mechanisms include: sight, smell and taste; the vomit reflex; stomach
acid; a natural flora; IgA secretions and Peyer’s patches in the gut wall.
• Dietary fat is mostly composed of triglycerides (esters of free fatty acids and glycerols).
The essential fatty acids are linoleic acid and α-linoleic acid. Dietary fat provides 37 kJ (9
kcal) of energy per gram.
• Vitamins are either fat soluble or water soluble. The fat-soluble vitamins are A, D, E and
K. These are stored in fatty tissue and are more abundant than stores of water-soluble
vitamins.
• The GI tract is derived from the endodermal germ layer. It forms passively and depends
on the cephalocaudal and lateral folding of the embryo.
• Between weeks 7 and 11 of gestation, the gut herniates and continues developing
outside the abdominal cavity.
• The gut is divided into foregut, midgut and hindgut, which all have separate blood
supplies: the celiac artery, superior mesenteric artery and inferior mesenteric artery,
respectively.
The mouth
• The oral cavity extends from the lips to the pillars of the fauces, which is the opening to
the pharynx. The oral cavity is divided into the vestibule (anterior to the teeth) and the
oral cavity proper (posterior to the incisors).
3. • The tongue comprises four pairs of intrinsic muscles: the superior and inferior longitudinal
and the transverse and vertical muscles. The extrinsic muscles of the tongue are called
genioglossus, hyoglossus, styloglossus and palatoglossus.
• The functional unit of a salivary gland is called a salivon and consists of an acinus and a
duct. Acini contain serous or mucous cells and their secretions are modified as they travel
through the duct.
• Swallowing involves a sequential swallowing motor program, which is generated in the
medullary centers and consists of three phases: buccal, pharyngeal and esophageal.
• Cleft lip and palate are common defects (1/100 and 1/2500 births, respectively). A cleft lip
is more common in girls because the palatine shelves in the female fetus fuse about 1
week later than in the male fetus.
• Herpes simplex virus 1 (HSV-1) infection usually affects the body above the waist but can
sometimes affect other parts of the body, including the genitalia. The virus can remain
latent in the trigeminal ganglia and can be reactivated to present as cold sores.
• Sialadenitis is inflammation of the salivary glands; it can be caused by mumps (infectious
parotitis). Individuals with reduced amounts of saliva (e.g. Sjögren’s syndrome) are at
increased risk of sialadenitis.
• The term ‘leukoplakia’ (hyperkeratosis and hyperplasia of squamous epithelium) is taken
from the Greek words meaning ‘white patches’. It is a premalignant condition associated
with excess alcohol, poor dental hygiene and smoking.
• Oral candidiasis is caused by a yeast infection (Candida albicans) and looks similar to
leukoplakia, but it can be scraped off. It responds well to nystatin, oral amphotericin or
miconazole.
• Sublingual or buccal absorption allows diffusion of substances directly into the systemic
circulation, bypassing the liver and avoiding first-pass metabolism. Glyceryl trinitrate is
given this way for angina.
The esophagus
• The esophagus is a fibromuscular tube that is about 25 cm in length and which
connects the pharynx to the stomach. It enters the abdomen through the diaphragm at
the level of T10.
• The upper third of the esophagus contains striated muscle and the lower third contains
smooth muscle. The middle third is made up of both types of muscle.
• The esophageal mucosa is lined by non-keratinized, stratified squamous epithelium.
• Esophageal atresia and fistula occur together in 90% of cases. The most common form
involves a blind ending in the upper part of the esophagus and a fistulous opening into
the trachea at the lower end.
• In gastroesophageal reflux disease (GORD), reflux causes injury to and desquamation
of the squamous esophageal cells. Increased loss of the cells is compensated by basal
cell proliferation (hyperplasia).
• Barrett’s esophagus is a premalignant disorder in which the normal squamous
epithelium is subjected to prolonged injury and undergoes a metaplastic change to be
replaced by columnar epithelium. People with Barrett’s esophagus are 30–40 times
more likely to develop adenocarcinoma than normal.
• Achalasia involves the loss of coordinated peristalsis of the lower esophageal sphincter.
This prevents the passage of food and liquid into the stomach. It can be caused by
damage to the esophageal innervation, as in Chagas’ disease.
• A hiatus hernia is the herniation of part of the stomach through the diaphragm. They can
be described as sliding or rolling hernias.
• Esophageal varices are dilated veins at the gastroesophageal junction. They are seen
most commonly in patients with liver cirrhosis and portal hypertension. The enlarged
veins are at risk of tearing, resulting in hematemesis – a medical emergency.
• Mallory–Weiss syndrome is hematemesis as a result of a tear at the gastroesophageal
junction. It is caused by prolonged retching or coughing, which causes a
sudden increase in intra-abdominal pressure.
The stomach
• The stomach is a mobile, muscular organ that acts as a reservoir for food. It can hold 2–3
L of food. It mixes food and digestive juices to form chyme.
4. • The stomach is divided anatomically into three parts: the fundus (the superior part of the
stomach), the body (which lies between the fundus and antrum) and the antrum (the
inferior part of the stomach).
• The gastric mucosa is lined with simple columnar epithelium and forms numerous gastric
pits, which are the openings for the gastric glands.
• Various cell types are found in the gastric glands: the mucus neck cells, parietal (oxyntic)
cells, chief (zymogen) cells, enteroendocrine (amine precursor uptake and
decarboxylation or APUD) cells and undifferentiated stem cells.
• The average adult produces 2–3 L of gastric juices every 24 h. Gastric juices contain
mucus, HCl, intrinsic factor and digestive enzymes (pepsinogen and lipase).
• Fatty acids in the duodenum cause the release of gastric inhibitory polypeptide (GIP) and
cholecystokinin (CCK), which both inhibit acid secretion. Together with secretin, GIP and
CCK are called enterogastrones.
• During gastric motility, large peristaltic contractions originate in the pacemaker zone of
the distal body (on the greater curvature). They sweep down into the antrum and occur at
a rate of three per minute, lasting between 2-20 seconds.
• Chronic gastritis can be classified as type A (autoimmune), type B (bacterial infection)
and type C (reflux). The bacterium Helicobacter pylori is present in about 90% of cases of
type B gastritis.
• Gastric ulcers are caused by hyperacidity, H. pylori infection, reflux of duodenal contents,
non-steroidal anti-inflammatory drugs (NSAIDs) and smoking; genetic factors are also
involved. Peptic ulceration is more common in individuals with blood group O.
• Pyloric stenosis is caused by hypertrophy of the circular muscles of the pylorus and
obstructs flow of chyme into the duodenum. It typically presents in infants 4–6 weeks
after birth, with projectile vomiting within 30 minutes of a feed.
The liver
• The liver is situated in the right upper quadrant, under the diaphragm, and weighs about
1.5 kg. It is surrounded by strong connective tissue, called Glisson’s capsule.
• The blood supply to the liver comes from the hepatic artery (a branch of the celiac
artery) and the portal vein, which carries venous blood, full of digestion products, from the
gut.
• Liver cells – hepatocytes – are arranged in cords, which radiate out in a spoke-like
fashion around a central vein. A network of capillaries (or sinusoids), which are lined with
discontinuous fenestrated epithelium and phagocytic Kupffer cells, is present between
the hepatocytes.
• The main functions of the liver are: to metabolize protein, fat and carbohydrate; to
produce bile; to store vitamins, minerals and glycogen; to biotransform unwanted
substances; and to detoxify and protect (by filtration of portal blood).
• Drug or hormone metabolism occurs via biotransformation in three stages:
- phase I: oxidation
- phase II: conjugation
- phase III: elimination
In acetaminophen (paracetamol) overdose, there is saturation of liver enzymes and depletion of
glutathione, a conjugation group. This leads to liver necrosis and kidney damage by toxic metabolites.
• Cirrhosis is a diffuse and irreversible condition that results from hepatocyte necrosis,
followed by the formation of regeneration nodules with fibrosis. It can lead to portal
hypertension, liver failure or hepatocellular carcinoma.
• Jaundice is a clinical sign resulting from serum bilirubin levels exceeding 45 µmol/L.
Hepatic causes include congenital or hepatocellular abnormalities; extrahepatic causes
are the result of hemolytic and obstructive (or cholestatic) disorders.
• Hepatitis A virus is spread by the fecal–oral route. Hepatitis B virus is transmitted
through blood, body fluids, sexual contact, transplacentally and in breast milk. Hepatitis C
virus is spread parentally (contaminated blood products or IV drug abuse).
• Hemochromatosis is an autosomal recessive disorder with a mutation in the HFE gene,
where too much iron accumulates in the liver, heart, pancreas and other endocrine
organs. Diabetes occurs in two-thirds of all cases.
• Alcohol damage in the liver can cause a number of diseases, including hepatic steatosis
(fatty liver), alcoholic hepatitis and alcoholic cirrhosis.
5. The pancreas and gall bladder
• The gall bladder is a pear-shaped sac that concentrates and stores bile secreted from the
liver. It can hold up to 60 ml of bile.
• Cholecystokinin causes strong contractions of the smooth muscle is the wall of the gall
bladder and relaxation of the sphincter of Oddi. This allows for release of bile into the
duodenum.
• Around 80% of gallstones are made up of cholesterol, although they can also be
composed of bile pigment or calcium. Asymptomatic gallstones remain in the gall bladder
but those that impact in the cystic duct cause biliary pain and acute cholecystitis.
• The pancreas has an exocrine function involving secretion of digestive enzymes (e.g.
lipase, amylase and trypsin). These are secreted as proenzymes (zymogens), to prevent
autodigestion of pancreatic tissue.
• The pancreas also has an endocrine function involving the secretion of the hormones
insulin, glucagon and somatostatin. These are secreted from β, α and δ cells, respectively.
• The main pancreatic duct travels across the gland from left to right and, with the bile duct,
opens into the second part of the duodenum at the ampulla of Vater.
• Pancreatic juice is rich in bicarbonate, which acts to neutralize the stomach acid.
• Annular pancreas is a congenital abnormality in which there is incomplete migration of
the embryonic ventral bud, or the left portion migrates in the opposite direction to the right
portion, resulting in a ring of pancreatic tissue surrounding the duodenum.
• Bruises on the flanks (Grey Turner’s sign) or around the umbilicus (Cullen’s sign) are
found in acute pancreatitis.
• Chronic pancreatitis normally presents with a history of prolonged ill health, steatorrhea,
weight loss, abdominal pain and diabetes mellitus.
The small intestine
• The small intestine is 6–7 m long and consists of the duodenum, jejunum and ileum. The
ileum makes up two-fifths of the length.
• The mucosa of the small intestine has a huge surface area for absorption of digestion
products. This is facilitated by plicae circulares, numerous villi and a striated border of
mircovilli, which increase the absorptive area 600-fold.
• Peyer’s patches are found in the mucosa of the ileum and extend into the submucosa.
They consist of aggregations of lymphoid nodules.
• Brunner’s glands are present only in the duodenum. They secrete mucus, bicarbonate,
growth factors and urogastrone, an inhibitor of acid secretion.
• The migrating motor complex occurs every 90–120 min during fasting in the small
intestine. It involves high frequency bursts of powerful contractions.
• Meckel’s diverticulum is a remnant of the vitelline duct that is present in embryonic life. It
is present in 2% of the population, is about 2 inches long and is found about 2 feet from
the cecum (rule of 2s).
• Celiac disease occurs due to an abnormal reaction to gluten, which damages the
enterocytes of the small intestine, causing villous atrophy and malabsorption.
• Atresia and stenosis occur most often in the duodenum. The incidence is 1 in 500 births.
• Exomphalos (umbilical hernia) occurs when the gut fails to return to the abdominal cavity
after physiological herniation and development during weeks 7–11 of gestation.
• Cholera produces a potentially fatal secretory diarrhea. The bacterium Vibrio cholerae
produces an enterotoxin that binds to receptors on immature cells, causing an increase in
adenylate cyclase, elevating cAMP and increasing the secretion of Na+ ions, Cl− ions and
water into the lumen.
The large intestine
• The outer, longitudinal muscle of the large intestine forms three bands called the taenia
coli. They gather the cecum and colon into a series of pouch-like folds called
haustrations or sacculations.
• The outer surface of the large intestine has appendices epiploicae, which are sacs of
omentum distended with fat.
• The main function of the colon is water absorption. It absorbs over 90% of the water from
the contents passing through it.
6. • ‘Mass movement’ describes the intense contraction beginning halfway along the
transverse colon. It pushes the contents towards the rectum and is responsible for
colonic evacuation.
• Hirschsprung’s disease is due to an absence of ganglion cells in Auerbach’s and
Meissner’s plexuses in the distal bowel. The colon can become distended with feces,
leading to megacolon and acute enterocolitis, which can be fatal.
• Crohn’s disease is an inflammatory bowel (IBD) disease characterized by skip lesions
(patches of normal bowel in between areas of diseased bowel), granulomas and rosethorn
ulcers. It involves both small and large bowel.
• Ulcerative colitis is another inflammatory bowel disease but does not present with skip
lesions. The mucosa is granular and hemorrhagic, but does not involve the muscle layer
like Crohn’s disease, and is confined to the colon.
• Irritable bowel syndrome (IBS) is diagnosed by the exclusion of structural or metabolic
abnormalities and the presence of symptoms. It is described as constipation or diarrhea
predominant.
• Inguinal hernias can be direct (protruding through the posterior wall of the inguinal canal)
or indirect (passing through the inguinal canal).
• ‘Diverticulitis’ describes outpouchings in the wall of the gut that have become inflamed.
GI malignancy
• Most esophageal carcinoma is squamous in origin, although adenocarcinoma can arise
from Barrett’s esophagus, where there are areas of the distal esophagus lined with
columnar epithelium.
• Gastric carcinoma is associated with blood group A, atrophic gastritis, H. pylori, smoking,
adenomatous polyps and low social class. It is especially common in Japan.
• Chronic hepatitis B or hepatitis C infections, alcoholic cirrhosis and hemochromatosis
can all cause hepatocellular carcinoma.
• Liver metastases may arise from the stomach, lung, colon, breast, uterus and rarely the
pancreas. Leukemias and lymphomas also affect the liver.
• Most carcinomas of the pancreas are ductal adenocarcinomas. Neither acute nor chronic
pancreatitis is a risk factor for this malignancy.
• Familial adenomatous polyposis is a rare autosomal dominant disorder that leads to
intestinal cancer in more than 90% of cases. It involves the APC gene and is
characterized by development of hundreds of adenomatous polyps throughout the intestines.
• Colorectal cancer is closely related to diet. The dietary risk factors are low fiber, high
carbohydrate and high fat.
• Staging of colorectal cancer is by Duke’s classification:
-stage A: confined to bowel wall
-stage B: extension through the bowel wall
-stage C: involvement of regional lymph nodes
-stage D: metastatic spread to other organs is sometimes used.
• Gastrointestinal lymphoma is rare and can be of B cell or T cell lineage. T cell
lymphomas are associated with celiac disease.
• Mesotheliomas arise from the mesothelium of the peritoneum. Secondary mesotheliomas
are often caused by transcoelomic metastases from the ovaries and pancreas.
Drugs
• Antacids (e.g. salts of magnesium and aluminium) act by neutralizing stomach acid. They
are useful in symptom relief for gastroesophageal reflux disease.
• H2-receptor antagonists (e.g. ranitidine) act on the H2-receptors on oxyntic cells in the
stomach and inhibit acid production.
• Proton pump inhibitors (e.g. lansoprazole) also act on the acid-secreting cells in the
stomach to inhibit acid production.
• Misoprostol is a synthetic prostaglandin analogue and helps protect against peptic ulcer
formation.
• NSAIDs stop the stomach’s protective mechanisms and can lead to peptic ulceration.
Therefore, NSAID treatment should be used concurrently with a proton pump inhibitor, Hreceptor
antagonist or misoprostol, to suppress acid production.
• H. pylori eradication therapy consists of a 2-week course of omeprazole and
