PBL

Question 1

Describe types of cells found within the stomach

Answer 1

MUCOUS NECK CELLS - Produce Mucous for the protection of epithelial surface from HCl. Also protects against ulcers caused by H.pylori
PARIETAL CELLS - Secretes HCl, serves to denature proteins + activate pepsinogen (converts to pepsin). Acts as barrier to microbes. Produces intrinsic factor - essential for vitamin B12 absorption
CHIEF CELLS - Secretes pepsinogen + gastric lipase
G CELLS - Secretes hormone gastrin

Question 2

Describe the anatomical parts of the stomach

Answer 2

CARDIA - oesophagus enters stomach via cardiac orifice
FUNDUS - superior portion of stomach, secretes many enzymes/acids required for digestion via gastric glands
BODY - largest part of stomach, acts as mixing tank for ingested food + stomach secretions. Also contains numerous glands that secret enzymes/acids required for digestion
PYLORUS - forma sharp curvature of J, consists if pyloric antrum (connects to body), pyloric canal (drains into duodenum) and a pyloric sphincter (regulates release of chyme into duodenum)

Question 3

Discuss microstructure of stomach

Answer 3

MUCOSA - Simple columnar epithelium (mucous neck, parietal, chief etc)
Lamina Propria (areolar connective tissue with glands + vessels)
Muscularis Mucosae (thin smooth muscle, puts mucous membrane into folds, allowing to be fully exposed to gastric contents)
SUBMUCOSA - Areola connective tissue, binds mucosa to muscularis, contains many blood vessels + lymphatics
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Question 4

Discuss enteric nervous system

Answer 4

MYENTERIC PLEXUS - located between longitudinal and circular smooth layers of the muscularis. Controls GI tract motility (movement), particularly frequency + strength of muscularis contraction
SUBMUCOSAL PLEXUS - plexus found in submucosa, causes surface mucous cells to produce mucus.
EXTRINSIC INNERVATION - Main input comes from vagus nerves arising from medulla oblongata. Vagus nerve innervates gut as far as descending colon, after this innervation is controlled by sacral outflow from S2-4.

Question 5

Describe gastric movements + emptying

Answer 5

MIXING WAVES - gentle, rippling, peristaltic movements pass over stomach, these waves macerate food, mix with secretions of gastric glands, and reduce it to chyme. Vigorous waves begin at stomach body & intensify as it reaches pylorus. Fundus is primarily storage.
Gastric emptying occurs with each mixing wave which forces 3ml of chyme into duodenum.
Distension of stomach wall by food activates STRETCH RECEPTORS, enhancing peristaltic contraction force

Question 6

Discuss basal electrical rhythm - BER

Answer 6

These are caused by smooth muscle cells in stomach, basic rhythm is set by spontaneous activity of pacemaker cells in longitudinal SM, near greater curvature of stomach.
They show spontaneous depolarisation and repolarisation every 20 seconds.

Question 7

Phases of gastric secretion

Answer 7

CEPHALIC PHASE (35-40%) - Stimulated by Sight, Smell and Taste of food. 30% of acid secretion occurs before food enters stomach.

• Sensory stimuli from food activates Dorsal Motor Neurones of Vagus nerve, resulting in: vagal postganglionic muscarinic nerves in stomach body to release Acetylcholine which stimulates parietal cells to release H+
• Release of gastrin from G cells in the astral glands. Gastrin reaches gastric glands by the bloodstream.
• Both vagal activity and gastrin stimulate the release of Histamine from mast cells/ECL cells (enterochromaffin-like cells)
• Histamine acts on H2 receptors on parietal cells to stimulate H+ secretion

GASTRIC PHASE (60%)
Swallowed food and semi-digested protein activates gastric activity here. Food causes stomach distension, this activates vago-vagal reflexes + short-loop myenteric reflexes. These both lead to ACh secretion.
- Vagal stimulation stimulates gastrin production
- Gastrin secretion inhibited when pH falls below 2 or 3
- Somatostatin produced from D cells inhibits gastrin release from G cells, this reduces acid secretion.

Intestinal phase (5-10%)
Short lived gastrin release from dudoenal G cells, as partially digested food begins to enter duodenum. Enterogastric reflex triggered by chyme distending the duodenum. Due to:
- Secretin released by S cells of duodenal mucosa in response to acid. Secretin reaches stomach via bloodstream t inhibit gastrin release and reduces affinity of parietal cells to gastrin.
- Cholecystokinin (CCK) and Gastric Inhibitory Peptide (GIP) are released in presence of lipids & carbs. Both inhibit gastrin release.

Question 8

Discuss secretions of the stomach fundus/body

Answer 8

Surface mucous neck cells: produce thick mucous for lubrication
Mucous neck cells: produce alkaline mucous for lubrication
Parietal cells: produce HCl for sterilisation and chemical hydrolysis and produce intrinsic factor for vitamin B12 absorption in ileum
Chief cells: produce pepsinogen which is activated to pepsin by HCl for protein digestion

Question 9

Discuss secretions of stomach antrum

Answer 9

Surface mucous cells: produce thick mucous for lubrication
Chief cells: produce pepsinogen which is activated to pepsin by HCl for protein digestion
G cells: produce gastrin, this is a hormone secreted into the bloodstream, to stimulate parietal cells to produce HCl and aids in gastric motility

Question 10

Define peptic ulcer disease

Answer 10

A peptic ulcer consists of a break in the superficial epithelial cells penetrating down to the muscularis mucosa f either the stomach or duodenum. There is a fibrous base and an increase in inflammatory cells.

Question 11

Clinical features of peptic ulcer disease

Answer 11

Characteristic feature is recurrent, burning, epigastric pain

Question 12

Discuss the pathophysiology of peptic ulcer disease

Answer 12

Caused by an imbalance between factors promoting mucosal damage and gastroduodenal defence.
Peptic ulceration is strongly correlated with H.pylori infection
Duodenal ulcer are mostly the result of gastric acid hypersecretion caused by H.pylori infection. However, in gastric ulcers, gastric acid secretion is normal or low.
In duodenal ulcers, chronic H.pylori infection - confined mainly to the gastric antrum - leads to impaired secretion of somatostatin, and consequently increased gastrin release resulting in gastric acid hypersecretion.
In gastric ulcers, there is chronic H.pylori throughout the stomach accompanied by severe inflammation, resulting in gastric mucous degradation, disruption of tight junctions between gastric epithelial cells& induction of gastric epithelial cell death.
NSAIDs cause injury directly (trapping H+ ions) & indirectly (systemic effect involving COX-1 inhibtion) & increase bleeding risk though anti-platelet action

Question 13

Diagnosis & experiments/tests associated with peptic ulcers

Answer 13

SEROLOGY - check blood serum to detect IgG antibodies
C13 UREA BREATH TEST - measurement of CO2 in breath after ingestion of C13 urea
STOOL ANTIGEN TEST - checking the stools for qualitative detection of H.pylori antigen (which is produced by the immune system in response to H.pylori infection)

Question 14

Pharmacological basis of treatment

Answer 14

Treatment is aimed at H.pylori eradication: PPI + 2x antibiotic
Proton Pump Inhibitors (PPIs) - inhibit the ATPase proton pump on parietal cells where H+ ions are pumped out into the lumen. Use Omeprazole
Antibiotics - to fight against the bacteria, H.pylori. Any TWO from Clarithromycin, Amoxycillin, Metronidazole
Example regimen: Omeprazole 200mg, Clarithromycin 500mg, Amoxycillin 1g - all TWICE daily

Question 15

Discuss maintenance of pH in the stomach

Answer 15

The pH of gastric juice during fasted conditions is 1
During a meal, there is more gastric secretions, however the pH rises to around 2-3 due to proteins acting as a buffer. The proteins have small side chains that can transfer small molecules for H+ ions, thus reducing acidity and raising pH.

Question 16

Discuss stomach protection from acid

Answer 16

The simple columnar epithelium in the stomach is only 1 cell thick.
Although it has a layer of protective mucosa to prevent acid from degrading the epithelium, it is primarily the action of bicarbonate ions that move through the fenestrated capillaries (that run underneath the epithelium) and enter the mucus that counteract the presence of H+ ions.

Question 17

Define Gastro-Oesophageal Reflux Disease and it’s causes

Answer 17

GORD is a common condition where gastric acid leaks out of the stomach and into the oesophagus
It is caused by incompetence of the LOS, resulting in oesophagitis, oesophageal ulceration and symptoms of heartburn

Question 18

Discuss a complication of GORD

Answer 18

Recurrent damage to the distal oesophagus can cause columnar/intestinal metaplasia. Extensive intestinal metaplasia = Barrett’s oesophagus, this can lead to adenocarcinoma

Question 19

Discuss treatment for acid reflux

Answer 19

Simple antacids (e.g. gaviscon) or alginates: These coat the surface of the distal oesophagus, producing symtomatic relief (short-term). However, these are inefficient at healing ulcerations/erosions
Main treatment is to inhibit gastric acid secretion - PPIs (omeprazole) & H2 receptor antagonists (Ranitidine)
Lifestyle: weight loss, precipitating factors should be avoided, dietary measures (reduce alcohol, caffeine) and smoking cessation

Question 20

Define hiatus hernia

Answer 20

A hiatus hernia is when the oesophageal-gastro junction and part of the stomach slides through the hiatus so that it lies above the diaphragm

Question 21

Describe the gross anatomy of the liver

Answer 21

The liver is wrapped in a tough fibrous layer and is covered in visceral peritoneum.
Comprised of 4 lobes: Right, Left, Caudate & Quadrate
Afferent structures (portal vein, hepatic artery & common bile duct) converge at the porta hepatitis

Question 22

Discuss the microstructure of the liver

Answer 22

Connective tissue divides each lobe of the liver into approximately 100,000 liver lobules, these are the basic functional units of the liver.
Each lobule is roughly 1mm (diameter) and are separated by an interlobular septum
The hepatocytes in a liver lobule form a series of irregular plates which are one cell thick
Within a lobule, sinusoids between adjacent plates empty into a central vein

Question 23

Describe functionality of liver sinusoids

Answer 23

The liver sinusoids lack a basement membrane, therefore large openings between the endothelial cells allow solutes (even large plasma proteins) to pass out of the bloodstreams and into the spaces surrounding the hepatocytes.
The lining of the sinusoids contain typical endothelial cells and a large number of Kupffer cells (phagocytes that engulf pathogens, cell debris & damaged blood cells). This can remove any pathogens that manage to get past GI defences
Blood enters the sinusoids from small branches of the hepatic portal vein and the hepatic artery

Question 24

Discuss the different zones of the acinus

Answer 24

The different zones carry out different functions
ZONE 1 - Closer to the afferent arterioles, oxidative functions tend to be carried out here. Other roles include; respiratory chain, citric acid cycle, fatty acid oxidation, gluconeogenesis, urea synthesis & production + bile excretion
ZONE 2 - Intermediate are
ZONE 3 - Closer to terminal hepatic veins. Roles involve lower oxygen, such as; Glycolysis, GLutmaine synthesis and zenobiotic (foreign) metabolism

Question 25

Discuss the blood supply to the liver

Answer 25

The liver has a double blood supply; the right and left hepatic arteries carry oxygenated blood to the liver and the portal vein carries venous blood from the GI tract to the liver.
The venous blood from the GI tract drains into the superior and inferior mesenteric veins; these two vessels are then joined by the splenic vein, just posterior to the neck of the pancreas to form the portal vein. This then splits to form the right and left branches, each supplying approx. half of the liver.
The portal venous blood contains all of the products of digestion absorbed from the GI tract, so all useful and non-useful products are processed by the liver before being either released back into the hepatic veins - which joining to the inferior vena cava, just inferior to diaphragm - pr stored in the liver for later use.

Question 26

Haemoglobin breakdown

Answer 26

By reticuloendothelial system
Produces 4x globin monomers which are broken down to constituent amino acids and recycled
Also produces 4x Haem groups containing iron and a porphyrin ring. The iron is recylced. The porphyrin ring is converted to bilirubin for transport to the liver for modification and excretion

Question 27

Bilirubin metabolism

Answer 27

Bilirubin is produced from haem break down, it is bound to albumin in order to be transported around in the blood. This is due to bilirubin’s hydrophobic nature, it also cannot be readily excreted in this form.
It is transported to the liver where it undergoes phase II conjugation (glucuronidation) to become conjugated bilirubin. This form is hydrophilic, and therefore can be transported out of hepatocytes into bile canaliculi for accumulation in the gallbladder.
Bile is released into the SI, conjugated bilirubin is converted to urobilinogen here by intestinal bacteria.
80% of the urobilinogen is converted to stercobilin (gives faeces brown colour) and 20% is reabsorbed.
This 20% is recirculated to the liver. It then travels to the kidneys where it is converted to urobilin which gives urine a yellow colour.

Question 28

Discuss the pathophysiology of portal hypertension

Answer 28

If there is slow blood flow through the liver due to increased resistance from fibrosis or degeneration of liver tissue (e.g. cirrhosis). The increased pressure in the portal circulation is known as portal hypertension.
Venous drainage of the GI tract is congested here. An increase in 5mmHg of the pressure gradient is indicative of portal hypertension
MM.
Blood finds alternative routes back to systemic circulation, bypassing liver due to the back for of blood and congestion in portal venous system.
Therefore, blood from the GI tract is filtered less efficiently and ascites may occur (free fluid in peritoneal cavity)

Question 29

Discuss complications of portal hypertension

Answer 29

Varisces- engorged blood vessels, often oesophageal, gastric or haemorrhoidal
Splenomeagaly- enlargement of spleen from accumulation of WBCs, RBCs and platelets
Hepatic encephalopathy

Question 30

Discuss diagnosis of portal hypertension

Answer 30

Often diagnosed on presentation of ascites or varies, seen durin physical abdominal or and exam.
Endoscopy usually used or ultrasound
CT & MRI angiography can detect extent of portal vein clot
Portal venous pressures - can b used to confirm diagnosis and differentiate between sinusoidal and pre-sinusoidal forms
Balloon catheter can be inserted using trans-jugular route to measure wedged hepatic venous pressure

Question 31

Discuss treatment options for portal hypertension

Answer 31

• Treatment involves a focus on prevention and/or control of variceal haemorrhage
• Beta-blockers for prophylaxis of a variceal haemorrhage e.g. Propranolol, effective in decreasing pressures and variceal pressure
• Endoscopic banding can be used during an acute bleeding episode, this involves the placement of rubber bands around a portion of oesophageal mucosa that contains the variceal
• Vasoactive drugs e.g. Terai pressing can be used to cause vasoconstriction of variceal and to prevent further bleeding

Question 32

Discuss pre-hepatic jaundice

Answer 32

• due to elevated haemolytic (RBC breakdown), increased RBC breakdown by reticule endothelial system results in the liver being overloaded by UCB and is unable to cope with it. Increased haemolysis can occur as a result of some tropical diseases such as malaria, yellow fever or sickle cell anaemia
• Clinical observations: Increase in UCB due to RBC breakdown by RES, some increase in CB due to metabolic pathways, If CB is increased there will be increased urobilinogen in urine, bilirubin in urine will not be seen as it is mainly in the UCB form and this is hydrophobic & bound to albumin.
  It is this UCB that causes the signs and symptoms of jaundice

Question 33

Discuss hepatic jaundice

Answer 33

Caused by conditions that result in liver damage, causing cholestasis due to swelling & oedema form inflammation, this could affect bilirubin metabolism in the following ways;
Impaired uptake of UCB
Impaired conjugation of bilirubin e.g. Gilbert’s syndrome
Impaired transport of CB into bile canals cult
Damage can be a result of cirrhosis, hepatoxic drugs and viral hepatitis
Clinical Obs: Increase in UCB+CB, more CB as bile excretion is a rate-limiting step. The levels of UCB + CB depend on which function is impaired
Increase in UCB if conjugation is impaired
Increase in CB if CB is not being excreted efficiently (inflam/impaired transport)
CB can be detected in urine if CB plasma levels increase
Increased urobilinogen if more CB is excreted in bile

Question 34

Discuss post-hepatic jaundice

Answer 34

Bile excretion is impeded by obstruction or loss of bile ducts
CB present in blood, som of which is excreted in urine
Faeces appears pale
Impaired fat absorption => statorrhea may occur
Gallstones are a common cause

Question 35

Discuss treatment of different types of jaundice I

Answer 35

Pre-hepatic: Can be treated with a blue light, objective is to prevent the rapid breakdown of RBCs that is causing bilirubin levels to build up.
Hepatic: Aims to prevent further damage, anti-virally can be administered in case of infection
Post-hepatic: Involves surgery to unblock bile duct

Question 36

Anatomy of SI & Pancreas

Answer 36

• The pancreas lies posterior to stomach, extends laterally from duodenum toward spleen, approx 15cm long,forms C-shape with duodenum
• Retroperitoneal, firmly bound to posterior wall of abdominal cavity
• Surface of pancreas has a lumpy, lobular texture with a thin, transparent capsule of connective tissue which wraps the entire organ
• Connective tissue divides the interior of the pancreas into distinct lobules. Blood vessels and pancreatic duct tributaries are situated within these
• Ducts branch repeatedly in each lobule before ending in pockets called pancreatic acini. Each acinus is lined with simple cuboidal epithelium.
• Acinar cells produce enzymes released into the duodenum via ducts
• Ductal cells release bicarbonate ions, these help to neutralise stomach acidity of chyme
• Pancreatic islets, endocrine tissues of pancreas are scattered amongst acini, islets account for only 1% of cel population of pancreas

Question 37

Discuss blood supply of SI and pancreas

Answer 37

Branches of splenic artery wrap around the body and tail of pancreas, branches of common hepatic artery go to the gastroduodenal artery and then the anterior & posterior pancreaticouodenal arteries

Question 38

Discuss nervous supply of pancreas & SI

Answer 38

Parasympathetic fibres from vagus nerve

Sympathetic fibres transverse from branches of plan chic nerves