Block 3 - Gastrointestinal

Question 1

Outline the anatomy involved in swallowing - ORAL CAVITY

• What is the function of the oral cavity?
• Epithelium?
• Innvervation?
• Chewing reflex? (5)

Answer 1

Oral Cavity:

• Function: Mastication (chewing) for mechanical breakdown of food
• Epithelium: Thick stratified squamous epithelium
• Innervation: Trigeminal nerve (CN V, sensory to teeth and motor to jaw), facial nerve (CN VII, motor and sensory to tongue and pharynx), glossopharyngeal nerve (CN IX, sensory to caudal 1/3 of tongue) and hypoglossal nerve (CN XII, motor to tongue)
• Chewing Reflex:
  
  1. Bolus of food in mouth
  2. Reflex inhibition of muscle of mastication, allowing lower jaw to drop
  3. Initiation of stretch reflex of jaw, allowing rebound contraction
  4. Jaw rises, teeth close and bolus compresses against linings of mouth
  5. Repeat

Question 2

Outline the anatomy involved in swallowing - PHARYNX

• Function?
• Anatomy - length and relation to spine?
• Divisions?
• Epithelium?
• Muscles?
• Innervation?

Answer 2

Pharynx:

• Function: Passageway for food from mouth to oesophagus
• Anatomy: Extends for about 13cm from base of skull to level of 6th cervical vertebra
• Divisions: Nasopharynx (skull to soft palate, no digestive role), oropharynx (soft palate to base of tongue) and laryngopharynx (valleculae to inferior margin of cricoid cartilage)
• Epithelium: Pseudostratified columnar epithelium (nasopharynx) to stratified squamous epithelium (oropharynx and laryngopharynx)
• Muscles: Outer circular muscle layer (superior, middle and inferior constrictor muscles) and inner longitudinal muscle layer (stylopharyngeus, salpingopharynegues and palatopharyrngeus muscles)
• Innervation: Vagus nerve (CN X) and glossopharyngeal nerve (CN IX)

Question 3

Answer 3

Question 4

Outline the anatomy involved in swallowing - OESOPHAGUS

• Function?
• Anatomy - length?
• Epithelium?
• Muscles?
• Innervation?
• Upper oesophageal sphincter?
• Lower oesophageal sphincter?

Answer 4

Oesophagus:

• Function: Passageway for food to stomach
• Anatomy: A hollow muscular tube about 18-26cm long, which is collapsed between swallows and is able to distend up to 3cm laterally to accommodate food bolus (due to longitudinal folds)
• Epithelium: Stratified squamous epithelium (no serosa as retroperitoneal)
• Muscles: Skeletal muscle (proximal 1/3) and smooth muscle (distal 2/3) structured into inner circular and outer longitudinal layers
• Innervation: Motor innervation predominately by vagus nerve (CN X) and sensory innervation by vagus and thoracic sympathetic nerves
• Upper Oesophageal Sphincter: Protects airway from swallowed material and gastric reflex, and allows entry of food into oesophagus. Includes thyropharyngeal and cricopharyngeal parts of inferior pharyngeal constrictor, which are contracted at rest, with slit-like configuration creating high pressure zone about 1cm in length.
• Lower Oesophageal Sphincter: Protects oesophagus from gastric reflux and allows entry of food into stomach upon relaxation. It is a 3-4cm length of thickened circular smooth muscle which is tonically contracted at rest, creating a high-pressure zone

Question 5

Answer 5

Question 6

Describe the Physiology of Swallowing (Deglutition) = 5 Steps

• Voluntary Phase (Oral)?
• Involuntary Reflex Phase? (3)

Answer 6

Physiology of Swallowing (Deglutition):

• Voluntary Phase (Oral): Upward movement of tongue pushes bolus against soft palate and back of mouth, triggering reflex
• Involuntary Reflex Phase:
  
  1. Pharyngeal Phase: Upper oesophageal sphincter relaxes (vagus nerve inhibited) and opens while epiglottis closes to keep swallowed material out of airway, and a fast peristaltic wave initiated by the nervous system of the pharynx forces the bolus of food into the upper esophagus. Respiration temporary suspended as swallowing centre in medulla inhibits respiratory centre.
  2. Oesophageal Phase: Food moves downward into oesophagus, propelled by peristaltic waves and aided by gravity. Upper oesophageal sphincter is closed.
  3. Gastro-Oesophageal Phase: The lower oesophageal sphincter undergoes receptive relaxation (via distension and vagus nerve acting on myenteric inhibitory neurons) ahead of the peristaltic wave, which allows easy propulsion of the swallowed food into the stomach

Question 7

Answer 7

Question 8

Describe the anatomy of the biliary tract.

• 3 Components?
• Function?
• 3 Ducts?
• Bile Flow?

Answer 8

Biliary Duct System:

• Components: Liver, gallbladder and bile ducts
• Function: Organs and ducts that create and store bile and release it into the duodenum. The system drains waste products from the liver into the duodenum (see diagram) and helps digestion through the controlled release of bile.
• Ducts:
  
  1. Common hepatic duct (convergence of left and right hepatic duct)
  2. Cystic duct (contains spiral valves of Heister)
  3. Common bile duct (convergence of common hepatic duct and cystic duct)
• Bile Flow: Flows both ways between gall bladder and left and right hepatic ducts and common bile duct

Question 9

Describe the anatomy of the biliary tract - LIVER

• Regions of the abdomen? Relation to spine?
• 4 Lobes?
• Bare area?
• 2 Indentations?
• Physical blood flow?
  
  • 2 vessels in from below?
  • 1 vessel out from below?
  • 1 vessel out above?

Answer 9

Liver:

• Regions: Right hypochondriac and epigastric (deep to the ribs T7-T11)
• Four Lobes: Right, Left, Quadrate and Caudate (divided into 8 functional segments)
• Bare Area: Superior section of the liver that touches the diaphragm and not covered by visceral peritoneum
• Indentations: Stomach (left inferior) and right kidney (right posterior)
• Physical Blood Flow:
  
  • Two vessels in from below: Hepatic artery and hepatic portal vein
  • One vessel out below: Common hepatic duct
  • One vessel out above: Hepatic vein (converges with IVC)

Question 10

5 Ligaments of the Liver?

Answer 10

Ligaments of the Liver

1. Falciform Ligament: Divides right and left lobes anteriorly and suspends liver from diaphragm and anterior abdominal wall
2. Round Ligament (Ligamentum Teres): Remnant of umbilical vein, free edge of the falciform ligament
3. Coronary Ligament: Attaches the superior surface of the liver to the inferior surface of the diaphragm and demarcates the bare area of the liver. The anterior and posterior folds unite to form the triangular ligaments on the right and left lobes of the liver
4. Triangular Ligaments: The left triangular ligament is formed by the union of the anterior and posterior layers of the coronary ligament at the apex of the liver and attaches the left lobe of the liver to the diaphragm. The right triangular ligament is formed in a similar fashion adjacent to the bare area and attaches the right lobe of the liver to the diaphragm
5. Lesser Omentum: Attaches the liver to the lesser curvature of the stomach and first part of the duodenum
   
   1. Hepatoduodenal Ligament: Extends from the duodenum to the liver
   2. Hepatogastric Ligament: Extends from stomach to the liver

Question 11

Answer 11

Question 12

Describe the anatomy of the biliary tract - GALL BLADDER

• Function?
• View?
• Regions?
• Diameter?
• Anatomy?
• Histology?
• Gallstones - Cholelithiasis?
• Gallstones - Choledocholithiasis?

Answer 12

Gall Bladder:

• Function: To store and concentrate (5-10x) bile prior to its expulsion into the GI Tract
• View: Right of liver, seen best from inferior posterior view, posterior end can be seen from anterior view
• Regions: Right hypochondriac region around the tip of the right 9th rib (normally impalpable)
• Diameter: 8cm long, 4cm wide, 100ml capacity
• Anatomy: Tapered greenish sac divided into three sections (fundus, body and neck)
• Histology: Simple columnar epithelium with microvilli
• Gallstones:
  
  • Cholelithiasis: Presence of gallstones in the gallbladder
  • Choledocholithiasis: If gallstones migrate into the ducts of the biliary tract

Question 13

Describe the anatomy of the biliary tract - PANCREAS

• Function?
  
  • Endocrine?
  • Exocrine?
• Anatomy?
• Intra-Abdominal Relations?
  
  • Hepatopancreatic Ampulla?
  • Hepatopancreatic Sphincter?
  • Major duodenal papilla?
• Blood Supply?

Answer 13

Pancreas:

• Function:
  
  • Endocrine: Pancreatic Islets of Langerhans (mini-endocrine glands) release insulin and glucagon hormones that play an important role in carbohydrate metabolism
  • Exocrine: Pancreatic acinar cells secrete enzyme-rich pancreatic juice into the duodenum via the main pancreatic duct (become hepatopancreatic ampulla) and epithelial cells lining the smallest pancreatic ducts secrete water and bicarbonate ions that make the pancreatic juice alkaline
• Anatomy: Soft, tadpole-shaped gland that extends across the abdomen from its tail (near the spleen) to its head, which is encircled by the C-shaped duodenum (parts incude head, neck, body, tail and ucinate process)
• Intra-Abdominal Relations: Most of the pancreas is retroperitoneal and lies deep to the greater curvature of the stomach, except tail which is intraperitoneal
  
  • Hepatopancreatic Ampulla: Convergence of bile duct and main pancreatic duct
  • Hepatopancreatic Sphincter: Smooth muscle valve controlling entry of bile and pancreatic juice into duodenum
  • Major Duodenal Papilla: Where the ampulla opens into the duodenum
• Blood Supply: Pancreas supplied by splenic artery (body and tail of pancreas) and common hepatic artery (head of pancreas) from celiac trunk, and superior mesenteric artery (head of pancreas)

Question 14

Answer 14

Question 15

Answer 15

Question 16

Outline the major physiological factors that control the gastro-oesophageal junction.

• Which 3 structures contribute to the gastro-oesophageal junction?
• Function of each?

Answer 16

Gastro-Oesophageal Junction Contributors (Functional Sphincter):

• Lower Oesophageal Sphincter:
  
  • Tonically contracted oesophageal smooth muscle (myogenic and neurogenic factors).
  • Pressure altered by hormones, nerves, foods and other agents (see image below).
  • Relaxes upon swallowing or as part of the reflex called transient LES relaxation (TLESR), independent of swallowing and peristalsis, due to vagally mediated inhibition involving nitric oxide as a neurotransmitter.
• Diaphragmatic Hiatus:
  
  • An opening in the diaphragm through which the oesophagus and the vagus nerve pass.
  • The right crus of the diaphragm loops around forming a sling around the oesophagus.
  • This sling constricts the oesophagus, forming a functional sphincter that prevents gastric reflux, when intra-abdominal pressure rises during inspiration, and relaxes with swallowing and TLESR.
• Intra-Abdominal Oesophagus and Gastric Cardia (Gastric Sling):
  
  • With gastric distension, increased tone in “clasp” muscle fibres draws anterior and posterior surfaces together, contributing to the high pressure zone of the gastro-oesophageal junction.

Question 17

Physiological Factors Controlling Lower Oesophageal Sphincter Pressure.

• 3 Hormones/Peptides that Increase LES Pressure?
• 4 Hormones/Peptides that Decrease LES Pressure?
• 3 Neural agents that Increase LES Pressure?
• 3 Neural agents that Decrease LES Pressure?
• 1 Food that Increases LES Pressure?
• 3 Foods that Decrease LES Pressure?
• Other factors?

Answer 17

Question 18

What does Bile consist of?

What is the Function of Bile?

Answer 18

Bile Function:

Bile: Consists of excess cholesterol (10%), bile salts and acids (70%), proteins (5%), bilirubin (1%), and phospholipids (5%)

Assists with fat digestion and absorption of fat-soluble vitamins in the small intestine

Eliminates waste products, including bilirubin and excess cholesterol

Question 19

Descibe the steps in the formation and secretion of bile =

Answer 19

Bile Formation and Secretion:

1. Parasympathetic impulses from vagus nerve stimulate hepatocytes to produce and secrete bile.
2. Initially, hepatocytes secrete bile into canaliculi, which is collected by a system of ducts that flow (in the opposite direction of blood) from the liver through the right and left hepatic ducts. This hepatic bile contains large quantities of bile acids, cholesterol and other organic molecules.
3. Right and left hepatic ducts drain bile into common hepatic duct, which joins with the cystic duct from the gallbladder. Bile can flow in both directions between the gallbladder and the common bile duct and the hepatic duct.
4. The gall bladder stores and concentrates (five-fold) bile via absorption of water and small electrolytes.
5. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of cholecystokinin and secretin.
6. Cholecystokinin (in response to fats) stimulates contractions of the gallbladder and common bile duct, and relaxation of the hepatopancreatic sphincter, resulting in delivery of bile into the gut. Secretin (in response to acids) stimulates biliary duct cells to secrete bicarbonate and water, which expands the volume of bile and increases its flow out into the intestine.
7. Bile travels from gallbladder down the common bile duct to the duodenum. As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.
8. Sphincter of Oddi (hepatopancreatic sphincter) is a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through the ampulla of Vater into the second part of the duodenum.
9. Bile is excreted (5%) or reabsorbed in the ileum (95%) and travels to liver via the enterohepatic circulation

Question 20

Describe the physiological processes involved in gastrointestinal (GI) motility and secretion.

• 5 stimulatory signals of GIT motility?
• 6 inhibitory signals of GIT motility?

Answer 20

GIT MOTILITY

Stimulatory Signals

1. Acetylcholine (PNS) and Vagal Stimulation
2. Myenteric (Auerbach’s) Plexus Local Reflex
3. Gastrin
4. Serotonin
5. Motilin Insulin

Inhibitory Signals

1. Adrenaline (SNS)
2. Secretin
3. Cholecystokinin (CCK)
4. Vasoactive Intestinal Peptide (VIP)
5. Gastric Inhibitory Polypeptide (GIP)
6. Glucagon

Question 21

Describe the physiological processes involved in gastrointestinal (GI) motility and secretion.

• 5 stimulatory signals of GIT secretion?
• 8 inhibitory signals of GIT secretion?

Answer 21

GIT SECRETION

Stimulatory Signals

1. Acetylcholine (PNS) and Vagal Stimulation
2. Submucosal (Meissner’s) Plexus Local Reflex
3. Gastrin
4. Histamine
5. Insulin

Inhibitory Signals

1. Adrenaline (SNS)
2. Secretin
3. Cholecystokinin (CCK)
4. Somatostatin
5. Vasoactive Intestinal Peptide (VIP)
6. Gastric Inhibitory Polypeptide (GIP)
7. Glucagon
8. PGE2

Question 22

Describe the underlying pathology of major diseases of the upper gastrointestinal tract (GIT) (including mouth, salivary glands, oesophagus and stomach) and biliary tree.

• What are 7 pathologies of the oral cavity?

Answer 22

Pathologies of the** **Oral Cavity

1. Cleft Lip and Palate: Full-thickness defect of lip or palate due to failure of facial prominences to fuse during early pregnancy.
2. Aphthous Ulcer: Painful, superficial ulceration of the oral mucosa which arises in relation to stress and resolves spontaneously, but often recurs. Characterised by a grayish base surrounded by erythema.
3. Behcet Syndrome: Recurrent aphthous ulcers, genital ulcers, and uveitis due to immune complex vasculitis involving small vessels, usually seen after viral infection.
4. Oral Herpes: Vesicles involving oral mucosa that rupture, resulting in shallow, painful, red ulcers, usually due to HSV-1 (or Zoster and EBV). Primary infection occurs in childhood where lesions heal but virus remains dormant in ganglia of the trigeminal nerve. Stress and sunlight cause reactivation of the virus, leading to vesicles that often arise on the lips (cold sore).
5. Squamous Cell Carcinoma: Malignant neoplasm of squamous cells lining the oral mucosa. Tobacco, alcohol and HPV are major risk factors. Floor of mouth is the most common location and oral leukoplakia (thick white patches on tongue and inside mouth that cannot be scraped away) and erythroplakia (fiery red patches) are precursor lesions.
6. Oral Candidiasis (Thrush): An infection of the mouth caused by a yeast fungus candida, usually seen in immunocompromised states. Presents with white deposit on tongue which can easily be scraped away.
7. Other: Gingivitis, tooth decay, periodontitis, glossitis and other

Question 23

PATHOLOGY OF THE ORAL CAVITY

What is Cleft Lip/Palate?

Answer 23

Pathology of the Oral Cavity

Cleft Lip and Palate: Full-thickness defect of lip or palate due to failure of facial prominences to fuse during early pregnancy.

Question 24

PATHOLOGY OF THE ORAL CAVITY

What is Behcet Syndrome?

Answer 24

Pathology of the Oral Cavity

Behcet Syndrome: Recurrent aphthous ulcers, genital ulcers, and uveitis due to immune complex vasculitis involving small vessels, usually seen after viral infection.

Question 25

PATHOLOGY OF THE ORAL CAVITY

What is Oral Herpes?

Answer 25

Pathology of the Oral Cavity

Oral Herpes: Vesicles involving oral mucosa that rupture, resulting in shallow, painful, red ulcers, usually due to HSV-1 (or Zoster and EBV). Primary infection occurs in childhood where lesions heal but virus remains dormant in ganglia of the trigeminal nerve. Stress and sunlight cause reactivation of the virus, leading to vesicles that often arise on the lips (cold sore).

Question 26

PATHOLOGY OF THE ORAL CAVITY

Squamous Cell Carcinoma?

Answer 26

Pathology of the Oral Cavity

Squamous Cell Carcinoma: Malignant neoplasm of squamous cells lining the oral mucosa. Tobacco, alcohol and HPV are major risk factors. Floor of mouth is the most common location and oral leukoplakia (thick white patches on tongue and inside mouth that cannot be scraped away) and erythroplakia (fiery red patches) are precursor lesions.

Question 27

PATHOLOGY OF THE ORAL CAVITY

Oral Candidiasis (Thrush)?

Answer 27

Pathology of the Oral Cavity

Oral Candidiasis (Thrush): An infection of the mouth caused by a yeast fungus candida, usually seen in immunocompromised states. Presents with white deposit on tongue which can easily be scraped away.

Question 28

Describe the underlying pathology of major diseases of the upper gastrointestinal tract (GIT) (including mouth, salivary glands, oesophagus and stomach) and biliary tree.

• What are 5 pathologies of the salivary glands?

Answer 28

Salivary Glands:

1. Mumps: Infection with mumps virus resulting in bilateral inflamed parotid glands (parotitis). Orchitis, pancreatitis, and aseptic meningitis may also be present. Serum amylase is increased due to salivary gland involvement.
2. Sialadenitis: Inflammation of the salivary gland (usually unilateral), most commonly due to an obstructing stone (sialolithiasis) leading to Staphylococcus aureus infection.
3. Pleomorphic Adenoma: Benign tumor composed of stromal (e.g. cartilage) and epithelial tissue and is the most common tumor of the salivary gland. Usually arises in parotids, presents as a mobile, painless, circumscribed mass at the angle of the jaw. High rate of recurrence but rarely may transform into carcinoma which presents with signs of facial nerve damage (facial nerve runs through parotid gland).
4. Warthin Tumour: Benign cystic tumor with abundant lymphocytes and germinal centers. Second most common tumor of the salivary gland and almost always arises in the parotids.
5. Mucoepidermoid Carcinoma: Malignant tumor composed of mucinous and squamous cells. Most common malignant tumor of the salivary gland and usually arises in the parotids (commonly involves the facial nerve).

Question 29

PATHOLOGY OF THE SALIVARY GLANDS

Mumps?

Answer 29

Pathology of the Salivary Glands

Mumps: Infection with mumps virus resulting in bilateral inflamed parotid glands (parotitis). Orchitis, pancreatitis, and aseptic meningitis may also be present. Serum amylase is increased due to salivary gland involvement.

Question 30

PATHOLOGY OF THE SALIVARY GLANDS

Sialadenitis?

Answer 30

Pathology of the Salivary Glands

Sialadenitis: Inflammation of the salivary gland (usually unilateral), most commonly due to an obstructing stone (sialolithiasis) leading to Staphylococcus aureus infection.

Question 31

PATHOLOGY OF THE SALIVARY GLANDS

Pleomorphic Adenoma?

Answer 31

Pathology of the Salivary Glands

Pleomorphic Adenoma: Benign tumor composed of stromal (e.g. cartilage) and epithelial tissue and is the most common tumor of the salivary gland. Usually arises in parotids, presents as a mobile, painless, circumscribed mass at the angle of the jaw. High rate of recurrence but rarely may transform into carcinoma which presents with signs of facial nerve damage (facial nerve runs through parotid gland).

Question 32

PATHOLOGY OF THE SALIVARY GLANDS

Warthin Tumour?

Answer 32

Pathology of the Salivary Glands

Warthin Tumour: Benign cystic tumor with abundant lymphocytes and germinal centers. Second most common tumor of the salivary gland and almost always arises in the parotids.

Question 33

Describe the underlying pathology of major diseases of the upper gastrointestinal tract (GIT) (including mouth, salivary glands, oesophagus and stomach) and biliary tree.

• What are 13 pathologies of the oesophagus?

Answer 33

Pathologies of the Oesophagus

1. Tracheoesophageal Fistula
2. Oesophageal Web
3. Diverticula
4. Mallory Weiss Syndrome
5. Boerhaave Syndrome
6. Oesophageal Varices
7. Achalasia
8. Gastroesophageal Reflux Disease (GORD)
9. Oesophagitis
10. Eosinophilic Oesophagitis
11. Oesophageal Strictures
12. Barrett Oesophagus
13. Squamous Cell Carcinoma

Question 34

PATHOLOGY OF THE OESOPHAGUS

Tracheoesophageal Fistula?

Answer 34

Pathology of the Oesophagus

Tracheoesophageal Fistula: Congenital defect resulting in a connection between the oesophagus and trachea. Most common variant consists of proximal esophageal atresia with the distal oesophagus arising from the trachea. Presents with vomiting, polyhydramnios, abdominal distension, and aspiration.

Question 35

PATHOLOGY OF THE OESOPHAGUS

Oesophageal Web?

Answer 35

Pathology of the Oesophagus

Oesophageal Web: Thin protrusion of oesophageal mucosa, most often in the upper oesophagus. Presents with dysphagia for poorly chewed food and increased risk for oesophageal squamous cell carcinoma. Plummer-Vinson syndrome is characterised by severe iron deficiency anemia, oesophageal web, and beefy- red tongue due to atrophic glossitis.

Question 36

PATHOLOGY OF THE OESOPHAGUS

Diverticula?

Answer 36

Pathology of the Oesophagus

Diverticula: Acquired outpouching of the oesophagus in the upper oesophagus (Zenker’s Diverticulum), at the tracheal burfications (Mid-Oesophageal Diverticulum) or at the gastroesophageal junction (Epi-phrenic Diverticulum). Presents with dysphagia, obstruction, and halitosis (bad breath). With infection it becomes diverticulitis.

Question 37

PATHOLOGY OF THE OESOPHAGUS

Mallory Weiss Syndrome?

Answer 37

Pathology of the Oesophagus

Mallory Weiss Syndrome: Longitudinal laceration (tears) of mucosa at the gastroesophageal junction caused by severe vomiting, usually due to alcoholism or bulimia. Presents with painful hematemesis.

Question 38

PATHOLOGY OF THE OESOPHAGUS

Boerhaave Syndrome?

Answer 38

Pathology of the Oesophagus

Boerhaave Syndrome: Transmural, usually distal esophageal rupture with pneumomediastinum due to violent retching. Subcutaneous emphysema may be due to dissecting air (crepitus may be felt in the neck region or chest wall). Surgical emergency.

Question 39

PATHOLOGY OF THE OESOPHAGUS

Oesophageal Varices?

Answer 39

Pathology of the Oesophagus

Oesophageal Varices: Dilated submucosal veins in the lower oesophagus which arises secondary to portal hypertension. Distal oesophageal vein normally drains into the portal vein via the left gastric vein. In portal hypertension, the left gastric vein backs up into the esophageal vein, resulting in dilation (varices). Asymptomatic, but risk of rupture exists which is fatal (most common cause of death in cirrhosis).

Question 40

PATHOLOGY OF THE OESOPHAGUS

Achalasia?

Answer 40

Pathology of the Oesophagus

Achalasia: Disordered oesophageal motility with inability to relax the lower oesophageal sphincter (LES), due to damaged ganglion cells in the myenteric plexus (loss of postganglionic inhibitory neurons). Clinical features include dysphagia for solids and liquids, putrid breath, high LES pressure on oesophageal manometry, ‘bird- beak’ sign on barium swallow study and increased risk for oesophageal squamous cell carcinoma.

Question 41

PATHOLOGY OF THE OESOPHAGUS

Gastroesophageal Reflux Disease (GORD)?

Answer 41

Pathology of the Oesophagus

Gastroesophageal Reflux Disease (GORD): Reflux of acid from the stomach due to transient relaxation of the LES or increased intrabdominal pressure. Risk factors include alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia. Clinical features include heart burn (chest pain), asthma and cough and damage to enamel of teeth. Complications include ulceration and Barrett’s oesophagus.

Question 42

PATHOLOGY OF THE OESOPHAGUS

Oesophagitis?

Answer 42

Pathology of the Oesophagus

Oesophagitis: Associated with reflux, infection in immunocompromised such as with Candida (white pseudomembrane), HSV-1 (punched-out ulcers) or CMV (linear ulcers), caustic ingestion, or pill esophagitis (bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).

Question 43

PATHOLOGY OF THE OESOPHAGUS

Eosinophilic Oesophagitis?

Answer 43

Pathology of the Oesophagus

Eosinophilic Oesophagitis: Infiltration of eosinophils in the oesophagus often in atopic patients. Food allergens cause dysphagia. Oesophageal rings and linear furrows often seen on endoscopy and unresponsive to GORD therapy.

Question 44

PATHOLOGY OF THE OESOPHAGUS

Oesophageal Strictures?

Answer 44

Pathology of the Oesophagus

Oesophageal Strictures: Narrowing of the oesophagus, typically occurs when stomach acid and other irritants damage the lining of the oesophagus over time resulting in inflammation and scar tissue. Associated with caustic ingestion and acid reflux.

Question 45

PATHOLOGY OF THE OESOPHAGUS

Barrett Oesophagus?

Answer 45

Pathology of the Oesophagus

Barrett Oesophagus: Metaplasia of the lower oesophageal mucosa from stratified squamous epithelium to non-ciliated columnar epithelium with goblet cells, which is a response of lower oesophageal stem cells to acidic stress. May progress to dysplasia and adenocarcinoma. Adenocarcinoma most common.

Question 46

PATHOLOGY OF THE OESOPHAGUS

Squamous Cell Carcinoma?

Answer 46

Pathology of the Oesophagus

Squamous Cell Carcinoma: Malignant proliferation of squamous cells which usually arises in upper or middle third of the oesophagus. Major risk factors include alcohol and tobacco (most common causes), very hot tea, achalasia, oesophageal web or oesophageal injury. Presents late with poor prognosis, and symptoms include progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis. May also present with hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement). Lymph node spread depends on the level of the esophagus that is involved (upper third to cervical LNs, middle third to mediastinal or tracheobronchial LNs and lower third to celiac and gastric LNs).

Question 47

Describe the underlying pathology of major diseases of the upper gastrointestinal tract (GIT) (including mouth, salivary glands, oesophagus and stomach) and biliary tree.

• What are 9 pathologies of the stomach?

Answer 47

Pathologies of the Stomach

1. Pyloric Stenosis
2. Hiatus Hernia
   
   1. Sliding Hiatal Hernia (Most Common)
   2. Para-Oesophageal Hernia
3. Gastropathy (Chemical or Hypertrophy): Mucosal injury without inflammation due to alcohol, NSAIDs, bile reflux, drugs etc.
4. Ménétrier Disease
5. Acute Gastritis
6. Chronic Gastritis
   
   1. Autoimmune Gastritis
   2. H. Pylori Gastritis
7. Peptic Ulcer Disease:
   
   1. Duodenal Ulcer
   2. Gastric Ulcer
8. Gastric Polyps
9. Gastric Carcinoma
   
   1. Intestinal Type
   2. Diffuse Type

Question 48

PATHOLOGY OF THE STOMACH

Pyloric Stenosis?

Answer 48

Pathology of the Stomach

Pyloric Stenosis: Congenital hypertrophy of pyloric smooth muscle. Classically presents two weeks after birth as projectile non-bilious vomiting, visible peristalsis and olive-like mass in the abdomen, more common in males.

Question 49

PATHOLOGY OF THE STOMACH

Hiatus Hernia?

Answer 49

Pathology of the Stomach

• Hiatus Hernia: Stomach herniates upward through the esophageal hiatus of the diaphragm.
  
  • Sliding Hiatal Hernia (Most Common): Gastroesophageal junction is displaced upward (hourglass stomach), the distal oesophagus and part of the cardia herniate up into the thorax. Sphincter impairment and acid reflux.
  • Para-Oesophageal Hernia: Gastroesophageal junction is usually normal. Fundus protrudes into the thorax. Generally sphincter undisturbed and no reflux.

Question 50

PATHOLOGY OF THE STOMACH

Ménétrier Disease?

Answer 50

Pathology of the Stomach

Ménétrier Disease: Hyperplasia of gastric mucosa leading to hypertrophied rugae, excess mucus production with resultant protein loss and parietal cell atrophy with decreased acid production. Precancerous.

Question 51

PATHOLOGY OF THE STOMACH

Acute Gastritis?

Answer 51

Pathology of the Stomach

Acute Gastritis: Acidic damage to the stomach mucosa due to imbalance between mucosal defenses (mucous, bicarbonate secretion, normal blood supply) and acidic environment. Risk factors include severe burn, hypovolemia (decreased blood supply), NSAIDs (decreased PGE2), heavy alcohol consumption, chemotherapy, increased intracranial pressure (Cushing ulcer, stimulation of vagus nerve leads to increased acid) and shock. Acid damage results in superficial inflammation, erosion (loss of superficial epithelium), or ulcer (loss of mucosal layer).

Question 52

PATHOLOGY OF THE STOMACH

Chronic Gastritis?

Answer 52

Pathology of the Stomach

Chronic Gastritis: Chronic inflammation of stomach mucosa due to chronic autoimmune gastritis (destruction of gastric parietal cells) or chronic H. pylori gastritis. Mucosal inflammation, often leading to atrophy (hypochlorhydria and hypergastrinemia) and intestinal G-cell metaplasia (risk of gastric cancers).

• Autoimmune Gastritis: Autoantibodies to parietal cells and intrinsic factor. Clinical features include atrophy of mucosa with intestinal metaplasia, achlorhydria with increased gastrin levels and antral G- cell hyperplasia, megaloblastic (pernicious) anemia due to lack of intrinsic factor and increased risk for gastric adenocarcinoma (intestinal type).
• H. Pylori Gastritis: Clinical features include epigastric abdominal pain, increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type), and MALT lymphoma. Treatment involves triple therapy.

Question 53

PATHOLOGY OF THE STOMACH

Peptic Ulcer Disease?

Answer 53

Pathology of the Stomach

Peptic Ulcer Disease: Solitary mucosal ulcer involving proximal duodenum (90%) or distal stomach (10%)

• Duodenal Ulcer: Almost always due to H. pylori (> 95%) and presents with epigastric pain that improves with meals. Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands. Usually arises in anterior duodenum, but when present in posterior duodenum, rupture may lead to bleeding from the gastroduodenal artery or acute pancreatitis.
• Gastric Ulcer: Usually due to H. pylori (75%) or NSAIDs and bile reflux. Presents with epigastric pain that worsens with meals. Ulcer is usually located on the lesser curvature of the antrum and rupture carries risk of bleeding from left gastric artery.

Question 54

PATHOLOGY OF THE STOMACH

Gastric Polyps?

Answer 54

Pathology of the Stomach

Gastric Polyps: Growth of tissue that projects above the level of surrounding mucosa, which may develop as a result of epithelial or stromal cell hyperplasia, inflammation, ectopia or neoplasia. Chronic inflammation/gastritis leads to reactive hyperplasia and polyp growth. Fundic gland polyps can occur spontaneously and can be due to PPI use and parietal gland growth.

Question 55

PATHOLOGY OF THE STOMACH

Gastric Carcinoma?

Answer 55

Pathology of the Stomach

Gastric Carcinoma: Malignant proliferation of surface epithelial cells (adenocarcinoma) which presents late with weight loss, abdominal pain, anemia, and early satiety. Spread to lymph nodes can involve the left supraclavicular node (Virchow node) and distant metastasis most commonly involves liver.

• Intestinal Type: More common and presents as a large, irregular ulcer with heaped up margins, most commonly involves the lesser curvature of the antrum. Risk factors include intestinal metaplasia (e.g. due to H. pylori and autoimmune gastritis), nitrosamines in smoked foods (Japan), and blood type A. Distant metastasis include periumbilical region (Sister Mary Joseph nodule).
• Diffuse Type: Characterised by signet ring cells that diffusely infiltrate the gastric wall, desmoplasia results in thickening of stomach wall (linitis plastica). Not associated with H. pylori, intestinal metaplasia, or nitrosamines. Distant metastasis include bilateral ovaries (Krukenberg tumor).

Question 56

Discuss how bile secretion is deranged in cholelithiasis and outline the complications of this condition.

• What is Cholelithiasis?
• Cholesterol stones?
• Black Pigment Stones?
• Risk Factors (6 Fs)?
• Clinical Features?

Answer 56

Cholelithiasis: Presence of gallstones in the gallbladder

• Precipitation of Cholesterol: Cholesterol supersaturation, not enough salts, acid or phospholipids and/or cholesterol stasis
• Cholesterol Stones (80%): Abnormal hepatic cholesterol metabolism → Increased cholesterol concentration in bile and decreased bile salts and lecithin → Hypersaturated bile → Precipitation of cholesterol and calcium carbonate → Cholesterol stones or mixed stones
• Black Pigment Stones (10%): Hemolysis → Increase in circulating unconjugated bilirubin → Increased uptake and conjugation of bilirubin → Precipitation of bilirubin polymers (and calcium) and stone formation
• Mixed Brown Pigment Stones (10%): Bacterial β-glucuronidase hydrolyzes conjugated bilirubin and lecithin in the bile → Increased unconjugated bilirubin and fatty acids → Precipitation of calcium carbonate, cholesterol, and calcium bilirubinate in bile
• Risk Factors: Six F’s (Fat, Female, Fertile, Forty, Fair-Skinned and Familial)
• Clinical Features: Mostly asymptomatic. Biliary colic (constant, dull RUQ pain lasting < 6 hours), pain post-prandially which may radiate to the epigastrium, right shoulder and back, nausea, vomiting, early satiety, bloating and dyspepsia.

Question 57

What are the Complications/Implications of Bile Secretion Stasis?

Answer 57

Bile Secretion Implications:

• The biliary system normally has low pressure and allows bile to flow freely through
• Gallstones act as an obstruction and impair the flow of bile
• The obstruction can occur throughout the biliary system (gallbladder, cystic duct, common bile duct, or hepatopancreatic ampulla/sphincter) resulting in a number of complications

Question 58

12 Complications of Cholelithiasis?

Answer 58

Complications of Cholelithiasis

1. Recurrence of Gallstones
2. Choledocholithiasis: Presence of gallstones in the common bile duct (causes biliary colic and obstruction)
3. Cholecystitis: Inflammation of the gallbladder that most commonly occurs after cystic duct obstruction from cholelithiasis (bacterial infection may or may not occur)
4. Ascending/Acute Cholangitis: Ascending bacterial infection of the biliary tract facilitated by bile stasis (bacteria ascend from the duodenum following partial obstruction of the hepatopancreatic sphincter by gallstones)
5. Acute (Gallstone) Pancreatitis: Inflammation of the pancreas due to obstruction of the Ampulla of Vater (hepatopancreatic ampulla)
6. Bacteraemia, Septicaemia and Sepsis: Usually a complication of cholangitis
7. Gallstone Ileus: Mechanical bowel obstruction by a gallstone that has eroded through the biliary system into the gastrointestinal system, creating a fistula.
8. Gallbladder Empyema: Accumulation of pus within gallbladder.
9. Hepatic Abscess: An enclosed collection of pus within liver caused by a bacterial infection.
10. Gangrenous Cholesystitis and Rupture: Secondary to gallbladder distension, causing increased tension and pressure on the gallbladder wall, which can lead to ischemic changes and necrosis and perforation of the gallbladder wall
11. Emphysematous Cholecystitis: A rare, severe complication of acute cholecystitis caused either by primary or secondary infection of the gallbladder with gas-forming bacteria or necrosis of the gallbladder wall.
12. Gallbladder Carcinoma: Invasive carcinoma arising in the gallbladder (most commonly adenocarcinoma)

Question 59

Review the importance of history in determining the cause of abdominal pain.

• 5 Extra-abdominal causes?

Answer 59

Abdominal Pain: There are many causes of abdominal pain, and careful history taking will often lead to the correct diagnosis (see image below for different causes of abdominal pain)

Extra-Abdominal Causes of Pain:

1. Cardiac: Inferior myocardial infarction can give epigastric pain
2. Respiratory: Base of lung pneumonia or pneumothorax
3. Neurological: Radiculopathy (spinal nerve root pathology such as pinched nerve or tumour)
4. Metabolic: Porphyria (a group of disorders caused by an over-accumulation of porphyrin which is essential for the function of haemoglobin)
5. Musculoskeletal: Costochondritis

Question 60

Type/Character/Site of Abdominal Pain

• What is Visceral Pain?
• Parietal/Somatic Pain?
• Referred Pain?
• Colicky Pain?

Answer 60

Type/Character/Site of Abdominal Pain

Visceral Pain: Dull, poorly localised achy pain due to distention or stretching of an organ. Produces vague discomfort often felt in the midline. Mediated by splanchnic sympathetic nerves.

Parietal/Somatic Pain: Sharp localised pain due to irritation to the parietal peritoneum. Mediated by pain fibres which pass to spinal cord via segmental nerves.

Referred Pain: Pain felt at a distance from the site of origin. Pain that radiates through to the back suggests pancreatic disease, AAA or a penetrating peptic ulcer. Pain due to inferior diaphragmatic irritation may radiate to the tip of the shoulder and that due to oesophageal reflux or spasm may radiate to the throat.

Colicky Pain: Pain coming and going in waves (intermittent) and related to peristaltic movements, due to muscular contractions of hollow tubes (i.e. biliary system, ureters, colon). Arises because of complete or partial blockage of the bowel (commonly small intestine) which triggers intestinal receptors.

Question 61

Causes of Acute and Severe Abdominal Pain?

• 7 of GI origin?
• 6 of Non-GI origin?

Answer 61

Acute and Severe Pain:

• GI Origin:
  
  1. Appendicitis
  2. Bowel obstruction
  3. Perforation
  4. Bowel ischaemia
  5. Diverticulitis
  6. Pancreatitis
  7. Biliary colic/cholecystitis
• Non-GI Origin:
  
  1. Ruptured aortic aneurysm
  2. Ectopic pregnancy
  3. Leak from ovarian cyst
  4. Renal tract calculus
  5. Inferior myocardial infarction
  6. Basal lung pathology e.g. basal pneumonia

Question 62

Explain the clinical distinction between functional and structural gastrointestinal (GI) disorders.

• Definitions of each?
• Symptoms?
• Classification systems?
• Routine investigations for each?
• Examples of each?

Answer 62

Functional Gastrointestinal Disorders: Disorders due to abnormal functioning of the GI tract and where symptoms (persistent and recurring) cannot be explained by the presence of a currently identifiable structural, biochemical or tissue abnormality.

• Symptoms include abdominal pain and cramps, excess gas, bloating and change in bowel movements.
• Rome IV classification system used for diagnosis.
• Routine investigations such as x-ray, CT scan, colonoscopy and biopsy are generally negative
• Examples: Functional heartburn, functional dyspepsia (indigestion), functional constipation, functional diarrhoea, functional bloating, gastroparesis and irritable bowel syndrome

Structural Gastrointestinal Disorders: Disorders due to a structural abnormality of the GI tract.

• Symptoms can be similar to functional disorders, but may also include obstructed bowel movements, unexplained weight loss and fatigue, significant changes to bowel habits and unusual pain or even bleeding.
• Routine investigations such as x-ray, CT scan, colonoscopy and biopsy commonly reveal pathology
• Examples: Haemorrhoids, diverticular disease, colon polyps, perianal abscess, anal fissures and fistulas, colon cancer, inflammatory bowel disease and colitis

Question 63

Describe the selection and interpretation of gastrointestinal (GI) investigations for common upper GI symptoms

• What are the 5 Principles of GI Investigations?

Answer 63

Principles of GI Investigations:

1. Start with the least invasive and safest tests
2. Start with the least unpleasant and cheapest tests
3. Appropriate amount of testing for the clinical scenario
4. Choice of tests can depend on the patient and their co-morbid conditions
5. Most tests assess for structural abnormalities. Less options to assess the function of the gut

Question 64

Investigations for GI Symptoms

• Blood Tests?
  
  • Routine = 5
  • Semi-Routine = 6
  • Disease-specific Serology & Markers = 4

Answer 64

GI INVESTIGATIONS - BLOOD TESTS

• Routine
  
  1. Full Blood picture (FBP): Haemoglobin, WCC, platelets, size of cells (MCV, MCH, MCHC) and a comment on film
  2. Urea and Electrolytes (U&E): Na+, K+, urea and creatinine
  3. Liver Function Tests (LFT): Albumin, bilirubin, ALT, ALP, GGT
  4. Erythrocyte Sedimentation Rate (ESR): Marker of inflammation
  5. C-Reactive Protein: Marker of inflammation
• Semi-Routine
  
  1. Calcium and Phosphate: To assess mineral homeostasis and absorptive function
  2. Thyroid Function Tests: To assess function of thyroid gland
  3. Iron Studies: Measure ferritin and transferrin saturation
  4. Vitamin B12, Folate and Vitamin D: Some measure of gut absorption
  5. Amylase and Lipase: Acute pain due to pancreatitis?
  6. Lipid Profile: High triglycerides as cause for pancreatitis?
• Disease-Specific Serology and Markers
  
  1. Helicobacter Serology: Detects specific IgA and IgG antibodies
  2. Coeliac Serology: Tissue transglutaminase IgA and genetic study (HLA DQ2/DQ8)
  3. Liver: Viral hepatitis, auto-immune (anti-smooth muscle for autoimmune hepatitis, anti- mitochondrial for primary biliary cirrhosis), caeruloplasmin, alpha-1 anti-trypsin
  4. Tumour Markers: CEA (colon), alpha fetoprotein (liver), CA19-9 (pancreaticobiliary)

Question 65

Investigations for GI Symptoms

• Stool Tests? (5)

Answer 65

GI INVESTIGATIONS - STOOL TESTS

1. Microscopy, Culture and PCR: To determine presence/cause of infection
2. Faecal Calprotectin-Colonic Inflammation: Such as ulcerative colitis
3. Faecal Elastase: To assess pancreatic function
4. Faecal Electrolytes: To evaluate chronic diarrhoea
5. Faecal Occult Blood Test: For average risk colorectal cancer screening and to detect tiny traces of blood in the stool

Question 66

Investigations for GI Symptoms

• Urine Tests? (4)

Answer 66

GI INVESTIGATIONS - URINE TESTS

1. Microscopy and Culture: To determine presence/cause of infection
2. 5-Hydroxyindoleacetic Acid (5-HIAA): To help diagnose and monitor carcinoid tumour (may be significantly increased when a person has a carcinoid tumour that produces serotonin)
3. Urinary Porphyrins: For genetic disorders, metabolic disturbances and diseases, anaemias, oxidative stress, and high-level exposure to toxic chemicals or metals
4. Urinary Copper Excretion: For Wilson’s disease

Question 67

Investigations for GI Symptoms

• Breath Tests? (3)

Answer 67

GI INVESTIGATIONS - BREATH TESTS

1. Urease Breath Test: For Helicobacter pylori infection
2. Lactose and Fructose Malabsorption Breath Tests: To detect absorptive function particularly with functional gastrointestinal disorders
3. Lactulose Breath Test: For small intestinal bacterial overgrowth (SIBO)

Question 68

Investigations for GI Symptoms

• Endoscopic Tests? (4)

Answer 68

GI INVESTIGATIONS - ENDOSCOPIC TESTS

1. Gastroscopy: A gastroscope is inserted into the mouth and used to examine the upper parts of the digestive tract (oesophagus, stomach and first part of the small intestine)
2. Flexible Sigmoidoscopy: A shorter tube is used to examine just the lower part of the colon (the sigmoid colon)
3. Colonoscopy: An endoscope is inserted into the anus and used to examine lower parts of the digestive tract (rectum and colon)
4. Endoscopic Retrograde Cholangio-Pancreatography (ERCP): An endoscope is inserted through mouth, oesophagus, stomach and into duodenum to find duodenal papilla, where a small catheter is then put down through the endoscope and used to inject special dye into the pancreatic and bile ducts. Used to view (and biopsy) the gallbladder, bile duct, pancreas, and pancreatic duct.

Question 69

Investigations for GI Symptoms

• Radiology/Nuclear Medicine? (10)

Answer 69

GI INVESTIGATIONS - Radiology/Nuclear Medicine

1. Plain Films: To detect faecal loading or bowel obstruction
2. Ultrasound: Allows for visualisation of solid organs, bile ducts, gallbladder for the detection of abnormalities
3. CT Scan (Enterography and Colography): Allows visualisation of solid organs, biliary tree, colon for the detection of abnormalities
4. CT Angiogram: For acute bleeding
5. Magnetic Resonance Cholangiopancreatography (MRCP): Produces detailed images of pancreatic and bile ducts
6. Magnetic Resonance Enterography: Produces detailed images of the small intestine
7. Barium Studies: Swallowing a liquid suspension of barium sulphate before a series of X- rays are taken of your upper digestive tract, the barium then coats the walls of the digestive tract, which allows the shape of your upper digestive tract to be outlined
   
   1. Barium Swallow/Meal: For oesophagus and stomach
   2. Small Bowel Study: For the small intestine (mostly gone) - Barium
   3. Enema: For colon (mostly gone)
8. Red Cell Scan: For bleeding
9. Gastric Emptying Study: For suspected delayed gastric emptying
10. PET Scan: For tumour localisation

Question 70

Investigations for GI Symptoms

• Other Tests? (5)

Answer 70

GI INVESTIGATIONS - Other Tests

1. Liver Biopsy: To assess liver damage or disease
2. Hepascore Blood Test and Hepatic Elastography (Ultrasound Based): As alternatives to detect advanced fibrosis/cirrhosis
3. Endoscopic Ultrasound: Endoscopy with mini-ultrasound probe to assess digestive system, also enables fine needle aspiration for mass lesions below the mucosal surface of GI tract
4. Capsule/Double Balloon Enteroscopy: Allows for extensive examination and endoscopic treatment of abnormalities found in the small intestine
5. Oesophageal pH Studies and Manometry: To assess oesophageal function and muscle function

Question 71

Outline the distribution of conditions causing upper abdominal pain in the community, focusing on variations by age and gender.

Answer 71

Question 72

Discuss the psychosocial aspects of functional gastrointestinal disease.

• Examples of Psychosocial Factors?
• Importance of Psychosocial Factors?
• Impact of Psychosocial Factors?

Answer 72

Psychosocial Aspects of Functional GI Disease:

Examples of Psychosocial Factors: Stress, history of sexual and physical abuse, psychiatric disorders, coping style, and learned illness behaviours

Importance of Psychosocial Factors: Influence gut physiology, the symptom experience, health behaviour, and outcome. These psychosocial factors are influenced by and influence GI symptoms in a bidirectional manner as mediated through the brain-gut axis (CNS and ENS pathways).

Impact of Psychosocial Factors: Affect gut function, the experience of pain, health-related quality of life, work absenteeism, health care use, and medical and societal costs

Question 73

Psychosocial Aspects of Functional GI Disease

• Life stress?
• Sexual and Physical Abuse?
• Anxiety Disorders?

Answer 73

Psychosocial Aspects of Functional GI Disease - Specific Examples:

Life Stress: Severe life stress has been found immediately before the onset of functional bowel disorders and plays an important part in explaining exacerbation of symptoms and treatment-seeking.

Sexual and Physical Abuse: A history of abuse is not etiologic for functional gastrointestinal disorders, but is associated with a tendency to communicate psychological distress through physical symptoms. It may also lower gastrointestinal symptom threshold or increase intestinal motility and modify the appraisal of bodily symptoms (i.e. increase medical help-seeking) due to altered cognitions (e.g. feeling ineffective and unable to control the symptoms).

Anxiety Disorders: May initiate or perpetuate functional gastrointestinal disease symptoms through their associated heightened autonomic arousal (in response to stress) or at the level of the brain, which can interfere with GI sensitivity and motor function

Question 74

Describe the embryological development of the peritoneum.

Answer 74

Development of the Peritoneum:

1. The mesoderm of the trilaminar embryo (week 3) differentiates into the lateral plate mesoderm, which becomes the intraembryonic coelom. This forms a horse-shaped body cavity around the gut tube.
2. The intraembryonic coelom separates into three regions, a single pericardial region at the top of the horseshoe, two pleural spaces, and two peritoneal spaces.
3. After embryonic folding (in week 4) this all becomes the anterior cavity of the body and is by then divided by the septum transversum into the thoracic and abdominopelvic cavities. These spaces are lined with mesodermally-derived serous membranes which both coat the organ (visceral) and line the cavity (parietal).
4. Meanwhile, folding has produced a gut tub (derived from the yolk sac) lined with endoderm and coated with mesoderm which develops between the two serous peritoneal sacs.
5. The gut tube develops into the foregut, midgut and hindgut as it lengthens, rotates and expands.
6. The foregut, midgut and hindgut becomes attached to the abdominal wall posteriorly by a double fold of peritoneum and the foregut also becomes attached to the abdominal wall anteriorly. The posterior attachment is the dorsal mesogastrium and the anterior attachment is the ventral mesogastrium.
7. As the foregut rotates, the dorsal and ventral mesogastrium rotate with it. The line of attachment of the ventral mesogastrium swings round to the right as the foregut develops and end up running along the lesser curvature of the stomach and the top of the proximal duodenum. The attachment of the dorsal mesogastrium swings round to the left and ends up running along the greater curve of the stomach and the underside of the proximal duodenum.
8. While the foregut develops, so do organs within the mesogastrium. The liver develops in the ventral mesogastrium and the spleen develops in the dorsal mesogastrium.
9. The part of the ventral mesogastrium attached from the foregut to the liver becomes the less omentum and the part of the dorsal mesogastrium attached from the foregut to the spleen will grow downwards in front of the transverse colon to become the greater omentum.

Question 75

Which 4 structures does the Ventral Mesogastrium become?

Which 4 structures does the Dorsal Mesogastrium become?

Answer 75

• Ventral Mesogastrium:
  
  1. Lesser omentum
  2. Falciform ligament
  3. Hepatogastric ligament
  4. Hepatoduodenal ligament
• Dorsal Mesogastrium:
  
  1. Greater omentum
  2. Gastrocolic ligament
  3. Gastrosplenic ligament
  4. Gastrophrenic ligament

Question 76

What is the histology of the large intestine vs. anus?

Answer 76

Histology: Colon has simple columnar epithelium with no villi but many more goblet cells, while anus contains non-keratinised stratified squamous epithelium which becomes keratinised at the surface. Submucosa also contains mucous-producing glands.

Question 77

What is the difference between the internal and external sphincter of the anal canal?

Answer 77

Internal Sphincter: Ring of smooth muscle

External Sphincter: Flat plane of skeletal muscle

Question 78

What are Taenia Coli?

3 types?

Answer 78

Taenia Coli: Three bands of longitudinal smooth muscle (muscularis externa condensed) which run the length of the organ on the outside of the ascending, transverse, descending and sigmoid colon (just below the serosa) and which contract lengthwise to form haustra.

1. Omental: A band of longitudinal muscle (the anterior and the largest) where the omental appendages attach
2. Free/Lateral: A band of longitudinal muscle where neither the mesocolon or appendices attach, and which can be followed on the surface of the colon
3. Mesocolic: A band of longitudinal muscle where the transverse and sigmoid mesocolon attach

Question 79

What are Epiploic Omental Appendages?

Answer 79

Epiploic Omental Appendages: Small normal outpouchings of peritoneal fat situated along the external surface of colon, most abundant along the transverse and sigmoid colon and absent in the rectum

Question 80

What are Paracolic Gutters?

Answer 80

Paracolic Gutters: Spaces between the colon and abdominal wall that runs lateral to the ascending and descending colons (sometimes there are medial gutters too). They provide a ready pathway for bile or infection escaping from lower or upper gut perforations to track up or down the abdominal cavity very quickly, and in supine subjects are a collecting point for such pleasant materials.

Question 81

What are Haustrations?

Answer 81

Haustrations: Sacculations of the colon formed by lengthwise contractions of the taenia coli. The haustra stay in formation for long periods, which helps store the chyme as it is dehydrated and made into faeces.

Question 82

What is the blood supply of the Large intestine and anorectal area?

Answer 82

Superior Mesenteric Artery (Midgut): Supplies distal half of duodenum, jejunum, ileum, cecum, appendix, ascending colon and proximal two-thirds of transverse colon

Inferior Mesenteric Artery (Hindgut): Supplies distal one-third of transverse colon, descending colon, sigmoid colon, rectum and superior portion of anal canal

Systemic Venous Drainage: Drains blood from the inferior part of the rectum and anal canal to the IVC

Portal Venous Drainage: Superior and inferior mesenteric veins drain blood from midgut and hindgut to the hepatic portal vein and liver

Question 83

Lymphatic drainage of the large intestine?

Answer 83

Lymphatic Drainage:

Midgut: Superior mesenteric LNs

Hindgut: Inferior mesenteric LNs

Question 84

Nerve supply of the large intestine?

(Midgut/Hindgut/External Anal Sphincter)

Answer 84

Nerve Supply:

Midgut: Superior mesenteric plexus (sympathetic) and vagus nerve (parasympathetic)

Hindgut: Inferior mesenteric plexus (sympathetic) and pelvic splanchnic nerve (parasympathetic)

External Anal Sphincter: Somatic nerve control

Question 85

What are Plain Abdominal X-rays used for?

• How are they taken?
• Indications?
• Interpretation?
• Structures visible?

Answer 85

Plain Abdominal Films: Still used primarily to assess intestinal perforation (intraperitoneal air), bowel obstruction or assessment for catheter placement.

• Normally AP supine (standard) and AP erect (gases and fluid line)
• Indications for plain AXR differ depending on the availability of CT or USS, which give considerably more information.
• Abdominal X-rays are useful for certain defined pathology such as abnormal gases, masses, bones and stones. Also for foreign bodies, suspected bowel obstruction and toxic megacolon (greater than 6cm).
• Interpretation:
  
  • BBC: Bowel and organs, Bones and Calcification
  • BOMBS: Bones, Organs, Masses, Bloating (Gas) and Stones
• Structures Visible on Plain Abdominal Film: Small bowel, large bowel, lungs (bases may be visible), liver, kidneys (and renal stones), spleen, gallbladder (rare except for stones), stomach (variable amount of air), psoas muscle, bladder (variable based on fullness), ribs, lumbar vertebrae, sacrum, coccyx, pelvis and proximal femur

Question 86

List 8 factors involved in absorption, their function and an example of when they go wrong.

Answer 86

• 1) Large Mucosal Surface Area → Increase the absorptive function of the small intestine
  
  • Example: Short bowel syndrome (after bowel resection) can disturb the normal absorption of nutrients and electrolytes, depending on areas removed.
• 2) Circular Folds → Deep, permanent folds of the mucosa and submucosa that force chyme to spiral through the lumen, slowing its movement and allowing time for full nutrient absorption.
• 3) Intestinal Villi → Fingerlike projections of the mucosa that increase the surface area for absorption.
  
  • Example: Giardia trophozoites can adhere to the intestinal mucosa via ventral adhesive discs and cause flattening of the villi, partial/full villous atrophy and shortening of microvilli, reducing absorption.
• 4) Intestinal Microvilli → Long slender projections from the surface of some cells that increase the surface area for absorption
  
  • Example: Coeliac disease involves the blunting of microvilli and villous atrophy, reducing the absorptive function of the intestine.
• 5) Enterocytes → Simple columnar absorptive cells which are primarily responsible for the absorbtion of nutrients and electrolytes.
• 6) Brush Border Enzymes and Transporters → Complete the digestion of carbohydrates and proteins in the small intestine, and facilitate transport of electrolytes and nutrients across apical and basolateral cell membranes into paracellular space and the bloodstream.
  
  • Example: Lactase deficiency can prevent the absorption of lactose (dairy products).
• 7) Co-Factors → A non-protein chemical compound or metallic ion that is required for an enzyme’s activity.
  
  • Example: Intrinsic factor is required for B12 absorption, and deficiency can cause reduced B12 absorption.
• 8) Intestinal Motility Rate of segmentation and peristalsis (intestinal motility) can affect rate of absorption.
  
  • Example: Increased motility can reduce absorption and cause diarrhoea

Question 87

What are 5 Consequences of Impaired Absorption?

Answer 87

Impaired Absorption Consequences:

1. Nutritional deficiency
2. Vitamin deficiency
3. Malnourishment
4. Diarrhoea
5. Weight loss

Question 88

What is the difference between Gastroenteritis and Dysentry?

What are the 4 principle microbiological causes?

Answer 88

Gastroenteritis: Inflammation (usually infection) of the digestive tract marked by diarrhoea, cramps, nausea, vomiting and fever

Dysentery: Painful, bloody, small-volume diarrhea due to inflammation of the intestines

Principle Microbiological Causes: Campylobacter, Salmonella, Shigella and Escherichia Coli

Question 89

What are 7 Non-Invasive Bacteria (Toxins) that cause Gastroenteritis and Dysentry?

• Mode of transmission?
• Impact on mucosa?

Answer 89

Principle Microbiological Causes of Dysentry - Non-Invasive Bacteria (Toxins):

• 1) Staphylococcusaureus** → Foodborne (produces heat-stable enterotoxin)
  
  • Toxin acts on mucosa
• 2) Bacilli cereus → Foodborne (spore formation and enterotoxin)
  
  • Toxin acts on the mucosa
• 3) Clostridium perfringens → Foodborne (spore formation and heat-stable enterotoxin)
  
  • Enterotoxin disrupts ion transport in SI so water enters lumen
• 4) Clostridium botulinum → Foodborne (spore formation and heat-stable neurotoxin)
  
  • Neurotoxin prevents Ach release at axon endings at the neuromuscular junction, causing flaccid paralysis
• 5) Escherichia coli (enterotoxigenic) → Foodborne/ waterborne (toxin production)
  
  • Toxin acts on mucosa
• 6) Vibrio cholerae → Waterborne or some foodborne (seafood) (exotoxin production)
  
  • Toxin acts on mucosa, activates G Protein, adenyl cyclase, cAMP which acts on transporter to increase ion/water efflux
• 7) Clostridium difficile → Proliferates as other normal flora eliminated (spore formation and produces enterotoxin, cytotoxic)
  
  • Toxin acts on mucosa

Question 90

What are 4 Invasive Bacteria (Toxins) that cause Gastroenteritis and Dysentry?

• Mode of transmission?
• Impact on mucosa?

Answer 90

Principle Microbiological Causes of Dysentry - Invasive Bacteria (Toxins):

• 1) Salmonella → Foodborne and waterborne
  
  • Adhere to intestinal M cells, invasion and internalisation into vesicles, then enter into macrophages
• 2) Shigella → Person-Person (fingers and faeces), food and flies
  
  • Invades, replicates, and disseminates within the colonic mucosa (intracellular motility)
• 3) Escherichia coli (enterohemorrhagic) → Foodborne, animals, faeces (produces Shiga-like toxin)
  
  • Translocate across the intestinal epithelium via M-cells
• 4) Campylobacter jejuni → Foodborne, waterborne or milk-borne or from animals (chickens)
  
  • Penetrates the mucus and colonises the intestinal crypts and reside in membrane- bound compartments

Question 91

What are 2 Viruses that cause Gastroenteritis and Dysentry?

• Mode of transmission?
• Impact on mucosa?

Answer 91

Principle Microbiological Causes of Dysentry - Viruses:

• 1) Rotavirus → Foodborne, waterborne and person- person (faecal-oral)
  
  • Invade epithelial cells, shedding of coat, replication with host machinery, budding from cell
• 2) Norovirus → Foodborne, waterborne (swimming)
  
  • Invade epithelial cells, shedding of coat, replication with host machinery, budding from cell

Question 92

What is Diarrhoea? 5 Types?

Answer 92

Diarrhoea: Defined as an increase in stool mass, frequency, or fluidity, typically greater than 200 gm per day

Question 93

What is the Pathophysiology and 4 Causes of Dysmotility Diarrhoea?

Answer 93

Pathophysiology of Diarrhoea (DOMES):

Dysmotility: Rapid intestinal passage due to increased bowel movements which decrease absorption.

Causes:

1. Hyperthyroidism
2. Diabetes
3. Carcinoma
4. Drugs (erythromycin).

Question 94

What is the Pathophysiology and 6 Causes of Osmotic Diarrhoea?

Answer 94

Pathophysiology of Diarrhoea (DOMES):

Osmotic: Water is drawn into the intestinal lumen due to the excessive osmotic forces exerted by unabsorbed luminal solutes. The diarrhea fluid is more than 50mOsm more concentrated than plasma and abates with fasting.

Causes:

1. Laxatives
2. Lactose intolerance
3. Malabsorption
4. Epson salts (MgSO4)
5. Some antacids (MgOH2)
6. Mannitol or sorbitol.

Question 95

What is the Pathophysiology and 6 Causes of Malabsorptive Diarrhoea?

Answer 95

Pathophysiology of Diarrhoea (DOMES):

Malabsorptive: Inability to absorb certain substances resulting in the osmotic movement of water into the lumen. Follows generalised failure of nutrient absorption, is associated with steatorrhea, and is relieved by fasting (low volume diarrhoea).

Causes:

1. Coeliac disease
2. Lactose intolerance
3. Crohn’s disease
4. Giardia
5. Exocrine pancreatic insufficiency
6. Hepatic insufficiency or other malabsorption disorders.

Question 96

What is the Pathophysiology and 5 Causes of Exudative Diarrhoea?

Answer 96

Pathophysiology of Diarrhoea (DOMES):

Exudative: Destruction of the intestinal epithelium which results in exudation of serum and blood into the lumen and destruction of absorptive epithelium. Due to inflammatory disease and is characterised by purulent, bloody stools that continue during fasting.

Causes:

1. Viral infection (rotaviruses, coronaviruses, parvoviruses (canine and feline) or norovirus)
2. Bacterial infection (Salmonella, Shigella, E. coli or Campylobacter)
3. Parasite infection (Cryptosporidium or Giardia)
4. Ulcerative colitis
5. Crohn’s disease.

Question 97

What is the Pathophysiology and Causes of Secretory Diarrhoea?

Answer 97

Pathophysiology of Diarrhoea (DOMES):

Secretory: Active secretion of water into the intestinal lumen via inhibition/activation of enzymes (for example, ↑ cAMP activity). Secretion of water into the intestinal lumen exceeds absorption. Characterised by isotonic stool and persists during fasting (high volume diarrhoea).

Causes: Bacterial infection such as vibrio cholerae where the enterotoxin acts on enterocytes to activate adenyl cyclase, activating cAMP and stimulating Cl- ion channels to open, resulting in efflux of Cl- ions into the lumen and subsequent water secretion.

Other agents can also induce intestinal water secretion including laxatives, drugs (some types of asthma medications, antidepressants, cardiac drugs) and certain metals, organic toxins, and plant products (arsenic, insecticides, mushroom toxins, caffeine).

Question 98

Discuss how the choice of therapy for diarrhoea depends upon the underlying cause of the disease.

• Primary therapy?
• DOMES?

Answer 98

• *Primary Therapy:** Rehydration!
• *Main Treatment of Diarrhoea:** Dependent on underlying cause

Dysmotility: Treat cause of increased motility i.e. hyperthyroidism or carcinoma

Osmotic: Prevent reasons for osmotic drive i.e. remove poorly absorbed foods and drugs from diet

Malabsorptive: Treat or manage cause of malabsorption i.e. giardia or pancreatic/hepatic insufficiencies or remove poorly absorbed foods or intolerances from diet such as gluten and lactose

Exudative: Treat underlying infection i.e. viral, bacterial or parasitic or manage underlying inflammatory condition i.e. inflammatory bowel disease

Secretory: Treat underlying infection i.e. cholera or remove causative agents from diet i.e. caffeine, drugs and toxins

Question 99

Describe the histopathological features of the small intestine in malabsorption states:

Cystic Fibrosis? (2)

Answer 99

Histopathological Features

• Intestinal obstruction (mucus plug and maldigestion) but unharmed enterocytes
• Formation of pancreatic intraductal concretions and low-grade chronic autodigestion of the pancreas

Question 100

Describe the histopathological features of the small intestine in malabsorption states:

Coeliac Disease? (3)

Answer 100

Histopathological Features of Coeliac Disease

1. Enterocyte damage, most damage done to distal duodenum and proximal jejunum due to highest exposure to gluten.
2. Increased numbers of intraepithelial CD8+ T lymphocytes (intraepithelial lymphocytosis), crypt hyperplasia, villous atrophy, loss of mucosal and brush- border surface area (flattened mucosa) and chronic inflammation.
3. Increased numbers of plasma cells, mast cells, and eosinophils, especially within the upper part of the lamina propria.

Question 101

Describe the histopathological features of the small intestine in malabsorption states:

Environmental Enteropathy (aka Tropical Sprue)

Answer 101

Environmental Enteropathy (aka Tropical Sprue)

• No accepted histopathological criteria that allows for diagnosis • Similar to severe celiac disease

Question 102

Describe the histopathological features of the small intestine in malabsorption states:

Lactase (Disaccharide) Deficiency (2)

Answer 102

Histopathological Features of Lactase (Disaccharide) Deficiency

1. Normal intestinal architecture
2. Down-regulation of lactase gene expression and activity (acquired deficiency) at brush border

Question 103

Describe the histopathological features of the small intestine in malabsorption states:

Giardia or Tapeworm (3)

Answer 103

Histopathological Features of Giardia or Tapeworm

1. Evidence of tapeworm or giardia trophozoites
2. Tapeworm obstructs lumen and absorptive surface
3. Trophozoites adhere to intestinal epithelium via large ventral discs and cause microvilli (brush border) shortening and retraction, villous atrophy and disruption of intestinal epithelial tight junctions and permeability

Question 104

What is Inflammatory Bowel Disease (IBD)?

2 Types?

Answer 104

Inflammatory Bowel Disease (IBD): Inappropriate mucosal immune activation

Ulcerative Colitis: Limited to the colon and rectum and extends only into the mucosa and submucosa

Crohn Disease: Has also been referred to as regional enteritis (because of frequent ileal involvement) and may involve any area of the GI tract and is typically transmural

Question 105

How does the pathology of Crohn’s Disease compare to that of Ulcerative Colitis?

Answer 105

Question 106

How does the histology of Crohn’s Disease compare to that of Ulcerative Colitis?

Answer 106

Question 107

Compare Crohn’s Disease and Ulcerative Colitis in terms of:

Answer 107

Question 108

Describe the Gross pathology of Crohn’s disease.

Answer 108

Question 109

Describe the microscopic pathology of Crohn disease.

Answer 109

Question 110

Describe the gross pathology of ulcerative colitis

Answer 110

Question 111

Describe the histopathology of ulcerative colitis

Answer 111

Question 112

What is an example of a Congenital Large Intestine Diseases and its Pathological Features?

Answer 112

Hirschsprung’s Disease: Defective relaxation and peristalsis of rectum and distal sigmoid colon, associated with Down syndrome. Due to congenital failure of ganglion cells (neural crest-derived) to descend into myenteric and submucosal plexus. Clinical features are based on obstruction such as failure to pass meconium, empty rectal vault on digital rectal exam and massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture.

Question 113

Describe the pathogenesis of infectious large bowel diarrhoea

Answer 113

Question 114

Describe the pathogenesis of infectious small bowel diarrhoea

Answer 114

Question 115

Describe the pathogenesis of infectious food poisoning

Answer 115

Question 116

What are the clinical findings of ulcerative colitis?

Answer 116

Question 117

What are the complications of celiac disease?

Answer 117

Question 118

What are the distinguishing features between diverticulosis and diverticulitis

Answer 118

Question 119

What are 4 causes of Acquired Intestinal Obstruction?

Answer 119

Acquired Intestinal Obstruction: Mechanical obstruction of the intestinal lumen due to…

1. Hernias: Protrusion of a serosa-lined pouch of peritoneum through a weakened/defective abdominal wall area, most frequent cause of intestinal obstruction and risk of strangulation
2. Intestinal Adhesions: Adhesions between bowel segments, abdominal wall or operative sites due to surgical procedures, infection, or other causes of peritoneal inflammation such as endometriosis
3. Intussusception: When a proximal segment of the intestine, constricted by a wave of peristalsis, telescopes into the immediately distal segment, resulting in obstruction and disruption of blood supply with infarction. Most common cause of intestinal obstruction in children younger than 2 years of age.
4. Volvulus: Twisting of bowel along its mesentery which results in obstruction and disruption of the blood supply with infarction. Most common locations are sigmoid colon due to large degree of mobility (elderly, coffee bean appearance of abdominal xray) and cecum (young adults).

Question 120

Clinical findings in Crohn’s Disease?

Answer 120

Question 121

Pathogenesis and Clinical features of acquired indirect + direct inguinal hernias?

Answer 121

Question 122

What are 6 Acquired Inflammation Diseases of the Large Intestine?

Answer 122

Acquired Inflammation:

1. Ischaemic Bowel Disease
2. Inflammatory Bowel Disease
3. Infectious Enterocolitis → Inflammation of the digestive tract caused by microbial infections such as with campylobacter, E.coli, salmonella and shigella
4. Pseudomembranous Colitis → Generally caused by C. difficile resulting in formation of tan pseudomembranes composed of neutrophils, dead epithelial cells, and inflammatory debris. Also referred to as antibiotic-associated colitis or antibiotic-associated diarrhea.
5. Diversion Colitis → An inflammation of the colon which can occur as a complication of ileostomy or colostomy, often occurring within the year following the surgery.
6. Graft vs Host Disease → Occurs following hematopoietic stem cell transplantation where donor T cells target antigens on the recipient’s GI epithelial cells.

Question 123

What is Ischaemic Bowel Disease?

Answer 123

Ischaemic Bowel Disease

Acute compromise of any major vessel (celiac, superior mesenteric and inferior mesenteric arteries) causing infarction of intestine. Damage can range from mucosal infarction extending no deeper than the muscularis mucosae, to mural infarction of mucosa and submucosa, to transmural infarction involving all three wall layers. Typically presents with sudden onset of cramping, left lower abdominal pain, a desire to defecate, and passage of blood or bloody diarrhea. Most common in patients older than 70 years of age, and occurs slightly more often in women. Frequently associated with coexisting cardiac or vascular disease ischemia as well as therapeutic vasoconstrictors, some illicit drugs (cocaine), endothelial damage and small vessel occlusion after CMV or E. coli infection, strangulated hernia, or vascular compromise due to prior surgery.

Question 124

What are 4 Large Intestine Diseases of Acquired Degeneration?

Answer 124

1. Colonic Diverticula: Outpouchings of mucosa and submucosa through the muscularis propria (false diverticulum). Unlike true diverticula (Meckel diverticulum) they are not invested by all three layers of the colonic wall. Most often occurs at sigmoid colon.
2. Angiodysplasia: Acquired malformation of submucosal and mucosal blood vessels, occurs most often in the cecum or right colon and usually presents after the age of 60 years old. Lesions are characterised by ectatic nests of tortuous veins, venules and capillaries. Risk of rupture and hemorrhage.
3. Irritable Bowel Syndrome: Abnormal functioning of the GI tract where symptoms cannot be explained by the presence of a currently identifiable structural, biochemical or tissue abnormality. Characterised by chronic, relapsing abdominal pain, bloating, and changes in bowel habits. Gross and microscopic evaluation is normal in most patients.
4. Rectal Prolapse: A condition that occurs when part of the large intestine slips outside the anus. Typically occurs in older women, but it can occur in men and women of any age. Risk factors include multiple births, vaginal delivery and straining during constipation .

Question 125

What are 6 Types of Colonic Polyps?

Answer 125

Colonic Polyps: Raised protrusions of colonic mucosa

1. Hyperplastic Polyps: Due to hyperplasia of glands which classically show a ‘serrated’ appearance on microscopy. Most common type of polyp and usually arise in the left colon (rectosigmoid). Benign, with no malignant potential.
2. Adenomatous Polyps: Due to neoplastic proliferation of glands. Second most common type of colonic polyp. Benign, but premalignant as may progress to adenocarcinoma.
3. Hamartomatous Polyps: Disorganised growth of tissue indigenous to the site.
4. Juvenile Polyp: Sporadic, hamartomatous (benign) polyp that arises in children (< 5 years). Usually presents as a solitary rectal polyp that prolapses and bleeds.
5. Peutz-Jeghers Syndrome: Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin caused by autosomal dominant disorder.
6. Familial Adenomatous Polyposis (FAP): Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps. Due to inherited APC mutation on chromosome 5.

Question 126

What is Colorectal Carcinoma? Most common type? Peak incidence age?

Answer 126

Colorectal Carcinoma:

• Carcinoma arising from colonic or rectal mucosa which is the third most common site of cancer and third most common cause of cancer-related death.
• Most commonly adenocarcinoma.
• Peak incidence is 60-70 years of age.

Question 127

What are the intestinal symptoms of Crohn’s vs. Ulcerative Colitis?

Answer 127

Question 128

What are the Extra-Intestinal Symptoms of Crohn Disease & Ulcerative Colitis?

• General?
• Joints?
• Eye?
• Liver/Bile Ducts?
• Dermatologic?

Answer 128

Extra-Intestinal Symptoms of Crohn Disease & Ulcerative Colitis

• General: Fatigue and fever
• Joints: Enteropathic arthritis (sacroiliitis, arthritis, ankylosing spondylitis)
• Eye: Iritis, episcleritis, uveitis
• Liver/Bile Ducts: Primary sclerosing cholangitis (less common than in UC)
• Dermatologic: Erythema nodosum acrodermatitis enteropathica (bullous skin abrasions due to zinc deficiency), pyoderma gangrenosum (very painful, rapidly progressive, red spots that can change into purulent pustules or deep, ulcerated lesions with central necrosis) and pyostomatitis vegetans (oral aphthae)

Question 129

What are the 12 General Principles of IBD Management?

Answer 129

General Principles of IBD Management:

1. Rehydration
2. Diet modification such as FODMAPs and modified Mediterranean
3. Probiotics
4. Supplementation of nutritional and vitamin deficiencies
5. Avoid nicotine (risk factor Crohn disease BUT protective and anti-inflammatory in ulcerative colitis)
6. Anti-diarrhoeal agents for symptomatic relief
7. Anti-inflammatories (i.e. 5-ASA) to induce and maintain remission in mild-moderate disease (note, in contrast to ulcerative colitis, 5-aminosalicylates has a limited role in Crohn disease)
8. Corticosteroids (i.e. prednisolone) to induce remission in acute disease
9. Immunomodulatory therapy (i.e. methotrexate) to maintain remission and used for corticosteroid-sparing effect
10. Biologics such as TNF-alpha inhibitors (i.e. infliximab) to induce and maintain remission in moderate-severe disease
11. Surgical intervention such as bowel re-section for severe cases (NB: surgical intervention alone cannot cure
12. Crohn disease) and complications

Question 130

Pharmacological Management of IBD?

Answer 130

Question 131

What are the 5 Main Functions of Terminal Ileum?

What are the 6 Other Functions of Terminal Ileum?

Issues with surgical removal of the terminal ileum?

Answer 131

Main Functions of Terminal Ileum:

1. Absorption of cobalamin (vitamin B12, requires intrinsic factor from stomach)
2. Absorption of bile salts/acids and lipids via specialised Na+ co-transport proteins (hepatoenteric circulation)
3. Absorption of products left over from jejunum
4. Immunological function with Peyer’s Patches and MALT (monitor intestinal bacteria and prevent the growth of pathogenic bacteria)
5. Absorption of vitamin C and fat-soluble vitamins (vitamins A, D, E and K)

Other Functions of Terminal Ileum:

1. Low absorption of carbohydrates, protein and lipids (mainly done in duodenum)
2. Low absorption of calcium
3. Low absorption of sodium (via SGLT1, amino acid transporters or parallel Na+/H+ NHE3 and Cl-/HCO3 exchangers transporter)
4. Low absorption of potassium (via paracellular solvent drag, pulled along by bulk water movement)
5. Low/Moderate chloride absorption (via passive ion channels (low), Cl-/HCO3 exchanger and parallel Na+/H+ and Cl-/HCO3 exchangers)
6. Water absorption (via paracellular osmotic movement)

NB: Surgical removal of the terminal ileum causes multiple problems, including loss of both bile recycling and vitamin B12 absorption. In this circumstance, bile production by the liver is upregulated, but production is not sufficient for absorption of fat contained in a normal meal, and some steatorrhea may result.

Question 132

Describe the site of absorption and mechanism of absorption of vitamins?

Answer 132

Question 133

Outline the anatomical and physiological factors affecting fluid exchange in the gastrointestinal tract.

Answer 133

Question 134

Demonstrate basic skills in rectal examination.

Answer 134

Question 135

Describe the Presentation and Causes of Gastrointestinal Bleeding?

• Haematemesis
• Malena
• Haematochezia

Answer 135

• Haematemesis → Vomiting blood. Indicates that site of bleeding is proximal to, or within, the duodenum.
  
  • Causes: Oesophagitis, Oesophageal Varices, Mallory-Weiss Tear, Peptic Ulcer Disease, Gastritis
• Melaena → Passage of jet-black tarry stools. Indicates bleeding from the oesophagus, stomach or duodenum, though right-sided colonic and small bowel lesions can sometimes be responsible. Due to the presence of blood digested by gastric acid and colonic bacteria.
  
  • Causes: Upper GI, Bleeding Oesophagitis, Oesophageal Varices, Mallory-Weiss Tear, Peptic Ulcer Disease, Gastritis
• Haematochezia → Passage of bright-red blood per rectum usually due to hemorrhage from left colon or rectum. The blood is usually mixed in with the bowel motion (occult) if it comes from above the anorectum, but if blood appears on the surface of the stool or only on the toilet paper this suggests, but does not guarantee, that bleeding is from a local rectal cause. Darker (maroon) blood suggests it has come from a more proximal site of the GI tract whereas frank red blood comes from a more distal site.
  
  • Causes: Haemorrhoids (not-mixed), Fissures and Fistulas (not-mixed), Inflammatory Bowel Disease (mixed), Colitis (mixed), Diverticulitis (mixed), Angiodysplasia (mixed), Neoplasm (mixed), Colonic Polyp (mixed)

Question 136

What are 8 Investigation of Lower Gastrointestinal Bleeding?

Answer 136

Investigation of Lower Gastrointestinal Bleeding:

1. Vital signs to assess haemodynamic stability
2. Abdominal examination, specifically looking for anaemia, masses, tenderness or organomegaly
3. Digital Rectal Examination and Proctoscopy
4. FBC including iron studies, Hb, WCC, platelet count, ESR and CRP
5. Stool culture and microscopy
6. Endoscopy, specifically colonoscopy or sigmoidoscopy
7. CT angiography
8. Abdominal CT scan

Question 137

Management of Lower Gastrointestinal Bleeding? (5)

Answer 137

Management of Lower Gastrointestinal Bleeding:

1. Consider IV fluid resuscitation and blood transfusion in haemodynamically unstable patients
2. Consider oral or IV iron infusion dependent on state of anaemia
3. Endoscopic therapy
4. Surgical intervention
5. Treat underlying condition i.e. IBD maintenance therapy or peptic ulcer disease

Question 138

Outline the procedure of, indications for and complications of rectal examination.

Answer 138

Rectal Examination:

Procedure: Examination of the anus, rectum, prostate and anal sphincter tone where a doctor uses their finger to assess for any masses, bleeding or abnormalities.

Indications: Rectal bleeding or altered bowel movements, or when hemorrhoids, anorectal diseases (i.e. fissures/fistulas), colorectal cancer, prostate disorders or nervous system disorders are suspected. It should be considered in all patients with bowel symptoms admitted to hospital and who are aged 40 or older, unless the examiner has no fingers, the patient no anus or acute illness such as myocardial infarction presents a temporary contraindication. DRE often completes an abdominal examination.

Complications: Patient discomfort and potentially pain, rectal irritation and rectal bleeding (i.e. if patient has anal fissures).

Question 139

Outline the procedures of, indications for and complications of proctoscopy

Answer 139

Proctoscopy:

Procedure: A common medical procedure in which an instrument called a proctoscope is used to examine the anal cavity, rectum, or sigmoid colon to look for any masses, bleeding or abnormalities. It also allows for biopsies to be taken.

Indications: Rectal bleeding, or when anorectal diseases, anorectal cancer, hemorrhoids or polyps are suspected. Also used if sample of anorectal tissue is needed for biopsy, to remove anorectal polyps or abnormal growths or to monitor rectal cancer.

Complications: Patient discomfort and potentially pain, rectal irritation and rectal bleeding (i.e. if patient has anal fissures). Less common complications include infection, belly pain or rectal tear.

Question 140

What is the pathogenesis and clinical findings of hemorrhoids?

Answer 140

Question 141

What is the pathogenesis and clinical findings of hemorrhoids?

Answer 141

Question 142

What is the pathogenesis and risk factors for a lower GI bleed?

Answer 142

Question 143

Describe the anatomy of the portal venous system.

• What are the Portal Systems?
• What is the function of the Hepatic Portl Venous System?
• 1st Capillary beds?
• 2nd Capillary beds?

Answer 143

Portal Systems: A series of vessels in which two separate capillary beds lie between the arterial supply and the final venous drainage. Occur when a capillary bed pools into another capillary bed through veins, without first going through the heart.

Hepatic Portal Venous System:

• Function: Carries nutrient-rich blood (which may also contain toxins and microorganisms) from digestive organs to the liver where it can be treated before it reaches the rest of the body. Portal vein supplies 75% of blood flow to the liver (partially deoxygenated blood), supplying 50% of the liver’s oxygen needs.
• First Capillary Beds: Stomach and intestines which drain into the hepatic portal vein
• Second Capillary Bed: Liver which drains into hepatic vein and inferior vena cava

Question 144

Anatomy of Hepatic Portal Venous System

• What does the SMV drain?
• What do the splenic veins drain?
• What does the IMV drain?
• Hepatic portal vein?
• Hepatic vein?

Answer 144

Anatomy of Hepatic Portal Venous System:

Superior Mesenteric Vein (Midgut): Drains the entire small intestine, part of the large intestine (ascending and transverse regions), and stomach

Splenic Vein: Collects blood from the spleen, parts of the stomach and pancreas, and then joins the superior mesenteric vein (at about L1) to form the hepatic portal vein

Inferior Mesenteric Vein (Hindgut): Drains the distal portions of the large intestine and rectum and joins the splenic vein just before that vessel unites with the superior mesenteric vein to form the hepatic portal vein

Hepatic Portal Vein: Ascending towards the liver, it passes posterior to the superior part of the duodenum and enters the right margin of the lesser omentum. It is anterior to the omental foramen and posterior to both the bile duct, which is slightly to the right, and the hepatic artery proper, which is slightly to the left. On approaching the liver, the portal vein divides into right and left branches which enter the liver parenchyma. It also receives directly the right and left gastric veins, cystic vein and paraumbilical veins.

Hepatic Vein: Delivers venous blood from liver to the IVC

Question 145

Answer 145

Question 146

Outline the changes that occur to the portal venous system with portal hypertension.

• What is Portal Hypertension?
• Mechanisms of Portal Hypertension?
  
  • Prehepatic = 2
  • Intrahepatic = 2
  • Posthepatic = 2

Answer 146

Portal Hypertension: Increase in portal venous pressure due to the occlusion (fibrosis, scarring and cirrhosis) of the portal vein or hepatic sinusoids. Normal portal venous pressure is 3 to 6 mm Hg but can exceed 12 mm Hg (portal hypertension).

Mechanisms of Portal Hypertension:

1. Prehepatic: Obstructed blood flow to the liver e.g. portal vein thrombosis or liver flukes
2. Intrahepatic: Obstructed hepatic sinusoidal blood flow e.g. cirrhosis or liver carcinoma
3. Posthepatic: Obstructed blood flow from the liver to the heart e.g. right-sided HF or Budd-Chiari syndrome (hepatic vein obstruction)

Question 147

Changes to Portal Venous System in Portal Hypertension?

Answer 147

Changes to Portal Venous System:

• Formation of portosystemic shunts via anastomotic channels (shunts from portal system to systemic circuit)
• There is a large volume of blood flowing from the portal system to the systemic system at the sites of portal-systemic anastomoses (collaterals)
• Veins become dilated and tortuous veins (varices) and prone to rupture (variceal rupture).
• Tortuous enlargement of the oesophageal and gastric veins (most common) and the duodenum and rectal veins, as the portal venous blood is shunted into the caval system using portosystemic anastomoses.
• In severe cases of portal obstruction, the engorgement of the superficial venous channels in the subcutaneous tissues of the abdominal wall (via the para-umbilical portosystemic route) can appear as a caput medusae (tortuous subcutaneous varices that resemble the snakes of Medusa’s head).

Question 148

Changes resulting from cirrhosis and portal hypertension?

Answer 148

Question 149

PATHOLOGY OF HEPATOBILIARY DISEASES

Hepatitis?

• Acute?
• Chronic?
• Viral?
• Autoimmune?

Answer 149

Pathologies of the Hepatobiliary System

Hepatitis: Inflammation of the liver

• Acute: Presents as jaundice (mixed CB and UCB) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzymes (ALT > AST). Inflammation involves lobules of the liver and portal tracts and is characterised by apoptosis of hepatocytes. Symptoms usually last less than 6 months but some cases may be asymptomatic with elevated liver enzymes. Due to diseases causing acute necrosis of hepatocytes associated with inflammation such as with viruses, toxins, abdominal sepsis, septicaemia, biliary disease and malaria.
• Chronic: Characterised by symptoms that last greater than 6 months. Hepatic inflammation predominantly involves portal tract. Risk of progression to cirrhosis. Marked by ongoing inflammation, fibrosis and regenerative changes. Due to viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, chronic drug hepatitis, Wilson’s disease and alpha-1 antitrypsin deficiency.
• Viral: Inflammation of liver parenchyma, usually due to hepatitis virus or other causes such as EBV and CMV (see LO below for more information). In viral hepatitis, fibrosis typically follows many years of slowly accumulating parenchymal injury.
• Autoimmune: A chronic, progressive hepatitis with all the features of autoimmune diseases in general including genetic predisposition, association with other autoimmune diseases, presence of autoantibodies, and therapeutic response to immunosuppression. In autoimmune hepatitis, there is an early phase of severe parenchymal destruction followed rapidly by scarring.

Question 150

PATHOLOGY OF HEPATOBILIARY DISEASES

Viral Hepatitis?

Answer 150

Question 151

PATHOLOGY OF HEPATOBILIARY DISEASES

Drug or Toxin Induced Liver Injury?

Answer 151

Drug or Toxin Induced Liver Injury: As the major drug metabolising and detoxifying organ in the body, the liver is subject to injury from an enormous array of therapeutic and environmental agents. Hepatotoxins may cause harm from direct cell toxicity, through hepatic conversion of a xenobiotic (foreign chemical substance) to an active toxin, or by immune mechanisms, such as by the drug or a metabolite acting as a hapten to convert a cellular protein into an immunogen. The most common hepatotoxin causing acute liver failure is acetaminophen (paracetamol) and the most common hepatotoxin causing chronic liver disease is alcohol.

Question 152

PATHOLOGY OF HEPATOBILIARY DISEASES

Alcohol Liver Disease?

Answer 152

Alcohol Liver Disease: Damage to hepatic parenchyma due to consumption of alcohol. Most common cause of liver disease in the West. There are three distinctive forms of alcoholic liver injury

Hepatic Steatosis (Fatty Liver): The accumulation of fat in hepatocytes after even moderate intake of alcohol. Results in a heavy, greasy liver and resolves with abstinence. Due to alcohol metabolism and increased NADH which shunts substrates away from catabolism and toward lipid biosynthesis, as well as impaired assembly and secretion of lipoproteins, and increased peripheral catabolism of fat.

Alcoholic Hepatitis: Results from chemical injury to hepatocytes, generally seen with binge drinking. Characterised by liver cell necrosis, inflammation, Mallory bodies and fatty change. Presents with painful hepatomegaly and elevated liver enzymes (AST > ALT) and may result in death. Can be resolved with abstinence, but more unlikely as liver damage progresses. Due to toxic by-products of ethanol and its metabolites.

Alcoholic Steatofibrosis/Cirrhosis: Chronic irreversible alcohol-induced liver damage which occurs in 10-20% of alcoholics. It may take 10 to 15 years of drinking for the development of cirrhosis.

Question 153

PATHOLOGY OF HEPATOBILIARY DISEASES

Autoimmune Hepatitis?

Answer 153

Question 154

PATHOLOGY OF HEPATOBILIARY DISEASES

Cirrhosis?

Answer 154

Cirrhosis: End-stage irreversible liver damage characterised by disruption of the normal hepatic parenchyma by diffuse bands of fibrosis and regenerative nodules of hepatocytes due to chronic liver damage by alcohol, viruses, haemochromatosis or other conditions. Fibrosis is mediated by paracrines from injured hepatocytes stimulating TGF-B from stellate cells which lie in the perisinusoidal space (between sinusoid and hepatocytes) causing the production of collagen. Causes portal hypertension, decreased detoxification and decreased protein synthesis.

Question 155

Normal Liver vs. Liver Fibrosis

• What is the result of Stellate cell activation?
• What is the result of Kupffer cell activation?

Answer 155

Question 156

PATHOLOGY OF HEPATOBILIARY DISEASES

Liver Failure? Acute vs. Chronic?

Answer 156

• Liver Failure: May follow acute injury or chronic injury, but may also occur as an acute insult superimposed on an otherwise well-compensated chronic liver disease (acute on chronic). Up to 80% to 90% of hepatic functional capacity must be lost before hepatic failure ensues and transplantation offers the best hope for survival. Serious and sometimes fatal sequelae of liver failure include coagulopathy, encephalopathy, portal hypertension, bleeding esophageal varices, hepatorenal syndrome, and portopulmonary hypertension. Causes include viral and autoimmune hepatitis, drugs and toxins, metabolic disease or fatty changes.

• Acute Liver Failure: Defined as an acute liver illness associated with encephalopathy and coagulopathy that occurs within 26 weeks of the initial liver injury in the absence of pre-existing liver disease. Manifests first with nausea, vomiting, and jaundice, followed by life-threatening encephalopathy, and coagulation defects.
• Chronic Liver Failure: Most often associated with cirrhosis. About 40% of individuals are asymptomatic until the most advanced stages of the disease. When symptomatic, they present with nonspecific manifestations such as anorexia, weight loss, weakness, and, in advanced disease, symptoms and signs of liver failure (as above). Note, not all cirrhosis leads inexorably to chronic liver failure and not all end- stage chronic liver disease is cirrhotic.

Question 157

Stimata of Chronic Liver Disease?

Answer 157

Question 158

4 Metabolic Diseases of the Liver?

Answer 158

Metabolic Diseases of the Liver

1. Non-Alcoholic Fatty Liver
2. Haemochromatosis
3. Wilson Disease
4. Alpha 1-Antitrypsin Deficiency

Question 159

Metabolic Diseases of the Liver

Non-Alcoholic Fatty Liver?

Answer 159

Metabolic Diseases of the Liver

Non-Alcoholic Fatty Liver: Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol (or other known insult). Associated with metabolic syndrome, obesity, type 2 DM or other impairments of insulin responsiveness, dyslipidemia, and hypertension. Diagnosis of exclusion where ALT > AST.

Question 160

Metabolic Diseases of the Liver

Haemochromatosis?

Answer 160

Metabolic Diseases of the Liver

Haemochromatosis: Characterised by excessive iron absorption, most of which is deposited in parenchymal organs such as the liver and pancreas, followed by heart, joints, and endocrine organs. Due to autosomal recessive mutation in HFE gene which regulates hepcidin levels (binds to FP and promotes internalisation to inhibit Fe release) or chronic transfusions. Increased risk of hepatocellular carcinoma.

Question 161

Metabolic Diseases of the Liver

Wilson Disease?

Answer 161

Metabolic Diseases of the Liver

Wilson Disease: Caused by a mutation in the metal ion transporter ATP7B, which results in accumulation of copper in the liver, brain (particularly basal ganglia), and eyes (“Kayser-Fleisher rings”). Copper builds up in hepatocytes, leaks into serum, and deposits in tissues and there is copper-mediated production of hydroxyl free radicals leads to tissue damage. Effects on the liver are versatile, presenting as acute massive hepatic necrosis, fatty liver disease, or chronic hepatitis and cirrhosis. Increased risk of hepatocellular carcinoma. Low serum ceruloplasmin (copper transport protein) concentrations and increased urinary copper excretion confirm the diagnosis.

Question 162

Metabolic Diseases of the Liver

Alpha 1-Antitrypsin Deficiency?

Answer 162

Metabolic Diseases of the Liver

Alpha 1-Antitrypsin Deficiency: A disease of protein misfolding that results in impaired secretion of α1 Antitrypsin into the serum. The main consequences are pulmonary emphysema caused by increased proteolytic elastase activity (deficiency predisposes lung to unopposed neutrophilic proteolytic elastase activity) and liver injury caused by the accumulation of abnormal α1-Antitrypsin.

Question 163

Cholestatic Diseases

• Conjugated (Direct) Bilirubin?
• Unconjugated (Indirect) Bilirubin?

Answer 163

Cholestatic Diseases:

• Conjugated (Direct) Bilirubin: Bilirubin bound to di-glucuronide in liver. Normally undetectable in urine, however, it may appear in the urine if concentrations are high such as if liver function is impaired or biliary drainage is obstructed (dark yellow/amber urine).
• Unconjugated (Indirect) Bilirubin: Bilirubin in plasma, normally transported via albumin. Should not appear in the urine as it is protein bound and therefore should be filtered by the kidney.

Question 164

Cholestatic Diseases

Primary Hepatolithiasis?

Answer 164

Cholestatic Diseases

Primary Hepatolithiasis: A disorder of intrahepatic gallstone formation that leads to repeated bouts of ascending cholangitis, progressive inflammatory destruction of hepatic parenchyma, and predisposes to biliary neoplasia. The disease has a high prevalence in East Asia, but elsewhere is rare. Individuals may present with repeated episodes of cholangitis due to secondary infections of the involved ducts, marked by fever and abdominal pain.

Question 165

Cholestatic Diseases

Primary Biliary Cholangitis and Cirrhosis?

Answer 165

Cholestatic Diseases

Primary Biliary Cholangitis and Cirrhosis: An autoimmune disease with progressive, inflammatory, often granulomatous, destruction of small to medium sized intrahepatic bile ducts. Classically arises in women (average age is 40 years). Associated with other autoimmune diseases and presents with features of obstructive jaundice.

Question 166

Cholestatic Diseases

Primary Sclerosing Cholangitis?

Answer 166

Cholestatic Diseases

Primary Sclerosing Cholangitis: An autoimmune disease with progressive inflammatory and sclerosing destruction of bile ducts of all sizes, intrahepatic and extrahepatic (destruction and fibrosis). Diagnosis is made by radiologic imaging of the biliary tree (beaded appearance). It occurs most often in younger men and has strong associations with ulcerative colitis and presents with obstructive jaundice.

Question 167

4 Neoplastic Diseases of the Liver?

Answer 167

Neoplastic Diseases of the Liver

Hepatic Adenoma: Benign tumor developing from hepatocytes associated with oral contraceptive and anabolic steroid use (regresses upon cessation of drug). Risk of rupture and intraperitoneal bleeding, especially during pregnancy. Tumors are subcapsular and grow with exposure to estrogen.

Metastatic Cancer: The liver is the most common site of metastatic cancers from primary tumours of the colon, pancreas, lung, and breast (due to blood flow).

Hepatocellular Carcinoma: Malignant tumor of hepatocytes (most common). Main risk factors include chronic hepatitis B and C, alcohol cirrhosis, non-alcoholic fatty liver disease and hemochromatosis. Tumours are often detected late because symptoms are masked by cirrhosis (poor prognosis). Serum tumor marker is alpha-fetoprotein.

Cholangiocarcinoma: Endemic in areas where liver flukes such as Opisthorchis and Clonorchis species are endemic. Chronic inflammatory diseases of bile ducts are also risk factors. The tumors may arise from extra hepatic or intrahepatic bile ducts. They have uniformly poor prognosis.

Question 168

5 Consequences of Hepatobiliary Disease?

Answer 168

Consequences of Hepatobiliary Disease

1. Hepatic Fibrosis and Scarring: Can transform smooth vascular channels to irregular and tortuous ones. This change is accompanied with an increase in intra-hepatic resistance and increased pressure resulting in portal hypertension. Increased hydrostatic pressure causes fluid shifts out of vasculature into surrounding tissues such as the peritoneal cavity and spleen.
2. Hepatocyte Damage: Can also impair functions of the liver, specifically serum chemical metabolism, detoxification of blood and the synthesis of serum proteins.
3. Portal Hypertension: Leads to ascites (fluid in the peritoneal cavity), congestive splenomegaly (and thrombocytopenia), portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae) and hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis).
4. Decreased Detoxification and Metabolism: Results in mental status changes, asterixis, and eventual coma (due to increased serum ammonia), gynecomastia, spider angiomata, palmar erythema and testicular atrophy (due to reduced estrogen metabolism), and jaundice (due to decreased bilirubin conjugation).
5. Decreased Protein Synthesis: Leads to hypoalbuminemia with oedema, and coagulopathy such as bruising, petechiae and purpura (due to decreased synthesis of clotting factor).

Question 169

Review the microbiology of the hepatitis viruses and be aware of toxic causes of hepatobiliary disease.

Answer 169

Question 170

Answer 170

Question 171

Answer 171

Question 172

5 Toxic Causes of Hepatobiliary Disease?

Examples of each.

Answer 172

Toxic Causes of Hepatobiliary Disease:

1. Ethanol: Most common cause of chronic toxicity damage
2. Chemicals: Vinyl chloride, carbon tetrachloride, paraquat and polychlorinated biphenyls
3. Herbal Supplements: Ma-Huang, germander, greater celandine, valerian, mistletoe, skullcap, chaparral, comfrey, toxic alkaloids, pennyroyal oil, kava, green tea extracts, black cohosh and ayurvedic herbs
4. Medications/Drugs: Acetaminophen (most common cause of acute toxicity damage), antibiotics, halothanes, NSAIDs, aspirin, statins, steroids, allopurinol, methotrexate and chemotherapy etc.
5. Microbial Toxins: α-Amanitin (a deadly cellular toxin found in Amanita phalloides death cap mushrooms) and aflatoxin (fungi products)

Question 173

List the 10 Liver Function Tests?

Answer 173

Liver Function Tests:

1. Alanine Aminotransferase (ALT): An enzyme mainly found in the liver, marker of hepatocyte integrity. Elevated levels can also be due to other infection, medication use, alcohol excess or fatty liver disease.
2. Aspartate Aminotransferase (AST): An enzyme found in the liver and a few other places, particularly the heart and other muscles in the body. Elevated following liver damage.
3. Alkaline Phosphatase (ALP): An enzyme related to the bile ducts, often increased when they are blocked. Marker of biliary obstruction or hepatitis.
4. Gamma-Glutamyl Transferase (GGT): An enzyme found mainly in the liver and is a useful marker for detecting bile duct problems. Is also elevated after large volume of alcohol.
5. Total Bilirubin: Measures all the yellow bilirubin pigment in the blood, produced via the breakdown of heme. High conjugated bilirubin indicates liver diseases whilst high unconjugated bilirubin indicates hemolysis.
6. Albumin: Main protein of human blood plasma, binds water, cations, fatty acids, hormones, bilirubin, thyroxine and pharmaceuticals, and regulates oncotic pressure in blood. Measures the main protein made by the liver and tells whether or not the liver is making an adequate amount of this protein. Will be reduced in cases of liver damage.
7. Total Protein: Measures albumin and all other proteins in blood, including antibodies made to help fight off infections.
8. Lactate Dehydrogenase (LD): A ubiquitous tissue enzyme that can be used as a non-specific indicator of disease. Elevated in cancers, heart attack, haemolytic anaemia, hepatitis, pancreatitis, shock, sepsis and alcohol/drug use.
9. Prothrombin Time (PT): Assesses how long it takes blood to clot by measuring the coagulation factors that are part of the extrinsic and common pathways of the coagulation cascade work together (factors I (Fibrinogen), II (Prothrombin), V, VII and X). Timing will be prolonged if there is a factor deficiency.
10. Activated Partial Thromboplastin Time (aPTT): Assesses how long it takes blood to clot by measuring the clotting factors that are part of the intrinsic and common pathways: (factors XII, XI, IX, VIII, X, V, II and I). Timing will be prolonged if there is a factor deficiency.

Question 174

Which liver function tests are used are used to distinguish between hepatocellular damage and cholestasis?

Which LFTs are used to assess the liver’s synthetic function?

Answer 174

ALT, AST, ALP and GGT are used to distinguish between hepatocellular damage and cholestasis.

Bilirubin, albumin, protein and PT are used to assess the liver’s synthetic function.

Question 175

Protocol for Interpreting LFTS?

5 steps

Answer 175

Interpreting LFTS:

• 1) Is ALT and/or ALP raised?
  
  • If the ALT is raised, decide if this is a more than a 10-fold rise (↑↑) or a less than a 10-fold rise (↑)
  • If the ALP is raised, decide if this is a more than a 3-fold rise (↑↑) or a less than a 3-fold rise (↑)
• 2) Compare ALT and ALP levels
  
  • A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury
  • A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis
• 3) Compare ALP with GGT levels
  
  • A markedly raised ALP with a raised GGT is highly suggestive of cholestasis.
  • A raised ALP in the absence of a raised GGT should raise your suspicion of non-hepatobiliary pathology such as recent bone fractures, vitamin D deficiency, bone metastases or sarcoma (GGT is liver specific)
• 4) Assess hepatic function
• 5) Common patterns of LFT

Question 176

Protocol for Interpreting LFTS?

How do we assess hepatic function?

Answer 176

LFTs - Assess hepatic function

• Serum bilirubin used to assess the conjugation and elimination of bilirubin
• Serum albumin used to assess the synthesis of albumin (chronicity or severity of liver)
• Prothrombin time and activated partial thromboplastin time used to assess the synthesis of clotting factors
• Serum blood glucose used to assess gluconeogenesis
• Albumin and PT assess actual liver function
• ALT > AST is seen in chronic liver disease
• AST > ALT is seen in cirrhosis and acute alcoholic hepatitis
• The AST/ALT ratio is typically > 1 in alcoholic liver disease
• The AST/ALT ratio < 1 in non-alcoholic liver disease
• AST raised in isolation indicates pathology outside of liver (ALT more specific to liver)
• Note, AST and ALT may be normal in chronic drinkers (all enzymes already secreted)

Question 177

What’s involved in a Liver screen? (9)

Answer 177

Liver Screen:

1. LFTs
2. Autoantibodies (autoimmune conditions)
3. Viral hepatitis serology
4. Alpha -1 antitrypsin
5. Ceruloplasmin (copper)
6. Iron studies
7. ESR and CRP
8. Lipid levels
9. Tumour marker alpha fetoprotein (AFP).

Question 178

Outline the pharmacokinetics of alcohol - ABSORPTION

• Administration?
• Chemical properties?
• Type of Transport?
• Diffusion Barrier?
• Path of Absorption? (5)

Answer 178

Alcohol Absorption:

• Administration: Oral (absorption begins within 5-10 minutes of ingestion)
• Chemical Properties: Small, uncharged and amphipathic (soluble in water yet can cross lipid membrane)
• Type of Transport:
  
  • Simple passive diffusion down concentration gradient from intestinal lumen into capillary
  • Through the water channels/pores that are embedded in the cell membrane
  • Diffusion Barrier: Intestinal lumen → Epithelial cells → Interstitial fluid → Endothelial cells
  • Path of Absorption:
    
    1. Small amounts absorbed in mouth and esophagus
    2. Readily absorbed in the stomach, but food will dilute the alcohol and delay gastric emptying (absorption delayed when taken with fatty foods)
    3. Primary site of absorption is the duodenum
    4. Vaporised alcohol can be absorbed by lungs
    5. Readily crosses the blood brain barrier

Question 179

Outline the pharmacokinetics of alcohol - DISTRIBUTION

• Pattern of Distribution?
• Males vs. Females?

Answer 179

Alcohol Distribution:

• Pattern of Distribution: Distributed uniformly in proportion to the water content of organs. Alcohol is completely soluble in water and thus has a similar volume of distribution to total body water (TBW)
• Alcohol is preferentially distributed in tissues with higher water contents and a good blood supply (i.e. brain and skeletal muscle)
• Differences in TBW will influence alcohol pharmacokinetics because it determines the volume of distribution available for alcohol distribution within the body (thus differences in male vs females)
  
  • VD Males: 0.62-0.90 L/kg (average value is 0.68 L/kg)
  • VD Females: 0.46-0.86 L/kg (average value is 0.60 L/kg)
  • For males, 60% of TBW is fluid, whilst for females 55% of TBW is fluid

Question 180

Outline the pharmacokinetics of alcohol - METABOLISM

• Site of metabolism
• Type of reaction?
• Biochemical reaction?
• 4 Enzymes involved?
• Enzyme Kinetics?
• Rate-Limiting Step?
• Enzyme cofactors?
• Products?

Answer 180

Alcohol Metabolism:

• Site of Metabolism: Liver (and some in the lining of the stomach)
• Type of Reaction: Oxidation (90-98% oxidised)
• Enzymes Involved: Alcohol is mainly metabolised by ADH and ALDH, but can be metabolised outside the liver (i.e. brain) via other enzymes
  
  1. Alcohol Dehydrogenase (ADH): Present in the fluid of the cell (cytosol) and converts ethanol to acetaldehyde (NADH by-product)
  2. Catalase: Located in cell bodies called peroxisomes, requires H2O2 to oxidise alcohol
  3. Cytochrome P450 (CYP2E1): Present predominantly in the cell’s microsomes, assumes an important role in metabolising ethanol to acetaldehyde at elevated ethanol concentrations (NADP+ by-product). Has low affinity to alcohol, so activated during high concentrations of alcohol)
  4. Acetaldehyde Dehydrogenase (ALDH): Present in the mitochondria and converts acetaldehyde to acetate (NB: Asian flush presents in those with genetic deficiency of enzyme)
• Enzyme Kinetics: ADH can become saturated and follows zero-order kinetics (approx. 7.5 grams/hours) (reaction occurs at constant rate, independent of concentration of alcohol)
• Rate-Limiting Step: The limited availability of NAD+
• Enzyme Cofactors: ADH and ALDH require the coenzyme NAD+ which is reduced to NADH
• Products: Acetate is metabolised to Acetyl CoA which is ultimately metabolised to H2O, CO2 and ATP

Question 181

Outline the pharmacokinetics of alcohol - EXCRETION?

Answer 181

Alcohol Excretion:

• Unmetabolised alcohol is excreted in urine, breath, perspiration, tears, milk, saliva and bile
• Alcohol does not appear in stool

Question 182

PATHOLOGY OF THE PANCREAS

Congenital Diseases? (1)

Answer 182

Congenital Diseases of the Pancreas

Annular Pancreas: A band-like ring of normal pancreatic tissue that completely encircles the second portion of the duodenum, which can produce duodenal obstruction.

Question 183

PATHOLOGY OF THE PANCREAS

Acute Pancreatitis?

Answer 183

Pathology of the Pancreas

Acute Pancreatitis: Characterised by reversible pancreatic parenchymal injury associated with inflammation due to toxic exposures (i.e. alcohol and drugs), pancreatic duct obstruction (i.e. gallstones, parasites or periampullary neoplasms), inherited genetic defects, vascular injury, and infections. Results from inappropriate release and activation of pancreatic enzymes, which destroy pancreatic tissue and elicit an acute inflammatory reaction. Clinical features include acute abdominal pain (upper back pain) frequently with anorexia, nausea and vomiting, as well as systemic inflammatory response syndrome and elevated serum lipase and amylase levels.

Question 184

PATHOLOGY OF THE PANCREAS

Complications of Acute Pancreatitis?

Answer 184

Question 185

PATHOLOGY OF THE PANCREAS

Chronic Pancreatitis?

Answer 185

Pathology of the Pancreas

Chronic: Defined as prolonged inflammation of the pancreas associated with irreversible destruction of exocrine parenchyma, fibrosis, and, in the late stages, the destruction of endocrine parenchyma. It often follows repeated episodes of acute pancreatitis. The most common cause is long-term alcohol abuse. Other causes include long-standing obstruction of the pancreatic duct, autoimmune injury to the gland or genetic factors. Clinical features include intermittent or persistent abdominal pain, intestinal malabsorption, and diabetes.

Question 186

PATHOLOGY OF THE PANCREAS

3 Mechanisms of Pathogenesis of Acute Pancreatitis

• Duct obstruction?
• Acinar cell injury?
• Defective intracellular transport?

Answer 186

Question 187

PATHOLOGY OF THE PANCREAS

Pancreatitis Mnemonic: I GET SMASHED?

Answer 187

Pancreatitis Mnemonic: I GET SMASHED

• Idiopathic
• Gallstones or genetic (i.e. CF)
• Ethanol
• Trauma
• Steroids
• Mumps
• Autoimmune
• Scorpion sting
• Hyperlipidaemia and hypercalcaemia
• ERCP – Endoscopic retrograde cholangiopancreatography
• Drugs

Question 188

PATHOLOGY OF THE PANCREAS

Non-neoplastic Cysts and Neoplasms? (6)

Answer 188

Non-neoplastic Cysts and Neoplasms of the Pancreas

1. Congenital Cysts
2. Pseudocysts
3. Cystic Neoplasms
4. Pancreatic Carcinoma
5. Acinar Cell Carcinoma
6. Islet Cell Tumours

Question 189

PATHOLOGY OF THE PANCREAS

Congenital Cysts?

Answer 189

Non-neoplastic Cysts and Neoplasms of the Pancreas

Congenital Cysts: Unilocular, thin-walled (microlesions to 5cm diameter) cysts that are believed to result from anomalous development of the pancreatic ducts. They are enclosed in a thin, fibrous capsule and are filled with a clear serous fluid and may be sporadic or part of an inherited condition.

Question 190

PATHOLOGY OF THE PANCREAS

Pseudocysts?

Answer 190

Non-neoplastic Cysts and Neoplasms of the Pancreas

Pseudocysts: Localised collections of necrotic and hemorrhagic material that are rich in pancreatic enzymes and lack an epithelial lining which account for approximately 75% of cysts in the pancreas. They usually arise following a bout of acute pancreatitis, particularly one superimposed on chronic alcoholic pancreatitis, or from traumatic injury. They usually resolve, but can become infected or compress adjacent structures.

Question 191

PATHOLOGY OF THE PANCREAS

• Cystic Neoplasms?
• Pancreatic Carcinoma?

Answer 191

Neoplasms of the Pancreas

Cystic Neoplasms: Diverse tumors that range from harmless benign cysts to lesions that may be precursors to invasive, potentially lethal cancers. Only 5% to 15% of all pancreatic cysts are neoplastic (most are pseudocysts). Serous cystic neoplasms are entirely benign, whereas other curable non-invasive cysts, such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, are precancerous.

Pancreatic Carcinoma: Infiltrating ductal adenocarcinoma which arise from well-defined noninvasive precursor lesions in small ducts referred to as pancreatic intraepithelial neoplasia. Most commonly seen in the elderly (average age is 70 years) and major risk factors are smoking and chronic pancreatitis. Clinically, most patients present with epigastric abdominal pain and weight loss, sometimes accompanied by jaundice, deep vein thrombosis and secondary diabetes mellitus and serum tumor marker is CA 19-9. Patients succumb to the disease within 1 to 2 years. Very poor prognosis as 1-year survival is less than 10%.

Question 192

PATHOLOGY OF THE PANCREAS

• Acinar Cell Carcinoma?
• Islet Cell Tumours?

Answer 192

Neoplasms of the Pancreas

Acinar Cell Carcinoma: Form zymogen granules and produce exocrine enzymes such as trypsin and lipase. Fifteen percent of individuals with acinar cell carcinoma develop the syndrome of metastatic fat necrosis caused by the release of lipase into the circulation.

Islet Cell Tumours: Rare neoplasms of the endocrine pancreas which usually present with the clinical features of excessive hormone secretion. The tumours may be either benign or malignant, solitary or multiple, or form part of the multiple endocrine neoplasia (MEN) syndrome. Examples include insulinoma (most frequent), gastrinoma, glucagonomas, VIPoma and Somatostatinoma. Diagnosis is almost always made biochemically.

Question 193

Diabetes Mellitus

Type 1 vs. Type 2?

Answer 193

Diabetes Mellitus: A metabolic disorder characterised by persistent hyperglycaemia which results from a deficiency of or resistance to insulin.

Type 1 DM: Autoimmune destruction of pancreatic β-cells and insulin production. Onset is usually childhood or adolescence (<35 years) onset (acute presentation). Risk factors (largely unknown) include genetics or infection.

Type 2 DM: Insulin resistance and pancreatic β-cell dysfunction. Onset is usually middle age (40-59 years), elderly and obesity onset (relatively asymptomatic). Risk factors include family history, obesity, inactive lifestyle, ethnicity (Aboriginal or Torres Strait Islander, Melanesian, Polynesian, Chinese, Southeast Asian, Middle Eastern or from the Indian sub-continent), have had gestational diabetes or have had polycystic ovarian syndrome.

Question 194

Type 2 DM Pathogenesis?

Answer 194

Question 195

Presentation and Causes of Upper GIT Bleeding

• Oral Cavity or Pharyngeal Bleed Description of Presentation?
  
  • 4 common causes?
• Haematemesis - Description of Presentation?
  
  • 7 common causes?
• Malaena - Description of Presentation?
  
  • 6 common causes?

Answer 195

Presentation and Causes of Upper GIT Bleeding

• Oral Cavity or Pharyngeal Bleed → Bleeding from oral cavity (i.e. mouth cuts), tooth socket or the nose.
  
  1. Trauma
  2. Dental Work
  3. Bleeding Disorders
  4. Nose Bleed (Injury, Allergic reaction, Nose Picking, Objects, Nose Blowing)
• Haematemesis → Vomiting blood or “coffee ground” material. Indicates that site of bleeding is proximal to, or within, the duodenum. Important to distinguish pharyngeal bleeding, or coughing up of blood (respiratory). Ask if the blood came up with the first vomit or not, and if there is blood in the stools.
  
  1. Oesophagitis (erosive/ulcerative)
  2. Oesophageal Varices
  3. Mallory-Weiss Tear (repeated vomiting)
  4. Peptic Ulcer Disease
  5. Gastritis
  6. Gastric carcinoma
  7. Vascular anomalies
• Maleana → Passage of jet-black tarry stools. Indicates bleeding from the oesophagus, stomach or duodenum), though right-sided colonic and small bowel lesions can sometimes be responsible. Due to the presence of blood digested by gastric acid and colonic bacteria.
  
  1. Upper GI Bleeding
  2. Oesophagitis
  3. Oesophageal Varices
  4. Mallory-Weiss Tear
  5. Peptic Ulcer
  6. Disease Gastritis

Question 196

9 Investigations of Upper Gastrointestinal Bleeding?

Answer 196

Investigation of Upper Gastrointestinal Bleeding:

1. Vital signs to assess haemodynamic stability (resuscitation and stabilisation)
2. Assessment of onset and severity of bleeding (secure airway)
3. Upper GIT and abdominal examination, specifically looking for anaemia, tenderness, masses or signs of portal hypertension (shrunk liver, ascites, hemorrhoids, splenomegaly or caput medusae)
4. Esophagogastroduodenoscopy and biopsy (diagnostic and therapeutic)
5. FBC including iron studies, Hb, WCC, platelet count, ESR and CRP
6. LFTs, coagulation profile and U&Es
7. H. pylori tests (urease breath test, serology, rapid urease test, salivary assay, stool culture)
8. If lower GIT bleeding suspected perform DRE, stool culture and microscopy and endoscopy (colonoscopy or sigmoidoscopy)
9. CT angiogram for negative endoscopy and major bleed

Question 197

Management of Upper Gastrointestinal Bleeding?

Answer 197

Management of Upper Gastrointestinal Bleeding:

• Consider IV fluid resuscitation and blood transfusion in haemodynamically unstable patients
• Consider oral or IV iron infusion dependent on state of anaemia
• Oral acid suppression (i.e. PPI)
• Endoscopic therapy (blood vessel cauterisation) and follow up endoscopy
• Surgical intervention
• Treat underlying condition i.e. H. pylori infection, peptic ulcer disease or portal hypertension
• Withhold medication post-endoscopy or as required (NSAIDs, aspirin, anticoagulants and antihypertensives)

Question 198

Explain the risks of blood transfusion

• 10 Acute complications?
• 10 Delayed complications?

Answer 198

Blood Transfusion: The process in which a recipient receives donor blood or blood products to replace the loss of blood or blood products (RBCs, platelets, plasma).

• Acute:
  
  1. Allergic reactions
  2. Anaphylaxis
  3. Acute hemolytic transfusion reaction
  4. Fever
  5. Transfusion-related acute lung injury (TRALI)
  6. Volume overload
  7. Phlebitis
  8. Citrate toxicity
  9. Hypothermia
  10. Microbial contamination
• Delayed:
  
  1. Delayed haemolytic transfusion reaction
  2. Post-transfusion purpura
  3. Infection (especially bloodborne virus or Creutzfeldt-Jakob disease)
  4. Iron overload (i.e. haemosiderosis)
  5. Phlebitis
  6. Graft versus host disease

Question 199

Explain the risks of blood transfusion - Acute hemolytic transfusion reaction?

Answer 199

Question 200

Explain the risks of blood transfusion - Transfusion-associated Graft-Versus-Host Disease?

Answer 200

Question 201

Explain the risks of blood transfusion - Transfusion-Associated Circulatory-Overload (TACO)?

Answer 201

Question 202

Outline the principles of management of common liver diseases

• Treating the Cause of Liver Disease (7)
• Other Management of Liver Disease (3)

Answer 202

Treating the Cause of Liver Disease:

1. Alcohol abstinence
2. Weight loss (fat reduction)
3. Antivirals for viral hepatitis
4. Stop drug use or risk-taking behaviour
5. Remove iron for haemochromatosis
6. Remove copper for Wilson’s disease
7. Immunosuppression for autoimmune hepatitis

Other Management of Liver Disease:

1. Ongoing monitoring of liver function
2. Surgical intervention for portosystemic shunts (TIPS)
3. Liver transplant for fulminant hepatic failure, decompensated cirrhosis or hepatocellular carcinoma

Question 203

Specific Management of Liver Disease Manifestations:

• Ascites?
• Bleeding?
• Encephalopathy?
• Hepatorenal Syndrome?
• Hepatocellular Carcinoma?

Answer 203

Specific Management of Liver Disease Manifestations:

• Ascites: Salt restriction, water restriction, diuretics, paracentesis (drain ascitic fluid), portosystemic shunting and transplantation.
• Bleeding: Resuscitation, Octreotide or Terlipressin (manage variceal bleeding), endoscopy, antibiotics, shunting and transplantation. B-Blockers (propranolol) also have a role in bleeding prophylaxis.
• Encephalopathy: Treat underlying liver disease, avoid triggers (azotemia, drugs, GIT hemorrhage, dietary protein, hypokalemic alkalosis, infection, constipation and hepatic necrosis), purge bowel, antibiotics and zinc.
• Hepatorenal Syndrome: Improve liver, treat precipitants, try vasopressors (protein infusion or Terlipressin) and transplant/dialysis.
• Hepatocellular Carcinoma: Transplant, resection and ablative techniques

Question 204

Pathogenesis and Clinical Findinds of Hepatic Encephalopathy?

Answer 204

Question 205

Demonstrate assessment of haemodynamic status and resuscitation.

• What is Haemodynamic Stability?
• What is Haemodynamic Instability?

Answer 205

Haemodynamic Stability: Ability to sufficiently perfuse organs in multiple conditions such as normal state, standing up and stress states.

Haemodynamic Instability: A clinical state of perfusion failure (inadequate blood flow to organs) due to circulatory shock and/or advanced heart failure.

Question 206

13 Clinical Signs of Haemodynamic Instability?

Answer 206

Assessment of Haemodynamic Instability: Physical examination (signs of reduced organ perfusion) and vital signs

1. Tachycardia and tachypnoea
2. Low blood pressure (hypotension)
3. Prolonged capillary refill time
4. Pale, cold extremities and peripheral cyanosis (or warm peripheries with distributive shock)
5. Decreased skin turgor
6. Dry mucous membranes
7. Decreased urine output
8. Loss of consciousness
9. Confusion
10. Chest pain
11. Restlessness
12. Loss of volume (i.e. bleed or dehydration)
13. Postural hypotension/orthostatic intolerance

Question 207

What does Haemodynamic Resuscitation involve? (6)

Answer 207

Haemodynamic Resuscitation: Optimisation of oxygen delivery to tissue through blood volume restoration and ionotropic support

1. Treat underlying cause
2. Stop fluid loss
3. IV fluid replacement (two IV lines)
4. Blood crossmatching if time permits (“blood group, hold and crossmatch”)
5. Blood transfusion (O- in emergencies!)
6. Vasopressors

Question 208

Demonstrate proficiency in clinical examination of the patient with liver disease.

Answer 208

Clinical Examination of Patient with Liver Disease:

• General Appearance: Jaundice of the skin, whites of eyes and under tongue (hyperbilirubinemia), scratch marks/pruritis (hyperbilirubinemia), peripheral oedema (hypoalbuminemia), petechiae and purpura (coagulopathy) and confusion or altered mental state (encephalopathy)
• Hands: Dupuytren’s contracture, palmar erythema (hyperestrogenism) and asterixis (encephalopathy)
• Arms: Jaundice, scratch marks, petechiae and purpura, and upper arm spider naevie (hyperestrogenism)
• Face: Periorbital purpura (coagulopathy) and sclera icterus
• Chest: Spider naevi and gynecomastia (hyperestrogenism)
• Abdomen: Tender, enlarged or small liver (hepatitis, injury or cirrhosis), splenomegaly, ascites and caput medusae (portal hypertension)
• Rectum/Testes: Haemorrhoids and bleeding (portal hypertension) and testicular atrophy (hyperestrogenism)
• Vital Signs: Temperature, blood pressure, heart rate and respiratory rate

Question 209

Demonstrate basic proficiency in the assessment of substance dependence.

• 7 Signs of Substance Dependence?

Answer 209

Signs of Substance Dependence:

1. Strong desire
2. Difficulty controlling
3. Physiological withdrawal
4. Tolerance
5. Neglecting interests
6. Continuing despite negative consequences
7. Enlarged RBCs.

Question 210

Demonstrate basic proficiency in the assessment of substance dependence.

• What should you ask/examine?

Answer 210

Assessment of Substance Dependence:

1. Ask about type, amount, frequency, and consequences of the patient’s substance use
2. Ask about patient’s perception of their use and readiness to change
3. Review history of prior substance use dependence and treatment
4. Assess mental state and co-occurring psychiatric disorders
5. Perform medical history, physical examination and laboratory tests (poor hygiene, weight loss/gain, injection scars, inhalation signs such as nasal atrophy and septum perforation, evidence of intoxication or withdrawal and signs of medical conditions that result from substance abuse)
6. Review family history of substance use disorders
7. Review social factors that may contribute to substance use or facilitate treatment

Question 211

What is the CAGE Questionnaire?

Answer 211

Question 212

a. H1 receptors in the central nervous system (CNS)
b. CB1 receptors in the GI tract
c. the chemoreceptor trigger zone (CTZ)
d. D2 receptors in the GI tract
e. anticholinergic action

Answer 212

= c. the chemoreceptor trigger zone (CTZ)
Other known stimuli which activate the vomiting reflex are migraine, strong sights, smells, emotions or therapeutic drugs, such as opioids, general anaesthetics and digoxin. Vomiting can also be frequent in the first trimester of pregnancy, when it becomes excessive it takes the clinical name of “hyperemesis gravidarum” and requires treatment.

Question 213

a. it is an H1 receptor antagonist
b. it is a NK1 receptor antagonist
c. it is a GABA receptor agonist
d. it is a 5-HT3 receptor antagonist
e. it is a D2 receptor antagonist

Answer 213

= e. it is a D2 receptor antagonist
Metoclopramide is a dopamine receptor antagonist. Dopamine receptors are found in the brain as well as throughout the gastrointestinal tract. Beside metoclopramide, several antiemetic agents are available, with distinct mechanisms of action, indications and side effects.

Question 214

Metoclopramide can be administered orally and by intramuscular or intravenous injection. The most common dosage is 10 mg every 4–8 hours. After oral administration, it is rapidly absorbed, metabolised in the liver by sulfation and glucuronide conjugation, and excreted in the urine. Its half-life is 4-5 h, the peak concentration is reached within 1 h, and the duration of action is 1-2 h.

What is/are the indication/s of metoclopramide?

Answer 214

**= e. all of the above
**
Metoclopramide is also used to treat hyperemesis gravidarum, that is severe and persistent nausea and vomiting during pregnancy, which can lead to dehydration and weight loss. It is more common among young, primigravid women and women with multifetal gestation or molar pregnancy. Metoclopramide should be administered cautiously in the first trimester of pregnancy, because antiemetics are potentially teratogenic.

Question 215

The side effects of metoclopramide are principally linked to its action on dopamine receptors in the CNS. The recommended duration of the treatment with metoclopramide should not exceed 12 weeks.

What is/are the main side effect/s of metoclopramide?

Answer 215

= a. extrapyramidal syndrome, reversible
Other side effects of metoclopramide include prolactin release (causing galactorrhoea and disorders of menstruation), diarrhea and abdominal pain, depression, fatigue, drowsiness and lowering of seizure threshold. Metoclopramide should not be co-administered with antipsychotics, digoxin and antidiabetic drugs, and is contraindicated in patients with suspected small bowel obstruction.

Question 216

a. it is an H1 receptor antagonist
b. it is a D2 receptor antagonist
c. it is a NK1 receptor antagonist
d. it is a GABA receptor agonist
e. it is a 5-HT3 receptor antagonist

Answer 216

= b. it is a D2 receptor antagonist
Phenotiazines also block histamine, muscarinic and alpha-adrenergic receptors. Beside prochlorperazine, other phenothiazines are chlorpromazine, fluphenazine, perphenazine and trifluorphenazine.

Question 217

Prochlorperazine administration can be oral, parenteral, intramuscular, and rectal. The typical dosing of prochlorperazine is 5-10 mg orally every 6-8 h, or 10 mg intramuscularly/ 2.5-10 mg intravenously every 3-4 h with a maximum dose of 40 mg/day, or 25 mg rectally every 12 h. The plasma half-life is about 7 h, the kinetics is not dose-related. Absorption of oral prochlorperazine is slow and the principal metabolite is prochlorperazine sulphoxide.

What is/are the indication/s of prochlorperazine as an antiemetic agent?

Answer 217

= answers a, b and c are correct.
Other indications of antipsychotic phenothiazines include severe nausea and vomiting associated with cancer, radiation therapy, cytotoxic drugs, opioids and anaesthetics. Prochlorperazine has a very weak antipsychotic activity.

Question 218

Even with a low antipsychotic activity, prochlorperazine retains some side effects linked to the antipsychotic action.
What is/are the main side effect/s of prochlorperazine?

Answer 218

= d. extrapyramidal syndrome, reversible
Other side effects of prochlorperazine include sedation and hypotension. Prochlorperazine should not be co-administered with metoclopramide, because this increases the risk of extrapyramidal syndrome. Due to an observed increased mortality, the treatment with prochlorperazine is contraindicated in elderly patients with dementia-related psychosis.

Question 219

Hypokalemia (serum K < 3.5 mEq/L) is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or treatment with diuretics). Mild hypokalemia may be asymptomatic or cause mild nonspecific symptoms such as nausea, muscle weakness, and fatigue. Severe deficiency is potentially fatal, by action on an organ performing a vital function.

On which organ does hypokalemia exert its most dangerous effect?

Answer 219

= a. the heart

Question 220

The treatment of hypokalemia consists of oral or IV supplementation in conjunction with the treatment of the underlying cause. Dosages, regimens and monitoring schedules depend on the serum K level.
When is potassium replacement therapy indicated?

Answer 220

= all of the above answers are correct.
Potassium replacement therapy is always indicated with serum K < 3.5 mEq/L. The therapeutic goal is to raise serum K level to ∼ 4.0 mEq/L. Physiological serum K levels in healthy adults must remain between 3.5 and 5.5 mEq/L.

Question 221

Potassium replacement therapy has a few side effects, of which some mild and others potentially life-threatening.

Which are the critical side effects, potentially life-threatening, of potassium replacement therapy?

Answer 221

= answers a and b are correct

Potassium should always be administered slowly, with rates limited within 20 mEq/L/hour, to avoid overcorrection. Overcorrection occurs more easily in patients with impaired renal function. Other side effects of potassium replacement therapy include phlebitis and extravasation in IV administration, and GI irritation in oral administration.

Question 222

Review the motor, secretory and absorptive functions of the small and large intestine.
- What are the 3 motor functions of the small intestines? (SOP)

Answer 222

Question 223

Review the motor, secretory and absorptive functions of the small and large intestine.
- What are 8 substances secreted by the small intestine?

Answer 223

Small Intestine Functions: Secretory
1. Gastrin
2. Secretin
3. Cholecystokinin
4. Somatostatin
5. Motilin
6. GIP
7. Mucous
8. Defensins

Question 224

• Which cells of the small intestine secrete Gastrin? Function?
• Which cells of the small intestine secrete Secretin? Function?

Answer 224

Question 225

• Which cells of the small intestine secrete Cholecystokinin? Function?
• Which cells of the small intestine secrete Somatostatin? Function?

Answer 225

Question 226

• Which cells of the small intestine secrete Motilin? Function?
• Which cells of the small intestine secrete GIP? Function?

Answer 226

Question 227

• Which cells of the small intestine secrete Mucous? Function?
• Which cells of the small intestine secrete Defensins? Function?

Answer 227

Question 228

Desribe how carbohydrates are absorbed in the SI?

Answer 228

Carbohydrates: Glucose and galactose absorbed across apical membrane via SGLT1 and then across basolateral membrane via GLUT2 before entering villi blood capillaries. Fructose absorbed across apical membrane via GLUT5 and then across basolateral membrane via GLUT2.

Question 229

Desribe how Proteins are absorbed in the SI?

Answer 229

Proteins: Amino Acids absorbed across apical membrane by Na+ co-transporter and then cross basolateral membrane via facilitated diffusion or Na+ dependent or independent amino acid symports (transport dependent on type of amino acid) before entering villi blood capillaries. Small peptides absorbed across apical membrane by different carrier and then broken down to amino acids by intracellular peptidases.

Question 230

Desribe how Fats are absorbed in the SI?

Answer 230

Fats: Monoglycerides and FAs transported to epithelial cell as micelles via bile salts. At brush border monoglycerides and free fatty acids leave micelle and passively diffuse through apical membrane. Inside enterocytes, monoglycerides and free fatty acids resynthesis into triglycerides. Triglycerides aggregate and are covered with layer of lipoprotein to form chylomicrons, which leave basal membrane by exocytosis and enter lacteals (lymphatic vessels).

Question 231

Desribe how Vitamins and Water are absorbed in the SI?

Answer 231

Vitamins: Mostly occurs at duodenum. Specifically, calcium, iron and folate are absorbed at duodenum and bile acids, vitamin B12 (bound to intrinsic factor), vitamin C and fat-soluble vitamins (A, D, E and K) are absorbed at the ileum.

Water: Most of the body fluid (95% of ~9L) is reabsorbed in the small intestine via osmosis.

Question 232

Review the motor, secretory and absorptive functions of the small and large intestine.
- 2 Motor functions of the Large Intestines?

Answer 232

Question 233

Secretory (1) and absorptive (2) functions of the large intestine?

Answer 233

Secretory:
1. Mucous: Produced by goblet cells which are abundant in the large bowel. Secreted in response to tactile stimulation on the lumen wall. Contains bicarbonate and serves both a protective and lubricative function. Also helps form faeces.

Absorptive
1. Vitamins: Harvests vitamins made by the bacterial flora (minimal)
2. Water: Reclaims most of the remaining water and some of the electrolytes (particularly sodium and chloride)

Question 234

What is Fluid Balance?
- Main intakes?
- Main outputs?
- Average intake/output per day?
- Normal urine output?
- Oliguria? Anuria? Polyuria?

Answer 234

Question 235

8 Clinical Features of Fluid overload?

Answer 235

** Features of Fluid Overload: **
1. Peripheral oedema (swollen ankles)
2. Pulmonary oedema (dyspnoea and basal crackles)
3. Pleural effusion (stony dullness on percussion)
4. Pericardial effusio
5. Ascites
6. Raised JVP
7. Raised BP
8. Lab findings: low urea, low creatinine, low haemoglobin, albumin and total protein and sometimes low sodium.

Question 236

12 Clinical Features of Fluid Depletion?

Answer 236

**Features of Fluid Depletion: **
1. Dry mucous membranes
2. Reduced skin turgor
3. Delayed capillary refill
4. Postural hypotension
5. Tachycardia
6. Impaired consciousness
7. Decreased urine output
8. Peripheral venoconstriction
9. Thirst
10. Low JVP
11. Low BP
12. Lab findings: raised urea, increased urea relative to creatinine (slow flow in renal tubule, urea is diffusible but creatinine is not), elevated albumin and total protein and increased haemoglobin (but not if patient was anaemic to start with!). Serum sodium is not always reliable for judging hydration.

Question 237

Clinical Features of Electrolyte Imbalances?

Answer 237

Question 238

What are the Principles of Fluid Balance?
3 Ways to Assess Fluid Balance?

Answer 238

Question 239

3 Fluids you could give to a Fluid depleted patient?

Answer 239

Fluid Replacement for Dehydration: Give normal daily requirement of fluid plus any abnormal losses. Adult fluid requirement is 35ml/kg/day and infant fluid requirement is 120 ml/kg/day.
1. Crystalloid IV Fluid (Saline)
2. Colloid IV Fluid
3. Packed Cells

Question 240

What is Crystalloid IV Fluid (Saline)? Examples?

Answer 240

Crystalloid IV Fluid (Saline): Are solutes that are easily mixed and dissolve in a solution. The solutes may be electrolytes or nonelectrolytes (dextrose) which are small molecules that flow across the semipermeable membrane, allowing transfer from bloodstream into cells and body tissues. Increases the fluid volume in both interstitial and intravascular spaces.
Examples: normal saline (0.9% NaCl solution), Hartman’s (NaCl, lactate, K and Ca in water) or Plasmalyte (Na, acetate, gluconate, Ca, Mg and K in water).

Question 241

What is Colloid IV Fluid? What are Packed cells?

Answer 241

Question 242

4 Methods of Fluid Removal for Overload?

Answer 242

Question 243

Review the physiological mechanisms of pain and describe, in principle, how pain is managed.
- What is Nociception?

Answer 243

Question 244

What is Pain?

Answer 244

Question 245

Compare the different types of primary afferent nerve fibres?

Answer 245

Question 246

Answer 246

Question 247

Describe the Physiological Mechanism of Pain:
- 6 steps in the Ascending Tract (Spinothalamic Tract)?

Answer 247

Question 248

Describe the Physiological Mechanism of Pain:
- 3 steps in the Descending Tract (Corticospinal Tract)?

Answer 248

Question 249

Pain Physiology:
What is Transduction?

Answer 249

Transduction: Nociceptors convert the chemical, thermal, mechanical energy of tissue damage into electro- chemical nerve signals.
- Noxious stimuli are detected by different types of receptors such as TRPV1 aka capsaicin/vanilloid receptor 1 (heat and acid), TRPM8 (cold) or mechanical receptors which leads to cell depolarisation and the propagation of a nerve signal.

Question 250

Pain Physiology:
What is Transmission?

Answer 250

Transmission: The propagation of the action potential/nerve signal by Aδ and C fibres (first order neurons) via voltage gated Na+ channel transmission (depolarisation).

Question 251

Pain Physiology:
What is Modulation (Amplification)?

Answer 251

Question 252

Pain Physiology:
What is Modulation (Dampening)?

Answer 252

Question 253

Inflammatory Pain Management (Headache/Mild Arthritis)
- 3 anti-inflammatory drugs and their MOA?

Answer 253

Question 254

MOA of Anti-inflammatories?

Answer 254

Question 255

** Neuropathic Pain Management: Tricyclic Antidepressants**
- 2 exampes?
- MOA?

Answer 255

Neuropathic Pain Management: Tricyclic Antidepressants (Imipramine/Amitriptyline)
- MOA: Act centrally by inhibiting noradrenaline reuptake.
- Highly effective in relieving neuropathic pain in some but not all patients.
- Their action is independent of their antidepressant effects.
- SSRIs are not effective.
- Noradrenaline is involved in the descending modulation (dampening) of pain, so preventing re-uptake would promote the pain damping effect.

Question 256

Physiological Pain Management (Severe or Chronic Pain): Opioids
- MOA?
- Examples - strong? moderate? mixed?

Answer 256

Question 257

List some important principles of chronic pain management?

Answer 257

Question 258

Pathologies of the Small Intestine:
- 2 Congenital pathologies of the SI?

Answer 258

Question 259

Duodenal Atresia:
- Definitions?
- Epidemiology?
- Pathophysiology?
- Clinical Features?

Answer 259

Question 260

Duodenal Atresia:
- Diagnostics?
- Differentials?
- Treatment?
- Prognosis?

Answer 260

Question 261

Pathogenesis and Clinical Findings of Acute diverticulitis?

Answer 261

Question 262

Distinguishing features of Diverticulitis vs. Diverticulosis?

Answer 262

Question 263

Meckel Diverticulum:
- Pathology & Causes?
- Complications?
- Diagnosis?
- Treatment?
- Mneumonic?

Answer 263

Question 264

4 Types of Intestinal Obstruction?

Answer 264

Question 265

Intestinal Obstruction: Intestinal Adhesions
- Pathology & Causes?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 265

Question 266

Intestinal Obstruction: Intussusception
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 266

Question 267

Intestinal Obstruction: Volvulus
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 267

Question 268

List 5 Inflammatory Pathologies of the SI?

Answer 268

Inflammatory Pathologies of the SI:
1. Ischaemic Bowel Disease
2. Small Bowel Infarction
3. Inflammatory Bowel Disease
4. Enteritis
5. Graft vs Host Disease

Question 269

Pathogenesis and Clinical Findings of Mechanical Bowel Obstruction & Ileus?

Answer 269

Question 270

Inflammatory Pathologies of the SI: Ischaemia & Infarction
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 270

Question 271

Pathogenesis & Clinical Findings of a Small Bowel Infarction?

Answer 271

Question 272

Inflammatory Pathologies of the SI: Inflammatory Bowel Disease
- Clinical Findings in UC?
- Clinical Findings in Crohns?

Answer 272

Question 273

Inflammatory Pathologies of the SI: Gastroenteritis
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 273

Question 274

Inflammatory Pathologies of the SI: Graft vs. Host Disease
- S&Ss?

Answer 274

Question 275

List 6 Malabsorptive Pathologies of the SI?

Answer 275

Malabsorptive Pathologies of the SI:
1. Cystic Fibrosis
2. Coeliac Disease
3. Tropical Sprue
4. Lactase Deficiency
5. Whipple Disease
6. Abetalipoproteinemia

Question 276

Malabsorptive Pathologies of the SI: Cystic Fibrosis
- Pathogenesis & Clinical Findings?

Answer 276

Question 277

Malabsorptive Pathologies of the SI: Celiac Disease
- Pathogenesis & Clinical Findings?
- Complications?

Answer 277

Question 278

Malabsorptive Pathologies of the SI: Celiac Disease
- Pathogenesis & Clinical Findings?

Answer 278

Question 279

Malabsorptive Pathologies of the SI: Tropical Sprue
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 279

**Tropical Sprue: **Damage to small bowel villi due to an unknown organism resulting in malabsorption. Similar to celiac disease except occurs in tropical regions, arises after infectious diarrhoea and responds to antibiotics, and damage is most prominent in jejunum and ileum (secondary vitamin B12 or folate deficiency may ensue).

Question 280

Malabsorptive Pathologies of the SI: Lactase Deficiency
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 280

Lactase Deficiency: Decreased function of the lactase enzyme found in the brush border of enterocytes. . Lactase normally breaks down lactose into glucose and galactose. Presents with abdominal distension and diarrhoea upon consumption of milk products as undigested lactose is osmotically active. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood). Temporary deficiency is seen after small bowel infection (lactase is highly susceptible to injury).

Question 281

Malabsorptive Pathologies of the SI: Lactase Deficiency
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 281

Lactase Deficiency: Decreased function of the lactase enzyme found in the brush border of enterocytes. . Lactase normally breaks down lactose into glucose and galactose. Presents with abdominal distension and diarrhoea upon consumption of milk products as undigested lactose is osmotically active. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood). Temporary deficiency is seen after small bowel infection (lactase is highly susceptible to injury).

Question 282

Malabsorptive Pathologies of the SI: Whipple Disease
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 282

**Whipple Disease: **Systemic tissue damage characterised by macrophages loaded with Tropheryma whippelii organisms. Partially destroyed organisms are present in macrophage lysosomes (positive for PAS). Classic site of involvement is the small bowel lamina propria. Results in fat malabsorption and steatorrhea as macrophages compress lacteals and chylomicrons cannot be transferred from enterocytes to lymphatics. Other sites of involvement include synovium of joints (arthritis), cardiac valves, lymph nodes and CNS.

Question 283

Malabsorptive Pathologies of the SI: Abetalipoproteinemia
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 283

Abetalipoproteinemia: Autosomal recessive deficiency of apolipoprotein B-48 and B-100. Clinical features include malabsorption due to defective chylomicron formation (requires B-48) and absent plasma VLDL and LDL (require B-100).

Question 284

List 3 Degenerative Pathologies of the SI?

Answer 284

Question 285

Degenerative Pathologies of the SI: Angiodysplasia
- Pathology?
- Clinical Feautures?

Answer 285

Question 286

Degenerative Pathologies of the SI: Irritable Bowel Syndrome
- Pathology?
- Clinical Feautures?

Answer 286

Question 287

List 2 Neoplastic pathologies of the SI?

Answer 287

Question 288

Gastric Outlet Obstruction (Pyloric):
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 288

Question 289

High Intestinal Obstruction:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 289

Question 290

Small Bowel obstruction - x-ray findings?

Answer 290

Question 291

High Intestinal Obstruction:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 291

Question 292

Strangulation:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 292

Question 293

Describe the 7 steps in the clinical course of a gut obstruction and the complications of a gut obstruction?

Answer 293

Question 294

Describe the 7 steps in the clinical course of a gut obstruction and the complications of a gut obstruction?

Answer 294

Question 295

What is Effect of Gut Obstruction on Fluid Balance?
- Normal water absorption?
- Obstruction?
- Vomiting?
- Management?

Answer 295

Question 296

9 clinical features of a bowel obstruction?

Answer 296

Question 297

8 radiological findings of a bowel obstruction?

Answer 297

Question 298

Describe the rationale that underlies decision making in the emergency situation.
- Naturalist or Event- Driven?
- Pattern Recognition?
- Rule-Using?
- Hypothetic - Deductive?

Answer 298

Question 299

Describe the neurotransmitters and pharmacology behind nausea and vomitting?

Answer 299

Question 300

Pathogenesis of Vomiting?

Answer 300

Question 301

List the appropriate investigations in the patient with an acute abdomen and how to interpret them.

Answer 301

Acute Abdominal Pain: A surgical emergency characterised by sudden onset of severe abdominal pain and tenderness and muscular rigidity. Due to the severe pain and potentially life-threatening conditions associated with it, rapid diagnosis and management are crucial.

Question 302

Acute GI related abdo pain - pathogenesis & clinical findings & differentials?

Answer 302

Question 303

4 ways to block a tube?

Answer 303

Question 304

a. H1 receptors in the central nervous system (CNS)
b. CB1 receptors in the GI tract
c. the chemoreceptor trigger zone (CTZ)
d. D2 receptors in the GI tract
e. anticholinergic action

Answer 304

= c. the chemoreceptor trigger zone (CTZ)
Other known stimuli which activate the vomiting reflex are migraine, strong sights, smells, emotions or therapeutic drugs, such as opioids, general anaesthetics and digoxin. Vomiting can also be frequent in the first trimester of pregnancy, when it becomes excessive it takes the clinical name of “hyperemesis gravidarum” and requires treatment.

Question 305

a. it is an H1 receptor antagonist
b. it is a NK1 receptor antagonist
c. it is a GABA receptor agonist
d. it is a 5-HT3 receptor antagonist
e. it is a D2 receptor antagonist

Answer 305

= e. it is a D2 receptor antagonist
Metoclopramide is a dopamine receptor antagonist. Dopamine receptors are found in the brain as well as throughout the gastrointestinal tract. Beside metoclopramide, several antiemetic agents are available, with distinct mechanisms of action, indications and side effects.

Question 306

Metoclopramide can be administered orally and by intramuscular or intravenous injection. The most common dosage is 10 mg every 4–8 hours. After oral administration, it is rapidly absorbed, metabolised in the liver by sulfation and glucuronide conjugation, and excreted in the urine. Its half-life is 4-5 h, the peak concentration is reached within 1 h, and the duration of action is 1-2 h.

What is/are the indication/s of metoclopramide?

Answer 306

**= e. all of the above
**
Metoclopramide is also used to treat hyperemesis gravidarum, that is severe and persistent nausea and vomiting during pregnancy, which can lead to dehydration and weight loss. It is more common among young, primigravid women and women with multifetal gestation or molar pregnancy. Metoclopramide should be administered cautiously in the first trimester of pregnancy, because antiemetics are potentially teratogenic.

Question 307

The side effects of metoclopramide are principally linked to its action on dopamine receptors in the CNS. The recommended duration of the treatment with metoclopramide should not exceed 12 weeks.

What is/are the main side effect/s of metoclopramide?

Answer 307

= a. extrapyramidal syndrome, reversible
Other side effects of metoclopramide include prolactin release (causing galactorrhoea and disorders of menstruation), diarrhea and abdominal pain, depression, fatigue, drowsiness and lowering of seizure threshold. Metoclopramide should not be co-administered with antipsychotics, digoxin and antidiabetic drugs, and is contraindicated in patients with suspected small bowel obstruction.

Question 308

a. it is an H1 receptor antagonist
b. it is a D2 receptor antagonist
c. it is a NK1 receptor antagonist
d. it is a GABA receptor agonist
e. it is a 5-HT3 receptor antagonist

Answer 308

= b. it is a D2 receptor antagonist
Phenotiazines also block histamine, muscarinic and alpha-adrenergic receptors. Beside prochlorperazine, other phenothiazines are chlorpromazine, fluphenazine, perphenazine and trifluorphenazine.

Question 309

Prochlorperazine administration can be oral, parenteral, intramuscular, and rectal. The typical dosing of prochlorperazine is 5-10 mg orally every 6-8 h, or 10 mg intramuscularly/ 2.5-10 mg intravenously every 3-4 h with a maximum dose of 40 mg/day, or 25 mg rectally every 12 h. The plasma half-life is about 7 h, the kinetics is not dose-related. Absorption of oral prochlorperazine is slow and the principal metabolite is prochlorperazine sulphoxide.

What is/are the indication/s of prochlorperazine as an antiemetic agent?

Answer 309

= answers a, b and c are correct.
Other indications of antipsychotic phenothiazines include severe nausea and vomiting associated with cancer, radiation therapy, cytotoxic drugs, opioids and anaesthetics. Prochlorperazine has a very weak antipsychotic activity.

Question 310

Even with a low antipsychotic activity, prochlorperazine retains some side effects linked to the antipsychotic action.
What is/are the main side effect/s of prochlorperazine?

Answer 310

= d. extrapyramidal syndrome, reversible
Other side effects of prochlorperazine include sedation and hypotension. Prochlorperazine should not be co-administered with metoclopramide, because this increases the risk of extrapyramidal syndrome. Due to an observed increased mortality, the treatment with prochlorperazine is contraindicated in elderly patients with dementia-related psychosis.

Question 311

Hypokalemia (serum K < 3.5 mEq/L) is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or treatment with diuretics). Mild hypokalemia may be asymptomatic or cause mild nonspecific symptoms such as nausea, muscle weakness, and fatigue. Severe deficiency is potentially fatal, by action on an organ performing a vital function.

On which organ does hypokalemia exert its most dangerous effect?

Answer 311

= a. the heart

Question 312

The treatment of hypokalemia consists of oral or IV supplementation in conjunction with the treatment of the underlying cause. Dosages, regimens and monitoring schedules depend on the serum K level.
When is potassium replacement therapy indicated?

Answer 312

= all of the above answers are correct.
Potassium replacement therapy is always indicated with serum K < 3.5 mEq/L. The therapeutic goal is to raise serum K level to ∼ 4.0 mEq/L. Physiological serum K levels in healthy adults must remain between 3.5 and 5.5 mEq/L.

Question 313

Potassium replacement therapy has a few side effects, of which some mild and others potentially life-threatening.

Which are the critical side effects, potentially life-threatening, of potassium replacement therapy?

Answer 313

= answers a and b are correct

Potassium should always be administered slowly, with rates limited within 20 mEq/L/hour, to avoid overcorrection. Overcorrection occurs more easily in patients with impaired renal function. Other side effects of potassium replacement therapy include phlebitis and extravasation in IV administration, and GI irritation in oral administration.

Question 314

Review the motor, secretory and absorptive functions of the small and large intestine.
- What are the 3 motor functions of the small intestines? (SOP)

Answer 314

Question 315

Review the motor, secretory and absorptive functions of the small and large intestine.
- What are 8 substances secreted by the small intestine?

Answer 315

Small Intestine Functions: Secretory
1. Gastrin
2. Secretin
3. Cholecystokinin
4. Somatostatin
5. Motilin
6. GIP
7. Mucous
8. Defensins

Question 316

• Which cells of the small intestine secrete Gastrin? Function?
• Which cells of the small intestine secrete Secretin? Function?

Answer 316

Question 317

• Which cells of the small intestine secrete Cholecystokinin? Function?
• Which cells of the small intestine secrete Somatostatin? Function?

Answer 317

Question 318

• Which cells of the small intestine secrete Motilin? Function?
• Which cells of the small intestine secrete GIP? Function?

Answer 318

Question 319

• Which cells of the small intestine secrete Mucous? Function?
• Which cells of the small intestine secrete Defensins? Function?

Answer 319

Question 320

Desribe how carbohydrates are absorbed in the SI?

Answer 320

Carbohydrates: Glucose and galactose absorbed across apical membrane via SGLT1 and then across basolateral membrane via GLUT2 before entering villi blood capillaries. Fructose absorbed across apical membrane via GLUT5 and then across basolateral membrane via GLUT2.

Question 321

Desribe how Proteins are absorbed in the SI?

Answer 321

Proteins: Amino Acids absorbed across apical membrane by Na+ co-transporter and then cross basolateral membrane via facilitated diffusion or Na+ dependent or independent amino acid symports (transport dependent on type of amino acid) before entering villi blood capillaries. Small peptides absorbed across apical membrane by different carrier and then broken down to amino acids by intracellular peptidases.

Question 322

Desribe how Fats are absorbed in the SI?

Answer 322

Fats: Monoglycerides and FAs transported to epithelial cell as micelles via bile salts. At brush border monoglycerides and free fatty acids leave micelle and passively diffuse through apical membrane. Inside enterocytes, monoglycerides and free fatty acids resynthesis into triglycerides. Triglycerides aggregate and are covered with layer of lipoprotein to form chylomicrons, which leave basal membrane by exocytosis and enter lacteals (lymphatic vessels).

Question 323

Desribe how Vitamins and Water are absorbed in the SI?

Answer 323

Vitamins: Mostly occurs at duodenum. Specifically, calcium, iron and folate are absorbed at duodenum and bile acids, vitamin B12 (bound to intrinsic factor), vitamin C and fat-soluble vitamins (A, D, E and K) are absorbed at the ileum.

Water: Most of the body fluid (95% of ~9L) is reabsorbed in the small intestine via osmosis.

Question 324

Review the motor, secretory and absorptive functions of the small and large intestine.
- 2 Motor functions of the Large Intestines?

Answer 324

Question 325

Secretory (1) and absorptive (2) functions of the large intestine?

Answer 325

Secretory:
1. Mucous: Produced by goblet cells which are abundant in the large bowel. Secreted in response to tactile stimulation on the lumen wall. Contains bicarbonate and serves both a protective and lubricative function. Also helps form faeces.

Absorptive
1. Vitamins: Harvests vitamins made by the bacterial flora (minimal)
2. Water: Reclaims most of the remaining water and some of the electrolytes (particularly sodium and chloride)

Question 326

What is Fluid Balance?
- Main intakes?
- Main outputs?
- Average intake/output per day?
- Normal urine output?
- Oliguria? Anuria? Polyuria?

Answer 326

Question 327

8 Clinical Features of Fluid overload?

Answer 327

** Features of Fluid Overload: **
1. Peripheral oedema (swollen ankles)
2. Pulmonary oedema (dyspnoea and basal crackles)
3. Pleural effusion (stony dullness on percussion)
4. Pericardial effusio
5. Ascites
6. Raised JVP
7. Raised BP
8. Lab findings: low urea, low creatinine, low haemoglobin, albumin and total protein and sometimes low sodium.

Question 328

12 Clinical Features of Fluid Depletion?

Answer 328

**Features of Fluid Depletion: **
1. Dry mucous membranes
2. Reduced skin turgor
3. Delayed capillary refill
4. Postural hypotension
5. Tachycardia
6. Impaired consciousness
7. Decreased urine output
8. Peripheral venoconstriction
9. Thirst
10. Low JVP
11. Low BP
12. Lab findings: raised urea, increased urea relative to creatinine (slow flow in renal tubule, urea is diffusible but creatinine is not), elevated albumin and total protein and increased haemoglobin (but not if patient was anaemic to start with!). Serum sodium is not always reliable for judging hydration.

Question 329

Clinical Features of Electrolyte Imbalances?

Answer 329

Question 330

What are the Principles of Fluid Balance?
3 Ways to Assess Fluid Balance?

Answer 330

Question 331

3 Fluids you could give to a Fluid depleted patient?

Answer 331

Fluid Replacement for Dehydration: Give normal daily requirement of fluid plus any abnormal losses. Adult fluid requirement is 35ml/kg/day and infant fluid requirement is 120 ml/kg/day.
1. Crystalloid IV Fluid (Saline)
2. Colloid IV Fluid
3. Packed Cells

Question 332

What is Crystalloid IV Fluid (Saline)? Examples?

Answer 332

Crystalloid IV Fluid (Saline): Are solutes that are easily mixed and dissolve in a solution. The solutes may be electrolytes or nonelectrolytes (dextrose) which are small molecules that flow across the semipermeable membrane, allowing transfer from bloodstream into cells and body tissues. Increases the fluid volume in both interstitial and intravascular spaces.
Examples: normal saline (0.9% NaCl solution), Hartman’s (NaCl, lactate, K and Ca in water) or Plasmalyte (Na, acetate, gluconate, Ca, Mg and K in water).

Question 333

What is Colloid IV Fluid? What are Packed cells?

Answer 333

Question 334

4 Methods of Fluid Removal for Overload?

Answer 334

Question 335

Review the physiological mechanisms of pain and describe, in principle, how pain is managed.
- What is Nociception?

Answer 335

Question 336

What is Pain?

Answer 336

Question 337

Compare the different types of primary afferent nerve fibres?

Answer 337

Question 338

Answer 338

Question 339

Describe the Physiological Mechanism of Pain:
- 6 steps in the Ascending Tract (Spinothalamic Tract)?

Answer 339

Question 340

Describe the Physiological Mechanism of Pain:
- 3 steps in the Descending Tract (Corticospinal Tract)?

Answer 340

Question 341

Pain Physiology:
What is Transduction?

Answer 341

Transduction: Nociceptors convert the chemical, thermal, mechanical energy of tissue damage into electro- chemical nerve signals.
- Noxious stimuli are detected by different types of receptors such as TRPV1 aka capsaicin/vanilloid receptor 1 (heat and acid), TRPM8 (cold) or mechanical receptors which leads to cell depolarisation and the propagation of a nerve signal.

Question 342

Pain Physiology:
What is Transmission?

Answer 342

Transmission: The propagation of the action potential/nerve signal by Aδ and C fibres (first order neurons) via voltage gated Na+ channel transmission (depolarisation).

Question 343

Pain Physiology:
What is Modulation (Amplification)?

Answer 343

Question 344

Pain Physiology:
What is Modulation (Dampening)?

Answer 344

Question 345

Inflammatory Pain Management (Headache/Mild Arthritis)
- 3 anti-inflammatory drugs and their MOA?

Answer 345

Question 346

MOA of Anti-inflammatories?

Answer 346

Question 347

** Neuropathic Pain Management: Tricyclic Antidepressants**
- 2 exampes?
- MOA?

Answer 347

Neuropathic Pain Management: Tricyclic Antidepressants (Imipramine/Amitriptyline)
- MOA: Act centrally by inhibiting noradrenaline reuptake.
- Highly effective in relieving neuropathic pain in some but not all patients.
- Their action is independent of their antidepressant effects.
- SSRIs are not effective.
- Noradrenaline is involved in the descending modulation (dampening) of pain, so preventing re-uptake would promote the pain damping effect.

Question 348

Physiological Pain Management (Severe or Chronic Pain): Opioids
- MOA?
- Examples - strong? moderate? mixed?

Answer 348

Question 349

List some important principles of chronic pain management?

Answer 349

Question 350

Pathologies of the Small Intestine:
- 2 Congenital pathologies of the SI?

Answer 350

Question 351

Duodenal Atresia:
- Definitions?
- Epidemiology?
- Pathophysiology?
- Clinical Features?

Answer 351

Question 352

Duodenal Atresia:
- Diagnostics?
- Differentials?
- Treatment?
- Prognosis?

Answer 352

Question 353

Pathogenesis and Clinical Findings of Acute diverticulitis?

Answer 353

Question 354

Distinguishing features of Diverticulitis vs. Diverticulosis?

Answer 354

Question 355

Meckel Diverticulum:
- Pathology & Causes?
- Complications?
- Diagnosis?
- Treatment?
- Mneumonic?

Answer 355

Question 356

4 Types of Intestinal Obstruction?

Answer 356

Question 357

Intestinal Obstruction: Intestinal Adhesions
- Pathology & Causes?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 357

Question 358

Intestinal Obstruction: Intussusception
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 358

Question 359

Intestinal Obstruction: Volvulus
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 359

Question 360

List 5 Inflammatory Pathologies of the SI?

Answer 360

Inflammatory Pathologies of the SI:
1. Ischaemic Bowel Disease
2. Small Bowel Infarction
3. Inflammatory Bowel Disease
4. Enteritis
5. Graft vs Host Disease

Question 361

Pathogenesis and Clinical Findings of Mechanical Bowel Obstruction & Ileus?

Answer 361

Question 362

Inflammatory Pathologies of the SI: Ischaemia & Infarction
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 362

Question 363

Pathogenesis & Clinical Findings of a Small Bowel Infarction?

Answer 363

Question 364

Inflammatory Pathologies of the SI: Inflammatory Bowel Disease
- Clinical Findings in UC?
- Clinical Findings in Crohns?

Answer 364

Question 365

Inflammatory Pathologies of the SI: Gastroenteritis
- Pathology & Causes?
- Risk Factors?
- Complications?
- S&Ss?
- Diagnosis?
- Treatment?

Answer 365

Question 366

Inflammatory Pathologies of the SI: Graft vs. Host Disease
- S&Ss?

Answer 366

Question 367

List 6 Malabsorptive Pathologies of the SI?

Answer 367

Malabsorptive Pathologies of the SI:
1. Cystic Fibrosis
2. Coeliac Disease
3. Tropical Sprue
4. Lactase Deficiency
5. Whipple Disease
6. Abetalipoproteinemia

Question 368

Malabsorptive Pathologies of the SI: Cystic Fibrosis
- Pathogenesis & Clinical Findings?

Answer 368

Question 369

Malabsorptive Pathologies of the SI: Celiac Disease
- Pathogenesis & Clinical Findings?
- Complications?

Answer 369

Question 370

Malabsorptive Pathologies of the SI: Celiac Disease
- Pathogenesis & Clinical Findings?

Answer 370

Question 371

Malabsorptive Pathologies of the SI: Tropical Sprue
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 371

**Tropical Sprue: **Damage to small bowel villi due to an unknown organism resulting in malabsorption. Similar to celiac disease except occurs in tropical regions, arises after infectious diarrhoea and responds to antibiotics, and damage is most prominent in jejunum and ileum (secondary vitamin B12 or folate deficiency may ensue).

Question 372

Malabsorptive Pathologies of the SI: Lactase Deficiency
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 372

Lactase Deficiency: Decreased function of the lactase enzyme found in the brush border of enterocytes. . Lactase normally breaks down lactose into glucose and galactose. Presents with abdominal distension and diarrhoea upon consumption of milk products as undigested lactose is osmotically active. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood). Temporary deficiency is seen after small bowel infection (lactase is highly susceptible to injury).

Question 373

Malabsorptive Pathologies of the SI: Lactase Deficiency
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 373

Lactase Deficiency: Decreased function of the lactase enzyme found in the brush border of enterocytes. . Lactase normally breaks down lactose into glucose and galactose. Presents with abdominal distension and diarrhoea upon consumption of milk products as undigested lactose is osmotically active. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood). Temporary deficiency is seen after small bowel infection (lactase is highly susceptible to injury).

Question 374

Malabsorptive Pathologies of the SI: Whipple Disease
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 374

**Whipple Disease: **Systemic tissue damage characterised by macrophages loaded with Tropheryma whippelii organisms. Partially destroyed organisms are present in macrophage lysosomes (positive for PAS). Classic site of involvement is the small bowel lamina propria. Results in fat malabsorption and steatorrhea as macrophages compress lacteals and chylomicrons cannot be transferred from enterocytes to lymphatics. Other sites of involvement include synovium of joints (arthritis), cardiac valves, lymph nodes and CNS.

Question 375

Malabsorptive Pathologies of the SI: Abetalipoproteinemia
- Pathogenesis & Clinical Findings?
- Diagnosis?
- Treatment?

Answer 375

Abetalipoproteinemia: Autosomal recessive deficiency of apolipoprotein B-48 and B-100. Clinical features include malabsorption due to defective chylomicron formation (requires B-48) and absent plasma VLDL and LDL (require B-100).

Question 376

List 3 Degenerative Pathologies of the SI?

Answer 376

Question 377

Degenerative Pathologies of the SI: Angiodysplasia
- Pathology?
- Clinical Feautures?

Answer 377

Question 378

Degenerative Pathologies of the SI: Irritable Bowel Syndrome
- Pathology?
- Clinical Feautures?

Answer 378

Question 379

List 2 Neoplastic pathologies of the SI?

Answer 379

Question 380

Gastric Outlet Obstruction (Pyloric):
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 380

Question 381

High Intestinal Obstruction:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 381

Question 382

Small Bowel obstruction - x-ray findings?

Answer 382

Question 383

High Intestinal Obstruction:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 383

Question 384

Strangulation:
- Aetiology?
- Clinical Features?
- Radiological Findings?

Answer 384

Question 385

Describe the 7 steps in the clinical course of a gut obstruction and the complications of a gut obstruction?

Answer 385

Question 386

Describe the 7 steps in the clinical course of a gut obstruction and the complications of a gut obstruction?

Answer 386

Question 387

What is Effect of Gut Obstruction on Fluid Balance?
- Normal water absorption?
- Obstruction?
- Vomiting?
- Management?

Answer 387

Question 388

9 clinical features of a bowel obstruction?

Answer 388

Question 389

8 radiological findings of a bowel obstruction?

Answer 389

Question 390

Describe the rationale that underlies decision making in the emergency situation.
- Naturalist or Event- Driven?
- Pattern Recognition?
- Rule-Using?
- Hypothetic - Deductive?

Answer 390

Question 391

Describe the neurotransmitters and pharmacology behind nausea and vomitting?

Answer 391

Question 392

Pathogenesis of Vomiting?

Answer 392

Question 393

List the appropriate investigations in the patient with an acute abdomen and how to interpret them.

Answer 393

Acute Abdominal Pain: A surgical emergency characterised by sudden onset of severe abdominal pain and tenderness and muscular rigidity. Due to the severe pain and potentially life-threatening conditions associated with it, rapid diagnosis and management are crucial.

Question 394

Acute GI related abdo pain - pathogenesis & clinical findings & differentials?

Answer 394

Question 395

4 ways to block a tube?

Answer 395