The Digestive System

Question 1

Boundaries of the Abdominal Cavity

Answer 1

Superior: Diraphragm, reaching up to the inferior apex of the sternum.
Inferior: Iliac crest and the pelvic inlet.

Question 2

Layers of the abdominal fascia from superficial to deep

Answer 2

Skin, superficial fascia, external oblique (inferomedial), internal oblique (superomedial), transversus abdominis, transversalis fascia, extraperitoneal fascia, parietal peritoneum.

Question 3

Rectus abdominis

Answer 3

Connects the pubic tubercle and the costal cartilage of the middle ribs.
Vertically oriented fibres separated into horizontal divisions by intertendinous bands.
F: Flexion of trunk. Compression of the abdominal wall.
N: Anterior rami of thoracic nerves.

Question 4

External oblique

Answer 4

O: Posterolateral aspects of the middle and lower ribs.
I: Iliac crest, linea alba via anterior rectus sheath, Inferior free edge forms the inguinal ligament.
F: Bilateral contraction causes trunk flexion. Unilateral contraction leads to rotation to the contralateral direction.
N: Anterior rami of thoracic nerves

Question 5

Internal oblique

Answer 5

O: Iliac crest and the thoracolumbar fascia.
I: Lower ribs, linea alba via the anterior and posterior rectus sheaths.
F: Bilateral contraction flexes trunk. Unilateral contraction leads to ipsilateral rotation and flexion.
N: Anterior rami of thoracic nerves and L1.

Question 6

Transversus abdominis

Answer 6

Longitudinal origin from lateral ribs to the iliac crest.
Longitudinal insertion from the linea alba to the pubic crest.
F: Bilateral contraction tenses abdominal wall.
N: Anterior rami of thoracic nerves and L1.

Question 7

Distribution of the rectus sheath

Answer 7

Anterior and posterior to the rectus abdominis muscle, but the posterior section is missing for the inferior 1/4. Allows the inferior epigastric artery to pierce through the sheath and move anteriorly to anastomose with the superior epigastric arteries, which descend from the suclavian artery along the plane of the transversalis fascia.

Question 8

Venous and lymphatic drainage of the abdominal cavity.

Answer 8

Superior venous: Thoracoepigastric into the axillary vein. 
Inferior venous: Superficial epigastric into femoral vein.
Superior lymphatic (above umbilicus): Drains into axillary nodes. 
Inferior lymphatic (below umbilicus): Drains in inguinal nodes.

Question 9

Innervation of the abdominal wall

Answer 9

Anterior rami of the thoracic (and L1) nerves. Wraps around the lateral side of the thoracic wall as it moves anteriorly. Pierces the superficial fascia adjacent to the linea alba to provide cutaneous innervation to the anterior abdominal wall.

Inferior regions of IO and TA are supplied by the iliohypogastric and the ilioinguinal nerves.

Question 10

Peritoneal structures

Answer 10

Foregut, jejunum and terminal ileum: The mesentery.
Transverse colon: transverse mesocolon.
Sigmoid colon: Sidmoid mesocolon.

Question 11

Omental bursa/ Lesser sac

Answer 11

Positioned posterior to the stomach and separates the intraperitoneal and retroperitoneal structures of the abdominal cavity. Roof is formed from the hepatogastric and hepatoduodenal ligaments.
Opens to the right at the omental foramen.

Question 12

Paracolic gutters and associated pathology

Answer 12

Sulci lateral to the ascending and descending colon to allow mass movement of pathologically accumulated fluids in the abdominal cavity.
Upright: Conducts fluid down to the appendix region of the abdominal cavity. Presents with appendicitis-like symptoms.
Supine: Fluid moves superiorly into the hepatorenal recess and into the lesser sac. Pain in the epigastric region.

Question 13

Embryonic Formation of the Oesophagus and pathology

Answer 13

Formed from the mesoderm and endoderm layers into a cylindrical shape during embryonic folding. Rapidly proliferates to the connect the gut to the oral membrane.
Respiratory diverticulum buds off at the tracheoesophageal ridge.
Congenital tracheoesophageal atresia: Failure for the respiratory diverticulum to bud off correctly, resulting in a blind-ended oesophagus that does not connect properly to the gut, or is connected to the trachea.
Congenital hiatal hernia: Failure of rapid oesophageal elongation means the stomach and the rest of the gut is pulled anteriorly.

Question 14

Embryonic formation of the stomach and pathology

Answer 14

Initially a narrow structure suspended by anterior and dorsal mesogastrium. Expands asymmetrically- faster rate on the posterior side.
Rotates 90 degrees clockwise in the transverse plane so the greater curvature faces left. Dorsal mesogastrium is pulled to the left to form an invagination that would become the omental bursa. Spleen is pushed against the dorsal abdominal wall.
Rotates 90 degrees clockwise in the coronal plane and the sac formed in the previous step is rotated inferiorly so it will proliferate downwards to become the omentum as the four layers of peritoneum fuse.
Congenital hypertrophic pyloric stenosis: Excess thickening of the pyloric sphincter muscles

Question 15

Embryonic liver, biliary tree and pancreatic development.

Answer 15

Originates as the hepatic diverticulum which buds off just caudal to the midgut, which separates into the liver, gallbladder and the ventral pancreatic bud, A dorsal pancreatic bud is also formed on the dorsal side of the pylorus of the stomach precursor.
Clockwise rotation of the stomach in the coronal plane will bring the two pancreatic buds together to form the pancreas, while the liver will be positioned to the right and anterior to the stomach. It will also position the liver up against the posterior abdominal wall to make it a retroperitoneal structure.

Question 16

Ligaments associated with the liver

Answer 16

The liver is formed within the anterior mesogastrium of your stomach. The anterior section holds the umbilical vein in its free inferior border which becomes the hepatic ligamentum teres. It becomes the falciform ligament between the lobes of the liver.
The mesentery between the liver and the stomach will become the hepatoduodenal and the hepatogastric ligaments, which form the lesser omentum.

Question 17

Midgut Twisting

Answer 17

1) Physiological herniation of the midgut precusor into the umbilical cord. Cranial limb is the small intestine precursor while caudal limb is the colon precursor.
2) Midgut spins anticlockwise 270 degrees as it is retracted back into the abdominal cavity.
3) The colon rotates clockwise so the caecum is positioned at the right groin region.
(Refer to notes for diagram to reinforce mechanism)

Question 18

Congenital Malformations of the Midgut

Answer 18

• Nonrotation: Failure of anticlockwise rotation of the midgut leads to separation of the small intestine and colon.
• Mixed rotation: Leads to volvulsus, where the twisting of the midgut severs itself from the stomach or occludes itself.
• Reverse rotation: Clockwise rotation of the midgut, resulting in the colon being trapped under the superior mesenteric artery.
• Umbilical herniation: Failure of the umbilical cord to close, which allows the herniation of the small intestine.

Question 19

Meckel’s Diverticulum

Answer 19

Remnant of the yolk stalk does not regress, so a stalk is formed from the ileum at the umbilicus, which sometimes joins to the umbilicus and opens up to the outside world via the omphaloenteric fistula.
The diverticulum usually acts like a tube that can be inflammed.
False diverticulum are formed when the protrusion is not due to malformation during development, but rather the herniation of a region of ileum through weakened smooth muscle.

Question 20

Hindgut development and congenital malformations.

Answer 20

Initially formed as the cloaca, which is the combined membrane-sealed orifice. The urorectal sphincter forms by week 4 to split the digestive and genitourinary systems.
Imperforate anus: Condition where the cloacal membrane fails to rupture during development.
Rectal atresia and fistula: Failure for the anal canal to form a continuous channel with the rectum. Fistula can intrude into the genitourinary tract.

Question 21

Division of the Anal canal `

Answer 21

Section above the pectinate line: Endoderm and part of digestive system.
Venous drainage to hepatic portal vein.
Poor somatic sensation as it is primarily innervated by the autonomous nervous system.
Section below pectinate line: Ectoderm and part of the integumentary system.
Good somatic sensation as there are cutaneous somatic sensory receptors.
Venous drainage to inferior vena cava.

Question 22

Role of the Upper Oesophageal Sphincter

Answer 22

Tonally contracted to keep the sphincter closed. Significant barrier function so high pressure needed to open.
Superior regions of the oesophagus contains skeletal muscle to confer somatic control over the swallowing process.
- Reduces airflow into stomach to prevent overextension and pain.
- Prevents gastric reflux into the oral cavity and lungs.
- Prevents reflux of oesophageal contents.
- Transient aperture during swallowing via relaxation of the inner smooth msucle sphincter.

Question 23

Primary and Secondary Peristalsis

Answer 23

Primary: Initiated by the pharyngeal phase of swallowing, where the peristaltic contraction of the pharynx pushes the the bolus into the oesophagus. Peristaltic contraction involves the generation of a pressure gradient by increasing pressure behind the bolus while relaxing of the oesophagus before the bolus to drive its movement.

Secondary peristalsis: Stretch receptors detect distension of the oesophagus which indicates remnants of the bolus is present in the oesophagus. Initiates peristaltic movement.

Peristalsis involves both layers of muscularis externa- OL: shortens oesophagus, IC: contracts lumen.

Regulated by the myenteric plexus of the enteric nervous system but activity is influenced by factors from the autonomous nervous system.

Question 24

Lower oesophageal sphincter function

Answer 24

Entirely consisting of smooth muscle- entirely autonomous control.
Contracts less strongly and aperture is less transient.
Demarcates the interface between the protective stratified squamous epithelium of the oesophagus and the secretory simple columnar epithelium of the stomach.
Relaxation of the sphincter results in relaxation of the fundus, which allows accomodation of more food.

Question 25

Phases of Swallowing

Answer 25

Voluntary oral phase: Preparatory--> Formation of bolus via mastication of food and lubrication with saliva. Transfer/Involuntary Pharyngeal phase--> Tongue presses against the hard palate to shut off anterior oral cavity Nasopharynx and larynx closed off. Sound-making apparatus in the trachea are adducted. Pharynx contracts peristaltically to push the bolus through the UOS. The involuntary phases are initiated by pressure receptors at the back of the oral cavity, which detect distension and sends the signal to the swallowing centre of the brainstem Involuntary oesophageal phase: Relaxation of the UOS and initiation of oesophageal peristaltic movement following peristaltic ejection from the pharynx.

Question 26

Causes of GORD

Answer 26

- Excessive acid in the fundic region of the stomach. - Hiatus hernia: Weakness of the diaphragm allows herniation of the stomach into the thoracic cavity. This forms a pocket where stomach acid can be 'stored' and refluxed into the oesophagus. - Hypotensive LOS: Failure of barrier function leaves the sphincter patent. Free movement of gastric acid into the oesophagus. - Impaired secondary peristalsis mechanism--> Failure to detect oesophageal distension due to refluxed food material.

Question 27

Symptoms of GORD

Answer 27

- Painful burning sensation (heartburn)-- > Due to disruption of the stratified squamous epithelium, which allows the acid to reach the submucosa where the nociceptors are. - Oesophagitis due to excess damage to the oesophageal lining causing inflammation. Formation of ulcers close to the LOS due to epithelium damage. - Submucosal damage can lead to damage of the submucosal blood vessels, which causes bleeding and presents as haematemesis. - Oesophageal stricture: Excess, repeated oesophageal damage leads to formation of hypertrophic scar tissue, which will protrude into the oesophageal lumen and reduce its diameter. Disrupts passage of food-dysphagia.

Question 28

Barrett's Oesophagus and oesophageal adenocarcinoma.

Answer 28

``` Repeated oesophageal mucosa damage leads to metaplasia of the oesopageal lining into columnar epithelium (which appears dark red instead of light pink). Metaplasia can lead to adenocarcinoma, where some cells become malignant due to interference with growth factors during the metaplasia process. Reversible process (reversed by stopping metaplasia) but can progress irreversibly to become a carcinoma. ```

Question 29

Zenker's Diverticulum

Answer 29

Failure for the UOS to relax during swallowing means the pharynx peristaltic contraction will push food into the wall. Causes a pocket to form at the weakest point at the region cranial to the UOS.

Question 30

Motility Disorders of the Oesophagus

Answer 30

Diffuse oesophageal spasm: Failured of coordinated smooth muscle contraction in the oesophageal wall. Leads to contortion of the oesophagus into a corkscrew. Dysphagia and chest pain. Achalasia: Degeneration of the myenteric plexus prevents signals which signal relaxation of the LOS sphincter muscles and peristalsis of the smooth muscles of the oesophageal wall. Results in accumulation of food in the oesophagus just before the sphincter. Manifests in enlarged oesophagus, dysphagia and chest pain. Scleroderma: Fibrosis of submucosa and muscularis leading to rigidity of the oesophagus. Poor peristaltic movement generated and loss of LOS tone. Severe acid reflux and weak peristaltic contractions.

Question 31

Anatomy and Vasculature of the Stomach

Answer 31

- Located at the Epigastric region. - Lesser curvature supplied by the right gastric artery inferiorly and the left gastric superiorly The right gastric is a branch of the hepatic artery while the left gastric forms directly from the coeliac trunk and moves cranially to pass along the oesophagus, but also forming a recurrent branch along the superior half of the lesser curvature. - Inferior greater curvature supplied by the left gastro-omental artery, which is formed from the SMA. The splenic artery forms the short gastric artery which supplies the superior half of the greater curvature. - Drained by the hepatic portal vein venously and the thoracic duct via the coeliac nodes.

Question 32

Anatomy and vasculature of the duodenum

Answer 32

Part 1: Travels along the transpyloric plane to the right. Intraperitoneal. Part 2: Moves dorsal to the head of the pancreas and inferiorly to the L3 level. The Ampulla of Vater (combined pancreatic and cystic duct) enters here as the major duodenal papila. Retroperitoneal. Part 3: Crosses back to the left between the SMA and the aorta. Part 4: Shifts superiorly to L2 before descending as the duodenojejunal flexure. Parts 1-2: Supplied by the superior pancreaticoduodenal arteries of the hepatic arteries. Drained by the hepatic portal vein venously and the preaortic coeliac nodes lymphatically. Parts 3-4: Supplied by the inferior PD arteries from the SMA. Drained by the superior mesenteric vein venously and the preaortic superior mesenteric nodes lymphatically.

Question 33

Vasculature of the jejunum and ileum

Answer 33

Jejunal and ileal arteries respectively. The jejunal arteries form a single layer of arcades and long arteria recta, while the ileal arteries form many layers of arcades. The ileal arteries originate from the loop formed by the ileocolic artery with the SMA. Drained by the SMV venously and the superior mesenteric nodes lymphatically.

Question 34

Vasculature of the large intestine

Answer 34

Caecum and appendix: Anterior and posterior caecal arteries and appendicular arteries from the ileocolic loop. Asc colon: Right colic artery. Transverse colon: Middle colic artery and the ascending branch of the left colic (which is a branch of the IMA). They are joined by the anastomosing marginal artery. Desc. colon: Descending branch of the right colic artery. Sigmoid: Sigmoid arteries of the IMA. Hindgut segment starts at 2/3 transverse colon.

Question 35

Vasculature and nervous supply of the rectum

Answer 35

Superior third considered to be digestive but the inferior 2/3 considered to be systemic. Superior third: Superior rectal artery of the IMA. Middle third: Middle rectal arteries of the internal iliacs Inferior third: Inferior rectal arteries of the internal pudendals. Venous drainage: Combination of IMV (superior) and internal iliac vein (inferior)--> portal systemic anastomoses. ANS supply: Superior: IMP at L3. Inferior: Superior and inferior hypogastric plexus.

Question 36

Autonomic innervation of the gut

Answer 36

Rami communicans --> Sympathetic chain-->preganglionic splanchnic--> pre-aortic plexus--> postganglionic fibres to form autonomic plexus. Foregut: Coeliac plexus= Greater splanchnic (T5-9)+ Vagus. Epigastric pain. Midgut: SMP= Lesser splanchnic (T10-11) + Vagus. Umbilical pain. Hindgut: IMP/sup. hypogastric= Lumbar and sacral splanchnic (L1+L2) + Pelvic splanchnic (S2+S4). Suprapubic pain. Visceral pain is registered as diffuse cutaneous pain as afferent fibres enter the CNS with the somatic afferents in the dorsal root.

Question 37

How does abdominal pain become more localised over time in appendicitis?

Answer 37

Initially inflammation only activates the visceral sensory receptors. Poor localisation of sensation resulting in diffuse pain. Progression of inflammation causes aggravation of the parietal peritoneum, and ehnce the sensory supply of the abdominal wall--> somatic sensation is better localised. Pain is located at the right inguinal quadrant and indicates severe inflammation.

Question 38

Outline the layers of the gastrointestinal tract wall (from lumen outwards)

Answer 38

Mucosa: Epithelium: Depends on region- stratified squamous for conduction, columnar for absorption or secretion. Lamina Propria: Functional support: Contains CT and other cells/glands relevant to function. Muscularis mucosae: Allows movement of the gut tube independent of the outer muscle layers. Submucosa: CT layer- similar to lamina propria. Muscularis externa: Contains an outer longitudinal and an inner circular layer which coordinate to allow peristaltic movement. Myenteric nervous plexus found between. Serosa/Adventitia: Different names for the mesothelial membrane around the structure. Adventitia if it makes contact with another structure, serosa if it is independent in the peritoneal cavity.

Question 39

Glands of the oral cavity

Answer 39

Parotid: Serous secretion- more watery and contains enzymes. Lateral to ears. Zymogen granules in the secretory cells cause it to be stained darker. 25% of total secretion. Sublingual: Entirely mucous so appears to be lighter when stained. Found inferiorly in the mouth, more anterior to the submandiular. 5% of total secretion. Submandibular: A mix of mucous and serous. Found posterior and inferior to the sublingual gland.

Question 40

Composition and function of Saliva

Answer 40

- Mucous contain mucins, which are slippery and aids in lubrication and binding food particles into a bolus. Also protects against bacterial adhesion and barrier against the stomach acid during vomiting. - Bicarbonate ions for similar buffering purposes against stomach acid. - Lysozymes, lactoferrins and immunoglobulins to provide protection against microbes. - Amylase: Initiates digestion of starches. - Lipase: Initiates lipid digestion. - Haptocorrin: Aids in the absorption of vitamin B12.

Question 41

Ductal organisation of the salivary glands.

Answer 41

- Terminates at acini (one type of secretory cell) or serous demilunes (both types of secretory cells). Surrounded by myoepithelial cells which contract to squeeze acini to release the secretions. - Intercalated ducts: Extensions of the acini to form a simple cuboidal epithelial duct, surrounded by myoepothelial cells. Appears as the smaller type of duct in histology slides. - Striated ducts: Secretory epithelium rich is mitochondria to secrete Na+, Cl-, K+ and HCO3- . Basement membrane forms thin striations into the epithelial cells. Appears in cross sections as acini but with a notable lumen. - Interlobular ducts: VERY large duct with a cuboidal epithelial lining

Question 42

Structures of the interlobular septa

Answer 42

Consists of collagenous connective tissue. Contains adipocytes which are round white structures. Small tubular structures are visible- blood vessels- arteries or veins dependent on size of lumen. Large grey bundles are nervous tissue.

Question 43

Factors influencing activity of the salivary glands

Answer 43

Stimulation: Increased PSNS activation. Detection of food. Nausea. Inhibition: SNS activation during a stress response. Sleep. Dehydration.

Question 44

Distinguishing features of the oesophageal wall.

Answer 44

Epithelium: Stratified non-keratinised squamous epithelium. Non-resistant to acid reflux- potential chemical damage. Use this to determine the true lumen instead of large blood vessels of the submucosa. Papillary protrusions of the lamina propria into the epithelium- prevents shearing motion. Muscularis mucosae: Absent in the upper oesophageal region but develops near the stomach. Muscularis externa: IC and OL layers present with nervous and vascular tissue in between. Forms physiological sphincters at the gastric and pharyngeal ends (smooth and skeletal muscle respectively). Skeletal muscle will appear as larger, more solid, dark bundles.

Question 45

Arrangement of glandular cells in gastric glands

Answer 45

Simple columnar mucous: Along the surface of the lumen and the more superficial region of the gastric pit. Mucous neck cells: Around the neck region where the pit bifurcates into glands. Parietal and chief cells: Interspersed in the gastric glands. Chief cells found deeper in the gland. Enteroendocrine cells: Found at the very bottom of the gastric glands- difficult to stain and see. Smooth muscle cells found between the glands to aid in secretion by contracting to squeeze the glands.

Question 46

Parietal Cell Function

Answer 46

Lightly stained cells. Secretes HCl via independent secretion of H+ and Cl- ions. H+ secretion via proton pumps, which are placed on the apical membrane via tubulovesicle fusion with intracellular canaliculi. Secretes HCO3- into, and uptakes Cl- from bloodstream. Secretes intrinsic factor for B12 absorption. Activity promoted by acetylcholine, NSAIDS and gastrin- overactivation may lead to ulceration.

Question 47

Chief Cell Function

Answer 47

Secretes pepsinogen (prevents autodigestion) so it is dark staining. Found in the terminal ends of the gastric glands as granular cells.

Question 48

Function of simple columnar mucous cells and mucous neck cells.

Answer 48

Simple: Mucous secretion to form a protective layer of mucous glycoproteins above the epithelium. Provides buffer against acidic gastric environment. Mucous neck: Secretes an ACIDIC mucous- similar protective function. Subject to constant chemical insult --> readily replaced.

Question 49

Enteroendocrine cell function

Answer 49

G cells: Gastrin. Stimulates mucous and acid production in preparation for digestion. Upregulates ECL cell and D cell activity. ECL cells: Secretes histamine which upregulates parietal cell activity. D cell: Secretes somatostatin which inhibits ECL and G cell activity and hence parietal cell secretion.

Question 50

Disruption of the Protective Mechanism of the Gastric Lining

Answer 50

Prostaglandin E2 is secreted as a stimulus for the production of mucus. NSAIDs interfere with the inflammatory cascade that produces PE2 and inhibits this production. PE2 also inhibits G cell and ECL cell activity, so disruption to PE2 leads to oversecretion of gastric acid. Combined effect leads to ulceration.

Question 51

Phases of Gastric Motility

Answer 51

1) Vagovagal reflex: Detection of oesophageal distension by bolus of food. Stimulates fundus relaxation and increase secretory mucosa activity. 2) Antral contraction in a wave to push the chyme towards the pyloric sphincter. Contraction of the terminal antrum will not be able to push the chyme through the pylorus, hence there would be backflow up into the proximal antrum. 3) However, the high pressure would be able to squeeze small amounts of chyme through the pyloric sphincter. This allows only small food particles to pass.

Question 52

Dumping Syndrome

Answer 52

Increased, uncontrolled shift of gastric material through the pylorus. Reduced exposure to gastric acid means poorer breakdown of proteins. Causes distension and pain of the duodenum. Hyperosmotic luminal contents draws water into the duodenum via osmosis and leads to diarrhoea. Due to pathological widening of the pyloric sphincter, or overstimulation of the muscularis externa of the stomach.

Question 53

Delayed Gastric Emptying

Answer 53

Weak antral contractions due to antral neuropathy- causes diabetic gastroparesis. Retention chyme in the stomach leads to prolonged distension of the stomach- ergo pain.

Question 54

Phases of gastric acid secretion

Answer 54

Cephalic: Initiates by detection of food. Stimulates vagus nerve activity and increases activity of parietal cells both directly and indirectly via ECL and G cell activation. Gastric: Gastric distension detected via stretch receptors to send the signal back to the CNS via autonomous afferent fibres. Stimulates vagal activation of parietal cells.. Chemoreceptors also detect increased concentration of fatty acids and amino acids, which stimulate gastrin release. Gastrin stimulates parietal cell activity. Intestinal: Increased acidity is detected as the chyme enters the duodenum. Stimulates D cell activity- somatostatin inhibition of parietal, ECL and G cells. Amino and fatty acids in the duodenum will stimulate cholecystokinin release to stimulate pancreatic secretion and cystic contraction.

Question 55

Peptic Ulcer Disease

Answer 55

Symptoms: Burning epigastric pain during (gastric) or after (duodenal) eating. Caused by a break in the mucosa which exposes nociceptors of the submucosa. Extensive damage can lead to perforation of the stomach wall. Treatment: Gastrectomy-- > remove the section of the stomach with the ulcer and then reattach the pylorus, or pyloroplasty, which is the removal of the pylorus, allowing the sphincter to relax, and then reattaching it so gastric emptying is faster and there is hence less irritation.

Question 56

Pathophysiology of H. pylori infection

Answer 56

- H. pylori produces urease, which converts urea to ammonia, which is toxic to the mucosa. Stimulates an inflammatory response. - Migrates to duodenum through causing duodenal metaplasia, by stimulating excess gastrin production and hence gastric acid production. - Atrophic gastritis: Condition following an inflammatory response where the parietal cells are damaged. Reduced gastric acid secretion --> achlorhydria. Leads to bacterial colonisation and carinogen accumulation.

Question 57

Gastric adenocarcinoma

Answer 57

Intestinal type: Malignant cells still well differentiated. Form a tubular macro arrangement. Diffuse type: Poorly differentiated malignant cells. Spreads throughout wall of stomach and can reach the mucosal layer to make that region rigid- interferes with antral contractions.

Question 58

Process of Vitamin B12 Absorption

Answer 58

1) Cobalamin is taken in with protein, so it is cleaved from the protein via hydrolysis by pepsin in the stomach, 2) Cobalamin binds to haptocorrin, which is secreted by the salivary glands. 3) At the descending duodenum, haptocorrin is cleaved off by protease and intrinsic factor is associated to Vit B12. 4) IF binds to receptors on the enteric brush border and is intaken along with the associated cobalamin. 5) IF is cleaved from the cobalamin inside the enterocytes. Either reassociated with haptocorrin and transferred venously to the liver for reintroduction into the duodenum, or associated with transcobalamin II and taken to tissue for DNA synthesis.

Question 59

Macrocytic/Pernicious Anaemia

Answer 59

- Absence of B12 means DNA cannot be formed to allow cells to proceed into the G2 phase. Cells therefore continue to proliferate and it's hence more difficult for them to leave the bone marrow. - Diagnosable by looking at the mean RBC volume. Diarrhoea like symptoms as the mucosa is not replaced due to the inability to form DNA. - Pernicious anaemia is an autoimmune disorder, when antibodies are formed against IF, hence preventing uptake. - Can also be due to loss of parietal cells via gastrectomy, and hence also leading to less IF production.

Question 60

Coeliac's Disease in B12 Deficiency

Answer 60

Leads to destruction of villi of the distal ileal enterocytes, which interferes with the absorptive function of the mucosa. Also destruction of cells in the proximal duodenal mucosa which secrete cholecystokinin --> promotes pancreatic secretion.

Question 61

Mechanism leading to cirrhosis.

Answer 61

Kupffer cells detect hepatocyte damage and secrete cytokines. Cytokines activate quiescent pericytes, becoming myofibroblasts. These secrete connective tissue fibres after being stimulated by TGF-b secreted by the Kupffer cells. This leads to fibrosis of the liver.

Question 62

Portal hypertension and its clinical presentation.

Answer 62

During cirrhosis, the fibrotic tissue would occlude the hepatic venous structures. This leads to increased pressure and causes accumulation and backflow of blood in the veins. This causes engorgement of the vessels in the portal-systemic anastomoses. - Caput medusae: Engorgement of vestigial veins around the umbilicus. - Haematemesis: Vomiting of blood following the rupture of engorged submucosal blood vessels. - Ascites: Disruption of the oncotic/hydrostatic pressure equilibrium--> increased filtration. Increased tissue fluid in the liver will drain into the peritoneal space and cause oedema. Liver damage also prevents synthesis of blood proteins

Question 63

Pathophysiology of Hepatitis B

Answer 63

Transmitted by blood or body fluids. Infects hepatocytes and leads to autoimmune destruction, leading to hepatic inflammation and impairment of hepatic function. Most cases are subclinical--> does not lead to clinical manifestation as the immune response is adequate. Acute hepatitis is when there is severe damage- presents clinically- but the immune response is still adequate. An extreme case is fulminant hepatitis, where there is extensive necrosis- requiring transplant. Chronic hepatitis: Immune response fails to eliminate virus completely, leads to chronic inflammation where there is continued cirrhosis and a small risk of hepatocellular carcinoma. Immune response may eliminate infection over time to lead to recovery.

Question 64

Progression of Fatty Liver Disease

Answer 64

Damage initially presents in zone 3 (closest to the central vein) but radiates outwards as the outer zones take over for the dying hepatocytes. Hepatocellular Steatosis: Accumulation of lipids in hepatocytes following alcohol consumption. Hepatocytes manifest as enlarged cells with large lipid filled vesicles, Mallory Denk bodies (eosinophilic aggregate of misfolded proteins) and heat shock proteins. The lipid itself appears to be yellow and greasy. Alcoholic hepatitis: Alcohol metabolism forms ethanal, which peroxidises the lipids in the liver into ROS. Alcohol stimulates cytochrome p450 --> metabolises drugs to toxic byproducts . Also releases bacterial endotoxins into portal systemic circulation to cause hepatitis.

Question 65

Haemochromatosis

Answer 65

Autosomal recessive genetic disorder- unregulated enterocyte uptake of iron. Iron can accumulate in liver and pancreas. Is a hepatotoxin- forms hydroxyl free radicals. Iron overload is only pathological when there is another stimulus of hepatitis.

Question 66

Enzymatic Activity Relevant to Protein Digestion

Answer 66

Gastric: Pepsinogen --> Pepsin via acidic environment. Pancreatic: Trypsinogen--> Trypsin via apical enteropeptidases on the surface of duodenal enterocytes. Hydrolyse peptide bonds adjacent to specific amino acids. Procarboxypeptidase--> carboxypeptidase via trypsin. Hydrolyse off terminal carboxylic acid groups. Chymotrypsinogen--> Chymotrypsin. Hydrolyse peptide bonds adjacent to specific amine groups. Elastase and Collagenase: General hydrolysis of peptides into smaller peptides. Intestinal: Tri/dipeptidases: Hydrolysis of tri/dipeptides into amino acids. Aminopeptidases: Hydrolysis of the terminal peptide bond.

Question 67

Causes and consequences of negative nitrogen balance

Answer 67

Transient reduced protein intake/absorption, trauma, burns, lactation, cancerous cachexia. Rate of tissue breakdown > formation. Leads to atrophy and breakdown of lean tissue.

Question 68

Causes and consequences of positive nitrogen balance

Answer 68

Rate of tissue breakdown< formation. Transient increase in protein intake, growth (increased growth factor concentration stimulates tissue formation),, pregnancy, recovery from injury, Increased protein consumption will not lead to increase in tissue mass as the body's metabolism will adjust to store it as lipids- increased tissue formation only occurs with increased signals/stimuli for tissue formation.

Question 69

Process of Carbohydrate Digestion and absorption

Answer 69

Mouth: Mechanical digestion- breakdown of fibrils. Salivary amylase causes hydrolysis of glycosidic bonds. Stomach: No digestion as acidic environment halts amylase activity. Small intestine: Pancreatic amylase continue to hydrolyse glycosidic bonds. Disaccharidases on the apical surfaces of enterocytes convert disaccharides into their constituent monosaccharides. Absorption: Through SGLTs, using energy from the Na+ gradient created by the Na+ ATPase. GLUT proteins allow passive diffusion of monosaccharides into the bloodstream. FRUCTOSE enters the enterocyte by facilitated diffusion. Colon: Some dietary fibres can be metabolised by commensal bacteria into short chain fatty acids, which allows the colic mucosal cells to resist cancer.

Question 70

Pathophysiology of Lactose Intolerance

Answer 70

Lactose is not broken down due to the absence of lactase in the duodenum. This leads to accumulation in the colon, where commensal bacteria will metabolise it to produce gas, which leads to bloating.

Question 71

ALT/AST and what causes elevation?

Answer 71

ALT/AST is involved in combining alanine/aspartic acid with a-ketoglutarate to form intermediates of the Krebs cycle during gluconeogenesis. Usually found only in hepatocytes. Elevated levels indicative of hepatitis- necrosis of hepatocytes cause these to spill out. Found in other metabolically active tissues (muscle, heart etc)- damage to those tissues would also cause increase.

Question 72

ALP and what causes elevation

Answer 72

Involved in phosphate group attachment/detachment from proteins. Shows biological variation- dependent on biological processes occuring- elevated during times of bone remodelling. Elevation can indicate presence of of carcinomas or obstruction of the biliary tree. Obstruction likely indicates Cirrhosis or cancer inpinging on the bile ducts.

Question 73

What causes GGT elevation?

Answer 73

- Alcohol intake, although effect subject to biological variation and also experiences delay. - Biliary tree obstruction and hepatitis- better specificity as all elevation causes are related to the liver. Obstruction likely indicates Cirrhosis or cancer inpinging on the bile ducts.

Question 74

Bilirubin formation and metabolism

Answer 74

Formed from the haem group of degenerated RBCs. Travels to the liver via the hepatic portal system in its unconjugated form- associated with albumin. Conjugated in the liver via conversion to bilirubin glucuronide. Secreted with bile and converted to urobilinogen and either re-uptaken into the blood or excreted with faeces. Urobilinogen returns to the liver via the enterohepatic circulation to potentially be reconjugated.

Question 75

Pathology involved with Bilirubin Metabolism

Answer 75

- Gilbert's Syndrome: Autosomal recessive condition leading to failure to produce bilirubin glucuronide. Leads to excess circulation of unconjugated bilirubin--> yellow appearance in sclera. Cholestasis: Inadequate movement of bilirubin/bile into the duodenum. Prevents emulsification of fats. Presence of lipids in faeces as well as light appearance. Cholestasis due to occlusion: Excess production of conjugated bilirubin- backflow into bloodstream. Increased blood concentration leads to increased expression of yellow pigment in the skin.

Question 76

Albumin (and other hepatic blood protein) concentration as a test for liver function

Answer 76

High specificity to the liver. 35-47g/L, although slight deviations can occur during mild inflammatory responses. Major reduction- loss of liver function either by hepatitis or Cirrhosis. Effect: Disruption to oncotic pressure provided by the blood proteins. Excess loss of tissue fluid into the peritoneal cavity leads to ascites.

Question 77

Prothrombin ratio

Answer 77

Denotes rate at which blood clots- indicates clotting factor concentration. Hepatic impairment elevates this number- caused by cirrhosis or hepatitis.

Question 78

Metabolic products as a test for liver function

Answer 78

Glucose: Excessive deviation indicates failure to carry out adequate modification to glucose for storage/release, hence indicating failed liver function. Ammonia: Usually converted to urea in the liver, which is less toxic. Impaired hepatic function leads to accumulation of ammonia, which can backflow into the circulation. Manifests clinically as hepatic encephalopathy- non-rhythmic 'jerking' flexion and extension of head and extremities.