Case 3 - GI

Question 0

Why does alcohol over consumption develop at first?

Answer 0

Positive Reinforcement, a feeling a euphoria that brings psychological rewards; negative reinforcement follows, that is using alcohol to lessen stress and anxiety.

Question 1

Describe the zones of a hepatocyte

Answer 1

Zone 1 is the periportal zone, Zone 2 is the Intermediate Zone and Zone 3 is the Centrilobular zone. Hepatocyte acinus is split into 3 concentric elliptical zones and in a hepatitis infection, Zone 1 is affected first as the cells in tho zone receive sinusoidal blood transport contents first, such as O2 and nutrients, so that these cells will receive the viral infection first.

Question 2

What two types of cells are found in the salivary glands and what are their functions?

Answer 2

Acinar cells - active transport of electrolytes and passive transport of water follows (saliva is isotonic to plasma here, in acinus) Duct cells - reabsorption of sodium and Chloride ions

Question 3

Describe the content of saliva at low and high rates of secretion

Answer 3

Low rate - Low Na+, HCO3-, Cl- K+ concentration higher here High rate - High Na+, HCO3- Cl-

Question 4

What are the stages of swallowing? What occurs during these phases? Mention control and whether phase is voluntary or involuntary

Answer 4

See notes for the 11 steps of these stages; 1) Oral - voluntary - initiates involuntary 2) Pharyngeal - involuntary - controlled by medulla and lower pons Swallowing centre inhibits respiratory centre 3) Oesophageal - involuntary - controlled by medulla and lower pons Starts with relaxation of lower oesophageal sphincter

Question 5

What do parietal cells secrete and How?

Answer 5

See diagram.. These secrete HCl and INTRINSIC FACTOR (IMPORTANT FOR Vitamin B12)

Question 6

What do chief cells secrete and how?

Answer 6

See diagram.. They secrete pepsinogen

Question 7

Why do chief cells stain darker than parietal cells?

Answer 7

Dye stains rough endoplasmic reticulum.Chief cells have more endoplasmic reticulum than parietal cells so chief cells appear darker than parietal cells

Question 8

What is the function of the HCl produced by parietal cells

Answer 8

Remember: A kitten does kill Activates pepsinogen to pepsin secreted by chief cells Kills microbes with lysozymes Denatures protein Breaks down

Question 9

What cells are found in the oxyntic mucosa?

Answer 9

Surface mucous cells Neck mucous cells Stem cells Parietal cells Chief cells

Question 10

What cells are found in the pyloric mucosa?

Answer 10

G cells D cells

Question 11

What is the difference between surface mucous cells and parietal cells?

Answer 11

Surface mucous cells - secrete viscous mucus forming a protective layer against acidic contents Neck mucous cells - secrete watery mucus, allowing mixing with chyme for lubrication

Question 12

What triggers the cephalic phase to begin producing gastric secretion before food even enters the stomach?

Answer 12

1) seeing, thinking, smelling and chewing food 2) stimulates vagal nerves of the myenteric plexus 3) stimulates chief cells and parietal cells DIRECTLY 4) Stimulates G cells, thus stimulating chief and parietal cells INDIRECTLY

Question 13

What is the major stimulation for gastric secretion in the gastric phase?

Answer 13

Protein present in the stomach

Question 14

What stimulates the intestinal phase of digestion (gastric secretion) ? Remember this phase is inhibitory.

Answer 14

Intestinal phase starts when food enters duodenum 1) gastric secretion inhibits as major stimulus : protein in stomach not there anymore 2) high gastric acidity, low pH (usually buffered by proteins but nit there anymore) 3) acid, lipid ( ** these cause release of enterogastrones)

Question 15

What are enterogastrones?

Answer 15

• Gastric inhibitory peptide (GIP) responds to fatty acids - Secretin, responds to acid - Cholecystekinin (CcK) responds to fatty acids - Somatostatin ,responds to fats and glucose They inhibit gastric secretion and motility

Question 16

How does acetylcholine stimulate parietal cells to secrete HCl?

Answer 16

Acetylcholine bind to its G coupled receptor Gq activates phospholipase C See schematic diagram in case 3 notes on Jeff’s lecture

Question 17

Within the Antrum of the stomach, what hormone is released? Why is there a decrease of this hormone in the intestinal phase?

Answer 17

Gastrin secreted from antrum of the stomach As protein leaves stomach and enters duodenum, there is less vagal stimulation as well as intrinsic.. So G cells are not stimulated as much, therefore a decrease in gastrin secretion

Question 18

What hormone is produced in the antrum and duodenum that responds to acidic gastric juice?

Answer 18

Somatostatin produced by D cells This decreases vagal stimulation thus decreasing stimulation of parietal cells, G cells, ECL cells

Question 19

What hormones associated with the intestinal phase of gastric secretion are produced in the duodenum?

Answer 19

The enterogastrones ; CCK - from I cells Secretin - from S cells

Question 20

In pancreatic secretion, what does secretin do?

Answer 20

Stimulates duct cells to secrete water and bicorbornate. It initiates the cAMP, Gs pathway, protein kinase A phophorylates CFTR channel so Cl- can leave to maintain a high Cl- gradient. See diagram under graph in case 3 notes of Jeff’s lecture

Question 21

Where does the majority of the pancreatic juice stimulation take place?

Answer 21

In the intestinal phase

Question 22

What controls HCO3- secretion from duct cells?

Answer 22

Secretin hormone is released in response to ACID in the duodenum during intestinal phase

Question 23

How does secretin cause more carbonate secretion?

Answer 23

Through the cAMP pathway, Gs coupled receptor Activates protein kinase A which phosphorylates CfTR channel to allow CL- to leave cell.. Allowing for the HcO3- antiporter with Cl- to continue to pump out carbonate

Question 24

To what stimulus does CCK get secreted from I cells in terms of pancreatic stimulation?

Answer 24

Presence of fats Also presence of proteins

Question 25

What are choleretics and what are the most potent choleretics?

Answer 25

Substances that increase bile secretion in the liver Most potent are bile salts themselves

Question 26

What are cholagogues? Name one.

Answer 26

Substances that increase the flow of bile by emptying the gall bladder CCK\*\*\*\*

Question 27

Name the two mechanisms of bile secretion

Answer 27

Bile acid dependent 1 Depends on rate of bile acid return Bile acid independent 2 Secretion of electrolytes and water from hepatocytes and duct cells

Question 28

What is secretin's role in bile formation?

Answer 28

Secretin causes increased bile independent bile secretion - increases bile flow - increases cell sensitivity to CCK - increases volume of bile by secreting bicarbonate and water

Question 29

Is secretin a choleretic?

Answer 29

No. Secretin is a hydrocholeretic as it only increases electrolytes and water in the bile

Question 30

Sarah has just started eating her lunch. What hormones have been released to initiate her appetite, what hormone would make her stop eating? Talking about short term hormones here, mention where these hormones would be released,

Answer 30

In response to no nutrients, ghrelin is secreted from duodenum Ghrelin promotes pathway for secretion of Orexins from lateral hypothalamus, promoting appetite \*\*ghrelin is the hunger hormone It is the hormone PYY secreted from the ilium of the GI tract that inhibits hypothalamus neurones from stimulated orexins by NPY

Question 31

Sarah has now finishing eating her lunch, which was at her favourite vintage cafe. What hormones will be released and where from, to stop Sarah eating?

Answer 31

1) PYY, secreted from ilium, inhibits pathway to promote orexins from promoting appetite. PYY is therefore anorexogenic 2) In response to digestive products from Sarah's lunch i.e. Increased fats, nutrients,, CCK is released from I cells. This stimulates satiety centre in brain stem.. Making Sarah feel full

Question 32

What is the role of leptin in terms of food intake, and where is it secreted from?

Answer 32

See the diagram I photocopied from Sherwood Human Physiology. Leptin is secreted from adipocytes. The more fat, the more leptin. Leptin inhibits pathway for promoting appetite by orexins, and stimulates pathway for appetite suppression.

Question 33

A 37 year old patient comes is complaining of long term epigastric pain. He mentions he has lost weight in the last couple of months, "it just hurts when I eat.". What tests would you order? What is the differential diagnosis?

Answer 33

Could have gastric ulceration. Biggest cause is usually H. Pylori, (NSAIDs, carcinoma possible as well) Tests; 1) Urea breath test 2) Stool antigen test 3) immunoassay to detect H Pylori antigen 3) IgG antibodies

Question 34

What is H. Pylori and what is its prevelance?

Answer 34

1) Gram-negative urease producing bacterium. 2) In greatest numbers under mucous layer of gastric pits, as ammonia is produced it neutralises stomach acid and is able to survive 3) Higher in developing countries

Question 35

What is the pathogenesis of H. Pylori?

Answer 35

1) Infects stomach mucosa (highly adapted urease producing bacterium) 2) Inflammatory response - Gastritis 3) G cells release gastrin 4) Gastric metaplasia 5) Damage to mucosa 6) Damage to mucosa

Question 36

Treament for H. Pylori?

Answer 36

Remember 3,2,1. 3 drugs: proton pump inhibitor, 2 antibiotics 2: times a day 1: week STOP NSAIDs Gastrectomy in severe cases

Question 37

Mechanism of action of proton pump inhibitors ? Side effects? \*\* Omeprazole / Lansoprazole

Answer 37

1) inhibit H+/K+ ATPase (LAST STEP in HCl secreion in parietal cell) 2) decreases H+, and acid secretion 3) Weak base accuulates in cannliculi in acid environment 4) Nausea, dizziness, diarrhoea \*Careful with liver disease patients, pegnant, breastfeeding patients \*\*more effective than antacids

Question 38

Mechanism of action of H2 antagonists? \*\*Ranitidine / Cimetidine

Answer 38

\*\* Remember histamine stimulate parietal cell to secrete HCL 1) Inhibits histamine2 receptors at mainly gastric acid secretions 2) decreases activation of pepsinogen as less HCL released (their stimulant for release) 3) also promote duodenal and gastric ulcer healing

Question 39

When would you as a doctor, request endoscopy for your patient?

Answer 39

Remember GUIDE Poly and Angel G- GI bleeding U- Unitintention weigth loss I- Iron defeciency anaemia D- Dysphagia E- Epigastric mass P- Persistent vomiting A- Age (Over 55) and acute onset dysphagia

Question 40

A patient comes to see you with occasional indigestion. He says he gets it once or twice a week and is worried. What woul you prescribe is anything? 3 weeeks later the same patient comes back saying he now gets indigestion constantly. Would would you do differently now?

Answer 40

Occasional - tell him avoid acidic spicy food, encourage lifestyle changes Suggest antacids Persisitent symptoms - Proton Pump Inhibitor Inhibitor therapy given once or twice daily