Gastrointestinal Physiology

Question 1

Daily water turnover in GIT

Answer 1

Ingested 2L

Secretions
Salivary - 1.5, Stomach 2.5, Bile 0.5, Pancreas 1.5, Intestine 1L

Reabsorbed
Jejunum 5.5L
Ileum 2L
Colon 1.3 L

BALANCE is -200mL through stool

Question 2

GIT hormones

Answer 2

Enteroendocrine cells

Gastrin - Gastrin and CCK
Secretion - Secretin, Glucagon, VIP, GIP

Question 3

Gastrin

Answer 3

Gastrin - G cells in stomach antrum - acts via CCK-B receptor

• Stimulation of gastric acid and pepsin secretion
• Stimulation of the growth of the mucosa of the stomach and small + large intestine (tropic action)

Things that affect
- Contents of stomach (including distension of antrum and duodenum), rate of DC of vagus and blood borne factors

GRP (released by post ganglion in vagal fibres - not ACH)

Products of protein digestion - phenylalanine and trophytophan —> act directly on G cells

Acid in antrum inhibits G cells directly and indirectly through somatostatin (negative feedback)

Calcium and epinephrine increase

Secretion, GIP, VIP, Glucagon and calcitonin decrease

G17 principal, G14, G17 have 2-3 mins half life, G34 15 min half life

Preprogastrin is precursor

Kidney and small intestine inactivate -

Gastrin is released by G cells in the stomach antrum in response to peptides in the lumen, and vagal stimulation. Its actions include stimulating growth of gastric and intestinal mucosa, increasing acid secretion by parietals cells in the stomach, and increasing secretion of pepsinogen (which is a precursor of pepsin) by the chief cells.

There are 3 phases of gastric regulation; cephalic, gastric and intestinal.

Gastrin is released during the cephalic phase and triggers the release of gastric juices. Once the pH in the stomach is < 2, it begins to exert a negative feedback to inhibit further acid secretion. GIP, secretin and CCK are released during the intestinal phase. The first two inhibit further release of gastric juices, while CCK inhibits stomach emptying.

Gastrin is a peptide hormone that stimulates HCl secretion by parietal cells of the stomach and pepsinogen secretion by the chief cells of the stomach. Gastrin is produced in the G cells, located in the antral mucosa of the stomach, duodenum and pancreas. Gastrin production depends on several factors. Luminal factors (i.e. stomach distention, amino acids, and peptides) and vagal stimulation via gastrin-releasing peptide will increase gastrin production. Gastrin is structurally and functionally similar to CCK. Structurally, both are in the gastrin–CCK family of peptide hormones and share the same five C-terminal amino acids. Functionally, both are digestive hormones that stimulate the secretion of various digestive enzymes for protein and fat digestion.

It can also trigger gallbladder contraction and pancreatic juice secretion.

In pernicious anaemia, atrophy of gastric mucosa with consequent decreased acid production causes feedback hypergastrinaemia. Somatostatin is inhibitory.

Question 4

CCK

Answer 4

Secreted by I cells in upper small intestine (includes jejunum)

5 min half life

Receptors for CCK A and B found in the brain

CCK actions - pancreatic enzyme secretion, contraction of gallbladder, relaxation of sphincter of Oddi, inhibits gastric emptying, tropic effect on pancreas, synthesis of enterokinase, motility enhancement, may augment contraction of the pyloric sphincter
Augments secretin

Factors affecting
Products of digestion increase + Fatty acids

CCK increases bile and pancreatic juice which enhances protein and fat digestion which positively feeds back on CCK (terminated by motility of products)

Cholecystokinin is produced by I cells in the mucosa of the proximal small bowel. It is also found in enteric nerves in the distal small and large bowels, and in the brain. It is stimulated by the presence of food products in the lumen of the gut. It has many effects, including gallbladder contraction and sphincter of Oddi relaxation, enzyme-rich pancreatic secretion, inhibition of gastric emptying, and increased small bowel motility. It is trophic to pancreatic tissue.

Cholecystokinin is produced by I cells in the mucosa of the proximal small bowel. It is also found in enteric nerves in the distal small and large bowels, and in the brain. It is stimulated by the presence of food products in the lumen of the gut. It has many effects, including gallbladder contraction and sphincter of Oddi relaxation, enzyme-rich pancreatic secretion, inhibition of gastric emptying and increased small bowel motility. It is trophic to pancreatic tissue. It also stimulates glucagon secretion and enterokinase synthesis.

Question 5

Secretin

Answer 5

S cells - upper small intestine

Half life of 5 mins

Increases bicarbonate, augments CCK

Decreases acid secretion
Inhibits motility and inhibits gastric acid secretion

Protein digestion and acid in upper small intestine —> causes secretion

Negatively feeds back against itself by neutralising acid

Secretin is produced and secreted by S cells found in the proximal small intestine. It stimulates pancreatic cells to produce a watery, bicarbonate-rich alkaline secretion. It inhibits acid production in the stomach and delays gastric emptying. Its production is stimulated by acidic chyme entering the duodenum. Its effects are synergistic with those of cholecystokinin.

Question 6

GIP

Answer 6

K cells

Glucose and fat in duodenum - inhibits gastric secretion and motility (only in high doses)

STIMULATES INSULIN (gastrin, CCK, Secretin and glucagon - also do it but not to the extent)

GLP 1 is more potent in this regard (Glucagon derivative)

Hypoglycemic action of gastric inhibitory peptide occurs when a high concentration of glucose is detected in the lumen of the duodenum. The K cells in the duodenal lumen will produce GIP, and GIP will stimulate insulin secretion that decreases the blood glucose level.

Question 7

VIP

Answer 7

Nerves in GIT (not a hormone)

Half life 2 mins

Intestinal secretion of electrolytes and water
Inhibits gastric acid secretion
Relaxation of smooth muscle
Dilation of peripheral blood vessels

VIP is found in nerves in the GI tract and, as such, is not considered a hormone. It causes vasodilation and smooth muscle relaxation in the intestine, with increased secretion of electrolytes and water into the lumen of the gut. In excess, this can produce profound diarrhoea, as is sometimes seen with carcinoid syndromes. It also inhibits gastric acid secretion.

Question 8

Motilin

Answer 8

Enterochromaffin cells and Mo cells in stomach, small intestine and colon

Contraction of smooth muscle

Question 9

Somatostatin

Answer 9

D cells. PARACRINE in pancreatic islets

Inhibits gastrin, CCK, GIP, VIP, Secretin and motilin

Acid in the lumen causes its secretion - also glucose, amino acids (Arginine and leucine), CCK also cause secretion

Inhibits exocrine secretion, gastric acid secretion and motility, gallbladder contraction, absorption of glucose, amino acids, TGL’s

INHIBITS BOTH INSULIN Glucagon and pancreatic polypeptide

SS 28 > SS 14 with inhibiting insulin

Somatostatinoma’s cause hyperglycaemia, dyspepsia, gallstones

Somatostatin is globally inhibitory to the gut, reducing secretions and motility. It is produced by D cells in the gastric mucosa and pancreatic islets, in response to acid in the gut lumen.

Somatostatin inhibits pancreatic secretion, gallbladder secretion, gastric acid secretion and motilin secretion

Question 10

Peptide YY

Answer 10

Same as GIP - less acid secretion and motility

Released by jejunum and is stimulated by fat

Question 11

Gammon Peptides

Answer 11

GGGP

Ghrelin - stimulates GH secretion
ALSO causes increased food intake, motility and gastric acid

GRP - increases gastrin secretion

Guanylin - intestinal mucosal cells secrete but made in cells from pyloric to rectum
cGMP - increased CL into lumen
- Certain diarrhoea producing strains of E. Coli have a structure similar to guanylin

Substance P
Increases motility

Question 12

Splanchic circulation

Answer 12

30% output to liver and viscera

1300mL/min from portal vein to liver
500mL/min from hepatic artery

Question 13

Composition of bile

Answer 13

Water 97%
Bile salts 0.7%, then bile pigments 0.2%
Inorganic salts are 0.7% same as bile salts
Phosphatidylcholine is 0.2% as well
Fat and fatty acids 0.1 and 0.15% respectively
Cholesterol 0.06%

10:3:1 ratio of BA: PHOSPHTidyl:cholesterol

Bile salts are reabsorbed from the small intestine and undergo enterohepatic circulation retaining more than 90% of the salts. Bile has a pH of 7-8. Bile is involved in the emulsification of fat and the absorption of the fat-soluble vitamins A, D, E, K. Approximately 500 ml of bile is produced by the liver per day and the gall bladder can store about 60 ml.

Bile is produced by the liver in response to fats entering the duodenum. It contains bile acids that help emulsify fats facilitating digestion. Lipid-soluble waste products are also excreted via the bile into the gut. Around 500 ml of an alkaline solution are produced each day, containing bile acids, pigments, cholesterol and other substances.

Primary bile acids are produced by the liver—these are cholic acid and chenodeoxycholic acid. These can be converted into secondary bile acids such as deoxycholic acid and lithocholic acid in the colon by colonic bacteria. The primary bile acids are conjugated with taurine or glycine in bile and almost entirely reabsorbed in the terminal ileum.

Cholecystokinin is secreted in response to food entering the duodenum. It stimulates enzyme-rich pancreatic secretion, gallbladder contraction, and relaxation of the Sphincter of Oddi to allow bile to be released into the duodenum.

Bile is produced by the liver in response to fats entering the duodenum. It contains bile acids that help emulsify fats and make them easier to digest. Lipid-soluble waste products are also excreted via the bile into the gut. Around 500 ml of an alkaline solution are produced each day, containing bile acids, pigments, cholesterol and other substances.

Primary bile acids are produced by the liver—these are cholic acid and chenodeoxycholic acid. Primary bile acids are conjugated with taurine or glycine and stored in the gallbladder. The majority are reabsorbed in the terminal ileum. In the colon, bile acids can be metabolised by gut bacteria into secondary bile acids—deoxycholic and lithocholic acid. Like steroid hormones and vitamin D, bile acids contain a steroid nucleus.

Cholecystokinin is secreted in response to food entering the duodenum. It stimulates enzyme-rich pancreatic secretion, gallbladder contraction, and relaxation of the sphincter of Oddi to allow bile to be released into the duodenum.

Question 14

Respiratory exchange ratio

Answer 14

Increasing. - hyperventilation, exercise, metabolic acidosis

Decrease - after exercise, metabolic alkalosis

Question 15

Ammonia cycle

Answer 15

Ammonia is toxic to the brain and must be converted to urea by the liver so that it can be excreted. It is primarily produced by the colon and the kidneys. Circulating ammonia enters hepatocytes, where it enters the ammonia cycle. It is converted to carbamoyl phosphate within the mitochondria. This reacts with ornithine to generate citrulline, which is then converted by a number of intermediaries to arginine. Arginine is then dehydrated to generate urea and ornithine. Urea can be excreted via the kidneys, and ornithine recycled.

Question 16

Gastric emptying

Answer 16

As the duodenum fills, stretch receptors are activated and inhibit vagal stimulation which results in reduced gut tone and motility, this reduces gastric emptying. Pregnancy does not alter gastric emptying but during labour it may be delayed secondary to the effects of pain, anxiety and opioids. Adrenaline will reduce gastric emptying, for example when in pain or anxious. The gastric emptying time for solids is 4-6 hours. Entry of fats into the duodenum decreases gastric emptying, slowing the entry for further fat into the duodenum.

Question 17

Secretion of saliva

Answer 17

When touch receptors in mouth, stimulation of vagal afferent fibres at lower end of oesophagus, stimulation of parasympathetic nerves to the glands, just before vomiting, administration of atropine

Question 18

LES

Answer 18

It is a physiological sphincter formed by the tonic contraction of the circular muscle of the lowest 2-4 cm of the oesophagus. It is not defined anatomically. The lower oesophageal sphincter closes with a pressure 15-25 mmHg above gastric pressure. This barrier pressure is maintained as intra-gastric pressure rises. On swallowing, the lower oesophageal sphincter relaxes to allow the food bolus to pass through into the stomach. It is under both myogenic and neural control. Opioids reduce the tone of the sphincter and make reflux more likely.

Question 19

Gut motility

Answer 19

The migrating motor complex is a distinct pattern of electromechanical activity observed in gastrointestinal smooth muscle during the periods between meals. The ingestion of food abolishes the migrating motor complex and restores a digestive pattern of motility. Gastric motility is controlled by a very complex set of neural and hormonal signals. The ligation of the vagus nerve will not eliminate gastric motility. Segmentation contractions promote progressive mixing of food with intestinal secretions and can cause retrograde movement of chyme. Adrenaline has an inhibitory action on the smooth muscle of the small intestine and it causes smooth muscle relaxation. It inhibits spontaneous spike activity and causes hyperpolarization.

Movements of the gut consist of segmentation contractions and peristaltic movements. Basic electrical rhythm consists of slow waves of smooth muscle membrane potential, whose frequency varies in different parts of the GI tract. It is around 4/minute in the stomach, 12/min in duodenum, 8/min in the ileum, 2/min in the caecum and 6/min in the sigmoid. The net movement of chyme along the small intestine is mainly antegrade but retrograde movement also normally occurs over small distances. Preceding emesis, the gross retrograde movement of chyme occurs along the small intestine.

Question 20

Gallstones

Answer 20

More than 75% of gallstones in Western populations are cholesterol gallstones. The remaining are pigmented, and are subdivided into black (10%–15%) and brown (5%–10%) gallstones. Brown gallstones are associated with biliary infection. Oxalate and cysteine stones are types of renal stones.

Question 21

Duodenal secretions

Answer 21

Isotonic intestinal secretion is released into the duodenal lumen to decrease luminal osmolarity and enhance digestion and absorption. Duodenal intestinal mucosa, particularly the goblet cells, also produces mucus. Mucus will form a barrier layer which separates luminal content and the duodenal epithelia.

Question 22

Accomodation reflex

Answer 22

Gastric distention mediates activation of the accommodation reflex in the stomach, which is a vagovagal inhibitory reflex. Due to the accommodation reflex, the intragastric pressures do not increase despite an increase in the intragastric volume. This property is confined to the proximal stomach only. Peristalsis, which is a rhythmic contractile activity, and retropulsion, which is a mixing of gastric contents, are functions of the distal stomach. “Segmentation” refers to the contractile pattern of the small intestine. “Saturation” is a generalized term used for receptors and enzymes, not specific to the proximal stomach.

Question 23

Functions of Liver

Answer 23

The liver has several primary functions. These include the production and excretion of bile, bilirubin, cholesterol, hormones including thyroxine, and drugs; in addition to the metabolism of fats, proteins, and carbohydrates; and the synthesis of plasma proteins, such as albumin, lipoproteins and clotting factors. Bilirubin is produced by a two-stage reaction that occurs in cells of the reticuloendothelial system, including phagocytes and cells in the spleen and bone marrow.

Gastric distention mediates activation of the accommodation reflex in the stomach, which is a vagovagal inhibitory reflex. Due to the accommodation reflex, the intragastric pressures do not increase despite an increase in the intragastric volume. This property is confined to the proximal stomach only. Peristalsis, which is a rhythmic contractile activity, and retropulsion, which is a mixing of gastric contents, are functions of the distal stomach. “Segmentation” refers to the contractile pattern of the small intestine. “Saturation” is a generalized term used for receptors and enzymes, not specific to the proximal stomach.

Question 24

Acid secretion in the stomach

Answer 24

Gastric distention mediates activation of the accommodation reflex in the stomach, which is a vagovagal inhibitory reflex. Due to the accommodation reflex, the intragastric pressures do not increase despite an increase in the intragastric volume. This property is confined to the proximal stomach only. Peristalsis, which is a rhythmic contractile activity, and retropulsion, which is a mixing of gastric contents, are functions of the distal stomach. “Segmentation” refers to the contractile pattern of the small intestine. “Saturation” is a generalized term used for receptors and enzymes, not specific to the proximal stomach.

Question 25

Blood flow to Liver

Answer 25

The blood flow is 1 ml/g/minute, which is 25% of the cardiac output. The portal vein drains the digestive tract and associated organs whilst the hepatic artery branches from the coeliac axis. The portal vein supplies 75% of blood flow whilst the hepatic artery supplies the remaining 25%. Oxygen is supplied equally by the portal vein and hepatic artery.

Hepatic blood flow decreases in the elderly and with exercise. It is reduced by noradrenaline due to the vasoconstriction of splanchnic and hepatic arteries. It is increased by prostacyclin due to hepatic artery dilatation. The blood flow is under autoregulation around a mean arterial pressure of 60 mmHg.

Question 26

Fat soluble vitamin absorption

Answer 26

Absorption of fat-soluble vitamins requires emulsification and incorporation into mixed micelles. For this purpose, bile salts and pancreatic lipase are required. Pancreatic lipase is one of the main enzymes required for fat digestion. Intrinsic factor is required for the absorption of vitamin B12 in the ileum. Chymotrypsin is a pancreatic enzyme that is required for the digestion of proteins. Pancreatic amylase is required for carbohydrate digestion. It hydrolyzes the starch and glycogen to disaccharides and trisaccharides.

Question 27

Gut plexi

Answer 27

There are two main nerve plexuses in the gut: Meissner’s (submucous) plexus between the mucosa and muscularis layers, and Auerbach’s (myenteric) plexus between the circular and longitudinal layers of muscle. It may contain around 100 million neurons, which is a similar number to that found in the spinal cord.

Question 28

Amino acid absorption

Answer 28

7 ways - 2 are Na independent

Amino acids are absorbed via sodium or chloride cotransporters in the luminal membranes of enterocytes. They are then transported across the basolateral membrane via facilitated diffusion. Dipeptides and tripeptides are absorbed via separate H+-dependent cotransporters and once inside the cell they are hydrolyzed to amino acids. A few amino acids do not require a cotransport mechanism but instead are transported by special membrane transport proteins by facilitated diffusion.

Question 29

Fat absorption

Answer 29

Fats smaller than 10–12 carbon chains are absorbed into the portal circulation.

Large aggregates of dietary triglyceride, which are virtually insoluble in an aqueous environment, must be broken down and held in suspension—a process called “emulsification”. The monoglycerides and free fatty acids are dissolved in the central lipid portions of bile micelles and carried to the surfaces of the microvilli of the intestinal cell brush border. Here they diffuse immediately out of the micelles and into the interior of the epithelial cells. 50% of fat can be absorbed in the absence of bile salts.

Question 30

Properties of the stomach

Answer 30

The stomach is a muscular, pouch-like organ in the abdomen, and plays a major role in the digestive system. The stomach receives food from the esophagus, and digests it with enzymes and HCl. As a food reservoir, the stomach has two major reflexes: adaptive relaxation and receptive relaxation. Adaptive relaxation is the fundus dilation reflex when intragastric pressure is increased by food. Receptive relaxation is the fundus dilation reflex when food passes down the pharynx and esophagus. The stomach also controls the rate of food passage to the duodenum. Food will be processed and mixed well onto acidic chyme before entering the duodenum. Fatty and large-volumed food tends to stay longer in the stomach. The stomach also produces digestive enzymes (pepsin and lipase), HCl (gastric acid), mucin (to protect stomach mucosa from HCl), gastrin (a hormone that stimulates HCl secretion), and intrinsic factor/IF (a glycoprotein that is essential for B12 absorption in the ileum).

The stomach contains multiple glands, in which cells responsible for secreting various active substances vital for stomach function are found. Parietal cells secrete hydrochloric acid and intrinsic factor. Chief cells secrete the inactive enzyme precursor pepsinogen and the enzyme lipase. The glands and epithelial cells of the stomach secrete an alkaline mucus rich in bicarbonate, to protect the mucosa from the acidic gastric secretions.

The vagus nerve is the major extrinsic innervation of the stomach. It contains sensory, secretomotor and motor fibers. Sympathetic innervation is via the splanchnic nerves from the coeliac plexus and contains sensory and motor fibers. Sympathetic stimulation will inhibit gastric motility. Vagal stimulation will increase gastrin secretion. Sensations of gastric pain and distension are transmitted by sensory fibers of both parasympathetic and sympathetic nerves.

Question 31

Physiological consequences of vomiting

Answer 31

Vomiting will result in a loss of hydrochloric acid resulting in metabolic alkalosis and a loss of chloride. This reduces the activity of the H/K ion exchange pump of the renal collecting duct resulting in reduced potassium reabsorption with reduced hydrogen excretion. Potassium content of gastric secretions is approximately 10 mmol/L. Also aldosterone release stimulated by the dehydration will promote sodium reabsorption in exchange for potassium excretion.

Severe vomiting can cause hypokalemia and hyponatremia. The kidney will compensate for this condition by increasing sodium and potassium reabsorption, in exchange for high excretion of hydrogen ions. An increase in hydrogen ion excretion will increase blood pH level (metabolic alkalosis) and decrease the pH of urine. Severe vomiting will also cause a hypovolemic state, which will stimulate the RAA system, thus aldosterone secretion will be increased.

Vomiting is an active process and is coordinated through the brainstem and is under the influence of the chemoreceptor trigger zone located in the area postrema near the fourth ventricle of the brain. The ejection phase of vomiting involves the contraction of abdominal and diaphragmatic muscles. Although nausea is frequently associated with vomiting, their neural pathways are not identical. Regurgitation is a passive process.

Question 32

Fructose

Answer 32

Fructose transport does not occur by the sodium cotransport mechanism. Rather, fructose is transported by facilitated diffusion through the intestinal epithelium involving GLUT5 transport proteins. As the concentration of fructose is higher in the lumen, fructose is able to flow down a concentration gradient into the enterocytes, assisted by transport proteins.

Question 33

PH of GIT secretions

Answer 33

The pH of saliva is usually between 6.5 and 7.5. The fundus or upper portion of the stomach has a pH between 4.0 and 6.5. The lower portion of the stomach has a pH between 1.5 and 4.0. In the duodenum the pH changes to 7.0–8.5. The pH gradually decreases in the colon (pH 4.0–7.0).

Question 34

Pepsin

Answer 34

Pepsin is a collection of proteolytic enzymes which facilitate protein digestion. It is stored as the precursor, pepsinogen, in the chief cells. After secretion pepsinogen is converted to pepsin in the stomach. The maximal proteolytic effect occurs at a pH of less than 3. Of the total protein digestion, 10-20% occurs in the stomach by the action of pepsin. It requires hydrochloric acid to provide the optimal pH for enzymatic action.

Question 35

Parietal cells

Answer 35

Gastric secretion is controlled by multiple hormones. Gastrin is produced and secreted by G cells found in the antrum of the stomach. It stimulates secretion of gastric acid by parietal cells, and histamine by enterochromaffin-like cells. Histamine also stimulates parietal cells to produce acid. Finally, vagal stimulation can activate parietal and chief cells through acetylcholine release.

In the gastrointestinal tract, somatostatin reduces the secretion of gastric acid and pepsin, and reduces the rate of gastric emptying.

Question 36

IgA GIT

Answer 36

In suckling infants, maternal IgA from breast milk is transported across the intestinal epithelium into the neonatal circulation. This transport occurs in the duodenum and jejunum where enterocytes express a surface membrane receptor able to bind the Fc of IgA. These membrane receptors complex with the immunoglobulins then undergo endocytosis.

Question 37

Sinusoids

Answer 37

The right and left hepatic ducts exit the liver at the porta hepatis and unite to form a common bile duct. Microscopically, each liver lobe is made up of hepatic lobules. The lobules are roughly hexagonal and consist of plates of hepatocytes radiating from a central vein. The portal triad, which can be found running along each of the lobules’ corners, consists of branches of the hepatic artery, portal vein and bile ducts. The direction of the flow of bile and portal vein blood are opposite to each other. Sinusoids are large-diameter capillaries lined by endothelial cells between rows of plates or cords of hepatocytes. Sinusoids also contain Kupffer cells (also called “stellate macrophages”) of the reticuloendothelial system (RES).

Question 38

Ileum

Answer 38

The ileum is critical for the absorption of vitamin B12, fat-soluble vitamins (A, D, E and K), bile salts, and acids. Iron absorption occurs predominantly in the duodenum and upper jejunum. The ileum reabsorbs bile salts for recycling via the enterohepatic circulation back to the proximal small intestinal lumen to aid in fat solubilization.

Question 39

Trypsin

Answer 39

Trypsin is secreted by the pancreas in an inactive form called “trypsinogen”, which is then converted to the active form by enteropeptidase or enterokinase secreted by the small intestine. The activated trypsin can further activate the inactive trypsinogen. Procarboxypeptidase is the inactive form of carboxypeptidase, which is a protease enzyme. It requires trypsin and enteropeptidase for its activation. Pancreatic lipase functions to hydrolyze neutral fat into monoglycerides and fatty acids. Trypsin works optimally at an alkaline pH (7.8–8.7) but cannot be activated without enteropeptidase.

Pancreatic proteases are secreted in an inactive zymogen form, along with a trypsin inhibitor, to prevent premature activation. Pancreatic trypsinogen is activated by duodenal enterokinase to become trypsin. Trypsin then acts on zymogens to form more trypsin (autocatalysis), chymotrypsin, and carboxypeptidases. α-amylase is secreted in an active form, as are lipases, ribonuclease, and deoxyribonuclease.

Question 40

Saliva

Answer 40

Saliva fluid is normally hypotonic because its main composition is water (99.5%).

Both the sympathetic and the parasympathetic nervous systems stimulate saliva secretion. The saliva stimulated by sympathetic innervation is thicker, and saliva stimulated parasympathetically is more watery.

Atropine is a drug that is commonly used to decrease saliva production during surgery by inhibiting the parasympathetic nervous system. Aldosterone increases sodium reabsorption and potassium secretion in the kidney, salivary gland, and sweat glands. 70%–75% of saliva is secreted by the submandibular gland; 20%–25% of it is secreted by the parotid gland, and the rest is secreted by other salivary glands.

Saliva serves multiple functions. It contains enzymes including amylase and lipase to commence digestion, mucosal defences like IgA and lysozyme, and mucins to provide lubrication to the oral cavity. It is hypotonic compared to plasma, and alkaline due to a higher bicarbonate and potassium content, but lower levels of chloride and sodium. Approximately 1–1.5 litres are produced per day.

Question 41

Pyloric Sphincter

Answer 41

The pyloric sphincter serves as a gateway between the stomach and the small intestine. It allows the contents of the stomach to pass into the duodenum. It also prevents partially digested food and digestive juices from re-entering the stomach. Normally, when food stretches the stomach, a “vagovagal reflex” to the brain stem and then back to the stomach reduces the tone in the muscular wall of the stomach body, causing receptive relaxation. Carbohydrates tend to spend the least amount of time in the stomach, while proteins stay in the stomach longer, and fats the longest. The hormones cholecystokinin and secretin have inhibitory effects on gastric emptying. They inhibit the pyloric pump and at the same time increase the strength of contraction of the pyloric sphincter.

Question 42

Phases of gastric secretion

Answer 42

The intestinal phase of gastric secretion occurs when the duodenum responds to the arriving chyme. 5%–10% of gastric secretion occurs during this phase. Two things occur simultaneously: duodenal stimulation and duodenal inhibition. Duodenal stimulation occurs when partially digested protein enters the duodenum, and the duodenum responds by stimulating gastric secretion. Duodenal inhibition is stimulated by acid and fat in the duodenal lumen. Many systems and substances take part in this inhibition, such as the neural system and hormones (secretin, cholecystokinin, gastric inhibitory peptide). Duodenal inhibition inhibits gastric secretion and motility.

Question 43

LES

Answer 43

The lower oesophageal sphincter normally remains tonically constricted. When a peristaltic swallowing wave passes down the esophagus, “receptive relaxation” of the lower esophageal sphincter occurs. The sphincter contains smooth muscles which contract in response to acetylcholine. Gastric reflux is prevented by a valve-like mechanism of a short portion of the esophagus that extends slightly into the stomach. Crural fibers from the diaphragm also supplement the sphincter.

Question 44

Short chain fatty acids

Answer 44

Short-chain fatty acids are fatty acids with fewer than 6 carbon (C) atoms. Short-chain fatty acids are produced by the gut microbiota in the large bowel as fermentation products from food components that are unabsorbed/undigested in the small intestine and are absorbed in the colon.

Question 45

Colonic absorption

Answer 45

The absorption of sodium across the colon is under the control of aldosterone which greatly increases the absorption of sodium ions. Bile acids are mostly reabsorbed in the terminal ileum; only a small amount reaches the colon. They do not increase the absorption of water from the colon that occurs due to the osmotic gradient caused by absorption of sodium and chloride ions. There is net secretion of the HCO3- ions by the colonic mucosa which is required to neutralize the acidic products of bacterial activity in the colon. An equal number of chloride ions, not potassium ions (K+), are absorbed in exchange for these bicarbonate ions, hence neutralizing the luminal potential of the colon.

Question 46

Fat absorption

Answer 46

Both monoglycerides and fatty acids diffuse immediately out of the micelles and into intestinal epithelial cells. This process leaves the bile micelles still in the chyme, where they repeatedly function to help absorb still more monoglycerides and fatty acids. After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell’s smooth endoplasmic reticulum. Here, they are mainly used to form new triglycerides that are subsequently released in the form of chylomicrons through the base of the epithelial cell, to flow upward through the thoracic lymph duct and empty into the circulating blood. Short-chain fatty acids are produced by the gut microbiota in the large bowel as fermentation products from food components and are absorbed in the colon.

The absorption of fats takes place in the small intestines. Once the triglycerides are broken down into fatty acids and glycerols, along with cholesterol, they will aggregate into structures called “micelles”. Fatty acids and monoglycerides leave the micelles and diffuse through the luminal membrane and enter the intestinal epithelial cells. Epithelial cells reform fatty acids and monoglycerides back into triglycerides. In the cytosol of epithelial cells, triglycerides and cholesterol form into chylomicrons, which are amphipathic structures that transport digested lipids. Chylomicrons will travel in the blood, and enter other organs and adipose tissue.

Question 47

Bilirubin

Answer 47

The conversion of the heme moiety to bilirubin requires the sequential action of two enzymes: heme oxygenase (to form the intermediate biliverdin) and biliverdin reductase (to form bilirubin). Bilirubin is transported in plasma bound to albumin. The intestinal mucosa is impermeable to conjugated bilirubin. Intestinal beta-glucuronidase hydrolyses the conjugated bilirubin, thus releasing free bilirubin, which is then reabsorbed and transported by the portal circulation to the liver. The most important bile pigments are the green pigment biliverdin and the reddish-yellow pigment bilirubin.

Question 48

Obstructive jaundice

Answer 48

The lack of bilirubin in the intestinal tract is responsible for the pale stools typically associated with obstructive jaundice. The presence of large amounts of conjugated bilirubin in urine may cause the urine to appear dark orange. Bile salts play an important role in the absorption of fatty acids in the small intestine. Bile salts cannot reach the intestinal lumen in biliary obstruction, causing fat malabsorption. A membrane-bound enzyme localised to the bile canalicular pole of hepatocytes (alkaline phosphatase) is markedly elevated in people with biliary obstruction.

Question 49

Na reabsorption

Answer 49

The major mechanism of Na+ absorption across the small intestine occurs along with chloride ions along osmotic pressure gradients. This is called “electroneutral absorption” as it is not associated with transmembrane currents. Sodium is also partially transported across the brush border by sodium–glucose cotransporters and sodium–amino acid cotransporters which are non-electrolytic cotransporters or nutrients coupled with Na+ transporters. The Na–K ATPase pump transports sodium out of the cells and potassium into the cells of the intestinal wall. Electrogenic Na+ transport occurs via ENaC (epithelial sodium ion channels). Sodium is absorbed in the jejunum by the mechanism of solvent drag, in which solute movement occurs secondary to the water flow.

Question 50

Histamine receptor blockers

Answer 50

H2-receptor antagonists inhibit both the gastrin-induced and vagally-mediated secretion of gastric acid. They compete with endogenous histamine and reversibly bind to the histamine receptors on the gastric parietal cells. They diminish cAMP levels and H+/K+ pump activity. Adenylyl cyclase is not directly activated by the gastrin; rather, this activation is induced by histamine. In the presence of H2 antagonists, this activation does not occur. Adenylyl cyclase is required for the H+/K+ ATPase pump. Hence, potassium transport is also decreased across the parietal cells.

Question 51

Iron

Answer 51

On average, the human body contains 3–4 grams of iron which is distributed throughout the body in hemoglobin, tissues, muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transported in plasma. The greatest portion of iron in humans is in hemoglobin.

Iron is absorbed from the duodenum and jejunum as either free iron or as part of the haem molecule. Once intracellular, it binds to apoferritin to form ferritin. The amount of iron absorbed is about 3-6% of the amount ingested. Intrinsic factor is not involved in the absorption of iron. It is part of the B12 absorption process in the terminal ileum.

Most of the iron in our diet is in the ferric (Fe3+) state, whereas when absorbed it is reduced to ferrous (Fe2+) iron before being transported into the mucosal cells by apical membrane iron transporter DMT1.

Women absorb more iron than men since women lose approximately twice as much iron than men due to menstruation. Ferritin represents iron stores in the body and will be decreased in anaemia. Around 70% of iron in the body is found in haemoglobin, with 3% in myoglobin and the remainder in ferritin.

Phytates (found in most plant food) and phosphates (which form Ca–phosphate–iron complexes) decrease iron absorption. Alcohol reduces the risk of iron deficiency anemia.

Question 52

Gastric fluid

Answer 52

Gastric fluid has a pH of 3 and contains sodium, potassium, magnesium, hydrogen cations and chloride, phosphate and sulphate anions. It does not contain bicarbonate. It is more acidic than saliva, bile and sweat. The stomach produces about 1200-2500ml per day.

Question 53

Massive small bowel resection

Answer 53

Massive small bowel resection results in malabsorption, diarrhea, steatorrhea, fluid and electrolyte disturbances, and malnutrition. Gastrin levels rise, causing gastric hypersecretion leading to peptic ulcer disease. Oxalate is normally bound by calcium in the small bowel and thus is insoluble when it reaches the colon. After a massive enterectomy, much of this calcium is bound by free intraluminal fats. Free oxalate is delivered to the colon, where it is absorbed. This can eventually lead to saturation of the urine with calcium oxalate crystals and result in stone formation and hypocalcemia. Malabsorption of proteins leads to hypoalbuminemia.

Question 54

Carbohydrate absorption

Answer 54

Glucose, fructose and galactose are the only complex sugar molecules that can be absorbed by the small bowel. Absorption of glucose and galactose is via protein channels that utilise ATP. Fructose absorption is by facilitated diffusion. Cellulose is a complex polysaccharide and there are no enzymes capable of its breakdown, therefore it cannot be absorbed. Digestion of carbohydrates is initiated by salivary amylase.

Question 55

Vitamin A excess

Answer 55

Headache, dizziness, visual changes and diarrhoea

Question 56

Pancreatic polypeptide

Answer 56

Pancreatic polypeptide is a 36-amino acid peptide secreted from the F (pancreatic polypeptide) cells of the pancreas especially at the head of pancreas. It has many functions in the gastrointestinal tract, e.g. it inhibits intestinal motility and increases the secretion of gastrointestinal enzymes. Pancreatic polypeptide secretion is stimulated by fasting, protein meals, hypoglycaemia and exercise, and is inhibited by intravenous glucose, hyperglycaemia, somatostatin and atropine.

Its secretion in humans is increased primarily after a protein meal and is biphasic, first as result of vagal stimulation and second, a more prolonged rise, which is hormonal (caused by cholecystokinin). Secretion is decreased by somatostatin and intravenous glucose.

Question 57

Glucagon

Answer 57

Glucagon is released by the alpha cells in the pancreas and functions to control the blood glucose level. Glucagon is released in response to low blood glucose levels or whenever the body needs additional energy from glucose, such as in vigorous exercise or infection. Salbutamol induces a rise in blood glucose and insulin, free fatty acids, glycerol, and ketonic bodies. Furthermore it increases glucagon secretion. Somatostatin is produced in the pancreas and inhibits the secretion of other pancreatic hormones such as insulin and glucagon.

Glucagon is a peptide hormone produced by the alpha cells of the pancreas. It works to raise the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. Glucagon is stimulated by amino acids such as arginine and alanine. Glucagon increases blood glucose levels in several ways, for example, by promoting glycogenolysis in the liver. Glucagon may have a positive inotropic effect on the heart by stimulating adenylyl cyclase stimulation. Glucagon is also known to be a stimulator of growth hormone production.

Glucagon’s main function is to increase blood glucose and fatty acids through various mechanisms. First, glucagon induces liver glycogenolysis, the conversion of the glycogen store in the liver into glucose. Second, glucagon increases lipolysis and breakdown of lipids in adipose tissue into free fatty acids. Third, glucagon increases the production of ketone bodies (ketogenesis), an alternative energy source. Finally, glucagon increases gluconeogenesis, mainly from amino acids and fatty acids.

Question 58

Pancreatic Islet cells

Answer 58

Glucagon is a peptide hormone involved in glucose homeostasis. It is secreted by alpha cells in the pancreas, and its main function is to elevate blood glucose levels by stimulating glycogenolysis and gluconeogenesis. There are five types of cells in the pancreatic islets, each of which secretes a specific neurotransmitter or hormone.

Alpha cells (A cells) secrete glucagon.

Beta cells (B cells) secrete insulin and amylin.

Delta cells (D cells) secrete somatostatin.

Epsilon cells secrete ghrelin.

PP cells (also known as “F cells”) secrete pancreatic polypeptide.

Delta cells constitute fewer than 10% of the pancreatic islet cells. Somatostatin inhibits alpha and beta cells (paracrine effect).

Question 59

Cholesterol

Answer 59

Cholesterol is a polycyclic steroid alcohol that can be synthesized from acetate precursors or absorbed from dietary or exogenous sources. Cholesterol synthesis is inhibited by thyroid hormones, statins, and glucagon, and stimulated by insulin and estrogen. Several mechanisms carefully regulate the maintenance of cholesterol homeostasis. Individuals with familial hypercholesterolemia have a defective LDL receptor, resulting in early cardiovascular disease and cholesterol deposition in the skin (xanthelasma).