Physiology

Question 1

What does the term motility mean?

Answer 1

Motility is mechanical activity mostly involving smooth muscle (skeletal at mouth, pharynx, upper oesophagus and external anal sphincter). It refers to the muscular contractions that mix and move food forward through the GI tract. It displays action potential bursts of movement as well as maintaining a low level of contraction called tone.

Question 2

What type of chemical reaction allows digestion?

Answer 2

Hydrolysis

Question 3

What four layers does the digestive tract wall have?

Answer 3

1. Mucosa - lines the luminal surface of the digestive tract; is highly folded
2. Submucosa - thick layer of connective tissue that provides the GI tract with its distensibility and elasticity
3. Muscularis externa - major SM coat of the GI tract
4. Serosa - outer connective tissue covering all of the GI tract, which secretes serous fluid, preventing friction between the surrounding organs and the digestive viscera

Question 4

Describe the mucosa

Answer 4

The mucosa has three layers:

1. Mucous membrane - the inner epithelial layer that serves as a protective surface
2. The lamina propria - a thin middle layer of connective tissue on which the epithelium rests. It hosts gut associated lymphoid tissue (GALT) which is important in immunology
3. Muscularis mucosa - a sparse layer of smooth muscle, at the outermost mucosal layer, lying adjacent to the submucosa

Question 5

What are the two layers of the muscularis externa?

Answer 5

1. Inner circular layer - contraction decreases the lumen

2. Outer longitudinal layer - shortens the tube

Question 6

How is SM in the GI tract electrically coupled?

Answer 6

Like in self-excitable cardiac muscle cells, clusters of SM cells are pacemaker cells that display rhythmic, spontaneous variations in membrane potential.
Adjacent smooth muscle cells are coupled by gap junctions – allow spread of electrical currents from cell to cell forming a functional syncytium.
Hundreds of cells are depolarized and contract at the same time as a synchronous wave (i.e. single unit smooth muscle – as opposed to multiunit smooth muscle).

Question 7

What is the character of electrical activity in the stomach, small and large intestine?
What are the interstitial cells that act as pacemakers to instigate cyclic slow wave activity called?

Answer 7

Spontaneous electrical activity occurs as slow waves - rhythmic patterns of membrane depolarization and repolarization that spread from cell to cell via gap junctions.
Interstitial cells of Cajal (ICC).

Question 8

How does the AP occur in SM of the GI tract?

Answer 8

Contraction only occurs if the slow wave amplitude is sufficient to trigger SMC action potentials (upstroke mediated by voltage-activated Ca2+ channels, downstroke by voltage-activated K+ channels). Force is related to number of action potentials discharged.
NB not all slow waves trigger contraction.

Question 9

Where are ICC cells located?

Answer 9

Between the longitudinal and circular muscle layers and in the submucosa

Question 10

What plexuses form the enteric nervous system?

What do they mainly regulate?

Answer 10

Submucosal plexus - regulates epithelial and blood vessels

Myenteric plexus - regulates motility and sphincters

Question 11

What is the basic electrical frequency (BEF) for:

(i) Stomach
(ii) Duodenum
(iii) Terminal ileum
(iv) Proximal colon
(v) Distal colon

Answer 11

(i) 3 slow waves per minute
(ii) 12 waves per minute
(iii) 8 waves per minute
(iv) 8 waves per minute
(v) 16 waves per minute

Question 12

What is the parasympathetic innervation to the GI tract and what stimulates it?

Answer 12

Preganglionic fibres (releasing ACh) synapse with ganglion cells (in essence post-ganglionic neurones) within the ENS
Excitatory influences - increased gastric, pancreatic and small intestinal secretion, blood flow and smooth muscle contraction
Inhibitory influences - relaxation of some sphincters, receptive relaxation of stomach

Question 13

What is the sympathetic supply to the GI tract and what stimulates it?

Answer 13

Preganglionic fibres (releasing ACh) synapse in the prevertebral ganglia. Postganglionic fibres (releasing NA) innervate mainly enteric neurones, but also other structures
Excitatory influences – increased sphincter tone
Inhibitory influences – decreased motility, secretion & blood flow

Question 14

What is segmentation?

Answer 14

rhythmic contractions of the circular muscle layer that mix and divide luminal contents - occurs in the small intestine (in the fed state) and in the large intestine (where it is called haustration).

Question 15

What is a colonic mass movement?

Answer 15

A powerful sweeping contraction that forces faeces into the rectum – occurs a few times a day.

Question 16

What are the three phases of deglution?

Describe each.

Answer 16

1. Oral phase
2. Pharyngeal phase
3. Oesophageal phase

Question 17

Describe the oral phase of deglution

Answer 17

Mouth closes, tongue moves to hard palate, mechanoreceptors are stimulated, stimulating afferent nerve impulses via CN IX and X, stimulating efferent nerve impulses via CN VII, X and XI to skeletal muscles of pharynx and larynx

Question 18

Describe the pharyngeal phase of deglution

Answer 18

Inhibition of ventilation
Laryngeal muscles close and raise larynx
Contraction of superior and middle pharyngeal constrictors propels bolus into hypopharynx
Bolus forced epiglottis over larynx
Bolus enters oesophagus through open oesophageal sphincter
Glottis reopens, ventilation recommences

Question 19

Describe the oesophgeal phase of deglution

Answer 19

Swallowing centre (pons and medulla) triggers closure of the upper oesophageal sphincter and a primary peristaltic wave (via vagus),
Wave mediated by skeletal muscle in upper oesophagus and smooth muscle in distal regions.
Peristalis (in smooth muscle) co-ordinated by the enteric nervous system.
Circular fibres behind bolus squeeze bolus down towards stomach - longitudinal fibres in front of bolus shorten distance of travel
Lower oesophageal sphincter opens within 2-3 s of the initiation of a swallow (closes after passage of bolus to prevent reflux)

Question 20

What are the three major pairs of salivary glands?

Answer 20

1. Parotid
2. Submandibular
3. Sublingual

Question 21

Parotid salivary gland
Where is it located?
What duct is it associated with?
Where does saliva from this gland enter the mouth?

Answer 21

Anterior to ear, below zygomatic arch – duct (of Stensen) enters mouth opposite second maxillary molar teeth

Question 22

Submandibular salivary gland
Where is it located?
What duct is it associated with?
Where does saliva from this gland enter the mouth?

Answer 22

Submandibular – medial to body of mandible – duct (of Wharton) enters mouth under tongue by lingual frenulum via sublingual caruncula

Question 23

Sublingual salivary gland
Where is it located?
What duct is it associated with?
Where does saliva from this gland enter the mouth?

Answer 23

Medial to submandibular glands – ducts (of Rivinus and common Bartholin) connect with Wharton’s at the sublingual caruncula

Question 24

What three things does a salivary gland consist of?

Answer 24

1. An external capsule
2. Septae separating lobes and lobules
3. Lobules composed of salivons - the functional unit of the gland

Question 25

What is an acinus? | What two types of cell make it up?

Answer 25

A lobe made up of pyramidal-shaped secretory acinar cells around a central lumen that are either: 1. Serous cells producing a watery secretion rich in α-amylase; contain small, dense, secretory granules 2. Mucous cells producing a thick mucus-rich secretion; contain relatively large, pale, secretory granules

Question 26

Give 7 functions of saliva

Answer 26

1. Begins digestion of carbohydrate in the mouth through salivary amylase 2. Facilitates swallowing by moistening food particles and holding them together 3. Exerts antibacterial activity, involving lysozyme, IgA, lactoferrin 4. Solvent for molecules that stimulate the taste buds 5. Aids speech by facilitating the movement of the lips and tongue 6. Flushes away food residues, keeping the mouth clean 7. Rich in bicarbonate buffers, which neutralize acids in food

Question 27

What ions in saliva are present at higher volumes than in the plasma?

Answer 27

K+ and HCO3-

Question 28

What are the two stages of saliva formation?

Answer 28

1. Primary secretion by acinar cells | 2. Secondary modification by duct cells

Question 29

Give some facts about primary secretion of saliva

Answer 29

It is driven by the basolateral Na+/K+-ATPase which by secondary active transport - Drives inward movement of Cl- across the basolateral membrane via the Na+/K+/2Cl- (triple) transporter, raising [Cl-]I - Creates an electrochemical gradient driving Cl- efflux, by facilitated diffusion, through apical membrane Ca2+-activated Cl- channels

Question 30

Give some facts about secondary secretion of saliva

Answer 30

Secondary modification by striated, intercalated and excretory ducts removes Na+ and Cl- from, and adds K+ and HCO3- to, the primary secretion. Influx of Na+ and Cl- exceeds efflux of K+ and HCO3- and since ducts are largely impermeable to H2O the overall effect is diluting It is driven by the basolateral Na+/K+-ATPase

Question 31

What are the two reflexes stimulating salivary production?

Answer 31

1. Simple - occurs when chemoreceptors and pressure receptors in the oral cavity respond to the presence of food. It involves afferent nerve fibers and the salivary center, parasympathetic nerves and CN VII, I 2. Conditioned - occurs without oral stimulation; just thinking, smelling or seeing the preparation of pleasant food stimulates this

Question 32

Give three functions of the stomach

Answer 32

1. Secreted HCL and enzymes to begin protein digestion 2. Stores ingested food before passing it into the duodenum as chyme 3. Mixes the food with gastric secretions to produce chyme

Question 33

What regulates gastric emptying?

Answer 33

1. Gastric factors e.g. the amount of chyme in the stomach; stomach distension; degree of fluidity of the chyme 2. Duodenal factors e.g. presence of fat, acid, hypertonicity,or distension activates duodenal receptors, triggering either a neural or a hormonal response that puts the breaks on gastric motility by reducing the excitability of gastric SM

Question 34

What are the three phases of gastric secretion?

Answer 34

1. Cephalic - before the food enters the stomach, vagus is activated, stimulating G cells, increasing secretion 2. Gastric - when food is in the stomach 3. Intestinal - as the stomach empties, the stimuli for secretion becomes less intense

Question 35

What are the two types of digestion that occur in the small intestine?

Answer 35

Luminal digestion - mediated by pancreatic enzymes secreted in the duodenum Membrane digestion - mediated by enzymes situated at the brush border of epithelial cells

Question 36

What is the apical membrane?

Answer 36

The membrane facing into the lumen of the GI tract | Aka brush border

Question 37

Describe carbohydrate digestion

Answer 37

E.g. starch Broken down in the mouth to an oligosaccharide by alpha amylase. Those which survive this are broken down in the small intestine by pancreatic amylase Dextrokinase breaks oligosaccharides into the dissacharides sucrose, maltose and lactose. Their associated enzymes break them down into monosaccharides that are then absorbed into the bloodstream

Question 38

What transporters are glucose, galactose and fructose associated with?

Answer 38

Glucose, galactose = SGLT1 | Fructose = GLUT5

Question 39

How are amino acids absorbed from the lumen into the bloodstream?

Answer 39

1. At the brush border - either by Na dependent co transporters (5 types) or Na independent co transporters (2 types) 2. At the basolateral membrane - Na dependent (2 types) or Na independent (3 types

Question 40

Summary of protein digestion Where is protein digested and what by? How are AAs transported across the apical membrane? How are oligopeptides transported across the apical membrane? How are AAs transported across the basolateral membrane?

Answer 40

Protein is digested in the lumen to amino acids, or oligopeptides, by pepsin and the pancreatic proteases Peptidases at the brush border further hydrolyse oligopeptides to amino acids Amino acids are transported across the apical membrane via a variety of amino acid transporters, some of which are Na+-dependent and others Na+-independent Oligopeptides are transported across the apical membrane by the H+/oligopeptide co-transporter, PepT1 Oligopeptides with the cytoplasm are hydrolysed to amino acids by peptidases within the enterocyte Amino acids exit the enterocyte across the basolateral membrane by several, Na+-independent. transporters

Question 41

What role does bile play in fat digestion?

Answer 41

Bile salts secreted in bile from the gall bladder in response to CCK act as detergents to emulsify large lipid droplets to small droplets. Bile salts increase surface area for attack by pancreatic lipase, but block access of the enzyme to the lipid with the hydrophobic core of the small droplets. Problem solved by colipase, an amphipathic polypeptide secreted with lipase by the pancreas – binds to bile salts and lipase allowing access by the latter to tri- and di-glycerides. Failure to secrete bile salts results in: - Lipid malabsorption - steatorrhoea (fat in faeces) - Secondary vitamin deficiency due to failure to absorb lipid vitamins

Question 42

How are mixed micelles transported across the apical membrane?

Answer 42

Passive diffusion

Question 43

Define satiation, satiety and adiposity

Answer 43

``` Satiation = sensation of fullness generated during a meal. Satiety = period of time between termination of one meal and the initiation of next. Adiposity = the state of being obese. ```

Question 44

What is the site of integration of CNS influences on energy balance and body weight?

Answer 44

Hypothalamus

Question 45

Name and briefly describe three satiation signals

Answer 45

CCK - secreted from endocrine cells in the duodenum and jejunum in proportion to lipids and protein in meal Peptide YY - levels increase rapidly post prandially to inhibit gastric motility, slow emptying and reduce food intake GLP-1 - same as peptide YY

Question 46

What is ghrelin?

Answer 46

A hunger signal - levels increase before meals and decrease after meals. Levels are raised by fasting and hypoglycaemia.

Question 47

What two hormones, produced in peripheral tissues, report fat levels to the brain?

Answer 47

Leptin - made & released from fat cells Insulin - made & released from pancreatic cells Reduced leptin mimics starvation, causing unrestrained appetite.

Question 48

What does Orlistat treat and how does it do this?

Answer 48

It treats obesity - Inhibits pancreatic lipase decreasing triglyceride absorption - Reduces efficiency of fat absorption (~30%) in small intestine - Side-effects include cramping and severe diarrhoea - Need to take vitamin supplements (fat soluble vitamins)

Question 49

Where does the major force of expulsion for vomiting come from?

Answer 49

The stomach, oesophagus, and associated sphincters are all relaxed during emesis. The major force for expulsion comes from contraction of the respiratory muscles - mainly the diaphragm and the abdominal muscles.

Question 50

Why does pregnancy induced vomiting occur?

Answer 50

It is an adaptive change - encourages picky eating during a time of rapid foetal growth (CNS vulnerable to toxicosis)

Question 51

Define emesis

Answer 51

Forceful propulsion of gastric/intestinal contents out of the mouth NB it is not due to stomach contraction

Question 52

What co-ordinates vomiting?

Answer 52

The vomiting center in the medulla oblongata of the brain stem

Question 53

Describe the events that occur during emesis

Answer 53

1. Deep inspiration and closure of the glottis to prevent aspiration 2. The contracting diaphragm descends downward on the stomach while simultaneous contraction of the abdominal mucles, increasing the abdominal pressure 3. The stomach is compressed and gastric contents are forced up through the flaccid sphincters and oesophagus and out through the mouth 4. This process may be repeated several times to completely empty the stomach When about to vomit, we salivate profusely in order to neutralise the stomach acid. Sweating and increased HR indicate use of the autonomic nervous system

Question 54

Describe the receptor and neural pathways in vomiting.

Answer 54

The presence of toxic materials in the gut lumen cause irritation of the mucosa of the GI tract. Embedded in the mucosa are a population of cells - enterochromaffin cells, which are endocrine cells which store most of the body's serotonin. In response to the toxic stimulus, EC cells release 5-HT, which stimulates vagal afferent signals e.g. vagus nerve which connects to the CTZ and NTS, initiating vomiting

Question 55

What is the vomiting center?

Answer 55

A group of interconnected neurones within the medulla that are driven by a central pattern generator (CPG) that in turn receives input from the NTS

Question 56

How does efferent output from the vomiting center affect somatic and autonomic nervous systems?

Answer 56

1. Parasympathetic system by vagus nerve – the longitudinal muscle of the oesophagus contracts, shortening the oesophagus; the stomach relaxes; the SI contracts. 2. Somatic motor output – the stomach is compressed as a results of abdo muscle and diaphragm contraction 3. Mixed A&S – in reased HR and force; increased salivation; vasoconstriction producing palor; sweating

Question 57

What two types of digestion occur in the small intestine?

Answer 57

1. Luminal digestion - mediated by pancreatic enzymes secreted into the duodenum 2. Membrane digestion - mediated by enzymes situated at the brush border of epithelial cells

Question 58

What is contained within a mixed micelle?

Answer 58

Free fatty acids 2-monoglycerides Cholesterol Other insignificant things e.g. phospholipids

Question 59

How does lipid absorption occur across the the apical membrane of the enterocytes?

Answer 59

The mixed micelle collides with the apical membrane, causing exchange of the free fatty acids and 2-monoglycerides into the apical membrane of the enterocyte The small and medium sized fatty acids go straight into the blood The long chain fatty acids are re-synthesized into triglycerides and are eventually incorporated into chylomicrons

Question 60

How is Ca2+ absorbed?

Answer 60

Enters the luminal membrane of the small intestine epithelial cells down its EC gradient through a specialised channel. It exits the basolateral membrane by two energy dependent mechanisms. Vitamin D greatly enhanced all of these mechanisms

Question 61

Is water absorption active or passive? | What ion is the main driving force for this?

Answer 61

Passive | Na+ - provides an osmotic force for reabsorption of water

Question 62

Where are Na+/glucose and Na+/amino acid the major mechanisms of postprandial Na+ absorption? What type of transport is this?

Answer 62

The jejunum | Secondary active

Question 63

What is an ENAC? | What does it do?

Answer 63

Epithelial Na+ channel | Mediates electogenic Na+ absorption in the distal colon

Question 64

The secretion of what ion is important in the development of secretory diarrhoea? Where is this ion secreted from?

Answer 64

Chloride | Cells in the Crypts of Langerhan

Question 65

What does closed CFTR do to Cl- secretion? What causes CFTR to be indirectly activated? What is the overall effect?

Answer 65

``` Secretion is very little Bacterial endotoxins, e.g. Cholera, E.coli, C.difficile Hormones e.g. 5-HT Some laxatives Secretory diarrhoea ```

Question 66

Causes of Diarrhoea | Name some causes of impaired absorption of NaCl

Answer 66

Congenital defects Inflammation Infection Excess bile acid in colon

Question 67

Causes of Diarrhoea | Name one serious cause of excessive secretion of NaCl

Answer 67

Cholera - CFTR goes into overdrive, allowing massive efflux of chloride from the enterocyte

Question 68

Describe the liver lobule

Answer 68

Hexagonal on cross section Has a branch of the hepatic vein at its centre Has a portal triad at each corner, containing - A branch of hepatic portal vein - A branch of hepatic artery - A bile duct The flow of blood and bile are in opposite directions - blood moves centrally towards the central vein, bile moves outwardly to each of the six corners Bile secreted by hepatocytes travels through the lobule in canaliculi to the bile duct

Question 69

What membrane of the hepatocytes faces the canaliculi? | What does the other mambrane face and what is this?

Answer 69

Apical membrane | Basolateral membrane faces a pericellular space called the space of Disse

Question 70

What are Kuppfer cells and where do they reside?

Answer 70

Macrophages resident in the sinusoidal vascular space - remove particulate matter e.g. bacteria

Question 71

Sinusoid What is this? What four things does this contain?

Answer 71

A location for mixing of the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein. Contains - Endothelial cells that form a fenestrated structure - Kuppfer cells - Stellate cells within the space of Disse - important in storage of VitA - Intrahepatic bile system

Question 72

Is bile constantly produced? What happens when no immediately needed? What stimulates the opening of the sphincter of Oddi?

Answer 72

Yes Sphincter of Oddi at the distal and of the common bile duct is closed; bile is redirected into the cystic duct and stored & concentratd in the gall bladder CCK - stimulates the gall bladder to contract - bile spurts into the duodenum via cystic and common bile ducts - mixed with bile from liver

Question 73

Aside from the liver hepatocytes, where else is bile produced?

Answer 73

Bile duct cells (25%)

Question 74

What does hepatic bile consist of?

Answer 74

1. Primary bile acids, e.g. cholic and chenodeoxycholic acids 2. Water and electrolytes 3. Lipids and phospholipids 4. Cholesterol 5. IgA 6. Bilirubin

Question 75

There is very little bile salt in the body. | How is this maintained?

Answer 75

Most of the bile salts which are secreted into the GI tract and biliary system are very effectively reabsorbed by active transport in the terminal ileum

Question 76

Morphine may be used for pain relief caused by gall stones. What is one adverse affect of this?

Answer 76

It constricts the sphincter of oddi