Week 1/2 - D(1) - Physiology 1,2,3,6 - Feeding/Satiety/Obesity Tx, Gastric/small&large intestine/pancreas motility and secretions

Question 1

Obesity correlates with increased body FAT How is a person’s body mass index calculated? * What is a normal-acceptable BMI? * What is underweight? * What is overweight? * What is obese? * What is morbidly obese?

Answer 1

BMI is calculated by dividing a person’s weight in kilograms by their height in metres squared (kg/m 2 ) * 18.5 - 24.9 = Normal BMI * /= 40.0 = Morbidly Obese BMI

Question 2

What are some contributing factors to the increasing prevalence of obesity? Obese is a major contributor to disease and premature mortality - give some disease examples

Answer 2

Higher levels of inactivity - TVs, cars, computers Increased consumption of high-fat foods (saturated fats especially which are bad) Obesity is a major contributor to conditions such as * Type 2 diabetes * High blood pressure * Myocardial infarction * Certain cancers eg colon and breast * Osteoarthritis

Question 3

What does long-term obesity cause that makes it difficult to lose this weight?

Answer 3

Long-term obesity can induce brain re-programming - the brain now views the extra weight (fat) as normal and dieting as threat to body survival and therefore defends the new weight

Question 4

Three basic concepts underline the control of energy intake and body weight * Satiety signalling * Adiposity negative feedback signialling * Food reward What is satiation? What is satiety? What is adiposity?

Answer 4

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

Question 5

When do statiation signals increase? What is the hunger hormone known as? What cells secretes it and which organ? What does it cause?

Answer 5

Satiation signals increase during meal to limit the meal size The hunger hormone is known as Grehlin It is secreted by cells in the stomach lining and levels increase before meals and decrease after meals It stimulates food intake, decreases energy expenditure and decreases fat utilisation - increases body weight

Question 6

What are the two hormones that report the fat status to the brain? What does this cause? The levels in blood of these hormone increase as more fat is stored What cells secrete these hormones?

Answer 6

Letpin (aka fullness hormone) is secreted from fat cells (adipocytes) Insulin is secreted from the pancreatic beta cells in the Islet’s of Langerhans The hormones inform the brain (hypothalamus) to alter energy balance - eat less and increase energy burn

Question 7

What happens to the sensitivity of the hypothalmus to leptin in insulin in obesity states?

Answer 7

In obesity, a decreased sensitivity to leptin occurs (similar to insulin resistance in type 2 diabetes), resulting in an inability to detect satiety despite high energy stores and high levels of leptin

Question 8

Drug therapy may be considered as an adjunct to diet and exercise (never as monotherapy) for patients with a BMI ≥30 kg/m². Pharmacotherapy has modest short-term efficacy but a lack of long-term efficacy. What is a first line and second line drug that is licensided for use in patients with a BMI >/=30 kg/m2 as an adjunct to diet and exercise?

Answer 8

Orlistat is the first line anti-obesity drug Liraglutide (sexenda) is licensed for use as a second line anti-obesity drug

Question 9

How do both orlistat and lireglutide work?

Answer 9

Orlistat - inhibits pancreatic lipase decrease trigylceride absoprtion in small intestine Liraglutide is a glucagon-like peptide receptor agonist . It works by increasing insulin release from the pancreas and decreases excessive glucagon release. Insulin increases stored glucose and signals hypothalamus to eat less and increase energy burn

Question 10

When should both orlistat or liraglutide be discotinued if the person has not lost 5% of their weight when starting the treatment?

Answer 10

Treatment should be discontinued after 12 weeks if the person has not lost at least 5% of their initial body weight as measured at the start of drug treatment

Question 11

What are the guidelines for bariatric surgery in a patient?

Answer 11

Bariatric surgery is recommended as a treatment option if all of the following criteria are fulfilled: The person has a body mass index (BMI) of 40 kg/m2 or more, or between 35 kg/m2 and 40 kg/m2 with other significant disease that could be improved if they lost weight, for example type 2 diabetes, hypertension, or severe mobility problems. All appropriate non-surgical measures have been tried but the person has not achieved or maintained adequate, clinically beneficial weight loss. The person is generally fit for anaesthesia and surgery. The person commits to the need for long-term follow up

Question 12

The main purpose of the stomach is to store and mix food with the gastric juices before it passes into the small intestine for further digestion and absoprtion What is the mix produced from the gastric secretions mixing with food known as? What governs the rate of stomach empyting?

Answer 12

The mix produces by the mixing in the stomach is known as chyme The control of stomach emptying is governed by both gastric factors and duodenal factors

Question 13

What are the gastric factors which increase the stomach emptying? (clue - * volume of what increases motility due to which influences, * consistency of what)

Answer 13

Rate of emptying is proportional to the volume of chyme in the stomach * Distension increases motility due to: * Stretch of smooth muscle * Stimulation of intrinisc nerve plexuses * Increased vagus nerve activity and gastrin release Consistency of chyme * Emptying facilitated by thin chyme liquid

Question 14

The duodenum must be ready to receive the chyme from the stomach Which duodendal factors delay gastric emptying? (which reflex, which hormone)

Answer 14

Neuronal response - enterogastric reflex - stretching of the wall of the duodenum results in inhibition of gastric motility and reduced rate of emptying of the stomach Hormonal response - release of cholecystokinin - inhibits gastrin release in stomach and gastric motility

Question 15

What are the stimuli within the duodenum that drive the neuronal (enterogastric reflex) and hormonal (cholecystokinin) response?

Answer 15

Stimuling driving duodenal factors to delay gastric empyting - Fat, acid, hypertenocity, distension * Fat - delay in gastric emptying required for digestion and absorption in small intestine * Acid - time required for neutralization of gastric acid * Hypertonicity - products of carbohydrate and protein digestion are osmotoically active and draw water into small intestine - danger of reduced plasma volume and circulatory disturbances * Distension of the duodenum

Question 16

Hypertonicity - products of carbohydrate and protein digestion are osmotoically active and draw water into small intestine - danger of reduced plasma volume and circulatory disturbances What is an example of a syndrome that can occur due to this?

Answer 16

An example of a syndrome that can occur due to increase hypertonicty due to high osmotic potential resulting in hypovalaemia due to water diffusion into small intestine is dumping syndrome Dumping syndrome is also known as rapid gastric emptying

Question 17

What happens in dumping syndrome? When does it most commonly occur?

Answer 17

Dumping syndrome occurs when food, especially sugar, moves too quickly from the stomach to the duodenum—the first part of the small intestine—in the upper gastrointestinal (GI) tract. This condition is also called rapid gastric emptying.[1] It is mostly associated with conditions following gastric bypass surgery or esophageal surgery

Question 18

What are the symptoms of dumping syndrome?

Answer 18

Early symptoms - fainting and sweating, abdominal bloating, cramps and nausea Late symptoms are due to rebound hypoglycaemia and occurs within 4 hours - flushing and hypoglycaemia * It results from excessive movement of sugar into the intestine, which raises the body’s blood glucose level and causes the pancreas to increase its release of the hormone insulin. The increased release of insulin causes a rapid drop in blood glucose levels

Question 19

The gastric mucosa is composed of a surface lining the stomach (simple columnar epithelium), pits (invaginations of the surface) and glands at the base of the pits responsible for several secretions What are the two different gland areas of the stomach?

Answer 19

Oxyntic gland area - proximal stomach including the fundus and body Pyloric gland area - distal stomach

Question 20

Different cells in both of the gland areas exist to secrete different enzymes/hormones What is secreted from the oxyntic mucosa (fundus and body)? Which cells in the oxyntic mucosa secretes these?

Answer 20

Parietal cells secrete * HCl (hydrocholoric acid) * Intrinsic factor * Gastroferrin Chief cells secrete * Pepsinogen Enterochromaffin like cells secrete * Histamine Mucous is secreted from the gland goblet cells

Question 21

What is the function of the different secretions in the oxyntic mucosa?

Answer 21

Parietal cells secrete * HCl (hydrocholoric acid) - activates pepsinogen to pepsin, denatures protein, kills most microorganisms * Intrinsic factor and gastroferrin - bind vit B12 and Fe2+ respectively, facilitating subsequent absoprtion Chief cells secrete * Pepsinogen - inactive pepsin precursor - (pepsin breaks down proteins) Enterochromaffin like cells secrete * Histamine - stimulates HCL secretion Mucous is secreted from the gland goblet cells - protective

Question 22

What is secreted from the pyloric gland area of the stomach? Which cells in this area secrete these?

Answer 22

G cells secrete Gastrin D cells secrete Somatostatin Mucous is secreted by the goblet cells in the glands

Question 23

What is the function of the different pyloric gland secretions?

Answer 23

Gastrin - stimulates HCL secretion and motility Somatostatin inhibits HCL secretion and motility Mucus is protective

Question 24

Name all the gastric acid secretions, the cells that secrete them and their function

Answer 24

* Gastric parietal cells * HCL - activates pepsinogen to pepsin, denatures proteins, kills microorgansims * Intrinsic factor and gastroferrin - bind vit B12 and Fe2+, facilitating subsequent absorption Chief cells - pepsinogen - inactive precursor to pepsin Enterochromaffin like cells * Histamine - stimulates HCL production G cells - secrete gastrin - promotes HCL secretion D cells - secrete somatostain - inhibits HCL secretion Goblet cells - secrete mucous which is protective

Question 25

An enterogastrone is any hormone secreted by the mucosa of the duodenum in the lower gastrointestinal tract in response to dietary lipids that inhibits the caudal (or “forward, analward”) motion of the contents of chyme. What are the two enterogastrones? What cells of the duodenum are they released from? What effect do they have?

Answer 25

Secretin - released from S cells in the duondeum in response to the H+ in the lumen * Promotes secretion of pancreatic and biliary HCO3- to neutralise the acididity Cholecystokinin - released from the I cells of duodenum and jejunujm in response to fat / protein in the lumen * inhibits gastric emptying * causes secretion of pancreatic enzymes, relaxation of sphincter of oddi and contraction of gallbladder * potentiates action of secretin

Question 26

A secretagogue is a substance which promotes secretions What are the three important secretagogues that induce acid secretion from the parietal cells?

Answer 26

ACh (acetylcholine) - from the vagus nerve activity Gastrin - secrete by G cells in pyloric gland area Histamine - secreted by enterochromaffin like cells in the oxyntic mucosa area All three stimulate the parietal cells to trigger the secretion of HCL into the lumen

Question 27

Which cells produced in the stomach / duodenum decrease gastric acid secretion?

Answer 27

Cholecystokinin - produced in I cells of duodenum and jejunum Sercetin - produced in S cells of duodenum Somatostatin - produced in D cells of pyloric gland area of stomach

Question 28

What is the major site for digestion and absorption? how long is it? What are the different parts? What does it recieve?

Answer 28

The major site for digestion and absorption is the small intestine - approximately 7m long Made up of the duodenum (approx 25cm), jejuunum (approx 3m) and ileum (approx 4m) Recieves * Chyme from stomach via pyloric sphincter * Pancreatic juices from pancreas and bile from liver / gall bladder - both via the sphincter of Oddi

Question 29

The small intestine is well adapted for absorption What increases the surface of the small intestine?

Answer 29

The large circular folds Villi Microvilli (brush border)

Question 30

What are the small intestine secretions collectively known as? What does the motility of the small intestine cause?

Answer 30

The small intestine intestine secretions are collectively known as succus (huice) entericus (of the intestine) - the clear alkaline fluid secreted by the glands of the small intestine Causes the mixing of chyme with digestive juices (segmentation), slow propulsion of the chyme aborally (peristalsis), removal of undigested residues to the large intestine via the ileocaecal valve

Question 31

What cells are secreted from the small intestine that both * stimulate insulin release from the pancreatic B cells * and inhibit gastric emptying? What are these hormones known as?

Answer 31

Incretins. Incretins are hormones produced in the small intestine during a meal that enter the vasculature and trigger insulin release by pancreatic beta cells. The two most important are below Glucose dependent Insulinotropic Peptide (GIP aka gastric inhibitory peptide) from K cells of duodenum and jejunum and Glucagon-like Peptide-1 from L cells of the small intestine - also decreases appetite (eg liraglutide used in obese patients)

Question 32

What are the exocrine secretions that come from the pancreas?

Answer 32

Digestive enzymes are secreted from the acinar cells - eg amylase, lipase (trypsinogen - gets activated by enterokinases in duodenum) Aqueous NaHCO3 is secreted from the duct cells - neutralised the acidic chyme in the duodenum They both are secreted to the dudodenum collectively as pancreatic juice

Question 33

What hormone released from where promotes the secretion of pancreatic duct cells and biliary HCO3- to neutralise the chyme acidity? What hormone released from where promotes the secretion of the pancreatic digestive enzymes from the pancreatic acinar cells?

Answer 33

Secretin released from the S cells of the dudodenum promotes the secretion of HCO3- from pancreatic and biliary duct cells Cholecystokinin released from the I cells of the duodenum promotes the secretion of digestive enzymes from the pancreatic acinar cells

Question 34

What is the gastroileal reflex? What stimulates this reflex?

Answer 34

The gastroileal reflex is a reflex stimulated by the presence of food in the stomach and gastric peristalsis * Gastrin and CCK mediate the reflex by relaxing the ileocaecal valve * Initiation of the reflex causes peristalsis in the ileum and the opening of the ileocecal valve (which allows the emptying of the ileal contents into the large intestine, or colon).

Question 35

What is the function of the ileocaecal valve? What controls the ileocaecal valve

Answer 35

Ileocaecal valve * Maintains a positive resting pressure * Relaxes in response to distension of the duodenum * Contracts in response to distension of the ascending colon * Is under control form the vagus nerve, sympathetic nerves, enteric neurons and hormonal signals

Question 36

What are the primary functions of the colon?

Answer 36

Absorption of water, salts (Na+ and Cl-) and short chain fatty acids Also secretes net potassium, bicarbonate and mucus And is a reservoir for the storage of colonic contents until ready for defecation

Question 37

What do the intestinal gases (flatus) arise from?

Answer 37

Intestinal gases arise from * Swallowed air * Bacterial fermentation in the colon The gas is expelled through the anus