Physiology. Flashcards
What is the digestive tract?
series of hollow organs, separated by sphincters to control movement.
What is the function of the mouth and oropharynx?
to chop and lubricate food and to start carb and fat digestion.
What is the function of the oesophagus?
delivery of food to the stomach.
What is the function of the stomach?
temporary food storage, continuation of carb and fat digestion, initiates protein digestion. regulates the delivery of chyme to the small intestines.
What is the function of the small intestine?
Principal site of digestion and absorption of nutrients.
What is the function of the large intestine?
reabsorbs fluid and electrolytes and stores fecal matter, before regulating expulsion.
What are the accessory structures of the Gi tract?
salivary glands, pancreas, liver and gall bladder.
What does aboral mean?
anal.
What are the four main digestive processes?
Motility, secretion, digestion and absorption.
What is GI motility?
Mechanical activity mostly involving: propulsive movements, churning movements and tonic contractions.
What is GI secretion?
digestive secretions go into the tract in response to hormonal and neural signs.
What is GI digestion?
biochemical breakdown of complex food stuffs to smaller absorbable units.
What is GI absorption?
transfer of the absorbable products of digestion from the digestive tract to the blood or lymph.
What do digestive secretions contain?
water (large volumes extracted from plasma), electrolytes and organic compounds e.g. enzymes, bile salts and mucus.
What is the basic principle of fat digestion?
mostly triglyderides converted to monoglycerides and free fatty acids. Mediated by lipases.
What is the basic principle of carbohydrate digestion?
Mostly poly and di-, converted to monosaccharides. Mediated by anylases and disaccharidases.
What is the basic principle of protein digestion?
protein broken down to amino acids, dipeptides and tripeptides. Mediated by proteases and dipeptidases.
Name the layers of the digestive tract starting from the outside and working in?
serosa, longitudinal muscle, myenteric plexus, circular muscle, submucosa, submucosal plexus, muscularis mucosae, mucosa and mesentery.
What comprises the digestive mucosa?
epithelial cells (absorption), exocrine cells (enzymes), endocrine gland cells (hormones), lamina proporia (capillaries, neurones and immune cells) and muscularis mucosa.
What comprises the digestive submucosa?
connective tissue, larger blood and lymph vessels and the submucous nerve plexus.
What comprises the digestive muscularis extrema?
circular muscle layer, nerve network - myenteric plexus and longitudinal muscle layer.
What comprises the digestive serosa?
connective tissue.
Where is the skeletal muscle in the GI tract?
mouth, pharynx, upper oesophagus and the external anal sphincter.
What are the three layers of smooth muscle in the GI tract and what do they do?
circular - lumen becomes narrower and longer.
Longitudinal - intestine becomes shorter and fatter.
Muscularis mucosae - changes the absorptive and secretory area of the smooth muscle.
What connects smooth muscle cells to each other?
Gap junctions.
What allows electrical currents to move between smooth muscle cells?
the gap junctions for a junctional synctium to allow hundreds of cells to contract and depolarise at the same time.
Describe the electrical activity of the stomach and large and small intestines.
spontaneous electrical activity occurs in slow waves via gap junctions, causing rhythmic contraction.
How is spontaneous activity modulated in the GI tract?
Intrinsic (enteric) and extrinsic (autonomic) nerves and also numerous hormones.
Describe slow wave electrical activity.
it determines the max frequency, direction and velocity of rhythmic contractions. Slow waves are driven by ICC’s (interstitial cells of cajal). Contraction only occurs if the slow wave amplitude is sufficient to trigger an action potential. The force is related to the number of action potentials discharged.
What are the pacemaker cells of the GI tract?
The interstitial cells of cajal.
What channels is the slow wave mediated by?
Upstroke of the wave is Ca channels and the downstroke is K channels.
Where are ICC’s found?
between the longitudinal and circular muscle layers and in the submucosa. They form gap junctions with each other and the smooth muscle cells.
What is the GI basic electrical rhythm?
The electrical rhythm that flows through the tissues, determined by the slow wave. It varies along the length of the GI tract as not all slow waves will trigger a contraction.
What determines whether the slow waves will reach the amplitude required to cause contraction?
neuronal stimuli, hormonal and mechanical stimuli etc.
What are the BER frequency’s of the different part of the GI tract?
stomach - 3 slow per minute.
Duodenum 1-12 waves per min. Tends to drive food in the aboral direction.
Terminal ileum - 8 waves per min.
Proximal colon 8 waves and distal = 16 waves per min. Favours retention of luminal contents facilitating absorption of water and electrolytes.
What is the enteric nervous system?
little brain of the gut. cell bodies are found in ganglia largely within the myenteric (Auerbachs) and submucous (Meissner’s) plexus. Ganglia are connected by interganglionic fibre tracts. It is located solely in the GI tissues (intrinsic). It forms a closed reflex circuit that can perform independently of the rest of the nervous system. But is strongly modulated by hormones and extrinsic nerve output.
What neurones comprise the enteric nervous system?
sensory - mechanoreceptors, chemoreceptors and thermoreceptors.
Interneurones (in the majority) co-ordinate reflexes and motor programs.
Effector neurones - excitory and inhibitory - supplying the smooth muscle, epithelium, endocrine cells and blood vessels.
What is the role of parasympathetic innervation of the GI tract?
preganglionic fibres synapse with the ganglion cells within the ENS.
excitory influences - increase pancreatic, gastric and small intestine secretion, increase blood flow and smooth muscle contraction.
Inhibitory - relaxation of some sphincters, receptive relaxation of the stomach.
What is the role of the sympathetic innervation of the GI tract?
Postganglionic fibres releasing NA innervate mainly enteric neurones but also other structures. Functionally less important than the parasympathetic division.
Inhibitory - decreased mobility, secretion and blood flow.
Describe local long and short reflexes on motor and secretory control in the GI system.
Local sensory, interneurone and effector neurone are all in the myenteric plexus.
Short - sensory neurone goes to the prevertebral ganglion, the interneurone goes back to the myenteric plexus and the effecor neurone goes back to the tissue.
Long is the same but goes all the way to the medulla oblongata.
Give an example of local, long and short reflexes.
Local = peristalsis.
Short - intestino-intestinal inhibitory reflex.
Long - gastroileal reflex.
Describe peristalsis.
distension of the gut wall activates sensory neurones. This alters the activity of inerneurones, which alter the activity of motoneurones. Longitudinal smooth muscle relaxes behind and contracts in front. Circular muscle contracts behind and relaxes in front.
What are the segments in front of and behind a bolus in the intestine called?
The propulsive segment is behind and the receiving segment in front.
What is segmentation and how does it occur?
Mixing or churning movements. Rhythmic contractions of the circular muscle mix and divide luminal contents, occurs in the small intestine in the fed state and in the large intestine.
What is segmentation in the large intestine called?
Haustration.
What are tonic contractions in the GI tract?
sustained contractions found in the sphincters of the tract.
Describe the sphincters of the GI tract (excluding the sphincter of oddi).
6 in total. composed of specialised circular mostly smooth muscle. Act as one way valves maintaining a resting positive pressure between the sections. Stimuli usually cause opening and closing.
Which sphincters in the GI tract are skeletal muscle?
Upper oesophageal sphincter and the anal sphincter.
What does the upper oesophageal sphincter do?
relaxes to allow swallowing and closes during inspiration.
What regulates internal (smooth) and external (skeletal) sphincters?
The defecation reflex.
What reflexes mediate mastication?
the masseteris and diagastric reflexes.
What are the two stages of deglutition? How long do the stages last?
the oropharyngeal (1 second) and the oesophageal (4-10 seconds).
Describe the oropharangeal stage of swallowing.
bolus formed in the mouth, the tongue voluntarily forces the bolus into the pharynx. Pressure stimulates the pharyngeal pressure receptors. an involunatary afferent impulse is sent to the swallowing centre in the medulla. efferents initiate an all or nithing reflex sequence of muscle movements. Upper oesophageal sphincter opens and food passes into the oesophagus.
Describe the oesophageal stage of swallowing.
medulla oblongata triggers primary peristaltic wave and closure of upper sphincter. peristalsis is controlled by the eneteric nervous system. fibres squeeze the bolus down. Longitudinal fibres in fron shorten the distance. Lower sphincter opens 2-3 seconds before and closes straight after to prevent reflux. If there is sticky food a more forceful second wave is made and increased saliva production is triggered.
What is another name for the myenteric plexus?
Auerbachs plexus.
What are the 6 main sphincters in the GI tract?
Upper oesophageal. Lower oesophageal. Pyloric. Illeocecal. Internal and external anal sphincter.
What size is the small intestine?
6m long and 3.5cm wide.
What are the three parts of the small intestine and what lengths are they?
Duodenum - 25cm
Jejunum - 2.5m
Ileum - 3m.
Where does the small intestine receive different fluids from?
Chyme from stomach.
Pancreatic juice from pancreas.
Bile from the gallbladder.
What 6 secretions come from the small intestine?
Gastrin, cholecystokinin, secretin, motilin, glucose dependent insulinotropic peptide and glucagon like peptide.
where is gastric secreted?
From G cells in the gastric antrum (mainly) and duodenum.
where is cholecystokinin (CCK) secreted?
From I cells of the duodenum and the jejunum.
where is secretin secreted?
From S cells in the duodenum.
where is motilin secreted?
From M cells in the duodenum and jejunum.
where is glucose dependent insulinotropic peptide (GIP) secreted?
Is an incretion from K cells of the duodenum and the jejunum.
where is glucagon like peptide 1 (GLP-1) secreted?
Is an incretion from L cells of the small and large intestine.
What type of receptors do all intestinal secretions act on?
G-protein coupled receptors.
What potentiates GIP?
Gliptins e.g. Sitagliptin used in treatment of type two DM.
What mimics the activity of GLP-1? And what potentiates the activity?
Potentiated by Gliptins e.g. Sitagliptin used in treatment of type two DM.
Mimicked by extenatide also used for treatment of DM type 2.
What is the juice of the intestine called?
Succus entericus.
How much intestinal juice is secreted per day roughly?
2 litres.
What 5 things increase secretion of intestinal juice?
Distension/irritation. Gastric. CCK. Secretin. Parasympathetic nerve activity.
What decreases secretion of intestinal juice?
Sympathetic nerve activity.
What do intestinal secretions contain, what do they do and where do they come from?
Mucus - protection/lubrication - goblet cells.
Aqueous salt - enzymatic digestion - mostly from the crypts.
No digestive enzymes.
How is chyme chopped up in the small intestine?
Segmentation. Chops and moves the chyme back and forth. Caused by contraction and relaxation of segments of circular muscle.
When is segmentation most vigorous?
After a meal, very little or none in between.
What primarily activates segmentation in the duodenum?
Distension by entering chyme.
What triggers segmentation in the empty ileum?
Gastric from the stomach (gastoileal reflex).
How many segmentation contractions does the duodenum have?
12 per min.
How many segmentation contractions does the ileum have?
9 per min.
What does the differing number is segmentation contractions in the duodenum and ileum result in?
Aboral movement of contents.
How long does movement take through the small intestine and what does this allow?
3-5 hours, allows for absorption.
What two types of peristalsis occur in the inter digestive or fasting state?
A few localised contractions and the migrating motor complex (MMC).
What is the migrating motor complex and what does it do?
Strong peristaltic contraction of entire length of intestine. Clears digested debris, epithelial cells etc. has a housekeeper function.
How often does MMC occur?
90-120 mins.
What inhibits MMC?
Feeding and vagal activity.
What triggers MMC?
Motilin.
What suppresses MMC?
Gastric and CCK.
What can macrolide antibiotics mimic and what does this cause?
Mimic the action of motilin and causes unpleasant GI disturbances.
What are the endocrine secretions of the pancreas and where do they go?
Insulin and glucagon, go into the bloodstream.
What are the exocrine secretions of the pancreas, what cells make them and where do they go?
Digestive enzymes form acinar cells.
Aqueous NaHCO3 solution from duct cells.
Both are secreted to the duodenum as pancreatic juice.
What kind of cells do pancreatic ducts and acini contain?
Duct cells. Alpha, beta and delta cells. Islets of langerhans. Acinar cells. PP cells.
What pancreatic enzymes are there?
Proteases - trypsinogen, chymotrypsinogen and procarboxypeptidase.
Pancreatic amylase.
Pancreatic lipase.
Where are enzymes stored in pancreatic acinar cells?
Zymogen granules.
What happens to the pancreatic proteases once they arrive in the duodenum?
Trypsinogen is turned into trypsin by enterokinase from mucosal cells.
Then chymotrypsinogen is turned into chymotrypsin by trypsin.
Procarboxypeptidase is also turned into carboxypeptidase by trypsin.
Trypsin can also autocatalyse trypsinogen to trypsin.
What are the three inactive pancreatic enzymes?
Trypsinogen, chymotrypsinogen and procarboxypeptidase.
What are the three active versions of the pancreatic proteases?
Trypsin, chymotrypsin and carboxypeptidase..
What do pancreatic duct cells secrete?
1-2 litres of Alkaline HCO3 rich fluid per day. Into the duodenum.
What is the function of the alkaline fluid secreted by pancreatic duct cells?
Neutralises chyme.
Provides optimum pH for pancreatic enzymes.
Protects the mucosa from erosion by the acid.
What are the three phases of the control of pancreatic secretion?
Cephalic, gastric and intestinal.
What is the cephalic phase of the control of pancreatic secretion?
Mediated by the vagal stimulation of mainly acinar cells. Makes up about 20% total secretion.
What is the gastric phase of the control of pancreatic secretion?
Gastric distension evokes a vasovagal reflex resulting in parasympathetic stimulation of acinar and duct cells. Makes up a total of 5-10% of the secretion.
What is the intestinal phase of the control of pancreatic secretion?
Makes up 70-80% of total secretion.
- Acid in the duodenal lumen causes increased release from S cells of secretin. The secretin is then carried in the blood to pancreatic duct cells. This causes increased secretion of aqueous NaHCO3 solution into the duodenal lumen which neutralises the acid.
- Fat and protein in the duodenal lumen causes increased CCK release from I cells. CCK is then carried in the blood towards pancreatic acinar cells which causes increased secretion of digestive enzymes into duodenal lumen, which digests the fat and protein.
How much bile is produced per day?
0.6-1.2 litres per day.
What sphincter prevents bile form entering the duodenum?
Oddi.
What stimulates the gall bladder to release bile and what happens?
Chyme in the duodenum stimulates release, the smooth muscle in the wall of the gallbladder contracts and the sphincter of Oddi opens.
What cells add secretions to bile?
Hepatocytes and bile duct cells.
Where is secretin carried to by the blood and what does this result in?
To the pancreatic duct cells - causes increased secretion of NaHCO3.
To the hepatocytes - causes increased secretion of NaHCO3 rich bile.
Also causes d creased gastric secretion and decreased gastric emptying.
Where all is CCK in the blood carried to and what are the results?
Pancreatic acinar cells - increased secretion of digestive enzymes.
Gall bladder and sphincter of Oddi - causes contraction of the gall bladder and relaxation of the sphincter of Oddi.
Also causes decreased gastric emptying and secretion.
What endogenous sources do we get proteins from?
Digestive enzymes and dead cells from the GI tract.
What different kinds of carbs do we get from our diet?
Starch, cellulose, glycogen and disaccharides.
What two types of digestion occur in the small intestine?
Luminal and membrane digestion.
What mediates digestion at the membrane?
Enzymes situated at the brush border of epithelial cells.
What two membranes do enterocytes have?
The apical membrane (brush border) and the basolateral membrane (facing the interstitium).
What is the name given to the overall process of digestion and absorption?
Assimilation.
How is glucose digested and absorbed in the small intestine?
Is doesn’t have to be digested, it is just absorbed.
How is protein digested and absorbed in the small intestine?
Protein undergoes luminal hydrolysis from the polymer to the monomer e.g. Proteins to amino acids which are then absorbed.
How is sucrose digested and absorbed in the small intestine?
Broken down to fructose and glucose by hydrolysis at the brush border and then absorbed.
How is peptides digested and absorbed in the small intestine?
They undergo intracellular hydrolysis in the enterocytes, so are absorbed as peptides and cross to the interstitium as amino acids.
How is triacylglycerols digested and absorbed in the small intestine?
Broken down to fatty acids and glycerol by luminal hydrolysis. Absorbed into enterocytes and then re synthesised inside the enterocytes to pass into the interstitium as triacylglycerol.
What three areas are carbs digested?
Mouth, stomach and the duodenum.
What breaks down carbs in the mouth?
Salivary alpha amylase.
What breaks down carbs in the stomach?
Salivary alpha amylase within the bolus.
What breaks down carbs in the duodenum?
Pancreatic alpha amylase that are free in the lumen.
Oligosaccharidases on the brush border membrane.
What are some Oligosaccharidases?
Isomaltase, sucrase, lactase and maltase.
What causes lactose intolerance?
Deficiency in lactase.
What is amylose?
Straight chain starch with alpha 1,4 linkages.
What is amylopectin?
Branched chain starch with alpha 1,4 linkages and alpha 1,6 linkages.
What is glycogen?
A branched chain polysaccharide with alpha 1,4 and alpha 1,6 linkages.
What is sucrose?
Table sugar made of glucose plus fructose. Contains alpha 1,2 linkages.
What is lactose?
Milk sugar comprising of glucose and galactose. Contains beta 1,4 linkages.
What are two monosaccharides?
Glucose and fructose.
What must carbohydrates by converted to in order to be absorbed?
Monosaccharides.
What are the final products of carb digestion?
Glucose, galactose and fructose.
Where does absorption of the final products of carb digestion occur?
Duodenum and jejunum.
How are the final products of carb digestion absorbed?
Two step process involving exit from the enterocytes via the apical and basolateral membranes.
Glucose and galactose are absorbed by secondary active transport mediated by SGLT1.
Fructose by facilitated diffusion by GLUT5.
Exit for all monos is facilitated diffusion by GLUT2.
What is the sequence of carbohydrate digestion?
Starch is broken down to Oligosaccharides by alpha amylase (salivary and pancreatic).
Oligosaccharides are not absorbed but are joined by lactose and sucrose from the diet.
These are then broken down by Oligosaccharides to monosaccharides. And joined by glucose and fructose from the diet and then absorbed.
What are some Oligosaccharides?
Lactase, maltase and sucrase-isomaltase.
What is alpha amylase and what does it do?
It is an endoenzyme.
It breaks down linear internal alpha1,4 linkages but not terminal alpha 1,4 linkages. Hence no production of glucose.
What can alpha amylase not cleave?
Alpha-1,6 linkages at branch points or alpha-1,4 linkages adjacent to branch points.
What are the products of alpha-amylase breakdowns?
Linear glucose Oligocene e.g. Maltotriose, maltose.
And also alpha limit dextrins.
What are the 6 steps in the mode of operation of SGLT1?
- 2 na+ binds.
- Affinity for glucose increases and it binds.
- Na+ and glucose translocation from extracellular to intracellular.
- 2 Na+ dissociate and affinity for glucose fails.
- Glucose dissociates.
- Cycle is repeated.
This means that sodium is also transported into the cytosol.
What is an oligosaccharidease?
An integral membrane protein with a catalytic domain facing the GI lumen.
What does lactase do?
Breaks down lactose to glucose and galactose.
How are maltose, maltotriose and alpha limit dextrins changed into glucose?
All Oligosaccharidases cleave the terminal alpha-1,4 linkages off.
What does maltase do in addition to normal breakdown of substances to glucose?
Can degrade alpha-1,4 linkages in straight chain Oligomers up to one monomers in length.
What does sucrase do in addition to normal breakdown of substances to glucose?
Specifically responsible for hydrolysing sucrose to glucose and fructose.
Why is isomaltase unique?
Only enzyme that can split branching alpha-1,6 linkages of alpha limit dextrins.
What speeds are the hydrolysis reactions of Maltese, sucrose, isomaltase and lactase?
Maltese, sucrose and isomaltase occur at a faster rate than the transport of the released monomers. Lactase the rate of hydrolysis is rate limiting in assimilation.
What normally happens to lactase activity post weaning and why?
It is usually lost. But humans have a variable degree of lactase persistence. Partially due to polymorphisms in the MCM6 gene that regulates expression of the lactase gene.
What three types of lactase deficiency are there?
Primary, secondary and congenital.
What causes primary lactase deficiency? (Hypolactasia)
Due to lack of lactase persistence allele and is the most common form worldwide.
What causes secondary lactase deficiency? (Hypolactasia)
Damage to/ infection of the proximal small intestine.
What causes congenital lactase deficiency? (Hypolactasia)
Rare autosomal recessive disease. Have no ability to digest lactose from birth.
When does hypolactasia cause problems.
If lactose containing food overwhelms the remaining lactase enzyme. This causes lactose to be delivered to the colon.
What do colonic microflora produce if exposed to lactose?
SCFA which can be absorbed.
H2 - which can be detected in the breath of lactase deficient individuals following a lactose challenge.
CO2
Methane
What do the products formed by the colonic flora of lactose intolerant individuals cause?
Bloating, abdominal pain and flatulence.
What does undigested lactose cause?
Acidification of the colon. Increased osmotic load and loose stools and diarrhoea.
How many major pathways of protein digestion absorption are there?
4.
What are the four pathways of protein breakdown/assimilation?
All have protein to peptides to amino acids to amino acid on enterocytes to amino acid in the blood.
- Uses luminal enzymes then apical membrane transformers then basolateral membrane transporters.
- The same except brush border enzymes in between the first two.
- The same as number 1 but intracellular hydrolysis occurs in between the last two.
- The peptide is transported out of the enterocyte without intervening intracellular hydrolysis by proteases.
What happens to proteins in the stomach?
Hcl begins to denature them. Pepsin cleaves proteins into peptides.
What is pepsin and what pH does it like?
Cleaves proteins. Is an endopeptidase with preference for bonds between aromatic and larger neutral amino acids. It’s not essential for protein digestion. Likes pH 1.8 to 3.5.
What are the two function categories of pancreatic proteases in the duodenum?
Endopeptidase sand exopeptidases.
What are the three endopeptidases and what do they do?
Trypsin, chymotrypsin and elastase.
They phreak down peptides into oligopeptides (2-6) amino acids long.
What are the two exopeptidases? And what do they do?
Procarboxypeptidase A and B. Break down proteins into single amino acids.
What are the final products of protein breakdown?
Amino acids, dipeptides, tripeptides, oligopeptides and some intact proteins.
What completes protein digestion?
Additional proteases present at the brush border.
What two types of brush border exopeptidases are there?
Aminopeptidases and carboxypeptidases.
Why are their numerous brush border peptidases?
Because each attacks a limited number of peptide bonds and the oligopeptides to be digested are very varied in structure.
What do brush border peptidases have an affinity for?
Larger oligopeptides. 3-8 amino acids.
What are the numbers of cytoplasmic peptidases and what do they do?
Less numerous than those at the brush border. Primarily hydrolyse dipeptides or tripeptides.
How many mechanisms of amino acid absorption are present at the brush border and what categories do they fall into?
7.
5 na dependent cotransporters mediating uphill movement.
2 na independent.
How many mechanisms of amino acid absorption are present at the basolateral membrane and what categories do they fall into?
What do these categories say about the movement of amino acids?
5.
3 mediate effluent and are na independent.
2 mediate influx and are na dependent.
Net movement is therefore bidirectional.
How are di tri and tetra peptides absorbed?
h+ dependent mechanisms at the brush border (co-transport).
Further hydrolysed to amino acids within the enterocyte.
Na + independent systems at the basolateral membrane (facilitated transport).
What kinds of lipid do we get from our diets?
Fats/oils (triacylglycerols), phospholipids, cholesterol and cholesterol esters. Fatty acids.
What is the solubility of ingested lipids?
Insoluble e.g. Cholesterol esters or poorly soluble.
What are the three phases in lipid digestion, how important are they and what do they do?
Mouth (lingual phase) unimportant.
Stomach (gastric phase)- modestly important.
Small intestine. Most important. Fats emulsified by bile and pancreatic lipase which hydrolyse TAGs to mono glycerine and free fatty acids.
How are TAGS digested by lipase in the stomach?
Heat and stomach movement mixes fats with gastric lipase forming an emulsion.
Hydrolysis initially slow due to largely separate aqueous/lipid interface.
As hydrolysis proceeds rate increases as produced fatty acids act as surfactants breaking down lipid globules aiding emulsification.
Emulsified fats are ejected from the stomach to the duodenum.
What juices assist in TAG breakdown in the duodenum and what do they do?
Pancreatic lipase aided by bile salts. HCO3 in pancreatic juice neutralises stomach acid and provides a suitable pH for optimal enzyme action.
Describe breakdown of triglycerides?
Triglyceride to diglyceride and free fatty acids by gastric lipase and water.
Free fatty acids stimulate CCK release from duodenum and secretion of pancreatic lipase.
What do bile salts do?
Act as detergents to emulsify large lipid droplets to small ones. They are ampiphatic. They increase the surface area for attack by pancreatic lipase.
What two things can failure to secrete bile salts result in?
Lipid malabsorption - streatorrhoea (fat in faeces).
Secondary vitamin deficiency due to failure to absorb lipid vitamins.
What is a problem created by bile salts and how is this solved?
Block access of pancreatic lipase to hydrophobic core of small lipid droplets.
Problem solved by colipase which binds to the bile salts and lipase and allows them access to the do and triglycerides.
What is colipase?
An amphiphatic polypeptide secreted with lipase by the pancreas.
What is the product of pancreatic lipase digestion?
2 mono glycerine sand free fatty acids.
What are the final products of lipid digestion stored in and released from?
Mixed micelles.
What do mixed micelles contain?
Cholesterol, monoglycerides, fatty acids, phospholipids and bile salts surrounding a hydrophobic core.
How are fatty acids and monoglycerides transferred from micelles to enterocyte membranes?
Passive diffusion.
How do short chain fatty acids exit enterocytes?
They diffuse through and exit the basolateral membrane to enter villus capillaries.
How do long chain fatty acids exit enterocytes?
They are re synthesised to triglycerides in the ER and are then incorporated into chylomicrons.
How are chylomicrons formed?
Mono and free fatty acids resynthesised to triglycerides in the enterocyte ER.
Cholesterol esters are added to make phospholipids.
This then makes a nascent cholymicron.
Apolipoprotein are added to make a cholymicron.
They then leave by executors is and are absorbed by the central lacteals.
How do cholymicrons enter the systemic circulation?
Into the subclavian vein via the thoracic duct.
Where are chylomicrons triglycerides metabolised? And by what?
In the capillaries, particularly muscle and adipose tissue.
By lipoprotein lipase on the surface of endothelial cells.
What happens to the free fatty acids and glycerol released initially after chylomicrons triglyceride metabolism?
They are bound to albumen and taken up by the tissues.
After metabolism of chylomicron triglycerides and binding to albumen, what is left over?
Chylomicron remnant. Containing phospholipids and cholesterol.
What happens to chylomicron remnants?
Undergo endocytosis by hepatocytes. The released cholesterol is either: stored, secreted unaltered in bile or oxidised to bile salts.
How is cholesterol absorbed?
Mainly due to transport by endocytosis in Clatherin coated pits by Niemann-Pick like 1 protein. (NPC1L1).
How does Ezetimibe work?
Binds to NPC1L1 and prevents internalisation and cholesterol absorption.
What are the two types of calcium absorption and where do they occur?
Passive- paracellular - whole length of small intestine.
Active - transcellular - mainly duodenum and upper jejunum.
What is active calcium absorption regulated by?
Calcitriol and parathyroid hormones.
What is the storage form of iron?
Ferratin.
What transforms iron into ferratin?
Apoferratin.
What transfers iron into the enterocytes and what inhibits it?
Ferroportin and hormone hepcidin, which is released from the liver when body iron levels are high stops it.
What transfers iron out of enterocytes?
Divalent metal transporter. It is coupled to H+ transport.
What is another name for vitamin B12?
Cobalamin.
Why is efficient vitamin B12 required?
It is only present in tiny amounts in the diet.
What are the steps in vitamin B12 absorption?
Vitamin B12 in food.
Salivary glands secrete haptocorin.
Stomach acid releases B12 from food.
Haptocorin binds to it in stomach.
Stomach parietal cells release intrinsic factor.
Haptocorin digested by pancreatic proteases in the SI releasing B12.
Binds to intrinsic factor in SI.
Complex of two absorbed in terminal ileum by endocytosis.
What are the fat soluble vitamins and how are they absorbed?
ADEK. Incorporated into micelles.
Passively transported into enterocytes. Incorporated into chylomicrons or VLDL’s, then distributed by intestinal lymphatics.
How are water soluble vitamins absorbed?
Transport proteins in apical membrane similar to monosaccharides etc.
Name some water soluble vitamins?
B9, C and H.
What is another name for vitamin B9?
Folic acid.
What is another name for vitamin C?
Ascorbate.
What is another name for vitamin H?
Biotin.
What causes obesity?
We consume more calories than we expend. But it’s not a single disorder it has multiple causes.
What are the three major components in development of obesity?
Genetics, environment and energy intake/expenditure imbalance.
How does the CNS influence energy balance and body weight?
Behaviour - feeding and physical activity.
ANS activity - regulates energy expenditure.
Neurone doctrine system - secretes hormones
What centre in the brain integrates feeding behaviour?
The hypothalamus.
What do lesions in different areas of the hypothalamus cause in relation to weight?
Ventromedial hypothalamus lesions cause obesity.
Lateral lesions cause leanness.
What three basic concepts underlie the weight control system?
Satiety signalling, adiposity negative feedback signalling and food reward.
What is satiation?
Sensation of fullness generated after a meal.
What is satiety?
Period of time between the termination of one meal and the initiation of the next.
What is adiposity?
The state of being obese.
What are 5 satiation signals?
Cholecystokinin. Peptide YY. Glucagon like peptide 1 GLP-1 Oxyntomodulin OXM Obestatin.
What is CCK in relation to satiation signalling?
Secreted by enteroendocrine cells in the duodenum and jejunum.
It is released in proportion to the lipids and proteins in a meal.it sends signals to the hindbrain and stimulates it directly.
What is peptide YY?
.
Secreted by endocrine mucosal L cells of GI tract. Levels increase rapidly after eating. It slows emptying and reduces food intake
What is GLP1 and what does it do?
It is product of the proglucagon gene. From GI L cells in response to eating. Also inhibits gastric emptying and reduces food intake.
What is oxytomodulin and what does it do?
From proglucagon gene and released from oxyntic cells of SI after a meal. It suppresses appetite.
What is obestatin and what does it do?
Peptide produced from a gene that encodes gherlin. Released from cells lining the stomach/small intestine. Reduces food intake by possibly antagonising the actions of gherlin.
What is gherlin?
A octanolyated peptide hunger signal.
What secretes gherlin?
Oxyntic cells in the stomach.
What increase or decreases gherlin levels?
Increases - before meals, fasting and hypoglycaemia.
Decreased after meals.
What does gherlin do?
Peripheral gherlin stimulates food intake and decreases fat utilisation.
What substances increase food intake when injected into hypothalamic centres?
How long do they last?
Glutamate, gaba and opioids. Effects are modest and shortlasting.
What substances decrease food intake when injected into hypothalamic centres?
Monoamines.
What two adiposity signal hormones act on the hypothalamus?
Leptin which is made by and released from fat cells.
Insulin.
How do the adiposity signal hormones work?
Levels in blood increase as fat is stored. They inform the brain to alter the energy balance. Eat less and increase energy burn. This malfunctions in the obese state?
What does reduced leptin mimic?
Starvation causing unrestrained appetite.
What is leptin and what seven biological roles does it have?
It is a pleiotropic hormones. Influences food intake and energy burn. Influence peripheral glucose homeostasis and insulin sensitivity. Helps maintain the immune system. Maintains the reproductive system. Angiogenesis. Tumourigenesis. Bone formation.
What is the role of insulin in relation to adiposity?
Circulates in proportion to body adiposity. There is a transport system for insulin to enter the brain and lots of receptors in the hypothalamus. Intercerebroventricular insulin inhibits food intake and decreases body weight in rodents. There are neurone specific deflections of insulin receptors in obesity.
What pathway plays an important role in food reward?
Dopamine pathways.
What areas of the brain are implicated in substance abuse and drug addiction?
The ventral tegmental area. Composed of : nucleus accumbens, striatum and the substantia nigra.
What are the functions of dopamine?
Reward, pleasure and euphoria, motor function, compulsion and preservation.
What are the functions of serotonin?
Mood, memory processing, sleep and cognition.
What limits the use of therapeutical leptin?
Severe leptin resistance, especially in diet induced obesity.
What are the two main theories for leptin resistance?
Defective leptin transport in brain.
Altered signal transduction following leptin binding to its receptor.
What are other names for orlistat? What does it do?
Xenical or Alli.
Inhibits pancreatic lipase and so inhibits triglyceride absorption.
Reduces efficacy of fat absorption in the small intestine.
Side effects include cramping and severe diarrhoea
Need vitamin supplements.
Not long term efficient
Rebound weight.
What are three new anti obesity drugs coming on the market?
Lorcaserin, qysmia and contrave.
What does bariatric surgery result in?
Frequently Complete resolution of type 2 diabetes.
May affect secretion of GLP1, PYY and Gherlin.
Where is brown adipose tissue in adults? (BAT)
Neck, clavicle and spinal cord.
What is adaptive thermogenesis?
Inducible browning of white adipose tissue (WAT).
What is another name for Liraglutide? What does it do?
Saxenda.
Type 2 DM treatment also causes weight loss.
GLP-1 receptor agonist, therefore a satiety peptide.
Higher doses for weight loss than for DM.
Has to be injected, mechanism for weight loss unclear.
Some concerns over thyroid and pancreatic cancer.
What is a tissue?
Group of cells with similar structure and a specialised function.
What is an organ?
Two or more tissues working together to carry out a specialised function.
What is a body system?
Group of organs that perform related functions and work together to achieve a common goal.
Where do many pharmacological agents act?
At the level of the cell membrane.
What are the two categories of homeostatic control systems?
Intrinsic - local controls inherent to an organ.
Extrinsic - regulatory mechanisms initiated outside an organ, accompanied by nervous and endocrine systems.
What is a feedforward system?
Term used for responses made in anticipation of a change.
What is feedback?
Response made after change is detected.
What are the two types of feedback systems?
Negative and positive.
What is negative feedback?
Primary system. Opposes initial change.
Promotes stability by regulation of a controlled variable through flow of information along a closed loop.
What is the plasmalemma?
Fluid lipid bilayer embedded with proteins - cell membrane.
It has a tri laminar appearance under the microscope.
What are the different parts of a phospholipid?
Negatively charged phosphate head and uncharged charged lipid tails. One is bent.
Head is polar and hydrophilic.
Tail is non polar and hydrophobic.
What are carrier or transport proteins?
Span the membrane.
Exhibit substrate specificity - accept only a particular ion or closely associated group.
What are docking marker acceptors?
Located on the inner membrane surface. Interact with secretory vehicle to allow exocytosis.
How does a vehicle from the Golgi apparatus leave the cell?
Secretory vesicle is formed from membrane of outer most Golgi sack.
Budding breaks the vesicle off.
It is then up coated in the cytosol.
It then docks at a docking marker acceptor and is discharged.
Where are receptors most commonly found and what do they do?
Commonly on outer surface. Bind to molecules in a specific manner.
What are CAMS?
Cell adhesion molecules.
Proteins like Cadherin and integrity hold cells together.
Also act as a link between internal and external environment.
What are self identity markers made out of?
Short carbohydrate chains.
What are the three types of specialised cell junctions?
Desmosomes, tight junctions and gap junctions.
What are desmosomes?
Adhering junctions that anchor cells together especially in tissues subject to stretching e.g. Skin, heart etc.
What is a tight junction?
Join the lateral edges of epithelial cells near their luminal (apical), Membranes.
Can be wither tight or leaky.
What is a gap junction?
Communicating junctions that allows the movement of charge carrying ions and small molecules between two adjacent cells.
What is an electrochemical gradient?
Both electrical and chemical acting on a molecule at the same time.
What two types of driving forces do we have?
Passive or active.
What are two forms of passive movement?
Diffusion down either a concentration or an electrical gradient.
What are the five factors of Ficks law of diffusion?
Magnitude of the concentration gradient.
Surface area of the membrane that diffusion is occurring across.
Lipid solubility of the substance.
Molecular weight of the substance.
Distance through which diffusion can take place.
What is a name for a membrane water channel?
Aquaporin.
What is osmolarity?
The concentration of osmotically active particles in a substance.
What is tonicity?
The effect a solution has on a cell e.g. Hypo ISO or hyper.
What is carrier mediated transport?
Substance binds to a carrier which undergoes a conformational shape to transport the substance.
What three characteristics determine the kind and amount of material that can be transported across the membrane by carrier mediated transport?
Specificity.
Saturation - the transport maximum.
Competitions - e.g. Amino acids.
