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large compound gland, both exo and endocrine. Its retroperitoneal. Main pancreatic duct with drains at the ampulla of Vater. Some have accesory duct of santorini, they drain exocrine hormones from acinar into duodenum. Islets of Langerhans contain the endocrine cells which drain to blood stream. Head supplied by S and I pancreaticoduodenal arteries, nech body and tail by splenic artery. Head drained by superior mesenteric and portal veins. the common bile duct meets the main pancreatic duct at ampulla of Vater. sphincter of Oddi. It has large stores of digestive carb and protein enzymes but not for lipids.


exocrine function of the pancreas

digestive enzymes secreted by pancreatic acini. sodium bicarbonate solution secreted by small ductules (duct cells) leading from acini. combined enzymes and NaHCO3-pancreatic juice flows through pancreatic duct joins bile duct empties duodenum through papilla of Vater surrounded by sphincter of Oddi. Pancreatic juice most when chyme present in duodenum.


endocrine function of the pancreas

secretes insulin and glucagon. Insulin by beta cells, glucagon alpha cells of islet of Langerhan. directly into blood. secretory unit composed acinus and intercalated duct, which merge to form interlobular ducts, then main pancreatic duct.


protein digestive enzymes

three protein digestive enzymes secreted by the pancreas: trypsin: most abundant, splits whole and partially digested proteins into peptides, dont cause release of amino acids.
Chymotrypsin: splits whole and partially digested proteins into peptides but no amino acids.
Carboxypolypeptidase: splits peptides into amino acids so completes digestion



the most abundant of the protein digestive enzymes to be secreted. It splits whole and partially digested proteins into peptides of various sizes but do not cause release of individual amino acids.



It splits whole and partially digested proteins into peptides of various sizes but do not cause release of individual amino acids.



this splits peptides into individual amino acids, thus completing the digestion of some proteins all the way to the amino acid state.


• When first synthesized in the pancreatic cells, the proteolytic digestive enzymes are in the inactive forms ( termed ‘zymogens’) which are inactive enzymatically:

1. Trypsinogen
o Activated by the enzyme enterokinase (secreted by the intestinal mucosa when chyme comes into contact with the mucosa).
o It can also be autocatalytically activated by trypsin that has already been formed from previously secreted trypsinogen.
2. Chymotrypsinogen
o Activated by trypsin to form chymotrypsin.
3. Procarboxypolypeptidase
o Activated by trypsin to form carboxypolypeptidase.
• They become activated only after they are secreted into the intestinal tract.



secreted intestinal mucosa when chyme comes into contact with mucosa, activates trypsinogen.


activation of chymotrypsinogen

trypsin to form chymotrypsin



activated trypsin to form carboxypolypeptidase, only after secreted into intestinal tract.


carbohydrates digestive enzymes

pancreatic amylase, hydrolyses starch, glycogen and other carbs except cellulose to form disaccharides and few trisaccharides.


fat digestive enzymes

pancreatic lipase: hydrolyses neutral fat into fatty acids and monoglycerides. Cholesterol esterase: causes hydrolysis of cholesterol esters. Phospholipase: splits fatty acids from phospholipids.


Trypsin Inhibitor

secretion prevents digestion of the pancreas itself. Its important proteolytic enzymes arent activated until theyve left the pancreas as trypsin would digest the pancreas itself. Cells that secrete enzymes also secrete trypsin inhibitor. formed in the cytoplasm of glandular cells prevents activation of trypsin both inside the secretory cell and in acini and ducts. This also prevents activation of the other enzymes that trypsin activates. When a duct is blocked large amounts of juice is pooled, so trypsin inhibitor is overwhelmed so the pancreas is digested giving rise to acute pancreatitis.


secretion of sodium carbonate solution

CO2 diffuses into ductal cells from blood, with carbonic anhydrase it combines with water to form carbonic acid, then dissociates into bicarbonate ions and H ions. some HCO3 enter cells across basolateral mem, via Na/HCO3 transporter. Then actively transported into lumen via Cl-HCO3 exchanger. H ions exchanged for Na ions through blood barrier by active transport. this supplies Na to provide nutrality. This causes osmotic pressure so water moves into P ducts.


stimuli causing pancreatic secretion

Ach (m3 receptors) released from parasymp vagus nerve. CCK secreted duodenal and jejunal mucosa in responce fats and amino acids. Secretin secreted duodenal mucosa in responce highly acidic food.


what do Ach and CCK stimulate the acinar cells to secrete

pancreatic digestive enzymes but small amounts water and electrolytes. without the water most enzymes remain stored in acini and ducts. Secretin stim ductal epithelial cells to secrete water solution of Na bicarbonate.


• The pancreatic acinar cell has at least two pathways for stimulating the insertion of zymogen granules and thus releasing digestive enzymes.

• ACh and CCK both activate Gαq, which stimulates PLC, which ultimately leads to the activation of PKC and the release of Ca2+.
• Elevated [Ca2+]i also activates calmodulin (CaM), which can activate protein kinases (PK) and phosphatases (PP).
• Finally, VIP and secretin both activate Gαs, which stimulates adenylyl cyclase (AC), leading to the production of cAMP and the activation of PKA.
• The duct cells have receptors for secretin, GRP, all of which stimulate HCO3- secretion.
• The duct cells have receptors for substance P which inhibits HCO3- secretion.


the presence of food in the stomach stimulates pancreatic secretions from acinar cells how?

distention of the stomach activates vagovagal reflex. protein digestion products stimulate g cells in the antrum to release gastrin which is a poor agonist of CCKA receptor on acinar cells.


s cells

secrete secretin stimulated by acidity of chyme which stim HCO3 production


I cells

stimulated by protein and lipid breakdown which secretes CCK which stim enzyme production. also causes gallbladder contractions



27 amino acid polypeptide. inactive form prosecretin in S cells in duo and jejunal mucosa.


what 4 enzymes are in enterocytes in the lining of villi of the small intestine

Lactase: lactose into galactose and glucose. Sucrase: sucrose into fructose and glucose. Maltase: split maltose into multiple molecules of glucose. alpha dextinase: splits small glucose polymers into multiple mol of glu.


which two peptidase enzymes are important in the SI

aminopolypeptidase and dipeptidase. split polypeptides into tripeptides and dipeptides and amino acids.


emulsification of fats

physical breakdown of fat globules into very small sizes so that the water-soluble digestive enzymes can act on the globule surfaces. first agitation in the stomach to mix fat with other. emulsification occurs in duodenum with bile which contains salts and phospholipid lecithin. The polar parts (the points where ionization occurs in water) of bile salts and lecithin molecules are soluble in water, whereas most of the remaining portions of their molecules are soluble in fat.
o Therefore, the fat-soluble portions of these liver secretions dissolve in the surface layer of the fat globules, with the polar portions projecting.


polar projections

5. The polar projections, in turn, are soluble in the surrounding watery fluids, which greatly decreases the interfacial tension of the fat and makes it soluble as well.
o When the interfacial tension of a globule of non-miscible fluid is low, this non-miscible fluid, on agitation, can be broken up into many very minute particles far more easily than it can when the interfacial tension is great.
o Consequently, a major function of the bile salts and lecithin, especially the lecithin, in the bile is to make the fat globules readily fragmentable by agitation with the water in the small bowel.


lipase enzymes

water-soluble compounds and can attack the fat globules only on their surfaces. The main enzyme to further break down fat globules is the pancreatic lipase enzyme.
o The triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides.


formation of micelles

hydrolysis of tri result in many monogly and fatty acids in the vicinity of digesting fats which blocks further digestion. Bile salts prevent this as form micelle around fat globule to be digested, develop because of hydrophilic and hydrophobic bile salts.• Micelles also help transport the monoglycerides and free fatty acids to the brush borders of the intestinal epithelial cells.
• There the monoglycerides and free fatty acids are absorbed into the blood, but the bile salts themselves are released back into the chyme to be used again


methods of absorption in the small intestine

simple diffusion-mainly by lipids.
Endocytosis-vit b12 and intrinsic factors
Carrier mediated-amino acids sugars and some lipids


sites of absorption

mouth oesophagus stomach-limited diffusion
Duo and jejunum-major sire of nutrient and ion absorb
Ileum-vit b12 and bile salts
colon-Na and H20 and short chain fatty acids
rectum-limited diffusion


why is the small intestine the main site of absorption

1. Large absorptive surface area.
2. Rich blood supply of blood vessels and lacteals (to drain lipids) found in the mucosal lining.
3. Expansion of nutrient specific transport proteins.
o These belong to a family of transport proteins called “Solute Carrier (SLC) Transport Proteins”.
o Although, these transport proteins are found on the plasma membrane of the intestinal epithelial cells, they too can be found on the organelles inside the cell itself, thus leading to undefined side effects.


surface area of small intestine comprises of

1. Folds of Kerckring
2. Villi (+ crypts of Lieberkuhn)
3. Microvilli


functional differences throughout the small intestine regarding absorption

segmental heterogenity: diff parts are involved in absorption of diff components of diet.
Crypt-villus/surface heterogenity: Absorptive function is located in villous cells in the small intestine, whereas secretory processes reside in the crypt cells.
Cellular heterogenity: specific transport mechanisms are restricted to certain cells.


3 monosaccharides absorbed in the small intestine

glucose most abundant monosaccharide absorbed (80%). This is because glucose is the final digestion product of carbohydrates, galactose, fructose. All absorbed by active transport process.


absorption of glucose

dependant on Na absorpt. Cotransport with active transport of Na. first Na AT into blood depleting in cell, so dec causes absorpt of Na from lumen into apical mem by facilitated diffusion, 2NA-glucose. Then gluvose moved out cell again into blood by facilitated diffusion.


absorption of galactose and fructose

galactose same as glucose. Fructose by facilitated diffusion,  Much of the fructose, on entering the cell, becomes phosphorylated, then converted to glucose, and finally transported in the form of glucose the rest of the way into the blood.
 Because fructose is not co-transported with sodium, its overall rate of transport is only about one half that of glucose or galactose


absorption of fats

bile micelles are soluble in chyme as charged exterior. monoglyceriddes and FA carried to microvilli where diffuse out micelles and into cell as soluble in epithelial cell mem. bile micelles when function again. 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.
• These chylomicrons are exocytosed through the base of the epithelial cell, and are transported in the lymphatic system to the liver.


absorption of proteins

absorbed when di tripeptides or amino acids. Na cotransport, Most peptide or amino acid molecules bind in the cell’s microvillus membrane with a specific transport protein that requires sodium binding before transport can occur.
 After binding, the sodium ion then moves down its electrochemical gradient to the interior of the cell and pulls the amino acid or peptide along with it.
 This is called co-transport (or secondary active transport) of the amino acids and peptides.
• A few amino acids do not require this sodium co-transport mechanism but instead are transported by special membrane transport proteins in the same way that fructose is transported, by facilitated diffusion.


absorpton of water

osmosis, through the tight junctions between the apical borders of the epithelial cells, but much also occurs through the cells themselves.


absorption of chloride ions

• In the upper part of the small intestine, chloride ion (Cl-) absorption is rapid and occurs mainly by diffusion.
• Absorption of sodium ions through the epithelium creates electronegativity in the chyme and electropositivity in the paracellular spaces between the epithelial cells.
• Then chloride ions move along this electrical gradient to “follow” the sodium ions.


absorption of bicarbonate ions in the duodenum and jejunum

• Often large quantities of bicarbonate ions must be reabsorbed from the upper small intestine because large amounts of bicarbonate ions have been secreted into the duodenum in both pancreatic secretion and bile.
• The bicarbonate ion is absorbed in an indirect way as follows:
o When sodium ions are absorbed, moderate amounts of hydrogen ions are secreted into the lumen of the gut in exchange for some of the sodium.
o These hydrogen ions in turn combine with the bicarbonate ions to form carbonic acid (H2CO3), which then dissociates to form water and carbon dioxide.
 The water remains as part of the chyme in the intestines, but the carbon dioxide is readily absorbed into the blood and subsequently expired through the lungs.
 Thus, this is so-called “active absorption of bicarbonate ions”.


1 unit alcohol

it takes 1 hour for the liver to clear 1 unit. its equivalent to 10ml or 8g.


reccomended safe limits of alcohol

used to be 14 for women 21 for men but its now 12 for both


alcohol metabolism

absorbed from upper SI via portal vein and transported to liver. some metabolised in stomach by alcohol dehydrogenase. Females lack this. In the liver converted acetaldehyde and excreted by conversion to CO2 in citric acid cycle, cytochrome p4502E1 involved.


effects of alcohol

• Alcohol has a stimulant effect at low levels.
• However, chronic use of alcohol (moderate to severe doses) has depressant effects on the CNS, mainly the depression of cardiovascular and respiratory centres in the brainstem.
• At low doses, alcohol has a protective effect against atheromas.


neg social effects of alcohol

 Unwanted pregnancy, sexually transmitted disease
 Cause of road traffic accidents (not only as a result of drink-driving, but also drunken pedestrians and cyclists).
 Domestic violence


neg physical effects of alcohol

fetal alcohol syndrome. alcohol cardiomyopathy. CNS problems. (e.g. Korsakoff’s psychosis – plausible answers that don’t make sense / e.g. Wernicke’s encephalopathy – decreased thyamine affects mammillary bodies in the brain) Withdrawl. Acute poisoning-confusion vomiting seizures blue pale skin.


alcohol affects on the GI

 Mouth/ Upper GI tract
o Increased incidence of cancers of upper GI tract / aerodigestive tract
o Especially tongue, buccal mucosa, pharynx, upper oesophagus
o Associated particularly with spirit use
o Possible a co-factor with cigarette smoking
 Oesophagus
o Carcinoma of oesophagus, especially squamous carcinoma
o Oesophageal varices (dilation of veins, subject to rupture), associated with chronic liver disease
 Stomach
o Acute gastritis
o Acute ulceration
o Chronic peptic ulceration
o Portal gastropathy
 Pancreas
o Acute pancreatitis
o Chronic pancreatitis
 Liver
o Alcohol liver disease
 Acute fatty change (early) - reversible
 Alcoholic hepatitis - reversible
 Hepatic fibrosis - reversible
 Cirrhosis (severe) – irreversible
 Hepatocellular carcinoma


hepatic fibrosis

reversible. o Starts in acinar zone 3
o Initially pericellular fibrosis
o Caused by activation of hepatic stellate (Ito) cell = facultative myofibroblast
o Reversible by TIMPs on withdrawal of alcohol


alcoholic hepatitis

reversible.  Alcoholic Steatohepatitis
o Fatty change, mainly large droplet
o Mallory’s hyaline
o Intracytoplasmic accumulation of cytoskeletal components (keratin)
o Associated neutrophil polymorph infiltration
o Reversible on withdrawal of alcohol

 Non-alcoholic steatohepatitis (NASH)
o Identical features to alcoholic hepatitis
o Associated with obesity, diabetes mellitus, hyperlipidaemia, drug use especially corticosteroids and amiodarone
o May progress to fibrosis and cirrhosis
o Reversible on correction of underlying factor



irreversible. o Liver Failure
 Protein synthesis: low albumin
 Coagulation factors: bleeding
 Hyperoestrogenism: gynaecomastia, gonadal atrophy, Dupuytren’s contracture, liver palms, spider naevi
 Jaundice
 Encephalopathy: confusion
o Portal Hypertension
 Ascites
 Varices
 Splenomegaly
o Hepatocellular Carcinoma
 Very common carcinoma where HBV endemic (SE Asia, Africa)
 Very poor prognosis i.e. 6-9 months
 Raised serum alpha-fetoprotein levels


alcohol burden

• Burden on the NHS, UK:
 £3.5billion per year
 1 million admissions per year caused by alcohol
 10% of the UK burden of disease and death
• Burden on Society:
 £21billion per year
 Crime- £11 billion per year (England 2010-11)
 40% Road Traffic Accidents
 40% deaths in fires
 20% child abuse
 2.6 million children live with parents drinking hazardously
 700,000 children live with dependent drinkers


public health measures against alcohol

 Price
 Place- restrict physical availability
 Prevent promotion/advertising
 Public education
 Public places- Alcohol-free zones
 Prosecute under-age sales, illicit and illegal alcohol
 Packaging- generic
 Penalise misleading industry messages
 Brief advice
 Treat dependent drinkers


price of alcohol

 Alcohol is now 61% more affordable than it was in 1980
 Proposed minimum unit price was 45p per unit
o Reduce alcohol consumption by 4.3%
o 123 lives saved in year 1; 624 lives saved every year from year 10
o 23,700 fewer hospital admissions per year from year 10
o Direct saving to NHS after 10 years: £417m
o 34,000 fewer crimes a year
o Saving from crime: £138m per year
 Floor price=cost of duty + VAT


tools to identify heavy drinkers

 Blood tests:
o Gamma glutamyl transferase (GGT)
o Mean corpuscular volume (MCV)
 Screening tools - CAGE or AUDIT can help identify heavy drinkers. • A CAGE questionnaire is used as a screening test for problem drinking and potential alcohol problems.
• A total score of 2 or greater is considered clinically significant.
• Alcohol Use Disorders Identification Test (AUDIT)
• Better at detecting harmful drinking
• Score >8 is 95% sensitive and 85% specific for harmful drinking



someone who ‘has no control over their behaviour’, ‘lacks moral fibre’, ‘uses a maladaptive coping mechanism’, ‘has an addictive behaviour’.



: ‘a need for a drug’, ‘the use of a substance that is psychologically and physiologically addictive’, ‘showing tolerance and withdrawal’



‘showing psychological and physiological withdrawal’.


3 models if addiction

1. Moral Model: addiction as the result of weakness and a lack of moral fibre
2. Biomedical Model: addiction as a disease
3. Social Learning Theories: behaviours that are learned according to the rules of learning theory


moral model

• Addicts are “weak” and can overcome a compulsion to use with willpower.
• Drug abusers choose to use drugs.
• Drug abusers are anti‐social and should be punished.
• Drugs are evil


biomedical model

• Addiction as a “brain disease”.
• Neurotransmitter imbalance.
• Disease Model:
 Agent: drug
 Vector: dealers
 Host: addict
• Need to “stamp out” the disease by eliminating drugs.
• Drug antagonist medications: Welbutrin; naltrexone; antabuse


social model

• Drug use is a learned behaviour:
 Classical conditioning: associative behaviour (e.g. associating drinking with feeling relaxed)
 Operant conditioning: probability of behaviour occurring is increased if it is either positively reinforced by the presence of a positive event, or negatively reinforced by the absence or removal of a negative event (e.g. probability of drinking increased by feelings of social acceptance, confidence and control and removal of withdrawal symptoms).
 Observational learning/ modelling: behaviours are learnt by observing significant others carrying them out (e.g. parents drinking).
 Cognitive factors: factors such as self-image, problem-solving behaviour, coping mechanisms.
People use drugs because drug use is modelled by others. Peer pressure. Environmental effects lead to drug use (advertising, etc). Drug use is a maladaptive relationship negotiation strategy.


alcohol and dopamine-reward sensation

• Alcohol inhibits the inhibition that GABA interneurones have on dopamine neurones.
• So now dopamine interneurones become dis-inhibited, hence why there is an increase in dopamine release.
• So you have extra dopamine in the brain – the dopamine receptors upregulate.
• So when you are presented with the stimulus of alcohol, your response is dampened.
• Therefore, you have to drink more to maintain the state of reward sensation and so you become addicted.


acute pancreatitis

an inflammatory condition that may cause extensive local damage to the pancreas, as well as compromise the function of other organs such as the lungs.
• Main causes:
 Alcohol ingestion and acute intoxication
 Gallstones (obstruction of pancreatic duct)
 Bile reflux
 Trauma
• Clinical presentation:
 Severe abdominal pain that radiates to the back
 Nausea and vomiting
 Rapid development of shock
 Greatly elevated serum amylase


chronic pancreatitis

• Main causes:
 Alcohol (especially chronic excessive consumption)
 Autoimmune pancreatitis
 Cystic fibrosis (Cl- ion channel dysfunction in the pancreas as well)
 Hyperlipidaemia
 Idiopathic
Clinical presentation:
 Intermittent severe upper abdominal and back pain
 Weight loss
 Exocrine tissue replaced by fibrosis
 Leads to pancreatic malabsorption (steatorrhoea and reduced vitamins A, D, E, K)
 Relative preservation of endocrine tissue


malnutrition/malabsorption symptoms

 Steatorrhea (bulky, greasy, light cream coloured, excessive foul smelling faeces) – “fatty stools”.
 Excessive flatus – this is because the intestinal bacteria usually only receive fibre. But due to indigestion and malabsorption, there is more food (mainly fats) available for the intestinal bacteria
 Diarrhea is rarely a feature of gastroduodenal disease, except coeliac disease. It is a symptom of pancreatitis.
 Excessive weight loss with a normal diet.


how NaCl causes neutralization of HCL

: HCl +NaHCO3 >>> NaCl +H2CO3
 Then the carbonic acid immediately dissociates into carbon dioxide and water.
 The carbon dioxide is absorbed into the blood and expired through the lungs, thus leaving a neutral solution of sodium chloride in the duodenum.
 In this way, the acid contents emptied into the duodenum from the stomach become neutralized, so that further peptic digestive activity by the gastric juices in the duodenum is immediately blocked.
 Because the mucosa of the small intestine cannot withstand the digestive action of acid gastric juice, this is an essential protective mechanism to prevent development of duodenal ulcers.
• Bicarbonate ion secretion by the pancreas provides an appropriate pH for action of the pancreatic digestive enzymes, which function optimally in a slightly alkaline or neutral medium, at a pH of 7.0 to 8.0.
 The pH of the sodium bicarbonate secretion averages 8.0.



• Cholecystokinin (CCK) is a polypeptide containing 33 amino acids.
• It is released by I-cells in the duodenal and upper jejunal mucosa.
• This release of CCK results especially from the presence of proteoses and peptones (products of partial protein digestion) and long-chain fatty acids in the chyme coming from the stomach.
• CCK, like secretin, passes by way of the blood to the pancreas, where it binds to CCKA receptors causing secretion of pancreatic digestive enzymes by the acinar cells.
• This accounts for 70-80% of the total secretion of the pancreatic digestive enzymes after a meal.
• Picture:
 Intense sodium bicarbonate secretion in response to acid in the duodenum, stimulated by secretin.
 A dual effect in response to soap (a fat).
 Intense digestive enzyme secretion (when peptones enter the duodenum) stimulated by cholecystokinin


Hydrolysis of Disaccharides and small glucose polymers into monosaccharides by intestinal epithelial enzymes

• The enterocytes lining the villi of the small intestine contain four enzymes:
1. Lactase: split lactose into galactose and glucose.
2. Sucrase: split sucrose into fructose and glucose.
3. Maltase: split maltose into multiple molecules of glucose.
4. α-dextrinase: split small glucose polymers into multiple molecules of glucose.

• The enzymes are located in the enterocytes covering the intestinal microvilli brush border, so that the disaccharides are digested as they come in contact with these enterocytes.
• Thus, the final products of carbohydrate digestion are all monosaccharides.
 They are all water soluble and are absorbed immediately into the portal blood.
• Glucose represents more than 80% of the final products of carbohydrate digestion, and galactose and fructose each seldom more than 10%.


digestion of peptidases in the enterocytes that line the small intestinal villi

• The brush border consists of hundreds of microvilli projecting from the surface of each cell.
• In the membrane of each of these microvilli are multiple peptidases that protrude through the membranes to the exterior, where they come in contact with the intestinal fluids.
• Two types of peptidase enzymes are especially important:
1. Aminopolypeptidase
2. Dipeptidases
• They split large polypeptides into tripeptides and dipeptides and a few into amino acids.
• The breakdown products of polypeptides are transported through the microvillar membrane to the interior of the enterocyte.
• There are more specific peptidases inside the enterocyte.
• Once the peptides have been broken down into amino acids, they enter the blood from the basolateral membrane of the enterocyte


digestion of fats in the intestine

• Some triglycerides are digested in the stomach by lingual lipase that is secreted by lingual glands in the mouth and swallowed with the saliva.
• This amounts for 10% of fat digestion.
• Fat digestion mainly occurs in the small intestine


emulsification of fat by bile acids and lecithin

• The first step in fat digestion is emulsification.
• This is the physical breakdown of fat globules into very small sizes so that the water-soluble digestive enzymes can act on the globule surfaces.
1.It begins by agitation in the stomach to mix the fat with the products of stomach digestion.
2.Then, most of the emulsification occurs in the duodenum under the influence of bile.
3.Bile doesn’t contain any digestive enzymes; however, it does contain a large quantity of bile salts as well as the phospholipid lecithin.
4.The polar parts (the points where ionization occurs in water) of the bile salts and lecithin molecules are highly soluble in water, whereas most of the remaining portions of their molecules are highly soluble in fat.
oTherefore, the fat-soluble portions of these liver secretions dissolve in the surface layer of the fat globules, with the polar portions projecting.
5.The polar projections, in turn, are soluble in the surrounding watery fluids, which greatly decreases the interfacial tension of the fat and makes it soluble as well.
oWhen the interfacial tension of a globule of non-miscible fluid is low, this non-miscible fluid, on agitation, can be broken up into many very minute particles far more easily than it can when the interfacial tension is great.
oConsequently, a major function of the bile salts and lecithin, especially the lecithin, in the bile is to make the fat globules readily fragmentable by agitation with the water in the small bowel.
6.As the fat globules are broken down (diameter is reduced) as a result of agitation in the small intestine, their surface area increases. Therefore, the emulsification process increases the surface area of the fat globules for the action of enzymes to follow.
7.The lipase enzymes are water-soluble compounds and can attack the fat globules only on their surfaces. The main enzyme to further break down fat globules is the pancreatic lipase enzyme.
oThe triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides.


SI prime site of absorption of food for a few reasons

1. Large absorptive surface area.
2. Rich blood supply of blood vessels and lacteals (to drain lipids) found in the mucosal lining.
3. Expansion of nutrient specific transport proteins.
o These belong to a family of transport proteins called “Solute Carrier (SLC) Transport Proteins”.
o Although, these transport proteins are found on the plasma membrane of the intestinal epithelial cells, they too can be found on the organelles inside the cell itself, thus leading to undefined side effects


direct absorption of fatty acids into the portal blood

• Small quantities of short- and medium-chain fatty acids are absorbed directly into the portal blood rather than being converted into triglycerides and absorbed by way of the lymphatics.
• The cause of this difference between short- and long-chain fatty acid absorption is that the short-chain fatty acids are more water-soluble and mostly are not reconverted into triglycerides by the endoplasmic reticulum.
• This allows direct diffusion of these short-chain fatty acids from the intestinal epithelial cells directly into the capillary blood of the intestinal villi.


active transport of Na

• Sodium ions (Na+) are actively transported from inside the epithelial cells through the basal and side walls of these cells into paracellular spaces.
• This occurs due to the Na+/K+ ATPase pump mainly.

• Part of the sodium is absorbed along with chloride ions - the negatively charged chloride ions are mainly passively “dragged” by the positive electrical charges of the sodium ions.
• Active transport of sodium through the basolateral membranes of the cell reduces the sodium concentration inside the cell to a low value (50 mEq/L).
• Because the sodium concentration in the chyme is normally about 142 mEq/L (that is, about equal to that in plasma), sodium moves down this steep electrochemical gradient from the chyme through the brush border of the epithelial cell into the epithelial cell cytoplasm.
• This provides still more sodium ions to be transported by the epithelial cells into the paracellular spaces.


aldosterone effect on Na absorption

• When a person becomes dehydrated, large amounts of aldosterone almost always are secreted by the cortices of the adrenal glands.
• Within 1 to 3 hours this aldosterone causes increased activation of the enzyme and transport mechanisms for all aspects of sodium absorption by the intestinal epithelium.
• And the increased sodium absorption in turn causes secondary increases in absorption of chloride ions, water (thereby overcoming the dehydration), and some other substances.
• This effect of aldosterone is especially important in the colon because it allows virtually no loss of sodium chloride in the faeces and also little water loss.


diagnosis of chronic pancreatitis

 Faecal elastase test – this is a stable proteolytic enzyme that can be picked up in the faeces. It indicates severe pancreatitis.
 Endoscopic ultrasound – this isn’t so good as there is a lot of bowel gas to go through when imaging the pancreas. However, it is a good way to look at the texture of the pancreas. It is useful, as it allows us to drain cysts, and dilate structures if needed.
 CT/MRI – cross section imaging
• Possible:
 Urine collection and test for PABA (para-amino Benzoic Acid)
 Direct hormonal stimulation
• Historical:
 Faecal fat analysis after a three day sample.


alcohol and chronic pancreatitis

• Alcohol causes an individual to produce more viscous secretions.
• Alcohol increases the protein secretions (enzymes) from the acinar cells of the pancreas.
• Alcohol reduces the secretion of bicarbonate ions and water from duct cells.
• This prevents the enzymes from being carried away as part of ‘pancreatic juice’.
• The enzymes accumulate in the acini (plugging of the pancreatic duct) and begin to digest the pancreas itself.



• Pancreatin is a mixture of several digestive enzymes produced by the exocrine cells of the pancreas.
• It is composed of amylase, lipase and protease (trypsin).
• This mixture is used to treat conditions in which pancreatic secretions are deficient, such as in pancreatitis.


chronic pancreatitis complications

1. Pseudocysts
 Localised fluid collection – this is as a response to chronic inflammation usually.
 Can be massive - obstruction and can cause pressure on the surrounding tissue and cause pain.
 Can become infected
To treat pseudocysts, the fluid can be drained:
 FNA fluid analysis : Amylase and Ca 19-9 will show if the pseudocyst is pancreatic.
There are new stents that can now be placed inside the cyst itself, which not only draws out the fluid, but provides access to the tissue inside the cyst. These stents have decreasaed the rates of surgery because of their success.

2. Bleeding:
 Variceal
 Due to underlying cause – ALD
 Splenic vein thrombosis
 Pseudocyst – when draining the cysts, they can pull on blood vessels and cause tears and ruptures.
 Pseudoaneurysm
3. Obstruction - Bile duct and duodenal


pancreatic cancer

 It’s not a common cancer but if you have chronic pancreatitis, then your risk of developing it increases by 20%.
 It causes increased pain, weight loss and obstructive jaundice.
 There is a poor prognosis:
 There is surgical management – a CT scan is carried out every 3 years to pick up early changes in chronic pancreatitis patients of a developing cancer.


oral rehydration solution

• The therapeutic use of oral rehydration solution (ORS) provides an excellent demonstration of applied physiology.
• Many diarrheal illnesses are caused by bacterial exotoxins that induce fluid and electrolyte secretion by the intestine.
• Hence such a toxin is referred to as an enterotoxin.
• Despite the massive toxin-induced fluid secretion, both intestinal morphology and nutrient coupled Na+ absorption are normal.
• Because nutrient-coupled (e.g., glucose or amino acid) fluid absorption is intact, therapeutically increasing the concentration of glucose or amino acids in the intestinal lumen can enhance absorption.
• ORS contains varying concentrations of glucose, Na+, Cl−, and HCO3 and is extremely effective in enhancing fluid and electrolyte absorption in secretory diarrhoea when the intestine secretes massive amounts of fluid.
• Administration of ORS can reverse the dehydration and metabolic acidosis that may occur in severe diarrhoea and that are often the primary cause of morbidity and mortality, especially in children younger than 5 years.


pancreatic vs gastric dysfunction

• Stomach disorders lead to imbalances in acid secretion (usually an excess).
• Therefore, drugs that act on acids (antacids) or acid secretion (PPIs / H2 antagonists etc) would be effective in gastric dysfunction.
• However, if it is pancreatic dysfunction then such drugs have little effect.

• In both cases, one of the most common symptoms will be pain.
 In pancreatitis, the pain is usually referred to the back of the body too, whereas with gastric pain, the pain is localized to the epigastrium.
 Analgesics and NSAIDs have little effect in visceral pain, but they are efficient for somatic pain.

• Brain-Gut Axis:
 This is the connection between the gut and the brain that brings about physiological deviations from the norm and pain.
 The vagus nerve goes to the brainstem, whereas the spinal cord projections go to higher centres in the brain.


investigations of the GI tract

• Endoscopy
 No role in diagnosis of pancreatitis.
 Maybe needed to rule out other causes of pain, vomiting or bleeding if uncertain.
 Specialised endoscopic therapy is sometimes needed (e.g. for gall stones).
• Endoscopic Retrograde Cholangiopancretography (ERCP)
 This involves injecting a dye into the pancreatic duct.
 In pancreatitis, there will be (1) clubbing of the side branches of the main pancreatic duct (2) the main pancreatic duct is dilated (1.5x normal diameter).
 It is RISKY
• CT and MRI imaging
• Pancreatic Function Testing
 Levels of faecal elastase enzyme are checked as this is a stable proteolytic enzyme.
 A 3 day faecal fat collection can be done, but this is inconvenient.


visceral pain

• Poorly localised in the brain
• Midline perception
• Upper/mid/lower ROUGHLY corresponds to fore/mid/hindgut
• BUT! Not reliable enough
• Autonomic activation if severe – Sweaty, faint (low BP), pale, nauseated

• Visceral pain is felt via the somatosensory receptor pathway (Spinothalamic tract):
 Visceral nociceptors
o Intense mechanical stimuli (distention and overstretching)
o Chemical stimuli
o Inflammation

o Not all organs have nociceptors though


visceral hypersensitivity

• Some visceral nociceptors become more active after inflammation.
• Lower pain threshold
• Normal levels of distension e.g. after eating can become painful
• This may be a part of functional dyspepsia/IBS pain
• And contribute to chronic pancreatitis pain


somatic pain

• More readily and precisely localised
• Parietal peritoneum is somatic – so e.g. perforation of an ulcer or appendicitis becomes more localised
• Retroperitoneal nerves are somatic too so pancreatic pain in the back is not necessarily entirely referred pain e.g. if an invasive cancer


referred pain

•Referred pain is pain felt in places remote from the location of the affected organ – e.g. cardiac pain perceived down the arm or jaw
•Abdominal pain can also be referred – e.g. perceived in back, pelvis, shoulder
•Referred pain occurs due to convergence on second order neurones. The same Spinothalamic pathways carry nerves from adjacent skin and muscles – “visceromotor convergence”.
The brain misinterprets the signals that originate from internal organs as coming from co-innervated somatic regions.



Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids.