Case 3 Flashcards

Question

without water in the duct what happens?

Answer 1

Without the water, most of the enzymes remain temporarily stored in the acini and ducts until more fluid secretion comes along to wash them into the duodenum.

Answer 2

stimulates ductal epithelial cells to secrete of large quantities of water solution of sodium bicarbonate.

Answer 3

* When these stimuli all occur at once, the total secretion is far greater than the sum of the secretions caused by each one separately. * Therefore, the various stimuli are said to ‘multiply’, or ‘potentiate’ on another.

Answer 4

* 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.

Answer 5

* The duct cells have receptors for secretin, GRP (gastrin-releasing peptide), all of which stimulate HCO3- secretion. * The duct cells have receptors for substance P which inhibits HCO3- secretion.

Answer 6

* The sight, taste, or smell of food stimulates pancreatic acinar cells, through the vagus nerve and M3 receptors (acetylcholine)(biggest stimulus to get pancreas working), to release digestive enzymes, and to a lesser extent, stimulates duct cells to secrete HCO3- and fluid. * However, only a small amount of the secretion flows immediately through the pancreatic ducts into the intestine because only small amounts of water and electrolytes are secreted along with the enzymes. - VIP (vasoactive intestinal peptide) - GRP (gastrin releasing peptide)

Answer 7

• The presence of food modulates pancreatic secretion by: 1. Affecting hormone release 2. Stimulating neural pathways 3. Modifying pH and availability of nutrients in the proximal part of the small intestine • The presence of food in the stomach stimulates pancreatic secretions – primarily from the acinar cells – through two routes: 1. Distention of the stomach activates a vagovagal reflex. 2. Protein digestion products (peptones) stimulate G-cells in the antrum of the stomach to release gastrin, which is a poor agonist of the CCKA receptors on acinar cells. - VIP - GRP - gastric phase smaller component

Answer 8

* Protein and lipid breakdown products stimulate a vagovagal reflex that stimulates primarily the acinar cells. * The acidity of the chyme stimulates S-cells in the duodenum to secrete secretin, which acts on receptors on duct cells, stimulating HCO3- secretion (main effect in this phase). * Protein and lipid breakdown products stimulate I-cells in duodenum to secrete CCK, which acts on receptors on acinar cells, stimulating enzyme secretion. - most important stimulus to get pancreas working – responsible for 80% of what pancreas produces

Answer 9

``` cephalic = 25% gastric = 10-20% intestinal = 50-80% ```

Answer 10

* Secretin is a polypeptide, containing 27 amino acids, present in an inactive form, prosecretin, in so-called S-cells in the duodenal and jejunal mucosa. * When acid chyme with pH less than 4.5 to 5.0 enters the duodenum from the stomach, it causes duodenal mucosal release and activation of secretin, which is then absorbed into the blood. * The constituent of chyme that causes this secretin release is the HCl from the stomach. * Secretin in turn causes the pancreas to secrete large quantities of fluid containing a high concentration of bicarbonate ion (up to 145mEq/L) but a low concentration of chloride ion.

Answer 11

• Sodium bicarbonate causes neutralization of the HCl. • This is followed by another reaction in the duodenum: 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.

Answer 12

• 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.

Answer 13

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.

Answer 14

in the enterocytes covering the intestinal microvilli brush border, so that the disaccharides are digested as they come in contact with these enterocytes.

Answer 15

• 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%.

Answer 16

* 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.

Answer 17

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.

Answer 18

* 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.

Answer 19

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. o Therefore, 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. 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. 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.

Answer 20

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. o The triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides.

Answer 21

• The hydrolysis of triglycerides results in accumulation of monoglycerides and free fatty acids in the vicinity of digesting fats, which block further digestion. • Bile salts help prevent this.  They form a ‘micelle’ around the fat globule that is to be digested.  These develop because of the hydrophilic and hydrophobic nature of 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 and again for this “ferrying” process. 1. Emulsification of large fat droplets (increase surface area for action of lipase) 2. Formation of mixed (contain mixture of monoglycerides, fatty acids, bile salts) micelles = stabilises products of TG hydrolysis (MG + FA) while they are ‘translocated’ to apical membrane from lumen

Answer 22

* Triglycerides do not stimulate pancreatic secretion, but their hydrolytic products – monoglycerides and free fatty acids – do. * The longer the chain of the fatty acid, the greater is the secretory response.

Answer 23

 Simple diffusion – this is the main way in which lipids are absorbed  Carrier-mediated – amino acids, sugars and possibly lipids - secondary active - facilitated diffusion  Endocytosis - (receptor-mediated) – vitamin B12 + intrinsic factor -cholesterol -small portion of absorption, although larger part when you are baby/younger

Answer 24

 Mouth, oesophagus, stomach – limited diffusion  Duodenum and jejunum – this is the major site of nutrient and ion absorption  Ileum – vitamin B12 and bile salts & K+ (huge length of small intestine) (used for absorption if duodenum and jejunum don’t do good enough job)  Colon – some Na+ and H2O (+short chain fatty acids)  Rectum – limited diffusion

Answer 25

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.

Answer 26

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

Answer 27

* The small intestine absorbs net amounts of water, Na+, Cl-, and K+. * The small intestine secretes HCO3-.

Answer 28

1. Segmental heterogeneity  Different parts of the small intestine are involved in the absorption of different components of diet. 2. Crypt-villus/surface heterogeneity  Absorptive function is located in villous cells in the small intestine, whereas secretory processes reside in the crypt cells. 3. Cellular heterogeneity  Specific transport mechanisms are restricted to certain cells.

Answer 29

• Essentially all the carbohydrates in the food are absorbed in the form of monosaccharides; only a small fraction are absorbed as disaccharides and almost none as larger carbohydrate compounds. • There are three monosaccharides that are absorbed: 1. Glucose – most abundant monosaccharide absorbed (80%). This is because glucose is the final digestion product of carbohydrates. 2. Galactose 3. Fructose • All monosaccharides are absorbed by an active transport process.

Answer 30

* Glucose absorption is dependent on Na+ ion absorption. | * Glucose absorption occurs in a cotransport mode with active transport of sodium.

Answer 31

• There are two stages in the transport of sodium through the intestinal membrane that cause absorption of glucose: 1. Active transport of sodium ions through the basolateral membranes of the intestinal epithelial cells into the blood, thereby depleting sodium inside the epithelial cells. 2. Decrease of sodium inside the cells causes absorption of sodium ions from the intestinal lumen across the apical membrane of the epithelial cells to the cell interiors by a process of facilitated diffusion.  2Na+ ions bind to a sodium-glucose transporter protein.  This causes absorption of glucose.  The low concentration of sodium inside the cell literally “drags” sodium to the interior of the cell and along with it the glucose at the same time.  Once inside the epithelial cell, other transport proteins and enzymes cause facilitated diffusion of the glucose through the cell’s basolateral membrane into the paracellular space and from there into the blood. - Na+/K+-ATPase pump – basolateral membrane - Na+-dependent co-transporter SGLT1 (sodium-glucose transporter 1)(secondary active into cell) (2Na+ and 1glc (glucose)) (works for glucose and galactose – they’re both hexose sugars) - GLUT2 (facilitated diffusion out of basolateral membrane) (glucose transporter) (fructose can also move out of the cell via this) Secondary active transport = against a concentration gradient – energy derived from Na+ gradient created by Na+ pump (Na+ pump = primary active transport)

Answer 32

by the same mechanism as glucose.

Answer 33

Fructose absorption does not occur by the sodium co-transport mechanism. Instead, fructose is transported by facilitated diffusion all the way through the intestinal epithelium but not coupled with sodium transport.  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. - GLUT5 (facilitated diffusion into cell) (fructose = pentose sugar) - GLUT2 (facilitated diffusion out of basolateral membrane) (glucose transporter) (fructose can also move out of the cell via this)

Answer 34

* The bile micelles, which develop during digestion of fats, are soluble in chyme because of their size and their highly charged exterior. * In this form, the monoglycerides and free fatty acids are carried to the surfaces of the microvilli of the intestinal cell brush border and then penetrate into the recesses among the moving, agitating microvilli. * Here, both the monoglycerides and fatty acids diffuse immediately out of the micelles and into the interior of the epithelial cells, which is possible because the lipids are also soluble in the epithelial cell membrane. * This leaves the bile micelles still in the chyme, where they function again and again to help absorb still more monoglycerides and fatty acids – a “ferrying” function. * After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell’s smooth endoplasmic reticulum; here, they are mainly used to form new triglycerides that are subsequently released in the form of chylomicrons. * These chylomicrons are exocytosed through the base of the epithelial cell, and are transported in the lymphatic system to the liver. FAT ABSORPTION (A DEVELOPING STORY) i. Simple diffusion of FA – limited with few FFAs in undissociated state (pKa about 4.9) ii. FFA transporters – FAT plus CD36 + others? (SCFA transporter in colon) iii. MG transport – evidence for carrier-mediated mechanisms (no detail) MG & FA ABSORPTION & TG RE-SYNTHESIS - FA & MG are absorbed (in some way) … (lets just say simple diffusion) THEN: - TG re-synthesised in ER, packaged in chylomicrons - Exocytosis of chylomicrons - Chylomicrons transported in lymphatic system to liver

Answer 35

* 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.

Answer 36

• Most proteins, after digestion, are absorbed through the luminal membranes of the intestinal epithelial cells in the form of dipeptides, tripeptides, and a few free amino acids. • The energy for most of this transport is supplied by a sodium co-transport mechanism in the same way that sodium co-transport of glucose occurs:  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. • At least five types of transport proteins for transporting amino acids and peptides have been found in the luminal membranes of intestinal epithelial cells. This multiplicity of transport proteins is required because of the diverse binding properties of different amino acids and peptides. AMINO ACIDS ABSORPTION - 20 dietary amino acids with a range of physical properties (e.g. neutral, acidic, basic, imino, etc.) - 50% absorbed by PepT1 as di- & tri-peptides (hydrolysed to a.a. in enterocyte – released from the basolateral membrane of cell as amino acids) - Other 50% by specific transporters - XAG- -> anionic (aspartate, glutamate) - B0 -> neutral a.a. - b0+ -> cationic & cystine - PAT1 -> proline AMINO ACIDS – SECONDARY ACTIVE TRANSPORT PepT1 – peptides, H+ (always a concentration gradient of H+ into cell) - cotransport B^0 – Na+, alanine – cotransport XAG- - 2Na+, glutamate-, H+, K+ (goes out) – cotransport

Answer 37

* Water is transported through the intestinal membrane entirely by diffusion (osmosis). * This is due to an osmotic gradient that is created as a result of absorption of ions in the paracellular spaces, and consequently into the blood. * Conversely, water can also be transported in the opposite direction—from plasma into the chyme. * Much of the osmosis occurs through the tight junctions between the apical borders of the epithelial cells, but much also occurs through the cells themselves. ABSORPTION OF H2O - H2O moves down osmotic gradient - Osmotic gradient created (mainly) by absorption of nutrients - 8.4 l absorbed in total per day (due to water consumed as well as all the secretions produced) -6.5 l absorbed in small intestine -whereas only 1.9 l absorbed in colon (fairly minor role contrary to what people believe) Route for H2O: (not quite sure) - Via junctional complexes between cells - Via SGLT1 & a.a. transporters - NOT aquaporin water channels (not expressed in small or large intestine tissues in any great number)

Answer 38

* 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. ‘ACTIVE’ TRANSPORT OF NA+ (AND Cl-) - Na-H exchanger (duodenum, jejunum) - Na/glucose or Na/amino acid cotransporters (jejunum, ileum) - Parallel Na-H and Cl-HCO3 exchangers (ileum, proximal colon) - Epithelial Na+ channel (distal colon) - Diets don’t contain a lot of sodium, so we’ll evolved to have a good absorption system of sodium so that we conserve it in our body – if you have a lot of sodium in your diet, then this can be contributory to hypertension

Answer 39

Aldosterone Greatly Enhances Sodium 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.

Answer 40

Absorption of Chloride Ions in the Duodenum and Jejunum • 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.

Answer 41

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”. - HCO3- no active absorption in SI or LI - Faces [K+] = 90 mM; [HCO3-] = 30 mM

Answer 42

10ml or 8g pure ethanol.

Answer 43

• Alcohol is absorbed from the upper small intestine via the portal vein and is then transported to the liver. - also absorbed in the stomach

Answer 44

• Some alcohol is metabolized in the stomach by alcohol dehydrogenase.  Females have a lack of this enzyme, therefore, their recommended safe limit is less than that of men. • The rest of the alcohol is metabolized in the liver:  Alcohol is converted to acetaldehyde and excreted by conversion to carbon dioxide in citric acid cycle.  The enzyme cytochrome p4502E1 is involved in the metabolism of alcohol in the liver. - I think some is metabolised in the stomach because some ADH is found there (first pass metabolism) but most in liver - ADH is found mostly in the liver and lining of stomach (but highest concentration in the liver) - about 20% of alcohol absorbed in the stomach and 80% in the small intestine

Answer 45

varies but is usually at a rate of 1 unit per hour.

Answer 46

* 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. - Alcohol does not protect from CVD except in women over 55- up to 5 units per week

Answer 47

``` o Confusion, Loss of coordination o Vomiting (this is a good sign as the person is trying to eliminate the toxins from their body, however, this can lead to complications like aspiration). o Seizures, Irregular or slow breathing (less than eight breaths a minute), Blue-tinged or pale skin (due to low oxyhaemoglobin), Low body temperature (hypothermia), Stupor (being conscious but unresponsive), Unconsciousness (passing out) ```

Answer 48

 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

Answer 49

- Protein synthesis (e.g. albumin 35-50g/L, clotting factors) - Glycogen storage - Deamination of polypeptides - Detoxification of xenobiotics, hormones, ingested drugs - Bilirubin metabolism - Coagulation factor synthesis

Answer 50

- Direct toxic effect - Indirect metabolite effect (e.g. acetaldehyde) - Activation of free radicals - Induction of enzyme systems, especially cytochrome p450 - Nutritional deficiencies, especially vitamin B - Liver function impairment

Answer 51

1. acute fatty change (early) - reversible 2. alcoholic hepatitis - reversible 3. hepatic fibrosis - reversible 4. cirrhosis (severe) - irreversible

Answer 52

 Predominantly acinar zone 3 – this area is furthest away from blood supply  Mainly large droplet (macrovesicular)  May cause acute hepatic failure  Reversible on withdrawal of alcohol (Krebs cycle diagram – if consume too much alcohol and the liver isn’t able to metabolise it, instead of going to CO2 and H2O, it goes through the acetaldehyde pathway and makes lipids – the lipids are accumulated within the liver cells)

Answer 53

 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 (if you keep drinking alcohol in excess for prolonged periods, you damage/break down the structural components of the liver cells and when you break down the cells and they are no longer recognised as cells, it induces an inflammatory response) (Mallory’s hyaline)

Answer 54

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 (epidemic)

Answer 55

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 (Tissue inhibitor of metalloproteinases) on withdrawal of alcohol (the result of prolonged inflammatory response – start to replace hepatocytes with scar tissue – collagen – made within the liver itself – the cells lie down collagen in the sinusoidal spaces)

Answer 56

``` 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 ``` (end stage liver disease) (complete nodularity of the liver)

Answer 57

 Blood tests: o Gamma glutamyl transferase (GGT) o Mean corpuscular volume (MCV)  Screening tools - CAGE or AUDIT can help identify heavy drinkers

Answer 58

* 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. - C = have you ever attempted to CUT down your drinking? - A = do you ever get ANNOYED when people complain about your drinking? - G = do you sometimes feel GUILTY about things you have done while drinking? - E = do you ever need a drink to get going the morning after (EYE OPENER)? - Any two positive responses are strongly indicative of alcoholism

Answer 59

* Alcohol Use Disorders Identification Test (AUDIT) * Better at detecting harmful drinking * Score >8 is 95% sensitive and 85% specific for harmful drinking

Answer 60

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

Answer 61

* 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.

Answer 62

``` • 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 ```

Answer 63

• 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.

Answer 64

* 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. (think there is actually a downregulation - so need more dopamine to produce response) * 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.

Answer 65

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.

Answer 66

 Alcohol ingestion and acute intoxication  Gallstones (obstruction of pancreatic duct)  Bile reflux  Trauma ``` I GET SMASHED I - idiopathic (20%) G - gallstones (50%) - microlithiasis E - ethanol (25%) T - trauma S - steroids M - mumps A - autoimmune S - scorpion venom H - hyperlipidaemia E - ERCP (Endoscopic Retrograde Cholangio-Pancreatography) D - drugs ``` - hypothermia - hyperparathyroidism

Answer 67

 Severe abdominal pain that radiates to the back  Nausea and vomiting  Rapid development of shock  Greatly elevated serum amylase - Respiratory distress - Fever - Haemorrhage - Shock - hypotension - tachycardia - oliguric (decreased production of urine)

Answer 68

 Alcohol (especially chronic excessive consumption) (60-70%)  Autoimmune pancreatitis - e.g. IgG4  Cystic fibrosis (Cl- ion channel dysfunction in the pancreas as well)  Hyperlipidaemia - hypertriglyceridemia  Idiopathic (20-30%) - Genetic – e.g. cystic fibrosis (CFTR), SPINK1, PRSS1 - Can occur after acute pancreatitis - Can occur without overt preceding illness - Can have acute flairs of chronic pancreatitis - Associated with hyperparathyroidism and aminoaciduria

Answer 69

 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 (preserved early on, therefore diabetes and complications of glucose metabolism are a relatively late event) - Pain (predominant complaint) - epigastric to back - episodic (relating to ongoing damage) - Malabsorption - weight loss - steatorrhoea – fat malabsorption - Diabetes – type 3 - Jaundice - due to bile duct obstruction

Answer 70

• Currently:  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) (less in those with pancreatitis?) (increasingly common)  Direct hormonal stimulation (research) - 14CO2 breath test – in use, not in Manchester • Historical:  Faecal fat analysis after a three day sample. (elastase = pancreatic enzyme that breaks down elastin)

Answer 71

* Tobacco smoke * Alcohol * Diabetes – independent predictor of mortality. It is difficult to manage a there is the risk of hypoglycaemia.

Answer 72

* 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.

Answer 73

they affect the oxidative pathways in the body: Tobacco smoke and alcohol metabolism -> Pancreatic oxidative stress (alcohol dehydrogenase) -> Cytochrome P450 non-oxidative pathway -> Reactive oxygen species -> Cell damage

Answer 74

• Lipase levels fall before protease and amylase, causing fat malabsorption and steatohhea (7g faecal fat/100g diet). - Fat malabsorption occurs when lipase production is reduced by 90% • Weight loss • Reduced bicarbonate in the intestine, leading to an acidic environment. This causes reduced bile acid secretion

Answer 75

- Replacement of pancreatic enzymes – Creon (pancrelipase)/pancreatin - combination of protease, lipase and amylase  Capsules/ granules taken before and during meals/ snacks.  Mimicking normal secretion - Titration to symptom -loss of steatorrhoea, weight stabilisation -improvement in pain?

Answer 76

* Dilation of the pancreatic ducts can occur as a result of blockage (e.g. gallstones) or from the viscous secretions (e.g. alcohol). * This will lead to increased pressure in the ducts and cause pressure pains. * These can also cause acute inflammation and pancreatic fibrosis. * Patients with chronic pancreatitis don’t deal with pain well and so have abnormal CNS pain processing. * Reduced bicarbonate secretion can cause pain elsewhere (e.g. stomach – gastritis) because of the lack of neutralization of stomach acid. - Pressure in duct or parenchyma causing pancreatic ischaemia - Inflammation and pancreatic fibrosis - Abnormal CNS pain processing - majority of patients don’t have a fixable cause of pain, it’s due to abnormal processing - Reduced bicarbonate secretion

Answer 77

1. Stop drinking 2. Pancreatic enzyme replacement (Pancreatin) –with a PPI and food 3. Dietary modification – reduced dietary fat 4. Pain relief 5. Support

Answer 78

* 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.

Answer 79

1. pseudocysts 2. bleeding 3. obstruction 4. pancreatic cancer

Answer 80

 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. - Drain if symptomatic - endoscopic - radiological - surgical

Answer 81

 Variceal  Due to underlying cause – ALD (alcoholic liver disease)  Splenic vein thrombosis  Pseudocyst – when draining the cysts, they can pull on blood vessels and cause tears and ruptures.  Pseudoaneurysm

Answer 82

- Bile duct -> jaundice | - Duodenal –> gastric outlet obstruction

Answer 83

 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. - Adenocarcinoma more common in chronic pancreatitis - 5% develop over 20yr period Poor prognosis - Surgical management - Chemotherapy - Palliative - Hard to detect - Don’t get symptoms until quite late - CT scans – hard to tell - No surveillance schedule – because group is so divergent and different

Answer 84

* 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.

Answer 85

* 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.

Answer 86

* 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.

Answer 87

• 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.

Answer 88

have little effect in visceral pain, but they are efficient for somatic pain. Somatic pain is a type of nociceptive pain that is also referred to as skin pain, tissue pain, or muscle pain. Unlike visceral pain (another type of nociceptive pain that arises from internal organs), the nerves that detect somatic pain are located in the skin and deep tissues.

Answer 89

 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. - ENS communicates with spinal cord and vagus nerve - spinal cord conveys pain - vagus conveys physiological signals

Answer 90

 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.

Answer 91

type 1 = separate hard lumps, like nuts (hard to pass) type 2 = sausage-shaped bu lumpy type 3 = like a sausage but with cracks on the surface type 4 = like a sausage or snake, smooth and soft type 5 = soft blobs with clear-cut edges type 6 = fluffy pieces with ragged edges, a mushy stool type 7 = watery, no solid pieces, entirely liquid

Answer 92

• Coeliac disease is an autoimmune disorder of the small intestine that results in an inflammatory response. • Symptoms:  Abdominal pain and bloating.  Chronic or occasional diarrhea (50% only).  Nausea or vomiting.  Weight loss  Iron-deficiency anaemia (but also folate and/or vitamin B12). • Upon endoscopic examination, the mucosal folds develop ridges. • To confirm the diagnosis, a biopsy is taken to look for villus atrophy.

Answer 93

• 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.

Answer 94

* 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

Answer 95

* 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

Answer 96

* 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

Answer 97

* 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. Causes of referred shoulder pain may include: Abdominal problems, such as gallstones or pancreatitis. (and liver and perforated duodenal ulcer)

Answer 98

- Pancreas is more on the left side | - Starts central/slightly to the right and extends to the left side

Answer 99

``` Endocrine function: - 20% (10%) by mass - Islet cells secrete hormones - Blood glucose homeostasis Exocrine function: - 80% (90%) by mass - Digestive enzymes - Acid buffering - Release into duodenum ``` FUNCTIONS OF THE EXOCRINE PANCREAS - Production of enzymes to facilitate digestion - lipase - proteases - amylase - nucleases - Release of enzymes into duodenum - NaHCO3 buffering of gastric juices

Answer 100

Centroacinar cells are spindle-shaped cells in the exocrine pancreas. Centroacinar cells are an extension of the intercalated duct cells into each pancreatic acinus. The intercalated ducts take the bicarbonate to intralobular ducts which become lobular ducts.

Answer 101

- Centroacinar cells - Intercalated duct - Acinar cells - Zymogen granules - Basal lamina

Answer 102

- Secreted from pancreas and salivary glands - Digest starch and glycogen - Produces maltose (disaccharide) and maltriose (trisaccharide) - Brush border enzymes complete digestion to glucose

Answer 103

- Inappropriate intra-pancreatic activation of trypsin leading to acinar auto-digestion and death - Mild – pancreatic inflammation and oedema - Severe – pancreatic necrosis and multi-organ failure, death - Don’t always know how - Final common pathway – increased intracellular calcium and inappropriate enzyme activation - pancreatic ductal obstruction - abnormal pancreatic secretion - ductal damage - direction toxin effect of alcohol – inflammation and membrane destruction, hypertriglyceridaemia, protein deposition

Answer 104

``` Severe abdominal pain And Enzyme release into blood stream - Amylase (normal in 10%) - Lipase (more sensitive/specific) + CXR – exclude perforation + CT – assess for pancreatic necrosis abscess or fluid collection ```

Answer 105

``` Recognise - A B C assessment Calculate severity - Glasgow/Imrie Score - Atlanta Support - Replace fluids - NG suction - Analgesia - Nutrition Are they getting better? - ITU? - Infection - Necrosis ```

Answer 106

Atlanta classification: - Mild – no organ failure, or complication - Moderate – transient organ failure OR complication - Severe – persistent organ dysfunction lasting > 48 hrs

Answer 107

- Acute fluid collection - common - usually self-resolving (acute – may need help if chronic) - Pseudocysts - organised fluid collections lined by granulation tissue - may self-resolve - symptoms due to mass effect (the effect of a growing mass that results in secondary pathological effects by pushing on or displacing surrounding tissue) - symptoms due to infection - Walled Off pancreatic Necrosis (WON) - dying/non-viable pancreatic tissue - requires drainage

Answer 108

- USS, MRCP (Magnetic resonance cholangiopancreatography), EUS (endoscopic ultrasound)– are there gallstones? - Remove gallstones if present - ERCP - cholecystectomy - Reduce alcohol (& smoking) - Consider drug causes - And autoimmune, familial, anatomical causes - Cystic fibrosis – normally carriers rather than people actually with CF – cystic fibrosis-associated pancreatitis

Answer 109

- Chronic, continuous inflammation - Fibrotic changes and acinar to ductal metaplasia - loss of functional unit - Impairment of pancreatic function - exocrine – digestive enzymes - endocrine – insulin - Chronic pain

Answer 110

``` - Increased acinar protein secreted & - Reduction in NaHCO3 + fluids -> Increased viscosity pancreatic duct plugging -> acinar atrophy -> fibrosis ```

Answer 111

``` Analgesia - Non-steroidal anti-inflammatory drugs - Opiates (avoid if possible) - Neuropathic – e.g. tricyclic antidepressants Optimise diabetic control Endoscopic therapy - Stone disease/structures Nerve blocks Surgery – decompression vs. resection - Big surgery, doesn’t always work ```

Answer 112

- 5-10% of all diabetes - Independent predictor of mortality – shows severity of the CP disease - Difficult to manage - patient characteristics - risk of hypoglycaemia - Usually low insulin requirements – but brittle - Insulin pumps can be useful

Answer 113

- 70% survival 10yrs | - 45% survival 20yrs

Answer 114

The predominant effect of secretin on the pancreas is to stimulate duct cells to secrete water and bicarbonate.

Answer 115

Cholecystokinin, officially called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.

Answer 116

SUMMARY – AP - Gallstones and alcohol - Multi-organ failure - High mortality - Reversible SUMMARY – CP - Alcohol - Chronic symptoms - pain - malabsorption - higher risk of cancer - Irreversible

Answer 117

Total volume of a drink (in ml) x its ABV (alcohol by volume) (percentage) / 1000 = units

Answer 118

1. Mouth & oesophagus – alcohol is diluted by saliva before being swallowed – some is immediately absorbed 2. Stomach – more alcohol is absorbed here, irritating the lining of the stomach and increasing the acidity 3. Small intestine – any remaining alcohol is passed here and is the site of most alcohol absorption 4. Bloodstream – alcohol quickly diffuses through the body, affecting almost all cells 5. Brain – these cells are more susceptible because they are usually protected from toxins by the blood-brain barrier 6. Liver – blood-alcohol is metabolised in two stages and then respired into CO2, H2O and fatty acids (Krebs cycle) 7. Excretion via urine, the lungs, and sweat

Answer 119

Proteins -> amino acids, di- & tripeptides (stomach, pancreas, brush border enzymes) Polysaccharides (disaccharides) -> monosaccharides (saliva, pancreas, brush border enzymes) Triglycerides -> free fatty acids, monoglycerides (STOMACH, pancreas, bile salts)

Answer 120

All blood from lower part of oesophagus all way down to colon go through portal vein to the liver after absorption has occurred, so if drugs are labile and liver is the first site of breakdown of drugs, then you get first-pass metabolism – large amounts of the drug gets broken down in the liver, so its rendered pretty ineffective The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.

Answer 121

1. Expansion of absorptive surface: total area about 200 m^2 (600x > tube of same dimensions) - foldings in wall -> villi -> microvilli ‘brush border’ - N.B. decrease surface area = malabsorption 2. Polarised expression of transport proteins (epithelial cells have two sides (apical and basolateral membrane)

Answer 122

- Uses two sodiums that have to bind to a binding site - They open up a binding site for sodium - Once they’ve all bound, the protein undergoes a conformational change, the glucose and sodium can move through and they can be released on the inside of the cell

Answer 123

- Genetic disease (autosomal recessive – extremely rare) - SGLT1 mutated = no absorption of glucose or galactose - Severe and potentially fatal diarrhoea in infants (potentially fatal – dehydration) - Treatment – avoid glucose and galactose - Emphasises the requirement of transport proteins for absorption

Answer 124

Rare genetic diseases = generally mild GI malabsorption, especially in developed countries where people have generally a more nutritionally-rich diet, and have PEPT1 transporter which transports a bulk of amino acids into our body BUT do cause appearance of amino acids in urine, e.g. Hartnup disease (B^0), Cystinuria (b^0+; kidney stones) (due to having these transporters in the kidney) N.B. SI and kidney proximal tubule share many properties

Answer 125

steatorrhea

Answer 126

- Duodenum - Niemann-Pick C1-Like 1 (NPC1L1) protein - Receptor-mediated endocytosis - Ezetimibe inhibits endocytosis = decrease plasma cholesterol

Answer 127

(butyrate, propionate, acetate) - SCFA’s not major component of diet, BUT produced by bacterial fermentation (colon) - Microbiome SCFA production of major interest in aetiology of both metabolic diseases and colon cancer - SMCT1 – transport SCFA & Na+ (Na+/K+-ATPase set up gradient for Na+ to come into cell) - SCFA used by colonocyte for intracellular metabolism

Answer 128

- Saliva – 1.5 L/day - Gastric secretion – 2.0 L/day - Pancreatic secretion – 1.5 L/day - Bile secretion – 0.5 L/day - Secreted by small intestine – 1 L/day - Reabsorbed by small intestine – 6.5 L/day - Reabsorbed by colon – 1.9 L/day = 8.5 L in = 8.4 L absorbed = the remainder about 100ml – in faeces

Answer 129

2500 ml = total in and out each day? - Ingested fluids = 1200 ml - Ingested food = 1000 ml - Metabolism = 300 ml - Total = 2500 ml - Urine = 1500 ml - Faces = 100 ml - Skin/sweat = 550 ml - Exhaled air = 350 ml - Total = 2500 ml

Answer 130

- Saliva – Na+ & Cl- - Gastric secretion – H+ & Cl- - Pancreatic secretion – HCO3- (duodenum) - Bile secretion – Na+ & Cl- (duodenum) - Secreted by small intestine – HCO3- (jejunum) - Secreted by colon – K+ & HCO3- (distal colon) - Reabsorbed by small intestine – Na+ & Cl- (duodenum, jejunum) & K+ (ileum) - Reabsorbed by colon – Na+ & Cl- (distal colon) - Excreted in faeces – HCO3- (hard to absorb, a lot turned into CO2 and water by neutralisation, but also lost in faeces) & K+

Answer 131

- K+ - SI = paracellular diffusion in ileum - LI = predominantly secretion - Faces [K+] = 90 mM; [HCO3-] = 30 mM

Answer 132

-> hypokalaemia & metabolic acidosis (due to loss of bicarbonate)

Answer 133

- Increase osmotic load (Un-absorbable, water-soluble solutes in the bowel that retain water through osmosis) in colon -> increase fluid in faeces - Osmotic load – incomplete digestion and absorption of food - lack of enzymes or transporters - damage to mucosal cells (coeliac disease, Crohn’s disease) - Osmotic load – secretion of ions by gut!

Answer 134

- Congenital (neonate) = ‘watery’ - glucose-galactose malabsorption (SGLT1) - lactase deficiency - Disease of pancreas and biliary systems = steatorrhoea - pancreatitis, cystic fibrosis - hepatitis, gall stones

Answer 135

- Immune/autoimmune -coeliac disease, Crohn’s disease - Infections (water & hygiene) -bacteria (Shigella & Campylobacter) -> destruction of intestinal wall (decrease surface area) -> blood in faeces (dysentery) -bacteria (Salmonella) -> inflammation -Protozoa (Giardia, Entamoeba) N.B. UK main causes rotavirus & norovirus (winter vomiting bug)

Answer 136

- Vibrio cholerae, some strains of E. coli & rotavirus - Toxin produced by bacteria which ‘hi-jacks’ normal cellular processes - Intestinal cells normally secrete H2O (together with mucus & HCO3-) about 1 litre/day - In cholera, secretion exceeds 20 litres/day - Toxins may also inhibit Na+ absorption BUT not SGLT1 (basis of oral rehydration therapy)

Answer 137

Failure to digest/absorb

Answer 138

Incomplete digestion results in malabsorption

Answer 139

- Fat soluble: A, D, E & K - evidence of facilitated diffusion and/or endocytosis at physiological concentrations - require optimal fat digestion – deficiencies with pancreatic and biliary disease

Answer 140

Water soluble: B group & C - specific transporters (facilitated & secondary) - B12 (endocytosis)

Answer 141

- Paracellular | - TRPV6 channel

Answer 142

- Dcytb reduces non-heme Fe3+ to Fe2+ - DMT cotransports Fe2+ with H+ - Heme Fe2+ enters by unknown mechanisms - Heme oxygenase oxides the Fe2+ in heme, and then releases Fe3+ - Fe2+ transfers to mobilferrin - Fe2+ leaves the cell via ferroportin (FP1) and after hephaestin oxidises it to Fe3+, the iron binds to transferrin in plasma

Answer 143

fast alcohol screening test FAST is an alcohol harm assessment tool. It consists of a subset of questions from the full alcohol use disorders identification test (AUDIT). FAST was developed for use in emergency departments, but can be used in a variety of health and social care settings.

Answer 144

AUDIT alcohol consumption questions - How often do you have a drink containing alcohol? - How many units of alcohol do you drink on a typical day when you are drinking? - How often have you had 6 or more units if female, or 8 or more if male, on a single occasion in the last year? Numbered scoring system – 0 to 4 Scoring: a total of 5+ indicates increasing or higher risk drinking – an overall total score of 5 or above is AUDIT-C positive

Answer 145

To identify intimate partner violence: H = humiliation - Within the last year, have you ever been humiliated or emotionally abused in other ways by your partner or ex-partner? A = afraid - Within the last year, have you been afraid of your partner of ex-partner? R = rape - Within the last year have you been raped or forced to have any kind of sexual activity by your partner or ex-partner? K = kick - Within the last year, have you been kicked, hit, slapped or otherwise physically hurt by your partner or ex-partner?

Answer 146

- Identification and Referral to Improve Safety - IRIS is a general practice-based domestic violence and abuse (DVA) training support and referral programme - Core areas of the programme are training and education, clinical enquiry, care pathways and an enhanced referral pathway to specialist domestic violence services - It is aimed at women who are experiencing DVA from a current partner, ex-partner or adult family member - IRIS also provides information and signposting for male victims and for perpetrators - IRIS is a collaboration between primary care and third sector organisations specialising in DVA - IRIS was the first European randomised controlled trial of an intervention to improve the health care response to domestic violence and abuse - It aimed to determine the cost-effectiveness of a general practice based domestic violence training and support programme and measure two outcomes: - referral of women to a domestic violence agency providing advocacy - recording of disclosure of domestic violence in the patient’s medical records

Answer 147

- Addiction is characterised by an inability to stop using a drug; failure to meet work, social, or family obligations; and sometimes, tolerance and withdrawal - Tolerance and withdrawal reflex physical dependence in which the body adapts to the drug, requiring more of it to achieve a certain effect (tolerance) and eliciting drug-specific physical or mental symptoms of drug use is abruptly ceased (withdrawal) - Physical independence can happen with the chronic use of many drugs – including many prescription drugs, even if taken as instructed - Thus, physical dependence does not constitute addiction, but it often accompanies addiction

Answer 148

ALT test = alanine aminotransferase test - Normally levels in the blood are low - If your liver is damaged, it will release more ALT into your blood - Doctors often do the ATL test along with other liver tests

Answer 149

ALP test = alkaline phosphatase test - Enzyme has a particularly important role in liver function and bone development - Elevated ALP levels are generally a sign of a liver or bone condition – an obstruction of the liver or damage to it will cause ALP levels to rise – this will also occur if there’s an increase in bone cell activity ALP can be used to evaluate the bile duct system of the liver.

Answer 150

- Aspartate aminotransferase (AST) is an enzyme that is found mostly in the liver, but also in muscles. When your liver is damaged, it releases AST into your bloodstream. An AST blood test measures the amount of AST in your blood. The test can help your health care provider diagnose liver damage or disease.

Answer 151

- Bilirubin is a waste product from breakdown of red blood cells - It passes through the liver and is processed before being excreted through your stool - A damaged liver can’t properly process bilirubin – this leads to an abnormally high level of bilirubin in the blood - A high result on the bilirubin test may indicate that the liver isn’t functioning properly

Answer 152

- Urea is the final breakdown product of amino acids - Nitrogen in the form of ammonia is produced in the liver when protein is broken down – the nitrogen combines with other chemicals in the liver to form the waste product urea - Urea is released into the bloodstream and carried to the kidneys where it’s filtered out of the blood and excreted in the urine - Healthy kidneys remove more than 90% of the urea, so blood levels can show how well your kidneys are working - Most diseases that affect the kidneys or liver can affect the amount of urea present in the blood – if increased amounts of urea are produced by the liver or decreased amounts are removed by the kidneys then blood urea concentrations will rise - If significant liver damage or disease reduces the production of urea, then urea concentrations may fall

Answer 153

- Creatinine is a waste product that forms when creatine, which is found in your muscle, breaks down - Creatinine levels in the blood can give doctor information about how well your kidneys are working If your kidneys aren't functioning properly, an increased level of creatinine may accumulate in your blood. A serum creatinine test measures the level of creatinine in your blood and provides an estimate of how well your kidneys filter (glomerular filtration rate).

Answer 154

- Level is routinely performed in people with type 1 and type 2 diabetes - Blood HbA1c levels are reflective of how well diabetes is controlled - HbA1c is your average blood glucose levels for the last two or three months - It’s glycated haemoglobin – something that’s made when the glucose in your body sticks to your red blood cells - Your body can’t use the sugar properly, so more of it sticks to your blood cells and builds up in your blood - Red blood cells are active for around 2-3 months, which is why the reading is taken quarterly

Answer 155

Omeprazole enhances the efficacy of pancreatin | - All pancreatic enzymes should be taken with a PPI

Answer 156

- There are seven types of stools according to the Bristol Stool Chart - The type of stool or faeces depends on the time it spends in the colon - After you pass faeces, what you see in the toilet bowl is basically the result of your diet, fluids, medications and lifestyle - Every person will have different bowel habits, but the important thing is that your stools are soft and easy to pass – like types 3 and 4 - Type 1-2 indicate constipation - Type 3-4 are ideal stools as they are easier to pass - Type 5-7 my indicate diarrhoea and urgency

Case 3 Flashcards

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