Gastrointestinal System Anatomy and Pathophysiology

Transcription

1 Student Submitted Resurces Gastrintestinal System Anatmy and Pathphysilgy Kimberley Dejng Last Update: June 2017 File ID: GASTR This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 1

2 Table f Cntents Histlgy... 3 GIT embrylgy... 4 Face and neck anatmy... 6 Peritneal anatmy... 8 Fregut anatmy Midgut anatmy Hindgut anatmy Additinal intestinal anatmy Hepatic prtal system Enteric nervus system Assciated lymphatics Inguinal regin anatmy Physilgy f swallwing and mtility Salivary glands secretins Gastric secretins and glands Digestin and nutrients Gastrintestinal histry Gastrintestinal examinatin Oral disrders Oesphageal disrders Gastric disrders Acute abdminal pain Peritneal disease GIT infectins Diseases f the small bwel Diseases f the cln and rectum Hepatic disrders Liver functin tests Biliary disrders Pancreatic disease Metablism and metablic disease This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 2

3 Histlgy Wall f the GIT cnsists f 4 cncentric layers Mucsa - (1) Epithelium: simple cubidal r simple clumnar epithelium with a secretry functin - (2) Lamina prpria: supprts vascular mucsal epithelium, cntains bld and lymphatic vessels - (3) Muscularis mucsae: typically, a duble layer f smth muscle where cntractin causes lcal mvement f mucsa Submucsa - Layer f cnnective tissue - Cntains large bld vessels and lymphatics - Cntains the submucsal (Meisnner s) nerve plexus Muscularis externa - Duble layer f smth muscle - Cntains myenteric (Auerbach s) nerve plexus - Cntractin causes peristalsis Adventitia /sersa - Cnnective tissue Oesphagus Oesphagus mucsa - Nn-keratinizing, stratified squamus epithelium (prtectin against abrasin) Oesphageal muscularis mucsa - Upper ne third = striated muscle - Middle ne third = striated and smth muscle - Lwer ne third muscle = smth muscle Stmach Gastric mucsa - Within the mucsa lie gastric glands simple, branched, tubular that extend frm muscularis externa t the bttm f the gastric pits - Cnsist f mucus cells, parietal cells, chief cells and G cells Small intestine Dudenum - Mucsa: crypts f Lieberkühn (r intestinal glands) that ccupy dudenal mucsa - Submucsa: Brunner s glands that elabrate alkaline secretins (neutralize acidic chyme prpelled by the stmach) Jejunum - Mucsa: crypts f Leiberkuhn (r intestinal glands) - Submucsa: plicae circulares are circularly arranged transverse flds cntaining a cre f submucsa that extend partially arund the lumen Ileum - Mucsa: Peyer s patches (aggregatin ndules f encapsulated lymphatic tissue) ccupy the lamina prpria; M cells verlap these Peyer s patches (antigen transprting cells); crypts f Leiberkuhn als This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 3

4 - Submucsa: plicae circulares Large intestine Cln - Clnic mucsa: smth surface with n villi; includes crypts f Leiberkuhn and a muscularis externa Anal canal - Mucsa: keratinizing, stratified squamus epithelium Pancreas Cnsists f clusters f acini which secrete enzymes (Islets f Langerhans) In the middle f each cluster is the centracinar cells secretin f electrlytes and water int the pancreatic ductal system Acinar cells surrund the centracinar cells these synthesize and secrete enzymes Within acinar cells, zymgen granules are fund these cntain digestive enzymes r their precursrs GIT embrylgy 1. The fregut starts as a straight tube, as it develps it rtates n its lng axis, lengthens in a duble curve and expands t becme the stmach and prximal dudenum 2. The fregut has tw attachments n the anterir and psterir wall the drsal and ventral mesgastrium. As the fregut (red) rtates, the drsal and ventral mesgastrium rtate with it Drsal mesgastrium Ventral mesgastrium 3. The attachment site f the ventral mesgastrium is the lesser curvature f the stmach and the tp prtin f the prximal dudenum. The attachment site f the drsal mesgastrium is the greater curvature f the stmach and the underside f the prximal dudenum This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 4

5 4. While the fregut is develping, the liver develps in the ventral mesgastrium and the spleen develps in the drsal mesgastrium Spleen Liver 5. The liver grws rapidly, pressing against the bdy wall bliterating the psterir wall f peritneum which leads t the frmatin f the lesser sac, lying directly behind the stmach. At this pint we can distinguish the greater and lesser mentum Liver destrys part f the peritneum Lesser mentum in ventral mesgastrium Lesser sac Greater mentum in drsal mesgastrium 6. As the gut develps, the lesser mentum stps grwing where the fregut ends in the prximal dudenum. This leaves a free brder between the dudenum and the liver the epiplic framen (r Framen f Winslw). The framen f Winslw allws cmmunicatin between the greater and lesser mentum Lesser mentum in ventral mesgastrium Framen f Winslw epiplic framen Greater mentum in drsal mesgastrium 7. At this pint, the greater mentum cntinues t grw. It extends belw the transverse cln in a duble fld, will its ther brder merges with the transverse mescln (ligament) while the duplicated layers are disslved. We are left with the greater mentum stuck t the transverse cln and hanging dwn belw it. The lesser sac still sits behind the lesser mentum and the stmach This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 5

6 Liver Lesser sac Greater mentum Transverse cln Pancreas Merged brder f the greater mentum and the transverse mescln (ligament) Face and neck anatmy Face, muth and mandible Alvelar prcess carries teeth f the upper jaw Main bdy f the maxilla is hllw = maxillary sinus Infrarbital framen carries infrarbital nerve and artery Hard palate cnsists f: - Tw palatine prcesses f the maxillae - Tw hrizntal plates f the palatine bnes Mandibular framen is guarded by a small bne lingula f the mandible Teeth 20 child teeth and 32 adult teeth Adult teeth are divided int fur quadrants f 8 teeth Each quadrant: - 2 incisrs (cutting/biting) - 1 canine (tearing) - 2 premlars (grinding) - 3 mlars (grinding) third mlar usually appears late in adlescence and is the wisdm tth Innervatin - Maxillary teeth: CN V2 prvides general sensry innervatin in a plexus f nerves frmed by anterir, middle and psterir superir alvelar nerves This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 6

7 - Maxillary gingivae: psterir, middle and anterir superir alvelar nerves innervate buccal surface and greater palatine and naspalatine innervate the lingual surface - Mandibular teeth: CN V3 (inferir alvelar branch) prvides general sensatin - Mandibular gingivae: buccal and mental nerves innervate buccal surface; lingual nerve innervates lingual surface Vascular supply (nte: veins mirrr arteries) - Psterir superir alvelar artery - Anterir superir alvelar artery - Inferir alvelar artery Clinical infrmatin - Inferir alvelar nerve blck administered t patients needing mandible dental wrk, resulting in numbness f the tngue and ral mucsa - Since a maxillary plexus is frmed by anterir, middle and psterir superir alvelar nerves anesthesia is much harder (a greater palatine and naspalatine nerve blck are ften administered) Hyid and muscles f masticatin Hyid - Des nt articulate with any ther bne directly - Suspended by ligaments frm stylid prcess f the skull - Attachments include: mylhyid, stylhyid, Hyglssus, genihyid, digastric, mhyid, sternhyid and thyrhyid Muscles f expressin - Buccinatr = cheek muscle, keeps fd between the teeth - Orbicularis ris = sphincter f the muth, cntrlling pening and clsure f the lips Muscles f masticatin - Tempralis - Masseter - Lateral pterygid - Medial pterygid This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 7

8 Tngue Intrinsic muscles - Change the shape f the tngue Extrinsic muscles - Change the psitin f the tngue - Geniglssus - Hyglssus - Stylglssus - Palatglssus Pharynx Cmprises f three circular muscles stacked inside ne anther the cnstrictrs All cnstrictrs are pen anterirly (nt a full circle) Cnstrictrs - Superir cnstrictr - Middle cnstrictr - Inferir cnstrictr Vertical muscles that frm the pharynx - Stylpharyngeus - Palatpharyngeus - Salpingpharyngeus Innervatin - Vagus and glsspharyngeal nerves (X and IX), which frm the pharyngeal plexus Peritneal anatmy Peritneal cavity, abdminal viscera and abdminal wall Peritneum = serus membrane that cnsists f tw layers Peritneal sac - True peritneal sac nly cntains thin film f fluid t allw structures t slide arund withut frictin there is n actual space it is a ptential space Parietal peritneum - Lines the internal walls f abdminal cavity, frming the peritneal cavity - Cmpletely clsed in males and has tw penings in females where uterine tubes, uterus and vagina prvide passage t utside - Reflects ff psterir abdminal wall frming a duble layer sac husing rgans, vessels and lymphatics = mesentery Visceral peritneum - Surrunds the gut tube - Prduces a serus fluid that lubricates the peritneal surfaces, enabling rgans t slide acrss ne anther with minimal frictin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 8

9 - Tw types: intraperitneal (rgans suspended frm abdminal wall) r retrperitneal (rgans nt suspended frm abdminal wall) - Nte: surgery invlving retrperitneal structures such as kidneys, can be accessed thrugh the bdy wall therefre leaving peritneum intact and aviding peritnitis Anterir abdminal wall - Layers: (1) Skin (2) Superficial fascia (where the fat is) (3) Deep fascia (usually tightly bund t the muscles and their apneurses) (4) Abdminal muscles external and internal blique s, transverse abdminis, rectus abdminis and psterir muscles including psas majr and quadratus lumbrum (5) Tranversalis fascia (fascia just deep t the muscles) (6) Extraperitneal fat (7) Peritneum - Muscles that cme arund frm the sides f the bdy, t meet the vertical muscles at the frnt: (1) External blique s directin f fibers is frwards and dwn; hands in pckets, same as the intercstal muscles f the chest wall (2) Internal blique s directin f fibers is backwards and dwn, hips t bra (3) Transversus abdminis fibers fan ut acrss the inner layer f the abdminal wall, the upper fibres arch upwards and the lwer fibers arch dwnwards, the middle fibres head hrizntally - Rectus sheath frmatin upper abdmen Anterir rectus sheath is frmed by apneursis f external blique and half the internal blique Psterir rectus sheath is frmed frm transversus apneursis and half the internal blique - Rectus sheath frmatin lwer abdmen The anterir rectus sheath is frmed by all three apneurses There is n psterir rectus sheath - Rectus sheath change in the abdmen Can clearly see where the anterir and psterir rectus sheaths change ver in the abdmen Usually halfway between the umbilicus and the pubis >> arcuate line This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 9

10 Psterir abdminal wall (n the inside f the abdminal wall) - Median umbilical ligament >> Shriveled piece f tissue that represents a remnant f embrynic urachus (canal that drains urinary bladder f the fetus) Extends frm the apex f the bladder t the umbilicus n the psterir abdminal wall - Medial umbilical ligaments >> Paired structures n the psterir abdminal wall, cvered by the medial umbilical flds Vascular supply - Intercstal, lumbar and epigastric arteries = parietal peritneum - Vessels f abdminal arta = visceral peritneum Gastrintestinal ligaments Lesser mentum - Attaches t liver, lesser curvature f stmach and prximal dudenum - Referred t as hepatgastric ligament and hepatdudenal ligament - Frms a lesser sac, which is a subdivisin f the peritneal cavity whilst the greater sac is a remaining part f the peritneal cavity - The tw sacs cmmunicate via the epiplic framen f Winslw Greater mentum - Attaches between transverse cln and greater curvature f stmach Fregut anatmy General details Supplied by celiac trunk and superir mesenteric artery Parasympathetic innervatin via the vagus nerve at T12 Cntains stmach and prximal dudenum, liver, gallbladder, pancreas and spleen Oesphagus Ttal length 25-30cm, depending n length f persn Cmpnents - Cervical esphagus skeletal muscle - Thracic esphagus smth muscle - Abdminal esphagus - smth muscle Curse - Starts behind cricid cartilage f larynx, cricpharyngeus muscle, which acts as the upper esphageal sphincter (nte: just abve this muscle is a weak area called Killian s area; where a Zenker s diverticulum is lcated) - Descends behind trachea, but in clse assciatin - Belw the tracheal bifurcatin, the esphagus is clsely applied t the left atrium f the heart (hence transesphageal echcardigrams are used here fr an ultrasnic view f the heart) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 10

11 - As the esphagus descends the psterir mediastinum, the arta swings behind it - Oesphagus passes thrugh diaphragm at T10 thrugh esphageal hiatus (frmed by right crus left f midline) - Junctin f esphagus and stmach = gastr-esphageal junctin/cardia - Here lie lping fibers f the right crus act as the lwer esphageal sphincter (nte: when hiatus is t lse, sliding and rlling hernias can develp) Innervatin - Left and right vagus nerves apprach the esphagus frm each side = frm a plexus n surface f esphagus - At diaphragm, plexus emerges as tw vagal trunks - Left vagus = anterir vagal trunk - Right vagus = psterir vagal trunk Vascular supply - Branches f inferir thyrid arteries in the rt f the neck - Branches f brnchial arteries in the chest - One r tw direct esphageal branches frm the descending arta - Left gastric artery in the lwer prtin Venus drainage - Anastmses f veins in lwer esphagus with left gastric vein imprtant prt-systemic anastmses relevant t prtal hypertensin Stmach Regins - Cardia = surrunds the gastr-esphageal pening - Fundus = dme shaped regin superir t cardia - Bdy = largest regin cnsisting f a lesser and greater curvature, where the lesser and greater mentum attach respectively - Rugae = flds in gastric mucsa in the bdy f the stmach - Pylrus = distal end f stmach cntaining pylric sphincter at L1 Vascular supply - Left gastric artery and right gastric artery = arterial sac arund lesser curvature This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 11

12 - Left gastrepiplic artery and right gastrepiplic artery = arterial sac arund greater curvature - Shrt gastric arteries arising frm splenic artery that supply fundus f stmach Dudenum 25cm lng Derived f bth fregut and midgut Curves arund pancreatic head 4 parts: - (1) Superir Intraperitneal Runs frm pylrus Cntains dudenal cap (large dilatin seen n imaging) Has a free edge up against the liver, with lesser mentum attached >> hepatdudenal ligament - (2) Descending Retrperitneal Site f the junctin between embrylgical fregut and midgut Curses in frnt f the right renal vessels and deep t transverse cln Cmmn bile duct receives the main pancreatic duct here - (3) Hrizntal Retrperitneal Turns left and passes hrizntally acrss IVC, arta and left psas muscle - (4) Ascending Retrperitneal transitining t intraperitneal Ascends anterir arta at L2 As it turns frward it becmes the jejunum >> dudenjejunal flexure This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 12

13 Liver Lcatin and general cnsideratins - Right upper quadrant >> mves dwn n inspiratin - 1.4kg in the adult - Cvered by a fibrus capsule - Arises frm the ventral mesgastrium during embrylgical develpment Lbules and ligaments - Attached t inferir surface f right diaphragm dme via crnary ligaments - Bare regin Where the liver is in direct cntact with diaphragm - Fur lbes Right, left, quadrate (functinally part f the left lbe) and caudate (functinally separate) - Falcifrm ligament Curses between left and right lbes This runs frm the midline f the anterir abdminal wall, and is attached ver the arched surface f the liver - Ligamentum teres (rund ligament) Embrylgical remnant f the bliterated umbilical vein; lies within Falcifrm ligament (as abve) - Ligamentum vensum Cntains the remnant f ductus vensus channel carried bld frm the umbilical vein t the IVC, bypassing the liver - Underside f the liver there is a H shape f fissures and grves The crss bar f the H is the prta hepatis which is the hilum f the liver (hepatic ducts, prtal vein and hepatic artery) - Ptential space psterir t the liver, in frnt f the right kidney Called the heptatrenal space / Rutherfrd-Mrrisn s puch / Mrrisn s puch where fluid can accumulate Macrscpic appearance - In life >> large, sft, easily traumatized, reddish in clur Circulatin - Receives nearly 25% f the bdy s cardiac utput (1500ml per minute) via tw surces venus flw frm the prtal vein (85%) and arterial flw frm the hepatic artery (15%) - Prtal vein >> venus bld frm the small intestine richly with absrbed nutrients pancreatic venus drainage als drains here - Prtal vein frms a capillary bed that allws individual hepatcytes t be bathed directly in prtal bld - The tw surces merge within the liver and the cmbined bld flw exits via the central veins > hepatic vein > IVC - The prtal triad >> lies between caudate and quadrate lbes; cnsists f (1) prtal vein (2) prper hepatic artery (3) cmmn hepatic duct Innervatin - Under autnmic cntrl frm sympathetic and parasympathetic nerves f the celiac plexus This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 13

14 Cellular rganisatin - Parenchyma >> rganized int plates f hepatcytes lying in a cage f reticulendthelial meshwrk; each plate is separated by vascular spaces (sinusids) - Sinusids >> hepatic arterial bld is mixed with prtal venus bld - Reticulendthelial meshwrk >> endthelial cells, Kupffer cells (liver macrphages), stellate cells (fat string cells) Functinal znatin - Zne 1 hepatcytes >> receive bld frm terminal veins and arteries; expsed t high cncentratins f xygen; very active in glucnegenesis, xidative energy metablism and urea synthesis - Zne 2 hepatcytes >> intermediate zne; displays attributes f bth zne 1 and 3 - Zne 3 hepatcytes >> Reached by bld that is leaving the liver via the central vein; expsed t much lwer cncentratins f xygen; active in glyclysis and lipgenesis Functins - Largest gland in the bdy - Energy metablism > glucse prductin, glucse cnsumptin, chlesterl synthesis, deaminatin f amin acids, cnversin f ammnia t urea via the urea cycle - Prtein synthesis > plasma prteins, cltting factrs, insulin like grwth factr 1, aplipprteins - Transprt and strage > drug and pisn detxificatin, synthesis f VLDL and pre-hdl, clearance f HDL and LDL, uptake and strage f vitamins A, D, B12 and flate - Prtectin and clearance > clearance f bacteria and damaged cells via phagcytsis frm Kupffer cells - Enterhepatic circulatin f bile acids - Drug metablism and secretin Receptr mediated uptake - Hepatcytes have three sides: (1) Apical surface > frms the wall f the bile canniculus (2) Baslateral surface > cntact with the bldstream via sinusids (3) Lateral dmain > brdered by ther tw surfaces - Each hepatcyte s sides are separated by tight junctins Capacity fr regeneratin - Nrmal liver cells cntain very few cells in mitsis - When hepatcytes are lst, the rest f the hepatcytes prliferate - Therefre, in mst cases f fulminant hepatic failure, if the patient survives the acute perid, then recvery will be cmplete Gallbladder Lcatin - Lies n visceral surface f liver, t the right f the quadrate lbe - Lies in a shallw depressin >> gall bladder fssa - Stres and cncentrates bile secreted by liver - Has a bdy, fundus and neck (which leads t cystic duct) - Sme gall bladders have a small puch at the junctin f the bdy and neck (Hartmann s puch) >> pathlgical as gallstnes can get stuck here Bile functin and synthesis - Digests and absrbs lipids - Synthesised and secreted by liver This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 14

15 - Stred in gallbladder Bile cmpsitin - Bile salts Chlesterl > primary bile acids > secndary bile acids > bile salts Cnjugatin in liver with amin acids t increase water slubility Acts t emulsify dietary lipids - Bile pigments >> bilirubin - Chlesterl - Phsphlipids - Electrlytes - Water Bile secretin - Mediated via CCK - Stimulates cntractin f gallbladder and relaxatin f sphincter f Oddi > bile flws frm gallbladder int dudenum > bile emulsifies lipids Bile release - Bile released int dudenum when gallbladder is stimulated after eating a fatty meal - Bile enters cystic duct which jins cmmn hepatic duct >> becming cmmn bile duct - Cmmn bile duct curses within hepatdudenal ligament f lesser mentum, where it jins the main pancreatic duct Gall bladder bld supply - Cystic artery >> a branch f the right hepatic artery - Triangle f Calt >> small triangle frmed by the cystic duct, inferir prtin f the liver and cmmn hepatic duct this is the regin f mst anatmical variatin and dissectin in this triangle is the mst cmmn cause f injuries t the bile duct Biliary system - (1) Right and left hepatic ducts emerge frm their crrespnding halves f the liver and merge t frm the cmmn hepatic duct - (2) Cmmn hepatic duct passes dwn the free edge f the lesser mentum, whilst uniting with the cystic duct frm the gallbladder - (3) Once the cystic duct has jined the cmmn hepatic duct, it becmes the cmmn bile duct - (4) The cmmn bile duct is jined by the pancreatic duct emptying int the secnd part f the dudenum >> where they unite frms a dilatin called hepatpancreatic ampulla f Vater This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 15

16 - (5) Arund the Ampulla f Vater lies muscle that frms the sphincter f Oddi Pancreas Lcatin and functin - Retrperitneal rgan at L2 - IVC, arta, renal and gnadal vessels lie behind the pancreas - Dual excrine and endcrine Excrine = prduces enzymes that digest carbs, prteins and fats; secreted int main pancreatic duct and int dudenum Endcrine = islands f endcrine tissue (pancreatic islets f Langerhans) prduce hrmnes insulin and glucagn; secreted int bld stream via pancreatic vein Anatmy f endcrine pancreas - Endcrine pancreas cmpsed f islets f Langerhans (nly 1% f ttal pancreas) - Mre than 70% f insulin secreting beta cells must be lss befre dysfunctin ccurs - Fur types f islet cells: (1) Insulin secreting beta cells (60%) (2) Glucagn secreting alpha cells (30%) (3) Smatstatin secreting delta cells (9%) (4) Pancreatic plypeptide secreting cells (1%) - Islets are highly vascularized ne arterile per islet - Islets are highly innervated S and PS axns are in direct cntact - Bld frm the islets drain t the prtal vein Regins - Head and neck: nestled near the dudenum, head als cntains the uncinate prcess - Bdy and tail: lcated anterirly near left kidney, with the tail tuching the spleen Ducts - Main pancreatic duct Runs frm tail t the end, n the psterir surface Near the neck, its jined by the bile duct t frm Ampulla f Vater within the sphincter f Oddi Cmbined ducts drain int secnd part f the dudenum via the greater dudenal papilla This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 16

17 - Accessry pancreatic duct Can smetimes be present, draining part f the head If present, it drains int the dudenum via the lesser dudenal papilla Innervatin - Parasympathetic stimulatin via vagus nerve MAY increase excrine secretins - Sympathetic input frm T5-T9, increases tne f smth muscle cells arund neck f secretry units Spleen Lcatin and appearance - Sft, vascular rgan - Lies against diaphragm and 9 th -11 th ribs n left side - Mstly intraperitneal Functin - Frmatin f red bld cells during fetal and early pstnatal life - Develpment f mnnuclear leukcytes, lymphcytes and clearance f red bld cells frm bld - Filters bld, remves irn frm hemglbin - Stres bld Regins - Left upper quadrant f the abdmen between stmach and diaphragm - Hilum >> frmed by a lne fissure, where the splenic artery enters and the splenic vein leaves Bld supply - Splenic artery >> arises frm celiac trunk Venus drainage - Via prtal circulatin Splenmegaly - Increase in RBCs may result in an enlarged spleen - Occurs in patients wh are diagnsed with diseases that change the shape f RBCs (malaria etc) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 17

18 Midgut anatmy General details Supplied by superir mesenteric artery Parasympathetic innervatin via the vagus nerve at L1 Cntains distal half f dudenum, jejunum, ileum, cecum, ascending cln Jejunum and ileum Bth suspended frm the psterir abdminal wall by the mesentery Arranged in cils, which ccupy mst f the abdminal cavity There is n fixed line f demarcatin between the tw Sme cmparisn features: - Jejunum tends t have thicker walls - Jejunum tends t be emptier than the ileum - Jejunum shws windws in the mesentery, with n fat - Jejunum has a pattern f bld vessels >> single layer f vascular arcades - Jejunum has many circular flds in the mucsa >> pilae circulares (ileum is rather smth in cmparisn) - Jejunum desn t have Peyer s patches Cecum and appendix Junctin between terminal ileum and cecum >> ilecaecal junctin and the ilececal valve (little mechanical functin) Cecum lies in the right illiac fssa and huses the appendix in this regin (pstermedial attachment t the cecum) Appendix lcatins - Appendix lies behind cecum >> retrcecal appendix - The appendix has its wn little mesentery >> mesappendix, cntaining appendiceal artery Ascending cln Retrperitneal Extends upwards frm the right iliac fssa t the hepatic flexure just belw the liver in frnt f the right kidney Hindgut anatmy General details Supplied by inferir mesenteric artery Parasympathetic innervatin via the pelvic nerve at L3 Cntains transverse, descending and sigmid cln, rectum and anus This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 18

19 Transverse, descending and sigmid cln Transverse cln - Extends t the left frm the right clic flexure and ends at the left clic flexure - Mst bvius feature >> its mbility - Has a mesentery f its wn >> transverse mescln Descending cln - Usually retrperitneal - Descends t the pelvic brim where the sigmid cln begins Sigmid cln - Has its wn mesentery >> sigmid mescln Rectum and anus The sigmid cln becmes the rectum and anrectal canal at the Rectsigmid junctin >> lined with taeniae cli (distinct banding ribbns) Anrectal canal can drain either int the prtal vein (via superir rectal vein) r int the systemic circulatin (via the inferir r middle rectal veins) - Clinical imprtance f this prtsystemic anastmsis - Patients with liver disease that results frm prtal hypertensin can result in varicsities f the middle and inferir rectal veins >> hemrrhids Additinal intestinal anatmy NOTE: THE SMA, CELIAC TRUNK AND IMA ALL FORM ONE ARTERY THAT RUNS AROUND THE MESENTERIC BORDER OF ALMOST THE ENTIRE LARGE INTESTINE. THIS IS CALLED THE MARGINAL ARTERY OF DRUMMOND. THIS IS VITAL TO SEVERAL SURGICAL PROCEDURES INVOLVING RESECTION OF PORTIONS OF THE COLON Additinal bld supply and venus drainage infrmatin intestines Superir mesenteric and inferir mesenteric veins drain int the prtal vein >> which is why the first pint f malignant metastasis is the liver instead f the IVC The prtal vein: Splenic vein and superir mesenteric vein = prtal vein Inferir mesenteric vein can jin any f these tw veins, r their junctin >> variable in the bdy Small intestine Supplied by autnmic and sensry fibers Vagal nerve (CNX parasympathetic) stimulates intestinal mvement and secretin Sympathetic stimulatin is generally inhibitry inhibits muscular cntractins such as peristalsis and secretins This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 19

20 Hepatic prtal system General cnsideratins Venus return frm almst the entire bwel drains int the prtal venus system headed t the liver Hw des the prtal system drain bld? Capillary beds f the bwel cnverge int venules and then veins These veins cnverge int larger veins The larger veins cnverge int the superir and inferir mesenteric veins The superir and inferir mesenteric veins are jined by the splenic vein returning frm the spleen >> triad frming the hepatic prtal vein/prtal vein The prtal vein reaches the liver and drains entering the prta hepatis zne n the psterir side Once the bld has been prcessed by the liver, it is drained frm the liver by 2-3 large hepatic veins directly int IVC Prtsystemic anastmses These are usually lw pressure znes but if the prtal system pressures increases, this causes increased pressure within the systemic circulatin These znes can develp varices due t this prtal hypertensin - Lwer esphageal varices >> can bleed prfusely - Paraumbilical varices >> caput medusae - Anrectal varices / hemrrhids >> can bleed r thrmbse Enteric nervus system Submucsal nerve plexus Knwn as Meissner s neve plexus Lies in the submucsa between muscularis mucsal epithelium and inner layer f smth muscle Regulates GI secretins, bld flw and absrptin Receives input frm sympathetic and parasympathetic nervus system Myenteric nerve plexus Knwn as Auerbach s nerve plexus Lies in the muscularis externa Regulates GI mtility Receives input frm sympathetic and parasympathetic nervus system Assciated lymphatics Cllecting system fr lymphatic drainage f stmach and upper intestine = cisterna chyli Named s because fatty substances (chyle) accumulate here frm upper bwels This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 20

21 The chyle accumulates in cisterna chyli and then the thracic duct drains upwards Thracic duct + venus drainage f the neck empty tgether int the venus circulatin = thus malignancies f upper GI tract can spread t the rt f the neck Inguinal regin anatmy Inguinal ligament Is the rlled under inferir free brder f the external blique apneurses, extending between the ASIS t the pubic tubercle Shaped like a gutter Attachment sites f the anterir abdminal muscles Internal blique - Extends pass ASIS and alng gutter f the inguinal ligament t abut 2/3 f the way alng the ligament - Attach t the pubic tubercle as first part f the cnjint tendn Transversus abdminis - Extends alng the gutter f the inguinal ligament, but nly half way alng it - Attaches t the pubic tubercle as the secnd part f the cnjint tendn Inguinal canal Small area lying just abve the inguinal ligament It is a pathway thrugh the lwer anterir abdminal wall layers 4cm lng Starts at the deep inguinal ring and ends at the superficial inguinal ring running in an blique directin frm entrance t exit Deep inguinal ring - Opening in transversalis fascia - Lies laterally t the inferir epigastric vessels that arise frm the external illiac vessels Superficial ring - Inverted V shaped gap between tw crura f the external blique apneursis that attach t the pubic tubercle and crest Cntents f the inguinal canal Spermatic crd (males) - Ductus deferens passes int deep inguinal ring, is jined by vessels and nerves t frm the spermatic crd - As it enters the deep ring, it picks up the transversalis fascia which then becmes the fascia cvering the crd - As the crd travels, it passes belw the transversus abdminis muscle fibres - As it emerges frm the superficial ring it picks up a layer frm the edges f the ring, becming the external spermatic fascia - Cre cmpnents f the spermatic crd: (1) Ductus deferens + its arteries and veins (2) Testicular artery (3) Cremasteric artery (4) Pampinifrm plexus leading t testicular vein This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 21

22 (5) Genital branch f the genitfemral nerve (6) Lymphatics (7) Surrunded by three layers f fascia: internal spermatic, cremasteric and external spermatic Rund ligament f the uterus (females) Iliinguinal nerve Fibers frm the inguinal ligament lacunar ligament Develpment f the gnads Develpment - Develp in bth sexes frm the urgenital ridge n the psterir bdy wall f the embry >> retrperitneal - Gnads then descend t their final psitins >> testes in the scrtum and the varies in the pelvis - This descent is relative - The gnads stay where they are, while the rest f the embry grws upwards and dwnwards Attachments - Attached t scrtum in the male and the labia majra in the female by a crd called the gubernaculum - The gubernaculum guides them n their relative descend and tethers them t lwer structures - In males, the gubernaculum tethers the testis t the scrtum and the testis is gradually pulled dwn thrugh the inguinal canal - In females, the gubernaculum guides the varies twards the uterus Relative utpuchings - Outpuching f peritneum that extends thrugh the deep inguinal ring and inguinal canal and dwn int scrtum f male >> prcessus vaginalis - Prcessus vaginalis extends t the testis in the male, mst f it being turned int fibrus tissue, but the distal prtin remains >> tunica vaginalis - This tends t stp in the female at the superficial ring - Smetimes the prcessus vaginalis remains patent and desn t underg fibrsis >> gives rise t the Canal f Nuck in females Bld supply - Because gnads develp n psterir bdy wall, they get their bld supply frm here - Gnadal vessels arise frm abdminal arta - Gnadal vessels drained int either IVC directly (right) r indirectly via the renal vein (left) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 22

23 Physilgy f swallwing and mtility Gastrintestinal mtility Cntractins - Cntractile tissue f GIT is almst always smth muscle which is electrically cupled via gap junctins (rapid cell t cell actin ptentials) - Exceptins fr smth muscle pharynx, upper 1/3 f esphagus and external anal sphincter (all have striated muscle) Slw waves - Unique feature f GIT smth muscle - Refers t the scillating deplarizatin and replarizatin f membrane ptential f smth muscle cells - Slw waves ccur at interstitial cells f Cajal (the pacemaker f the GIT) - Frequency f slw waves varies alng the GIT: stmach has the slwest frequency (3/min), ileum (8-9/min) and dudenum has the fastest frequency (12/min) - Mechanism: cyclic pening f Ca+ channels deplarizes the cell membrane, and cyclic pening f K+ channels replarizes the cell membrane Swallwing Oral phase - Swallwing under vluntary cntrl f the muth - (1) Fd blus prpelled frm the muth t the pharynx via the tngue - (2) Smatsensry receptrs in the pharynx are activated which initiates invluntary swallwing reflex in the swallwing center in the medulla Pharyngeal phase - Swallwing under invluntary cntrl reflex peristaltic wave f cntractin - Breathing is inhibited during this phase - (3) Fd blus is prpelled frm the pharynx t the esphagus by the sft palate rising t prtect naspharynx, the epiglttis cvering the larynx pening t prevent aspiratin, and the upper esphageal sphincter pening Oesphageal phase - Swallwing under invluntary reflex primary and secndary waves f peristalsis - (4) Fd blus is prpelled frm the pharynx t the lwer esphagus; after which the upper esphageal sphincter clses t prevent reflux int the pharynx Oesphageal mtility Overlaps with esphageal phase f swallwing under invluntary reflex (5) Fd prpels dwn t the lwer esphageal sphincter via sequential cntractins f smth muscle and peristaltic waves If the primary peristaltic waves d nt clear the esphagus, then a secnd wave will prceed mediated by the enteric nervus system (6) Lwer esphageal (cardiac) sphincter relaxes and pens and the rad stmach relaxes via receptive relaxatin (decreasing in pressure t pull the fd blus dwnwards) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 23

24 (7) LOS cntracts and clses t prevent the blus frm refluxing int the esphagus Gastric mtility Functins - Oral stmach = fundus and prximal prtin; relaxes and receives the fd blus frm the esphagus - Caudad stmach = distal prtin and antrum; cntractins here reduce the size f the blus and mix it with secretins t initiate digestin (8) Receptive relaxatin (a reductin in pressure and increase in vlume f the rad stmach) - Vasvagal afferent fibers (sensry): mechanreceptrs detect distentin f the lwer esphagus and rad stmach by the incming blus they relay sensry infrmatin t the CNS via vagus nerve - Vasvagal efferent fibers (mtr): CNS relays mtr infrmatin t the smth muscle walls f the lwer esphagus and the rad stmach via vagus nerve; releasing vasactive intestinal plypeptide (VIP), which relaxes the LOS and smth muscle (9) Mixing and digestin - Occurs in the caudad f the stmach which has a thick muscular wall fr prductin f cntractins needed t break up the blus - Mixing cntents is prpelled t the antrum and then back twards the bdy f the stmach (retrpulsin) (10) Gastric emptying - Cntractins prpel sme f the cntents thrugh the pylri sphincter and int the dudenum f small intestine - Clsely regulated t allw time fr neutralizatin f gastric acid in the dudenum - H+ receptrs detect lw ph/high H+ and act via interneurns in the myenteric plexus t slw gastric emptying (allws time fr neutralizatin by pancreatic HCO3-) - When fatty acids are encuntered in the dudenum, chlecystkinin (CCK) is secreted by I cells in the small intestine t slw gastric emptying (allwing time fr acid digestin and absrptin) Small intestine mtility Functins - Digestin and absrptin f nutrients - Mixes chyme with digestive enzymes and pancreatic secretins - Prpels unabsrbed chyme alng GIT Small intestine cntractins - Segmental cntractins (in sectins) which splits the chyme and sends it in bth directins - Sectins then relax, and the chyme mixes back tgether - Peristaltic cntractins prpel intestinal cntents alng GIT t the large intestine Migrating myelectric cmplexes (MMCs) Perids f small intestinal cntractins that ccur during the fasting state (90 min intervals) Helps t clear the small intestine f any residual cntents Mediated by mtilin Large intestine mtility Functins - Fecal material mves thrugh the cecum > cln (ascending, transverse, descending and sigmid) > rectum > anal canal This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 24

25 - Fecal material is excreted Segmentatin cntractins - Mix intestinal cntents f the large intestine - Occurs in the cecum and prximal cln - Cntractins assciated with characteristic sac-like segments called haustra Mass mvements - Cntents is mved ver lng distance 1-3 times per day - Fecal material in distal cln is semi-slid and mves slwly cnsequence f clnic water absrptin Defecatin - Rectsphincteric reflex - As rectum fills with fecal material the smth muscle walls f the rectum cntracts and the internal anal sphincter relaxes - At this pint defecatin, des nt ccur because the external sphincter is still tnically cntracted (under vluntary cntrl) - Once rectum is 25% full, the urge t defecate ccurs - Defecatin causes smth muscle wall f rectum t cntract and generate sufficient pressure t push material thrugh anal canal Salivary glands secretins Salivary secretins Partid glands, submandibular glands and sublingual glands Frmatin f saliva - Acinar (pancreatic) cells prduce initial saliva cmpsed f water, ins, enzymes and mucus (istnic) - Initial salvia passes frm acinus t duct - Ductal cells (lining the pancreatic duct) mdify initial saliva t prduce final saliva by altering varius element cncentratins (decreasing Na+ and Cl-, increasing K+ and HCO3-) (hyptnic) Salivary enzymes - (1) a-amylase begins initial digestin f carbhydrates - (2) Lingual lipase begins initial digestin f lipids - (3) Kallikrein catalyses prtelytic cleavage f kiningen int bradykinin > ptent vasdilatr > increases salivary gland activity and bld flw - Acinar cells secrete IgA Flw rate and cmpsitin - Highest flw rates final saliva resembles plasma (istnic) > ductal cells have less time t mdify the saliva - Lwest flw rates final saliva is mst dissimilar t plasma (hyptnic) > ductal cells have mre time t mdify the saliva Regulatin - Stimulated bth sympathetic and parasympathetic nervus system - Sympathetic input t the salivary glands via thracic segment (T1-T3) where pstganglinic nerves release NE > stimulates adenylyl cyclase > increased camp > increased secretin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 25

26 - Parasympathetic input t the salivary glands via facial nerve (CNVII) and glsspharyngeal nerve (CN IX) > increased Ach > stimulates muscarinic receptrs > increased IP3 and calcium > increased saliva secretin Gastric secretins and glands Overview Cells f gastric mucsa secrete gastric juice Gastric secretins cmpsed f hydrchlric acid, pepsingen, intrinsic factr and mucus HCl and pepsingen = initiate prtein digestin Intrinsic factr = required fr vitamin B12 absrptin in ileum and is the ONLY essential secretin f the stmach; deficiency causes pernicius anemia Mucus = prtectin fr gastric mucsa and lubricates cntents Gastric glands Oxyntic glands - In the bdy f the stmach - Lie within the gastric pits f the stmach - These glands cntain parietal cells (secrete HCl and IF) and chief cells (secrete pepsingen) Pylric glands - In the antrum f the stmach - Lie within the gastric pits f the stmach - Cntain G cells (secrete gastrin int systemic circulatin) and mucsal neck cells (secrete mucus and HCO3- int pylric ducts Gastric parietal cell Apical membrane - Cntains H+-K+ ATPase and Cl- channels Baslateral membrane - Na+ - K+ ATPase and Cl-/HCO3- exchanger Rle f parietal cells - Secreting HCl and IF int xyntic ducts that empty int the stmach, this HCl acidifies gastric cntents Parietal cells are activated by - Smelling, tasting and cnditined reflexes fr anticipated fd - Distentin f the stmach - Presence f breakdwn prducts f prtein - Vagal stimulatin - Phenylalanine and tryptphan are mst ptent stimuli fr gastric secretin Vagal stimulatin direct pathway - Ach is released at synapse and binds t M3 muscarinic receptrs > increasing DAG and IP3 secnd messengers > increasing intracellular calcium > PKC (prtein kinase C) breaks dwn DAG and calcium > HCl secretin is increased Vagal stimulatin indirect pathway - Innervatin f the gastric G cells > at synapse, gastrin-releasing peptide (GRP) is released - GRP increases gastrin secretin indirectly via G cells Vagal stimulatin atrpine This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 26

27 - Atrpine inhibits HCl secretin via parietal cells, because it s a chlinergic muscarinic antagnist Histamine - Released via enterchrmaffin-like(ecl) cells in gastric mucsa > binds t H2 receptrs n parietal cells > increase camp secnd messenger > H+K+ ATPase > increases HCl secretin Gastrin - Released frm G cells f antrum int systemic circulatin and is delivered back t the stmach via systemic circulatin - Stimulates HCl secretin by a) binding t CCK-B receptrs (chlecystkinin) n parietal cells r b) binding t CCK-B receptrs n ECL cells, increasing histamine and HCl secretin Inhibitin f HCl secretin - Inhibitin f HCl is required when the chyme is being prpelled alng the GIT frm the stmach - Smatstatin is secreted by D cells f gastric mucsa t reduce HCl secretin - Prstaglandins bind t G prteins n parietal cells t reduce HCl secretin Gastric chief cell Functin - Secrete pepsingen int xyntic ducts within the gastric pits f the stmach - Pepsingen = zymgen (inactive enzyme) that must be activated thrugh cleavage Activatin f pepsingen secretin - Vagal stimulatin = increase in pepsingen secretin frm chief cells - Increased hydrgen ins = increase in pepsingen secretin frm chief cells Pancreatic secretins Cmpnents f pancreatic juice - HCO3-, Cl-, Na+ and K+ - HCO3- is very imprtant as it alkalizes pancreatic juice which in turn assists t neutralize stmach acid entering the dudenum Enzymes that digest carbhydrates (1) Amylase Secreted by acinar cells in their active frm Digest starch bnds f plysaccharides frming maltse, dextrin s and malttrise These simple sugars are hydrlyzed int glucse by brush brder enzymes and then transprted acrss the intestinal wall via Na+ cuple transprt Enzymes that digest lipids (1) Lipase-clipase Secreted by acinar cells in their active frm Hydrlyses triglycerides int fatty acids - Phsphlipase A2 Enzymes that digest prteins (these are all secreted by the zygmen granules within acinar cells) - Trypsingen > trypsin (active) - Chymtrypsingen > chymtrypsin (active) - Prelastase > elastase (active) - Prcarbxypeptidase A/B > carbxypeptidase A/B (active) Regulatin f pancreatic juice secretin - Tw hrmnes: This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 27

28 (1) Secretin triggered by gastric acid; acts n centracinar and acinar cells t raise pancreatic juice ph; als increases secretin f H2O, increasing the vlume f pancreatic juice) (2) Chlecystkinin (CCK) triggered by peptides, amin acids and fatty acids as they enter the dudenum; activates neurns that cntrl PS signals; directly act n the acinar cells by raising intracellular Ca2+, therefre frcing the secretin f enzymes frm zymgen cells GI hrmnes and secretins summary Hrmne Surce Actin Regulatin Ntes Gastrin G cells (stmach antrum) Chlecystkinin (CCK) Secretin Smstatin Glucse dependent insulintrpic peptide (GIP) Vasactive intestinal plypeptide (VIP) I cells (dudenum, jejunum) S cells (dudenum) D cells (GI mucsa) Delta cells (endcrine pancreas) K cells (dudenum, jejunum) Parasympathetic ganglia in sphincters, gallbladder and small intestine Increase gastric H+ secretin Increase grwth f gastric mucsa Increase gastric mtility Increase pancreatic secretin Increase gallbladder cntractin and relaxatin f sphincter f Oddi Decrease gastric emptying Increase HCO3- secretin Increase biliary HCO3- secretin Decrease gastric H+ and pepsingen Decrease pancreatic and small intestine fluid secretin Decreased gallbladder cntractin Decrease insulin and glucagn release Excrine: decrease gastric H+ secretin Endcrine: increase insulin secretin by pancreatic beta cells Increase intestinal water and electrlyte secretin Increase relaxatin f intestinal smth muscle and sphincters Increased by stmach distentin Increased by amin acids, small peptides Increased by vagal stimulatin (GRP) Decreased by a stmach ph f <1.5 Decreased by smstatin Increase by amin acids, small peptides Increased by fatty acids Increased by H+ in dudenum Increased by fatty acids in dudenum Increased by H+ Decreased by vagal stimulatin Increased by fatty acids Increased by amin acids Increased by ral glucse Increased by distentin and vagal stimulatin Decreased by adrenergic input Highly elevated in Zllinger-Ellisn syndrme Phenylalanine and tryptphan are ptent stimulatrs A patient with chlelithiasis experiences wrsened pain after eating fatty fd due t the increased release f CCK Increased HCO3- neutralizes gastric H+ in dudenum, essential fr fat digestin Inhibitry hrmne Antigrwth hrmne effects An ral glucse lad is utilized by cells mre rapidly than an IV glucse lad VIPma is a nnalpha, nn-beta islet cell pancreatic tumr that secretes VIP and causes massive diarrhea This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 28

29 Mtilin Ghrelin Neurpeptide Y Glucagn-like peptide 1 (GLP- 1) Small intestine (upper dudenum) P/D1 cells (stmach) Neurnes f the SNS L cells (endcrine cells f the intestinal epithelium) Increase GI mtility Prduces migrating mtr cmplexes (MMCs) Increase grwth hrmne, ACTH, crtisl and prlactin secretin frm pituitary Increase appetite Decrease energy expenditure Increased glucse-induced insulin secretin frm pancreatic beta cells Decreased glucagn secretin Decreased GI mtility and secretins Prmtes satiety Increased in fasting state Decreased befre meals Increased after meals Respnds t increased ghrelin release Secreted in respnse t meal intake Degraded by dipeptidyl peptidase IV Regulates hunger, meal initiatin Lst fllwing gastric bypass surgery Assciated with hyperphagia in Prader-Willi syndrme Digestin and nutrients Micrnutrients Cmpunds that are required fr nrmal functin but nly in minute amunts. They are typically cenzymes in metablic prcesses and can be water sluble, fat sluble, metallic and nn-metallic Water sluble vitamins Vitamin C - Scurvy Bleeding and easy bruising (lack f vitamin C => pr wund healing and bld vessel fragility) Hair and teeth lss Jint pain and swelling Fatigue and lack f cncentratin Thiamine (B1) - Beri Beri - Wernicke-Krsakff syndrme Ribflavin (B2) Niacin (B3) Pantthenate (B5) Pyridxal (B6) Bitin (B7) Flate (B9) - Micrcytic anemia Cbalamin (B12) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 29

30 Absrptin f water sluble vitamins Absrbed in the jejunum via classic prtein transprters APART FROM B12, which is absrbed in the terminal ileum with intrinsic factr Water sluble vitamins that are ph dependent Thiamine (B1) Flate (B9) Pyridxal (B6) Niacin (B3) Fat sluble vitamins Vitamin K synthesis Factrs 2, 7, 9, 10 Prtein C and Prtein S Metallic micrnutrients Calcium Magnesium Cpper Nickel Zinc - It is an imprtant part f ver 300 enzymes due t its strng but interchangeable interactins with many ligands - Zinc deficiency: pr appetite and weight lss, delayed wund healing, taste abnrmalities, mental lethargy, hair lss and dermatitis, diarrhea - The immune system wrst affected, with deficiency resulting in: This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 30

31 Reduced circulating Ig Reduced T cell number and functining Recurrent infectins Pr wund healing Increased gluccrticid secretin Nn-metallic micrnutrients Flurine Idine - Essential cmpnent f the thyrid hrmnes: T3 (triidthyrnine) T4 (tetraidthyrnine/thyrxine) Phsphrus Selenium - Cvalently binds t cysteine t create an selencysteine, the 21st natural AA - Selencysteine fund in perxidases, reductases, thyrid hrmne enzymes and ther prteins - Deficiency >> Keshan disease (cmmn in China, cardimegaly and pr functining f heart) - Als, causes prmte prgressin f HIV t AIDS, increases risk f prstate, cln, lung cancer, Silica prduces prblems in M+F fertility Phases f nutrient absrptin (1) Intraluminal digestin - Prteins, carbs and fats are brken dwn int frms suitable fr absrptin (2) Terminal digestin - Hydrlysis f carbs and peptides by disaccharides and peptidases in the brush brder f the small intestine mucsa (3) Trans epithelial transprt - Nutrients, fluid and electrlytes are transprted acrss and prcessed within the SI f the epithelium (4) Lymphatic transprt f lipids Carbhydrate digestin Overview - Carbs = plysaccharides, disaccharides and mnsaccharides - The intestinal cells can nly absrb mnsaccharides (glucse, galactse and fructse), which is why digestin is s imprtant Digestin f plysaccharides >> mnsaccharides (1) Muth: - Carbs are cnsumed - Salivary alpha amylase is secreted t initiate digestin f plysaccharides in the muth (small rle) - Plysaccharides are brken dwn int dextrins, sucrse, lactse and maltse (2) Stmach and small intestine: - Pancreatic alpha amylase is secreted int the lumen f the dudenum and small intestine t further digest the plysaccharides and disaccharides - Intestinal brush brder enzymes begin t digest the remaining mlecules t mnsaccharides - Alpha dextrinase catalyses dextrins >> glucse - Maltase catalyses maltse >> glucse This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 31

32 - Sucrase catalyses malttrise >> glucse (3) Intestinal lining: - Via active transprt, the mnsaccharides are absrbed thrugh the intestinal lining int the bldstream (water sluble) r lymphatics (fat sluble) Carbhydrate absrptin Glucse and galactse - Absrbed by entercytes via secndary active transprt (Na+ - glucse ctransprter; SGLT1) - Pass frm entercytes t the bldstream via facilitated diffusin (GLUT2) Fructse - Absrbed by entercytes by facilitated diffusin (GLUT2) Prtein absrptin Prtein degradatin via trypsin and pepsin >> becme amin acids Amin acids are absrbed by the gut with different transprters, depending n whether they are basic amin acids r large neutral amin acids Vitamin and mineral absrptin Vitamin B12 (Cbalamin) - Absrptin ccurs at the terminal ileum - Requires intrinsic factr (IF) - IF deficiency can ccur cnsequently t lss f parietal cells, resulting in a vitamin B12 deficiency and may cause pernicius anemia Irn - Absrptin ccurs in the dudenum by entercytes (intestinal epithelium) as free irn; free irn binds t apferritin in the entercytes; this irn-ferritin cmplex is transprted acrss the membrane int the bldstream; here irn binds t transferrin and is taken t the liver fr strage - Absrptin f irn can als be in the frm f heme irn int the entercytes; this is digested by lyssmal enzymes; which then releases free irn; which is bund t apferritin >> etc Flic acid - Absrptin ccurs in the jejunum - Small reserve pl is stred in the liver Gastrintestinal histry Abdminal pain PUD pain >> dull r burning in epigastrium that s relived by fd and antacids, episdic and may ccur at night Pancreatic pain >> steady epigastric pain that may be partly relieved by sitting up and leaning frwards, radiatin t the back is cmmn Biliary pain >> epigastric pain, usually is mre severe and lasts several hurs Renal clic pain >> clicky pain superimpsed n a backgrund f cnstant pain in the renal angle, ften with radiatin t the grin Bwel bstructin pain >> clicky pain, small bwel bstructin causes mre frequent episdes (every 2-3 mins) versus large bwel bstructin frequency (every mins), ften assciated with vmiting, cnstipatin and abdminal distentin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 32

33 Appetite and weight change Anrexia and weight lss = malignancy, depressin Weight lss and increased appetite = malabsrptin f nutrients r a hypermetablic state Disturbance f taste = liver disease Early satiatin and pstprandial fullness Inability t finish a nrmal meal = gastric disease, including cancer and peptic ulcers Feeling f inapprpriate fullness after eating = functinal dyspepsia Nausea and vmiting Acute symptms >> GIT infectin r small bwel bstructin Chrnic symptms >> pregnancy and drug use (digxin, piates, dpamine agnists), gastric utlet bstructin, mtr diseases, hepatbiliary disease, psychgenic vmiting (bulimia) and alchlism Nte: vmiting is different frm ruminatin. Ruminatin is effrtless regurgitatin f fd int the muth after eating Heartburn and acid regurgitatin Retrsternal burning pain r discmfrt that usually travels up twards the thrat Occurs after meals r is aggravated by lying supine Antacids relieve the pain Pain is aggravated by alchl, chclate, caffeine, a fatty meal, thephylline, calcium channel blckers and antichlinergic drugs Nte >> regurgitatin is nt t be cnfused with water brash; which is an excessive secretin f saliva Dysphagia Difficulty swallwing (this is different frm painful swallwing dynphagia) Patients may cmplain f fd getting stuck in the esphagus (anatmical blckage) If the patient cmplains f prgressive dysphagia (stricture, carcinma r achalasia) Diarrhea Small intestine diarrhea tends t be nn-inflammatry >> linked with ETEC, staph, bacillus, giardia Large intestine diarrhea tends t be inflammatry >> linked with shingella, salmnella, campylbacter, clstridium diff Watery, high vlume stl - (1) Secretry diarrhea >> net secretin f the cln r small bwel exceeds absrptin; due t infectin, hrmnal cnditins r villus adenma - (2) Osmtic diarrhea >> disappears with fasting; ccurs due t excessive slute drag; due t lactse intlerance, magnesium antacids r gastric surgery - (3) Abnrmal intestinal mtility >> if patient has thyrtxicsis r IBS Bld cntaining stl - (1) Exudative diarrhea >> inflammatin f the cln Fat cntaining stl - (1) Malabsrptin >> f nutrients and steatrrhea; stls are pale, fatty, extremely smelly and flat/hard t flush away - Steatrrhea is the presence f mre than 7g f fat in a 24-hur cllectin f stl Cnstipatin Ingestin f drugs >> cdeine, antidepressants, aluminum r calcium antacids Metablic r endcrine disease >> hypthyridism, hypercalcemia, diabetes mellitus, phaechrmcytma This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 33

34 Neurlgical disrders >> autnmic neurpathy, multiple sclersis, Hirschsprung s disease Bwel related >> Carcinma r partial clnic bstructin Pruritus Think abut chlestatic liver disease Questins t ask: Recurrent vmiting - Describe an episde (rule ut ruminatin) - Hw lng have the attacks been happening? - Des it ccur with nausea r withut warning? - Abdminal pain assciated with the vmiting? - Des it ccur in specific episdes? (Cyclical vmiting syndrme) - What des it lk like, is it bld stained, bile-stained r felucent (bleeding)? - Have yu been lsing weight? GORD - D yu have heartburn? Hw ften des it ccur? - Des the heartburn ccur straight after eating? - Is the pain relieved by antacids? (Typical acid reflux) - Des the pain radiate acrss yur chest dwn yur left arm r int yur jaw? (MI) - Have yu had truble swallwing? (Dysphagia) Dysphagia - D yu have truble swallwing slids, liquids r bth? (Slids and liquids suggest a mtr prblem) - Where des the hldup ccur in yur thrat? - D yu cugh r start t chke n starting t swallw? - D yu have asthma r hay fever? (esinphilic Oesphagitis) - Have yu been lsing weight? Diarrhea - Hw many stls per day d yu pass? What d they lk like? - D yu have t race t the bathrm fr a bwel mvement? (Urgency in clnic disease) - Have yu been wken frm sleep during the night by Diarrhea? - Have yu had prblems with leakage f stl? (Fecal incntinence) - Have yu seen any bright red bld in the stls, r mucus r pus? (Clnic disease) - Have yu lst weight? (Cancer, malabsrptin) - Have yu had a recent fever, rigr, chills? (Infectin, lymphma) Cnstipatin - Hw ften is the bwel mvement? Are they hard r difficult t pass? What d they lk like? - Has yur bwel habit changed recently? - Any bld in the stl? - Any weight lss? - D yu have a histry f cln plyps r cancer? Hematemesis - Befre any bld was seen, did yu experience any intense retching r vmiting? (Mallry-Weiss tear) - Was there fresh bld in the vmitus? Or was the vmitus cffee-stained? This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 34

35 - Have yu passed any black stls r bld in the stl? - Have yu lst weight? Jaundice - Is yur urine dark? Are yur stls pale? (Obstructive jaundice) - D yu have skin itching? - D yu drink alchl? (CAGE questins) - D yu have a fever? (Chlangitis) - Have yu had a change in yur appetite? (Malignancy) Relevant histry Lethargy >> acute r chrnic liver disease, anemia NSAID use >> induce bleeding frm GIT Other drugs and anablic sterids Paracetaml verdse >> acute liver cell necrsis Surgical prcedures >> jaundice can result r direct damage t bile duct PMH >> IBS; culd be a flare up f a past disease Scial histry >> ccupatin, like expsure t hepatitis; alchl histry; sexual histry Family histry >> cln cancer, familial plyps, inflammatry bwel disease, jaundice, anemia, splenectmy, hemlytic anemia, cngenital r familial hyperbilirubinemia Gastrintestinal examinatin Examinatin anatmy Liver - Lwer brder extends frm tip f right 10 th rib t just belw the left nipple - Nrmally nt palpable may just be able t feel the lwer ledge in healthy peple Spleen - Underlies the 9 th, 10 th and 11 th ribs psterirly n the left - Usually nt palpable in health Kidneys - Lie anterirly fur finger breadths frm midline and psterirly under the 12 th rib - Right kidney nrmally extends 2.5cm lwer than the left - Lwer left ple f right kidney may be felt in healthy peple Gallbladder - Tip f the 9 th cstal cartilage - Cannt be felt in health Pancreas - In retrperitneum with head tucked int a C shape Arta - Lies in midline and terminates left f the midline at the iliac crest Stmach - 1.5m in length - Appendix in RLQ This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 35

36 General appearance Jaundice Hands Palms - Yellw disclratin f sclera and skin resulting frm hyperbilirubinemia Skin pigmentatin - Generalized pigmentatin can result frm chrnic liver disease, especially hemchrmatsis - Addisnian-type pigmentatin (sunkissed pigmentatin) sign f malabsrptin - Freckle like spts arund the muth and buccal mucsa, and n fingers and tes are assciated with hamartmas f the small bwel and cln - Brwn-black velvety elevatins f the epidermis f the neck and axilla assciated with acanthsis nigricans - Presence f fragile vesicles appear n expsed areas f the skin ccurs in prphyria cutanea tarda - Tense leathery skin indicates systemic sclersis assciated with GORD r mtility disrders Mental state - Neurlgical disturbance can be nticed in hepatic encephalpathy due t decmpensated advanced cirrhsis - Hepatic encephalpathy >> disturbance in prtein metablism in the liver due t hepatcyte failure r prtal-t-systemic shunting, causing a net effect f elevatin f centrally acting txins Leuknychia - Due t hypalbuminemia frm chrnic liver disease, causing pacificatin f the nail beds - Giving them a milky white appearance - Cmpressin f capillary flw by extracellular fluid Muehrcke s lines - Transverse white lines n the nails, ccurring in hypalbuminemia states Clubbing - Indicatin f cirrhsis, AV shunting in the lungs and cyansis - Caused by IBD, celiac disease, r nutritinal depletin Palmar erythema - Liver palms als related t rheumatid arthritis, plycythemia, raised estrgen levels - Redding f the palms invlving thenar and hypthenar eminences - Sles f the feet can be affected t - Can be a nrmal finding in pregnancy Anemia - Palmar crease pallr - May result frm GI bld lss, malabsrptin r chrnic disease Dupuytren s cntracture - Visible and palpable thickening and cntractin f palmar fascia causing permanent flexin, mst ften f the ring ringer - Palmar fascia f these patients cntains abnrmal amunts f xanthine - Often bilateral and n the feet - Assciated with alchlism and in sme manual wrkers Hepatic flap Hlding ut the arms fr 15 secnds This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 36

37 Tremr Arms Eyes Jerky, irregular flexin-extensin mvements f the hands Assciated with hepatic encephalpathy Due t interference with inflw f jint psitin sense infrmatin (prpriceptin) t the reticular frmatin in the brainstem Results in rhythmic lapses in pstural tne Apparent tremr - Wilsns disease Resting tremr - Alchlism Large bruises (ecchymses) - Due t cltting abnrmalities prduced by hepatcellular damage Petechiae - Pinhead bruises - Assciated with chrnic excessive alchl cnsumptin resulting in bne marrw depressin; als splenmegaly due t prtal hypertensin Scratch marks - Pruritus - Occur in patients with bstructive r chlestatic jaundice, biliary cirrhsis Spider naevi - Cnsist f a central arterile frm which radiate numerus small vessels that lk like spider s legs - Usually lcatin is in the area drained by the superir vena cava - Pressure applied t the area results in blanching f the whle lesin - Mre than tw is abnrmal >> may indicate cirrhsis, viral hepatitis - Differentials fr these lesins: Campbell de Mrgan spts, venus stars Bitt s spts - Yellw keratinized areas f the sclera - Result frm severe vitamin A deficiency due t malabsrptin r malnutritin - Retinal damage and blindness can ccur Kayser-Fleischer rings - Brwnish-green rings ccurring in the periphery f the crnea, affecting upper ple mre than lwer - Due t depsits f excess cpper in the crnea - Assciated with Wilsns disease (cpper strage disease) Xanthelasma - Yellwish plaques in the subcutaneus tissue under the eye due t depsits f lipids - Pathgenesis: disturbance f lipid metablism r destructin f the bile ducts, causing decreased lipid clearance by bile - Assciated with chlestasis, biliary cirrhsis Perirbital purpura - Black eye syndrme - Characteristic f amylidsis, very rare Salivary glands Partid enlargement This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 37

38 - Bilaterally assciated with alchlism, due t fatty infiltratin - Lumpy partid gland assciated with partid tumr - Mumps can als cause this Submandibular gland enlargement - Mst ften due t calculus r chrnic liver disease Teeth and muth Fetr hepaticus - Sweet smelling breath - Indicatin f severe hepatcellular disease - May be due t methylmercaptans/methinine - substances are knwn t be exhaled in the breath Lingua nigra (black tngue) - Due t elngatin f papillae ver psterir part f the tngue, which appears dark brwn because f accumulatin f keratin - Bismuth cmpunds may als cause black tngue Gegraphical tngue - Describes slwly changing red rings and lines that ccur n the surface f the tngue - Can be a sign f vitamin B2 deficiency Leukplakia - White clured thickening f the mucsa f the tngue and muth - Premalignant - Assciated with sre teeth (pr dental hygiene), smking, spirits, sepsis, syphilis Glssitis - Smth appearance f the tngue - Due t atrphy f the papillae resulting frm nutritinal deficiencies r a rare carcinid syndrme Macrglssia - Enlargement f the tngue - Assciated with cngenital cnditins such as Dwn syndrme and tumr infiltratin Apthus ulceratin - Mst cmmn type - Begins as a small painful vesicle n the tngue which may break dwn t frm a painful, shallw ulcer - Dn t indicate serius pathlgy but are assciated with Crhns disease Angular stmatitis - Cracks at the sides f the muth - Caused by deficiencies in vitamin B6, B12, flate and irn Thrush - Candida albicans infectin - Causes white-curd like patches in the muth that are remved nly with difficulty and leave a bleeding surface - Caused by immunsuppressin, antibitics, bad ral hygiene and diabetes Neck and chest Triser s sign - Large left supraclavicular nde (Virchw s nde) in cmbinatin with carcinma Gynaecmastia - In males, enlargement f the breasts This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 38

39 - Sign f chrnic liver disease, gastric cancer and cirrhsis Abdmen Acute abdmen - Patient lying very still, with shallw breathing Generalised abdminal distentin - Caused by things that start with F - Fat (grss besity), fluid (ascites), fetus (pregnant), flatus, faeces, phantm pregnancy Caput Medusae - Sign f engrged distended umbilical veins that are respnsible fr systemic flw due t prtal hypertensin - Very rare - Medusa s hair appearance Pulsatins - Indicate AAA r can be seen in nrmally thin peple Visible peristalsis - Can be seen in nrmal thin peple - Usually suggests intestinal bstructin Herpes Zster - Vesicles f herpes zster, in a radicular Patten Sister Mary Jseph ndule - Metastatic tumr depsit in the umbilicus Cullen s sign - The umbilical black eye - Disclratin f the umbilicus where a faintly bluish hue is present - Acute pancreatitis Striae - Stretch marks seen in Cushing s syndrme Abdminal guarding - Guarding frm the patient when palpatin f the abdmen ccurs Rebund tenderness - Present when the abdminal wall, having been cmpressed slwly, is released rapidly and a sudden stab f pain ccurs Rigidity - Cnstant invluntary reflex cntractin f the abdminal muscles always assciated with tenderness - Indicates peritnitis Divaricatin - Weakness in the abdminal wall apneursis is very cmmn and causes a bulging f the rectus sheath when intra-abdminal pressure increases Shifting dullness - Des the dullness n percussin stay there when the patient rlls n their side? - If the dull area is then resnant, peritneal fluid has shifted when being rlled - If the dull percussin remains, a mre lcalised and attached pathlgy is ccurring Ascites - Detected by bulging f the flanks and shifting dullness Frictin rub This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 39

40 - Indicate abnrmality f the parietal and visceral peritneum due t inflammatin - Splenic rub indicated a splenic infarct Venus hum - Cntinuus, lw pitched, sft murmur that may becme luder with inspiratin and diminish when mre pressure is applied t the stethscpe - Can be smetimes heard ver large veins Bwel sunds - Bwel sunds can be heard all ver the abdmen in healthy peple prly lcalised, mst in the stmach - Cmplete absence f bwel sunds ver a 4-minute perid indicates paralytic ileus (due t paralyzed bwel) - An bstructed bwel will prduce a luder, high pitched sund with tinkling quality due t presence f air and liquid - Intestinal hurry r rush is characterised by gurgling sunds diarrhea based Bruits - Higher pitched than a venus hum, nn-cntinuus and well lcalised - Usually due t hepatcellular cancer r intestinal ischemia if heard in the epigastrium Gallbladder Murphy s sign - Shuld be sught is chlecystitis is suspected - On taking a deep breath, the patient catches his r her breath when an inflamed gallbladder presses n the examiners hand Curvisier s law - If the gallbladder is enlarged and the patient is jaundiced, the cause is unlikely t be gallstnes - Carcinma f the pancreas r lwer biliary tree is likely t be present Kidneys Mves inferirly n inspiratin Are balltable because f their retrperitneal psitin Frictin rubs are never heard ver the kidneys as they are t psterir Bladder Empty bladder is nt palpable If palpable urinary retentin Rectal examinatin Hemrrhids - Small, tense, bluish swellings seen n the anal margin - Painful due t rupture f a vein Skin tags - Assciated with hemrrhids r Crhns disease Rectal prlapse - Circumferential flds f red mucsa are visible prtruding frm the anus Anal fissure - Crack in the anal wall - Pain can be elicited n DRE Faecal cntents Melaena - Prly frmed, black and tarry with and ffensive smell This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 40

41 - Presence f bld digested by gastric acid and clnic bacteria - Usually indicates bleeding frm the esphagus, stmach and dudenum Hematchezia - Bright red bld in the stl - Results frm hemrrhage frm the rectum r left cln Steatrrhea - Pale, ffensive, smelly and bulky stl - Often flating - Results frm malabsrptin f fat due t severe pancreatic disease Tthpaste stls - Expressed like tthpaste frm a tube - Cnditin usually due t severe cnstipatin with diarrhea - Assciated with IBS, stricture f Hirschsprung s disease Rice-water stls - Can be caused by chlera - Results in severe secretry diarrhea Vmitus Cffee grund vmit - Can be caused by an ld clt, red wine and irn tablets Hematemesis - Bright red bld - Usually indicates a fresh clt r bleeding frm the GIT Yellw-green vmitus - Results frm the vmiting f bile and upper small bwel cntents Feculent vmit - Brwn ffensive material frm the small bwel is then vmited - A medical emergency due t risk f aspiratin Prjectile vmit - Assciated with pylric stensis r raised ICP Oral disrders Sjrgens syndrme General cnsideratins - Inflammatry disease that affects primarily the salivary and lacrimal glands, causing dryness f the muth and eyes - Thught t be autimmune T cell related reactin against antigens f the glands Clinical presentatin - Presents cmmnly in middle aged wmen - Enlargement f the salivary glands - Dryness f the muth and eyes Assciatins - Epstein-Barr virus This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 41

42 - Systemic lupus erythematsus Cmplicatins - 40 x increased risk in develping nn-hdgkin s B cell lymphma in the marginal zne (MALT lymphma) Siallithiasis General cnsideratins - Salivary gland calculi Clinical presentatin - Acute swelling and erythema f the duct pening - Dry muth - Pain prir t eating r thinking abut fd (when saliva is mstly prduced) Plemrphic adenma General cnsideratins - Cmmn benign salivary gland neplasm Etilgy - Mst cmmn tumr f the salivary (40%) and partid glands (60%) Micrscpic features - Circumscribed lesin, encapsulated mass - Neplastic prliferatin f parenchyma glandular cells with malignant ptentiality Leukplakia General cnsideratins - Cnditin in which thick, white patches frm n the tngue and the lining f the cheeks and muth - Differs frm erythrplakia >> red, velvety, erded area f mucsa, highly assciated with malignancy Etilgy - Mst cmmn cause >> smking - Generally self-limiting and will reslve spntaneusly % f leukplakia findings are malignant Macrscpic features - Yu cannt scrape it ff the tngue - Thick, white patches Hairy leukplakia General cnsideratins - Cnditin characterised by irregular white patches n the lateral sides f the tngue, due t chrnic irritatin Macrscpic features - Cannt be scraped ff - Lateral tngue and muth - Nt a pre-cancerus lesin Assciatins - Caused by EBV in immuncmprmised patients This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 42

43 Oral squamus cell carcinma General cnsideratins - Oral cancer very cmmnly fund n ventral tngue, flr f the muth and lwer lip, sft palate Etilgy - Accunts fr 95% f cancers in the ral cavity - Risk factrs >> smking and chewing tbacc, alchl, HPV, chewing betel quid and paan (in India) Pathgenesis - Develps frm dysplastic precursr tumrs - (1) nrmal squamus cell epithelium (2) hyperplasia (3) dysplasia (4) tumr in situ (5) malignancy Histlgy - Ranges frm well differentiated keratinizing neplasms t sacrmatid tumrs Prgnsis - Pr - Survival rate less than 50% since they are diagnsed a at much later stage cmpared t ther cancers Oesphageal disrders Achalasia Clinical presentatin - Dysphagia - Regurgitatin - Chest pain - If nt treated: wrsening chest pain, severe weight lss, mucsal ulceratin, infectin and esphageal rupture and death Etilgy - Unknwn; degeneratin f the myenteric plexus and lss f inhibitry neurnes may cntribute - Assciatin with HLA-DQw1 - Lw incidence rate Pathlgy - Sphincter is even mre tightly cntracted than nrmal and des nt relax prperly in respnse t swallwing because f partial lss f neurns in wall f esphagus - Resulting in functinal bstructin - Serve radigraphic distrtin f the esphagus develps - Injectin f btulinum txin int the LOS diminished the excitatry pathways and reduced symptms - Chrnic manifestatin, results in massive enlargement f esphagus ver time >> increasing its vlume capacity fr infected material >> high risk f aspiratin Assciated cnditins - Chagas s disease - Sclerderma Evaluatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 43

44 - Barium swallw test will shw = narrwing f distal esphagus, lss f peristalsis in distal tw thirds, dilated prximal esphagus - Manmetry studies will shw = increased LOS pressure and diffuse esphageal spasm Treatment - Medicatins t reduce LOS tne >> nifedipine, lng acting nitrates, btulinum txin - Surgical >> endscpic balln dilatin f LOS Cmplicatins - Oesphageal carcinma Gastr-esphageal reflex disease (GORD) Clinical presentatin - Burning chest pain (heartburn) when lying supine, wrse at night r after cnsumptin f fd f drugs that diminish lwer esphageal tne, imprves with antacids - Regurgitatin - May mimic MI r asthma Etilgy - Caused by cnditins where esphageal mucsa is expsed t persistent acid expsure - Causes: disrders that increase the transient relaxatin f the LOS r impair reflexes that nrmally fllw transient relaxatin f LOS, cnditins that increase gastric vlume r pressure, delayed gastric emptying, cnditins f alkaline injury, hiatal hernia s, besity, pregnancy Pathlgy - Nrmally tnically cntracted LOS is effective barrier against reflux alng with peristaltic waves - Barrier is lst when LOS underges transient relaxatin - Recurrent reflux can damage the mucsa >> inflammatin and scarring Evaluatin - Diagnsis based n histry given - Upper GI endscpy - 24hr intraesphageal ph prbe mnitring >> gld standard - Manmetry t reveal decreased LOS pressure Treatment - (1) lifestyle mdificatin - (2) H2 receptr antagnists (ranitidine, cimetidine) r pr-mtility agent (cisapride) - (3) prtn pump inhibitrs (meprazle, lansprazle) - (4) surgical fundplicatin r hiatal hernia repair Clinical utcmes - Stricture f distal esphagus - Hemrrhage r perfratin - Harseness, cughing and wheezing - Barretts esphagus >> increasing risk f adencarcinma This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 44

45 Barrett s Oesphagus Etilgy - 10:1 males t females Pathlgy - Cmplicatin f chrnic GORD - Nrmal squamus epithelium in esphagus underges metaplasia >> metaplastic clumnar tissue Evaluatin - Bipsy >> glandular metaplasia f distal esphagus due t presence f stmach acid Cmplicatins - Ulceratin leading t stricture frmatin - Increased risk f esphageal adencarcinma Hiatal hernias Clinical presentatin - Similar symptms t GORD - Bwel sunds can be auscultated ver left lwer lung - Present in 80% f patients with reflux Classificatin - Type 1 >> sliding hernia, mst cmmn, GO junctin slides up int mediastinum thrugh hiatus, lss f diaphragm reinfrcement allws reflux f stmach acid - Type 2 >> rlling/paraesphageal hernia, less cmmn, herniatin f the fundus f the stmach thrugh the diaphragm parallel t esphagus Treatment - Type 1 >> medical therapy similar t GORD - Type 2 >> mandatry surgical repair due t risk f strangulatin Gastric disrders Upper GI bleed Clinical presentatin - Hematemesis - Hematchezia passing f fresh bld thrugh the anus, usually in r with stls - Hyptensin - O/E: abdminal pain, anrexia, bldy emesis, dark stls (melena), bld per rectum Etilgy - Causes >> PUD, gastritis, esphageal varices, gastric cancer, vascular abnrmalities, Mallry-Weis tear - Risk factrs >> ethanl, tbacc, liver disease, NSAID use, vmiting This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 45

46 Evaluatin - NG tube and endscpy Treatment - IV fluid resuscitatin and transfusin >> restre hemdynamic stability - Endscpy with banding, surgical explratin may be required Mallry-Weiss tear General cnsideratins - Characterised by upper GI bleeding secndary t lngitudinal mucsal laceratins (Mallry-Weiss tears) at the gastresphageal junctin r gastric cardia Risk factrs - Retching, vmiting, straining, hiccupping, cughing, blunt abdminal trauma and CPR - Presence f hiatal hernia - Presence f ther mucsal lesins - Can be caused by medical prcedures such as transesphageal echcardigraphy Pathlgical mechanisms - Tear ccurs due t a large, rapidly ccurring, and transient transmural pressure gradient alng the GO junctin - A rapid rise in intragastric pressure thrugh precipitating factrs causes the transmural pressure gradient t increase dramatically - If the frce is high enugh, a lngitudinal laceratin will ccur Clinical presentatin - Hematemesis >> fllwing a but f retching r vmiting (#1 symptm) - Melena - Hematchezia - Syncpe - Abdminal pain Management - Stabilize the patient and mnitr vitals - Transfuse if necessary - Cntrl precipitating factrs - Endscpic management >> thermal treatment, epinephrine injectin, sclersing injectin, argn plasma cagulatin, band ligatin, hemclip placement - Angitherapy Cmplicatins - MI - Hypvlemic shck - Death if the bleeding is prlnged and untreated Berhaave syndrme General cnsideratins - Spntaneus rupture f the esphagus typically fllwing frceful emesis - Transmural perfratin (differs frm Mallry Weiss which is nn-transmural) Clinical presentatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 46

47 - The Mackler Triad >> vmiting, lwer thracic pain and subcutaneus emphysema - Plus >> tachycardia, diaphresis, fever, hyptensin Pathphysilgy - Sudden rise in intraluminal esphageal pressure prduced during vmiting, because f neurmuscular incrdinatin causing a failure f the cricpharyngeus muscle t relax - Cmmnest lcatin >> left psterlateral wall f the lwer third f the esphagus (2-3 cm prximal t GO junctin) Treatment - IV fluid resuscitatin - Brad spectrum antibitics - Prmpt surgical interventin Cmplicatins and prgnsis - Mrtality rate is high >> is the mst lethal perfratin f the GI tract - Mrtality due t subsequent infectin - Cmplicatins: septicemia, mediastinitis, massive pleural effusin, empyema, respiratry distress syndrme, pneumthrax Cngenital pylric stensis Clinical presentatin - Prjectile vmiting des nt cntain bile - O/E: palpable live in epigastrium and hyperperistalsis Etilgy - Nt present at birth; develps within first mnth f life Evaluatin - Ultrasund is diagnstic Treatment - IV fluid resuscitatin - Electrlyte management pre-peratively - Pylrmytmy >> incisin is made in the lngitudinal and circular muscles f the pylrus; this lsens the muscle s that fd can empty int the small intestine Gastritis Clinical presentatin - Recurrent upper abdminal pain - Hematemesis Etilgy and classificatin - Acute (ersive) = inflammatin and neutrphil infiltratin, result f NSAIDs, ethanl, uremia, burns, brain injury and Anisakis wrm infestatin - Chrnic (nn-ersive) = mixture f plasma cells, lymphcytes and macrphages (1) Type A >> fundus/bdy, caused by pernicius anemia and autimmune cnditins, increased risk f gastric carcinma (2) Type B >> antrum/pylrus, caused by infectin and chrnic NSAID use, increased risk f MALT lymphma and adencarcinma Pathlgenesis (H. pylri) This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 47

48 - Ptential virulence factrs >> urease (neutralizes gastric acid by prducing ammnia), mucinase (degrades gastric mucsa) - General virulence factrs >> flagella, adhesins (t attach itself t the cell wall) and LPS (this is where mst H. pylri stp, hwever sme may prgress) - Specific strains f H. pylri may then sit attached t the bld vessel wall and express CagA, this causes an inflammatry respnse within the hst cell - Prlnged inflammatry respnse leads t ulceratin - Huge crrelatin between CagA H. pylri strains and ncgenic behaviur (cancer) H. pylri mde f transmissin - Persn-t-persn (ral-ral r fecal-ral) - Prevalence increased in ld age, lw SES, dmestic crwding and large families, hygiene related H. pylri virulence factrs - Urease >> neutralizes gastric acid by prducing ammnia, t help the bacteria survive - Mucinase >> degrades gastric mucus - Crrelated with CagA >> has a mutagenic effect - VacA >> damages lcal epithelial cells - Flagella >> mtility - Adhesins >> t bind t the hst cell Evaluatin - Endscpy with bipsy >> gld standard - H. pylri detectin and culture via stl antigen test r urea breath test - The urea breath test >> give the patient a capsule, it has urea in it; if the patient has H. pylri then it will break dwn the urea in the capsule via urease that it secretes. The breakdwn causes there t be radiactive carbn dixide t be emitted, which can be measured p Treatment (1) Acute: Triple therapy >> cmbinatin f acid lwering drug and 2 antibitics, ver tw weeks Quadruple therapy >> cmbinatin f acid lwering drug and 3 antibitics, ver tw weeks Acid lwering drug used = meprazle Antibitics used = amxicillin, clarithrmycin, tetracycline and metrnidazle Avidance f gastric irritants Misprstl (2) Chrnic: H. pylri treatment Pernicius anemia treatment with vitamin B12 Stress ulcer treatment Peptic ulcer disease Clinical presentatin - Mid epigastric, gnawing pain - Wrse with meals - Signs f ulcer perfratin: pain in right shulder, rebund tenderness, ileus, peritneal signs Etilgy - Cmmn assciatins: NSAIDs, H. pylri and smking Classificatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 48

49 - Gastric ulcers = less cmmn, usually in lesser curvature, higher risk f malignancy, nt caused by acid hypersecretin - Dudenal ulcers = mre cmmn, usually in prximal half, typically due t H. pylri which infects the antrum, lw risk f malignancy, caused by acid hypersecretin Pathlgy - Painful sres/ulcers in the lining f the stmach r dudenum - Occurs when gastric acid secretin utweighs mucsal defenses Evaluatin - Culture fr H. pylri >> CagA and VacA strains - Upper GI endscpy with bipsy t exclude malignancy - Serum gastrin t rule ut Zllinger-Ellisn syndrme Treatment - (1) Stp smking - (2) Mucsal prtectrs >> bismuths, misprstl - (3) Acid cntrl >> PPIs and H2 receptr antagnists - (4) Antibitics t eradicate H. pylri - (5) Surgery >> parietal cell vagtmy Cmplicatins - Perfratins and infectin >> air under the diaphragm - Hemrrhage >> hematemesis and melena - Gastric utlet bstructin Zllinger-Ellisn syndrme Clinical presentatin - Like PUD and GORD - Diarrhea present >> acidity in dudenum inactivates pancreatic enzymes Etilgy - Caused by a malignant dudenal r pancreatic islet cell tumr that ectpically secretes excessive amunts f gastrin - Results in increased secretin f acid by parietal cells - Assciated with multiple endcrine neplasia type 1 Evaluatin - Increased basal t maximum acid utput rati (BAO: MAO) - Increased insulin, glucagn and gastrin n serlgy Treatment - PPIs and chemtherapy - Surgical resectin f the tumr Gastrparesis Clinical presentatin - Nausea - Blating - Vmiting - Cnstipatin r diarrhea This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 49

50 Etilgy - Cmmn cmplicatin f prly cntrlled diabetes mellitus with cnsequent autnmic neurpathy Pathlgy - Gastrparesis = delayed gastric emptying - Due t alteratins in nrmal gastric functining - Can ccur silently, prducing metablic derangements in the absence f smatic symptms Clinical utcmes - Develpment f bezars (stny frmatin) frm retained gastric cntents - Bacterial vergrwth >> resulting in malabsrptin and diarrhea - Erratic bld glucse cntrl - Severe weight lss >> due t nausea and vmiting Gastric cancer (usually adencarcinma) Clinical presentatin - Indigestin - Nausea r vmiting - Dysphagia - Pstprandial fullness (during r directly after fd) - Lss f appetite - Melena r pallr frm anemia - Hematemesis - Weight lss - Palpable enlarged stmach with succussin splash (slushing sund within abdmen n auscultatin) - Enlarged lymph ndes (Virchw ndes supraclavicular & Irish ndes anterir axillary) - Periumbilical metastases (Sister Mary Jseph ndule) Etilgy - Mst cmmn cause f cancer-related death in the wrld - Mre prevalent in Asian and Suth America than in Western cuntries - Affects men mre than wmen (2:1) - Median age at diagnsis 69YO - Risk factrs >> diet, H. pylri infectin (strngest risk factr), smking, previus gastric surgery, pernicius anemia, radiatin expsure, chrnic atrphic gastritis, genetics, EBV, besity, bisphsphnates - E-cadherin >> plays an imprtant rle in cell adhesin within the bdy, a mutatin linked t gastric cancer and ther germ line mutatins in CHD1 Classificatins and frequency - Adencarcinma (90%) - Lymphma (5%) - Strmal tumrs/leimymas (2%) - Carcinids (1%) - Adencanthmas (1%) - Squamus cell carcinmas (1%) Pathlgy This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 50

51 - Three ncgenic pathways: (1) prliferatin/stem cell (2) NF-kappaB (3) Wnt/beta-catenin - Direct extensin int the menta, pancreas, diaphragm, transverse cln, mescln and dudenum - Peritneal invlvement can ccur - Easy micrscpic spread via lymphatics within the submucsal and subsersal layers f gastric wall - Hemtgenus spread cmmnly results in liver metastases - Punched ut effect Evaluatin - Labs >> CBC, electrlyte panel, EnLFTS, tumur markers such as CEA (carcinembrynic antigen) and CA (cancer antigen) - Imaging >> endscpy, upper GI series, CXR t evaluate fr metastases, CT abdmen - Bipsy >> at least 6 specimens frm arund the lesin Histlgy - Signet ring cells filled with mucus - Stiffening f the gastric wall Treatment - Surgery >> depends n the size, lcatin and lcal invasin; lymph nde dissectin - Chemtherapy >> Epiribicin/cisplatin/5-FU (platinum analgues) - Neadjuvant, adjuvant and palliative raditherapy - Antineplastic antimetablite >> Flururacil - Antineplastic anti-her2 >> Trastuzumab - Antineplastic VEGF inhibitr >> Ramucircumab Cmplicatins - Metastasis >> supraclavicular ndes (Virchw s ndes), anterir axillary ndes, lcal invasin int dudenum, pancreas and ther retrperitneal structures - Peritneal r pleural effusins - Obstructin f gastric utlet - Bleeding in stmach frm esphageal varices - Jaundice Prgnsis - Only a small number f peple are cured frm the disease - Extremely high recurrence rate Acute abdminal pain Main causes f abdminal pain: inflammatin, perfratin, hemrrhage, ischemia and bstructin Types f abdminal pain Visceral (splanchnic) pain - Frm abdminal viscera (slid and hllw) - Sympathetic pathways (autnmic pain) transmitted up the celiac plexus and lumbar trunk - Can riginate frm fregut (epigastrium), mid (peri-umbilical) r hindgut (lwer abdmen) - NOTE: the appendix is cnsidered midgut; therefre, pain is initially felt at the umbilicus This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 51

52 - Diffuse pain, prly lcalised (deep, inside the patient), usually midline and inflammatin lwers this threshld Smatic pain - Frm parietal peristeum - Spinal nerve pathways (T5-11) and phrenic nerve (C3,4,5) - Sharp, intense and well lcalised pain Shifting pain Is felt where the actual rgan is Where a distended, inflamed rgan can be felt at bth the visceral and parietal levels in a shifting pattern Referred pain Cnvergence prjectin hypthesis brain wrngly interprets the pain as having cme frm smewhere else, because f the small prtin f innervatin that area takes in the spinal crd (lateral and ventral spinthalamic tracts) Examples: biliary clic (scapula pain) and ureteric clic (grin pain) Additinal symptms Anrexia/weight lss Nausea and vmiting Cnstipatin/diarrhea Bld per rectum if patient has acute abdmen and bld per rectum, then they have dead gut until prven therwise Pale r dark stls Painful spasm irritable bwel syndrme Chemtherapy Abdminal distentin ascites, intra-abdminal mass, intestinal bstructin Disclured, hard umbilicus sister Mary Jseph sign (a result f metastatic pancreatic cancer) Be aware f acute gyneclgy Pregnancy ectpic and ruptured uterus Infectin pelvic inflammatry disease Endmetrisis Ovary trsin r bleed Nn-abdminal causes f abdminal pain Cardiac - Mycardial ischemia/infarctin/mycarditis - Endcarditis - Cngestive heart failure Thracic - Pneumnia/pneumnitis - PE and infarctin - Pneumthrax - Oesphageal rupture (Berhaave syndrme) r spasm - Emphysema Neurlgic - Radiculitis This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 52

53 - Abdminal epilepsy - Tabes drsalis Metablic - Ketacidsis - Uremia - Hyperthyridism - Acute adrenal insufficiency - Electrlyte imbalance (hypercalcemia) Peritneal disease Ascites General cnsideratins - Pathlgic accumulatin f fluid in the peritneal cavity - Healthy men have little/n intraperitneal fluid, whereas wmen may have up t 20mL depending n the stage f the menstrual cycle - Mst cmmn cause is secndary t liver disease Etilgy - Causes (nrmal peritneum) >> (1) Prtal hypertensin (hepatic cngestin, liver disease r prtal vein cclusin) (2) Hypalbuminemia (nephrtic syndrme, prtein lsing enterpathy) (3) Miscellaneus (pancreatic, chylus, bile, nephrgenic ascites) - Causes (diseased peritneum) >> (1) Infectin (2) Malignant cnditins (3) Other (vasculitis, esinphilic peritnitis) Pathphysilgy hyptheses (in patients with liver disease) - Peripheral vasdilatin - Increased peripheral tne - Increased endthelin-1 secretin Clinical presentatin (liver disease patient) - Increasing abdminal girth - Presence f abdminal pain - Histry reveals: prtal hypertensin, alchl cnsumptin, transfusins, tatts, IV drug use, viral hepatitis r jaundice, birth in a hepatitis endemic area - O/E (lk fr): elevated JVP, large tender liver, large abdminal wall veins, palmar erythema, muscle wasting, hepatic flap, frim lymph ndes Evaluatin - Labs >> abdminal paracentesis, CBC, WBC, albumin and ttal prtein, culture and gram stain blds, glucse and lactate dehydrgenase - Abdminal ultrasund - Laparscpy Malignant ascites This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 53

54 General cnsideratins - 2/3 f all malignant ascites cases >> peritneal carcinmatsis caused by adencarcinma f the vary, uterus, pancreas, stmach, cln, lung r breast - 1/3 f all malignant ascites cases >> lymphatic bstructin r prtal hypertensin Clinical presentatin - Nn-specific abdminal discmfrt - Weight lss - Increased abdminal girth - Nausea and vmiting Evaluatin - Paracentesis demnstrates lw ascites-albumin gradient, increased prtein, elevated WCC with lymphcytic predminance Treatment - Large vlume paracentesis - Indwelling catheters >> end f life symptmatic relief - Intraperitneal chemtherapy - Prgnsis is extremely pr >> 10% survival rate at 6 mnths Mesthelima General cnsideratins - Primary abdminal malignant mesthelima is a rare tumr - 70% f cases have Hx f asbests expsure Clinical presentatin - Abdminal pain and signs f bwel bstructin - Increased abdminal girth - Small t mderate ascites Treatment and prgnsis - Prgnsis is pr - Surgical debulking f tumr - Chemtherapy GIT infectins Nrmal gut flra (these can als be pathgenic) Lactbacillus Streptcccus Bacterides Bifidbacterium Peptcccus Clstridium E. Cli - Mst cmmn pathgenic strains include ETEC (entertxin), EPEC (adherence factrs) and EHEC (secretes Shinga-txin) - Antibitics nt indicated; rest and rehydratin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 54

55 - Virulence factrs: fimbrae, K antigen, LPS endtxin (septic shck), H antigen (flagella) Klebsiella Prteus Entercccus Staphylcccus Pathgenic gut flra (these bacteria are never seen as residential flra) Salmnella - Mst cmmn frm f fd assciated diarrhea with GIT - Nrmally self-limiting (mild sertypes) - Sme salmnella sertypes can be dangerus; S. typhi and paratyphi; invades the hsts macrphages in Peyer s patches; cause enteric fevers (Typhid fever) - Antibitics nt indicated; rest and rehydratin Campylbacter - One f the mre severe gut bacteria - Antibitics are needed >> especially fr severe infectin Shigella - Cnsistently invasive - Invades the mucsa, uses the hst macrphages as a shield, secretes an extxin - Antibitics are needed >> especially fr severe infectin Vibri chlera - Rice water stl - Free flwing and cnstant while bacteria are present - Free living in fresh water - Secretes an entertxin, drawing water alng with it as it passes thrugh the GIT, causing mass dehydratin - Antibitics nt indicated; rest and rehydratin Pathgenic helminths Enterbius vermicularis (pinwrm) - Persn t persn transmissin - Perianal itchiness - Cmmn in crwded areas such as daycare centres - Test fr eggs in the perianal area (perianal tape test) - Treatment with antihelmintics >> mebendazle, albendazle Ascaris lumbricides (rundwrm) - Persn t persn thrugh ingestin f eggs - Infectins are ften asymptmatic - Can lead t mechanical blckages, malnutritin and allergies Bristl stl frm scale Type 1 and 2 cnstipatin Type 3 and 4 nrmal fecal mvement (mst healthy types) Type 5, 6 and 7 diarrhea This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 55

56 Diarrhea (gastrenteritis, enterclitis) Definitins - Acute <2 weeks - Chrnic >4 weeks - Cnsidered t be greater than 3 t 5 times the patient s nrmal bwel mvements per day Watery diarrhea (nn-inflammatry) - N red bld cells present in stl (n inflammatin), typically afebrile, large vlume, infectin is typically in small intestine - Pathgens >> entertxigenic e. Cli, vibri chlera, s. aureus, rtavirus, giardia lamblia Bldy diarrhea (inflammatry) - Bth red and white bld cells present (inflammatin), ften febrile, small vlume, infectin is typically in cln - Pathgens >> shingatxin-prducing e. cli, shingella species, salmnella, campylbacter jejuni, clstridium, Entameba Clinical manifestatins and pathgens Pathgen Presentatin Treatment Cmments Acute nn-inflammatry diarrhea Bacteria S. Aureus Vmiting, epigastric pain, diarrhea Supprtive care Usually within 6 hurs f eating infected fd (dairy, may, meat) Bacillus cereus Vmiting, epigastric pain, diarrhea Supprtive care Usually within 6 hurs f eating infected fd (reheated rice) ETEC Afebrile, watery diarrhea Ciprflxacin Travellers diarrhea Viruses Nrvirus Afebrile, vmiting, headaches, diarrhea Supprtive care Cruise ship and nursing hme utbreaks Rtavirus Fever and vmiting prdrme, then Supprtive care Cmmn in children/infants diarrhea Prtza Giardia lamblia/dudenalis Cryptspridium STEC Abdminal cramps, flatulence, diarrhea, stls are fatty and ful smelling, may flat Abdminal pain and cramps, watery diarrhea Bldy diarrhea, abdminal pain, usually afebrile Metrnidazle and tinidazle Nitazxanide Acute inflammatry diarrhea Bacteria Nne, antibitics may increase risk f hemlytic-uremic syndrme Clstridium Bldy diarrhea, fever Oral r IV metrnidazle r ral vancmycin Diarrhea may persist fr weeks Flagellated prtzan, vid shape, tw nuclei Can evade immune clearance Causes f large cmmunity-wide utbreaks frm cntaminated water supply Assciated with undercked beef and cntaminated prduce Assciated with antimicrbial drug use r cmmunity acquired This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 56

57 Shigella Diarrhea with bld r pus, abdminal cramps, can be febrile Ciprflxacin Persn t persn spread Salmnella Campylbacter jejuni Entameba Diarrhea can be bldy, lw grade fever Fever, diarrhea Prtza Bldy diarrhea, fever and abdminal pain Ciprflxacin Ciprflxacin r azithrmycin Metrnidazle Acquired by ingestin f undercked eggs, raw veges r undercked pultry Assciated with GBS Can cause hepatic abscesses Infectin kinetics Vibri chlera - Incubatin = 1 t 3d - Duratin = 5 t 7d ETEC - Incubatin = 1-3d - Duratin = 5-10d Campylbacter - Incubatin = 1-4d - Duratin = 3-21d Salmnella spp. - Incubatin = 1-2d - Duratin = 2-7d Rtavirus - Incubatin = 1-4d - Duratin = 4-7d Antibitic assciated clitis (pseudmembranus clitis/clstridium clitis) General cnsideratins - Cmmn - Occurs during the perid f antibitic expsure, is dse related and reslves spntaneusly after discntinuatin - Clstridium diffcile related r due t changes in clnic bacteria fermentatin f carbhydrates - Mst cmmn cause f hspital-acquired infectius diarrhea - Acquired by fecal-ral transmissin Clinical presentatin - Extremely painful fr the patient - Mild t mderate greenish, ful-smelling watery diarrhea 5-15 times per day >> with bld - Lwer abdminal cramps - Left lwer quadrant tenderness - Severe disease >> hemdynamic instability, abdminal distentin, pain and tenderness Histlgical presentatin - Cln is cated in pseudmembranes, cmpsed f neutrphils and dead epithelial cells This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 57

58 - Damaged crypts, distended by exudate that erupts like a vlcan Evaluatin - Stl studies >> pathgenic strains f C diff prduce tw txins: txin A (entertxin) and txin B (cyttxin) - Flexible sigmidscpy >> severe symptms - Abdminal radigraphs and CT Treatment - Immediate Rx: discntinue antibitic therapy; therapy with metrnidazle, vancmycin - Hand washing - Prphylactic prbitics >> lactbacillus bulgaricus Cmplicatins and prgnsis - Prgresses quickly - Patients can be left with IBS years after the infectin - Severe clitis may becme hemdynamically unstable, experience respiratry failure, megacln, perfratin and death - Txic megacln >> causes hemdynamic instability and dilatin f the cln; presenting with pain, fever, hyptensin; can result in perfratin and is a medical emergency Appendicitis General cnsideratins - Inflammatin f the vestigial vermifrm appendix that extends int the muscularis prpria - Mst cmmn abdminal surgery emergency; therefre, diagnsis usually cmes after the appendectmy - 10% f ppulatin affected - Between 10 and 30 YOA Pathphysilgy - Obstructin f the appendix (infectin via parasites, tumr, fecal impactin) leads t an increase in intraluminal pressure - Increased pressure causes cclusin f the vessels supplying the appendix, and venus cngestin - Visceral afferent nerve fibers are activated, which aids in lcalizing pain t the right iliac fssa - Stasis f the luminal cntents causes bacterial prliferatin and infectin - If untreated, gangrene and necrsis fllwed by perfratin will ccur within 36 hurs Clinical presentatin - Early pain vague periumbilical pain - Within 12 hurs right lwer quadrant pain and tenderness, ver McBurney s pint (shifting pain between these tw areas frm here n) - Anrexia - Nausea and vmiting - Obstipatin >> severe r cmplete cnstipatin Findings O/E - Tenderness and rigidity at McBurney pint >> name given t the right side f the abdmen that is ne third f the distance frm the ASIS t umbilicus (appendix area) - Abdminal guarding f right lwer quadrant This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 58

59 - Lw grade fever and leukcytsis - When asked t cugh, patients may be able t lcalize the painful area >> sign f peritneal irritatin - Light percussin may elicit pain and rebund tenderness will elicit pain (this is a last resrt, as it will significantly hurt the patient) - Psitive psas sign >> pain n passive extensin f the right hip - Psitive bturatr sign >> pain with passive flexin and internal rtatin f the right hip Atypical presentatins - Abdminal tenderness may be minimal r elicited in right flank >> anatmical variatin f appendix - Diagnsis ften delayed in elderly as they present with minimal, vague symptms and mild abdminal tenderness - Can be assciated with pregnancy >> displacement f the appendix by the uterus Pathgens - Predminant rganisms are anaerbic >> e. cli, pseudmnas, peptstreptcccus Evaluatin and diagnsis - Mderate leukcytsis with neutrphilia - Micrscpic hematuria and pyuria may als be present - Abdminal ultrasund and CT >> CT slightly mre accurate, can help t pick up perfratin r abscesses als Treatment - Surgery is a definitive treatment >> lapartmy - Cnjunctin with periperative brad spectrum antibitics Cmplicatins and prgnsis - Lcalised perfratin >> abscess - Free perfratin >> suppurative peritnitis with txicity - Septic thrmbphlebitis >> rare - Mrtality rate is extremely lw Appendical cancer Etilgy - Usually indistinguishable frm acute appendicitis - Carcinid tumr is mst cmmn > adencarcinma - Carcinid tumr invlves the distal tip f the appendix, causing swelling - Pseudmyxma peritnei >> rare type f cancer than usually begins in the appendix as a small plyp; prduces mucinus fluid, eventually spreads thrughut the whle tumr, then disseminates int the abdmen Enteric fever (typhid fever) Definitin - Clinical syndrme cmprised f cnstitutinal symptms (fever, headache, nausea, vmiting, abdminal pain) - Significant glbal health prblem Pathphysilgy - Fllwing cnsumptin f cntaminated fd, salmnella bacteria enter thrugh the intestinal mucsal epithelium by transcytsis - Micrbes replicate in the macrphages f Peyer patches, mesenteric lymph ndes and the spleen This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 59

60 - Bacteremia then ccurs with disseminatin t the lungs, gallbladder, kidneys and CNS Clinical presentatin - Prdrmal phase with cnstitutinal symptms, with fever increasing ver the next few days - During secnd week, a typical transient rash f pink maculpapular lesins (rse spts) may be seen - Splenmegaly and/r hepatmegaly, bradycardia and leukpenia are ften bserved Pathgens - Salmnella typhi ( typhid fever ) Diagnsis - Histry f travel t endemic areas, with cmpatible presentatin - Bld cultures and stl cultures Treatment - Oral r IV ciprflxacin OR IV ceftriaxne Nausea and vmiting Definitin - Intense sensatin f sickness Pathphysilgy - Brainstem vmiting center is cmpsed f a grup f neurnal areas within the medulla >> area pstrema, nucleus tractus slitarius and central pattern generatr - Fur different surces f input: (1) Afferent vagal fibers frm GIT viscera which may be stimulated by distentin, irritatin r infectin (2) Fibers f the vestibular system, which have high cncentratins f histamine H1 and muscarinic chlinergic receptrs (3) Higher CNS centers such as the amygdala, where certain sights, smells r emtinal experiences may induce vmiting (4) Chemreceptr trigger zne, lcated utside BBB in area pstrema, which is rich in piid, sertnin, neurkinin and dpamine D2 receptrs may be stimulated by drugs, txins, hypxia, uremia, acidsis and radiatin therapy Causes - Acute vmiting withut abdminal pain >> fd pisning, infectius gastrenteritis, drugs - Acute vmiting with severe abdminal pain >> peritneal irritatin, gastric r intestinal bstructin, pancreatbiliary disease - Persistent vmiting >> pregnancy, gastric utlet bstructin, gastrparesis - Vmiting befre breakfast >> pregnancy, uremia, alchl intake and increased ICP - Vmiting immediately after meals >> psychgenic bulimia - Vmiting undigested fd >> gastrparesis r gastric utlet bstructin Specific examinatins - Serum electrlytes - Flat and upright abdminal x-rays r CT - Endscpy Treatment - Mst cases are mild and self-limiting - Sertnin 5-HT 3- receptr antagnists >> ndansetrn, dlasetrn - Crticsterids >> dexamethasne - Neurkinin receptr antagnists >> aprepitant This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 60

61 - Dpamine antagnists >> phenthiazines Diseases f the small bwel Celiac disease Definitin - Permanent dietary disrder caused by an immunlgic respnse t gluten, that results in diffuse damage t the prximal small intestine mucsa with malabsrptin f nutrients - Attributed t Gliadin triggered, T cell prductin f cytkines - Phase 2 and 3 f the phases f nutrient absrptin are affected in celiac disease Etilgy - Develps in peple with the HLA-DQ2 r DQ8 class II mlecules, present in 40% f ppulatin - Grssly underdiagnsed in adults Clinical presentatin - Diarrhea, steatrrhea, malabsrptin and weight lss, abdminal distentin, weakness, muscle wasting r grwth retardatin, vmiting, rash - Atypical symptms >> fatigue, depressin, irn deficiency anemia, steprsis, shrt stature, delayed puberty, amenrrhea r reduced fertility - O/E: pallr due t anemia, easy bruising due t vitamin K deficiency, hyperkeratsis due t vitamin A deficiency, bne pain due t Ostemalacia, r neurlgic signs due t vitamin B12 r E deficiency Evaluatin - Labs >> serlgy IgA tissue transglutaminase, DQ2/DQ8 gentyping - Mucsal bipsy frm prximal dudenum (gld standard) cllected frm here because this is where the highest amunt f dietary gluten absrptin ccurs Histlgy - Crypt hyperplasia - Villus blunting and atrphy - Intraepithelial lymphcytsis Treatment - Gluten free diet - Dietary supplements shuld be prvided in initial stages f therapy Prgnsis and cmplicatins - Usually excellent prgnsis >> nce diagnsis and treatment is applied - Celiac disease may be assciated with ther autimmune diseases - Assciated with higher rates f malignancy especially lymphma Bacterial vergrwth General cnsideratins - Small intestine nrmally cntains small number f bacteria, but bacterial vergrwth can ccur and result in malabsrptin - Causes direct damage t intestinal epithelial cells and the brush brder, impairing absrptin - Causes: (1) gastric achlrhydria (absence f HCl in gastric secretins) (2) anatmic abnrmalities with stagnatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 61

62 (3) small intestine mtility disrders (4) gastrclic r clenteric fistula Clinical presentatin - Asymptmatic - Flatulence - Weight lss - Abdminal pain - Diarrhea and steatrrhea - Severe cases may cause significant vitamin and mineral deficiencies Diagnsis and treatment - Diagnsis made by aspirate and culture f prximal jejunal secretins demnstrating ver 10 5 bacterial rganisms/ml >> invasive - Breath hydrgen and methane tests with glucse r lactse substrates >> less invasive - Treatment f 1-2 weeks ral brad spectrum antibitics against enteric anerbes >> ciprflxacin, Nrflxacin, amxicillin clavulanate - If symptms recur when ff antibitics, cyclic therapy (1 week ut f 4) may be needed >> try t avid antibitic resistance Lactase deficiency General cnsideratins - Brush brder enzyme that hydrlyses the disaccharide lactse int glucse and galactse - Cncentratin f lactase enzyme levels is high at birth but declines steadily in mst peple f nn- Eurpean ancestry during childhd and adlescence Etilgy - Very cmmn - Deficiency may arise frm ther GIT disrders that affect the prximal small intestinal mucsa >> Crhn s disease, sprue, viral gastrenteritis, giardiasis, shrt bwel syndrme and malnutritin Clinical presentatin - Blating, abdminal cramps and flatulence, smtic diarrhea (with high ingestin) after ingestin f milk-cntaining prducts Evaluatin - Hydrgen breath test - Diagnsis supprted by symptmatic imprvement n lactse free diet Treatment - Help the patient find their lactase threshld - Calcium supplementatin is recmmended fr steprtic susceptible patients Small bwel bstructin General cnsideratins - Inability f the intestinal tract t allw passage f fd and bwel cntents due t mechanical bstructin r ileus - Causes >> stensis, freign bdies, strictures, superir mesenteric artery syndrme, adhesins, hernia, intussusceptin (inversin f the small bwel lining), lymphma Ileus versus mechanical bwel bstructin Ileus Mechanical bstructin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 62

63 Pain Mild t mderate Mderate t severe Lcatin Diffuse May lcalize O/E Mild distentin with/withut tenderness, decreased bwel sunds Mild distentin, tenderness, high pitched bwel sunds Labs Pssible dehydratin nted Leukcytsis Imaging May be nrmal Abnrmal Treatment Observatin, hydratin with/withut nasgastric tube Nasgastric tube and surgery Diseases f the cln and rectum Irritable bwel syndrme General cnsideratins - Idipathic syndrme characterised by chrnic (>6 mnths) abdminal pain r discmfrt that ccurs in assciatin with altered bwel habits - Diagnsis made by chrnic abdminal pain with 2/3 features: (1) relieved with defecatin (2) nset assciated with a change in frequency f the stl (3) nset assciated with a change in appearance f stl Pathgenesis - (1) Abnrmal mtility - (2) Visceral hypersensitivity - lwer visceral pain threshld - (3) Enteric infectin can be a pst infectius IBS frm gastrenteritis - (4) Psychlgical abnrmalities depressin, anxiety r smatizatin Clinical presentatin - Symptms may be cntinuus r intermittent >> but it is chrnic - Abdminal pain >> intermittent and crampy - Three categries: (1) IBS with diarrhea (2) IBS with cnstipatin (3) IBS with mixed cnstipatin and diarrhea - Smatic r psychlgical cmplaints >> dyspepsia, heartburn, chest pain, headaches, fatigue, myalgia Evaluatin - Diagnsis made via criteria - Sigmidscpy and clnscpy is indicated fr patients with IBS and alarm symptms >> ncturnal diarrhea, severe cnstipatin r diarrhea, hematchezia, weight lss and fever Treatment - Reassurance, educatin and supprt - Dietary therapy fr fd intlerances - Medicatins >> antispasmdic agents (hysycamine), antidiarrheal agents (lperamide), anticnstipatin (smtic laxatives), psychtrpic agents (ral sertnin reuptake inhibitrs), prbitics - Cgnitive behaviural therapy, relaxatin techniques and hypntherapy Prgnsis - Learn t cpe with symptms Inflammatry bwel disease (Crhn s disease) General cnsideratins This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 63

64 - Chrnic, recurrent disease characterised by patchy transmural inflammatin invlving any segment f the GIT - Sme cases invlve the terminal ileus; sme cases invlve the small bwel and the cln - Strngly assciated with cigarette smking Etilgy - White and Jewish peple - Often presents in early 20 s Assciated cnditins - Erythema nsdum - Uveitis - Ankylsing spndylitis Clinical presentatin - Variable symptms due t variatin in severity and lcatin - Insidius nset and nn-cntiguus - RLQ clicky abdminal pain - Watery diarrhea - Weight lss - Intestinal bstructin - Lw grade fever - O/E >> penetrating disease and fistula, perianal disease Evaluatin - CBC, serum albumin, cltting factrs, EnLFTS, irn, vitamin B12 - Clnscpy >> linear and stellate ulcers, strictures, cbblestne mucsa, skip lesins, creeping fat - CT r barium upper GI series - Capsule imaging >> patient swallws a pill and it takes pictures alng the GIT, befre passing ut thrugh the rectum Treatment - Diet >> well balanced, supplements - Medicatins >> chlestyramine, 5-aminsalicyclic acid agents, antibitics, crticsterids, immunmdulatin (azathiprine), anti-tnf therapies (infliximab) - Surgery >> indicated fr patients with chrnic bstructive symptms Cmplicatins - Abscess frmatin - Small bwel bstructin - Abdminal and retrvaginal fistula - Perianal disease - Carcinma - Hemrrhage - Malabsrptin Inflammatry bwel disease (Ulcerative clitis) General cnsideratins - Idipathic inflammatry cnditin that invlves the mucsal surface f the cln causing bldy diarrhea This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 64

65 - Mre cmmn in nn-smkers and ex-smkers (smking acts as a prtective barrier) Lcatins - (1) Rectsigmid clitis - (2) Left sided clitis extends t the splenic flexure - (3) Extensive clitis prximal Etilgy - White and Jewish peple - Slightly mre prevalent in females - Generally, presents in early 20 s Pathphysilgy - Always starts in the rectum and spreads prximally - Cntiguus - Unlikely t have skip lesins (wund/inflammatin that it clearly patchy) Clinical presentatin - Highly variable - Bldy diarrhea is the hallmark - Mild t mderate >> Gradual nset f infrequent diarrhea with intermittent rectal bleeding and mucus, fecal urgency and tenesmus (cntinual need t defecate), left lwer quadrant cramps relieved by defecatin, mild fever, anemia and hypalbuminemia - Severe >> Mre than 6 bldy bwel mvements per day, results in severe anemia, hypvlemia and impaired nutritin with hypalbuminemia, abdminal pain and tenderness Evaluatin - CBC, ESR, hematcrit, serum albumin, p-anca psitive antibdies - Clnscpy w/bipsy >> diffuse ulceratins nly invlving mucsa and submucsa, friable mucsal patches, pseudplyps, crypt abscesses with PMNs, lss f nrmal vascular pattern - Plain abdminal x-ray >> clnic dilatin - Barium enema >> shrtening f the bwel, lss f haustra, small serratins, lead pipe appearance Treatment - Mild t mderate >> Limit caffeine and gas prducing vegetables, can be treated with tpical mesalamine (5-ASA) r crticsterids (methylprednislne), immunmdulatry agents (azathiprine), anti-tnf agents (infliximab), prbitics - Severe >> Nil by muth fr hurs, discntinue piids r antichlinergics, restre circulating vlume with fluids, crrect electrlyte abnrmalities, cnsider transfusin fr anemia, crticsterid therapy (methylprednislne r hydrcrtisne), anti-tnf agents (infliximab), IV cyclsprine, surgery (ttal clectmy) Cmplicatins - Txic megacln >> develps in 2% f cases, characterised by clnic dilatin mre than 6cm with signs f txicity - Markedly increased risk f develping cln carcinma - Malnutritin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 65

66 Crhns disease and ulcerative clitis cmparisn Feature Crhns disease Ulcerative clitis Type f inflammatin Chrnic granulmatus inflammatin Nn-cntinuus and patchy Limited mucsal and submucsal invlvement; starts in the rectum and extends prximally; lesins are cnstant and cntinuus thrughut the GIT Lcatin in GIT Anywhere frm the muth t the anus Distal t prximal; begins at rectum and extends t cecum Grss appearance Cbblestne mucsa, strictures, Pseudplyps creeping fat Nature f ulcers Transmural fissuring ulceratin Mucsal layers, superficial and brad extends thrugh muscularis prpria; granulmas are evident Nature f the lumen Firm thick wall with narrw lumen Wall is thin with a dilated lumen Skip lesins and fistula frmatin Bth present Neither present Features f malabsrptin Present with nutritinal deficiencies Nt present such as B12 Fibrsis Present Absent Imaging Cbblestne mucsa, string sign Lead pipe sign due t lss f haustra shwing a narrwed lumen and creeping fat S + S Genetics Disease specific cmplicatins Diarrhea with/withut bld Clic Right illiac fssa mass Obstructin symptms (vmiting, pain) Perianal fistula NOD2 and IL23R Seen in ileal Crhns Cdes fr cytplasmic element that detects bacteria Strictures Fistulas Chlelithiasis Tenesmus Urgency Bldy diarrhea Clic This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 66 HLA Txic megacln Primary sclersing chlangitis Increased risk f cln cancer

67 Malabsrptin Perianal disease Infertility Kidney stnes Gallstnes Clnic diverticulitis General cnsideratins - Risk increases with age - Mst cmmnly invlves the sigmid and descending cln - Mst cmmn cause f acute lwer GI bleed in patients lder than 40 YOA - Three times mre cmmn n the left than the right Pathphysilgy - Lw fiber diet causes chrnic cnstipatin > increases intraluminal pressure > muscular hypertrphy > herniatin f mucsa thrugh muscular wall - True diverticula >> rare herniatin that invlves full bwel wall thickness - False diverticula >> cmmn mucsal herniatin s thrugh nly the muscular wall cntaining mucsa and submucsa Assciated cnditins - Cllagen disrders (Marfans syndrme) - ADPKD Clinical presentatin - (1) Uncmplicated diverticulsis >> mre than 90% f cases and is asymptmatic - (2) Diverticulitis >> 10% f cases and is symptmatic - Symptms f diverticulitis >> mderate LLQ abdminal pain, lw grade fever, nausea and vmiting, abdminal tenderness, palpable mass, bld in stl Evaluatin - Clnscpy - CT abdmen Treatment - Cnservative measures (high fiber intake) with brad spectrum antibitics - Patients with mre severe symptms shuld be hspitalised >> nil by muth, nasgastric tube, IV antibitics, cnsider surgical management (signs f peritnitis, abscess frmatin) Cmplicatins - Fistula may invlve surrunding structures - Stricture frmatin in the cln with partial r cmplete bstructin - Peritnitis Meckel s diverticulitis General cnsideratins - The disease f 2 s >> ccurs in 2% f ppulatin, usually presents in first 2 years f life, fund 2 feet frm the ilececal valve, is 2 inches in length, 2 times mre cmmn in males - Outpuching f the bwel cmmunicating with the lumen, invlving all three layers f the bwel wall This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 67

68 - Caused by failure f invlutin f the vitelline duct with cnnects the lumen with the develping ylk sac Clinical presentatin - Painless rectal bleeding - Signs f bstructin - RLQ pain very hard t distinguish this frm appendicitis - Fecal matter in umbilicus Evaluatin - Meckel s radinuclide scan highlights ectpic gastric mucsa Histlgy - Fci f pancreatic and gastric tissue within nrmal tissue, likely t cause acute inflammatin Treatment - Surgical excisin f the diverticulum Plyps f the cln General cnsideratins - Discrete mass lesins that prtrude unt the intestinal lumen - Mstly spradic, althugh sme may be inherited as part f family adenmatus plypsis (see belw) - Fur pathlgic grups: (1) Mucsal adenmatus plyps (2) Mucsal serrated plyps (3) Mucsal nn-neplastic plyps (4) Submucsal lesins - Of all plyps remved frm the ppulatin, 70% are adenmatus and mstly cme frm adenma and serrated plyps - Cancers arise in adenmas after inactivatin f APC gene leading t chrmsmal instability - Cancers arise in serrated plyps when a Kras gene mutatin ccurs Clinical presentatin - Mstly asymptmatic - Chrnic mystery bld lss may lead t irn deficiency anemia - Large plyps may ulcerate resulting in intermittent hematchezia Evaluatin - FOBT (faecal ccult bld test) and faecal DNA tests clrectal screening - Barium enema examinatins - CT clngraphy - Clnscpy Treatment - Mst are amendable via clnscpic remval with bipsy frceps r snare cautery - Larger plyps may require surgical resectin - Fllw up clnscpies are indicated in the fllwing years Cmplicatins - Perfratin during surgery causing clinically significant bleeding rare Peutz-Jeghers syndrme General cnsideratins This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 68

69 - Rare autsmal dminant disrder characterised by the presence f multiple GI hamartmatus plyps in the GIT and hyperpigmented macules n the lips and ral mucsa (melansis) Etilgy - Germline mutatin f STK11 / LKB1 (serine/threnine 11) tumr suppressr gene Clinical presentatin - Hyperpigmentatin f the lips and muth (melansis) - Repeated buts f abdminal pain - Unexplained intestinal bleeding - Prlapse f tissue frm rectum - Menstrual irregularities in females - Gynecmastia in males - GI intussusceptin with bwel bstructin - Melena - Hematemesis - Weakness due t anemia Pathphysilgy - Overexpressin f the gene can induce a grwth arrest f the cell at the G1 checkpint in the cell cycle Histlgy - Smth muscle hyperplasia with elngated, arbrized pattern f plyp frmatin twards the epithelial layer Cmplicatins - 15x increased risk f develping intestinal cancer - Obstructin and infarctin - Rectal bleeding and ulceratin Familial adenmatus plypsis General cnsideratins - An inherited cnditin characterised by the early develpment f hundreds t thusands f clnic adenmatus plyps and adencarcinma with a variety f extra-clnic manifestatins - Autsmal dminant inheritance - Syndrme that affects 1:10,000 peple Clinical presentatin - Develp by 15 years and cancer at 40 years - Extra intestinal manifestatins >> stemas, sft tissue tumurs f the skin, desmid tumrs, Gardner s syndrme, Turcts syndrme Genetic testing - Mutatin f the APC gene (90% cases) - Mutatin f MYH gene (8% cases) Treatment - Cmplete prctclectmy with ileanal anastmses Lynch syndrme General cnsideratins - Als, knwn as HNPCC hereditary nnplypsis cln cancer This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 69

70 - Autsmal dminant inherited cnditin - Characterised by markedly increased risk f develping clrectal cancer as well as ther cancers including endmetrial, varian, renal r vesical, gastric etc - These plyps underg rapid transfrmatin ver 1-2 years frm nrmal tissue > adenma > cancer - Defect f genes that detect and repair DNA base-pair mismatches >> MLH1, MSH2, MSH6 Clinical presentatin - Diagnsed by the Bethesda criteria Treatment - Clnscpies starting at age 25 - If cancer is fund, subttal clectmy with ilerectal anastmses Hirschsprung s disease General cnsideratins - Obstructin secndary t clnic aperistalsis because f n ganglinic cells in the Meissner s submucsal plexus and Auerbach s myenteric plexus - 99% f cases lcalised t the rectum - Assciated cnditins >> Dwn syndrme and Chagas s disease Clinical presentatin - Almst always ccurs after birth when the newbrn is unable t pass mecnium - Abdminal pain and chrnic cnstipatin due t fecal build up in the dilated zne - O/E: absence f stl in the rectal vault n rectal exam Evaluatin - Rectal bipsy fr absence f ganglin cells Treatment and cmplicatins - Surgical resectin f the aganglinic cln segments - Cmplicatins >> enterclitis, perfratin and peritnitis Acute (cclusive) mesenteric ischemia General cnsideratins - Medical emergency, challenging diagnsis - Mrtality rate exceeds 50% - Can be categrized as arterial vs venus, emblic vs thrmbtic and cclusive vs nn-cclusive - Additinal causes >> adhesins, hernias, malignancy, vasculitis Pathgenesis - Caused by reductin in intestinal bld flw >> cclusin, vasspasm, hypperfusin - Mst cmmnly an emblism is invlved (50% f cases) - Disldged thrmbus frm left atrium, left ventricle r cardiac valves Clinical presentatin - Severe, acute, unremitting abdminal pain strikingly ut f prprtin t the initial physical findings - O/E: abdmen may be sft and nntender, distentin, signs f peritnitis, ccult bld in stl, transient diarrhea, nausea, emesis Evaluatin - Labs are usually nrmal >> except leukcytsis - Initially >> radigraph imaging This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 70

71 - Gld standard >> mesenteric angigraphy Treatment - Hemdynamic resuscitatin, crrect f precipitating cause, mnitring, crrectin f electrlytes and brad spectrum antibitics - Surgical revascularizatin f ischemic bwel Chrnic mesenteric ischemia General cnsideratins - Result f reduced bld flw due t athersclertic narrwing f at least tw f three majr vessels (celiac trunk, SMA r IMA) - Usually, adequate cllateral circulatin develps t maintain perfusin and avid intestinal infarctin, hwever in CMI, infarctin can develp quickly if thrmbsis r emblism ccurs Clinical presentatin - Diagnstic triad >> pstprandial pain, weight lss and abdminal bruit - Pain is dull, crampy, epigastric and periumbilical that ccurs after eating meals when the gut is mst metablically active - Fd fear ccurs due t the pain resulting in weight lss and cachexia - O/E: Hx f PVD, sft abdmen withut tenderness during episdes f pain, nausea, emesis, early satiety Evaluatin - Mesenteric angigraphy >> demnstratin f stensis in at least tw vessels Treatment - Gld standard >> pen surgical revascularizatin using artmesenteric grafting Large bwel bstructin Causes - Mst cmmn cause is neplasm - Vlvulus >> twisting f a lp f bwel as its mesenteric pint, resulting in luminal and vascular cmprmise - Herniatin >> bwel becmes trapped within a defect in the abdminal wall - Adhesins t the lumen >> neplasm, fecal impactin - Intussusceptin >> segment f the intestine is cnstricted due a prximal piece f intestine that telescpes dwnwards and invaginates itself upn the bwel distally Pathphysilgy - Nrmal bwel cntains gas and gastric secretins and fd - Intraluminal accumulatin f these secretins cntinues even when there is n ral intake - As bstructin develps, the bwel becmes cngested and intestinal cntents fail t be absrbed - Vmiting and decreased ral intake fllw this - Intraluminal pressure exceeds the capillary and venus pressure within bwel wall, absrptin and lymphatic drainage decrease and the bwel becmes rapidly ischemic - Cmbining these factrs, results in vlume depletin with hemcncentratin and electrlyte imbalance - Leads t renal failure, septicemia, bwel necrsis and shck Clinical presentatin - Depends n the site and nature f bstructin - Abdminal pain >> usually hypgastric This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 71

72 - Bwel distentin >> accumulatin f fluids within the lumen - Diminished r absent bwel sunds - Vmiting - Inability t pass a bwel mvement r flatus - Cnstipatin Evaluatin - CBC, EnLFTS, WCC, hematcrit - Serum amylase and lipase - Bld urea nitrgen and creatinine - Abdminal X-ray and CT Treatment - Surgical interventin - IV fluid replacement and mnitr vitals - Nasgastric tube - Pre-perative antibitics Bwel vlvulus General cnsideratins - Mst cmmnly in the sigmid cln and cecum - If it ccurs in an infant, mst likely due t malrtatin f the intestines (develpmental defect) Bwel intussusceptin General cnsideratins - Telescping f the prximal bwel int the distal bwel, frming an bstructin Clinical presentatin - Red currant jelly stl hallmark Pathphysilgy in children - Usually due t a bwel infectin - Infectin results in enlargement f the bwel lymphid tissue - This frms an anchr pint fr telescping f the bwel dwnwards Pathphysilgy in adults - Usually due t neplasia, frming the anchr pint, rather than lymphatic invlvement Carcinid tumr carcinid syndrme (paraneplastic) General cnsideratins - Arises frm neurendcrine rgans and neurendcrine GI epithelial cells - It s a paraneplastic syndrme prduced by the hrmnes frm the tumr - If carcinid syndrme is present >> highly likely that there is mets Clinical presentatin - Vasactive substances secreted by the tumr result in varius symptms - Cutaneus flushing - Sweating - Brnchspasm - Clicky abdminal pain This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 72

73 - Diarrhea - Right sided cardiac valvular fibrsis Hernias General cnsideratins - Prtrusin f any viscus frm its surrunding tissue walls - Reducible hernias >> hernia sac is sft and easy t replace back thrugh the hernia neck defect - Incarcerated hernia >> firm, ften painful and nn-reducible by direct manual pressure - Strangulated hernia >> develps because f incarceratin, presents as severe pain, with signs f bwel bstructin, txic appearance r skin changes Inguinal hernias - Very cmmn (75% f all hernias) males - In males, a patent prcessus vaginalis can allw small bwel cntents r the greater mentum t herniate and reach the scrtum - (1) Direct: hernia sac passes directly thrugh a weakness in the transversalis fascia in Hesselbach triangle, causing a bulge frwards; pass medial t inferir epigastric vessels - (2) Indirect: hernia passes frm the internal inguinal ring int the scrtum; pass lateral t inferir epigastric vessels Ventral hernias - Cmmn - Develp as result f a defect in the anterir abdminal wall - Named per the quadrant they are in Incisinal hernias - Cmmn - Result f excess anterir abdminal wall tensin r inadequate wund healing Umbilical hernias - Cmmn - Mstly acquired due t medical cnditins that increase intra-abdminal pressure r cngenital defects Femral hernias - Uncmmn females > males - Hernia sac prtrudes thrugh the femral canal and prduces a mass belw the inguinal ring - Usually present as a lump belw the inguinal ligament, medial t the femral vein - Prne t cmplicatins such as incarceratin r strangulatin Obturatr hernias - Rare and difficult t clinically diagnse - Bwel herniatin thrugh the bturatr canal, nearly always present as a partial/cmplete bwel bstructin - Typical patient is an eldery fragile female with signs f intestinal bstructin Richter hernia - Invlves nly the anti-mesenteric brder f the intestine and a prtin f the wall circumference - Presents withut vmiting r intestinal bstructin due t incmplete invlvement f the intestinal wall - Mre prne t strangulatin and gangrene can g undetected Divaricatin f the recti (diastasis) - Patients with a very brad linea alba, which is mre prnunced when lying dwn This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 73

74 - This is simply the rectus muscles diverging a little >> is nt a hernia Treatment - Hernial reductin >> IV narctic analgesia, apply cld packs t the site, grasp and elngate the neck f the hernia, cnsult surgery if unsuccessful Hemrrhids General cnsideratins - Internal hemrrhids are sub epithelial cushins cnsisting f cnnective tissue, smth muscle fibers and arterivenus cmmunicatins between terminating branches f rectal arteries and veins - Primary lcatins: right anterir, right psterir and left lateral - External hemrrhids arise frm inferir hemrrhidal veins lcated belw the dentate line - May becme symptmatic because f activities that increase venus pressure >> resulting in distentin and engrgement f these veins - Cntributing factrs >> pregnancy, straining and cnstipatin, besity, lw fiber diet Stages f develpment - (1) Internal hemrrhids are cnfined t the anal canal - (2) Over time they gradually enlarge and prtrude frm the anal pening; firstly, upn straining but they reduce spntaneusly - (3) Over time the prlapsed hemrrhids may require manual reductin after bwel mvements - (4) The hemrrhids chrnically prtrude Clinical presentatin - Bright red bld per rectum >> is uncmmn t be prlnged r cause anemia - Perianal irritatin (if chrnically prlapsed) - Pain is unusual, nly ccurring with inflammatin and thrmbsis O/E - External hemrrhids are visible, nn-prlapsed internal hemrrhids are nt visible - Lk fr: fistulas, fissures, skin tags, cancer, dermatitis Treatment - Stage ne and tw can be treated cnservatively >> high fiber diet, increase fluid intake with meals - Recurrent bleeding >> injectin sclertherapy (eliminatin f veins), rubber band ligatin, electrcagulatin, tpical creams, surgical excisin f the hemrrhids Anrectal infectin General cnsideratins - Inflammatin f the anal and rectal mucsa (prctitis) - Mst causes are sexually transmitted Clinical presentatin - Anrectal discmfrt, tenesmus (cnstant need t evacuate the bwels), mucpurulent discharge Neisseria gnrrheae - Itching, burning, tenesmus and mucpurulent discharge - Cultures taken frm the pharynx and urethra in men; pharynx and cervix fr wmen - Cmplicatins >> strictures, fistulas, perirectal abscesses Trepnema pallidum - Anal syphilis - Perianal pain and discharge This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 74

75 - VDRL r RPR test psitive in mst cases Chlamydia trachmatis - Similar symptms t gnrrheal prctitis r can be asymptmatic - Can cause lymphgranulma venerum - Diagnsed by serlgy, culture and PCR f rectal discharge - Recmmended Rx >> dxycycline Herpes simplex type 2 - Cmmn - Symptms develp 4-21 days after expsure - Severe pain, itching, cnstipatin, tenesmus, urinary retentin, radicular pain frm lumbar r sacral nerve rts, vesicles in perianal area - Diagnsis made via viral culture, PCR r antigen detectin assays f vesicular fluid - Symptms reslve within 2 weeks, viral shedding may cntinue fr several weeks - Recmmended Rx >> acyclvir Cndylmata acuminata - Anal warts caused by HPV - Occur in perianal area, anal canal and genitals - Asymptmatic, itching, bleeding r pain - Diagnsis made via bipsy f the warts - Recmmended Rx >> all partners examined and treated, vaccines Rectal prlapse Prtrusin thrugh the anus f sme r all the layers f the rectum Usually due t surgical r traumatic injury r hemrrhids Cmplete rectal prlapse requires surgical crrectin Anal fissures General cnsideratins - Linear shaped ulcers that are usually less than 5mm in length - Usually ccur at the psterir midline - If they are nt midline be suspicius f >> Crhns disease, HIV/AIDS, TB, syphilis r anal carcinma - Acute fissures lk like cracks in the epithelium - Chrnic fissures have fibrsis f the skin and the develpment f a skin tag at the utermst edge Clinical presentatin - Severe tearing pain during defecatin fllwed by a thrbbing discmfrt - Mild hematchezia Treatment - Fiber supplements - Sitz baths - Tpical nitrglycerin r diltiazem Perianal abscess and fistula General cnsideratins - Infectin f the anal glands can lead t abscess frmatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 75

76 - Once the abscess is drained, fistulas are ften fund underlying Clinical presentatin - Thrbbing, cntinuus perianal pain - Erythema, flatulence, swelling Treatment - Lcal incisin and drainage Perianal pruritus General cnsideratins - Perianal itching and discmfrt - Causes >> pr hygiene, fissures, prlapsed hemrrhids, skin tags, minr incntinence, ver cleaning the area, cntact dermatitis, bacterial infectins, STIs, candida infectin, spicy fd, cffee Treatment - Cleansing f the perianal area after defecatin - Piece f cttn wl tucked int the anal pening fr cmfrt and seepage - Shrt curse f crticsterids Mecnium ileus General cnsideratins - Mecnium >> dark green substance frming the first faeces f the newbrn infant - Mecnium ileus >> mst cmmnly seen because f cystic fibrsis in babies; mecnium is t viscus due t dehydratin f the bwel fluids Clinical presentatin - Inability t pass first mecnium - Assciated with bwel bstructin and cystic fibrsis symptms Hepatic disrders Bilirubin functin Yellw clured byprduct f hemglbin metablism Is elevated in jaundice Bilirubin prductin t excretin Every haem mlecule will prduce ne mlecule f bilirubin Occurs mainly in the spleen (macrphages) and liver (Kupffer cells) If the liver cannt excrete cnjugated bilirubin the kidneys will take ver Steps f prductin and excretin (1) Haem mlecules are taken up by reticulendthelial cells (2) Inside these cells, haem xygenase enzymes break dwn the haem, remving irn (which is recycled) and carbn mnxide >> this leaves biliverdin NOTE: the detectin f carbn mnxide in breath can be used t determine hw much haem is being turned int biliverdin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 76

77 (3) Biliverdin is then cnverted t bilirubin by the enzyme biliverdin reductase, whilst still in the reticulendthelial cell (4) After bilirubin is released frm the reticulendthelial cells, it travels in the bld, bund t albumin This ensures that n bilirubin is excreted in the urine NOTE: at very high cncentratins, bilirubin can diffuse int the peripheral tissues where its txic (5) Bilirubin is then remved frm the circulatin in the sinusids by hepatcytes Passive prcess, that ccurs dwn a cncentratin gradient (6) As sn as bilirubin enters the hepatcyte, it becmes bund t glucurnyl transferase which cnjugates the bilirubin ready fr excretin A very small amunt f bilirubin evades this prcess and ends up in the bile as uncnjugated bilirubin (7) Bilirubin is excreted int gastrintestinal system and is decnjugated by bacteria befre being reabsrbed in the cln This prcess is mre likely in the presence f increased bile acids (8) Mst f the bilirubin in the cln is turned int stercbilgens (brwn) and urbilgens (clrless) Alchl metablism in the liver Basic metablism - Occurs within the cytsl - Alchl cnverted t acetaldehyde by alchl dehydrgenase This reactin requires the reductin f NAD+ t NADH Acetaldehyde is essentially a txin t cells, s causes the side effects - Abut ALDH: ALDH1 - fund in liver cytsl ALDH2 - fund in liver mitchndria (MC) - Many peple f Asian descent are KO fr ALDH, thus get acetaldehyde buildup when drinking - Acetaldehyde is a vasdilatr, causing flushing - Als, hits CTZ, causing nausea - Acetaldehyde then enters the mitchndria and is cnverted int acetate by acetylaldehyde dehydrgenase This reactin als requires the reductin f NAD+ t NADH - What is the rate limiting agent f alchl metablism? NAD+ Overflw pathways - In situatins where there is a heavy EtOH lad, there are 2 ther systems that metablize it CYP2E1 in the smth ER High Km (lw affinity) explains why this system is nly active at high alchl cncentratins Atalase in the perxisme Nt imprtant, as peple wh are acatalsemic have nrmal alchl metablism Bth systems lead t a buildup f acetaldehyde, which is ne f the factrs that causes alchlic liver disease Mechanism f metablic effects f alchl metablism (acute and chrnic) - NADH is created, thus, the NADH/NAD+ rati increases; the cell nw is in a highly reduced state This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 77

78 Jaundice - Because ALDH and acetaldehyde dehydrgenase bth require NAD+, pathways requiring NADH increase t frm mre NAD+ (because alchl is effectively txic t the cell, the first gal is t remve the alchl, even if that damages the cell) - Increased glyclysis (pyruvate > lactate) Pyruvate + NADH > Lactate + NAD+ This can cause lactic acidsis - Decreased glucnegenesis - Pyruvate depleted (see abve) - Oxalacetate and ther TCA intermediates depleted (xalacetate > malate t generate NAD+) - These depletins cause the decreased glucnegenesis, resulting in fasting hypglycemia - Increased lipgenesis - Transient fatty liver - Decreased prtein synthesis General cnsideratins - Yellw discluratin f the skin and sclera that ccurs when systemic retentin f bilirubin prduces serum levels abve 2.0mg/dL - It is classified by the rati f cnjugated bilirubin: ttal bilirubin Pathphysilgy - Hepatcytes cnvert uncnjugated (indirect) bilirubin int cnjugated (direct) bilirubin - This is perfrmed by glucurnyl transferase enzyme - Nrmally bilirubin is nt txic at mderate levels, but dysfunctin f hepatcytes and decreased cnversin f bilirubin causes an increase bilirubin - This can eventually lead t jaundice, kernicterus (depsitin f bilirubin in the brain) and death Cnjugated bilirubin levels and assciatins - CB <20% = Gilbert s / Crigler Najjar syndrmes, physilgic jaundice f the newbrn, hemlysis - CB 20-50% = viral hepatitis - CB >50% = drugs (OCP), Rtr syndrme, primary biliary cirrhsis r bstructin Types f jaundice (1) Hemlytic (pre-hepatic) Excessive RBC breakdwn, mre than what the cnjugatin/excretin system can handle Causes: hereditary hemlytic anemia (sickle cell anemia and thalassemia), Rh incmpatibility, malaria Liver + LFTs nrmal Dark urine and stls >> entire systemic increase in bilirubin Often splenmegaly >> increased reticulendthelial activity Pallr nrmally present (2) Hepatcellular Inability f the liver t excrete and/r cnjugate bilirubin >> due t liver tissue damage Causes: viral hepatitis, pisns, drug induced heptatits (paracetaml) and liver cirrhsis Levels f bth cnjugated and uncnjugated bilirubin increase (3) Obstructive /chlestatic (pst-hepatic) Obstructin t the bile duct >> the liver can cnjugate bilirubin but nt excrete it Causes: OCP, gallbladder stnes, carcinma f the head f the pancreas, pregnancy, alchl, drugs Presents as elevated cnjugated bilirubin in serum, dark urine and clay/light clured stl This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 78

79 Nenatal jaundice (purexia) Physilgic jaundice in babies - Occurs between days 3-5 f life, affecting 50% f nenates - Clinically benign - This rise in bilirubin is the indirect (uncnjugated frm) - Results frm >> increased bilirubin prductin due t degradatin f HbF (fetal hemglbin) r a deficiency in glucurnyl transferase in the immature liver Pathlgic jaundice in babies - Jaundice in the first day f life - Can be due t direct r indirect hyperbilirubinemia - Indirect causes >> Crigler Najjar syndrme, Gilberts syndrme, breastfeeding, hemlytic anemia - Direct causes >> Rtrs syndrme, infectins, metablic disease (including alpha 1-antitrypsin deficiency) Evaluatin - Labs >> elevated direct and ttal bilirubin Treatment - Physilgic des nt require treatment - Pathlgic may require phttherapy Prgnsis and cmplicatins - Can lead t kernicterus and is ptentially fatal if left untreated Acute hepatitis General cnsideratins - Inflammatry prcess causing liver cell death either by necrsis r by triggering apptsis Etilgy - Cmmnly caused by 1/5 majr viruses >> hepatitis A, B, C, D r E A B C D E Onset Abrupt Insidius Insidius Insidius Abrupt Symptms Asymptmatic, nausea and vmiting Initially like serum sickness, arthralgia, rash, nausea and vmiting Nausea and vmiting Fever, nausea and vmiting, jaundice Arthralgia, rash, fever, nausea and vmiting, jaundice Virus type RNA DNA RNA RNA RNA Serlgy IgM anti-hav HBsAg IgM anti-hbc Screening assay (EIA r CIA) fr anti-hcv This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 79

80 Disease severity Mild Mderate Mild Can be severe Severe especially in pregnant wmen Chrnic N Yes Yes Yes Yes Assciated with N Yes Yes Yes N malignancy Transmissin Oral, sexual Oral, sexual, percutaneus and perinatal Percutaneus, sexual and perinatal Percutaneus and sexual Oral, percutaneus and perinatal Vaccine Yes Yes N N N Carrier state N carrier state Carrier state Carrier state cmmn cmmn Liver bipsy Hepatcyte swelling, mncyte infiltratin, Cuncilman bdies Granular esinphilic grund glass appearance, cyttxic T cells mediate damage Lymphid aggregates with fcal areas f macrvascular steatsis Defective virus, depends n having superinfectin with HBV Similar t HBV Enteric, epidemic, n carrier state Patchy necrsis - Additinal, less cmmn causative agents >> EBV, CMV, varicella virus, herpes simplex, rubella, yellw fever - Hepatitis can als be drug induced Pathgenesis viral - (1) Viral agent infects the first hepatcyte - (2) During the incubatin perid, intense viral replicatin in the liver leads t the appearance f viral cmpnents (first antigens and then antibdies) in urine, stl and bdy fluids - (3) Liver cell death and inflammatry respnse result in changes in liver functin (1) Prdrme phase days - (1) Systemic symptms malaise, fatigue and mild fever - (2) GI symptms anrexia, nausea, vmiting, altered sense f lfactin and taste, RUQ discmfrt - (3) Extrahepatic symptms headache, phtphbia, cugh, hematuria and prteinuria (2) Icteric phase weeks - Cnstitutinal symptms imprve - RUQ pain because f large tender liver - Splenmegaly nted in sme patients - Jaundice elevatin f cnjugated bilirubin in the bldstream - Changes in stl clur and urine clur - Ecchymses - cagulpathy, maybe due t lss f vitamin K absrptive capacity frm intestine - Subtle r prfund mental status changes can be seen in severe disease (3) Cnvalescent phase - Cmplete disappearance f cnstitutinal symptms but persistent abnrmalities in liver functin tests This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 80

81 - S+S gradually imprve Histlgy findings - (1) Fcal liver cell degeneratin and necrsis, cell drput, ballning and cell shrinking - (2) Inflammatin f prtal areas, with infiltratin f mnnuclear cells lymphcytes, plasma cells, esinphils - (3) Prminence f Kupffer cells and bile ducts - (4) Chlestasis (arrested bile flw) with bile plugs Severe histlgy findings - Lesin called bridging hepatic necrsis ccurs between lbules, resulting in large areas f hepatic cell lss - Severe atrphy and sftening f the liver acute yellw atrphy Hepatitis B General cnsideratins - Transmitted by infected bld r bdily fluids >> vertical transmissin, hrizntal transmissin (frm an infected t unvaccinated husehld cntacts), sexually, percutaneusly, salivary transmissin (rare) and medically acquired (transfusins and needle stick injury) - The virus enters the bldstream thrugh a break in the skin r thrugh mucus membranes - HBV can survive utside the bdy fr up t 7 days - HBV is times mre infectius than HIV - 70% f peple living with chrnic hepatitis B cme frm verseas cuntries r as Abriginal and Trres Strait Islander Natural histry (acute) (1) Incubatin phase (2) Symptmatic hepatitis Fever, fatigue, anrexia, nausea, dark urine, jaundice, myalgia, RUQ pain Elevated amintransferase levels (3) Recvery perid Nrmalizatin f alanine amintransferase levels (ALT) (4) Clearance phase HBsAg clears frm serum after a few mnths; this cincides with the develpment f anti-hbs antibdies Natural histry (chrnic) Immune tlerance Immune clearance Immune cntrl Immune escape Psitive HBeAg High HBV DNA levels Nrmal ALT Fluctuating HBV DNA and ALT levels Psitive HBeAg HBV DNA is lw r undetectable LFTs are nrmal Negative HBeAg Psitive anti-hbe Detectable viral lad Indicates active, immune mediated cyttxic respnse t infected liver cells Patients are at risk f prgressin t cirrhsis and HCC cnsider treatment Patients d nt need treatment unless there is advanced liver disease Patients are at risk f prgressin t cirrhsis and HCC cnsider treatment Testing and interpretatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 81

82 - Must gain cnsent fr testing - Order HBsAg (surface antigen), anti-hbc (cre antibdy) and anti-hbs (surface antibdy) - Interpretatin >> Vaccinatin recmmendatins - Infants - Adlescents aged Men wh have sex with men, peple with multiple sexual partners, sex wrkers - Abriginal and Trres Strait Islander peple - Prisn inmates and staff - IVD users - Travellers t endemic places - Health care wrkers - Hemdialysis patients, thse wh require transplant r transfusins HBV and pregnancy - Pregnant wmen shuld have screening fr HBV in antenatal perid - Within 12 hurs f birth, babies shuld be given HBIG and HBV vaccine Cmplicatins - Liver cancer, cirrhsis Hepatitis C General cnsideratins - Bld brne virus, transmitted via bld-t-bld cntact - IVDU (95% f cases) - Vertical transmissin is lw (5%) Natural histry - Acute >> 25% f cases clear the infectin spntaneusly within 6 mnths f infectin; 75% prgress t chrnic hepatitis - Incidence is expected t increase and peak by Remains underdiagnsed Wh shuld we screen? - Patients with abnrmal LFTs - Histry f past r current IVDU - Received a bld transfusin r bld prducts befre Migrants frm high prevalence regins - Histry f tatts r piercings - Histry f incarceratin - Children f mthers with HCV - Healthcare wrkers perfrming expsure prne prcedures Examinatin findings - Usually asymptmatic - Palmar erythema, Dupuytren s cntracture, clubbing, leuknychia, peripheral hair lss - Asterixis, Petechiae r ecchymses, muscle wasting, ankle edema - Jaundice, fetr hepaticus, gynecmastia This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 82

83 - Partid enlargement, spider naevi - Splenmegaly, ascites, caput medusae - Hepatmegaly Treatment - N vaccinatin available Prgnsis and cmplicatins - Is curable, particularly when treated early - HVC and HIV c-infectin Chrnic hepatitis General cnsideratins - Categry f disrders characterised by cmbinatin f liver cell necrsis and inflammatin persisting mre than 6 mnths Etilgy - Causes: Viral hepatitis B with r withut hepatitis D superinfectin Drugs and txins ethanl, acetaminphen, aspirin, amidarne, methyldpa Metablic and genetic alpha 1 antitrypsin deficiency, Wilsn disease Autimmune r idipathic Clinical presentatin - Fatigue, malaise, lw grade fever - Anrexia and weight lss - Mild intermittent jaundice - Mild hepatsplenmegaly Histpathlgy - (1) Inflammatry infiltrate f hepatic prtal areas with mnnuclear cells - (2) Necrsis f hepatcytes within the parenchyma r immediately adjacent t the prtal areas Cmplicatins - Prgressin t cirrhsis - Cagulpathy - Hypersplenism - Ascites Hepatic steatsis General cnsideratins - Accumulatin f triglycerides and ther fats in the liver cells - Ptential mechanisms: Decreased mitchndrial fatty acid xidatin Increased endgenus fatty acid synthesis r enhanced delivery f FAs t liver Deficient exprtatin f triglycerides as VLDLs 3 classificatins (1) Alchlic fatty liver (2) Alchlic hepatitis (3) Alchl-related cirrhsis This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 83

84 Alchlic hepatitis (steathepatitis) General cnsideratins - Characterised by prgressive inflammatry changes t the liver assciated with lng term intake f ethanl - CAGE questinnaire can be helpful (have yu ever felt the need t CUT dwn; have yu felt ANNOYED at the suggestin that yu might have an alchl prblem; have yu felt GUILTY abut excessive drinking; d yu need an EYE OPENER in the mrning?) - Scial disruptin, including dmestic vilence, multiple hspital admissins - Family histry f alchl abuse is cmmn Clinical presentatin - Subacute nset f fever, hepatmegaly, leukcytsis, marked impairment f liver functin and manifestatins f prtal hypertensin (ascites, encephalpathy and varices) Pathgenesis ethanl - (1) Ethanl disrganises the lipid prtin f the cell membrane, leading t adaptive changes in their cmpsitin - (2) This alters the capacity f liver cells t cpe with envirnmental txins - (3) Oxidatin f ethanl prduces acetaldehyde, a txic and reactive intermediate - (4) Alters metablism f cfactrs essential fr enzymatic activity - (5) Induces malnutritin Investigatins - CBC + WCC leukcytsis - Raised transaminase levels with AST higher than ALT in a rati f 2:1, but neither abve 300 IU/dL - Raised Gamma GT n LFTs - Elevated bilirubin, hypalbuminemia and prlnged prthrmbin time - Ash serum bimarker + serum ethanl - Multiple healed fractures f the ribs r clavicle n CXR >> fall related - Abdminal US - Percutaneus r transjugular liver bipsy Histlgy findings - Zne 3 hepatcytes mst affected - Hepatcyte ballning >> fci r cells underging swelling and necrsis, filled with fat - Mallry-Denk bdies >> tangles f intermediate filaments, visible esinphilic cytplasmic inclusins - Infiltratin f plymrphnuclear leukcytes Treatment and management - Abstinence - Crrectin f vitamin deficiencies, high energy and prtein diet - Immunizatins against pneumcccal, meningcccal and influenza immuncmprmised and hypsplenic patients - Early referral t specialist care Prgnsis - Once signs f clinical decmpensatin ccur, patients with alchlic cirrhsis wh stp drinking have a 5-year survival rate f abut 60% versus thse wh d nt stp drinking Liver cirrhsis and prtal hypertensin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 84

85 General cnsideratins - Irreversible distrtin f nrmal liver architecture characterised by hepatic injury, fibrsis and ndular regeneratin Etilgy - Hepatitis A, B, C, D, E - Alchl abuse - Primary biliary cirrhsis - Wilsn disease and hemchrmatsis - Acute fatty liver disease - Sarcidsis - Tuberculsis - Chlestatic syndrmes - Drug induced - Autimmune Pathgenesis - (1) Initatin f hepatic stellate (fat strage cells) is prvked by sluble stimuli that include xidant stress signals, appttic bdes, LPS, Kupffer cells and hepatcytes - (2) Perpetuatin fllws characterised by phentypic changes including prliferatin, cntractility, fibrgenesis, chemtaxis and inflammatry signaling Clinical presentatin - Prtal hypertensin >> due t a rise in intrahepatic vascular resistance - Oesphageal varices >> due t prtal hypertensin - Hepatrenal syndrme >> distinct frm f kidney injury resulting frm renal vascnstrictin that develps in respnse t the systemic and splanchnic arterial vasdilatin in patients with advanced liver disease - Cagulpathy and bleeding tendency >> lss f hepatic synthesis f cltting factrs; hepatcytes als invlved in maintenance f nrmal cagulatin cascade thrugh absrptin f vitamin K, necessary t activate cltting factrs 2, 7, 9 and 10 - Encephalpathy >> reversible neurpsychiatric abnrmalities due t advanced liver disease r prtalt-systemic shunting - Splenmegaly >> cnsequence f elevated prtal venus pressure - Pulmnary cmplicatins >> hepatpulmnary syndrme, prtpulmnary syndrme and hepatic hydrthrax - Caput medusae - Ascites >> due t prtal hypertensin; cnfirmed by presence f serum-t-ascites albumin gradient (SAAG) - Bacterial peritnitis >> infectin resulting frm presence f ascitic fluid in peritneal space - Rectal varices - Jaundice >> decreased excretin f bilirubin - Spider nevi >> prminent bld vessels with a central arterile and little bld vessels radiating utwards - Dupuytren cntractures >> fibrsis f palmar fascia, resulting in permanent flexed ring finger This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 85

86 - Fetr hepaticus and hepatic flap >> accumulatin f ammnia - Peripheral edema >> caused by hemdynamic imbalance fllwing plasma prtein [ ] shifts - Hypalbuminemia >> wrsening hepatcellular functin can result in a drp in [ ] f albumin synthesised by liver - Testicular atrphy, lss f sexual hair and Gynaecmastia >> due t decreased clearance f estrgen Histpathlgy - (1) Marked distrtin f hepatic architecture - (2) Scarring because f increased depsitin f fibrus tissue and cllagen - (3) Regenerative ndules surrunded by scar tissue Treatment - Liver transplant - Prtal shunting Prgnsis and cmplicatins - Increased risk f hepatcellular carcinma - Cmplicatins f prtal HTN >> esphageal varices, external hemrrhids, bacterial peritnitis Hepatic encephalpathy General cnsideratins - AKA prtsystemic encephalpathy - Reversible syndrme f impaired brain functin caused by advanced liver disease - Liver dysfunctin results in decreased detxificatin capabilities and metablic abnrmalities >> accumulatin f ammnia, activatin f inhibitry neurtransmitters, impairment f excitatry neurtransmitters - Increased risk with >> sepsis, neurinflammatin, alteratins t gut flra Clinical presentatin - Irritability, dementia, seizures, btundatin and cma - O/E: hyperreflexia and asterixis Treatment - Lactulse >> acidificatin f gut lumen results in ammnia trapping and less reabsrptin - Rifaximin >> destructin f the gut bacteria (antibitic) - Prtein diet restrictins Gilbert s syndrme General cnsideratins - Hereditary uncnjugated hyperbilirubinemia - Due t defect in prmtr gene fr UGT1A1 Clinical presentatin - Mst asymptmatic - Occasinal recurrent mild jaundice assciated with fasting, stress and EtOH intake Diagnsis - Made with islated uncnjugated hyperbilirubinemia withut evidence f hepatitis r hemlysis Treatment - Supprtive medical management Prgnsis and cmplicatins This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 86

87 - N clinical cnsequences apart frm needing t avid sme medicatins Crigler-Najjar syndrme General cnsideratins - Infancy disease - Hereditary uncnjugated hyperbilirubinemia - Type 1 = severe jaundice and kernicterus, type 2 = less severe (Arias syndrme) Clinical presentatin - Nenatal jaundice - Sepsis - Hyptnia - Kernicterus - Oculmtr palsy - Deafness and pr mental prgressin/develpment Evaluatin - Nrmal LFTs - Uncnjugated hyperbilirubinemia - Pylric stensis might be evident Treatment - Plasmapheresis - Phttherapy - Phenbarbital - Liver transplant >> in severe cases Prgnsis and cmplicatins - Kernicterus >> depsitin f bilirubin in the brain - If severe, patients die within a few years Dubin-Jhnsn/Rtr s syndrme General cnsideratins - Hereditary cnjugated hyperbilirubinemia due t decreased hepatic excretin - Tw types: (1) Dubin-Jhnsn syndrme Grssly black liver due t the impaired secretin Benign Autsmal recessive inheritance (2) Rtr s syndrme Even mre mild than DJ syndrme Reye s syndrme Des nt cause the black liver Clinical presentatin - Mstly asymptmatic - Patients may becme jaundiced during pregnancy r while n OCPs Treatment - N treatment is needed This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 87

88 General cnsideratins - Hepatencephalpathy assciated with aspirin ingestin during a flu-like illness r varicella - Usually ccurs 4-12 YOA - Acute changes seen in liver architecture >> micrvascular fatty change Clinical presentatin (1) Prdrme Afebrile initially Sleepy and lethargic (2) Encephalpathy (in rder f increasing ICP) - Vmiting - Stupr - Cma - Death Evaluatin - Increased transaminases, hypglycemia Treatment - Cntrl ICP via mannitl, fluid resus and hyperventilatin Prgnsis and cmplicatins - Death will ccur withut aggressive medical management Alpha 1 Antitrypsin deficiency General cnsideratins - Autsmal dminant inheritance - Misflded alpha 1 antitrypsin (AAT) - AAT nrmally functins t inhibit elastase - Withut AAT, elastase is ver active and destrys elastic tissues Clinical presentatin - SOB - Symptms f cirrhsis - Hyperinflated lungs - Hepatmegaly Evaluatin - Spirmetry >> decreased FEV1, decreased FEV1/FVC rati and increases TLC Cmplicatins - Results in panacinar emphysema - The deficiency results in accumulatin within the ER in hepatcytes, which causes liver damage and cirrhsis Wilsn s disease General cnsideratins - Disease f free cpper accumulatin in bdy tissues (liver, brain, crnea, jints) - Autsmal recessive - Mutatin in ATP7B gene >> causes inadequate cpper excretin by liver int bile and failure f cpper t enter circulatin bund t cerulplasmin prtein Clinical presentatin - Parkinsn like symptms >> secndary t cpper depsits in the putamen This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 88

89 - Hemiballismus >> secndary t cpper depsits in the subthalamic nucleus - Dementia >> secndary t cpper depsits in cerebral crtex - O/E: Kayser-Fleischer rings in the eyes Evaluatin - Labs >> decreased ttal serum cpper, increased nn-cerulplasmin bund cpper, increased urine/serum free cpper, hemlytic anemia Prgnsis and cmplicatins - Hepatitis, cirrhsis and carcinma - Fancni s disease in the prximal tubules Hemchrmatsis General cnsideratins - Disease caused by excess irn depsitin in nearly all the tissues f the bdy - Autsmal recessive n chrmsme 6 - Slw curse > will usually present in 5 th decade f life fr men, and years pst menpause fr wmen - Primary = mutatin in HFE gene - Secndary = accumulatin f irn secndary t frequent bld transfusins r alchlism Clinical presentatin - Cirrhsis - Malabsrptin - Amenrrhea and decreased libid - Arthritis Prgnsis and cmplicatins - Cmplicated by cardimypathy, CHF - Increased risk f hepatcellular carcinma Fulminant liver failure General cnsideratins - Liver failure and encephalpathy within <8 weeks nset - Caused by: Reye s syndrme, drugs r infectin Clinical presentatin - Vmiting, stupr, cma and death - O/E: hepatmegaly and jaundice Treatment - Liver transplant Liver functin tests Serum bilirubin Haem metablite Cmes in tw frms (1) Cnjugated (direct) water sluble, and can be excreted by the kidney This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 89

90 (2) Uncnjugated (indirect) insluble in water and is bund t albumin in bld Elevated uncnjugated bilirubin rarely due t liver disease; seen mre in hemlytic disrders and genetic cnditins such as Crigler-Najjar syndrme Elevated cnjugated bilirubin almst always implies liver r biliary tract disease Urine bilirubin The nly bilirubin that is fund in the urine is cnjugated Presence f bilirubinuria implies liver disease Urine dipstick fr this is extremely accurate Bld ammnia Ammnia is prduced in the bdy during nrmal prtein metablism and by intestinal bacteria The liver plays a rle in detxificatin f ammnia by cnverting it t urea, and then excreting it via the kidneys Small crrelatin between elevated ammnia levels and liver disease and encephalpathy Serum enzymes Enzymes that reflect damage t hepatcytes (1) AST aspartate amintransferase - Fund in the liver, cardiac muscle, kidneys, brain, pancreas, lungs, leukcytes and erythrcytes (2) ALT alanine amintransferase - Fund primarily in the liver and is mre specific f liver injury (3) In acute hepatcellular disrders, ALT > r equal t AST (4) In chrnic liver diseases, AST: ALT rati is nrmally <1 (5) An AST: ALT rati f >2:1 is suggestive f cirrhsis (6) An AST: ALT rati f >3:1 is highly suggestive f alchlic liver disease (7) Causes: infectin, alchl, fatty liver disease, drugs, metal verlad, hypxia, autimmune cnditins Enzymes that reflect chlestasis (1) GGT gamma-glutamyl transferase (2) ALP alkaline phsphatase (3) 5 - nucletidase (4) Causes: biliary bstructin, pregnancy, drugs, infiltratin f malignancy Serum albumin Synthesised by hepatcytes in the liver Half-life f abut 20 days Hypalbuminemia mre cmmn in chrnic liver disease Serum glbulins Prteins made up f immunglbulins prduced by B lymphcytes and alpha and beta glbulins prduced by hepatcytes Immunglbulins are increased in chrnic liver disease Cagulatin factrs All bld cltting factrs (except factr VIII made by vascular endthelial cells) are made by hepatcytes Because f their rapid turnver, measuring these is the single best acute measure f hepatic synthetic functin T measure this, we lk at serum prthrmbin time (PT) which measures CFs II, VII, IX, X (all vitamin K dependent) This is expressed as INR internatinal nrmalized rati fr warfarin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 90

91 PT may be elevated in hepatitis and cirrhsis Grading liver functin Child-Turctte-Pugh scre Per the degree f ascites, plasma cncentratins f bilirubin and albumin, prthrmbin time and degree f encephalpathy Ttal scre f 5-6 = grade A (well cmpensated disease) Ttal scre f 7-9 = grade B (significant functinal cmprmise) Ttal scre f = grade C (decmpensated disease) These grades crrelate t 1 t 2-year patient survival: grade A (85-100%), grade B (60-80%) and grade C (35-45%) Hepatitis serlgic markers HBsAg - Antigen fund n the surface f HBV - This indicates hepatitis B infectin Anti-HBs - Antibdy t HBsAg - This indicates immunity t heptatits B HBcAg - Antigen assciated with the cre f HBV Anti-HBc - Antibdy t HBcAg - IgM indicates acute/recent infectin - IgG indicates prir expsure f chrnic infectin HBeAg - Secreted by the infected hepatcyte int the circulatin - This is nt part f the HBV virin - Indicates active viral replicatin and therefre this persn has high transmissibility Anti-HBe - Antibdy t HBeAg - Indicates lw transmissibility Anti-HAV (IgM) - IgM antibdy t HAV - Best test t detect the presence f acute hepatitis A Anti-HAV (IgG) - IgG antibdy indicates prir HAV infectin and/r prir vaccinatin - Prtects against reinfectin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 91

92 Biliary disrders Chlelithiasis General cnsideratins - Gallstnes Stne classes (1) Pigmented stnes Brwn result frm cmmn bile duct infectin Black cmpsed f calcium bilirubinate, result f increased liver excretin f bilirubin Risk factrs hemglbinpathies, alchl cirrhsis (2) Chlesterl stnes Mixed cmpsitin Risk factrs five Fs, OCPs, nrth American Indian, rapid weight lss, Crhns disease Clinical presentatin - Often asymptmatic, discvered incidentally - Biliary clic - Right upper quadrant pain - Nausea - Jaundice Etilgy - Five F s >> female, fat, fertile (multiple pregnancies), fibre (lw intake), frty years f age - Mst are largely cmpsed f chlesterl with/withut calcium depsits - Smetimes bilirubin stnes may frm >> in assciatin with ther disease Pathgenesis Multifactrial: factrs that affect bile cmpsitin and factrs that affect gallbladder mtility (1) Factrs that affect bile cmpsitin Stasis Chlesterl saturatin Rate f bile frmatin Rate f water and electrlyte absrptin Bacterial infectin Estrgen and prstaglandins Altered bile salt pl This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 92

93 (2) Factrs affecting gallbladder mtility Decreased sphincter f Oddi relaxatin Decreased gallbladder wall muscular cntractin Hrmnes Neural cntrl (vagal tne) Treatment - Chlecystectmy Cmplicatins - Chlelithiasis - Peritnitis due t bstructin f the cystic duct - Pst inflammatry fibrsis - Increased risk f carcinma - Calcificatin f the gallbladder wall - Acute and chrnic pancreatitis - Gallstne ileus Primary biliary cirrhsis General cnsideratins - Autimmune destructin f bile ducts in the prtal triads - Invlves granulmatus inflammatin and prgressin t cirrhsis Clinical presentatin - Pruritus - Jaundice - O/E: Kayser-Fleischer rings Prgnsis and cmplicatins - Increased risk f hepatcellular carcinma Acute chlecystitis General cnsideratins - Acute infectin f the gallbladder due t prlnged blckage f the cystic duct Pathgenesis - (1) Ldgment f stne in the cystic duct - (2) Accumulatin f mucus behind stne with bacterial vergrwth - (3) Bacterial invasin f the gallbladder wall - (4) Perfratin f gallbladder with gangrenus necrsis Etilgy - Caused by: E.Cli, Enterbacter clacae, clstridium - Can rarely ccur withut stnes >> CMV infectin in AIDS and severe vlume depletin Clinical presentatin - RUQ pain >> sudden nset, mins after eating, steady and aching, radiates t the right scapula - Nausea and vmiting - O/E: Charct s triad (RUQ tenderness, fever, jaundice) and psitive Murphy s sign Evaluatin - US is gld standard - Labs >> neutrphilic leukcytsis, elevated AST/ALT, elevated bilirubin, elevated amylase This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 93

94 Treatment - IV antibitics and fluids and electrlytes - DO NOT USE MORPHINE FOR ANALGESIA (may wrsen pain due t cntractin f sphincter f Oddi) - Chlecystectmy Prgnsis and cmplicatins - Gangrene, fistulas, perfratin, sepsis Pancreatic disease Acute pancreatitis General cnsideratin - Clinical syndrme resulting frm acute inflammatin and destructive autdigestin f the pancreas and peripancreatic tissues Etilgy - I GET SMASHED: idipathic, gallstnes, ethanl, trauma, sterids, mumps, autimmune, scrpin bite, hyperlipidemia, ERCP, drugs - Can result frm infectius agents mumps, hepatitis A, HIV, CMV - Familial pancreatitis rare usually mutatins f the catinic trypsingen gene - Emergence f autimmune pancreatitis >> type 1 and 2 Pathgenesis - Pancreatic duct bstructin, acinar cell injury, defective intracellular transprt f prenzymes - Thught t be invlved with the activatin f trypsin, causing widespread cellular effects due t the activatin f varius ther mediatrs - Elastase activatin >> vascular damage and hemrrhage - Chymtrypsin activatin >> edema and vascular damage - Lipase activatin >> fat necrsis - Phsphlipase A2 activatin >> cagulatin necrsis - Kalikrenin-kinin activatin >> edema and inflammatin - Inflammatry mediatrs >> TNF, IL-1, nitric xide and platelet activating factr Key mrphlgical features - (1) Micrvascular leakage causing edema - (2) Necrsis by fat lipases release f lipases results in splitting f triglycerides fund in the peritneum, then free fatty acids are released t cmbine with calcium in the interstitial fluid >> causing fat sapnificatin and the chalky white appearance n the utside f the pancreas - (3) Acute inflammatry reactin - (4) Prtelytic enzyme destructin f the pancreatic parenchyma - (5) Destructin f the bld vessels leading t hemrrhage Exists in tw frms - (1) Interstitial edematus pancreatitis >> enlargement f parenchyma - (2) Necrtizing pancreatitis >> necrsis f parenchyma Clinical presentatin - Can be mild and self-limiting - Abdminal pain universal hallmark >> intense, deep and searing, radiates t the back This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 94

95 - Nausea and vmiting >> due t stretching f the pancreatic capsule - Marked abdminal distentin with/withut ileus >> due t peritneal irritatin and electrlyte imbalance - Fever >> due t extensive tissue injury, inflammatin and necrsis endgenus pyrgens are released (mstly IL-1) - O/E: palpable gallbladder, abdminal tenderness with guarding r rebund tenderness, diminished bwel sunds frm ileus, Grey Turners sign (purple disclratin f the flank), Cullen s sign (periumbilical purple disclratin) Evaluatin - Labs >> elevated serum amylase, lipase - CT is gld standard - Ransn criteria used t determine prgnsis Treatment - IV fluids, bwel rest (nil by muth), BG decmpressin, antibitics, xygen - Pain cntrl >> meperidine Early cmplicatins - Shck >> due t hypvlemia, hyptensin, vasdilatin - Disseminated intravascular cagulatin >> tissue factr release may cause activatin f plasma cagulatin cascade - Pulmnary cmplicatins >> endthelial cell destructin and increased permeability f alvelar capillary membrane, causes respiratry failure Late cmplicatins - Pancreatic pseudcysts >> cavities that cntain bld, pus r pancreatic juice (can prgress t pancreatic abscess) - Walled ff necrsis >> encapsulated cllectin f debris - Pancreatic ascites >> direct cnnectin develps between the pancreatic duct and the peritneal cavity - Pancreatic fistulas Prgnsis - Mst peple recver cmpletely with medical management - The pancreas regenerates and returns t nrmal apart frm sme mild residual scarring Chrnic pancreatitis General cnsideratins - Chrnic relapsing f inflammatin, fibrsis and destructin f the pancreas - Damage is irreversible Etilgy - Alchl abuse, duct bstructin, pancreas divisum, metablic disrders, drugs, autimmune Pathgenesis (1) Large duct Biliary pancreatic reflux Sphincter f Oddi bstructin (2) Small duct Increased lactferrin Decreased lithstathine (pancreatic stne prtein) (3) Acinar cell This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 95

96 Txic metablites Stellate cell induced fibrsis Macrscpic features - Parenchymal fibrsis - Reduced number and size f acini - Dilatin f sme pancreatic ducts - Relative sparing f the islets f Langerhans Clinical presentatin - Persistent epigastric pain - Nausea and vmiting - Weight lss - Malabsrptin - Hyperglycemia and diabetes mellitus - Buts f jaundice Cmplicatins - Pseudcyst frmatin, fistulas, ascites, pleural effusin Cystic fibrsis General cnsideratins - Autsmal recessive defect - Disrder f epithelial transprt (dysfunctin f chlride channels) affecting fluid secretin in excrine glands and epithelial lining f the respiratry, GI and reprductive tracts Etilgy - Mst cmmn lethal genetic abnrmality f Caucasian ppulatins Changes that ccur in the pancreas - Abnrmal viscus mucsa secretins blck the pancreatic ducts resulting in pancreatic insufficiency - Ducts becme dilated and plugged with esinphilic mucin - This may lead t bstructin by a thick viscus plug, malabsrptin, increased fecal lss, ful smelling stls, abdminal distentin, pr weight gain Pancreatic carcinma General cnsideratins - Knwn as infiltrating ductal adencarcinma f the pancreas Etilgy - Usually ccurs after 50 YOA - Men > wmen - Precursr lesin >> PanINS (pancreatic intraepithelial neplasia) - Strngest envirnmental link >> smking - Additinal risk factrs >> high intake f saturated fat, expsure t slvents, pesticides, alchl Pathphysilgy - Invlves the gradual accumulatin f genetic defects - (1) Telmere shrtening - (2) Mutatin f K-RAS - (3) Inactivatin f p16 This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 96

97 - (4) Inactivatin f p53, SMAD4 and BRCA2 Mrphlgical features - Mst cmmnly ccurs in the head f the pancreas - Mst are adencarcinmas - Hard, gray-white, stellate, prly defined masses - Generally, bstructs the cmmn bile duct Clinical presentatin (in rder f likelihd) - Severe epigastric abdminal pain - Anrexia - Unexplained weight lss - Jaundice - Diarrhea - Weakness - Cnstipatin - Hematemesis r melena - Vmiting Evaluatin - Elevated ALP, 5 -nucletidase, LDH, AST, bilirubin, amylase, alpha fetprtein, and carcinembrynic antigen - Decreased albumin Treatment - Surgical resectin - Systemic chemtherapy - Radiatin therapy Prgnsis and cmplicatins - Extremely high mrtality rate (5-year survival rate 20%) - Metastasis (1) Hemtgenus spread - liver, lungs (2) Lymph nde spread peripancreatic, artic and extra-abdminal (3) Direct invasin SMAs, prtal vein, retrperitneum, peritneum, nearby rgans Metablism and metablic disease Metablic pathways Anablic pathway - Building cmpunds - Synthesis f larger and mre cmplex cmpunds frm smaller precursrs - Endthermic reactin Catablic pathway - Breaking dwn cmpunds - Breakdwn f larger mlecules, cmmnly invlving xidative mechanisms - Exthermic reactin, prducing reducing equivalents mainly via respiratry chain, ATP Amphiblic pathway This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 97

98 - Occurs at the crssrads f metablism, acting as links between the anablic and catablic pathways - Such as the citric acid cycle The fed, fasted and starving states The fed state hurs after eating, while the prducts f digestin are being absrbed, there is abundant supply f metablic fuels - In this cnditin, glucse is the majr fuel fr xidatin - Glucse uptake int muscle and adipse tissue is cntrlled by insulin (secreted by beta-islet cells in the pancreas in respnse t increased cncentratin f glucse in prtal bld The fasting state - Small fall in plasma glucse - As fasting is prlnged, the plasma cncentratin f ketne bdies increases markedly - Glucagn predminant The starving state - Dietary glucse and hepatic glycgen have been exhausted, yet the brain still requires glucse - Glucnegenesis can prvide the brain glucse - Substrates fr glucnegenesis include: Liver glycgen Lactate Glycerl Sme AA - Liver glycgen is exhausted, s isn't viable ptin in starvatin - Thus, ketnes can be synthesized frm the FFAs liberated using glycerl in glucnegenesis - In nrmal beta-xidatin, FFA are cnverted t acetyl-ca and are passed thrugh the CAC - Hwever, in starvatin, the intermediate carriers within this cycle are limited - This shunts acetyl CA int the ketgenic pathway - Because the reactin can prgress in bth directins, nce the ketne reaches the brain, it can be cnverted back int acetyl CA and pass thrugh the CAC Starvatin past 7 days - As starvatin cntinues past 7 days, the favred substrate glucnegenesis becmes glycerl, resulting in prtein sparing and increased cncentratin f ketnes in the bld, reducing the requirement fr glucse - The shift in fuel utilizatin is thught t be a result f decreased thyrid hrmne secretin - Prtein lss is usually the cause f death in starvatin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 98

99 Glucse metablism Glucse is a majr fuel surce (1) Dietary glucse (2) Glyclysis - (a) Cnverted t glucse phsphates fr further degradatin - (b) Stred as glycgen in the skeletal muscle and liver - (c) Metablised as part f the pentse phsphate pathway RNA/DNA synthesis (3) If glucse cntinues, it is cnverted t trise phsphates via glyclysis (4) Cnverted t pyruvate via glyclysis (5) Anerbic tissues metablise pyruvate t acetyl-ca (6) Acetyl-CA enters the citric acid cycle Glucnegenesis Prcess f synthesizing glucse frm nn-carbhydrate precursrs such as lactate, amin acids and glycerl Fatty acid metablism (1) Triacylglycerl is the bdy s main fuel reserve (2) Triacylglycerl cnverted t fatty acids via liplysis (3) Fatty acids are cnverted t acetyl-ca via beta-xidatin (4) Acetyl-CA has three fates - (a) Oxidized via the citric acid cycle - (b) Is the precursr fr synthesis f chlesterl and ther sterids - (c) In the liver, it is used t frm ketne bdies imprtant fuels in prlnged fasting and starvatin Amin acid metablism (1) Essential amin acids cannt be made in the bdy and are required thrugh diet these are brken dwn via the citric acid cycle (2) Nn-essential amin acids can be made in the bdy via transaminatin (3) The amin acid then underges deaminatin and amin nitrgen is excreted as urea The citric acid cycle All prducts f digestin are metablized t a cmmn prduct acetyl-ca, which is then xidized by TCA cycle Summary f metablic hmestatic reactins This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 99

100 Prcess Reactin Cnsequence Hrmne Glycgenesis Glucse => glycgen Decrease bld glucse levels Insulin Glycgenlysis Glycgen => glucse Increase bld glucse levels Glucagn Glucnegenesis AA => glucse Increase bld glucse levels Glucagn Prtein synthesis AA => prtein Decrease bld AA levels Insulin Prtein degradatin (deaminatin) Prtein => AA Increase bld AA levels Glucagn Lipgenesis FA and glycerl => TG Decrease bld FA Insulin Liplysis TG => FA and glycerl Increase bld FA Glucagn Lipgenesis FA and glycerl => TG Decrease bld FA Insulin Liplysis TG => FA and glycerl Increase bld FA Glucagn Insulin synthesis and metablism Synthesis - Insulin = prtein with tw peptide chains - Stages f synthesis (1) Precursr t insulin = preprinsulin (2) Preprinsulin synthesised in ribsmes and enters ER f beta cells; here its cleaved t frm prinsulin This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 100

101 (3) Prinsulin is transprted t Glgi apparatus and packaged int vesicles (4) Whilst inside the vesicle, prinsulin is cleaved in tw parts t frm insulin - 50% f insulin is catablized n its first pass thrugh the liver Regulatin f insulin secretin Glucse is the primary stimulant f insulin release Stages f regulatin (1) Glucse enters pancreatic beta cells facilitated by ne r mre glucse transprters (GLUT1, GLUT2, GLUT3) (2) Once in the cell, metablism f glucse stimulated secretin f insulin Insulin secretin can als be regulated by enteric hrmnes, such as glucagn-like peptide 1 GLUT transprters GLUT1- glucse acrss BBB GLUT2-beta cells, kidney GLUT3-glucse int neurns GLUT4-mst bdy cells, resting skeletal muscle, adipse Nt present in the plasma membrane in the absence f insulin, whereas all thers are present Muscle cntractin triggers insertin f GLUT4 int exercising muscle cells in the absence f insulin; imprtant fr managing DM Mechanism f insulin activatin Stages f actin (1) Insulin binds directly t insulin receptrs present n surfaces f target cells (liver, muscle, fat) and nnclassic target tissues (vary) (2) Binding f insulin t its receptrs causes activatin f the tyrsine kinase regin f the receptr (3) Activatin f tyrsine kinase regin causes activatin f the whle receptr (4) Activatin f the insulin receptr initiates a phsphrylatin cascade within the cell, beginning with the phsphrylatin f a netwrk f dcking prteins (insulin receptr substrates) that engages with signaling mlecules dwnstream The effects f insulin Fuel hmestasis in liver, muscle and fat Liver - Insulin prmtes fuel strage by stimulatin f glycgen synthesis and strage - Inhibits hepatic glucse utput by inhibiting glucnegenesis (glucse synthesis) and glycgenlysis (glycgen breakdwn) - Insulin stimulates lipgenesis Muscle - Insulin prmtes strage f glucse by stimulating glycgen synthesis and inhibiting glycgen catablism Adipse tissue - Insulin stimulates lipprtein lipase >> enzyme that hydrlyses the triglycerides carried in VLDLs When is insulin secretin INCREASED? High bld glucse High bld AA (arginine, lysine, leucine) High bld FA Incretins like GIP, which causes insulin secretin in respnse t ral glucse lad This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 101

102 Parasympathetic activatin (vagal stimulatin, due t eating) When is insulin secretin DECREASED? Decrease in bld glucse Smatstatin Catechlamines Glucagn synthesis and metablism Prduced in alpha cells f the pancreas + (intestine and brain) Stages f synthesis (1) Prglucagn precursr prtein underges prtelytic prcessing (2) Metablised in liver and kidneys Regulatin f glucagn secretin Glucagn secretin is inhibited by glucse, smstatin, and tw additinal beta cell secretry prducts Mechanism f glucagn actin Main rle is t maintain nrmal glucse levels during fasting by inducing hepatic glucse prductin, thus cunteracting the hepatic effects f insulin Activatin (1) Glucagn binds t a GPCR present n the surface f all hepatcytes, activating adenylyl cyclase and generating camp (2) camp activates prtein kinase A (3) Prtein kinase A activated gene transcriptin fr the enzymes respnsible fr the activity f glucagn in the liver Effects f glucagn Cunter-regulatry hrmne t ppse the effects f insulin Injectins used t treat severe hypglycemia Hepatic effects include: (1) Increased hepatic glucse utput via release f glycgen stres (2) Increased hepatic uptake f amin acids, which fuels glucnegenesis (3) Stimulatin f fatty acid xidatin and ketgenesis When is glucagn secretin INCREASED? Lw bld glucse Ketsis, starvatin High bld AA (esp. arginine) CCK (alerts alpha cells t a prtein meal) Catechlamines (beta receptrs nly) When is glucagn secretin DECREASED? High bld glucse Insulin presence Smatstatin presence Regulatin f appetite Energy requirements in a healthy persn - Amunt f energy required in a day is a cmbinatin f a persn's basal metablic rate (BMR), activity levels, thermic effect f fd, as well as stress, disease, and hrmnal status This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 102

103 - This energy can cme frm ingested fd r stred fat, which the satiety center f the brain determining the favred surce What is the site f feeding and satiety regulatin? - The hypthalamus, specifically varius nuclei within the hypthalamus have different effects n feeding What is the majr feeding center? - Lateral nuclei f hypthalamus What is the majr satiety center? - Ventrmedial nuclei f hypthalamus What is the rle f the arcuate nucleus in satiety and feeding? - Prvides general input t bth lateral nuclei and ventrmedial nuclei What are the five main inputs t the arcuate nucleus regarding satiety? - Bld glucse levels - Vagus afferent (signaling f stmach stretch) - GI hrmnes (CCK, peptide YY, insulin) - Leptin frm adipse tissue, secreted in increasing amunts as the cells grw - Ghrelin frm the stmach during fasting t stimulate appetite BMI BMI = mass (kg) / height (m) 2 <18.5 = underweight = gd = verweight = bese Diabetes mellitus General cnsideratins - Hetergeneus disrder defined by the presence f hyperglycemia - Diagnstic criteria: (1) Fasting plasma glucse f 126 mg/dl r mre (2) Classic symptms f hyperglycemia plus a randm plasma glucse f 200mg/dL r mre (3) Plasma level f 200mg/dL r mre after an ral dse f 75g f glucse (ral glucse tlerance test) (4) HbA1c level f 6.5% r mre Pre-diabetes - Defined by a fasting bld glucse level f mg/dL r a 2 hur OGTT glucse level f mg/dL Type 1 diabetes - Pathphysilgy (1) In early disease, lymphcytic infiltrates f macrphage activating CD4+ cells and cytkine secreting CD8+ cells surrund the necrtic B-cells in the pancreas (2) The autimmune destructin f these B-cells ccurs gradually ver years until there sufficient B- cell mass is lst t cause symptms f insulin deficiency (3) At time f diagnsis, nging inflammatin is present in sme islets, whereas thers are atrphic and cnsist f nly glucagn-secreting alpha cells and smatstatin secreting delta cells Type 2 diabetes - Pathphysilgy Tw metablic effects are respnsible fr hyperglycemia in DMII target tissue resistance t the effects f insulin and inadequate pancreatic B-cell insulin secretin in the setting f insulin resistance This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 103

104 (1) Nutritinal excess f any surces leads t increased free fatty acid strage as triglyceride in adipse tissue (2) Increased release f varius factrs frm adipse tissue (particularly visceral adipse tissue), drives insulin resistance (3) Increased insulin resistance causes: Txic effects f excess FFAs released frm adipse tissue liptxicity Dysregulated secretin f fat-specific prteins adipnectin, leptin Increased prductin f inflammatry cytkines within adipse tissue TNF - Visceral adipse tissue mst clses crrelated with insulin resistance since its mst susceptible t increased liplysis therefre the mre visceral fat, the higher the likelihd fr DMII Clinical presentatin (bth types) - N matter the type, bth result in deficiency f insulin actin and a high glucagn-insulin rati >> metablic derangement develps - Plyuria and ncturia - Plydipsia - Plyphagia - Weight lss - Tiredness - Lack f interest and cncentratin - Tingling sensatin r numbness in hands and feet - Blurred visin - Frequent infectins and slw healing wunds - Hypertensin - Orthstatic hypertensin due t autnmic neurpathy - Diabetic retinpathy - Diabetic ft diminished pedal pulses, ft ulcers, pitting edema, atrpic hair changes, decreased sensatin - Pst-prandial hyperglycemia - inability f insulin sensitive tissues t clear glucse lads - Fasting hyperglycemia - ccurs when there is severe lss f insulin actin and glucagn s effects n the liver are nt cunterbalanced Cmparisn f type 1 and type 2 Features Type 1 diabetes Type 2 diabetes Age at diagnsis Childhd Adulthd Prevalence 0.2% 11% - cmmn Risk factrs Genetic susceptibility Viruses (entervirus, mumps, rubella) Txic chemicals Expsure t cw s milk in infancy Cyttxins Age >45 Obesity Family Hx f DMII Hispanic, native American, Asian American and pacific islander heritage Hx f impaired OGTT Hypertensin Dyslipidemia Hx f gestatinal diabetes/preeclampsia Plycystic varian syndrme This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 104

105 Pathgenic pathway (described abve) Autimmune destructin f pancreatic beta cells by T lymphcytes targeting ill-defined B- cell antigens; with resultant severe insulin deficiency Depressin Schizphrenia Increased resistance t the effects f insulin at its sites f actin and a decrease in insulin secretin by the pancreas Insulin resistance is the hallmark Beta cell insulin secretin abnrmal Abslute deficiency Impaired secretin Insulin resistance N Yes Obese N Yes BMI Usually <25 >25 Autimmune diseases Yes N Envirnmental triggers Incidence in ffspring (bth parents affected) Genetic lci assciated with risk Treatment Cmplicatins Viral infectins, dietary expsures, Obesity vitamin D deficiency 10% 50% HLA class II genes Specifically, DR, DQ and DP Insulin treatment Glycemic cntrl Self-mnitring Diet and exercise Diabetic ketacidsis (cmmn) Increased risk f infectins Micrvascular cmplicatins Macrvascular cmplicatins Neurpathies Hetergeneus sets f interacting genes: HNF-4-alpha Gluckinase gene HNF-1-alpha IPF-1 Lifestyle mdificatins Medicatins (sulfnylureas, incretins, metfrmin) Diabetic ketacidsis (rare) Hypersmlar cma Hypglycemia frm treatment Nephrpathy glmerulsclersis Neurpathy autnmic and plyneurpathy Retinpathy Crnary artery disease Cerebrvascular disease Peripheral vascular disease Ft ulcers Infectins Skeletal fractures lwer bne mass Diabetes treatment (depends n the stage and severity f disease) Drug class Drug name Details AEs Type 1 Diabetes Rapid acting insulin Lispr insulin Substitutes cmpnents f the beta Glulisine insulin chain t allw the drug t be Aspart insulin absrbed mre quickly 5-10-minute nset f actin Type 2 Diabetes This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 105

106 Shrt acting insulin Regular insulin A preparatin f zinc insulin crystals in slutin 0.5-hur nset f actin Intermediate acting insulin Lng acting insulin NPH insulin Lantus Levemir Crystalline suspensin f human insulin with prtamine and zinc 1-2-hur nset f actin Des nt have a peak, prducing a relatively stable level lasting mre than 24 hurs Glucse slutin Blus used t treat hypglycemia Biguanide Metfrmin Lwers basal and pstprandial plasma glucse levels; by decreasing hepatic glucnegenesis prductin Lactic acidsis Sulfnylureas Glucagnlike peptide 1 agnists Meglitinide derivatives Alpha-glucsidase inhibitrs Thiazlidinedines Dipeptidyl peptidase IV inhibitrs Glyburide Glimepiride Exenatide Liraglutide Albiglutide Repaglinide Nateglinide Rsiglitazne (Avandia) Sitagliptin Saxagliptin Linagliptin Stimulate insulin release frm pancreatic beta cells and prbably have the best efficacy fr glycemic lwering Stimulate glucse dependent insulin release, reduce glucagn and slw gastric emptying Risk f hypglycemia Weight gain Nausea Vmiting Weight lss URTI Hypglycemia Similar MOA t abve, except shrter acting Prevent pstprandial glucse surges GI disturbances Insulin sensitizers; thus, requiring the presence f insulin Must be taken fr weeks t take maximal effect Nt used much anymre Prlng the actin f incretin hrmnes (hrmne that stimulates insulin secretin in respnse t meals GLP-1 amd GIP) Weight gain Oedema Hepattxicity URTI Weight neutral - DMII Metfrmin first, then add a drug, then start triple therapy - Sme peple with DMII becme insulinpenic and the nly thing that can crrect this is insulin (red ticks are last resrt) Pathphysilgy f micrvascular diabetes cmplicatins - (1) Increased plyl pathway flux - (2) Increased frmatin f advanced glycatin prduct (AGE) - (3) Activatin f prtein kinase C - (4) Increased hexsamine pathway flux - Result f these pathways = increase in prtein accumulatin in vessel walls, endthelial cell dysfunctin, lss f endthelial cells and cclusin f the vessels Gals f diabetes management - Fasting BSL shuld be 5-7mml/L - Pst-prandial BSL shuld be <10 Mnitr BSL via glucmeter This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 106

107 - HbA1c shuld be 6.5-7% - Measures glycsylatin f hemglbin (Hb); the higher the BSL, the mre glycsylated the Hb; RBC circulate fr 3 mnths, and s taking a HbA1c every 3 mnths will give a gd idea f glycemic cntrl (caveat: HbA1c is nt indicative f high and lw glucse levels - it is nly an average) - Avid hypglycemia - Tight cntrl f CVS risks BP cntrl Lipid cntrl Obstructive sleep apnea Obesity cntrl Smking cessatin Gestatinal diabetes General cnsideratins - Occurs in pregnant wmen and tends t reslve nce the baby is delivered - Mre cmmn in the secnd half f gestatin, precipitated by increasing levels f hrmnes such as chrinic smatmammtrpin, prgesterne, crtisl and prlactin that all have a cunter regulatry anti-insulin effects - Tested at 24 weeks gestatin via OGTT Latent autimmune diabetes in adults (LADA) Same pathgenesis as T1DM, but slwer autimmune destructin f B cells Mixed phentype - lder, mre range in BMI The disease can be mistaken fr T2, patient may have been n ral medicatins fr several mnths + autantibdies Eventually need insulin Risk f DKA Maturity nset diabetes f the yung (MODY) Variety f mngenic mutatins in genes cntrlling glucse sensing and insulin secretin Strng family histry Hyperglycemia frm a very yung age, nt discvered until later Respnds t sulfnylureas GK (gluckinase mutatin) Hypglycemia Cmplicatin f insulin treatment in bth DMI and II (type I especially prne due t almst absent glucagn respnse t hypglycemia) Often ccurs with exercise r fasting Symptms - Tremr / shakiness - Anxiety - Palpitatins and tachycardia - Sweating - Hunger - Weakness / fatigue - Cnfusin and headache This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 107

108 - Difficulty speaking - Seizures - Night sweats / nightmares / restlessness / mrning headache - Cma Treatment - Rapid ral administratin f glucse at the nset f warning symptms Hyperglycemia Clinical presentatin - Glycsuria - Osmtic diuresis - Plyuria - Dehydratin - Plydipsia Retinpathy - Pathgenesis: prliferating retinal vessels hemrrhage int vitreus fluid, increasing pressure n the macula, leading t blindness - Symptms: asymptmatic until late; curtain falling, flaters, decreased visual acuity - Findings: micraneurysms, dt and blt hemrrhages, hard exudates, cttn wl spts, nevascularizatin, vitreus hemrrhages, macular edema - Treatment: imprve glucse cntrl, imprve BP cntrl, laser, VEGFi, vitrectmy Nephrpathy - Pathgenesis: hyperglycemia, hyperfiltratin, glmerular sclersis - MCC f renal failure/dialysis, as it is asymptmatic until CKD manifests - Early stage =>> increased egfr, increased glberular size and micralbuminuria - Late stage >> increasing prteinuria, marked decline in egfr, uremia - Treatment: bld glucse cntrl, BP cntrl, ACEi Neurpathy - Pathgenesis: Micrangipathy in small vessels arund nerves and altered glucse metablism in nerves - Can present: Peripheral >> symmetric length-dependent sensry plyneurpathy r paresthesia Gastrparesis Autnmic Plyradiculpathy mnneurpathy Ischemic heart disease Present nrmal, with atypical symptms (SOB, vmiting, HF) r nne Treat: glucse cntrl, BP, lipids, smking cessatin, weight-lss, aspirin, stenting Strke 1.5x risk Treat: typical strke - anti-platelets, BP, lipids, smking cessatin Peripheral vascular disease Intermittent claudicatin, gangrenus te Treat: nrmal - anti-platelets, BP, lipids, smking cessatin, weight-lss, angiplasty This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 108

109 Hypersmlar hyperglycemic state General cnsideratins - Hyperglycemia, hypersmlar, little r n ketacids Etilgy - Inadequate treatment f DM and underlying illness - Decreased water intake, leading t a gradual, but severe dehydratin Pathgenesis - Frm inadequate, but present, amunt f insulin and increased regulatry hrmnes Clinical presentatin - Irritability - Restlessness - Stupr - Muscle twitching - Hyperreflexia - Spasticity - Seizure - Cma Metablic syndrme General cnsideratins - Multiplex risk factr that arises frm insulin resistance accmpanying abnrmal adipse tissue depsitin and functin - Majr risk factr fr chrnic diseases Clinical presentatin - Hypertensin - Hyperglycemia - Hypertriglyceridemia - Reduced HDL chlesterl This dcument is a student submissin made t the Australian Medical Students Assciatin Limited (AMSA). All use is subject t ur Terms f Service available at Page 109