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Semester 4 PBL Cases 1 - 3 Catch-up ISOC MedEd Introduction ● Who are we? ● Our mission ● Our team ● Our plan Upcoming ISoc Events ● Friday Social TOMORROW! Free scran at 8:15pm ● Charity Stalls - Monday ISoc x PalSoc - Tuesday Baking comp - Thursday ISoc x PakSoc ● Tuesdays - Roots - Sisters Q&A ● Wednesday - Charity Dinner ● Friday Social ● Sunday - Ladies Badminton Social, Sugden, 12:30-1:30pm ● Sunday - Guys Football Social, Trinity, 5-6pm ● Sunday - Man City vs Liverpool Screening - HIVE SUCase 1 - Swallowing & Oesophageal Cancer Mohammad AlkalbaniBy Mohammad Al-Kalbani Enteric Nervous System Histol(just kidding) ● Serosa ● Longitudinal smooth muscle ● Circular smooth muscle ● Submucosa ● Mucosa ● Epithelial lining Histology(just kidding) ● Serosa ● Longitudinal smooth muscle ● Circular smooth muscle ● Submucosa ● Mucosa ● Epithelial lining Two Main plexus that concern us(in reality none) 1. Submucosal plexus/Meissner’s plexus: ○ Lies in the submucosa ○ Controls gastrointestinal secretion and local blood flow 2. Myenteric plexus: ○ Between longitudinal and circular muscle layers – motility ○ Includes sensory, motor and interneurons ○ Detects mechanical and chemical conditionsSwallowing Stages of Swallowing ● Oral stage ● Pharyngeal stage ● Oesophageal stageCNS control ▪ Afferent signals are processed by the nucleus tractus soliterious (NTS) ▪ The NTS communicates with efferent nuclei in the nucleus ambiguous ▪ Together these form the central pattern generator (CPG) Oral Stage -Oral Preparatory, Oral Transportation CHEWING – MASTICATION SALIVATION MOVEMENT OF BOLUSMastication ● Voluntary ● First step of digestion ● Increases surface area for enzymes ● Mechanical breakdown - cellulose ● Muscles (trigeminal V3): ○ Masseter ○ Temporalis ○ Lateral pterygoid ○ Medial pterygoidSalivationSalivation ● Saliva is secreted by : ○ Parotid glands – serous ○ Submandibular gland – serous and mucous ○ Sublingual glands – serous and mucous ○ Buccal glands – mucous ● Serous - contains ptyalin (alpha-amylase) ● Mucus – contains mucin for lubricating and for surface protective purposes ● pH 6-7(why?)Salivation(continued) ● Saliva contains: ○ Large amounts of potassium and bicarbonate ions ○ Small amounts of sodium and chloride ions ● Salivary glands are made of : ○ Acini ducts ○ Salivary ducts ● The final product is hypotonicAcini secretionDuctal secretionPharyngeal Stage ● Once the food enters the posterior mouth ● Automatic series of contractions(semi-involuntary): 1. Soft palate is pulled upwards to close the posterior nares – prevent the reflux into the nasopharynx 2. Palatopharyngeal folds – sagittal slit (why?) 3. Epiglottis swing backward and the larynx move upwards (why?) 4. Suprahyoid and geniohyoid muscles contract 5. Upward and forward movement of larynx 6. Hyoid bone is pulled forward 7. Upper Oesophageal sphincter relaxed 8. Entire wall of the pharynx contracts beginning in the superior part of the pharynx – spreading downwards -> peristalsis into the oesophagus ● How long does this process take?Oesophageal Phase ● Two movements: o Primary peristalsis – intitated by the pharynx o Secondary peristalsis – initiated by intrinsic neural circuits in the myenteric nervous system o (basically, you swallow the bolus then you swallow it again) ● Pressure zones(cool word for sphincters): o Upper oesophageal sphincter(UOS) - 100 mmHg o Lower oesophageal sphincter(LOS) - 20mmHg ● Why is there a negative pressure in the oesophagus? Upper Oesophageal Sphincter(UOS) ● Musculature: o Cricopharyngeus muscle o Inferior pharyngeal constrictor? ● Innervation – mainly vagus nerve ● At rest -> it is closed (why?) ● What does the body need to do to open it? Lower Oesophageal Sphincter  ● Musculature: o None specific – ring of smooth muscle o It is a physiological sphincter ● How does it open?Help me Doc! I am having difficulty swallowing ☹ First of all lets check our knowledgeDifferentials for dysphagia? - Gastro-oesophageal reflux - Hiatus hernia - Oesophageal cancer - Oesophageal candidiasis - Achalasia - Muscle tension dysphagia - Diffuse oesophageal spasm - Pharyngitis - Other neurological disorders such as cerebrovascular accidents (CVAs) -Pharyngeal pouchQuestions to Ask pt? - Symptom onset? Dysphagia primarily to solid foods more likely to be structural lesion. Dysphagia to both solid and liquid from the onset of symptoms is likely to be caused by myomotility or neurological disorders. - Duration and progression of symptoms? Rapid progression may be suggestive of malignancy. - Weight loss (unexplained)? Suggestive of malignancy - Dyspepsia/GORD? Metaplasia of the oesophagus (Barrett’s oesophagus) leading to dysplastic changes that predispose to oesophageal adenocarcinoma - Pain on swallowing (odynophagia)? May be a symptom of a locally advanced tumour - Has he been vomiting, and has he noticed any blood in his vomit? Long history of vomiting may suggest Mallory-Weiss tear. - Any change in bowel habit? Possible melaena with an upper GI bleed Pharyngeal pouch ● Its also known as? ● It is an outpouching of the pharyngeal mucosa through an area of weakness ● Risks: oOld(70+) oMale oFH ● Main clinical findings: oDysphagia (I cant swallow doctor) oRegurgitaion of food oAspiration oHalitosis(unless you're fasting) ● What investigations?Achalasia ● Failure of oeophageal peristalsis and of relaxation of LOS ● Due to loss of ganglia from Auerbach's plexus ● Achalasia typically presents in MIDDLE AGED (25-60) ● Clinical features: o Dysphagia BOTH liquids and solids o Heartburn o Occasional regurgitation of undigested food ● What investigations?Manometry ▪ Manometric examination usually required for confirmation ▪ Three primary findings ▪ Elevated resting LES pressure - >45 mmHg ▪ Incomplete LES relaxation ▪ Aperistalsis Treatments • Pneumatic dilation: o First line o Less invasive o Low risk • Heller/POEM cardiomyotomy • Drugs (nitrates, CCB) not really good • Botox (shmexy) Oesophageal Cancer • Clinical features: o Dysphagia o Weight loss(this is in every dysphagia case duhh) o Vomiting • What investigations?FEEDING • Enteral Feeding: Providing nutrition directly into the GI tract • Parenteral: into the blood • Why Enteral? Oral (preferred, if safe) ○ Modified diet ○ Pureed food, Thickened liquids Enteral ○ NG ○ NJ ○ PEG ○ J Tube Parenteral ○ IV Investigations Bedside Investigations: Case history: Detailed inquiry into the onset, duration, progression, and associated symptoms of dysphagia. Physical examination: Assessing for signs of aspiration, such as coughing or choking, and identifying any structural abnormalities in the oral cavity and neck. Imaging Investigations: Barium swallow study: Evaluates the anatomy and function of the swallowing mechanism, identifying strictures, diverticula, or motility disorders. Endoscopy (ophagogastroduodenoscopy or OGD): Direct visualization of the esophagus, stomach, and duodenum to detect any mucosal abnormalities, tumors, or strictures. Videofluoroscopic swallowing study (VFSS): Real-time imaging of swallowing function using fluoroscopy, providing dynamic assessment of bolus movement and detecting aspiration risk. Esophageal cancer (barium swallow) | Radiology Case | Radiopaedia.org Investigations Con. Referral Investigations: Speech and language therapy (SLT): Comprehensive evaluation of swallowing function and formulation of tailored swallowing rehabilitation plans. Gastroenterology referral: Consultation for further evaluation and management of underlying gastrointestinal disorders, such as gastroesophageal reflux disease (GERD) or esophageal cancer. ENT referral: Assessment of upper aerodigestive tract pathology, including evaluation for pharyngeal pouches or laryngeal abnormalities. Secondary Investigations: Esophageal manometry: Measures esophageal motility and pressure dynamics, aiding in the diagnosis of conditions like achalasia or esophageal spasm. pH monitoring: Assessing esophageal acid exposure over a prolonged period to diagnose GERD or assess treatment efficacy. Computed tomography (CT) or magnetic resonance imaging (MRI): Imaging modalities for detailed assessment of structural abnormalities, such as tumors, strictures, or masses compressing the esophagus. Case 1 • A 68-year-old male presents with a recent onset of dysphagia swallowing solids and liquids, accompanied by frequent coughinglty and occasional choking episodes. •He reports no prior history of swallowing difficulties or neurological deficits. • Physical examination reveals decreased sensation on the right side of his face, dysarthria, and dysphonia. • Modified barium swallow study confirms impaired pharyngeal phase with aspiration risk. • He iongoing speech therapy and dysphagia management.ds with Case 2 • A 55-year-old female presents with progressive dysphagia to solids, initially starting with meat and progressing to softer textures over the past six months. • She reports associated weight loss of 15 pounds despite maintaining her usual dietary intake. • She denies any history of gastroesophageal reflux disease or chronic heartburn. • Endoscopic examination reveals a friable, ulcerated mass in the mid-esophagus causing luminal narrowing, and biopsy confirms adenocarcinoma. • Further staging investigations are planned to determine the extent of the disease and appropriate management options. Case 3 • A 40-year-old male presents with a longstanding history of dysphagia to both solids and liquids, with symptoms worsening gradually over the past two years. • He describes a sensation of food sticking in his chest, often necessitating multiple swallows or the need to wash food down with liquids. • He reports occasional regurgitation of undigested food, especially when lying flat. • Endoscopic evaluation reveals esophageal dilation and a classic "bird's beak" appearance at the gastroesophageal junction • consistent with achalasia • Further evaluation with esophageal manometry confirms absent esophageal peristalsis and impaired lower esophageal sphincter relaxation, supporting the diagnosis. • Treatment options including pneumatic dilation or surgical myotomy are being discussed with the patient. Case 4 • A 65-year-old female presents with a history of dysphagia, particularly for solids, associated with regurgitation of undigested food and occasional coughing after meals. • She describes a sensation of food getting stuck in her throat, especially when swallowing liquids. • On examination, a palpable mass is noted in the left lateral aspect of the neck, • consistent with a pharyngeal pouch. • Fiberoptic nasendoscopy reveals a pouch arising from the posterior pharyngeal wall just above the cricopharyngeus muscle. • Further evaluation with barium swallow confirms the presence of a Zenker's diverticulum, and surgical consultation for diverticulectomy is being arranged.Case 2 - Stomach Ulcers Omar Kiwan Structure ● Relevant basic anatomy & histology ● Stomach physiology ○Phases ○Secretions ○HCl production ○Mucous ● Stomach ulcers ● Motivational interviewingStomach anatomy ● Intraperitoneal organ ● Split into 4 parts: ○ Cardia - the opening of stomach ○ Fundus – gas filled portion ○ Body ○ Pylorus – can further be split into antrum, canal and sphincter ● Innervation: ○ Sympathetic – greater splanchnic nerve ○ Parasympathetic – vagus nerve ● Vasculature complex and out of scope, see final slides.Histology ● Will focus on mucosa ● Epithelium is simple columnar ● Whenever you see this think secretions! ● and outer longitudinal smoothr muscle fibres Structure ● Relevant basic anatomy & histology ● Stomach physiology ○Phases ○Secretions ○HCl production ○Mucous ● Stomach ulcers ● Motivational interviewing Phases of gastric activity ● Cephalic ○ Preparation phase, happens before food enters stomach ○ Controlled by vagus nerve ○ Eg. Drooling when seeing food ● Gastric ○ Get stomach motility and secretion, most of the physiology will focus on this phase ● Intestinal ○ Adjustments to stomach activity based on food that enters duodenum Motility fundamentals ● Types of stomach motility ○ Segmentation/mixing ○ Propulsion/peristalsis ○ Reservoir – done by sphincters ● Pacemaker cells are the interstitial cells of Cajal, found between middle circular & outer longitudinal muscle layers Motility process ● Cephalic phase: Stomach is relaxed, ready to receive food ● Once food enters, segmentation begins to mix and break down food ● Peristaltic system ○ Contractions increase in intensity down the stomach, so its much stronger at the bottom, however it also means the lumen is almost occluded at the end ○ Only small substances can therefore pass pyloric canal ○ Everything else is forced back into stomach body by retropulsion ● Pyloric pump ○ Intense stomach contractions to move food out of stomach ○ Start at pylorus but as stomach empties this goes up its body Gastric Secretions ● Stomach made of columnar epithelium - secretory ● 2 types of glands ○ Oxyntic/gastric glands – contains mucous neck cells, parietal cells and chief cells ○ Pyloric glands– secrete gastrin and mucous ● Will split into cephalic/gastric phase secretions and intestinal phase secretion ● Important to note vagus nerve has a big role – in addition to secretory functions it also stimulates insulin release, gallbladder contraction and sphincter of oddi relaxation Cephalic and Gastric Phase Secretions Secretion Cell produced by Function Stimulating factors Inhibiting factors Extra notes HCl Parietal Cells Create acidic Histamine Prostaglandin E2 Process discussed environment for ACh Somatostatin later on inshaalah digestion Gastrin Pepsinogen Chief cells Breaks down Gastrin Activated to pepsin proteins Histamine at pH 1.5-2. Pepsin Ach is an Secretin enteropeptidase Histamine Enterochromaffin Increases HCl and ACh Somatostatin like cells pepsinogen Gastrin G cells Increases HCl and PDPs Somatostatin Two forms G17 pepsinogen Bombesin (Vagus (more potent) and nerve NT) G34 (lasts longer) Somatostatin D cells Inhibits acid Highly acidic lumen Gastrin production Intrinsic factor Parietal cells Needed for B12 Histamine, gastrin, absorption ACh Intestinal Phase Secretions: Secretion Cell produced by Function Stimulating factors GIP (gastric K Cells (duodenum) Inhibits HCl release, Increased glucose inhibitory peptide) releases insulin and carbs Secretin S Cells Inhibits G Cells and Increased acid and (Duodenum) gastrin release to fat in chyme decrease HCl Stimulates bile, pepsinogen and bicarb production CCK Enteroendocrine Stimulates Fats and partially (cholecystokinin) cells (SI) pancreatic digested proteins secretion, gallbladder contraction and inhibits gastric emptying HCl production ● Made by parietal cells ● CO2 produced by respiration, as parietal cells have lots of mitochondria ● This combines with water to form bicarb and H+, H+ is pumped into lumen in exchange for potassium. Bicarb is pumped out basolateral membrane in exchange for Cl-, which is then pumped into lumen ● K+ ATPase pump pumps potassium into lumen to create a gradient ● H+/K+ pump exists on basolateral to regulate acid secretion Mucous ● Mucous producing cells are mostly in the cardia of stomach ● Secreted by foveolar cells to avoid bacterial, acid and enzyme penetration of stomach ● Mucous layer consists of two parts ○ Mucous gel layer on top made of water phospholipids and mucin ○ Glycoprotein layer w high bicarb concentration below to neutralise acid and make pepsinogen inactive ● Mucin unit is essentially a protein rich core w/ sugars coating the middle bit. The ends are still protein on the surface ● Types of mucin ○ MUC6 - inhibits bacterial growth ○ MUC5AC - bait for bacteria - binds to adhesins on bacteria ○ MUC1 same function as 5ac but attached to cell surface, sheds upon bacterial binding Structure ● Relevant basic anatomy & histology ● Stomach physiology ○Phases ○Secretions ○HCl production ○Mucous ● Stomach ulcers ● Motivational interviewing Peptic Ulcers ● Symptoms ○ Pain ■ Epigastric, can radiate to back ■ Worsened by eating in gastric ulcers ■ Improved by eating in duodenal ulcers ○ Vomiting and hematemesis ■ (Blood in vomit) ○ Reflux and obstruction ● Notable causes ○ H Pylori ○ NSAIDs - inhibit prostaglandin synthesis which leads to increased acid, decreased mucous & bicarb ○ Zollinger Ellison Syndrome – gastrin releasing tumor, increases HCl ● Complications can be severe like erosion & perforation. Leads to bleeding and severe pain and can be deadlyH. Pylori ● Gram-negative, rod-shaped bacteria ● Found in 50% of people ● Typically found in Antrum of stomach ● Adaptations ○ Flagella for motility ○ Circular DNA ○ Lipopolysaccharide adhesins ○ Urease enzyme ○ Cag A and Vac A toxin secretion Investigations for ulcers ● Endoscopy ● Oesophageal manometry for pH, this checks for reflux ● H Pylori Testing ○ Stool antigen test ○ CLO test (biopsy in endoscopy) ○ Urea breath test ■ H Pylori has urease enzyme, converts urea and water to CO2 and ammonia ■ Give patient urea with C13 isotope and check CO2 in breath for this isotopeTreating Ulcers ● Triple Therapy (CAP) ○ Clarithromycin ○ Amoxicillin (clarithromycin if allergic) ○ PPI ● PPIs work by permanently blocking H+/K+ pump in parietal cell apical membrane ● Resistant H. Pylori may need quadruple therapy ○ PPI ○ Metronidazole ○ Tetracycline ○ Ranitidine/Bisthmuth Structure ● Relevant basic anatomy & histology ● Stomach physiology ○Phases ○Secretions ○HCl production ○Mucous ● Stomach ulcers ● Motivational interviewingMotivational interviewing ● Change vs sustain talk ○ In change talk the patient talks about the reasons they want to change vs why they should stay the same in sustain talk ● Types of change talk ○ Desire – I hope to ○ Ability – I am able to ○ Reasons – I think I would feel less down ○ Need – I need to ○ Commitment – I will/promise ○ Activation – I am ready to ○ Taking steps – I bought some nicotine patches Thank you! See further slides for anatomyAbdominal Aorta DiagramCoeliac Trunk ● At T12 ● Branches ○ Left gastric ■ Supplies lesser curvature of stomach and distal oesophagus ○ Splenic ■ Passes behind stomach, enters hilum of spleen right after splitting into superior and inferior trunks ■ Gives off short gastric arteries (supplies fundus), Left gastroepiploic artery which supplies greater curvature - anastomoses w/ LGE ○ Common hepatic ■ Hepatic artery proper, supplies hepatobiliary tree ■ Gastroduodenal artery. Further bifurcates into: ● Right gastroepiploic artery, suppliesgreater curvature ● Superior pancreaticoduodenal artery ■ Right gastric artery - lesser curvatureSplanchnic nerves ● Sympathetic innervation of internal organs - Not just abdomen ● Foregut - T5-T9 - greater splanchnic nerve - coeliac ganglia. ● Midgut - T10-T11 - Lesser splanchnic - superior mesenteric ganglion ● Hindgut - L1-L3 - Lumbar splanchnic nerve - Inferior mesenteric ganglion ● Kidney and adrenal gland - T12 - Least splanchnic nerve - Aorticorenal ganglionCase3:Pancreatitis lamisah.aamir@student.manchester.ac.uk Upcoming ISoc Events ● Friday Social TOMORROW! Free scran at 8:15pm ● Charity Stalls - Monday ISoc x PalSoc - Tuesday Baking comp - Thursday ISoc x PakSoc ● Tuesdays - Roots - Sisters Q&A ● Wednesday - Charity Dinner ● Friday Social ● Sunday - Ladies Badminton Social, Sugden, 12:30-1:30pm ● Sunday - Guys Football Social, Trinity, 5-6pm ● Sunday - Man City vs Liverpool Screening - HIVE SUCase3:Pancreatitis lamisah.aamir@student.manchester.ac.ukILOs • Thestructureandfunctionofthepancreas • Themovementofwaterandelectrolytesacrossthegutwall • Howpainissensedintheabdomenandtheanatomical/physiologicalbasisofreferredpain • Basicknowledgeoftheclinicalinvestigationofthegastro-intestinaltract • Howtodifferentiatebetweengastricandpancreaticdysfunction • Theeffectofmalnutritiononphysiologicalfunction • Thepathophysiologicaleffectsofalcoholaddiction • TheCAGEquestionsforalcoholaddiction • Theservicesavailableforpeoplewithalcoholrelatedproblems • GoodMedicalPracticeandhowthiscompelsustorespectourpatients • Thepsychologicaltheoriesofaddiction • Theethicalargumentsforimposinglimitationsuponstate-fundedhealthcare • Thepublichealthproblemsassociatedwithalcoholabuse • Thebasisofprioritisinginhealthcare • Recogniseanddescribewaysinwhichdomesticviolenceandabusecanpresentinclinicalpractice • UnderstandtheconceptofRightsandResponsibilitywhenitcomestoourownhealthToday’sAgenda 1. ExocrinePancreas 2. DigestionandAbsorptionofmacroandmicronutrients 3. AcutePancreatitis 4. ChronicPancreatitis 5. EffectsofAlcohol ThePancreas PartoftheFOREGUT 1. Endocrinefunction Only15%ofcells  2. Exocrinefunction(thiscase!): a. Digestiveenzymes b. Bicarbonatesecretion Endocrinefunctionofpancreas ●IsletsofLangerhans: • Clustersofcellswithinthepancreas (1%ofallcells) • Eachclusterhasdifferentcelltypes ● Cellswithintheislet: • Alphacells->glucagon • Betacells->insulin • Epsiloncells->ghrelin • Deltacells->somatostatin Exocrinefunctionofthepancreas Proteases Lipases Amylases Proteins Triglycerides,monoglycerides,FFA’s Starch,disaccharides • Lipasesactivatedinduodenum • Amylasesactivatedin • Chymotrypsinogenand • Actonemulsifiedfat(afterbile) duodenum trypsinogen • Actonsugars • Trypsinogen->trypsin • Trypsinfurtheractivatesthe otherenzymes • Producedbyacinarcells->intercalatedducts->interlobarducts-> pancreaticduct • Trypsininhibitoralso • Chymotrypsinogenandtrypsinogen(proteases)breakdown producedtoprevent proteinsandpeptidestosingleaminoacids • Pancreaticlipasebreaksdownfat autodigestion • Amylasebreaksdownstarchandmaltose Hormonalregulationfromdifferentcells ● 3phasesofsecretion 1. Cephalicviavagalpathway++bysightsmelltaste 2. Gastricviavagalpathway++bydistention  3. IntestinalviaCCK,Secretin++byAAs,fattyacids,H+ ● Stimuli:  ● Acetylcholine–parasympatheticvagalnerveendings ● Cholecystokinin  ● ReleasedbyIcellsinresponsetofattyacids,peptonesandacidicpH  ● Promotessecretionofdigestiveenzymesinthepancreaticjuices,relaxationofthesphincterofOddiandgallbladder contraction ● Secretin  • ReleasedbyScellsinresponsetoacidicchymepromotessecretionofthealkalinepartsofthepancreaticjuices Bicarbonatesecretion • CO diffusesintotheductalcells 2 • H2O+CO2 -> H2CO3catalysedby carbonicanhydrase • H2CO3dissociatesintoH+andHCO3- • H+exchangedforNa+fromblood • TheNa+istransportedintolumenvia Na+/H+/ATPase • HCO3-exchangedforCl-inlumen • ToavoidCl-buildupitstransportedback intothelumenviaCFTRDigestionandabsorption-basics ● Enterocytes are columnar cells with microvilli ● Methods  ● Simple diffusion: lipids ● Endocytosis: cholesterol, vitamin B12 and intrinsic factor ● Carrier mediated: AAs, sugars ● Sites ● Mouth/Oesophagus/Stomach – very limited, but remember alcohol is absorbed in the stomach! ● Duodenum/Jejunum – where most absorption occurs ● Ileum – vitamin B12, bile salts, K+ ● Large intestine – some Na+, some water and short chain fatty acidsProteins ● Digestion  ● Small%instomach  ● Mostdigestionoccursinduodenum/jejunumbypancreaticenzymes  ● Enterocytescontainaminopolypeptidaseanddipeptidase  ● Absorption ● Na+co-transportorfacilitateddiffusion  ● KEYTRANSPORTER:PEPT1di/tripeptides ● Others:XAG,B ,PAT1Carbohydrates ● Digestion ● Absorption ● Intoenterocyte: ● Glucose+Galactose  • Co-transportwithNa+viaSGLT1 ● Fructose  • FacilitateddiffusionviaGLUT5(FforFive) ● Intobloodstream: ● Glucose+Galactose+Fructose  ● FacilitateddiffusionviaGLUT2 Lipids ● Digestion ● Emulsified then broken down by lipases ● Absorption ● Via simple diffusion ● Chylomicrons synthesised in enterocyte  ● Transported to lymphatic system via exocytosis Ironabsorption Ferritin – how we store Iron in cells! Ironiseitherhaemornonhaem! DMT1 – HowFe2+entersthecellbysecondaryactivetransportfromthelumen withH+ DuodenalcytochromeBreductase –  ReducesFe3+toFe2+inlumentobeabsorbed Mobilferrin – Fe2+bindstothisinthecell Ferroportin(FP1) – TransporterbywhichFe2+leavesthecelltobloodstreamviafacilitated diffusion Haemoxygenase – OxidisesFe2+inHaemtoFe3+thatisreleased Hephaestin – OnthebasolateralsideconvertsFe2+toFe3+ Transferrin – TheFe3+thatisreleasedbindstothisintheplasma Hepcidin – Howweregulateironabsorption,producedbytheliverfunctionsby bindingtoFP1anddegradingit(can’tleavecell)Othernutrients ● Cholesterol  ● Absorbed by receptor mediated endocytosis via NPC1L1 protein ● Short chain fatty acids  ● Produced due to bacterial fermentation of polysaccharides absorbed by Na+ coupled transporter SMCT1 ● Water  ● 8.4L of water is absorbed per day!  ● Absorbed by junctional complexes between cells or through SGLT1 and amino acid transporters ● Calcium ● Transcellular route – regulated by Vitamin D  ● Ca2+ enters via TRPV6, binds to calbindin and then removed by Na+ exchanger NXC1AlcoholEffectsofAlcohol ● Learnthebasicmetabolismofalcohol Oesophagus ● Increasedriskofsquamouscarcinoma  ● Oesophagealvaricesareassociatedwith chronicliverdisease ● Stomach  ● Acutegastritis→acuteulcerationandevenPUD Learnthesefacts! ● Pancreas ● AcuteandChronicPancreatitis •1unit=10mlor8gofpurealcohol   ● Cardiac •Units=volume(ml)xABV(%)/1000 ● IncreasedriskofAtrialFibrillation,canleadtocongestivecardiacfailure  ● Other ● MacrocyticanaemiaEffectsonLiver • Theliveriswheremostalcoholismetabolised • Alcohol-relatedfattyliver(reverses2weeks) • Alcoholichepatitis(acuteusuallyreversible) • Cirrhosis(irreversible)-Endstageliverdisease+fibrosis+regenerativenodulesSignsofalcoholicliverdisease • NailClubbing  • PalmarErythema  • Dupetryn’sContracture  • Jaundice  • SpiderNavie • Gynecomastia  • Caputmedusae • Ascites  • Oedema Pathophysiologicaleffectsofalcohol Alcoholinthebody Alcoholdependence Alcohol Excessivealcohol DecreaseGABA IncreaseCa 2+ Increase IncreaseGABA Decrease receptors Glutamate Glutamate receptors receptors 2+ DecreaseCa Morealcohol flowintoaxon requiredto terminal achieveeffects • Relaxation • Intoxication • Intoxication • Amnesia Withdrawal • Anaesthesia • Anaesthesia • Anxiety • Hallucination • Confusion • SeizuresNeuropsychiatriceffectsofalcohol ● Delirium Tremens ● Delirium with hallucinations and autonomic disturbances in alcohol withdrawal  ● The following 2 phenomenon occur due to thiamine deficiency (poorly absorbed) ● Wernicke’s encephalopathy  ● Acute confused state, present with delirium ataxia and ophthalmoplegia ● Korsakoff’s Psychosis ● Chronic, associated with memory impairment and behavioural changesAlcoholwithdrawaltreatment ●Treatment ○ Benzodiazepines(diazepamorchlordiazepoxide) ○ CBT-explorereasonforaddictioninfirstplace ○ Naltrexone ■ Mu-opioidreceptorblocker ■ Blockseuphoriceffectofalcoholandintoxication ○ Acamprosate ■ Preventsrelapse ○ Disulfiram ■ Inhibitsalcoholdehydrogenase ■ Alcohol→acetyldehyde→acetate ■ Patientexperienceshangoversymptomsimmediatelyafterdrinking(nausea, vomiting,flushing,sweating,tachycardia,palpitations)Theoriesofaddiction Moralmodel Sociallearningtheories 1 3 • Addictionasaresultofweakness • Druguseisalearnedbehavior andlackofmoralfibre. • Peerpressure • Addictsareweakandchooseto • Environment use,theycanovercomeby • Conditioning:classical,operant willpower 2 Biomedicalmodel 4 Diseasemodel • Diseaseisadiscreteentity(eitheraddictedornot) • Addictionasadisease • Addictionisirreversible • NTimbalance • Eliminatethediseaseby • Emphasizeabstinenceastreatment • Issues:lifelongabstinencerareanddifficultto eliminatingthedrug achieve,inconsistentwithevidencethatsome peoplereturntonormaldrinkingpatternsBSSCont. ● Beawareof:  ● Typesofdomesticabuse ● IdentificationandReferraltoImproveSafety(IRIS) ● HARKQuestionnaire ● KeyprinciplesofadultsafeguardingPancreatitis Inflammationofpancreas • Underlyingpathophysiologyistheprematureactivationoftrypsinwithintheacinarcells • Trypsinactivatesotherdigestiveenzymescausingauto-destructionofthecells Twotypes: • Acute • Rapidonsetofinflammationandsymptoms • Resolveswithinafewdays • Normalpancreaticfunctionreturns • Chronic • Longer-terminflammation • Progressionofsymptoms • PermanentdeteriorationinfunctionPancreatitis-PathophysiologyPancreatitis-Causes TIGARO ● Toxic/metabolic: alcohol, smoking, high triglycerides, hypercalcaemia ● Idiopathic (we don’t know the cause) ● Genetic ● Autoimmune ● Recurrent and severe acute pancreatitis ● Obstructive factorsPancreatitis-SignsandsymptomsPancreatitis-InvestigationsandDiagnosisPancreatitis-Treatmentandcomplications Feedback Form How did we do?Thank you for coming!