European Stakeholder Model for Patient Safety in Europe

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The European Stakeholder Model (ESM) focuses on combating counterfeit medicines to ensure patient safety in Europe. The model outlines governance, timelines, and the role of pharmacists in implementing safety features. The Directive Safety Features mandate authenticity verification and tamper evidence for medicines, with stakeholders managing repositories. ESM emerges as a response to the Falsified Medicines Directive, aiming to enhance supply chain reliability and patient safety cost-effectively.

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Complicationsoflivercirrhosis

Complicationsoflivercirrhosis Recognizethemajorcomplicationsofcirrhosis Understandthepathogeneticmechanisms underlyingtheoccurrenceofthecomplications Recognizetheclinicalfeaturesinherenttothe abovementionedcomplications Describethepathologicalfindingsofthe differentcomplications

. Complicationsof livercirrhosis Portalhypertension Varicealbleeding Splenomegaly Ascites Spontaneousbacterialperitonitis Jaundiceandcholestasis Coagulopathy Hepaticencephalopathy Hepatorenalsyndrome Hepatocellularcarcinoma

Complicationsoflivercirrhosis PORTALHYPERTENSION:

Complicationsoflivercirrhosis PORTALHYPERTENSION: Resistancetobloodflow prehepatic,intrahepatic,andposthepatic Thedominantintrahepaticcauseiscirrhosis (Thisisaccountingformostcasesof portalhypertension) Portosystemicshuntsdevelopwhenbloodflowis reversedfromtheportaltosystemiccirculation.

Complicationsoflivercirrhosis ESOPHAGEALVARICES

Complicationsoflivercirrhosis ESOPHAGEALVARICES: Insteadofreturningdirectlytotheheart, venousbloodfromtheGItractisdeliveredto theliverviatheportalveinbeforereaching theinferiorvenacava. Thiscirculatorypatternisresponsibleforthefirst- passeffectinwhichdrugsandothermaterials absorbedintheintestinesareprocessedbytheliver beforeenteringthesystemiccirculation..

Complicationsoflivercirrhosis ESOPHAGEALVARICES: Diseasesthatimpedethisflowcauseportal hypertensionandcanleadtothedevelopment ofesophagealvarices,animportantcauseof esophagealbleeding

Complicationsoflivercirrhosis Portal Portalhypertention PortosystemicShunt PortosystemicShunt Rectum(hemorrhoids) Abdominalwallcollaterals(caputmedusae) Cardioesophagealjunction(esophagogastricvarices)

Complicationsoflivercirrhosis ESOPHAGEALVARICES: Pathogenesis Portalhypertensionresultsinthedevelopmentof collateralchannelsatsiteswheretheportaland cavalsystemscommunicate.Althoughthese collateralveinsallowsomedrainagetooccur,they leadtodevelopmentofacongestedsubepithelial andsubmucosalvenousplexuswithinthedistal esophagus.(varices):90%ofcirrhoticpatients Alcohol-Hepaticschistosomiasis

Complicationsoflivercirrhosis ESOPHAGEALVARICES Morphology: Varicescanbedetectedbyvenogram:tortuousdilatedveinslying primarilywithinthesubmucosaofthedistalesophagusand proximalstomach.Venouschannelsdirectlybeneaththe esophagealepitheliummayalsobecomemassivelydilated. Varicesmaynotbegrosslyobviousinsurgicalorpostmortem specimens,becausetheycollapseintheabsenceofbloodflow. Varicealruptureresultsinhemorrhageintothelumenor esophagealwall,inwhichcasetheoverlyingmucosaappears ulceratedandnecrotic.Ifrupturehasoccurredinthepast,venous thrombosis,inflammation,andevidenceofpriortherapymayalso bepresent.

Complicationsoflivercirrhosis ESOPHAGEALVARICES: Clinicalfeatures: Asymptomaticorrupture- massivehematemesis. Inflammatoryerosionofthinnedoverlyingmucosa Increasedtensioninprogressivelydilatedveins Increasedvascularhydrostaticpressureassociatedwith vomitingarelikelytocontributetomedicalemergencythat istreatedbyanyofseveralmethods: 1. 2. 3. Endoscopicrubberbandligation Sclerotherapy Endoscopicballoontamponade

Complicationsoflivercirrhosis ESOPHAGEALVARICES: Halfofpatientsdiefromthefirstbleedingepisodeeitherasa directconsequenceofhemorrhageorfollowinghepaticcoma triggeredbyhypovolemicshock. Additional50%within1year. Eachepisodehasasimilarrateofmortality. Overhalfofdeathsamongindividualswithadvanced cirrhosisresultfromvaricealrupture.

ESOPHAGEALVARICES: Complicationsoflivercirrhosis

Complicationsoflivercirrhosis Splenomegaly:Long-standingcongestion maycausecongestivesplenomegaly (spleenweightmayreachupto1000gm) Themassivesplenomegalymayinduce hematologicabnormalitiesattributableto hypersplenism,suchasthrombocytopenia orpancytopenia

Complicationsoflivercirrhosis Ascitesistheaccumulationofexcessfluidin theperitonealcavity:85% Serous:lessthan3gm/dLofprotein

Complicationsoflivercirrhosis Spontaneousbacterialperitonitis

Complicationsoflivercirrhosis JAUNDICEANDCHOLESTASIS

Complicationsoflivercirrhosis JAUNDICEANDCHOLESTASIS: Jaundiceandicterus:ayellowishorgreenish pigmentationoftheskinandscleraoftheeyes respectivelyduetohighbilirubinlevels. Cholestasis,characterizedbysystemicretention ofnotonlybilirubinbutalsoothersolutes eliminatedinbile.

Bilirubinmetabolism andelimination

Complicationsoflivercirrhosis CauseofJaundice 1.Prehepaticcausesofjaundice:Bilirubinoverproduction duetohemolysisandhematomaresorption,leadtoelevated levelsofunconjugated(indirect)bilirubin. 2.Intrahepaticdisorders canleadtounconjugatedorconjugatedhyperbilirubinemia.The conjugated(direct)bilirubinlevelisoftenelevatedbyalcohol, infectioushepatitis,drugreactions,andautoimmunedisorders. 3.Posthepaticdisorders(Obstructionoftheflowofbile) alsocancauseconjugatedhyperbilirubinemia.Gallstone formationisthemostcommonposthepaticprocessthatcauses jaundice;however,thedifferentialdiagnosisalsoincludes seriousconditionssuchasbiliarytractinfection,pancreatitis, andmalignancies

Complicationsoflivercirrhosis Coagulopathy

Coagulopathy Theliveristhesourceofanumberofcoagulationfactorsthat declineinthefaceofliverfailure,leadingtoeasybruising andbleeding

Complicationsoflivercirrhosis Hepaticencephalopathy

Complicationsoflivercirrhosis Hepaticencephalopathy spectrumofdisturbancesinconsciousnessrangingfrom subtlebehavioralabnormalities,toconfusionandstupor,to comaanddeath. maydevelopoverdays,weeks,orafewmonths Duetoelevatedammonialevelsinbloodandthecentral nervoussystemandbrainedema.

Complicationsoflivercirrhosis Hepatorenalsyndrome:

Complicationsoflivercirrhosis Hepatorenalsyndrome: Appearanceofrenalfailureinindividualswith severechronicliverdisease---nointrinsic morphologicorfunctionalcausesfortherenal failure. Theincidenceofthissyndromeisabout8%per yearamongpatientswhohavecirrhosisand ascites

Complicationsoflivercirrhosis Hepatorenalsyndrome: Decreasedrenalperfusionpressuredueto systemicvasodilation Activationoftherenalsympatheticnervous systemwithvasoconstrictionoftheafferent renalarterioles Increasedsynthesisofrenalvasoactive mediators,thatdecreaseglomerularfiltration.