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@About this App@Contributers@DeveloperACTH (Adrenocorticotropic hormone)AFP (Alpha-fetoprotein) TestingAIDS Dementia Complex (HIV)AIDS HIV InfectionAPGAR Scoring (Children)APTT and CoagulationAbacavirAbataceptAbbreviated Mental Test Score (AMTS)AbciximabAbdominal Aortic AneurysmAbdominal paracentesis for ascitesAbducent NerveAbetalipoproteinaemiaAbnormal Vaginal bleedingAcamprosateAcanthocytosisAcanthosis NigricansAcarboseAccelerated Idioventricular RhythmAcetazolamideAcetylcholine Receptor AntibodiesAcetylcholinesterase inhibitorsAchalasiaAchilles Tendon ruptureAchondroplasia (Children)AciclovirAcid maltase deficiency (Pompe disease)Acne RosaceaAcne VulgarisAcoustic Neuroma (Schwannoma)Acrodermatitis enteropathica (Children)Acromegaly and GiantismAcromio-clavicular jointActinomyces israeliAction PotentialActivated CharcoalActrapid (Insulin)Acute Abdominal Pain - Acute PeritonitisAcute Acalculous CholecystitisAcute Anaphylactoid ReactionsAcute AnaphylaxisAcute Angle Closure GlaucomaAcute AppendicitisAcute Bacterial MeningitisAcute BronchitisAcute CholangitisAcute CholecystitisAcute Colonic Pseudo-obstructionAcute Coronary Syndrome (ACS) GeneralAcute Coronary Syndrome (ACS) NSTEMI USAAcute Coronary Syndrome (ACS) STEMIAcute Coronary Syndrome (Cardiac Troponins)Acute Coronary Syndrome Grace scoreAcute DeliriumAcute Disc lesionsAcute Disseminated EncephalomyelitisAcute Diverticulitis - Diverticular diseaseAcute Dystonic ReactionAcute EncephalitisAcute Eosinophilic PneumoniaAcute EpiglottitisAcute Exacerbation of COPDAcute HepatitisAcute HydrocephalusAcute HypotensionAcute InflammationAcute Intermittent Porphyria (AIP)Acute Interstitial nephritisAcute Kidney Injury (AKI)Acute Limb IschaemiaAcute Liver FailureAcute Lymphoblastic Leukaemia (ALL)Acute MastoiditisAcute MonoarthritisAcute Myeloid Leukaemia (AML)Acute MyocarditisAcute PancreatitisAcute Pelvic Inflammatory DiseaseAcute PericarditisAcute Phase reactantsAcute PorphyriasAcute Promyelocytic LeukaemiaAcute Respiratory Distress Syndrome (Adults)Acute Retroviral Syndrome (HIV)Acute RhabdomyolysisAcute Rheumatic feverAcute Rotator cuff tearAcute Severe AsthmaAcute Severe ColitisAcute SinusitisAcute Stroke Assessment (ROSIER&NIHSS)Acute TonsilitisAcute Urinary RetentionAcute and Chronic GoutAcute and Chronic Heart FailureAcute on Chronic Liver Disease DecompensationAcutely Ill PatientAdalimumabAddenbrooke's Cognitive Examination-Revised (ACER)Addison Disease (Adrenal Insufficiency)AdefovirAdenosineAdenosine deaminase deficiencyAdhesive Capsulitis (Frozen Shoulder)Adjustment - Anxiety disordersAdrenal AntibodiesAdrenal PhysiologyAdrenaline (Epinephrine)AdrenoleukodystrophyAdrenomyeloneuropathyAdult Onset Still's DiseaseAfrican Trypanosomiasis (Sleeping sickness)Age related macular degenerationAicardi syndromeAir EmbolismAlbuminAlbumin-Protein Creatinine Ratio (PCR)Alcohol AbuseAlcohol Withdrawal (Delirium Tremens)Alcoholic (Steato)HepatitisAlcoholic KetoacidosisAldosterone PhysiologyAlendronate (Alendronic acid)AlfacalcidolAlkaline phosphatase (ALP)Alkalinisation of urineAlkaptonuriaAllergic Bronchopulmonary AspergillosisAllogeneic stem cell transplantationAllopurinolAlogliptin (Vipidia)AlopeciaAlpha FetoproteinAlpha ThalassaemiaAlpha subunit (ASU) of TSHAlpha-1 Antitrypsin (AAT) deficiencyAlport's SyndromeAlteplaseAltitude sicknessAluminium and Magnesium AntacidsAlveolar Gas EquationAlzheimer disease (Dementia)AmantadineAmenorrhoeaAmerican Trypanosomiasis (Chagas Disease)AmilorideAmino acidsAminoglycosidesAminophyllineAminosalicylatesAmiodaroneAmiodarone and Thyroid diseaseAmitriptylineAmlodipineAmmonia EncephalopathyAmnestic syndromesAmoebiasis (Entamoeba histolytica)AmoxicillinAmphetamine toxicityAmphotericin BAmpicillinAnaemia of Chronic DiseaseAnagrelideAnakinraAnal CancerAndexanet alfaAndrogen insensitivity syndromeAneurysmsAngina bullosa haemorrhagicaAngiodysplasiaAngiomyolipomaAngioneurotic OedemaAngiotensin Converting Enzyme InhibitorsAngiotensin Converting enzyme (ACE)Angular Stomatitis - CheilitisAnion GapAnkle and Foot fractures and InjuriesAnkle-Brachial pressure Index (ABPI)Ankylosing spondylitisAnorexia NervosaAntacid medicationAntepartum haemorrhageAnterior Horn Cell diseasesAnterior circulationAnti Dementia DrugsAnti-Cyclic Citrullinated Peptide (CCP) AntibodyAnti-D immunoglobulinAnti-Hu antibodiesAnti-OKT3 antibodiesAnti-RNP AntibodyAnti-Yo antibodiesAnti-neutrophilic cytoplasmic antibodies (ANCA)Antibiotics for Abdominal InfectionsAnticholinergic BurdenAnticholinergic syndromeAnticipationAnticoagulation and AntithromboticsAntidiuretic hormone (Vasopressin)Antigen presenting cellsAntimicrobial ChoicesAntimuscarinic drugsAntiphospholipid syndromeAntithrombin III deficiency (AT3)Aorta anatomyAortic DissectionAortic Regurgitation (Incompetence)Aortic SclerosisAortic StenosisAortoenteric fistulaApathetic thyrotoxicosisApixabanAplastic anaemiaApomorphineAppendix Cancer TumoursApproach to Assessing Sick ChildApproach to child with Acute GastroenteritisApproach to child with respiratory DistressArnold Chiari malformationArrhythmogenic Right ventricular CardiomyopathyArtemisininsArterial Blood gas analysisArterial Pulse assessmentArterial blood gas samplingArterial vs Venous vs Other Leg UlcersArteriovenous malformationsArtery of Percheron strokeArtery-to-artery embolic strokeArtesunateAsbestos Related Lung diseaseAscites Assessment and ManagementAspergillomaAspergillus fumigatusAspirinAspirin Salicylates toxicityAssessing Abdominal PainAssessing BreathlessnessAssessing Chest PainAssessing FallsAsteatotic eczemaAsthmaAstigmatismAstrocytomasAsystoleAtaxia TelangiectasiaAtazanavirAtenololAtherosclerosisAtopic Eczema or Atopic DermatitisAtorvastatinAtracuriumAtrial Ectopic beatsAtrial Fibrillation (Chemical cardioversion)Atrial Natriuretic Peptide (ANP)Atrial fibrillation (AF)Atrial flutterAtrial myxomaAtrial septal defect (ASD)Atrioventricular nodal reentrant tachycardiaAtropine SulfateAutoantibodiesAutoimmune Haemolytic anaemia (AIHA)Autoimmune HepatitisAutonomic neuropathyAutosomal DominantAutosomal Dominant Polycystic kidney diseaseAutosomal RecessiveAzathioprineAzithromycinB lymphocytesBRCA genes (Familial Breast Cancer)Bacillus anthracisBacillus cereus poisoningBackpain / BackacheBaclofenBacteriaBacteroides fragilisBalanitis (Adults)Balanitis (Children)Balkan endemic nephropathy (BEN)Balsalazide (Aminosalicylate)Barrett's oesophagusBartonellaBartters syndromeBasal Cell Carcinoma (BCC)Basic Fracture managementBasilar artery thrombosisBecker Muscular dystrophyBeclometasoneBeer PotomaniaBehavioural and Psychological Symptoms of DementiaBehcet's syndromeBell's palsyBendroflumethiazide (Bendrofluazide)Benign Paroxysmal Positional Vertigo (BPPV)Benign Prostatic HyperplasiaBenign recurrent intrahepatic cholestasisBenzodiazepine ToxicityBenzodiazepinesBenzylpenicillin Sodium (Penicillin G)Berg Balance ScaleBeriplexBerylliosisBeta AgonistsBeta Blocker toxicityBeta ThalassaemiaBeta-2 MicroglobulinBeta-lactamasesBetahistine (Serc)BezafibrateBiceps ruptureBilateral adrenalectomyBiliary atresiaBilirubinBiochemical Lab valuesBisacodylBisoprololBisphosphonatesBladder CancerBladder StonesBleedingBleeding disordersBleeding due to DrugsBleomycinBlindness - global causesBlood products - Packed cells blood transfusionBlood Products - CryoprecipitateBlood Products - Fresh Frozen PlasmaBlood Products - PlateletsBlood film interpretationBlood gas valuesBloody DiarrhoeaBlotting Techniques: Gel ElectrophoresisBone Marrow TransplantationBone disease Lab resultsBone metabolism RANK RANKL OPG pathwayBone scintigraphy (Bone scan)Bordetella pertussis - Whooping coughBorrelia burgdorferiBorrelia recurrentisBotulismBrachial neuritis (neuralgic amyotrophy)Brachial plexus anatomyBrachial plexus and associated injuryBrain AbscessBrain Anatomy and functionBrain MRIBrain Natriuretic Peptide (BNP)Brain PhysiologyBrain Tumours (Cancer)Brainstem anatomyBranchial cleft cystBreast CancerBreast FibroadenomaBretyliumBroad complex TachycardiaBromocriptineBronchial adenomaBronchiectasisBronchiolitisBronchoscopyBrown-Sequard syndromeBrucellaBrugada syndromeBudd-Chiari syndromeBudesonideBuerger disease (Thromboangiitis obliterans )Bulbar vs Pseudobulbar palsyBulimia NervosaBullous PemphigoidBumetanideBunionsBuprenorphineBupropionBurkholderia cepaciaBurkitt's lymphomaBurnsBusulphan (Busulfan)ByssinosisC reactive protein (CRP)CADASILCARASILCHADS2 - CHA2DS2-VASc scoreCMV retinitisCNS fungal InfectionsCNS infectionsCSF RhinorrhoeaCT Head Basics (Stroke)CT Pulmonary angiogram (CTPA)CT imaging basics for StrokeCURB 65 scoreCabergolineCaecal VolvulusCaisson Disease - Decompression sicknessCalcitoninCalcitriol (1,25 Dihydroxycholecalciferol)Calcium Chloride or GluconateCalcium PhysiologyCalcium Pyrophosphate Deposition (Pseudogout)Calcium ResoniumCalcium channel blockers toxicityCalot's triangleCampylobacterCancer of Unknown PrimarCandesartanCandidiasisCannabis toxicityCapecitabineCapnocytophaga canimorsusCapnographyCapreomycinCaptopriCarbamazepineCarbapenemase-producing EnterobacteriaceaeCarbimazoleCarbon monoxide poisoningCarcinoembryonic antigen (CEA)Carcinoid Heart DiseaseCarcinoid Tumour SyndromeCarcinoma of the Bile DuctCarcinoma of the GallbladderCardiac Amyloid heart diseaseCardiac Anatomy and PhysiologyCardiac Catheter ablationCardiac InfectionsCardiac MRICardiac Resynchronisation Therapy (CRT) PacemakerCardiac Valve replacementCardioembolic strokeCardiogenic Pulmonary OedemaCardiogenic shockCardiology - History TakingCardiology Exam ListCardiology ExaminationCardiology Valves SummaryCardiopulmonary bypassCarmustineCarotid Artery anatomyCarotid Body TumourCarotid EndarterectomyCarotid Sinus SyncopeCarotid StentingCarotid artery DissectionCarotid sinus massageCarpal tunnel syndromeCarvedilolCase 01 Sudden weaknessCase 02 Loss of speechCase 03 Adult male weak legsCase 04 High calciumCase 05 High Potassium and heart failureCase 06 High calcium and weight lossCase 07 Weak eyesCase 08 Weak faceCase 09 A cause of DeliriumCase 10 Older patient presenting post strokeCase 11 Young patient with acute headacheCase 20 Young patient with acute headacheCase 21 HypoglycaemiaCase 22Case 23 Old man with tremorCase 24 Cancer and weakCase 99 (Acute breathlessness)Case TemplateCat Scratch DiseaseCataractCatheter Related Urinary Tract infection UTICatheter related Blood stream infectionCatheter related UTICauda equina syndromeCaudate NucleusCauses of Airway ObstructionCauses of Avascular Necrosis of Femoral headCauses of Sore throatCauses of WeaknessCavernous angiomas (Cavernomas)Cavernous sinusCavernous sinus thrombosisCefaclorCefalexinCefotaximeCeftazidimeCeftriaxoneCefuroximeCelecoxibCell Response to InjuryCellular Anatomy and PhysiologyCellulitisCentral Cord SyndromeCentral Retinal Vein Occlusion (CRVO)Central Retinal artery Occlusion (CRAO)Central Venous line InsertionCentral pontine myelinolysisCephalosporinsCerebellar Anatomy Physiology Signs DiseaseCerebellar HaemorrhageCerebellar StrokeCerebral Amyloid angiopathy (CAA)Cerebral AneurysmsCerebral AngiitisCerebral Atrophy vs HydrocephalusCerebral CortexCerebral MetastasesCerebral PalsyCerebral PerfusionCerebral Salt WastingCerebral Venous Sinus thrombosisCerebral arteritisCerebral microbleedsCervical Cancer screeningCervical Spine injuryCervical cancerCervical spondylosisCetirizineChancroidCharcot Foot Syndrome (CFS)Charcot Marie Tooth (CMT) diseaseChediak Higashi syndromeChest Abdomen anatomyChest X Ray #1Chest X Ray InterpretationChest drain InsertionChlamydia - Chlamydophila pneumoniaeChlamydia psittaciChlamydia trachomatisChlorambucilChloramphenicolChlordiazepoxideChloroquineChlorphenamine(Chlorpheniramine)ChlorpromazineCholangiocarcinomaCholera (Vibrio cholera)Cholestatic JaundiceCholesteatomaCholesterol - LipidsCholinergic crisis-syndromeChondrocalcinosisChorea - BallismusChoreoacanthocytosisChromosome instability syndromesChronic BronchitisChronic HepatitisChronic InflammationChronic Inflammatory Demyelinating polyneuropathyChronic Interstitial NephritisChronic Kidney Disease (CKD)Chronic Lymphocytic leukaemia (CLL)Chronic Myeloid Leukaemia (CML)Chronic Obstructive Pulmonary Disease (COPD)Chronic PancreatitisChronic PeritonitisChronic Radiation EnteritisChronic Urinary RetentionChronic Vision Uni-Bilateral loss (Blindness)Chronic and recurrent MeningitisChronic liver diseaseChronic mucocutaneous candidiasisChronic stable anginaChylomicronsCiclosporinCimetidineCinacalcetCiprofloxacinCirrhosisCisplatinCitalopramCladribineClarithromycinCleft lip or palateClindamycinClopidogrelClostridium botulinumClostridium difficileClostridium perfringensClostridium tetani - TetanusClotrimazole creamClotting pathwaysClozapineCo Careldopa (Sinemet)Co-Amoxiclav (Augmentin)Co-Beneldopa (Madopar)Co-codamolCo-trimoxazoleCoagulopathyCoal Worker's PneumoconiosisCoarctation of the Aorta (CoA aortopathy)Cocaine abuseCocaine induced chest painCocaine toxicityCoccidioidomycosisCodeineCoeliac diseaseCogan SyndromeColchicineCold Agglutinin Disease (CAD/AIHA)CollagenColloid cyst in the third ventricleColloidsColonic (Large bowel) ObstructionColonoscopyColorectal cancerColorectal polypsColposcopyComa managementCombined Oral contraceptive pill (COCP)Common Peroneal Nerve (CPN)Common variable immunodeficiencyComparing Rheumatoid and OsteoarthritisComplementComprehensive Geriatric Assessment (CGA)Confirming DeathCongenital Acyanotic Heart Disease (Children)Congenital Adrenal hyperplasiaCongenital Complete Heart BlockCongenital Cyanotic Heart Disease (Children)Congenital HypothyroidismCongenital Talipes Equinovarus - ClubfootConstipationConstrictive PericarditisContact allergic dermatitisContinuous Positive Airways Pressure (CPAP)Continuous ambulatory peritoneal dialysisContraceptionConus Medullaris syndromeCor PulmonaleCoronary artery bypass graft surgeryCoronavirus SARS-CoV-2 COVID 19Corticobasal degeneration (Dementia)Corticosteroid-related psychosisCorticosteroidsCorynebacterium diphtheriaeCotard delusionCoxiella BurnetiiCranial nerves and examinationCraniopharyngiomaCreatinine ClearanceCremation forms (UK)Creutzfeldt Jakob disease (Dementia)Crimean-Congo haemorrhagic feverCritical illness neuromuscular weaknessCrohn's diseaseCroupCryptococcus neoformans infectionsCryptogenic Fibrosing AlveolitisCryptogenic Organising Pneumonia (COP-BOOP)CryptosporidiosisCrysal arthritisCrystalloidsCushing diseaseCushing syndromeCutaneous LeishmaniasisCyanide toxicityCyanosis - Central and PeripheralCyclizineCyclo-oxygenase (COX) enzymesCyclophosphamideCycloserineCys leukotriene receptor antagonistsCystic FibrosisCystinosisCystinuriaCytokinesCytomegalovirus infectionsD DimerDNA and RNA short notesDNA replicationDabigatranDalteparinDandy Walker syndromeDantroleneDapagliflozinDarier's DiseaseDarunavirDeQuervain's thyroiditisDeath Certificates (UK)Deep brain stimulationDeep vein thrombosis (DVT)Dehydration PhysiologyDelayed Puberty CriteriaDemeclocyclineDementia with Lewy bodiesDementiasDemyelinating DiseasesDengue FeverDenosumab (Prolia)Dental AnatomyDentatorubral pallidoluysian atrophyDepressionDermatitis HerpetiformisDermatology termsDermatomesDermatomyositisDermoid cystsDesferrioxamineDesmopressin (DDAVP)Desogestrel (Progestogen Only Pill)Developmental Dislocation (Dysplasia) of the HipDevelopmental MilestonesDexamethasoneDiGeorge syndrome (thymic aplasia)Diabetes Insipidus (Cranial and Nephrogenic)Diabetes Mellitus Type 1Diabetes Mellitus Type 1 and DKA (children)Diabetes Mellitus Type 2Diabetes Mellitus in pregnancyDiabetes on the wardDiabetic Autonomic Neuropathy (DAN)Diabetic Ketoacidosis (DKA) AdultsDiabetic Ketoacidosis (DKA) with SGLT2 InhibitorsDiabetic NephropathyDiabetic RetinopathyDiabetic amyotrophyDiabetic footDiamond-Blackfan anaemiaDiamorphineDiaphragmatic disordersDiarrhoeaDiazepamDidanosine (ddI)DiethylstilbestrolDifferentials causes of Foot DropDifferentials of ABCDifferentials of Generalised lymphadenopathyDifferentials of Painful thighDifferentials of XXXDiffuse Oesophageal spasmDiffuse large B-cell lymphomaDiffusion CapacityDigoxinDigoxin ToxicityDihydrocodeineDilated cardiomyopathyDiltiazemDiphtheriaDipyridamoleDischarges against adviceDiscoid lupus erythematosus (DLE)Disease templateDiseases with associated cancersDislocation Sternoclaivcular jointDisopyramideDisseminated Intravascular Coagulation (DIC)Distributive ShockDisulfiram (Antabuse)DobutamineDog BitesDog Bites HandDominant R wave in V1DomperidoneDonepezil (Aricept)DonovanosisDopamine HydrochlorideDopamine agonistsDown's syndrome (Trisomy 21)DoxapramDoxazosin (Cardura)DoxepinDoxorubicin (Adriamycin)DoxycyclineDrivingDrowningDrug Induced Parkinson diseaseDrug Reaction Eosinophilia Systemic Symptoms DRESSDrug TemplateDrug Toxicity - clinical assessmentDrug Toxicity with Specific AntidotesDrug induced Lupus ErythematosusDrug induced liver diseaseDrugsDrugs ListDrugs to Avoid in Acute Renal failureDrugs to avoid ElderlyDrugs to avoid in Liver failureDry and Wet GangreneDual X-ray absorptiometry (DEXA)Duchenne muscular dystrophyDulaglutide GLP-1 agonistDuloxetineDuodenal Atresia (Children)Dupuytrens contractureDysenteryDysphagiaECG - Acute Coronary SyndromeECG - Acute ST Elevation Myocardial InfarctionECG - Atrial fibrillationECG - Atrial flutterECG - BasicsECG - Broad complex tachycardia (possible VT)ECG - Brugada syndromeECG - Causes of a Dominant R wave in V1ECG - Early Repolarisation vs STEMIECG - First degree AV BlockECG - Heart BlockECG - HyperkalaemiaECG - InterpretationECG - Ischaemic Heart DiseaseECG - Left Axis DeviationECG - Left Bundle Branch Block LBBBECG - Left Ventricular HypertrophyECG - Low Voltage ComplexesECG - Narrow complex tachycardiaECG - Normal appearanceECG - Pathological Q wavesECG - QT intervalECG - Right Axis DeviationECG - Right Bundle Branch Block RBBBECG - ST-T T waves changesECG - Supraventricular tachycardia ECG - The QRS complexECG - Tutorial from Queens UniversityECG - Ventricular fibrillationECG - Ventricular tachycardiaECG - Wolff Parkinson White syndrome (WPW)ECG - short PR intervalECG - sinus pauseECG - tall R wave V1ENT Exam - Assessing hearingENT infectionsEbola Virus DiseaseEbstein anomalyEchinocytesEchocardiogramEcstasy toxicityEctopia lentis (subluxation of the lens)Ectopic PregnancyEctropionEculizumabEdoxaban (Lixiana)Edward syndrome (trisomy 18 syndrome)Efavirenz (Sustiva) EFVEhlers-Danlos syndromesEhrlichiosisEikenella corrodensEisenmenger's syndrome (Children)Elbow fractures and InjuriesElectrical injuryEloquent brainEmergency DrugsEmphysemaEmpty sella syndromeEmtricitabine (Emtriva) FTCEnalaprilEnd of Life Care PrescribingEndocarditis and StrokeEndocrinology Lab valuesEndometrial (Uterine) CancerEndometriosisEndoscopic Retrograde Cholangiopancreatography XEndothelinsEnfuvirtideEnoxaparin Sodium (Clexane-Lovenox)EnoximoneEntacaponeEnterococciEnteropathic SpondyloarthritisEnzyme inducers and inhibitorsEosinophilic granulomatosis (Churg Strauss)EpendymomaEpidural HaematomaEpidural abscessEpilepsy - General ManagementEpilepsy - Idiopathic Generalised EpilepsyEpilepsy - Mesial temporal lobe epilepsyEpilepsy - Post TraumaticEpilepsy in PregnancyEpiscleritisEpistaxisEplerenoneEponymous brainstem strokesEpstein-Barr Virus infectionEquivalent doses of OpiatesErb PalsyErgocalciferol (Calciferol)Erlotinib (Tarceva)Erysipelothrix rhusiopathiaeErythema MultiformeErythema NodosumErythrocyte Sedimentation rate (ESR)ErythrocytesErythrodermic PsoriasisErythromycinEscherichia coliEscitalopramEsomeprazoleEssential Thrombocythaemia (ET)Essential TremorEtanerceptEthambutolEthanolEthanol toxicityEthylene glycol toxicityEtomidateEtravirine (intelence) ETREwing sarcomaExenatide (Byetta) GLP1 agonistExercise stress testExploding head syndromeExtradural haematomaExtrapyramidal symptomsExtrinsic Allergic alveolitis (Hypersensitivity)Eye infectionsEzetimibeFabry diseaseFacial NerveFacioscapulohumeral muscular dystrophyFactor V Leiden DeficiencyFaecal CalprotectinFahr syndromeFailure to thrive or Faltering growthFamilial Adenomatous polyposis (FAP)Familial AmyloidosisFamilial HypercholesterolaemiaFamilial Mediterranean Fever (FMF)Familial hypocalciuric hypercalcaemia (FHH)Family Tree (Pedigree)FamotidineFanconi AnaemiaFanconi SyndromeFat embolismFatigue - CausesFatty acidsFebrile seizuresFelodipine (Dihydropyridine)Femoral HerniaFemoral triangleFemur fractures and InuriesFentanyl - FentanilFerritinFerrous Fumarate - Gluconate - SulphateFetal Alcohol SyndromeFetal circulationFever - Pyrexia of unknown origin (FUO PUO)Fever in a travellerFibratesFibrinogenFibromuscular dysplasiaFibromyalgiaFidaxomicinFinasteride (5 alpha-reductase inhibitor)First SeizureFitz-Hugh Curtis SyndromeFlail ChestFlecainide AcetateFlexor sheath infection (flexor tenosynovitis)FlucloxacillinFluconazoleFlucytosineFludrocortisoneFluid balances statusFlumazenil (Annexate - Romazicon)FluoxetineFocal Segmental Glomerulosclerosis (FSGS)Foix-Alajouanine syndromeFolate (Folic) acidFolate deficiencyFolinic acid (Leucovorin)FomepizoleFondaparinuxFood borne diseaseFoscarnet SodiumFosfomycinFosphenytoinFoster Kennedy SyndromeFournier's gangreneFracture TemplateFractured ClavicleFractured Neck of FemurFractured Pubic RamusFractured ScapulaFractured Shaft FemurFractured Tibia and FibulaFractures Shaft HumerusFractures in ChildrenFractures of Upper humerusFragile X syndromeFrailtyFraser guidelines and Gillick CompetenceFree RadicalsFriedreich's AtaxiaFrontotemporal dementiaFull or Complete Blood Count (FBC CBC)FungiFurosemide (Frusemide)Fusidic acidFusobacteria - Tropical ulcerFusobacteriumG protein-coupled receptorsGP Emergency Drugs CarriedGabapentinGalactorrhoeaGalantamineGamete intra-fallopian tube transfer (GIFT)Gamma Glutamyl Transferase (GGT)Gamma hydroxy butyrate (GHB) toxicityGanciclovir - ValganciclovirGardner syndromeGardnerella vaginalisGas GangreneGastric (MALT) LymphomaGastric CancerGastric Outlet obstruction (pyloric stenosis)GastrinomaGastro Intestinal Stromal Tumours (GIST)Gastro-Oesophageal Reflux (Adult GORD)Gastro-Oesophgeal Reflux (Paediatrics GORD)GastroenteritisGastroenterology Exam ListsGastroenterology ExaminationGastroenterology HistoryGastroenterology assessment - JaundiceGastrointestinal anatomy and physiologyGastrointestinal perforationGastrostomy (PEG) tubesGaucher's diseaseGene componentsGenetic DiseasesGentamicinGiardiasisGilbert's syndromeGingival (Gum) hyperplasia-hypertrophyGitelman's syndromeGlasgow Blatchford ScoreGlasgow Coma scaleGlatiramer acetate (Copaxone)GlibenclamideGliclazideGlimepirideGlipizideGlobus PallidusGlomerulonephritisGlossitisGlucagonGlucagonomaGlucose 6 phosphate dehydrogenase deficiencyGlucose Tolerance TestGlutamateGlycated HaemoglobinGlyceryl Trinitrate (GTN)Glycogen storage diseasesGlycolysis_Krebs_Electron_Transport_ChainGlycopyrronium BromideGoitreGolfer's ElbowGolimumab (Simponi)Goodpasture's syndrome (Anti GBM disease)Goserelin (Zoladex)Gradenigo's syndromeGrades of RecommendationGram StainGranuloma annulareGranulomatosis with Polyangitis GPA (Wegener)Graves DiseaseGriseofulvinGrowth Hormone DeficiencyGuillain Barre SyndromeGum hypertrophyGuthrie test New Born blood spotGynaecological History TakingGynaecomastiaHAS-BLED scoreHIV and Post-Exposure Prophylaxis (PEP)HIV and Pre-exposure prophylaxisHIV associated nephropathy (HIVAN)HIV disease AssessmentHTLV-1 Associated myelopathyHaematemesisHaematology Examination - SplenomegalyHaematology Lab valuesHaematuria Mild to SevereHaemodialysisHaemoglobinsHaemolysisHaemolytic AnaemiaHaemolytic Uraemic syndromeHaemolytic disease of the newbornHaemophilia AHaemophilia BHaemophilus aegyptiusHaemophilus ducreyiHaemophilus influenzaeHaemophilus parainfluenzaeHaemopoiesisHaemorrhagic TransformationHaemorrhagic strokeHaemorrhoids (Piles)Hairy Cell LeukaemiaHairy LeukoplakiaHallervorden-Spatz disease (PKAN)HaloperidolHamman-Rich syndromeHand foot and mouth diseaseHand fractures and InjuriesHantavirus infectionsHartmann's solution (Ringer's lactate)Hartnup disease*Hashimoto's (Steroid responsive) EncephalopathyHashimoto's thyroiditisHbA1cHead (Brain) InjuryHead and Neck CancersHeadache - Analgesic overuseHeadache - Assessing Acute and SevereHeadache - Basilar MigraineHeadache - ClusterHeadache - Low CSF pressureHeadache - MigraineHeadache - TensionHeadaches - GeneralHearing aidsHeat StrokeHelicobacter pyloriHelvetica Spotted feverHemicraniectomyHenoch-Schonlein purpuraHeparin - GeneralHeparin - Low Molecular Weight HeparinHeparin - Unfractionated HeparinHeparin-induced thrombocytopenia (HIT)Hepatic EncephalopathyHepatitis AHepatitis BHepatitis CHepatitis DHepatitis EHepatocellular CarcinomaHepatorenal syndromesHereditary ElliptocytosisHereditary HaemochromatosisHereditary Haemorrhagic TelangiectasiaHereditary Spastic ParaparesisHereditary SpherocytosisHereditary angio-oedemaHereditary neuropathy with pressure palsiesHereditary non polyposis coli (Lynch syndrome)Herpes GestationisHerpes SimplexHerpes Simplex Encephalitis (HSV)Herpes VirusesHerpes Zoster Ophthalmicus (HZO) ShinglesHerpes simplex keratitis (HSK)Heyde syndromeHiatus herniaHiccups (Singultus)High Dose Dexamethasone Suppression TestHip pain in childrenHirschsprung disease (congenital megacolon)Hirsuitism XXXHistonesHistoplasmosisHodgkin LymphomaHolt-Oram syndromeHolter monitor (tape) 24-72 hHomocystinuriaHookwormHorner's syndromeHospital acquired Pneumonia (NICE 139)Human albumin solution (HAS)Human prion diseasesHumeral fractures and injuriesHunter's syndrome (MPS-2)Huntington ChoreaHurler's syndrome (MPS-1)Hydatid disease (Echinococcus)Hydatidiform moleHydralazineHydrocortisoneHydrogen BondsHydrops fetalisHydroxocobalaminHydroxocobalamin - Cyanocobalamin (B12)HydroxychloroquineHydroxyurea-HydroxycarbamideHyoscine (Buscopan)Hyper IgM syndromeHyperbaric Oxygen therapyHypercalcaemiaHyperglycaemic Hyperosmolar State (HHS)Hyperinsulinaemic-euglycemic therapy (HIET)HyperkalaemiaHyperkalaemic and Hypokalaemic Periodic ParalysisHypermagnesaemiaHypernatraemiaHyperphosphataemia (High phosphate)HyperprolactinaemiaHypersensitivity reactionsHypertensionHypertension in PregnancyHypertriglyceridaemia (HTG)Hypertrophic cardiomyopathy (HCM - HOCM)Hyperventilation SyndromeHyperviscosity syndromeHypocalcaemiaHypoglycaemiaHypogonadism (Female)Hypogonadism (male)HypokalaemiaHypokalaemic Periodic ParalysisHypomagnesaemiaHyponatraemiaHypoparathyroidismHypophosphataemia (Low phosphate)Hypopituitarism (Pituitary Failure)HypospadiasHypothermiaHypothyroidismHypovolaemic or Haemorrhagic ShockIL-12 receptor deficiencyIV ImmunoglobulinIbandronic acid (Bisphosphonate)IbuprofenIcatibantIdiopathic Intracranial hypertensionIdiopathic Parkinson diseaseIdiopathic Pulmonary FibrosisIgA Nephropathy (Berger's disease)Images - Spot diagosesImatinib mesylateImipenem (Primaxin) with CilastinImmune Reconstitution SyndromeImmune(Idiopathic) Thrombocytopenic Purpura (ITP)Immunoglobulin G4-related disease (IgG4-RD)ImpetigoImplantable cardioverter defibrillator (ICD)Impulse control disordersInclusion Body MyositisIncubation periodsIndapamideIndinavir (IND)Infection screening in Septic patientInfections and their Microbial causeInfectious MononucleosisInfective ConjunctivitisInfective EndocarditisInfertilityInfliximabInfluenzaInguinal HerniaInitial Trauma AssessmentInjury Severity Score (ISS)Insomnia - sleep issuesInsulinInsulinomaInterferon BetaIntermittent ClaudicationInternal CapsuleInternuclear OphthalmoplegiaInterpreting HaematinicsInterstitial KeratitisIntestinal obstruction (Children)Intra Aortic Balloon PumpIntraabdominal abscessIntracerebral Haemorrhage (ICH) ScoreIntracranial HypertensionXIntravenous Iron Replacement (Ferrous)Intraventricular haemorrhage (neonates)Intubation and Mechanical VentilationIntussusception (Adults)Intussusception (Children)Iodine deficiency GoitreIpratropium Bromide (Atrovent)IrbesartanIron SaltsIron deficiency AnaemiaIron toxicityIrritable bowel syndromeIschaemic ColitisIschaemic StrokeIschaemic heart diseaseIsoniazidIsoprenalineIsosorbide DinitrateIsosorbide mononitrateIsotretinoin (Accutane)Ispaghula Husk (Fybogel)IvabradineJansen DiseaseJanus kinase 2Jervell and Lange-Nielsen syndromeJob Syndrome (Hyper IgE syndrome)Jugular Venous Pressure (JVP)Junctional TachycardiaJuvenile DermatomyositisJuvenile Idiopathic arthritis (Stills Disease)Juvenile Myoclonic epilepsy (JME)Kallmann's syndromeKaposi sarcoma (KS)Karnofsky performance status scaleKawasaki diseaseKennedy SyndromeKeratoconusKernicterusKetamineKetoconazoleKlebsiella pneumoniaKlinefelter Syndrome (Children)Klumpke palsyKnee fractures and InjuriesKoebner phenomenonKugelberg Welander syndromeKwashiorkorL-Thyroxine (T4)Labetalol (Trandate)Labyrinthitis - Vestibular NeuronitisLactateLactate dehydrogenase (LDH)Lactic acidosisLactobacillus acidophilusLactose IntoleranceLactuloseLady Windermere syndromeLambert-Eaton syndrome (LEMS)Lamivudine (3TC)LamotrigineLangerhans Cell Histiocytosis XLansoprazoleLanthanumLateral Medullary SyndromeLaxativesLe Fort FracturesLead toxicityLeber hereditary optic neuropathy (LHON)LeflunomideLegal definition of BlindnessLegionella pneumophilaLeishmaniasis (Cutaenous and Visceral)Lemierre's syndromeLenalidomide (Revlimid)Length Dependent PolyneuropathyLennox-Gastaut syndromeLenticulostriate branch occlusionLeprosyLeptinLeptospira interrogansLeptospirosis (Weil's Disease) (Notifiable)Leriche syndrome (aortoiliac occlusive disease)Lesch-Nyhan syndrome (Children)LeukaemiaLeukaemias in GeneralLeukoariosisLeukocytoclastic vasculitisLeukotrienesLevetiracetam (Keppra)LevodopaLevomepromazineLevosimendanLi Fraumeni syndromeLichen PlanusLiddle's syndromeLidocaine(Lignocaine)Lightning strikeLimb girdle dystrophyLimbic EncephalitisLinagliptin (Trajenta)LinezolidLinkageLiothyronine Sodium L-Triodothyronine (T3)Lipid emulsion therapy - IntralipidLipid management [NICE 2014]LipoatrophyLipoprotein lipase deficiencyLiraglutide (Victoza)LisinoprilListerial MeningitisListeriosisLithiumLithium toxicityLivedo ReticularisLiver Anatomy PhysiologyLiver BiopsyLiver Function TestsLiver TransplantationLiver abscessLiver disease in PregnancyLocalisation of cortical functionLofepramineLong QT syndrome (LQTS) AcquiredLong QT syndrome (LQTS) CongenitalLong term Oxygen therapy (LTOT)Loop diureticsLooser's zonesLoperamideLopinavirLoratadineLorazepamLosartanLow Dose Dexamethasone Suppression TestLower Gastrointestinal BleedingLugol iodineLumbar puncture and CSF interpretationLumbrosacral radiculopathyLung AbscessLung CancerLung ComplianceLung EmpyemaLung TransplantLupus NephritisLupus VulgarisLyme diseaseLymphocytic HypophysitisLymphogranuloma Venereum (LGV)LyonizationLysosomal storage diseasesMCune Albright syndromeMELASMacrocytic anaemiaMacroglossiaMagnesium PhysiologyMagnesium Sulphate - SulfateMagnetic resonance cholangiopancreatographyMagnetic resonance imagingMajor Histocompatibility complexMalabsorption - small intestineMalaria (non falciparum)Malaria FalciparumMale InfertilityMale Urethral CatheterisationMale erectile dysfunctionMalignant AscitesMalignant Hyperpyrexia (Malignant Hyperthermia)Malignant HypertensionMalignant MelanomaMalignant pleural mesotheliomaMallet FingerMallory-Weiss TearMalnutrition Universal Screening ToolManiaMannitolMantle cell lymphomaMarantic EndocarditisMarasmusMaraviroc (Celsentri)Marfan syndromeMarginal Zone LymphomaMassive HaemoptysisMaturity Onset Diabetes of the Young (MODY)McArdles disease (type V)Measles (notifiable)MebeverineMeckel's diverticulumMeconiumMedian NerveMedical Mnemonics Basic SciencesMedical Mnemonics CardiologyMedical Mnemonics EndocrineMedical Mnemonics Mental HealthMedical Mnemonics MiscellaneousMedical Mnemonics NeurologyMedical ProceduresMedical TeethMedullary Sponge kidneyMedulloblastomaMefenamic acidMefloquine (Larium)Megaloblastic anaemiaMelatoninMelioidosisMemantine HydrochlorideMembranous GlomerulonephritisMenetrier diseaseMeniere diseaseMeningiomaMeningitis in the ImmunocompromisedMenopauseMenstrual cycleMental Capacity Act 2005Mental Health Act 1983Mental State ExaminationMercaptopurineMeropenemMesalazine (Aminosalicylate)Mesangiocapillary GlomerulonephritisMesenteric infarctionMetabolic Syndrome XMetabolic acidosisMetabolic alkalosisMetachromic leucodystrophyMetastatic AdenocarcinomaMetastatic bone diseaseMetforminMethaemoglobinaemiaMethanol ToxicityMethodoneMethods to reduce toxin absorptionMethotrexateMethylcelluloseMethylprednisoloneMetoclopramideMetolazoneMetoprololMetronidazole (Flagyl)Metyrapone (Metopirone)MiconazoleMicroangiopathic Haemolytic anaemiaMicrocytic anaemiaMicroscopic PolyangiitisMicroscopic colitisMicrostomiaMidazolamMiddle East Resp Syndrome (MERS) CoronavirusMidodrineMigraine Disability Assessment (MIDAS)Miller-Fisher syndromeMilwaukee shoulder syndromeMini Mental State Examination (MMSE)Minimal Change Disease GlomerulonephritisMinocyclineMinoxidilMirabegronMirizzi syndromeMirtazapineMiscarriageMisoprostolMitochondrial diseasesMitral Regurgitation (Incompetence)Mitral StenosisMitral Stenosis vs Regurgitation - DominanceMitral Valve prolapseMittleschmerzMixed Connective Tissue Disease (MCTD)Mobility aidsModified Duke Criteria for EndocarditisModified Oxford Handicap Scale (MOHS)Modified Rankin ScoreMolluscum contagiosumMonoclonal gammopathy of undetermined significanceMonocular loss of visionMonocytesMonosodium glutamate (MSG) syndromeMontelukastMontreal Cognitive Assessment (MOCA)Moraxella catarrhalisMorphine SulphateMosquito borne diseasesMotor Neuron Disease (MND-ALS)Moyamoya diseaseMucormycosisMultifocal Atrial TachycardiaMultifocal Motor Neuropathy with Conduction blockMultiple Antithrombotics AnticoagulantsMultiple Endocrine Neoplasia type 1 (MEN1)Multiple Endocrine Neoplasia type II (MEN2)Multiple MyelomaMultiple PregnancyMultiple Sclerosis (MS) DemyelinationMultiple System Atrophy (MSA)Mumps (Notifiable)Muscles of the Abdominal RegionMuscles of the BackMuscles of the Head and NeckMuscles of the Lower LimbMuscles of the Pelvis and PerineumMuscles of the Thoracic RegionMuscles of the Upper limbMyasthenia GravisMycobacterium TuberculosisMycophenolate mofetilMycoplasma pneumoniaeMycoplasmasMycosis Fungoides (Sezary Syndrome)Myelodysplastic syndrome (Myelodysplasia)MyelofibrosisMyelofibrosis vs CMLMyelopathyMyeloproliferative disordersMyobacterium avium Complex InfectionMyocardial perfusionMyoclonusMyotonic dystrophy - Dystropica myotonicaMyxoedema comaN-Acetylcysteine (Parvolex)NEWS Reacting to Low Oxygen SaturationsNICE Guidelines LinksNICE Trauma Guidance Summary 2016NSAID toxicityNaloxone (Narcan) Opiate antagonistNaproxenNarcolepsyNasal polypsNasogastric tube insertionNatalizumab (Tysabri)National Early Warning Score NEWS 2 ScoreNeck PainNeck swellings and lumpsNecrotising Enterocolitis (Infants)Necrotising fasciitisNeedlestick injuryNefopamNeisseria gonorrhoeaeNeisseria meningitidisNelson SyndromeNeomycinNeonatal Abstinence Syndrome NASNeonatal JaundiceNeonatal Lupus ErythematosusNeonatal meningitisNeostigmineNephritic syndromeNephroblastoma (Wilm's tumour)Nephrotic syndromeNephrotoxic drugsNerve conduction studiesNerve fibresNeuroanatomy 101Neuroanatomy imagesNeuroblastomaNeurocysticercosisNeuroferrinopathyNeurofibromatosis Type 1Neurofibromatosis Type 2Neuroleptic Malignant SyndromeNeurological - Relative Afferent pupillary defectNeurological - Vision and Eye movementsNeurological Examination - CognitionNeurological Examination - Cortical FunctionsNeurological Examination - MotorNeurological Examination - SensoryNeurological Examination - Speech&LanguageNeurological ListsNeurological assessment - PtosisNeurological examination - EyesNeurological or ENT Examination - NystagmusNeurology - History takingNeurology Exam - Reflex findingsNeuromyelitis optica*Neuropathic Pain ManagementNeurotransmittersNeutropeniaNeutropenic SepsisNeutrophil Alkaline PhosphataseNeutrophilsNevirapine (Viramune) NEV-NVPNiacin deficiency (Pellagra Vitamin B6)Nicardipine (Cardene)NicorandilNiemann-Pick diseaseNifedipineNimodipine (Nimotop)Nitric OxideNitrofurantoinNitrous oxideNizatidineNocardiaNoise induced hearing lossNon Alcoholic Fatty Liver Disease NAFLDNon Convulsive Status EpilepticusNon Hodgkin LymphomaNon alcoholic steatohepatitis (NASH)Non gonococcal urethritisNon invasive ventilation (NIV)Non steroidal anti inflammatory drugs (NSAIDs)Non sustained Ventricular tachycardiaNoonan syndromeNoradrenalineNormal DistributionNormal Pressure HydrocephalusNormal Saline 0.9%Normocytic anaemiaNortriptylineNosocomial infectionsNotifiable disease and organisms UKNutrition in Infants BreatsfeedingNystatinOSCE - Administer IV InjectionOSCE - Blood cultureOSCE - VenepunctureOSCE - Venous Cannula InsertionObsessive-Compulsive disorderObstetric definitionsObstructive ShockObstructive Sleep ApnoeaOctreotideOculomotor Nerve (IIIrd Cranial Nerve)OedemaOesophageal CarcinomaOesophageal Perforation - RuptureOesophageal Variceal BleedingOesophagogastroduodenoscopyOlanzapineOlfactory Nerve (I)OligodendrogliomaOlmersartanOlsalazine (Aminosalicylate)OmalizumabOmeprazoleOnchocerciasisOncogenic virusesOncological emergenciesOndansetronOne Table TemplateOphthalmology Exam ListsOpiate ToxicityOpiatesOpicaponeOpioid toxicityOptic Neuritis-NeuropathyOptic atrophyOptic tract anatomyOral Aphthous UlcersOral CandidiasisOral LeukoplakiaOrbital vs Preorbital CellulitisOrganism and sensitivitiesOrganophosphate (OP) PoisoningOrphenadrineOrthopaedic infectionsOrthostatic - Postural hypotensionOscillopsiaOseltamivir - TamifluOsteoarthritisOsteogenesis ImperfectaOsteogenic sarcoma (Osteosarcoma)Osteomalacia-Rickets-Vitamin DOsteomyelitisOsteonecrosis of the jawOsteopetrosisOsteoporosisOtitis Externa (Malignant)Otitis MediaOtosclerosisOttawa rules for ankle and foot x-rayOvarian CancerOvarian CystOvaryOxford community stroke project (Bamford)Oxybutynin (Ditropan)Oxycodone (Oxycontin-Oxynorm)Oxygen delivery devicesOxytetracyclinePEDIS Score for Diabetic Foot UlcersPOEMS syndromePabrinexPacemaker DDDPacemaker VVIPacemaker syndromePacemakersPacing - Indications for temporary pacingPaediatric emergenciesPaediatricsPaget's (Bone) diseasePain ManagementPainful Shoulder syndromesPalliatiion - Nausea Dyspnoea Secretions PainPalliation prescribingPalpitationsPamidronate (Bisphosphonate)Pancoast tumour (Cancer)Pancreatic CancerPanton-Valentine leucocidin toxinPantoprazolePapilloedemaParacetamol (Acetaminophen)Paracetamol toxicityParadoxical embolisationParaneoplastic Encephalitis with NMDA antibodiesParaneoplastic Limbic Encephalitis (Dementia)Paraneoplastic cerebellar degenerationParaphimosisParaquat toxicityParkinson Plus syndromesParkinsonismParonychiaParoxetineParoxysmal Nocturnal HaemoglobinuriaParvovirus (Erythrovirus 19) B19 infectionPasteurella multocidaPatau syndrome (trisomy 13)Patent Ductus arteriosus (PDA) (Children)Patent Foramen Ovale (PFO)Pathogen - pattern recognition receptorsPathological bone fracturePegvisomantPelvic fracturesPemphigus VulgarisPenetrating Abdominal TraumaPenetrating Thoracic TraumaPenicillaminePenicillinsPenile CancerPeptic ulcer diseasePercutaenous Coronary Intervention (PCI ACS)PergolidePericardial Effusion_TamponadePerimesencephalic Subarachnoid haemorrhagePerindoprilPerinephric abscessPerioperative AnticoagulationPeripartum cardiomyopathyPeripheral Arterial Disease (PAD)Peripheral Cannula InsertionPeripheral Nerve Palsies*Peripheral neuropathyPeripherally inserted central cathetersPernicious anaemiaPerthes disease (Osteochondritis of the Hip)PethidinePeutz-Jeghers syndromePhaeochromocytomaPhagocytesPharmacokinetic notesPharmacokineticsPharyngeal arch derivativesPhenobarbital sodiumPhenoxymethylpenicillin (Penicillin V)PhentolaminePhenylketonuria (PKU)Phenytoin (Dilantin)Philadelphia chromosomePhimosisPhobic disordersPhocomelia and ThalidomidePhosphorusPhysiology of visionPicolax - CitrafleetPilonidal Abscess (sinus)Pioglitazone (Thiazolidinediones)Pituitary AdenomaPituitary Anatomy and PhysiologyPituitary ApoplexyPityriasis or Tinea versicolor infectionsPityriasis roseaPivmecillinam (a penicillin antibiotic)Placenta praeviaPlacental abruptionPlantar fasciitisPlasmacytomaPlasmapharesisPlasmidsPleural effusionPleural tap (thoracentesis)Pneumococcal meningititisPneumoconiosisPneumocystis jirovecii pneumoniaPneumoniaPneumothoraxPoisons eliminated Haemodialysis - perfusionPoliomyelitisPolyarteritis nodosa (PAN)Polyarticular arthritisPolycystic Ovary syndromePolycythaemia Vera (primary polycythaemia)Polymerase chain reactionPolymorphic light eruptionPolymyalgia RheumaticaPolymyositisPolypharmacy Start CriteriaPolypharmacy Stop CriteriaPolyuriaPontine-Midbrain haemorrhagePorphyria Cutanea Tarda (PCT)Porphyria TestingPortal HypertensionPositron Emission TomographyPost Menopausal BleedingPost Operative ManagementPost Partum ThyroiditisPost Polio SyndromePost SplenectomyPost Streptococcal/Infectious GlomerulonephritisPost Stroke Epilepsy (PSE)Post traumatic stress disorderPost-exposure prophylaxis with ImmunoglobulinsPosterior Reversible Encephalopathy Syndrome (PRESPosterior circulationPostpartum haemorrhagePotassium PhysiologyPralidoximePramipexole (Mirapexin)PrasugrelPravastatinPraxbind - IdarucizumabPraziquantelPrazosinPre-Operative AssessmentPreEclampsia, Eclapsmia and HELLPPrednisolonePrednisonePregabalinPremature LabourPremature MenopausePresbyacusisPrescribing InformationPrescribing in PregnancyPressure soresPrevotella (Bacteroides) melaninogenicaPriapismPrimaquinePrimary (Chronic simple) Open angle GlaucomaPrimary Biliary CirrhosisPrimary CNS LymphomaPrimary HyperparathyroidismPrimary Sclerosing CholangitisPrimary ciliary dyskinesiaPrimary hyperaldosteronism (Conn's syndrome)Primary progressive aphasia (Dementia)ProbenicidProchlorperazine (Stemetil)ProcyclidineProgressive Multifocal Leukoencephalopathy (PML)Progressive Supranuclear Palsy (PSP)ProlactinomaPropafenonePropanthelinePropionibacteriumPropofolPropranololPropylthiouracilProstate cancerProsthetic ValvesProtamine SulfateProtein C DeficiencyProtein S DeficiencyProtein losing enteropathyProtein p53Protein synthesisProteusProthrombin 20210A mutationProthrombin Complex Concentrates (PCC)Prothrombin time and CoagulationProthrombotic disordersProton Pump InhibitorsProximal myopathyPrucalopridePsammoma bodiesPseudohypoparathyroidismPseudomonas infection (Pseudomonas aeruginosa)Psoas AbscessPsoriasisPsoriatic arthritisPsychogenic PolydipsiaPubic Lice (Pediculosis Pubis)Pulmonary Alveolar ProteinosisPulmonary Arteriovenous malformationPulmonary EmbolismPulmonary Eosinophilia and CXR changesPulmonary HypertensionPulmonary Hypertension - PrimaryPulmonary RegurgitationPulmonary StenosisPulmonary hypertension - SecondaryPulse oximetryPutamenPutaminal HaemorrhagePyloric stenosis (Children)Pyoderma gangrenosumPyonephrosisPyrazinamidePyridostigminePyruvate Kinase deficiencyQuetiapineQuinineQuinine toxicityRabiesRadial PulseRadial nerveRadiation exposureRadioactive iodine (I 131)Radiofrequency Catheter AblationRadius and Ulna fractures and InjuriesRaloxifeneRaltegravirRamiprilRamsay Hunt syndromeRanitidineRanolazineRapid sequence intubation (RSI)Rapidly Progressive GlomerulonephritisRasagilineRasburicaseRaynaud's PhenomenonReactive arthritisRectal ProlapseRed cell aplasiaRed eyeRefeeding syndromeReferring to Level 2 or 3 care (ITU ICU HDU)Refractive ErrorsRefsum's diseaseRelapsing polychondritisRemdesvir (Veklury)Renal Artery StenosisRenal Papillary NecrosisRenal Physiology IRenal Stones (Nephrolithiasis)Renal TransplantationRenal Tubular AcidosisRenal Vein ThrombosisRenal cell carcinomaRenal physiologyRenin and Aldosterone Renin ratio (ARR)Renin-angiotensin systemRespiratory (Chest) infections and pneumoniaRespiratory - History TakingRespiratory AcidosisRespiratory AlkalosisRespiratory Anatomy and PhysiologyRespiratory Disease InvestigationsRespiratory Distress Syndrome (Neonates)Respiratory ExaminationRespiratory Examination - Finger ClubbingRespiratory Failure (hypoxia-hypercarbia)Resting membrane potentialRestless legs syndromeRestriction enzymesRestrictive CardiomyopathyResuscitation - Adult Bradycardia AlgorithmResuscitation - Adult Tachycardia AlgorithmResuscitation - Advanced Life SupportResuscitation - Basic Life Support ABCDEResuscitation - Choking AlgorithmResuscitation - Post Resuscitation AlgorithmReteplaseReticulocytesRetinal detachmentRetinitis pigmentosaRetinoblastomaRetinoidsRetroperitoneal fibrosisRett SyndromeReversible cerebral vasoconstriction syndromeReye syndromeRhesus haemolytic diseaseRheumatoid arthritisRheumatology AutoantibodiesRheumatology Lab valuesRhodococcus equiRibavirinRicin ToxicityRickettsia (General Principles)Rickettsia africae (Tick Bite Fever)Rickettsia akariRickettsia conorii (Tick Bite Fever)Rickettsia prowazekiiRickettsia rickettsiiRickettsia tsutsugamushiRickettsia typhiRifampicin (Rifabutin Rifampin)RifaximinRilipivirine (Edurant) RVPRiluzole (Rilutek)Risedronate (Bisphosphonate)RisperidoneRitonavir (Norvir) RTVRituximab (Mabthera)Rivaroxaban (Xarelto)Rivastigmine (Exelon)Rocky Mountain Spotted FeverRocuroniumRotigotineRubella (German Measles) NotifiableSCL70 AntibodySMASH U Intracerebral Haemorrhage ClassificationSOCRATES mnemonicST segment changesSacubitril with ValsartanSalivary Gland DiseaseSalivary glandsSalmonella entericaSalmonella typhiSaquinivir (Invirase) SQVSarcoidosisSaxagliptin (Onglyza)ScabiesScarlet Fever (Scarlatina)SchistosomiasisSchizophreniaSchmidt's syndromeSciaticaSeborrheic DermatitisSecondary Brain TumoursSecondary MessengersSecondary dysmenorrhoeaSecondary hyperparathyroidismSedation and Analgesia on ITUSelective IgA deficiencySelective Serotonin reuptake Inhibitor toxicitySelective serotonin reuptake inhibitors (SSRI)SelegilineSelenium deficiencySennaSeptic Shock and Sepsis 3Septic arthritisSepticaemiaSeronegative SpondyloarthropathiesSerotonin syndromeSerratiaSevelamerSevere combined immunodeficiency disordersSex Linked RecessiveSheehan's syndromeShigella characteristicsShigellosis (Bacillary Dysentery)Shock (General Assessment)Short Synacthen test (SST)Short and Tall stature Growth in ChildrenShoulder dislocationsSick Euthyroid SyndromeSickle Cell DiseaseSideroblastic AnaemiaSigmoid VolvulusSildenafil (Viagra)SilicosisSilver Trauma - Age over 65SimvastatinSinus BradycardiaSinus Node diseaseSinus TachycardiaSitagliptinSitosterolemiaSjogren's syndromeSkin and soft tissue infectionsSkull AnatomySleep physiologySlipped Upper Femoral Epiphysis (SUFE)Small Bowel IschaemiaSmall Bowel ObstructionSmall vessel diseaseSmallpoxSmokingSnake BitesSneddon SyndromeSodium BicarbonateSodium NitroprussideSodium PhysiologySodium PicosulfateSodium Thiopental - Sodium ThiopentoneSodium Valproate (Epilim Depakote)Sodium Zirconium Cyclosilicate (Lokelma)Soft tissue injuries (sprains, strains)SolifenacinSolitary Pulmonary NoduleSotalol HydrochlorideSpetzler-Martin Grading of AVMSpina BifidaSpinal Cord AnatomySpinal Cord Arteriovenous MalformationsSpinal Cord CompressionSpinal Cord HaematomaSpinal Cord InfarctionSpinal StenosisSpirometrySpironolactoneSpleenSplenic RuptureSpondylolisthesisSpontaneous Bacterial PeritonitisSpontaneous intracranial hypotensionSquamous Cell CarcinomaSt John's WortStaphylococcal InfectionsStaphylococcus aureusStaphylococcus epidermidisStaphylococcus saprophyticusStatinStatus Epilepticus (Epilepsy)Stavudine (Zerit) d4TStevens-Johnson SyndromeStiff Person SyndromeStrabismus (Lazy Eye)Streptobacillus moniliformisStreptococci - anaerobesStreptococcusStreptococcus agalactiaeStreptococcus milleriStreptococcus pneumoniae (Pneumococcus)Streptococcus pyogenesStreptococcus viridansStreptokinaseStreptomycinStridorStroke - Arterial Occlusion and clinical correlateStroke - Epidemiology and risk factorsStroke - General ManagementStroke - ImagingStroke ASPECTS scoringStroke CollateralsStroke Risk FactorsStroke ThrombolysisStrongyloides stercoralis (threadworm)StrontiumSubacute Sclerosing PanencephalitisSubacute ThyroiditisSubarachnoid HaemorrhageSubclavian Steal SyndromeSubclavian vein thrombosisSubdural haematomaSucralfateSudden Cardiac Death (SCD)Sudden Infant Death Syndrome (SIDS)Sudden sensorineural hearing loss (SNHL)SuicideSulfasalazine - SulphasalazineSulphonamide (Sulphamethoxazole)SumatriptanSuperior Mesenteric Artery (SMA) SyndromeSuperior Sagittal Sinus ThrombosisSuperior vena caval obstruction syndromeSupracondylar Femur FracturesSupracondylar Humerus FracturesSupraspinatus tendonitisSupraventricular TachycardiaSurgical CricothyroidotomySurgical prophylaxisSurgical site infectionSusac syndromeSuxamethoniumSydenham's choreaSynchronised DC CardioversionSyncopeSyndrome X (Cardiology)Syndrome of Inappropriate ADH (SIADH) secretionSyndromes with Severe Cognitive IssuesSyphilisSyringobulbiaSyringomyeliaSystemic AmyloidosisSystemic Lupus Erythematosus (SLE)Systemic MastocytosisSystemic SclerosisT cellsTIMI scoreTMN Staging tumoursTNF receptor-associated periodic syndromeTORCH infectionsTURP Hyponatraemia syndromeTabes dorsalisTacrolimusTafamidisTakayasu arteritis (pulseless disease)Takotsubo CardiomyopathyTamoxifenTamsulosin (Flomax)Tanner Stages of Pubertal DevelopmentTardive DyskinesiasTay-Sachs diseaseTazocin (Tazobactam - 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Basic Neuroscience



Cells in the CNS

It is impossible to understand stroke without a firm understanding of brain anatomy and physiology and pathophysiology. This is a brief run through the necessary basics. The brain contains 1011 neurons and approximately 10-50 times as many glial cells. Neurones are actually in the minority. About 40% of the human genome is involved in some part with its development and structure. The excitability of neurons is key to how the brain works. The brain requires an uninterrupted supply of ATP derived from oxidative phosphorylation to preserve this excitability. The Brain consists of two main types of cells - neurons and glial cells. Later in the neuropathology section we will talk a little about the neurovascular unit which is a hypothesised subunit of neurone and other associated cells and acts as a model upon which to discuss stroke pathophysiology. First we will deal with the components.

Neuronal Cells

Neurons are the main "brain cells" involved in information processing, information storage, sensing input and generating output. Their cell bodies which and when many are packed together are known as grey matter and can be seen on the cortical surface and within subcortical nuclei and brainstem nuclei and cerebellum and are peripherally called ganglia. The structure of individual neurons also varies depending on the individual role they play. Neurons are packed within the central nervous system at about 80,000 per mm3 of cortex and this is uniform across most of the cortex. The exception is the high density of 200,000 per mm3 in the primary visual cortex.

Neurons are highly variable in their appearance and the function they perform, from Purkinje cells of the cerebellum to those that lie in the retina (the eye is an outgrowth of the brain) and to hair cells in the auditory system. Neurons in their simplest form consist of one end with a cell body which receives input from the dendrites. It is the inputs here which if occurring together or closely related in time can cause the neuron to fire off an action potential. This arises on the distal side of the cell body at an area called the axon hillock. There is localised depolarisation and this, in turn, passes along the axon to the axon terminal with what are called terminal boutons at the end which releases neurotransmitters into a synaptic cleft and can cause depolarisation of the next neurone through its dendrites. Collections of cell bodies are the grey matter and the often myelinated "wire like" axons are the white matter.

Neurons have a cell nucleus surrounded by a soma or cell body rich in mitochondria, Golgi complexes, ribosomes, and smooth endoplasmic reticulum. Huge amounts of protein synthesis happen within the cell body and the dendrites but not in the axons. A sign of the protein production is the presence of Nissl substance which represents ribosomes. The axons transport substances including neurotransmitters, mitochondria, enzymes to make neurotransmitters from the cell body to the axon terminal. This is called anterograde flow. This is done actively using microtubules and molecules developed for the purpose. There are two kinds of anterograde transport - fast (30 cm/day) and slow (1 cm/day). Fast or rapid transplant carries proteins, vesicles, mitochondria. slow transport contains more structural elements. The soma also sends brain-derived neurotrophic factor which maintains axonal and synaptic health. Old organelles can be transported retrogradely at 15 cm/day. Anterograde transport uses tubulin and ATPases. Retrograde uses dynein ATPase. Retrograde transport is important in the pathogenesis of some diseases such as tetanus and rabies.

Non Neuronal Cells

Glial cells: glial comes from the Greek for "glue", are not involved with information processing (as far as we can tell). They perform general housekeeping and other functions in the CNS as will be discussed later. They also hold the cellular structures together and acts as a scaffold. There are several subtypes of glial cells, namely astrocytes, microglial cells and ependymal cells as well as oligodendrocytes (Schwann cells peripherally)

Astrocytes: These are the largest and commonest of the glial cells. They have a star like shape with a number of long processes which can make them resemble neurons. The cytoplasm is abundant with intermediate filaments which give the cells some rigidity helping to support the brain structure and form a scaffold for growing neurons. They contain Glycogen granules acting as a glucose store. Astrocytes contain fine filaments that stain for glial fibrillary acidic protein which is cell-type specific. Unlike neurons, they can multiply and can form scar tissue when there is localised injury (gliosis). Astrocytes have foot processes which abut onto capillaries or pia mater forming a glial membrane. Astrocytes can resemble neurons in having long processes which resemble dendrites. Astrocytes do not contain Nissl bodies (densely packed rough endoplasmic reticulum seen in neuron cell bodies). Astrocytes can also take up and metabolise or neutralise neurotransmitters. Astrocytes can have multiple other functions including mopping up Potassium ions which are then dumped into capillaries, the uptake and recycling of glutamate and GABA, removal of small neurotransmitter molecules from synaptic cleft, provide glucose and/or lactate to neurons, remove and process ammonia, provide a structure for brain development and ensure integrity of the blood-brain barrier

Microglia: These are small cells hence their name but become much larger when activated by infection or inflammation. These are derived from the bone marrow and are cells of the immune system. They have several functions including acting as macrophages phagocytosing debris and fighting infection.

Ependymal cells: These line the ventricles and have cilia on their surface which help direct the flow of CSF. They can give rise to rare tumours called ependymomas.

Oligodendrocytes:These are responsible for myelination within the central nervous system. Myelination continues after birth and is not complete until teenage years. It is fundamental to allow axon conduction at faster speeds. Within the CNS one oligodendrocyte can myelinate 20-30 axons at one time. Within grey matter, there are many very short unmyelinated axonal fibres.

Cell Electrophysiology

The resting membrane potential is the electrical potential of the cell at its basal state. There are two forces acting at any one time across a selectively permeable membrane, first ions moving along their concentration gradient and secondly ions moving according to their electrical gradient such as a positive ions moving towards a negative charge. In the resting neuron there is a small potassium leak. Potassium concentration within the neuron is high. The membrane is impermeable to sodium and proteins and chloride. The potassium moves out of the cell along its concentration gradient. This leads to an increasing negative charge inside the cell which prevents further net movement. This gives us a resting potential of -60 mV. The Nernst equation is used to calculate the membrane potential. It assumes that the membrane is selectively permeable to an ion. Imagine we have 2 liquids separated by a semipermeable membrane but one side has a very high potassium concentration and the other a very low one. Both sides are electrically neutral due to the presence of other ions. When the experiment starts potassium will move down its concentration gradient. However the high concentration side will have lost positive charge and this will try to retain potassium. Eventually an equilibrium is reached. The Nernst equation defines this. All one needs is the concentration of the ions on either side of the membrane and their charge. Although changes of potassium are vitally important the absolute number of molecules that are involved in passing across the cell membrane is only a very tiny percentage of the total.

Action Potential

To cause a neuron to depolarise it needs the correct stimulation at its dendrites and the net charge on the neuronal cell membrane of perhaps tens, hundreds or even thousands of axons synapsing on dendrites will determine whether sufficient stimulus is achieved to cause an action potential to be generated.. This can be by temporal excitatory summation where a series of impulses from one excitatory fibre over a period of time produce a membrane potential high enough to result in depolarisation or by spatial excitatory summation occurs when impulses in at least two excitatory fibres trigger an action potential. Note that not all stimulations are excitatory, indeed some GABA ion channels open chloride channels allowing the cell interior to become more negative and therefore hyperpolarised. Glutamate an excitatory transmitter however causes depolarisation. Hyperpolarisation is either due to movement in of chloride ions or movement out of potassium ions. The extreme negative charge closes sodium channels and renders the cell refractory until the membrane potential returns to normal.

With an action potential stimulates a cell sufficiently the internal voltage increases to greater than 55mV. The threshold value for depolarisation is usually about 10 mV above the resting potential. At this level there is a transient increase in Na+ permeability by voltage gated sodium channels and this leads to Na+ movement into the cell and the inside of the cell becomes more positive which acts to cause even greater Na+ permeability with a positive feedback loop that rapidly increases the membrane potential. There follows a transient rise in potassium permeability such that it flows out of the cell making the inside more negative even more so then at rest. The ions pass through voltage gated ion channels. During an action potential the charge inside the cell can become even more negative and this is called hyperpolarisation often due to further movement out of potassium ions which can render the cells refractory for a short period. The Nernst equation can be used to calculate resting membrane potentials. Interestingly different cells in the body have similar but not always identical resting membrane potentials e.g. neurons -70 mV, glial cells -90mV skeletal muscle cells - 80mV and smooth muscle cells -70 mV. E K = - 90 mV , E Na = + 60 mV, Resting membrane potential = - 70 mV.

Neuronal conduction is due to the passage of an action potential propagating along the axonal membrane. As one area of membrane depolarises this changes the condition for the adjacent cells and a continuous depolarisation occurs. This can be improved and speeded up dramatically by myelination which enables the depolarisation to jump from node of ranvier to the next one. This is known as saltatory conduction. One of the earliest signs of demyelination is slowing of the transmission of axon potentials along demyelinated fibres.

Depolarisation at the axon hillock can cause an action potential to propagate as the membrane depolarises it causes adjacent membrane to depolarise and so on until it reaches the axon terminal. This causes the activation of voltage gated calcium channels which allows calcium to enter which causes the synaptic vesicles to fuse with the terminal membrane. Here the electrical transmission becomes chemical as neurotransmitters are released into synaptic clefts (exocytosis) and either have an affect on other neurons or muscle cells. This process of passage across the gap of 200 nm takes 0.05 ms. The gap is tiny and has been calculated as the width of a row of 200 atoms. The neurotransmitter then attaches to its post synaptic receptor and is then released and either reuptaken by the neuron or broken down.

Electrical synapses also occur within the CNS and are much narrower between adjacent cells with distance of 2 nm involved. These are often called a nexus or a gap junction. These tend to be seen between glial cells rather than neurons. There is passage of ions which allows depolarisation. Outside the CNS this is seen in cardiac tissue, between adjacent myocytes.

Synapses, Neurotransmitters and receptors

Most synapses between neurons are either axodendritic with the bouton applied to the dendritic spine of another neuron or axosomatic with the bouton against the cell body of another neuron. Axodendritic synapses are usually excitatory but axosomatic are usually inhibitory. The arrival of a neurotransmitter molecule at a post synaptic receptor can have several different outcomes. It can do nothing, it can depolarise that part of the membrane of the dendrite or axon it or the effect can be hyperpolarisation. This all depends on the receptor and the neurotransmitter. There are two main classes of receptors : ionotropic which consist of a central ion channel surrounded by multiple protein subunits which deliver a very fast and specific response. The other are metabotroptic receptors which involve G proteins and intracellular secondary messengers and have a more delayed response. Some neurotransmitters for example acetyl choline act at both types.

Glutamate is the major excitatory neurotransmitter. Acts at fast ionotropic membrane receptors. It binds at NMDA receptors as well as AMPA and metabotropic glutamate receptors. GABA and glycine are the main inhibitory neurotransmitter and act at fast ionotropic GABA A membrane receptors and slow metabotropic receptors. GABA B membrane receptors are slow and metabotropic. There are many more neurotransmitters involved in brain function and any of these can be released from vesicles by a neuronal axon into the synaptic cleft to act on the post synaptic membrane. Examples of neurotransmitters include the

  • Monoamines eg Noradrenaline, Dopamine, Serotonin, Histamine
  • Acetyl choline a quaternary amine which acts at both muscarinic and nicotinic receptors
  • Neuropeptides eg substance P

The interaction of a neurotransmitter on depolarising the area of membrane that is activated by a receptor may be an excitatory post synaptic potential. If the neurotransmitter hyperpolarises the cell this causes an Inhibitory post synaptic potential reducing the likelihood that the neurone with fire of an action potential down its axon. Remember 100s or even 1000s of these may be happening at any one time. It is the summation of all these that determine neuronal response. Summation can be temporal when rapidly repeated stimuli occur during depolarisation at one terminal or spatially when stimuli are received simultaneously from adjacent terminals. In practice both are important. For interest sake don't forget that both tetanus toxin and botulinum prevent the release of neurotransmitters. Botulinum prevents the release of Ach at the neuromuscular junction. Following binding the neurotransmitters become free and are either degraded locally or reuptaken back into the neuron or by the glial cells where they can be reprocessed or degraded.

Synapses occur at the junction between the axon and an adjacent neuronal dendritic spine or cell body. It is fascinating that the density of dendritic spines is thought to play a role in learning and memory. Sometimes the axon bouton can synapse adjacent to another axon bouton and can alter its behavior through stimulation or what is termed pre synaptic inhibition often mediated by GABA which opens chloride channels hyperpolarising the membrane. There may be an assumption that there is a single signal sent and then all is quiet. In practice there is often a constant tonic level of firing and it is the change in frequency and intensity that changes. The frequencies can be from up to 100 Hz at some junctions. The firing pattern can itself carry information.

There is evidence that synapses can change 'Plasticity' depending on the degree and frequency of stimulation. This can be seen by changes in the post synaptic thresholds. May play a role in memory. To make changes the stimulus must be strong such as due to multiple simultaneous inputs. There should be the resultant firing of the post synaptic action potential. Calcium flux appears to be important. Plasticity can be short and long term.

Brain Physiology

The brain makes up only 1-2% of body mass but gets about 15% of the cardiac output, 20% of the total body oxygen consumption and 25% of total body glucose utilisation. The brain does not store glucose in any form as do other organs and is incapable of anaerobic metabolism. It is a very vascular organ. It needs to be as metabolism in the brain is high especially in the grey matter. The highest demand per volume is in the occipital cortex. The work of maintaining the excitability of cells which requires the movement of ions across cell membranes demands the manufacture of large quantities of ATP. It is not just the neurones but also the astrocytes that require a steady supply of blood flow. Astrocytes perform vital important functions such as maintaining extracellular K+ homeostasis and ensuring the rapid reuptake of neurotransmitters released by neurons.

Cerebral Vasoactive substances
  • Myogenic mechanisms (originating from vascular smooth muscle), which increase tone in response to stretch
  • Vasodilators: These act on vascular smooth muscle cells by riaising either cAMP or cGMP
    • Raised cAMP: Prostacyclin, PGE2, Adenosine, Calcitonin gene related peptide (CGRP), VIP, Beta agonists, Adrenomedullin
    • Raised cGMP: Nitric oxide produced in endothelim by Endothelial NO synthase (NOS) oxygen-dependent conversion of L-arginine to NO and L-citrulline
    • Potassium channel activation
Cerebral Perfusion

Cerebral perfusion studies looking at local flow have shown that changes of 100% to 150% of flow can occur within seconds of increased neuronal activity for instance in the contralateral primary motor cortex on asking a subject to clench a fist. It has also been seen that sudden rises in systemic BP are compensated for by increased sympathetic tone constricting the large and medium sized arteries to protect the distal circulation. Autoregulation of cerebral blood flow is the ability of the brain to maintain relatively constant blood flow despite changes in perfusion pressure. Autoregulation is well developed in the brain, likely due to the need for a constant blood supply.

The metabolic demand is so high that about 90% of normal brain consumption of ATP is required to maintain ion gradients and transmit electrical impulses comes from the oxidative breakdown of glucose. Molecules such as ketone bodies may be metabolised in severe starvation and lactate can also be metabolised. Neuronal cells have a very nigh metabolic rate and glycogen storage is poor. Anaerobic metabolism is not possible to any real extent. Glucose and oxygen supply must be continuous to match the high metabolic rate.

Global blood flow is in the range of 50-60 ml/100g/minute. The brains extracts 50% of oxygen and 10% of glucose from arterial blood. Brain tissue does not require insulin for glucose to enter cells. The brain is very responsive or 'coupled' to localised increases in demand and there is an almost instant increase in blood flow to areas with a higher metabolic rate. This autoregulatory system is impaired in acute stroke [Pierre at al 2000]. The critical level at which cellular function becomes compromised varies from region to region but is roughly about 20 ml/100 g/minute and irreversible injury will occur at levels below 8-10 ml/100g/minute. Infarction occurs where flow is most limiting or zero. This depends on both degree of hypoperfusion and the duration of hypoperfusion and the neurones involved. In terms of treatment 'time really is brain'. Newer imaging techniques can help to delineate this as MRI-DWI marks infraction and MRI perfusion identifies hypoperfused brain tissue at risk.

It is quite evident then that any impairment of local supply of glucose or oxygen reduces even for seconds there will be focal symptoms depending on the area of the brain which is compromised and its actions. Stroke as we will talk about is a vascular injury with obstruction of either large or small vessels by thrombi or microthrombi or emboli and downstream ischaemia. The small penetrating arteries that perfuse the subcortex and brainstem tend to be end arteries and cause small focal rounded infarcts. The larger branches of the circle of Willis are also end arteries and depending on how proximal the occlusion and the extend of collaterals tend to cause a characteristic wedge-shaped infarct extending to the cortical surface. Sometimes cortical tissue can be supplied by leptomeningeal or other vessels and can be preserved so that the infarct does not extend as far.

Haemorrhage will also lead to downstream ischaemia of the tissues supplied by the vessel ruptured also compromised with localised pressure from haematoma collection. Studies have shown that bleeding the 'haemorrhage growth' can persist for hours after the initial clinical event, even in those with normal clotting function [Kazui S et al. 1996]. Ischaemic and Haemorrhagic lesions are also compromised by localised cytotoxic and eventual vasogenic oedema which can also cause pressure on surrounding large and small vessels. Not to be forgotten is the fact that ischaemic strokes can bleed and this has certainly increased with thrombolysis though often these bleeds are asymptomatic possibly as the bleeding has been into the already infarcted brain. However, occasionally haemorrhagic transformation of an infarct can be overwhelming and catastrophic.

It is easier to start the whole pathophysiology process at the cellular and cellular infrastructure level before working our way up to the more macroscopic events that happen with ischaemic and haemorrhagic stroke. In stroke, the persisting focal loss of brain function is due to neuronal cell death. In vascular disorders Neuronal cell death happens when there is a localised area of reduced perfusion such that cellular respiration fails and normal cellular processes which are predominantly maintaining ionic balance, manufacturing ATP used to fuel active transport of ions across the membrane cannot continue and if this is prolonged there is no way for cellular function to be restored.

Cells in the immediate area around the core of stroke tissue can stop working but can regain function when perfusion is restored or when clot is evacuated or a hemicraniectomy performed to reduced ICP. The area containing these salvageable cells is called the stroke penumbra. Preserving the cells of the penumbra is what hyperacute stroke therapies try to do [Ginsberg et al. 1994].
Factors involved in the extent of brain injury in stroke
  • Ischaemic episodes of short duration or very gradual onset are better tolerated
  • The existence of a collateral circulation to maintain perfusion above the critical limit
  • Systemic circulatory able to maintain sufficient filling pressures
  • Hypercoagulable state enhances clot formation
  • Defective fibrinolytic system reduces ability to break down thrombus
  • Core temperature - elevated is associated with increased injury
  • Hyperglycaemia also associated with increased tissue injury

The 3 states of a neuronal tissue post stroke
Irreversible Cell death beyond salvage Calcium enters cell, Osmolysis, Cell death
Penumbra salvageable if circulation re-establishes otherwise cell death: Fall in oxygen utilisation, fall in pH, Lactic acidosis, Voltage gated calcium receptors open, rising glutamate levels
Mild hypoperfusion Viable neurons unaffected: Oxygen usage increases, Glucose use increases, Free radicals may be generated

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