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All of medicine in 12 hours… Dr. Alan McLeod (F2) The Plan Day One Day Two • • • • • • • • • • • • • • • • • • • A systematic approach Chest Pain Acute sob Chronic sob Haemoptysis TATT Painful Limb Breast Pain Emergency management Maximising your marks Swallowing Change in bowel habits Hepatomegaly Abdo pain Pregnancy / Birth Recurrent Infections Headache Stroke Pharmacology basics 2 Minutes 10 Causes of Chest Pain Puzzled? You Need A SYSTEM… Puzzled? What do I do? I GET VINO… I G E T V I N O Infectious / inflammatory Genetic / Idiopathic Endocrine Trauma Vascular Iatrogenic / ingested Neoplastic Organs 2 Minutes 10 Causes of Chest Pain Chest Pain? Where’s that wine… I G E T Infectious / inflammatory Pneumonia, pleurisy, Costochonditis Trauma Fractured rib, pulled muscle, pneumothorax V Vascular Myocardial infarction, angina, aortic dissection, PE I N Iatrogenic / ingested Surgical scar Neoplastic Bony mets Organs / other Oesophagus (spasm, reflux), heart (pericarditis) Lung, Aorta, bones, muscle, cartilege, anxiety O Genetic / ideopathic Endocrine Ischaemic Heart Disease • Approx 1/3rd of all male deaths • Approx ¼ of all female deaths • Atheroma of coronary vessels Right: Right Ventricle, most of Right Atrium, Part of Left Atrium Left: Left Ventricle, part of Right atrium, most of Left atrium Left circumflex: Left margin of heart and its entire posterior wall, Left atrium, posterior IV septum LAD: Anterior 2/3 of IV septum, anterior portion of LV, whole apex SA Node: Right 51-65%, Left 35-45%, Bilateral <10% AV Node: Right 80-90%, Left 10-20% ALL HIGHLY VARIABLE!!! Coronary Arteries: Fill During DIASTOLE Arterial Disease Arteriosclerosis • Thickening and hardening of wall – Reduced lumen – Reduced flow – Reduced elasticity – Reduced contrractility • Diabetes • Hypertension Atherosclerosis • Commonest cause of arteriosclerosis • Specific disease • Tunica intima • Mostly large and medium vessels • Small in prolonged systemic hypertension Atherosclerosis • Changes in intima Smaller vessel thrombus formation atherosclerosis • Reduced lumenal size • Ischaemic heart disease – Poor perfusion/hypoxia • Most strokes – Tissue death • Peripheral heart • Loss of elasticity disease – Aneurysm formation Plaque Formation Plaque Formation Plaque Formation Plaque Formation Plaque Anatomy Plaque Anatomy (early) • Free Lipid • Foam cells • Increased myointimal cells • Collagen • Disruption of internal elastic lamina Plaque Anatomy (later) • Collagen cap • Extracellular lipid mass • Foam cells • Myointimal cells • Disrupted internal elastic lamina • Pressure atrophy of muscle collagenous replacement Atheroma – Risk factors Non-preventable • Increasing age • Male sex • Family history Preventable • Hyperlipidaemia – LDL and Cholesterol • Hypertension – Diastolic most important • Diabetes • Smoking Fibrous Pericardium Pericardial Space Fold Myocardium Layers of the Heart Endocardium Parietal Layer of Serous Pericardium Visceral Layer of Serous Pericardium Compare Skeletal and Cardiac Muscle Muscle Comparison Skeletal Cardiac Smooth Voluntary Involuntary Involuntary Striated Striated Non-striated Multinucleated Mononucleated Mononucleated Unbranched Branched Unbranched No gap junctions Gap junctions No gap junctions Myocyte Action Potential Phase Ion Voltage 0 Na+ IN 1 K+ OUT -ve 2 Ca++ IN Steady + K OUT 3 K+ OUT -ve 4 K+ OUT -ve (slow) +ve (rapid) NAK-CAKKK In Detail Membrane potential (mV) Pacemaker Action Potential 0 Ca++ In -40 -80 K+ Out Comparison of action potentials Pacemaker cell Myocyte Slow diastolic repolarisation in phase 4 Pot. Approx -65 to -40mV Constant phase 4 (resting) potential Resting Pot. approx -90 mV Phase 0 less steep Phase 0 via slow channels Phase 0 more steep Phase 0 via fast Na channels Plateau not sustained Plateau sustained Repolarisation more gradual Repolarisation less gradual Excitation-contraction coupling • Electrical signal • In The Heart • Stimulates contraction • Calcium induced calcium release • Act Pot from SA Node Generally • Signal causes depolarisation • CA++ entry results • Causing contraction Excitation-contraction coupling SAN Excitation L Type Calcium Channel Ca++ Ca++ Ca++ Ca++ Ca++ Ca++ SR Ca Ca++ Ca++ Ca++ ++ Excitation-contraction coupling L Type Calcium Channel Ca++ Ca++ Ca++ Ca++ Ryanodine Receptor Ca++ Ca++ SR Ca Ca++ Ca++ Ca++ ++ Excitation-contraction coupling L Type Calcium Channel Ca++ Ca++ Ca++ Ca++ Ryanodine Receptor Ca++ Ca++ SR Ca Ca++ Ca++ Ca++ ++ Excitation-contraction coupling Ca++ Ca++ Tropomysin Ca++ Ca++ SR Ca++ Ca++ Ca++ Ca++ Ca++ Excitation-contraction coupling Ca++ Ca++ Tropomysin Ca++ Ca++ SR Ca++ Ca++ Ca++ Ca++ Ca++ Excitation-contraction coupling Ca++ Ca++ Ca++ Ca++ Tropomysin ++ Ca Ca++ Ca++ Ca++ Contraction CA++ SR Describe Sliding Filament Theory Sliding Filament Theory http://uk.youtube.com/w atch?v=gJ309LfHQ3M& feature=related • Calcium enters • Binding sites on actin uncovered by movement of Tropomyosin / troponin complex • Myosin binds to site powerstroke • ATP binds to myosin release from binding • ATP ADP + Pi – cocks myosin for another Powerstroke • Continues as long as ATP and Ca present Sliding Filament Theory Normal Lead 2 A Segment is Shorter than an interval The Normal ECG PR interval: first deflection of P first deflection of QRS – 120-200 ms (3-5 small sq) QRS interval: first deflection of QRS end of last deflection – <100 ms (<3 small sq) QT interval (QTc is QT corrected for heart rate). Start of QRS end of T wave – 360-440 ms (<11 small sq) Additional Abnormalities • Pathological Q wave – Duration > 1 small sq • ST Depression – 1mm or more over isoelectric line • ST Elevation – 0.5mm or more below isoelectric line • T wave abnormality – Normally upright in I, II & V1 – V3 – Normally inverted in aVr – Variable in others STEMI and NSTEMI STEMI • ST Elevation MI NSTEMI • Non ST Elevation MI • ST elevation on ECG • Positive enzyme tests • No ST elevation • Positive enzyme tests STEMI and NSTEMI ST Segment A I P T A: Normal ECG B: ST Elevation C: ST Depression QRS B C ST elevation in response to Isoelectric line (I) Evolution of ECG Changes in STEMI • Minutes to hours – Peaked T waves • Hours – ST elevation • Hours to days – T wave inversion – Loss of R wave • Days – Pathological Q wave Cardiac Enzymes Fibrinolysis • tPa • Streptokinase ACS? GO CARDIO ABCD G GTN O Oxygen C Clot prevention - enoxaparin A Aspirin ± clopidogrel R Raised position D Diamorphine + antiemetic I Investigate: ECG, enzymes, Troponin, CXR O Observe: Repeat ECG + Basic obs, A ACE inhibitor within 24 hours B Beta blocker C Cholesterol - statin D Diabetic control – tight control for at least 24 hours 2 Minutes 5 Causes of acute Dyspnoea Acute Dyspnoea? Need alcohol! I G E T V I N O Infectious / inflammatory Asthma, Pneumonia, COPD exacerbation (e.g. upper resp tract infection) Genetic / ideopathic Endocrine Trauma Pneumothorax Vascular Myocardial infarction, PE Iatrogenic / ingested Foreign body (mostly children) Neoplastic Organs / other Lungs Lung Anatomy Cupular Mediastinal Costal 2 Lobes 3 Lobes Diaphragmatic The Alveolus Muscles of Breathing Diaphragm • Phrenic nerve C3,4 & 5 Intercostal muscles • External • Internal Compare the bronchial and pulmonary arteries Vessels in the Lung • Pulmonary Artery – – – – Deoxygenated blood From Right Ventricle Oxygenated in lungs Affected in PE • Bronchial Artery – Oxygenated blood – From systemic supply – Supplies tissues of lung • Pulmonary vein – Oxygenated blood – From lungs – To Left atrium Velocity and Flow Velocity • Displacement of single particle per unit time • Inversely proportional to cross sectional area – Faster in thinner tubes • Aorta is thinner than total mass of capillaries – V slow capillary flow – Time for gaseous exch Flow • Volume of fluid passing point A at time B • Proportional to pressure difference • Inversely proportional to tube length • Proportional to r4 • Inversely proportional to viscosity Resistance (R) In Parallel: 1/RTOT = 1/R1 + 1/R2 + 1/R3 In Series: RTOT = R1 + R2 + R3 Resistance may be varied in arteries and arterioles by control of lumen cross sectional area via smooth muscle contraction / relaxation Laminar and Turbulant Flow Laminar: • Concentric thin adjacent layers of fluid • ‘Rings within rings’ • Speed max at centre • Elements stay in one lamina Laminar and Turbulant Flow Turbulant: • Fluid elements not contained in one lamina • Radial and circumferential mixing • Vortex generation • Pressure needed to maintain flow is increased Venous Thromboembolism Virchow’s Triad • Or FECing blood… – Flow disturbances • Stasis • Slow • turbulant – Endothelial damage • E.g. atheroma • Stasis / turbulance Genetic Disorders • Factor V Leiden – Factor V not inactivated • Anticoagulant lack – Protein C deficiency – Protein S deficiency – Antithrombin III defic. – Coagulability changes • Genetic • Oral contraceptive pill • You may not need to know these… Consequences of VTE PORT • Propagation – Grows along vessel • Organisation – Granulation tissue • Recanalisation – New passages through granulation tissue • Thromboembolism – E.g PE Embolism ‘Occlusion of a vessel by a mass of material transported through the bloodstream’ A Variety of materials • Thrombus • Tumour mass • Fat/ bone marrow • Amniotic fluid • Air A variety of consequences • Unstable angina • Stroke / TIA • Pulmonary embolism • Other infarct • Lower limb muscle DVT and PE From Vein to Artery… • DVT in leg • Loss of embolus – Travels in systemic circ • Lodges in pulmonary artery – – – – 85% Minor PE 10% Major 5% Massive Rarely recurrent Major • Dyspnoea • Haemoptysis • Pleuritic chest pain Minor • Possibly assymptomatic • Dyspnoea • Pleuritic chest pain Predisposing Factors To PE • Previous PE • DVT To DVT • Immobility • Post-operative • Pregnancy / post partum • OCP • Nephrotic syndrome • Trauma esp severe burns • Cardiac failure Asthma COS of Three Pathologies Airway Constriction Oedema Secretions ABGs - pH Henderson-Hasselbalch (H-H) equation pH = 6.1 + log [HCO3-] / pCO2 x 0.23 What are the main factors measured on an ABG? What are the Reference Ranges? Reference Ranges pH: pCO2: pO2: [HCO3-]: Base excess: 7.35 – 7.45 4.7 – 6.0 kPa (about 35-45 mmHg) >10.6 kPa (>80 mmHg) 22-25 mmol/L* +/- 2 mmol/L* * standardised, as if pCO2 were 5.3 ROD: Respiratory cause if pH and pCO2 move in Opposite Directions 2 Minutes 5 Causes of Chronic Dyspnoea Chronic Dyspnoea? Gimme Wine! I G E T V I N Infectious / inflammatory COPD Neoplastic Lung Cancer O Organs / other Lungs: fibrosis, pleural effusion Heart: failure, pericardial effusion Genetic / ideopathic Endocrine Trauma Vascular Anaemia Iatrogenic / ingested Heart Failure 'failure of heart to pump blood forwards at a sufficient rate to meet metabolic demand' (forward failure) 'ability to pump sufficient blood to meet metabolic demand only if cardiac filling pressures are abnormally high’ (backward demand) Heart Failure • Left sided (varied causes – see right) • Right sided – caused by LEFT heart failure or cor pulmonale Pathological causes • Myocardial disease • Congestive failure – failure of both left and right sides • Pressure overload – Myocardial infarction • Volume overload – Regurgitation – Arteriovenous shunts – Hypertension (including pulmonary in RHF) – Stenosis Define Preload and Afterload Useful Terms Preload • Stretch on myocardial fibre before contraction Afterload • Ventricular wall tension during contraction – The resistance that must be overcome Ejection fraction • Fraction of end diastolic volume ejected from ventricle during systole – 55-70% normal Remember • CO = SV x HR List Clinical Features of Right Heart failure Heart Failure - Features L eft sided U •Dyspnoea N •Orthopnoea G •PND •Fatigue R E •Tachypnoea L •Haemoptysis A •Tachycardia T •Sweating E D R ight E S T •Swollen legs •RUQ discomfort •Nausea •Anorexia sided O F •Pitting periph. oedema •Elevated JVP B •Hepatomegaly O D Y Central Venous Pressure • • • • Pressure measured in central veins. Indicates mean right atrial pressure Frequently used as an estimate of right ventr. preload. CVP rises with poor right ventr. Function or obstructed pulmonary circulation. Measuring CVP • Central Line • Catheter placed thorugh subclavian vein • Invasive • Alternative is CVP Measuring CVP Jugular venous pressure • Use right internal jugular vein • Patient at a 45° angle, head to the left • Light source that shines obliquely from the left • Locate the anatomical landmarks • Locate the JVP • Measure the level of the JVP Anatomical landmarks • Medial end of clavicle • To ear lobe • Under medial aspect of sternocleidomastoid • Level is measured from the sternal angle of Louis to top of column JVP JVP vs Carotid pulse • The JVP pulse is • Not palpable • Obliterated by pressure • Characterised by a double waveform • Varies with respiration decreases with inspiration • Enhanced by the hepatojugular reflux The Hepatojugular Reflux • Firm pressure is applied to the right upper quadrant using the palm of the hand • A transient increase in the JVP will be seen in normal patients • There may be a delayed recovery back to baseline which is more marked in right ventricular failure a x c x’ v y Jugular venous waveform a wave: rise in right atrial pressure during atrial contraction x descent: atrial relaxation + RV contraction (pulls atrium downward) c wave: bowing of tricuspid valve into RA during systole v wave: right atrial filling, tricuspid valve closed y descent: emptying of right atrium after tricuspid valve opens Starling Curve Heart has reached limit of response, insensitive to further changes in RAP Normal physiological range, high sensitivity to RAP changes RAP (mmHg) • RAP=Right Atrial Pressure • CO=Cardiac Output • Remember: too much stretch reduces ability to contract… (blue dashed line) Vol (ml) Pressure (mmHg) Flow / Volume Loops Vol (ml) Pressure (mmHg) Flow / Volume Loops 280 ms 700 ms List the common diastolic and systolic murmurs A Piratical Crew… Dire Stolic Ms ARrrrrr A Piratical Crew… DIASTOLIC murmurs are: MS: Mitral stenosis AR: Atrial regurg. MS ARrrrrr… Systolic? Meet MR ASs Sympathetic stimulation Location Receptor Type Action if stimulated Heart Beta Increased HR and contractility Vasodilatation Blood vessels in Beta skeletal muscle Blood vessels elsewhere Alpha Vasoconstriction Bronchioles Beta Relaxes smooth musc. Pupil of eye Salivary glands Sweat glands Liver Beta Beta Alpha Alpha, Beta Gut Secretion Gut motility None Alpha, Beta Dilates (darkness) Little, thicker secr Promotes sweat Glycogenolysis Gluconeogenesis Inhibits peristalsis GPCRs http://uk.youtube.com/watch?v=tOcGbnBCdMM http://uk.youtube.com/watch?v=bU4955rLv_8&feature=rela ted GPCR Summary • Receptor complex + G protein • G Protein has 3 subunits (alpha, beta & gamma) • Receptor binds ligand • Conformational change • Loss of GDP from G protein alpha subunit • Binding of GTP • Separation of alpha subunit from betagamma dimer • Alpha and beta-gamma freed to interact with effectors. • Cascade effect. • Cycle starts again GPCRs in the heart Beta receptors • GPCRs • Gs activates adenylate cyclase – Increased cAMP – ATP cAMP • cAMP activates PKA • PKA phosphorylates alpha-1 subunit on voltage-gated Ca++ channels • Increased Ca++ influx • Increased inotropy • Increased rate Ca++ In Beta-adrenergic antagonists ‘Beta blockers’ • Combat the harmful activation of the sympathetic nervous system • Decrease HR • Decrease contractility Examples • Propranalol • Sotalol Side effects • Bronchoconstriction • Bradycardia GPCRs in the lung Beta receptors • GPCRs • Gs actvates adenylate cyclase – Increased cAMP – ATP cAMP • cAMP causes relaxation of the smooth muscle • Decreases sensitivity of the IP3 receptor, decreasing release of calcium from intracellular stores in response to IP31 • Some proponents argue for a cAMP independent PKA mechanism as well2 Parasympathetic stimulation Location Action if stimulated Heart Decreased HR Blood vessels in skeletal muscle - Blood vessels elsewhere - Bronchioles Pupil of eye Salivary glands Sweat glands Liver Gut Secretion Gut motility Constricts (light) Abundant watery secr Glycogen formation Stimulates Stim peristalsis Parasympathetic vs Sympathetic Long Presynaptic N ACh Synapse Near Target Organ Parasympathetic CN 3, 7, 9, 10 S2,3,4 Target Organ Synapse Near CNS Origin ACh Sympathetic T1 – L2 ACh Long Postsynaptic N NA ACE Inhibitors • In HF the reninangiotensinaldosterone pathway is activated inappropriately – Poor renal perfusion – Sympathetic activation (beta receptors) – Diuretics Effects • Reduce vasc. resitance – Reduce afterload – Improve perfusion • Inhibit aldosterone & reduce Na+ reabsorp – Cause naturiuresis • Proven to prolong life Heart Failure – ACE Inhibitors • Reduce ATII formation • So reducing Na+ reabsorption • So reducing water retention • So reducing central venous pressure • So reducing load upon heart TB (or not TB…) Re-emerging organism • HIV • Drug resistance • Mycobacterium – – – – Mycolic acid wax coat Resistant to drying Acid fast Slow growing Spread: • Coughed into air • Remain for hours as micronuclei • Bypass cilliary cells • Enter alveoli • Enter resident macrophages Two disease forms Primary Secondary • 91% no disease • Reactivation • 3% progressive • Damage is from host systemic leading to immune response death • Remainder pulmonary or extrapulmonary TB Tuberculosis Features • Shortness of breath • Fever and sweating, especially at night • Haemoptysis • Loss of appetite • Weight loss • Fatigue and tiredness • Lymphadenopathy Demographics • Black African (211 per 100,000) • Pakistani (145 per 100,000) • Indian (104 per 100,000) Diagnosis and Management Diagnosis Management • PPD / Mantoux • Sputum culture BCG Vaccine – Acid Fast Stain (ZN) • Chest X-ray • Bronchoscopy ± biopsy RIPE • Rifampicin 6 months • Isoniazid 6 months • Pyrazinamide 2 months • Ethambutol 2 months What is meant by ‘concordance’ Social Science: Taking the pills… • Compliance – Extent to which patient’s behaviour matches recommendations from the prescriber • Adherence – Extent to which the patient’s behaviour matches agreed recommendations from the prescriber. • Concordance – Extent to which the patient’s behaviour matches agreed recommendations from the prescriber after exploring and discussing the patients beliefs, views and opinions. Social Science: Taking the pills… Poor concordance • The homeless • Minority groups • Learning difficulties • Dementia • Psychological illness • Those with a history of non-concordance Increasing concordance • Directly observed therapy • Key workers • Home visits • Health education • Reminder letters • Foreign lang materials 2 Minutes 5 Causes of Haemoptysis Haemoptysis? Where’s that wine… I G E T V I N O Infectious / inflammatory Pulmonary tuberculosis Genetic / idiopathic Endocrine Trauma Chest trauma Vascular Pulmonary embolism Iatrogenic / ingested Neoplastic Bronchial carcinoma Organs / other Nose: epistaxis; oesophagus: maller weiss tear Lung: bronchiectasis; Heart: mitral stenosis Lung cancer • Male: Female 7:1 • Decreasing • Male peak in 60s • Female peak in 70s • Rare under 25 years Presenting complaints • 90% symptomatic – – – – – 40% Haemoptysis 75% Anorexia 75% Dyspnoea 75% Cough 75% Pain • Remember Weight Loss • 10% Incidental imaging Lung Cancer - Diagnosis • Imaging – Plain film – CT – MRI Biopsy • Peripheral lesions – Percutaneous biopsy • Proximal lesions – Bronchoscopic biopsy • Cytology – Sputum – Bronchoscopic washings • Pleural Effusions – Fine needle aspiration Lung Cancer Types • Small Cell (20-30%) • Non-small Cell – Large Cell (10-15%) – Adenocarcinoma (~20%) • Commonest non-smoking – Squamous cell carcinoma (40-60%) • Commonest smoking related Treatment • Small cell – Early metastasis – Chemotherapy and radiotherapy first line • Non-small cell – Surgery first line • Lobectomy • Pneumonectomy – Radio / chemo as req Haemostasis Stops your blood falling on the floor… • Vasoconstriction • Platelet aggregation • Clotting cascade Platelets • Made from Megakaryocytes • Last ~10 days • Do nothing until activated • Collagen • Thromboxane A2 (TXA2) • Thrombin (from clotting) • ADP Platelet Aggregation Activated Platelets • Release TXA2 • Change form • Form plug by adhering to – Other platelets – Collagen under epithelium – Via Von Willibrand’s Factor • Promote Coagulation • Prostacyclin and CD39 prevent activation Clotting Extrinsic Intrinsic Damage to tissue outside vessel Damage to the blood vessel Common Factor X (inactive) Tissue Thromboplastin Clotting cascade Factor Xa (active) Factor II - Prothrombin (inactive) Fibrinogen Factor IIa - Thrombin (active) Fibrinogen Clot Clotting Extrinsic Intrinsic Damage to tissue outside vessel Damage to the blood vessel Common Factor X (inactive) Tissue Thromboplastin Factor 9 Factor 8 Clotting cascade Factor Xa (active) Factor II - Prothrombin (inactive) Fibrinogen Factor IIa - Thrombin (active) Fibrinogen Clot Clotting Extrinsic Intrinsic Haemophilia B Damage to tissue outside vessel Damage to the blood vessel Common Factor X (inactive) Tissue Thromboplastin Factor 9 Factor 8 Clotting cascade Factor Xa (active) Factor II - Prothrombin (inactive) Fibrinogen Haemophilia A Factor IIa - Thrombin (active) Fibrinogen Clot Clotting Extrinsic Intrinsic B Damage to tissue outside vessel Damage to the blood vessel Common Factor X (inactive) Tissue Thromboplastin Factor 9 Factor 8 Clotting cascade INR / PT Factor II - Prothrombin (inactive) Fibrinogen Factor Xa (active) aPTT (PTT) A Factor IIa - Thrombin (active) Fibrinogen Clot Haemophilia X-Linked Recessive What is the role of vitamin K in blood clotting? Vitamin K and Warfarin • Factors 2,7,9 & 10 must be gamma carboxylated • Vitamin K is a vital cofactor • Warfarin inhibits enzyme – Prevents Vitamin K recycling Factors 2,7,9 & 10 Gamma carboxylated Reduced Vitamin K Oxidised Vitamin K Vitamin K Reductase Vitamin K - Vitamin K Reductase Warfarin Vitamin K Dependent Factors INR / PT K K aPTT (PTT) K Intrinsic Pathway K Extrinsic Pathway Common Pathway ATIII and Unfractionated Heparin Heparin IIa Factor IIa (Thrombin) IIa IIa * ATIII Xa Factor Xa Xa Xa * * Note the change in ATII conformation ATIII and LMW Heparin No substrate binding LMW Heparin IIa IIa IIa * No substrate binding needed Xa Factor Xa Xa Xa * * Note the change in ATII conformation ATIII and Heparin - Summary • Antithrombin III deactivates clotting factors IIa (thrombin) & Xa • It does NOT need heparin to do this • BUT heparin makes it go FASTER • LMWH only works on Xa • Longer molecules in unfractionated heparin work on IIa (thrombin) as well The Clot • Platelet activation • Fibrinogen fibrin • Fibrin assembles into long fibrils • Platelets + Fibils = Clot • RBCs join later 2 Minutes 10 Causes of a Painful Limb Painful Limb? Time for some Wine! I G E Infectious / inflammatory Cellulitis, septic arthritis Genetic / ideopathic Osteogenesis imperfecta related fracture Endocrine Osteoporosis related fracture T Trauma Fracture, dislocation, pulled muscle, ligamentous injury V I N Vascular Claudication Iatrogenic / ingested Corticosteroid osteoporis fracture Neoplastic Bony mets, Primary bone cancer (rare) O Organs / other Joints: osteoarthritis, rheumatoid arthritis Nerves: sciatica Fracture • • • • Pain Swelling Deformity Loss of function • High impact • Repetitive impact (stress) • Pathologic Fractured Neck of Femur Blood supply to head - In order of importance • Capsular supply – From Med + Lat circumflex – From Deep femoral • Nutrient artery – From deep femoral • Ligamentum teres – From Medial epiphyseal Fractured Neck of Femur Fractured Neck of Femur Colles & Smiths Fractures Colles • Distal radius • Dorsal angulation • FOOSH • Elderly • Osteoporosis Smiths - as above but • Volar angulation Scaphoid fracture • FOOSH • Tenderness in anatomical snuffbox – Structures of snuffbox • Three X-ray views • Blood supply enters distally – Potential avascular necrosis Humeral fracture • Most Commonly at Surgical neck – Axillary nerve damage • Also mid shaft • If involves radial groove – Radial nerve damage • Distal radius uncommon Humeral fracture Distal radius uncommon • Supracondylar – Median nerve • Medial epicondyle – Ulnar Nerve What is this fracture? Monteggia and Galleazzi Fracture-dislocations Medics Under Monteggia (a) Ulnar shaft Pressure Get Proximal Radioulnar Joint Galleazzi (b) Really Drunk Radial Shaft Distal RUJ Fracture Management The “Three R’s” • Reduce • Retain – Cast – Internal fixation – External fixation • Rehabilitate Pulled elbow • Mostly Children 1-4 yrs • Dislocation of radial head from annular ligament • 50% have no Hx • Not using limb • Extension + pronation No deformity In adults Monteggia fracture dislocation is likely differential Bone Healing Mins – 3 days • Haematoma and Necrotic tissue 2 days – 2 weeks • Phagocytosis • Provisional callus 3 weeks on • Firm callus • Mineralisation Weeks - months • Remodeling Factors influencing Healing Local Systemic • • • • • • • • • Tissue damage Tissue loss Infection Foreign body Patient age Nutritional status Smoking / alcohol Steroids Systemic illnesses such as diabetes, renal, lung, cardiac. Synovial Joint Video Link Collagen Synthesis http://depts.washing ton.edu/bonebio/AS BMRed/collagen/col lagen.swf Compare and contrast rheumatoid arthritis with osteoarthritis Osteo and Rheumatoid Osteoarthritis • Disease of cartilage • No immune component – M=F – Rheumatoid factor -ve • Assymetric • Large > small joints • DIP Joints Rheumatoid arthritis • Disease of synovium • Autoimmune – M<F (approx 1 : 3-4) – Rheumatoid factor 80% • Symmetrical • Small > large joints • MCP + PIP Joints Septic Arthritis ‘joint inflammation caused by the presence of live intra-articular micro-organisms’ •Acute •Painful •Swollen •Effectively immobile Risk of rapid joint loss Management • Aspirate pus – Send for analysis • Surgical washout • IV antibiotics • Differential: Gout Septic Arthritis Routes of infection 1.Haematogenous 2.Direct Trauma 3.Iatrogenic 4.Osteomyelitis 5.Inflamed extraarticular structures 2 Minutes 5 Causes of Breast pain Breast Pain? Back to the Drinking… I G E T V I N O Infectious / inflammatory Costochonditis Genetic / ideopathic Endocrine Trauma Vascular Cardiac Pain Iatrogenic / ingested Neoplastic Benigng or malignant breast cancer Organs / other Oesophagus: spasm; Heart :cardiac pain Lung: pleurisy Non-cancer conditions Abnormalities of development • Cyclical mastalgia • Non-cyclical mastalgia • Epithelial Hyperplasia • Sclerosis • Cysts • Fibroadenoma • Duct ectasia Benign tumours • Ductal papilloma • Lipoma • Oil cysts • Sebaceous cysts • Lymph nodes • TB Cancers Non-invasive • Lobular carcinoma in situ • Ductal carcinoma in situ Invasive • 80% carcinomas are ductal – 5% lobular – poorer outcome Management • Social / psych support • Surgery – Local / mastectomy – reconstruction • Radiotherapy – Breast / axilla • Chemotherapy Modifying Oestrogen • Oestrogen • Progesterone • Therapy aims to reduce oestrogen production • Normal breast tissue • AND 60% of tumours • Ovarian ablation • Pre-menopause prod. – Ovaries • Post Menopause – Peripheral fats – GNRH agonists – Surigal or radiation • Aromatase Inhibitors – Post menopausal Risk Risk factors • Menarche <11 • Menopause >54 • Western diet • OCP and HRT • Radiation • Family history (only 5% of Br. Ca are familial) Inherited breast cancers • BRCA1 – 51% by age 50 – 85% by age 70 – Also ovarian cancer • BRCA2 – Male breast cancer – Prostatic cancer – Ovarian cancer • Present early with advanced disease Risk Assessment Think Benign • Young patient • No family history • Smooth lump • Movable lump • Cyclical symptoms Think Malignant • Patient >55 • Family history br. Ca. • Fixed mass Testing for breast cancer Triple Assessment • Physical examination • Imaging – Ultrasonography (<35) – Mammography • Sampling – USS guided core biopsy – Or FNA + cytology – Ideally after imaging The screening programme • Women • Aged 50+ • Every 3 years • 2 view mammography • Will save ~1,250 lives annually by 2010 • 1 / 500 screened Describe some of the features that make a disease suitable for screening A good screening Programme • An important public health problem • In which early detection is possible and advantageous • With a reliable, acceptable test • And available, effective treatment • There should be agreement on who is suitable to investigate and treat. Neoplasia • 'Irreversible changes in genetic material of cells, due to exposure to certain noxious stimuli, leading to abnormal cellular growth patterns.’ • Tumours develop from a single cell – they are monoclonal • Normal tissue is polyclonal • Learn – Breast – Bowel – Lung Neoplasia • Oncogenes – Abnormal expression – Genes controlling cell growth – Dominant • Tumor suppressor genes – Loss of activity – Protect against neoplasia – Recessive Neoplasia • Tumor suppressor genes – Loss of activity – Protect against neoplasia – Recessive • p53, Chromosome 17 – initiates DNA repair – prevents division of cells with irreparable DNA damage • Rb, Chromosome 13. – Abnormal copies of this gene are implicated in retinoblastoma. Growth Characteristics Benign Expands only Grows locally Generally slower Malignant Expands and invades local tissues May metastasise Generally faster Cytoplasmic Characteristics Benign Normal or slight increase in nucleus:cytoplasm ratio Resembles cell of origin (well differentiated) Retains specialisations Diploid Malignant High nucleus:cytoplasm ratio Failure of differentiation Loses specialisations Range of ploidy Histological Characteristics Benign Few Mitoses Cell uniform throughout tumour Organised tissue Malignant Many mitoses – some of which are abnormal Cells vary in shape and size (cellular pleomorphism) and/or Nuclei vary in shape and size (nuclear pleomorphism) Disorganised tissue Invasion and Metastasis • Invasion is the spread into adjacent tissues – may occur along natural tissue planes such as along nerves • Metastasis is the spread of cells to distant parts of the body – there are several mechanisms for this To Metastasise • Changes occur in only some cells of the tumour • By random mutation • Binds to basement membr • Becomes motile • Becomes able to attach to extracellular matrix • Becomes able to degrade extracellular matrix • Must be able to survive and grow at site of implantation Routes of Metastasis • Vascular • Lymphatic • Coelomic Local and systemic effects Local • Pressure • Invasion • Ulceration • Obstruction Systemic • Weight loss (cachexia) • Loss of appetite (anorexia) • Fever • Anaemia • General Malaise • Paraneoplastic Who gets Cancers? Inherited tendencies • Xeroderma pigmentosum • Down’s syndrome • Ataxia telangectasia Genes • Breast / ovarian – BRCA1 – BRCA2 • Colon – MLH1 Diseases predisposing to cancer • FPC: Colon • HNPPC: Colon • DNA mismatch repair • Dominant – MSH2 What is a carcinogen? Suggest one together with its mode of action. Carcinogens Cigarette smoke UV Radiation Chemicals • PAH • Aromatic amines • Nitrosamines Ionising radiation • Radiotherapy • Radon gas (lung) • Industry/military Carcinogens Viruses • EBV (Epstein-Barr) • HPV (Papilloma virus) • HBV (Hepatitis B virus) Stages in carcinogenesis • Initiation • Promotion • Progression