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Dennis, Bowen and Cho2nd Edition

Mechanisms ofCliniCal SignS

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Mechanisms of CLINICAL SIGNS

2nd Edition

Mark Dennis MBBS (Honours)

Cardiology Advance Trainee /Intensive Care Trainee,

Royal Prince Alfred Hospital, Clinical Lecturer, Sydney Medical School,

University of Sydney, NSW, Australia

William Talbot Bowen MBBS, MD

Emergency Medicine Physician, Board Eligible

Louisiana State University Health Sciences Center

New Orleans, LA, United States

Lucy Cho BA, MBBS, MIPH

General Practice Registrar

Appletree Family Practice

Newcastle, NSW, Australia

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Contents

Contents by condition ixForeword xvPreface xviAcknowledgements xviReviewers xviiAbbreviations xixSign value xxii

Chapter 1Musculoskeletal Signs 1

Anterior drawer test 2Apley’s grind test 3Apley’s scratch test 4Apparent leg length inequality

(functional leg length) 5Apprehension test 7Apprehension–relocation test

(Fowler’s sign) 8Bouchard’s and Heberden’s nodes 9Boutonnière deformity 10Bulge/wipe/stroke test 12Butterfly rash (malar rash) 13Calcinosis/calcinosis cutis 15Charcot foot 17Crepitus 19Dropped arm test 20Finkelstein’s test 21Gottron’s papules 22Hawkins’ impingement test 23Heliotrope rash 25Kyphosis 26Lachman’s test 28Livedo reticularis 29McMurray’s test 32Neer’s impingement test 33Patellar apprehension test 35Patellar tap 36Patrick’s test (FABER test) 37Phalen’s sign 38Proximal weakness/proximal myopathy 39Psoriatic nails/psoriatic nail dystrophy 40Raynaud’s syndrome/phenomenon 42Saddle nose deformity 45Sausage-shaped digits (dactylitis) 46Sclerodactyly 48Shawl sign 49Simmonds–Thompson test 50Speed’s test 51Subcutaneous nodules

(rheumatoid nodules) 52Sulcus sign 53Supraspinatus test (empty-can test) 54Swan-neck deformity 55Telangiectasia 57Thomas’ test 59

Tinel’s sign 60Trendelenburg’s sign 61True leg length inequality

(anatomic leg length inequality) 62Ulnar deviation 63V-sign 64Valgus deformity 65Varus deformity 68Yergason’s sign 70

Chapter 2Respiratory Signs 77

Accessory muscle breathing 78Agonal respiration 80Apneustic breathing (also apneusis) 81Apnoea 82Asterixis 85Asymmetrical chest expansion 86Asynchronous respiration 89Ataxic (Biot’s) breathing 90Barrel chest 92Bradypnoea 94Breath sounds 95Breath sounds: bronchial 98Breath sounds: reduced or diminished 99Cough reflex 104Crackles (rales) 107Dahl’s sign and tripod position 110Dyspnoea 111Funnel chest (pectus excavatum) 116Grunting 117Haemoptysis 118Harrison’s sulcus (also Harrison’s

groove) 119Hoover’s sign 121Hypertrophic pulmonary

osteoarthropathy (HPOA) 122Hyperventilation 124Intercostal recession 126Kussmaul’s breathing 127Orthopnoea 129Paradoxical abdominal movements

(also abdominal paradox) 132Paradoxical respiration/breathing 133Paroxysmal nocturnal dyspnoea (PND) 134Percussion 135Percussion: dullness 136Percussion: resonance/hyper-resonance 137Periodic breathing 138Pigeon chest (pectus carinatum) 139Platypnoea/orthodeoxia 140Pleural friction rub 143Pursed-lip breathing (PLB) 144Sputum 145Stertor 146Stridor 147Subcutaneous emphysema/surgical

emphysema 149Tachypnoea 151

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Tracheal tug 153Trepopnoea 154Vocal fremitus/tactile fremitus 155Vocal resonance 156Wheeze 157

Chapter 3Cardiovascular Signs 165

Apex beat (also cardiac impulse) 166Apex beat: displaced 167Apex beat: double or triple impulse 168Apex beat: hyperdynamic apical

impulse/volume-loaded 169Apex beat: left ventricular

heave/sustained apical impulse/pressure-loaded apex 170

Apex beat: tapping 171Arterial pulse 172Arterial pulse: anacrotic pulse 175Arterial pulse: bigeminal 176Arterial pulse: dicrotic 177Arterial pulse: pulsus alternans 178Arterial pulse: pulsus bisferiens 180Arterial pulse: pulsus parvus et tardus 182Arterial pulse: sinus arrhythmia 184Bradycardia 185Buerger’s sign 187Capillary return decreased/delayed 188Cardiac cachexia 190Carotid bruit 192Cheyne–Stokes breathing 193Clubbing 196Crackles (also rales) 198Cyanosis 199Cyanosis: central 200Cyanosis: peripheral 202Ewart’s sign 203Hepatojugular reflux

(also abdominojugular reflux) 204Hypertensive retinopathy 206Hypertensive retinopathy:

arteriovenous (AV) nipping (or AV nicking) 207

Hypertensive retinopathy: copper and silver wiring 208

Hypertensive retinopathy: cotton wool spots 209

Hypertensive retinopathy: microaneurysms 210

Hypertensive retinopathy: retinal haemorrhage 211

Hypertrophic obstructive cardiomyopathy murmur 212

Janeway lesions 214Jugular venous pressure (JVP) 215JVP: Kussmaul’s sign 217JVP: raised 219JVP: the normal waveform 221

JVP waveform variations: a-waves – cannon 222

JVP waveform variations: a-waves – prominent or giant 224

JVP waveform variations: v-waves – large 226

JVP waveform variations: x-descent – absent 227

JVP waveform variations: x-descent – prominent 228

JVP waveform variations: y-descent – absent 229

JVP waveform variations: y-descent – prominent (Friedrich’s sign) 231

Mid-systolic click 233Mitral facies 235Mottling 236Murmurs 237Murmurs – systolic: aortic stenotic

murmur 238Murmurs – systolic: mitral

regurgitation murmur 241Murmurs – systolic: pulmonary

stenotic murmur 243Murmurs – systolic:

tricuspid regurgitation murmur (also Carvello’s sign) 244

Murmurs – systolic: ventricular septal defect murmur 246

Murmurs – diastolic: aortic regurgitation 248

Murmurs – diastolic: eponymous signs of aortic regurgitation 250

Murmurs – diastolic: Graham Steell murmur 252

Murmurs – diastolic: mitral stenotic murmur 253

Murmurs – diastolic: opening snap (OS) 254

Murmurs – diastolic: pulmonary regurgitation murmur 255

Murmurs – diastolic: tricuspid stenotic murmur 256

Murmurs – continuous: patent ductus arteriosus murmur 257

Osler’s nodes 259Passive leg raise with blood pressure

or pulse pressure change 260Pericardial knock 261Pericardial rub 262Peripheral oedema 263Pulse pressure 267Pulse pressure: narrow 268Pulse pressure variation 270Pulse pressure: widened 274Pulsus paradoxus 277Radial–radial delay 281Radio-femoral delay 282Right ventricular heave 283Roth spots 284


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S1 (first heart sound): normal 286S1 (first heart sound): accentuated 287S1 (first heart sound): diminished 288S2: loud (or loud P2 – pulmonary

component of second heart sounds) 289S3 (third heart sound) 290S4 (fourth heart sound) 291Skin turgor: decreased 292Splinter haemorrhages 293Splitting of the heart sounds 294Splitting heart sounds:

physiological splitting 295Splitting heart sounds: paradoxical

(reverse) splitting 297Splitting heart sounds:

widened splitting 299Splitting heart sounds:

widened splitting – fixed 300Tachycardia (sinus) 301Xanthelasmata 303

Chapter 4Haematological and Oncological Signs 313

Angular stomatitis 314Atrophic glossitis 315Bone tenderness/bone pain 316Chipmunk facies 319Conjunctival pallor 321Ecchymoses, purpura and petechiae 322Gum hypertrophy (gingival hyperplasia) 325Haemolytic/pre-hepatic jaundice 326Koilonychia 329Leser–Trélat sign 330Leucoplakia 331Lymphadenopathy 332Neoplastic fever 337Peau d’orange 338Prostate (abnormal) 340Rectal mass 341Trousseau’s sign of malignancy 342

Chapter 5Neurological Signs 347

Guide to the ‘Relevant neuroanatomy and topographical anatomy’ boxes 349

Abducens nerve (CNVI) palsy 351Anisocoria 355Anosmia 360Argyll Robertson pupils and light–near

dissociation 363Ataxic gait 366Atrophy (muscle wasting) 369Babinski response 373Bradykinesia 375Broca’s aphasia (expressive aphasia) 378Brown-Séquard syndrome 381

Brudzinski sign 384Cavernous sinus syndrome 385Clasp-knife phenomenon 388Clonus 389Cogwheel rigidity 391Corneal reflex 393Crossed-adductor reflex 396Dysarthria 397Dysdiadochokinesis 399Dysmetria 401Dysphonia 403Essential tremor 405Facial muscle weakness (unilateral) 407Fasciculations 412Gag reflex 414Gerstmann’s syndrome 417Glabellar tap (Myerson’s sign) 419Global aphasia 420Grasp reflex 422Hand dominance 423Hearing impairment 424Hemineglect syndrome 427High stepping gait 429Hoarseness 432Hoffman’s sign 435Horner’s syndrome 437Hutchinson’s pupil 441Hutchinson’s sign 443Hyperreflexia 444Hyporeflexia and areflexia 447Hypotonia 452Intention tremor 454Internuclear ophthalmoplegia (INO) 456Jaw jerk reflex 458Jolt accentuation 460Kernig’s sign 461Light–near dissociation 462Myotonia – percussion, grip 465Oculomotor nerve (CNIII) palsy 467Optic atrophy 474Orbital apex syndrome 476Palmomental reflex 479Papilloedema 480Parkinsonian gait 482Parkinsonian tremor 483Photophobia 484Physiological tremor 486Pinpoint pupils 487Pronator drift 492Ptosis 495Relative afferent pupillary defect

(RAPD) (Marcus Gunn pupil) 498Rigidity 501Romberg’s test 503Sensory level 505Sensory loss 507Spasticity 516Sternocleidomastoid and

trapezius muscle weakness (accessory nerve [CNXI] palsy) 518


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Tongue deviation (hypoglossal nerve [CNXII] palsy) 520

Trochlear nerve (CNIV) palsy 522Truncal ataxia 526Uvular deviation 528Vertical gaze palsy 530Visual acuity 532Visual field defects 535Waddling gait (bilateral

Trendelenburg gait) 541Wallenberg’s syndrome

(lateral medullary syndrome) 543Weakness 545Wernicke’s aphasia (receptive aphasia) 558

Chapter 6Gastroenterological Signs 571

Ascites 572Asterixis (also hepatic flap) 581Bowel sounds 582Bowel sounds: absent 583Bowel sounds: hyperactive

(borborygmus) 585Bowel sounds: tinkling 586Caput medusae 587Cheilitis granulomatosa 589Coffee ground vomiting/bloody

vomitus/haematemesis 590Courvoisier’s sign 592Cullen’s sign 594Erythema nodosum 596Grey Turner’s sign 598Guarding 599Gynaecomastia 600Haematuria 603Hepatic encephalopathy 605Hepatic foetor 608Hepatic venous hum 609Hepatomegaly 610Jaundice 612Kayser–Fleischer rings 616Leuconychia 618McBurney’s point tenderness

(Surgical sign) 620Melaena 621Mouth ulcers (aphthous ulcer) 622Muehrcke’s lines 623Murphy’s sign (Surgical sign) 624Obturator sign (Surgical sign) 625Oliguria/anuria 627Palmar erythema 629Pruritic scratch marks/pruritus 632Psoas sign (Surgical sign) 636Pyoderma gangrenosum 637Rebound tenderness (Surgical sign) 638Rigidity and involuntary guarding

(Surgical sign) 639Rovsing’s sign (Surgical sign) 640Scleral icterus 641

Sialadenosis 642Sister Mary Joseph nodule

(Surgical sign) 643Spider naevus 644Splenomegaly 646Steatorrhoea 649Striae 651Uveitis/iritis 652

Chapter 7Endocrinological Signs 661

Acanthosis nigricans (AN) 662Angioid streaks 665Atrophic testicles 666Ballotable kidney 668Bruising 669Chvostek’s sign 671Cushingoid habitus 673Diabetic amyotrophy

(lumbar plexopathy) 675Diabetic retinopathy 676Frontal bossing 680Galactorrhoea 681Goitre 684Granuloma annulare 686Graves’ ophthalmopathy

(orbitopathy) 687Hirsutism 692Hypercarotinaemia/carotenoderma 694Hyperpigmentation and bronzing 696Hyperreflexia 699Hyperthyroid tremor 700Hyporeflexia/delayed ankle jerks

(Woltman’s sign) 701Hypotension 703Macroglossia 706Necrobiosis lipoidica

diabeticorum (NLD) 708Onycholysis (Plummer’s nail) 709Pemberton’s sign 710Periodic paralysis 712Plethora 713Polydipsia 715Polyuria 716Polyuria: Cushing’s syndrome 719Pre-tibial myxoedema

(thyroid dermopathy) 720Prognathism 722Proximal myopathy 723Skin tags (acrochordon) 726Steroid acne 727Trousseau’s sign 728Uraemic frost 729Vitiligo 730Webbed neck

(pterygium colli deformity) 732

Figure credits 739Index 746


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Acidotic states: diabetic ketoacidosis

Kussmaul’s respiration 127

AcromegalyFrontal bossing 680Acanthosis nigricans 662Prognathism 722Skin tags 726

Addison’s diseaseHyperpigmentation 696Hypotension 703Vitiligo 730

Airway obstructionStertor 146Stridor 147

Anaemia and nutrient deficiencyDyspnoea 111Hyperventilation 124Intercostal recession 126Angular stomatitis 314Atrophic glossitis 315Koilonychia 329Conjunctival pallor 321Jaundice 612Cyanosis 199Tachycardia 301Hyperdynamic/volume-loaded beat 169Carotid bruit 192Widened pulse pressure 274Diminished S1 288

Ankle/foot signsCharcot foot 17Simmonds –Thompson test 50Valgus deformity 65Varus deformity 68

Aortic regurgitationHyperdynamic/volume-loaded beat 169Pulsus bisferiens 180Diastolic murmur 250Austin Flint murmur 250Becker’s sign 250Corrigan’s sign 250De Musset’s sign 250Duroziez’s sign 250Gerhardt’s sign 251Hill’s sign 251Mayne’s sign 251Müller’s sign 251Quincke’s sign 251

Traube’s sign 251Widened pulse pressure 274

Aortic stenosisLeft ventricular heave/sustained apical

impulse/pressure-loaded apex 170Displaced apex beat 167Anacrotic pulse 175Pulsus parvus 182Pulsus tardus 182Ejection systolic murmur 238Narrow pulse pressure 268S4 (fourth heart sound) 291Paradoxical splitting of the heart

sounds 297

AphasiaWernicke’s aphasia 558Broca’s aphasia 378Global aphasia 420

AppendicitisMcBurney’s point tenderness 620Obturator sign 625Rovsing’s sign 640Psoas sign 636

Atrial septal defect/ventricular septal defect

Platypnoea 140Hyperdynamic/volume-loaded beat 169Displaced apex beat 167Pansystolic murmur 237Splitting heart sounds:

widened splitting: fixed 300

AsthmaTachypnoea 151Respiratory distress signs 117, 126, 133,

134, 140, 153Cough 104Wheeze 157Pulsus paradoxus 277Dyspnoea 111Intercostal recession 126Paradoxical respiration 133

BronchiectasisCough 104Crackles 107Dyspnoea 111Hyperventilation 124Intercostal recession 126Paradoxical respiration 133Sputum 145

Contents by Condition

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Cardiac tamponade/pericardial effusion

Bigeminal pulse 176Ewart’s sign 203Jugular venous pressure (JVP): raised 219JVP: prominent x-descent 228JVP: absent y-descent 229Pulsus paradoxus 277

Cerebellar signsDysdiadochokinesis 399Dysmetria 401Dysarthria 397Hypotonia 452Truncal ataxia 526Romberg’s test 503Pronator drift 492

Chronic renal failureBruising 669Uraemic frost 729Pruritic marks 632Peripheral oedema 263

Congestive heart failureCough 104Wheeze 157Crackles 107Tachypnoea 151Hyperventilation 124Intercostal recession 126Orthopnoea 129Paroxysmal nocturnal dyspnoea 134Pulsus alternans 178S3 (third heart sound) 290Ascites 572Caput medusae 587Splenomegaly 646Displaced apex beat 167Bigeminal pulse 176Dicrotic pulse 177Pulsus alternans 178Cardiac cachexia 190Cheyne–Stokes respiration 193Cyanosis 199Hepatojugular reflux 204Hepatomegaly 610Raised jugular venous pressure 219Kussmaul’s sign 217Peripheral oedema 263Narrow pulse pressure 268Tachycardia 301

Chronic obstructive pulmonary disease (COPD)

Dyspnoea 111Harrison’s sulcus 119Tachypnoea 151Pursed-lip breathing 144Barrel chest 92

Crackles 107Wheeze 157Hyperventilation 124Clubbing 196Intercostal recession 126Paradoxical respiration 133Hyper-resonance to percussion 137Vocal fremitus 155Vocal resonance 156Breath sounds: reduced 99Dahl’s sign 110

Cranial nerve signsVisual acuity 532Oculomotor (CNIII) palsy 467Trochlear (CNIV) palsy 522Abducens (CNVI) palsy 351Facial muscle weakness 407Gag reflex 414Relative afferent pupillary defect

(Marcus Gunn pupil) 498Jaw jerk reflex 458Corneal reflex 393Tongue deviation 520Sternocleidomastoid weakness 518Uvular deviation 528Hoarseness 432Dysarthria 397Hearing impairment 424

Cushing’s syndromeBruising 669Central adiposity 673Buffalo hump 673Moon facies 673Striae 651Hirsutism 692Plethora 713Polyuria 716Proximal myopathy 723Steroid acne 727Gynaecomastia 600

Cystic fibrosisHarrison’s sulcus 119Intercostal recession 126Sputum 145

DermatomyositisShawl sign 49Gottron’s papules 22V-sign 64Proximal myopathy 723Calcinosis 15Heliotrope rash 25Telangiectasia 57

DiabetesAcanthosis nigricans 662Charcot foot 17


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Diabetic amyotrophy 675Diabetic retinopathy 676Granuloma annulare 686Necrobiosis lipoidica diabeticorum 708Polyuria 716Polydipsia 715Skin tags 726Steroid acne 727Cotton wool spots 209Xanthelasmata 303

EndocarditisClubbing 196Janeway lesions 214Roth spots 284Osler’s nodes 259Splinter haemorrhages 293

Fluid StatusTachycardia 301Hypotension 703Capillary return decreased/delayed 188Passive leg raise 260Pulse pressure variation 270Skin turgor: reduced 292Oliguria 627Narrow pulse pressure 268

Gait abnormalitiesAtaxic gait 366High stepping gait 429Parkinsonian gait 482Spasticity 541Waddling gait 195

HaemochromatosisHyperpigmentation 696

Heart blockBradycardia 185Cannon a-waves 222

Hip signsApparent leg length 5Patrick’s test (FABER test) 37Thomas’ test 59Trendelenburg’s sign 61True leg length discrepancy 62Valgus deformity 65Varus deformity 68

HypertensionLeft ventricular heave/sustained apical

impulse/pressure-loaded apex 170Displaced apex beat 167Av nipping 207Copper wiring 208Silver wiring 208Microaneurysms 210Retinal haemorrhage 211

Cotton wool spots 209S4 (fourth heart sound) 291

HyperthyroidismGynaecomastia 600Palmar erythema 629Goitre 684Graves’ ophthalmopathy 687Lid lag 688Von Graefe’s sign 689Chemosis 690Lagophthalmos 689Abadie’s sign 689Dalrymple’s sign 689Griffith’s sign 689Diplopia 690Ballet’s sign 690Proptosis 690Riesman’s sign 690Hyperreflexia 444Hyperthyroid tremor 700Onycholysis 709Pemberton’s sign 710Periodic paralysis 712Pre-tibial myxoedema 720Proximal myopathy 723Vitiligo 730

Hypertrophic obstructive cardiomyopathy

Left ventricular heave/sustained apical impulse/pressure-loaded apex 170

Pulsus bisferiens 180Narrow pulse pressure 268S4 (fourth heart sound) 291Apex beat: double or triple impulse 168

HypocalcaemiaChvostek’s sign 671Trousseau’s sign 728

HypothyroidismGoitre 684Hyporeflexia/delayed ankle jerks 701Hypotension 703Macroglossia 706Pemberton’s sign 710Proximal myopathy 723

Inflammatory bowel diseaseUveitis/iritis 652Erythema nodosum 596Mouth ulcer 622Pyoderma gangrenosum 637

Knee signsAnterior drawer test 2Apley’s grind test 3Bulge/wipe/stroke test 12Crepitus 19


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Lachman’s test 28McMurray’s test 32Patellar apprehension test 35Patellar tap 36Valgus deformity 65Varus deformity 68

Left bundle branch blockParadoxical splitting of heart sounds 297

Leukaemia/lymphomaLymphadenopathy 332Gum hypertrophy 325Splenomegaly 646

Liver disease/cirrhosisAscites 572Atrophic testicles 666Hepatic flap/asterixis 581Caput medusae 587Clubbing 196Gynaecomastia 600Hepatic encephalopathy 605Hepatic foetor 608Jaundice 612Hepatomegaly 610Leuconychia 618Muehrcke lines 623Palmar erythema 629Platypnoea 140Pruritic scratch marks 632Scleral icterus 641Spider naevus 644Splenomegaly 646Peripheral oedema 263

Lung cancer malignancy: primary or secondary

Hypertrophic pulmonary osteoarthropathy 122

Cough 104Haemoptysis 118Bronchial breath sounds 98Crackles 107Hyperventilation 124Intercostal recession 126Pemberton’s sign 710Sputum 145Vocal fremitus 155Vocal resonance 156

Malignancy: otherBone pain 316Lymphadenopathy 332Leser–Trélat sign 330Virchow’s node 336Neoplastic fever 337Trousseau’s sign of malignancy 342Hepatomegaly 610Sister Mary Joseph nodule 643

MeningitisBrudzinski sign 384Jolt accentuation 460Kernig’s sign 461Photophobia 484

Mitral regurgitationHyperdynamic/volume-loaded beat 169Displaced apex beat 167Pansystolic murmur 237Right ventricular heave 283Diminished S1 288

Mitral stenosisMitral facies 235Diastolic rumbling murmur 253Opening snap 254Narrow pulse pressure 268Right ventricular heave 283Accentuated S1 287Diminished S1 288Plethora 713Apex beat: tapping 171

OsteoarthritisCrepitus 19Boutonnière deformity 10Heberden’s nodes 9Bouchard’s nodes 9

Parkinson’s diseaseClasp-knife phenomenon 388Rigidity 501Cogwheel rigidity 391Parkinsonian tremor 483Glabellar reflex/tap 419Bradykinesia 375

Patent ductus arteriosisHyperdynamic/volume-loaded beat 169Displaced apex beat 167Pulsus bisferiens 180Continuous/machinery murmur 257

Pericarditis/constrictive pericarditisKussmaul’s sign 217Pericardial knock 261Pericardial rub 262

Pleural effusionAsymmetrical chest expansion 86Bronchial breath sounds 98Dyspnoea 111Intercostal recession 126Dullness to percussion 136Breath sounds: reduced 99

PneumoniaAsymmetrical chest expansion 86Bronchial breath sounds 98


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Cough 104Wheeze 157Crackles 107Dyspnoea 111Hyperventilation 124Intercostal recession 126Paradoxical respiration 133Dullness to percussion 136Pleural rub 143Sputum 145Vocal fremitus 155Vocal resonance 156

PneumothoraxHyper-resonance to

percussion 137Vocal fremitus 155Tachypnoea 151Dyspnoea 111Asymmetrical chest expansion 86

PowerWeakness: various patterns 545Muscle wasting 369

Psoriatic arthritisOnycholysis 709Psoriatic nails 40Sausage-shaped digits 46

Pulmonary embolusTachypnoea 151Cough 104Dyspnoea 111Haemoptysis 118Hyperventilation 124Intercostal recession 126Paradoxical respiration 133Pleural rub 143Right ventricular heave 283Tachycardia 301

Pulmonary fibrosisCrackles 107Dyspnoea 111Tachypnoea 151Cough 104Harrison’s sulcus 119Hyperventilation 124Intercostal recession 126

Pulmonary hypertensionRaised jugular venous pressure 219S2 loud 289Right ventricular heave 283Kussmaul’s sign 217Giant a-waves 224Large v-waves 226Graham Steell murmur 252Split S1 294

Pulmonary regurgitationDiastolic murmur 255

Pulmonary stenosisEjection systolic murmur 238Right ventricular heave 283Split S1 294

ReflexesJaw jerk reflex 458Gag reflex 414Crossed-adductor reflex 396Corneal reflex 393Grasp reflex 422Palmomental reflex 479Glabellar reflex/tap 419Hyperreflexia 444Hyporeflexia and areflexia 447

Renal failureGynaecomastia 600Leuconychia 618Pruritic marks 632

Rheumatoid arthritisSubcutaneous rheumatoid

nodules 52Swan-neck deformity 55Ulnar deviation 63Pleural friction rub 143

Right bundle branch blockSplit S1 294

SclerodermaSclerodactyly 48Telangiectasia 57Splinter haemorrhages 293Calcinosis/calcinosis cutis 15

SensationSensory level 505Sensory loss patterns 507

SepsisBigeminal pulse 176Dicrotic pulse 177Widened pulse pressure 274Mottling 236

Shoulder signsApley’s scratch test 4Apprehension test (crank test) 7Apprehension–relocation test

(Fowler’s test) 8Dropped arm test 20Hawkins’ impingement sign/test 23Neer’s impingement sign 33Speed’s test 51Sulcus sign 53


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Supraspinatus test (empty-can test) 54Yergason’s sign 70

Solid malignanciesBone pain 316Lymphadenopathy 332Leser–Trélat sign 330Virchow’s node 336Neoplastic fever 337Trousseau’s sign of malignancy 342Hepatomegaly 610Petechiae 322Ecchymoses 322Purpura 322

Surgical signsMcBurney’s point tenderness 620Obturator sign 625Rovsing’s sign 640Psoas sign 636Rigidity and guarding 639Murphy’s sign 624Bowel sounds 582Sister Mary Joseph nodule 643Rectal mass 341

Systemic lupus erythematosusMouth ulcer 622Butterfly rash 13Telangiectasia 57Calcinosis 15Livedo reticularis 29Pleural friction rub 143Raynaud’s syndrome 42

ToneClasp-knife phenomenon 388Hypotonia 452Myotonia 465Spasticity 516

TremorEssential tremor 405Intention tremor 454Parkinsonian tremor 483Physiological tremor 486

Tricuspid regurgitationLarge v-wave 226Raised jugular venous pressure 219Absent x-descent of jugular venous

pressure 227Pansystolic murmur 237Tachycardia 301

Tricuspid stenosisDiastolic murmur 256

Vision defects/neurological eye signsVisual acuity 532Altitudinal scotoma 536, 537Bitemporal hemianopia 537Central scotoma 537, 539Tunnel vision 537Homonymous hemianopia with

macular sparing 537, 539Homonymous hemianopia 537Homonymous quadrantanopia 537Horner’s syndrome 437Ptosis 495Papilloedema 480Photophobia 484Orbital apex syndrome 476Optic atrophy 474Internuclear ophthalmoplegia 456Relative afferent pupillary defect

(Marcus Gunn pupil) 498Pinpoint pupils 487Light–near dissociation

(Argyll Robertson pupil) 363Anisocoria 355


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Foreword

In the 21st-century world of advanced imaging and other diagnostic techniques, it is tempting to consign clinical signs from careful physical examination to the ‘dustbin of history’. This would be a terrible error. Not only are physical signs and their accurate interpretation of primary importance in resource-poor environments, they are also necessary to allow clinicians to triage appropriate further high-technology investigations and to appropriately question those results when they do not tally with the physical signs obtained. These are vital skills for every medical student and qualified practitioner.

Some physical signs are very difficult, such as JVP interpretation in the obese patient or hearing the abdominal bruit in the young hypertensive patient with renal artery stenosis. Some signs are easy to elicit but too easily forgotten, such as the ‘tell-tale’ radio-femoral delay of aortic coarctation. A careful understanding of the mechanisms of clinical signs not only adds to the intellectual satisfaction of understanding disease pathophysiology, but also provides the key learning reinforcement to appreciate the value of a thorough and caring physical examination.

This book is well organised; there are systems-based chapters (such as musculoskeletal, respiratory etc.) and then short sub-sections on common signs, arranged in alphabetical order. Almost each sign is illustrated by a photograph, a figure and/or a relevant diagram. The large font and clearly drawn diagrams render this a very easy-to-read and comprehensible tour-de-force of medical education. Readers will use it as a specific reference for particular questions, or as a book to read from cover-to-cover, to optimise their ability to interpret signs and to practise maximally effective ‘laying on of hands’. To my knowledge, there is no other book quite like it.

This is the second edition of Mechanisms of Clinical Signs and it remains a clear and thorough reference covering the major aspects of clinically apparent manifestations of human disease. The second edition contains additional features of interest and importance such as audio and video files, as well as easy-to-follow ‘flow diagrams’ and highlighted ‘Clinical Pearls’.

This textbook will be a joy for medical trainees both at medical school and at postgraduate level. Even seasoned clinicians will enjoy learning more about the mechanisms behind many of the clinical signs that they elicit on a frequent basis. As practised by our medical forebears, clinical history and physical examination remain the underpinnings of accurate diagnosis and our ability to serve our patients well. This book provides a wonderful resource to those wishing to become more complete physicians.

David S Celermajer AO MB BS PhD DSc FRACP

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Preface

Much has changed in the three years since the release of the first edition of this book. Accurate physical exam interpretation remains pertinent to medical decision making in an age of readily available advanced diagnostic tests. The authors are grateful for and heartened by the feedback from students and junior and senior clinicians alike who have found the first edition valuable in patient care.

Reader feedback has driven the updates and improvements to the second edition. The same focus remains – understanding the mechanisms of clinical signs in medicine. There is a fine line between too much content and oversimplification – the authors have strengthened some entries and simplified others. Several new clinical signs have been added to the text. Many new photographs, illustrations and flow diagrams are available to improve understanding. Finally, in this technological age, it would be remiss if a textbook was not enhanced by the use of online material. Audio and video files, demonstrating and/or explaining signs, are available to the reader.

The evidence base for each clinical sign has been re-examined. The predictive value for a sign has been reviewed and revised where possible. Signs of particular clinical value have been highlighted under the heading ‘Clinical Pearl’.

In many ways modern medicine has become more algorithmic or guideline focused. The accurate retrieval and interpretation of bedside patient information via the history and physical exam remains the art and science of medicine and the foundation upon which all good clinical decisions are made.

Acknowledgements

The authors would like to thank their families and friends for their unwavering support: it takes a village. Finally, to all the medical students who continue to ask ‘why’ and who have, with more senior clinician guidance, provided direction for improvements of the text – thank you.

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Sign Value

Eliciting or identifying a clinical sign is a requisite skill in medicine – however, it is merely the beginning of the story. More importantly, a good clinician understands a sign’s predictive value, evidence base and role in diagnostic evaluation. The presence or absence of a clinical sign offers a data point, allowing us to refine the probability of the disease of interest as the differential diagnosis (i.e. the process of risk stratification).

In the Sign Value section, the reader will find a brief précis of the evidence base for the given sign, including (where available), sensitivity, specificity, positive or negative predictive values and/or likelihood ratios. With a positive LR (sign is present) or negative LR (sign is absent) value, one can determine the post-test probability of disease, using the following equation (a component of Bayesian Theory):

Pre-test probability likelihood ratio post-test probabilit× = yy

Example:A 20-year-old, immunocompetent, male student presents to his local Emergency Department, complaining of severe headache. The junior doctor assessing him notes that he appears toxic, is febrile and has a non-blanching purpuric rash and non-focal neurological signs. The doctor specifically identifies the absence of Kernig’s sign. The entire clinical scenario is suspicious for bacterial meningitis due to Neisseria meningitides, complicated by meningococcaemia. This patient has a very high pre-test probability of bacterial meningitis. The absence of Kernig’s sign (–LR 1.0) does not affect the probability of meningitis being present.

Very high pre test probability very high post test probabili- -× =1 0. tty

It is critical to understand the predictive value of the presence or absence of a clinical sign. The junior clinician should not be swayed by the absence of Kernig’s sign. This patient requires emergent administration of IV antibiotics, lumbar puncture and public health notification. CT imaging prior to lumbar puncture may be considered in certain clinical scenarios.

The sensible clinician will judiciously consider examination findings and/or diagnostic tests and how they affect the probability of the diagnosis and management plan.

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Chapter 1

Musculoskeletal signs

Dennis_2371_Chapter 1_main.indd 1 7/7/2015 5:41:17 PM

To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter Toppan Best-set. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication.

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anterior drawer test

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anterior drawer test

Mechanism/sThe ACL arises from the anterior aspect of the tibial plateau and inserts into the medial aspect of the lateral femoral condyle. It limits anterior movement of the tibia upon the femur. Loss of continuity of the ACL permits inappropriate anterior movement of the tibia and thus knee joint instability.

sign valueA literature review of six studies reported a sensitivity of 27–88%, specificity of 91–99%, positive LR of 11.5 and negative LR of 0.5.2 A literature review by Solomon DH et al. of nine studies reported a sensitivity of 9–93% and specificity of 23–100%.1

A positive anterior drawer sign (+LR 11.5)2 is strong evidence of ACL injury. A negative anterior drawer sign cannot reliably exclude ACL injury (sensitivity 27–88%; –LR 0.5).2 When significant clinical suspicion persists, despite a negative anterior drawer sign, further diagnostic considerations are necessary (e.g. interval re-examination, MRI, arthroscopy).

DescriptionWith the patient lying supine, the knee at 90° flexion and the foot immobilised by the examiner, the proximal third of the tibia is pulled towards the examiner. In a positive test, there is anterior (forward) movement of the tibia without an abrupt stop.1

condition/s associated with

• Anterior cruciate ligament (ACL) injury

FIGUre 1.1 Anterior drawer test for anterior cruciate ligament injury

90º



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apley’s grind test

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1apley’s grind test

to the lower leg. The test is considered positive if tenderness is elicited.

condition/s associated with

• Meniscal injury

Mechanism/sDirect mechanical force upon the injured meniscus elicits tenderness.

sign valueA review by Hegedus EJ et al. reported a pooled sensitivity of 60.7% and specificity of 70.2% with an odds ratio of 3.4.3 Significant heterogeneity in the data limits its accuracy. Overall, Apley’s grind test has limited diagnostic utility, limited supporting data and, in the acute setting, the manoeuvre produces severe pain.4

McMurray’s grind test has more robust supporting data.

DescriptionWith the patient lying prone and the knee at 90° flexion, the lower leg is passively internally and externally rotated while axial pressure is applied

FIGUre 1.2 Apley’s grind test



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Chapter 2

RespiRatoRy signs



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Respiratory system revisited

apart from the lungs, the respiratory system is made up of three main components: the central control centre, sensors and effectors.

the brainstem contains several centres in the pons and medulla, which (in addition to other parts of the brain) regulate inspiration and expiration. it receives information from a variety of receptors that monitor the partial pressure of oxygen and carbon dioxide as well as the stretch and compliance of the lung and irritants in the lung and upper airways. the central control system sends messages via nerve fibres such as the phrenic nerve to control respiratory rate and depth of breathing, in response to the data it receives.

Damage, disruption or alterations to any of these three – brainstem, nerves, receptors – can cause specific signs.

FIGUre 2.1 Simplified respiratory control

Based on West JB, West’s Respiratory Physiology, 7th edn, Philadelphia: Lippincott Williams & Wilkins, 2005: Fig 8-1.

Central control

Areas located in brainstem

Sensors

Chemoreceptors, lungreceptors

Effectors

Nerves to respiratory musclesand the respiratory muscles

themselves



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Condition/s associated withAny state resulting in an increased effort of breathing:

• Chronic obstructive pulmonary disease (COPD)

• Asthma

• Pneumonia

• Pneumothorax

• Pulmonary embolism

• Congestive heart failure (CHF)

Mechanism/sIn times of increased respiratory effort, the accessory muscles of breathing are invoked to exaggerate the normal respiratory process. Use of the accessory muscles can create more negative intrathoracic pressure on inspiration (pulling more air in and possibly causing tracheal tug) and more positive pressure on expiration (pushing air out).

On inspiration, the scalene and sternocleidomastoid muscles help lift and expand the chest wall, allowing for a decrease in intrathoracic pressure and increased air entry.

On expiration, the abdominal muscles help push air out of the lungs.

sign valueThe use of accessory muscles is a non-specific finding but is valuable in assessing the severity of respiratory difficulty (i.e. the ‘work’ of breathing). More than 90% of acute exacerbations of COPD present with accessory muscle use.1 One study showed a sensitivity of 39% and specificity of 89% with a PLR of 4.75.2 In children, accessory muscle use is a clear sign of increased respiratory effort.

FIGUre 2.2 Physiology behind accessory muscle respiration

Decreased O2, increased CO2,exercise, stressed states

Increased respiratory effort stimulated by brainstem

Activation of scalene, sternocleidomastoid muscles

First two ribs and sternum raised

Increased intrathoracic volume

Further decreased intrathoracic pressure

Increased pressure gradient

Greater volume inspired

VIdeo 2.1

Video 2.1 access through student Consult.

DescriptionNormal inspiration involves only the diaphragm. Expiration occurs passively due to elastic recoil of the lungs. When inspiratory effort requires the use of the sternocleidomastoid, scalene, trapezius, internal intercostal and abdominal muscles, the ‘accessory muscles’ of breathing are said to be in use.



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agonal respiration

VIdeo 2.2

Video 2.2 access through student Consult.

DescriptionSlow inspirations with irregular pauses. Patients are often described as gasping for air. Agonal breathing is usually closely followed by death unless intervention is provided.

Condition/s associated withAny aetiology leading to imminent death.

Mechanism/sAgonal respiration is thought to be a brainstem reflex, providing a last-ditch

respiratory effort for the body to try to save itself. It is thought of as the last respiratory effort before terminal apnoea.3

sign valueWithout intervention, agonal respiration heralds impending death. Studies have shown that recognition of agonal breathing may improve recognition of cardiac arrest,4 and implementation of protocols designed to identify agonal breathing over the phone can significantly increase the diagnosis of cardiac arrest by emergency dispatchers.5 It is absolutely a sign that must be managed without delay.



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Chapter 3

CardiovasCular signs



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apex beat (also cardiac impulse)

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apex beat (also cardiac impulse)

The normal impulse is described as a brief outward thrust occurring in early systole and will disappear before S2 is heard. It coincides with isovolumetric contraction.

descriptionThe normal cardiac impulse or ‘apex beat’ should be felt in the left fifth intercostal space in the midclavicular line over an area 2–3 cm2 in diameter.1



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apex beat: displaced

Mechanism/sThe displacement of the apex beat is related to changes in the heart size, whether via hypertrophy of the muscle (e.g. aortic stenosis and left ventricular hypertrophy), dilatation of the heart (e.g. dilated cardiomyopathy) or displacement of the heart (tension pneumothorax). With enlargement and/or dilatation of the heart, the apex moves laterally/downwards.

sign valueIf detected, a valuable sign.

Kelder et al. found after a review of over 700 patients that in suspected heart failure, a displaced apex had the strongest predictive value out of clinical signs assessed.2

One systematic review of 10 000 patients looked at history, examination findings, chest radiography and natriuretic peptides. A displaced apex beat had a pooled PLR (Positive Likelihood Ratio) of 16 (8.2–30.9) for left ventricular systolic dysfunction, which was higher than the other elements analysed in the systematic review.3

The displaced apex beat may not be frequently detected; thus its absence does not rule out systolic dysfunction.

descriptionNormally the apex beat of the heart is palpated in the left fifth intercostal space in the midclavicular line. A ‘displaced’ apex beat usually implies that the impulse is felt lateral to the midclavicular line or more distally.

Condition/s associated withSimilar conditions to the pressure- and volume-loaded beats described below.

More common• Skeletal abnormality – scoliosis or

pectus excavatum

• Left ventricular enlargement of any cause – apex is usually displaced downwards and laterally

• Right ventricular enlargement of any cause – apex is displaced laterally

• Cardiomyopathies and dilatation of the heart

• Congestive heart failure

• Valvular heart disease

Less common• Situs inversus dextrocardia/isolated

dextrocardia

• Intra-thoracic disorders e.g. tension pneumothorax, large right pleural effusion



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Chapter 4

Haematological and oncological

SignS



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angular stomatitis

condition/s associated withMore common

•Oralcandidiasis

•Poorlyfittingdentures

•Bacterialinfection

Less common•Nutritionaldeficiencies(especially

riboflavin,ironandpyridoxine)

•Humanimmunodeficiencyvirus(HIV)

nutritional deficiency mechanism/sIronandothernutrientsarenecessarytogenetranscriptionforessentialcellreplication,repairandprotection.Nutrientdeficiencyleadstoimpededprotection,repairandreplacementoftheepithelialcellsontheedgesofthemouthresultinginatrophicstomatitis.

Sign valueThereislimitedevidenceonthevalueofangularstomatitisasasign.

descriptionMaculopapularandvesicularlesionsgroupedontheskinatthecorners(or‘angles’)ofthemouthandmucocutaneousjunction.

FIGUre 4.1 AngularstomatitisNoteatrophicglossitisisalsopresent.

Reproduced, with permission, from Forbes CD, Jackson WF, ColorAtlasandTextofClinicalMedicine, 3rd edn, London: Mosby, 2003.



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atrophic glossitis

micronutrientsneededforcellproliferationorcellmembranestabilisationmayleadtodepapillation.2

Nutritionaldeficiencyisalsothoughttochangethepatternofmicrobialflora,thuscontributingtoglossitis.3

Sign valueThereisgrowingevidencethatatrophicglossitisisamarkerformalnutritionanddecreasedmusclefunction.1Inonelarge-scalestudy,1atrophicglossitiswasfoundin13.2%ofmenand5.6%ofwomenathomeandin26.6%ofmenand37%ofwomeninhospital.Itwasalsocorrelatedwithdecreasedweight,decreasedBMI,pooranthropometrymeasurementsanddecreasedvitaminB12.

Inonestudy4ofpatientswithatrophicglossitis,22.2%ofpatientshadahaemoglobindeficiency,26.7%wereirondeficient,7.4%werevitaminB12deficientand21.6%hadraisedhomocysteineorgastricparietalcellantibodies.

Othersmallercasereports2,5havealsofoundatrophicglossitisusefulinidentifyingmicronutrientdeficiencies.

descriptionTheabsenceorflatteningofthefiliformpapillaeofthetongue.1SeeFigure4.1.

condition/s associated withMore commonAssociatedwithmicronutrientdeficiency,including:

•Irondeficiency

•VitaminB12deficiency

•Folicaciddeficiency

•Thiaminedeficiency

•Niacindeficiency

•VitaminEdeficiency

•Pyridoxinedeficiency

•H.pyloriinfection

Less common•Amyloidosis

•Sjögren’ssyndrome

mechanism/sItisbelievedthatmicronutrientdeficiencyimpedesmucosalproliferation.

Ascellsofthetonguepapillaehaveahighturnover,deficienciesin



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CHAPTER 5

NEUROLOGICAL SIGNS


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Neurological signs

Understanding the clinical significance of neurological signs poses several challenges that require pre-requisite knowledge of:

• neuroanatomy and topographical anatomy (relevant adjacent structures)

• pathophysiology of neurological disorders and relevant adjacent structures

• pattern recognition of multiple clinical signs


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Guide to the ‘Relevant neuroanatomy and topographical anatomy’ boxes

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Guide to the ‘Relevant neuroanatomy and topographical anatomy’ boxes

This chapter includes additional sections in boxes titled ‘Relevant neuroanatomy and topographical anatomy’ depicting the neural pathways and associated non-neural structures. Symbols have been used to signify important components of the relevant anatomical pathways.

For example, the most common mechanism of bitemporal hemianopia is compression of the optic chiasm by an enlarging pituitary macroadenoma.

Key to the symbols used in the ‘Relevant neuroanatomy and topographical

anatomy’ boxes

• Primary neuroanatomical structures in the pathway(s)⇒ Significant topographical anatomical structure(s)→ Associated neuroanatomical pathway(s)∅ Decussation (i.e. where the structure crosses the midline)× An effector (e.g. muscle)⊗ A sensory receptor↔ Structure receives bilateral innervation

The pituitary gland is located directly inferior to the optic chiasm (i.e. the relevant topographical anatomy). The nerve fibres of the optic chiasm supply each medial hemiretina (i.e. the relevant neuroanatomy), and transmit visual information from each temporal visual hemifield. Dysfunction of these nerve fibres causes impaired vision in bilateral lateral visual hemifields (called bitemporal hemianopia).

See the example below.


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Relevant neuroanatomy and topographical anatomy


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DescriptionThere is ipsilateral impaired abduction, and mild esotropia (i.e. medial axis deviation) in the primary gaze position.1 Dysconjugate gaze worsens when the patient looks towards the side of the lesion (see Figure 5.1B).

Condition/s associated with1-3

Common• Diabetic mononeuropathy/

microvascular infarction

• Elevated intracranial pressure (called a ‘false localising sign’)

Less common• Wernicke’s encephalopathy

• Cavernous sinus syndrome

• Cavernous carotid artery aneurysm

• Giant cell arteritis

• Cerebellopontine angle tumour

Mechanism/sAbducens nerve dysfunction causes ipsilateral lateral rectus muscle weakness (see Table 5.1). Abducens nerve palsy is caused by a peripheral lesion of the abducens nerve. Lesions of the abducens nuclei typically result in horizontal gaze paresis (i.e. ipsilateral abduction paresis and contralateral adduction weakness) due to an impaired coordination of conjugate eye movements with the oculomotor motor nuclei, via the medial longitudinal fasciculus (MLF).

Causes of abducens nerve palsy include:

• disorders of the subarachnoid space

• diabetic mononeuropathy, microvascular infarction, and metabolic disorders

• elevated intracranial pressure

• cavernous sinus syndrome – typically multiple cranial nerve abnormalities

• orbital apex syndrome – typically multiple cranial nerve abnormalities.

Disorders of the subarachnoid spaceMass lesions (e.g. aneurysm, tumour, abscess) may compress the abducens nerve as it traverses the subarachnoid space. The abducens nerve emerges from the brainstem adjacent to the basilar and vertebral arteries, and the

Relevant neuroanatomy and

topographical anatomy1,2


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FIGURE 5.1 Right abducens nerve (CNVI) palsy A Primary gaze position with mild esotropia (right eye deviates nasally); B right gaze with impaired abduction; C normal left gaze.

Reproduced, with permission, from Daroff RB, Bradley WG et al., Neurology in Clinical Practice, 5th edn, Philadelphia: Butterworth-Heinemann, 2008: Fig 74-7.

A

C

B

FIGURE 5.2 Anatomy of the abducens nuclei and facial nerve fascicles

Reproduced, with permission, from Yanoff M, Duker JS, Ophthalmology, 3rd edn, St Louis: Mosby, 2008: Fig 9-14-4.

Anatomy of the sixth nerve nucleus in the pons

Fourthventricle

Abducensnucleus

Spinal nucleusand tract of the

trigeminal nerve

Paramedianpontine reticular

formation

Medial longitudinalfasciculus

Corticospinal tract

Sixth nerve

Seventh nerve

Nucleus of facial nerve

Basilar artery


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TABLE 5.1 Mechanisms of clinical features in abducens nerve palsy

Clinical features

Mechanism

• Impaired abduction

→ Lateral rectus muscle weakness

• Esotropia → Unopposed medial rectus muscle

clivus. Aneurysmal dilation of these vessels and/or infectious or inflammatory conditions of the clivus can compress the abducens nerve.1 Often, multiple cranial nerve abnormalities (e.g. CNVI, VII, VIII) coexist since these structures lie in close proximity to one another upon exiting the brainstem.1

Diabetic mononeuropathy and microvascular infarctionDiabetic vasculopathy of the vasa nervorum (i.e. disease of the blood supply of the nerve) may result in microvascular infarction of the abducens nerve.3

Elevated intracranial pressure, the ‘false localising sign’Due to the relatively fixed nature of the abducens nerve at the

pontomedullary sulcus and at the point of entry into Dorello’s canal, it is vulnerable to stretch and/or compression injury secondary to elevated intracranial pressure.1,2 In this setting, abducens nerve palsy is referred to as a ‘false localising sign’ as the clinical findings are not solely due to an isolated peripheral lesion of the abducens nerve. Causes of elevated intracranial pressure include mass lesions (e.g. tumour, abscess), hydrocephalus, idiopathic intracranial hypertension (IIH; formerly called pseudotumour cerebri) and central venous sinus thrombosis.

Cavernous carotid artery aneurysm and cavernous sinus syndromeThe cavernous segment of the abducens nerve is located adjacent to the cavernous carotid artery, and is prone to compression by aneurysmal dilation of the vessel. See ‘Cavernous sinus syndrome’ in this chapter.

Orbital apex syndromeSee ‘Orbital apex syndrome’ in this chapter.

Sign valueAbducens nerve palsy is the most common ‘false localising sign’ in elevated intracranial pressure.


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CHAPTER 6

GASTROENTEROLOGICAL SIGNS


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Ascites

DescriptionA pathological accumulation of fluid in the peritoneal cavity.

Condition/s associated withAs in oedema, variations in oncotic and hydrostatic pressure and vascular wall integrity are central to the development of ascites (see ‘Peripheral oedema’ in Chapter 3, ‘Cardiovascular signs’). All the pathologies that create ascites effect one or more of these factors.

The causes of ascites can be broadly arranged into four categories according to mechanism (see Table 6.1).

Mechanism/sPeripheral arterial vasodilatation theoryThis hypothesis, shown in Figure 6.2, combines two premises: the ‘underfill’ and ‘overflow’ theories. Key initiating elements in both are portal hypertension and nitric oxide-induced splanchnic vasodilatation.

FIGURE 6.1 A person with massive ascites caused by portal hypertension due to cirrhosis

Copyright James Heilman MD.

TABLE 6.1 Causes of ascites

Fluid imbalance (arterial vasodilatation theory)

Exudative

Cirrhosis – common Exudate-secreting tumours (peritoneal carcinomatosis)

Congestive heart failure – common Infections (e.g. TB)

Myxoedema Inflammatory disease (e.g. SLE)

Budd–Chiari syndrome

Chylous NephrogenicObstruction (e.g. malignant lymphoma) Haemodialysis

Iatrogenic (e.g. transection of the lymphatics) Nephrotic syndrome

Retroperitoneal lymph node dissection

Although itself not strictly a sign, a variety of clinical signs indicate the presence of ascites. Having an understanding of the different causes of ascites will assist with interpretation of additional signs present on physical examination.


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6• Overflow theory: Primary renal

sodium retention in patients with cirrhosis causes intravascular hypervolaemia. This increase in intravascular fluid, in turn, causes increased hydrostatic pressure that forces fluid to overflow into the peritoneal cavity.2

Further research following these two theories found that portal hypertension causes the release of nitric oxide and splanchnic bed vasodilatation, which reduces effective arterial blood flow to the kidneys. The RAAS is employed to increase plasma volume, further contributing to fluid overload and ascites.3-5

Contrary to popular belief, hypoalbuminaemia and low oncotic

• Underfill theory: Imbalance in hydrostatic versus oncotic pressure causes the intravascular fluid to leak into the peritoneal cavity.1 The resulting low blood volume activates the renin–angiotensin–aldosterone (RAA) pathway and the sympathetic nervous system to commence renal sodium and fluid retention, in an attempt to maintain volume.1 As more volume is retained the hydrostatic pressure in the sinusoids causes fluid to be pushed out into the interstitial space. If the patient’s lymphatic system is not robust enough to export the additional fluid away, it spills over into the peritoneal cavity to form ascites.

FIGURE 6.2 Mechanisms in the development of ascites

Liver failure, CHF, myxoedema, Budd–Chiari syndrome

Portalhypertension

Endothelialdysfunction

Splanchnic vasodilatation

Reduced effective circulation volume

Neurohormonal compensation: RAAS activated,increased sympathetic drive etc.

Sodium and water retention

Increasing hydrostatic pressure

Ascites

Contributing factors

Lymphatic blockage? R

educed albumin?


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pressure have NOT been shown to play a substantial role in the development of ascites.6

Liver diseaseIn liver cirrhosis, destruction of the normal architecture, fibrosis and other structural changes contribute to increased sinusoidal pressure and raised portal hypertension. Exacerbating this is the presence of defective nitric oxide synthesis in the liver (responsible for vasodilatation) and the presence of vasoconstrictors, including endothelin,6 angiotensin II, catecholamines and leukotrienes, all of which serve to favour sinusoidal constriction and the development of portal hypertension,6 with the resultant driving hydrostatic force pushing fluid out into the peritoneal cavity.

Splanchnic vasodilatation, as mentioned above, is crucial to the development of ascites. It is thought that vasodilatation of the splanchnic bed is caused by the release of vasodilators, either due to sheer stress in the splanchnic circulation or as a result of neurohormonal signalling from the liver to the brain.6-8 Nitric oxide, although decreased in the liver, is present and released in increased quantities from the systemic endothelium.6 Other vasodilators, including calcitonin gene-related peptide (CGRP) and adrenomedulin, have also been implicated.6

As a result of this splanchnic vasodilatation, systemic vascular resistance falls, leading to decreased effective blood volume and, ultimately, the activation of the sympathetic and renin–aldosterone systems, and salt and water retention.

Finally, renal dysfunction is also seen in cirrhotic liver patients, with a reduction in GFR and salt and water excretion further contributing to the development of fluid retention and ascites.6

Congestive heart failure, Budd–Chiari syndromePeople with these conditions are thought to develop ascites because of reduced effective arterial volumes, leading to activation of the RAAS and salt and fluid retention (underfill theory).3-5,9,10 Figure 6.3 shows the postulated mechanism of fluid retention and ascites in heart failure.

Nephrotic syndromeHypo-albuminaemia is universal in patients with nephrotic syndrome; however, the development of ascites in these patients is not solely caused by low albumin. Though not completely understood, ascites in this setting is likely to be much more complex and low albumin not the predominant mechanism.

Intra-renal pathology leading to inadequate salt excretion may play a role. Increased tubular reabsorption of salt has been demonstrated in animal models of nephrotic syndrome3 and may also play a role in human pathology.

‘Underfilling’ may also play a role in some patients who have proteinuria and hypoalbuminaemia, contributing to a decreased circulating volume and activation of compensatory mechanisms, resulting in salt and water retention.3

These mechanisms have been summarised in Figure 6.4.

In a study looking at patients with nephrotic syndrome and ascites, concomitant liver disease and/or a degree of heart failure were also present and contributory to ascitic fluid development,11 probably via a decrease in effective circulating volume and activation of RAAS and the sympathetic nervous system, with resulting salt and fluid retention.


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6prevents it from being picked up and returned to the circulation via the lymphatic system.12

In severe hypothyroidism, a variety of changes occur in the cardiovascular system and renal system including decreased myocardial contractility and renal dysfunction with inability to excrete excess water (free water clearance), which may also contribute to fluid retention. Direct research on these changes and ascites is lacking.

Exudative ascitesExudative ascites may be caused by:

• increased intraperitoneal oncotic pressure (e.g. peritoneal carcinomatosis causes the tumour cells lining the peritoneum to produce exudates)

Myxoedema mechanism/sThe mechanism of ascites in hypothyroidism or myxoedema is unclear. Previously two theories have existed. Firstly, that low levels of thyroid hormones cause increased extravasation of plasma proteins due to increased capillary permeability combined with a lack of compensatory lymphatic and protein flow return rate to the plasma.12,13

The second theory suggested that hyaluronic acid accumulates in the skin and produces oedema through its ability to absorb or adsorp water (i.e. its ability to attract and hold water molecules), although there is minimal evidence for this direct effect.12,14 The hyaluronic acid is also thought to form complexes with albumin which

FIGURE 6.3 High-output and low-output cardiac failure Although the initiating ‘underfill’ event differs in high- and low-output failure, the subsequent pathways leading to renal sodium and water retention are similar.

Schrier R. Pathogenesis of sodium and water retention in high output and low output cardiac failure, nephrotic syndrome, cirrhosis and pregnancy. First of 2 parts. NEJM 1988; 319(16): Fig 1.

High-outputcardiac failure

OsmoticAVP release

Sympatheticnervous system

Peripheralvascular resistance

Cardiacoutput

Low-outputcardiac failure

Effective arterialblood volume

Renin–angiolensin–aldosterone system

Diminishedrenal haemodynamics

andsodium and water

retention


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Nephrogenic – haemodialysisThe causes of ascites in patients who receive haemodialysis are largely unknown. One possible explanation is that uraemia induces an inflammatory response that causes immune-complex formation and obstruction of lymphatic channels.18,19

Ascites clinical signsSeveral clinical signs indicate the presence of ascites but none indicate the underlying cause. They are summarised in Table 6.2.

• disruption of vessel wall integrity that allows fluid to leak through (e.g. patients with systemic lupus erythematosus can develop an inflammatory serositis, leading to exudate).10,15

Chylous ascitesObstruction of lymphatic flow is the main underlying mechanism. This can be due to a pathological obstruction raising lymphatic pressures, resulting in fluid being pushed out and/or disrupting vessel integrity leading to leakage. Examples of these two scenarios are malignant lymphoma and surgical rupture of lymph nodes or vessels.16,17

FIGURE 6.4 Nephrotic syndrome The albuminuria and decrease in plasma oncotic pressure initiate the underfilling in nephrotic syndrome. Renal impairment and intra-renal factors may intervene, however, and in some circumstances restore or even expand effective blood volume.

Schrier R. Pathogenesis of sodium and water retention in high output and low output cardiac failure, nephrotic syndrome, cirrhosis and pregnancy. First of 2 parts. NEJM 1988; 319(16): Fig 3.

Nephrotic syndrome

Proteinuriaand

hypoalbuminuria

Effective arterialblood volume

Sympatheticnervous system

Renin–angiotensin–aldosterone system

Non-osmoticAVP release

Renal haemodynamics and

renal sodium and waterexcretion


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FIGURE 6.5 Pathophysiology of the development of ascites in cirrhosis and potential targets for treatment SNS = sympathetic nervous system; RAAS = renin–angiotensin–aldosterone system; AVP = arginine vasopressin.

Moller S, Henriksen J, Bendtsen F. Ascites: pathogenesis and therapeutic principles. Scandinavian Journal of Gastroenterology 2009; 44: 902–911, Fig 1, Informa PLC.

Increased lymphformation

Ascites

Plasma volumeexpansion

Sodium and waterretention

Activation ofSNS

Central hypovolaemia

Arterial hypotension

Deloading of arterialbaroreceptors

Activation ofRAAS

Activation ofvasopressin

Splanchnicarteriolarvasodilatation

Increased splanchniccapillary pressure

TIPSb-adrenergicblockers

b-adrenergicblockers

V1 receptoragonists

a-1 agonist

ParacentesisplasmaVolumeexpansion

Loop-diuretics

Aldosteroneantagonists

V2 receptorantagonists

Increased productionof vasodilators

Cirrhosis and liverdysfunction

Portalhypertension

Sign valueThe presence of ascites in a patient with liver disease suggests the presence of underlying cirrhosis with a PLR of 7.2 (CI 2.9-12),20 and thus is helpful in understanding the extent and chronicity of disease.

Appreciating the mechanism behind ascites, and in particular cirrhosis-induced ascites, has substantial value in aiding understanding of the disease

state and its sequelae, as well as insight into how therapeutic interventions act. In Figure 6.5, the pathogenesis of ascites is shown along with targets for various treatment opportunities.

In terms of the various signs that are used to detect the presence of ascites, there are variable sensitivities and specificities. A review21 summarising available studies is shown in Tables 6.3 and 6.4. As seen in Table 6.2, all have


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value in clinical examination. In patients with abdominal distension, the sign with the best positive likelihood ratio (most likely to have ascites) is the

fluid wave.22 The best signs to exclude ascites are the absence of oedema (NLR 0.2) and absence of flank dullness.22

Serum albumin/ascitic gradient (SAAG) – a guide to pathophysiology and diagnosis

of the sign

The serum albumin ascitic gradient (SAAG) is used to identify the presence of portal hypertension.

SAAG = serum albumin – ascitic fluid albumin

The theory is based on Starling’s forces between the serum and ascitic fluid and the relationship between oncotic pressure, hydrostatic pressure and endothelial permeability.

In conditions when hydrostatic pressure is elevated (e.g. in portal hypertension), fluid is pushed out into the abdomen, and thus the serum albumin level becomes more concentrated compared to the ascitic fluid albumin, and the gap or gradient widens.

Conditions in which there is either low albumin in the serum (e.g. nephrotic syndrome) or protein leakage into the peritoneal cavity (e.g. inflammation, malignancy) result in higher protein and/or albumin content entering the peritoneal cavity, creating a low SAAG. Table 6.4 shows examples of causes of both high and low albumin gradients.

TABLE 6.4 Serum albumin ascitic gradient and pathologies

High albumin gradient (SAAG >11.1g/l)

Low albumin gradient (SAAG <11.1g/l)

Cirrhosis Peritoneal carcinmatosis

Alcoholic hepatitis Pancreatitis

Heart failure Nephrotic syndrome

Budd–Chiari syndrome Bacterial peritonitis

Portal vein thrombosis


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Asterixis (also hepatic flap)

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Asterixis (also hepatic flap)

See also ‘Asterixis’ in Chapter 2, ‘Respiratory signs’.

DescriptionWhen the patient is asked to hold the arms extended with the hands dorsiflexed, a flapping hand movement that is brief, rhythmless and of low frequency (3–5 Hz) becomes apparent. Asterixis may be bilateral or unilateral.

Condition/s associated with

• Liver disease – most common

• Chronic obstructive pulmonary disease

• Stroke – rare

Hepatic mechanism/sLittle is known about the mechanism of asterixis induced by hepatic encephalopathy. Limited studies have suggested:

• Slowed oscillations in the primary motor cortex cause mini-asterixis, which may or may not be caused by problems in the motor cortex itself.23

• Dysfunction of the basal ganglia–thalamocortical loop may be involved.24

The net result of the pathology is the failure of the diencephalic motor centres in regulating tone between the agonist and antagonist muscles needed to maintain position and posture.25

Sign valueAsterixis is perhaps more valuable as a marker of severe disease, whatever the aetiology, rather than as a diagnostic tool.26 One study used asterixis as a predictor of mortality in patients admitted with alcohol-related liver disease. It found that mortality rate was 56% in those with asterixis compared to 26% in those without.27


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Chapter 7

Endocrinological SignS



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acanthosis nigricans (an)

662

CL

INIC

aL

pe

ar

L

acanthosis nigricans (aN)

insulin resistance. This leads to hyperinsulinaemia, which in turn stimulates the proliferation of keratinocytes (which contain melanin) and fibroblasts.

Detailed mechanism/sKeratinocytes normally multiply to form a thickened keratin (a fibrous structural protein) layer of the skin. Melanin is taken up and deposited within the nuclei. Further proliferation of keratinocytes, stimulated by hyperinsulinaemia, leads to a thicker keratin layer with darker pigmentation, due to the melanin present.

Similarly, fibroblasts produce collagen. Excess proliferation leads to additional collagen deposition, which when combined with the additional keratin layer, may contribute to the distinctive ‘velvet’ feel of acanthosis nigricans.

Hyperinsulinaemia stimulates proliferation by:

• directly stimulating insulin-like growth factor-1 (IGF-1) receptors on fibroblasts and keratinocytes, causing proliferation

• decreasing levels of some IGF-1-binding proteins. This causes an increased level of free IGF-1 in circulation, which stimulates the IGF-1 receptor on fibroblasts and keratinocytes leading to proliferation.1

Other mediators may include:

• epidermal growth factor receptor (EGFR)

• fibroblast growth factor receptor (FGFR)

• androgens.Three types of insulin resistance

have been described:2

descriptionA grey-black, papillomatous thickening of the skin at the flexor areas. It is usually symmetrical and feels akin to velvet. Acanthosis nigricans (AN) is most common around the posterolateral neck, axillae, groin and abdominal folds.


• Type 2 diabetes

• Obesity

Less common• Cushing’s syndrome

• Acromegaly

• Malignancy

• PCOS

• Other states of hyperinsulinaemia

general mechanism/sThe mechanism is complex, with most cases occurring in the presence of

FIGUre 7.1 Acanthosis nigricans

Reproduced, with permission, from Weston WL, Lane AT, Morelli JG, Color Textbook of Pediatric Dermatology, 4th edn, London: Mosby, 2007: Fig 17-62.



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insulin activate IGF-1 receptors on keratinocytes, leading to excess proliferation.

In the case of acromegaly there are two contributory pathways. Firstly, excess of growth hormone causes increased production of IGF-1, which stimulates the IGF-1 receptor on keratinocytes. Secondly, insulin resistance may be present, leading to hyperinsulinaemia and insulin-based stimulation of keratinocytes and fibroblasts.3

1 type A – dysfunction of insulin receptors

2 type B – caused by antibodies against insulin receptors

3 type C – post-insulin receptor defects.

Any of these pathways may cause hyperinsulinaemia and result in acanthosis nigricans.

There is evidence that obesity is associated with dysfunction of insulin receptors, leading to a compensatory rise in insulin levels. The high levels of

FIGUre 7.2 Mechanisms of acanthosis nigricans

Obesity

Dysfunctional receptorsInsulin receptor antibodies

Post-insulin receptor defectsOther mechanisms

Insulin resistance

Growth hormone

Hyperinsulinaemia

Binding proteins

Malignancy

EGFR activationFGFR activation

Increased freeIGF-1

Keratinocytes and fibroblastproliferation

Acanthosis nigricans

Increased IGF-1 receptor activation

PCOSCushing’ssyndrome

Acromegaly



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and is strongly correlated with the level of obesity. It has also been suggested that it is an independent risk factor for the development of diabetes.11 Research is still ongoing regarding its utility as a prognostic indicator for the development of diabetes in children. Recent research has shown that, in patients aged 8–12 years who have AN, more than 25% had altered glucose metabolism.5 In a study of middle school students in the USA, acanthosis nigricans was present in 28% of the cohort and was associated with a 50–100% increased likelihood of dysglycemia, even after consideration of established diabetes risk factors.12

Some malignancies can cause AN, such as those which produce insulin receptor antibodies (stimulating secretion of insulin) or epidermal growth factor,4 which can also contribute to this sign.

Sign valueThe exact prevalence of AN is unclear and varies with different population groups. AN has been shown to be a valuable indicator of hyperinsulinism and insulin resistance in adults and children.5-7 Further, AN has been strongly associated with multiple risk factors for type 2 diabetes8-10 and the development of metabolic syndrome,5



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angioid streaks

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angioid streaks

calcified Bruch’s membrane. The specific mechanism for the abnormality in Bruch’s membrane has not been established and calcification is not significant in some disease associations. Suggested contributing factors include:

• elastic degeneration of the membrane

• iron deposition in elastic fibres from haemolysis with secondary mineralisation14

• nutritional impairment due to sickling, stasis and small vessel occlusion.

It is thought that lines of force from intra- and extraocular eye muscles cause cracking of the brittle membrane.

Sign valueNearly 50% of patients with angioid streaks have an underlying disease, so further investigation is warranted. Some studies have demonstrated associations with the following disease states:

• Present in 80–87% of patients with pseudoxanthoma elasticum.14

• Present in 2–15% of patients with Paget’s disease.14

• 0–6% of patients with haemoglobinopathy will develop angioid streaks.15

• It is not a valuable sign for acromegaly.

descriptionAngioid streaks appear as irregular, jagged, tapering lines radiating from the peri-papillary retina into the macula and peripheral fundus.13


• Pseudoxanthoma elasticum

• Paget’s disease of bone

• Haemoglobinopathies

Less common• Ehlers–Danlos syndrome

• Acromegaly

• Neurofibromatosis

Mechanism/sAngioid streaks are believed to result from small breaks within a brittle or

FIGUre 7.3 Angioid streaks

Reproduced, with permission, from Kanski JJ, Clinical Diagnosis in Ophthalmology, 1st edn, Philadelphia: Mosby, 2006: Fig 13-78.



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Australia Elsevier proofs Sample CliniCal SignS Mechanisms of · Brudzinski sign 384 Cavernous...

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