Klinisk'kemisk'diagnos.k' ' Johan'Malm'

Transkript

1 Klinisk'kemisk'diagnos.k' ' Johan'Malm'

2 Man,'63'år'söker'inkommer'med'ambulans'.ll'med'akut' bröstsmärta'sedan'3'.mmar'.digare'frisk' inga'mediciner'

3 smärtpåverkad' blodtryck'165/95' kallsveeg'

4 Hb,'LPK,'TPK' EKG' troponin' glukos' Na' K' Ca' krea.nin' ASAT,'ALAT' blodgaser' 'po2,'pco2' koagula.onsstatus'

5 *Smärtlindring' ' *An.Tischemisk'behandling' ' *Trombosbehandling' ' *Sviktbehandling' ' *Arytmibehandling' '

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7 Dag'3'blir'pat.'medvetslös'och'avlider' trots'återupplivningsförsök.' '

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9 Handläggning'av'pa.ent' Anamnes' Fysikalisk'undersökning' Differen.aldiagnoser' Utredning' 'tex'lab,'röntgen' Diagnos'' Terapi'' Utvärdering'

10 En'majoritet'av'medicinska'beslut'' baseras'på'laboratoriemedicinska'resultat'

11 Laboratoriemedicin' klinisk'kemi' klinisk'mikrobiologi' klinisk'patologi' klinisk'immunologi'och' transfusionsmedicin' klinisk'gene.k' arbetst'och'miljömedicin' vårdhygien' biobank'

12 Vem'arbetar'inom'laboratoriemedicin?' ' biomedicinska'analy.ker' kemister' ingenjörer' läkare' gene.ker' administra.v'personal'

13 Varifrån'kommer'proven?' ' vårdcentraler' sjukhus' privatprak.ker' övriga'

14 Olika'sek.oner'inom'klinisk'kemi' ' allmänkemi' hematologi' farmakologi'och'toxikologi' koagula.on' endokrinologi' molekylärbiologi' pa.entnära'diagnos.k'(poct,' point'of'care'tes.ng)' proteiner' '

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17 Provtagningsmaterial' blod' urin' likvor'(csf,'cerebrospinalvätska)' annan'vätska'eller'vävnad' ' ' ' ' '

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19 Speciella'provtagningsföreskri`er' fasteprov' 'glukos,'triglycerider' morgonprov' 'järn,'kor.sol'

20 Vad'är'normalt?'

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22 Paus'

23 Acute'Myocardial'Infarc.on' End'result'of'luminal'narrowing'of' coronary'arteries' Reduc.on'of'blood'supply' Reduc.on'of'O 2 'supply'

24 Risk%factors% Older'age' Male'gender' Cigarede'smoking' Hypercholesterolemia'' Diabetes'' High'blood'pressure' Obesity'

25 Pathophysiology' Result%of%Atherosclerosis% disease'affec.ng'arterial'blood'vessels'' It'is'a'chronic'inflammatory'response'in'the'walls'of' arteries,'' deposi.on'of'lipoproteins'(plasma'proteins'that'carry' cholesterol'and'triglycerides).'' forma.on'of'mul.ple'plaques'within'the'arteries.' ''

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35 Hur'diagnos.seras'hjär.nfarkt?'

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40 Paus'

41 man,'54'år' söker'på'vårdcentral' har'insulinbehandlad'diabetes' problem'med'kroniska'sår'' ''

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43 dagliga'såromläggningar' intensifierad'glukoskontroll' blir'ini.alt'bädre' ''

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45 diabetes'mellitus'

46 The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

47 The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

48 The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

49 The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

50 Type 1 diabetes in the young The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

51 4.6'million' deaths'due'to' diabetes'in'2011' 8.2%'of'allT cause'mortality' 48%'in'people' under'60' The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

52 Prevalence (%) by region and age and sex The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'

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56 Ac.on'of'Insulin'on'Cell'Metabolism' '

57 Ac.on'of'Insulin'on'Carbohydrate,'Protein'and' Fat'Metabolism' facilitates'the'transport'of'glucose'into' muscle'and'adipose'cells,'' facilitates'the'conversion'of'glucose'to' glycogen'in'the'liver'and'muscle' s.mulates'protein'synthesis' s.mulates'lipogenesis' ' ' ' '

58 What'goes'wrong'in'diabetes?'

59 Type'I'Diabetes'Cell'

60 Type'I'Diabetes' Low'or'absent'endogenous'insulin' Dependent'on'exogenous'insulin'for'life' Onset'generally'<'30'years' 5T10%'of'cases'of'diabetes' Onset'sudden' Symptoms:'3'P s:'polyuria,'polydypsia,' polyphagia'

61 Type'I'Diabetes' Gene.c'component'to'disease'

62 Type'II'Diabetes'

63 Type'II'Diabetes' Insulin'levels'may'be'normal,'elevated'or' depressed' Characterized'by'insulin'resistance,'' diminished'.ssue'sensi.vity'to'insulin,' and'impaired'beta'cell'func.on'(delayed'or' inadequate'insulin'release)' O`en'occurs'>40'years'

64 Type'II'Diabetes' Risk'factors:'family'history,'sedentary' lifestyle,'obesity'and'aging' Controlled'by'weight'loss,'oral' hypoglycemic'agents'and/or'insulin' '

65 Gesta.onal'diabetes' (graviditetsdiabetes)''! Glucose'intolerance'during'pregnancy.''! More'common'among'obese'women.''! Requires'treatment''to'avoid'complica.ons'in' the'infant.''! A`er'pregnancy,'5T10%'have'type'2'diabetes.''! Women'who'have'had'gesta.onal'diabetes'T'' 20T50%'develop'diabetes'in'the'next'5T10' years.'

66 Labtester'vid'diabetes' BTglukos' BTHbA1c' Urins.cka' UTalbumin' '

67 HbA1c' glucose'(green)' HbA1c'(red)'.me'

68 Labtester'vid'diabetes' BTglukos' BTHbA1c' Urins.cka' UTalbumin' '

69 Hur'diagnos.seras'diabetes?'

70 WHO'2006'

71 Glucose'concentra.on'

72 Diabetes Complications Cardiovascular disease Coronary Heart disease (CHD) Stroke Peripheral arterial disease (PAD)/amputation) Eye disease (retinopathy) Kidney disease (nephropathy) Liver disease Nerve disease (neuropathy) All cause mortality risk

73 Avoiding Diabetes Complications Blood glucose control HbA1c Treat cholesterol profiles to targets Treat blood pressure to target <130/<80

74 Type 1 Diabetes Microvascular Complications Relative Risk Retinopathy Nephropathy Neuropathy Microalbuminuria A1C (%) Skyler J. Endocrinol Metab Clin North Am. 1996;25:243 DCCT Research Group. N Engl J Med. 1993;329:977

75 Cardiovascular Disease Risk: Stroke 2 to 4 times higher Heart Disease 2 to 4 times higher ~75% of diabetes patients have high blood pressure (hypertension) ~75% of people with diabetes have a dyslipidemia (cholesterol disease)

76 Peripheral Arterial Disease Blockage of arteries in legs Contributing factor to amputations in diabetes: ~60% of lower limb amputations occur in people with diabetes Amputation rate is 10 times higher in diabetes

77 Diabetic Nephropathy Characterized by proteinuria Prevalence 15-40% in type 1 Prevalence 5-20% in type 2 Associated with risk of CVD

78 Nephropathy - Screening Microalbumin

79 microalbumin'

80 Nephropathy - Screening Microalbumin and serum creatinine screening

81 crea.nine'

82 Nephropathy- Screening Microalbumin and serum creatinine screening HbA1c BP s <130/<80, weight reduction, lipid control, tobacco cessation

83 Diabetic Eye Disease Cataracts Macular edema Glaucoma

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86 Diabetic Neuropathy Diabetic Peripheral Neuropathy Autonomic Neuropathy

87 Diabetic Neuropathy

88 Paus'

89 kvinna,'53'år,'.digare'frisk,'vill'bli'blodgivare' pat'visar'sig'ha'ed'bthb'103g/l'och'remideras'.ll'vårdcentral'' Vad'gör'du?' '

90 Lab'utredning' Hb' BTEPK'inkl.'MCV'(erytrocytpar.kelkonc.)' LPK'inkl.'diff'(leukocytpar.kelkonc.)' Re.kulocyter' Trombocyter'

91 Hem'''''''Hemoglobin'''''''Erytrocyt'''''

92 Hemoglobin' Referensintervall% Vuxna' Kvinnor:'117T153'g/L' Män:'134T170'g/L' ' Barn' 0T1'dag:'150T240'g/L' 1T6'dagar:'140T220'g/L' 6T14'dagar:'130T200'g/L' 2T4'veckor:'100T180'g/L' 1T3'månader:'100T160'g/L' 3T12'månader:'100T140'g/L' 1T6'år:'100T150'g/L' 6T10'år:'105T150'g/L' 10T18'år:'110T160'g/L' ''

93 Lab'utredning' Hb' BTEPK'inkl.'MCV'(erytrocytpar.kelkonc.)' LPK'inkl.'diff'(leukocytpar.kelkonc.)' Re.kulocyter' Trombocyter'

94 MCV' (Mean'Corpuscular'Volume)' Mikrocytär' <80fL' Normocytär' 80T100fL' Makrocytär' >100fL'

95 Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Trombocyter' Re.kulocyter' '

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97 Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Trombocyter' Re.kulocyter' '

98 Re.kulocyter'

99 Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Re.kulocyter' Trombocyter'

100 Blödning' Hb' Järnbrist' 'Fe,'transferrin,'ferri.n' Hemolysis' LD,'haptoglobin' B12'eller'folsyrabrist' SR'(sänkningsreak.on)' CRP'(CTreac.ve'protein)'

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103 'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on' Klassificera'anemin'T'morfologi' Normocytär' Mikrocytär' Makrocytär'

104 Blödningsanemi' Akut' Trauma.sk' ' Kronisk' Occult'blödning' gastrointes.nal,'urinvägar,' gynekologisk'

105 Minskad'Produk.on' Näringsbrist' Inflamma.on' Neoplas.sk' 't.ex.'blodmalignitet' Anemi'associerad'med'kronisk'sjukdom' Endokrin'sjukdom' 't.ex.'njursvikt' '

106 'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on'

107 Hemolys'

108 'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on' Klassificera'anemin'T'morfologi' Normocytär' Mikrocytär' Makrocytär'

109 Mikrocytär'Anemi'(MCV<80fL)' ' Järnbrist' Diet/Absorp.on' Ökat'behov' Blodförlust' ' Kronisk'sjukdom' Lågt'PTFe,'lågt'TIBC,'normalt'PTFerri.n' Kronisk'infek.on,'inflamma.on,'cancer,'etc.' ' Thalassemi' ' '

110 Makrocytär'Anemi'(MCV>100fL)' ' B12Tbrist' ' Folsyrabrist' ' Etanol'

111 Vad'hände'med'pa.enten?' ' kvinna,'53'år,'.digare'frisk,'vill'bli'blodgivare' pat'visar'sig'ha'ed'bthb'103g/l'och'remideras'.ll'vårdcentral'' '

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145 Prostatacancer'

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147 PSA'test' ' DRE' ' Diagnosis'is'confirmed'with'a'biopsy' ' Transrectal'ultrasound'(TRUS)' ' Imaging'tests'can'determine'if'the'cancer'has' spread'

148 Stage'I'or'Stage'A'Prostate'Cancer' Stage'I'cancer'is' found'only'in'the' prostate'and'usually' grows'slowly'

149 Stage'II'or'Stage'B'Prostate'Cancer' ' Stage'II'cancer'has' not'spread'beyond' the'prostate'gland,' but'involves'more' than'one'part'of'the' prostate,'and'may' tend'to'grow'more' quickly'

150 Stage'III'or'Stage'C'Prostate'Cancer' Stage'III'cancer'has' spread'beyond'the' outer'layer'of'the' prostate'into'nearby'.ssues'or'to'the'seminal' vesicles,'the'glands'that' help'produce'semen'

151 Stage'IV'or'Stage'D'Prostate'Cancer' Stage'IV'cancer'has'spread'to'other' areas'of'the'body'such'as'the' bladder,'rectum,'bone,'liver,'lungs,'or' lymph'nodes'

152 Bröstcancer'

153 Breast'cancer'primarily'effects'women' but'about'1'percent'of'all'cases'effect' men' ' Breast'cancer'is'the'second'leading'cause' of'death'in'women'next'to'lung'cancer' ' One'out'of'nine'women'will'develop' breast'cancer'in'their'life.me' One'out'of'twenty'in'1960' '

154 Gene Causes'of'Hereditary'' Suscep.bility'to'Breast'Cancer' 5'to'10%'of'breast'cancers'can'be'adributed'to''inherited'factors' Contribution to Hereditary Breast Cancer BRCA1 BRCA2 TP53 PTEN Undiscovered genes 20% 40% 10% 30% <1% <1% 30% 70%

155 BRCA1TAssociated'Cancers:'Life.me'Risk' Breast cancer 50%-85% (often early age at onset, less than 40 years) Second primary breast cancer 40%-60% Ovarian cancer 15%-45% Possible increased risk of other cancers (e.g. prostate, colon)

156 Comparing Breast Cancer Risk Estimates in BRCA Mutation Carriers Breast cancer risk (%) BRCA1+ carriers (BCLC) BRCA1+ carriers (Ashkenazi Jews) Easton DF et al. Am J Hum Genet 56:265, 1995 Struewing JP et al. N Engl J Med 336:1401, 1997 General population Age

157 BRCA2TAssociated'Cancers:'Life.me'Risk' breast%cancer%% (50%B85%)% ovarian%cancer%% (10%B20%)% male%breast%cancer%% (6%)% Increased%risk%of%prostate,%laryngeal,%and% pancrea9c%cancers%(magnitude%unknown)%

158 HERT2/neu' GrowthTs.mula.ng'protein' Normal'cells'express'a'small' amount'on'their'plasma' membranes' On'surface'of'breast'cancer' cells' Sends'messages'from'cell'to' growth'factors 'outside'cell' Overabundant'on'surface'of' cancer'cells'in'30%'of'women' with'breast'cancer'

159 Type'of'biologic'therapy' Breast'cancer'treatment' drug' Monoclonal'an.body' therapy' Blocks'HERT2/neu' Effec.ve'in'metasta.c' HERT2/neu'posi.ve'breast' cancer' Lidle'effect'with'HERT2/ neu'nega.ve'breast' cancer' Hercep.n'

160 PAUS'

161 The'Metabolic'Syndrome''

162 Increased waist circumference PLUS any two of the following: 1) Dyslipidemia 2) Systolic blood pressure >130, diastolic blood pressure >85, 3) Hyperglycemia or DM2 Interna.onal'Diabetes'Federa.on'T'2004'

163 Metabolic'Syndrome:'' Prevalence'In'Adults*'Worldwide' Men Women Lima, Peru 21.6% 30% Mexico City 55.6% 64% Spain 27.3% 31.7% Greece 24.5% Hong Kong 7.4% of Chinese men and women USA 39% Germany 57% 46% *as defined by IDF criteria Adapted'from'hdp://

164 What'Are'The'Contribu.ng'Causes'Of'' The'Metabolic'Syndrome?'' At present, no single pathogenesis has been elicited, and it appears that it can be precipitated by multiple underlying risk factors Insulin%% Resistance% Abdominal%% Obesity%

165 Obesity Trends* Among U.S. Adults BRFSS, 1990, 1999, 2009 (*BMI 30, or about 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

166 Health'Consequences'Of'Obesity' Risk increases with BMI Cancer% Respiratory% disease% GallB% bladder% disease% HyperB% tension% %Obesity% Kidney% failure% Type%2% diabetes% Stroke% AtheroB% sclerosis% Heart% failure% Adapted'from'hdp://

167 Significance'of'Metabolic'Syndrome'! Cardiovascular'disease'' " People'with'metabolic'syndrome'are'2x'as'likely' to'die'from,'and'3x'as'likely'to'have'a'heart' adack'or'stroke'! Type'2'diabetes' " People'with'metabolic'syndrome'have'a'5x' greater'risk'of'developing'type'2'diabetes'' ' # Up'to'80%'of'the'200'million'people'with'diabetes' globally'will'die'of'cardiovascular'disease''