Klinisk'kemisk'diagnos.k' ' Johan'Malm'
Man,'63'år'söker'inkommer'med'ambulans'.ll'med'akut' bröstsmärta'sedan'3'.mmar'.digare'frisk' inga'mediciner'
smärtpåverkad' blodtryck'165/95' kallsveeg'
Hb,'LPK,'TPK' EKG' troponin' glukos' Na' K' Ca' krea.nin' ASAT,'ALAT' blodgaser' 'po2,'pco2' koagula.onsstatus'
*Smärtlindring' ' *An.Tischemisk'behandling' ' *Trombosbehandling' ' *Sviktbehandling' ' *Arytmibehandling' '
Dag'3'blir'pat.'medvetslös'och'avlider' trots'återupplivningsförsök.' '
Handläggning'av'pa.ent' Anamnes' Fysikalisk'undersökning' Differen.aldiagnoser' Utredning' 'tex'lab,'röntgen' Diagnos'' Terapi'' Utvärdering'
En'majoritet'av'medicinska'beslut'' baseras'på'laboratoriemedicinska'resultat'
Laboratoriemedicin' klinisk'kemi' klinisk'mikrobiologi' klinisk'patologi' klinisk'immunologi'och' transfusionsmedicin' klinisk'gene.k' arbetst'och'miljömedicin' vårdhygien' biobank'
Vem'arbetar'inom'laboratoriemedicin?' ' biomedicinska'analy.ker' kemister' ingenjörer' läkare' gene.ker' administra.v'personal'
Varifrån'kommer'proven?' ' vårdcentraler' sjukhus' privatprak.ker' övriga'
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' '
Provtagningsmaterial' blod' urin' likvor'(csf,'cerebrospinalvätska)' annan'vätska'eller'vävnad' ' ' ' ' '
Speciella'provtagningsföreskri`er' fasteprov' 'glukos,'triglycerider' morgonprov' 'järn,'kor.sol'
Vad'är'normalt?'
Paus'
Acute'Myocardial'Infarc.on' End'result'of'luminal'narrowing'of' coronary'arteries' Reduc.on'of'blood'supply' Reduc.on'of'O 2 'supply'
Risk%factors% Older'age' Male'gender' Cigarede'smoking' Hypercholesterolemia'' Diabetes'' High'blood'pressure' Obesity'
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.' ''
Hur'diagnos.seras'hjär.nfarkt?'
Paus'
man,'54'år' söker'på'vårdcentral' har'insulinbehandlad'diabetes' problem'med'kroniska'sår'' ''
dagliga'såromläggningar' intensifierad'glukoskontroll' blir'ini.alt'bädre' ''
diabetes'mellitus'
The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
Type 1 diabetes in the young The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
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'
Prevalence (%) by region and age and sex The'Interna.onal'Diabetes'Federa.on'Diabetes'Atlas,'5th'ed'
Ac.on'of'Insulin'on'Cell'Metabolism' '
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' ' ' ' '
What'goes'wrong'in'diabetes?'
Type'I'Diabetes'Cell'
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'
Type'I'Diabetes' Gene.c'component'to'disease'
Type'II'Diabetes'
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'
Type'II'Diabetes' Risk'factors:'family'history,'sedentary' lifestyle,'obesity'and'aging' Controlled'by'weight'loss,'oral' hypoglycemic'agents'and/or'insulin' '
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.'
Labtester'vid'diabetes' BTglukos' BTHbA1c' Urins.cka' UTalbumin' '
HbA1c' glucose'(green)' HbA1c'(red)'.me'
Labtester'vid'diabetes' BTglukos' BTHbA1c' Urins.cka' UTalbumin' '
Hur'diagnos.seras'diabetes?'
WHO'2006'
Glucose'concentra.on'
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
Avoiding Diabetes Complications Blood glucose control HbA1c Treat cholesterol profiles to targets Treat blood pressure to target <130/<80
Type 1 Diabetes Microvascular Complications Relative Risk 15 13 11 9 7 5 Retinopathy Nephropathy Neuropathy Microalbuminuria 3 1 6 7 8 9 10 11 12 A1C (%) Skyler J. Endocrinol Metab Clin North Am. 1996;25:243 DCCT Research Group. N Engl J Med. 1993;329:977
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)
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
Diabetic Nephropathy Characterized by proteinuria Prevalence 15-40% in type 1 Prevalence 5-20% in type 2 Associated with risk of CVD
Nephropathy - Screening Microalbumin
microalbumin'
Nephropathy - Screening Microalbumin and serum creatinine screening
crea.nine'
Nephropathy- Screening Microalbumin and serum creatinine screening HbA1c BP s <130/<80, weight reduction, lipid control, tobacco cessation
Diabetic Eye Disease Cataracts Macular edema Glaucoma
Diabetic Neuropathy Diabetic Peripheral Neuropathy Autonomic Neuropathy
Diabetic Neuropathy
Paus'
kvinna,'53'år,'.digare'frisk,'vill'bli'blodgivare' pat'visar'sig'ha'ed'bthb'103g/l'och'remideras'.ll'vårdcentral'' Vad'gör'du?' '
Lab'utredning' Hb' BTEPK'inkl.'MCV'(erytrocytpar.kelkonc.)' LPK'inkl.'diff'(leukocytpar.kelkonc.)' Re.kulocyter' Trombocyter'
Hem'''''''Hemoglobin'''''''Erytrocyt'''''
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' ''
Lab'utredning' Hb' BTEPK'inkl.'MCV'(erytrocytpar.kelkonc.)' LPK'inkl.'diff'(leukocytpar.kelkonc.)' Re.kulocyter' Trombocyter'
MCV' (Mean'Corpuscular'Volume)' Mikrocytär' <80fL' Normocytär' 80T100fL' Makrocytär' >100fL'
Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Trombocyter' Re.kulocyter' '
Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Trombocyter' Re.kulocyter' '
Re.kulocyter'
Lab'utredning' Hb' BTEPK'inkl.'MCV' LPK'inkl.'diff'' Re.kulocyter' Trombocyter'
Blödning' Hb' Järnbrist' 'Fe,'transferrin,'ferri.n' Hemolysis' LD,'haptoglobin' B12'eller'folsyrabrist' SR'(sänkningsreak.on)' CRP'(CTreac.ve'protein)'
'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on' Klassificera'anemin'T'morfologi' Normocytär' Mikrocytär' Makrocytär'
Blödningsanemi' Akut' Trauma.sk' ' Kronisk' Occult'blödning' gastrointes.nal,'urinvägar,' gynekologisk'
Minskad'Produk.on' Näringsbrist' Inflamma.on' Neoplas.sk' 't.ex.'blodmalignitet' Anemi'associerad'med'kronisk'sjukdom' Endokrin'sjukdom' 't.ex.'njursvikt' '
'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on'
Hemolys'
'Klassificera'anemin'T'patofysiologi' Blödningsanemi' Minskad'produk.on' Ökad'destruk.on' Klassificera'anemin'T'morfologi' Normocytär' Mikrocytär' Makrocytär'
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' ' '
Makrocytär'Anemi'(MCV>100fL)' ' B12Tbrist' ' Folsyrabrist' ' Etanol'
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'' '
Paus!'
Prostatacancer'
PSA'test' ' DRE' ' Diagnosis'is'confirmed'with'a'biopsy' ' Transrectal'ultrasound'(TRUS)' ' Imaging'tests'can'determine'if'the'cancer'has' spread'
Stage'I'or'Stage'A'Prostate'Cancer' Stage'I'cancer'is' found'only'in'the' prostate'and'usually' grows'slowly'
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'
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'
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'
Bröstcancer'
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' '
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%
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)
Comparing Breast Cancer Risk Estimates in BRCA Mutation Carriers Breast cancer risk (%) 100 80 60 40 BRCA1+ carriers (BCLC) BRCA1+ carriers (Ashkenazi Jews) 20 0 40 50 60 70 80 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
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)%
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'
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'
PAUS'
The'Metabolic'Syndrome''
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'
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://www.idf.org/webdata/docs/IDF_T2D_slides_final_aug06'
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%
Obesity Trends* Among U.S. Adults BRFSS, 1990, 1999, 2009 (*BMI 30, or about 30 lbs. overweight for 5 4 person) 1990 1999 2009 No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%
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://www.idf.org/webdata/docs/IDF_T2D_slides_final_aug06'
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''