fibrose cistica
DESCRIPTION
Aula de fibrose cística para graduandos de medicina. Por que precisamos conhecer esta doença? Quando pensar neste diagnóstico? Como confirmar?TRANSCRIPT
![Page 1: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/1.jpg)
FIBROSE CÍSTICA
Mônica de Cássia Firmida
Maio, 2010
![Page 2: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/2.jpg)
FIBROSE CÍSTICA
Definição e aspectos epidemiológicos
http://www.cff.org (em 17/05/2010)
Fibrose Cística (FC) ou Mucoviscidose é uma doença crônica, de origem genética autossômico-recessiva, que afeta principalmente os pulmões e o sistema digestivo de cerca de 30.000 crianças e adultos nos EUA (70.000 no mundo).
É a doença genética letal mais comum na população Caucasiana.
Incidência de 1:3.500 nascidos vivos. (Brasil: 1:9.500)
Doenças Respiratórias. USP, 2008
![Page 3: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/3.jpg)
FIBROSE CÍSTICA
Epidemiologia
http://www.cff.org (em 17/05/2010)
Cerca de 1000 novos casos são diagnosticados a cada ano.
Mais de 70% dos pacientes têm sido diagnosticados até os 2 anos
de idade.
Mais de 45% dos pacientes com FC têm mais de 18 anos de idade.
A sobrevida vem aumentando. Média é maior do que 37 anos.
Maior proporção de problemas médicos relacionados com a idade e
com a progressão da doença.
![Page 4: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/4.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 5: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/5.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 6: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/6.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 7: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/7.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 8: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/8.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 9: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/9.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 10: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/10.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 11: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/11.jpg)
FIBROSE CÍSTICA
Genética
Autossômico-recessivaGene no Cromossomo 7Mais de 1500 mutações http://www.genet.sickkids.on.ca/cftr/app
“Clássica”: ΔF508CFTR: canal de cloro
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 12: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/12.jpg)
FIBROSE CÍSTICA
A proteína CFTR
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 13: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/13.jpg)
FIBROSE CÍSTICA
Influência das mutações na biossíntese da CFTR
Cecil, 23rd ed, 2007
![Page 14: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/14.jpg)
FIBROSE CÍSTICA
A Função da proteína CFTR e as alterações produzidas pelas diferentes classes de mutações do gene CFTR Giselda MK Cabello – Laboratório de Genética Humana – IOC/Fiocruz
Créditos da imagem: Philippe Rousseau - La Mucoviscidose et le gène cftr
![Page 15: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/15.jpg)
FIBROSE CÍSTICA
http://www.cff.org
![Page 16: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/16.jpg)
FIBROSE CÍSTICA
Relação entre a quantidade de CFTR funcionante e o fenótipoRelação entre a quantidade de CFTR funcionante e o fenótipo
<1%
<4,5%
<5%
<10%
Ins. Pancreática Exócrina
Infecção Pulmonar Progressiva
Anormalidade no teste do suor
Agenesia dos ductos deferentes
STERN, NEJM, 1997
![Page 17: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/17.jpg)
FIBROSE CÍSTICA
Principais síndromes fenotípicas
Doença sino-pulmonar crônica.
Anormalidades gastro-intestinais e nutricionais.
Síndromes de perda de sal: depleção aguda de sal, alcalose metabólica crônica.
Anormalidades urogenitais masculinas, resultando em azoospermia obstrutiva.
Rosenstein. J Pediatr. 1998;132:389-95
![Page 18: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/18.jpg)
FIBROSE CÍSTICA
www.nhlbi.nih.gov/.../cysticfibrosis01.jpg
![Page 19: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/19.jpg)
A DOENÇA PULMONAR
FIBROSE CÍSTICA
A doença pulmonar na FC
![Page 20: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/20.jpg)
Doença sino-pulmonar
A) Colonização / infecção persistentes por patógenos típicos da FC como Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa e Burkholderia cepacia
B) Tosse crônica e produtiva
C) Anormalidades persistentes à radiografia de tórax
D) Obstrução das vias aéreas
E) Pólipos nasais, sinusiteF) Baqueteamento digital
Rosenstein. J Pediatr. 1998;132:389-95
FIBROSE CÍSTICA
![Page 21: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/21.jpg)
Patient Registry Education, 2007Richard B. Moss, MD. Stanford University Medical Center
![Page 22: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/22.jpg)
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed., 2007
FIBROSE CÍSTICA
![Page 23: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/23.jpg)
FIBROSE CÍSTICA
![Page 24: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/24.jpg)
FIBROSE CÍSTICA
![Page 25: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/25.jpg)
![Page 26: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/26.jpg)
![Page 27: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/27.jpg)
![Page 28: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/28.jpg)
![Page 29: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/29.jpg)
![Page 30: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/30.jpg)
![Page 31: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/31.jpg)
Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed., 2009
FIBROSE CÍSTICA
![Page 32: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/32.jpg)
A) Intestinal: íleo meconial, síndrome da obstrução intestinal distal, prolapso retal.
B) Pancreática: insuficiência pancreática, pancreatite recorrente.
C) Hepática: doença hepática crônica
D) Nutricional: hipodesenvolvimento pôndero-estatural , hipoproteinemia e edema, complicações secundárias à deficiência de vitaminas lipossolúveis.
Doença gastro-intestinal e nuricional
Rosenstein. J Pediatr. 1998;132:389-95
FIBROSE CÍSTICA
![Page 33: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/33.jpg)
FIBROSE CÍSTICA
![Page 34: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/34.jpg)
FIBROSE CÍSTICA
![Page 35: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/35.jpg)
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed., 2007
FIBROSE CÍSTICA
![Page 36: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/36.jpg)
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed., 2007
FIBROSE CÍSTICA
![Page 37: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/37.jpg)
FIBROSE CÍSTICA
COMPLICAÇÕES DA FIBROSE CÍSTICA
RESPIRATÓRIASBronquiectasiasAtelectasiasHemoptisePneumotóraxPólipos nasaisSinusiteHiperreatividadeCor PulmonaleIns. RespiratóriaImpactação mucóideABPA
GASTROINTESTINAISÍleo meconialPeritonite meconialSOIDProlapso retalIntussucepçãoVolvo intestinalColonopatia fibrosanteApendiciteAtresia intestinalPancreatite(s)Cirrose biliarIcterícia neonatal colestáticaEsteatose hepáticaDRGEColelitíaseFailure to thriveDef vits ADEKIn PancreáticaDiabetes
OUTRASInfetilidadeAtraso puberalEdema-hipoproteinemiaDesidratação grave/choqueOsteoartropatia hipertróficaBaqueteamento digitalAmiloidoseDiabetes mellitus
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 38: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/38.jpg)
NA PRÁTICA MÉDICA, QUANDO PENSAR EM FC?
![Page 39: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/39.jpg)
FIBROSE CÍSTICA
Lactentes
Íleo meconialIcterícia obstrutiva (colestase).“Failure to thrive”Edema, hipoproteinemia e anemiaBonquiolite ou pneumonia recorrenteProlapso retalPele salgada
VOYNOW, JA & SCANLIN, TF. Cystic Fibrosis
In: BELL, LM. Pediatric Pulmonology, 2005
![Page 40: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/40.jpg)
VOYNOW, JA & SCANLIN, TF. Cystic Fibrosis
In: BELL, LM. Pediatric Pulmonology, 2005
Pré-escolares e escolares
“Failure to thrive”EsteatorréiaProstração / distúrbio hidro-eletrolítico com calor“Asma”, bronquiectasias, baqueteamento digitalPolipose nasal.Prolapso retal.Pele salgada.
FIBROSE CÍSTICA
![Page 41: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/41.jpg)
VOYNOW, JA & SCANLIN, TF. Cystic Fibrosis
In: BELL, LM. Pediatric Pulmonology, 2005
Adolescentes e adultos
Atraso no desenvolvimento sexualAzoospermia obstrutivaBronquite crônica com Pseudomonas aeruginosa PansinusiteDor abdominal crônica, pancreatite idiopática, cirroseHemoptise, pneumotórax
FIBROSE CÍSTICA
![Page 42: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/42.jpg)
Rosenstein . J Pediatr 1998; 132:589-95
Critérios diagnósticosFIBRO
SE CÍSTICA
![Page 43: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/43.jpg)
Teste do Pezinho
Tripsina imunorreativa séricaScreening
FIBROSE CÍSTICA
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 44: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/44.jpg)
LeGrys. J Pediatr 1996;129(6):893-7
Teste do Suor
Método quantitativo descrito por Gibson e Cooke (1958).Estimulação da sudorese com pilocarpina.Amostras adequadas: peso acima de 50 mg; Mínimo de 2 amostras colhidas em datas separadas.Interpretação:-Normal: valores de cloro < 40 mEq/L -Limítrofe: entre 40 - 60 mEq/L - FC: igual ou > 60 mEq/L
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 45: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/45.jpg)
FIBROSE CÍSTICA
Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed., 2009
![Page 46: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/46.jpg)
Pesquisa de Mutações Genéticas
Muitos laboratórios pesquisam as 30-80 mutações mais comuns.Estes testes identificam >= 90% dos pacientes com 2 mutações. Alguns pacientes tem apenas 1 ou nenhuma das mutações identificadas por este método. Outros testes tentam detectar se há ou não mutações para FC, considerando todas, sem identificá-las.
FIBROSE CÍSTICA
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 47: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/47.jpg)
Potencial Diferencial Nasal (PDN)
Auxilia especialmente do diagnóstico de casos atípicos.
FC: PDN aumentado
Exame ainda pouco disponível
FIBROSE CÍSTICA
Kliegman: Nelson Textbook of Pediatrics, 18th ed., 2007
![Page 48: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/48.jpg)
Princípios do tratamento
Melhorar o clearance pulmonar;
Tratar a inflamação pulmonar crônica;
Repor enzimas pancreáticas e
Otimizar o estado nutricional Etc
FIBROSE CÍSTICA
![Page 49: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/49.jpg)
FIBROSE CÍSTICA
Sugestões de Leitura
Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report (J Pediatr. 2008;153:S4-S14)
BEHRMAN, RE; KLIEGMAN, RM; JENSON, HB. Nelson Textbook of Pediatrics, 18th ed, Elservier, 2007.
RODRIGUES, JC; ADEE, FV; DA SILVA FILHO, LVR (coord). Doenças respiratórias. Barueri, SP: Manole, 2008 – (Coleção pediatria. Instituto da Criança HC-USP. Editores da coleção Benita G. Soares Schvartzman, Paulo Taufi Maluf Jr.)
![Page 50: Fibrose cistica](https://reader031.vdocuments.pub/reader031/viewer/2022012306/5480d37db4af9f89308b477f/html5/thumbnails/50.jpg)
UM PACIENTE NUNCA DEVE TER O SEU
DIAGNÓSTICO EXCLUÍDO POR ESTAR MUITO BEM PARA TER
FIBROSE CÍSTICA
FIBROSE CÍSTICA