PATOFISIOLOGI TRAUMADefinisi :TRAUMA adalah semua jenis kekerasan yang menimpa tubuh sehingga terjadi kerusakan/gangguan pada struktur dan fungsi jaringan/organ tubuh yang terkena, bahkan Widjoseno GardjitoDepartment of Urology Medical School Airlangga University - Dr. Soetomo Hospital Surabaya1

secara sistemik dapat berdampak pada aspek fisiologis, kejiwaan dan kondisi sosial insan yang bersangkutan.2

JENIS TRAUMATRAUMA pada JARINGAN/ORGAN Ledakan benda berkecepatan tinggi, benda tajam (tusukan, irisan, sabetan), benda tumpul Suhu tinggi/rendah uap panas luka bakar

KERUSAKAN PERDARAHAN NYERI3

frostbite (suhu dingin) Arus listrik tegangan tinggi Bahan kimia Radiasi, ionisasi Gigitan, sengatan4

KERUSAKAN AKIBAT TRAUMABentuk :Diastase (kerobekan), memar, erosi, lecet, hancur (crush injury), jaringan hilang

Lokalisasi : Jaringan lunak + kulit

: - luka terbuka - luka tertutup

Tulang / sendi : fraktura / dislokasi Organ berongga (lambung, usus) : perforasi Organ Padat (hati, limpaa,ginjal, otak : ruptur, memar5 6

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AKIBAT TRAUMA SEMBUH CACAT (anatomis + fisiologis + psikologis) MENINGGAL

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INSULTHEBAT TUNGGAL GANDA

HEBAT / BERAT 4 I-s

TRAUMA

RINGAN

LOKAL

Injury Infection Inflammation IschemiaTANDA + GEJALA

REAKSI TUBUH(Bagian dari proses Penyembuhan secara alami)

SISTEMIK

SIRS(Systemic Inflammatory Response Syndrome)11 12

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Bacteremia

SIRS can be identified by the presence of two or more of the following manifestations :Other

1. A body temperature greater than 38C or less than 36C. 2. Heart rate greater than 90 beats per minute 3. Tachypnea (respiratory rate > 20 breaths per minute or

Fungemia

INFECTIONParasitemia

SEPSISViremia Other

SIRS

Trauma

Pa CO2 < 32 mmHg 4. White blood cell count greater than 12.0 x 109/L or less than 4.0 x 109/L or the presence of more than 10% immature neutrophils (bands).

BURNS

Pancreatitis

Beal et al, JAMA, 1994;271;226-233

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SIRS and MODS

Inflammatory and organ dysfunction responses to injury. Normal response to an injury or insult may decrease after 3 to 5 days or be reactivated by a complication. A continuous inflammatory response is seen with systemic inflammatory response syndrome (SIRS) and can eventually progress to organ dysfunction (reprinted from 4). Beal et al, JAMA, 1994;271;226-233

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SEPSIS :SIRS plus a documented infection site (documented by positive culture for organisms)

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Severe Sepsis :Sepsis associated with organ dysfunction, hypoperfusion abnormalities, or hypotension. Hypoperfusion abnormalities include but are not limited to : 1. lactic acidosis, 2. oliguria 3. or an acute alteration in mental status19

Septic Shock :Sepsis-induced hypotension despite fluid resuscitation PLUS hypoperfusion abnormalities

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MODSOrgan Dysfunction associated with Severe Sepsis and Septic Shock : Lungs : early fall in arterial PaO2 , Acute Respiratory Distress Syndrome (ARDS): Capillary-leakage into alveoli; tachypnea, hyperpnea Kidney : (acute renal failure): oliguria, anuria, azotemia, proteinuria Liver : elevated levels of serum phosphatase, cholestatic jaundice bilirubin, alkaline

MODS Organ Dysfunction associated with Severe Sepsis and Septic Shock : Skin : ecthyma gangrenosum (think Pseudomonas aeruginosa in neutropenic patients), Petechia or purpura (think Neisseria meningitidis or Rickettsia rickettsia (if evidence of tick bite)), Hemorrhage or bullous lesions in patient who has eaten raw oysters (Vibrio vulnificus), generalized erythroderma (Toxic Shock Syndrome= Staphylococcus aureus or Streptococcus pyogenes) Heart : cardiac output is initially normal or elevated,21

Digestive tract : nausea, vomiting, diarrhea and ileus

Brain : confusion

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OSLERS DICTUMPatients usually die of complications of their disease, rather than from the disease itself

SIRS

MODS

MOF

BUKAN PENYAKIT BUKAN SINDROMAMERUPAKAN PERUBAHAN BERKELANJUTAN DARI FUNGSI

ORGAN YANG MENYANGKUT ASPEK FISIOLOGIS DAN METABOLIK SEBAGAI RESPONS TERHADAP SUATU INSULT YANG SERIUS. HUBUNGAN ANTARA RESPONS-RESPONS SERIAL DAN FUNGSI ORGAN BERSIFAT DINAMIS DAN BERKELANJUTAN23 24

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SIRS MODS MOF MSOF ARDS DIC

Systemic Inflammatory Response Syndrome Multiple Organ Dysfunction Syndrome

DEAR SIRS WE ARE SORRY TO SAY

Multiple Organ Failure Multiple-Sytem Organ Failure Acute Respiratory Distress Syndrome Disseminated Intravascular Coagulation

THAT WE DONT LIKE YOU

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Sir Isaac Newton :To every action is always an equal reaction or The mutual action of two bodies upon each other are always equal, and directed to contrary parts Philosophiae Naturalis principia Mathematica1687Bone RC Crit. Cave Med, 1996;24:1125-112827 28

BIOLOGICAL SYSTEMS, such as the human body, are more complicated than the simple physical systems Sir Isaac was describing

MACROPHAGE ( morfologi ) :

Sel besar Inti bulat/indented Golgi apparatus developed Vakuol endositotik > Lisosom + fagolisosom Plasma membrane diselubungi mikrovili/ruffles

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MACROPHAGE ( fungsi ) : Nonspecific phagocytosis/pinocytosis Specific phagocytosis opsomized microorganisms (Fc receptors + complement receptor) Killing ingested microorganims Digestion + presentation of antigens to T + B lymphocyte Secretion of :

MACROPHAGE ( jenis ) : Histiosit Sel Kupffer Osteoclasts Microglial cells Synovial type A cells Interdigititating cells Langerhans cell Langerhans, epitheloid cells Multinucleated giant cells31

enzymes : lysozyme, collagenases, elastase, acid hydrogenases complements + coagulation factors some prostaglandins and leukotrienes several regulatory molecules (interferon, Interleukin-1)

Inflamed tissues32

MACROPHAGE

MEDIATORMononuclear phagocytes di dalam jaringan : Bone marrow : STEM CELL

Bahan yang dilepaskan oleh sel sebagaimonoblast promocyte Blood (40 hours): MONOCYT Tissue : MACOPHAGES : - size - phagocytic activity - lysosomal enzym content33 34

hasil interaksi antigen-antibodi atau antigen dengan sel limfosit yang sudah mengalami sensitisasi

SITOKIN CYTOKINE (SITOKIN) : (cyto + kinesis)movement

Anggapan Nonantibody protein released by one cell population (eg. Primed T-lymphocytes) on contact with specific antigen, which act as intercellular mediators, as in the generations of immune response. Examples include : Lymphokines, monokines Sitokin

: sitokin

~

patologi

: Melindungi tubuh tapi juga bisa SIRS

Mulai ditemukan antogonis sitokin Mencegah SIRS ?35 36

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Proses dilepasnyaPro inflamatori sitokin + mediator-mediator merupakan Mekanisme pertahanan tubuh melokalisir + menetralisir kuman yang menyerang membersihkan sel yang mati / rusak memulihkan jaringan NAMUN Aktivasi yang berkelanjutan / berlebihan justru MERUGIKAN

NORMAL STRESS RESPONSE PERUBAHAN KARDIOVASKULERtakikardi, kontraktilitas, curah jantung (CO), konsumsi oksigen RESPONSE SISTEM NEUROENDOKRIN Dilepasnya katekolamin, kortisol, ADH, glukagon, insulin. CASCADE : - koagulasi - komplemen - sistem fibrinolitik : 3 5 hari 7 10 hari

Growth

Hormone,

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Puncak reaksi reda

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PATOGENESIS SIRS4 - I (Injury Infection Ischemia Inflammation) Stage I Lokal

SITOKIN Circulating form (misal : IL-1 beta) (sistemik) Cell associated form (misal : IL-1 alpha) (lokal) Asumsi : lokal prekursor sistemik Bila produksi sitokin lokal melampui batas ambang tumpah sistemik40

: Sitokin sel

(penyembuhan luka merangsang mematikan organisme patogen)

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Stage II- Sejumlah kecil sitokin masuk sirkulasi merekrut : makrofag, trombosit growth factor Terjadi reaksi akut :

Stage IIIHomeostasis tak berhasil dipulihkan Sitokin ( semula protektif ) Destruktif

Sirkulasi penuh dengan mediator inflamasiterkendali - pro inflamm, mediator - endogenous antogonist (misal : IL-1 receptor antagonist) - antibodi Luka sembuh Infeksi teratasi Homeostasis pulih tidak terkendali Stage III

Intergritas dinding kapiler rusak Sitokin masuk organ / jaringan MOD41 42

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Figure 1. First hit, second hit, and sustained hit that can occur with systemic inflammatory response syndrome (SIRS). ARDS, adult respiratory distress syndrome; MODS, multiple organ dysfunction syndrome.

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Figure 2. Three stages of the systemic inflammatory response syndrome reaction Crit Care Med 1996 Vol. 24, No. 1

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TRAUMAmay be considered to be an inflammatory disease KADAR : - berbagai mediator - indikator respons inflamasi pada trauma berat. MARKERS inflamasi dapat digunakan : - menilai beratnya trauma - meramalkan prognosis (outcome)45

TRAUMA BERAT dan KEMATIAN POLA DISTRIBUSI TRI MODAL Kematian Sesaat (Immediate Deaths) Segera setelah trauma Kematian Dini (Early Deaths) Beberapa jam setelah trauma Kematian Lambat (Late Deaths) Berhari-hari hingga berminggu-minggu setelah trauma46

TRAUMA BERAT dan KEMATIAN POLA SITRIBUSI TRI MODAL

JALAN TOL menuju kematian Trauma multipel Sumber infeksi Immunocompromised

1

2

3

Sistem Penunjang berbagai organ (ICU) SIRS

Immediate

Early

Late

MODS ARDS, DIC, ARF, KARDIOMIOPATI Meninggal47 48

TRAUMA BERAT

8

1991

Concensus Conference

Dirintis konsistensi

Me