Nama

Tim Kurikulum Pendidikan Preklinik

Program Pendidikan Dokter

Universitas Islam Malang

2 0 1 1

*No more medical records were addedI. Identifikasi kata sulit : Mahasiswa mencari kata sulit yang dianggap perlu untuk diketahui

II. Identifikasi masalah :

1. Mengapa pasien mengalami nyeri seluruh otot dan badan sumer? (menjelaskan proses inflamasi pada otot skeletal yang berpengaruh pada keadaan sistemik)2. Bagaimana hubungan etiologi dengan patofisiologi terjadinya tanda dan gejala pada pasien tersebut? (menjelaskan mikroorganisme Trichinella spiralis menimbulkan gejala dan tanda pada pasien)3. Bagaimana cara menegakkan diagnose pasien tersebut?

4. Bagaimanakah penatalaksanaan pada pasien ini?5. Terangkan tindakan yang dilakukan menurut tahapan upaya pencegahan! III. Brain storming1. Patofisiologi inflamasi pada otot skeletal dan pengaruhnya terhadap gangguan fungsi otot.2. Berbagai jenis penyakit/kelainan pada otot skeletal sebagai deferential diagnosis3. Regenerasi dan mekanisme adaptasi injury/cedera otot skeletal4. Nematoda jaringan pada manusia, penularan dan penatalaksanaannya5. Farmakologi obat-obat anti parasit (pharmacology parasitic diseases.)

6. Komplikasi akibat penyakit inflamasi pada otot skeletal IV. MappingsV. Learning Objectives1. Mahasiswa menjelaskan anatomi, histologi dan perbedaan otot/ muskulus skeletal dengan otot polos dan otot jantung2. Mahasiswa menjelaskan etiologi dan patofisiologi gangguan muskulus/otot skeletal3. Mahasiswa menjelaskan proses diagnosis berbagai gangguan muskulus/otot skeletal 4. Mahasiswa menjelaskan berbagai pemeriksaan penunjang yang diperlukan untuk menegakkan diagnosa gangguan muskulus/otot skeletal 5. Mahasiswa menjelaskan penatalaksanaan komprehensif (termasuk upaya pencegahan) gangguan muskulus /otot skeletal6. Mahasiswa menjelaskan human tissue parasitic diseases pada umumnya dan nematoda jaringan otot pada khususnya.VI. Self Directed LearningVII. ReportingReferensiBhushan, Vikas, et. al. 2002. Blackwells Underground Clinical Vignette. Microbiology volume II, 3E. Blackwell Publishing. USABrooker, Simon. Bundy, Donald A. P.. Mansons Tropical Diseases. 22nd edition. Edited by Manson, Patrick. et. al. Section 11. Chapter 85.pg 1540. Appendix I.Clinical laboratory Diagnosis,pg 1600. Appendix III.Medical Helminthology.,pg 1683

Mapping ConceptLanjutan Mapping conceptMapping Kasus

Mapping Patofisiologi pada Kasus

Mapping Alur Penegakan Diagnosis Gangguan Muskuler dan NMJ

Persamaan persepsi

Skenario Kedua

Skenario 2

An. TS, laki-laki 5 tahun datang ke RS dengan keluhan utama nyeri seluruh otot dan badan sumer. Beberapa minggu yang lalu pasien mengeluhkan nyeri perut yang parah disertai diare. Pasien tinggal bersama orang tuanya yang bekerja bertahun-tahun sebagai peternak babi.

Pemeriksaan fisik didapatkan tanda febris, edema wajah dan periorbita; Nyeri pada otot bagian betis, paha dan pundak; perdarahan conjunctiva dan sklera tidak terdapat defisit neurologi.

Laboratorium darah menunjukkan eosinofilia, laju endap darah normal, peningkatan serum CPK (Creatinin Protein Kinase), LDH dan AST; aglutinasi latex menunjukkan hasil positif untuk Trichinella. Biopsi PA menunjukkan adanya kista Trichinella spiralis.

Apa diagnosa pasien tersebut dan bagaimana penatalaksanaannya?

OTOT SKELET

Energy Supply

Anaerob Glycolysis

Aerob Glycolysis/ oksidasi fosforilasi

Fosfokreatinin o/ creatinin-kinase

RELAKSASI

Thin Filamen

KONTRAKSI

Myofibril

Perimysium

Fungsi

Sliding Of Thick & Thin Filament

Asetil Kolin release

Struktur

Endomysium

(>> kolagen + kapiler)

Bind with Nikotinik rec.

Ca Bind to Troponin C

End Plate Potensial

If Terganggu

Na+ K+ Konduktansi pd motor end plate

Muscle fiber Action Potential

Ca2+ Release o/ Sarcoplasmic retikulum

Inward Potential sepanjang T Tubules

Ca2+ sitosol

Ca2+ dipompa masuk kembali

Motor Neuron Signal

Type I (Slow Red/ felderstruktur)

>> Oxydative Enzyme

>> mitokondria

>> Myoglobin

>> Lipid

Protracted Slow Action

Tonic Activity

Low ATP-ase activity of Myosin

Slow Calsium/Strontium Activation

Extrasellular K+

Kontraksi

Binding Ca2+ dg Troponin C

Pemendekan/ Kontraksi otot

Myosin Binding Site opening

Crosslink Formation of Actin & myosin

Type II (Fast white/ Fibrillenstruktur)

>> Glycogen & Glycolitic Enzyme

Fast Powerfull Tonic Contraction

Phasic Activity

HighATP-ase activity of Myosin

Fast Calsium/Strontium Activation

Irritabilitas & kontraktilitas

Tenaga relaksasi

Spasme Otot

Mild Membrane Depol

Open Na Channel (Inaktivasi Na Channel AbN)

Persistant Inward Of Na+ Current

Depolarization of Muscle cell prolong

Inactivation of Na Channel

Loss of electrical exitability of muscle membranes

Weakness

If Terganggu

Thick Filamen

Associated Parts

Myosin

Heavy Chain (HC)

Type Gen

I (slow) MHY-7

II (fast) IIa MHY-2

IIb MHY-4

IIc MHY-1

IIx MHY 1

Light Chain (LC)

Essential LC (Alkali LC/ Non Phosphorylatable)

Regulatory LC (DNTB LC/Phosphorilateble by MLCK)

Myosin Chaperone

M-Line

- Creatinine Kinase

- M-Protein

- Myonesin

Non Myosin Components

(C-Protein, X-Protein, H-Protein, Titin)

Actin

(G-Actin, F- Actin, Actin Filaments)

Regulatory Proteins

(Tropomyosin, Troponin (TN-I, TN-C, TN-T), Profilin, Cofilins) + Calponin & caldesmon in otot polos)

Costameres

Aciculin,dystroglycan, / actin, Dystropin, Integrin

Structural Components &Associated Structures

Nebulin, nebulin related anchoring protein

Z-Lines

Desmin, Desmuslin, Capping protein, Calpain 3, Calsineurin, Aciculin,dystroglycan, / actin, Dystropin

NMJ

Post Sinaptic membrane

Extracellular Proteins

Intracellular proteins

Dystrophin-Glycoprotein

Muscle membrane

Extracellular Proteins

Intracellular proteins (Structural/signaling)

Dystroglycan Complex

(sarcoglycan,sarco-glycan complex, dsyferlin Integrin, Caveolin, dll)

Other Protein (extracellular matrix protein)

(Kolagen, Basal lamina, reticular lamina, laminin, agrin, heparan sulfat proteoglycan, byglycan, nidogen, fibronectin dll)

HEREDITER

Muscular dystropy/MD (timbul akibat mutasi Dystropin & dystropin related protein) ( duchennes MD, beckers MD, emery dreifuss MD, Limb-girdle MD, Congenital MD (with & w.o CNS involvement), Distal MD & others

Congenital Myopathy (akibat defek gen) (Central core M, Nemaline M, Myotubular M,sarcotubular M, Myofibrilar M, dll

Myotonic Dystriophy (akibat DNA repeat problems yg ganggu sintesa & fungsi protein kinase (Myotonin) ( myotonia + ( DM-1 & DM-2

Channellopathy (mutasi gen protein kanal) ( Cloride, Sodium, Potassium aggravated, calcium Channellopathies, DLL

Metabolic Myopathy (Defek Enzym pada metabolisme) ( glycogen, Lipid, Purine metabolism deficiency)

Mitocondrial Myopathy (defek enzym Ox-Phos ( Energi Otot ( myopathy)

DIDAPAT

Inflammatory Myopathies

Idiopatic cause/autoimmune? ( Polymyositis, Dermatomyositis, inclusion Body myositis, Focal myositis, myositis ossificans dll

Infeksi (bakteri, Virus, parasit & jamur)

Endocrin Myopathies (Adrenal/glucocorticoid Disorder, Thyroid, paratyroid, Pituitary disorder, DM, Vitamin deficiency)

Myopathies associated with systemic Illness (e.g.electrolytes imbalance, Hormonal problems)

Drug Induced/Toxic Myopathies ( damaged due to toxic or drugs effect to muscle ( inflamatory tipes, vacuolar (non inflamatory-necrotizing, Rhabdomyolysis & myoglobinuria, malignant hyperthermia, Mitochondrial damage, Myotonia types, Myosin loss

Higiene perorangan buruk

sanitasi lingkungan buruk (daerah endemik)

Konsumsi daging yang kurang masak

Status imun kurang adekuat

Levels of preventions

An.TS/5thn

Infestasi larva T spiralis via contaminated food

Sakit perut yang parah kmdn diare

Terjadi reaksi Ag-Ab, infeksi jaringan otot skeletal

Dx Fungsional:Trichinosis

Dx Etiologi:Myositis e.c Trichinella spiralis

Berlanjut

Simptoms: nyeri perut yang parah disertai diare( nyeri seluruh otot dan badan sumer

Sign: febris, edema wajah dan periorbita; Nyeri pada otot bagian betis, paha dan pundak; perdarahan conjunctiva dan sklera; tidak terdapat defisit neurologi.

Pemeriksaan penunjang

DL (eosinofil(,LED N,CPK (, LDH (, AST(

Tes aglutinasi (+positif untuk Trichinella. Biopsi PA menunjukkan adanya kista Trichinella spiralis(lihat gambar)

nyeri seluruh otot dan badan sumer

Prinsip Terapi:

Atasi gejala

Anti parasit (see drug of choice)

Cegah reinfeksi atau infeksi sekunder

Cegah komplikasi ke jaringan/organ lain

Bed rest

Rehabilitasi

Cegah relaps

KIE keluarga

Kontrol

Community Control

(1) mass chemotherapy; (2) sanitation;

(3) health education; (4) community participation; and

(5)monitoring and evaluation

Consumed flesh of pig which contaminated with cyst

FAKTOR RESIKO

Sanitasi lingk

Imunocompromized

Gizi Buruk

Inkubasi (4 16 mgg)

Myonecrosis

Foreign body giant cells may be present. The infi ltrate subsides and fat is deposited at the poles

and after 6 months calcifi cation takes place, eventually leading to death of the larva.

Release of Inflamatory sitokines

Replace myofibril loss/ Myofiber Formation

Invasi MN & PMN ke Jar Otot

Regenerasi < Destruksi

Endomysial Fibrous formation

Muscle Mass

Loss Of Muscle Mass

At first there is a basophilic degeneration of the muscle fi bres followed by formation of a hyaline capsule around the larva with an infl ammatory infi ltrate of lymphocytes and a few eosinophils

Corticotropin injeksi

Encyst become larvae and Larvae, after travelling through the circulation, encyst in muscles of the diaphragm, masseters, intercostals, and laryngeal, tongue and ocular muscles.

Protein Fase Akut release

Systemic Reaction (Eosinofilia, LED,CPK

Nociceptive Receptor

Muscle Atropi

Myofiber diganti dg Jar. Lemak & Fibrosa/ kolagen

Myonuclei of adjacent segment, endomysosin

Karakteristik dan siklus hidup T psiralis Man is not the normal host

.

Edema

Efek imunosupresi

Inflamasi

Penyembuhan/Resolusi

- (granulasi)

- Fibrosis

- Jar. Parut

Proliferasi +

Hipertrofi sisa massa otot

Damages Structure of Muscle (Internal Nuclei, Internal Split Irregularity Orientation of Myofilamen)

Organisasi

(fagositosis & pembentukan Jar. Granulasi)

Kerusakan Muscle Fiber

Disuse otot

Destruksi Myofiber oleh T sipralis terus menerus (Loss Of Myofiber)

Removed parasite & organization

Imbalance Regeneration & Myonecrosis +

Pain +

Disuse Otot +

Muscle Stiffness & Contracture

Myofiber regeneration

Pyrogen Release

Febris +

An. TS/5 Th

Asymthomatic Infeksi pada Otot

Symthomatic Infection (myositis)

Ggx Sarcolemna, gangguan homeostasis Ca, Digesti Myofiber

Suspected Neuromuscular Problems

Defek Neurologis +

Neuropathy

Systemic Illness +

Neuromuscular problems Associated with systemic illness

NMJ characteristic +

NMJ Problems/Myastenic syndrome

Muscle Problems

Myopathy Characteristic

- Proximal Weakness

- Usually Creatinin Kinase level

- Myopathic EMG changes (low voltage, Short motor unit potential e.c myofiber)

Denervation

- Distal Weakness

- Muscle atropi lbh prominen

- Neuropathic EMG changes

Lab Study

- Creatinine Kinase level ( pd myonecrosis +)

- DL, LED,kultur (infection causes)

- Serologis (autoimune, Immune muscle)

- EMG, Tensilon Test

- Biopsi Otot, genetic studies

- DLL

Therapetic

- Kausal

- Sympthomatic

- Farmakologic

- Non Farmacologic

Ax khas Muscle Problems

- Fatiquability/mudah lelah

- Muscle Pain/Myalgias (Soreness/kemeng)

- Skin Rash (if skin affected +)

- Muscle Atropi

- Fasikulasi, Kram/cramps

- Muscle Mass

- Muscle tenderness (local or general)

Muscle Swelling

Physical Diagnosis

- Weakness sign +

- Motoric/sensoric defect

- Mass or tenderness or Swelling +

- Gait/Posture changes

- Myotonia, Stiffness

- Damage of nerve

Inflamasi,fagositosis(?), aktivasi komplemen.IL 4 dan IL5 dr Th 2