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INFLAMATION, FEVER

AND PAIN
Aguslina Kirtishanti
Fakultas Farmasi Ubaya

INFLAMASI/RADANG
Inflamasi/Radang adalah respon vaskular yang
hasilnya merupakan pengiriman cairan, zat-zat
yang terlarut, dan sel-sel dari sirkulasi darah
ke jaringan-jaringan interstisial pada daerah
cedera atau nekrosis.
Tujuan peradangan adalah : netralisasi dan
pembuangan agen penyerang (mikroba dan
toksin) dan sel/jaringan yang nekrosis serta
mengadakan proses perbaikan atau
pemulihan.

Dalam respon inflamasi/radang


melibatkan sel intravaskular, sel dan
matrik jaringan penghubung.
Sel intravaskular yang bersirkulasi
adalah : neutrofil, monosit, eosinofil,
limfosit, basofil, dan platelet.
Sel jaringan penghubung adalah : sel
mast, fibroblast dan makrofag.
Matrix jaringan penghubung/matrix
ekstraselular : kolagen, elastin,
glikoprotein (fibronektin, laminin,
tenascin), proteoglikan.

Radang dibedakan menjadi 2


yaitu :
1. Radang akut
2. Radang kronis

RADANG AKUT
Radang akut adalah respon awal dan segera
terhadap agen penyebab injury.
Proses pada radang akut mempunyai 3 komponen
utama yaitu:
1. Perubahan vaskular yang berakibat
peningkatan aliran darah
2. Perubahan struktur mikrovaskular yang
menyebabkan protein plasma dan leukosit
meninggalkan sirkulasi.
3. Emigrasi leukosit menuju daerah radang.

3 Komponen Proses Radang Akut


vasodilatasi

1.vasokontriksi

Sirkulasi darah lambat

2.Sirkulasi lambat

stasis

Kalor & rubor

Permeabilitas vaskular

stasis

3.

Aliran darah

Marginasi leukosit

tumor

dolor

Viskositas drh

Emigrasi leukosit

BAGAN ALIRAN DARAH DALAM MIKROSIRKULASI


B
KARENA
ADANYA INJURY
Injury
Arteriolar
dilation
Increased BHP
Fluid loss to
Tissue spaces
Increased
Blood viscosity

Reduced flow

RBC
aggregation

Stasis

RESPON INFLAMASI

MEDIATOR KIMIA PADA RADANG AKUT


Mediator

Source

Action
Vascular
leakage

Chemotaxis

Other

Histamine

Mast cell, platelets

Bradykinin

Plasma substrate

Pain

C3a

Plasma protein via


lever

Opsonic
fragment
(C3b)

C5a

Macrophages

Leukocyte
adhesion,activ
ation

Prostaglandins

Mast cells, from


membrane
phospholipids

Potentiate other
mediators

Vasodilation,
pain, fever

Leukotriene B4

Leukocytes

Leukocyte
adhesion,activ
ation

MEDIATOR KIMIA PADA RADANG AKUT


Leukotriene
C4,D4,E4

Leukocytes, mast cells

Bronchocontriction,
vasocontriction

Oxygen
metabolites

Leukocytes

Endothelial
damage, tissue
damage

PAF

Leukocytes, mast cells

Bronchocontriction,
leukocyte priming

IL-1 and TNF

Macrophage, other

Acute phase
reaction,
endothelial
activation

Chemokines

Leukocytes, other

Leukocyte
activation

Nitric oxide

Macrophage,
endothelium

Vasodilation,
cytotoxicity

Most Likely Mediators in Inflammation


Vasodilation
prostaglandins
nitric oxide
Increased vascular permeability
vasoactive amines
C3a and C5a
bradykinin
leukotrienes C4, D4, E4
PAF
Substance P
Chemotaxis, leukocyte activation
C5a
leukotriene B4
Chemokines
bacterial products

Fever
IL-1, IL-6, TNF
prostaglandins
Pain
prostaglandins
bradykinin
Tissue damage
neutrophil and macrophage
lysosomal enzymes
oxygen metabolites
nitric oxide

Outcome of Acute Inflammation


Resolution
injury

mediators
Acute inflammation

Abscess Formation

mediators

Chronic inflammation

Persistent infection
Persistent toxin
Autoimmune diseases

Healing
Regeneration
Scarring

RADANG KRONIS
Radang kronis adalah radang dengan durasi
yang lama (minggu atau bulan), terjadi
kerusakan jaringan dan perbaikan jaringan
terjadi secara simultan.
Radang kronis terjadi karena hal berikut :
1. Infeksi yang menetap karena
mikroorganisme seperti Mycobacterium
tuberculosis, Treponema pallidum dan
beberapa fungi.
2. Pemaparan yang berlangsung lama
terhadap agen toksik, baik eksogen
maupun endogen, cth : silicosis dan
atherosclerosis.
3. Autoimmune diseases

KARAKTERISTIK RADANG
KRONIS
Infiltrasi sel mononuklear :
makrofag, limfosit, dan sel plasma.
Kerusakan jaringan : diinduksi oleh
sel radang.
Perbaikan jaringan oleh jaringan
penghubung/connective :
angiogenesis dan fibrosis.

PATOGENESIS RADANG
KRONIS

Activated T cell

Cytokine (IFN-)
Nonimmune Activation
(endotoxin, fibronektin,
Chemical mediators)

Monocyte/macrophage

Activated macrophage

Tissue Injury :
Toxic oxygen metabolites
Proteases
Neutrophil chemotactic
factors
Coagulation factors
AA metabolites
Nitric oxide

Fibrosis :
Growth factors (PDGF, FGF,
TGF)
Fibrogenic cytokines
Angiogenesis factors (FGF)
Collagenases

FEVER
Temperatur oral normal rata-rata adalah
36,7 C dan tidak boleh dari 0,5C.
Temperatur rektal lebih tinggi 0,5C dari
oral sedangkan temperatur aksilaris lebih
rendah 0,5C.
Perubahan temperatur dapat
mempengaruhi fungsi selular karena
kecepatan metabolisme sel bergantung
pada temperatur. Dikatakan fever jika
temperatur meningkat dari 1 - 4 C.

Mekanisme Hilangnya Panas


dan Mekanisme Produksi
Panas
Hilangnya panas dapat melalui 4 mekanisme :
1. Radiasi
2. Evaporasi
3. Konduksi
4. Konveksi
Produksi panas dihasilkan oleh metabolisme
sel dan selanjutnya harus dibuang untuk
mencegah kelebihan panas dalam tubuh.
Jika suhu tubuh turun maka panas diproduksi
melalui reflex fisiologis (gemetar) dan
respon behavioral (jumping in place).

MEKANISME TERMOREGULASI
Thermoreceptors

Cerebral
cortex

Hypothalamus

Sweat
glands

Dermal
arterioles

Shivering

Behavioral
responses

Sweat at
Skin surface

Dermal
Blood flow

PATOGENESIS FEVER
Trauma/
Ischemic injury

Inflammation

Endogenous
pyrogen

Set point
elevation

Fever

Infection

Exogenous
pyrogen

EXOGENOUS PYROGENS

Endotoxin (LPS)
Virus
Bakteri
Jamur
Substansi toksik seperti : bahan kimia
dan obat-obatan.

Endogenous Pyrogens

IL-1 (Interleukin-1)
TNF (Tumor Necrosis Factor)
IFN (Interferon)
MIP-1 (Macrophage Inflammatory Protein)
IL-6

Endogenous pyrogen dihasilkan oleh sel


fagositik (PMN, limfosit dan makrofag).

Rangkuman Mekanisme Fever


Infections, toxins, immune complexes, neoplasia
IL-1/TNF

IL-6

Hypothalamus
Prostaglandins E, NO, cytokines (IL-1)
Vasomotor center
Sympathetic nerves
Skin vasocontriction

Fever

Heat dissipation

PAIN
Pain is an unpleasant sensory and
emotional experience associated with
actual or potential tissue damage
Pain is frequently the result of
nociception, activity in the nervous
system that results from the
stimulation of nociceptors (paindetecting neurons).

Classification of Pain
Pain can be acute or chronic.
Acute Pain
Acute pain usually is caused by soft tissue
damage, infection and/or inflammation. Acute
pain serves to alert after an injury or
malfunction of the body.
Chronic Pain
Chronic pain may have no apparent cause or
may be caused by a developing illness or
imbalance. Duration of chronic pain is lasted
6 months or longer. The failure to treat acute
pain properly may lead to chronic pain in
some cases.

Sources of
Pain
Cutaneous pain
Somatic pain
Visceral pain
Phantom limb pain
Neuropathic pain

Physiology of
Nociception
Nociception is the system that carries
signals of damage and pain from the
tissues.
Nociceptors can detect mechanical,
thermal and chemical stimuli.
There are two ways for nociceptive
information to reach the central
nervous system :
a. Neospinothalamic pain pathways
b. Paleospinothalamic pain pathways

A. Neospinothalamic pain
pathways
Type of fibers : A delta fibers [small and
myelinated fibers that conduct their action
potentials relatively quickly (5 to 30
m/sec)].
They are distributed only to the skin,
mucous membranes, and selected serous
membranes.
They tend to fire immediately upon
(intense) stimulation and cease firing
when the stimulus is removed, producing
the sensation of sharp pain.

B. Paleospinothalamic pain pathways


Pain fibers : C fibers (smaller than A delta in
diameter, unmyelinated, and conducted impuls 0,5
2 m/sec).
They are distributed to the same areas as the A delta
fibers, but with much greater density. They are very
widely distributed in deep tissue : in muscle and
tendon, visceral peritoneum and the visceral organs
themselves (myocardium, stomach, intestines).
Action potentials in these fibers tend to be generated
by substances that are associated with tissue
damage or insult.
C fibers carry information related to long-lasting,
burning, often called dull pain, which is poorly
localized and more diffusely distressing.

The General Scheme for Underlying Perception of


The Two Types of Pain
A delta nociceptors
(sharp pain)

C nociceptors
(dull pain)

Dorsal horn
interneurons
Neospinothalamic
pathway

Paleospinothalamic
pathway
Higher perception
centers

Acute
Sharp pain

Chronic
Dull pain

Pain Pathway