Kuliah Pakar

Modul 3.1

Dr. dr. Awal Prasetyo, M.Kes, Sp-

Curriculum Vitae
Taman Kradenan Asri H-11 Semarang
50221
Telpon: 024-8503635 HP:08122810954
Email: [email protected]
SD Dewantara Semarang (1979)
SMP Domenico Savio Semarang (1982)
Awal
Prasetyo

SMA 3 Semarang (1985)

Drs. Med.-FK UNDIP (1990)
Dokter-FK UNDIP (1993)
M.Kes (Pathobiologist)-UNDIP (2002)
Sp.THT-KL-FK UNDIP (2009)
S3 (Doktor)-UGM (2014)

1) Bagaimana mekanisme terjadinya

DEMAM?

Pathogenesis of FEVER
Pyrogens
Pyrogenic Cytokines
Elevation of The
Hypothalamic Set Point
by Cytokines
Production of Cytokines
in the CNS

FIGURE16-1 Chronology of events required for the induction of

fever.
Abbreviations: AMP, adenosine 5-monophosphate; IFN, interferon; IL,

Pyrogens
The term pyrogen is used to describe any
substance that causes fever.
Exogenous pyrogens (microbial products,
microbial toxins, or whole microorganisms).
The classic example of an exogenous pyrogen:
Lipopolysaccharide endotoxin produced by all
gram-negative bacteria .
Gram-positive organisms, includes
enterotoxins
of Staphylococcus aureus
& group A & B streptococcal toxins.
Endogenous pyrogens (fever-producing
molecules inducted by products of activated
leukocytes).

Pyrogenic Cytokines
Cytokines: small proteins (10,000-20,000 Da) that regulate
immune, inflammatory & hematopoietic processes.
Some cytokines cause fever and hence are called
pyrogenic cytokines.
The known pyrogenic cytokines include IL-1, IL-6, tumor
necrosis factor (TNF), ciliary neurotropic factor (CNTF) &
interferon (IFN).
The microbial infection, inflammation, trauma, tissue
necrosis, or Ag-Ab complexes can induce the production of
IL-1, TNF, and/or IL-6, whichindividually or in
combinationtrigger the hypothalamus to raise the set
point to febrile levels.

The cellular sources of pyrogenic cytokines are primarily

monocytes, neutrophils & lymphocytes, although
many other types of cells can synthesize these
molecules when stimulated.

Pada respon radang terdapat tumor.

Bagaimana tumor tersebut kembali ke
keadaan
normal?
1)

2) Apakah perbedaan makros & mikros tonsil &

faring
pada infeksi akibat virus dan bakteri?
3) Kenapa pasien pada kasus ini merasa mual &
muntah?
4) Apa yang dimaksud reaktivitas silang antara
antibodi
pada katup jantung dengan Nasetylglucosamin?
5) Secara teori, komplikasi rematik dan sesak di
dada

CAUSES OF DISEASE
CONGENITAL
Inherited or familial
Congenital

ACQUIRED
Injury
Inflammations
Mechanical
Metabolic
Circulatory
Endocrine
Degeneration & infiltrations
Tumours
Other varians

 Acute

INFLAMMATION

Acute inflammation is rapid in onset & of short

duration, lasting from a few minutes to as long as
a few days, and is characterized by fluid &
plasma protein exudation (swelling=TUMOR) & a
predominantly neutrophilic leukocyte
accumulation.

Chronic
May be more insidious, is of longer duration (days
to years), and is typified by influx of
lymphocytes & macrophages with associated
vascular proliferation & fibrosis (scarring).

However, as we will see later, these basic forms of

inflammation can overlap, and many variables
modify their course and histologic appearance.

Acute inflammation
has two major components (Fig. 22 ):

1)Vascular changes:

Alterations in vessel caliber resulting in increased

blood flow (vasodilation ) & structural changes that
permit plasma proteins to leave the circulation
(increased vascular permeability).

2) Cellular events:
Emigration of the leukocytes from the
microcirculation & accumulation in the focus of
injury (cellular recruitment & activation ).
The principal leukocytes in acute inflammation are
neutrophils (polymorphonuclear leukocytes).

Figure 2-2.
The major local
manifestations of acute
inflammation, compared to
normal.
(1) Vascular dilation &
increased blood flow
(causing erythema/RUBOR
& warmth/KALOR)
(2) extravasation &
deposition of plasma fluid &
proteins (edema/TUMOR),
& (3) leukocyte (mainly

Vascular changes
Changes in Vascular Caliber & Flow
As the microvasculature becomes more
permeable, protein-rich fluid moves into the
extravascular tissues.
This causes the red blood cells to become more
concentrated, thereby increasing blood viscosity &
slowing the circulation.
These changes are reflected microscopically by
numerous dilated small vessels packed with
erythrocytes & slowly flowing blood, a process
called stasis.
As stasis develops, leukocytes (principally
neutrophils) begin to accumulate along the
vascular endothelial surface, a process called
margination.

Vascular changes
Increased Vascular Permeability

Figure 2-3.
Formation of transudates & exudates.
A) Normal hydrostatic pressure (blue arrows ) is about 32
mm Hg at the arterial end of a capillary bed & 12 mm Hg
at the venous end; the mean
colloid osmotic pressure of tissues is approximately 25
mm Hg (green arrows ), which is equal to the mean
capillary pressure. Therefore, the net flow of fluid across
the vascular bed is almost nil.
B) A transudate is formed when fluid leaks out because
of increased hydrostatic pressure or decreased osmotic
pressure.
C) An exudate is formed in inflammation because
vascular permeability increases as a result of increased
interendothelial spaces.

The steps of the inflammatory

response (the five Rs):
(1)Recognition of the injurious agent
(2)Recruitment of leukocytes
(3)Removal of the agent
(4)Regulation (control) of the response
(5)Resolution (repair)

Resolution (repair)#1
If: injury is limited or short-lived, no or minimal tissue
damage & tissue is capable of replacing any irreversibly
injured cells (restoration to histologic & functional
normalcy).
Termination of acute inflammatory response involves;
neutralization, decay or enzymatic degradation of various
chemical mediators, normalization of vascular permeability
& cessation of leukocyte emigration with subsequent death
(by apoptosis) of extravasated neutrophils.
Furthermore, leukocytes begin to produce mediators that
inhibit inflammation & thus limit the reaction.
Eventually, the combined efforts of lymphatic drainage
& macrophage ingestion of necrotic debris lead to
clearance
of edema fluid, inflammatory
cells & detritus from the battlefield (Fig. 2-9 ).

Resolution (repair)#2
Progression to chronic inflammation may follow acute
inflammation if the offending agent is not removed.
Depending on the extent of the initial & continuing tissue
injury, as well as capacity of affected tissues to regrow,
chronic inflammation may be followed by restoration of
normal structure & function or may lead to scarring.
Scarring or fibrosis results after substantial tissue
destruction or when inflammation occurs in tissues that do not
regenerate.
Extensive fibrinous exudates (due to increased vascular
permeability) may not be completely absorbed & are
organized by ingrowth of connective tissue, with resultant
fibrosis.
Abscesses may form in setting of extensive neutrophilic
infiltrates or in certain bacterial or fungal infections (pyogenic
or "pus forming"), because of underlying tissue destruction,
the usual outcome of abscess formation is scarring.

Figure 2-9
Events in the
resolution of
inflammation.
Phagocytes
clear the fluid,
leukocytes &
dead tissue,
and fluid &
proteins are
removed by
lymphatic
drainage.

1) Pada respon radang terdapat tumor.

Bagaimana tumor tersebut kembali ke keadaan
normal?
2) Apakah perbedaan makros & mikros

tonsil &
faring pada infeksi akibat virus dan
bakteri?
3) Kenapa pasien pada kasus ini merasa mual &
muntah?
4) Apa yang dimaksud reaktivitas silang antara
antibodi
pada katup jantung dengan Nasetylglucosamin?
5) Secara teori, komplikasi rematik dan sesak di
dada

Dx Etiologi: Tonsilitis

Perbedaan Makroskopik
Akut

Kronik

Bacterial Tonsillitis
Bacterial suppurative tonsillitis is among the most frequent
paediatric infections.
Group A beta-haemolytic streptococci are most frequent
cause.
Other isolates in bacterial tonsillitis are Hemophilus
influenza, Streptococcus pyogenes, Streptococcus milleri &
Staphylococcus aureus.
Children with acute streptococcal tonsillitis are significantly
older than children with viral tonsillitis.
Surgical specimens of acute tonsillitis are rarely
encountered.
The surface epithelium may be ulcerated & the surface and
crypt epithelium is infiltrated by neutrophilic granulocytes
producing
a cryptitis with crypt abscesses.
Rare other bacteria causing acute necrotising tonsillitis
include Clostridium perfringens and Bartonella henselae
with an unusual presentation of cat scratch disease.

Viral Tonsillitis
The most common causes of upper respiratory tract infections
& pharyngo-tonsillitis in general population, are viruses;
influenza virus, Coxsackies virus (group A), adenovirus &
Epstein-Barr virus.
The symptoms: enlarged swollen palatine tonsils, occasionally
with peritonsillar abscesses, sore throat, fever, malaise,
cervical lymphadenopathy, lymphocytosis & hepatosplenomegaly .
Histologically:
EBV tonsilitis: surface epithelium of the palatine tonsils is often
necrotic. Follicular hyperplasia with fused or bizarre-shaped
follicles & numerous tangible body macrophages & distended
interfollicular areas with atypical immunoblasts, plasma
cells, plasmacytoid lymphocytes & histiocytes,
occasionally grouped around necrotic foci, are typical.
Mitoses are numerous. Rare Reed-Sternberg-like cells with
single or multiple nuclei without nucleoli be present beneath
crypt epithelium.

Fig. EBV tonsillitis. A) The hypertrophic palatine tonsil contains

reactive lymph follicles which are distended by a dense
interfollicular infiltrate. B) The surface epithelium is also heavily
infiltrated by numerous atypical lymphocytes, plasma cells,

C-D
The atypical large immunoblasts
with prominent nucleoli show
numerous mitoses and merge with
the germinal centres.
E
The atypical immunoblasts may be
binuclear atypical lymphoblasts

Fig. 4.54a, b
Infectious
Mononucleosis
(Viral
tonsilitis).

Viral Chronic & Recurrent

Tonsillitis

Chronic & recurrent tonsillitis typically associated with

respiratory syncytial virus, reactivation of latent Epstein-Barr
virus, H. influenza & Staphylococcus aureus.
After episodes of recurrent tonsillitis, palatine tonsils show
extensive fibrosis at site of former capsule & scarring with
entrapped, pulled up skeletal muscle fibres at base of tonsil
& atrophic lymphoid tissue with small lymphoid follicles with
atrophic germinal centres. Granulomas may be present.
The crypts are distended & filled with keratinous debris,
inflammatory cells & occasional aggregates of actinomyces.
Retention cysts can be formed within deep crypts of
chronically irritated palatine tonsils after occlusion of orifice.
The crypt epithelium becomes keratinised. Calcification of
desquamated debris following deposition of inorganic salts
may result in tonsillar calculi, so-called tonsilloliths.

Dx Klinik
(Prognostik)
: Tonsilitis
akut
Fig. 4.52
Acute tonsillitis.
Diffuse or
punctate.

Fig.
Chronic
adenotonsillitis
hypertrophy.

Dx Klinik
(Prognostik)
: Tonsilitis

1) Pada respon radang terdapat tumor.

Bagaimana tumor tersebut kembali ke keadaan
normal?
2) Apakah perbedaan makros & mikros tonsil &
faring pada infeksi akibat virus dan bakteri?
3) Kenapa pasien pada kasus ini merasa

mual &
muntah?
4) Apa yang dimaksud reaktivitas silang antara
antibodi
pada katup jantung dengan Nasetylglucosamin?
5) Secara teori, komplikasi rematik dan sesak di
dada
pada kasus tonsilitis bakteri seharusnya muncul

Emetic stimuli act at several anatomic sites.

1)Provoked by noxious thoughts or smells originates
in
the cerebral cortex.
2)Cranial nerves mediate vomiting after gag reflex
activation.
3)Motion sickness & inner ear disorders act on the
labyrinthine apparatus.
4)Gastric irritants & emetogenic anticancer agents
such as cisplatin stimulate gastroduodenal vagal
afferent nerves.
5)Nongastric visceral afferents are activated by
small intestinal and colonic obstruction and
mesenteric ischemia.
6)The area postrema, a medullary nucleus,
responds to bloodborne emetic stimuli & is termed
the chemoreceptor trigger zone. Many emetic drugs
act on the area postrema
as do

1) Pada respon radang terdapat tumor.

Bagaimana tumor tersebut kembali ke keadaan
normal?
2) Apakah perbedaan makros & mikros tonsil &
faring pada infeksi akibat virus dan bakteri?
3) Kenapa pasien pada kasus ini merasa mual &
muntah?

4) Apa yang dimaksud reaktivitas silang

antara
antibodi pada katup jantung dengan
N-asetylglucosamin?
5) Secara teori, komplikasi rematik dan sesak di
dada
pada kasus tonsilitis bakteri seharusnya muncul
setelah

Environmenta
l factors
exposure of
hidden antigen
molecular
mimicry

1) Pada respon radang terdapat tumor.

Bagaimana tumor tersebut kembali ke keadaan
normal?
2) Apakah perbedaan makros & mikros tonsil &
faring pada infeksi akibat virus dan bakteri?
3) Kenapa pasien pada kasus ini merasa mual &
muntah?
4) Apa yang dimaksud reaktivitas silang antara
antibodi pada katup jantung dengan
N-asetylglucosamin?

5) Secara teori, komplikasi rematik dan sesak

di dada
pada kasus tonsilitis bakteri seharusnya
muncul setelah
10 hari paska infeksi tonsil. Mengapa pada
kasus ini

1)Kapan makrofag akan mengeluarkan IL-1?

Kapan TNF?
Kapan IL? Apakah tiap inflamasi semua jenis
sitokin dikeluarkan semua?
2) Proses terjadinya kalsifikasi jaringan pada
tuberkulosis paru?
3) Apa beda autoimun dan alergi? Anafilaktik

1)Kapan makrofag akan mengeluarkan IL-1?

Kapan TNF?
Kapan IL? Apakah tiap inflamasi semua jenis
sitokin dikeluarkan semua?
2) Proses terjadinya kalsifikasi jaringan pada
tuberkulosis paru?
3) Apa beda autoimun dan alergi? Anafilaktik

1)Kapan makrofag akan mengeluarkan IL-1?

Kapan TNF?
Kapan IL? Apakah tiap inflamasi semua jenis
sitokin dikeluarkan semua?
2) Proses terjadinya kalsifikasi jaringan pada
tuberkulosis paru?
3) Apa beda autoimun dan alergi? Anafilaktik

The Killing Mechanism of NEOPLASMS#1

The neoplasm can destroy by its invasion
certain
vital organs, such as the
brain or hemopoetic tissues. The destruction
of normal tissue due to a mixture
of toxic influences emanating from neoplastic
cells, compression & displacement,
interference with
blood supply
of invanded area (due to compression of
vessels or promotion of thrombosis).

The Killing Mechanism of NEOPLASMS#2

The rapidly growing neoplasm can starve the
host
to death, by claiming of the
calorie & nitrogen intake (the lions share),
the more the tumor grows,
the more the host shrinks.
By stopping the host appetite
through chemical effects on its
cerebral appetite center, by
stimulating adrenocortical
secretion & gluconeogenesis &
melting down host tissue protein
turn it into glucose, obstructing
the alimentary tube
with
resulting cessation of food of food
absorption & vomiting.

CAUSES OF NEOPLASIA#1
Changes of The Proliferation-Regulating
Function of DNA
Production by Viruses
Induction by Chemical Agents
Induction by Physical Agents
Heredity