Patogenesis Diare pada anak

Feces from humans or animals containing pathogenic

microbes or their toxins

food fluids fingers

Ingestion of organism and/ or toxin

Organisms multiply and toxin Organism invade or toxins absorbed

produced but infection remain in
GI tract
dissemination
DIARE
Symptoms of
systemic
infection ex.
Fever etc.
1. Virus ( rotavirus, enterovirus,
adenovirus dll...)
Menembus dinding usus

Kerusakan sel (?)

Infeksi lokal

DIARE

Sel darah ±
www1.qiagen.com/GeneGlobe/PathwayView.aspx?
pa...
• During the first cycle of rotavirus replication in mucosal epithelial cells, the
synthesis of rotaviral proteins in the cell cytoplasm leads to an increase in the
plasma-membrane permeability to Ca2+, to activation of regulatory mechanisms
and to an increase in the concentration of Ca2+ in the endoplasmic reticulum
through SERCA (Sarco- and Endoplasmic Reticulum Ca2+ ATPase). In the
extracellular medium, Ca2+ stabilizes the structure of the viral capsid but the
increased concentration of cytosolic Ca2+ in infected cells promotes the
activation of Ca2+ dependent enzyme, which in turn induces cell lysis and the
release of viral proteins and viral progeny (Ref.5). NSP4 also act as a viral
enterotoxin to induce secretory diarrhea through Ca2+-dependent secretion by
intestinal cells, Ca2+-dependent secretion of peptides and amines to stimulate
the ENS, or by further activation of epithelial-cell chloride (Cl-) secretion by the
ENS. NSP4 increases [Ca2+]i and this elevation in [Ca2+]i is not due to an
increased influx of extracellular Ca2+ but due to result from the increase in Ca2+
efflux from the endoplasmic reticulum through a PLC (Phospholipase-C)-
dependent mechanism. Exogenous NSP4 induce both Ca2+ release from
intracellular stores and plasmalemma Ca2+ influx, through receptor-mediated
PLC activation and IP3 (Inositol 1,4,5-triphosphate) production (Ref.6). In parallel,
released virus infects downstream absorptive cells. This leads to a massive cell
death and, as a consequence, reduction of the absorptive surface of the intestinal
epithelium and an osmotic component of diarrhea.
2.Bakteri non invasif
ETEC ( enterotoxin E.coli)

Tidak menembus dinding usus

Enterotoksin, LT (labile toxin)

Dan ST ( stable toxin)

LT bekerja cepat pada mukosa usus halus tetapi

hanya memberikan stimulasi terbatas thp enzim
adenilat siklase.

Meningkatkan kadar CAMP

Sekresi aktif anion klorida diikuti oleh air,

natrium bikarbonat, dan kalium ke dalam diare
lumen usus.
 Vibrio Cholera
Tidak menembus dinding usus

enterotoksin

Mengakibatkan kegiatan berlebihan nikotinamid

adenin dinukleotid pada sel dinding usus

Meningkatkan kadar CAMP

Sekresi aktif anion klorida diikuti olh air,

natrium bikarbonat, dan kalium ke dalam diare
lumen usus.
3. Bakteri invasif
EPEC
• Effects of EPEC infection on host intestinal epithelial cells. EPEC
initially adheres to the host cell by its bundle-forming pili, which also
mediate bacterial aggregation. Following initial attachment, EPEC
secretes several virulence factors by a type III-secretion system.
Signal transduction events occur within the host, including activation
of phospholipase C (PLC) and protein kinase C (PKC), inositol
triphosphate (IP3) fluxes, and Ca2+ release from internal stores.
The bacterium intimately adheres to the cell by secreting its own
receptor, Tir, into the host and binding to it with its outer membrane
ligand, intimin. Intimin can also bind ß1-integrins. Several
cytoskeletal proteins are recruited to the site of EPEC attachment,
including actin, -actinin, talin, and ezrin. Cytoskeletal
rearrangements occur following Tir-intimin binding, resulting in the
formation of a pedestal-like structure upon which the pathogen
resides.
EIEC ( enteroinvasive E.Coli)
Bakteri, salmonella
 Shigella
Menembus dinding usus

Kerusakan jaringan

Berlipat ganda dalam sel epitel

Infeksi lokal dan sistemik

Leukosit ++++
Eritrosit ++++
4. parasit
Entamoeba histolitica

Memasuki mukosa usus besar yang utuh

dan mengeluarkan enzim

Histolisin, suatu cystein proteinase.

Lisis jaringan

Memasuki submukosa Gerakan peristaltik

ulkus ameba

Pengeluaran isi ulkus Diare bercampur

darah dan lendir
• Invasion of intestinal mucosa by E. histolytica is an active process
mediated by the parasite and distinct steps can be recognized
Trophozoites adhere to the mucus layer (step 1). This adherence
per se probably does not contribute to pathogenesis and is simply a
mechanism for the ameba to crawl along the substratum. Depletion
of the mucus barrier allows for the trophozoite to come in contact
with epithelial cells. Epithelial cells are killed in a contact dependent
manner leading to a disruption of the intestinal mucosa (step 2). The
trophozoites will continue to kill host cells in the submucosa and
further disrupt the tissue as they advance (step 3). Disruption of the
intestinal wall (step 4) or metastasis via the circulatory system (step
5) is also possible. Adherence, cytotoxicity, and disruption of the
tissues are important factors in the pathogenesis of E. histolytica.
Parasite proteins which could play a role in these processes include:
the Eh-lectin, amebapore, and proteases
• Adherence of E. histolytica trophozoites to host cells and colonic
mucins is mediated by a lectin-activity expressed on the ameba's
surface.
• Amebapore is localized to vacuolar compartments (eg, food
vacuoles) within the trophozoite and is most active at acidic pH
suggesting that the major function of amebapore is to lyse ingested
bacteria.
• Proteases are enzymes that degrade other proteins and could
contribute to the pathogenesis cause by E. histolytica .
Cysteine proteases have been shown to disrupt the polymerization
of MUC2, the major component of colonic mucus. This degraded
mucus is less efficient at blocking adherence of trophozoites to
epithelial cells. Destruction of the extracellular matrix (ECM) by
proteases may also facilitate trophozoite invasion.
5. Keracunan makanan dan
alergi
 Clostridium perfringens food – assosiated infections

Common rare
Enterotoxin producing Beta toxin producing type
type A strain C strain

Organisms and spores

in animal guts or soils

Contaminated raw meat products

Spores survive cooking Inadequately cook meat,

germinate and multiply especially pork

Reheating insuffient to kill organisms,

large number ingested Large number ingested
by person with low
protein diet, thus
Organism sporulate and inadequate intestinal
produce enterotoxin in large trypsin
intestine
Glucose transport inhibited, Organism produce beta
damage of intestinal toxin in small intestine
epithelium, prtein loss in to
lumen
Toxin is trypsin sensitive but
in absence of trypsin
unaffected.
DIARRHEA

Acute necrotizing disease

( ‘pig bel’)
Abdominal pain, bloody diarrhea,
50 % mortality from intestinal perforation.
 Bacillus cereus spores and vegetable
cells contaminated many food

Rice , pulse Various food

Cooking destroy vegetable cells but Spore survive in cooking

heat resistant spores survive to
Germinate and multiply in food
germinate in food when cooled to room
temperature.
Organism ingested
Enterotoxin heat stable produced in
food and not destroy by reheating food Enterotoxin heat labile
ex. Fried rice. produced in gut similiar
mode of actions in
Enterotoxin ingested cholera

Rapid onset vomitting DIARRHEA

Alergi susu sapi