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 produced but infection remain in GI tract

Organism invade or toxins absorbed

dissemination

Symptoms of systemic infection ex. Fever etc.

DIARE

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.

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.

Sekresi aktif anion klorida diikuti oleh air, natrium bikarbonat, dan kalium ke dalam lumen usus.

diare

Meningkatkan kadar CAMP

2.Bakteri non invasif

Vibrio CholeraTidak 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 lumen usus.

diare

EPEC3. Bakteri invasif

• 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 ++++

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

4. parasit

• 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 type A strain

Beta toxin producing type C strain

Organisms and spores in animal guts or soils

Contaminated raw meat products

Spores survive cooking germinate and multiply

Reheating insuffient to kill organisms, large number ingested

Organism sporulate and produce enterotoxin in large intestine

Inadequately cook meat, especially pork

Large number ingested by person with low protein diet, thus inadequate intestinal trypsin

Glucose transport inhibited, damage of intestinal epithelium, prtein loss in to lumen

DIARRHEA

Organism produce beta toxin in small intestine

Toxin is trypsin sensitive but in absence of trypsin unaffected.

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

Cooking destroy vegetable cells but heat resistant spores survive to germinate in food when cooled to room temperature.

Enterotoxin heat stable produced in food and not destroy by reheating food ex. Fried rice.

Enterotoxin ingested

Rapid onset vomitting

Various food

Spore survive in cooking

Germinate and multiply in food

Organism ingested

Enterotoxin heat labile produced in gut similiar mode of actions in cholera

DIARRHEA

Alergi susu sapi