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DIARRHEA

Diare :
BAB dengan konsistensi cair/semisolid 3 x/ hari (source: lupa)
Diare akut< 15 hari
Definisi
PERSARAFAN :

OTONOM DAN VOLUNTER

BLOOD SUPPLY

ARTERI ARTERI
MESENTRICA MESENTRICA
SUPERIOR INFERIOR
ANATOMI

KANAN KIRI

SUPLAI DARAH TAMBAHAN: ARTERI


HEMOROIDALIS MEDIA DAN INFERIOR

ALIRAN BALIK VENA : VIA VENA


MESENTRIKA SUPERIOR, INFERIOR DAN
HEMOROIDALIS
Fisiologi (FUNCTIONS OF THE
GASTROINTESTINAL TRACT)

GI TRACTS FUNCTION
10s

ELIMINATION OF
WASTE
1-3h
ASSIMILATION OF
NUTRTIENTS

7-9h
25-30 h

25-120 h
Fisiologi (FUNCTIONS OF THE
GASTROINTESTINAL TRACT)
Fisiologi (FUNCTIONS OF THE
GASTROINTESTINAL TRACT)
Satu atau lebih patofisiologi
Patophysiology of diarrhea
noninvasif
Diare osmotik Diare infeksi

Diare sekretorik
Lendir &
invasif darah
Diare malabsorbsi lemak

Diare defek pertukaran


elektrolit
E. Histolitika
Diare motilitas &waktu & G. Lamblia
transit abnormal

Diare inflamatorik Common


cause
Diare gg permeabilitas
Diarrheal : Giardia lamblia

is found on surfaces or in soil, food, or water that has been contaminated with feces (poop) from
infected humans or animals.

Giardia is protected by an outer shell that allows it to survive outside the body for long periods of time and
makes it tolerant to chlorine disinfection. While the parasite can be spread in different ways, water (drinking
water and recreational water) is the most common mode of transmission.
Diarrheal : Giardia lamblia
Both cysts and trophozoites can be found in the feces
(diagnostic stages)

cysts are hardy and can survive several months in cold


water.

Trophozoites multiply by longitudinal binary fission,


remaining in the lumen of the proximal small bowel where
they can be free or attached to the mucosa by a ventral
sucking disk
PATOFISIOLOGI : DIARE G. Lamblia
Mekanisme pasti infeksi G. Lamblia menimbulkan diare : unclear

Hipotesa

G. Lamblia bergerombol pada mukosa usus


sehingga mengganggu proses pada usus-> G. Lamblia mengganggu aktivitas flora
merusak vili-> mengganggu transportasi normal-terjadi peradangan-diare
cairan-> diare

Site of infection : Duodenaliscdc


Diarrheal : Giardia lamblia Epidemiologi :
Prevalensi giardiasis berkisar 10% di Amerika Utara, Eropa dan hingga mencapai 20%-30% di negara
berkembang. Prevalensi tinggi ditemukan pada anak usia prasekolah dan pada anak dengan gangguan
gizi.

Acute symptoms include 2,4,6:


Diarrhea
Gas
Greasy stools that tend to float(steator)
Stomach or abdominal cramps
Upset stomach or nausea/vomiting
Dehydration (loss of fluids)
Other, less common symptoms : itchy skin, hives, and swelling of the eye and joints.
Sometimes, the symptoms of giardiasis might seem to resolve, only to come back again
after several days or weeks.
Giardiasis can cause weight loss and failure to absorb fat, lactose, vitamin A and vitamin B12 .
In children, severe giardiasis might delay physical and mental growth, slow development,
and cause malnutrition
Diarrheal : Giardia lamblia

Giardiasis Infection with Giardia lamblia may cause a persistent


infection. Making a positive diagnosis on culture may prove difficult
(even with culture of duodenal aspirates). Empirical treatment with
tinidazole or metronidazole is effective1
Therapy (amubiasis)

tinidazole or metronidazole is effective


metronidazole
Nitroimidazoles.
tinidazole
Pharmacotherapy

ornidazole

secnidazole
Metronidazole : [1-(b-hydroxyethyl)-2-methyl-5-nitroimidazole.

utilizes the anaerobic metabolic pathways

drug enters the trophozoite

ferredoxins
-e -
-e e
Metronidazole

-e nitro group
-e

activated
This results in DNA damage in the form of
loss of helical structure, impaired
Reduced metronidazole serves as a terminal electron acceptor template function, and strand
which binds covalently to DNA macromolecules breakage, with subsequent trophozoite
Ferredoxins are iron-sulfur proteins that mediate
electron transfer in a range of metabolic reactions.
death
Paromomycin (Humatin), a member of the aminoglycoside family

Paromomycin inhibits G. Lamblia protein synthesis by interfering with the


50S and 30S ribosomal subunits (the parasite rRNA has an unusual size and sequence) and causing
misreading of mRNA codons
As with other aminoglycosides, if absorbed systemically paromomycin can cause ototoxicity and nephrotoxicity.
Paromomycin
Quinacrine (Atabrine) was first introduced as an antimalarial agent in 1930, following the
work of Kikuth, and became the antimalarial of choice for allied troops in World War II because of its greater
availability and better tolerance compared with quinine

The drug intercalates readily with G. Lamblia DNA, and it is this interaction which is thought to cause an inhibition
of nucleic acid synthesis.
Quinacrine
Pregnancy and lactation.
The management of symptomatic G. Lamblia infection during pregnancy is a challenge for the
because no therapeutic agent combines optimal efficacy
clinician
and safety. Women who are asymptomatic, have mild disease, or are in their first trimester
should usually avoid being treated. However, women in whom adequate hydration and nutritional
status cannot be maintained should be treated, even in the first trimester.

Metronidazole, which rapidly enters the fetal circulation after absorption by the mother, has
demonstrated mutagenicity in bacteria and carcinogenicity in mice and rats

While this information raises concern about the use of the drug during pregnancy, carcinogenicity has
not been demonstration in humans nor has there been teratogenicity in rodents
One report: relative risk of 0.92 for birth defects

there may be a slightly increased risk when using metronidazole during the first trimester, and thus
its use should be avoided during this period. High-dose (>/= 2.0 g), short-course regimens should not
be given during pregnancy
Metronidazole is actively excreted in breast milk in concentrations similar to those in plasma.
The American Academy of Pediatrics (AAP) recommends giving a single 2-g dose in nursing mothers, followed
by discontinuation of nursing for 12 to 24 h. The AAP also recommends that mothers taking tinidazole discontinue
nursing for the same time period as those taking metronidazole. However, metronidazole is approved for use
in children for therapy of amebiasis and is used in children for therapy of anaerobic infections, so it
would seem that the small amount secreted in breast milk would not be deleterious. Also, since single, high-dose
regimens of metronidazole have poor efficacy and would be expected to lead to higher levels in breast milk, these
findings favor traditional treatment with lower doses over 5 to 7 days.

Paromomycin is generally considered safe because it is poorly


absorbed from the intestine and excreted almost 100% unchanged in the feces. Therefore, little if any of the drug
will reach the fetus. However, it is not as effective as metronidazole or
quinacrine. In addition, no clinical trials have addressed the effects of high serum concentrations of
paromomycin during pregnancy. Nevertheless, paromomycin has been used success-fully to eradicate G. Lamblia
infection in the gravid patient and is an important agent to consider during the first trimester, when
metronidazole should not be used
Diarreal : Enteromoeba histolytica

more common in people who live in tropical areas with


poor sanitary conditions
Diarreal : Enteromoeba histolytica
The motile form of E. histolytica, the trophozoite,
lives in the lumen of the large intestine, where it
multiplies and differentiates into the cyst, the
resistant form responsible for the transmission of
the infection. Cysts are excreted in stools and
may be ingested by a new host via contaminated
food or water. The parasite excysts in the
terminal ileum, with each emerging
quadrinucleate trophozoite giving rise to eight
uninucleated trophozoites. Trophozoites may
invade the colonic mucosa and cause dysentery
and, through spreading via the bloodstream, may
give rise to extraintestinal lesions, mainly liver
abscesses.
Pathogenesis of Intestinal Amebiasis
Diarreal : Enteromoeba histolytica

Infection of the human colon by E. histolytica produces focal ulceration of the intestinal
mucosa, resulting in dysentery (diarrhea with blood and mucus).

the basic mechanisms involved in the production of focal lytic lesions include complex
multifactorial

lectins facilitate adhesion proteases degrade extracellular matrix components

porins help nourish the parasite and may also kill


incoming polymorphonuclear leukocytes and
macrophages

motility is used by the parasite to invade deeper


layers of the colon.
Pathogenesis of Intestinal Amebiasis
Diarreal : Enteromoeba histolytica

E. histolytica

Organ affected

intestinal extraintestinal

- dysentery or bloody diarrhea (90%) the most frequent : amebic liver


- fulminating colitis abscess.
- amebic appendicitis
10 times more common in adults
- ameboma of the colon
3 times more frequent in males
Diarreal : Enteromoeba histolytica

Amoebiasis Infection with Entamoeba histolytica may cause a variety


of clinical presentations: asymptomatic excretion of cysts is the most
common finding, amoebic dysentery, non-dysenteric colonic disease
and inva-sive disease/hepatic abscess also can occur. The diagnosis
may be made by microscopy of hot stool looking for ova cysts and
parasites or by histology of colonic biopsies and/or serology.
Treatment is with metronidazole followed by diloxanide furoate1.
The following consultations may be helpful:

Infectious disease specialist


General surgeon
GI specialist
Several clinical scenarios may favor inpatient care, as follows:
Severe colitis and hypovolemia requiring intravenous (IV) volume
replacement
Liver abscess that is of uncertain etiology or is not responding to
empiric therapy
Fulminant colitis requiring surgical
evaluation
Peritonitis and suspected amebic liver abscess rupture
Invasive amebiasis (e.g., colitis, liver abscess) should be treated with
metronidazole for 10 days. Although metronidazole has some
unpleasant side effects, such as headache, nausea, metallic taste, and a
disulfiram-like reaction to alcohol, reaction is rarely severe. Uncommon
neurological side effects, such as vertigo or encephalitis, or neutropenia may
necessitate discontinuation of treatment. Therapy with metronidazole should be
followed with a luminal agent, since patients are otherwise at risk of relapsing
from residual infection in the intestine [60]. The majority of patients with amebic
liver abscess defervesce after 34 days of treatment with metronidazole.
Chloroquine and/or percutaneous drainage of the liver abscess are options in
addition to metronidazole treatment for the rare patient who does not respond
to metronidazole alone
Metronidazoles dosage

Side effects develop in about one third of patients who are receiving the recommended oral
dosage of metronidazole (750 mg tid). If side effects persist, the dosage can
be reduced to 500 mg tid.
Metronidazole should be administered preferably with or immediately after food.
Various dosage regimens are used. The following regimen is widely accepted but definitive
recommendations should be based on local experience.
Invasive amoebiasis
Adults and children: 30 mg/kg daily orally in three divided doses after meals for 8-10 days, or i.v. in
three divided injections daily until the patient is able to take oral formulations.
The efficacy of shorter oral regimens is currently being evaluated in controlled trials.
Metronidazole may also be used to treat asymptomatic carriers in non-endemic areas if no luminal
amoebicide is available, but it is less effective.
Tx for Pregnant
Paromomycin (a nonabsorbable aminoglycoside) is effective and safe for pregnant women.
Individuals traveling to endemic areas should be advised on practices that minimize the risk of amebiasis,
such as the following:
Avoid drinking contaminated water; use bottled water while traveling if possible

If local water is to be drunk, purify it by (a) boiling it for more than 1 minute, (b) using 0.22 m
filtration, or (c) iodinating it with tetraglycine hydroperiodide

Avoid eating raw fruits and salads, which are difficult to sterilize; eat only cooked food or self-peeled
fruits if possible

Wash uncooked vegetables and soak them in acetic acid or vinegar for 10-15 minutes
Prognosis
Amebic infections can lead to significant morbidity while causing variable mortality.

The severity of amebiasis is increased in the following groups:


Children, especially neonates
Pregnant and postpartum women
Those using corticosteroids
Those with malignancies
Malnourished individuals

With the introduction of effective medical treatment, mortality has fallen below 1% for patients with
uncomplicated amebic liver abscess. However, amebic liver abscess can be complicated by sudden
intraperitoneal rupture in 2-7% of patients, and this complication leads to a higher mortality.[4]

Case-fatality rates associated with amebic colitis range from 1.9% to 9.1%. Amebic colitis evolves to
fulminant necrotizing colitis or rupture in approximately 0.5% of cases; in such cases, mortality may exceeds
40%[39] or even, according to some reports, 50%.
Pleuropulmonary amebiasis has a 15-20% mortality rate. Amebic pericarditis has a case-fatality rate
of 40%. Cerebral amebiasis carries a very high mortality (90%).

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