VIDI PRASETYO UTOMO / 0910710128 / PD-B 2009

MODULE TASK NONALCOHOLIC FATTY LIVER DISEASES (NAFLD), LIVER

ABSCESS, DISORDER OF GALL BLADDER AND BILIARY TRACT
1.

What are the causes of NAFLD?

Spektrum NAFLD termasuk simple hepatic stetosis yang dapat berkembang
menjadi Nonalcoholic steatosis hepatic (NASH) dengan adanya perkembangan
fibrosis dan sirosis. Penyebab dari macrovesicular steatosis diantaranya :
Causes
of
Macrovesicular
Steatosis

Insulin
resistance,
hyperinsulinemia
Centripetal obesity
Type 2 diabetes
Medications
Glucocorticoids
Estrogens
Tamoxifen
Amiodarone
Nutritional
Starvation
Protein
(Kwashiorkor)

deficiency

Choline deficiency
Liver disease
Wilson disease
Chronic
hepatitis
genotype 3

Indian childhood cirrhosis

Jejunoileal bypass
2. Please explain the pathogenesis of NAFLD.
The liver plays a central role in lipid metabolism, importing serum free fatty acids and
manufacturing, storing and exporting lipids and lipoproteins. However, the
pathophysiology that leads to NAFLD is not well understood; in particular, the factors
that lead to progressive hepatocellular damage after triglyceride accumulation are not
well elucidated. It appears that alteration of local and systemic factors (particularly
insulin resistance) that control the balance between the influx or synthesis of hepatic
lipids and their export or oxidation leads to hepatic triglyceride accumulation. The
steatotic liver is then thought to be vulnerable to secondary insults, which lead to
hepatocellular inflammation and fibrosis. A variety of factors have been implicated to
produce a second hit, including hormones derived from adipose tissue
(adipocytokines), oxidative stress and gut-derived bacterial endotoxin.
Insulin resistance
The pathogenesis of insulin resistance is complex and is likely to involve many genetic
polymorphisms that influence insulin secretion and action as well as environmental

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factors that promote obesity and immobility. Hyperinsulinemia increases serum free
fatty acid levels, which are taken up by the liver and drive triglyceride production and
hepatic steatosis. In addition, chronic hyperinsulinemia promotes de novo hepatic
lipogenesis through upregulation of lipogenic transcription factors 21,22,23 and may
activate profibrotic cytokines such as connective tissue growth factor.
Hepatic lipid metabolism
Lipids are normally exported from the liver in very-low-density lipoproteins (VLDL),
which are formed by microsomal triglyceride transfer protein (MTP) incorporating
triglyceride into apolipoprotein B (apo B). A reduction in MTP activity and apo B
synthesis and secretion may impair hepatic lipid export and favour hepatic triglyceride
accumulation.
Inflammatory and fibrotic mediators in NAFLD
Adipocytokines (tumour necrosis factor- [TNF-], leptin and adiponectin), free fatty
acids, mitochondrial dysfunction, bacterial endotoxin and vascular disturbance have
all been implicated in the development of hepatic inflammation and fibrosis in
patients with NAFLD. These factors may be directly hepatotoxic or generate oxygen
radicals with subsequent lipid peroxidation, cytokine induction and liver damage.
TNF- promotes insulin resistance and liver inflammation. Levels are increased in
patients with NAFLD, perhaps secondary to gut-derived endotoxin or TNF-
polymorphisms. Leptin and adiponectin are important regulators of adiposity and
insulin resistance and have been found to promote liver fibrogenesis in animal
models. Leptin and adiponectin levels are altered in patients with NASH; however,
their exact pathogenic role has yet to be elucidated.
As a result of insulin resistance, serum free fatty acid levels are increased in NASH
patients and may be directly hepatotoxic or produce damaging reactive oxygen
species. Oxidative stress may be exacerbated further by ultrastructural mitochondrial
lesions, which impair respiratory chain function.
As liver injury progresses, fat-laden hepatocytes and perisinusoidal fibrosis may impair
microvascular hepatic blood flow. This effect may decrease oxygen and nutrient
exchange and thus stimulate a microvascular inflammatory response and an
escalating cycle of liver damage and vascular insufficiency.
3.

Please describe more detail the management of NAFLD

Treatment fatty liver disease adalah dengan penurunan berat badan dan
berolah raga. Bisa jug dengan pemberian orlistat yang merupakan inhibitor
reversible lipase gaster dan pancreas.
Bariatric surgery juga merupakan salah satu treatment untuk menurunkan
berat badan.
Study terakhir menyatakan bahwa ada keterlibatan resistensi insulin pada
mekanisme
patofisiologis
NAFLD
sehingga
pengobatan
dengan
thiazolidinedione, inhibitor PPAR gamma, dapat meningkatkan sensitivitas
insulin dalam adeposit dan otot skelet dengan upregulasi protein kinase spesifik
yang terlibat dalam penurunan sintesis asam lemak. Obat lain yang tersedia
dan sedang dievaluasi penggunaannya untuk NAFLD adalah pioglitazone dan
rosiglitizone.

4.

Please explain the pathogenesis of Pyogenic Liver Abscess

There is often disagreement about whether an abscess represents a disease
state or a host response. In a sense, it represents both: while an abscess is an
infection in which viable infecting organisms and PMNs are contained in a
fibrous capsule, it is also a process by which the host confines microbes to a
limited space, thereby preventing further spread of infection. In any event,
abscesses do cause significant symptoms, and patients with abscesses can be
quite ill. Experimental work has helped to define both the host cells and the
bacterial virulence factors responsiblemost notably, in the case of B. fragilis.

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This organism, although accounting for only 0.5% of the normal colonic flora, is
the anaerobe most frequently isolated from intraabdominal infections, is
especially prominent in abscesses, and is the most common anaerobic
bloodstream isolate. On clinical grounds, therefore, B. fragilis appears to be
uniquely virulent. Moreover, B. fragilis acts alone to cause abscesses in animal
models of intraabdominal infection, whereas most other Bacteroides species
must act synergistically with a facultative organism to induce abscess
formation.
Of the several virulence factors identified in B. fragilis, one is critical: the
capsular polysaccharide complex (CPC) found on the bacterial surface. The CPC
comprises at least eight distinct surface polysaccharides. Structural analysis of
these polysaccharides has shown an unusual motif of oppositely charged
sugars. Polysaccharides having these zwitterionic characteristics, such as
polysaccharide A (PSA), evoke a host response in the peritoneal cavity that
localizes bacteria into abscesses. B. fragilis and PSA have been found to adhere
to primary mesothelial cells in vitro; this adherence, in turn, stimulates the
production of tumor necrosis factor (TNF-) and intercellular adhesion
molecule 1 (ICAM-1) by peritoneal macrophages. Although abscesses
characteristically contain PMNs, the process of abscess induction depends on
the stimulation of T lymphocytes by these unique zwitterionic polysaccharides.
The stimulated CD4+ T lymphocytes secrete leukoattractant cytokines and
chemokines. The alternative pathway of complement and fibrinogen also
participate in abscess formation.
While antibodies to the CPC enhance bloodstream clearance of B. fragilis, CD4+
T cells are critical in immunity to abscesses. When administered
subcutaneously, B. fragilis PSA has immunomodulatory characteristics and
stimulates CD4+ T regulatory cells via an interleukin (IL) 2dependent
mechanism to produce IL-10. IL-10 downregulates the inflammatory response,
thereby preventing abscess formation.
5.

Please explain the management of Pyogenic Liver Abscess

While drainageeither percutaneous (with a pigtail catheter kept in place) or
surgicalis the mainstay of therapy for intraabdominal abscesses (including liver
abscesses), there is growing interest in medical management alone for pyogenic
liver abscesses. The drugs used for empirical therapy include the same ones used
in intraabdominal sepsis and secondary bacterial peritonitis. Usually, a diagnostic
aspirate of abscess contents should be obtained before the initiation of empirical
therapy, with antibiotic choices adjusted when the results of Gram's staining and
culture become available. Cases treated without definitive drainage generally
require longer courses of antibiotic therapy. When percutaneous drainage was
compared with open surgical drainage, the average length of hospital stay for the
former was almost twice that for the latter, although both the time required for
fever to resolve and the mortality rate were the same for the two procedures.
Mortality was appreciable despite treatment, averaging 15%. Several factors
predict the failure of percutaneous drainage and therefore may favor primary
surgical intervention. These factors include the presence of multiple, sizable
abscesses; viscous abscess contents that tend to plug the catheter; associated
disease (e.g., disease of the biliary tract) requiring surgery; or the lack of a clinical
response to percutaneous drainage in 47 days.
Treatment of candidal liver abscesses often entails initial administration of
amphotericin B or liposomal amphotericin, with subsequent fluconazole therapy
(Chap. 196). In some cases, therapy with fluconazole alone (6 mg/kg daily) may be
usede.g., in clinically stable patients whose infecting isolate is susceptible to this
drug.

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6.

Please describe the clinical manifestations and diagnosis of amoebic

liver abscess
Manifestation
Febris, nyeri abdomen kanan atas yang tumpul atau pleuritik dan menyebar
ke bahu. Tenderness pada daerah liver dan dapat terjadi efusi pleura kanan.
Jaundice jarang terjadi. Walaupun asal infeksi berasal dari kolon, kurang
dari sepertiga pasien dengan amoebic liver abscess memiliki gejala diare
aktif.
Berat badan turun dan hepatomegaly.
Diagnosis
Prosedur diagnosis amebiasis dapat dilakukan dengan pemeriksaan feses, tes
serologis, dan imaging noninvasive.
Diagnosis definitive dari amebic colitis adalah ditemukannya trophozoit dari
E. histolytica. Pemeriksaan feses perlu dilakukan pada tiga specimen feses
yang masih baru karena tropozoit mudah mati pada air, pengeringan, dan
barium. Tropozoit jarang ditemukan pada aspirat liver abses karena
tropozoit menempel pada dinding abses bukan di pusat nekrosisnya.
Pemeriksaan serologis dapat dilakukan dengan ELISA dan agar gel diffusion
assays. Pemeriksaan serologis positif mengindikasikan bahwa penyakit
sedang aktif. Setelah 6 12 bulan serologis dapat berubah menjadi negatif.
Sampai 10% pasien dengan amebic liver abscess dapat memberikan hasil
serologis yang negatif. Pada suspek infeksi dengan hasil serologis negatif,
pemeriksaan harus diulang satu minggu kemudian
Pemeriksaan darah dan kimia biasanya tidak banyak membantu. Tiga per
empat pasien terdapat leukositosis (>10.000 cell/L). Meskipun dengan
liver abscess yang besar, enzim liver dapat normal atau sedikit naik.
Alkaline phosphatase sering meningkat dan bertahan selama beberapa
bulan.
Radiologi : Barium enema berbahaya untuk acute amebic colitis. Imaging
yang membantu adalah USG, CT, MRI.

7.

What are the clinical manifestations of acute cholecystitis?

Kolesistitis
kalkulosa
akut
mungkin
tidak
menimbulkan
gejala
atau
memperlihatkan gejala hebat dengan nyeri abdomen atas yang hebat dan
menetap dan sering menyebar ke bahu kanan. Nyeri kolik dapat terjadi jika batu
terletak pada leher kandung empedu atau duktus. Gejala klasik terdiri dari
demam, mual, leukositosis, dan lemah. Regio subkosta kanan sengat nyeri tekan
dan kaku akibat spasme otot abdomen. Kadang juga bisa teraba kandung empedu
yang membesar dan nyeri tekan.

8.

Please describe the clinical manifestations and complications of

gallstone
Manifestasi klinis :
Nyeri saluran empedu cenderung hebat baik menetap maupun kolik/spasmodic
akibat obstruksi kandung empedu.
Komplikasi :
Dapat terjadi penyulit yang parah berupa empyema, perforasi, fistula, peradangan
saluran empedu, dan pankreatitis.

9.

Please describe the clinical manifestation and diagnosis of acute

pancreatitis
Manifestasi klinis :
Nyeri abdomen adalah tanda utama pankreatitis akut. Nyeri khas pada bagian
epigastrium dan menyebar ke punggung. Syok dapat terjadi disebabkan oleh
perdarahn pancreas dan pembebasan zat prostaglandin dan bradikinin.

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Diagnosis :
Terjadi peningkatan amylase serum pada 12 jam pertama dan menurun ke normal
dalam 48 72 jam meskipun dapat disebabkan oleh penyakit lain. Kadar lipase
serum juga meningkat dan tetap tinggi setelah kadar amylase serum kembali
normal (7 10 hari).
10. Please describe the clinical manifestation and diagnosis of chronic
pancreatitis
Manifestasi klinis :
Penyakit ini mungkin bermanifestasi sebagai serangan berulang nyeri abdomen
stengah berat, sebagai serangan berulang nyeri yang ringan, atau sebagai nyeri
abdomen dan punggung yang menetap. Namun, penyakit local mungkin benar
benar asimtomatik sampai terjadi insufisiensi pancreas dan diabetes mellitus.
Pada kasus lain, penyakit ditandai dengan serangan berulang icterus atau
serangan indigesti samar.
Diagnosis :
Setelah penyakit berlangsung kronis, peningkatan amylase dan lipase serum
dapat menghilang karena kerusakan sel asinus. Terdapat gambaran kalsifikasi dan
pseudokista pada pancreas dengan sinar X, CT, dan USG.