HATI (LIVER)
Dua
model anatomi mikroskopik hati
- Hepatic lobular model.
- Acinar model
Hepatic
lobular model:
Vena Hepatik
terminal berada di central (CV,Central Vein) sebagai senter dari lobul
(centerolobuler) dan Vena Porta (PV) di perifer (Periportal) .
Acinar
Model :
Berbasis pada
supley darah (3 zona), Zona 1 yg terdekat dgn supley darah, Zona 3 terjauh
GAMBARAN
UMUM PENY. HATI



Deteksi
adanya liver damage
Adanya liver
damage bisah dideteksi melalui pemeriksaan laboratorium (darah atau urine) untuk menilai:
1.
Integritas sel hati,
apakah ada enzim yg tumpah dan masuk ke darah.
2.
Empedu yang dihasilkan.
3.
Fungsi sel hati
dengan menilai protein yang dihasilkannya.

GAGAL HATI
Ada 3
kemungkinan patogenesis :
- Acut Liver Failure (Gagal hati Akut), misalnya infeksi virus hepatitis menyebabkab banyak sel hati yang mati (fulminant hepatitis)’
- Chronic Liver Disease (Penyakit hati kronis), misalnya hepatitis virus yang berlanjut dengan sirosis.
- Disfungsi hati tanpa nekrosis, mis keracunan obat tetracyclin
KOMPLIKASI GAGAL HATI



LIVER CIRRHOSIS (Sirosis Hati)


-
Progressive liver
failure,
-
Komplikasi berhubungan
dengan hipertensi portal.
-
Berekembang menjadi
kanker hati.
Morfologi
Sirosis Hati
•
Bridging
Fibrous. Terbentuknya jaringan ikat
(fibrosis) seperti jembatan dari
periportal ke centrolobuler. Petanda kerusakan hati yang progressif.
•
Parenchymal
nodules, hepatcytes yang dikelilingi oleh
jaringan ikat (fibrosis) dgn ukuran dari yg kecil <0,3cm (mikronoduler)
sampai yang besar (makronoduler).
•
Kerusakan
arsitektur jaringan hati menyeluruh (diffus).
Patogenesis
utama pada sirosis hati.



Mekanisme terjadinya sirosis hati

1. Sebagai
respon adanya kematian sel hati, Sel Kupfer
aktip sebagai makrofag menghasilkan sitokin
2. Sitokin
dihasilkan juga oleh adanya inflamasi kronis pd jaringan hati.

Kupffer cell activation leads to secretion of multiple cytokines.
Platelet-derived growth factor (PDGF) and tumor necrosis factor (TNF) activate
stellate cells, and contraction of the activated stellate cells is stimulated
by endothelin-1 (ET-1). Fibrogenesis is stimulated by transforming growth factor
beta; (TGF-beta;). Chemotaxis of activated stellate cells to areas of injury is
promoted by PDGF and monocyte chemotactic protein-1 (MCP-1).
Akibat
Sirosis Hati



HIPERTENSI PORTAL

1. Hambatan
pada alran darah portal.
2. Meningkatnya
aliran darah portal akibat hyperdynamic circulation


The major clinical consequences of
portal hypertension in the setting of cirrhosis, shown for the male. In women,
oligomenorrhea, amenorrhea, and sterility are frequent, as a result of
hypogonadism.
AKIBAT
HIPERTENSI PORTAL
1. Ascites
2.
Terbentuknya Portosystemic Venous
Shunt.
3.
Congestive
splenomegali
4. Hepatic Encephalopathy
Patogenesis
ASCITES
•
Sinusoidal
hypertension, mendorong cairan masuk ke space
of Disse dan dikeluarkan melalui aliran limpe.
•
Volume cairan limpe
sangat meningkat sehingga terjadi pelepasan
cairan yg kaya protein ke dalam
rongga peritonium.
•
Vasodilatasi pembuluh
limpa dan hyperdynamic circulation, akan menurunkan
tekanan darah. Memicu
aktipasi vasokontraktor dan produksi
antidiuretik hormon.
•
Kombinasi hipertensi portal,
vasodilatasi dan retensi Na dan air akan meningkatkan tekanan
perfusi pada interstitiel kapiler, sehingga cairan keluar (ekstravasasi)
ke rongga peritonium
PORTOSYSTEMIC
SHUNT
•
Akibat lain Hipertensi
portal adalah mengalirnya darah dari
portal ke sirkulasi sistemik melalui shunt
(pembuluh darah lama atau baru) pada daerah kapiler.
•
Shunt ini bisah
terjadi dimana saja tetapi yang menonjol di esopagus (varices esopagus),
rektum (hemorrhoid) dan
ligament falsiforum (periumbilical caput medusae)
IKTERUS/
JAUNDICE
PATOGENESIS
Peninggian
kadar bilirubin darah (Hyperalbuminemia)
menyebabkan warna kuning pada kulit (jaundice) dan sklera (ikterus)
PENYEBAB
HYPERALBUMINEMIA
•
Produksi berlebihan
bilirubin
•
Hepatitis
•
Obstruksi aliran
empedu
Bilirubin metabolism and elimination.
(1) Normal bilirubin production from heme
(0.2-0.3 gm/day) is derived primarily from the breakdown of senescent
circulating erythrocytes.
(2) Extrahepatic bilirubin
(unconjugated bilirubin) is bound to serum albumin and delivered to the liver.
(3) Hepatocellular uptake and
(4) glucuronidation in the endoplasmic reticulum
generate bilirubin monoglucuronides and diglucuronides
(conjugated bilirubin), which are water soluble and readily excreted into bile.
(5) Gut bacteria deconjugate the bilirubin
and degrade it to colorless urobilinogens. The urobilinogens and the
residue of intact pigments are excreted in the feces, with some reabsorption
and excretion into urine.
Patogenesis IKTERUS
•
Unconjugated
bilrubin
terikat protein dan tak bisah larut dalam air sehingga bagaaimanapun tingginya
kadar dalam darah tidak bisah diekskresi ke urine.
•
Sebagian besar unconjugated bilrubin
terikat dengan protein, sebagian kecil bebas. Yg bebas inilah yg bisah masuk ke jaringan. Pada
anak-anak bisah masuk ke otak
menyebabkan toksik (kernicterus).
•
Conyugated
bilirubin nontoksik, bisah larut dalam
air, terkat lemah dengan protein, sehingga kalau ada peninggian kadar dalam
plasma akan diekskresi melalui urine
IKTERUS
FISIOLOGIS
•
Ikterus yang terjadi
pada anak baru lahir karena fungsi hati mengkonyugasi bilirubin belum berjalan
baik. Normal kembali dalam waktu 2 minggu.
MORPHOLOGY OF
CHOLESTASIS
Morphologic features of cholestasis (right) and comparison with normal
liver (left).
In the parenchyma (upper panel) cholestatic hepatocytes
1.
are
enlarged with dilated canalicular spaces
2.
Apoptotic
cells may be seen,
3.
and
Kupffer cells
4.
frequently
contain regurgitated bile pigments. In the portal tracts of obstructed liver
(lower panel) there is also bile ductular proliferation
5.
edema,
6.
bile
pigment retention and eventually neutrophilic
inflammation (not
shown).
7.
Surrounding
hepatocytes are swollen and undergoing degeneration.
PENYAKIT
INFEKSI HATI
•
Masalah utama adalah
kematian sel hati dan pengerahan sel-sel radang (Inflamasi).
•
Banyak yang
berlangsung kronis
•
Agen penyebab utama
adalah virus (Virus Epstein Barr, Cytomegalovirus dan Virus Hepatitis)
•
Yg banyak adalah causa
virus hepatitis
ACUTE HEPATITIS
Causes:
•
Virus (A, B,C,D dan E),
•
Toxins (alcohol),
•
Drugs
(halothane,isoniazid) and
•
Systemic infection
(Leptospira, Toxoplasma).
Potential outcomes of hepatitis B infection in adults,
with their approximate frequencies in the United States.*Recovery from acute
hepatitis refers to complete recovery as well as latent infections with
maintenance of T cell response.**Recovery from chronic hepatitis is indicated
by negative test for HBsAg.***Healthy carrier state is indicated by positive
HBsAg >6 months; HBeAg negative; serum HBV DNA 105 copies/mL;
persistently normal AST and ALT levels; absence of significant inflammation and
necrosis on liver biopsy.
ACUTE VIRAL
HEPATITIS
Histopathology (Morphology)





ALCOHOLIC
HEPATITIS
Histopathology
(Morphology)
•
Fatty change
(accumulation of lipid in the form of large cytoplasmic vacuoles within some hepatocytes.
•
Balloning
degeneration (sweling of hepatocytes)
•
Necrosis
of hepatocytes is marked by infiltration of neutrophyl and
lymphocytes.
•
Mallory’s
hyaline (cytokeratin intermediate
filaments)
•
Hepatocytes around
central vein most vulnerable º
delicate fibrosis.
•
Prolonged abuse º
Alcoholic Cirrhosis.
CHRONIC
HEPATITIS
Histopathology.
•
Necrosis of hepatocytes and the presence of inflammatory cells (either concentrated around portal tracts or
scattered within the liver lobules, or both.
•
The presence of fibrosis causing architectural distortion.
•
Regeneration of liver cells ( binucleate cells).
•
Virus Hep B : the cytoplasmic of hepatocytes may assume a ground glass pale pink appearance (accumulation of
viral protein)p
•
Spotty necrosis
(individual necrosis of hepatocytes).
CHRONIC
HEPATITIS
Bridging necrosis (and fibrosis) is shown only for chronic hepatitis but may
also occur in acute hepatitis.
Cirrhosis can be resulting from chronic viral hepatitis. Note the broad
scar and coarse nodular surface.
FULLMINANT HEPATITIS
•
Nekrose
massif sel hati sehingga hati mengecil.
•
Portal dan vena
centralis berdekatan
•
Terlihat adanya
perdarahan
•
Tanda2 regenerasi
duktus biliaris.
•
Infiltrasi sel radang
mononuklear.
FULLMINANT
HEPATITIS





OBAT DAN TOKSIN MERUSAK HATI
•
Efek
langsung obat atau toksin yang mematikan
(nekrose atau apoptosis) hepatosit.
•
Hasil
metabolisme oleh sel hati sendiri membuat obat
yang tidak toksik berubah menjadi toksin aktip.
•
Respon imun
akibat obat sebagai hapten berikatan dengan protein seluler memicu respon imun
terhadap sel hati.
BENTUK KERUSAKAN HATI OLEH OBAT DAN TOKSIN
•
Nekrosis sel hati.
•
Cholestatis
•
Tiba-tiba terjadi
disfungsi hati.
MORPHOLOGY OF
ALCOHOLIC HEPATITIS
A. The cluster of inflammatory cells marks
the site of a necrotic hepatocyte (arrow).
B. Eosinophilic Mallory bodies are seen in
hepatocytes, which are surrounded by fibrous (Masson stain) tissue.
NON-ALCOHOLIC
FATTY LIVER DISEASE (NAFLD)


1) Akkumulasi lemak dalam sel hati
dan
2) ada
stress oxidative pada sel
hati.

1. Steatosis,
2. Steatohepatitis,
3. Cirrhosis
MORPHOLOGY
OF NON-ALCOHOLIC FATTY LIVER DISEASE
A.
Steatosis, Macrovesicular
and microvesicular droplets of fat
B.
Steatohepatitis (Non
Alcoholic Steatohepatitis), steatotis with multifocal parenchymal inflamation
and sinusoidal fibrosis
TUMOR HATI
BENIGN (JINAK).
•
Focal nodular hyperplasia
•
Hemangioma.
•
Liver cell adenoma
MALIGNANT
(GANAS)
•
Hepatoblastoma.
•
Hepatocellular carcinoma
•
Fibrolamellar carcinoma
•
Cholangiocarcinoma.
Ø Focal nodular hyperplasia. (Benign)
Resected specimen showing lobulated contours and a
central stellate scar.
Ø Focal nodular hyperplasia. (Benign)
Low-power photomicrograph showing a broad fibrous scar with
hepatic arterial and bile duct elements and chronic inflammation, present
within hepatic parenchyma that lacks the normal sinusoidal plate architecture.
Ø Hemangioma. (Benign)
The photomicrograph shows the vesicular channels embedded
in fibrous stroma.
Ø Liver cell adenoma. (Benign)
Resected specimen presenting as a pendulous mass arising
from the liver.
Ø Liver cell adenoma. (Benign)
Microscopic view showing cords of hepatocytes, with an
arterial vascular supply (arrow) and no portal tracts.
Ø Hepatoblastoma. (Malignant)
The photograph shows proliferating hepatoblasts.
Ø Hepatocellular carcinoma. (Malignant)
Liver removed at autopsy showing a unifocal, massive
neoplasm replacing most of the right hepatic lobe in a noncirrhotic liver; a
satellite tumor nodule is directly adjacent.
Ø Hepatocellular carcinoma., (Malignant)
Microscopic view of a well-differentiated lesion; tumor
cells are arranged in nests, sometimes with a central lumen.
Ø Fibrolamellar carcinoma. (Malignant)
Resected specimen showing a demarcated nodule in an
otherwise normal liver. The
microscopic
images showing
nests and cords of malignant-appearing hepatocytes separated by dense
bundles of collagen.
Ø Cholangiocarcinoma. (Malignant)
Liver removed at autopsy showing a massive neoplasm in
the right hepatic lobe and innumerable metastases permeating the entire liver.
Ø Cholangiocarcinoma. (Malignant)
Microscopic view showing tubular glandular structures
embedded in a dense sclerotic stroma.
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