CEREBRAL CEREBRAL SCHISTOSOMIASISSCHISTOSOMIASIS

SUBSEC A6SUBSEC A6

DRA. NAVARRADRA. NAVARRA

1. Pathogenesis of hepato-1. Pathogenesis of hepato-splenic manifestations of splenic manifestations of

Schistosoma infectionSchistosoma infection

CENTENO, Lisa Joy S.CENTENO, Lisa Joy S.

Ova carried in the portal blood Ova carried in the portal blood embolize to the liver embolize to the liver lodge in the lodge in the sinusoids sinusoids granuloma formation. granuloma formation.

Hemodynamic changes resultHemodynamic changes result Portal hypertension Portal hypertension Development of portosystemic collaterals at Development of portosystemic collaterals at

the esophagogastric junction and other sites.the esophagogastric junction and other sites. Esophageal varices can rupture causing Esophageal varices can rupture causing

hematemesishematemesis

Compensatory arterialization of blood Compensatory arterialization of blood flow through the liver is established flow through the liver is established retention of hepatic perfusion retention of hepatic perfusion maintenance of normal liver function maintenance of normal liver function for several years.for several years.

Periportal (Symmers’ clay pipe-stem) fibrosis then Periportal (Symmers’ clay pipe-stem) fibrosis then ensues:ensues: In areas of egg deposition and granuloma formation In areas of egg deposition and granuloma formation

but may also be in periportal areas.but may also be in periportal areas. It is a pure fibrosis vs. the cirrhosis involving other It is a pure fibrosis vs. the cirrhosis involving other

nutritional factors or infectious agents (i.e. Hepatitis B nutritional factors or infectious agents (i.e. Hepatitis B and C).and C).

Fibrinogenesis as a result of cytokine stimulation by Fibrinogenesis as a result of cytokine stimulation by IL2, IL4, IL1 and TGFIL2, IL4, IL1 and TGFββ. .

Interaction of T lymphocytes and cells of the Interaction of T lymphocytes and cells of the fibroblast series deposits fibrotic tissue in the fibroblast series deposits fibrotic tissue in the extracellular matrix.extracellular matrix.

Hepatic splenic manifestations can Hepatic splenic manifestations can occur early in the disease with liver occur early in the disease with liver enlargement due to granulomatous enlargement due to granulomatous lesions. lesions.

May be correlated roughly with May be correlated roughly with intensity of infection, occurring more intensity of infection, occurring more often in children and related to often in children and related to specific HLA haplotypes. specific HLA haplotypes.

Subsequent phases: Portal Subsequent phases: Portal hypertension and splenomegaly due to hypertension and splenomegaly due to presinusoidal blockage of blood flow.presinusoidal blockage of blood flow. VaricesVarices at the lower end of the esophagus at the lower end of the esophagus

and at other sites.and at other sites. Bleeding from esophageal varices Bleeding from esophageal varices may be may be

first clinical manifestation of first clinical manifestation of hepatosplenic phase.hepatosplenic phase.

RUQ “dragging” pain RUQ “dragging” pain that may move that may move to the LUQ as splenomegaly to the LUQ as splenomegaly progressesprogresses

Late-stage disease:Late-stage disease: Fibrotic changes with deteriorating liver functionFibrotic changes with deteriorating liver function Onset of ascites, hypoalbuminemia and Onset of ascites, hypoalbuminemia and

coagulation defects.coagulation defects.

Accelerating or exacerbating factors to Accelerating or exacerbating factors to hepatic function deterioration:hepatic function deterioration: Concurrent viral infections of the liver (esp. Concurrent viral infections of the liver (esp.

hepatitis B and C) or nutritional deficiencies.hepatitis B and C) or nutritional deficiencies. HCC risk can increase.HCC risk can increase.

Complications:Complications: Through portosystemic collaterals, or Through portosystemic collaterals, or

directly from the IVC in the case of bladder directly from the IVC in the case of bladder wall schistosomiasis, eggs can reach the wall schistosomiasis, eggs can reach the pulmonary circulation leading to pulmonary pulmonary circulation leading to pulmonary granulomatosis and fibrosis, pulmonary granulomatosis and fibrosis, pulmonary hypertension, and cor pulmonale with a hypertension, and cor pulmonale with a high mortality rate.high mortality rate.

Gallbladder cancer can also be associated.Gallbladder cancer can also be associated.

2. Differentiate the clinical features of 2. Differentiate the clinical features of schistosomal hepatomegaly from that of schistosomal hepatomegaly from that of viral hepatitis, miliary tuberculosis, and viral hepatitis, miliary tuberculosis, and

malariamalaria

Rosalyn ChanRosalyn Chan

Schistosomal HepatomegalySchistosomal Hepatomegaly Ova are carried by portal blood embolize to the liver and lodge Ova are carried by portal blood embolize to the liver and lodge

at presinusoidal sites, where granulomas are formedat presinusoidal sites, where granulomas are formed Class I and Class II human leukocyte antigen (HLA) Class I and Class II human leukocyte antigen (HLA)

haplotypes and markers – genetic basis appears to be haplotypes and markers – genetic basis appears to be multigenicmultigenic

Presinusoidal blockage causes several hemodynamic changes, Presinusoidal blockage causes several hemodynamic changes, including portal hypertension and associated development of including portal hypertension and associated development of portosystemic collaterals at the esophagogastric junction and portosystemic collaterals at the esophagogastric junction and other sitesother sites

Esophageal varices are present and can lead to recurring Esophageal varices are present and can lead to recurring hematemesishematemesis

Since changes in hepatic portal blood flow occur slowly, Since changes in hepatic portal blood flow occur slowly, compensatory arterialization of the blood flow through the compensatory arterialization of the blood flow through the liver is established – retention of hepatocyte perfusion permits liver is established – retention of hepatocyte perfusion permits maintenance of normal liver function for yearsmaintenance of normal liver function for years

Periportal fibrosis (Symmers’ clay pipe-stem Periportal fibrosis (Symmers’ clay pipe-stem fibrosis) but can also be diffusefibrosis) but can also be diffuse

Fibrosis, when diffuse, may be seen in areas of egg Fibrosis, when diffuse, may be seen in areas of egg deposition and granuloma formation but is also see deposition and granuloma formation but is also see in distant locations such as portal tractsin distant locations such as portal tracts

Pure fibrosis lesions – deposition of fibrotic tissue in Pure fibrosis lesions – deposition of fibrotic tissue in the extracellular matrix results from the interaction the extracellular matrix results from the interaction of T lymphocytes with cells of the fibroblast series; of T lymphocytes with cells of the fibroblast series; several cytokines such as IL-2, IL-4, IL-1, and several cytokines such as IL-2, IL-4, IL-1, and transforming growth factor beta (TGF-B) are know transforming growth factor beta (TGF-B) are know to stimulate fibrogenesisto stimulate fibrogenesis

Viral HepatitisViral Hepatitis

Esophageal varices common as a result of portal Esophageal varices common as a result of portal hypertensionhypertension

Stigmata of liver cirrhosis due to viral hepatitis:Stigmata of liver cirrhosis due to viral hepatitis: Spider angiomaSpider angioma Palmar erythemaPalmar erythema AsterixisAsterixis GynecomastiaGynecomastia

Acute HepatitisAcute Hepatitis

Enlarged, reddened liver; greenish if cholestaticEnlarged, reddened liver; greenish if cholestatic Parenchymal changes:Parenchymal changes:

Hepatocyte injury (swelling, ballooning degeneration)Hepatocyte injury (swelling, ballooning degeneration) Cholestasis: canalicular bile plugsCholestasis: canalicular bile plugs HCV: mild focal fatty change of hepatocytesHCV: mild focal fatty change of hepatocytes

Hepatocyte necrosis: isolated cells or clustersHepatocyte necrosis: isolated cells or clusters Cytolysis (rupture) or apoptosis (shrinkage)Cytolysis (rupture) or apoptosis (shrinkage) If severe: bridging necrosis (portal-portal, central-central, portal-central)If severe: bridging necrosis (portal-portal, central-central, portal-central) Lobular disarray: loss of normal architectureLobular disarray: loss of normal architecture

Regenerative changes: hepatocyte proliferationRegenerative changes: hepatocyte proliferation Sinusoidal cell reactive changes:Sinusoidal cell reactive changes:

Accumulation of phagocytosed cellular debris in Kupffer cellsAccumulation of phagocytosed cellular debris in Kupffer cells Influx of mononuclear cells into sinusoidsInflux of mononuclear cells into sinusoids

Portal tracts:Portal tracts: Inflammation: predominantly mononuclearInflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosisInflammatory spillover into adjacent parenchyma, with hepatocyte necrosis

Chronic HepatitisChronic Hepatitis Changes shared with acute hepatitisChanges shared with acute hepatitis

Hepatocyte injury, necrosis, and regenerationHepatocyte injury, necrosis, and regeneration Sinusoidal cell reactive changesSinusoidal cell reactive changes

Portal TractsPortal Tracts Inflammation:Inflammation:

Confined to portal tractsConfined to portal tracts Spillover into adjacent parenchyma, with necrosis of hepatocytes (interface Spillover into adjacent parenchyma, with necrosis of hepatocytes (interface

hepatitis)hepatitis) Bridging inflammation and necrosisBridging inflammation and necrosis

Fibrosis:Fibrosis: Portal depositionPortal deposition Portal and periportal depositionPortal and periportal deposition Formation of bridging fibrous septaFormation of bridging fibrous septa

HBV: HBV: “gr“ground glassound glass”” hepatocytes, hepatocytes, “sa“sandednded”” nuclei nuclei HCV: bile duct epithelial cell proliferation, lymphoid aggregate formationHCV: bile duct epithelial cell proliferation, lymphoid aggregate formation

Miliary TuberculosisMiliary Tuberculosis

Hepatic granuloma and resulting hepatomegaly occurs in more Hepatic granuloma and resulting hepatomegaly occurs in more than 90% of patients with military tuberculosisthan 90% of patients with military tuberculosis

Clinical symptoms: fever, night sweat, fatigue, and weight loss. Clinical symptoms: fever, night sweat, fatigue, and weight loss. Jaundice is an unusual findingJaundice is an unusual finding

Granulomas are found randomly scattered in the parenchyma and Granulomas are found randomly scattered in the parenchyma and also in the portal tracts, though therea re reports of granulomas in also in the portal tracts, though therea re reports of granulomas in the portal area and caseation may be seen.the portal area and caseation may be seen.

Acid-fast organisms are not usually found in liver smears but PCR Acid-fast organisms are not usually found in liver smears but PCR for mycobacterium tuberculosis can be performed (Sp = 96%, Sn= for mycobacterium tuberculosis can be performed (Sp = 96%, Sn= 53%)53%)

MalariaMalaria

Budd-Chiari Syndrome: the obstruction of two or more major Budd-Chiari Syndrome: the obstruction of two or more major hepatic veins produces liver enlargement, pain, and ascites due to hepatic veins produces liver enlargement, pain, and ascites due to increased intrahepatic blood pressure and an inability of the massie increased intrahepatic blood pressure and an inability of the massie hepatic blood flow to shunt around the blocked outflow tracthepatic blood flow to shunt around the blocked outflow tract

Sequestration in the hepatic microvasculature and increased Sequestration in the hepatic microvasculature and increased coaguation cascade activity through intrinsic pathway activation coaguation cascade activity through intrinsic pathway activation have been proposed as likely mechanisms. Antithrombin III have been proposed as likely mechanisms. Antithrombin III depletion in severe falciparum malaria may produce a depletion in severe falciparum malaria may produce a hypercoaguable state and hepatic vein thrombosis. Cytokine hypercoaguable state and hepatic vein thrombosis. Cytokine release is also procoagulant and may add to the mechanism of release is also procoagulant and may add to the mechanism of venous block. Disseminated intravascular coagulation is important venous block. Disseminated intravascular coagulation is important in the pathogenesis of severe malaria. Thus, coagulopathy can play in the pathogenesis of severe malaria. Thus, coagulopathy can play a major role in producing a complication like Budd-Chiari a major role in producing a complication like Budd-Chiari syndrome in falciparum malaria.syndrome in falciparum malaria.

With acutely developing thrombosis of the hepatic With acutely developing thrombosis of the hepatic veins the liver is swollen and red-purple and has a veins the liver is swollen and red-purple and has a tense capsule. Microscopically the affected hepatic tense capsule. Microscopically the affected hepatic parenchyma reveals severe centrilobular congestion parenchyma reveals severe centrilobular congestion and necrosis. Centrilobular fibrosis develops in and necrosis. Centrilobular fibrosis develops in instances in which the thrombosis is more slowly instances in which the thrombosis is more slowly developing.developing.

The major veins may contain totally occlusive fresh The major veins may contain totally occlusive fresh thrombi, subtotal occlusion, or, in chronic cases, thrombi, subtotal occlusion, or, in chronic cases, organized adherent thrombi.organized adherent thrombi.

3. Outline Instructions for a 3. Outline Instructions for a Person Planning to Travel to Person Planning to Travel to

an Endemic Area an Endemic Area

Chavez, Justin Karlo B.Chavez, Justin Karlo B.

Prevention and ControlPrevention and Control

It is prudent for travelers to avoid It is prudent for travelers to avoid contact with all freshwater bodies.contact with all freshwater bodies.

If exposure occurs, a follow-up visit If exposure occurs, a follow-up visit with a health care provider is with a health care provider is strongly recommended.strongly recommended.

Usage of molluscicides, provision of Usage of molluscicides, provision of sanitary water, sewage disposal, sanitary water, sewage disposal, chemotherapy and health education chemotherapy and health education may be a valuable tool to prevent may be a valuable tool to prevent schistosomiasis.schistosomiasis.

DiagnosisDiagnosis

The afflicted patient usually presents The afflicted patient usually presents with:with: Cercarial dermatitisCercarial dermatitis Katayama FeverKatayama Fever

High level peripheral blood eosinophilia, (+) High level peripheral blood eosinophilia, (+) serologic assay for schistosomal antibodies (FAST-serologic assay for schistosomal antibodies (FAST-ELISA, EITB). ELISA, EITB).

* To make a correct diagnosis, it is important * To make a correct diagnosis, it is important to note the recent travel history of the to note the recent travel history of the patient and exposure to freshwater bodies.patient and exposure to freshwater bodies.

Geographic history, characteristic clinical Geographic history, characteristic clinical presentation and presence of schistosome presentation and presence of schistosome ova in excretaova in excreta

Serologic assays may be used to detect Serologic assays may be used to detect circulating schistosome antigencirculating schistosome antigen

Kato thick smear of feces may be done to Kato thick smear of feces may be done to detect disease in a lightly infected individualdetect disease in a lightly infected individual

Nucleopore filter of urine may be done to Nucleopore filter of urine may be done to check for check for S. HematobiumS. Hematobium

Tissue biopsy may also be doneTissue biopsy may also be done

TreatmentTreatment

S. mansoni, S. intercalatum, S. S. mansoni, S. intercalatum, S. haematobium, S. japonicum, S. haematobium, S. japonicum, S. mekongi – Drug of choice: mekongi – Drug of choice: Praziquantel, 20/mgkg, 2 doses in a Praziquantel, 20/mgkg, 2 doses in a day and 3 doses for S. japonicum and day and 3 doses for S. japonicum and mekongimekongi Cure rate is 85%, reduces egg counts Cure rate is 85%, reduces egg counts

>90%>90%

THANK YOU!THANK YOU!