1、Hemorrhagic Fever with Renal Syndrome,Zhang Dazhi, M.D Department of Infectious Disease The second hospital of CMU,Overview,Pathogen: Hantaviruses Clinical features: fever；renal failure；shock; hemorrhagic manifestations Hemorrhagic fever with renal syndrome(HFRS) includes a group of clinically simil
2、ar illnesses Epidemic hemorrhagic fever(China) Korean hemorrhagic fever(Korean) Nephropathis epidemica(Puumala,Virology of Hantaviruse,Belong to the family Bun-yaviridae Spherical enveloped viruses about 80-120 nm in diameter Genome consists of three single-stranded, negative sense RNA segments-S, M
3、, LS (small): encodes neucleocapsid proteinM (medium): encodes envelope glycoproteinL(large): encodes polymerase,The viruses that cause hemorrhagic fever with renal syndrome include: Hantaan Dobrava-Belgrade SeoulPuumala Sin Nombre virus can cause hantavirus pulmonary syndrome (America),Virology of
4、Hantaviruse,Epidemiology,Sources of transmission: rodent reservoirs,Striped field mouse,Norway rat,Bank voles,Yellow-necked field mouse,Occurs mainly in Europe and Asia,Striped field mouse Apodemus agrarius,Norway rat Rattus norvegicus,Bank voles Clethrionomys glareolus,Yellow-necked field mouse A.
5、flavicollis,Epidemiology,Route of transmission Exposure to aerosolized urine, droppings, or saliva of infected rodents Direct introduction of infectious material through broken skin or onto mucous membranes Through rodent bites from infected animals From mother to child Transmission from human to hu
6、man is extremely rare.,Epizootic Cycle,Rodent breeding,Epidemiology,Susceptibility of population People are generally susceptible Commonly reported in male adult Subclinical infection rate is 2.54.3% Stable and persistent immunity,Pathogenesis,Immune mechanisms may play an major pathogenic role Vire
7、mia is only present in early stage of infectionNo cytopathic effect At the time that severe symptoms begin Viremia is absent Specific antibodies and T cells are detected marked cytokine production, kallikrein-kinin activation, complement pathway activation,Pathogenesis,Basic pathological changesSyst
8、emic microvascular endothelial edema, degeneration and necrosis The most dramatic damage is seen in the kidneys,Immune mediated vascular endothelial injuryIncreased capillary permeabilityPlasma extravasationInsufficient blood volumePrimary shock occurs before oliguric stage,Massive hemorrhage or Sec
9、ondary infection or Insufficient water-electrolyte supply during polyuric stageInsufficient blood volumeSecondary shock: occurs after oliguric stage,Pathogenesis: shock,Pathogenesis: hemorrhage tendency,Damage of the blood vessel wall Thrombocytopenia Uremic bleeding defects Increase of heparinlike
10、substances DIC,Decreased blood flow Direct injury to the kidney,Pathogenesis: acute renal failure,Histopathologic changes in kidney (cortex) Small arrow: interstitial edema with mild infiltration of mononuclear cells Large arrow : degeneration of renal tubules Arrow head: proteinaceous casts and exu
11、date,Histopathologic changes in kidney (medulla) Most prominent change in the medulla is welldefined necrotic lesion (asterisk),*,Intracranial hemorrhage in HFRS patient,Clinical Manifestations: overview,Incubation period: usually 1 to 2 weeks A triad of fever, hemorrhage, and renal insufficiency 5
12、progressive stages: Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stage Skipping of phase is common in atypical and mild individuals. The individual phases may overlap in severe cases.,Clinical Manifestations: Febrile stage,Abrupt onset of fever lasting 3-7 days Gastroin
13、testinal discomfortAnorexia, nausea , vomiting and abdominal pain Systemic toxic symptomsMyalgia, triad of pains (Headache, lumbago and retroorbital pain),Clinical Manifestations: Febrile stage,Signs of Capillary injuryCongestionHemorrhagic tendencyExudation and edema,Clinical Manifestations: Febril
14、e stage,Congestion Dermathemia: triad of flushingsFlushing over Face, the V area of the neck (drunken face), and the back Mucosal hyperemiaConjunctival suffusion, pharyngeal injection,Drunken face,Clinical Manifestations: Febrile stage,Hemorrhagic tendency DermatorrhagiaPetechiae often develop in ar
15、eas of pressure, axillaEcchymosis in severe case Mucosal bleeding Petechiae in the conjunctivae, soft palate Visceral bleedingEpistaxis, bloody stool, hemoptysis, cerebral bleeding,Petechiae on axilla,Ecchymosis in severe case,Subconjunctival hemorrhage,Petechiae on the soft palate,Clinical Manifest
16、ations: Febrile stage,Exudation and edema cause pain Periorbital edema, chemosis Retroperitoneal edema AscitesAbdominal pain: Differential diagnosis?,chemosis,Clinical Manifestations: Hypotensive stage,Lasts approximately a few hours to 2 days Exacerbation of the disease after defervescence Falling
17、blood pressure and TachycardiaIn severe case shock (primary shock),Clinical Manifestations: Oliguric stage,Persists for 2-5 daysOliguria: urine output 400 ml /dAnuria: urine out put50 ml/d Hemorrhagic tendencies continue Onset of renal failureSymptoms associated with uremia Water-sodium retentionHyp
18、entension; pulmonary edema; ascitesAcidosis, electrolyte imbalance, BUN ，Cr ,Clinical Manifestations: Diuretic stage,Last for a couple of days up to weeks Characterized by diuresis and hyposthenuria Migratory stage: daily urine volume increases from 400ml to 2000ml; exacerbation of the azotemia Earl
19、y polyuric stage: Daily urine volume 2000ml; stabilization of the azotemia Late polyuric stage: Daily urine volume 3000ml; recover of the azotemia Fluid replacement is inadequate secondary shock,Clinical Manifestations: Convalescent stage,last for as long as 1-3 months Daily urine volume returns to
20、normal,Clinical Manifestations,What are five progressive stages of HFRS?Febrile stage; Hypotensive stage; Oliguric stage; Polyuric stage; Convalescent stage,Laboratory findings,Blood routine test Leukocytosis with a left shift Elevated hematocrit lever Thrombocytopenia Atypical lymphocytes Q:Viral i
21、nfections causing leukocytosis HFRS Infectious mononucleosis Japanese encephalitis Rabies,Laboratory findings,Urine routine test Heavy proteinuria Hematuria Cast,Massive protein and shedded epithelial cells in urine form Membrane-like substance,Laboratory findings,Biochemical tests Elevated levels o
22、f liver enzymes, BUN, and serum creatinine Electrolyte disturbancesAltered coagulation profile,Laboratory findings,Etiological diagnosis Enzyme-linked immunosorbent assay (ELISA) Antihantaviral-specific IgM1:20(+)Early diagnostic valueAntihantaviral-specific IgG1:40(+) Fourfold or greater rise in Ig
23、G titer can also confirm suspected cases Isolation of virus RT-PCR: identify viral RNA,Summary of the clinical features,A triad of fever, hemorrhage, and renal insufficiency 5 progressive stages: Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stage Laboratory finding:Leuk
24、ocytosis and thrombocytopeniaProteinuriaElevated levels of BUN, and serum creatinine,Complication,Digestive tract bleeding Intracranial hemorrhages Myocardial damage Pulmonary edema :ARDS, heart failure Secondary Infections Spontaneous kidney rupture,Treatment: overview,Early recognition and hospita
25、lization, bed rest Treatment is supportive Prevent for secondary infection Prevent the GI bleeding,Treatment: Febrile stage,Anti-viral therapy: IV ribavirinPreferably begun within the first 4 days of illness Reduce exudate: Rutosids and vitamin C Management of the fever and toxic symptoms Physical c
26、ooling Short course dexamethasone Prevent DIC,Treatment: Hypotensive stage,Supplement of blood volume Modest crystalloid infusion Human serum albumin Plasma Vasoactive agents Dopamine, norepinephrine Correction of acidosis5% Sodium Bicarbonate Injection,Treatment: Oliguric stage,Maintenance of inter
27、nal environment homeostasis Restrict the volume of infusionDaily urine volume + 500-700ml Control the azotemiaSupply sufficient carbohydrate to reduce the protein degradation Maintaining electrolyte balance Treatment of Hyperkalemia Correction of acidosis5% Sodium Bicarbonate Injection,Treatment of
28、hyperkalemia,Stop further potassium accumulation Protect the cardiac membrane Calcium gluconate 10% Shift the potassium from the blood into the cellInsulin Removal of potassium from the bodyHaemodialysis, Furosemide,Treatment: Oliguric stage,Diuretics: furosemide Catharsis :rheum officinale Consider
29、 Dialysis in following conditions Severe azotemia Fluid overload that cannot be managed with diuretics Hyperkalemia refractory to medical therapy Severe acid-base disturbances,Treatment,Polyuric stage Maintain fluid and electrolyte balance Prevent secondary infectionAntibiotics with nephrotoxic pote
30、ntial should be avoided Convalescent stage Monitored in rest home,Prognosis,Fatality rate ranges from 5 to 15% with Hantaan virus to less than 1% for Puumala virus infection For survivors, convalescence can take several months but recovery is often complete,Prevention,Rodent control Avoid contact wi
31、th rodent urine, droppings, saliva, and nesting materials Vaccination,Home work,1 .Hantaan virus is mainly transmitted by Patients Carriers Swine Mosquitoes Rodents,（E）,Home work,2 .The most cardinal reason of bleeding in febrile period of EHF is A. DIC B. Heparin-like substance increasing C. Thromb
32、ocytopenia and vascular injury D. Azotemia E. Coagulation factor decreasing,（C）,Home work,3.The main reason for early shock in EHF is Infection. Blood plasma-losing Hypervolemia Hemorrhage Vomiting .,(B),Home work,4.The patient had fever, lumbago, headache for three days. Physical examination: drunk
33、en face, petechiae in axillary folds, chemosis. Blood routine test: WBC 19109，N 83%, PLT 20109. Urine protein (+), RBC 3-5/HP .The diagnosis may be Typhoid fever Typhus Acute glumerulonephritis Epidemic hemorrhagic fever Leptospirosis,(D),Home work,5. Which is not proper in management of hemorrhagic
34、 fever with renal syndrome when hyperkalemia occurs A. Insulin and dextrose solutions B.10% calcium gluconate C. 5% sodium bicarbonate D. Hemodialysis E. Whole blood transfusion,(E),Home work,6.Canonical hemorrhagic fever with renal syndrome caused by Hantaan virus evolve in five identifiable stages:_, _, _, _ and _. 7. Give a introduction about the management principle of the oliguric phase of the hemorrhagic fever with renal syndrome,THE END THANK YOU!,
