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MALARIA ASSOCIATED MALARIA ASSOCIATED RENAL FAILURERENAL FAILURE
Common in the tropics
Plasmodium falciparum
Renal tubules
Acute intravascular hemolysis
Heavy parasitic infection
INTRAVASCULAR INTRAVASCULAR HEMOLYSISHEMOLYSIS
Malarial infectionAntimalarial drugsG-6-P-D DeficiencyQuinine, Phosphates, Pyrimethamine
BLACKWATER FEVERBLACKWATER FEVER
HemoglobinemiaHemoglobinuriaExclude drug causationScanty parasitemiaRe-infection in non-immune immigrants Acute renal failureUncommon in Kenya
RENAL HISTOPATHOLOGY RENAL HISTOPATHOLOGY OF BLACKWATER FEVEROF BLACKWATER FEVER
Tubular AtrophyInterstitial Lymphocyte infiltrationFocal fibrosisIron pigments in fibroblasts and tubulesHeme casts in tubular lumen
CAUSES OF HEMOLYSIS IN CAUSES OF HEMOLYSIS IN FALCIPARUM MALARIAFALCIPARUM MALARIA
Impairment in physiologic deformityIncreased mechanical fragilityInterference with RBC ATPInterference with Na-K RBC ATPAltered charges on RBC surfaceImmunologic reactions
MALARIA ASSOCIATED MALARIA ASSOCIATED ACUTE RENAL FAILUREACUTE RENAL FAILURE
Common cause of MARF Heavy parasitemia 1% to 4% develop ARF 60% in Malignant malaria Usually oliguric Catabolic State Cholestatic Jaundice Rarely hepatocellular Lasts a few days to several weeks
MALARIA ASSOCIATED MALARIA ASSOCIATED ACUTE RENAL FAILUREACUTE RENAL FAILURE
Occurs 4 - 7 days from onset of feverEarly onset hyperkalemiaHyperuricemia commonHigh urinary uric acid-creatinine ratioOliguria lasts a few days to several weeks
HISTOPATHOLOGY OF HISTOPATHOLOGY OF MARFMARF
Distal tubules, Necrosis, Degeneration Proximal tubules
– Cloudy swelling and Vacuolisation– Hemoglobin in lumen– Hemosiderin in Lumen
Oedematous interstitium Tubular degeneration Regeneration of epithelial cells Dilatation of tubules Features of acute tubular necrosis
GLOMERULONEPHRITIS IN GLOMERULONEPHRITIS IN FALCIPARUM MALARIAFALCIPARUM MALARIA
Manifestations include:– Mild proteinuria– Hematuria– Casts
Non-progressive,and reversibleARF and Hypertension rareResolves in 4 – 6 weeks after antimalarialsNephrotic syndrome is rare
HISTOPATHOLOGY OF HISTOPATHOLOGY OF GLOMERULONEPHRITISGLOMERULONEPHRITIS
Mild mononuclear cell infiltrationProminent mesangial proliferationIncreased mesangial matrixNormal glomerular capillariesImmune complex mediated
IMMUNOFLUORESCENCE IMMUNOFLUORESCENCE OF GLOMERULAR LESIONSOF GLOMERULAR LESIONSFine granular deposits of IgM and C3
– Capillary walls– Mesangium
Malarial antigens– Glomerular endothelium– Medullary capillaries
ELECTRON MICROSCOPY ELECTRON MICROSCOPY OF GLOMERULONEPHRITISOF GLOMERULONEPHRITISElectron dense depositsGranular, Fibrillar, and Amorphous materialSituated in
– Subendothelial, – Mesangial, – Paramesangial regions
PATHOGENESIS OF MARFPATHOGENESIS OF MARF
Hypovolemia– Release of Kinins, Kallikreins, Histamine– Increased capillary permeability– Insensible fluid loss– Renin Angiotensin System stimulation– Increased catecholamine secretion– Hyperviscosity
Decreased RBC deformability Elevated fibrinogen
Causes renal ischemia and MARF
PATHOGENESIS OF MARFPATHOGENESIS OF MARF
INTRAVASCULAR COAGULATION Fibrin degradation products Prolonged pro-thrombin time Thrombocytopenia Decreased platelet life span
– Platelet agglutination– Splenic pooling
Alteration in coagulation factors Low grade regional intra-vascular coagulation
– Stasis and Inflammation Hemolysis and MARF
PATHOGENESIS OF MARFPATHOGENESIS OF MARF
FeverCholestatic Jaundice
– Obstructive Jaundice and ARF– Tubulotoxicity of Bile acids– Severe oliguria in association with Jaundice
Rhabdomyolysis. Rare– Myoadenyl deaminase deficiency MAD
CYTOKINES IN MARFCYTOKINES IN MARF
Serum soluble CD14– Marker of inflammatory response – Elevated in complicated Malaria
TNFalfa. – Associated with tissue damage– Stimulates expression of adhesion molecules
ELAM 1 and ICAM-1 Facilitates thrombospondin secretion
IL-1, IL-6, IL-8– Acute phase reactions– Expression of adhesion molecules– Release of vasoactive mediators– Plasma leakage from intravascular compartments
CYTOKINES IN MARFCYTOKINES IN MARF
GPI. Glycosilphosphatidylinositol– Elevated in MARF– Glycolipid substances – Acts like an endotoxin– Can induce TNF and IL-1– Cause hypoglycemia and pyrexia
HUMORAL FACTORS IN HUMORAL FACTORS IN MARFMARF
Elevated catecholaminesIncreased plasma renin activitySIADHSInflammatory mediators
– Kinins, Prosaglandins, – Histamine, Serotinin– Nitric Oxide, Endothelin,– Complement, Superoxidase
ELECTROLYTE IMBALANCEELECTROLYTE IMBALANCEIN MARFIN MARF
Hyponatremia– 67% in heavy parasitemia– Dilutional– Water retention in renal failure– Resetting of osmoreceptors– SIADH due to fever
Delayed response to water load Caution with IV fluids Pulmonary edema a hazard
ELECTROLYTE IMBALANCEELECTROLYTE IMBALANCEIN MARFIN MARF
Hypernatremia. Rare– Pure water depletion– Cerebral edema
Blunted thirst Inadequate provision of water
Hypokalemia in uncomplicated malaria Hyperkalemia Hypocalcemia with severe infection Hypophosphatemia wih severe infection
TREATMENT OF MARFTREATMENT OF MARF
Antimalarial therapy essential Quinine.
– Normal doses in MARF for first 24 to 48 hours– Thereafter reduce dose to 10 mg/kg 12 hourly– Or 24 hourly for 7
Artemesin derivatives. Potent– Inhibit adherence properties– Reduce parasite count remarkably
Exchange transfusion
TREATMENT OF MARFTREATMENT OF MARF
Dialysis in hypercatabolic states Hemodialysis or Hemofiltraion Peritoneal dialysis less preferable
– Impaired peritoneal microcirculation– Parasitised erythocytes– Vasoconstriction– Reduced solute transport– Improved efficiency as parasitemia declines– Continuous PD beneficial
MULTIORGAN FAILURE IN MULTIORGAN FAILURE IN MARFMARF
Cerebral malariaHemodynamic shockRespiratory distressMARFHematological disordersDigestive disordersOften fatal
MARF AT KNHMARF AT KNH
Were et al 47 Patients with ARF 21 (45%) with medical causes 9 (19%) developed MARF Overall mortality 40.4% MARF mortality 33.3% Cholestatic Jaundice in 4 patients All patients with MARF were oliguric
MARF AT KNHMARF AT KNH
Onset phase 2.9 daysOliguria lasted 9.8 days5 patients not dialysed. 2 died4 patients had PD. 1 diedMean duration of PD 11 daysContinuous PD. 8 cycles dailyAll had heavy parasitemia. No BWF
MARF IN VIETNAMMARF IN VIETNAM (TANG ET AL) (TANG ET AL)
64 (MARF) vs 66 (Severe Malaria only)Clinically and biochemically, ATNAssociated cholestatic jaundice, & liver dysFatality associated with
– Anuria, Short duration of illness– Hyperparasitemia, Multisystem involvement
Recovery unrelated to parasitemia
MARF IN VIETNAMMARF IN VIETNAM (TANG ET AL) (TANG ET AL)
Recovery unrelated to hemoglobinuria Oliguria 4 days (0-19) Normal biochemistry 17 days (11-23) Treated by PD Mortality decreased from 75% to 26% Good condition initially Complications develop rapidly Treat as ATN with circulatory shock Early diagnosis and dialysis mandatory