2. HPI
CC : Syncope/Seizures
HPI : 70 yo AAM with no sig PMH presented
to the ER via EMS.
Patient reported to have a witnessed seizure
while waiting for a bus. When EMS found the
patient he had change in Mental Status, was
confused and was wearing multiple layers of
cloth despite temp being warm. No details of
seizure/syncope were available.
4. on Floor
Patient admitted to Teaching service.
WBC 3.6, Hb 15.1, Plt 143
NA 131, Cl 94, Hco3 21,BS 140 , Creatinine 1.1
Patient evaluated for seizures, CT head
negative, MRI head no acute pathology, Bld Cx
negative.
Pt Platelets started to fall , upto 23K in 4 days,
Pts Heparin was stopped , suspecting HIT.
5. on Floor
Patient was spiking Fevers daily in evening upto 104 F,
associated with Change in Mental status and profuse
sweating with pt being afebrile in 2-3 hrs with Tylenol,
and patient feeling Cold, Mild nausea, no vomiting, Dec
PO intake.
ICU was consulted after 4 days on the floor and Patient
with Temp of 104.3 Platelets of 23K.-ve cultures. On Abx,
Mild Hypotension.
Patient was Tfx to ICU with Probable Dx of septic Shock.
6. in ICU
Patient admitted, Sepsis Order sheet filled out and executed.
Resident and Intern went to lab and saw the slide to look for
DIC (Shistocytes) Findings. No +ve finding.
Next morning Lab called with some ???? Finding on the
smear.
Peripheral smear (Thick & Thin) for Malarial Parasite
Ordered.
On questioning , Patient added that he just returned from a
21 day trip to Haiti and DR. he returned 2 days before
coming to hospital.
7. in ICU
Peripheral Smear came back +ve with Plasmodium Falciparum
>10% Parasitemia.
Patient condition deteriorated , Sedated, Intubated started on
Pressors, became Neutropenic.
ID consulted. Dx Cerebral Malaria
Seizure, DVT, GI prophylaxix
Patient started on Rx as per CDC recommendation on Quinidine
and Doxy IV.
Heam/Onc Consulted for possibility of Exchange Transfusion.
Not done later.
8. in ICU
Treatment continued, % Parasitemia checked
every other day .
% parasitemia was down to <1% in 4 days
CT abd showed Hepatosplenomegaly (done on
day of transfer)
Patient became anemic and required Transfxn.
Acute Liver faliure, Hyperbilirubinemia
9. Nephrology Consulted!!
Pt’s creatinine started to rise 1 day after ICU
transfer and he went into ARF.
urine output progressively decreased to less
than 250ml/day over 5 days
Cr increased 1.1 to 9 in 5 days.
Nephrology was consulted on day 3
Dx of ATN was made secondary to Septic
shock and Plasmodium Falciparum Malaria
10. MARF
Malaria is one of top 10 killer diseases in world
Acute renal failure (ARF) is a common complication in severe
falciparum malaria
Prevalence of ARF in malaria all over the world has been
reported as 0.57% to 60%
ARF occurs commonly in plasmodium falciparum malaria,
although its rare occurrence has been reported in plasmodium
vivax malaria
Diagnosed when sr. creat.>3mg/dl or urine output <400ml/24 hrs
12. Mechanisms
Effect of pRBC on microcirculation- knob like processes formation
on surface of RBC which helps in anchoring the endothelium
Cytoadherence
Loss of deformability of pRBC according to need of
microcirculation
Hypovolumia, Fever, sweating, Dec intake, vomiting
DIC
Increased plasma viscosity due to infection
Release of chemical mediators
15. Types of MARF
Chronic Malarial Nephropathy
P. malariae is the established cause of chronic malarial
nephropathy, TH2 predominenece
The disease affects children
It presents as a steroid-resistant nephrotic syndrome
The characteristic histopathologic lesion is mesangiocapillary
glomerulonephritis, with subendothelial immune complex
deposits containing IgG, C3, and malarial antigens
These deposits typically are seen as small lacunae in
silverstained biopsy sections
The disease proceeds to renal failure even after successful
eradication of the infection
16. Quartan malarial nephropathies
P. malariae nephropathy, non specific
Proteinuria is encountered in a variable proportion of patients,
Microhaematuria is occasionally noted
Overt nephrotic syndrome develops in a undefined fraction, and
hypertension is a late symptom
Serum complement is normal, and blood cholesterol is usually not
elevated because of the associated nutritional deficiency
The disease is progressive despite successful eradication of the
infection
CRF in 3-5 yrs
17. Quartan malarial nephropathies
Light microscopy, subendothelial deposits as thickening of the
capillary walls, giving a double-contour appearance to the basement
membrane
By immunofluorescence ,a coarsely granular pattern along the
capillary endothelium containing IgG & malarial antigen
Electron Microscopy, subendothelial deposits of electron dense or
basement-membrane-like material, with formation of intra-
membranous lacunae
A proliferative lesion, mainly involving the mesangium
Initially Focal and segmental, in majority of cases soon becomes
diffuse with global sclerosis.
18. Quartan malarial nephropathy. Left, glomerulus, showing
thickening of the capillary wall with mesangial hyperplasia (H&E);
right,splitting of the glomerular basement membrane with
subendothelial deposits (Silver stain)
19. Acute Malarial Nephropathy
P. falciparum is the causative species in the
overwhelming majority of cases
Three renal complications falciparum malaria:
acute tubular necrosis
acute interstitial nephritis, and
proliferative, occasionally exudative
glomerulonephritis
Acute tubular necrosis is the principal & most serious
pathologic mechanism in malaria induced ARF.
20. Interaction of the hemodynamic and immunologic perturbations in the pathogenesis of acute renal disease in
falciparum malaria. ATN, acute tubular necrosis; AIN, acute interstitial nephritis; PIGN, postinfectious
glomerulonephritis (includes exudative and necrotizing variants); MPGN, mesangioproliferative glomerulonephritis.
21. Renal lesions associated with malarial acute renal failure. Top left: Acute tubular necrosis (note
the remarkable epithelial disruption, red cells in the tubular lumen, and interstitial edema and
cellular infiltration). Top right: Acute interstitial nephritis. Bottom left: Proliferative
glomerulonephritis. Bottom right: Segmental necrotizing glomerulonephritis.
22. Acute Tubular Necrosis
Usually Oliguric
microcirculatory disorder, peripheral vasodilatation, hemolysis, rhabdomyolysis, DIC,
Peripheral pooling, reduction of the effective blood volume and diminished tissue
perfusion.
TNF-a,reactive oxygen radicles, and inducible nitric oxide.
Relative hypovolaemia, hypercatecholaminaemia, inc levels of plasma renin activity,
dilatory prostaglandins and vasopressin.
Impaired tissue perfusion leads to lactic acidosis
Inhibition of sodium–potassium ATPase leads to internal loss of sodium and dilutional
hyponatraemia,
reported mortality ranges from 15 to 30%
23. Acute interstitial nephritis
Acute interstitial inflammation is a well-recognized
pattern of malarial nephritis in rodents and following
vaccination with P. falciparum antigens in monkeys.
massive influx of TH1lymphocytes and associated
with acute glomerular lesions
Although isolated interstitial nephritis has not been
reported in humans, interstitial inflammation is
commonly seen along with other ATN and
glomerulonephritis.
24. Glomerulonephritis
proliferative, occasionally exudative glomerulonephritis
Mostly in children
Mild proteinuria, microhaematuria, and casts are reported in
20–50% of cases.
Nephrotic and acute nephritic syndromes are occasionally seen
Serum C3 and C4 may be reduced during the acute phase
In contrast to quartan malarial nephropathy, falciparum
glomerulopathy is reversible within 2–6 weeks upon
eradication of the infection
25. Glomerulonephritis
Light Microscopy, mesangial proliferation, Mesangial matrix expansion,
Deposition of an eosinophilic granular material along the capillary walls, in the
mesangium, and in Bowman’s capsule
glomerular capillaries may contain a few parasitized red cells or giant nuclear
masses in patients who develop intravascular coagulation, Malarial antigens are
occasionally seen
Immunofluorescence shows finely granular IgMand C3 deposits along the
capillary walls and in the mesangium
EM, subendothelial and mesangial electron-dense deposits along with granular,
fibrillar and amorphous material
Tubular changes include cloudy swelling, haemosiderin granular deposits and
variable cell necrosis. The tubular lumina often contain haemoglobin casts
The interstitium is oedematous with a moderate to dense mononuclear cellular
infiltration and venules may show clumps of parasitized erythrocytes
29. Treatment
Appropriate antimalarial at the earliest,
Chloroquine or Intravenous quinidine
Maintenance of fluid & electrolytes
Recording of intake output chart
Prevention of fluid overload & secondary
infection including pneumonia
Treatment of acquired infection at the earliest
30. Treatment
Early dialysis is often needed
Large doses of frusemide have been consistently ineffective in
altering the course of MARF. However, when used in conjunction
with "renal dose" dopamine in early cases, it may obviate the need
for dialysis
Intravenous prostacyclin and direct intrarenal infusion of the
calcium channel blocker gallopamil have reported to be effective in
reducing the need for dialysis in MARF
PD is less effective
• Exchange transfusion is helpful in patients with heavy parasitaemia
• Apheresis has been reported to successfully support anuric patients
with cerebral and pulmonary complications
• There is no place for corticosteroids in the treatment
31. Back to the Patient
• HD was started on day 5 with creatinine on 9 and urine output
<250 ml/hr, initially HD was given daily and later 3 times a week.
• Pt was off pressors on day 6 of his ICU stay, which was also
complicated by PNA.
• Pt was off vent on day 13 and his urine out put did improve a
little by that time.
• Pt was transferred to floors where he stayed for another 8 days
and was discharged to SNF for rehab.
• Pt was eventually off HD in 3 months and Cr was at 1.9
