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  Table of Contents    
CASE REPORT  
Year : 2022  |  Volume : 65  |  Issue : 4  |  Page : 934-937
Renal and hepatic changes in a case of envenomation by snake bite: Case report and review of literature


1 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Medicine, Armed Forces Medical College, Pune, Maharashtra, India

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Date of Submission10-Feb-2021
Date of Decision05-Apr-2021
Date of Acceptance11-Apr-2021
Date of Web Publication27-Apr-2022
 

   Abstract 


Snake bite is a major health hazard, moreover in tropical countries where the density of snakes, frequent human contact, lack of diagnostic and treatment facilities further add-on to the high morbidity and mortality. No organ escapes the effect of envenomation from Heart to liver and kidney, CNS to local bite site. While the effect of snake venom on kidney has been documented, the literature available on the pathological effects of envenomation in human liver is lacking. We present a case of an elderly male with renal and hepatic manifestations of envenomation.

Keywords: Snake bite nephropathy, snake bite hepatopathy, snake envenomation, snake bite

How to cite this article:
Paliwal G, Prakash S, Kashif A W. Renal and hepatic changes in a case of envenomation by snake bite: Case report and review of literature. Indian J Pathol Microbiol 2022;65:934-7

How to cite this URL:
Paliwal G, Prakash S, Kashif A W. Renal and hepatic changes in a case of envenomation by snake bite: Case report and review of literature. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Dec 7];65:934-7. Available from: https://www.ijpmonline.org/text.asp?2022/65/4/934/344192





   Introduction Top


Snakebite is a major health hazard with high morbidity and mortality, especially in tropical countries.[1] While the effect of snake venom on the kidney has been documented, mostly during the 1980s and 1990s; the literature available on the pathological effects of envenomation in the human liver is lacking. We present a case of an elderly male with presenting symptoms of right hemiparesis, altered sensorium, and fever. He was diagnosed with renal and hepatic manifestations of envenomation. Here we present the classical manifestations of envenomation and review the available literature on the topic.


   Case History Top


86 years old known post-CABG (15 years back) patient presented to emergency OPD with history of right-sided weakness of upper and lower limbs and altered sensorium of 02 days duration accompanied with intermittent low-grade fever of 01 day duration. There was no history of seizure, loss of consciousness, fall, neck rigidity, headache, chest pain, syncope, breathlessness, cough, pain abdomen, burning micturition, or altered frequency of urine.

On examination, he was febrile (Temp 100°F) and had tachypnea (RR 36/min) with pallor. His GCS was 8/15 (E1, V2, M5). All other parameters were within normal limits. Systemic examination revealed bilateral fine inspiratory crackles in infra axillary and infra scapular areas.

Laboratory investigations revealed anemia (Hb 10.4 g%) with schistocytes (1.5%) and left shift in neutrophil series (TLC-7800/cm). Biochemistry showed elevated Direct and total bilirubin (2/2.9 mg/dL) and elevated liver enzymes (ALT- 515 IU/L, AST- 702 IU/L), serum LDH of 1259 U/L, and reversal of Albumin-Globulin ratio (2.8/4.1 g/dL). The renal functions (blood urea 276 mg/dL, creatinine 5.4 mg/d/L) and coagulation profile were deranged (PT/INR 38.2/3.2/42.4). A reduced fibrinogen (150 mg/dL) and elevated FDP and D-Dimer levels (20 μg/mL) confirmed the diagnosis of DIC in a setting of Sepsis (with serum procalcitonin 4.82 μg/L). USG revealed normal-sized kidneys with increased echotexture and minimal pleural effusion in right lung. NCCT head showed Subacute SDH (right parietal region).

In view of the renal dysfunction kidney biopsy was performed which revealed features of Snakebite nephropathy in the form of mesangiolysis, segmental mesangial hypercellularity, widespread ATN and accumulation of RBC casts, hyaline casts as well as pigmented cast [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Direct immunofluorescence (DIF) study showed focal non-specific trapping for antisera specific against IgM and C3 in the glomerular capillary wall.
Figure 1: Renal biopsy (a): Mesangiolysis with dilated capillary loops (black arrows) (MT 400x); (b): Mesangial hypercellularity (black arrow) (MT 400x); (c): Acute Tubular Necrosis evident as denudation of tubular epithelium with loss of brush border and sloughing of epithelial cells, flattening of renal tubular cells due to tubular dilation and intratubular cast formation (H&E 200x); (d): Intratubular myoglobin casts (black arrows)(MT 200x) positive for myoglobin by IHC (Inset)

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Sections from Liver biopsy revealed pale areas of hepatocyte necrosis and steatosis alternating with the dark areas of viable hepatocytes arranged in 2 cell plate thickness. Cholestasis was noted. The Sinusoids appeared congested with increased Kupffer cell activity and presence of hemosiderin-laden macrophages that were confirmed by perl's stain [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. There was no evidence of periportal congestion or hepatic vein thrombi.
Figure 2: Liver biopsy: (a): alternate pale and light areas (H&E 100x); (b): pale areas showing hepatocyte necrosis and steatosis with dark areas showing viable hepatocytes arranged in 2 cell plate thickness (H&E 200x); (c): Cholestasis (blue arrows) and hemosiderin laden macrophages (black arrows) evident at higher magnification (H&E 400x); (d): Hemosiderin laden macrophages (Perl's iron stain 400x)

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The patient was managed as a case of Disseminated intravascular Coagulation (ISTH score- 5), and Sepsis with parenteral Vitamin K, Blood component support, parenteral antibiotics, three sessions of hemodialysis, and other supportive therapy. He, however, had a stormy course in the hospital, desaturated, and suffered cardiac arrest, succumbing to his illness.


   Discussion Top


Out of more than 2000 species distributed worldwide only about 450 species of snakes are venomous. The major burden of snakebite-related mortality and morbidity is shared by tropical countries in Asia, Africa, and Latin America. Every year approximately 45,900 snakebite-related deaths are reported from India, which is a sizeable.[1] The Venomous snakes are categorized into 4 broad families: Elapidae, Viperidae, Hydrophidae, Colubridae of which the most common cause of envenomation in India is snake bite of Viperidae family.[2] The clinical manifestations depend on species and dose of venom that is injected and range from local symptoms like pain swelling, blistering to extensive multi systemic manifestations.[3] The most striking abnormalities following viper bites are bleeding and coagulation defects leading to severe bleeding manifestations.

The kidney is very susceptible to venom toxicity and renal involvement has been widely reported in the literature. All the renal compartments are variably involved in a case of snakebite envenomation and hematuria, proteinuria are common clinical manifestations.[4] The pathogenesis of renal lesions is multifactorial and includes direct nephrotoxic action of snake venom, inflammatory effects due to endogenous cytokines and mediators, hypotension, and DIC due to intravascular hemolysis, bleeding and coagulation abnormalities.[5]

Acute Kidney Injury (AKI) develops in about 5–30% of patients with children more prone to develop acute renal failure than adults.[4],[5] As reported by Chugh et al.,[5] oliguric or anuric renal failure was overwhelmingly seen in 94% of the patients within 2-72 hours of snakebite, which were mostly due to hemotoxic or myotoxic snakes.[5] The predominant change observed in patients with acute kidney injury was acute tubular necrosis (ATN). Vikrant et al.[6] reported ATN to be the dominant feature in 91% patients of snake bite whereas Mittal et al.[7] found it in 53.6% cases.[6],[7] Renal biopsies done during the first week after envenomation reveal the degenerative and regenerative changes in the tubular epithelial cells. Another typical finding is that of hemoglobin casts in cases of hemotoxic snakebites and myoglobin casts in myotoxic snake bites. These appear as pigment casts in the renal biopsies and with the help of immunohistochemistry, using specific antibody against hemoglobin and myoglobin, one can differentiate between the two closely resembling entities.[8] Consistent with these findings, widespread ATN and RBC casts along with pigmented casts which were myoglobin positive, were noted in our case.

Varying degrees of interstitial edema and mixed inflammatory cell infiltrate usually accompanies cases of viper bites resulting in acute diffuse interstitial nephritis (AIN). In a single-centre study done by Priyamvada et al.,[9] AIN accounted for 5.7% of snakebite-related acute kidney injury. It is very important to accurately determine this complication as timely treatment with corticosteroids leads to good response in almost 80% of the patients.[9] Apart from the features of AIN and ATN, Chugh et al.[10] also observed that increased apoptosis in the distal tubules and presence of eosinophils, mast cells and hyperplastic fibroblasts.[10]

One of the most sinister complications of snakebite is hemorrhagic infarct followed by Acute Cortical Necrosis. Mittal et al.[7] observed cortical necrosis in 24.3% of patients developing acute renal failure following snake bite.[11] Hemorrhagic Infarcts may develop and are evident as fibrin platelet thrombi in interlobular arteries located around and/or within the infarcted areas. Tubules in such cases show hemoglobin casts. Acute cortical necrosis either patchy or diffuse is typically seen at the latter end of spectrum. According to Chugh et al.[10] Snakebite can be attributed as the second most common cause of acute cortical necrosis accounting for 3.5-12% of causation amongst cortical necrosis cases reported.[10] It is characterized by necrosis of all the elements of kidney with thrombi in renal vasculature. Late in the course, evidence of healing is apparent in the form of fibroblastic proliferation, organization of thrombi in the vasculature and fibrosis of the vessel wall.

The concept of Snakebite nephropathy was introduced by Sitprija to include Mesangiolysis, glomerulonephritis, vasculitis, and tubular necrosis.[4] Glomerular involvement in snake bite cases is variable and can be overlooked. In the early stages only mesangiolysis is evident with proliferation and hypercellularity of mesangial cells later in the course.[11] Our case exhibited mesangiolysis and segmental mesangial hypercellularity. Glomerular involvement can range from proliferative glomerulonephritis, extra-capillary proliferative glomerulonephritis, diffuse proliferative glomerulonephritis to crescentric glomerulonephritis in rare cases. Sitprija et al. have also shown the subtle involvement of the vascular compartment ranging from segmental necrotizing arteritis of the interlobular arteries to segmental thrombophlebitis of the arcuate vein. This can be easily missed in case of a superficial renal biopsy.

The role of DIF in such renal biopsies is limited. Deposition of IgM and C3 may not be apparent in the early stage, however, fine and granular deposition can be seen in mesangial areas and sometimes along glomerular capillary loops late in the course of glomerulonephritis. IgM deposits are more prominent in Russel viper bites and C3 in Cobra bites.[12] DIF in our case revealed focal non-specific trapping for antisera specific against IgM and C3 in the glomerular capillary wall.

A scrupulous literature search on the effect of envenomation on liver in humans has shown extreme paucity of documented work with just one short report from Srilanka by De Silva et al.[12] There are few animal experimental studies and fewcase reports from veterinary medicine which have contributed to the literature available on liver changes in case of snakebite. Hence, to the best of our knowledge, our exemplification of findings in the human liver in a case of snakebite is among the first of its kind.

Among the experimental study done by Jarrar et al. on effects of envenomation by hemotoxic venom on sheep, the liver exhibited necrosis and steatosis of hepatocytes.[13] Necrosis was more evident in lobular periportal hepatocytes while steatosis was observed mainly in the hepatocytes around central vein. Necrotic changes included loss of normal cytoplasmic eosinophilia with cytoplasmic vacuolation pushing the nucleus to periphery. Nuclear changes in the form of karyopyknosis are mostly encountered and karyorrhexis & karyolysis may also be seen. The vascular compartment may occasionally show central vein occlusion with congestion of sinusoids and thrombosis of portal veins. An interesting finding, documented along some sinusoids in all the cases, was the presence of amorphous extracellular material, confirmed to be amyloid with Congo red straining. It resulted in compression and atrophy of hepatocytes especially in the periportal zone. Our case also had features of increased Kupffer cell activity and cholestasis. Though cholestasis hasn't been reported in animals; increased Kupffer cell activity is seen and may indicate the degenerative changes of hepatocytes owing to snakebite envenomation. Glycogen depletion was also observed in hepatocytes (seen on PAS stained sections). In a report on snakebite in buffalo, Tandale et al.[14] elucidated moderate necrotic changes in hepatic parenchyma with moderate infiltration of inflammatory cells.[14] Partial obliteration of the liver architecture with lobular disarray was seen in some of the cases.

Disseminated Intravascular Coagulation (DIC) is a consistent finding in both clinical and experimental studies of envenomation. The mechanism causing DIC varies with the type of venom but ultimate result is increased thrombin activity. The role of DIC can be appreciated by the presence of fibrin thrombi in renal microvasculature and in glomerular capillaries along with findings of microangiopathic hemolytic anemia and thrombocytopenia in patients with cortical necrosis. Chug et al. in a study of 36 patients with ARF and evidence of DIC, concluded 56% of patients with AKI showed the evidence of acute DIC, 30% showed compensated DIC and the remaining 14% showed isolated thrombocytopenia. However, in patients where there was no Renal failure post snake bite, only 17% showed evidence of acute DIC, with another 38% showing compensated DIC5. Among the major organs showing histopathological changes in DIC, the liver is less commonly involved. Autopsy studies have demonstrated microinfarcts and focal hepatic necrosis as major histological changes.[15] Though we did find evidence of hepatocellular necrosis in the index case, there were no microinfarcts. However, considering that this was a core biopsy, the possibility of microinfarcts remains in unsampled areas.


   Conclusion Top


Incidence of snakebite is quite common in tropical countries. Many times the diagnosis is delayed leading to fatal outcome. Our case report is unique in two ways firstly it highlights the characteristic renal changes that occur in snake envenomation and secondly it details the histological changes in liver in such cases, something which has hardly been reported in the world. The case report also underscores the importance of renal and liver biopsies in arriving at correct diagnosis which can lead to timely management and better outcome. It is pertinent to mention that more biopsy and autopsy studies are warranted in cases of snake bites to help us understand the pathogenesis better.

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Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Mohapatra B, Warrell DA, Suraweera W, Bhatia P, Dhingra N, Jotkar RM, et al. Million Death Study Collaborators. Snakebite mortality in India: A nationally representative mortality survey. PLoS Negl Trop Dis 2011;5:1018.  Back to cited text no. 1
    
2.
Kohli HS, Sakhuja V. Snake bites and acute renal failure. Saudi J Kidney Dis Transpl 2003;14:165-76.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Hifumi T, Sakai A, Kondo Y, Yamamoto A, Morine N, Ato M, et al. Venomous snake bites: Clinical diagnosis and treatment. J Intensive Care 2015;3:1-9.  Back to cited text no. 3
    
4.
Sitprija V. Snakebite nephropathy. Nephrology 2006;11:442-8.  Back to cited text no. 4
    
5.
Chugh KS. Snake-bite-induced acute renal failure in India. Kidney Int 1989;35:891-907.  Back to cited text no. 5
    
6.
Vikrant S, Jaryal A, Parashar A. Clinicopathological spectrum of snake bite- induced acute kidney injury from India. World J Nephrol 2017;6:150-61.  Back to cited text no. 6
    
7.
Mittal BV. Acute renal failure following poisonous snake bite. J Postgrad Med 1994;40:123-6.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Kashif AW, Jadhav T, Panda SK. Pigment cast nephropathy: Time to revisit the diagnosis. J Nephropathol 2021;10:e14.  Back to cited text no. 8
    
9.
Priyamvada PS, Shankar V, Srinivas BH, Rajesh NG, Parameswaran S. Acute interstitial nephritis following snake envenomation: A single-center experience. Wilderness Environ Med 2016;27:302-6.  Back to cited text no. 9
    
10.
Chugh KS, Singhal PC, Kher VK, Gupta VK, Malik GH, Narayan G, et al. Spectrum of acute cortical necrosis in Indian patients. Am J Med Sci 1983;286:10-20.  Back to cited text no. 10
    
11.
Sitprija V, Boonpucknavig V. Glomerular changes in tropical viper bite in man. Toxicon 1983;21:401-3.  Back to cited text no. 11
    
12.
De Silva HJ, Ratnatunga N, De Silva U, Kularatne WN, Wijewickrema R. Severe fatty change with hepatocellular necrosis following bite by a Russell's viper. Trans R Soc Trop Med Hyg 1992;86:565.  Back to cited text no. 12
    
13.
Jarrar BM. Histological alterations and biochemical changes in the liver of sheep following Echis coloratus envenomation. Saudi J Biol Sci 2011;18:169-74.  Back to cited text no. 13
    
14.
Tandale RU, Moregaonkar SD, Gangane GR, Narote SR, Chavan PA, Choudhari AN. Snake bite in a buffalo- a case report. Int J Sci Environ Technol 2019;8:645-8.  Back to cited text no. 14
    
15.
Watanabe T, Imamura T, Nakagaki K, Tanaka K. Disseminated intravascular coagulation in autopsy cases its incidence and clinicopathologic significance. Pathol Res Pract 1979;165:311-22.  Back to cited text no. 15
    

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Correspondence Address:
A W Kashif
Department of Pathology, Armed Forces Medical College, Pune - 411 040, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpm.ijpm_155_21

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