TANATOGENESIS IN LEPTOSPIROSIS

During the period 1982 2004 in our clinic 84 patients with leptospirosis have been treated. This study dynamically compares changes of laboratory parameters in survivors and fatal cases, and reveals following post mortem founded tanatogenic factors: brain edema in 100% of non survivors, lung edema (100%), severe cardiovascular disorders with shock (100%), and hemorrhagic syndrome (80%).


MATERIAL AND METHODS:
Clinical, epidemiological, and laboratory parameters have been studied retrospectively and prospectively in 84 cases with leptospirosis treated in Clinic of Infectious Diseases -Pleven (1982 to 2004).
The illness is with acute onset with fever above 38 o C, chills, headache, myalgia (specific for leptospirosis pains in calf muscles), abdominal pains, nausea and vomiting, oligoanuria.
Blood urea nitrogen (BUN) level is elevated in 80,95% of cases (av. 26,1 mmol/L), and serum creatinine level is elevated in 72,62% (av. 303,2 µmol/L). The comparison of these parameters in severe cases with favorable and fatal outcome reveals interesting dynamics: average BUN level of survivors in admission and before discharge is respectively 33,9 and 7,4 mmol/L. In fatal cases BUN level in admission and before the death is respectively 41,4 and 41,6 mmol/L. Average serum creatinine level of survivors in admission and before discharge is 503 and 112 µmol/L respectively. In fatal cases serum creatinine level is av. 443 µmol/L in admission and 283 µmol/L before the death. Serum bilirubin is elevated in 70,24% (av. 167,9 µmol/L), with prevalence of conjugated fraction. In survivors average serum bilirubin level in admission and before discharge is 231,3 µmol/L and 62,9 µmol/L respectively. In fatal cases average serum bilirubin level is 333,7 µmol/L in admission, and 303,6 µmol/L terminally.
The levels of serum transaminases are moderate elevated and rarely exceed 200 U/L, accompanied by modest elevation of alkaline phosphatase (in 54,76% of cases; av. 358 U/L in admission and 315 U/L finally, independent of outcome).

DISCUSSION:
Leptospires enter the body through skin, mucous membranes or conjunctiva, aerosol inhalation and possibly ingestion. Once they entering in lymphatic and blood stream, leptospires are carried rapidly to organs through the body. Intensive multiplication of leptospires occurs in both blood and tissues, resulting in acute and intense organ dysfunction. The fact that there is marked peripheral leucocytosis in the absence of neutrophilic infiltration in the tissues suggests the role of toxins in the pathogenesis of the disease. The kidney and the liver are most affected by leptospires. In the kidney, leptospires cause interstitial nephritis and tubular necrosis. In the liver, there is centrilobular necrosis with a proliferation of Kupffer cells being responsible for jaundice. At severe pathological changes occur at a time when leptospires are rarely found in the lesions, it seem plausible that the toxin released by the organisms is responsible for liver injury. Leptospires are present in the cerebrospinal fluid early in the course of the disease, but meningeal symptoms appear in immune phase and meningitis is immunological in mechanism. All these pathological changes are marked in severe forms. In part of severe cases illness is with favorable course, in other -with rapid progression of toxicity, untreatable acute renal failure, appear severe bleeding, cardiovascular disorders with shock (1,2,4,5,6,7,8,9,10,11,12,13,14,15). The observed course of illness and pathological laboratory findings in our cases have been correlated with references (3,4,6,8,10,13,14).

CONCLUSION:
Leptospirosis has interesting and not fully clear pathogenesis, broad clinical spectrum and high mortality rate in severe cases. The illness requires correct diagnostic approach purposed to an early diagnosis and adequate treatment including early hemodiaperfusion in acute renal failure for prevention of brain and lung edema -the major tanatogenic factors. More experiments are necessary about specific factors of serotypes, and about the role of immunological changes in humans with leptospirosis, especially in severe cases.