What is the pathophysiology of leptospirosis?

The pathophysiology of leptospirosis is complex, involving multiple stages and mechanisms:

Entry and Initial Replication:

Leptospires gain entry into the human body through abraded skin, mucous membranes, or conjunctiva. Once inside, they multiply locally, primarily in the blood, without causing significant symptoms in many cases.

Incubation Period:

Following initial infection, there is an incubation period of 2 to 30 days before the onset of symptoms.

Biphasic Course:

Leptospirosis is characterized by a biphasic clinical course.

First Phase (Saprophytic Phase)

1. Leptospiremic Phase: During the first phase, leptospires rapidly multiply in the bloodstream, causing fever, chills, headache, myalgia, and conjunctival suffusion.

2. Leptospiremia and Tissue Invasion: The organisms invade various tissues, including the liver, kidneys, spleen, lungs, heart, and central nervous system.

3. Capillary Damage: The spirochetes bind to endothelial cells, causing damage to blood vessel walls and resulting in increased capillary permeability.

Second Phase (Immune Phase)

1. Immune Response: As the immune system mounts a response against the infection, antibodies and inflammatory mediators are produced.

2. Immune-Mediated Injury: The immune response leads to immune complex deposition in affected tissues, activation of complement, and recruitment of neutrophils. This inflammatory response can cause damage to tissues and organs, resulting in the clinical manifestations of the second phase.

3. Organ-Specific Manifestations: The involvement of different organs can lead to specific symptoms, such as:

- Liver: Jaundice, elevated liver enzymes, and hepatomegaly.

- Kidneys: Renal failure, proteinuria, and hematuria.

- Lungs: Pulmonary hemorrhage and respiratory distress.

- CNS: Meningoencephalitis leading to neurologic symptoms such as headaches, altered mental status, seizures, and cranial nerve palsies.

- Hemorrhages: Petechiae, ecchymosis, or gastrointestinal bleeding may occur due to capillary damage and impaired coagulation.

Following the immune phase, some individuals may experience a period of convalescence and gradual recovery, while others may develop severe organ dysfunction or complications such as acute renal failure, liver failure, ARDS, or disseminated intravascular coagulation (DIC). In severe cases, leptospirosis can lead to multiple organ failure and death.