Hemolytic-Uremic Syndrome (HUS) in Untreated Shigella Infection

Hemolytic-Uremic Syndrome (HUS) in Untreated Shigella Infection:


  • Complication: Untreated Shigella infection, particularly in children, can lead to the development of Hemolytic-Uremic Syndrome (HUS).
  • Frequency: Although HUS is a rare complication, it poses a severe threat to affected individuals.


1. Toxin Production:

Shigella Toxin: Shigella bacteria, particularly certain subtypes, produce a potent toxin known as Shiga toxin.

Subtype Influence: Shigella dysenteriae, specifically subtype 1, is associated with a higher risk of Shiga toxin production.

2. Mechanism of Shiga Toxin:

Red Blood Cell Destruction: Shiga toxin targets and damages red blood cells through various mechanisms.

Inhibition of Protein Synthesis: The toxin interferes with protein synthesis, inducing cellular stress and eventual lysis.

3. Renal Involvement:

Filtering Function Obstruction: Shiga toxin can obstruct the kidney’s filtering function by forming complexes with specific cellular components.

Microthrombi Formation: Formation of microthrombi composed of cell compounds and immune organelles occurs in the renal vasculature.

4. HUS Progression:

Pathogenetic Antigen: The interaction between Shiga toxin and pathogenetic antigens triggers an immune response.

Inflammatory Cascade: An inflammatory cascade ensues, leading to damage of blood vessels, particularly in the kidneys.

5. Kidney Failure:

Timeline: If left untreated, the progression from uncontrolled Shigella infection to kidney failure can occur within a matter of days.

Contributing Factors: Factors such as the patient’s overall health, age, and immune response influence the timeline.

Mortality and Statistics:

  • Mortality Rate: HUS carries a mortality rate, and fatalities can occur due to complications such as kidney failure.
  • Incidence: While HUS is relatively rare, statistics indicate its occurrence in a percentage of Shigella-infected individuals.

The intricate mechanisms by which Shiga toxin targets red blood cells and interferes with protein synthesis, as well as the cellular components involved in obstructing the kidney’s filtering function:

Shiga Toxin Mechanisms and Renal Obstruction:

Shiga Toxin and Red Blood Cells:

1. Binding to Receptors:

Shiga toxin initially binds to specific receptors on the surface of red blood cells.

Shiga toxins primarily bind to glycolipid receptors on the surface of host cells, including red blood cells (RBCs). The main receptor for Shiga toxins is the glycosphingolipid Gb3 (globotriaosylceramide), also known as CD77. Gb3 is abundantly present on the cell membranes of certain cells, including endothelial cells, renal cells, and red blood cells.

2. Internalization:

Following binding, the toxin is internalized into the red blood cell.

The interaction between Shiga toxins and Gb3 receptors plays a crucial role in the internalization of the toxins into cells, leading to their toxic effects. Once inside the cells, Shiga toxins inhibit protein synthesis, causing cellular damage and, in severe cases, contributing to the development of conditions like Hemolytic-Uremic Syndrome (HUS).

3. Ribosome Interaction:

Shiga toxin interacts with the ribosomes, which are cellular organelles responsible for protein synthesis.

The interaction of Shiga toxins with ribosomes involves a complex process that ultimately inhibits protein synthesis. Here’s a detailed description of how Shiga toxins interfere with ribosomal function:

1. Binding to Receptors:

Shiga toxins, specifically Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2), initially bind to the Gb3 receptors on the surface of target cells. Gb3 is a glycolipid receptor present on the cell membrane.

2. Endocytosis and Intracellular Transport:

Following receptor binding, the toxin-receptor complex is internalized through endocytosis, forming endocytic vesicles.

3. Vesicle Trafficking to the Endoplasmic Reticulum (ER):

The endocytic vesicles containing the Shiga toxin make their way to the endoplasmic reticulum (ER), a cellular organelle involved in protein synthesis and processing.

4. Translocation into the Cytosol:

Shiga toxins have a unique ability to translocate from the endoplasmic reticulum into the cytosol of the host cell. This translocation is facilitated by the A subunit of the toxin.

5. Cleavage of Ribosomal RNA:

Once in the cytosol, the A subunit of Shiga toxin acts as an RNA N-glycosidase. It cleaves a specific adenine residue from the 28S ribosomal RNA (rRNA) present in the 60S subunit of eukaryotic ribosomes.

6. Inhibition of Protein Synthesis:

The cleavage of the adenine residue in the 28S rRNA disrupts the function of the ribosome, particularly the peptidyl transferase activity. This interference inhibits the elongation phase of protein synthesis.

7. Cellular Damage and Apoptosis:

The inhibition of protein synthesis leads to cellular stress and damage. Cells, particularly those in the kidneys and other affected tissues, may undergo apoptosis (programmed cell death).

8. Contribution to Hemolytic-Uremic Syndrome (HUS):

The damage to endothelial cells, renal cells, and other cell types contributes to the development of conditions like Hemolytic-Uremic Syndrome (HUS), characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury.

By disrupting ribosomal function, Shiga toxins exert their toxic effects, causing cellular damage and contributing to the pathogenesis of diseases associated with Shiga toxin-producing bacteria, such as certain strains of Shigella and Escherichia coli (E. coli)

4. Inhibition of Protein Synthesis:

Shiga toxin disrupts protein synthesis by inhibiting the ribosomal machinery at the translation stage.

This interference occurs during protein elongation, preventing the synthesis of essential cellular proteins.

5. Cellular Stress:

The inhibition of protein synthesis induces cellular stress, compromising the normal functioning of red blood cells.

6. Formation of Membrane Lesions:

Shiga toxin contributes to the formation of membrane lesions on red blood cells.

7. Lysis:

The combination of inhibited protein synthesis, cellular stress, and membrane lesions leads to the lysis (rupture) of red blood cells.

Kidney’s Filtering Function Obstruction:

1. Formation of Microthrombi:

Shiga toxin, in combination with pathogenetic antigens, triggers an immune response leading to the formation of microthrombi.

Microthrombi are aggregates composed of cellular components and immune organelles.

2. Inflammatory Cascade:

The immune response initiates an inflammatory cascade, causing damage to blood vessels, particularly within the renal vasculature.

3. Obstruction of Glomerular Filtration:

Microthrombi obstruct the glomerular filtration units in the kidneys.

This obstruction interferes with the normal filtration of blood, leading to impaired kidney function.

Investigation and Confirmation:

1. Clinical Assessment:

Symptoms such as persistent dysentery, abdominal pain, and signs of renal impairment prompt clinical suspicion.

2. Laboratory Tests:

Hematological Studies: Assessing blood parameters, including red blood cell count, may reveal features indicative of hemolysis.

Renal Function Tests: Evaluate markers of renal function to identify impairment.

3. Imaging:

Renal Imaging: Techniques like ultrasound can help visualize structural abnormalities in the kidneys.

4. Pathological Examination:

Renal Biopsy: In cases of chronic dysentery, a renal biopsy may be performed to examine tissue for the presence of microthrombi and inflammatory changes.

Outcome of Hemolytic-Uremic Syndrome (HUS) with Aggressive Treatment:

Survival Rates and Renal Outcomes:

1. Survival Rates:

With prompt and aggressive treatment, the survival rates for the acute phase of HUS exceed 90%.

Aggressive treatment aims to mitigate the progression of complications associated with HUS.

2. End-Stage Renal Disease (ESRD):

Approximately 9% of patients may develop End-Stage Renal Disease (ESRD) during the course of HUS.

ESRD is a condition where the kidneys function at a significantly reduced capacity, often necessitating renal replacement therapy.

Long-Term Renal Function:

1. Abnormal Kidney Function:

Despite survival through the acute phase, more than one-third of individuals with HUS may exhibit abnormal kidney function in the years following the initial episode.

Abnormalities can manifest as impaired glomerular filtration and compromised renal function.

2. Long-Term Dialysis:

A minority of individuals, albeit a few, may require long-term dialysis to manage persistent renal dysfunction.

Long-term dialysis involves the use of external devices to filter and purify blood, compensating for impaired kidney function.

Medical Terminology:

1. Glomerular Filtration:

Glomerular filtration refers to the process by which blood is filtered through the glomeruli in the kidneys, allowing for the removal of waste products.

Impaired glomerular filtration is a hallmark of renal dysfunction.

2. Renal Replacement Therapy:

Renal replacement therapy encompasses treatments such as dialysis and kidney transplantation.

It becomes necessary when the kidneys are unable to adequately perform their physiological functions.

3. End-Stage Renal Disease (ESRD):

ESRD denotes the advanced stage of kidney disease where renal function is severely compromised, requiring intervention to sustain life.

4. Hemolytic-Uremic Syndrome (HUS):

HUS is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury.

The syndrome often follows Shiga toxin-producing bacterial infections, such as Shigella.

Verified by: Dr.Diab (February 3, 2024)

Citation: Dr.Diab. (February 3, 2024). Hemolytic-Uremic Syndrome (HUS) in Untreated Shigella Infection. Medcoi Journal of Medicine, 5(2). urn:medcoi:article32202.

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