Streptococcal Septic Shock

Epidemiology

This is Dr. Cal Shipley with a review of toxic shock syndrome caused by Group A streptococcus. Before we get to the animation, let’s review a few facts about Group A streptococcus. Group A Strep is also referred to by the acronym GAS. It refers to a single bacterium – Streptococcus pyogenes. In the human body, GAS’s most commonly causes localized infections of the throat, also known as pharyngitis, and infections of the skin such as erysipelas or impetigo. Localized GAS infections are common throughout the world and account for some 700 million cases annually. In the West, localized GAS infections rarely cause serious disease, particularly if they are properly diagnosed and treated.

Invasive GAS disease occurs when the bacterium enters the bloodstream or otherwise sterile parts of the body, such as muscles or fascia. It is estimated that there are about 600,000 new cases of invasive GAS disease annually worldwide. While this is a significant number, it pales in comparison to the 700 million estimated cases of localized GAS infection yearly. One form of invasive GAS disease is Streptococcal toxic shock syndrome, also known as Streptococcal septic shock.

Streptococcal Septic Shock Definition

Streptococcal Toxic Shock Syndrome, also known by the acronym STSS, is characterized by the presence of the bacteria in the bloodstream or normally sterile body area, and accompanied by low blood pressure, rapid heart rate and evidence of organ failure. Approximately, 10,000 cases of STSS occur in the United States annually with a fatality rate of close to 50%. Compared to septic shock from all infectious sources, STSS composes about 10% of cases annually. The average mortality rate for septic shock from all sources is similar to that for STSS, about 50%.

Streptococcal Septic Shock versus Toxic Shock Syndrome

I also want to mention that, even though they have a very similar clinical presentation and severity, Streptococcal toxic shock syndrome should not be confused with the toxic shock syndrome associated with menstruating females who are using tampons. This form of toxic shock is generally caused by Staphylococcus aureus. Fortunately, due to the redesign of tampons, the incidence of menstrually-related toxic shock syndrome has dropped sharply in recent years. Let’s take a look now at the pathophysiology of Group A Streptococcus septic shock. I should mention that the pathophysiology of Group A strep septic shock is very similar to other forms of bacterial-induced septic shock, with some minor variations.

Pathophysiology of Streptococcal Septic Shock

The human vascular system carries oxygenated blood to the furthest reaches of the body, and then returns it to the heart via a complex web of arteries and veins. Blood which courses through the vascular system is composed of serum which contains proteins, electrolytes, and nutrients such as glucose and blood cells; red blood cells to carry oxygen to tissues, and white blood cells whose primary function is to provide immune protection against invading bacteria and viruses.

Uncontrolled GAS infections of the throat, skin or lungs provide the most common access points for the entry of the bacteria into the bloodstream. However, the bacteria may access the bloodstream from any localized source of infection in the body. In many cases, the exact source of infection at entry point remains a mystery. The word “strepto” has a Greek root meaning twisted chains. Group A Streptococcus is commonly found in chains of 2 to 20 individuals. Let’s look at the structure of a single bacterium. In cross-section, we see the cell wall lined on its inner wall by the membrane, and surrounded by the capsule. Centrally located within the bacterium is its DNA.

Virulence Factors

The genome of one species of strep pyogenes has been sequenced and found to contain 1.8 million base pairs, and about 1,700 protein-encoding genes, as well as 40 virulence-related genes, which may explain why strep pyogenes causes a wider variety of diseases in humans than any other bacteria. Two examples of virulence factor proteins are protein F, which allows Strep pyogenes to bind tightly to respiratory epithelial cells, and protein M, which allows the bacterium to resist phagocytosis by white blood cells. Also within the cell are particles known as ribosomes. Ribosomes use the instructions contained in messenger RNA to link amino acids together forming proteins.

Onset of Sepsis

Cytokines and Exotoxins in Streptococcal Septic Shock

Once the bacterium is in the bloodstream, ribosomes migrate to the cellular membrane. Once at the cellular membrane, they begin to produce a protein known as an exotoxin, also sometimes referred to as a superantigen. The exotoxin is excreted from the cell into the intercellular space, where it binds to receptors on T-cell lymphocytes. Once bound to the T-cell lymphocytes, the exotoxins cause the lymphocytes to produce cytokines. In Group A Streptococcus septic shock, exotoxins may stimulate up to 20% of T-cell lymphocytes to produce cytokines. The cytokines excreted by T-cell lymphocytes rapidly spread throughout the body via the vascular system.

Cytokines are a group of cell-signaling proteins that are critical in the initiation and regulation of the immune response to infectious invaders such as Group A streptococcus. Cytokine stimulates white blood cell production in the bone marrow resulting in leukocytosis, an increased white blood cell count in response to infection. Cytokines also signal neutrophil white blood cells to come to the site of infection. The neutrophils are capable of destroying the GAS organisms. The total population of GAS is capable of doubling every 20 to 30 minutes. Depending on the rapidity and the strength of the initial immune response, the group A Strep may quickly overwhelm the body’s ability to contain the infection.

As the numbers of Group A strep increase, so too does the amount of exotoxin excreted, with a corresponding rise in total certain serum levels of cytokines. As levels rise, the cytokines go from being helpful to being harmful. This is the beginning of septic shock. Cytokines toxicity causes excessive expansion (dilation) of blood vessels. Contractility (pumping action) of the heart is impaired. At toxic levels, cytokines also increase vascular permeability, particularly at the capillary level.

Capillary Permeability and Leakage

Capillaries are the smallest branches of the arterial system. They serve as the point at which oxygen and nutrients are transferred to bodily tissues, and their inside diameter is just large enough to accommodate a column of red blood cells moving in single file. The wall of a capillary consist of a single layer of cells held together by chemical bonds. Toxic levels of cytokines cause the bonds between cells to loosen. This creates gaps between the cells allowing leakage of serum from the capillary.

This leakage of serum can occur on a widespread basis throughout the body, resulting in a profound decrease in total blood volume. Increased capillary permeability, in conjunction with abnormal dilation of blood vessels and decreased heart contractility, results in a profound lowering of blood pressure, also known as hypotension. This is septic shock. A loss of blood pressure results in a drastic reduction in the body’s ability to deliver oxygen tissues via the vascular system, a situation known as ischemia. The ischemia associated with septic shock threatens all bodily tissues and organs, and if not reversed, can result in stroke, kidney failure, respiratory failure, cardiac arrest and death.

Cal Shipley, M.D. copyright 2020