Pathophysiology

 

Septic Shock

Septic shock is

“A life-threatening organ dysfunction caused by a dysregulated host response to infection” (McCance & Huether, 2019, p. 1550).

The infectious process starts with an infectious agent entering the bloodstream and causing bacteremia either directly from the site of infection or indirectly by releasing toxic substances into the bloodstream. Some of the most common causes of septic shock are gram-negative or gram-positive bacteria, viruses, and fungi. The most common sites of infection are the lungs, bloodstream, intravascular catheters, intra-abdominal, urinary tract, and surgical wounds (McCance & Huether, 2019).

Normal Physiology

In normal physiology, when a pathogen invades the body, the body will react with local and systemic responses.

• Our first line of defense is the body’s natural physical, mechanical, and biochemical barriers such as the epithelial cells and surfaces of the skin. These defenses prevent microorganisms from getting into tissues and also have the ability to remove infectious microorganisms. The surfaces of the skin and mucous membranes of the body also contain normal microbiomes (“normal flora”) that also protects the body by releasing chemicals to prevent pathogens from being colonized (McCance & Huether, 2019).
• The body’s second line of defense is the inflammatory response. Inflammation causes a vascular response that makes vessel walls become leaky and more permeable and makes white blood cells adhere to vessel walls and migrate out into the tissues. Symptoms usually produced by inflammation are the heat, redness, edema and pain. The goal of inflammation is to prevent and limit infection and interact with components of the adaptive immune system as well as prepare the body for healing (McCance & Huether, 2019). 

There are three important plasma protein systems involved to provide an active barrier against invading pathogens in the inflammatory response.

• One is complement system which destroys pathogens directly and work with other components of the immune responses by three pathways: (1) classic, (2) lectin and (3) alternative. The main functions of these are to induce rapid mast cell degranulation, attract white blood cells to pathogens, and “tag” pathogens for destruction (McCance & Huether, 2019).
• Second is the clotting or coagulation system which forms blood clots that include a meshwork of protein strands at the injured or inflamed site to stop bleeding, trap pathogens to prevent the spread of infection, and provide a framework for repair and healing (McCance & Huether, 2019).
• The last important inflammatory response is from the kinin system which activates and assists inflammatory cells by the release of mainly bradykinin which causes dilation of blood vessels, pain, smooth muscle contraction, increase vascular permeability and leukocyte chemotaxis (McCance & Huether, 2019). 

There are also many biochemical mediators of the innate immune system that secrete cytokines responsible for activating other cells such as interleukins, chemokines, interferons, and other molecules. These chemicals are important to the vascular changes that occur during the inflammatory process (McCance & Huether, 2019).

Along with the cellular mediators are the cellular components such as platelets, phagocytes (neutrophils, eosinophils, monocytes, macrophages and dendritic cells), natural killer cells, and lymphocytes. The components respond to the site of the injury together to limit the tissue injury, kill pathogens, remove the debris, and prepare for healing and tissue repair (McCance & Huether, 2019). 

Pathophysiology

Septic shock begins when the pathogen enters the bloodstream. This stimulates the release toxic substances called the triggering molecules, which triggers the body to activate the proinflammatory responses and release proinflammatory cells such as leukocytes, macrophages, monocytes and platelets as well as proinflammatory mediators such as cytokines (interleukins, tumor necrosis factor alpha and other mediators). Cytokines along with the vasoactive peptides cause vasodilation causing hypotension, relative hypovolemia, and decreased in oxygen delivery to the tissues. The release of proinflammatory cytokines also activate plasma protein systems of the complement, coagulation and kinin systems (McCance & Huether, 2019).

Dysfunction of epithelial cells cause further capillary leaking and microvascular thrombus, tissue hypoxia and apoptosis. Due to tissue hypoxia, the body will start breaking down carbohydrates to make ATP or energy for the body. As more anaerobic cells are being used for energy, the more lactic acid is produced. Without correction, the accumulation will lead to metabolic acidosis causing further damage to the tissues (McCance & Huether, 2019).  

As the responses of proinflammatory and antiinflammatory mediators intensify the body experiences persistent low arterial pressure, low tissue perfusion, low systemic vascular resistance which will profoundly affect the circulatory, cellular and metabolic systems. These responses will lead to multiple organ dysfunction syndrome (MODS) due to dysfunction of the kidneys, liver, intestines, lungs and brain as a result of tissue hypoxia and lack of tissue perfusion (McCance & Huether, 2019). 

Tools

Septic shock is measured by the SOFA score and assessing different systems in relation to the severity of the organ failure. The quick SOFA criteria include a respiratory rate equal or greater than 22 per minutes, altered mentation and systolic blood pressure less than 100 mmHg. The standard SOFA scoring includes respiration, coagulation of platelets, bilirubin level of the liver, mean arterial pressure, glasgow coma scale score, creatinine level, and urine output.

Clinical manifestations

Clinical manifestations of septic shock usually include fever, chills, sweating, warm progressing to cool skin, respiratory distress, altered mentation, decreased urine output, hypotension, elevated liver enzymes, and decreased platelet counts (McCance & Huether, 2019).