NURS3015 Health Variations 4: Sepsis Part 1

SIRS (Systemic Inflammatory Response Syndrome)

• SIRS is a systemic inflammatory response to various insults, including infection, ischemia, infarction, and injury
• Characterized by generalized inflammation in organs remote from the initial insult
• SIRS criteria:
  • Tachycardia (heart rate >90 beats/min)
  • Tachypnoea (respiratory rate >20 breaths/min)
  • Fever or hypothermia (temperature >38°C or <36°C)
  • Leukocytosis (white blood cell count >12,000/mm³ or <4,000/mm³)

Sepsis

• Life-threatening organ dysfunction caused by a dysregulated host response to infection
• Sepsis definition: a dysregulated host response to infection that causes life-threatening organ dysfunction
• Risk factors of sepsis:
  • Genetic predisposition
  • Large microbiological load
  • High virulence of the organism
  • Delay in source control (surgical or antimicrobial)
  • Resistance of the organism to treatment
  • Patient factors (immune status, nutrition, frailty)

Sepsis Causes

• Infection is the primary cause of sepsis
• Factors contributing to sepsis:
  • Delay in source control
  • Resistance to treatment
  • Patient factors (immune status, nutrition, frailty)

Sepsis Pathophysiology

• Pathogens enter the host's body, releasing toxic substances such as endotoxin, which damages tissues and endothelial cells, and activates tissue factor.
• The inflammatory cascade is triggered, stimulating mast cells to release histamines, chemotactic agents, leukotrienes, and prostaglandins.
• The coagulation pathway is activated, leading to the formation of plasminogen activator inhibitor and plasmin, which causes disseminated intravascular coagulopathy (alternate bleeding and clotting).
• Microvascular occlusion occurs due to clots, leading to tissue hypoxia and organ dysfunction.

Inflammatory Response

• Inflammatory mediators are released, triggering vasodilation and increased vascular permeability.
• Leaky capillaries allow fluid to accumulate in the interstitial space, leading to edema and organ dysfunction.
• The immune system is triggered, attracting more white blood cells (WBCs), including monocytes and neutrophils, which undergo phagocytosis.
• Proteases are released, further exacerbating the inflammatory response.

Definitions and Criteria for Sepsis and Septic Shock

• Sepsis is a life-threatening condition that arises from the body's response to an infection
• Septic shock is a subset of sepsis in which circulatory and cellular metabolism are impaired, leading to organ dysfunction

Clinical Manifestations

Cardiovascular

• Vasodilation (both arteries and veins) causes profound hypotension
• Myocardial depression occurs

Pulmonary

• Acute Respiratory Distress Syndrome (ARDS)
• Non-cardiogenic pulmonary edema
• Tachypnea (rapid breathing rate)

Renal

• Acute Kidney Injury (AKI)

Hematological

• Anemia, neutropenia, and thrombocytopenia
• Disseminated Intravascular Coagulopathy (DIC)

Gastrointestinal

• Hypoxic hepatitis
• Sepsis-induced cholestasis
• Hyperammonemia, causing hepatic encephalopathy

Endocrine

• Hyperglycemia (high blood sugar)

Neurologic

• No specific manifestations mentioned

Sepsis Management and Post-Sepsis Syndrome

• Complications and post-sepsis management are crucial aspects of sepsis care.
• Understanding the pathophysiology of post-sepsis syndrome is essential to identify therapeutic opportunities.

Sepsis References

• ABC of Sepsis by Daniels and Nutbeam (2010) provides a comprehensive overview of sepsis.
• Understanding Pathophysiology (3e, Australian and New Zealand ed., 2019) by Craft, Gordon, Huether, McCance, and Rote is a valuable resource for understanding sepsis pathophysiology.
• Medical-Surgical Nursing (7th ed., 2020) by Linton and Matteson provides insight into sepsis management in a medical-surgical setting.
• Harrison's Principles of Internal Medicine (20th ed., 2018) and Davidson's Principles and Practice of Medicine (23rd ed., 2018) are authoritative sources for sepsis diagnosis and management.
• The Medical Clinics of North America (104.4, 2020) provides an overview of sepsis diagnosis, pathophysiology, and clinical decision-making.

Post-Sepsis Syndrome Research

• The LANCET EBioMedicine (2020) article by Van der Slikke, Hancock, and Bouma explores the pathophysiology of post-sepsis syndrome to identify therapeutic opportunities.

Shock

• Shock is a clinical condition characterized by organ dysfunction resulting from an imbalance between cellular oxygen supply and demand.

Pathophysiology of Shock

• Impaired oxygen delivery can lead to anaerobic metabolism, disrupting the cell's ability to maintain osmotic, ionic, and intracellular pH homeostasis.
• This can result in cell death and organ failure if left untreated.

Classification of Shock

• Types of shock:
  • Hypovolemic shock: caused by absolute or relative hypovolemia (e.g., hemorrhage, burns, GI loss).
  • Cardiogenic shock: caused by pump failure (e.g., MI, myocarditis).
  • Obstructive shock: caused by obstruction of blood flow (e.g., massive pulmonary embolism, tension pneumothorax).
  • Distributive shock:
    • Septic shock: caused by infection.
    • Anaphylactic shock: caused by allergic reactions.
    • Neurogenic shock: caused by damage to the spinal cord, leading to loss of sympathetic tone and uncontrolled vasodilation.

Specific Types of Shock

• Hypovolemic shock: characterized by decreased blood volume, which can be absolute (e.g., hemorrhage) or relative (e.g., vasodilation).
• Cardiogenic shock: characterized by decreased cardiac output due to pump failure.
• Obstructive shock: characterized by decreased cardiac output due to right ventricular overload, impairing left ventricular function.
• Anaphylactic shock: characterized by vasodilation, decreased cardiac output, and hypotension.
• Neurogenic shock: characterized by uncontrolled vasodilation, hypotension, and decreased cardiac output due to autonomic blockade.

Stages of Shock

• Initial stage: anaerobic metabolism and lactic acidosis occur due to decreased oxygen delivery and increased carbon dioxide retention.
• Compensatory (reversible) stage: neurochemical responses are triggered, and clinical signs and symptoms of shock are present.
• Progressive stage: the body's attempt to return to homeostasis fails, leading to cellular and tissue injury.
• Refractory stage: the final stage of shock, which is irreversible, and cellular damage leads to necrosis.

Initial Stage

• Cardiac output stimulates the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS).
• Compensatory mechanisms are activated in response to shock.

Compensatory Stage

• Mechanisms begin to fail, leading to metabolic and circulatory derangements.
• Inflammatory and immune responses become fully activated.
• Signs of dysfunction in one or more organs may become apparent.

Progressive Stage

• Cellular and tissue injury are severe, making the patient's life unsustainable even if metabolic, circulatory, and inflammatory derangements are corrected.
• Full-blown multi-organ dysfunction syndrome (MODS) may be evident.

Refractory Stage

• No response to therapy, and death is likely.
• Loss of autoregulation, capillary permeability changes, and fluid shifts occur.
• Venous return and cardiac output are almost negligible, leading to reduced cardiac output and impaired tissue perfusion.

The Endocrine System

• The endocrine system involves a feedback system of the hypothalamus, pituitary, and target glands.

Alterations of Pituitary Function

• Disorders of pituitary secretion include:
  • Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
  • Diabetes insipidus (related to an insufficiency of antidiuretic hormone)

Posterior Pituitary Disorders

• SIADH:
  • High levels of antidiuretic hormone without normal physiological stimuli
  • Symptoms: water intoxication, hyponatremia (low serum sodium), and increased total body water
• Diabetes insipidus:
  • Two forms: neurogenic and nephrogenic
  • Neurogenic form: caused by the absence of antidiuretic hormone
  • Nephrogenic form: caused by inadequate response of the renal tubules to antidiuretic hormone
  • Symptoms: polyuria (excretion of large volumes of dilute urine), polydipsia (thirst mechanism stimulated)

Alterations of Adrenal Function

• Hypoadrenalism:
  • Primary (Addison's): adrenal insufficiency
  • Secondary: impaired secretion of cortisol and aldosterone
  • Symptoms: hypoglycemia, hyperkalemia
  • Acute Adrenal Crisis (Addisonian Crisis): sudden marked decrease in available adrenal hormones, leading to hypotension, tachycardia, dehydration, confusion, hyponatremia, hyperkalemia, hypercalcemia, and hypoglycemia

Adrenal Hypersecretion (Cushing Syndrome)

• Hypersecretion of the adrenal cortex, leading to hypercortisolism
• Causes: endogenous (e.g., pituitary tumors) and exogenous (e.g., prolonged administration of high doses of corticosteroids)
• Hallmark findings: truncal obesity, protein wasting, facial fullness, purple striae on the abdomen, breasts, buttocks, or thighs, osteoporosis, hypokalemia
• Management: drug therapy, radiation, and surgery

Alterations of Thyroid Function

• Hyperthyroidism (Thyrotoxicosis):

  • Abnormally increased synthesis and secretion of thyroid hormones
  • Causes: Graves' disease (an autoimmune condition)
  • Clinical features: hypermetabolic state
  • Management: antithyroid medication
  • Complication: thyrotoxic crisis (thyroid storm)

• Hypothyroidism:

  • Deficient production of thyroid hormone by the thyroid gland
  • Clinical features: hypothyroid state
  • Management: supplemental thyroxine

Diabetic Ketoacidosis (DKA)

• DKA occurs when ketone bodies accumulate due to the breakdown of fats for energy associated with inadequate insulin.

Pathophysiology of DKA

• Insulin deficiency or insulin demand leads to glucose not entering cells, stimulating lipolysis and releasing free fatty acids.
• Free fatty acids are converted into ketone bodies (e.g., acetoacetate), which release H+ protons and enter the bloodstream, causing acidosis.
• The body responds to the cellular need for fuel by converting glycogen to glucose and manufacturing additional glucose, making the situation worse.
• As glycogen stores are depleted, the body begins to burn fat and protein for energy.

Clinical Features of DKA

• Early signs and symptoms: anorexia, headache, fatigue, polydipsia, polyuria, and polyphagia
• Late signs: dehydration, weakness, lethargy, abdominal pain, nausea, vomiting, fruity breath, increased respiratory rate, tachycardia, blurred vision, and hypothermia
• If untreated, it can lead to air hunger, coma, and death

Management of DKA

• Main goals: correction of dehydration, electrolyte imbalance, and acidosis
• Dehydration: replace fluids with normal saline to aid the kidneys in eliminating excess glucose
• Electrolyte imbalance: treat hyperkalemia with fluid replacement and insulin administration; monitor and correct sodium, phosphate, magnesium, and calcium levels
• Acidosis: treat with slow intravenous infusion of insulin; add dextrose solution when serum glucose level reaches 25-30 mmol/L

Multi-Organ Dysfunction Syndrome (MODS)

• MODS is a progressive dysfunction of two or more organ systems resulting from an uncontrolled inflammatory response to severe illness or injury.
• Organ dysfunction can progress to organ failure and death.
• MODS is defined by the simultaneous presence of physiologic dysfunction and/or failure of two or more organs.

Characteristics of MODS

• Risk of death associated with MODS is 54% when two organ systems fail and increases to 100% when five organ systems fail.
• Organ failure that persists more than 24 hours.
• Mortality risk increases with the accrual of failing organs.
• The prognosis worsens with increased duration of organ failure.

Causes of MODS

• Sepsis and septic shock (most common).
• Any type of shock.
• Severe inflammatory conditions such as pancreatitis and trauma.
• Other less common causes include:
  • Toxins from envenomation (snake bite).
  • Myoglobin in rhabdomyolysis.
  • Profound physical injury to cells (e.g., nuclear radiation, heat exposure).

Types of MODS

• Primary MODS: direct injury to an organ.
• Secondary MODS: consequence of widespread systemic inflammation.

Pathogenesis of MODS

• Insult/injury to organ triggers a systemic response.
• Systemic inflammatory response syndrome (SIRS) leads to an overwhelming insult.
• Excessive inflammatory response leads to endothelial and organ damage, hypermetabolism, and impaired tissue perfusion.

Pathophysiology of MODS

• Excessive production of inflammatory cells and biochemical mediators.
• Vasodilation, capillary permeability, and impaired microvascular circulation.
• Impaired tissue perfusion, leading to oxygen supply to cells.
• Anaerobic cellular changes.

Multi Organ Dysfunction Syndrome (MODS)

• MODS is a clinical manifestation that involves multiple organ dysfunction.

Clinical Manifestations of MODS

• MODS can cause various clinical manifestations, including acid-base disturbances.
• Choudhary et al. (2021) discussed Biopharmaceutics and Pharmacokinetics Considerations in relation to MODS.

SOFA Score and Marshall MODS Score

• The SOFA score and Marshall MODS score are used to assess the severity of MODS.

Acid-Base Disturbances

• Acid-base disturbances can occur in MODS, including:
  • Metabolic acidosis
  • Respiratory acidosis
  • Metabolic alkalosis
  • Respiratory alkalosis
• The pH, PCO2, and HCO3 levels can be affected in acid-base disturbances.

Key References

• Brown, D., Edwards, H., Buckley, T., Aitkin, R. (2020) - Lewis's Medical Surgical Nursing (5th Ed.)
• Craft, J.A. et al. (2023) - Understanding Pathophysiology (4th edition, Australia and New Zealand edition)
• Ladd, M.R. & Vaught, A.J. (2020) - Multiple Organ Dysfunction and Failure (in Current Surgical Therapy, Thirteenth Edition)
• Linton, A.D. (2020) - Medical-Surgical Nursing (7th edition)

Management of Multi-Organ Dysfunction Syndrome (MODS)

• The management of MODS involves four key aspects: prevention and treatment of infection, maintenance of tissue oxygenation, nutritional and metabolic support, and appropriate support of individual failing organs.
• Prevention and treatment of infection is a crucial aspect of MODS management.
• Maintenance of tissue oxygenation is essential to prevent further organ damage.
• Nutritional and metabolic support is necessary to maintain the body's energy needs.
• Support of individual failing organs is critical to prevent further deterioration.

Heart Failure

• Heart failure is a complex clinical syndrome characterized by an underlying structural abnormality or cardiac dysfunction that impairs the ability of the left ventricle to fill with or eject blood, particularly during physical activity.
• It is the inability of the heart to maintain an output, at rest or during stress, necessary for the metabolic needs of the body.

Types of Heart Failure

• Diastolic failure/preserved ejection fraction (HFpEF)
• Systolic failure/reduced ejection fraction (HFrEF)
• Left heart failure
• Right heart failure

Physiological Terminologies

• End Diastolic Volume (EDV): the amount of blood returning to the heart and filling the ventricle
• End Systolic Volume (ESV): the volume of blood that remains in the ventricle at the end of systole
• Stroke Volume (SV): the volume of blood pumped out of the heart by the left ventricle with each beat (typically 70 mL/beat)
• Preload: the amount of blood at the end of diastole prior to contraction, influenced by the factors just prior to ventricular contraction and determined by the end-diastolic volume (and the associated end-diastolic pressure)
• Contractility: the ability of the myocardial fibers to shorten or contract when loaded, determining the force of contraction
• Afterload: the force which the ventricle has to overcome to eject blood, such as Systemic Vascular Resistance (SVR)

Cardiac Output and Ejection Fraction

• Cardiac Output (CO): the amount of blood pumped around the body in one minute (e.g. 4.9 L/minute for a healthy person weighing 70 kg)
• Ejection Fraction (EF): the percentage of blood the left ventricle pumps out with each contraction (normal range: 55-70%)

Frank-Starling Law of the Heart

• The Frank-Starling law states that an increase in stretch (preload) increases cardiac output
• The law is altered in cases of reduced contractility, resulting in decreased stretch and cardiac output

Heart Failure

• Heart failure is a complex clinical syndrome characterized by an underlying structural abnormality or cardiac dysfunction that impairs the ability of the left ventricle to fill with or eject blood, particularly during physical activity.
• Congestive Cardiac Failure (CCF) is the inability of the heart to maintain an output, at rest or during stress, necessary for the metabolic needs of the body.

Types of Heart Failure

• Systolic failure/reduced ejection fraction (HFrEF)/left heart failure
• Diastolic failure/preserved ejection fraction failure (HFpEF)/right heart failure

Risk Factors for Heart Failure

• Coronary artery disease
• Myocardial Infarction
• Cardiomyopathy
• Hypertension
• Chronic obstructive pulmonary disorder (COPD)
• Pulmonary hypertension
• Anemia
• Disease of the heart valves
• Fluid volume overload

Pathophysiology of Heart Failure

• Acute compensatory mechanisms:
  • Stimulates baroreceptors and chemoreceptors in the carotid sinus and aortic sinus
  • Stimulates cardio-regulatory and vasomotor centers in the medulla oblongata
  • Stimulates the Sympathetic Nervous System (SNS) and Renin Angiotensin Aldosterone System (RAAS)

Renin Angiotensin Aldosterone System (RAAS)

• Stimulates Juxta Glomerular cells in the kidneys to produce Renin
• Renin converts Angiotensinogen to Angiotensin I
• Angiotensin Converting Enzyme (ACE) converts Angiotensin I to Angiotensin II
• Angiotensin II:
  • Causes direct vasoconstriction of blood vessels
  • Stimulates the adrenal cortex to produce aldosterone
  • Stimulates the pituitary gland to produce Anti-Diuretic Hormone (ADH)

Ventricular Remodeling

• Progression of heart failure leads to ventricular remodeling

Pulmonary System

• The pulmonary system's structure and function are crucial for understanding respiratory health and diseases.

Lung Function

• Elastic recoil: the tendency of the lungs to return to their resting state after inspiration, similar to an elastic band springing back into place after being stretched.
• Compliance: the measure of lung and chest wall distensibility (stretchiness), defined as volume change per unit of pressure change.
• Airway resistance: determined by the length, radius, and cross-sectional area of the airways, as well as the density, viscosity, and velocity of the gas (Poiseuille's law).

Ventilation and Respiration

• Ventilation: the mechanical movement of gas or air into and out of the lungs.
• Tidal volume: the amount of gas inspired or exhaled with each breath.
• Partial pressure: directly proportional to the percentage of a gas in a mixture of gases.

Oxygen Hemoglobin Dissociation Curve

• The curve shows the relationship between hemoglobin saturation and oxygen partial pressure.

V/Q Ratio and Mismatch

• V/Q ratio: the ratio of ventilation to perfusion in the lungs, which affects gas exchange.

References

• Various sources cited, including Meyring-Wösten et al. (2016), Craft et al. (2019), Linton et al. (2020), and Lewis et al. (2017).

Asthma Definition

• Asthma is a chronic inflammatory disorder of the airways characterized by hyperresponsiveness and bronchospasm leading to airway limitation (obstruction).
• In clinical practice, asthma is defined by the presence of both excessive variation in lung function and respiratory symptoms.

Clinical Practice Definition

• Excessive variation in lung function: variation in expiratory airflow that is greater than that seen in healthy people.
• Respiratory symptoms: wheeze, shortness of breath, cough, chest tightness that vary over time and may be present or absent at any point in time.

Risk Factors and Triggers

• Allergen triggers an immune response, leading to a Type 1 Hypersensitivity response.

Pathophysiology

• Dendritic cells process and present allergens to CD4 TH2 helper cells.
• CD4 TH2 helper cells release Interleukin 4, 5, and 13, which stimulate the activation of B cells and plasma cells.
• Plasma cells produce Immunoglobulin E (IgE), which binds to mast cells and basophils.
• Cross-linking of IgE on mast cells triggers degranulation, releasing Histamines, Leukotrienes, and Prostaglandins.
• These chemical mediators cause bronchospasm, increased mucus production, and inflammation, leading to asthma symptoms.