Pathophysiology of the Febrile Reaction PDF

Pathophysiology of the febrile reaction Acclimatization to temperature variation Contents: I. Homeothermy II. Febrile reaction III. Acclimatization to heat and hyperthermia IV. Acclimatization to cold and hypothermia V. Local effects of cold HOMEOTHERMY Maintaining a con...

Pathophysiology of the febrile reaction Acclimatization to temperature variation Contents: I. Homeothermy II. Febrile reaction III. Acclimatization to heat and hyperthermia IV. Acclimatization to cold and hypothermia V. Local effects of cold HOMEOTHERMY Maintaining a constant internal body temperature (T) regardless of variations in ambient temperature and physical effort. Normal values: At rest: 37 ± 0.6°C Oral temperature ~ 36.7°C Rectal temperature > 0.5°C compared to oral temperature Axillary temperature < 0.5°C compared to oral temperature Severe/prolonged physical effort: 38°C Circadian variation rhythm (~ 0.6°C) Lower values in the morning (3 a.m) Higher values in the evening (6 p.m) TEMPERATURE It is the difference between heat production and heat loss. It varies with physical effort and extreme temperatures. It was measured by Carl Wunderlich in 1869. Temperature Regulation TEMPERATURE = THERMOGENESIS – THERMOLYSIS THERMOREGULATI ON Ø NERVOUS CONTROL Ø VASCULAR CONTROL Ø SKIN Ø BEHAVIOR Body Temperature Regulation Thermoregulation is ensured by a suitable nervous system that adjusts thermogenic and thermolytic processes according to the body's needs and the thermal variations of the surrounding environment. A well-protected human body can withstand temperature variations between –50°C and +50°C; individual cells can only tolerate these variations for a short time (internal temperature of +41°C). At –10°C, ice crystals form; at +45°C, proteins will coagulate. Body Temperature Regulation Muscles and viscera (the body's central core) produce most of the heat. They are protected against heat loss by subcutaneous cellular tissue (which transmits heat with an efficiency of 1/3 compared to other tissues) and skin. Heat transfer from the central core to the skin occurs through blood circulation. If this heat loss did not occur, the body would overheat by 10°C/h, and during exertion, by 20°C/h The thermoregulation centers are located in the hypothalamus (H) The anterior hypothalamus, through the preoptic area, coordinates heat loss. The posterior hypothalamus coordinates thermogenesis. There are receptors Central receptors in the anterior hypothalamus where there are temperature sensors in the form of neurons sensitive to cold and heat Extranevraxial Superficial receptors in the skin Deep receptors in the spinal cord, abdominal viscera, and around large veins The thermoregulation centers are located in the hypothalamus (H) Posterior hypothalamus: - The command center that integrates signals from these receptors - Controls reactions for heat production or loss The activity of these centers is influenced by: Stimuli coming from the periphery of the body Hormones such as thyroxine and corticosteroids Catecholamines Thermal variations of the blood that irrigates them The thermoregulation centers are located in the hypothalamus (H) Neurons in the anterior hypothalamus Are irrigated by a rich and permeable vascular network called the organum vasculosum laminae terminalis (OVLT), Whose endothelial cells, when exposed to endogenous pyrogens, release metabolites of arachidonic acid responsible for fever production. The mechanisms that adapt the body to temperature variations are: For temperature decrease: Vasodilation through sympathetic inhibition in the hypothalamus, Sweating, reduction of heat production. For temperature increase: Vasoconstriction through sympathetic stimulation in the hypothalamus; Piloerection through stimulation of the hair follicle erector muscles and increased heat production. Values above 41°C or below 34°C indicate a failure of thermoregulation. The thermostatic reference point of the thermoregulation center is set so that the body temperature is regulated within the range of 35.8°C to 37.4°C.  1. Age: Infants and young children have higher body temperatures, while older adults may have lower average temperatures. 2. Gender: Hormonal fluctuations, especially during menstrual cycles, can cause variations in body temperature in women. 3. Time of Day: Body temperature typically fluctuates throughout the day, being lower in the morning and higher in the late afternoon and FACTORS evening. 4. Physical Activity: Exercise increases body temperature due to THAT increased metabolic activity and heat production. 5. Environment: External temperatures and humidity levels can influence AFFECT body temperature regulation. BODY 6. Illness: Infections and inflammatory conditions can lead to fever, raising body temperature. TEMPERATU 7. Hormones: Hormonal changes, such as those during puberty, pregnancy, or due to thyroid function, can impact body temperature. RE 8. Diet: Food intake can influence metabolism and, consequently, body temperature. 9. Hydration: Dehydration can impair the body’s ability to regulate temperature, leading to overheating. 10.Sleep: Sleep patterns can affect the body's thermoregulation, with temperature often decreasing during sleep.  The fight against cold It is a chemical mechanism. Heat production is explained by: Shivering with the center in the dorsomedial region of the posterior hypothalamus. Shivering increases heat production by 6-7 times. THERMOGENE Activation of the sympathetic system, which SIS participates in chemical thermogenesis by increasing cellular metabolism. Adrenaline and noradrenaline are released when temperature drops, influencing cellular metabolism in such a way that ATP production decreases and heat production increases (explaining the weakness and fatigue that occur during fever). Activation of hypothalamic TRH secretion with an increase in thyroid hormones, a process that occurs more slowly over weeks.  - Peripheral vasoconstriction directs blood from the superficial territory (skin) to the deeper territory. - Contraction of the smooth muscle in the skin (goosebumps). - Increase in basal metabolism THERMOGENE (increases by 7% for a temperature SIS increase of 0.56°C). - Physical effort raises body temperature. In intense effort, 3/4 of the energy appears in the form of heat (Q), while the rest is in the form of work (L.M.) TERMOLYSIS It is a physical process. Most of the heat is lost through the skin. At the subcutaneous level, there are arteriovenous shunts that allow blood to flow directly from the arterial system to the venous system (they can be likened to a radiator in a heating system). When these anastomoses are closed under sympathetic stimulation, heat loss ceases. Blood flow is under sympathetic control Contraction of the piloerector muscles reduces the exchange surface. Heat loss occurs through: Conduction: 3% Radiation: 60% Convection: 15% Evaporation of water (insensible perspiration): 22% Heating and humidifying inspired air; urine and feces.  Conduction is the transfer of heat from one molecule to another. Blood carries heat from the central core to the surface of the skin. Radiation represents the transfer of heat through air or vacuum (60-70% of the body's heat), varying with the temperature of the environment (it must be lower than the body's temperature). - Heat from the sun is transported by radiation.  Convection is the transfer of heat through air currents. Convection removes the warm layer of air from the surface of the skin, replacing it with a cooler one. Sweating occurs at the sweat glands. It is controlled by the sympathetic nervous system through acetylcholine. Anticholinergic drugs (such as atropine) interfere with heat loss by stopping sweating. Temperature >37°C Thermoreceptors Hypothalamus nerves Relaxation of Increases the vascular the smooth Decrease secretion muscles in the Arterial in muscle of sweat skin vasodilatation in the activity glands skin and heat loss through radiation and conduction Transpiration and evaporation Temperature drop  Negative Blood feedback temperature Relaxation of the vascular Thermoreceptors smooth muscle Temperature Increa Temp. Returns >37°C Thermoreceptors Hypothalamus nerves sed drop to 37°C sweat secreti on Decrease m. activity Temperature 37°C) Increased catabolism of muscle proteins with the release of amino acids that are: Used for hepatic synthesis of acute phase reactants, leading to dysproteinemia and increased ESR Used as a substrate for gluconeogenesis, resulting in hyperglycemia Excreted in urine, leading to aminoaciduria Increased bone catabolism, resulting in hypercalciuria Alteration of hydro-electrolytic metabolism: Water loss is greater than Na+ loss (sweat is hypotonic), leading to hypertonic extracellular dehydration, which causes compensatory water exit from cells and intracellular dehydration responsible for the sensation of thirst, resulting in global extra- and intracellular dehydration. The role of fever in the body: INDICATOR OF HEALTH SIGN OF INFECTION SURVIVAL RATE STATUS INCREASES IN THOSE WITH FEBRILE REACTION  The beneficial role of increased temperature: Intensifies the inflammatory reaction and specific immune response: Increases the activity of helper T lymphocytes Enhances interferon synthesis Promotes B lymphocyte proliferation Stimulates antibody synthesis Weakens the membranes of viruses Reduces viral and bacterial proliferation Inhibits the development of microbial antigens (rhinoviruses develop at a temperature of 33°C in the tissues of the nasopharynx).  The harmful role of increased temperature Hydro-electrolytic imbalance due to sweating during the reduction phase Weight loss due to hypercatabolism and anorexia Decreased hematopoiesis Reduced digestive secretions Development of metabolic acidosis Immunodepression at very high temperatures Appearance of cerebral edema due to vasodilation and hypoxia, followed by headache Increased heart rate by 15 beats with a 1°C rise in temperature Occurrence of extrasystoles Increased cardiac output and tachypnea that can decompensate a preexisting illness. Types of fever: Intermittent fever: Where the temperature returns to normal at least once a day, with a significant difference between morning and evening temperatures. It occurs in pleurisy and septicemia. Remittent fever: Shows a difference of at least 20°C between morning and evening temperatures. It does not return to normal during the day. It occurs in tuberculosis, localized suppurations, bronchopneumonia, viral infections, and rheumatism.  Continuous fever: Shows variations of less than one degree. It occurs in pneumococcal pneumonia, typhoid fever, and paratyphoid fever. Recurrent fever: Presents episodes of temperature rises lasting a few days, followed by a few days of afebrility. It occurs in malignant granulomatosis and brucellosis. Irregular fever: Occurs in bronchiectasis, cholecystitis, prostatitis, extrapulmonary tuberculosis, and rickettsioses. ACCLIMATIZATION TO HIGH TEMPERATURES Consists of: Increased thermolysis through: Cutaneous vasodilation Initiation of sweating (the most effective method of thermolysis when atmospheric humidity is low) Decreased thermogenesis through: decreased tone of skeletal muscles Exceeding the adaptation mechanisms leads to a progressive increase in internal temperature, resulting in HYPERTHERMIA. Insulation - “Heat stroke” Refers to the condition resulting from prolonged exposure to direct sunlight, leading to overheating of the body. It can cause symptoms such as headache, dizziness, nausea, and even loss of consciousness. - is a severe disorder of thermoregulation in which the core temperature rises above 40°C, sweating is absent, and the state of consciousness is abolished. Insulation – “Heat stroke” In high-temperature environments, the mechanism of thermolysis is evaporation. Disruption of this mechanism leads to increased temperature and heatstroke. It has a high mortality rate and occurs more frequently in the elderly.  Insulation – “Heat stroke” Clinical manifestations include: fatigue, nausea, vomiting, dizziness, delirium, seizures, visual disturbances, coma, hot and dry skin, hypotension with vascular collapse, EKG changes, coagulopathy, electrolyte disturbances: hyponatremia, hypokalemia, signs of liver distress, tissue damage when the core temperature rises above 43°C Hyperthermia: DEFINITION: Pathological conditions characterized by a progressive increase in internal temperature, while the set point of thermoregulatory centers remains unchanged. CLASSIFICATION – CLINICAL FORMS: I. EXOGENOUS Hyperthermias - the increase in internal temperature is caused by exposure to an overheated environment. 1. Heat cramps 2. Heat exhaustion (thermal collapse) 3. Heat syncope 4. Heat shock II. ENDOGENOUS Hyperthermia - the increase in internal temperature occurs at a normal ambient temperature. III. MALIGNANT Hyperthermia Heat Cramps This is the mildest form. Cause: Intense exertion in an overheated environment (especially if it is also saturated with water vapor, e.g., in mines). Clinical Features: Painful spasms in the skeletal striated muscles, extrasystoles, tachycardia. Paraclinical Findings: Hypovolemia/hemoconcentration ± electrolyte imbalances.  Heat Exhaustion (Thermal Collapse) This is the most common form of hyperthermia in practice. Cause: Intense and prolonged physical exertion in an overheated environment, particularly in the elderly treated abruptly with diuretics and exposed to high temperatures (increased diuresis + intense sweating). Effect: Exhaustion of the cardiovascular system in response to adaptation to an overheated environment. Clinical Features: Dizziness, headache, fatigue, nausea and vomiting, muscle cramps, tachycardia, prostration, delirium. Paraclinical Findings: Hypotension and decreased cardiac output (CO) Hypovolemia/hemoconcentration ± electrolyte imbalances Internal temperature < 40°C, and sweating is present (skin is moist, in contrast to heat shock where the skin is dry).  Heat Syncope Description: Sudden episodes of loss of consciousness. Cause: Intense physical exertion or prolonged exposure to an overheated environment. Clinical Features: Dizziness, headache, fatigue, nausea and vomiting, muscle cramps, tachycardia, prostration, delirium. Paraclinical Findings: Hypotension (systolic blood pressure < 100 mmHg) and decreased cardiac output (CO) Hypovolemia/hemoconcentration ± electrolyte imbalances Internal temperature < 40°C, and sweating is present (skin is moist, in contrast to heat shock where the skin is dry). Treatment: Placement in a cool area in a supine position and parenteral hydration and electrolyte rebalancing, ± interventions for body cooling, possible hospitalization.  This is the most severe form of hyperthermia. Description: Internal temperature > 40°C + dysfunction of the central nervous system with delirium, seizures, coma + absence of sweating (the skin is initially hot and dry but becomes cold as vascular collapse occurs). Clinical Forms Related to Etiological Factors: Classical Heat Shock and Exertional Heat Shock Heat a) Determining Factors: Prolonged exposure to an overheated environment = classical heat Shock shock. Exposure to exhausting physical exertion in an overheated environment = exertional heat shock. b) Contributing Factors: Classical Heat Shock: Occurs in immobilized elderly individuals, those living alone, unable to hydrate adequately, and individuals with comorbidities (diabetes, obesity, chronic alcoholism with liver disease, chronic heart or kidney failure, mental illnesses). Exertional Heat Shock: Occurs in athletes, soldiers, and workers subjected to extreme physical exertion.  Pathogenesis: Multifactorial, consisting of the association of: Direct harmful effects of heat on the body’s cells. Release of endogenous pyrogens, initially protective against cellular damage, but leading to an exaggerated acute phase reaction. Acute thermoregulatory failure. Functional Changes: a) Hemodynamic Changes, occurring in two stages: Heat Initial Stages: Cutaneous vasodilation → decreased peripheral vascular resistance (PVR) → increased cardiac output (CO). Shock Normal blood pressure or divergent hypertension. Advanced Stages: Decreased CO and blood pressure. b) Acute Circulatory Failure (Shock) with hypoperfusion and tissue ischemia responsible for: MULTI-ORGAN DYSFUNCTION SYNDROME, organ failure with vital risk affecting 2 or more organs (e.g., acute respiratory failure, acute renal failure). Disseminated intravascular coagulation (DIC). Rhabdomyolysis.  Clinical and Paraclinical Changes: Clinical Features: Tachycardia (initially a strong pulse that then decreases). Dizziness, severe fatigue. Nausea, vomiting. Confusion, delirium, visual disturbances, seizures, coma. Paraclinical Findings: Heat PaCO2 < 20 mmHg (due to hyperventilation). Electrolyte imbalances: hyponatremia, hypocalcemia, Shock hyperkalemia, hyperphosphatemia (in cases of rhabdomyolysis with myoglobinuria). Coagulation disorders. Increased blood urea. ECG changes due to cardiac involvement. Signs of liver damage. Positive Diagnosis: Hyperthermia > 40°C + CNS dysfunction/coma + hot and dry skin. Malignant Hyperthermia Definition: An inherited disorder with autosomal dominant/recessive transmission characterized by a rapid increase in internal temperature to 39-40°C, under conditions of normal ambient temperature. Cause: Excessive thermogenesis triggered by: Inhalational anesthetics (halothane, ether) Muscle relaxants (succinylcholine) Malignant Hyperthermia Pathogenesis: Explosive release of Ca2+ ions from the sarcoplasmic reticulum (SR) of striated muscle cells that have a genetic defect in calcium storage (mutation of the ryanodine receptor at the SR level). The sudden increase in intracellular Ca2+ concentration leads to: Muscle contractions → rigidity Activation of the calcium pump (ATPase) at the sarcoplasmic reticulum, resulting in increased ATP consumption. Hypermetabolic state with: i) Activation of anaerobic glycolysis with hyperproduction of lactate and heat release, and ii) Increased mitochondrial oxygen consumption. Cellular damage leads to hyperkalemia with a risk of ventricular arrhythmias. ACCLIMATIZATION TO LOW TEMPERATURES It consists of: Decreased thermolysis through cutaneous vasoconstriction. Increased thermogenesis through: Increased tone of skeletal muscles → shivering. Increased rate of biological oxidation in the liver (catecholamines, thyroxine). → Sympathetic stimulation triggers circulatory changes: increased heart rate and blood pressure. → Stimulation of the cerebral cortex triggers behavioral changes (posture, seeking a heated environment, and clothing). Exceeding the adaptation mechanisms leads to a progressive decrease in internal temperature, resulting in HYPOTHERMIA HYPOTHERMIA DEFINITION: A decrease in the body's core temperature to ≤ 35°C. CLASSIFICATION: According to severity, hypothermia can be: Mild: < 35°C Moderate: 30-34°C Severe: < 30°C RISK FACTORS: Extreme ages (elderly individuals living alone in unheated homes during winter) Homeless individuals in winter Malnutrition Chronic alcoholism Mental illnesses Use of sedative medication HYPOTHERMIA PATHOGENESIS: → Excessive heat loss (increased thermolysis) caused by: Accidental exposure to a cold environment: e.g., immersion hypothermia Intensified blood circulation at the skin level: e.g., burns → Inadequate heat production (decreased thermogenesis) caused by: Reduced metabolic rate in malnutrition, hypothyroidism, liver failure, hypoglycemia – leading to endogenous hypothermia. Impaired thermoregulation control due to brain injuries, septic or toxic states: uremia, diabetic ketoacidosis inducing hypothalamic dysfunction. Medication-induced (phenothiazines, barbiturates, opioids, benzodiazepines). CLASSIFICATION – CLINICAL FORMS: 1.Immersion Hypothermia: Causes: Occurs in: Individuals accidentally immersed in cold water – swimmers during prolonged exposure. Pathogenesis: Includes 3 evolutionary phases: a) Excitation Phase: Internal temperature drops to 35 °C. → Increased thermogenesis through voluntary movements and shivering. → Decreased thermolysis through peripheral vasoconstriction. b) Inhibition Phase: Internal temperature drops between 34 – 30 °C. → Inhibition of central nervous system activity. → Reduction of voluntary movements. → Shivering is replaced by muscle rigidity. c) Critical Phase: Internal temperature drops below 30 °C. → Ventricular arrhythmias with a risk of cardiac arrest. 2.Endogenous Hypothermia Definition: Hypothermia that occurs at a normal ambient temperature due to: Decreased thermogenesis (see above), which may be associated with Decreased capacity to conserve heat. Pathogenesis: Acute thermoregulation failure caused by the absence of shivering. Contributing Factors: Presence of comorbidities (hypothyroidism, hypopituitarism, diabetes, congestive heart failure). Presence of conditions that alter thermoregulation control (brain injuries, septic or toxic states: uremia, diabetic ketoacidosis inducing hypothalamic dysfunction) LOCAL EFFECTS OF COLD: 1. DIRECT Effects: Affect cells and extracellular fluid. Consist of: Crystallization of extracellular water with physical displacement of cells → increased tissue damage in dense tissues and reduced damage in loose tissues. Appearance of areas with increased ionic concentration → leading to irreversible denaturation of cell membranes. 2. INDIRECT Effects: Affect blood vessels. Consist of: Capillary injuries affecting microcirculation → leading to cellular ischemia and hypoxia. Release of vasoactive mediators (histamine): Hyperpermeability of capillaries → resulting in the outflow of water into the interstitium. Favoring the adhesion/aggregation of platelets due to hemoconcentration → leading to irreversible occlusion of small vessels and extensive tissue necrosis.