Control Of Body Temperature &disorders Of Its

CONTROL OF BODY TEMPERATURE & DISORDERS OF TEMPERATURE REGULATION Dr G.Gireesh, PG Resident, Dept .of Gen.Medicine Sincere thanks Dr sujit,Dramit,Dr salaah.

Normal Body Temperatures Core Temperature • The temperature of the deep tissues of the body • remains constant all the time, within ±1°F(±0.6°C) • Altered when a person develops a febrile illness

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Skin Temperature. • The skin temperature, rises and falls with the temperature of the surroundings. Normal Core Temperature. • The average normal core temperature is generally considered to be between 98.0° and 98.6°F when measured orally and about 1°F higher when measured rectally. • During strenuous exercise, the temperature can rise temporarily to as high as 101° to 104°F. • When the body is exposed to extreme cold, the temperature can often fall to values below 96°F.

• Normal mean oral temperature is 36.8° ± 0.4°C (98.2° ± 0.7°F) With low levels at 6 A.M. & higher levels at 4–6 P.M. The maximum normal oral temperature is 37.2°C (98.9°F) at 6 A.M. and 37.7°C (99.9°F) at 4 P.M. • Fever is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point (e.g., from 37°C to 39°C). • Fever : temperature of >37.2°C (>98.9°F) am or a temperature of >37.7°C (>99.9°F) pm

Heat Production (1) Basal rate of metabolism of all the cells of the body (2) Extra rate of metabolism caused by muscle activity (3) Extra metabolism caused by the effect of thyroxine and, to a less extent, other hormones, such as growth hormone and testosterone on the cells (4) Extra metabolism caused by the effect of epinephrine, nor-epinephrine, and sympathetic stimulation on the cells (5) Extra metabolism caused by increased chemical activity in cells (6) Thermogenic effect of food.

Heat Loss

Sweating and its regulation • Stimulation of the anterior hypothalamus-preoptic area in the brain either electrically or by excess heat causes sweating. • Ant. hypothalamus Spinal cord aut.path symp.fl

Skin Mechanism of sweating and the role of aldosterone..

Rate of flow of sweat and its concentration depend on the amount of stimulation of the sweat gland. Unacclimatised persons tend to lose more salts in their sweat. Later the action of the aldosterone decreases the amount of the salt.

Regulation of Body Temperature—Role of the Hypothalamus • It occurs by nervous feedback mechanisms • These operate through temperature-regulating centers located in the hypothalamus. • Temperature detectors play a major role • Preoptic and anterior hypothalamic nuclei of the hypothalamus are the centres for this action • The anterior hypothalamic-preoptic area Heat sensitive neurons Fire when temp ses

Cold sensitive neurons Fire when temp ses

Posterior Hypothalamus Integrates the Central and Peripheral Temperature Sensory Signals Body response to cold • 1. Skin vasoconstriction throughout the body. • 2. Piloerection. • 3. Increase in thermogenesis (heat production). Dorsomedial portion of the posterior hypothalamus near the wall of the third ventricle is an area called the primary motor center for shivering. During maximum shivering, body heat production can rise to four to five times normal.

Concept of a “Set-Point” for Temperature Control Critical body core temperature of about 37.1°C (98.8 0F), This crucial temperature level is called the “set-point” of the temperature control mechanism. That is, all the temperature control mechanisms continually attempt to bring the body temperature back to this set-point level. Skin Temperature can slightly alter the Set-Point for Core Temperature Control

FACTORS PREDISPOSING TO COLD INJURY INDIVIDUAL FACTORS Inadequate clothing and shelter Lean and low body fat Low physical fitness Advanced age Young children Black men and women MEDICATIONS Alcohol Anesthetics Antidepressants Antithyroid agents Sedatives and narcotics

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HEALTH CONDITIONS Burns Diabetes Hypoglycemia Neurologic lesions Dementia Hypoadrenalism, Hypopituitarism, Hypothyroidism Raynaud's phenomenon Sickle cell trait Trauma Spinal cord injury

ENVIRONMENTAL FACTORS • • • • • • • •

Cold temperatures High air motion Rain and immersion Skin contact with metal and fuels Repeated cold exposure Physical fatigue Immobility High-altitude and low–oxygen tension environments

HYPOTHERMIA: STAGES AND ASSOCIATED CLINICAL MANIFESTATIONS

FROST BITE Peripheral cold injuries include both freezing and nonfreezing injuries to tissue. PREDISPOSING FACTORS metal or volatile solutions. constrictive clothing or boots, immobility, vasoconstrictive medications. Frostbite occurs when the tissue temperature drops below 0°C. Ice crystal formation subsequently distorts and destroys the cellular architecture. Once the vascular endothelium is damaged, stasis progresses rapidly to microvascular thrombosis.

After the tissue thaws, there is progressive dermal ischemia. Finally, thrombosis, ischemia, and superficial necrosis appear. The development of mummification and demarcation may take weeks to months. CLINICAL PRESENTATION The initial presentation can be deceptively benign. The symptoms include a sensory deficiency affecting light touch, pain, and temperature perception. The acral areas and distal extremities are the most common insensate areas.

• Deep frostbitten tissue appears waxy, mottled, yellow, or violaceous-white. • Presenting signs include warmth or sensation with normal color. • Injury is superficial if the subcutaneous tissue is pliable or dermis can be rolled over boney prominences. • Can be classified as superficial or deep. Superficial does not entail tissue loss, retrospectively graded like a burn. • First-degree frostbite causes only anesthesia and erythema. • Second degree: superficial vesiculation surrounded by edema and erythema • Third-degree:hemorrhagic vesicles reflect a serious injury to the microvasculature and indicate. • Fourth-degree injuries damage subcuticular, muscular, and osseous tissues.

FEVER AND HYPERTHERMIA

• Elevation of the Hypothalamic Set Point by Cytokines • During fever, PGE2 are elevated in hypothalamic tissue and the third cerebral ventricle. The concentrations of PGE2 are highest near the circumventricular vascular organs (organum vasculosum of lamina terminalis)— networks of enlarged capillaries surrounding the hypothalamic regulatory centers. • Pyrogenic cytokines such as IL-1, IL-6, and TNF are released from the cells and enter the systemic circulation. Although the systemic effects of these circulating cytokines lead to fever by inducing the synthesis of PGE2, they also induce PGE2 in peripheral tissues.causing the nonspecific myalgias and arthralgias that often accompany fever • it is the elevation of PGE2 in the brain that starts the process of raising the hypothalamic set point for core temperature.

• As hypothalamic set point ,neurons in the vasomotor center are activated and vasoconstriction commences, due to which the individual first notices vasoconstriction in the hands and feet. • Shunting of blood away from the periphery to the internal organs essentially decreases heat loss from the skin, and the person feels cold. For most fevers, body temperature increases by 1°–2°C. • Shivering, which increases heat production from the muscles, may begin at this time,but shivering is not required if heat conservation mechanisms raise blood temperature sufficiently. Nonshivering heat production from the liver also contributes to increasing core temperature

• The mechanisms for heat conservation continue until the temperature of the blood bathing the hypothalamic neurons matches the new thermostat setting. Once that point is reached, the hypothalamus maintains the temperature at the febrile level by the same mechanisms of heat balance that function in the afebrile state. • When the hypothalamic set point is again reset downward (in response to either a reduction in the concentration of pyrogens or the use of antipyretics), the processes of heat loss through vasodilation and sweating are initiated. Loss of heat by sweating and vasodilation continues until the blood temperature at the hypothalamic level matches the lower setting

• Hyperpyrexia-A fever of >41.5°C (>106.7°F) extraordinarily high fever Develops in patients with severe infections, commonly occurs in patients with CNS hemorrhages • Hypothalamic fever - elevated temperature caused by abnormal hypothalamic function due to local trauma, hemorrhage, tumor, or intrinsic hypothalamic malfunction. • Hyperthermia is characterized by an uncontrolled increase in body temperature that exceeds the body's ability to lose heat. Results from1.Exogenous heat exposure 2.Endogenous heat production • Dangerous as compensatory mechanisms can’t cope up.

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CAUSES OF HYPERTHERMIA SYNDROMES Heat Stroke : Exertional: Exercise in higher than normal in heat and/or humidity Nonexertional: Anticholinergics, including antihistamines; antiparkinsonian drugs; diuretics; phenothiazines Drug-Induced Hyperthermia Amphetamines, cocaine, phencyclidine (PCP), methylenedioxymethamphetamine (MDMA), salicylates, lithium, anticholinergics, sympathomimetics Neuroleptic Malignant Syndrome Phenothiazines; butyrophenones, including haloperidol, bromperidol; fluoxetine; loxapine; metoclopramide; Serotonin Syndrome Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants Malignant Hyperthermia Inhalational anesthetics, succinylcholine Endocrinopathy Thyrotoxicosis, pheochromocytoma Central Nervous System Damage Cerebral hemorrhage, status epilepticus, hypothalamic injury

• Heat stroke can be1.exertional 2.nonexertional. • Exertional heat stroke typically occurs in individuals exercising at elevated ambient temperatures and/or humidities. In a dry environment and at maximal efficiency, sweating can dissipate ~600 kcal/h, requiring the production of >1 L of sweat in healthy individuals, dehydration or the use of medications (e.g., overthe-counter antihistamines with anticholinergic side effects) may precipitate exertional heat stroke. • Non-exertional heat stroke typically occurs in either very young or elderly individuals, particularly during heat waves

• Drug-induced hyperthermiacommon with the increased use of prescription psychotropic drugs and illicit drugs. Drug-induced hyperthermia may be caused by (MAOIs),TCA’S, amphetamines, phencyclidine (PCP), LSD, methylenedioxymethamphetamine • Malignant hyperthermia Fatal Condn.,occurs in individuals with an inherited abnormality of skeletal-muscle sarcoplasmic reticulum that causes a rapid increase in intracellular calcium levels in response to halothane and other inhalational anesthetics or to succinylcholine. Elevated temperature, increased muscle metabolism, muscle rigidity, rhabdomyolysis, acidosis, and cardiovascular instability develop within minutes..

• The neuroleptic malignant syndrome Caused by the inhibition of central dopamine receptors in the hypothalamus, Seen as increased heat generation and decreased heat dissipation and is characterized by "lead-pipe" muscle rigidity, extrapyramidal side effects, autonomic dysregulation, and hyperthermia. occurs in the setting of neuroleptic agent use (antipsychotic phenothiazines, haloperidol, prochlorperazine, metoclopramide) or the withdrawal of dopaminergic drugs • The serotonin syndrome, seen with (SSRIs), MAOIs, and other serotonergic medications, has many overlapping features, including hyperthermia, but distinguished by the presence of diarrhea, tremor, and myoclonus and absence of the lead-pipe rigidity

Pathogenesis of Fever • Pyrogen is a any substance that causes fever. • Exogenous pyrogens are derived from outside the patient; most are microbial products, microbial toxins, or whole microorganisms. E.glipopolysaccharide (endotoxin) produced by all gram-negative bacteria. • Pyrogenic products of gram-positive organisms include the enterotoxins of Staphylococcus aureus and the group A and B streptococcal toxins, also called superantigens. One staphylococcal toxin of clinical importance is of S. aureus from patients with toxic shock syndrome.

• Pyrogenic Cytokines • Cytokines are small proteins (molecular mass, 10,000–20,000 Da) that regulate immune, inflammatory, and hematopoietic processes • Each cytokine is encoded by a separate gene, and each pyrogenic cytokine has been shown to cause fever in laboratory animals and in humans • The pyrogenic cytokines include IL-1, IL-6, tumor necrosis factor (TNF), ciliary neurotropic factor (CNTF), and interferon (IFN)

• There are four receptors for PGE2, and each signals the cell in different ways. Of the four receptors, the third (EP-3) is essential for fever • Release of PGE2 from the brain side of the hypothalamic endothelium triggers the PGE2 receptor on glial cells, and this stimulation results in the rapid release of cyclic adenosine 5'-monophosphate (cyclic AMP), which is a neurotransmitter, the release of cyclic AMP from the glial cells activates neuronal endings from the thermoregulatory center that extend into the area. The elevation of cyclic AMP is thought to account for changes in the hypothalamic set point either directly or indirectly (by inducing the release of neurotransmitters). receptors for microbial products are located on the hypothalamic endothelium. These receptors are called Toll-like receptors and are similar in many ways to IL-1 receptors. The direct activation of Toll-like receptors also results in PGE2 production and fever.

Approach to Fever

MECHANISMS OF ANTIPYRETIC AGENTS • THE REDUCTION OF FEVER BY lowering of the elevated hypothalamic set point is a direct function of reducing the level of PGE2 in the thermoregulatory center. • The synthesis of PGE2 depends on the constitutively expressed enzyme cyclooxygenase. The substrate for cyclooxygenase is arachidonic acid released from the cell membrane, and this release is the rate-limiting step in the synthesis of PGE2. Therefore, inhibitors of cyclooxygenase are potent antipyretics. The antipyretic potency of various drugs is directly correlated with the inhibition of brain cyclooxygenase. Acetaminophen is a poor cyclooxygenase inhibitor in peripheral tissue and lacks anti-inflammatory activity; in the brain • acetaminophen is oxidized by the p450 cytochrome system, and the oxidized form inhibits cyclooxygenase activity.

• Oral aspirin and acetaminophen are equally effective in reducing fever. Nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen and COX-2 inhibitors are also excellent antipyretics. • Glucocorticoids :act at two levels. First, similar to the cyclooxygenase inhibitors, glucocorticoids reduce PGE2 synthesis by inhibiting the activity of phospholipase A2, which is needed to release arachidonic acid from the cell membrane. Second, glucocorticoids block the transcription of the mRNA for the pyrogenic cytokines.

TREATMENT OF FEVER • The objectives in treating fever are first to reduce the elevated hypothalamic set point and second to facilitate heat loss. Reducing fever with antipyretics also reduces systemic symptoms of headache, myalgias, and arthralgias. • Oral aspirin and NSAIDs effectively reduce fever but can adversely affect platelets and the gastrointestinal tract. so acetaminophen is preferred . In children, acetaminophen must be used because aspirin increases the risk of Reye's syndrome. If the patient cannot take oral antipyretics, parenteral preparations of NSAIDs,rectal suppository preparations of can be used.

• In hyperpyrexia, the use of cooling blankets facilitates the reduction of temperature; however, cooling blankets should not be used without oral antipyretics • Hyperthermia • A high core temperature in a patient with an appropriate history (e.g., environmental heat exposure or treatment with anticholinergic or neuroleptic drugs, tricyclic, succinylcholine, or halothane) along with appropriate clinical findings (dry skin, hallucinations, delirium, pupil dilation, muscle rigidity, and/or elevated levels of creatine phosphokinase) suggests hyperthermia • Physical cooling with sponging, fans, cooling blankets, and ice baths should be initiated immediately in conjunction with IV fluids and appropriate pharmacologic agents. If insufficient cooling is achieved by external means, internal cooling can be achieved by gastric or peritoneal lavage with iced saline

• In extreme circumstances, hemodialysis or even cardiopulmonary bypass with cooling of blood performed. • Malignant hyperthermia : treated with cessation of anesthesia and IV administration of dantrolene sodium (1–2.5 mg/kg 6 h) for at least 24–48 h—until oral dantrolene can be administered . • Procainamide should also be administered to patients with malignant hyperthermia because of the likelihood of ventricular fibrillation in this syndrome. • Neuroleptic malignant syndrome : RX with Dantrolene • The neuroleptic malignant syndrome may also be treated with bromocriptine, levodopa, amantadine, or nifedipine or by induction of muscle paralysis with curare and pancuronium. • drug-induced hyperthermia &hyperthermia of the serotonin syndrome – both treated with dantrolene