THE BODY RESPONDS TO INJURY KITI SIRIWATANA 3210303 GENERAL SURGERY
OBJECTIVE Can explain about local and systemic response to injury.
Can explain metabolic change due to body response to injury.
Can explain the neuroendocrine system’s role in the body response to injury.
Can apply the knowledge to the clinical practice.
Stress response VS Body response to injury What happens when you’re feeling angry? What happens when you’re feeling nervous or stressed? What happens when you’re feeling pain? ◦ Tachycardia ◦ Increase Blood pressure ◦ Increase Respiratory rate
Why?, How?
Stress response = Body response to injury
Stress Response : How?
Pain, Sensory Afferents
Fear, Emotion
The Sympathoadrenal system, SAS Thalamus
Limbic system
Hypothalamus
Adrenal Medulla
Epinephrine
Body response to injury: How?
Pain, Sensory Afferents
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia
Fear, Emotion
Chemoreceptor
Thalamus
Baroreceptors
Medulla oblongata
Limbic system
Hypothalamus Cardiovascular Reflexes Respiratory Reflexes
Body response to injury Adrenal Medulla
Epinephrine
Cardiovascular effects of Body response to injury Tachycardia Increase Blood pressure Increase Respiratory rate ◦ Cardiovascular homeostasis ◦ Oxygen delivery ◦ Energetic substrate delivery
Something missing
Adapted from Demling RH, DeSantiL. Complications of acute weight loss due to stress response to injury. Curr OpinCrit Care 1996;2:482–91
Metabolic change Catabolism Energetic substrate preparation ◦ Glucose ◦ Resource of Glucose ◦ Glycogen : Glycogenolysis ◦ Lipid: Lipolysis Gluconeogenesis ◦ Protein: Protein breakdown Gluconeogenesis
Metabolic change Catabolism Repair-Wound healing, Immune response, Plasma protein substrate preparation ◦ Essential Amino Acid ◦ Resource of Amino Acid ◦ Protein breakdown
Metabolic change Carbohydrate catabolism Glycogenolysis Hyperglycemia Lipid catabolism Hyperglycemia+Ketone bodies Protein catabolism Hyperglycemia+Urea-Ureogenesis, Negative Nitrogen Balance
Fluid and electrolyte balance Cardiovascular homeostasis
Metabolic change+Fluid and electrolyte balance : How? Fluid and electrolyte control by ◦ ADH/AVP ◦ Posterior pituitary
◦ Aldosterone The-renin-angiotensin system ◦ Adrenal Cortex
Preservation of adequate body fluid volumes Keep water and electrolyte to preserve of adequate body fluid volumes â—Ś Vasopressin (ADH, AVP) â—Ś The renin-angiotensin system : Aldosterone
Increase peripheral vascular resistance : Hypertension
Metabolic change+Fluid and electrolyte balance : How? Metabolic change control by ◦ Cortisol ◦ Adrenal Cortex
◦ Growth hormone ◦ Anterior pituitary
Metabolic change control by Cortisol ◦ Glycogenolysis ◦ Gluconeogenesis ◦ Protein breakdown ◦ Lipolysis
◦ Anti-inflammatory activity ◦ Anti-insulin effect (Glucose use)
Growth hormone ◦ Protein synthesis ◦ Lipolysis ◦ Anti-insulin effect (Glucose uptake and use)
Endocrinological effect Anterior pituitary ◦ Growth hormone
Posterior pituitary ◦ ADH/AVP
Adrenal Cortex ◦ Cortisol ◦ Aldosterone
Pain, Sensory Afferents
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia
Fear, Emotion
Chemoreceptor
Thalamus
Baroreceptors
Medulla oblongata
Limbic system
Hypothalamus Cardiovascular Reflexes Respiratory Reflexes
Body response to injury Adrenal Medulla
Epinephrine
Pain, Sensory Afferents
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia
Fear, Emotion
Chemoreceptor
Thalamus
Baroreceptors
Medulla oblongata
Limbic system
Hypothalamus CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Cardiovascular Reflexes Respiratory Reflexes
Adrenal Medulla
Epinephrine
Hypothalamic-pituitary-adrenal axis The Hypothalamic-Pituitary-Adrenal axis ◦ Hypothalamus ◦ Corticotrophin-releasing hormone: CRH
◦ Anterior pituitary ◦ Adrenocorticotrophic hormone: ACTH ◦ Growth hormone
◦ Posterior pituitary ◦ ADH/AVP
◦ Adrenal Cortex ◦ Cortisol ◦ Aldosterone
Hypothalamic-pituitary-adrenal axis HPA-axis ◦ Metabolic change : ◦ Increase catabolism ◦ Providing energy sources ◦ Providing amino acid
◦ Cardiovascular homeostasis/ Fluid and Electrolyte balance
Stress response = Body response to injury
Pain, Sensory Afferents
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia
Fear, Emotion
Chemoreceptor
Thalamus
Baroreceptors
Medulla oblongata
Limbic system
Hypothalamus CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Cardiovascular Reflexes Respiratory Reflexes
Adrenal Medulla
Epinephrine
Local response VS Systemic response What is relation between local response and systemic response? Trauma/injury, Infection ◦ Inflammation ◦ To remove injurious stimuli ◦ Initiate healing process
Chemical mediated protein in inflammation and immunity, produced by several nucleated cell ◦ Cytokine ◦ IL1, IL6, TNF
◦ Acute phase response ◦ C-reactive protein ◦ Complement
Cytokine Role â—Ś Maintaining the inflammatory response to tissue injury â—Ś Systemic response
IL-1,IL-6,TNF
Il-1 Produced by macrophages, monocytes, fibroblasts in inflammatory process Inflammatory process against infection Pyrogen : hypothalamus thermoregulatory center Fever
IL-6 Produced by T cells and macrophages in response to trauma Depend on degree of tissue trauma Initiate Acute phase response Pyrogen : hypothalamus thermoregulatory center Fever
TNF TNF-α : Systemic inflammation Potent chemoattractant for Neutrophils Produced majority by macrophage Initiate Acute phase reaction Others function ◦ Inhibit tumorigenesis ◦ Inhibit viral replication
IL-1,IL-6 and TNF in systemic response Hypothalamus ◦ Hypothalamus thermoregulatory center : Fever ◦ IL-1,IL-6
◦ Hypothalamic-pituitary-adrenal axis ◦ Endocrine response to injury ◦ IL-1,IL-6 and TNF
Initiate Acute phase response ◦ Hepatic protein synthesis ◦ IL-6,TNF
Acute phase response One of the innate immune system During acute illness Produce acute phase protein ◦ C-reactive protien (CRP): opsonin microbes ◦ Complement factors : opsonization ◦ Alpha 2- macroglobulin : inhibitor of coagulation ◦ : inhibitor of fibrinolysis
IL1,IL6,TNF Trauma, Infection
Hypothalamus
Fever
CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Adrenal Medulla
Epinephrine
Body response to injury Neurological effect Endocrinological effect Immunological effect Hematological effect
Neurological effect
Pain, Sensory Afferents
Fear, Emotion
The Sympathoadrenal system, SAS Thalamus
Limbic system
Hypothalamus
Adrenal Medulla
Epinephrine
Hematological effect
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia Chemoreceptor
Baroreceptors
Medulla oblongata Hypothalamus Cardiovascular Reflexes Respiratory Reflexes
Adrenal Medulla
Epinephrine
Endocrinological effect
Hypothalamus CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Adrenal Medulla
Epinephrine
Immunological effect
IL1,IL6,TNF Trauma, Infection
Hypothalamus
Fever
CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Adrenal Medulla
Epinephrine
Body response to trauma/ Stress response Activator ◦ Emotion ◦ Pain, Tissue injuries ◦ Infection
Stress circuit : HPA,SAS Objective : Flee, Fight ,Survivor
Conclusion : Body response to trauma/stress Result : ◦ ◦ ◦ ◦
Increase Metabolism Catabolism Gaining Energy Source from Body Reserve Preserve fluid and electrolyte Preparing resource for immune response, inflammation, wound healing Protein breakdown
Mediated chemical ◦ Cortisol , Epinephrine , Growth hormone ◦ AVP , Aldosterone ◦ Cytokine , Acute phrase protein
Pain, Sensory Afferents
Hemorrhage Hypovolemia Fluid Shifts
Hypoxia Hypercapnia
Fear, Emotion
Chemoreceptor
Limbic system
Thalamus
Baroreceptors
Medulla oblongata
IL1,IL6,TNF Trauma, Infection
Cardiovascular Reflexes Respiratory Reflexes
Hypothalamus CRS
Growth H., AVP
Pituitary ACTH
Cortisol, Aldosterone
Adrenal Cortex
Adrenal Medulla
Epinephrine
Metabolic rate and temperature control Metabolic rate : Energy + Heat Gradient mechanisms ◦ ◦ ◦ ◦
Radiation Conduction Convection Evaporation
Hypothalamus ◦ Hypothalamic thermostat ◦ Body core temperature set point : 37○ C
Decrease core temperature Subcutaneous capillaries : Vasodilatation
Increase perspiration
Inhibit shivering and muscle activity
Increase body core temperature Subcutaneous capillaries : Vasoconstriction
Stimulate shivering
Stimulate piloerection
Fever Pyrogen : increase Body core temperature set point Fever provide ◦ Increasing in immunity quality : 20 folds of T cells and antibodies synthesis ◦ Kill foreign microbes ◦ But if >40○ C harm to body function
Fever Shivering with subcutaneous capillaries constriction to increase body core temperature Warm skin Return to normal core temperature set point Flush skin Sweating cold skin :sign of heat loss Normal body temperature
Fever Required more energy Required adequate fluid and nutrition supplement
Dental emergency situation related to the stress response -
Stress system malfunction could lead to serious, Life threatening disease The body’s response to stress can be both helpful and harmful. The stress response gives us the strength and speed to ward off or flee from and impending threat. When persists, stress can put us at risk for obesity, heart disease, cancer, and a variety of other illnesses.
The stress response could lead to serious life treatening disease Stress in dental office : Emergency situation
Prolonged stress, serious illness : ◦ ◦ ◦ ◦
Impaired wound healing Impaired immune system Impaired normal body metabolism Etc.
Syncope (โรควูบ) Transient inadequate brain perfusion A transient, self-limited loss of consciousness with an inability to maintain postural tone that is followed by spontaneous recovery Categorization into reflex (neurally mediated), orthostatic, and cardiac (cardiovascular) Stress induced syncope
Flight or Flee Fear and anxiety emotion : Limbic system Excess vagal tone and decreased sympathetic skeletal muscle response to central nervous system stimulation : Flee response
stress-related vasovagal syncope Anxiety Nausea Weakness Dizziness Associated signs include tremor, diaphoresis, pallor, transient loss of consciousness, and, in rare instances, seizure Symptoms may also occur without an accompanying loss of consciousness
PATHOPHYSIOLOGY Caused by excess vagal tone and decreased sympathetic skeletal muscle response to central nervous system stimulation (for example, fear) A hypotensive–bradycardic reflex syndrome Inadequate vasoconstriction with an abrupt drop in systolic blood pressure, followed shortly by profound bradycardia and a decrease in cardiac output The drop in blood pressure is primarily due to impaired venous return, rather than to effects on the arterial system Any anxiety or fear-inducing event can stimulate stress-related vasovagal symptoms
Hypoglycemia and stress response Most common in DM ◦ Over dose of anti hyperglycemic drug ◦ Starvation
the counterregulatory hormones of insulin ◦ Epinephrine ◦ Glucagon
Body response to stress
Hypoglycemia a lower than normal level of blood glucose an inadequate supply of glucose to the brain resulting in impairment of function (neuroglycopenia) Effects can range from vaguely "feeling bad" to seizures, unconsciousness, and (rarely) permanent brain damage or death. Most healthy adults maintain fasting glucose levels above 70 mg/dL (3.9 mmol/L), and develop symptoms of hypoglycemia when the glucose falls below 55 mg/dL (3 mmol/L).
Adrenergic manifestations Shakiness, anxiety, nervousness Palpitations, tachycardia Sweating, feeling of warmth (although sweat glands have muscarinic receptors, thus "adrenergic manifestations" is not entirely accurate) Pallor, coldness, clamminess Dilated pupils (mydriasis) Feeling of numbness "pins and needles" (paresthesia)
Glucagon manifestations Hunger, borborygmus Nausea, vomiting, abdominal discomfort Headache
Neuroglycopenic manifestations Abnormal mentation, impaired judgment Nonspecific dysphoria, anxiety, moodiness, depression, crying Negativism, irritability, belligerence, combativeness, rage Personality change, emotional lability Fatigue, weakness, apathy, lethargy, daydreaming, sleep Confusion, amnesia, dizziness, delirium Staring, "glassy" look, blurred vision, double vision Automatic behavior, also known as automatism Difficulty speaking, slurred speech Ataxia, incoordination, sometimes mistaken for "drunkenness" Focal or general motor deficit, paralysis, hemiparesis Tardiness Paresthesia, headache Stupor, coma, abnormal breathing Generalized or focal seizures
Hyperglycemia : Diabetic ketoacidosis Diabetic ketoacidosis : DKA Diabetes Type I > Type II Hyperglycemia + Ketoacidosis Glycosuria : Osmotic diuresis :Dehydration + Electrolyte :Volume depletion Hypotension : Shock Acidosis :Kussmaul repiration Respiratory center depression Unconcious Vasodilatation
imbalance
Adrenal crisis/acute adrenal insufficiency Cortisol and aldosterone â—Ś The primary hormone of importance in acute adrenal crisis is cortisol â—Ś Aldosterone is relatively minor
Critical illness-related corticosteroid insufficiency : Specific features Hypotension resistant to volume resuscitation Hypoglycemia (usually mild) Hyponatremia and hyperkalemia (rare and usually mild) Pituitary deficiencies (gonadotrophin, thyroid, diabetes indipidus)
Critical illness-related corticosteroid insufficiency : Nonspecific features Unexplained fever Unexplained mental status changes Hyperdynamic circulation Anemia Metabolic acidosis Nausea/vomiting Diarrhea
Prolonged stress Leading to a variety of other illnesses Obesity Cardiovascular disease Growth retardation Suppresses the reproductive system at various levels vulnerable to infections GI disturbance
Is Stress creating a Quasi cushing syndrome? There is new research to indicate individuals suffering from extreme stress exposure, releasing an over abundance of cortisol, may develop a condition similar to that of Cushing’s syndrome
Cushing's syndrome is a hormone (endocrine) disorder caused by high levels of cortisol (hypercortisolism) in the blood. insulin resistance abnormal fasting glucose levels (Hyperglycemia) hypertension obesity and dyslipidemia (free fatty acids, steatosis, amp-activated protein kinase)
Lipid metabolism in Acute and Chronic stress response. In acute conditions such as stress, glucocorticoids increase whole body lipolysis, FFA uptake, spillover and turnover resulting in a hyperdynamic fatty acid system. On the contrary, during recovery from stress, because of the fall of catecholamines and hyperinsulinemia, lypolysis decreases and triacylglycerides storage increases in the liver and visceral adipose tissue. This latter condition with absence of counter-regulatory hormones and insulin resistance is the condition observed in Cushing’s syndrome.
Lipid metabolism in Acute and Chronic stress response. Glucocorticoids changed AMPK activities in a tissue-specific manner explaining the increase in appetite, visceral obesity and dyslipidemia. Adenosine 5'-monophosphate-activated protein kinase (AMPK) AMPK is turned on when the cellular energy state of the cell drops.
The gastrointestinal tract and stress CRH directly hinders the release of stomach acid and emptying of the stomach. CRH also directly stimulates the colon, speeding up the emptying of its contents. HPA axis autonomic nervous system also hinders stomach acid secretion and emptying, as well as increasing the movement of the colon. Ischemia-an insufficient flow of blood to the GI system was the main cause of stress ulcer. Chronic/Prolonged: High levels of cortisol can increase appetite and lead to weight gain.
The immune system and stress The HPA axis also interacts with the immune system , making more vulnerable to colds and flu, fatigue and infections. Cortisol suppress the release IL-1 IL-6 and TNF in the process switching off the inflammatory response. When the HPA axis is continually running at a high level, however, that damping down can have a down side, leading to decreased ability to release the interleukins and fight infection
The immune system and stress Conversely, there is evidence that a depressed HPA Axis, can lead to a hyperactive immune system and increased risk of developing autoimmune diseases.
Growth and stress The hormones of the HPA axis also influence hormones needed for growth Prolonged HPA activation will hinder the release of growth hormone and insulin-like growth factor 1, both of which are essential for normal growth Glucocorticoids released during prolonged stress also cause tissues to be less likely to respond to IGF-1 High glucocorticoid levels – lose about 7.5 to 8.0 centimeters from their adult height. Growth retardation
Stress and the reproductive system Suppresses the reproductive system at various levels. CRH prevents the release of gonadotropin releasing hormone, the master hormone that signals a cascade of hormones that direct reproduction and sexual behavior. Cortisol not only inhibit the release of GnRH, but also the release of luteinizing hormone, which prompts ovulation and sperm release. Cortisol also inhibit the testes and ovaries directly.
Prolonged high level of cortisol Hypertension Dyslipidemia Obesity from apetite,Stress induced peptic ulcer Diabetes type 2 Cardiovascular disease? Growth retardation Suppresses the reproductive system Compromised immune system
How to prevention the adverse result from body response to injury Local anesthesia reduce degree of body response to injury by block neuroendocrine response Degree of body response depend on degree of tissue injury Steroid supplement in some situation Protein supplement is necessary especially in prolonged illness Antacid or H2 receptor antagonists for stress ulcer prophylaxis in ICU Fluid and Nutrition supplement should be considered in fever 150 g of glucose/day prevent gluconeogenesis Stress reduction protocol : Anxiolytic drug (oral , IV sedation)
การให้ กลูโคสจากภายนอกในขนาด 150 g. ต่อวันจะไม่ช่วยยับยังขบวนการ Catabolism ของโปรตีนและไขมันได้ มีความจําเป็ นที)จะต้ องให้ สารอาหารเสริ มโดยเฉพาะโปรตีนให้ เพียงพอแก่ผ้ ปู ่ วย ได้ แก่ โปรตีนจํานวน 2.5 g. ต่อนําหนัก 1 kg. ในหนึง) วัน ร่วมกับพลังงานจากกลูโคสราวๆ 2,500 calories ในหนึง) วัน[5] ในทางปฏิบตั ิจงึ มักให้ อาหารโปรตีนสูงขนาด 2,500 calories โดยการรับประทานหรื อทางสายยางร่วมกับการ ให้ concentrated amino acids ทาง a central venous catheter กับผู้ป่วยที)ได้ รับบาดเจ็บและมีปัญหาแทรกซ้ อนอย่าง ยาวนาน ( The Prolonged Trauma State)