Blood flow to one or more organs burns - PDF

P.06 BURNS Organ malperfusion – blood flow to one or more organs is reduced or blocked. DR. ABRAHAM CINIO | FEBRUARY 06, 2025...

P.06 BURNS Organ malperfusion – blood flow to one or more organs is reduced or blocked. DR. ABRAHAM CINIO | FEBRUARY 06, 2025 Multiple system organ failure (MSOF) – a life-threatening condition OUTLINE where two or more organs fail to function properly. I. Introduction VI. Secondary Survey Thermal burn injury → cell damage → cell death Cellular and tissue II. Etiologic & Classifications VII. Burn Assessment injury secondary from exposure to extreme temperatures. of Burns VIII. Fluid Resuscitation Cellular injury starts at temperature above 44°C. III. Physical Examination IX. Wound Management Most cell damage are seen at the capillary endothelium Damaged capillaries will leak, as a result, water, electrolytes and plasma (P.E.) X. Escharotomies proteins are lost. IV. Introduction to Approach XI. Nutrition Metabolic Response: Hypermetabolism – increase glucose a Patient with Trauma metabolism, lipolysis, and proteolysis (Burns) Neuroendocrine response – increase catecholamines, Low Thyroid V. Primary Survey hormone, ↑Cortisol. Low Thyroid hormone is may be due to sepsis I. INTRODUCTION Note: “Burns are the most catabolic injury that humans can sustain.” A burn injury is a type of tissue damage that results from exposure C. MAJOR PROBLEMS ENCOUNTERED IN BURN PATIENTS to heat, electricity, radiation, chemicals, or friction. Fluid loss → Dehydration →Shock Burn injuries can vary in severity, depending on the depth, size, and Fluid loss will depend on the percentage of the burnt area, so location of the affected skin and tissues. we expect that for every 1% of surface area, it loses around 4 Burn injuries can cause pain, swelling, blistering, scarring, infection, mL of water. and organ dysfunction. Fluid and electrolyte management to prevent shock Burn injuries require different treatments, depending on the degree Tissue loss → Loss of Barrier → Infection of the burn and the cause of the injury. Patients with severe burns have several entry points for Some burn injuries can be treated at home, while others need microorganisms, so they are very prone to infection medical attention and specialized care. Infection Inability to maintain body temperature Multidisciplinary Physical and functional deformities = contractures Surgeons Burns in children – rule out abuse even in small burns Nurses Burns in injured patients – comorbidities Specialists Burn contractures – nag peklat at di ginagalaw ng patient, titigas at Fluid resuscitation magreresulta ng limited range of motion Early wound management Critical care D. GUIDELINES FOR REFERRAL TO BURN CENTER Burn Unit Organization and Personnel Experienced burn surgeons (burn unit director and qualified surgeons) Dedicated nursing personnel Physical and occupational therapists Social workers Dietitians Pharmacists Respiratory therapists Psychiatrists and clinical psychologists – gives advice for the patient and their parents Prosthetists A. PHYSIOLOGIC FUNCTION OF SKIN DISRUPTED BY BURNS Barrier to microorganisms Temperature regulation Fluid retention Sensory Cosmesis B. PATHOPHYSIOLOGY OF BURNS Thermal burns, in particular, cause damage to the skin and occasionally underlying through abrupt temperature change that exceed biologic tolerance → membrane disruption, protein denaturation, and necrosis. Figure 1. Guidelines for Referral to a Burn Center. May cause severe inflammatory reactions: Capillary leak – because “Lifted from lecturer ppt” of exposed dermis and maybe subcutaneous tissues Intravascular fluid loss High fevers – this is a concern especially if patients are admitted. NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 1 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  II. ETIOLOGIC & CLASSIFICATIONS OF BURNS A. JACKSON LEVELS OF BURN INJURY A.1 ZONE OF COAGULATION Necrotic area of burn where cells were directly disrupted Occupies the central area Area of most severe burn injury No capillary blood flow “Whitish” Most affected area Contains dead skin and has no vasculature A.2 ZONE OF STASIS The area immediately surrounding the necrotic zone (zone of coagulation) Has a moderate degree of insult with decreased tissue perfusion (blood flow) Depending on the wound environment, can either survive or go on to coagulative necrosis Associated with vascular damage and vessel leakage Salvageable by appropriate resuscitation Figure 2. Burn Classifications. Gray area of the burn “Lifted from lecturer ppt” Some cells live and some die If lacks O2 and nutrients may turn to 3rd degree burn Flame, scald, and contact burn injury induce cellular damage primarily by the transfer of energy inducing coagulative necrosis A.3 ZONE OF HYPEREMIA (except for cold injuries, which do not engender protein Outermost area surrounding the zone of stasis denaturation). Characterized by vasodilatation from inflammation surrounding the Electricity and chemical burn injuries cause direct injury to cellular burn wound. membranes in addition to the transfer of heat. This region contains the clearly viable tissue from which the healing process begins and is generally not at risk for further necrosis. “Reddish” Most cells survive Figure 3. Formulas for Fluid Resuscitaion. Figure 4. Burn Classifications. “Lifted from lecturer ppt” “Lifted from lecturer ppt” The response of local tissues can lead to injury in the deeper layers. Heat (and other injury mechanisms) can denature proteins, leading The area of cutaneous injury has been divided into three zones: to loss of plasma membrane integrity and cell necrosis Zone of coagulation Dry and leathery, not painful, sensate, or blanching and can feel Zone of stasis firm and waxy on palpation Zone of hyperemia Dead tissue and dried secretions from a skin wound Provides temporary coverage of and protection to the wound NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 2 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Persists for less than a month before sloughing off or dissolving itself Stages of burns: Stage of shock Stage of eschar Stage of healing and reconstruction Phases of burn: Emergent phase: 24-48hrs Acute phase: 48hrs to wound closure Chronic phase: wound closure to functional ADL regainment B. THERMAL BURNS Flame burns Most common cause of hospital admission, accompanied by inhalation injury and highest mortality rate Contact When a hot object comes in contact with the skin Scald burns Burns related to hot water, common in children Figure 5. Treatment of Acid and Alkali burns. Vapors from steam is considered a scald burn “Lifted from lecturer ppt” C. CHEMICAL BURNS D. ELECTRICAL BURNS Secondary to exposure to high acid and alkali concentration 3% of US hospital admission 3% of admitted burn patients Has direct effects on the body such as the heart. Can potentially result in severe burns The heart is an electrical organ with nerves and areas offering the least resistance (blood vessels). ACID ALKALI Can result in coagulation Liquefactive necrosis (except Special concerns of electrical burns: necrosis hydrofluoric acid which also Cardiac arrythmia Formic acid – causes cause liquefactive necrosis) o Baseline ECG is recommended in all patients hemolysis and hemoglobinuria Compartment syndrome and rhabdomyolysis o Common in high-voltage injuries; muscles are literally destroyed that causes edema and results to compartment Initial therapy is to irrigate the affected area with water for a syndrome minimum of 30 minutes o Vigilance for neurologic or vascular compromise, & fasciotomies should be done even in cases of clinical Hydrofluoric acid behaves like an alkali that can cause severe suspicion hypocalcemia. If swallowed, drink large amounts of water and milk or Long-term neurologic symptoms and cataract antacids to dilute the acid. development If poured on your skin or eyes, immediately flush the o Neurologic and Ophthalmologic consultations should be affected area for at least 30 minutes and apply calcium obtained to define baseline function. gluconate gel if available. Do NOT induce vomiting or take baking soda E. INHALATION BURNS Inhalation injury – admissible agad ang pasyente Table 1. Acid vs Alkali Chemical Burns Inhalational burn injury is a very severe type of injury that can occur when you breathe in smoke in an enclosed area. Smoke can cause three life-threatening conditions: Carbon monoxide poisoning Irritation or inflammation of the respiratory tract that leads to respiratory depression Asphyxia NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 3 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Figure 6. Inhalation Treatments of Smoke Inhalation Injury. “Lifted from lecturer ppt” Classification of Inhalation Injury Injury Subtype Mechanism Clinical Consequences Upper airway Thermal burns Airway edema injury from heat obstruction transfer Lower airway/ Chemical and Fibrin casts that obstruct lung parenchyma particulate lower airways irritants Inflammation Ventilation/ perfusion mismatch Atelectasis Bronchospasm Systemic cellular Asphyxia/ Lactic acidosis Figure 7. Management of Burn Injuries dysfunction from hypoxia Central nervous system “Lifted from lecturer ppt” carbon monoxide insults and cyanide Cardiovascular insults Initial Management: MAJOR and CRITICAL Burns exposure Intubate if with: o Burns 50% BSA Table 2. Classification of Inhalation Injury o Suspected inhalation injury o Smoke inhalation III. PHYSICAL EXAMINATION (P.E.) Do not compete PE, check for other injuries ABC’s same as for any other trauma patient (Airway, Breathing, Insert IV line for fluid resuscitation Circulation). Insert Foley catheter (to monitor UO) Burn wound extent Insert NGT (to decompress stomach). Start IV PPI (to avoid Burn wound depth Curling’s ulcer). Do not debride or dress burns until examination is complete Get the patient’s weight Note: ABC’s are part of primary survey, while complete PE and history are part of secondary survey. Figure 8. Management of Burn Injuries “Lifted from lecturer ppt” NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 4 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Acute From beginning of Wound care and diuresis to near closure completion of wound Prevention of closure treatment of complications, including infection Nutritional support Rehabilitation From major wound Prevention of scars and closure to return to contractures individual’s optimal Physical, occupational, level of physical and and vocational psychosocial rehabilitation adjustment Functional and cosmetic reconstruction Psychosocial counseling Table 2. Phases of Burn Care Figure 9. Immediate Concerns in Burn Care “Lifted from lecturer ppt” Figure 12. ATLS Way of Trauma Management Lifted from lecturer ppt” Figure 10. Management of Burn Injuries “Lifted from lecturer ppt” PHASES OF BURN CARE Phase Duration Priorities Emergent or From onset of injury First aid immediate to completion of Prevention of shock resuscitative fluid resuscitation Prevention of respiratory distress Detection and treatment of Figure 13. Trauma Resuscitation Checklist concomitant injuries “Lifted from lecturer ppt” Wound assessment and initial care NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 5 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  A. BURNS: SUSPECT ASSOCIATED INJURIES Escharotomy and Fasciotomy are performed in cases of Explosion compartment syndrome Falls Motor vehicle crash with fire E.1 SUPERFICIAL BURNS (1ST DEGREE BURNS) High voltage electrical Injury confined to the dermis Note: Treat the associated injuries first Painful, erythematous (red), and blanch to the touch with an intact Do not focus on just the burn! epidermal barrier. e.g. Sunburn The burn patient initially should be treated as a trauma patient (not Usually heals within few days a dermatology patient) Does not result to scarring A major burn causes multi-organ dysfunction and is not just a skin Treatment is aimed at comfort with the use of topical soothing salves injury; these patients can be the sickest & complex you may ever and oral NSAIDs care for. NOT counted in calculations of total burn surface area (TBSA) B. BURNS: HISTORY Type of burn (flame, chemical, electrical, flash) Substances involved Associated trauma If in closed space Time of injury Duration of contact with smoke “AMPLE” – useful means of remembering key elements of the history, and it stands for: Allergies Medications Prior illness/ Past medical history Last meal (time) or other intake Events preceding the injury “S” is often added for ‘Signs and symptoms’ to make it S.A.M.P.L.E. C. PRIMARY SCENE CARE Most important: Do NOT become a victim yourself! Turn off gas or pump or electric power, etc. if possible Remove patient from heat source (push with dry nonconductive Figure 14. Superficial Burn. material if in contact with electricity). “Lifted from lecturer ppt” Immediately move patient from the vicinity if there is a danger of explosion. E.2 PARTIAL-THICKNESS BURNS (2ND DEGREE BURNS) Keep low to avoid smoke; use protective breathing apparatus if Divided into superficial and deep available. Superficial partial-thickness burns Put fire out; extinguish burning clothing (H2O or CO2 extinguisher). Limited to the papillary dermis First thing to do: Assess if the scene is safe! Erythematous (red), very painful, blanch to touch, and often blister. D. SECONDARY SCENE CARE Hair follicles remain viable and intact Position airway; start O2 and/ or CPR if needed. o E.g. Scald injuries and flash flame burns Get off all potentially affected clothing. Heals within 7 to 14 days Soak clothing or the burn area if heat transfer is still possible; With minimal scarring continue to irrigate copiously if it is a chemical burn. Counted in calculations of TBSA Ventilate the area if there is smoke present. Arrange a transport. Deep partial-thickness burns Immobilize the neck & back, etc., if needed. Burn within the reticular dermis Note: Secure the neck with a neck brace or cervical collar if there is Appear paler and more mottled a suspicion of spinal injury. Do not blanch to touch For referral of patients called by the EMT/EMS to your hospital, the Remain painful to pinprick first thing to do is to protect yourself first by wearing PPEs. Heals within 15 to 21 days Often with severe scarring as a result of loss of dermal integrity. E. BURN DEPTH Counted in calculations of TBSA Classified by penetrance from the surface to the epidermis, dermis, subcutaneous fat, and underlying structures. Eschar with surrounding erythema is not wound healing thus is removed via Escharotomy Full-thickness burns with a rigid eschar can form a tourniquet effect as the edema progresses, leading to compromised venous flow and eventually arterial inflow NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 6 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Figure 176. Skin Layers Affected by Burn Depth. “Lifted from lecturer ppt” Wound healing of full-thickness burns differs from normal wound Figure 15. Deep Partial-thickness Burn. healing “Lifted from lecturer ppt” Alterations in hemostasis, inflammation and granulation tissue formation E.3 FULL-THICKNESS BURNS (3RD DEGREE BURNS) Burn injury coagulates the superficial blood vessels hindering fibrin Extend through the epidermis and dermis into the underlying fat clot formation Characterized by a hard-leathery eschar that is painless and black, Presence of eschar on the wound bed prohibits granulation white, or cherry red in color depending on the temperature of the tissue formation source. Granulation tissue is characterized by a high density of fibroblasts, Loss of pinprick sensation → painless granulocytes, macrophages and micro capillaries. No epidermal of dermal keratinocytes remain; thus, these wounds In full-thickness burn wounds the cells required for wound healing must heal by re-epithelialization from the wound edges. have to migrate form the wound edges, from the subcutaneous Requires skin grafting adipose tissue or other origins Counted in calculations of TBSA Blanching of the skin means that the skin turns white or pale when lightly flow of the skin is reduced. Note: Critical monitoring of a burn patient is 3 days Figure 17. Biofilm Complications. “Lifted from lecturer ppt” Biofilm must be removed during change of dressing E.4 4th DEGREE BURNS Affects underlying soft tissue The most serious, involving deeper injury to muscles, tendons, fat, and even bones. The burn is often charred black, and the burned part may require surgical removal or amputation. Figure 17. Full-thickness Burn. “Lifted from lecturer ppt” NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 7 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Contraindications Never insert an IV catheter on a patient with genital injury Rule out basal skull fracture because NGT might enter the brain Curling’s ulcer Note: Although at times restoring Circulatory volume may proceed active Airway intervention. Note: Life-threatening injuries must be identified and treated before progressing to the secondary survey. The purpose of Primary Survey is to rapidly identify and manage impending or actual life threats to the patient. Figure 18. Fourth-degree burns. “Lifted from lecturer ppt” E.5 5th DEGREE BURNS Affects through muscle to bone E.6 6th DEGREE BURNS “Charring bone" Less common IV. INTRODUCTION TO APPROACH TO A PATIENT WITH TRAUMA (BURNS) The Advanced Trauma Life Support (ATLS) course of the American College of Surgeons Committee on Trauma was developed in the late 1970s, based on the premise that appropriate and timely care can improve the outcome for the injured patient. ATLS provides a structured approach to the trauma patient with standard algorithms of care; it emphasizes the “golden hour” concept that timely, prioritized interventions are necessary to prevent death and disability. Trauma is defined as cellular disruption caused by an exchange with environmental energy that is beyond the body’s resilience which is compounded by cell death due to ischemia or reperfusion. Figure 19. Inhalation Treatments of Smoke Inhalation Injury. The ATLS provides a structured approach to trauma: “Lifted from lecturer ppt” Primary survey or concurrent resuscitation Secondary survey or diagnostic evaluation A. AIRWAY MANAGEMENT WITH CERVICAL SPINE Definitive or diagnostic evaluation PROTECTION Tertiary survey The first priority in the primary survey is ensuring a patent airway. Management of blisters in the ER: This is crucial because O2 delivery to the blood depends on a patent 1st and 2nd day – leave it alone airway, and without O2, the cardiovascular system cannot function 3rd day – can be popped but leave the dead skin to provide a properly. temporary covering of the wound At the same time, all patients with blunt trauma require cervical Water from the blister is removed as it contain stasis bacteria spine immobilization until injury is excluded. This is accomplished by Irrigate and apply wet to dry dressing if the wound is large placing: Placing sandbags on both sides of the head with the patient’s V. PRIMARY SURVEY forehead taped across the bag. Cervical collars are NOT recommended for penetrating neck The first step in patient management is performing the primary wounds because they provide no benefit and may interfere with survey (concurrent resuscitation), the goal of which is to identify assessment and treatment. and treat conditions that constitute an immediate threat to life. ATLS course refers to the primary survey as assessment of the Must ensure patency of airway and consider airway protection. “ABCDEs” Visual inspection: airway cleared of any debris, blood and Airway management with cervical spine protection foreign bodies Breathing Administration of oxygen is needed Circulation with hemorrhage control Application of hard cervical collar or sandbags on both sides of Disability and Neurologic status the neck to immobilize neck (except with penetrating trauma) Exposure/Environmental NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 8 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Manual airway maneuvers: serve to elevate the tongue out of the Hemorrhage Temporize with direct pressure, tourniquets, hypopharynx control or tying blood vessels Jaw thrust (Esmarch maneuver) Surgical intervention Chin lift Head tilt is inappropriate with cervical spine control Table 3. Approach to Shock Indications for Emergency Endotracheal Intubation D. DISABILITY AND NEUROLOGIC STATUS Acute airway obstruction The Glasgow Coma Scale (GCS) score should be determined for all Hypoventilation injured patients. Severe hypoxemia despite supplemental oxygen It is calculated by adding the scores of the best motor response, Altered mental status (e.g., GCS 60 mmHg Palpable femoral pulse: SBP >70 mmHg Palpable radial pulse: SBP >80 mmHg Pail skin or nail bed capillary refill time >2 seconds indicates poor peripheral perfusion Figure 21. GCS Computation if Patient is Intubated/Unable to Verbalize. APPROACH TO SHOCK “Lifted from lecturer ppt” Differential Hemorrhagic or blood loss for shock Cardiogenic (tension pneumothorax, Management of disability: tamponade, blunt cardiac injury, ACS) Airway maintenance Neurogenic Supportive: seizure control, treat hypoglycemia Treat increased intracranial pressure (e.g., sedation, mannitol, Venous IV catheterization with two large-bore (14- hypertonic saline, surgical decompression) access 16 gauge) catheters Venous cutdown (basilic or saphenous vein) VI. SECONDARY SURVEY Insertion of central line (internal jugular, Once the immediate threats to life have been addressed, a thorough subclavian or femoral vein) history is obtained, and the patient is examined in a systematic Intraosseous route (either the proximal tibia fashion. or distal femur) The patient and surrogates should be queried to obtain an AMPLE history: Initial fluid 20 mL/Kg IV bolus isotonic crystalloid (plain Allergies resuscitation lactated ringer’s) Medications Assessment of response to fluid Past illnesses or pregnancy resuscitation Last meal and time of meal Facilitate blood transfusion as needed Events and Environment related to the injury NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 9 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  It is a rapid, systematic, and head-to-toe examination approach to Zones can be broken down into smaller sections or added together the injured patient. (i.e., front & back of the arms are 4.5% each) Aside from history and physical examination, it includes special Example: an adult with burn injury to both legs (18% x 2), groin procedures such as radiography, laboratory tests, scans, and (1%), chest (9%), and abdomen (9%) would involve 55% of the peritoneal lavage body If referral from EMS, Do your own assessment of the patient. Repeat Hx, PE, VS- Don’t rely on the endorsement. ALWAYS remember to protect yourself first- PPE Listen to the endorsement, go directly to the patient for the hx- If pt. is incapable of providing information (especially since they are in pain)- go to the relative/guardian. If the patient is living alone-without support, it is best to admit the patient One may immediately insert the IVF line for appropriate fluid resuscitation. Never insert a foley catheter in a patient with genital burn especially those with hematuria. In head trauma, we perform head CT to ensure that there is no basal skull fracture before we insert an NGT due to the possibility of the tube being inserted at the fracture site itself directly to the brain. ALWAYS KNOW THE MECHANISM OF INJURY. VII. BURN ASSESSMENT This is a process of evaluating the severity and extent of a burn Figure 22. Rule of Nines injury, as well as the potential complications and treatment options. “Lifted from the Lecturer’s Ppt The depth and degree of the burn, which indicate how much of the skin and underlying tissues are damaged. The size and location of the burn, which determine the percentage of the total body surface area (TBSA). RESUSCUTATIVE PERIOD DEFINITIVE MANAGEMENT (First 48 HOURS) PERIOD (>48 HOURS) Assessment of burn injury Excision and grafting Classification of burn injury Control of infection Criteria for admission Nutrition Initial (ER) management Rehabilitation Fluid resuscitation Complication Wound dressing Monitoring Table 5. Overview of Burn Injury Management A. ESTIMATION OF BURN SIZE (TBSA) Burn size is expressed as percent total body surface area burned (%TBSA). Count only those areas with partial (second degree) or full thickness (third degree) burns. For estimating smaller, irregularly placed burns: consider the area of the open hand (including the palm an extended fingers) of the patient to be approximately 1% of TBSA. Other tools are available to estimate burn size (see below): A.1 RULE OF NINES OR RULE OF WALLACE Figure 23. Rule of Nines in Adults and Children “Lifted from the Lecturer’s ppt“ Assesses the percentage burn, used to help guide fluid resuscitation. Rough estimate only (not accurate on children). The number corresponds to the % involvement (usually 9%) for that body part: Each arm = 9% Each leg = 18% Front of torso (chest & abdomen) = 18% Back of torso (upper & lower back) = 18% Head = 9% Groin = 1% NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 10 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Figure 25. Lund-Browder Chart “Lifted From Pinterest“ A.3 BERKOW DIAGRAM TO ESTIMATE BURN SIZE (%) BASED ON AREA IN AN ISOLATED BODY PART For estimation of the extent of burn, one should use a burn diagram in which the % of BSA represented by anatomic parts at various ages is reflected. Example: A 6-year-old male was seen at the ER for burn injury. Half if his anterior trunk is burned. Using the chart below, %BSA burned is 6.5% (1/2 of 13%) Figure 24. Palmar Method “Lifted from the Vicburns.org“ A.2 LUND-BROWDER CHART More accurate method of assessing burn extent for children. Takes into consideration the age of the patient, with decreasing %BSA for the head and increasing %BSA for the legs as the child ages. There are three zones of the body that varies depending on age Table 6. Berkow Diagram to Estimate Burn Size (e.g., head, thighs, & lower legs). Example: A 5-year-old female with burns in her right buttocks and entire right thigh has a 10.5% BSA involvement (8% for entire right thigh and 2.5% for right buttocks). Table 7. Assessment of Burn Depth NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 11 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Time of injury Consideration of abuse Height and weight Possibility of Carbon Monoxide intoxication Facial burns Tetanus immune status VIII. FLUID RESUSCITATION Most common cause of mortality in the 1st 48 hours following a burn injury is inadequate fluid Patients with moderate and major burns will require fluid resuscitation via intravenous route (those with minor burns are encouraged to increase oral intake) It is possible to insert on the burned area- always choose site that is least burnt- femoral and jugular may be used. For young patients, last option may be on the bone- Intraosseous, in the Proximal Tibia and the Distal Femur The calculated fluid requirement should only serve as a general guideline to the amount of fluid needed, and end-points of resuscitation need to be monitored (sensorium, temperature, urine output, pulse, blood pressure, base deficit). Most common formula used is the Parkland or Baxter formula (for initial 24 hours): Table 8. Classification of Burn Injury IVF Requirement= TBSA burned (%) x Weight(Kg) x 4mL/Kg o IV fluid required is 3 to 4 mL/Kg per %TBSA burned (Lactated Ringer’s) o Half given during the first 8 hours after burn o Remaining half over subsequent 16 hours o Calculate fluid loss from the time of injury, and take into account the fluid administered by prehospital personnel for fluid replacement o Example: A 75 kg adult sustains a 20% body surface area burn. The fluid replacement will be delivered as follows: o IVF req= 20(%) x 75 (Kg) x 4ml/Kg = 6,000 mL/cc =3,000mL given within 8 Hours =3,000 given for the next 16 Hours For children, use the Galveston formula (for initial 24 hours): 5,000 mL per BSA (m2) per %TBSA burned + 2,000 mL per BSA (m2) D5% Lactated Ringer’s o Half given during the first 8 hours after burn o Remaining half over subsequent 16 hours Add dextrose to the resuscitation fluid in children to prevent hypoglycemia, because children have smaller glycogen stores than adults The standard Parkland formula commonly underestimates fluid Table 9. Burn Severity Categorization and Management requirements in a burned child B. INITIAL EMERGENCY ROOM MANAGEMENT Fluid needs for the Second 24 hours Postburn: Application of Emergency Room Management After the capillary leak has reversed itself, colloids (5% albumin Primary Survey and Concurrent Resuscitation: in Ringer’s lactate or fresh frozen plasma 0.5%mL/Kg/%TBSA A: Airway burned/day) are administered in the second 24 hours following B: Breathing burn. C: Circulation Colloid volume is subtracted from the calculated crystalloid rate D: Disability Amount of crystalloids (D5 Water for adults, D5 ½ or ¼ Normal E: Environment control and exposure Saline for children) depends in the maintenance requirements F: Fluid resuscitation plus the amount of transcutaneous evaporative losses from burn In patients with burns in the face especially flame burns: wounds (1 mL/Kg/%TBSA/day). ALWAYS CONSIDER INHALATION INJURY: Act Amount is titrated to maintain normal urine output and mean immediately to stabilize the patient: Ready Intubation arterial pressure (MAP) Optimal MAP (for adequate end-organ perfusion) = 60 mmHg Secondary Survey (burn-specific): Urine output goals: History o Adults: 0.5 mL/Kg/hr Detection of the mechanism of injury o Children: 1-1.5 mL/Kg/hr NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 12 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Deep partial- Consider excision and grafting; initial thickness or full dressing should control bacterial thickness wounds proliferation and provide occlusion. Table 12. Choice of Dressing Table 10. Resuscitation Formulas Table 13. Biologic Coverings IX. WOUND MANAGEMENT A. WOUND DRESSING C. TOPICAL ANTIMICROBIAL AGENTS USED IN BURN CARE Performed in the sterile areas Antimicrobials are used to prevent and treat invasive wound Give patient a full body bath using warm water & soap infections in burn patients. Debride the burned areas, removing dead skin and unroofing blisters They can be given topically or systematically, depending on the type Wash the burn areas with betadine soap and rinse with sterile water and extent of the burn wound. Dress wounds with a topical antibacterial or another dressing Topical antibiotics can be classified into salves, soaks, and modality antimicrobial dressings, each with its own pros and cons. Salves are applied directly to the wound with cotton dressings, but may lose their effectiveness over time and cause shearing and pain during dressing changes. Soaks are solutions poured into cotton dressings, but may cause skin maceration and require constant monitoring of the solution level. Antimicrobial dressings are impregnated with silver or other agents, but may need to be kept moist and changed less frequently. X. ESCHAROTOMIES Escharotomies are surgical procedures (can be done at bedside) to release the burn eschar that constricts the circulation or ventilation of the affected body parts. They are indicated for deep partial-thickness or full-thickness burns that encompass the circumference of an extremity or the trunk. Table 11. Burn Wound Dressings They are performed by incising the eschar longitudinally along the lateral and medial aspects of the extremity or the chest. B. WOUND CARE They aim to restore the venous outflow and arterial inflow to the After the airway is used and resuscitation is underway, attention distal beds or to improve the chest excursion and tidal volume. must be turned to the burn wound. They are usually done at the bedside with a scalpel or electrocautery Treatment depends on the characteristics and size of the wound, unit, and may be followed by excision and grafting of the wound. and all treatments are aimed at a rapid and less painful healing. They may cause complication such as blood loss, transient hypotension, reactive hyperemia, and further edema formation in Burn wound treatment involves 3 stages: the muscle. Assessment, Management, and Rehabilitation: They may require additional fasciotomies if the muscle compartment o After assessing the extent and depth of the wounds, pressures remain high after the escharotomy. proceed to wound management. o Thoroughly clean and debride the wounds during this phase. Dressing functions: Protect damaged epithelium Minimize bacterial and fungal colonization Provide splinting action to maintain function Reduce evaporative heat loss and cold stress Offer comfort over painful wounds WOUND TYPE DRESSING Superficial epidermal No dressing needed; topical salves keep wounds skin moist Partial-thickness Daily dressing changes with topical wounds antibiotics, cotton gauze, and elastic wraps or longer dressings containing silver NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 13 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  Table 15. Formulas to predict calorie needs in severely burned children RECALL CHECK POINT! A. Identify the corresponding equivalent % of each body part using the Rule of Nines: 1. Each arm 2. Each leg 3. Front of torso (chest & abdomen) 4. Back of torso (upper & lower back) 5. Head 6. Groin B. TRUE OR FALSE 7. In estimating smaller, irregularly placed burns: we consider the area of our open hand (including the palm an extended Figure 26. Recommended escharotomies. In limbs requiring fingers) to be approximately 1% of TBSA escharotomies. The incisions are made on the medial and lateral sides 8. Deep partial-thickness burns are those that are limited to of the extremity through the eschar. In the case of the hand. Incisions the papillary dermis are made on the medial and lateral digits and on the dorsum of the 9. The zone of Stasis is the necrotic area of burn where cells hand. were directly disrupted “Lifted from https://thoracickey.com/burns/“ 10. Smoke burn injury, a very severe type of injury occurs when you breathe in smoke, hot air, vapor in an enclosed area XI. NUTRITION Severe burn causes hypermetabolism, which is a state of increased 1. 9% O2 consumption, metabolic rate, urinary nitrogen excretion, and 2. 18% 3. 18% lipolysis. 4. 18% Hypermetabolism is proportional to the size of the burn and can last 5. 9% 1% for 9 to 12 months after injury. 6. 7. F. The patient’s hand Hypermetabolism leads to high energy utilization and depletion of 8. F. Superficial partial-thickness burns carbohydrate, fat, and protein stores, resulting in malnutrition and 9. F. Zone of Coagulation F. Inhalational burn injury its complications. 10. Malnutrition affects the function of many organs, the healing of the wound, and the immunity of the patient. References: Malnutrition can be prevented by providing adequate exogenous Schwartz’s Principles of Surgery 11th ed., pages 183 and 251 nutritional support, which is the main goal of nutrition therapy in Sabiston Textbook of Surgery 21st ed., page 484 burn patients. Surgery Platinum 1st ed., page 161 Caloric requirements in burn patients can be estimated by using the Dr. Cinio’s Lecture Harris-Benedict formula, (2 x basal energy expenditure). However, this formula may overestimate the actual energy Legend: expenditure, which is: COLOR SCHEME CODES BURN PATIENT ENERGY EXPENDITURE Black Exactly from lecture presented #262626 (PowerPoint slide) Pediatric burn patients (>40% 1.3 x predicted basal energy Red Important concepts #C00000 TBSA) expenditure Pink Clinical correlations or significance #CF6E8A Convalescent burn patients 1.1 x predicted basal energy Blue Explanation of doctor not found in slide #0070C0 expenditure Green From old transes but not presented in #549E39 Table 14. Energy expenditure in specific burn patients class Violet Additional info from book #7030A0 Curreri formula is another common method to estimate caloric Orange Reading assignment answers #E36C0A requirements in burn patients. It is based on 25 kcal/kg/day plus 40 kcal per %TBSA burned per day, which covers the maintenance and burn-related needs. It was derived from nitrogen balance data in severely burned adults, but may not be suitable for children. The recommended formulas for children vary by age group: NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 14 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 15 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 16 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 17 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 18 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 19 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 20 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 21 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 22 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 23 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  NOTE TAKERS: ʕ ᴥ ʔっ♡PELLARADA, PAAC ฅ(՞ ‫ ﻌ‬՞)ฅ MED212 SEM2 Page 24 of 24 Last date edited: 02/11/2025 | Editor / QC: Rivera  P.03A SYSTEMIC RESPONSE TO INJURY AND METABOLIC SUPPORT DR. ABRAHAM CINIO | JANUARY 18, 2025 OUTLINE I. OVERVIEW II. INFLAMMATION III. MULTIPLE ORGAN FAILURE IV. SEPSIS V. PERSISTENT INFLAMMATION, IMMUNOSUPPRESSION, AND CATABOLISM SYNDROME (PICS) VI. PHASES OF SYSTEMIC RESPONSE TO INJURY VII. INDUCERS VIII. PPRs / PATTERN RECOGNITION RECEPTORS (GERM- LINE ENCODED) IX. GENERAL CLASSIFICATIONS OF HORMONES X. CNS REGULATION OF INFLAMMATION IN RESPONSE TO INJURY XI. NEURO-ENDOCRINE RESPONSE TO INJURY Figure 1. Process of inflammation and innate immunity. I. OVERVIEW Lifted from lecturer’s ppt. Inflammatory response to injury Sign to restore tissue function and eradicate invading II. INFLAMMATION microorganism Defense mechanism by which the immune system recognizes and Injuries of limited duration are usually followed by functional removes harmful foreign stimuli and begins the healing process. restoration with minimal intervention. By contrast, major insults Response to 2 kinds of insults: to the host are associated with an overwhelming inflammatory Injury in the epidermal & dermal layer of the skin response that without appropriate and timely intervention, can Contamination of the wound by bacteria lead to multiple organ failure and adversely impact the patient’s survival. TYPES OF INFLAMMATION ACUTE SUB-ACUTE CHRONIC Trauma Causes Tissue damage → Insidious Leading cause of mortality and morbidity for individuals under trauma, microbial age 45 invasion, or A cellular disruption caused by an exchange with environmental noxious energy that is beyond the body’s resilience which is compounded compounds by cell death due to ischemia/reperfusion. Onset Rapidly → severe Long-term Understanding the complex pathways that regulate the local and in a short time inflammation systemic inflammatory response following severe traumatic injury Duration Few days 2-6 weeks Months to years is necessary to develop appropriate and targeted therapeutic Examples Cellulitis acute Diabetes strategies that will improve outcomes for these patients. Minor pneumonia mellitus (DM) host insults, result in a localized inflammatory response that is Irritable bowel transient. disease (IBD) Chronic kidney Immune system disease (CKD) Prevent or limit infection E.g: Immune compromised people including those with genetic Generally, the extent and effects of chronic inflammation may vary immune disorders, immune debilitating infections like HIV, and with the cause of the injury and the ability of the body to repair and even pregnant women who are susceptible to a range of microbes overcome the damage. that do not typically cause infections in healthy individuals. Danger Associated Molecular Patterns (DAMPS) Danger queues used by the immune system distinguishing from normal healthy cells and unhealthy cells. Ligand for damaged cells Pathogen Associated Molecular Patterns (PAMPS) Signals released by infectious microbes Ligand for microbial components Unhealthy cells due to: Infection Cellular damage by non-infectious agents (sunburn or cancer) NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 1 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  There is a substantial heterogeneity among each macrophage population which most probably reflects the required level of specialization within the environment in a given tissue. This heterogeneity is reflected in their morphology, the types of pathogens they can recognize, as well the levels of the inflammatory cytokines they produce. Cytokines, Interleukins (IL) and Tissue Necrosis Factor (TNF) Produce ROS (NO) killing phagocytosed bacteria 7. Inflammatory response continues until the foreign material is eliminated and the wound is repaired. III. MULTIPLE ORGAN FAILURE Figure 2. Steps of inflammation. Lifted from lecturer’s ppt. Steps: 1. Presence of the 2 insults > Bacteria and other pathogen enter wound. 2. Platelets from blood, release blood-clotting proteins at wound site. Platelets are mobilized to prevent further blood loss on the site of the wound. 3. Mast cells secrete factors that mediate vasodilation and vascular constriction. Delivery of blood, plasma, and cells to injured area increases. Mast cells have a widespread distribution and are seen predominantly at the interface between the host and the external environment. They are immune cells of the myeloid lineage and are present in the connective tissues throughout the body. The activation and degranulation of mast cells significantly modulate many aspects of physiological and pathological conditions in various settings. Mast cells normal physiological functions: Regulate: o Vasodilation o Vascular homeostasis o Innate and adaptive immune responses o Angiogenesis o Detoxification Figure 3. Severe burn injuries. 4. Neutrophils produced by the bone marrow making up the largest Lifted from semanticscholar.org. fraction of WBCs secrete factors that kill and degrade pathogens. A local inflammatory response always occurs in relation to trauma First responders playing the role of the first line of defense against and severe injury, or multiple traumas evoke a system inflammatory infectious organisms response caused by hormonal metabolic and immunological Address foreign invaders by eating them (phagocytosis) or mediators and is associated with the hemodynamic response. By taking them up into the cell (endocytosis). CASE: A subset of these patients will die within 24 hours of hospital admission, succumbing to overwhelming tissue injury and 5. Neutrophils and macrophages remove pathogens by phagocytosis. immediate organ damage. A second subgroup of patients who suffer 6. Macrophages secrete hormones called cytokines that attract a major host insult succumb to secondary organ damage remote from the injury site and die later (weeks) in their hospital course immune system cells to the site and activate cells involved in form an increasing percentage of the in-hospital trauma-related tissue repair. deaths. Hence, a dysregulated, overwhelming systemic Macrophages inflammatory response to the injury/hemorrhage and associated ischemia/reperfusion events → implicated as the cause of multiple Specialized cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. organ failure in these patients → + linked to immune suppression Present antigens to T- cells and initiate inflammation by releasing that increases the risk of infectious complications and poor outcome. molecules known as cytokines that activate other cells Originate from blood monocytes that leave the circulation to differentiate in deferent tissues. NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 2 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  IV. SEPSIS Normal recovery after injury requires some period of systemic A systemic inflammatory response to a confirmed or suspected inflammation followed by a return to homeostasis, accompanied by infection. the suppression of the adaptive immunity. Infection → fever, chills, rapid breathing, confusion, extreme pain or discomfort → untimely treatment → organ failure and death. VI. PHASES OF SYSTEMIC RESPONSE TO INJURY So, the initial injury and subsequent operative treatments promote A. SYSTEMIC INFLAMMATORY SYNDROME (SIRS) a pro-inflammatory response which is exaggerated and may cause Pro-inflammatory phase organ injury like acute respiratory distress syndrome or multiple Characterized by activation of cellular processes designed to restore organ failure. Meanwhile, an anti-inflammatory response is involved tissue function and eradicate invading microorganisms. in reducing the potentially harmful effects of the pro-inflammatory response and enhances susceptibility to secondary infections which B. COMPENSATORY ANTI-INFLAMMATORY RESPONSE increases the risk of sepsis and septic complications. (CARS) Anti-inflammatory phase or counter regulatory phase in preventing excessive pro-inflammatory activities and in restoring homeostasis. Figure 5. Pattern of systemic inflammatory response. Figure 4. Postinjury systemic response can follow multiple Lifted from iacld.com. trajectories. MOF: multiple organ failures; PICS: persistent inflammation, immunosuppression, and catabolism syndrome; LTAC: long-term acute care facility. Lifted from bmjopen.bmj.com. Traumatic injury → activates innate immune system → systemic inflammatory response (SIR): acute pro-inflammatory response (from innate immune system recognition of ligands); anti- inflammatory response (modulates the proinflammatory phase & direct a return to homeostasis) → limit damage → restore homeostasis. V. PERSISTENT INFLAMMATION, IMMUNOSUPPRESSION, AND CATABOLISM SYNDROME (PICS) Characterized by extended length of stay in the ICU, complicated post-discharge courses, and failure to regain/recover to their preinjury status. Linked to persistent inflammation and suppressed host protective immunity Degree and duration of dysregulated acute inflammatory response Common denominator on the survivors of severely injured patients in all cases. Convalescence period Mediated by the counter regulatory anti- inflammatory response syndrome Period following Systemic Inflammatory Response Syndrome (SIRS) after injury Severe inflammation may lead to acute multiple organ failure and early death after injury. A lesser inflammatory response followed by an excessive counter regulatory anti-inflammatory response syndrome may induce a Table 1. Clinical spectrum of infection and systemic inflammatory prolonged immunosuppressed state that can also be deleterious to response syndrome (SIRS). (Review and Memorize!!!!) the host. NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 3 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  SEPSIS SEPTIC SHOCK Life threatening organ dysfunction Subset of sepsis with caused by a dysregulated host circulatory and cellular or response to infection. metabolic dysfunction associated with a higher risk of mortality. Clinical features of the injury-mediated SIR: Increased body temperature, heart rate, respirations, and white blood cell count similar to infection. Most common ways of monitoring patients: Monitoring vital signs and laboratory tests Degree of the SIR following trauma is proportional to injury severity → independent predictor of subsequent organ dysfunction and resultant mortality. The systemic inflammatory response is required for tissue repair and as evolved in all mammals to optimize the healing potential of an organism. In uncomplicated trauma patients with systemic inflammatory Table 2. Damage-associated molecular patterns (DAMPS) and their response, it is temporary, predictable, and is well balanced between receptors. pro and anti-inflammatory mediators. If the patient is exposed to major severe trauma, an initial B.1 HIGH MOBILITY GROUP BOX 1 PROTEIN (HMGB1) exaggerated proinflammatory response may be observed. The best characterized DAMP with significant preclinical evidence for post trauma release, as well as a direct link to the systemic VII. INDUCERS inflammatory response. Produced as a consequence of tissue damage or cellular stress as It is a constitutively expressed, non-histone chromosomal protein systemic inflammation following trauma is sterile. that participates in a variety of nuclear events, including DNA repair and transcription. A. PATHOGEN ASSOCIATED MOLECULAR PATTERNS Released passively (PAMPS) From damaged or necrotic cells and is detected rapidly in the Exogenous ligand circulation within 30 minutes post injury. Ex. In bacterial infection: Toll-like receptors (TLR) Released actively NOD-like receptors From immune-competent cells stimulated by bacterial-derived C-type lectin lipoproteins (e.g., PAMPS-endotoxin) or by inflammatory cytokines (e.g., tumor necrosis factor and IL-1). B. DAMAGE ASSOCIATED MOLECULAR PATTERNS (DAMPS) Abundant non-histone component of chromatin known for its two OR ALARMINS binding domains (HMGB1 box A and box B). Endogenous ligands Main characteristic is as architectural factor for its ability to Immunologically active recognize and bind with high affinity to distorted DNA and its ability Released passively from necrotic or damaged cells (actively from to induce kinks in linear DNA fragments. physiologically stressed cells) Correlated to cancer progression, elevated expression occurred in Interact with specific cell receptors that are located both on the cell certain types of primary tumor including melanoma, colon, prostate, surface and intracellularly. pancreatic and breast cancers. ATP, NO, Fatty Acids In majority of cases, it is associated with invasion and metastasis. MOA: Release of DAMPs → outside the cell → activation of innate In normal tissues: immune cells + recruitment + activation of antigen presenting Proteins: soluble form cells → host defense. Tumor cell: insoluble form and membrane bound Trauma DAMPS Structurally diverse endogenous molecules that are immunologically active. NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 4 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  Figure 7. The role of HMGB1/TLR4 in tendon disease. Figure 6. The HMGB1 signaling pathway. Lifted from rmdopen.bmj.com. Lifted from lecturer’s ppt. HMGB1 binding to TLR4 triggers the proinflammatory cytokine Inflammatory signaling can redirect HMGB1 to the cytosol in both release that mediates “sickness behavior.” monocytes and macrophages, as a result of post translational Once outside the cell, HMGB1 has been shown to signal via the Toll- modification. like receptors (TLR2, TLR4, TLR9), the Receptor for Advanced Main signaling pathway is activated through the interaction of Glycosylation End products (RAGE), CD24, and others. HMGB1 with its Receptor for Advance Glycation End products The activation of TLRs by HMGB1 occurs mainly in myeloid cells, (RAGE). whereas RAGE is thought to be the receptor target for HMGB1 in Elevated expression of RAGE and HMGB1 is not always a endothelial cells. prerequisite of poor prognosis of tumor development. The data concerning HMGB1 protein and RAGE in various tissues and tumor cells reflect the overall production of the proteins. However, they do not refer to their cellular localization and there is no direct evidence for the formation of a stable complex between them. In studies, they have investigated the subcellular distribution of HMGB1 and RAGE in various organs compared to ascites and tumor cells. HMGB1 forms a stable complex with RAGE only in their protein extract derived from the cancer cells predominantly in the membrane fraction. Pro-inflammatory cytokine and receptors are found on the myeloid cells and receptor target ion endothelial and somatic cells. The diverse pro-inflammatory biological responses that result from HMGB1 signaling include: The release of cytokines and chemokines from macrophage/monocytes and dendritic cells. Neutrophil activation and chemotaxis. Alterations in epithelial barrier function, including increased permeability. Increased pro-coagulant activity on platelet surfaces; among others. Figure 8. HMGB1 release and redox activity. HMGB1 can be passively released or actively secreted from the indicated immune and cancer cells under stress. The activity of HMGB1 varies with the redox states of the cysteine residues (C23, C45, and C106). All-reduced HMGB1 has sole chemokine activity, whereas disulfideHMGB1 has only cytokine NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 5 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  activity, and all-oxidized HMGB1 has neither. DC, dendritic cell; NK, Characteristics: natural killer cell. Part of innate immune system, non-adaptable and doesn’t change Lifted from semanticscholar.org. over the course of individual’s lifetime. Can be recruited and be brought into action by antibodies The biologic function of HMGB1 is regulated by its redox state. generated by the adaptive immune system. Ex. A thiol at C106 is required for HMGB1 to promote macrophage Consists of a number of small proteins found in the blood which TNF release, while a disulfide bond between C23 and C45 confers is synthesized by the liver that circulates as inactive precursors or pro-inflammatory properties. pro-proteins. With all three cysteines in the thiol (reduced) state, HMGB1 loses When stimulated by one of several triggers, proteases in the its DAMP function, but gains the capacity to serve as a system cleave specific proteins to release cytokines and initiate chemotactic mediator. an amplifying cascade of further cleavages. Importantly, shifts between the redox states have been The end result of this compliment activation cascade is demonstrated and indicate that redox state dynamics are stimulation of the phagocytes to clear foreign and damaged important regulators of HMGB1. material inflammation to attract additional phagocytes and activation of cell killing membrane attack complex HMGB1 levels in human subjects following injury correlate with the: Over 30 proteins and protein fragments make up the complement Injury severity score system including serum proteins and cell membrane receptors. Complement activation Account for 10% of globulin fraction of blood serum. Increase in circulating inflammatory mediators such as tumor necrosis factor Figure 9. Injury severity score sample. APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment Score; SIRS: Systemic Inflammatory Response. Syndrome Score; PATI: Penetrating Abdominal Trauma Index; ICISS: CD-based Injury Severity Score; TMPM-ICD9: Trauma Mortality Prediction Model; TRISS: Trauma Related Injury Severity Score; ASCOT: A Severity Characterization of Trauma; ICISS: international Classification of Figure 11. The end result of the cascade. Diseases Injury Severity Score. Lifted from lecturers ppt. Lifted from lecturer’s ppt Complement System B.2 HEAT SHOCK PROTEINS Figure 10. The complement system. Lifted from slideshare.net. Functions: Enhances ability of the antibodies and phagocytic cells to clear Figure 12. Diverse roles of HSP70 in carcinogenesis in response to microbes and damaged cells from an organism. stress. Activation of HSF1 in response to heat shock stress and Promotes inflammation and attacks the pathogen’s cell oncogenic activation (orange lightning) leads to overexpression of membrane. HSP70 and its co-chaperones (e.g., Bag3) promoting tumorigenesis through the following mechanisms: (A) Suppression of apoptosis: Hsp70 inhibits both intrinsic and extrinsic apoptotic pathways by NOTE TAKERS: BULAYUNGAN, CORPUZ, DIARON, MARTINEZ MED212 SEM2 Page 6 of 30 Last date edited: 01/31/2024 | Editor / QC: RIVERA  blocking APAF1 recruitment to apoptosome, inhibiting BAX Release of mitochondrial DNA and formyl peptides from damage or translocation to mitochondria, suppressing AIF-1 expression and other dysfunctional mitochondria has been implicated in the activation of stress-induced kinases; (B) Bypass of senescence: HSP70 inhibits both the macrophage inflammasome, a cytosolic signaling complex that p53-dependent and-independent senescence pathways; (C) Promotion responds to stress. of autophagy: Localization of HSP70 to the lysosomes in cancer cells stabilizes the lysosomal membrane to promote autophagy, and (D) Activation of additional HSPs: HSP70 serves as a co-chaperone to HSP90 and is required for the proper maturation of HSP90 client proteins such as HER2, AKT, and CRAF. Lifted from m.cafe.daum.net. “Stress proteins” Large and diverse family of intracellular proteins expressed during times of inflammation and oxidative stress or following tissue injury. Very highly conserved across species. Function as molecular chaperones to monitor and maintain appropriate protein folding. Capable of binding foreign proteins and thereby function as intracellular chaperones for ligands such as bacterial DNA and endotoxin. Presumed to protect cells from the effects of traumatic stress and when released by damaged cells, alert the immune system of the tissue damage by activating both innate and acquired immunity. Released from intact cells via a non-classical secretory pathway, both via “secretory lysosomes” as well as the exosome pathway. MOA: Once outside the cell, free HSPs can bind to pattern-recognition receptors (PRR) as well as other cell surface receptors to modulate the inflammatory response. In the context of massive cell damage or large exosome release, HSPs may serve as proinflammatory DAMPs. In contrast, HSPs released by active secretion may exert anti- inflammatory immune dampening signals. B.3 MITOCHONDRIAL DAMPS Mitochondrial proteins and/or DNA can act as DAMPs by triggering an inflammatory response to cellular necrosis and stress. Mitochondrial DNA (mt DNA) released from damaged or dysfunctional mitochondria leads both to inflammasome activation Figure 13. Working model of the innate immune sensing of tumors and activation of the Stimulator of Interferon Gene pathway leading to spontaneous T-cell responses in vivo. (STING). Lifted from europepmc.org. Cold Inducible