Environmental Flashcards
What are consequences of CO toxicity that are unrelated to Hb
- Binding to myoglobin -> myocardial and muscular hypoxia -> arrhythmia, rhabdomyolysis
- Binding to guanylyl cyclase -> increased cGMP -> vasodilation (including cerebral) ->altered mentation
- Binding to cytochromes oxidase system -> disrupted oxidative metabolism -> generation for free radicals -> neuronal necrosis
- Increased platelet adherence -> increased risk of thromboembolic event
What are the 2 consequences of CO toxicity on Hb
- CO binds 2 of the 4 available hemes ->reduces O2 carrying capacity by 50%
- CO shifts the Hb dissociation curve to the left -> decreased O2 release to tissues
What is the affinity of CO for Hb compared to O2
200-240 times the affinity
What is the normal COHb
Up to 1%
What contributes to VQ mismatch following smoke inhalation
- Inhalation of irritants -> inflammatory response with secretion of neurokinins, calcitonin-gene related peptides (CGRP), other pro-inflammatory peptides -> bronchoconstriction, vasoconstriction, airway fluid accumulation
- Increased production of NO -> inhibition of hypoxic vasoconstriction
What is the mechanism of cyanide toxicity
- Inhibition of electron transport chain in the mitochondria -> impaired cellular ATP production
- Neurotoxicity
- Stimulation of chemoreceptors -> tachypnea
- Arrhythmias
What is the common delay for development of lung injury / neurological signs following smoke inhalation
Lung injury: 24-48h
Neuro signs: 10h to 6 days
In smoke inhalation, hydrogen cyanide toxicosis should be suspected in case of combustion of what materials
Wool, silk, cotton, paper, plastic
What is the half-life of CO in patients breathing room air vs breathing 100% O2
Room air -> 320 min
100% O2 -> 70 min
What inhaled therapies could be beneficial in smoke inhalation patients
- Beta2-agonists: cause bronchodilation, decrease inflammation, help airway clearance
- Epinephrine: causes bronchodilation and vasoconstriction, help airway clearance
- N-acetylcysteine: mucolytic, could help airway clearance but causes bronchoconstriction
- Heparin: reduces fibrin casts formation
What antidotes can be used for hydrogen cyanide toxicity
- Hydroxocobalamin (vitamin B12a) -> binds cyanide to form cyanocobalamin which is excreted via the kidney
(/!\ most commercially available vitamin B12 is already in the form of cyanocobalamin which has no benefit) - Amyl nitrate and sodium thiosulfate -> transform Hb into MetHb which binds cyanide, but also decreases O2 distribution to tissues
What are the different degrees of severity of primary hypothermia and their common clinical signs
- Mild (32-37°C): ataxia, thermoregulatory mechanisms intact (-> shivering, vasoconstriction)
- Moderate (28-32°C): decreased level of consciousness, hypotension, atrial dysrhythmias, loss of shivering
- Severe (20-28°C): coma, ventricular dysrhythmias (prone to Vfib), no shivering
- Critical (<20°C): imminent death
/!\ stages are different for secondary hypothermia
Where are temperature-sensing receptors located
- Anterior hypothalamus
- Spinal cord, abdominal viscera, great abdominal and thoracic veins (-> input to posterior hypothalamus)
- Skin (-> input to posterior hypothalamus)
What are the 4 mechanisms of heat loss
- Convection: transfer of heat from body surfaces to surrounding air
- Conduction: transfer of heat from body surfaces to objects in contact
- Radiation: transfer of heat to objects not in contact (eg. walls) regardless of the temperature of air
- Evaporation: loss of heat from moisture on body surfaces or through respiratory tract
(70% lost via radiation and convection)
What are the effects of hypothermia on cardiac rhythm
- Mild hypothermia leads to sympathetic activation -> vasoconstriction, tachycardia
- With progressive hypothermia -> decreased rate of SA node depolarization -> bradycardia (non-responsive to atropine)
- Prolonged duration of action potential and decreased conduction -> widening of QRS, prolonged PR interval, positive deflection of ST segment (“J-wave”)
- Progression to atrial fibrillation then ventricular arrhythmias and eventually Vfib
What are the effects of hypothermia on coagulation
- Primary hemostasis
- Sequestration of platelets in liver and spleen -> thrombocytopenia
- Decreased production of thromboxane B2, decreased platelet granule secretion, decreased P selectin expression, decreased vWF receptor expression -> decreased platelet aggregation - Secondary hemostasis
- Decreased enzymatic activity of coagulation factors
- Hypercoagulability and DIC due to release of catecholamines, steroids, thromboplastin
Coagulation testing commonly performed at 37°C ->will not reflect function in vivo
What is the effect of hypothermia on urine production
- Early peripheral vasoconstriction -> sensed increased effective circulating volume -> increased diuresis
- With progressive hypothermia, the distal tubule becomes less responsive to vasopressin
- Ultimately, decreased CO leads to decreased GFR
What electrolyte imbalances can be seen with hypothermia
Hyponatremia and hyperkalemia due to decreased Na-K ATPase function
What are the risks with Active external rewarming
- Cardiovascular shock due to peripheral vasodilation
- Rewarming acidosis (blood carrying lactate and metabolites returning to the core)
- Afterdrop (colder blood from extremities returning to the core)
- Thermal skin injury
What are methods of active core rewarming
- Heated intravenous fluids infusion (only works with high rates)
- Delivery of warmed humidified air (face mask, ET tube, HFNC)
- Warm peritoneal or thoracic lavage
(- Extracorporeal life support)
List different warming methods and their warming rates
- Passive external rewarming (only efficient if patient able to produce heat) -> 0.5-5°C/h
- Active external rewarming -> 0.5-4°C/h
- Active core rewarming:
- Warm air inhalation -> 1.0-2.5°C/h
- Peritoneal / thoracic lavage -> 1.5-2.5°C/h
- Extra-corporeal life support -> 4-10°C/h
What are the 3 mechanisms of protection from heat (which fail in heat stroke)
- Thermoregulation
- Acute-phase response: balanced production of pro-inflammatory and anti-inflammatory mediators
- Heat shock proteins
Explain the pathophysiology of heat stroke
- Failure of thermoregulation due to increased heat load (environment / exercise) and/or failure of heat loss mechanisms (airway obstruction, obesity) -> increased core temperature
- Direct injury of muscles due to heat -> rhabdomyolysis, release of IL-6 and IL-1
- Direct injury of GI -> translocation of endotoxin
-> trigger of inflammatory response - Inflammation + direct endothelial injury by heat -> activation of coagulation (release of thromboplastin = factor III which activates factor VII + release of kallikrein which activates intrinsic pathway), inhibition of fibrinolysis -> microthrombi + factor and platelet consumption
- Direct heat injury + hypoperfusion + cytokines + myoglobinuria + endotoxemia (tubular and glomerular damage) -> AKI
- Direct heat injury + cytokines -> endothelial injury in lungs and myocardium -> ARDS, myocardial injury, arrhythmias
- Cerebral hypoperfusion, hypoxia, hypoglycemia, microthrombi ->cerebral damage (very little direct heat injury in brain)
=> SIRS, MODS, DIC
What CBC parameter has a prognostic value in heat stroke
Nucleated red blood cells
nRBC > 18 / 100 WBC on presentation has Se 91% and Sp 88% to predict death
What are mechanisms of VQ mismatch in drowning
- Bronchospasm
- Wash out of surfactant by water leading to atelectasis
- Alveoli filled with water
- Infectious or chemical pneumonitis
- NCPE, ARDS
