Environmental/Toxicology Flashcards
What is the toxic dose for xylitol?
100mg/kg → hypoglycemia secondary to insulin stimulation (within 30-60 min)
500mg/kg → hepatotoxicity, acute hepatic necrosis (6-72 hours)
What is the MOA of anticoagulant rodenticide?
Inhibit Vitamin K epoxide reductase
What is the difference in terms of the treatment duration for 1st and 2nd generation anticoagulant rodenticide toxicity?
1st generation: 2 weeks
2nd generation: 4 weeks
For anticoagulant rodenticide intoxication, why do we measure PT instead of PTT?
PT is used to assess extrinsic pathway, and factor VII has the shortest half-life (6.2hr) → being able to detect the abnormalities earlier
For anticoagulant rodenticide intoxication, when should you check PT if vitamin K is not administered?
48 hours after exposure (this is when factor VII are all used up)
What is the onset of the clinical signs of cholecalciferol rodenticide toxicity?
4-36 hours
What is the lethal dose for cholecalciferol in dogs?
1.5 - 8 mg/kg
What is the general MOA of bromethalin?
Bromethalin and its more potent metabolite, desmethylbromethalin, cross the blood-brain barrier and uncouple mitochondrail oxidative phosphorylation by allowing H+ into the mitochondrial matrix –> no gradient to provide energy for ATP synthase –> no ATP –> failure of Na/K pumps –> cytotoxic oedema –> increased intracranial pressure.
What is the lethal dose of bromethalin for dogs and cats?
Dog: 4.7 mg/kg
Cat: 1.8 mg/kg
ER textbook: LD50 dog 2.4 mg/kg; cat 0.3 mg/kg
Main symptoms of bromethalin toxicity in dogs and cats
Dogs ingesting >LD50 present with acute convulsant syndrome vs CNS depression and paralysis with lower doses.
Cats have predominantly a depressive CNS form although seizures have also been reported.
Mortality is high in dogs but 100% in cats.
Does Strychnine cause a net inhibitory or excitatory effect of the CNS?
Net excitatory effect (because it inhibits the inhibitory pathway)
It blocks post-synaptic glycine receptor -> block the inhibitory effect of glycine on the spinal cord motor neuron -> exaggerated excitatory effect
What is the MOA of organophosphate toxicity?
Irreversibly binds to AChE → prevent breakdown of ACh → overstimulation of both the muscarinic and nicotinic receptors
True or False: Polyradiculoneuritis usually doesn’t cause autonomic dysfunction.
True
What is the MOA of metaldehyde toxicity?
In the stomach, metaldehyde undergoes partial hydrolysis in the stomach to produce acetaldehyde.
Metaldehyde decreases the concentration of GABA, serotonin and norepinephrine in the CNS → decrease the threshold for **seizures. **
**Monoamine oxidase **activity is increased following metaldehyde exposure.
Muscle tremors and the production of acidic metaldehyde metabolites cause severe electrolyte disturbances and metabolic acidosis.
What is the clinical triad for serotonin syndrome?
Altered mentation
Autonomic instability
Neuromuscular abnormalities
Where are most of the serotonin stored at?
Enterochromaffin cells and the myenteric plexus in the GI tract
List 5 effects of serotonin in peripheral nervous system.
Vasoconstriction
Bronchoconstriction
Urinary retention
Increased GI peristalsis
Platelet aggregration
Which amino acid is essential for serotonin formation?
Tryptophan
- Serotonin is formed in the body by hydroxylation and decarboxylation of the essential amino acid tryptophan by tryptophan hydroxylase
Can serotonin cross the BBB?
No
What are the two receptors mainly responsible for serotonin syndrome?
5-HT1
5-HT2A
What are the 5 mechanisms of serotonin toxicity?
1) Increased L-tryptophan → increased serotonin level in the neuron
2) Amphatamines → increased release of serotonin
3) MAO inhibitors → decreased serotonin metabolism → increased pre-synaptic level
4) Selective serotonin reuptake inhibitors (SSRI) → increased serotonin level at the synapse
5) Serotonin agonist → increased serotonin receptor activation
What type of drug is cyproheptadine?
Non-specific 5-HT1A and 5-HT2 receptor antagonist
What type of drug is chlorpromazine?
5-HT2 receptor antagonist; dopamine D2 receptor antagonist; phenothiazine derivative
* Side effect: hypotension
Similar to ACP but less potent
Does xylitol bind to activated charcoal? What about ethylene glycol?
Both toxins do not bind to activated charcoal
For NSAID intoxication, normally how long should the treatment be?
At least 3 half-lives
What are the 5 indications for extracorporeal therapies in AKI patients?
- Azotemia refractory to conventional medical management
- Anuria or severe oliguria
- Severe uremic signs
- Severe electrolyte or acid-base disturbances
- Life-threatening volume overload
What is the lethal dose of ethylene glycol in dogs and cats?
Dogs: 6.6 ml/kg
Cats: 1.5 ml/kg
What are the toxic metabolites of ethylene glycol?
In a retrospective study published in 2020 by Groover and colleague looking at extracorporeal blood purification in acutely intoxicated veterinary patients, what are the 4 most common complications? What is the survival rate and average time of hospitalization?
Complications (18.3%)
- Mild hypotension
- Thrombocytopenia
- Clotting of the extracorporeal circuit
- Hemorrhage
Survival rate: 83.3%
Average time of hospitalization: 49.2 ± 37.7 h
What is half-life of phenobarbital in dogs?
48 hours
What are half-life of diazepam and midazolam in dogs?
Diazepam: 2.5 hr
Midazolam: 1.9 hr
What is the dose of flumazenil for diazepam toxicity?
0.05 mg/kg IV
What is the MOA of Baclofen?
GABAb agonist
Why opioid can cause miosis in dogs?
Opioid stimulates the visceral nuclei of the oculomotor nuclear complex and the parasympathetic nerve that innervates the pupil.
True or False: Naloxone is a synthetic derivative of oxymorphone.
True
What is the dose of naloxone and what is the onset and duration?
Dose: 0.01-0.04 mg/kg
Onset: 1-2 minutes
Duration: 45-90 minutes
Why in 𝜷-blocker overdose/toxicity, mild hyperkalemia may be seen (2 reasons)
1) decreased cellular uptake of K+
2) lower aldosterone levels (β-blocker can suppress the catecholamine-induced renin release)
In a study published in 2004 by Vnuk and colleagues about high-rise syndrome in cats, falling from which floor or about which floor is associated with thoracic trauma?
7th floor or above
There are four degrees of burn wounds, what is their depth?
First-degree: only epidermis affected
Second-degree:
- Epidermis+ superficial part of dermis - Painful to touch, hair follicles preserved
- Epidermis + deep part of the dermis - hair follicle destroyed, decreased pain sensation
- Healing by contraction and epithelialization (may need surgery)
Third-degree: Epidermis + full thickness of dermis
- Insensitive to touch
Fourth-degree: full thickness burn with extension to muscles, bone and tendon
- In the JVECC review paper in 2012, they use superficial, superficial & partial thickness, deep partial thickeness, full thickness
In burn injury, how many percentage of the body surface area being involved can have severe metabolic derangement?
> 20%
- It is also classified as severe burn injury
In a study published in 2021 by Henriksson and colleagues about body surface area in dogs, what are the BSA of the follow body parts?
Head
Thorax
Abdomen
Thoracic limbs
Pelvic limbs
Head 14%
Thorax 18%
Abdomen 14%
Thoracic limbs 9%
Pelvic limbs 11%
In a study published in 2021 by Henriksson and colleagues about body surface area in cats, what are the BSA of the follow body parts?
Head
Thorax
Abdomen
Thoracic limbs
Pelvic limbs
Head 13%
Thorax 20%
Abdomen 15%
Thoracic limbs 7%
Pelvic limbs 12%
After severe burn injury, patients usually will experience two phases with very different hemodynamic status. What are these two phases and what are the timing?
1) Resuscitation phase (hypodynamic or ebb phase)
- immediately after injury till 24-72 hours later
- Hypovolemic, decreased cardiac output, increased vascular permeability, vasoconstriction, decreased peripheral blood flow
2) Hyperdynamic hypermetabolic phase (flow phase)
- 3-5 days after injury
- decreased vascular permeability, increased heart rate, and decreased peripheral vascular resistance resulting in an increase in CO
- Release of counter-regulatory hormones, cortisol, glucagon, and catecholamines are the drive
When do the exfoliation of tracheal epithelial lining of the trachea and main-stem bronchi occur after smoke inhalation?
3-5 days later
- High risk of bronchial obstruction
What is the definition of primary and secondary hypothermia?
Hypothermia: core body temperature **< 37 C **(98.6 F)
Primary: caused by excessive exposure to low environmental temperatures.
Secondary: a result of disease, trauma, surgery, or drug-induced alteration in heat production and thermoregulation
Where is the thermoregulatory center in the body?
Hypothalamus
What are the 4 primary mechanisms of heat loss?
Convection - body surface to air
Conduction -body surface to object
Radiation
Evaporation
Why hypotension develops in hypothermic patients?
Vascular responsiveness to norepinephrine at the α1-receptor decreases
Does hypothermia-induced bradycardia atropine responsive?
No
Why during severe hypothermia patient’s respiratory rate and tidal volume usually reduce?
Decrease CO2 production from the tissue → decreased respiratory drive
What is the most commonly seen acid-base imbalance during marked hypothermia?
Respiratory acidosis & metabolic acidosis
- Metabolic acidosis - decreased blood buffering capacity, decreased hepatic metabolism, decreased acid excretion from the urine, increased lactate due to shivering and decreased tissue perfusion
List 3 coagulation changes during hypothermia.
1) Thrombocytopenia (sequestration by the liver and spleen)
2) Decreased platelet aggregation (secondary to decreased production of thromboxane B2, decreased platelet granule secretion, attenuation of P selectin expression, and diminished expression of the von Willebrand factor receptor )
3) Prolonged aPTT/PT
For every 1C decrease in the temperature, how will the HCT change?
Increase by 2%
Explain the pathophysiology of cold diuresis.
Vasoconstriction (before core temperature drops) → relatively increased blood volume → diuresis
Core temperature drops → decreased response to vasopressin → unable to reabsorb water at collecting tubule
In moderate hypothermia, GFR decreases due to decreased cardiac output and renal blood flow
Explain the cause of hyperglycemia during moderate hypothermia.
1) Decreased cardiac output and renal blood flow → reduced renal clearance of glucose
2) Decreased insulin sensitivity
3) Decreased insulin secretion from the pancreas
What is the pathophysiology of rewarming shock?
Active external rewarming can cause peripheral vasodilation → relative hypovolemia and hypotension
What is core temperature afterdrop during the rewarming process?
- Usually happens at the beginning of the rewarming
- The cold peripheral blood returns to the core → decrease core body temperature even more
- These complications are most likely to occur when the extremities are warmed before the core; therefore application of external heat should be focused on the truncal regions of the body, not the extrem- ities.
What is the pathophysiology of rewarming acidosis.
The return of the peripheral blood is colder and has higher level of lactate → causes acidosis
- These complications are most likely to occur when the extremities are warmed before the core; therefore application of external heat should be focused on the truncal regions of the body, not the extrem- ities.
What is the recommended rewarming rate?
0.5 - 2 C/hr
When the environmental temperature increases, which two of the heat dissipation mechanisms are responsible for 70% of the thermoregulation?
Convection
Radiation
What are the three protective mechanisms of the body during increased heat?
1) thermoregulation
2) acute-phase response
- leukocytosis
- synthesis of acute-phase proteins ↑
- stimulate the hypothalamic-pituitary-adrenal axis, - activate endothelial cells and WBCs
3) intracellular heat shock proteins
- protect against denaturation of intracellular proteins - help to regulate the baroreceptor response during heat stress → preventing hypotension
Describe the pathophysiology of heat stroke
Release of IL-1 & IL-6 from the muscles + endotoxin from GI tract → WBCs & endothelium activation → proinflammatory and antiinflammatory cytokines + activation of coagulation cascade → microthrombosis & tissue injury → MODS
What number of NRBC is highly associated with death?
18 NRBC/100 leukocytes
When should the active cooling be discontinued in heat stroke to prevent rebound hypothermia?
103F
List 8 poor prognosis indicators in heat stroke.
Hypoglycemia
DIC
MODS
> 18 NRBC/100 leukocyte
Hypocholesterolemia
Hyperbilirubinemia
Hypoalbuminemia
Elevated creatinine
Ventricular arrhythmias
Obesity
Seizure
Prolonged aPTT/PT
At the same amperage, which will cause more severe injury, alternating current or direct current?
Alternating current
What type of arrhythmias does low-voltage current more likely to cause? What about high-voltage current?
Low-voltage current: V-fib
High-voltage current: asystole
Describe 4 types of hypersensitivity reactions and what immunoglobulins or cells are involved.
List 5 anaphylaxis mediators in the classic pathway.
Preformed
Histamine
Tryptase (activates complement and kallikreins)
Heparin (counteracts tryptase as it is an anti-complement and anticoagulant)
Chymase (conversion of angiotensin I –> angiotensin II to counteract profound hypotension)
Newly formed
PAF
Cytokines (Il-4, IL-13, TNF𝛼)
PGD2
SRS-A (Leukotrienes of late anaphylaxis)
What are the three mechanisms of anaphylaxis?
Immunologic
1) Classic pathway
Body is sensitized → IgE is produced and bind to mast cells or basophils (through FcεRI) → repeated exposure of the antigen → cross-link of bound IgE → cell degranulation (histamine, tryptophan, heparin, kallikreins, proteases, proteoglycans)
2) Alternative pathway (no pre-sensitization) due to mast cell activation via complement or immune-complexes deposition
Non-immunologic
* mechanical or chemical contact elicits degranulation of mast cells
Which anaphylaxis pathways cause more severe clinical signs?
Classic pathway (IgE)
There are the four types of histamine receptors. What are their functions?
H1
* Gq coupled
* Systemic vasodilation (H1 on epithelium not smooth muscle –> Gq increases release of NO –> diffuses to smooth muscle)
* Increase vascular permeability
* coronary artery vasoconstriction
H2
* Gs coupled
* gastric acid production
* produce coronary and systemic vasodilation
* increases in HR and ventricular contractility
H3
* counter balance presynaptic autoreceptor
* inhibit histamine release
* activation of sympathetic nerve system
H4
* increased chemotaxis and cytokine release from mast cells
What is the epinephrine dose for anaphylaxis?
0.05 mcg/kg/min IV via CRI
2.5-5.0 mcg/kg IV
If patient is on 𝜷-blocker and has anaphylaxis, what drug should you reach for?
IM or IV administration of glucagon
What is the rationale of glucocorticoid in anaphylaxis?
Suppress the arachidonic acid cascade → reduce the severity of the late-phase inflammatory reaction (4-6 hours)
Which type of hypersensitivity does serum sickness belong to?
Type III
What is the MOA of apomorphine?
Dopamine agonist (induce vomiting via D2 receptor)
What is the dose for gastric lavage in dogs?
60 - 90 ml/kg for 5-10 times
True or False: Intralipid 20% is hypertonic.
False
Isotonic (so can be given at peripheral vein)
What is the antidote for ethylene glycol? What is the MOA?
Fomepizole (4-MP)
Fomepizole is a competitive inhibitor of alcohol dehydrogenase
What are the two antidote for organophosphate?
Atropine
Pralidoxime chloride (2-PAM): competes for OP on acetylcholinesterase and prevents retention of OP on the receptor
How is intralipid metabolized?
cleared up by skeletal muscles, splanchnic viscera, myocardial cells, and subcutaneous tissues
→ broken down into glycerol, free fatty acids, and choline
Does activated charcoal work for bromethalin intoxication?
Yes
And it does undergo enterohepatic recirculation
Does activated charcoal work for cholecalciferol intoxication?
Yes
it also does undergo enterohepatic recirculation
List 4 treatments for cholecalciferol.
1) IV fluid therapy
2) Furosemide
3) Steroid administration (2–3 mg/kg/day prednisone or 0.1 mg/kg/day dexamethasone SP)
4) Bisphosphonates (pamidronate 1.05–2 mg/kg IV diluted in saline and given over 2 hours)
Write down the metabolism of ethylene glycol and the enzymes involved.
What clinical signs can glycoaldehyde cause?
CNS signs
- Ethylene glycol itself is also CNS depressant and can cause GI irritation
What metabolites from ethylene glycol contribute to AKI?
Glycolic acid → direct renal tubular epithelium injury
Oxalic acid → form calcium oxalate crystal and deposit in the tubular lumen
In ethylene glycol intoxication, when does the second phase kicks in? What about 3rd phase? What are the clinical findings in each phase?
Second phase: 12-24 hours after ingestion
- Metabolic acidosis, hypocalcemia, tachyarrhythmias
Third phase: 24-72 hours in dogs and 12-24 hours in cats after ingestion
- AKI, oliguria
In ethylene glycol intoxication, what is the earliest blood work change? What is normal osmolal gap?
Increased osmolal gap
Normal: < 10 mOsm/L
Why hyperglycemia may be seen in ethylene glycol intoxication?
Aldehyde metabolites can inhibit glucose metabolism
When does calcium oxalate monohydrate present in the urine?
3-6 hours after ingestion
What is the time frame for Kacey test?
Step 1: 45 minutes after exposure up to 8-10 hours for a positive on the Ethylene glycol test pad.
Step 2: 9 -16 hours Positive for Oxalate & Negative for Ethylene Glycol.
What is the MOA of fomepizole (4-MP) and ethanol?
inhibiting the function of alcohol dehydrogenase (ADH) so EG can be peed out
What is the dose for 4-MP?
20mg/ kg 5% IV initially, followed by 15mg/kg IV at 12 and 24 hours and 5mg/kg IV at 36 hours
In cats, a higher dose is required at 125 mg/kg IV initially, then 31.25 mg/kg IV at 12, 24, and 36 hours
True or False: Both COX-1 and COX-2 play a role in prostaglandin synthesis and maintenance of gastric mucosal integrity.
True
Does aspirin under enterohepatic recirculation?
No
What is the toxic dose for Naproxen and the organs involved?
> 5 mg/kg: GI signs
10–25 mg/kg: renal damage
50 mg/kg: CNS signs
List 3 electrolyte abnormalities in dogs with grapes/raisins toxicity.
Hypercalemia
Hyperphosphatemia
Hypokalemia/Hyperkalemia
What is the pathophysiology of cocaine toxicity? How is it metabolized?
Sympathomimetic effects from reuptake inhibition of NE, serotonin, and dopamine
Metabolized via hydrolysis by plasma and hepatic esterase and 10-20% is excreted unchanged in urine
- Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels.
What is the pathophysiology of Methamphetamine toxicity?
Sympathomimetic effects from inhibition of monoamine oxidase (MAO), increased catecholamine release, and direct dopamine and serotonin receptor agonism.
What is the toxic dose for xylitol to cause hepatic necrosis and hypoglycemia?
Hypoglycemia: > 0.1 g/kg
Hepatic necrosis: > 0.5 g/kg
What are the three main components in chocolate that contributes to its toxicity?
Caffeine
Methylxanthines
Theobromine
CNS stimulant
True or False: In human studies of burn injury, inhalation injury is an independent predictor of death.
True
Particularly in patients with cutaneous burns ≥ 20% BSA
According to 2016 NEJM Fire-Related Inhalation Injury, what is the recommended mechanical ventilation mode for smoke inhalation injury?
Pressure control, lung-protective ventilation
In patient with burn injury, what lab abnormalities raises concerns for cyanide toxicity?
persistent metabolic acidosis despite hemodynamic normalization
What is hunting reaction/response?
When the extremities/skin is exposed to cold temperature, there may be alternating vasoconstriction and vasodilation
Name 4 substances in the crotalinae snake venom and the clinical signs caused by each substance.
Crotalis are part of VIPERS
Venom mainly enzymatic:
* Hyaluronidase - break-down of connective tissue
* Phospholipase A2 - cytotoxicity, echinocytes, anti-Xa activity
* Proteinases - anticoagulants
* Phosphodiesterases - hypotension
* Snake Venom Metalloproteinases (SVMPs) - platelet dysfunction
Neurotoxin
Myotoxin - cardiotoxicity
True or False: The antivenom with F(ab’)2 has larger volume of distribution, less antigenic and shorter half-life compared to complete immunoglobins
True
What are the toxins for Coral snakes?
𝛼Neurotoxin
Hemolysin (phospholipidase)
Elapid snake
Ventilator
How do elapid snake neurotoxin work?
Pre-synaptic: phospholipase A2 group of toxins → prevent release of acetylcholine
Post-synaptic: antagonist at acetylcholine receptors
What is the Consensus formula (Parkland formula) for burn injury fluid therapy?
Administer isotonic crystalloid at (4ml x percentage of TBSA x BW) in the first 24 hours, with half of this amount administered at the first 8 hours, and the remainder over the rest of 16 hours.
- For cats: reduce the amount by 25-50%
True or False: According to the ABA guidelines, preload-driven strategies for burn resuscitation are strongly recommended to prevent fluid overload.
False
Preload-driven strategies for burn resuscitation are not advisable because neither preload or cardiac output restoration is achievable within the first 24 hours.
What is the recommended target urine output in patient with severe burn injury?
0.5-1 ml/kg/hr
- Human:
Adult 0.4 ml/kg/hr
Pediatric 1 ml/kg/hr
Mafenide acetate can be used in burn wound. What is the MOA?
Potent carbonic anhydrase inhibitor
True or False: According to the ABA guidelines, vitamin C is recommended for severe burn injury.
True
True or False: In severe burn injury, early and more aggressive surgical debridement attenuates hypermetabolic response and decreases infection rate.
True
Ethylene glycol is absorbed rapidly by the GI tract and metabolised by the liver within ____ h from ingestion. The non-metabolised portion is excreted unchanged via ____
2-3h
renal route
ways to diagnose ethylene glycol toxicity
- gas chromatography
- freezing point depression
- POC strips (Kasey)
- VBG (anion gap)
- Urinalysis (calcium oxalate monohydrate)
- Wood’s lamp
- Imaging with ‘halo’ sign
Main differences between vipers and elapids
Vipers
* movable front fangs
* mainly enzymatic venom with coagulopathy, myopathy, cardiotoxicity and hemotoxicity
* 25% dry bites
Elapids
* fixed fangs
* neurotoxicity with need of MV
If the antivenom is given soon enough it can reverse coagulopathy and tissue damage
False: can reverse only coagulopathy
Black widow venom
**𝛼-Latroxin **
Ach independent activation of Ca++ channels in NMJ leading to tetanic paralysis which then progresses into flaccid LMN paralysis
Antivenom available
Pain relief very important
Consider benzodiazepines
Violin spider
**Sphingomyelinase D **
Dermonecrotic
Coagulopathy
Hemolysis –> AKI
Bee stings - lethal dose
> 20 stings/kg
Bee venom
- Phospholipidase A (main allergen)
- Hyaluronidase (tissue damage and venom spread)
- Apamin (neurotoxin)
- Adolapin (anti-inflammatory)
- Mellitin (pain and hemolysis)
- Mast cell degranulation protein
PHAAMM
Wasp venom
Antigen 5 and phospholipidase
Fire ants
- Alkaloid (pain)
- Hyaluronidase
- Phospholipidase
Formation of sterile pustules
Bufo toads
- Parotid glands on dorsum - dogs lick them
- Lethal dose is full content of both glands
Bufagenin and bufotoxin –> digitalis –> cardiotoxic –> ventricular arrhythmia (propanolol)
Bufotenine –> similar to norepi and allucinogenic –> seizure watch
Metabolism of NSAIDs mainly via ____
Glucuronidation in liver
* cats more susceptible to toxicity
NSAIDs damage in the distal GI tract is due to….
Entero-hepatic recirculation and prolonged mucosal exposure
Grapiprant mechanism of action
EP4 (PGE2 receptor) antagonist
Reduction of inflammation and sensitization of peripheral nociceptors
Metamizole and dypirone mechanism of action
Anti cox-3
Very weak anti-inflammatory but potent analgesics
Similar to paracetamol, but can be given to cats
Classification of hypothermia
Mainly based on severity of clinical signs rather than core temperature
* Mild –> thermoregulatory mechanisms still intact (shiver, heat seeking) - ataxia and severe vasoconstriction
* Moderate –> decreased consciousness and CV instability
* Severe –> complete loss of thermoregulation, coma and ventricular arrhythmias
Pathophysiology of hypothermia
- hypothalamus senses low temp from central and peripheral afferents –> SNS activation with vasoconstriction + shivering + behavior
- initial vasoconstriction followed by loss of vascular response and vasodilation and bradycardia (J waves)
- decreased CO2 production with decreased respiratory drive
- loss of SNS responsiveness = broncoconstricion and increased secretions
- left shift of Hb curve contributing to hypoxemia
- metabolic acidosis due to lactate production, decrease liver metabolism and tissue hypoperfusion
- coagulopathy
- decreased CNS metabolism
- cold diuresis followed by drop in GFR
- immunoparalysis
Each drop of 1C = drop of …. in cerebral flow
6-10%
Ventricular fibrillation occurs in ____ of dogs with a temp of ____
This can only be defibrillated when temperature reaches ____
50%
23.5C
28C
For each drop of 2C GA recovery delayed by ….
40 min
due to drop in hepatic metabolism
Classification of hyperthermia
- True fever (new hypothalamic set point)
- Decreased heat dissipation (humid environment)
- Increased heat production (exercise induced)
- Pathologic/Drug-induced (malignant hyperthermia, MAO disorder)
Each increase of 0.6C increases caloric requirement by…
7%
Damage by electrocution is two folded…
Electrical current
* direct cell damage
* electrophoration
Heat
* burns
* coagulopathy with microthrombi formation
List and briefly explain the 3 phases of anaphylaxis
- Early phase: antigen cross-link IGg on mast cell –> TK linked –> IP3 –> Ca++ release –> exocytosis granules
- Midphase: activated TK phosphorylates PLC-B –> cPLA2 –> arachidonic cascade + PAF
- Late phase: synthesis of cytokines
PAF synthesis
Produced in mid-phase by PLA2 cleaving membrane phospholipids –> Lyso PAF (inactive) activated by LPCAT into PAF
Very important PAF can be reverted back into lyso-PAF by PAF-AH (acetyhydrolase)
if deficient higher odds of death in anaphylaxis
PAF role in anaphylaxis
- it is a vasoactive phopholipid causing severe hypotension via NO induction
- responsible for myocardial depressive factor
- vascular permeability activates endothelial cell contraction via Gq creating wider gaps –> massive loss of fluid (up to 35% IV volume over the first 10 minutes)
epinephrine blocks PAF receptors
Burn lesion - histological areas
- coagulation
- stasis
- hyperemia
Myocardial dysfunciton in burn injury
- inflammatory cytokinesrelease
- caspases activation by ROS and consequent cardiomyocyte apoptosis
- MIF released by damaged tissues
Smoke inhalation injury includes…
- upper airway injury: thermal direct
- lower airway injury: vasomotor and neural reaction to chemical exposure + obstruction
- parenchymal injury: epithelial damage from fine soot and toxins
Classification of drowning injury
- dry: laryngospasm (10%)
- wet: aspiration of fluid (90%)
Survivors of drowning usually aspirate less than ____
22ml/kg
Pathogenesis of drowning injury
Hypoxia due to combination of laryngospasm + aspiration of water –> dilution of surfactant –> atelectasia –> v/q mismatch
Hypoxia leads to cardiac and neurologic sequelae
Up to 20% of drowning victim will develop ARDS
Does cold or warm water drowing have better prognosis? Why?
Cold water
Diving reflex: bradycardia and vasoconstriction shunting blood to central organ and lowering metabolic rate
At 41C …
At 43C…
Over 43C…
permanent brain damage
severe organ damage with significant increase of mortality odds
diffuse cell necrosis and melting of protein structure
Up to ____ % of heat stroke patients develop DIC and ____ % develop AKI
48%
33%
Pathogenesis of CO toxicity
- hypoxemia due to formation of COHb
- binding to myoglobin –> myopathy and cardiomyopathy
- direct cytotoxic damage due to interaction with mitochondrial cytochromes
- binding with cGMP and independent induction of iNOs –> vasodilation with increased ICP and cherry membranes
Delayed neuropsychyatricsyndrome developing 3-10 days after due to severe neurologic hypoxia followed by re-introduction of O2 –> form or IRI
