21/6 Flashcards
Describe protamine and its desired effects
Protamine is a polycationic peptide that binds to heparin to form a stable ion pair without anticoagulation activity.
Ionic complex is removed by reticuloendothelial system.
Returns ACT to baseline.
Can have weak anticoagulation effect at large doses
Describe the adverse effects of protamine
Type 1 - hypotension from histamine release. Avoid by slow injection
Type 2 - anaphylactic reaction. IgE or anaphylactoid
Type 3 - catastrophic pulmonary vasoconstriction from activation of heparin-protamine complex with leucocyte aggregation or arachidonic acid pathway released TXA
What is the normal range of activated clotting time?
ACT 70-120s
What is the MoA of gabapentinoids?
Binds to the alpha2 delta subunit of VG Ca Channel on the presynaptic membrane -> reduces glutamate release and decreases activation of NMDA receptors
Describe the side effects of gabapentin
Sedation, dizziness, withdrawal seizures
What is the MOA of paracetamol
COX inhibitor centrally -> inhibits PG synthesis in CNA
How many lung segments are there?
10 in right lung (3 upper, 2 middle, 5 lower)
- Upper: apical, posterior, anterior (APA)
- Middle: medial, lateral
- Lower: add basal to the five segments above (apical basal)
9 in left lung (5 upper, 4 lower lobes)
- Upper: apical, posterior, anterior, inferior division superior and inferior.
- Lower: apical, anterior/lateral/posterior basal
What is the clinical diagnosis of inadequate reversal from NMB?
tidal volume <5ml/kg, vital capacity <20ml/kg, inspiratory force <40cmH2O, head lift <5s, hand grip <5s, sustained jaw clench.
Only sensitive for <50% receptor occupancy
Describe ToF
4 supra maximal stimuli over 2 secs, detection of fade, Ratio of >0.9 is adequate reversal.
Describe double burst stimulus
2 short bursts of 50Hz tetanus (3 impulses) separated by 750ms, more accurate for fade, able to detect up to 60% receptors occupancy.
How can one avoid increase in PVR under GA?
Blunt SNS response on laryngoscopy, which can increase PVR
Avoid nitrous
Avoid hypercapnia and acidosis
High FiO2
Optimal ventilation
What drugs can lower PVR
GTN, inhaled nitric oxide, inhaled prostacyclin (iloprost), milrinone, vasopressin
What is vasopressin
Vasopressin is a nonapeptide produced in the supra-optic and paraventricular nuclei of hypothalamus and stored in the posterior pituitary
Describe the action of vasopressin
What are the analogues?
V1 - vasoconstriction
V2 - insertion of aquaporin to collecting duct, increases plasma VWF and factor VIII
V3 - found mainly in pituitary
Vasopressin, DDAVP, terlipressin
Describe the use of vasopressin in the peri-op setting
Bleeding - DDAVP has 1500x VC activity, increases vWF by 4x, dose 0.3microg/kg
Variceal bleeding - terlipressing on V1, portal VC, also useful for hepatorenal syndrome
Shock - infusion of 1-4U/hr in catecholamine refractory shock
Diabetes insipidus - 2microg IV to treat cranial DI
What is laser and what does it comprise?
light amplification by stimulated emission of radiation and comprises 3 main components
- energy source
- lasing medium (solid, gas, liquid)
- optical resonator
Describe the hazards of laser
- energy transfer to inappropriate location (eye damage, skin burn, fire risk from nearby fuel)
- Laser plume can cause bronchospasm / laryngospasm
- embolism
- Tissue/vessel perforation
What is microshock
low current that is delivered directly through heart muscle at 0.05 to 0.1mA
Structure the answer for how to minimise risk of microshock
Equipment
- Grounding of equipment
- Residual current device will protect against macro but not microshock
- Line isolation monitors, also no protection from microshock.
Environment
- General wiring standards to ensure safety of electrical equipments
- isolation transformers
- Equipotential earthing system
Patient
- ensure patient is not earthed
- Insulated from any metal
- patient skin kept dry
- on a non-conducting mattress
Describe the principle of an automated oscillometric non-invasive monitor
Oscillometry - variation in oscillatory amplitude of pressure within a deflating cuff overlying an artery
Cuff is inflated to completely occlude artery, slow deflate, and analyse oscillatory signals
What are the components of a non-invasive BP cuff
- cuff with inflatable bladder
2. Air insufflation port and pressure transduction port
Describe the oscillometric analysis
First onset - approximate systolic pressure
Point of maximal oscillatory amplitude - MAP
Point of maximum reduction in rate of change - DBP
- Can also assume diastole as a fixed fraction (3MAP - SBP)/2
Describe the sources of error from blood pressure cuff
Patient erros
- Irregulat pulse rate
- Excessive movement
- Very low BP
- Calcified non-compressible artery
- Pain from high NIBP
Equipment
- Wrong cuff size, which should be 20% larger than arm diameter
- Placement (need to be at heart level)
- External compression
- Calibration or transducer errors
What is the shunt equation
What are the sources of physiological shunt?
Qs/Qt = (CcO2-CaO2) / (CcO2-CvO2)
Bronchial veins and Thebesian veins
Discuss the factors that affect oxygen transport from alveoli to tissues
Oxygen cascade.
Fick’s law of diffusion at the alveolar level.
- Alveolar gas equation
- Pressure gradient: high supplemental FiO2, hyperbaric
- Decreased PaCO2
- High Hb, CO, pulmonary perfusion
Pulmonary -> systemic circulation
- Venous admixture
- V/Q mismatch and shunt
Systemic to tissues
- pressure gradient by O2Hb curve, offloading capacity determined by degree of right shift.
- P2 decreases if there is increased myoglobin or O2 extraction
- Recruitment and distension to aerobic exercise, of capillary bed.
Cytotoxic
- Cyanide inhibition of oxidative phosphorylation.
What is the effect of sevoflurane on the airway anatomy?
Bronchodilation and increases anatomical DS
Decrease airway reflex for toleration of LMA, increases aspiration risk
decreases pharyngeal dilator tone
Decreases ciliary activity
What is the shelf lives of suxamathonium and rocuronium at room temp?
sux 2/52
roc 2/12
What is the volume of distribution of muscle relaxants?
0.2L/kg
What is the breakdown product of sux?
choline and succinic acid
Describe the metabolism and eliminination of rocuronium
95% excreted unchanged
- 60% via bile, 40% via kidneys
- Reduced dose in either impairments, or prolonged blockade.
- 5% liver metabolism into active 17-desacetylrocuronium
What is the percentage change in cardiac output in pregnancy and what are the contributions
What is the change in blood pressure?
50% increased in cardiac output by third trimester
20% increased heart rate from baseline
40% increased in stroke volume from baseline
10% reduction in overall blood pressure (due to reduced SVR) - drop in DBP more than SBP, increased pulse pressure
What changes lead to hypercoagulability in pregnancy
Increased level of factors I, VII, VIII, IX, X, XII, vWF
Reduced level of protein S
Due to oestrogen
Outline the storage lesion changes for PRBCs
Cellular: spheroidal, rigid and fragile RBCs, 25% loss at 4/52, antigenic WBCs, PLTs inactive at 48 hrs.
Biochemical - pH 6.7 due to additives, K+ up to 30mM, 2.3 DPG at 50% by 2/52, 5% at 4/52, increase free haemoglobin
How would you calculate the dose of protamine?
1mg per 100U heparin.
Lower dose used in cardiac theatre, around 50% of dose to account for metabolism for lapse of time.
Anti-coagulant effect at high dose.
According to ACT/APTT normalisation
Comparatively shorter half life of protamine may result in a heparin rebound.
What amount of blood transfusion will constitute a massive transfusion
50% of blood volume over 4 hours, or 100% of volume over 24 hours
Describe storage lesion
Adverse effects associated with the storage of blood.
Cellular
- spherical red cells.
- 25% loss at 4/52
- Inactivated but still antigenic white cells.
- Platelets inactivated at 48 hours
Coag factors - FV 50% at 3/52, FVIII 30% at 3/52
Metabolic - cold storage at 4 degrees, pH 6.7, K up to 30mmol, Citrate, reduced 2.3 DPG 5% at 4/52
Describe the immunological effects of blood transfusion
acute - anaphylaxis, febrile non-haemolytic (cytokines), febrile haemolytic due to ABO/RhD, TRALI
delayed
- alloimmunisation: delayed haemolysis (Kell/Kidd/Duffy), haemolytic disease of new born
- Graft vs host donor WBC overwhelms host bone marrow.
- Transfusion related immune modulation (TRIM): MOA unknown, due to WCC releasing cytokines.
What is a competitive antagonist and how does it affect the quantal response curve?
Drugs with intrinsic activity of 0
Right shift of the quantal response curve. Reduce potency, but still able to achieve max efficacy at higher dose.
What is the therapeutic index, LD50 and ED 50 of morhpine?
ED50 7mg
LD50 500mg /kg
TI = 70mg
What is glomerulotubular feedback
A constant amount of Na/Cl/H2O reabsorbed from proximal tubule.
Reduce glomerular filtration -> increase oncotic pressure at the peri-tubular capillary which favours reabsorption
Describe renal potassium handling
180L/day x 4mM/L = 720mM filtered per day.
Fixed reabsorption 95% (65% PCT, 30% LoH)
Compulsory excretion of 5%
Secretion stimulated by aldosterone
How much acid can the renal phosphate system secrete daily?
30mmol/day at baseline
Up to 60mmol day
H2PO4 -> H+ + HPO4- at pKa 6.8
List the regions important for autonomic innervation
Nucleus tracts solitarius - receives afferent signals.
RVLM - SNS
dorsal vagal nucleus / nucleus ambiguus - PNS
How the the vagus nerve innervate the heart?
R branch - SA node
L branch - AV node
m2 receptors, Gi -> reduce cAMP
Fast onset compared to SNS
Minimal inotropic effect, but can reduce inotropy by interneuronal effect
What is the mechanism of milrinone?
PGE3 inhibitor -> reduce cAMP breakdown
Midazolam
- PO bioavailability?
- Onset and peak effect
- Duration
- Protein binding
- VDSS
- T1/2Ke0
- Clearance
- T1/2b
50% 2 and 10 mins 1-6 hours 98% 1.5L/kg 4 mins 5-10ml/kg/min 2 hours
Describe the metabolism and excretion of midazolam
liver phase 1 via CYP3A4 then phase 2 conjugation
Active metabolite a-OH-midaz (50% active), oxazepam
- These undergo glucuronidation
<1% excreted unchanged.
What hormones increase BGL?
glucagon, cortisol, catecholamines, growth hormones.
Ratio of insulin: glucagon determines effect
List the key enzymes for glucose / glycogen metabolism
Glycolysis - glycogen phosphorylase
Glycogenesis - glycogen synthase
Lipolysis - hormone-sensitive lipase
Lipogenesis - lipase, acetyl-CoA carboxylase, fatty acid synthase
Ketogenesis - acetyl-coa thiolase
Describe the stimuli that increase insulin secretion
- Increase BGL
- increase amino acid, fatty acid
- GIT secretagogues like GLP-1, GIP
What is the mechanism for B-islet cells to secrete insulin?
Increase BGL -> increase ATP -> inhibition of K+ channel -> depolarisation -> calcium influx -> exocytosis
1st phase - preformed insulin, onset 2 mins, duration 15 mins
2nd phase - newly synthesised, onset 15 mins, duration 2 hours.
Describe the effect of catecholamine on BGL
Generally increase BGL
- binds to B2 receptor on a-islet cells -> increase glucagon
- Also b2 on SKM -> stimulates glycogenolysis
- B3 on brown fat -> lipolysis
- B1 on what fat -> reduce glucose uptake
What is the side effect of misoprostol?
diarrhoea
Describe prostaglandins
Groups of arachidonic acid derivatives
- Autocrine and/or paracrine
- inhibitory or excitatory
- PGs may have opposing effects
- Different effect on different tissues.
What is the effect of PGI2 on different tissues?
Vascular smooth muscle - vasodilation
Bronchiole - Bronchodilation
Uterus / GIT / Utreters - none
Renal - direct vasodilation / activation of RAAS for VC
What are the different PGE receptors and GPCR?
EP1 - Gq
EP2,4 - Gs
EP3 - Gi
what are the effects of PGE2 on different tissues
Bronchioles - EP2/4 BD, EP1/3 BC
Vascular SM - EP2/4 VD
Uterus / GIT - EP1/3 contraction
- Think misoprostolol
Ureters - dilation
Renal - direct VD, activation of RAAS for VC
What are the effects of PGD2 and PGF2a
On bronchioles - BC
PGF2a also causes uterine and ureteric contraction
PGD2 in mast cells, which cause BC
