Other physiology Flashcards
Hormone
Hormone is chemical secreted by a gland, transported in the circulatory system to transmit a message to a distant cell or other gland
Four classes of hormones
- Amine derived e.g. catecholamines
- Peptide - short chain e.g. ADH, long chain e.g. insulin
- Steroid e.g. cortisol
- Eicosanoids e.g. leukotrienes
Innate immune system
Immune system complex network of cells and organs designed to fight infection
Innate: first line, no prior exposure, non-specific rapid response to threat
- Anatomical - skin, mucociliary escalator, acidic stomach acid
- cellular
- neutrophils - phagocytosis
- monocytes - become macrophages in tissue
- NK cells - destroy virus infected cells
- mast cells - inflammatory mediators
- proteins
- compleement
Inflammation
non-specific response to
- trauma - mechanical damage causes vessel disruption and mast cell activation and haemostasis
- infection - macrophage phagocytose organisms and release cytokines il-1 il-6 TNF
Symptoms - pain, redness, swelling, heat
series of events
- vasodilation (histamine)
- capillary leak (TNF, histamine)
- Migration of phagocytes
- microorganism killing, removal of debris
Complement
Plasma proteins activated
- contact with bacterial cell wall
- exposure to antibody-antigen complex
Once activated
- bacterial cell lysis (membrane attack complex)
- opsonisation - coat microorganism, binding site for phagocytes
- chemotaxis - attract phagocytes
Peri-operative period and immune function
Disruption of barriers - site of surgery, endotracheal intubation
Exposure to allergens
Depression of immune system
- stress response - depress lymphocyte
- opioids impair macrophages
- transfusion related immunomodulation
- preoperative hypothermia
Normal nutritional requirements for healthy adult
25kcal/kg/day (Harris-Benedict equation estimates BMR)
Critical illness recovery - 30kcal/kg/day
- Protein 1.5g/kg/day
- lipids 40%
- Carbohydrates rest
Electrolytes
- 1-2mmol/kg/day sodium
- 1mmol/kg/day potassium
Malnutrition
Condition of insufficient vitamins, minerals and other nutrients to maintain health.
In ITU can lead to
- poor wound healing
- increased risk of infection
- muscle weakness - delayed ventilation and mobilisation
Refeeding syndrome
Metabolic disturbances occurring after reinstitution of nutrition to a patient who has been malnourished for a prolonged period. Characterised by severe hypophosphataemia. complications include rhabdomyolysis, cardiac failure, seizures.
Sudden shift from fat to carbohydrate metabolism leading to sudden increase in insulin –> massive cellular uptake of phosphate, Na, K, Mg –> low serum levels and fluid shifts
Management
- Slow nutrition 10kcal/kg/day
- aggressive treatment of electrolyte abnormalities
- careful fluid balance
Pathophysiology of alcoholic liver disease
Steatosis
- metabolism of alcohol leads accumulation of lipids
Alcoholic hepatitis
- alcohol metabolism generates reactive oxygen species which trigger inflammation
Cirrhosis
- prolonged hepatocellular damage generates my-fibroblast like cells that produce collagen
- as hepatocytes are destroyed and liver architecture changes, hepatic function falls and there is increased resistance to portal blood flow
Hepatorenal syndrome
Advanced liver disease causing reduced GFR
Creatinine > 133 in patient with ascites when all other pathologies excluded
Generalised vasodilation causes AngII, SNS, ADH, subjecting kidney to reduced perfusion
HRS 1 - rapid and severe progressive renal failure (< 2 weeks). precipitated by infection, GIB etc
HRS 2 - slowly progressive moderate deterioration in renal function
Hepatic encephalopathy
Confusion, altered level of conscious and coma due to liver failure (neuro toxins)
1 - confused
2 - drowsy
3 - stupor, rowsable, agitated
4 - coma
Child - Pugh
prognosis, necessity for transplant
1 / 2 / 3 points
- Encephalopathy grade none / 1-2 / 3-4
- Ascites none / easy controlled / poor control
- Bili
- Albumin
- PT
Anaesthetic implications for end-stage liver disease
Preop
- assessment / MDT
- optimise fluid, electrolytes, nutrition, coagulopathy
- consider paracentesis
- delayed gastric emptying
Intraop
- drugs - altered handling, reduced metabolism, increase Vd
- neuraxial caution due to coagulopathy
- invasive monitoring but caution ODM
- glycemic control
- thermoregulation
- abx prophylaxis
Haemostasis
- Vessel injury - vasoconstriction, expose collagen, TF with platelet binding via VwF
- Initial platelet activation by binding to collagen. initial activation of V and VII to generate small amounts of thrombin. forms procoagulant surface
- Next cohort of platelet activation via ADP receptors causing release of numerous molecules (TXA2, ADP, thrombin, Ca) and crosslinking fibrinogen via GPIIb/IIIa receptors to make soft platelet plug
- Massive generation of thrombin - amplification phase
- Thrombin catalyses fibrinogen to fibrin and formation of firm scaffold - propagation phase
- Anticoagualant pathways - Protein C, S, fibrinolysis. Fibrinogen cleaves by plasmin (formed from plasminogen). FDP, d-dimer. TXA inhibit action of plasminogen
Initiation, amplification, propagation
Clotting tests
PT - test of extrinsic pathway (VII, II, X of common). TF added to sample. INR is ratio of PT to average PT of control sample. Prolonged by warfarin, liver disease, DIC
APTT - intrinsic (VIII, IX, XI, XII) and common pathway. Prolonged by UFH, haemophilia, VWF, DIC
Hypothermia definitions
Temp < 35
Mild 32-35
mod 28-32
sev < 28
Physiological consequences of severe hypothermia
CVS
- Bradycardia
- Reduced CO
- Peripheral vasoconstriction
- J waves and arrhythmias
- Increased blood viscosity
RS
- Apnoea below 24
- reduced O2 delivery - reduce CO, left shift oxyHb dissociation curve
Neuro
- confusion < 35 unconscious < 30
- Reduced MAC
Other
- diuresis
- acidosis
- reduced BMR
methods of rewarming
Passive
- blankets, remove wet clothing, increase ambient temperature
Peripheral Active
- forced air warmer
- Chemical heat pad
Central Active
- warmed fluids 42C
- warm bladder irrigation
- warm inspired gases if intubated
- RRT / ECMO
In cardiac arrest - VF shock 3x below 30 then wait until 30
No adrenaline until 30 then every 10 mims
Rewarming and IV fluid ++ as vasodilation causes expansion of IV space
IOP
- increased or decreased volume of globe content e.g. aq / vit humour, haemorrhage
- external pressure - retrobulbar haematoma, prone position
regulation by control aq humour
Aqueous humour
- ciliary bodies - active secretion and untrafiltreation
- flows from posterior chamber over lens through iris and into anterior chamber
- drained via trabecular network and canal of schlemm (between cornea and lens)
- reabsorption depends on IOP and venous pressure
- raised in IOP can be compensated by increased drainage. production is constant
- glaucoma reduces draiange
- prone position increases episcleral venous pressure
Occular blood flow
- arterial - similar factors to cerebral blood flow e.g. vasodilation from hypercapnoea and hypoxia
- venous drainage impairs by increased pressure outside globe each head down and prone
IOP in peri-operative period
increased
- positioning -p prone, trendelenberg
- induction - laryngoscopy, ETT ties, suxamethonium (fasciculation’s of EOM increased IOP)
- extubation - cough, strain
Control of IOP
- head up 20-30 degrees
- induction - obtund reflex to laryngoscope, avoid ETT ties, avoid sux
- maintenance - PCO2 4.5-5, PO2 > 13
- smooth emergence or deep extubation
- all iv and volatile agents apart from ketamine reduce IOP
- antimetics to reduced PONV
- acetazolamide reduced AQH production, mannitol draws water out
Liver physiological functions
Metabolic
- Storage of glycogen
- Breakdown of glycogen to increase glucose, glycolysis and glyuconeogeneis
- lipolysis and lipogenesis
- protein metabolism
- storage of other compounds e.g. iron, copper
- break down of drugs
Immuno
- kipper cells specialised macrophages antigen recognition phagocytosis
Synthetic functions
- albumin and plasma proteins
- clotting factors
Endocrine
- hormones e.g. IGF-1 and angiotensinogen, hepcidin
- hormone binding proteins e.g. thyroxine binding globulin
- Vit d 25-hydroxilation
Blood reservoir
Drug metabolism
Phase 1
- aim to make water soluble - more polar, hydrophilic via CYp450
- oxidation, reduction, hydrolysis
- drugs then transported in plasma to kidneys and excreted
Phase 2
- drugs that aren’t rendered water soluble by phase 1
- addition of further group and increasing polarity - sulphation, gluroindation, acetylation
Jaundice
Pre-hepatic
- bili prduced exceeds liver capacity to conjugate - unconjugated (water insoluble, negative urine)
Post-hepatic
- conjugated leaks into circulation - water soluble
Hepatic
- reduced ability to conjugate and excrete. can be conjugated and unconjugated
Functional liver
Acinus
2 porta triads and central vein in middle
- zone 1 - high o2 - most energy consuming processed e.g. gluconeogenes
- zone 2 - intermediate
- zone 3 - least energy consuming e.g. drug metabolism
hepatic blood floow
1/3 arterial 2/3 portal venous
auto regulation to MAP of 60 via HA
PV flow directly proportional to pressure gradient
HA buffer response - compensate for reduced PV flow - vasodilation via adenosine
extrinsic mechanisms
- SNS - constrict HA
- SNS activation causes benoconstriction and 250ml blood returning to circulation
Physiological effects of magnesium
- Antagonism of Ca
CVS - reduce vascular smooth musclee tone - decreased PVR, SVR
- inhibition of catecholamine
- reduced myocardial contractility
Resp - reduce smooth muscle tone - bronchodilator
MSK - Ca responsible for nerve impulse transmission at NMJ - antagonised by Mg. Loff deep tendon reflexes, muscle paralysis, cardiac conduction abnormalities
Massive transfusion
circulating volume within 24hrs
half circulating volume in 4 hrs
Blood products
RBC - plasm removed, citrate adenine and glucose added. stored at 4C, 42 shelf life
FFP - plasma removed from whole blood, stored at -30, 1yr shelf life. coagulation factors
Cryoprecipitate - FFP frozen to -70, thawed and centrifuged. Factors VIII, XIII, fibrinogen, VwF
platelet - pooled from multiple donors, room temp, 5 day shelf life, irradiated
Immune complications red cell transfusion
haemolytic
- recipients plasma contains antibodies to donor red cells leading to haemolysis
- Immediate - ABO incompatibility rapid intravascular haemolysis
- delayed - exposure to minor rh antigens - re-exposure delayed reaction 7-21 days later
febrile non-hemolytic
-recipient antibodies react with antigesn on donor leucocytes. rare since leucodepletion
anphylaxis
- foreign protein in donor blood cross reacts with recipient IgE
TRALI
- antibodies in donor blood attack recipient tissue (immune TRALI). Non-immune TRALIE - neutrophil activated
GVHD
- imunocompormised patient T lymphocytes in donor blood launch immune response against recipient
Non-immune complications of blood transfusion
infective
- septicaemia - bacterial contamination e.g. platelets stored at room temp
- ID transmission - Hep, HIV
non-infective
- TACO
- haemosierosis
Additional complications of massive transfusion
Hypothermia (cold blood transfused)
Dilutional coagulopathy (balanced protocols)
Hypocalcaemia / citrate toxicity - citrate used in storage to prevent coagulation. massive transfusion –> citrate toxicity
hyperkalaemia - stored blood has high K+
acidosis - stored blood has pH 6.8=
Obesity definitions
BMI < 18.5 underweight
18.4 - 24.9 - healthy weight
25 - 29.9 - overweight
30 - 34.9 - class 1 obesity
35- 39.9 - class 2 obesity
40 + = class 3 obesity
Pathophysiology of obesity
Resp
- difficult airway, OSA
- reduced complicance
- reduced FRC (below CC) - atelectasis, V/Q mismatch
- Increased O2 consumption
CVS
- Increased CO
- Hypertension
- IHD - dyslipidaemia, DM
- HPVC –> RVF
GI
- GORD - intragastric pressure
- Fatty liver and gallstones
Endocrine
- Insulin resistance and T2DM
MSK
- OA
- Gout
Immune
- low grade inflammatory state - cancer
Practical problems with anaesthesia
- higher difficulty with practical procedure, including access, RA, surgery, intubation
- monitoring - BP cuffs
- positioning
- special equipment
TIVA and obesity
PK models derived from normal weight
Marsh - TBW for induction and maintenance. in morbid obesity will lead to overdose, limited to 150kg
Scnider - age, height, TBW to calculate LBM, only accurate up to BMI 42 - higher maintenance infusion
NICE paediatric fluid regimes
resuscitation
- glucose free crystalloid Na 131 - 154
- 10ml/kg (10-20ml/kg in neonate)
maintenance
- isotonic, non-glucose
- 4:2:1 ml/kg/hr
- 100:50:20 ml/kg/day
Measure plasma electrolytes daily
in neonatal period may need glucose
frailty
decline in physiological reserve across numerous organ systems which results in reduced capacity to compensate for external stressors
- adverse outcomes
- assessed by rockwood, Edmonton, timed up and go
Physiological changes of aging
Resp
- Airway - edentulous - easier laryngoscopy, harder BVM. cervical spondylosis - reduced neck ext.
- loss of elastic tissue - increased compliance, offset by reduced chest wall compliance (calcification of costal cartilages).
- FRC increases, higher resting lung volume
- weaker respiratory muscles
- greater A-a gradient - V/Q mismatch, reduced diffusion capacity of alveoli
CVS
- stiff arteries - hypertension
- greater pressure required by LV - LVH
- LVH impairs relaxation, diastolic dysfunction, dependent on atrial kick
- reduced Beta adrenergic activity - less increase in HR with exervise
- conduction system fibrosis - arrhythmias
- valvular calcification and degeneration
CNS
- loss of brain cells - atrophy
- loss of DA - PD
- cognitive impairment 20% 80+
- sensory impairment - visual / auditory
Renal
- reduced GFR - progressive loss of glomeruli
Hepatic
-reduced size and blood flow, reduced protein synthesis
skin/msk
- thin skin, reduced subset tissue
- fragile veins
- pressure sores
- sarcopenia
- bone deformity and thinning, arthritis
Functions of skeletal muscle
- locomotion
- posture and joint stability
- support of soft tissues e.g. pelvic floor
- sphincters - voluntary control over swallowing, mictuiriton
- heat production
- venous return
structure of skeletal muscle
macroscopic
- muscle fibres (myocytes) supported by connective tissue
- endomysium - CT surrounding each myocyte
- perimysium - surrounds 100 myocytes
- epimysium - thick CT surrounding whole muscle
all merge to form tendon, connecting to bone
microscopic
- sarcoplasmic reticulum containing calcium
- t-tubules - invaginations in muscle surface memrane which relays action potential into interior
- myofibrils - contractile apparatus of cell - length of myocyte, anchored to sarcolemma so when contract shortens / extends
- myofilament - actin / myosin. bundles make up myofibrils
sarcomere
functional unit of the myocyte
- thick filament - myosin
- thin filament - actin
1:6
my-filaments regular overlapping pattern - striated appearance
myosin - 2 heads , long tail, heads have actin / ATP binding site
actin- double strand chains, myosin binding sites along length. two proteins lie in actin - tropomyosin (obstructs access) and troponin T / C / I.
Different bands ZIAH z –> I –> A –> H
Excitation-contraction coupling
process of muscle fibre contraction following excitatory stimulus
AP from NMJ –> depolarisation –> T-tubule –> DHPR –> SR –> Ryanodine receptor –> calcium from SR –> trop C –> tropomyosin away from actin –> myosin/actin crosslink
Sliding-filament
Myosin head binds ATP, hydrolysed to ADP, energised myosin head binds to actin
myosin head flexes on actin binding site, pulling actin closer to centre of sarcomere
myosin head binds another ATP which allows dissociation from actin
crosslinking continues until intracellular calcium level drops and tropomyosin and troponin return to resting configuration
motor unit
single alpha motor neurone and the muscle cells it innervates - single AP will cause contraction of all the myecites within the motor unit
type 1 - slow twitch - postural muscles, fatigue resistant
2b - fast twitch, anaerobic - short, powerful movements
Thyroid hormones
- T4 - 90% of hormone released by thyroid gland. Weakly biologically active. highly protein bound to thyroxine binding globulin, long half life. 50% converted to T3.
- T3 - 10% thyroid output. highly bound to albumin, short half life.
Physiological effects of thyroid hormones
T3 regulates gene transcription in cell nucleus
- increase BMR, increased availability of metabolic substrates
- resp - increased MV due to increased o2 consumption and co2 production
- CVS - increased CO, increased HR (increases B receptors in heart)
- CNS - increased anxiety
- MSK - protein catabolism and proximal myopathy
Synthesis of thyroid hormones
Thyroid gland - spheres of follicular cells, surrounding thyroglobulin
Iodide uptake (secondary active transport from Na cotransporter) stimulated by TSH
Iodide diffuses across follicular cell
Iodide oxidised to I2 using H2O2 - promoted by TSH
I2 reacts with tyrosine residues on thryoglubilin
Iodination in 1 (MIT) or 2 (DIT) positions
Iodidinated tyrosine residuals couple together DIT + DIT = T4 MIT + DIT = T3
Autoimmune thyroid disease
Graves disease - Autoantibodies IgG mimic action of TSH - stimulating thyroid gland to release T3/4. also targets extraoccular muscles - proptosis, exophthalmos
Hashimotos thyroiditis - autoantibodies against thyroglobulin - reduced T3/4 output
Red cell antigens
30 + groups
Most important are ABO and rhesus
ABO - carbohydrate based antigen
Either -
O - none
A
B
A + B
Immune antibodies to red cell antigens
Immune system develops antibodies to foreign matierial, including non-self RBC antigens
- exposure to similar environment antigens
- exposure to foreign RBCs e.g. following transfusion
Antibodies to ABO antigens are IgM
Blood group O - anti-A and anti-B antibodies
A - Anti-B antibodies
B - Anti-A antibodies
AB - No antibodies
Antibodies to rhesus D
- IgG therefore cross placenta
- acquired on exposure to foreign RH (fetal-metrnal haemorrhage - of blood of RH+ fetus and RH- mother mix)
