Physiology Flashcards
1
Q
Tidal volume
A
The volume of gas inhaled or exhaled during a normal breath
2
Q
Residual volume
A
Volume of gas remaining after a maximal forced expiration
3
Q
Inspiratory Reserve Volume
A
Volume of gas that can be further inhaled at the end of a normal tidal inhalation
4
Q
Expiratory Reserve Volume
A
Volume of gas that can be further exhaled at the end of a normal tidal exhalation
5
Q
Vital capacity
A
Volume of gas inhaled when maximal expiration is followed by maximal inhalation
Sum of ERV, TV and IRV
6
Q
Functional Residual Capacity
A
Volume of gas that remains after a normal tidal expiration
Sum of ERV and RV
3000ml
7
Q
Closing Volume
A
Volume of gas over and above residual volume that remains in the lungs when small airways begin to close
8
Q
Closing Capacity
A
Lung capacity at which small airways begin to close
Sum of RV and CV
9
Q
Equation for Pulmonary Vascular Resistance
A
PVR = (MPAP - LAP)/CO X 80
Dyne.s-1/cm-5
10
Q
Factors Increasing PVR
A
PaCO2
Acidosis
Hypoxia
Adrenaline/Noradrenaline
Thromboxane A2
Angiotensin II
5-HT3
Histamine
High or low lung volume
11
Q
Factors Decreasing PVR
A
Alkalosis
Isoprenaline
Acetylcholine
Prostaglandins
Nitric Oxide
Increased peak airway pressures/pulmonary venous pressure
Volatile agents
12
Q
Dead Space
A
The volume of the airways in which no gas exchange occurs
13
Q
Anatomical Dead Space
A
Volume of the conducting airways that does not contain any respiratory epithelium
Nasal cavity to generation 16 terminal bronchioles
Measured by Fowler’s method - 2mls.kg
14
Q
Alveolar Dead Space
A
The volume of those alveoli that are ventilated but not perfused
15
Q
Physiological Dead Space
A
The sum of anatomical and alveolar dead space
Calculated using the Bohr equation
16
Q
Fowler’s Method
A
Measures anatomical dead space
Vital capacity breath of oxygen and then exhales through a nitrogen analyser
17
Q
Bohr Equation
A
Calculates physiological dead space ratio to TV
Normally around 30% / ratio 0.3
VD/VT = (PaCO2-PeCO2)/PaCO2
18
Q
The Pasteur Point
A
The oxygen concentration below which oxidative phosphorylation cannot occur in the mitochondria.
1mmHg (0.13kPa)
19
Q
Oxygen Extraction Ratio
A
The fraction of delivered oxygen that is taken up by the tissues
O2ER = VO2/DO2. Normally 0.2-0.3
Differs between organs, the heart having an OER of 0.6
Doubles in exercise.
20
Q
P50
A
Partial pressure of O2 in the blood at which haemoglobin is 50% saturated.
21
Q
Factors causing Left Shift - increased affinity
A
Decreased PaCO2
Alkalosis
Decreased temperature
Decreased DPG
Fetal haemoglobin
Carbon monoxide
Methaemoglobin
22
Q
Factors causing Right Shift - increased offloading
A
Increased PaCO2
Acidosis
Increased temperature
Increased DPG
Pregnancy
Altitude
Haemoglobin
23
Q
Bohr Effect
A
The affinity of haemoglobin for oxygen is reduced by a reduction in pH and increased by an increase in pH
24
Q
Haldane Effect
A
Deoxygenated haemoglobin is able to carry more CO2 than oxygenated haemoglobin
-deoxyHb forms carb amino complexes with CO2
-deoxyHb is a better buffer of H+ forming more HCO3
In tissues - Hb gives up O2, affinity for CO2 increases
In lungs - Hb binds O2, affinity for CO2 decreases
25
Compliance
Volume change per unit change in pressure
ml/cmH2O-1 or L/kPa-1
26
Static compliance
Compliance of the lung measured when gas flow has ceased
27
Dynamic compliance
Compliance of the lung measured during the respiratory cycle when gas flow is ongoing
ml/cmH2O-1 or L/kPa-1
27
Resistance
Pressure change per unit volume
28
Tell me about sources of physiological acid production…
Respiratory - carbonic
Metabolic
-organic (lactic, FFA, hydroxybutryic) metabolised by liver +/- renal excretion
-inorganic (sulphuric, phosphoric (from proteins)) excreted by kidneys unchanged
29
Systems for Acid Base Homeostasis
1. Buffers - immediate > seconds to minutes. Intracellular and extracelluar
2. Respiratory - rapid > minutes to hours
3. Renal - slow > hours to days
30
Definition of Buffer
Solution of a weak acid and its conjugate base, or weak base and its conjugate acid, which resists a pH change when a stronger acid or base is added
31
Factors affecting Buffers
Amount of buffer presents
pKa of buffer system
pH of carrying solution
Open or closed system
32
Haemoglobin as a buffer
Intracellular
38 histidine residues on Hb
Very powerful
33
Albumin as a buffer
Aminyl and carboxyl groups as side chains
Less effective than Hb
34
Phosphate as a buffer
pKa 6.8
Good intracellular buffer but small amount
Mostly in urine
35
Carbonic acid/bicarbonate buffer
pKa 6.1
Main ECF buffer
Catalysed by carbonic anhydrase both ways
So rapid that in the Henderson-Hasselbach, PCO2 can be substituted for bicarbonate
36
Carbon dioxide carriage in blood
25x more soluble than O2
Carried in 3 forms; dissolved in plasma, bicarbonate, carbamino compounds
Arterial-venous difference explained by Haldane Effect
In arterial blood - mostly bicarb
In venous blood - mostly carbamino compounds
37
Carbon dioxide carriage in red cells
Dissolves into red cells
Can be combined with Hb or catalysed by CA to form bicarb
Both create H+ which needs buffering - deoxyHb(Haldane) and chloride shift (Bohr)
Carbamino compounds form 3.5x more readily with deoxyHb than Hb-O2
38
Renal buffering
Bulk of H+ secretion and HCO3- reabsorption in PCT
-Na/H antiporter in tubular cells secretes H+ and reabsorbs HCO3- (with Na)
Urine pH determined by intercalated cells in DCT
Final pH controlled by aldosterone - minimum is 4.5
39
ABG interpretation
1. pH - acidaemia or alkalaemia?
2. PCO2 and HCO3- respiratory or metabolic?
3. Compensation - moves pH back towards normal range
(Bicarb not ideal, because affected by resp and metabolic, and is calculated not measured)
4. Base excess - negative in metabolic acidosis, positive in metabolic alkalosis
40
Standard Base Excess
SBE is dose of acid or alkali required to return the ECF (equating to an Hb of 5) to normal pH (7.4) under standard conditions ( 37oC, PCO2 of 5 kPa)
Better reflects buffering of the entire ECF, rather than just whole blood
41
Davenport Diagram
Shows relationship between pH, PCO2 and bicarbonate
Explains compensatory mechanisms
Not used very much in clinical settings
42
Anion Gap
In order to maintain electroneutrality, all cations and anions must be balances
Cations - Na and K+
Anions - bicarb and Cl, albumin
AG = [Na+ + K+] - [Cl- + HCO3+]
(8-16)
43
Causes of High Anion Gap (KILU)
Ketones
Ingestion
Lactate
Urea (renal gain)
44
Causes of Normal Anion Gap (ABCD)
Addisons
Bicarbonate loss (GI or RTA)
Chloride excess
Diuretics (acetazolamide)
45
Stewart Model - Strong Ion Difference
Principles of electroneutrality, dissociation and mass conservation must be obeyed
Explains disturbances caused by Cl- or albumin abnormalities
Strong ions lead, weak ions follow
Cl- rise causes a fall in HCO3- to maintain electroneutrality
46
Five function of the Kidney
1. Regulate fluid and electrolyte balance
2. Excretion and metabolism of waste
3. Acid-base balance
4. Long term regulation of blood volume and arterial BP
5. Production of Vitamin D and EPO
47
Gross anatomy of Kidney
Tough renal capsule
Outer cortex
Inner medulla
Renal artery and renal vein (afferent arterioles, capillaries, efferent arterioles, vasa recta)
48
Structure of a Nephron
1 million nephrons per kidney
Single layer of epithelial cells with variable intercellular junctions
GFR 7L per hour - majority reabsorbed
Multiple selective, adaptable reabsorption mechanisms
49
Renal tubular cell
Some passive movement of H2O and K+ into interstitium
50
EPO
Fall in oxygen levels stimulated renal tissues
EPO produced by peritubular cells
Stimulates erythropoiesis by bone marrow
51
Tell me about Vitamin D...
Skin/UV light produced cholecalciferol from dietary precursors
Liver converts to 25-OH D3
Kidney (pct) converts to 1,25-(OH)2 D
Increases Ca by promoting GI absorption, tubular reabsorption and bone reabsorption
Stimulated by inc PTH, switched off by hyperphosphataemia
52
Tell me about the Glomerulus...
Produces 120ml/min, or 170L/day of filtrate
Channels between podocytes
Negatively charged so cations and uncharged pass more easily than anions
Filtrate contains
-water
-Na, HCO3, glucose and amino acids in same concentration as plasma (MW<7000)
-no large proteins (55-60kDa)
-no cells
53
How is net filtration pressure within the glomerulus calculated?
Capillary at high pressure - hydrostatic gradient 40mmHg out
Oncotic pressure into capillary - 26mmHg in
Net filtration pressure of 14mmHg
Proportion of plasma flow filtered = filtration fraction
54
Glomerular filtration fraction - calculation
RBF = 1.2Lmin (20-25% of output)
Cortical blood flow 10x medullary
RPF = 600-720ml/min
GFR 120ml/min
Therefore FF = 120/720 = 17%
Renal oxygen consumption is approx 18mls/min
55
GFR Measurement
Compound needs to be readily filtered, not metabolised, reabsorbed or secreted
filtration flow x filtrate conc = urine flow x urine conc
Creatinine - produced at steady state, but small amount of secretion so overestimates
Inulin - freely filtered, has to be infused (not naturally occuring, research tool only)
Cystatin C - no tubular secretion, small protein produced by all cells
GFR proportional to 1/plasma conc
56
GFR Autoregulation
RBF and GFR remain constant between MAP 70-160mmHg
Capillary bed has afferent and efferent arteriole
-reduced RBF dilates afferent arteriole and constricts efferent arteriole
57
Tubulo-glomerular feedback
Adenosine
-released in normal state from macula dense
-constricts afferent arteriole
PGE2
-produced in DCT in response to fall in filtration
-dilates afferent arteriole
-inhibit by NSAIDS
Angiotensin II
-produced from RAAS in response to reduced RBF
-constricts efferent arteriole
-inhibited by ACEI and ARBs
58
Proximal Convoluted Tubule - reabsorption of compounds
Reabsorption of
- Na 70%
- H2O 70%
- HCO3, glucose 99%
Resulting filtrate composition is Na same as plasma, but nil HCO3 or glucose
Glomerulotubular balance - Na/H2O reabsorption is adjusted to match GFR
Has a brush border; rich in mitochondria
59
How is sodium reabsorbed in the PCT?
Luminal membrane
Na+/H+ antiporter
Na+/Glucose symporter
basement membrane
Co-transport with HCO3-
Na/K ATPase pump
Leaky junctions allow H2O (and Cl-) to follow Na
60
How is glucose reabsorbed in the PCT?
Normally all filtered via Na+/glucose symporter in the PCT
Can become saturated - Transport maximum (Tmax) = 1.5-2mmol/min
380mg/min - renal threshold 11mmol/L
Resultant glycosuria causes osmotic diuresis
61
How is bicarbonate reabsorbed in the PCT?
Filtered HCO3- combines with H+ from the Na+/H+ antiporter
Makes H2CO3 which is converted to H2O and CO2 by carbonic anhydrase
CO2 enters tubular cell and reversed into H2CO2 then H+ and HCO3-
HCO3- moves into interstitium via Na/HCO3 co-transport
99% normally reabsorbed
62
Two Mechanisms of Glomerulotubular balance
(Na/H2O reabsorption is adjusted to match GFR)
1. Glucose Load
- As GFR increases, so does filtered load of glucose
- Na/Glucose co-transport means increased reabsorption of both, water follows.
2. Oncotic pressure
- As GFR increases, protein content in glomerular capillaries increases, so increasing oncotic pressure
- favours movement of ions and water into the capillaries from the interstitial space
63
What compounds are secreted by the PCT?
Organic anions via active transport carriers
-urate, bile salts, fatty acids and prostaglandins
Organic cations via active transport mechanism
-ACH, catecholamines, histamine and creatinine
Drugs
- aspirin, penicillin, morphine and atropine
64
What is the role of the Loop of Henle?
Produce hypertonic hyperosmolar interstitial fluid in medulla
Produce hypotonic tubular fluid
Some reabsorption of Na, K and Cl.
65
Differential Osmolarity through the LOH
Initial tubular fluid - 300 mOsm/L
Medullary interstitium - 1200 mOsm/L
Resulting tubular fluid - 100 mOsm/L
Mechanisms:
-Selective permeability to H2O and ions in descending and ascending limbs
Active reabsorption of Na, K and Cl (& urea) in ascending limb
Counter current multiplier
66
Descending limb of LOH
Permeable to water
Impermeable to ions
Tubular fluid becomes more concentrated as H2O is lost via AQP1 but ions are retained
67
Ascending limb of LOH
Impermeable to water
Permeable to ions
Thick portion - tubular fluid becomes more dilute as ions are lost but water remains
Medullary interstitium becomes more concentrated
68
Ion reabsorption in thick ascending limb
Luminal membrane
-NKCC co-transporter (Na, K, 2 x Cl-)
Basement membrane
passive conductance of K+
Na/K ATPase pump
69
How does the countercurrent mechanism work?
Starting at 300 mOsm/L at the beginning of the descending limb
-water leaves and fluid becomes hypertonic
-reaches 1200 mOsm/L by the bottom - equal to the medullary interstitium
-travels up the ascending limb and ions leave, water remains, fluid becomes hypotonic
-back to 300 mOsm/L
Vasa recta alongside this - capillary system from the glomerulus
-ions from ascending limb of LoH into descending limb of VR
-water from descending limb of LoH into ascending limb of VR
70
What is the role of the DCT and CD?
1. Fine tuning of H, K, Na excreted in urine
2. Buffering of H in filtrate
3. Control of fluid composition
71
How is sodium reabsorbed in the DCT?
Principal cells
-coupled channels ENaC - control Na reabsorption/K excretion
EnaC stimulated by aldosterone, hyperkalaemia, alkalosis, inc tubular flow
Amiloride works on ENaC
72
What is the function of Aldosterone?
Mineralocorticoid from the zona glomerulosa of the adrenal cortex
- secreted in response to angiotensin II, hyperkalaemia, ACTH
- stimulates Na reabsorption and K secretion by the principal cells in DCT
- determines urinary Na and hence ECF volume
-also inc Na reabsorption in gut and sweat/salivary glands
Steroid - inc gene expression for ENaC channels, also increases activity in Na/KATPase pump on basement membrane
Increases blood pressure via inc in blood volume
73
How are potassium and hydrogen handled by the DCT?
Intercalated cells
- K+/H+ ATPase pump secretes H+ in exchange for K+
- Stimulated by acidosis or hypokalaemia
- Determines final acidity of urine
74
Phosphate buffering in DCT
Intercalated cells secrete H+ ions
Filtered HPO4(2-) in lumen combines with free H+ to create H2PO4
Everytime a H+ is secreted into lumen, a HCO3 is reabsorbed into the blood
75
Ammonia buffering in DCT
Glutamine in intercalated cells broken down to ammonia NH3
Excreted into lumen and combines with free H+ to make NH4+
Largest capacity to increase in acidosis
76
Acid Base regulation through the Kidney
Urine pH varies from 4.5-8
PCT reabsorbs 99% of HCO3 and bulk of H+ secretion
DCT intercalated cells determine final urine acidity through further H+ secretion
Phosphate and ammonia buffering also occurs in DCT
77
Sodium in the Kidney
Glomerular filtration of 25000 mmol/day (main ECF ion)
PCT - 70% reabsorbed
LOH - 15-20% reabsorbed in thick ascending limb
DCT - fine tuning
100ml/day excreted (10-500 in extremes)
78
Potassium in the Kidney
Glomerular filtration of 720mmol/day
PCT - 55-65% reabsorbed
LOH - 25-30% reabsorbed in thick ascending limb
DCT - fine tuning
60mmol/day excreted per day (6-800 in extremes)
79
What is the role of the medullary Collecting Duct?
Final regulation of H2O and hence urine concentration
Normally impermeable to all ions and H2O but has aquaporins in luminal membrane for movement of H2O
Able to vary from 60-1400 mOsm/L regulated by ADH via hypothalamic osmoreceptors
1-20% of filtered H20 remains
Urine output 1.5-30L/day
80
Tell me about aquaporins...
A family of channels created by trans-membrane proteins with a narrow hour glass shape made up of helical peptides
The narrow part has positively charged walls which only allow water to pass
8 subtypes - renal ones are:
AQP1 in the basal membrane of PCT and descending LOH
AQP 3 & 4 in the basal membrane of the CD
AQP2 inserted into the luminal membrane of the CD in response to ADH
81
How is water reabsorbed in the collecting duct?
Tubule lumen 100 mOsm/L
Interstitium 1200 mOsm/L
ADH V2 receptor binding leads to AQP2 inserted on luminal membrane via cAMP
-H2O moves from lumen into tubular cell
AQP 3 & 4 on basal membrane can then freely move H2O from tubular cell into interstitium
82
Tell me about ADH...
Anti diuretic hormone
Nonapeptide hormone synthesised in hypothalamus and stored in/secreted from posterior pituitary
Also known as vasopressin
Release controlled by hypothalamic osmoreceptors
- increase in osmotic pressure detected by paraventricular and supraoptic nuclei
- hypovolaemia detected by atrial baroreceptors, and carotid sinus/aortic arch baroreceptors
Binds to 3 types of G-protein receptors - 2nd messenger cAMP
V1 (V1a) - peripheral arterioles = vasoconstriction
V2 - renal collecting duct - insertion of AQP2 channels into tubular cell luminal membrane
V3 (V1b) - CNS = ACTH release
83
Tell me about fluid homeostasis...
Change in fluid balance either through osmolarity or volume
osmolarity rise = ^ADH = retain H2O = osmolarity falls
osmolarity falls = less ADH = excrete H2O = osmolarity rises
volume high = less aldosterone, more ANP = excrete Na + H2O
volume low = more aldosterone, less ANP = retain Na + H2O
84
Tell me about ANP...
Atrial naturietic peptide - 28 amino acid polypeptide hormone
Released from atrial walls in response to stretch in high volume states
Promotes Na + H2O excretion by increasisng GFR
- afferent arteriole dilates
- efferent arteriole constricts
- increased filtration pressure to increase fluid loss
Also inhibits renin and aldosterone secretion = reduces volume
85
Tell me about the juxta-glomerular apparatus...
Located between the afferent arteriole and the DCT
Two types of specialised cells
- Macula densa - senses drop in Na in DCT
- Granular cells - senses drop in pressure in DCT
Triggering the JGA results in renin release and afferent arteriolar dilatation
86
Tell me about the renal response to hypovolaemia...
JGA senses less Na/pressure in DCT
Causes increase in Renin secretion from granular cells
Renin converts Angiotensinogen to AG1 in plasma
ACE converts AG1 to AG2 in lungs
Actions of AG2:
- vasoconstriction of systemic arterioles
- acts on the hypothalamus to increase ADH secretion
- acts on the adrenal cortex to increase secretion of aldosterone
87
Tell me about Angiotensin II...
Actions of AG2:
- vasoconstriction of systemic arterioles
- acts on the hypothalamus to increase ADH secretion
- acts on the adrenal cortex to increase secretion of aldosterone
88
How is MAP calculated?
Diastolic pressure + 1/3 pulse pressure
Mathematical mean derived from AUC
89
Tell me about central venous pressure...
Equal to pressure at junction of VC and RA
5-20mmHg
Central venous pressure waveform
A wave: atrial contraction
C wave: tricuspid valve bulging back into RA
X descent: atrial relaxation
V wave: atrial filling with tricuspid valve closed
Y descent: atria empties into ventricle
90
When will each cardiac valve be open/closed?
Valves open or close because of pressure either side
Mitral/tricuspid valves open when Ventricular pressure > atrial pressure
Aortic/pulmonary when ventricular pressure > vessel pressure
91
When in the cardiac cycle does systole occur?
Systole starts at the beginning of ventricular contraction and ends when relaxation means that ventricular pressure is below that of the aorta
92
Tell me about isovolumetric contraction...
Marks the onset of systole, and closure of the MV and TV (first heart sound)
Ventricular pressure rises rapidly while blood volume stays the same
The c wave shows tricuspid valve bulging back into the RA
93
Tell me about isovolumetric relaxation...
Once the aortic and pulmonary valves close (second heart sound) ventricular pressure falls with no change in volume
94
Tell me about regulation of coronary blood flow...
250ml/min - around 5% cardiac output
Can increase by 4-7 times during exercise
Even at rest, there's a higher OER than the rest of the body (0.55-.06)
Autoregulates between MAP 5-0-120mmHg via metabolic, neural or hormonal mediators.
95
What factors causes coronary vasoconstriction?
Metabolic - high PO2, low PCO2 (alkalosis)
Neural - alpha stimulation
Hormonal - ADH, angiotensin, thromboxane
96
What factors causes coronary vasodilatation?
Metabolic - low PO2, high PCO2 (acidosis)
Neural - Beta stimulation
Hormonal - prostacyclin
97
What are the 5 phases of the cardiac cycle?
1. Atrial contraction: p wave of ECG, a wave of CVP trace; 30% of ventricular filling
2. Ventricular isovolumetric contraction: closure of MV and TV (s1), overlaps QRS complex, C wave is tricuspid bulge
3. Systole: aortic and pulmonary valves opened by high ventricular pressure, t wave is repolarisation
4. Ventricular isovolumetric relaxation: A/P valves close (s2), aortic valve closure is dicrotic notch, aortic pressure now exceeds ventricular pressure
5. Ventricular filling: passive filling during diastole, initially rapid then slower, y descent as the atrium empties
98
What is the difference between the Nernst and the Goldman-Hodgkin-Katz equations?
Nernst - considers only a single ion
99
Describe the action potential of cardiac contractile cells...
Resting membrane potential of ~85mV
Phase 0: rapid depolarisation - fast Na+ channels open
Phase 1: early repolarisation - Na+ close, K+ open
Phase 2: plateau - Ca2+ L-type in ARP - prevents tetany
Phase 3: repolarisation - Ca2+ close, K+ efflux, RRP
Phase 4: Na+/K+ pump restores RMP
(sodium, potassium, calcium, potassium)
L-type channel opening is voltage triggered; closing is a timed event
100
Describe the action potential of cardiac pacemaker cells...
Phase 0: spontaneous baseline drift, L-type calcium channels open
Phase 3: repolarisation, Ca2+ close, K+ open
Phase 4: hyperpolarisation (pre-potential), Na+ leak, T-type Ca2+ open, Na+/Ca2+ pump
Slope of phase 4 determines HR:
- SNS inc slope, more Na/Ca influx
- PNS dec slope, more K+ efflux
101
How do pacemaker cells compare with contractile cells?
Pacemaker cells have:
- slower response time
- less negative phase 4
- less negative threshold potential
- slower depolarisation
Rate of spontaneous discharge varies according to location
- SA node 70-80/min
- AV node 60/min
- Ventricles 40/min
102
Pacemaker or Contractile?
Maximal Negative Potential: - 60 mV
Threshold: - 40 mV
Peak Positive Potential: +20 mV
Duration: 150 ms
Pacemaker
103
Pacemaker or Contractile?
Maximal Negative Potential: - 90mV
Threshold: - 70 mV
Peak Positive Potential: +20mV
Duration: 200 ms
Contractile
104
Categorisation of ECG leads
Limb
Augmented limb
Chest
Limb: bipolar leads - voltage between two active electrodes
Augmented limb: unipolar - voltage between one active limb electrode and a reference
105
What are the most common causes of mitral regurgitation?
Acute - ruptured chordae tendinae, post MI, trauma
Chronic - mitral valve prolapse, rhematic fever, connective tissue diseases, dilated cardiomyopathy
Can cause increased in left atrium end-diastolic volume, and progressive dilatation of the left heart
106
What are the common clinical features of mitral regurgitation?
S+S; fatigue, SOB, orthopnoea, reduced ET
Ausc; pansystolic murmur, maximal at apex and radiating to axilla
ECG; p mitrale/AF from dilated atrium, voltage criteria for LVH
CXR; cardiac enlargement, pulmonary oedema
107
How is MR graded?
1. NYHA functional classes
2. Measurement of the regurgitant fraction ( >0.3 mild, >0.6 severe)
3. Degree of LV dysfunction
108
How would you tailor your anaesthetic management to favour optimal CO for a patient with MR?
Fast and loose!
Avoid bradycardia - increases time within which regurgitation occurs
Minimise vasoconstrictors - dilated circulation needed for good forward flow
Avoid large increase in preload - can cause decompensation
109
What are the most common causes of aortic stenosis?
Congential: bicuspid or unicuspid valve
Acquired; rheumatic heart disease, degenerative calcification
110
What are the effects of AS on cardiac function?
- As valve area decreases, pressure gradient between LV and aorta develops
- Outflow obstruction increases LV pressure further
- LV wall thickness increases - concentric hypertrophy
- Decreased compliance leads to reduced passive filling, inc work of atrial systole
- Myocardial oxygen demand increases
- Increased LV pressure reduces coronary blood flow - subendocardium vulnerable to ischaemia
111
What are the common clinical features of aortic stenosis?
S+S: exertional dyspnoea, fatigue
Classic triad of chest paint, heart failure and syncope
Coarse ejection systolic murmur, maximal over aortic area radiating to carotids
Quiet S2
Narrowed pulse pressure
ECG: LAD, LVH, TWI +/- STD (strain pattern), heart block if conduction pathways involved
CXR: aortic valve calcification, cardiomegaly
112
How would you tailor your anaesthetic management to favour optimal CO for a patient with AS?
Slow and tight!
Avoid tachycardia -further reduces coronary flow
Maintain SVR/avoid vasodilation - preserves pressure gradient for coronary filling
Maintain preload and sinus rhythm
113
How is AS graded?
1. NYHA functional assessment
2. Echocardiographic
-mean gradient
-aortic valve area >1.5cm2 mild, <0.5cm2 critical
114
Explain the NYHA functional capacity classes...
I - Patients with disease but with no resulting limitations
II - Cardiac disease with only slight limitation in physical activity, ordinary activity results in symptoms
III - Marked limitations, but comfortable at rest. Less than ordinary activity results in symptoms
IV - Unable to carry out any physical activity without discomfort, symptoms present at rest.
115
What is the Fick Principle?
The uptake or relase of a substance from tissues is equal to the product of blood flow to those tissues, and A-V concentration difference.
VO2 = (CO - Cv) X (CO - Ca)
CO = VO2/Cv - Ca
116
Describe the nerve supply to the heart
The sympathetic nerve supply to the heart is provided by the superficial and deep cardiac plexuses;
- Superficial cardiac plexus - branches from the left superior cervical sympathetic ganglion and the left vagus
- Deep cardiac plexus is formed by branches from both the left and right inferior and middle, cervical sympathetic ganglia, both vagi and the upper four thoracic sympathetic gangli
117
Tell me about the structure of immunoglobulins...
Large Y shaped protein, 150kDa
Either membrane bound on B cells or free within plasma
Occur in 5 classes/isotypes - IgA, IgD, IgE, IgG and IgM
Two heavy chains and two light chains connected by disulphide bonds
Antigen binding fragments (Fab) - arms of the Y
Crystallisable fragment (Fc) - trunk of the Y
118
Tell me about the antibody isotypes
IgA - mucosal areas preventing colonisation; also saliva, tears and breast milk
IgD - antigen receptor on B cells, activates basophils and mast cells
IgE - triggers mast cells and basophils; allergy, asthma, parasites
IgG - crosses the placenta, provides the majority of antibody based immunity
IgM - expressed on surface of naïve b cells
119
Tell me about surfactant...
Dipalmitoyl phosphatidyl choline synthesised by type II pneumocytes from FFA in blood
Amphipathic; t1/2 = 2 hours
Reduces surface tension of alveolar wall - increasing compliance and preventing pulmonary oedema - via alignment of SP-A and SP-D (hydrophilic)
Works best at smaller lung volumes
La Place's Law - P = 2T/R (for a sphere)
P = pressure within sphere (outward force)
T = surface tension (inward force)
120
Respiratory changes during pregnancy - anatomical
Airway engorgement
Flaring of the ribs increased the circumference of the thoracic cage by 5-7cm
Enlarging uterus displaces diaphragm upwards
121
Haematological changes in pregnancy - plasma proteins
Albumin and pseudocholinesterase reduced
Globulin and fibrinogen increased
Overall drops to 65-70g/L
- decreased total colloid osmotic pressure
- altered drug binding capacity
- inc ESR and blood viscosity
122
Haematological changes in pregnancy - coagulation
Enhanced PLT turnover, clotting and fibrinolysis
-thrombocytopaenia in up to 1%
Most coagulation factors increase
- XI, XIII and antithrombin III are reduced (3, 11, 13)
- II and V stay the same (2, 5)
Increase in fibrinogen degradation products and plasminogen - increased fibrinolysis
PT, PTT and bleeding time all fall slightly
123
Haematological changes in pregnancy - red and white cells
Plasma volume, RBC volume both increase
-plasma volume rises by 50% by term, further 1L 24hrs post delivery
-RBC falls during first 8 weeks, back to normal by 16 then rises to +30% by term
PV rises by more than RBC - hence dilutional anaemia (lower haematocrit)
Total blood volume increases by 10, 30 and 45% at the end of each trimester
Plasma volume returns to normal around 6 days pp
White cell count rises to 9-11 x 10(9) - rises again to 15 during labour - PMN cells
124
Tell me about aortocaval compression...
Compression of the aorta and IVC by the gravid uterus
Reduces cardiac output through reduced preload
Begins as early as 13/40 - maybe decline from 36-38/40 due to descent of the head
LEFT LATERAL POSITION
125
Contra-indications to epidural analgesia...
Absolute; patient refusal, allergy, infection, coagulopathy, raised ICP, profound hypovolaemia
Relative; bacteraemia, neuro disorder, fixed cardiac output states e.g. aortic stenosis, spinal abnormality e.g. spina bifida, previous surgery
126
Tell me about pre-eclampsia...
Characterised by hypertension and proteinuria after 20/40
Occurs in 5-6% of pregnancies - caution with primips
Partner related
Eclamptic fits can occur up to 1 week pp
Commonly results in thrombocytopaenia
May progress to HELLP
127
During pregnancy, progesterone is responsible for...
Bronchodilatation
Generalised vasodilatation
Decreased GI motility, smooth muscle relaxation
Renal tract dilatation
128
Cardiovascular changes during pregnancy
Cardiac output increased due to an increase in stroke volume
Blood volume increased by 45-50% at term
Decrease in systemic vascular resistance leading to overall drop in BP - 8%
increase in red cell volume but overall decrease in haematocrit
129
Gastrointestinal changes during pregnancy
LOS decreased but gastric emptying time unchanged
Heartburn suffered by most women due to decreased LOS
Smooth muscle relaxation causes constipation
RSI necessary from start of 2nd trimester
130
Respiratory changes during pregnancy - physiological
PaCO2 decreases to 4kPa in first trimester
FRC reduced to 80%
Oxygen consumption increased by 35%
Alveolar ventilation up by 70%
RR up by 10%
Tidal volume up by 45% at term - minute ventilation up by 50%
Oestrogen and progesterone both act as respiratory stimuli
Right shift in OxyHb curve due to inc 2,3-DPG (P50 = 4.0)
131
What factors can cause prolonged neuromuscular block?
Hypokalaemia
Hypocalcaemia
Hypermagnesaemia
Metabolic alkalosis
Respiratory acidosis
Hypothermia
132
Describe nervous control of heart rate...
Resting HR of 60-80bpm from dominant vagal tone; intrinsic rate if SA node is 110.
Sympathetic - cardioaccelerator (T1-5)
Rostral ventrolateral medulla
Right sympathetics to SA node; left sympathetics to the AV node
Increased gradient of phase 4 leads to inc HR
(Sympathetic stimulation also causes positive inotropy)
Parasympathetic - vagus nerve
Nucleus ambiguus of vagus nerve
Right vagus to SA node; left vagus to AV node
Decreased gradient of phase 4 leads to dec HR
133
How does blood flow vary between different organ systems?
The carotid bodies have the highest blood flow per unit weight of any organ in the body. This enables them readily to detect falls in PaO2.
Organ Blood Flow (ml/minute/100g)
Hepatoportal 58
Kidney 420
Skin 13
Skeletal muscle 2.7
Heart 87
Carotid body 2000
Thyroid gland 560
134
What is a MET?
Metabolic equivalent
1 MET approximates to a consumption of 3.5ml O2/ kg/ min
VO2 = 3.5 x weight x METS
e.g. 8 METs for a 50kg patient
3.5 x 50 x 8 = 1400ml/min
135
Tell me about insulin...
Insulin is composed of two polypeptide chains (A and B) linked by two disulphide bridges. A chain contains 21 amino acids, B chain contains 30.
Passage of glucose into cells requires glucose transporters.
There are four glucose transport proteins:
GLUT1: universally distributed
GLUT2: gut, liver, and pancreatic islets
GLUT3: central nervous system and brain
GLUT4: insulin-responsive tissues, skeletal muscle, adipose tissue, and heart.
GLUT3 is not dependent on insulin.
136
What is haematocrit?
Also known as packed cell volume - total red blood cell volume as a proportion of blood volume.
Normal values are 40-54% (0.4-0.54) in males and 37-47% (0.37-0.47) in females.
Venous blood has a higher haematocrit than arterial blood because of the entry of chloride ions into red cells (chloride shift) which is followed by water entry by osmosis.
A fall in haematocrit decreases the viscosity and thus increases the flow. Therefore, a haematocrit of about 30% (0.3) after acute blood loss is thought to be optimal.
137
Tell me about total body water...
Total body water is about 60% of body weight in men - 50-55% in women.
So 70kg = 42L water
ECF = 14L, ICF = 28L
Measured using deuterium oxide.
138
Tell me about hypoxic pulmonary vasoconstriction...
HPV is a reflex contraction of pulmonary arterial smooth muscle cells in response to low regional partial pressure of oxygen, diverting blood away from hypoxic areas of lung to those with better oxygenation.
In normal lung;
Apex - high V/Q more ventilation less perfusion
Bases - low V/Q more perfusion less ventilation
Stimulus is the pp of O2 in the pulmonary arteriole - determined by PAO2 and PVO2.
Phase 1 within seconds to 15 mins - phase 2 if hypoxia sustained (e.g. in OLV) after 30-60mins maximal at 2 hrs.
Inhibited by halothane, ether, desflurane > 1.6 MAC, supplemental O2
139
Tell me about pulmonary vascular resistance...
PVR = ((MPAP-LAP) * 80) / cardiac output
Dyne.s-1.cm-5
Increased by: Decreased by:
Inc PaCO2/acidosis Dec PaCO2/alkalosis
Hypoxia Inc PaO2
Adr/norad Isoprenaline
TBXA2 Acetylcholine
AGII Prostaglandin I2
5HT3 Nitrous Oxide
Histamine Volatiles
Extremes of lung volume
140
Tell me about pulmonary artery hypertension...
Defined as a MPAP at rest > 25mmHg (Mild 25-40, moderate 41-55, severe >55)
Acute or chronic
Classified into groups according to haemodynamic, aetiology and pathology:
1. Idiopathic, CTD, congenital, HIV, drug/toxin induced
2. Left-sided heart disease, increased pulmonary capillary wedge pressure
3. Lung disease and chronic hypoxia
4. Chronic thromboembolic
5. Multi system disorders e.g. sarcoidosis, haematological
Treatment depends on aetiology; vasodilators for group 1 and group 4; endarterectomy for group 4, group 2 and 3 is mostly underlying cause.
Transplant ultimate treatment option.
Increased risk of perioperative adverse events.
141
Tell me about West Zones....
Way of describing pressure across lung regions and how this effects blood flow
Zone 1 - apex - PA > Pa > Pv - vessel compressed, no flow (dead space)
Zone 2 - middle - Pa > PA > Pv - perfusion varies with cardiac/resp cycles
Zone 3 - base - Pa > Pv > PA - blood flow is consistent (shunt)
142
Tell me about high frequency ventilation...
Uses small tidal volumes (1-3ml/kg) delivered at high frequencies 4 times the normal rate, maintaining gas exchange without barotrauma or other deleterious effects of IPPV.
Three main modes
- high frequency positive pressure ventilation
- high frequency jet ventilation
- high frequency oscillation
143
What is normal V/Q matching and how does it vary across the lung zones?
V represents ventilation, which is usually around 4 - 5 litres per minute
Q represents perfusion, which is usually around 5 litres per minute
A normal V/Q ratio is therefore around 0.9
Perfusion and ventilation are highest at the bases
VQ ratio is lower at the bottom and increases towards the top of the lungs
144
Tell me about cord hemi-section...
Brown-Sequard Syndrome
Flaccid paralysis at the level of the legion (LMN injury)
Ipsilateral spastic paralysis and loss of proprioception, touch and vibration (UMN injury, lateral corticospinal tracts, dorsal columns, spinocerebellar)
Contralateral loss of pain and temperature (spinothalamic)
145
Tell me about anterior spinal cord injury...
Ipsilateral motor loss but preservation of proprioception, touch and vibration.
(anterior corticospinal tracts)
146
What is the anaerobic threshold?
Measurement taken from CPET - marker of combined efficiency of the lungs, heart and circulation.
With inc exercise, oxygen demand will exceed supply and muscles switch to anaerobic ATP generation, producing lactic acid, buffered by bicarbonate and leading to an increased CO2.
The VO2 at the point the uptick in CO2 production occurs is the AT.
AT > 11ml.kg.min required for safe surgery.
147
According to the Frank-Starling mechanism, how does increasing preload increase stroke volume?
Enhanced calcium sensitivity of the myofilaments at greater sarcomere lengths leads to stronger cardiac contractions
148
Tell me about red blood cells...
Anucleate cells about 7.5um in diameter and 2um thick. Biconcave shape.
Produced by bone marrow under action of EPO - initially released as reticulocytes containing residual ribosomal RNA and able to synthesis Hb.
Express surface antigens for blood groups.
Survive for around 120 days.
149
Tell me about malignant hyperthermia...
A genetically inherited condition of skeletal muscle with an autosomal dominant mode of inheritance.
MY susceptibility trait is at the ryanodine receptor locus on chromosome 19; encodes the skeletal muscle sarcoplasmic reticulum calcium release channel, necessary for excitation-contraction coupling.
Diagnosed by in vitro contracture testing with caffeine and halothane using muscle biopsy from vastus medialis/lateralis
150
Tell me about the oxygen cascade...
A graph that shows stepwise decrease in pp O2 from the airways down to systemic tissues.
1. Inhaled gas - 20kPa
2. Alveoli - 15kPa
3. Capillaries - 15kPa
4. Arterial - 13.3
5. Tissues - 1.5-3.5
Can overlay classification of hypoxia over the oxygen cascade in order to work out why patient is hypoxic and therefore how to correct
150
Oxygen delivery equation
DO2 = Q x O2 content
where Q = flow, cardiac output
O2 content = [Hb x Sa02/100 x 1.34] + [PaO2 x 0.023]
150
Tell me about the Alveolar Gas Equation...
Estimates the PAO2 of a perfect alveolus with varying fractions of inspired oxygen
PAO2 = [FiO2 x (Patm - Ph2o)] - PaCO2/R
where R is the respiratory quotient for a mixed diet = 0.8
151
Tell me about causes of hypoxia...
Classified into 4 main causes
1. Anoxic/Hypoxic
- PiO2
- Hypoventilation
- Diffusion defect
- Shunt (true)
- VQ Mismatch
2. Anaemic
3. Circulatory
4. Histotoxic
152
Tell me about the shunt equation...
QS/QT = CcO2 - CaO2 / CcO2 - CvO2 (shunt fraction)
Things you need to calculate:
SaO2, PaO2, PaCO2, RQ
You can substitute CcO2 and CvO2 into the CaO2 equation in order to calculate each of them
153
How would you define endocrine function?
Transmission of a molecular signal, a hormone, through the blood to its target cell to exert a function+.
May be autocrine or paracrine.
154
Tell me about protein/peptide hormones...
Insulin, angiotensin, gastrin, calcitonin, ghrelin, ANP, anterior pituitary. etc
Largest group; chain or multiple chain of amino acids.
Some have sugar molecules attached as side chains and are termed glycoproteins.
Water soluble - need membrane bound receptors
Produced as large preprohormones by the RER - then processed and packaged by the ER and GA.
Stored in vesicles then secreted by exocytosis following stimulus - inc cytosolic Ca2+
155
Tell me about amine hormones...
Catecholamines
Thyroid hormones
All contain an alpha amine group on a benzene ring - derived from tyrosine
Adrenaline, noradrenaline and dopamine produced from the adrenal medulla; contains the phenylethanolamine N-methyltransferase enzyme needed to convert NA to Ad - lost in phaemochromocytoma.
Catecholamines stored in vesicles and released following SNS-ACh stimulation - 50% albumin bound.
Thyroid hormones stored with thyroglobulin; once split active hormone diffuses out of cell and bind to plasma carrier thyroid binding protein
156
Tell me about steroid hormones...
Aldosterone, cortisol, testosterone
Cholesterol is the common precursor; retain basic 4 ring structure - 3 hexamic, 1 pentamic.
Lots of common intermediates, specific glands have the necessary enzymes to produce their "finished" hormone
Highly lipid-soluble - receptors are within the cytosol, affects mRNA transcription
157
Tell me about the control of hormone production and release...
Three main systems:
Negative feedback - T4 inhibits release of TSH and TRH
Positive feedback - days 12-14 of cycle, LH stimulates oestrogen which stimulates LH
Neuronal activity - preganglionic SNS fibre to the adrenal medulla > catecholamines
Can be a combination e.g. insulin
Some have cyclical variations
158
Tell me about muscle fibres...
Three main groups, two sub groups:
Cardiac
Smooth
Skeletal:
-Type I - slow twitch. lots of mitochondria, myoglobin, good blood supply, resistant to fatigue.
-Type IIa - fast twitch
-Type IIb - faster twitch
159
What is the respiratory quotient, and how does it vary with diet?
Ratio of CO2 produced to O2 consumed per unit time.
RQ = 200/250
Normal/Mixed = 0.8
Glucose = 1
Protein = 0.8-0.9
Fat = 0.7
Ethyl alcohol = 0.67
160
Tell me about ACTH...
Adrenocorticotrophic hormone - polypeptide hormone secreted by anterior pit.
HPA axis - CRH stimulates ACTH, ACTH stimulates cortisol.
Peaks in the AM, nadir at midnight.
High in stress, disease and pregnancy
Hypercortisolism; Cushing's, ectopic CRH or ACTH, adrenal hyperplasia
Hypocortisolism: Addison's, HPA insufficiency, congenital adrenal hyperplasia
161
Oxygen consumption through organ systems...
(ml/min/100g)
Heart 11
Kidney 6.8
Brain 3.7
Hepatoportal 2.2
Skin 0.38
Skeletal muscle 0.18
162
Tell me about the oculocardiac reflex...
Bradycardia occuring in response to compression of the eye, or traction on the extra-ocular muscles.
Afferent limb - opthalmic division of the trigeminal nerve
Efferent limb - vagus nerve increases PNS tone on the heart
163
Physiological changes at altitude...
(acclimatization)
Reduced PatmO2 leads to reduced PAO2 - thereby DO2 needs to increase.
Cardiac - inc SNS, inc HR
Respiratory - inc MV, resp alkalosis, inc HCO3
Haematological - acute left shift of OxyHb, then inc 2,3DPG creates right shift;
acute reduced plasma volume = inc HCT, chronic inc EPO
164
Features of Horner's syndrome...
Ptosis
Miosis
Anhidrosis
Enopthlamos
Stuffy nose
165
ATLS classification of haemorrhagic shock...
Class 1: 15%
- minimal tachycardia, no change to BP, RR or pulse pressure
Class 2: 15-30%
-750-1500ml lost, tachycardia, tachypnoea, dec pulse pressure (diastolic raised due to catecholamines)
- stabilise with crystalloids
Class 3: 30-40%
- changes in mental state, measurable drop in SBP
- transfuse
Class 4: >40%
- periarrest
166
Types of nerve fibres
A alpha
A beta
A delta
C
A alpha - proprioception - myelinated - 100m/s
A beta - touch - myelinated - 75m/s
A delta - pain - myelinated - 25m/s
C - non myelinated - 2m/s
167
Blood flow through organ systems...
(ml/min/100g)
Carotid body 2000
Thyroid 560
Kidney 420
Heart 87
Hepatoportal 58
Brain 54
Skin 13
Skeletal muscle 2.7
168
Parasympathetic ganglia and their associated cranial nerves
Ciliary - sphincter pupillae and the ciliary muscle - CNIII
Pterygopalatine - lacrimal gland and glands of the nasal cavity - CNVII
Submandibular - submandibular and sublingual glands - CNVII
Otic - parotid gland - CN IX
169
Sympathetic ganglia
Coeliac
Superior mesenteric
Inferior mesenteric
170
Tell me about the Child-Pugh score...
Assess the prognosis of chronic liver disease, mainly cirrhosis
5 elements each scoring 1-3;
A - ascites
A - albumin
B - bilirubin
E - encephalopathy
I - INR
Class A 5-6; Class B 7-9; Class C 10-15 mortality increases with score
171
Tell me about the carotid bodies...
Chemoreceptors in the tunica adventitia, at the bifurcation of the common carotid.
3-5mm in diameter, weighs 12mg; blood flow 2000mL/min/100g
Derived from neural crest - type 1 glomus cells, surrounded by type 2 sustenacular
1. Senses changes in oxygen tension
-inhibits O2 sensitive K+ channels in glomus cells, leading to depolarisation, Ca2+ entry and release of NT that activate afferent nerve fibres
2. Responds to changes in PaCO2, pH, hypoperfusion and hyperthermia
Response includes hyperventilation, hypertension and tachycardia
Vascular supply from Meyer's ligament (ECA)
Nerve supply from glossopharyngeal
172
Where is the renal failure?
Low urinary sodium and chloride concentration (<20 mEq/L)
High urinary urea and creatinine concentration (>20 mEq/L)
High urine osmolality (>400 mosmol/kg)
High urine:plasma osmolality ratio (>1.8).
Pre-renal
173
Where is the renal failure?
High urinary sodium and chloride concentration (>40 mEq/L)
Low urinary urea and creatinine concentrations
Low urine osmolality (<350)
Low urine:plasma osmolality ratio (1.2).
Intrinsic e.g. acute tubular necrosis
May also see red cell casts, epithelial casts
White cell casts in pyelonephritis
