organ blood flow long Flashcards
PO 1.46
factors determining myocardial oxygen supply and demand
formulars
Supply = blood flow x arterial O2 content
OR
supply = (CO x [Hb] x saturation x 1.34) +(CO x 0.003 x paO2)
1.34 is the oxygen combining power of hb – less than the theoretical value of 1.39 due to non o2 carrying forms of hb (methaemoglobin, carbodyhaemoglobin, sulfhaemoglobin)
FIck principle:
Demand (consumption) = flow x (arterial – venous O2 content)
OR
MVO2 (mlO2/min per 100gm)= coronary blood flow (CBF) x (AO2 – VO2, amount of O2 extracted from the blood by heart)
PO 1.46
factors determining myocardial oxygen supply and demand
demand
Demand (consumption) = flow x (arterial – venous O2 content)
Myocardium has Highest O2 extraction ratio from coronary blood, ~ 60% because its blood supply is low relative to its consumption (Rest of body is 25% extraction)
- Need O2 to resynthesize ATP – the energy needed to maintain ionic pumps and contraction/relaxation
- limited anaerobic capacity to meet ATP requirement- without O2 can only contract for 1 minute
SO if need more must increase flow:
- Factors influencing consumption, Flow is CO = HR x SV
o HR
- If doubles, increases myocardial work, consumption doubles
- But also less supply - less time in diastole, less flow/supply of O2, vulnerable to LV subendocardial ischaemia, therefore local metabolic mechanisms act to vasodilate and increase flow
o Afterload
- Myocardial wall tension (la place law, wall stress/myocardial work = (intraventricular pressure - internal ventricular radius)/ wall thickness)
- If ventricle need to generate 50% more pressure, wall stress generated by individual myocytes need to increase by 50%, increases O2 consumption of each myoctye by 50% (not whole heart – therefore LVH may reduce wall stress because of wall thickness but more muscle mass so more O2 consumption)
- If increase EDV by 50% wall stress only up by 14% due to ventricular volume formular image 40
o Inotropic state
o Preload – less so than other factors
Therefore drugs that decrease afterload, heart rate and inotropy reduce myocardial O2 consumption and are good antianginals
- Rather than lift weights and cause high BP better to walk to increase preload to augment CO without drastically increasing O2 consumption
- Minimize stress which activates sympathetic so increased HR, inotropy and afterload
o Efficiency
- Less efficient heart (LVH) performs less work per O2 unit consumed
o Decrease demand by sedation, muscle relax, artificial ventilation, avoid hyperthermia and shivering, don’t use inotropes
PO 1.46
factors determining myocardial oxygen supply and demand
Supply
Supply = blood flow x arterial O2 content
Depends mainly on flow = change in pressure/resistance
o Resistance, depends on radius, depends on
- Autonimc input
- Autoregulation - pressure and metabolic
- Mechanical compression- decreased in systole
- if increased HR there are biochemical signals to dilate coronary blood vessels to meet increased O2 demands (chap 8)
- so has lots of mitochondria
- uses
- 60% fatty acids – or can use amino acids and ketones in place of this
- 40% carbohydrates – can use exclusively post high carb intake. Or can use lactate in place of glucose when exercising
PO 1.46
factors determining myocardial oxygen supply and demand
how you measure myocardial O2 consumption
o CBF measurement
• Probe on coronary artery
• Thermodilution catheter in coronary sinus
o Venous O2 content measurement
• Catheter through right atrium into coronary sinus pO2 20mmHg
o As these are both invasive another option is looking at change in pressure-rate product, as this correlates to change in myocardial O2 consumption
• Pressure rate product = HR x systolic arterial pressure
• Assume ventricle pressure is same as aortic pressure (noAS)
PO 1.47 control of BP and blood volume distribution
relationship between organ blood flow and demand
(how to answer organ flow/resistance questions)
Flow must meet metabolic and functional demands
- organ flow depends on perfusion pressure and vascular resistance
- Flow = pressure difference/Resistance
- Perfusion pressure usually constant due to baroreceptors (extrinsic - neurohormonal)
- So primary mean of flow change is resistance
- Resistance = viscosity x length/ radius to the 4
- Viscosity increased polycythaemia, decreased anaemia, length is constant, so mainly radius that is important
Radius changed by:
o intrinsic – 5 things (2 types of autoregulation most importan)t:
- Pressure autoregulation - myogenic
- metabolic autoregulation
- endothelial factors
- paracrine hormones
- mechanical compressive forces
- tissue pressure theory
o extrinsic – sympathetic nerves and hormones, less important in resistance for individual organs, more important in keeping MAP and pressure difference up
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
intro
- Allow organs to regulate own blood flow, despite changes to perfusion pressure, to meet metabolic and functional requirements, by changing their resistance (through 5 intrinsic factors of last slide)
- independent of extrinsic forces (neurohormoal) image 46a
blood flow = (Parterial – Pvenous)/resistance
- distribution cardiac output at rest (basal flow)
o if hot increased to skin
o exercise – increase to skeletal muscles, heart and skin
o after eating – increased to GI
o note – kidneys have small vasodilator reserve as not much difference between basal and max flow
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
where intrinsic forces come from and how they act
Where they come from
o from within blood vessel - endothelial factors, myogenic mechanisms
o from surrounding tissue
- tissue metabolites – products of cellular metabolism, hence metabolic activity can autoregulate blood flow.
- local paracrine hormones released by vasoactive substances
- mechanical factors like compressive forces
o act:
- indirectly - affecting endothelial function or affecting relase of norad by sympathetic nerves
- directly - causing vasodilation
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
diagram of how autoregulation works
hypotension and coronary stenosis
o left - drop in perfusion pressure, drops flow, activates metabolic or myogenic mechanism to vasodilate and decrease resistance
o right - autoregulatory range – range of perfusion pressures over which blood flow can be kept constant. Below this point can’t dilate any more
• Diff for diff organs
• better in coronary, cerebral, renal
• worse in skeletal muscle and GI
• none in skin
• neurohumoral influences and disease can move curve
• sympathetic shifts to right
Hypotension:
o baroreceptor constrict systemic vasculature but don’t have to constrict flow to brain and heart unless perfusion pressure falls below autoregulatory range – so it escapes sympathetic vasoconstriction so get adequate blood flow and O2 delivery
Coronary stenosis:
o increased resistance and pressure drop – so lower pressure downstream in distal arteries so they dilate (myogenic) and low flow means they dilate more (metabolic)
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
active/functional hyperemia
Increased organ blood flow from increased metabolic activity of organ/tissue
Due to vasodilation and vascular recruitment
- increased metabolic activity causes hypoxia, increased vasodilator metabolites like K, CO2, NO, adenosine
Occurs in
- Muscle contraction – exercise, functional hyperemia
- Increased cardiac activity
- Increased mental activity
- ncreased GI activity
o At high levels of activity vasculature max dilated so can’t get further increase in flow
o Enhances removal of metabolic waste products
o Ability to vasodilate different between organs
- Can increased 20-50 times in skeletal muscle
- Only increases 2 times in cerebral (low vascular tone as higher metabolic rate under basal conditions)
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
reactive hypereamia
- transient increase in organ blood flow following brief period of ischemia caused by tempory arterial occlusion
- happens as during occlusion tissue hypoxia and build up of vasoactive metabolites dilate arterioles, also decreased pressure causes myogenic mediated vasodialtion, occlusion released and perfusion pressure restored while R still low
- endothelial release of NO contributes
- longer occlusion, increased peak flow and duration of hyperemia
- diff organs need diff amounts of time to get max reactive hyperemic response
- ocoronary occlusion, <1 min
- skeletal muscle, several minutes
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
describe each intrinsic factor
metabolic autoregulation
Tissue metabolites (vasodilators):
Adenosine
o vasodilator in organs except renal vessels
o formation
- dephosphorylation of AMP by 5’nucleotidase
- AMP comes from hydrolysis of ATP and ADP
o Increased in hypoxia and increased O2 consumption (increased ATP hydrolysis)
o Especially important in myocardial blood flow
Potassium
o Vasodilation, especially in skeletal muscle
o Formation
- Contracting cardiac and skeletal muscle if Na+/K+ pump doesn’t keep up with rapid depolarizations
o K+ accumulates around blood vessels, hyperpolarizes as increased K+ conductance through K+ channels, vasodilates
Inorganic phosphate
o Vasodilates skeletal muscle but less important than adenosine, K and NO
o Formation:
- Hydrolysis of AMP, ATP and ADP
CO2
o Vasodilation, important in cerebral blood flow through formation of H+
o Formation
- In oxidative metabolism
o Increases when blood flow reduced
Hydrogen ion
o vasodilation
o Formation
- When acid metabolites like lactic acid produced
o Increased in ischemia/hypoxia
O2
o Decreased tissue partial pressure causes vasodilation directly, except in pulmonary vasculature
o Indirectly via adenosine, lactic acid, H+
Osmolarity
o Hyperosmolarity cause vasodilation
o Increased in tissue ischaemia and raised metabolic activity
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
describe each intrinsic factor
pressure autoregulation
Myogenic mechansims (vasoconstrictor)
- Happens in renal and intestinal and skeletal
- when vessel expanded by increased pressure it contracts (smooth muscle cells depolarize when stretched) to restore diameter and resistance - myogenic response to vascular stretch is contraction
- when decreased pressure get vasodilation
- increased transmural pressure cause vascular smooth muscle to contract (caused by increased venous pressure in intestines)
- BUT increased pressure reduces flow and metabolic mechansims override and cause vasodilation
- Do not occure
- in uterine circulation – vascular bed fully dilated, flow can decrease by half before foetal oxygenation affected
- hepatic portal circulation
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
describe each intrinsic factor
endothelial factors
- Nitric oxide – vasodilator, (see also page 25)
o Most important, basally released
o Stimulated by acetylcholine and bradykinin
o Flow dependant vasodilation - Increased flow causes increased shearing foces increases NO, vasodilates - Important in coronary blood flow increase for increased cardiac activity and metabolism
- Impaired in CAD, hypertension, cerebrovascular disease, diabetes
o Inhibited by nitric oxide synthase inhibitors - vasoconstrction
Prostatyclin – vasodilator
Endothelin-1 – vasoconstrictor
Endothelial derived hyperpolarizing factor (EDHF) –
o Vasodilation from smooth muscle hyperpolarization
o Stimulated by acetylcholine and bradykinin
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
describe each intrinsic factor
paracrine hormones
Histamine (via H1 and H2 receptors)
o causes arteriolar vasodilation, venous constriction, increased permeability
o formation:
- released by mast cells in injury, inflammation, allergic
Bradykinin
o Vasodilates arterioles, stimulates NO and prostacyclin formation by endothelium
o Formation:
- Kallikrein (enzyme) acts on alpha2-globin (kiniogen) in blood and tissues
o Broken down by ACE, so ACE inhibitor increases bradykinin
Arachidonic acid metabolites (eicosanoids)
o Prostacyclin and prostaglandin, vasodilate
o PGF2, thromboxanes and leukotrienes, vasoconstrict
o Affected by asprin/NSAIDS (cyclooxygenase inhibitor) which stops formation of these eicosanoids
PO 1.47 control of BP and blood volume distribution
role of local (intrinsic) regulatory mechnisms (autoregulation is one of them) in organ blood flow
describe each intrinsic factor
mechanical compressive forces
tissue pressure theory
mechanical compressive forces:
- increases pressure outside vessel so transmural pressure decreases, if high enough vessel can collapse
- happens in cardiac systole or skeletal muscle contraction, breathing
- pathological
- gastric distension can increase vascular resistance causing tissue ischaemia
- oedma in brain
Tissue pressure theory:
increased flow means more interstial fluid which compresses vessel from outside and increases resistance
PO 1.47 control of BP and blood volume distribution
features of coronary circulation
anatomy
o Left and Right main coronary arteris from coronary ostia above aortic vavle
o Left main is 1cm, goes behind pulmonary artery, divides
- Left anterior descending, interventricular groove, supply anterior heart
- Circumflex, leftatrioventriclar groove, supply left vent and atrium
o Right main, goes between right atrium and ventricle towards posterior heart, supply right atrium and ventricle and inferoposterior LV
Vessels
o Vessels lie on epicardiac surface – low resistance distribution
o smaller branches dive into myocardium – microvascular resistance vessels regulate flow
o each myocyte has several capillaries, short diffusion distance, max O2 transport and removal of CO2, H+
o veins adjacent to arteries, drain into coronary sinus into RA (90%) and into thebesian vessels (anterior cardiac veins) which drain directly into chambers
o high vasodilator reserve capacity – 80 – 400ml/min/100gm rest vs exercise
PO 1.47 control of BP and blood volume distribution
features of coronary circulation
- High O2 consumption and needs oxidative metabolism so need reliable flow = aortic root pressure (mean arterial diastolic pressure) – intraventricular EDP or RAP(coronary sinus)/ resistance
o These pressures change in the cardiac cycle (pg 70 brandis)
o Aortic pressure usually tightly controlled by baroreceptors
o Intraventricular pressure varies in the cardiac cycle between L and R
Flow:
o not steady as in most other organs – phasic, espec in Left coronary artery
o increases in diastole – most of flow to myocardium occurs, peaks early, decreases as aortic pressure falls so aortic pressure in diastole is crucial
o decreases in systole – contraction compreses microvasculature, mostly at innermost subendocardium of LV as most pressure – more susceptible to ischemia. Flow ceases only in the left subendocardium. Blood flow to left is RATE dependant as increased rate decreases diastolic time and flow
o RV still gets some flow in systole (pressure only 25mmHg vs 120 in left)
Control of flow:
o O2 consumption most important
o adenosine and NO in flow dependent vasodilation important
o mechanical compression as above
o myogenic mechanism functions between 60-160mmHg
o functional sympatholysis - sympathetic only causes trainsietn vasoconstriction (A1) then vasodilate cos increased HR through B1 causes vasodilator metabolites
- if BB – get coronary vasoconstriction
- blackbook says coronary vasodilation via B2
o parasympathetic activation of heart initially causes vasodilation but if significant decrease in myocardial O2 demand, local metabolic mechansims vasoconstrict
PO 1.47 control of BP and blood volume distribution
features of coronary circulation
pathology - CAD and LVH and AS
- CAD
o Narrowing (increased resistance) and impaired vascular function (less NO and prostacyclin→vasoconstric and thrombus) reduces max coronary blood flow, can’t increase when O2 demand increases
o Need 60-70% narrowing oflarge artery as its only a small fraction of total coronary vascular resistance
o Collateral vessels – angiogenesis from hypoxia, collateral vessels decreasese resistance, increases flow - LVH
o Increased muscle mass, compresses arteries, increased resistance - AS
o Increases afterload, higher LV pressure in systole, more coronary artery compression, increased resistance
PO 1.47 control of BP and blood volume distribution
features of cerebral circulation
CPP and how to lower ICP
monroe kellie doctrine
Flow = CPP/SVR
CPP = MAP – ICP (ICP 0-10mmHg) OR VP
- If venous pressure (jugular bulb pressure) is higher than ICP then CPP = MAP –VP
- This is the Starling resistor mechanism – also functions in heart and lung
• May want to decrease flow to decrease ICP or if aneurysm bleeding
- Head up – hydrostatic effects
- Ensure no obstructed venous drainage
- Avoid vasodilators
- Hyperventilate to decrease CO2 and constrict – beware as ph back to normal in few hours and if increase pCO2 now will increase flow and pressure pg 68 brandis
- Mannitol – hypertonic and doesn’t cross BBB so draws water out, then also get diuresis. Hypertonic urea does the same
- Controlled hypotension
Monro kellie doctrine image 79
o Brain enclosed and volume fixed, if increase volume get rapid increase in pressure
o Initially pressure doesn’t go up cos CSF moved out - buffering
PO 1.47 control of BP and blood volume distribution
features of cerebral circulation
autoregulation, functional sympatholysis
o Autoregulates between MAP 60-130mmHg
• Can have MAP on x axis as usually not very diff to CPP as ICP low, can’t do this in pathological conditions tho
• Via metabolic and pressure (myogenic) autoregulation
• Important for moment to moment control of regional flow
- < 60 – low flow, depressed neuronal function, confusion, LOC
- >130 – high flow, can damage endothelium, disrupt blood brain barrier, hemorrhagic stroke
- hypertension - curve shifts right in chronic hypertension to protect brain from high BP but more susceptible to low BP
o Functional sympatholysis
• Sympathetic system only important in maintaining MAP and therefore CPP (increased HR, contractility, peripheral vasoconstriction), does not alter SVR much
• Low CO2 and O2 also stimulate chemoreceptors and low CPP with standing activates barorecptors, these increase sympathetic but this is overiden by dominant local regulation by metabolic mechanisms
• Sympathetic can only increase cerebral vascular resistance by 20-30% (skeletal muslces 500%)
• Esstential to maintain cerebral perfusion (unchanged total flow) when stand or exercise to abort the sympathetic activation
- When exercise regional flow to brain changes – get more to motor cortex
- Shifts curve to right
- Cushing reflex – last attempt at systemic vasoconstriction in CNS ischaemia
PO 1.47 control of BP and blood volume distribution
features of cerebral circulation
CO2 and O2
other vasodilators/constrictors
o arterial CO2 important
• Increased oxidative metabolism increases CO2, diffuses into CSF, forms H+ (due to carbonic anhydrase), vasodilation
• Also increased in impaired perfusion due to low washout
• Very sensitive to small changes in pCO2
• Hyperventilation – decreased pCO2, vasoconstrict, lightheaded. If get sustained hypocapnea, bicarb equilibrates across BBB in 4-6 hrs and flow returned to normal
o Severe Arterial hypoxia
• pO2 <50mmHg, strong vasodilator response in brain to compensate for reduced arterial O2 content
• has to be servere due to shape of oxygen dissociation curve – as pO2 falls O2 content of blood not altered much as flat of curve, until get to 50-60mmHg
o Other vasodilators
• Parasympathetic release NO and vasoactive intestinal polypeptide (VIP)
• Calcitonin gene related peptide (CGRP)
• Substance P
o Other vasoconstrictors
• Neuropeptide Y (NPY), released by sympathetic adrenergic nerves
• Noradrenaline
o Note
• Jugular veins collapsed when sit up due to hydrostatic pressure, in neurosurg, dural sinus walls rigid and pressure inside negative so can suck air in and get embolus
PO 1.47 control of BP and blood volume distribution
features of skeletal muscle circulation
- 3-4 capillaries run parallel to each muscle fibres
- low perfusion distance so efficient exchange
- if not contracting only ¼ of capillaries perfused, all 4 used (recruitment) when contracting
- large flow reserve (capcitiy) so large tone, constriction dominates at rest due to:
- sympathetic
- myogenic
- inactive local tissue metabolites
- contraction
o in exercise flow increased and phasic due to mechanical compression - decreases in contraction
- increases in relaxation
o in sustained muscle contraction – lifting, get decresed flow then hyperemic response when contraction finished
- adenosine, K+ and pO2 important.
- Lactic acid, CO2, H+, hyperosmolarity probably important too
- Muscle pump facilitates blood flow
- Sympathetic adrenergic innervation
- Noradrenaline to A, vasoconstriction in resting, but if it needs more O2 first it extracts more causing increased arterial-venous difference then activates anaerobic pathway for ATP production.
- If this is prolonged get vasodilator mechanisms dominating of sympathetic vasoconstrcion – sympathetic escape
- Can get increased blood flow in sympathetic activation due to B2 and NO
- Can go into oxygen debt – get ATP from anaesrobic metabolism, lactate produced. When stop exercise get increased O2 uptake to metaobolise lactate and replenish ATP
PO 1.47 control of BP and blood volume distribution
features of cutaneous circulation
Anatomy
o small arteries in subcut tissue
o arterioles penetrate dermis
o capillaries loop under epidermis – resistance vessels
o venules extensive interconnecint venous plexus – most of the cutaneous blood volume, responsible for skin colour
o ateriovenous anastomoses – give blood from small subcut arteries to venous plexus – resistance vessels
- low requirement compared to other organs
- flow outweights O2 requirement as role is thermoregulation
- main role is heat exchange to regulate temperature
- controlled by hypothalamic thermoregulatory center
- adjusts sympathetic outflow to cutaneous vasculature
- normal temp – high sympathetic tone
- high temp – decreased sympathetic outflow, vasodilate, increased blood flow, heat energy conducted to environment
- very powerful, flow can range from 1 – 30% of cardiac output
- Resistance vessels
o Capillary loops and AV anastomosis
o Mostly controlled by sympathetic innervation
• Causes activation of sweat glands
o also sensitive to A vasoconstriction from circulating catecholamines
o also sensitive to local regulation but less so than other organs
autoregulation:
- paracrine in sweating and tissue injury – bradykinin →NO →vasodilation
- injury →histamine and bradykinin →vasodilation →oedema
- triple response/active vasodilation (not due to withdrawal of sympathetic
- stroke affected skin, blanches cos of vasoconstriction but then RED LINE that spreads away from injury (FLARE) from increased blood flow then swelling (WHEAL) from permeability leakage
- o due to an unidentified vasodilator substance released as a co-transmitter by sympathetic
• local changes are due to local factors rather than sympathetic
o eg heat one piece of skin, vasodilation due to NO due to local axon reflexes
• cold induced vasodilation
o following initial vasoconstriction, makes cheeks, ears, nose red when cold
o due to impaired local axon reflexes and impaired vasoconstriction ability due to hypothermia
• reactive hyperemia
PO 1.47 control of BP and blood volume distribution
features of renal circulation
intro and anatomy
- highest blood flow (apart from pituitary and carotid bodies)
- Unlike ther organs, flow greatly exceeds need for O2 even though O2 consumption is high (5mlO2/min per 100gm, 18mlO2/min). Flow is instead dependant on meeting the filtering function of the kidney – need to excrete waste and balance Na and water
Anatomy
- cortex – outer with glomeruli, where most filtering happens, gets 90% of blood flow
- medulla – middle with capillaries and tubules to concentrate urine
- hilum – inner where artery, vein, nerves and lymphatics enter/leave
o vascular
• renal artery to each kidney hilum
• interlobar arteries towards cortex
- arcuate and interlobar arteries form afferent arterioles to each glomerulus
- glomerular capillaries
- form efferent arteriole
- forms peritubular capillaries
- then venules and veins and exit kidney as renal vein
• summary – 2 capillary beds, glomerular capillaries between 2 resistance arterioles and peritubular capillaries in series with glomerular capillaries
- Bowmans capsule filters fluid from glomerular capillaries into renal proximal tubule
- Peritubulat capillaries surround renal tubules
- Efferent arterioles are associated with juxtamedullary nephrons – ones located in inner cortex, give rise to vasa recta that loop deep into medulla
- Maintain medullary osmotic gradient
PO 1.47 control of BP and blood volume distribution
features of renal circulation
filtration and autoregulation
- Changes in afferent and efferent arteriole resistance affect flow and hydrostatic pressure in the capillary networks
- Glomerular capillary pressure 50mmHg (higher than other capillaries in body), drives fluid filtration
- Peritubular capillary pressure low10-20mmHg to allow fluid resorption to limit water loss
- Afferent constriction
- Decreased flow, GFR and distal pressure
- Efferent constriction
- Reduces flow and peritubular capillary pressure but increases GFR
o Autoregulates between 80-180mmHg
• flow to kidney and GFR both unchanged – so need contant glomerular capillary pressure, happens because autoregulation happens at afferent arteriole
- BP drops, afferent dilates
- Need to maintain GFR cos 5% increase = 9L urine/day, too much for tubules to reabsorb
- In reality slight increase in pressure slightly increases GFR – this is how u get rid of xs volume persumably
Mechanisms
• Myogenic – vasc smooth muscle relaxes in response to decreased arteriole pressure
• Tubuloglomerular feedback
- Decreased perfusion pressure decrease GFR → decreased tubular flow and Na delivery to macula densa of juxtaglomerular apparatus → afferent dilates
- Macula densa are specialized cells in distal tubule where it loops back up to glomerulus, adjacent to afferent arteriole
- Vasoconstrictors – adenosine, AN II
- Vasodilators- NO, prostaglandin E2, prostacycline
- ANII strong on efferent, so ACE inhibitors dilate, so decreased GFR
- COX inhibitors inhibit vasoconstrictors prostaglandin and prostacyclin
Sympathetic – normally minimally active
• Increased with exercise or severe hemorrhage so renal function shuts down, significantly increases total SVR and helps to maintain arterial pressure
PO 1.46
factors determining myocardial oxygen supply and demand
affect of aortic stenosis on this
see amanda diaz 2008b14 for more
- Chronic condition, reduced cross sectional area of valve and immobile leaflets, causes increased mean pressure gradient across valve
- Impeded ventricular ejection so increased afterload, increased LV pressure, LV hypertropy
- increases myocardial demand and reduces supply – imbalance can lead to ischaemia , infarction, arrhythmia, LV failure. Worse in exercise
- supply reduced
- increased afterload so increased ventricular pressure in systole obliterates flow
- compensatory increased HR from reduced SV decreases diastolic perfusion time
- decreased aortic root pressure means decreased flow (Bernoulli principle)
- increased muscle mass means more resistance to flow in systole
- demand increased
- la place law for increased myocardial work/afterload
- increased ventricular radius
- increased pressure
- increased thickness decreases work but increased bulk muscle therefore more O2 demand
