G4 peripheral and coronary circulation Flashcards
What is the Starling model of fluid equation
Jv = Lp S [ (Pc - Pi) - σ (Πc - Πi) ]; where
What does LpS stand for in the Starling model of fluid equation
- Lp S is the permeability coefficient/filtration coefficient of the capillary surface, and is affected by shear stress and endothelial dysfunction.
◦ It is a product of the hydrolic permability coefficient (Lp) and surface area of the capillaries (S)
◦ High Kf indicates high water permeability
What is the hydrostatic pressure gradient in normal capillary blood vessels
◦ Pc, capillary hydrostatic pressure is usually:
‣ 32 mmHg at the arteriolar end of the cpaillary
‣ 15 mm Hg at the venular end
What affects capillary blood pressure
Systemic blood pressure
Precapillary vasoconstriction - shock states
Veinous obstruction
Posture
What is the normal intersititial hydrostatic pressure>
‣ negative (-5-0 mmHg) in most tissues (except for encapsulated organs, where it is slightly positive, +3 to +6 mmHg)
What modifies capillary hydrostatic pressure?
‣ Affected by anything that modifies lymphatic drainage, eg.:
* Tourniquet
* Immobility, decreased muscle pump activity
* Lymph node removal
* Inflammation, eg burns (where it becomes extremely negative, eg. -20 to -30 mmHg)
Capillary oncotic pressure and its influencing factors? What is the intersitial osmotic pressure?
- Πc - Πi is the capillary-interstitial oncotic pressure gradient
◦ Πc, capillary oncotic pressure = 25mmHg
◦ Affected by the protein content of blood, eg.:
‣ hypoalbuminaemia (eg. liver disease)
‣ Hypoproteinaemia (eg. malnutrition, nephrotic syndrome)
◦ Πi, interstitial oncotic pressure = 5 mmHg
‣ Affected by the protein content of interstitial fluid, which is usually low but which can increase in local inflammation
What is teh reflection ocoefficent
- σ is the reflection coefficient for protein permeability and is a dimensionless number which is specific for each membrane and protein - it modifies the oncotic pressure to reflect the effect leakage of protein across the membrane will have on forces and correct the magnitude of the measured gradient to account for he in effectiveness of some of the oncotic pressure gradient
◦ σ = 0 means the membrane is maximally permeable
◦ σ = 1 means the membrane is totally impermeable
◦ In the muscles, σ for total body protein is high (0.9)
◦ In the intestine and lung, σ is low (0.5-0.7)
What is the balance of the Starling forces?
The balance of these forces is for filtration (20ml/min out; 18ml/min back in) with bulk flow out of the capillary - usually 2-4L of net filtration fluid per day (2mL/min_. This is mobilised back into venous circulation via lymphatics.
How is blood flow regulated?
Explain the main mechanisms by which peripheral circulations autoregulate
- Myogenic
- Metabolic
- Flow related - Proximal vasodialtion, paracrine signalling
- Non metabolic humeral mediators
- Organ specific buffer responses - kidneys, liver, maternoplacental
Explain the myogenic mechanisms of peripheral autoregulation
◦ This is an intrinsic property of all vascular smooth muscle - peripheral circulation control may occur via end organ arteries (muscular arteries) or resistance arterioles
‣ Seen in the brain, heart and kidney in particular, notably not in the skin
‣ E.g. flow maintained constant in cerebral circulation over range of 50-150 mean carotid artery pressure
◦ Vessel wall stretch produces smooth muscle cell depolarisation —>opening mechanical gated calcium channels in response to stretch —> calcium influx —> vasoconstriction by myosin light chain phosphorylation
How is metabolic autoregulation performed? What are potential mediators>
◦ Blood flow increases in response to increased tissue demand, eg. in exercising skeletal muscle; whereby metabolic byproducts which reflect tissue activity have local vasoconstriction/dilation properties
◦ Vasodilation in response to increased demand allows for increased oxygen tissue delivery module to reduced resistance and increased flow
◦ Potential mediators include potassium, hydrogen peroxide, lactate, hydrogen ions (pH), adenosine, ATP and carbon dioxide, endothelin, prostacyclin, nitric oxide
What is non metabolic mediators
Histamine, bradykinin release
◦ Bradykinin - vasodilation in salivary glands, gut and skin ◦ Histamine - released from basophils as a part o the inflammatory response causing vasodilation and increasing flow - can be regional regulation ◦ In contrast locally released serotonin and TXA2 in response to local tissue injury from platelet activation causes vasoconstriction reducing regional flow to a specific area
What is flow related autoregulation
- Flow or shear-associated regulation
◦ This is the phenomenon of proximal vasodilation in response to distal vasodilation.
◦ This shear stress promotes the release of various vasodilatory mediators from the affected endothelium and produces vasodilation of the larger proximal arteriole. - Conducted vasomotor responses
◦ Regional control of one region by the vasomotor events of another neighbouring region.
◦ Mediated by conduction of cell-to-cell signals from a small arteriole upstream to a larger arteriole
Organ specific regulatory mechanisms
- Renal
- Hepatic
- Organ-specific regulatory mechanisms:
◦ Hepatic arterial buffer response:
‣ hepatic arterial flow increases if portal venous flow decreases, and vice versa.
◦ Renal tubuloglomerular feedback
‣ This is a negative feedback loop which decreases renal blood in response to increased sodium delivery to the tubule
‣ The mechanism is mediated by ATP and adenosine secreted by macula densa cells, which cause afferent arterolar vasoconstriction
◦ Maternoplacental blood flow
‣ Blood flow is gradually increased over the course of pregnancy by the actions of the trophoblast asit invades the spiral arteries of the uterus however the vascular bed of the pregnant uterus is generally fully dilated and autoregulation capacity is absent and flow is pressure dependent
Where do the coronary vessels arise from
Sinuses of valsalva above the aortic cusps in the aortic root
Where does the left main arise from
- Left main - from the left posterior coronary sinus above the L cusp of the aortic valve
What are the cusps of the aortic valve
Left, right, anteiror
What are the cusps of the tricuspid valve
anterior, septal and posterior
What are the cusps of the mitral valve
Anterior and posterior
What are the cusps of the pulmonary valve
anterior cusp (AC), the left cusp (LC), and the right cusp (RC).
Describe the apth of the left coronary artery and its branches
◦ Divides into left anterior descending (from which the diagonal and septal branches arise) and left circumflex (runs in AV groove posteriorly) from which obtuse marginal branches arise +/- RCA anastomoses for posterior descending
◦ Supplies most of the septum and LV; 40% SA node by circumflex
What % of people have a dominant SA node supply from left
◦ Divides into left anterior descending (from which the diagonal and septal branches arise) and left circumflex (runs in AV groove posteriorly) from which obtuse marginal branches arise +/- RCA anastomoses for posterior descending
◦ Supplies most of the septum and LV; 40% SA node by circumflex
What % of people have their AV node from the left
10%
What % of people have their Sinoatrial node supplied by the right
60%
What % of people have their AV node supplied by the right
90%
Right coronary originates from?
Anterior coronary sinus, right cusp
Where does the Rightt coronary run
- Right coronary - from the anterior coronary sinus / right cusp - in groove between RV and RA running anteriorly then posteirorly to encircle the heart
◦ Supplies the RV (via marginal artery) , the sinoatrial node (60%), posterior inter ventricular artery and AV node
Coronary sinus receives what % of coronary arterial flow?
90%
Where does the coronary sinus drain into
◦ Drains into the right atrium; opening is between the IVC and the tricuspid valve
◦ Venous blood oxygen saturation here is ~ 30% (PaO2 20mmHg) - very high oxygen extraction ratio (70% at rest)
What is the hearts resting coronary oxygen extraction
◦ Drains into the right atrium; opening is between the IVC and the tricuspid valve
◦ Venous blood oxygen saturation here is ~ 30% (PaO2 20mmHg) - very high oxygen extraction ratio (70% at rest)
What % of cardiac output goes to the coronaries?
5%
What is the ml/100g/min of the coronaries
50-120ml/100g of myocardial mass
What is the ml/min flow to coronaries? What can it increase up to?
250ml/min and can increase up to 5x
How much oxygen per minute does the heart use?
13-20ml/min
Describe LV coronary bllod flow
75% of flow in diastole
1. ◦ Sharp decrease during isometric contraction - can be negative - due to high chamber pressure
◦ Sharp increase during early part of systole - systolic maximum during summit of aortic pressure
◦ Decreases significantly with a decrease in aortic pressure (again can be negative),
◦ Increases sharpy during isovolumetric relaxation
◦ Maximal mid-diastole
◦ Decreases gradually in late diastole following DBP gradient
◦ Thus, diastolic time is more important for LV perfusion, and it can be compromised by tachycardia
Draw a graph representing coronary blood flow over time
Demonstrate graphically the different blood flows between left and right coronaries
What is the driving pressure in coronary circulation
aortic DIASTOLC pressure - (LVEDP or RAP or coronary sinus pressure - whichever is larger)
What flow is required for adequate blood supply to the LV
5-100ml/100g/min
What is the flow required for adequate blood supply to the RV
30-60ml/100g/min
How is coronary blood flow controlled intrinsically
Important to state that oxygen extraction can not increase, increase in oxygen supply has to come from increased flow
Mechanisms of intrinsic regulation
1. Myogenic autoregulation - perfusion pressure constant between MAP 60-180
2. Metabolic - adenosine release from cells, O2, CO2, nitric oxide, lactate, pH and potassium. ATP sensitive potassium channels open in response to decreased ATP
3. Flow regulation
Atherosclerosis is an inhibition to flow occuring appropriately
What factors influence coronary blood flow extrinsically
- HR
- Autonomic
- Alpha 1 vasoconstriction
- Beta vasodilation
- Muscurinic - weak vasodilation - Medications
- Vasodilators - adenosine, GTN, dipyridamole
- Vasoconstrictors - vasopressin, COX inhibition
How does the autonomic system affect coronary artery tone
- Alpha 1 vasoconstriction
- Beta vasodilation
- Muscurinic - weak vasodilation
How do you calculate coronary oxygen consumption
Fick principle
VO2 = CO x (Ca - Cv)
What is the resting myocardial oxygen consumption in arrest? How does this change at baseline function? What about maximal function
◦ = 2ml/100g/min under conditions of cardiac arrest, 8ml at rest, or 90ml/100g/min at maximal inotropy.
◦ Oxygen extraction ratio is about 75%, and remains stable over a wide range of myocardial workloads (i.e. flow rate is increase to increase O2 delivery)
How is the resting energy consumption divided into the various components of the heart?
◦ 60% of this is used for contraction, 15% for relaxation, 20% for basal metabolism and 3-5% for electrical activation
The PV volume loop provides a mechanism to discuss myocardial work - what are the 2 subdivisions and what do they mean?
- Internal work - This is the work done by the ventricle to CHANGE SHAPE and CHANGE PRESSURE during isovolumetric phases (no ejection)
- External work - work done to eject ventricular stroke volume - this is represented by the enclosed area of the PV loop. 85-90% of cardiac work, some sources provided 50/50, and is at higher proportions during increased myocardial work
Draw a PV volume loop and indicate how work is reflected
- Internal work - This is the work done by the ventricle to CHANGE SHAPE and CHANGE PRESSURE during isovolumetric phases (no ejection)
- External work - work done to eject ventricular stroke volume - this is represented by the enclosed area of the PV loop. 85-90% of cardiac work, some sources provided 50/50, and is at higher proportions during increased myocardial work
Compare the oxygen demand of the LV and RV?
Compare myocardial oxygen supply between LV and RV
What is hepatic clearance equation
Hepatic blood flow x hepatic extraction ratio
How is drug metabolism influenced by liver blood flow
- What happens to drug metabolism with decreasing liver blood flow depends on the intrinsic hepatic clearance of that drug.
◦ The higher the intrinsic clearance, the more blood-flow-dependent the clearance of that drug.
◦ Thus, for drugs with low intrinsic clearance, hepatic clearance will not increase significantly with increasing blood flow.
◦ For drugs with high intrinsic clearance, hepatic clearance will decrease in a fairly linear fashion, in proportion to hepatic blood flow.
Compare renal and hepatic regional circulations
- Anatomy of blood supply
- Flow
- Flow as a % of cardiac output
- Venous drainage
- Oxygen consumption
- Flow distribution
- Capillary beds - anything unique
- Function
Describe the pituitary portal system
- Anatomy
◦ Feeding artery:
‣ superior hypophyseal artery (from ACA) to hypothalamus
‣ Inferior hypophyseal artery from ICA to posterior pituitary
◦ Primary capillary beds:
‣ hypothalamic capillaries –> long portal vessels
‣ posterior pituitary capillaries –> short portal vessels
◦ Portal vessel: the long portal vessels and short portal vessels
‣ Inferior hypophyseal veins drain into the cavernous sinus (offshoot)
◦ Secondary capillary bed: capillaries of the anterior pituitary - does not have any direct arterial supply therefore susceptable to ischaemia and infarction
‣ (fenestrated to allow rapid passage of large hormones)
◦ Draining vein: hypophyseal veins, which variably drain into the cavernous sinuses - Function
◦ To efficiently present hypothalamic regulatory hormones to the pituitary gland in high concentration (rather than releasing them into the systemic circulation)
Describe the renal portal system
- Anatomy
◦ Feeding artery: afferent arteriole
◦ Primary capillary bed: glomerular capillaries
◦ Portal vessel: efferent arterioles
◦ Secondary capillary beds:
‣ Peritubular capillaries
‣ Vasa recta
◦ Draining vein: Renal vein - Function
◦ To reclaim solutes from the glomerular ultrafiltrate fluid.
◦ To deliver solutes fr active excretion by the proximal tubule
◦ To maintain concentration gradients in the renal medulla, (to reabsorb water).
