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
What is external cardiac work
- 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
What si internal cardiac work
- 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
What resources does the heart use to obtain energy?
fatty acids (65%), glucose (15%), lactate (12%). amino acids 3% and anaerobic glycolysis 5%
‣ Adaptable to substrate availability (eg. in ketosis, will use ketones)
‣ If fatty acids are high glucose metabolism suppressed and fatty acid use can be 90% of total
What is the main source of metabolic fuel for the heart?
fatty acids (65%), glucose (15%), lactate (12%). amino acids 3% and anaerobic glycolysis 5%
‣ Adaptable to substrate availability (eg. in ketosis, will use ketones)
‣ If fatty acids are high glucose metabolism suppressed and fatty acid use can be 90% of total
How much ATP is stored in heart muscle>
◦ Very small ATP store compared to demands - 4-8% of total myocardial ATP is consumed with each beat, therefore consumed rapidly in absence of substrate
What does the foetal heart use as fuel source
Glucose and lactate
What is sthe oxygen consumption of the brain in ml/100g/min
3ml/100g/min
What is the kidney oxygen consumption in ml/100g/min
5ml/100g/min
What is the resting skeletal muscle oxygen consumption in ml/100g.min? How does this change with exercise
1ml/100g/min –> 50ml/100g/min
What is skin blood flow per 100g/min
0.2ml/100g/min
What is the main determinant of coronary oxygen demand?
Heart rate - linear relationship. Increase HR by 50 –> increased O2 consumption by 50%
How does preload affect myocardial oxygen demand?
Minimal influence, increase by 50% increases work by 4%
How does contractility affect myocardial oxygen demand?
◦ Contractility is a major contributor (dP/dT) - if dP/dT is icnreased by 50% myocardial oxygen consumption increases by 45%
How does afterload affect myocardial oxygen demand
◦ Afterload is a major contributor - Increasing afterload by 50% increases oxygen demand by 50%
‣ This is determined by myocardiac wall tension - generating pressure without ejection of volume. Wall tension is defined by the Law of Laplace –> Wall tension = pressure during contraction x radius/2
‣ Wall tension is therefore a function of:
* Afterload
◦ Increasing afterload will increase the pressure during contraction.
* Preload
◦ Increasing preload will increase radius, but to a lesser extent than increasing afterload.
‣ This is because volume and radius are not directly proportional
What are the main detterminants of myocardial oxygen consumption
◦ Heart rate is the main determinant - linear relationship - increasing HR by 50% increases myocardial O2 consumption by 50%
◦ Preload is a minor contributor - increasing preload by 50% increases work by 4%
◦ Contractility is a major contributor (dP/dT) - if dP/dT is icnreased by 50% myocardial oxygen consumption increases by 45%
◦ Afterload is a major contributor - Increasing afterload by 50% increases oxygen demand by 50%
‣ This is determined by myocardiac wall tension - generating pressure without ejection of volume. Wall tension is defined by the Law of Laplace –> Wall tension = pressure during contraction x radius/2
‣ Wall tension is therefore a function of:
* Afterload
◦ Increasing afterload will increase the pressure during contraction.
* Preload
◦ Increasing preload will increase radius, but to a lesser extent than increasing afterload.
‣ This is because volume and radius are not directly proportional
◦ Cost of electrical conduction: thought to be minimal 0.5 - 5%
◦ Basal cost of cardiac metabolism, and the factors which affect it, which are:
‣ Temperature, eg. hypothermia decreases cardiac metabolism both directly and indirectly rthough effect on HR and contractility
‣ Metabolic enzyme function modifiers, eg. perhexiline
How would you calculate DO2 of the heart
Coronary O2 delivery = Coronary blood flow × (sO2 × ceHb × BO2 ) + (PaO2 × 0.003)
Where
- Coronary blood flow = 80-160ml/100g/min (wide range of reported values)
- ceHb = the effective haemoglobin concentration (Let’s say 100g/L in ICU patients)
- PaO2 = the partial pressure of oxygen in arterial gas (let’s say about 75 in ICU patients)
- 0.003 = the content, in ml/L/mmHg, of dissolved oxygen in blood
- BO2 = the O2 carrying capacity of blood (normally 1.39ml/ml)
- sO2 = oxygen saturation (let’s face it , its going to be 90-100%)
What is the oxygen consumption at a HR of 70 by the hart
At baseline the heart has a resting oxygen consumption in the absence of contraction that is 8x that of the body in a resting state (whole body 0.3ml/100g/min or 3ml/kg/min –> heart 2.2 ml/100g/min when not contracting and at resting HR is 7-10ml/100g/min)
What is coronary perfusion pressure? What is it dependent on? What relationship exists between these factors?
- Coronary perfusion pressure: difference between aortic and ventricular pressure
◦ Linear relationship
◦ Exercise shifts this curve to the right - less flow per unit pressure due to diastole impairing effects of tachycardia
What effect does exercise have on coronary perfusion pressure?
- Coronary perfusion pressure: difference between aortic and ventricular pressure
◦ Linear relationship
◦ Exercise shifts this curve to the right - less flow per unit pressure due to diastole impairing effects of tachycardia
Where is the resistance in coronary vessels to flow?
- Coronary vascular resistance, which is affected by the resistance of the small endocardial arteries - larger epicardial arteries do not contribute majorly to resistance (essentially no pressure drop along the vessel even with changing blood flows). Resistance mostly occurs in vessels 0.1mm in diamtre by
What metabolic factors influence coronary artery vascular resistance
◦ Metabolic activity eg. ischaemia and hypoxia –> produces coronary vasodilation.
‣ Adenosine is thought to be one of the primary mediators; but potentially not as important in day to day regulation in response ot exercise etc.
‣ Hypoxia and hypercaribia both increase coronary blodo flow
‣ Potassium - Potassium-mediated vasodilation can also occur as the result of opening ATP-sensitive potassium channels. These channels are inhibited by intracellular ATP; i.e. wherever ATP is deficient, the channels open and hyperpolarise the membrane, resulting in smooth muscle vasodilation.
‣ Hydrogen peroxide
‣ pH and lactate
What are the modifying factors to the basal cost of myocardial metabolism?
- Basal cost of cardiac metabolism, and the factors which affect it, which are:
◦ Temperature (which may increase cardiac oxygen consumption if it is associated with an increased heart rate, eg. when the patient is febrile)
◦ Drugs, some of which may cause tachycardia as well as an alteration in cardiac metabolism
Compare the oxygen demand of the LV and RV?
Compare myocardial oxygen supply between LV and RV
What is normal skeletal muscle flow at rest
◦ At rest, 1-4ml/min/100g of muscle tissue
With peak exercise what can skeletal blood flow levels reach
◦ With vigorous exercise, up to 400ml/min/100g - where it comprises 90% of cardiac output
‣ Blood flow response to exercise is linear
In shock states what can skeletal blood flow get down to
0.1 - 0.4 ml/100g/min
What is the autoregulation range of muscular blood flow
◦ Vessel wall stretch produces a calcium-mediated reflex vasoconstriction - leading flow to remain stable over a MAP range of 40-140mmHg and perfusion remains 2-3 ml/100g/min
What are examples of vasoactive mediators utilised in skeletal muscle for dilation
- Vasoactive substrates and products of muscle metabolism
◦ Muscle hypoxia produces vasodilation
◦ Metabolic byproducts (CO2, lactate, hydrogen peroxide and potassium ions) act as vasodilators
◦ Regional decreases in pH produce vasodilation independently of CO2 and lactate - Vasoactive mediators released by the endothelium can alter skeletal muscle blood flow, though they do not seem to be essential for exercise-induced hyperemia:
◦ Nitric oxide (NO)
◦ Adenosite triphosphate (ATP)
◦ Adenosine
◦ Prostaglandins
◦ Endothelium-derived hyperpolarization factors (EDHFs)
Where is skeletal muscle vasculature innervated
Arterioles
Nil to venules or capillaries
What receptors does skeletal muscle vasculature have for ANS stimulus
◦ α-1 receptor activation leads to skeletal muscle vasoconstriction
‣ Sympathetic innervation vasconstricts skeletal muscle arterioles to maintain a high resting vessel tone for inactive muscle
‣ In haemorrhagic shock, α-1 receptor activation helps redistribute blood flow away from muscle
◦ β-2 receptor activation leads to skeletal muscle vasodilation
‣ Systemic adrenaline release increases muscle blood flow for “fight or flight” responses, in addition to increasing cardiac output, increasing the capacity for muscle activity
What is normal hepatic blood flow as a % of cardiac output?
25%
What is the normal hepatic blood flow in ml/min
1200-1800ml/min
What is the oxygenm delivery to the liver
100ml/100g/min
What is hepatic oxygen consumption
6ml/100g/min from 16ml/100g/min
Hepatic veinous oxygen saturation is?
65% normally
What is the hepatic blood supply form
Coeiliac trunk –> common hepatic artery –> hepatic artery proper
- 35% of flow –> 45% of DO2
Portal vein
- 65% of flow 55% DO2
What is the MAP of hepatic arterial supply
Closely resembling aortic - 60-90
What % of blood flow in the liver is arterial
30-40%
What % of oxygen supply to the liver is arterial
40-50%
Portal vein comes from what tributaries? Where do they combine?
‣ Confluence of mesenteric and splenic veins - behind the pancreas body
Describe the characteristics of the portal system? (3)
‣ Valveless, low pressure venous system (8-10 mmHg) - minimal smooth muscle in their walls - flow is mainly driven from the transmitted pressure of splanchnic arterioles
* Pressure drops to post sinusoidal venules and hepatic vein pressures of 2-4mmHg
What is the pressure in portal system? How does this still promote flow?
‣ Valveless, low pressure venous system (8-10 mmHg) - minimal smooth muscle in their walls - flow is mainly driven from the transmitted pressure of splanchnic arterioles
* Pressure drops to post sinusoidal venules and hepatic vein pressures of 2-4mmHg
Why can portal flow be reversed
‣ Valveless, low pressure venous system (8-10 mmHg) - minimal smooth muscle in their walls - flow is mainly driven from the transmitted pressure of splanchnic arterioles
* Pressure drops to post sinusoidal venules and hepatic vein pressures of 2-4mmHg
What is the hepatic vein pressure
‣ Valveless, low pressure venous system (8-10 mmHg) - minimal smooth muscle in their walls - flow is mainly driven from the transmitted pressure of splanchnic arterioles
* Pressure drops to post sinusoidal venules and hepatic vein pressures of 2-4mmHg
What % of liver blood flow is portal? how much blood flow is this? What are the SVO2 of portal veinous blood? How can this change
‣ 70% of the total blood flow (SvO2=85% (lower after a meal ~70%); 50-60% of the DO2) 800-1200ml/min
Hepatic outflow is via?
Right, middle and left hepatic veins
Hepatic microcirculation features
◦ Consists of the anastomosis of hepatic arterioles and portal venules
◦ These vessels join to form hepatic sinusoids
◦ Sinusoids are highly modified large-caliber capillaries with discontinuous endothelium
◦ Unique features:
‣ Low pressure, to prevent retrograde flow in the valveless portal system –> 3-5mmHg
‣ Low flow velocity, to enhance extraction of oxygen and other molecules of interest
What % of total circulation is a reservoir in the liver
8%
Portal veinous flow rate is mainly dependent on?
Splanchic arterial flow rate
- Humeral signals e.g. reduced perfusion in shock
- Local; endocrine signals following a meal - can increase by 80%
- Hypocapnoea reduces flow
Veinous return factors
- During pspontneosu breathing inspiration increases hepatic veinous flow, PPV changes this
Hepatic arterial flow is regulated by?
- Systemic factors
◦ Arterial baroreflex control (increased BP leads to a increase in SVR) fails below MAP 60mmHg
◦ Peripheral and central chemoreceptors (hypoxia leads to increased SVR)
◦ Hormones (eg. vasopressin and angiotensin)
◦ Temperature (hypothermia leads to increased SVR)
* Local
◦ Intrinsic myogenic regulation in response to stretch
◦ Tissue metbaolic regulation
◦ Flow or shear strewss associated regulation
◦ Neighbouring vascular site vasomotor responses
◦ Cooling
◦ Immunological
hepatic arterial buffer response refers to? How does this work?
hepatic arterial flow increases if portal venous flow decreases, and to a lesser extent vice versa.
* Hepatic arterial resistance is proportional to portal venous blood flow - linear, rapidly adapting.
* Adenosine washout hypothesis - adenosine releases in periportal space, then trapped and can only diffuse into vessels. The portal vein usually has a high flow rate so washout is rapid, and as adenosine is a vasodilator when it is lost it leads to vasoconstriciton. The hepatic artery is most prone to vasodilator/constrictor action so when portal flow is lost exclusive uptake in the hepatic artery of a vasodilating substance increases flow
How does the liver respond to increased tissue demand for O2?
Increased extraction
Most mechanisms for increasing flow are about achieving stable flow
What external factors infleucne blood flow in the liver
◦ Venous return: affects hepatic venous drainage (eg. during positive pressure ventilation or heart failure)
‣ Increased by spontaneous breathing on inspiration
‣ Decreased by PPV, heart failure (RHF) and fluid overload
◦ Cardiac output: influences hepatic arterial flow directly, and portal flow indirectly (eg. in heart failue)
‣ Increased arterial blood flow in increased cardiac output states
‣ Decreased cardiac output states decrease arterial blood flow, especially things which redistribute splanchnic blodo flow e.g. exercise
◦ Portal blood flow
‣ Increased after a meal with splanchnic vasodialtion
‣ Decreased in shock
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
What are the vessels coming off the coeiliac trunk
‣ Coeliac trunk - left gastric artery, common hepatic artery and splenic artery. Largest branch, most proximal highest flow
* Supplying the abdominal part of the oesophagus, stomach, superior duodenum, liver, superior half of pancreas and spleen
Which of the GI vessels has the highest flow
coeliac trunk
What does the SMA supply
‣ Superior mesenteric artery - supplying int he lower half of the duodenum and the intestine to the splenic flexure
* Inferior pancreaticoduodenal artery
* Intestinal arteries
* Ileocolic artery
* Right and middle colic artery
What does the IMA supply
‣ Inferior mesenteric artery - supplying the colon from the splenic flexure to the sigmoid and upper portion of th erectum
* Left colic rtery
* Sigmoid artery
* Superior rectal artery
‣ There is an extensive collateral circulation which protects against ischaemia
Veinous drainage of the gut is via?
◦ The venous drainage is into the portal vein, and then into the liver
‣ oesophagus via azygous veins and inferior thyroid
‣ Mesenteric circulation drains via superior and inferior mesenteric veins
* these join to form the splenic vein
* The portal vein is formed from this whch then splits to form the right and left branches in the liver
‣ Lower third of rectum and anus drain into the middle rectal vein directly into the IVC
What % of cardiac output goes to the gut? What does this increase to post prandially?
20%
–> 35% post prandial
At rest tissue blood flow to the gut per 100g/min is?
30ml/100g/min
Oxygen extraction in the gut is? Why?
◦ Oxygen extraction ratio is low (~ 10%) - partly due to countercurrent villus mechanism allowing arterial oxuygen to diffuse into veinous blood - this can predispose the intestine to ischameia (the muscularis layer receives the least blood supply whereas the mucosal surfaces the most)
◦ The splanchnic organs tend to extract more oxygen as flow decreases, and autoregulatory input into blood flow is therefore minimal under normal circumstances
◦ Extensive anastomosis (no end arteries) with lots of collateral circulation
◦ Stomach and large bowel = less perfusion; pancreaus and small intestine more perfusion
Which areas of the gut get the most perfusion
◦ Oxygen extraction ratio is low (~ 10%) - partly due to countercurrent villus mechanism allowing arterial oxuygen to diffuse into veinous blood - this can predispose the intestine to ischameia (the muscularis layer receives the least blood supply whereas the mucosal surfaces the most)
◦ The splanchnic organs tend to extract more oxygen as flow decreases, and autoregulatory input into blood flow is therefore minimal under normal circumstances
◦ Extensive anastomosis (no end arteries) with lots of collateral circulation
◦ Stomach and large bowel = less perfusion; pancreaus and small intestine more perfusion
How does the gut autoregulate its flow to get more O2?
◦ Oxygen extraction ratio is low (~ 10%) - partly due to countercurrent villus mechanism allowing arterial oxuygen to diffuse into veinous blood - this can predispose the intestine to ischameia (the muscularis layer receives the least blood supply whereas the mucosal surfaces the most)
◦ The splanchnic organs tend to extract more oxygen as flow decreases, and autoregulatory input into blood flow is therefore minimal under normal circumstances
◦ Extensive anastomosis (no end arteries) with lots of collateral circulation
◦ Stomach and large bowel = less perfusion; pancreaus and small intestine more perfusion
What are the primary mediators of blood flow to the gut?
◦ Intrinsic autoregulation: main mechanism of oxygen utilisation however is just increased extraction rather than increased flow
‣ Myogenic autoregulation (stretch-mediated calcium release and vasoconstriction in vascular smooth muscle)
‣ Metabolic autoregulation (likely mediated by adenosine)
◦ Autonomic regulation
‣ Sympathetic vasoconstriction (noreadrenergic α-1 effect)
* Decreased gastric and especially mucosal blood flow
* Markedly decreased intestinal blood flow - some autoregulatory escape
* Decreased blood flow to the colon
‣ Parasympathetic vasodilation (acetylcholine-mediated NO release)
* Increased gastric blood flow (not ACh associated)
* Increased intestinal blood flow - not vagal but definitely ACh mediated
* Increased colonic and rectal blood flow
◦ Humoural and hormonal regulation
‣ Vasoactive mediators (of which there are many)
‣ Exogenous drugs
What effect does SNS have on the gut?
‣ Sympathetic vasoconstriction (noreadrenergic α-1 effect)
* Decreased gastric and especially mucosal blood flow
* Markedly decreased intestinal blood flow - some autoregulatory escape
* Decreased blood flow to the colon
What is a portal circulation?
- Definition of a portal circulation:
◦ An arrangement by which blood collected from one set of capillaries passes through a large vessel or vessels, to another set of capillaries before returning to the systemic circulation.
Describe the hepatic portal system of circulation
Hepatic
* Anatomy
◦ Feeding artery: SMA, IMA, coeliac trunk
◦ Primary capillary bed: intestinal villous capillaries
◦ Portal vessel: the portal vein (confluence of mesenteric and splenic vein)
◦ Secondary capillary bed: hepatic sinusoids (with anastomosing hepatic artery cpiallaries)
◦ Draining vein: hepatic veins
* Function
◦ Portal blood undergoes metabolic and immune modifications in the hepatic sinusoid, which allow for the biotransformation of drugs or metabolic substrates and the clearance of pathogens.
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).
What % of blood flow does the liver need? WHat % of body oxygen consumption?
25% of blood flow 1250-1500ml/min
Liver needs 20% of total body O2 consumption (VO2) ie approx. 50ml/min
Cerebral blood flow at baseline?
CBF is 750ml/min (50ml/100g/min), 14% CO
