- Clinical science
The circulatory system, which is also called the vascular system or cardiovascular system, consists of the systemic circulation, pulmonary circulation, the heart, and the lymphatic system. Blood flow through the circulatory system is generated by the heart. Vascular resistance is the amount of resistance in the systematic circulation that must be overcome to create blood flow. The Poiseuille equation describes the relationship between vascular resistance, the length and radius of the vessel, and the viscosity of blood. Blood pressure is generated by the heart, creating a pulsatile blood flow that leads to systolic blood pressure (maximum pressure reached during a cardiac cycle) and diastolic blood pressure (minimum pressure reached during a cardiac cycle) within the circulatory system. The pressure gradient across the circulatory system drives the blood flow from high pressure to low pressure. Blood pressure regulation involves a complex interaction of various sensors (baroreceptors, volume receptors, chemoreceptors) and mechanisms, including the autonomic nervous system, the renin-angiotensin-aldosterone system (RAAS), and atrial reflex and diuresis reflex. Perfusion is the passage of the blood through the circulatory system to the capillary bed to deliver oxygen and nutrients to the tissue and remove waste products (e.g., removal of CO2 to the lungs, removal of urea to the kidneys). Perfusion levels differ in organs and fluctuate depending on the activity (e.g., rest, physical activity). Autoregulatory mechanisms (myogenic autoregulation, local metabolite production), as well as central regulatory mechanisms, modulate perfusion levels in organs. The exchange of substances in the microcirculation occurs via diffusion, filtration, and reabsorption. Capillary fluid exchange is described by the Starling equation, which states that the net fluid flow is dependent on the capillary and interstitial hydrostatic pressures, oncotic pressures, and the vascular permeability to fluid and proteins.
- Systemic circulation: Oxygenated blood flows from the left ventricle into the systemic circulation and, after passing through the capillary bed, flows back in a deoxygenated state to the right atrium of the heart to restart the process.
- Pulmonary circulation: Deoxygenated blood in the right heart flows into the lungs, where it is oxygenated and returned to the left atrium.
Heart: connects systemic circulation and pulmonary circulation
- See and for details.
- Lymphatic system: a network of lymphatic vessels that transport lymph toward the heart (see lymphatic drainage for details)
Pressure, flow, and resistance
- The relationship between pressure, flow, and resistance in the circulatory system is expressed as ΔP = Q x R
- ΔP = pressure gradient
- Q = blood flow
- R = vascular resistance
- Blood flow is driven by cardiac activity pumping blood through the circulatory system.
- Volume of blood returning to the heart per minute = cardiac output (CO)
- Rate of blood flow = blood flow / total cross-sectional area of the blood vessel
- The rate of blood flow (blood velocity cm/s) is inversely proportional to the total cross-sectional area of the blood vessel.
Capillaries have the largest total cross-sectional area of all blood vessels (i.e., 4500–6000 cm2 compared to 3–5 cm2 in the aorta) and, thus, the slowest blood velocity (0.03 cm/s) compared to the aorta (40 cm/s).
Laminar and turbulent blood flow
Blood flow in vessels is eitheror depending on the smoothness of the blood vessel walls, the viscosity of the blood, the blood velocity, and the diameter of the lumen.
Laminar blood flow
- Definition: a layered flow pattern
- Effect: The layer with the highest velocity flows in the center of the vessel lumen.
- Occurrence: throughout the vascular system
- Turbulent blood flow
- Definition: resistance offered by the circulatory system that must be overcome to create blood flow (R = ΔP / Q)
Vascular resistance comprises:
- Total peripheral resistance (TPR): the amount of resistance to blood flow in the systemic circulation = () - / CO
- This equation describes the relationship between systemic vascular resistance (R) and the length of the vessel (L), the radius of the vessel (r), and the viscosity of blood (η).
Resistance to flow: R = 8ηL/(πr4)
- Systemic vascular resistance is inversely proportional to vessel radius to the 4th power.
- Systemic vascular resistance is proportional to blood viscosity, which is primarily determined by hematocrit.
- Systemic vascular resistance is proportional to blood vessel length.
Vascular stenosis (e.g., coronary artery disease) increases systemic vascular resistance significantly! When the length of the vessel and viscosity of the blood remain constant, the relationship between systemic vascular resistance and the radius of the vessel can be simplified to R ∼ 1/r4. So, if there is a 50% reduction in radius, R = 1/(0.5 x r)^4 → 1/(0.0625 x r4) → 16/r4, there is a 16x increase in resistance (1600%).
Serial and parallel circuits
The total resistance in blood vessels depends on whether these vessels are arranged as serial or parallel circuits.
|Serial circuit||Parallel circuit|
Arterioles account for most of the TPR and, thus, are the blood vessels that contribute the most to blood pressure regulation.
- Blood pressure is generated by the pumping of the heart, which results in pulsatile blood flow (ΔP = Q x R).
- The ΔP drives blood flow from high pressure to low pressure.
- Systolic blood pressure: maximum pressure reached during a cardiac cycle
- Diastolic blood pressure: minimum pressure reached during a cardiac cycle
- MAP): simplified value of systolic and diastolic blood pressure (
Pulse pressure: the difference between diastolic blood pressure (DP) and systolic blood pressure (SP) of the heart cycle (SP - DP)
- Normally: 30–40 mm Hg
- Directly proportional to SV and inversely proportional to arterial compliance
- Definition: the force within vessel walls that counteracts vessel rupture during expansion, thus holding the vascular wall together
Equation: σt = (Ptm × r) / h
- Units: σt = wall tension (mm Hg); Ptm = transmural pressure (mm Hg); r = inner radius (cm); h = wall thickness (cm)
- Increases in wall tension are proportional to increases in pressure across the vessel wall (transmural pressure).
- Equation: σt = (Ptm × r) / h
- Wall tension increases with decreasing wall thickness, increasing transmural pressure and/or increasing the inner diameter.
- Given a constant transmural pressure, the smaller the vascular radius and thicker the vascular wall, the less wall tension generated.
Vessels of the high-pressure system (arteries) have thick vessel walls and smaller internal diameters that enable them to withstand high internal pressures, while vessels of the low-pressure system (veins) have thin vascular walls and larger diameters.
Blood vessel elasticity
- Definition: the ability of a blood vessel to return to its original shape after expanding
- Definition: the ability of a vessel to expand in response to changes in pressure
Equation: C = ΔV/ΔP
- Units: C = compliance (mL/mm Hg); ΔV = change in volume (mL); ΔP = change in pressure (mm Hg)
- Greater compliance: greater increase in vascular volume during an increase in pressure (e.g., elastic arteries)
- Less compliance: less increase in vascular volume during an increase in pressure (e.g., muscular arteries)
- Definition: the ability of a vessel to adapt to intraluminal pressure in response to changes in volume (i.e., the reciprocal of compliance)
Equation: E' = ΔP/ΔV
- Units: E' = elastance (mm Hg/mL); C = compliance (mL/mm Hg); ΔP = change in pressure (mm Hg); ΔV = change in volume (mL)
- Greater elastance: greater change in blood pressure during blood volume change
- Less elastance: less change in blood pressure during blood volume change
Compliance is mainly determined by the muscle tone of vessel walls. Arterioles, which are abundant in smooth muscle, have low compliance and are, therefore, considered resistance vessels. Veins are less abundant in smooth muscle, have much higher compliance, and are considered capacitance vessels.
- Definition: stretch-sensitive nerve endings that detect and regulate blood pressure in systemic circulation via signaling to the autonomic nervous system
- Location: wall of the carotid sinus, aortic arch, atria, and venae cavae
Mechanism of action: baroreceptor reflex
- Baroreceptors; detect ↓ BP → ↓ firing frequency of baroreceptors → ↓ signaling to the brain stem (vasomotor center) → ↓ parasympathetic stimulation and ↑ sympathetic innervation → vasoconstriction → ↑ HR, SV, and BP
- Baroreceptors; detect ↑ BP → ↑ firing frequency of baroreceptors → triggering of baroreceptor reflex in brain stem (vasomotor center) → ↑ parasympathetic stimulation and ↓ sympathetic innervation → vasodilatation → ↓ HR, SV, and BP
- Only suitable for making short-term changes in blood pressure because their activity (i.e., their firing frequency) adapts to a new blood pressure level within a few days.
- A component of hypertension, bradycardia, and respiratory depression) (
- Definition: specialized receptors that detect blood flow changes in the pulmonary circulation and regulate blood flow through the autonomic nervous system, atrial natriuretic peptide (ANP), and antidiuretic hormone (ADH)
- Location: atria, pulmonary artery, and cardiac atria (low-pressure system)
- Mechanism of action: : See and .
- Definition: specialized receptors that detect changes in pH and respiratory gases and regulate pH level, O2, and CO2 concentrations through respiration
- Mechanisms of action
If the baroreceptors of the carotid sinus are too sensitive, even small stimuli, such as turning the head or the pressure of a shirt collar, can lead to excessive blood pressure reduction and even fainting. This is referred to as carotid sinus syndrome.
Central blood pressure regulation
- Localization: solitary nucleus in the medulla oblongata
- Receives information (afferents) via:
- Sends information (efferents) via:
|Sympathetic stimulation||Parasympathetic stimulation|
Atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) regulation
- Definition: a physiologic reflex characterized by an increased heart rate in response to atrial distention (increased venous return to the heart). It is mediated by stretch receptors in the atria.
Mechanisms of action
- ↑ Volume → atrial stretching
- ↓ Volume → less atrial stretching
- Definition: a physiological reflex that adapts ADH release in the hypothalamus according to blood pressure
- Mechanisms of action
- Mechanism of action: release of renin from the juxtaglomerular cells → activation of RAAS → direct vasoconstriction and ↑ extracellular volume (↑ sodium and water reabsorption, ↓ K+, ↑ pH)
- RAAS is stimulated by:
The RAAS plays a key role in long-term blood pressure regulation and is, therefore, an ideal target for the treatment of arterial hypertension. While beta blockers decrease renin release by the kidneys, the conversion of angiotensin I to angiotensin II by angiotensin-converting enzyme (ACE) can be influenced by ACE inhibitors (e.g., ramipril, enalapril). The effect of angiotensin II on target cell receptors can be inhibited by AT1 receptor antagonists (e.g., candesartan, losartan).
|Perfusion levels of various organs|
|Organs||% of cardiac output at rest||% of cardiac output during exercise|
|Viscera (hepatic-splanchnic circulation)||24||1|
Regulation of organ perfusion
Although blood pressure is the main determinant of perfusion, various other mechanisms maintain constant blood flow within organs.
: Myocytes in the walls of arteries and arterioles react to changes in blood pressure to maintain constant blood flow in the blood vessels.
- Mechanism of action: ↑ BP → ↑ transmural pressure in arteries and arterioles → stretch-activated ion channels opening up in myocytes → myocyte depolarization and subsequent Ca2+ influx → smooth muscle contraction → vasoconstriction
- Sites of action: almost all organs (especially the kidneys and brain) except the lungs
- Mechanism of action: the release of vasoactive substances
- NO: produced in endothelium by NO-synthase from arginine → vasodilation
- Other substances: kinin, histamine, serotonin, prostaglandins, thromboxane
- Sites of action: arteries and arterioles
- Mechanism of action: the release of vasoactive substances
Differing effects of catecholamines
- Epinephrine: acts on both receptor types but has a greater affinity for beta-2 receptors
- Norepinephrine: mainly acts on alpha-1 receptors → vasoconstriction
Autoregulation of specific organs
- Local metabolic autoregulation: Adenosine and NO cause vasodilation of the coronary arteries to increase blood flow and oxygen delivery to the myocardium.
- Has the highest arteriovenous O2 difference of all organs (O2 extraction at rest ∼ 60–80%)
- During exercise, there is limited capacity to increase myocardial oxygen extraction (small coronary flow reserve).
- At rest: sympathetic innervation
- During exercise: local metabolic and chemical autoregulation, e.g., lactate, CO2, adenosine, K+, H+
- Blood flow can be increased (20–30 times) during exercise
The lungs are the only organs in which hypoxia causes vasoconstriction. This is to ensure that perfusion only occurs in areas that are well ventilated. In all other organs, hypoxia leads to vasodilation to improve perfusion and maintain oxygen supply.
Hypoperfusion of vital organs (e.g., hypovolemic shock, cardiogenic shock) is detected by baroreceptors and volume receptors, leading to an increase in sympathetic tone. Autoregulatory mechanisms are then triggered and lead to centralization of blood flow away from the extremities (skeletal muscle, skin), the GI tract, and other internal organs to maintain perfusion of the heart and brain. In addition, vasoconstriction of precapillary resistance vessels raises systemic vascular resistance and reduces hydrostatic pressure in capillaries, increasing the reabsorption of interstitial fluids into vessels.
To remember the local metabolites used in autoregulation of skeletal muscle, think “CHALK”: CO2, H+, Adenosine, Lactate, K+.
- Hydrostatic pressure: the pressure exerted by any fluid on the wall of an enclosed space
Osmotic pressure: the minimum pressure needed to prevent the flow of a solvent across a semi-permeable membrane
- Determined by concentration gradients: Solvent from a lower concentration solution is drawn across a semi-permeable membrane (via osmosis) into a higher concentration solution.
- Directly proportional to the concentration of solute in the solvent
- Opposes hydrostatic pressure
Oncotic pressure (colloid osmotic pressure): an intravascular osmotic pressure generated by proteins (especially albumin)
- Keeps intravascular fluid within blood vessels and opposes intravascular hydrostatic pressure
For information on thesee in .
- Four Starling forces determine the net flow of fluid between the capillaries and interstitium.
Net fluid flow = Jv = Kf [(Pc - Pi) - σ(πc - πi)]
- Kf = coefficient for vessel permeability to fluid
- σ = Staverman reflection coefficient for vessel permeability to protein
Net filtration (capillary fluid exchange)
- Depends on the hydrostatic pressure gradient (Pc - Pi) and the oncotic pressure gradient (πc - πi)
- Filtration of fluid out of the capillary usually occurs on the arterial side of the capillary bed, mostly because of pressure from the arterial circulation (increased Pc) and high plasma fluid levels (decreased πc).
- Filtration of fluid into the capillary usually occurs on the venous side of the capillary bed, mostly because of capillary flow resistance (decreased Pc) and higher relative plasma protein levels following water filtration into the interstitium (increased πc).
- Outward filtration volume (arterial side) = inward filtration volume (venous side) + 10%
- 10% of the filtered fluid is returned via lymphatics rather than blood vessels.
Edema is caused by the net movement of fluid into the interstitium if there is an increase in capillary hydrostatic pressure (due to heart failure or Na+ retention) or a decrease in oncotic pressure (due to cirrhosis, nephrotic syndrome).