Summary
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.
The heart and cardiac physiology, as well as the lymphatic system, are discussed in separate articles.
Circulatory system
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Systemic circulation
- Oxygenated blood flows from the left heart 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.
- Left atrium → mitral valve → left ventricle → aortic valve → aorta→ arteries → arterioles → capillary beds → veins → superior vena cava (SVC) and inferior vena cava (IVC) → right atrium
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Pulmonary circulation
- Deoxygenated blood in the right heart flows into the lungs, where it is oxygenated and returned to the left atrium.
- Right atrium → tricuspid valve → right ventricle → pulmonary valve → pulmonary trunk → pulmonary arteries → lungs → four pulmonary veins → left atrium
- Heart: connects systemic circulation and pulmonary circulation (see “Heart” and “Cardiac physiology”)
- Lymphatic system: a network of lymphatic vessels that transport lymph toward the heart (see lymphatic drainage for details)
Hemodynamics
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
- Blood flow is driven by cardiac activity pumping blood through the circulatory system.
- Volume of blood the heart pumps through the circulatory system per minute = cardiac output (CO)
- Rate of blood flow = blood flow / total cross-sectional area of the blood vessel
The capillaries have the largest total cross-sectional area of all blood vessels (4,500–6,000 cm2) and, therefore, have the slowest body velocity (0.03 cm/s). The aorta, on the other hand, has the smallest cross-sectional area (3–5 cm2) but the highest blood velocity (40 cm/s).
Laminar and turbulent blood flow
Blood flow in vessels is either laminar or turbulent depending on the smoothness of the blood vessel walls, the viscosity of the blood, the blood velocity, and the diameter of the lumen.
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Laminar blood flow
- Definition: a layered flow pattern
- Effect: The layer with the highest velocity flows in the center of the vessel lumen.
- Reynolds number: low
- Occurrence: throughout the vascular system
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Turbulent blood flow
- Definition: a chaotic flow pattern
- Effects
- Increases vascular resistance
- Promotes thrombus formation
- Creates murmurs (e.g., bruits in a stenotic vessel)
- Reynolds number: high
- Occurrence
- Vessels with a large diameter (e.g., aorta)
- High viscosity
- Low viscosity (e.g., anemia)
- Vascular bifurcations
- Vascular stenosis
Vascular resistance
- Definition: resistance in the circulatory system that must be overcome to create blood flow (R = ΔP / Q)
- Types of resistance
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Total peripheral resistance (TPR): the amount of resistance to blood flow in the systemic circulation = (MAP - CVP) / CO
- ↑ TPR in vasoconstriction of arterioles (e.g., in hemorrhage, ↑ vasopressor) → ↑ afterload and ↓ venous return → ↓ CO
- ↓ TPR in vasodilation of arterioles (e.g., in exercise, AV shunts) → ↓ afterload and ↑ venous return → ↑ CO
- Pulmonary vascular resistance
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Total peripheral resistance (TPR): the amount of resistance to blood flow in the systemic circulation = (MAP - CVP) / CO
Poiseuille equation
- 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).
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Resistance to flow: R = 8ηL/(πr4)
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Systemic vascular resistance is inversely proportional to vessel radius to the 4th power.
- ↓ Vessel radius (i.e., vasoconstriction) → ↑ systemic vascular resistance → ↓ blood flow → ↑ pressure upstream (i.e., MAP) and ↓ pressure downstream (i.e., in capillaries)
- ↑ Vessel radius (i.e., vasodilation) → ↓ systemic vascular resistance → ↑ blood flow → ↓ MAP and ↑ capillary pressure
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Systemic vascular resistance is proportional to blood viscosity, which is primarily determined by hematocrit.
- ↑ Viscosity (e.g., polycythemia, hyperproteinemia) → ↑ systemic vascular resistance
- ↓ Viscosity (e.g., anemia) → ↓ resistance
- Systemic vascular resistance is proportional to blood vessel length.
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Systemic vascular resistance is inversely proportional to vessel radius to the 4th power.
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 | |
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Definition | ||
Examples |
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Arterioles are the blood vessels that contribute most to TPR and, therefore, also to blood pressure regulation.
Pressure
- 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
- Mean arterial pressure (MAP): simplified value of systolic and diastolic blood pressure at resting heart rate
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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
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Directly proportional to SV and inversely proportional to arterial compliance
- Low/narrow pulse pressure due to ↓ SV (e.g., advanced congestive heart failure, shock, cardiac tamponade, aortic stenosis)
- High/wide pulse pressure due to ↑ SV (e.g., exercise, hyperthyroidism, aortic regurgitation, anemia, obstructive sleep apnea) or stiff arteries (isolated systolic hypertension in elderly)
Wall tension
- Definition: the force within vessel walls that counteracts vessel rupture during expansion, thus holding the vascular wall together
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Laplace's law
- Equation: σt = (Ptm × r) / 2h
- σt = wall tension (mm Hg)
- Ptm = transmural pressure (mm Hg)
- r = inner radius (cm)
- h = wall thickness (cm)
- Interpretation:
- Increases in wall tension are proportional to increases in pressure across the vessel wall (transmural pressure).
- 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.
- Equation: σt = (Ptm × r) / 2h
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
Vascular compliance
- Definition: the ability of a vessel to expand in response to changes in pressure
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Equation: C = ΔV/ΔP
- 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)
Vascular elastance
- Definition: the ability of a vessel to adapt to intraluminal pressure in response to changes in volume (i.e., the reciprocal of compliance)
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Equation: E' = ΔP/ΔV
- 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.
Blood pressure regulation
Sensors of blood flow regulation
Baroreceptors
- 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
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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 (e.g., acute hemorrhage) because their activity (i.e., their firing frequency) adapts to a new blood pressure level within a few days.
- A component of Cushing reflex (hypertension, bradycardia, and respiratory depression): ↑ intracranial pressure → compensatory constriction of cerebral arterioles → ↓ cerebral perfusion → hypercapnia and acidosis → chemoreceptor mediated sympathetic response → ↑ blood pressure → stimulation of aortic arch baroreceptors → activation of the parasympathetic nervous system (vagus) → reflex bradycardia
Volume receptors
- 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: pulmonary artery and cardiac atria (low-pressure system)
- Mechanism of action: See atrial reflex and diuresis reflex.
Chemoreceptors
- Definition: specialized receptors that detect changes in pH and respiratory gases and regulate pH level, O2, and CO2 concentrations through respiration
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Types
- Peripheral chemoreceptors
- Central chemoreceptors
- Location: medulla oblongata
- Function: measure PaCO2 and pH of the cerebral interstitial fluid
- Central chemoreceptors are less sensitive to PO2 levels, compared to the peripheral ones.
- Central chemoreceptors become desensitized in response to chronic hypoxia and hypercapnia (e.g., COPD).
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Mechanisms of action
- ↑ CO2, ↓ O2, and ↓ pH → ↑ sympathetic innervation
- Modulate breathing via the respiratory center in the medulla
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.
Carotid massage, which stimulates the baroreceptors in the carotid sinus, is an effective way of reducing the heart rate by increasing the refractory period of the AV node.
Peripheral chemoreceptors are more effective in responding to chronic hypoxia than central chemoreceptors.
Central blood pressure regulation
- Localization: solitary nucleus in the medulla oblongata
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Receives information (afferents) via:
- The glossopharyngeal nerve (IX): from carotid sinus (vascular dilatation located at carotid artery bifurcation) baroreceptor and carotid body chemoreceptor
- The vagus nerve (X): from aortic chemoreceptor, aortic baroreceptor, and atrial volume receptors
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Sends information (efferents) via:
- Sympathetic cervical chain and sympathetic fibers: to blood vessels, SA node, and AV node
- Parasympathetic vagus nerve: to AV node and SA node
Sympathetic stimulation | Parasympathetic stimulation | |
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Arteries |
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Veins |
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Heart |
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Atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) regulation
Atrial reflex
- 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 stretch receptors stimulation → activation of stretch receptors (B-fibers) in the atria → ↑ sympathetic innervation and no change in parasympathetic innervation → ↑ HR
Atrial natriuretic peptide (ANP) secretion pathway
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↑ Volume → ↑ atrial stretch receptors stimulation→ release of ANP from atrial cardiomyocytes ; which results in:
- ↑ Excretion of NaCl and water by the kidneys (via afferent arterioles dilations and efferent arterioles constriction)
- ↓ Na+ reabsorption at the renal collecting tubule (via ↑ cGMP)
- Inhibition of renin
- Vasodilation of veins and arteries (↓ preload and ↓ afterload)
- ↓ Volume → ↓ atrial stretch receptors stimulation → ↓ Release of ANP → ↓ excretion of NaCl and water by the kidneys
Diuresis reflex (Gauer-Henry reflex)
- Definition: a physiological reflex that adapts ADH release in the hypothalamus according to blood pressure
- Mechanisms of action
Renal regulation
- Mechanism of action: release of renin from the juxtaglomerular cells → activation of RAAS → direct vasoconstriction and ↑ extracellular volume (↑ sodium and water reabsorption, ↓ K+, ↑ pH)
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RAAS is stimulated by:
- Hyponatremia
- Decreased blood osmolality
- Decreased renal blood flow
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
Perfusion
Definition: 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)
Perfusion levels of various organs | ||
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Organs | % of cardiac output at rest | % of cardiac output during exercise |
Viscera (hepatic-splanchnic circulation) | 24 | 1 |
Skeletal muscle | 20 | 88 |
Kidneys | 19 | 1 |
Brain | 13 | 3 |
Other organs | 10 | 1 |
Skin | 8 | 2 |
Heart muscle | 3 | 4 |
Regulation of organ perfusion
Although blood pressure is the primary determinant of perfusion, various other mechanisms maintain constant blood flow within organs.
Autoregulation
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Myogenic autoregulation: 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 (e.g., during strenuous exercise, the transition from supine to upright position) → 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
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Local metabolites
- Mechanism of action: the release of vasoactive substances
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Nitric oxide (NO)
- Produced in endothelium by NO-synthase from arginine → vasodilation
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NO production is triggered by:
- Increased BP
- Activation of endothelial receptors by binding of vasoactive substances (e.g., serotonin, bradykinin) → increased release of NO
- Other substances: kinin, histamine, serotonin, prostaglandins, thromboxane
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Nitric oxide (NO)
- Sites of action: arteries and arterioles
- Mechanism of action: the release of vasoactive substances
Central regulation
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Mechanisms
- Sympathetic innervation
- Catecholamines from adrenal medulla
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Receptors
- Alpha-1 receptors → vasoconstriction
- Beta-2 receptors → vasodilation
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Differing effects of catecholamines
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Epinephrine: acts on both receptor types but has a greater affinity for beta-2 receptors
- Low concentrations: stronger effect on beta-2 receptors → vasodilation
- High concentrations: stronger effect on alpha-1 receptors → vasoconstriction
- Norepinephrine: mainly acts on alpha-1 receptors → vasoconstriction
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Epinephrine: acts on both receptor types but has a greater affinity for beta-2 receptors
Autoregulation of specific organs
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Heart
- 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).
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Lungs
- Adjustment of vascular perfusion to ventilation
- Hypoventilation (hypoxia) causes vasoconstriction (Euler-Liljestrand mechanism).
- Kidneys
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Brain
- Local metabolic autoregulation (CO2, pH) → vasodilation
- Myogenic autoregulation
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Skeletal muscle
- At rest: sympathetic innervation
- During exercise: local metabolic and chemical autoregulation due to an increase in H+, lactate, CO2, adenosine, and K+
- Blood flow can be increased (20–30 times) during exercise
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Skin
- Thermoregulation (via capillaries and arteriovenous anastomoses) determines perfusion levels.
- Mainly sympathetic innervation (vasoconstriction)
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, consider to “CAll HuLK”: CO2, Adenosine, H+, Lactate, K+.
Capillary fluid exchange
Capillaries, which have the highest total cross-sectional area and lowest flow rate of all blood vessels, are the site of fluid exchange.
Definitions
- Hydrostatic pressure: the pressure exerted by any fluid on the wall of an enclosed space
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Intravascular hydrostatic pressure
- The force exerted by the blood confined within blood vessel walls (e.g., capillary hydrostatic pressure)
- Drives fluid out of capillaries and into the interstitium
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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
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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
Starling forces
For information on the Starling equation for the glomerulus see measurement of renal function in physiology of the kidney.
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Four Starling forces determine the net flow of fluid between the capillaries and interstitium.
- Capillary hydrostatic pressure (Pc): drives fluid out of the capillary
- Interstitial hydrostatic pressure (Pi): attenuates filtration or drives fluid into capillaries
- Plasma colloid (oncotic) pressure (πc): drives fluid into the capillary
- Interstitial fluid colloid osmotic pressure (πi): drives fluid out of the capillary
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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
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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).
- Absorption 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), an increase in interstitial fluid oncotic pressure (due to lymphatic stasis) or a decrease in capillary oncotic pressure (due to cirrhosis, nephrotic syndrome, heart failure).
Burns, infections or toxins can affect vessel permeability (increased Kf) and can, therefore, result in the formation of edema.