книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Endothelial Exchange Processes

the lungs, the pulmonary Peff is very low). Δπ occurs because the concentration of proteins (especially albumin) in the plasma is much higher than their interstitial concentration. The closer the reflection coefficient of the

plasma proteins (σprot) to 1.0, the higher Δπ and, consequently, the lower the permeability

of the membrane to these proteins (!p. 377).

According to Starling’s relationship, water reab-

208sorption should occur as long as Peff is negative. However, recent data suggest that a negative Peff re-

sults in only transient reabsorption. After several minutes it stops because the interstitial oncotic pressure rises due to “self-regulation”. Thus, a major part of the 18 L/d expected to be reabsorbed from the exchange vessels (see above) might actually be reabsorbed in the lymph nodes. Rhythmic contraction of the arterioles (vasomotion) may also play a role by decreasing Peff and thus by allowing intermittent capillary reabsorption.

In parts of the body below the heart, the effects of hydrostatic pressure from the blood column increase the pressure in the capillary lumen (in the feet !90 mmHg). The filtration rate in these regions therefore rise, especially when standing still. This is counteracted by two “self-regulatory” mechanisms:

(1) the outflow of water results in an increase in the luminal protein concentration (and thus Δπ) along the capillaries (normally the case in glomerular capillaries, !p. 152); (2) increased filtration results in an increase in Pint and a consequent decrease in P.

Edema. Fluid will accumulate in the interstitial space (extracellular edema), portal venous system (ascites), and pulmonary interstice (pulmonary edema) if the volume of filtered fluid is higher than the amount returned to the blood.

Causes of edema (!B):

Increased capillary pressure (!B1) due to precapil-

lary vasodilatation (Pcap"), especially when the capillary permeability to proteins also increases (σprot # and Δπ #) due, for example, to infection or anaphylaxis (histamine etc.). Hypertension in the portal vein leads to ascites.

Increased venous pressure (Pcap ", !B2) due, for example, to venous thrombosis or cardiac insufficiency (cardiac edema).

Decreased concentration of plasma proteins, especially albumin, leading to a drop in Δπ (!B3 and p. 379 A) due, for example, to loss of proteins (proteinuria), decreased hepatic protein synthesis (e.g., in liver cirrhosis), or to increased breakdown of plasma proteins to meet energy requirements (hunger edema).

Decreased lymph drainage due, e.g., to lymph tract compression (tumors), severance (surgery), obliteration (radiation therapy) or obstruction (bilharziosis) can lead to localized edema (!B4).

Increased hydrostatic pressure promotes edema formation in lower regions of the body (e.g., in the ankles; !B).

Diffusion. Although dissolved particles are dragged through capillary walls along with filtered and reabsorbed water (solvent drag; !p. 24), diffusion plays a much greater role in the exchange of solutes. Net diffusion of a substance (e.g., O2, CO2) occurs if its plasma and interstitial conc. are different.

8 Cardiovascular System

210

Myocardial Oxygen Supply

Coronary arteries. The blood flow to the myocardium is supplied by the two coronary arteries that arise from the aortic root. The right coronary artery (approx. 1/7th of the blood) usually supplies the greater portion of the right ventricle, while the left coronary artery (6/7th of the blood) supplies the left ventricle (!A). The contribution of both arteries to blood flow in the septum and posterior wall of the left ventricle varies.

.

Coronary blood flow (Qcor) is phasic, i.e., the amount of blood in the coronary arteries fluctuates during the cardiac cycle due to extremely high rises in extravascular tissue pressure during systole (!B, C). The blood flow in the epicardial coronary artery branches and subepicardial vessels remains largely unaffected by these pressure fluctuations. However, the subendocardial vessels of the left ventricle are compressed during systole when the extravascular pressure in that region (! pressure in left ventricle, PLV) exceeds the pressure in the lumen of the vessels (!C). Consequently, the left ventricle is mainly supplied during diastole (!B middle). The fluctuations in right ventricular blood flow are much less distinct because right ventricular pressure

(PRV) is lower (!B, C). .

Myocardial. O2 consumption (VO2) is defined as Qcor times the arteriovenous O2 concentration difference, (Ca–Cv)O2. The myocardial (Ca–Cv)O2 is relatively high (0.12 L/L blood), and oxygen extraction at rest ([Ca–Cv]O2/CaO2 = 0.12/ 0.21) is almost 60% and, thus, not able to. rise much further. Therefore, an increase in Qcor is practically. the only way to increase myocardial VO2 when the O2 demand rises (!D, right side).

Adaptation of the myocardial O2 supply according to need is therefore primarily achieved by adjusting vascular resistance (!D, left side). The (distal) coronary vessel resistance can normally be reduced to about 1/4 the resting value (.coronary reserve). The coronary blood flow Qcor (approx. 250 mL/min at rest) can therefore be increased as much as 4–5 fold. In other words, approx. 4 to 5 times more O2 can be supplied during maximum physical exertion.

Arteriosclerosis (atherosclerosis) of the coronary arteries leads to luminal narrowing and a resultant decrease in poststenotic pressure. Dilatation of the distal vessels then occurs as an autoregulatory response (see below). Depending on the extent of the stenosis, it may be necessary to use a fraction of the coronary reserve, even during rest. As a result, lower or insufficient quantities of O2 will be available to satisfy increased O2 demand, and coronary insufficiency may occur (!D)

Myocardial O2 demand increases with cardiac output (increased pressure–volume–work/time), i.e., in response to increases in heart rate and/or contractility, e.g., during physical exercise (!D, right).

It also increases as a function of mural tension (Tventr) times the duration of systole (tension–time index).

Since Tventr = Pventr · rventr/2w (Laplace’s law !Eq. 8.4b, p. 188), O2 demand is greater when the ventricular

pressure (Pventr) is high and the stroke volume small than when Pventr is low and the stroke volume high, even when the same amount of work (P ! V) is per-

formed. In the first case, the efficiency of the heart

is reduced. When the ventricular pressure Pventr is elevated, e.g., in hypertension, the myocardium there-

fore requires more O2 to perform the same amount of work (!D, right).

Since the myocardial metabolism is aerobic, an increased O2 demand quickly has to lead to vasodilatation. The following factors are involved in the coronary vasodilatation:

Metabolic factors: (a) oxygen deficiency since O2 acts as a vasoconstrictor; (b) Adenosine; oxygen deficiencies result in insufficient quantities of AMP being re-converted to ATP, leading to accumulation of adenosine, a degradation product of AMP. This leads to

A2 receptor-mediated vasodilatation; (c) Accumulation of lactate and H+ ions (from the anaerobic myocardial metabolism); (d) prostaglandin I2.

Endothelial factors: ATP (e.g., from platelets), bradykinin, histamine and acetylcholine are vasodilators. They liberate nitric oxide (NO) from the endothelium, which diffuses into vascular muscle cells to stimulate vasodilatation (!p. 279 E).

Neurohumoral factors: Norepinephrine released from sympathetic nerve endings and adrenal epinephrine have a vasodilatory effect on the distal

coronary vessels via !2 adrenoceptors.

Myocardial energy sources. The myocardium can use the available glucose, free fatty acids, lactate and other molecules for ATP production. The oxidation of each of these three energy substrates consumes a

certain fraction of myocardial O2 (O2 extraction coefficient); accordingly, each contributes approx. one-third of the produced ATP at rest. The myocardium consumes increasing quantities of lactate from the skeletal muscles during physical exercise (!A, !p. 72 and 282).

Plate 8.13 Myocardial Oxygen Supply

Regulation of the Circulation

Autoregulatory mechanisms help to maintain a constant blood flow to certain organs when the blood pressure changes (e.g., renal vessels constrict in response to rises in blood pressure; !p. 150).

Autoregulation also functions to adjust the blood flow according to changes in metabolic activity of an organ (metabolic autoregulation); the amount of blood flow to the organ (e.g., cardiac and skeletal muscle; !A and p. 201) can thereby increase many times higher than the resting level.

Types of autoregulatory mechanism:

Myogenic effects arising from the vascular musculature of the lesser arteries and arterioles (Bayliss effect) ensure that these vessels contract in response to blood pressure-related dilatation (!B2a) in certain organs (e.g., kidneys, gastrointestinal tract and brain), but not in others (e.g., skin and lungs).

Oxygen deficiencies generally cause the blood vessels to dilate. Hence, the degree of blood flow and O2 uptake increase with in-

212 creasing O2 consumption. In the lungs, on the

other hand, a low PO2 in the surrounding alveoli causes the vessels to contract (hypoxic vasoconstriction; !p. 122).

Local metabolic (chemical) effects: An increase in local concentrations of metabolic

products such as CO2, H+, ADP, AMP, adenosine, and K+ in the interstitium has a vasodilatory effect, especially in precapillary arterioles. The resulting rise in blood flow not only improves

the supply of substrates and O2, but also accelerates the efflux of these metabolic products from the tissue. The blood flow to the brain and myocardium (!p. 210) is almost entirely subject to local metabolic control. Both local meta-

bolic effects and O2 deficiencies lead to an up to 5-fold increase in blood flow to an affected region in response to the decreased blood flow (reactive hyperemia).

Vasoactive substances: A number of vasoactive substances such as prostaglandins play a role in autoregulation (see below).

Hormonal Control of Circulation

Vasoactive substances. Vasoactive hormones either have a direct effect on the vascular musculature (e.g., epinephrine) or lead to the local release of vasoactive substances (e.g., nitric oxide, endothelin) that exert local paracrine effects (!B).

Nitric (mon)oxide (NO) acts as a vasodilatory agent. NO is released from the endothelium when acetylcholine (M receptors),

ATP, endothelin (ETB receptors), or histamine (H1 receptors) binds with an endothelial cell (!p. 278). NO then diffuses to and relaxes vascular myocytes in the vicinity.

Endothelin-1 can lead to vasodilatation by inducing the release of NO from the en-

dothelium by way of ETB receptors (see above), or can cause vasoconstriction via ETA receptors in the vascular musculature. When substances such as angiotensin II or ADH (= vasopressin;

V1 receptor) bind to an endothelial cell, they release endothelin-1, which diffuses to and constricts the adjacent vascular muscles with the aid of ETA receptors.

Epinephrine (E): High concentrations of E from the adrenal medulla (!p. 86) have a

vasoconstrictive effect (α1-adrenoceptors), whereas low concentrations exert vasodilatory effects by way of "2 adrenoceptors in the myo-

the cerebral cortex to circulatory centers when a muscle group is activated, or (b) via neuronal feedback from the organs whose activity level and metabolism have changed. If the neuronal and local metabolic mechanisms are conflicting (e.g., when sympathetic nervous stimulation occurs during skeletal muscle activity), the metabolic factors will predominate. Vasodilatation therefore occurs in the active muscle while the sympathetic nervous system reduces the blood flow to the inactive muscles. Blood flow to the skin is mainly regulated by neuronal mechanisms for the purpose of controlling heat disposal (temperature control; !p. 224). Hypovolemia and hypotension lead to centralization of blood flow, i.e., vasoconstriction in the kidney (oliguria) and skin (pallor) occurs to increase the supply of blood to vital organs such as the heart and central nervous system (!p. 218).

During exposure to extremely low temperatures, the cold-induced vasoconstriction of cutaneous vessels is periodically interrupted to supply the skin with blood to prevent tissue damage (Lewis response). Axoaxonal reflexes in the periphery play a role in this response, as afferent cutaneous nerve fibers transmit signals to efferent vasomotor axons. Skin reddening in response to scratching (dermatographism) is also the result of axoaxonal reflexes.

Central regulation of blood flow (!C) is the responsibility of the CNS areas in the medulla oblongata and pons. They receive information from circulatory sensors (S) or receptors (a) in the high-pressure system (barosensors or pressure sensors, SP, in the aorta and carotid artery); (b) in the low-pressure system (stretch sensors in the vena cava and atria, SA and SB); and (c) in the left ventricle (SV). The sensors measure arterial blood pressure (SP), pulse rate

(SP and SV) and filling pressure in the low pressure system (indirect measure of blood volume). The A sensors (SA) mainly react to atrial contraction, whereas the B sensors (SB) react to passive filling stretch (!C2). If the measured values differ from the set-point value, the circulatory control centers of the CNS transmit regulatory impulses through efferent nerve fibers to the heart and blood vessels (!D and p. 5 C2).

Situated laterally in the circulatory “center” is a pressor area (!C, reddish zone), the neu-

Plate 8.15 Regulation of the Circulation II

215

!p. 204), the resulting change in venous return would lead to a sharp drop in arterial blood pressure. The circulatory centers also respond to falling PO2 or rising PCO2 in the blood (cross-links from respiratory center) to raise the blood pressure as needed.

In individuals with chronic hypertension, the input from the pressosensors is normal because they are fully adapted. Therefore, circulatory control centers

216 cannot respond to and decrease the high pressures. On the contrary, they may even help to “fix” the

blood pressure at the high levels. Chronic hypertension leads to stiffening of the carotid sinus. This may also contribute to decreasing the sensitivity of carotid pressosensors in hypertension.

A temporary increase in venous return (e.g., after an intravenous infusion) also leads to an increase in heart action (!D, right). This mechanism is known as the Bainbridge reflex. The physiological significance of this reflex is, however, not entirely clear, but it may complement the Frank–Starling mechanism (!p. 202ff.).

Hypertension

Hypertension is defined as a chronic increase in the systemic arterial blood pressure. The general criterion for diagnosis of hypertension is consistent elevation of resting blood pressure to more than 90 mmHg diastolic (!p. 206). Untreated or inadequately managed hypertension results in stress and compensatory hypertrophy of the left ventricle which can ultimately progress to left heart failure. Individuals with hypertension are also at risk for arteriosclerosis and its sequelae (myocardial infarction, stroke, renal damage, etc.). Therefore, hypertension considerably shortens the life expectancy of a large fraction of the population.

The main causes of hypertension are (a) increased extracellular fluid (ECF) volume with increased venous return and therefore increased cardiac output (volume hypertension) and (b) increased total peripheral resistance (resistance hypertension). As hypertension always leads to vascular changes resulting in increased peripheral resistance, type a hypertension eventually proceeds to type b which, regardless of how it started, ends in a vicious circle.

The ECF volume increases when more NaCl (and water) is absorbed than excreted. The usually high intake of dietary salt may therefore play a role in the development of essential hypertension (primary hypertension), the most common type of hypertension, at least in patients sensitive to salt. Volume hypertension can even occur when a relatively low salt intake can no longer be balanced. This can occur in renal insufficiency or when an adrenocortical tumor produces uncontrolled amounts of aldosterone, resulting in Na+ retention.

Other important cause of hypertension is pheochromocytoma, a tumor that secretes epinephrine and norepinephrine and therefore raises the CO and TPR. Renal hypertension can occur due to renal artery stenosis and renal disease. This results in the increased secretion of renin, which in turn raises the blood pressure via the renin–angiotensin– aldosterone (RAA) system (!p. 184).

SP

2b

2a SP

Plate 8.16 Regulation of the Circulation III

217