Normal Blood flow to the gastrocnemius muscle

Normal Arteries Pressure and Flow:

Under resting conditions, blood flow to the normal human leg averages about 300 to 400 mL/min. Calf blood flow is in the range of 1.5 to 6.5 mL/g of calf per minute, with an average value of about 3.5 mL/g/min. Blood flow to the gastrocnemius muscle is usually about 2.0 mL/g/min. This rate of flow is more than adequate to supply all the resting limb. When blood flow is restored to a normal limb that has been rendered ischemic for 5 minutes by means of a proximally placed pneumatic tourniquet, the peripheral arteriolar bed becomes vasodilated. The resulting “reactive hyperemia” reaches peak values of 30 to 40 mL/g/min and then rapidly subsides to resting levels within a minute or two. Moderate exercise normally increases total leg blood flow by 5 to 10 times. Muscle blood flow rises to 30 ± 14 mL/g/min and reaches mL/g/min during strenuous exercise . On cessation of exercise, blood flow decreases rapidly, often reaching pre-exercise levels within 1 to 5 minutes. The mean drop in blood pressure across normal arteries from the heart to the ankle is only a few millimeters of mercury. As the pressure wave travels distally, systolic pressure increases, diastolic pressure decreases, and the pulse pressure widens. These pressure changes are due to reflection of waves from the high-resistance peripheral arteriolar bed. Under resting conditions, ankle systolic pressure exceeds brachial systolic pressure in normal individuals by about 10% .This explains why the normal resting ankle-brachial pressure index is greater than 1.0. In normal extremities, moderate exercise produces little or no drop in systolic pressure at ankle level. With very strenuous exercise, the pressure may fall a few millimeters of mercury, but it rapidly recovers within a minute or so. These findings contrast sharply with the extreme drops in ankle pressure that follow exercise in limbs with occlusive arterial disease(7).

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control of Peripheral Vascular Resistance:

Blood vessels in the skin are well supplied with sympathetic vasoconstrictor fibers, especially in the terminal portions such as the fingers, hands, and feet(7). Therefore, most reflex vasodilatation of cutaneous vessels results from withdrawal of sympathetic impulses. In contrast, blood vessels within skeletal muscles are innervated by both vasodilator and vasoconstrictor fibers. The former respond to emotional stress and the latter to postural changes(7). However, these actions are easily overcome by the powerful vasodilator effect of locally produced metabolites that accumulate during exercise or ischemia. Exercise is perhaps the single best vasodilator of resistance vessels within skeletal muscle. Arteriolar constriction also occurs in response to dependency (the venoarterial reflex). By restricting arterial inflow, this reflex serves to limit the increase in venous blood volume that accompanies elevated hydrostatic pressure(7).

“Autoregulation” is a term used to describe the ability of most vascular beds to maintain a constant level of blood flow over a wide range of perfusion pressures(7). This occurs when the resistance vessels constrict in response to an increase in blood pressure and dilate in response to a decrease(7). The mechanism of autoregulation appears to involve a myogenic response to stretch that is modified by the local chemical factors and sympathetic control(7). Autoregulation can compensate for a drop in perfusion pressure only until it falls below a critical level (e.g., about 20 to 30 mm Hg for skeletal muscle and about 50 to 60 mm Hg for the brain). With pressures below this level, normal blood flow is no longer maintained, and flow responds passively to changes in perfusion pressure(7).


 Hypertension is a major health problem in the developed world(5). Although it occasionally manifests in an acute aggressive form, high blood pressure is much more often asymptomatic for many years. This insidious condition is sometimes referred to as benign hypertension, but it is in fact far from harmless(5). Besides increasing the risk of stroke and atherosclerotic coronary heart disease, hypertension can lead to cardiac hypertrophy and heart failure (hypertensive heart disease), aortic dissection, multi-infarct dementia, and renal failure(5). While the molecular pathways of blood pressure regulation are reasonably well understood, the mechanisms leading to hypertension in the vast majority of affected persons remain unknown. The accepted wisdom is that such “essential hypertension” results from the interplay of genetic polymorphisms (which individually might be inconsequential) and environmental factors, which conspire to increase blood volume and/or peripheral resistance(5).  the major cause of hypertension,  is idiopathic (essential hypertension)(95%)(5). This form is compatible with long life unless a myocardial infarction, stroke, or another complication supervenes(5). Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing (renovascular hypertension), or adrenal disorders(5).

Mechanisms of Essential Hypertension:

Although the specific triggers are unknown, it appears that both altered renal sodium handling and increased vascular resistance contribute to essential hypertension(5). Increased vascular resistance may stem from vasoconstriction or structural changes in vessel walls(5). These are not necessarily independent factors, as chronic vasoconstriction may result in permanent thickening of the walls of affected vessels(5).


Fundamental to a wide variety of vascular disorders is injury to the vessel wall, in particular endothelial cells. Such injurious stimuli may be biochemical, immunologic, or hemodynamic(5). As the main cellular components of the blood vessel walls, endothelial cells and smooth muscle cells play central roles in vascular pathology. The integrated function of these cells is critical for the vasculature to respond to various stimuli, and its responses can be adaptive or lead to pathologic lesions(5). Thus, endothelial injury or dysfunction (see earlier discussion) contributes to a host of pathologic processes including thrombosis, atherosclerosis, and hypertensive vascular lesions. Smooth muscle cell proliferation and matrix synthesis can help to repair a damaged vessel wall but also can lead to luminal occlusion(5).


Endothelial cell injury is the cornerstone of the response to injury hypothesis(5). Endothelial dysfunction is regarded as the earliest manifestation of vessel injury and is present before histologic evidence of atherosclerosis. Hence functional testing of the endothelium is an important tool for investigators studying atherosclerosis(5). Endothelial cell loss due to any kind of injury—induced experimentally by mechanical denudation, hemodynamic forces, immune complex deposition, irradiation, or chemicals—results in intimal thickening; in the presence of high-lipid diets, typical atheromas ensue. However, early human atherosclerotic lesions begin at sites of intact, but dysfunctional, endothelium. These dysfunctional endothelial cells exhibit increased permeability, enhanced leukocyte adhesion, and altered gene expression, all of which may contribute to the development of atherosclerosis. Suspected triggers of early atheromatous lesions include hypertension, hyperlipidemia, toxins from cigarette smoke, homocysteine, and even infectious agents(5). Inflammatory cytokines (e.g., tumor necrosis factor TNF) also can stimulate proatherogenic patterns of endothelial cell gene expression. Nevertheless, the two most important causes of endothelial dysfunction are hemodynamic disturbances and hypercholesterolemia. the response-to-injury hypothesis, the model views atherosclerosis as a chronic inflammatory response of the arterial wall to endothelial injury. Lesion progression involves interaction of modified lipoproteins, monocytederived macrophages, T lymphocytes, and the cellular constituents of the arterial wall(5) .

According to this model (see fig 1.9), atherosclerosis results from the following pathogenic events(5):

  1- Endothelial injury—and resultant endothelial dysfunction—leading to increased permeability, leukocyte adhesion, and thrombosis (5).

2- Accumulation of lipoproteins (mainly oxidized LDL  and cholesterol crystals) in the vessel wall(5).

3- Platelet adhesion(5).

4- Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and foam cells(5).

 5- Lipid accumulation within macrophages, which release  inflammatory cytokines(5).

6- Smooth muscle cell recruitment due to factors released from activated platelets, macrophages, and vascular wall cells(5).

1-    Smooth muscle cell proliferation and ECM(5).













fig 1.9 atherosclerosis  pathogenic events