Where does vasoconstriction occur in limbs?

Where does vasoconstriction occur in limbs?

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When cold or in shock a person's blood vessels constrict in order to preserve heat or to move blood flow to protect vital organs. I am interested in the mechanism by which this is achieved. Does this occur along the entire length of the limb or are there 'pinch points' (for example is it possible to simply have a point of vasoconstriction just below the shoulder which would reduce blood flow to the entire arm)? Am I correct in thinking that the response is neurological rather than endocrinological ?

Reduced blood flow to a region of the body occurs through 2 principal mechanisms.

1) The smooth muscle fibers in the tunica media layer of the arteries contract and reduce the diameter of the artery, limiting blood flow due to increased resistance (this is the mechanism in @agrimaldi's answer).

2) Circularly oriented smooth muscle fibers at the junction of a metarteriole (the distal end of an arteriole) and a capillary bed form a precapillary sphincter, which serves as a valve and prevents blood flow into a the capillary bed.

So to answer your question, it is both. The narrowing of the arteries would occur rather continuously across the limb but there are "pinch points" where metarterioles joint the capillary beds.

The endocrine and nervous systems are pretty integrated so in most cases it would be the result of the actions of both systems.

Vasoconstriction is a phenomenon that can be caused by many factors, from mechanical events (such as stretching) to hormones (epinephrin, neurepinephrin, angiotensin… ). But no matter what is the cause, the end-result is an increase in intracellular calcium concentration in smooth muscle cells (which compose the arteries and veins). So it seems that constriction does not happen in specific points but rather all along the limb. Furthermore angiotensin receptors are found in high concentration in smooth muscle cells [1], suggesting that every such cell has the ability to change it's morphology in order to induce vasoconstriction.

As for your second point, I think the response is as much endocrinological as neurological, since it involves both peripheral and central regulations. (Well, as a side note, endocrine systems rarely have no interaction with central ones).

Angiotensin receptors : distribution, signalling and function

Age-Related Changes in Thermoreception and Thermoregulation

Autonomic Heat Retention by Peripheral Vasoconstriction

Peripheral vasoconstriction is an important autonomic response to cold exposure, which restricts heat transfer from the core to the environment through the skin. Peripheral vasoconstriction is more dependent on core than on skin temperature (cf. Bulcao et al., 2000 Cheng et al., 1995 Daanen, 1996 Grahn et al., 1998 ). Cutaneous vasoconstriction is predominantly controlled through the sympathetic part of the autonomic nervous system. Most sympathetic activation promotes vasoconstriction. During cold stress, norepinephrine is released from sympathetic nerve endings and induces vasoconstriction through α-receptors or vasodilation via β-receptors. The skin of the extremities mainly contains α2 receptors and thus shows strong vasoconstriction (cf. Frank et al., 1997 Kellogg et al., 1989 ). In contrast, there is poor vasoconstrictive capacity in the face, resulting in poorly attenuated heat loss from this site during cold exposure (cf. MacKenzie, 1996 ).

When exposed to cold, increased sympathetic output to the adrenal medulla induces it to release more epinephrine as well as some norepinephrine into the bloodstream. As mentioned above norepinephrine is a strong vasoconstrictive agent, as is epinephrine but to a lesser extent. Other powerful vasoconstrictive agents are angiotensin, acting on all arterioles, and vasopressin (cf. Guyton, 1991 ).

Age-related changes: under thermoneutral ambient conditions the elderly have a lower skin temperature at the extremities ( Rasmussen et al., 2001 ), suggesting enhanced vasoconstriction. The vasoconstrictive response to cold exposure, however, is attenuated in elderly people, more so in men than women, and this may be the most important factor involved in poor cold defense ( Florez-Duquet & McDonald, 1998 ). The age-related loss of vasoconstriction is present at the threshold, gain, and maximum level. Frank and colleagues (2000) demonstrated that the threshold for cold-induced vasoconstriction lies at a lower core temperature in old age and that the maximal vasoconstriction is reduced, possibly because of an attenuated release of norepinephrine. The mechanism underlying the decreased cold-induced vasoconstriction is most likely an increased arterial wall stiffness. A decrease in the smooth muscle α-adrenergic receptor density has also been demonstrated, which is, however, compensated for by an increased sympathetic nervous system activity, leaving the net result unchanged (cf. Florez-Duquet & McDonald, 1998 ).

In summary, the delayed and slower evolving vasoconstrictive response to a cool environment will contribute to a lower and more variable body temperature in elderly people.


This physiological response has been mentioned so many times that I decided it needed its own specific post to plug into the Cold Water Swimming articles section.

Peripheral Vasoconstriction in fingers demonstrated using Infrared, red is warmest, blue is coldest

What is peripheral vasoconstriction?

Following immersion in cold water, blood flow is reduced in human limbs and skin.

Why does peripheral vasoconstriction happen?

Peripheral vasoconstriction occurs to allow the body to retain core heat for longer as protection against hypothermia by allowing the skin to act as an insulating layer between core organs and the water.

It also allows more oxygen to be delivered to important and oxygen-sensitive organs such as heart and brain.

When does peripheral vasoconstriction happen?

Immediately on entering cold water, it’s initiated by cold receptors (aka thermoreceptors, which are different kinds of heat or cold detecting nerves) in the skin. The body doesn’t have to be fully immersed, just the lower legs being in cold water is sufficient.

Is any part of the body not affected by peripheral vasoconstriction?

The head is not effected. (Heat loss during cold water immersion is greatest in the head, neck, upper chest and groin).

At what water temperature does peripheral vasoconstriction happen?

Some sources seem to indicate that peripheral vasoconstriction occurs at temperatures of below the Lower Critical Temperature (LCT). Lower Critical Temperature is the temperature at which heat will leave the body regardless of peripheral vasoconstriction. LCT can be as high as 35º Celsius (95º Fahrenheit) though this is based on a non-swimming person. For swimmers the LCT is affected by many more factors such are body size, sub-cutaneous fat, metabolic rate, muscles work and wind. In thermo-neutral temperature water, which is water between 35º Celsius and body temperature, peripheral vasoconstriction alone is sufficient to retain core body heat.

It’s important to note that the difference between water and ambient air temperature plays an important part. For cold-acclimatized swimmers, LCT will be much cooler than 35º. Scientific studies of hypothermia in cold water use 18º Celsius (64º Fahrenheit) as the upper level of “cold” water.

What are the effects of peripheral vasoconstriction ?

  • The entire body surface will get cold and the skin will feel clammy, even when normal core temperature is retained. (I’ve measured my own skin temperature at 17º Celsius after a s wim while I still felt fine and you can see in the image below that after a short swim the subject was barely over 17º Celsius).
  • Fingers and toes will turn white.
  • Blood pressure will rise.
  • There will be a sudden desire to urinate (due to increased blood pressure). This is called cold water diuresis (aka “why do I have to pee after swimming?“)
  • Longer term or more severe effects such as loss of motor control and shivering etc. are effects of hypothermia.

Peripheral Vasoconstriction in body demonstrated using Infrared – blue areas are coldest

How long does peripheral vasoconstriction last?

Peripheral vasoconstriction is not a continuous process. One research paper indicates that cold water immersion can also cause a paradoxical response of an intermittent recurring peripheral vasodilation (“cold-induced vasodilation” aka CIVD), which opens up blood vessels and accelerates blood loss. This seems to alternate with peripheral vasoconstriction with the cycle repeating from three to five times an hour.

When does peripheral vasoconstriction stop?

One important factor with peripheral vasoconstriction is that it stops shortly after leaving water and the person regains a standing position. This results in the well-known effect to open water swimmers of Afterdrop. Afterdrop occurs because the cold blood in the periphery which was previously acting as barrier layer and protection quickly flows into the warmer core and causes internal organs to suddenly decrease in temperature.


Veins are defined as blood vessels that carry blood toward the heart. Blood traveling through veins is not under pressure from the beating heart. It gets help moving along by the squeezing action of skeletal muscles, for example, when you walk or breathe. It is also prevented from flowing backward by valves in the larger veins, as illustrated in Figure 14.4.3. and as seen in the ultrasonography image in Figure 14.4.4. Veins are called capacitance blood vessels, because the majority of the body’s total volume of blood (about 60 per cent) is contained within veins.

Figure 14.4.3 The two flaps that make up a venous valve can open in just one direction, so blood can flow in only one direction through the vein. Figure 14.4.4 Here you can see the venous valve opening and closing to allow blood to flow closer to the heart with each contraction of the surrounding skeletal muscle.

Most veins carry deoxygenated blood, but there are a few exceptions, including the four pulmonary veins. These veins carry oxygenated blood from the lungs to the heart, which then pumps the blood to the rest of the body. In virtually all other veins, hemoglobin is relatively unsaturated with oxygen (about 75 per cent).

Figure 14.4.5 The Superior and Inferior Vena Cava are the largest veins in the body. They deliver deoxygenated blood directly to the right atrium.

The two largest veins in the body are the superior vena cava — which carries blood from the upper body directly to the right atrium of the heart — and the inferior vena cava, which carries blood from the lower body directly to the right atrium (shown in Figure 14.4.5). Like arteries, veins form a complex, branching system of larger and smaller vessels. The smallest veins are called venules. They receive blood from capillaries and transport it to larger veins. Each venule receives blood from multiple capillaries. See the major veins of the human body in Figure 14.4.6.

Figure 14.4.6 This diagram shows the heart and major veins of the cardiovascular system. The pulmonary arteries are included in the diagram because, like veins, they carry deoxygenated blood.


Background and Purpose Some stroke patients complain of an unpleasant sensation of coldness in the hemiplegic arm. This study aimed to determine the prevalence of this symptom and any associated features.

Methods A questionnaire about symptoms in the arms was sent to patients at least 12 months after stroke. Reflex sympathetic dystrophy (RSD) was diagnosed if four typical symptoms were present in the arm.

Results One hundred patients were recruited and 75 complete replies received. The mean age of the patients was 74 years, and the mean time since the stroke was 19 months. Forty patients (53%) experienced unilateral coldness in the hemiplegic arm. In 14 this sensation was constant, and 10 rated the symptom as troublesome. The symptom developed at a median time of 1 month after stroke, but only 13 patients (32%) sought advice from a doctor. Sensory symptoms and arm and shoulder pain were common, but the only symptoms associated with coldness were numbness (P<.001) and color change (P<.05). Fifteen patients fulfilled the diagnostic criteria for RSD, 13 of whom had coldness only in the hemiplegic arm.

Conclusions A sensation of coldness in the hemiplegic arm is common and distressing. It is associated with numbness and color changes in the arm. Some cases are caused by RSD, but other patients have coldness that may be due to other causes such as a vasomotor abnormality.

A number of unilateral phenomena occur in the hemiplegic arm after a stroke. 1 2 3 4 We have noticed that some patients complain of an unpleasant cold sensation in the affected arm. How often the symptom occurs and how significant it is to patients after a stroke are not known. Coldness was rated highly as an important symptom compared with other symptoms caused by stroke in one study, but numbers were small. 5 Patients with coldness in the hemiplegic arm have reduced blood flow to the hand and abnormal rewarming after cold stress testing. 5 These vasomotor changes may be responsible for the feeling of coldness, but other mechanisms may be important, including sensory or perceptual disturbances caused by the stroke, reflex sympathetic dystrophy (RSD), or simply disuse.

This aims of this study were to determine the prevalence of coldness in the hemiplegic arm and to identify any associated features that might improve our understanding of why some stroke patients develop this symptom.

Subjects and Method

A questionnaire was designed to obtain details about the patients and current symptoms in the arms. A single standard question was to detect the presence of each of the symptoms. Several supplementary questions about the symptoms of coldness and pain were used to obtain more detail. The overall design was short (three legal-sized sheets), simple, and produced in large print. The questionnaire was first used on a trial basis by six inpatients with stroke and was found to be clear and unambiguous. The questionnaire was then sent to stroke patients living at home.

The subjects were consecutive patients with hemiplegia, aged 60 years or older, who had been discharged home from a district general hospital after a new stroke. Stroke was defined according to World Health Organization criteria. 6 Patients were recruited from all wards in the hospital and had suffered a stroke that had caused new disability (resulting in a decrease in the modified Barthel Index score compared with the score before admission).

The questionnaire was sent out to patients at least 1 year after the stroke because we had observed that the symptom did not develop immediately after the stroke in many patients. Those patients with language difficulties were assessed by one author (A.F.) with the use of the Frenchay Aphasia Screening Test 7 and were not included in the study if they could not complete the test satisfactorily (score <25).

Head CT scans were sought for all patients who replied to the questionnaire. The study was given approval by the local Ethical Committee. The questionnaire covered the following areas: (1) patient details (age, sex, medication) and details of the stroke (2) coldness in the arms (3) sensory symptoms (numbness, pins and needles) (4) skin changes (dry or sweaty skin) (5) swelling and color change in the affected arm (6) shoulder pain and (7) other arm pain (and its site).

The overall severity of the symptom of coldness was assessed on a visual analog scale from 0 (no problem) to 5 (severe problem).

We were particularly interested in the prevalence of the symptom of coldness and its relation to sensory symptoms and RSD. The diagnosis of RSD was based on criteria outlined by Veldman et al 8 and consisted of the presence of the following symptoms in the arm: coldness, swelling, color change, pain in the shoulder, pain in the arm, dry skin, and sweaty skin. RSD was diagnosed as definite if four of the above symptoms were present and possible if only three were present.

When no reply was received, the patient was telephoned and the questionnaire completed verbally. In some cases the patient preferred to send the written questionnaire after the telephone call.

Results were analyzed for the difference between patients with and without coldness with the use of the χ 2 test.


One hundred patients were recruited to the study, and 82 replies were received (3 by telephone inquiry). Seven of the returned questionnaires were incomplete and were therefore not included. Of the respondents, 44 were men and 31 were women, with a mean age of 74 years (range, 61 to 88 years). Thirty-five patients had had a left hemiplegia and 40 a right hemiplegia. The mean time since stroke onset was 19 months (range, 12 to 32 months). Head CT scans had been performed in 21 cases: 9 patients had cortical infarcts (8 middle cerebral artery territory, 1 posterior territory), 5 had subcortical infarcts, 4 had multiple infarcts, 2 had hemorrhages, and 1 scan was normal.

Forty-eight patients (64%) had arm coldness. Forty patients (53%) had coldness only in the hemiplegic arm, and 8 had coldness in both arms. Further details were obtained from those patients with unilateral coldness of the hemiplegic arm. In 26 patients the feeling was infrequent, but in 14 the symptom was constantly present. Based on our rating scale from 0 to 5, the mean symptom score was 2.4, with 10 patients rating the symptom as 4 or 5 (Table 1 ). It can also be seen from Table 1 that 5 patients had constant severe coldness.

Measures taken by patients to alleviate the coldness included local heat (10), rubbing (7), gloves or wrapping in clothes (6), or vigorous movement of the arm (2). However, in 8 patients there was nothing that the patient could do to relieve the symptom. The median time from the stroke to the development of the coldness was 1 month (interquartile range, 0 to 6). No association was found between coldness and the site or type of stroke on CT scan, although the number of scans in patients with unilateral coldness was small (n=9). Of the 40 patients with unilateral coldness, only 13 (32%) had told a physician about the symptom.

Sensory and perceptual symptoms were common in the entire group of 75 respondents (Table 2 ). Thirty-five patients had numbness, and 28 complained of a symptom of pins and needles in the arm.

Skin changes were less common, with 26 patients noting abnormally dry skin and 10 noting excessive sweating on the hemiplegic side. Only 15 patients had swelling of the hemiplegic arm lasting for a month or more. Intermittent color changes occurred in the hemiplegic arm in 16 cases: 9 patients reported a blue color, 3 patients a change to red, 2 a change to purple, and 2 a change to white.

Pain in the hemiplegic arm was also common, with 43 suffering shoulder pain and 15 having pain elsewhere in the arm. The shoulder pain was only present on movement in 25 patients, constant in 10, at night in 7, and occasional in 1. Pain elsewhere in the arm was felt at the elbow or upper arm in 11 patients, in the hand in 2, at the wrist in 1, and generalized in 1.

We also considered the prevalence of arm symptoms in the subgroup of patients with coldness in the arm. Eight patients had the sensation of coldness in both arms. The significance of the symptom in this group is less clear, and they may have a generalized disorder rather than one related specifically to the hemiplegic arm. We have therefore excluded this group of patients when analyzing the association of symptoms. Patients with unilateral coldness of the hemiplegic arm reported more arm symptoms overall than those without coldness (Table 3 ). The various arm symptoms were analyzed in the groups with and without coldness to assess possible associations. The symptom of unilateral coldness was associated with numbness (P<.001) and color change (P<.05). Coldness in the hemiplegic arm was not associated with the side of the hemiplegia or any of the other symptoms.

Using our classification, we found that 15 patients (20%) fulfilled the diagnostic criteria for RSD and 14 (19%) had possible RSD. Thirteen patients with RSD and 11 with possible RSD had unilateral coldness of the hemiplegic arm 16 patients with unilateral coldness in the hemiplegic arm did not have evidence of RSD.


Several unilateral phenomena occur in the hemiplegic arm, including unilateral clubbing, 1 sparing of arthritis, 2 unilateral eczema, 3 and lowered minimal erythema dose for UV light. 4 We have noticed that some patients develop an unpleasant feeling of coldness in the hemiplegic arm, which some find difficult to relieve. We have previously shown that vasomotor abnormalities exist in this group of patients with abnormal vasoconstriction occurring in the hemiplegic arm. 5

The results of our present survey show that coldness in the hemiplegic arm is common, being present in 48 (64%) of the patients we studied. This sensation of coldness was felt solely in the hemiplegic arm in 40 (53%). Although most of these patients suffered coldness in the arm intermittently, in 14 subjects the symptom was constant.

This problem is unfamiliar to clinicians dealing with stroke patients. Why is this? First, the symptom may develop after a few months when the patient may have been discharged from hospital follow-up. Second, the symptom is variable in its severity, and only 32% of patients with the problem sought advice from a physician.

There are probably several causes of coldness in the hemiplegic arm. One possibility is that the coldness is caused by RSD. RSD is a term for a complex disorder that occurs after direct or indirect trauma to a limb. The features of the condition are pain, limited range of movement, edema, and altered skin temperature and color. The symptoms generally occur diffusely in the affected limb and are frequently worse after use. 8 RSD is difficult to study because there are no standardized diagnostic criteria and no diagnostic test that is sufficiently sensitive and specific. 8 In addition, some of the features of RSD may be altered by the stroke. An example of this is the increase in limb symptoms after use that occurs in RSD. This may be more difficult to ascertain in patients with limited arm function after stroke. Another symptom that may be less specific for RSD after stroke is unexplained diffuse pain. This pain may be due to other causes such as central pain (“thalamic syndrome”) after a stroke. 9 Swelling of the hemiplegic arm is common but may be due to the disuse resulting from the stroke or perhaps as a result of axillary vein thrombosis.

With these limitations in mind, we defined probable and possible RSD using a classification similar to that of Veldman et al 8 based on common symptoms of the condition. RSD is reported to occur in between 12% and 25% of patients after a stroke. 10 11 Vasomotor abnormalities occur in many cases of RSD, but the associated skin temperature changes are variable. 12 13 14 In a recent comprehensive survey of patients with RSD, more than 90% of patients described changes in skin temperature of the affected limb, but in only 13% was the limb cooler on objective assessment by the investigators. 8 However, this study only included 2 patients with stroke of 829 studied. We found that among the 40 patients with unilateral coldness, 13 had probable RSD and 11 had possible RSD.

RSD is associated with coldness in the hemiplegic arm, but 16 patients in our study had unexplained unilateral coldness with no other features of RSD. We have not addressed the relationship between severity of paralysis and coldness in this study. However, coldness was not associated with more severe paralysis in a previous smaller study. 5 The only symptoms that were associated with unilateral coldness were numbness and color change. This lends some support to the view that coldness is related to sensory deficits in some patients, although the mechanism is not clear. However, if this were the only factor involved, one might expect coldness to be more common in patients with a left hemiplegia because these patients are more likely to develop abnormalities of interpreting sensory input. There was no such association between side of the hemiplegia and the feeling of coldness.

Vasomotor instability may cause the color changes noted frequently by the patients with coldness. Our previous work has shown objective changes in skin temperature and blood flow in patients with symptomatic coldness of the hemiplegic arm. Patients with coldness in the hemiplegic arm had reduced blood flow in the hand and abnormal rewarming after cold stress compared with a group without the symptom of coldness. 5 This suggests that abnormal vasoconstriction is responsible for the sensation of coldness in this group. After deep inspiration or cough, vasoconstriction occurs in the limbs, which is spinally mediated. 15 16 This vasoconstriction is greater in tetraplegic subjects, indicating a descending inhibitory influence on the area of the cord responsible for the response. 17 Abnormal persistent vasoconstriction due to a spinal reflex would explain the reduced blood flow to the hemiplegic hand previously reported in patients with coldness.

The best treatment for this distressing coldness is not known, although some patients tried simple local measures such as rubbing, wrapping, or warming the arm. RSD is amenable to simple treatment with analgesics, heat, or cold packs. Exercise for the affected limb may be effective if started early in the course of the disease but in late cases is disappointing. 18 Other treatments, including vasodilators 19 20 and local blockade of the sympathetic system with guanethidine infusions or sympathectomy, 21 have been used with limited success.

If the coldness is caused by a sensory deficit, there is currently no treatment known to produce benefit.

In patients with no features of RSD and abnormal vasoconstriction, some may benefit from vasodilators. There have been no controlled trials of these agents in patients with a cold hemiplegic arm this is now the subject of our current research.


The symptom of coldness in the hemiplegic arm is common after a stroke. Some patients find it very distressing, although relatively few complain to a physician. The coldness may be produced by a number of conditions, including RSD and vasomotor changes caused by the stroke. The role of sensory deficits is not clear, although a feeling of coldness is associated with numbness in the arm. All clinicians and therapists caring for stroke patients should be aware of the problem. Further work is required to find treatments for the cold hemiplegic arm that are both effective and well tolerated.

Table 1. Severity of the Symptom of Unilateral Coldness

Metarterioles and Capillary Beds

A metarteriole is a type of vessel that has structural characteristics of both an arteriole and a capillary. Slightly larger than the typical capillary, the smooth muscle of the tunica media of the metarteriole is not continuous but forms rings of smooth muscle (sphincters) prior to the entrance to the capillaries. Each metarteriole arises from a terminal arteriole and branches to supply blood to a capillary bed that may consist of 10–100 capillaries.

The precapillary sphincters, circular smooth muscle cells that surround the capillary at its origin with the metarteriole, tightly regulate the flow of blood from a metarteriole to the capillaries it supplies. Their function is critical: If all of the capillary beds in the body were to open simultaneously, they would collectively hold every drop of blood in the body and there would be none in the arteries, arterioles, venules, veins, or the heart itself. Normally, the precapillary sphincters are closed. When the surrounding tissues need oxygen and have excess waste products, the precapillary sphincters open, allowing blood to flow through and exchange to occur before closing once more (see Figure 5). If all of the precapillary sphincters in a capillary bed are closed, blood will flow from the metarteriole directly into a thoroughfare channel and then into the venous circulation, bypassing the capillary bed entirely. This creates what is known as a vascular shunt. In addition, an arteriovenous anastomosis may bypass the capillary bed and lead directly to the venous system.

Figure 5. In a capillary bed, arterioles give rise to metarterioles. Precapillary sphincters located at the junction of a metarteriole with a capillary regulate blood flow. A thoroughfare channel connects the metarteriole to a venule. An arteriovenous anastomosis, which directly connects the arteriole with the venule, is shown at the bottom.

What can cause vasoconstriction or constricted blood vessels?

Now that we have looked at what vasoconstriction is, let&rsquos get right to the causes. The truth is that there are a lot of different factors that can contribute to vasoconstriction. Vasoconstriction and blood pressure are closely related. As blood vessels constrict, blood flow changes, which can lead to an increase in blood pressure. If the constricting goes on, it could result in chronic high blood pressure, which is a risk factor for heart attack and stroke.

Here&rsquos a look at some specific vasoconstriction causes, starting with diet.

  • Caffeinated foods and drinks: Coffee, tea, soda, and chocolates can actually narrow blood vessels. While a little caffeine usually doesn&rsquot harm a person, too much caffeine can lead to vasoconstriction.
  • Salt: Sodium causes water retention and water retention increases the volume of blood in your system that has the potential to constrict vessels. People who eat a diet that is high in salt are prone to vasoconstriction. Avoiding processed foods is one way to cut down on sodium.
  • Bad cholesterol: Foods that contain saturated and trans fat have a negative impact on blood circulation, so selecting foods with healthy cholesterol is best if you want to avoid vasoconstriction.
  • Refined carbohydrates: Consumption of food that raises glucose levels can lead to vasoconstriction. White bread and white pasta are examples. Complex carbs, such as whole grains, vegetables, and fruit can help you avoid constricted blood vessels.
  • Stress and anxiety: Research shows that stress can impact blood vessels.

A sedentary lifestyle can also put people at a higher risk for vasoconstriction. The same goes for substance abuse, including street drugs. Below we look at medications and substances that can cause vasoconstriction.

  • Decongestants
  • Alcohol (Moderate consumption)
  • MSG (Monosodium glutamate)
  • Stimulant drugs
  • Cocaine
  • Nicotine
  • Tyramine (Natural substance in foods)
  • Sympathomimetic drugs (Used to treat hypotension)
  • Vasopressin analogs (Used to treat low sodium levels in blood)

There can be cases where an underlying health issue is causing the vasoconstriction, including some of the health conditions noted below:

  • Raynaud&rsquos disease: Small arteries narrow, limiting blood supply to the skin
  • Buerger&rsquos disease: Swelling and inflammation of the blood vessels
  • Migraine sufferers: Severe headache, accompanied by nausea and vision issues
  • Post-traumatic dystrophy: Pain, swelling, and vasomotor dysfunction of an extremity
  • Inflammatory diseases: Conditions that involve severe inflammation

When we think about vasoconstriction, we have to consider RCVS as well. RCVS stands for reversible cerebral vasoconstriction syndrome. It is a group of disorders that include severe headaches and narrowing of the blood vessels in the brain. While RCVS can be reversed and many patients have been known to recover in a matter of a few months, the diagnosis is often missed. RCVS occurs when there is persistent vasoconstriction and as a result, blood flow and oxygen delivery is reduced to the affected area of the body. When constriction to blood vessels of the brain occurs, it is referred to as cerebral vasoconstriction.

RCVS can lead to serious complications when it is not diagnosed and treated quickly. Stroke is one potential complication.

Vasoconstriction in Athletes

Cold therapy is often used for injuries caused during sports or in athletes. Cold therapy is nothing but induced vasoconstriction in the injured area as well as its surroundings and can actually help in speeding up the healing procedure. Not only does it reduce the swelling and the pain, but also stops the blood flow by constricting the blood vessels so that too much blood isn’t lost. Moreover, lower blood to the injured area reduces the rate of metabolism in that area, thus diminishing the rate of cell death and promoting faster recovery.

Phases of Acute Wound Healing


Haemostasis occurs immediately following an injury. 5 To prevent exsanguination, vasoconstriction occurs and platelets undergo activation, adhesion and aggregation at the site of injury. Platelets become activated when exposed to extravascular collagen (such as type I collagen), which they detect via specific integrin receptors, cell surface receptors that mediate a cell’s interactions with the extracellular matrix. Once in contact with collagen, platelets release the soluble mediators (growth factors and cyclic AMP) and adhesive glycoproteins, which signal them to become sticky and aggregate. The key glycoproteins released from the platelet alpha granules include fibrinogen, fibronectin, thrombospondin, and von Willebrand factor. As platelet aggregation proceeds, clotting factors are released resulting in the deposition of a fibrin clot at the site of injury. The fibrin clot serves as a provisional matrix. 6 the aggregated platelets become trapped in the fibrin web and provide the bulk of the clot (Figure 23.2). Their membranes provide a surface on which inactive clotting enzyme proteases are bound, become activated and accelerate the clotting cascade.


Haemostasis Phase. At the time of injury, the fibrin clot forms the provisional wound matrix and platelets release multiple growth factors initiating the repair process.

Growth factors are also released from the platelet alpha granules, and include platelet derived growth factor (PDGF), transforming growth factor beta (TGF-β), transforming growth factor alpha (TGF-α), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF). Major growth factor families are presented in Table 23.1. Neutrophils and monocytes are then recruited by PDGF and TGF-β from the vasculature to initiate the inflammatory response. A breakdown fragment generated from complement, C5a, and a bacterial waste product, f-Met-Leu-Phe, also provide additional chemotactic signals for the recruitment of neutrophils to the site of injury. Meanwhile, endothelial cells are activated by VEGF, TGF-α and bFGF to initiate angiogenesis. Fibroblasts are then activated and recruited by PDGF to migrate to the wound site and begin production of collagen and glycosaminoglycans, proteins in the extracellular matrix which facilitate cellular migration and interactions with the matrix supporting framework. Thus, the healing process begins with hemostasis, platelet deposition at the site of injury, and interactions of soluble mediators and growth factors with the extracellular matrix to set the stage for subsequent healing events. 1 , 2 , 7

TABLE 23.1

Major growth factor families.


Inflammation, the next stage of wound healing occurs within the first 24 hours after injury and can last for up to 2 weeks in normal wounds and significantly longer in chronic non-healing wounds (Figure 23.3). Mast cells release granules filled with enzymes, histamine and other active amines, which are responsible for the characteristic signs of inflammation, the rubor (redness), calor (heat), tumor (swelling) and dolor (pain) around the wound site. Neutrophils, monocytes, and macrophages are the key cells during the inflammatory phase. They cleanse the wound of infection and debris and release soluble mediators such as proinflammatory cytokines (including IL-1, IL-6, IL-8, and TNF-α), and growth factors (such as PDGF, TGF-β, TGF-α, IGF-1, and FGF) that are involved in the recruitment and activation of fibroblasts and epithelial cells in preparation for the next phase in healing. Cytokines that play important roles in regulating inflammation in wound healing are described in Table 23.2.


Inflammation Phase. Within a day following injury, the inflammatory phase is initiated by neutrophils that attach to endothelial cells in the vessel walls surrounding the wound (margination), change shape and move through the cell junctions (diapedesis), (more. )

TABLE 23.2

Cytokines involved in wound healing.

In addition to the growth factors and cytokines, a third important group of small regulatory proteins, listed in Table 23.3, has been identified, and are collectively named chemokines, from a contraction of chemoattractive cytokine(s). 8 , 9 , 10 the structural and functional similarities among chemokines were not initially appreciated, and this has led to an idiosyncratic nomenclature consisting of many acronyms that were based on their biological functions, (e.g., monocyte chemo-attractant protein-1 (MCP-1), macrophage inflammatory protein-1, MIP-1), their source for isolation (platelet factor-4, PF-4) or their biochemical properties (interferon-inducible protein of 10 kD a (IP-10), or regulated upon activation normal T-cell expressed and secreted, RANTES). As their biochemical properties were established, it was recognized that the approximately 40 chemokines could be grouped into four major classes based on the pattern of cysteine residues located near the N-terminus. In fact, there has been a recent trend to re-establish a more organized nomenclature system based on these four major classes. In general, chemokines have two primary functions: 1) they regulate the trafficking of leukocyte populations during normal health and development, and 2) they direct the recruitment and activation of neutrophils, lymphocytes, macro-phages, eosinophils and basophils during inflammation.

TABLE 23.3

Chemokine familes involved in wound healing.


Neutrophils are the first inflammatory cells to respond to the soluble mediators released by platelets and the coagulation cascade. They serve as the first line of defense against infection by phagocytosing and killing bacteria, and by removing foreign materials and devitalized tissue. During the process of extravasation of inflammatory cells into a wound, important interactions occur between adhesion molecules (selectins, cell adhesion molecules (CAMS) and cadherins) and receptors (integrins) that are associated with the plasma membranes of circulating leukocytes and vascular endothelial cells. 11 , 12 Initially, leukocytes weakly adhere to the endothelial cell walls via their selectin molecules which causes them to decelerate and begin to roll on the surface of endothelial cells. While rolling, leukocytes can become activated by chemoattractants (cytokines, growth factors or bacterial products). After activation, leukocytes firmly adhere to endothelial cells as a result of the binding between their integrin receptors and ligands such as VCAM and ICAM that are expressed on activated endothelial cells. Chemotactic signals present outside the venule then induce leukocytes to squeeze between endothelial cells of the venule and migrate into the wounded tissue using their integrin receptors to recognize and bind to extracellular matrix components. The inflammatory cells release elastase and collagenase to help them migrate through the endothelial cell basement membrane and to migrate into the extracellular matrix (ECM) at the site of the wound. Neutrophils also produce and release inflammatory mediators such as TNF-α and IL-1 that further recruit and activate fibroblasts and epithelial cells. After the neutrophils migrate into the wound site, they generate oxygen free radicals, which kill phagocytized bacteria, and they release high levels of proteases (neutrophil elastase and neutrophil collagenase) which remove components of the extracellular matrix that were damaged by the injury. The persistent presence of bacteria in a wound may contribute to chronicity through continued recruitment of neutrophils and their release of proteases, cytokines and reactive oxygen species. Usually neutrophils are depleted in the wound after 2 to 3 days by the process of apoptosis, and they are replaced by tissue monocytes.


Activated macrophages play pivotal roles in the regulation of healing, and the healing process does not proceed normally without macrophages. Macrophages begin as circulating monocytes that are attracted to the wound site beginning about 24 hours after injury (Figure 23.4). They extravasate by the mechanisms described for neutrophils, and are stimulated to differentiate into activated tissue macrophages in response to chemokines, cytokines, growth factors and soluble fragments of extracellular matrix components produced by proteolytic degradation of collagen and fibronectin. 13 Similar to neutrophils, tissue macrophages have a dual role in the healing process. They patrol the wound area ingesting and killing bacteria, and removing devitalized tissue through the actions of secreted MMPs and elastase. Macrophages differ from neutrophils in their ability to more closely regulate the proteolytic destruction of wound tissue by secreting inhibitors for the proteases. As important as their phagocytic role, macrophages also mediate the transition from the inflammatory phase to the proliferative phase of healing. They release a wide variety of growth factors and cytokines including PDGF, TGF-β, TGF-α, FGF, IGF-1, TNFα, IL -1, and IL-6. Some of these soluble mediators recruit and activate fibroblasts, which will then synthesize, deposit, and organize the new tissue matrix, while others promote angiogenesis. The absence of neutrophils and a decrease in the number of macrophages in the wound is an indication that the inflammatory phase is nearing an end, and that the proliferative phase is beginning.


Proliferation Phase. Fixed tissue monocytes activate, move into the site of injury, transform into activated wound macrophages that kill bacteria, release proteases that remove denatured ECM, and secrete growth factors that stimulate fibroblasts, epidermal (more. )

Proliferative phase

The milestones during the proliferative phase include replacement of the provisional fibrin matrix with a new matrix of collagen fibers, proteoglycans, and fibronectin to restore the structure and function to the tissue. Another important event in healing is angiogenesis, the in-growth of new capillaries to replace the previously damaged vessels and restore circulation. Other significant events in this phase of healing are the formation of granulation tissue and epithelialization. Fibroblasts are the key cells in the proliferative phase of healing.

Fibroblast migration

Fibroblasts migrate into the wound in response to multiple soluble mediators released initially by platelets and later by macrophages (Figure 23.4). Fibroblast migration in the extracellular matrix depends on precise recognition and interaction with specific components of the matrix. Fibroblasts in normal dermis are typically quiescent and sparsely distributed, whereas in the provisional matrix of the wound site and in the granulation tissue, they are quite active and numerous. Their migration and accumulation in the wound site requires them to change their morphology and to produce and secrete proteases to clear a path for their movement from the ECM into the wound site.

Fibroblasts begin moving by first binding to matrix components such as fibronectin, vitronectin and fibrin via their integrin receptors. Integrin receptors attach to specific amino acid sequences (such as R-G-D or arginine-glycine-aspartic acid) or binding sites in these matrix components. While one end of the fibroblast remains bound to the matrix component the cell extends a cytoplasmic projection to find another binding site. When the next site is found, the original site is released (apparently by local protease activity), and the cell uses its cytoskeleton network of actin fibers to pull itself forward.

The direction of fibroblast movement is determined by the concentration gradient of chemotactic growth factors, cytokines and chemokines, and by the alignment of the fibrils in the ECM and provisional matrix. Fibroblasts tend to migrate along these fibrils as opposed to across them. Fibroblasts secrete proteolytic enzymes locally to facilitate their forward motion through the matrix. The enzymes secreted by the fibroblasts include three types of MMPs, collagenase (MMP-1), gelatinases (MMP-2 and MMP-9) which degrade gelatin substrates, and stromelysin (MMP-3) which has multiple protein substrates in the ECM.

Collagen and extracellular matrix production

The collagen, proteoglycans and other components that comprise granulation tissue are synthesized and deposited primarily by fibroblasts. PDGF and TGF-β are two of the most important growth factors that regulate fibroblast activity. PDGF, which predominantly originates from platelets and macro-phages, stimulates a number of fibroblast functions including proliferation, chemo-taxis, and collagenase expression. TGF-β, also secreted by platelets and macrophages is considered to be the master control signal that regulates extracellular matrix deposition. Through the stimulation of gene transcription for collagen, proteoglycans and fibronectin, TGF-β increases the overall production of matrix proteins. At the same time, TGF-β down-regulates the secretion of proteases responsible for matrix degradation and also stimulates synthesis of tissue inhibitor of metalloproteinases (TIMP), to further inhibit break down of the matrix. Recent data indicate that a new growth factor, named connective tissue growth factor (CTGF), mediates many of the effects of TGF-β on the synthesis of extracellular matrix. 14

Once the fibroblasts have migrated into the matrix they again change their morphology, settle down and begin to proliferate and to synthesize granulation tissue components including collagen, elastin and proteoglycans. Fibroblasts attach to the cables of the provisional fibrin matrix and begin to produce collagen. At least 20 individual types of collagen have been identified to date. Type III collagen is initially synthesized at high levels, along with other extracellular matrix proteins and proteoglycans. After transcription and processing of the collagen mRNA, it is attached to polyribosomes on the endoplasmic reticulum where the new collagen chains are produced. During this process, there is an important step involving hydroxylation of proline and lysine residues. Three protein chains associate and begin to form the characteristic triple helical structure of the fibrillar collagen molecule, and the nascent chains undergo further modification by the process of glycosylation. Hydroxyproline in collagen is important because it plays a major role in stabilizing the triple helical conformation of collagen molecules. Fully hydroxylated collagen has a higher melting temperature. When levels of hydroxyproline are low, for example in vitamin C-deficient conditions (scurvy), the collagen triple helix has an altered structure and denatures (unwinds) much more rapidly and at lower temperatures. To ensure optimal wound healing, wound care specialists should be sure patients are receiving good nutritional support with a diet with ample protein and vitamin C.

Finally, procollagen molecules are secreted into the extracellular space where they undergo further processing by proteolytic cleavage of the short, non-helical segments at the N-and C-termini. The collagen molecules then spontaneously associate in a head-to-tail and side-by-side arrangement forming collagen fibrils, which associate into larger bundles that form collagen fibers. In the extra-cellular spaces an important enzyme, lysyl oxidase, acts on the collagen molecules to form stable, covalent, cross-links. As the collagen matures and becomes older, more and more of these intramolecular and intermolecular cross-links are placed in the molecules. This important cross-linking step gives collagen its strength and stability, and the older the collagen the more cross-link formation has occurred.

Dermal collagen on a per weight basis approaches the tensile strength of steel. In normal tissue, it is a strong molecule and highly organized. In contrast, collagen fibers formed in scar tissue are much smaller and have a random appearance. Scar tissue is always weaker and will break apart before the surrounding normal tissue.


Damaged vasculature must be replaced to maintain tissue viability. The process of angiogenesis is stimulated by local factors of the microenvironment including low oxygen tension, low pH, and high lactate levels. 15 Also, certain soluble mediators are potent angiogenic signals for endothelial cells. Many of these are produced by epidermal cells, fibroblasts, vascular endothelial cells and macrophages, and include bFGF, TGF-β, and VEGF. It is now recognized that oxygen levels in tissues directly regulate angiogenesis by interacting with oxygen sensing proteins that regulate transcription of angiogenic and anti-angiogenic genes. For example, synthesis of VEGF by capillary endothelial cells is directly increased by hypoxia through the activation of the recently identified transcription factor, hypoxia-inducible factor (HIF), which binds oxygen. 16 when oxygen levels surrounding capillary endothelial cells drop, levels of HIF increase inside the cells. HIF-1 binds to specific DNA sequences and stimulates transcription of specific genes such as VEGF that promote angiogenesis. When oxygen levels in wound tissue increase, oxygen binds to HIF, leading to the destruction of HIF molecules in cells and decreased synthesis of angiogenic factors. Regulation of angiogenesis involves both stimulatory factors like VEGF and anti-angiogenic factors like angiostatin, endostatin, thrombospondin, and pigment epithelium-derived factor (PEDF).

Binding of angiogenic factors causes endothelial cells of the capillaries adjacent to the devascularized site to begin to migrate into the matrix and then proliferate to form buds or sprouts. Once again the migration of these cells into the matrix requires the local secretion of proteolytic enzymes, especially MMPs. As the tip of the sprouts extend from endothelial cells and encounter another sprout, they develop a cleft that subsequently becomes the lumen of the evolving vessel and complete a new vascular loop. This process continues until the capillary system is sufficiently repaired and the tissue oxygenation and metabolic needs are met. It is these new capillary tuffs that give granulation tissue its characteristic bumpy or granular appearance.


Granulation tissue is a transitional replacement for normal dermis, which eventually matures into a scar during the remodelling phase of healing. It is characterized from unwounded dermis by an extremely dense network of blood vessels and capillaries, elevated cellular density of fibroblasts and macrophages and randomly organized collagen fibers. It also has an elevated metabolic rate compared to normal dermis, which reflects the activity required for cellular migration and division and protein synthesis.


All dermal wounds heal by three basic mechanisms: contraction, connective tissue matrix deposition and epithelialization. Wounds that remain open heal by contraction the interaction between cells and matrix results in movement of tissue toward the center of the wound. As previously described, matrix deposition is the process by which collagen, proteoglycans and attachment proteins are deposited to form a new extracellular matrix. Epithelialization is the process where epithelial cells around the margin of the wound or in residual skin appendages such as hair follicles and sebaceous glands lose contact inhibition and by the process of epiboly begin to migrate into the wound area. As migration proceeds, cells in the basal layers begin to proliferate to provide additional epithelial cells.

Epithelialization is a multi-step process that involves epithelial cell detachment and change in their internal structure, migration, proliferation and differentiation. 17 The intact mature epidermis consists of 5 layers of differentiated epithelial cells ranging from the cuboidal basal keratinocytes nearest the dermis up to the flattened, hexagonal, tough keratinocytes in the uppermost layer. Only the basal epithelial cells are capable of proliferation. These basal cells are normally attached to their neighboring cells by intercellular connectors called desmosomes and to the basement membrane by hemi-desmosomes. When growth factors such as epidermal growth factor (EGF), keratinocyte growth factor (KGF) and TGF-α are released during the healing process, they bind to receptors on these epithelial cells and stimulate migration and proliferation. The binding of the growth factors triggers the desmosomes and hemi-desmosomes to dissolve so the cells can detach in preparation for migration. Integrin receptors are then expressed and the normally cuboidal basal epithelial cells flatten in shape and begin to migrate as a monolayer over the newly deposited granulation tissue, following along collagen fibers. Proliferation of the basal epithelial cells near the wound margin supply new cells to the advancing monolayer apron of cells (cells that are actively migrating are incapable of proliferation). Epithelial cells in the leading edge of the monolayer produce and secrete proteolytic enzymes (MMPs) which enable the cells to penetrate scab, surface necrosis, or eschar. Migration continues until the epithelial cells contact other advancing cells to form a confluent sheet. Once this contact has been made, the entire epithelial mono layer enters a proliferative mode and the stratified layers of the epidermis are re-established and begin to mature to restore barrier function. TGF-β is one growth factor that can speed up the maturation (differentiation and keratinization) of the epidermal layers. The intercellular desmosomes and the hemi-desmosome attachments to the newly formed basement membrane are also re-established. Epithelialization is the clinical hallmark of healing but it is not the final event – remodelling of the granulation tissue is yet to occur.

Recent studies by Sen, et al. have demonstrated that under conditions of hypoxia, HIF-1alpha is stabilized which in turn induces the expression of specific micro RNAs that then down-regulate epithelial cell proliferation (1). Therefore it appears that there are very complex mechanisms involved in the role of oxygen and hypoxia during the process of wound healing.


Remodelling is the final phase of the healing process in which the granulation tissue matures into scar and tissue tensile strength is increased (Figure 23.5). The maturation of granulation tissue also involves a reduction in the number of capillaries via aggregation into larger vessels and a decrease in the amount of glycosaminoglycans and the water associated with the glycosaminoglycans (GAGs) and proteoglycans. Cell density and metabolic activity in the granulation tissue decrease during maturation. Changes also occur in the type, amount, and organization of collagen, which enhance tensile strength. Initially, type III collagen was synthesized at high levels, but it becomes replaced by type I collagen, the dominant fibrillar collagen in skin. The tensile strength of a newly epithelialized wound is only about 25% of normal tissue. Healed or repaired tissue is never as strong as normal tissues that have never been wounded. Tissue tensile strength is enhanced primarily by the reorganization of collagen fibers that were deposited randomly during granulation and increased covalent cross-linking of collagen molecules by the enzyme, lysyl oxidase, which is secreted into the ECM by fibroblasts. Over several months or more, changes in collagen organization in the repaired tissue will slowly increase the tensile strength to a maximum of about 80% of normal tissue.


Remodelling Phase. The initial, disorganized scar tissue is slowly replaced by a matrix that more closely resembles the organized ECM of normal skin.

Remodelling of the extracellular matrix proteins occurs through the actions of several different classes of proteolytic enzymes pro-duced by cells in the wound bed at different times during the healing process. Two of the most important families are the matrix metalloproteinases (MMPs) (Table 23.4), and serine proteases. Specific MMP proteases that are necessary for wound healing are the collagenases (which degrade intact fibrillar collagen molecules), the gelatinases (which degrade damaged fibrillar collagen molecules) and the stromelysins (which very effectively degrade proteoglycans). An important serine protease is neutrophil elastase which can degrade almost all types of protein molecules. Under normal conditions, the destructive actions of the proteolytic enzymes are tightly regulated by specific enzyme inhibitors, which are also produced by cells in the wound bed. The specific inhibitors of the MMPs are the tissue inhibitors of metalloproteinases (TIMPs) and specific inhibitors of serine protease are 㬑-protease inhibitor (㬑-PI) and 㬒 macroglobulin.

TABLE 23.4

Matrix metalloproteinases and tissue inhibitors of metalloproteinases.

Summary of acute wound healing

Cellular functions during the different phases of wound healing are regulated by key cytokines, chemokines and growth factors. Cell actions are also influenced by interaction with components of the ECM through their integrin receptors and adhesion molecules. MMPs produced by epidermal cells, fibroblasts and vascular endothelial cells assist in migration of the cells, while proteolytic enzymes produced by neutrophils and macrophages remove denatured ECM components and assist in remodelling of initial scar tissue.




Historic Images

Fig. 233. Lateral view of a human embryo at the 28th day, showing the Limb Buds, Lateral Edges, and Primitive Segments.

Fig. 234. Development of the Upper Limb.

Fig. 235. Development of the Lower Limb.

Fig. 237. Section of the Arm Bud of a human embryo at the end of the 4th week.

Fig. 238. Schematic Section showing the Origin and Arrangement of the Muscles and Nerves of the Limbs.

Fig. 239. The Distribution of the Posterior Roots of the Spinal Nerves on the Flexor Aspect of the Arm.

Fig. 240. Diagram to show the typical Manner in which the Posterior Nerve Roots are distributed in the Lower Limb.

Fig. 241. Flexor Aspect of the Lower Limb showing the Sensory Distribution of the Segmental or Spinal nerves.

Fig. 242. Diagram of the Pelvic Girdle of a Lizard.

Fig. 243. The Pelvic Girdle of a Human Foetus at the 5th week.

Fig. 244. The Shoulder Girdle of Ornithorynchus.

Fig. 245. The Parts in the Shoulder Girdle of a human foetus which correspond with those of Ornithorynehus.

Fig. 246. The Carpal Bones of a Tortoise.

Fig. 247. The Os Trigenum and Bones of the Tarsus

Fig. 248. The Foetal and Adult (in dotted outline) Forma of the Astralagus contrasted.

Fig. 249. Latissimo-condyloideus Muscle.

Fig. 250. The Morphology of the Short Muscles of the Digits.

Fig. 251. Showing the Origin of the Ligamentum Teres and Reflected Bundle of the Capsular Ligament.

Fig. 252. Showing the Origin of the Crucial Ligaments of the Knee.