The Management of Hypertension (Pathophysiologic Basises)

September 10, 2015 Cardiology, Pharmacology, Physiology and Pathophysiology No comments , , , , , , , , , , ,

Hypertension is a common diseases and is defined as persistently elevated arterial blood pressure of >= 140/90 mm Hg. Most of patients belong to essential hypertension and a small percentage belong to secondary hypertension for which the most common causes include renal dysfunction resulting from severe chronic kidney disease (CKD) or renovascular disease. Besides, certain drugs or other products (Table 3-1), either directly or indirectly, can cause hypertension or exacerbate hypertension by increase BP.

Table 3-1 Secondary Causes for Hypertesnion

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Classification of Hypertension

  • Normal: Systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg
  • Prehypertension: Systolic 120-139 mm Hg, diastolic 80-89 mm Hg
  • Stage 1: Systolic 140-159 mm Hg, diastolic 90-99 mm Hg
  • Stage 2: Systolic 160 mm Hg or greater, diastolic 100 mm Hg or greater

Hypertension Crisis: These are clinical situations where BP values are very elevated, typically >180/120 mm Hg. They are categorized as either hypertensive emergency or hypertensive urgency. The former are extreme elevations in BP that are accompanied by acute or processing target-organ damage. The latter are high elevations in BP without acute or progressing target-organ injury. Prehypertension is not considered a disease category but identifies patients whose BP is likely to increase into the classification of hypertension in the future.

Cardiovascular Risk and Blood Pressure

Hypertension must be treated and the reason why is that hypertension is a major cardiovascular risk factor and there indeed is a causal relationship between hypertension and cardiovascular diseases. Also, epidemiologic data demonstrate a strong correlation between BP and CV morbidity and mortality. (Starting at a BP of 115/75 mm Hg, risk of CV disease doubles with every 20/10 mm Hg increase.) Even patients with prehypertension have an increased risk of CV disease. Because hypertension and CV morbidity/mortality has a casual relationship, treating patients with hypertension with antihypertensive drug therapy provides significant clinical benefits.


To further discuss the pathophysiology, we first need to know the mathematic formula to estimate arterial BP. According to the physic law, steady flow (Q) through a closed hydraulic circuit is directly related to the pressure gradient across the circuit (Pin – Pout), and inversely related to the resistance to flow (R) through the circuit. So Q=(Pin – Pout)/R. In the cardiovascular system, Q is cardiac output (CO), Pin is mean arterial pressure (MAP) and Pout is right atrial pressure (RAP), whereas resistance to flow (R) is total peripheral resistance (TPR). So CO=(MAP – RAP)/TPR. Because in normal conditions RAP approaches zero mm Hg, so CO=MAP/TPR and after we make a rearrange we finally get the formula of MAP=CO * TPR. Note that in some pathophysiology status RAP increases significantly and cannot be removed from the formula above.

After the discuss above, the two determinants for MAP is the cardiac output (CO) and the total peripheral resistance (TPR). If we distinguish MAP to systolic BP (SBP) and diastolic BP (DPB), CO is the major determinant of SBP, whereas TPR largely determines DBP. So factors that elevate CO or TPR can elevate BP. We category these factors into 1.humoral; 2.neuronal; 3.peripheral autoregulation; and 4.disturbances in sodium, calcium, and natriuretic hormone.

Humoral Mechanisms


RAAS stands for the rennin-angiotensin-aldosterone system, which is a complex endogenous system that play a range of functions including the regulation of arterial pressure. The RAAS regulars sodium, potassium, blood volume, and most important the vascular tone. Because the total periphery resistance (TPR) is primarily generated by arterioles, so elevated TPR could be a result of activation of RAAS – the angiotensin II (angII). For the detail discussion of TPR please refer to the threads of and, respectively, by Tom Hsiung. First, angII increase the vascular tone, including arterioles. Second, angII induced increased aldosterone synthesis and secretion sodium and water retention, which increase the blood volume. Increased blood volume and TPR eventually result in elevation of BP.


Vasopressin is a polypeptide hormone, also known as antidiuretic hormone/ADH, which plays an important role in extracellular fluid homeostasis (blood volume/plasma volume). Vasopressin acts on collecting ducts in the kidneys to decrease renal excretion of water. This is the most important and wide-known function of vasopressin. However, vasopressin is also a potent arteriolar vasoconstrictor.

Natriuretic Hormone

Natriuretic hormones inhibits sodium and potassium-ATPase and thus interferes with sodium transport across cell membranes. Natriuretic hormone theoretically could increase urinary exertion of sodium and water. However, this hormone might block the active transport of sodium out of arteriolar smooth muscle cells. The increased intracellular sodium concentration concentration ultimately would increase vascular tone and BP.

Insulin Resistance and Hyperinsulinemia

Hypothetically, increased insulin concentrations may lead to hypertension because of increased renal sodium retention and enhanced sympathetic nervous system activity. Moreover, insulin has growth hormone-like actions that can induce hypertrophy of vascular smooth muscle cells. Insulin also may elevated BP by increasing intracellular calcium, which lead to increased vascular resistance. The exact mechanism by which insulin resistance and hyperinsulinemia occur in hypertension is unknown. However, this association is strong because many of the criteria used to define this population (i.e., elevated BP, abdominal obesity, high, triglycerides, low high-density lipoprotein cholesterol, and elevated fasting glucose) are often present in patients with hypertension.

Circulating Catecholamines

It is easy to understand the causal relationship between elevated levels of circulating catecholamines and the hypertension, from the perspective of MAP = CO * TPR.

Neuronal Regulation

Synaptic receptors, baroreceptor reflex system, and CNS are involved in the regulation of vascular resistances, cardiac outputs.

Central and autonomic nervous system are intricately involved in the regulation of arterial BP. Many receptors that either enhance or inhibit norepinephrine release are located on the presynaptic surface of sympathetic terminals. The alpha and beta presynaptic receptors play a role in negative and positive feedback to the norepinephrine-containing vesicles, respectively. Stimulation presynaptic alpha-receptors (α2) exerted a negative inhibition on norepinephrine release. Stimulation of presynaptic beta-receptors facilitates norepinephrine release.

Sympathetic neuronal fibers located on the surface of effector cells innervate the alpha- and beta-receptors. Stimulation of postsynaptic alpha-receptors (α1) on arterioles and venues results in vasoconstriction. There are two types of postsynaptic beta-receptors, β1 and β2. Both are present in all tissues innervated by the sympathetic nervous system. However, in some tissues β1-receptors predominate (e.g., heart), and in other tissues β2-receptors predominate (e.g., bronchioles). Stimulation of β1-receptors in the heart results in an increase in heart rate, and the force of contraction (so cardiac output is increased), whereas stimulation of β2-receptors in the arterioles and venues causes vasodilation.

So after the discussion of the two paragraph above, we know that the disturbance of the function of presynaptic and/or postsynaptic receptors would result the imbalance of autonomic nervous system.

Same with the autonomic nervous system but from a different aspect (above is output of autonomic nervous system and now it’s the input of nervous system),  the baroreceptor reflex system is the major negative feedback mechanism the controls sympathetic activity. Baroreceptors are nerve endings lying in the walls of large arteries, especially in the carotid arteries and aortic arch. Changes in arterial BP rapid activate baroreceptors that then transmit impulses to the brain stem through the ninth cranial nerve and vagus nerve. In this reflex system, a decrease in arterial BP stimulates baroreceptors, causing reflex vasoconstriction and increased heart rate and force of cardiac contraction. Also the periphery vascular tone increase too (TPR).

Stimulation of certain areas within the central nervous system can either increase or decrease BP. I think this mechanism must be rather complex, which involves with neurology. If we have time in future, I will take a look at the neurology.

OK. The purpose of the neuronal mechanisms is to regulate BP and maintain homeostasis. Pathologic disturbances in neuronal systems could chronically elevate BP. These systems are physiologically interrelated. A defect in one component may alter normal function in another. Therefore, cumulative abnormalities may explain the development of essential hypertension.

Peripheral/Local Mechanisms (including autoregulatory, etc.) 

Abnormalities in renal or tissue autoregulatory systems, which is just one of several local vascular regulatory mechanisms of human, could cause hypertension. Recall the formula that MAP = CO * TPR. Similarly, the disorders of local vascular regulatory .For detail information of local vascular regulatory mechanisms please refer to the thread of by Tom Hsiung.


Epidemiologic and clinical data have associated excess sodium intake with hypertension. Population-based studies indicate that high-sodium diets are associated with a high prevalence of stroke and hypertension. Conversely, low-sodium diets are associated with a lower prevalence of hypertension. For the perspective of pathophysiology, more sodium, more water. We will discuss this phenomenon in threads that discuss the kidney.

Altered calcium homeostasis also may play an important role in the pathogenesis of hypertension. A lack of dietary calcium hypothetically can disturb the balance between intracellular and extracellular calcium, resulting in an increased intracellular calcium concentration. This imbalance can alter vascular smooth muscle function by increasing PVR (peripheral vascular resistance). Some studies have shown that dietary calcium supplementation results in a modest BP reduction for patients with hypertension.

The role of potassium fluctuations is also inadequately understood. Potassium depletion may increase PVR, but the clinical significance of small serum potassium concentration changes is unclear. Furthermore, data demonstrating reduced CV risk with dietary potassium supplementation are very limited.

Arteriolar Tone and Its Regulation (Local Mechanisms)

July 17, 2015 Cardiology, Physiology and Pathophysiology No comments , , , , , , , , , , , , , , , , ,


I.Arteriolar Tone

A.Basal tone


C.Adrenal Glands


1.Metabolic substances

2.Endothelial cells secretion

3.Other local chemical influences

4.Transmural pressure (myogenic response)

II.Venous Tone

A.Basal tone (little)


C.Adrenal glands

D.Internal pressure (recall deltaV/deltaP = C)

E.External compression (muscle pump)

Because the body's needs are continually changing, the cardiovascular system must continually make adjustments in the diameter of its vessels. The purposes of these vascular change are efficiently distribute the cardiac output among tissues with different current needs (the job of arterioles) and regulate the distribute of blood volume and cardiac filling (the job of veins). So besides central regulatory mechanisms for vascular system (CNS, autonomic nerves system) and hormonal regulatory mechanisms (RAAS/angII and vasopressin, natriuretic hormone, insulin resistance and hyperinsulinemia, circulating catecholamines), there are another vascular regulatory mechanism – peripheral regulatory mechanisms/local mechanisms.

Total peripheral resistance (TPR) is determined by resistances of each primary organs and tissues, whereas resistance of an single organ or tissue region is primarily determined by resistances of arterioles that distribute within this organ or tissue. Therefore, TPR is determined primarily by resistance of arterioles. According to the famous Hagen–Poiseuille equation, resistance to flow is inversely and directly related to the radius of the vessel.

(Note: Q = ΔP/R, and R is resistance of the vessel)

Because resistances of arterioles are so important for TPR and the resultant blood flow (Q), we need to study the characteristics of arteriolar resistance carefully. Vascular tone is a term commonly used to characterize the general contractile state (so the radius of the vessel) or a vascular region. The "vascular tone" of a region can be taken as an indication of the "level of activation" of the individual smooth muscle cells in that region. Because the blood flow through any organ is determined largely by its vascular resistance, which dependent primarily on the diameter of its arterioles, thus an organ's flow is controlled by factors that influence the arteriolar smooth muscle tone.

Arterioles remain in a state of partial constriction even all external influences on them are removed; hence, they are said to have a degree of basal tone. The understanding of the mechanism is incomplete, but basal arteriolar tone may be a reflection of the fact that smooth muscle cells inherently and actively resist being stretched as they continually are in pressurized arterioles. Another hypothesis is that the basal tone of arterioles is the result of a tonic production of local vasoconstrictor substances by the endothelial cells that line their inner surface. Nevertheless, the arterioles have basal tone, and several factors externally influence it, including local influences, neural influences, and hormonal influences.


The capacity of tissues to regulate their own blood flow is referred to as auto regulation. Most vascular beds have an intrinsic capacity to compensate for moderate changes in perfusion pressure by change in vascular resistance, so that blood flow remains relatively constant. The ability of vascular autoregulation is probably due in part to the intrinsic contractile response of smooth muscle to stretch (myogenic theory of autoregulation). That is, as the perfusion pressure rises, the blood vessels are distended and the vascular smooth muscle fivers that surround the vessels contract, which increases the vascular resistance so that the blood flow remains constant (Q = ΔP/R). At the last section of this thread you can find more detail information for the mechanisms and rationales about vascular autoregulation.

General Mechanisms for Activation of the Vascular Smooth Muscle

The task of the vascular smooth muscle is unique, because to maintain a certain vessel diameter in the face of the continual distending pressure of the blood within it, the vascular smooth muscle must be able to sustain active tension for prolonged periods. Compared with other muscle types, smooth muscle cells have these different characteristics, including:

1.Contract and relax much more slowly;

2.Can change their contractile activity as a result of either action potentials or changes in resting membrane potential;

3.Can change their contractile activity in the absence of any change in membrane potential;

4.Can maintain tension for prolonged periods at low energy cost;


5.Can be activated by stretch.

Local Influences on Basal Tone

Local factors influencing arteriolar basal tone (and the diameter of arterioles) include metabolic influences, endothelial cells, other chemical influences, and transmural pressure.

Metabolic Substances. The arterioles that control flow through a given organ lie within the organ tissue itself. Thus, arterioles and the smooth muscle in their walls are exposed to the chemical composition of the interstitial fluid of the organ they serve. The interstitial concentrations of many substances reflect the balance between the metabolic activity of the tissue and its blood supply. Exposure to low oxygen, and metabolic substances such as high H+, high K+, high CO2, high osmolarity, and adenosine, cause reduced arteriolar tone and vasodilation. By contrary, exposure to high oxygen and low metabolic substances induce increased arteriolar tone and vasoconstriction. When metabolic activity is over the blood supply, oxygen pressure in that tissue gets lower and the metabolic wastes accumulate in the tissue, which cause vasodilation of arterioles. As a result of arteriolar vasodilation, the blood supply to that tissue is improved and oxygen pressure gets back to normal or even higher, whereas increased amount of metabolic wastes are washed away by the improved blood flow therefore the accumulation of metabolic wastes is resolved. Finally, the basal tone gets back to normal.

Endothelial cells cover the entire inner surface of the cardiovascular system. A large number of studies have shown that the blood vessels respond very differently to certain vascular influences when their endothelial lining is missing. In the case of the vasodilator effect of infusing acetylcholine through intact vessels, the vasodilator influence produced by endothelial cells has been identified as nitric oxide. Nitric oxide is produced within endothelial cells from the amino acid, L-arginine, by the action of an enzyme, nitric oxide synthase. Nitric oxide synthase is activated by a rise in the intracellular level of the Ca2+. And nitric oxide is a small lipid-soluble molecule that, once formed, easily diffuses into adjacent smooth muscle cells where it causes relaxation by stimulating cGMP production.

Acetylcholine and several other agents such as bradykinin, vasoactive intestinal peptide, and substance P stimulate endothelial cell nitric oxide production because their receipts on endothelial cells are linked to receptor-operated Ca2+ channels. Probably more importantly from a physiological standpoint, flow-related shear stresses on endothelial cells stimulate their nitric oxide production presumably because stretch-sensitive channels for Ca2+ are activated. Such flow-related endothelial cell nitric oxide production may explain why, for example, exercise and increased blood flow through muscles of the lower leg can cause dilation of the blood-supplying femoral artery at points far upstream of the exercising muscle itself.

One general unresolved issue with the concept that arteriolar tone is regulated by factors produced by arteriolar endothelial cells is how these cells could know what the metabolic needs of the downstream tissue are. This is because the endothelial cells lining arterioles are exposed to arterial blood whose composition is constant regardless of flow rate or what is happening downstream. One hypothesis is that there exists some sort of communication system between vascular endothelial cells. That way, endothelial cells in capillaries or venules could telegraph upstream information about whether the blood flow is indeed adequate.

Other local chemical influences. Many specific locally-produced and locally-reacting chemical substances have been identified that have vascular effects and therefore could be important in local vascular regulation in certain instances. In most cases, however, definite information about the relative importance of these substances in cardiovascular regulation is lacking. Prostaglandins are a group of several chemically related products of the cyclooxyrgenase pathways of arachidonic acid metabolism, which have vasoactive effects. Certain prostaglandins are potent vasodilators, while some are potent vasoconstrictors. However, despite the vasoactive potency of the prostaglandin and the fact that most tissues are capable of synthesizing prostaglandins, it has not been demonstrated convincingly that prostaglandins play a crucial role in the normal vascular control.

Histamine is synthesized and stored in high concentrations in secretory granules of tissue mast cells and circulating basophils. When released, histamine produces arteriolar vasodilation (via the cAMP pathway) and increases vascular permeability (by causing separations in the junctions between the endothelial cells that line the vascular system), which leads to edema formation and local tissue swelling. Other effects that histamine plays include stimulation of sensory nerve endings to produce itching and pain sensation.

Bradykinin is a small polypeptide that has approximately ten times the vasodilator potency of histamine on a molar basis. It also acts to increase capillary permeability by opening the junctions between endothelial cells. Bradykinin is formed from certain plasma globulin substances by the action of an enzyme, kvllikrein, and is subsequently rapidly degraded into inactive fragments by various tissue kinases.

Transmural pressure. The effect of transmural pressure on arteriolar diameter is more complex because arterioles respond both passively and actively to changes in transmural pressure. For example, a sudden increases in the internal pressure within an arteriole produces: 1.first an initial slight passive mechanical distention, and 2.then an active constriction that, within seconds, may completely reverse the initial distention. A sudden decrease in transmural pressure elicits essentially the opposite response, that is, an immediate passive decrease in diameter followed shortly by a decrease in active tone, which returns the arteriolar diameter to near that which existed before the pressure change. The active phase of such behavior is referred to as a myogenic response, because it seems to originate within the smooth muscle itself. The mechanism of the myogenic response is not known for certain, but stretch-sensitive ion channels on arteriolar vascular smooth muscle cells are likely candidates for involvement.

Examples of Local Regulation

Active Hyperemia – In organs with a highly variable metabolic rate, such as skeletal and cardiac muscles, the blood flow closely follows the tissue's metabolic rate. For example, skeletal muscle blood flow increases within seconds of the onset of muscle exercise and returns to control values shortly after exercise ceases. This phenomenon, which is illustrated in Figure 7-3A, is known as exercise or active hyperemia. Active hyperemia could be explained by mechanisms related to local metabolic theory and to local flow-related shear stresses theory.Screen Shot 2015-07-17 at 8.11.32 PM

Reactive Hyperemia – In this case, the higher-than-normal blood flow occurs transiently after the removal of any restriction that has caused a period of lower-than-normal blood flow and is sometimes referred to as post occlusion hyperemia. The phenomenon is illustrated in Figure 7-3B. For example, flow through an extremity is higher than normal for a period after a tourniquet is removed from the extremity. Both local metabolic and myogenic mechanisms may be involved in producing reactive hyperemia.

Autoregulation talks about the arterioles' reaction to the changes of the perfusion pressure. Except when displaying active and reactive hyperemia, nearly all organs tend to keep their blood flow constant despite variations in arterial pressure – that is, they autoregulate their blood flow. For example, an abrupt increase in arterial pressure is normally accompanied by an initial abrupt increase in organ blood flow that then gradually returns toward normal despite the sustained elevation in arterial pressure. The later autoregulation that returns the flow toward the normal level is caused by a gradual increase in active arteriolar tone and resistance to blood flow. Ultimately, a new steady state is reached with only slightly elevated blood flow because the increased driving pressure is counteracted by a higher-than-normal vascular resistance. The mechanisms for autoregulation are believed to be both local metabolic feedback theory and myogenic theory. Also, tissue pressure hypothesis of blood flow auto regulation for which it is assumed that an abrupt increase in arterial pressure causes transcapillary fluid filtration and thus leads to a gradual increase in interstitial fluid volume and pressure. Presumably the increase in extravascular pressure would cause a decrease in vessel diameter by simple compression. This mechanism might be especially important in organs such as the kidney and brain whose volumes are constrained by external structures.


Vascular Resistances and Compliance, MAP and Pulse Pressure

July 9, 2015 Cardiology, Physiology and Pathophysiology No comments , , , , , , ,

Resistances In A Single Organ

In an organ, the consecutive vascular segments are arranged in series within an organ. Therefore, the overall vascular resistance of the organ must equal the sum of the resistances of its consecutive vascular segments,

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Because arterioles have a large vascular resistance in comparison to the other vascular segments (see above), the overall vascular resistance of any organ is determined to a very large extent by the resistance of its arterioles. And according to its histologic characteristics, we can change the diameter of arterioles either spontaneously or with will (i.e., arterioles inside the penis). Thus, the blood flow through an organ is primarily regulated by adjustments in the internal diameter of arterioles caused by contraction or relaxation of their muscular arteriolar walls.

When the arterioles of an organ change diameter, not only does the flow (in general flow is decreased) to the organ change but also the manner in which the pressures drop within the organ is also modified. Arteriolar constriction causes a greater pressure drop  across the arterioles, and this tends to increase the arterial pressure while it decreases the pressure in capillaries and veins. Conversely, increased organ blood flow caused by arteriolar dilation is accompanied by decreased arterial pressure and increased capillary pressure. Because of the changes in capillary hydrostatic pressure, arteriolar constriction tends to cause transcapillary fluid reabsorption, whereas arteriolar dilation tends to promote transcapillary fluid filtration (see thread Transcapillary Transport at
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Resistances In A Whole Body

The overall resistance to flow through the entire systemic circulation is called the total peripheral resistance. Because the systemic organs are generally arranged in parallel, the vascular resistance of each organ contributes to the total peripheral resistance according to the following  parallel resistance equation:

Screen Shot 2015-07-08 at 10.51.03 PMAccording to the parallel vascular model, the TPR must always be less than that of any of the elements in the network (organ1, organ2, …, organn).

Compliance of Vassels

As indicated earlier, arteries and veins contribute only a small portion to the overall resistance to flow through a vascular bed. Therefore, changes in their diameters have no significant effect on the blood flow through systemic organs. The elastic behavior of arteries and veins is however every important to overall cardiovascular function because they can act as reservoirs and substantial amounts of blood can be stored in them.

Arteries or veins behave more like balloons with one pressure throughout rather than as resistive pipes with a flow-related pressure difference from end to end. Thus, we often think of an “arterial compartment” and a “venous compartment,” each with an internal pressure that is related to the volume of blood within it at any instant and how elastic its walls are.

The elastic nature of a vascular region is characterized by a parameter called compliance that describes how much its volume changes (ΔV) in response to a given change in distending pressure (ΔP): C = ΔV/ΔP. Distending pressure is the difference between the internal and external pressures on the vascular walls. The volume-pressure curves for the systemic arterial and venous compartments are shown in Figure 6-8. It is immediately apparent from the disparate slopes of the curve in this figure that the elastic properties of arteries and veins are very different. For the arterial compartment, the ΔV/ΔP measured near a normal operating pressure of 100 mm Hg indicates a compliance of approximately 2 mL/mm Hg. By contrast, the venous pool has a compliance of more than 100 mL/mm Hg near its normal operating pressure of 5 to 10 mm Hg.

Besides, arterial compliance also decreases with increasing MAP. Otherwise, arterial compliance is a relatively stable parameter.
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Because veins are so compliant, even small changes in peripheral venous pressure can cause a significant amount of the circulation blood volume to shift into or out of the peripheral venous pool. Standing upright, for example, increases venous pressure in the lower extremities, distends the compliant veins, and promotes blood accumulation (pooling) in these vessels, as might be represented by as shift from point A to point B in Figure 6-8. Fortunately, this process can be counteracted by active venous constriction. The dashed line in Figure 6-8 shows the venous volume-pressure relationship that exists when veins are constricted by activation of venous smooth muscle. In constricted veins, volume may be normal (point C) or even below normal (point D) despite higher-than-normal venous pressure. Peripheral venous constriction tends to increase peripheral venous pressure and shift blood out of the peripheral venous compartment.

Mean Arterial Pressure

Mean arterial pressure is a critically important cardiovascular variable because it is the average effective pressure that drives blood through the systemic organs. One of the most fundamental equations of cardiovascular physiology is that which indicates how mean arterial pressure is related to cardiac output and total peripheral resistance:

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This equation is simply a rearrangement of the basic flow equation (Q = ΔP/R) applied to the entire systemic circulation with the single assumption that central venous pressure is approximately zero so that ΔP = MAP. Of note is that all changes in MAP result from changes in either cardiac output or total peripheral resistance.

Arterial Pulse Pressure

The arterial pulse pressure (PP) is defined simply as systolic pressure minus diastolic pressure,

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To be able to use pulse pressure to deduce something about how the cardiovascular system is operating, one must do more than just define it. It is important to understand what determines pulse pressure; that is, what causes it to be what it is and what can cause it to change. As a consequence of the compliance of the arterial vessels, arterial pressure increases as arterial blood volume is expanded during cardiac ejection. The magnitude of the pressure increase (ΔP) caused by an increase in arterial volume depends on how large the volume change (ΔV) is and on how compliant (CA) the arterial compartment is: ΔP = ΔV/CA. If, for the moment, the fact that some blood leaves the arterial compartment during cardiac eject is neglected, then the increase in arterial volume during each heartbeat is equal to the stroke volume (SV). Thus, pulse pressure is, to a first approximation, equal to stoke volume divided by arterial compliance:

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If the stoke volume of a normal resting young man is approximately 80 mL and the arterial compliance is approximately 2 mL/mm Hg, arterial pulse should be approximately 40 mm Hg, according to the equation above. Because the compliance of arteries decrease as age grows, the arterial pulse pressure increases as age grows. Of note, arterial blood volume and mean arterial pressure tend to increase with age. The increase in mean arterial pressure is not caused by the decreased arterial compliance because compliance changes do not directly influence either cardiac output or total peripheral resistance, which are the sole determinants of MAP. And, the decrease in arterial compliance is sufficient to cause increased pulse pressure even through stroke volume tends to decrease with age.

In addition, MAP tends to increase with age because of an age-dependent increase in total peripheral resistance, which is controlled primarily by arterioles, not arteries.

The preceding equation for pulse pressure is a much-simplified description of some very complex hemodynamic processes. It correctly identifies stroke volume and arterial compliance as the major determinants of arterial pulse pressure but is based on the assumption that no blood leaves the aorta during systolic ejection. Obviously, this is not strictly correct. It is therefore not surprising that several factors other than arterial compliance and stroke volume have minor influences on pulse pressure. For example, because the arteries have viscous properties as well as elastic characteristics, faster cardiac ejection caused by increased myocardial contractility tends to increase pulse pressure somewhat even if stroke volume remains constant. Changes in peripheral resistance, however, have little or no effect on pulse pressure, because a change in total peripheral resistance causes parallel change in both systolic and diastolic pressures.