MAP

[Clinical Art][Circulation] Hemodynamic Monitoring – Tissue Oxygenation and Cardiac Output

October 24, 2016 Cardiology, Clinical Skills, Critical Care, Hemodynamics No comments , , , , , , , , , , , , , , , ,

Key Points

  • No hemodynamic monitoring device will improve patient outcome unless coupled to a treatment, which itself improves outcome.
  • Low venous oxygen saturations need not mean circulatory shock but do imply circulatory stress, as they may occur in the setting of hypoxemia, anemia, exercise, as well as circulatory shock.
  • There is no "normal" cardiac output, only one that is adequate or inadequate to meet the metabolic demands of the body. Thus, targeting a specific cardiac output value without reference to metabolic need, or oxygen-carrying capacity of the blood, is dangerous.
  • Cardiac output is estimated, not measured, by all devices routinely used in bedside monitoring (though we shall call it measured in this text).
  • Cardiac output estimates using arterial pulse pressure contour analysis cannot be interchanged among devices and all suffer to a greater or lesser extent by changes of peripheral vasomotor tone commonly seen in the critically ill.
  • Since metabolic demands can vary rapidly, continuous or frequent measures of cardiac output are preferred to single or widely spaced individual measures.
  • Integrating several physiologic variables in the assessment of the adequacy of the circulation usually gives a clearer picture than just looking at one variable.
  • Integrating cardiac output with other measures, like venous oxygen saturation, can be very helpful in defining the adequacy of blood flow.

Clinical Judgement of Hypoperfusion

Tissue hypoperfusion is a clinical syndrome, thus the presentation depends on which organ(s)/organ system(s) are being hypoperfused.

Table 1 Common Clinical Presentations of Tissue Hypoperfusion
Brain/CNS altered mental status, confusion
Pulmonary system dyspnea on exertion
Gastrointestinal tract slowed bowel function, abdominal discomfort, nausea/vomiting, anorexia
Renal system decrease urine output, increased serum creatinine
Hepatic system increased transaminases
Extremities/constitutional cool extremities, poor capillary refill, general fatigue/malaise
SvO2 in the case of normal CaO2 and VO2, SvO2 would decrease
Serum lactate level elevated serum lactate level

Note that some factors other than tissue hypoperfusion are able to cause the "hypoperfusion"-like presentation(s) which are similar as the one discussed above. For example, in the sepsis, the elevated levels of lactic acid might be caused by reasons other than hypoperfusion. In another case, the low urine output of a patient might be caused by the patient's ESRD per se rather than the low perfusion of kidneys. Also, if the patient had hypoglycemia or severe hyponatremia (which cause the neurons to edema), he or she would definitely lose the consciousness (differential diagnosis? or differential clinical judgement).


Tissue Oxygenation

Although mean artieral pressure (MAP) is a primary determinant of organ perfusion, normotension can coexist with circulatory shock.

Since metabolic demand of tissues varies by external (exercise) and internal (basal metabolism, digestion, fever) stresses, there is no "normal" cardiac ouput that the bedside caregiver can target and be assured of perfusion adequacy. Cardiac output is either adequate or inadequate to meet the metabolic demands of the body. Thus, although measures of cardiac output are important, their absolute values are relevant only in the extremes and when targeting specific clinical conditions, such as preoptimization therapy.

How then does one know that circulatory sufficiency is present or that circulatory shock exists? Clearly, since arterial pressure is the primary determinant of organ blood flow, systemic hypotension (i.e., mean arterial pressure <60 mm Hg) must result in tissue hypotension. Organ perfusion pressure can be approximated as mean arterial pressure (MAP) relative to tissue or outflow pressure. But, if intracranial pressure or intra-abdominal pressure increases, then estimating cerebral or splanchnic perfusion pressure using MAP alone will grossly overestimate organ perfusion pressure. In addition, baroreceptors in the carotid body and aortic arch increase vasomotor tone to keep cerebral perfusion constant if flow decreases, and the associated increased systemic sympathetic tone alters local vasomotor tone to redistribute blood flow away from more efficient O2 extracting tissues to sustain MAP and global O2 consumption (VO2) in the setting of inappropriately decreasing DO2. Thus, although systemic hypotension is a medical emergency and reflects severe circulatory shock, the absence of systemic hypotension does not ensure that all tissues are being adequately perfused.


  • Arterial pulse oximetry: SaO2
  • Venous Oximetry: ScvO2, SvO2
  • Tissue Oximetry
  • StO2 vascular occlusion test

Arterial Pulse Oximetry

SaO2

Arterial blood O2 saturation (SaO2) can be estimated quite accurately at the bedside using pulse oximetry. Routinely, pulse oximeters are placed on a finger for convenience sake. However, if no pulse is sensed, then the readings are meaningless. Such finger pulselessness can be seen with peripheral vasoconstriction associated with hypothermia, circulatory shock, or vasospasm. Central pulse oximetry using transmission technology can be applied to the ear or bridge of the nose and reflectance oximetry can be applied to the forehead, all of which tend to retain pulsatility if central pulsatile flow is present. Similarly, during cardiopulmonary bypass when arterial flow is constant, pulse oximetry is inaccurate. The primary important functions of SaO2 are summarized below.

  • SaO2 is routinely used to identify hypoxemia. Hypoxemia is usually defined as an SaO2 of <90% (PaO2 of <60 mm Hg).
  • SaO2 is also used to identify the causes of hypoxemia. The most common causes of hypoxemia are ventilation-perfusion (V/Q) mismatch (we will discuss this topic in the clinical art of respiratory medicine) and shunt. With V/Q mismatch alveolar hypoxia ocurs in lung regions with increased flow relative to ventilation, such that the high blood flow rapidly depletes alveolar O2 before the next breath can refresh it. Accordingly, this process readily lends itself to improve oxygenation by increasing FiO2 and minimizing regional alveolar hypoxia. Collapsed or flooded lung units will not alter their alveolar O2 levels by this maneuver and are said to be refractory to increase in FiO2. Accordingly, by measuring the SaO2 response to slight increases in FiO2 one can separate V/Q mismatch (shuntlike states) from shunt (absolute intrapulmonary shunt, anatomical intracardiac shunts, alveolar flooding, atelectasis [collapse]). One merely measures SaO2 while switching from room air FiO2 of 0.21 to 2 to 4 L/min nasal cannula (FiO2 ~0.3). Importantly, atelectatic lung units (collapse alveoli) should be recruitable by lung expansion whereas flooded lung units and anatomical shunts should not. Thus, by performing sustained deep inspirations and having the patient sit up and take deep breaths one should be able to separate easily recruitable atelectasis from shunt caused by anatomy and alveolar flooding. Sitting up and taking deep breaths is a form of exercise that may increaes O2 extraction by the tissues, thus decreasing SvO2. The patient with atelectasis will increase alveolar ventilation increasing SaO2 despite the decrease in SvO2, whereas the patient with unrecruitable shunt will realize a fall in SaO2 as the shunted blood will carry the lower SvO2 to the arterial side. Summary: SaO2 is used to identify V/Q mismatch and shunt, atelectasis and anatomical/flooding shunt, respectively.
  • Detection of volume responsiveness. Recent interest in the clinical applications of heart-lung interactions has centered on the effect of positive-pressure ventilation on venous return and subsequently cardiac output. In those subjects who are volume responsive, arterial pulse pressure, as a measure of left ventricular (LV) stroke volume, phasically decreases in phase with expiration, the magnitude of which is proportional to their volume responsiveness. Since the pulse oximeter's plethysmographic waveform is a manifestation of the arterial pulse pressure, if pulse pressure varies from beat-to-beat so will the plethysmographic deflection, which can be quantified. Several groups have documented that the maximal variations in pulse oximeter's plethysmographic waveform during positive-pressure ventilation covaries with arterial pulse pressure variation and can be used in a similar fashion to identify those subjects who are volume responsive.

PS: Intrapulmonary shunt fraction is increased in the following situations:

  • When the small airways are occluded; e.g., asthma
  • When the alveoli are filled with fluid; e.g., pulmonary edema, pneumonia
  • When the alveoli collapse; e.g., atelectasis
  • When capillary flow is excessive; e.g., in nonembolized regions of the lung in pulmonary embolism

Venous Oximetery

SvO2

SvO2 is the gold standard for assessing circulatory stress. A low SvO2 defines increased circulatory stress, which may or may not be pathological.

To the extent that SaO2 and hemoglobin concentration result in an adequate arterial O2 content (CaO2), then ScvO2 and SvO2 levels can be taken to reflect the adeuqacy of the circulation to meet the metabolic demands of the tissues. This is the truth. But attention must be paid that one needs to examine the determinants of DO2, global oxygen consumption (VO2), and effective O2 extraction by the tissues before using ScvO2, or SvO2 as markers of circulatory sufficiency.

Since VO2 must equal cardiac output times the difference in CaO2 and mixed venous O2 content (CvO2) (VO2 = CO x [CaO2 – CvO2]),if CaO2 remains relatively constant then CvOwill vary in proportion to cardiac output (CvO2 = CaO2 – VO2 / CO). Since the amount of O2 dissolved in the plasma is very small, the primary factor determining changes in CvO2 will be SvO2. Thus, SvO2 correlates well with the O2 supply-to-demand ratio.

Several relevant conditions may limit this simple application of SvO2 in assessing circulatory sufficiency and cardiac output (Table 32-1). If VO2 were to increase (as occurs with exercise), hemoglobin-carrying capacity to decrease (as occurs with anemia, hemoglobinopathies, and severe hemorrhage), or SaO2 to decrease (as occurs with hypoxic respiratory failure), then for the same cardiac output, SvO2 would also decrease. Similarly, if more blood flows through nonmetabolically extracting tissues as occurs with intravascular shunts, or mitochondrial dysfunction limits O2 uptake by tissues, then SvO2 will increase for a constant cardiac output and VO2 even though circulatory stress exists and may cause organ dysfunction.

Table 32-1 Limitations to the Use of SvO2 to Trend Circulatory Sufficiency
Independent events that decrease SvO2 independent of cardiac output
Event Process
Exercise Increased VO2
Anemia Decreased O2-carrying capacity
Hypoxemia Decreased arterial O2 content
Independent events that increase SvO2 independent of cardiac output
Event Process
Sepsis Microvascular shunting
End-stage hepatic failure Macrovascular shunting
Carbon monoxide poisoning Mitochondrial respiratory chain inhibition

ScvO2

SvO2 and ScvO2 covary in the extremes but may change in opposite directions as conditions change.

ScvO2 threshold values to define circulatory stress are only relevant if low (a high ScvO2 is nondiagnostic).

ScvO2 does not sample true mixed venous blood and most vena cacal blood flow is laminar, thus if the tip is in one of these laminar flow sites it will preferentially report a highly localized venous drainage site O2 saturation. Clearly, the potential exists for spurious estimates of SvO2. Most central venous catheters are inserted from internal jugular or subclavian venous sites with their distal tip residing in the superior vena cava, usually about 5 cm above the right atrium. Thus, even if measuring a mixed venous sample of blood at that site, ScvO2 reflects upper body venous blood while ignoring venous drainage from the lower body. Accordingly, ScvO2 is usually higher than SvO2 by 2% to 3% in a sedated resting patient because cerebral O2 consumption is minimal and always sustained above other organs.

Tissue Oximetry

Tissue O2 saturation (StO2) varies little until severe tissue hypoperfusion occurs.

StO2 coupled to a VOT allows one to diagnose circulatory stress before hypotension develops.

The most currently used technique to measure peripheral tissue O2 saturation (StO2) is near-infrared spectroscopy (NIRS). NIRS is a noninvasive technique based in the differential absorption properties of oxygenated and deoxygenated hemoglobin to assess the muscle oxygenation. Although there is a good correlation between the absolute StO2 value and some other cardiovascular indexes, the capacity of the baseline StO2 values to identify impending cardiovascular insufficiency is limited (sensitivity, 78%; specificity, 39%).

screen-shot-2016-10-24-at-12-52-46-pmHowever, the addition of a dynamic vascular occlusion test (VOT) that induces a controlled local ischemic challenge with subsequent release has been shown to markedly improve and expand the predictive ability of StO2 to identify tissue hypoperfusion. The VOT StO2 response derives from the functional hemodynamic monitoring concept, in which the response of a system to a predetermined stress is the monitored variable. The rate of DeO2 is a function of local metabolic rate and blood flow distribution. If metabolic rate is increased by muscle contraction, the DeO2 slope increases, whereas in the setting of altered blood flow distribution the rate of global O2 delivery is decreased. Sepsis decreases the DeO2. The ReO2 slope is dependent on how low StO2 is at the time of release, being less steep if StO2 is above 40% than if the recovery starts at 30%, suggesting that the magnitude of the ischemic signal determines maximal local vasodilation. This dynamic technique has been used to assess circulatory sufficiency in patients with trauma, sepsis and during weaning from mechanical ventilation.


Cardiac Output

There is no "normal" cardiac output (QT).

QT is either adequate or inadequate

Other measures besides QT define adequacy

Shock reflects an inadequate DO2 to meet the body's metabolic demand and cardiac output is a primary determinant of DO2. Indeed, except for extreme hypoxemia and anemia, most of the increase in DO2 that occurs with resuscitation and normal biological adaptation is due to increasing cardiac output. Since cardiac output should vary to match metabolic demands, there is no "normal" cardiac output. Cardiac output is merely adequate or inadequate to meet the metabolic demands of the body. Measures other than cardiac output need to be made to ascertain if the measured cardiac output values are adequate to meet metabolic demands. The two most common catheter-related methods of estimating cardiac output are indicator dilution and arterial pulse contour analysis.

Indicator Dilution

The principle of indicator dilution cardiac output measures is that if a small amount of a measurable substance (indicator) is ejected upstream of a sampling site and then thoroughly mixed with the passing blood then measured continuously downstream, the area under the time-concentration curve will be inversely proportional to flow based on the Stewart-Hamilton equation. The greater the indicator level, the slower the flow, and the lower the indicator level, the higher the flow. The most commonly used indicator is temperature (hot or cold) because it is readily available and indwelling thermistors can be made to be highly accurate.

Arterial Pulse Contour Analysis

screen-shot-2016-10-24-at-8-44-47-pmThe primary determinants of the arterial pulse pressure are LV stroke volume and central arterial compliance (pulse pressure ≈ SV / C). Compliance is a function of size, age, sex, and physiological inputs, like sympathetic tone, hypoglycemia, temperature, and autonomic responsiveness of the vasculature. Hamilton and Remington explored this interaction over 50 years ago developing the overall approach used by most of the companies who attempt to report cardiac output from the arterial pulse. The main advantage of these arterial pressure-based cardiac output monitoring systems over indicator dilution measurements is their less invasive nature.

However, since all these devices presume a fixed relation between pressure propagation alnog the vascular three and LV stroke volume, if vascular elastance (reciprocal of compliance) changes, then these assumptions may become invalid. Thus, a major weakness of any pulse contour device is the potential for artificial drift in reported values if major changes in arterial compliance occur.

Hemodynamic Monitoring

October 17, 2015 Cardiology, Critical Care No comments , , , , , , , , , , , ,

Screen Shot 2015-10-16 at 8.06.09 PMIntraarterial pressure is typically measured from the radial, brachial, axillary, or femoral arteries.

Systolic Amplification

The contour of the arterial pressure waveform changes as it moves away from the proximal aorta. This i shown in Figure 7.4. Note that as the pressure wave moves toward the periphery, the systolic pressure gradually increases and the systolic portion of the waveform narrows. The systolic pressure can increase as much as 20 mm Hg from the proximal aorta to the radial or femoral arteries. This increase in peak systolic pressure is offset by the narrowing of the systolic pressure wave, so the mean arterial pressure remains unchanged.

The increase in systolic pressure in peripheral arteries is the result of pressure waves that are reflected back from vascular bifurcations and narrowed blood vessels. Reflected waves move faster when the arteries are stiff (the rigidity of arteries increases as with age), and they reach the arterial pressure waveform before it has time to decrement; the convergence of antegrade and retrograde pressure waves serves to heighten the peak of antegrade pressure waveform. Amplification of the systolic pressure by reflected waves is the mechanism for systolic hypertension in the elderly. Because systolic amplification is the result of retrograde pressure waves, it does not promote systemic blood flow.


Mean Arterial Pressure

The mean arterial pressure (MAP) is the time-averaged pressure in the major arteries, and is the principal driving force for systemic blood flow. The MAP is measured electronically as the area under the arterial pressure wave, divided by the duration of the cardiac cycle.

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. Therefore we get the following formula:

Q = (Pin – Pout)/R [Equation 1]

If the hydraulic circuit is the circulatory system, volumetric flow becomes cardiac output (CO), the inflow pressure is the mean arterial pressure (MAP), the outflow pressure is the mean right atrial pressure (mRAP), and the resistance to flow is the systemic vascular resistance (SVR). The equation 1 relationship can be demonstrated as below in circulatory system:

CO = (MAP – mRAP) /SVR

In normal conditions, mRAP=RAP=CVP=RVEDP

Recording Artifacts

Fluid-filled recording systems can produce artifacts that further distort the arterial pressure waveform. Failure to recognize these artifacts can lead to errors in blood pressure management.

Resonant System

Screen Shot 2015-10-16 at 8.56.27 PMVascular pressures are transmitted through fluid-filled plastic tubes that connect the arterial catheter to the pressure transducer. This fluid-filled system can oscillate spontaneously, and the oscillations can distort the arterial pressure waveform. The performance of a resonant system is defined by two factors: the resonant frequency and the damping factor. The resonant frequency is the frequency of oscillations that occur when the system is disturbed. When the frequency of an incoming signal approaches the resonant frequency of the system, the resident oscillations add to the incoming signal and amplify it. This type of system is called an underdamped system. The damping factor is a measure of the tendency for the system to attenuate the incoming signal. A resonant system with a high damping factor is called overdamped system.

Waveform Distortion

Three waveforms from different recording systems are shown in Figure 7.5. The wave form in panel A, with the rounded peak and the dicrotic notch, is the normal waveform expected from a recording system with no distortion. The waveform in panel B, with the sharp systolic peak, is from an underdamped recording system. Underdamped systems are popular for pressure recording because their rapid response characteristics, but these systems can amplify the systolic pressure by as much as 25 mm Hg. The final waveform in panel C has an attenuated peak and a narrow pulse pressure. This waveform is from an overdamped system. Overdamping reduces the gain of the system and attenuates the pressure waveform. Overdamping can be the result of partial obstruction of the catheter with a thrombus, or air bubbles in the recording circuit.

Fast Flush Test

A pressurized flush of the catheter-tubing system can also help to identify a recording circuit that is distorting the pressure waveform. Most commercially available transducer system are equipped with a one-way valve that can be used to deliver a flush from a pressurized source. Figure 7.5 shows the results of a flush test in three different situations; the response when the flush is released will help characterize the system.

In panel A, the flush release is followed by a high-frequency burst. This is the normal behavior of a fluid-filled system. In panel B, the flush release produces a more sluggish frequency response. This is characteristic of an underdamped system, which will produce some degree of systolic amplification. The flush release in panel C does not produce oscillations. This is a sign of an over damped system, which will attenuate the arterial pressure waveform and produce a spuriously low systolic pressure.


Central Venous Pressure

When the PA catheter is properly placed, the proximal port of the catheter should be situated in the right atrium, and the pressure recorded from this port should be the right atrial pressure. The pressure in the right atrium is the same as the pressure in the superior vena cava, and these pressures are collectively called the central venous pressure/CVP. In the absence of tricuspid valve dysfunction, the RAP should be equivalent to the right-ventricular end-diastolic pressure (RVEDP), and RAP is the same as the pressure in the superior vena cava.

CVP=RAP=RVEDP


Pulmonary Wedge Pressure

The wedge pressure is obtained by slowly inflating the balloon at the tip of the RA catheter until the pulsatile pressure disappears, as shown in Figure 8.3. Note that the wedge pressure is at the same level as the diastolic pressure in the pulmonary artery. This relationship is altered in pulmonary hypertension, where the wedge pressure is lower than the pulmonary artery diastolic pressure.Screen Shot 2015-10-16 at 10.04.35 PM

The wedge pressure represents the venous pressure on the left side of the heart, and the magnified section of the wedge pressure in Figure 8.3 shows a typical venous contour that is similar to the venous pressure on the right side of the heart. The a wave is produced by left atrial contraction, the c wave is produced by closure of the mitral valve, and the v wave is produced by systolic contraction of the left ventricle against a closed mitral valve.

When the balloon on the PA catheter is inflated to obstruct flow (Q=0), there is a static column of blood between the tip of the catheter and the left atrium, and the wedge pressure at the tip of the catheter (Pw) is equivalent to the pulmonary capillary pressure (Pc) and the pressure in the left atrium (P[LA]). To summarize: if Q=0, then Pw=Pc=P[LA]. If the mitral valve is behaving normally, the left atrial pressure will be equivalent to the end-diastolic pressure (the filling pressure) of the left ventricle. Therefore, in the absence of mitral valve disease, the wedge pressure is a measure of left ventricular end-diastolic pressure/filling pressure.

PAWP=LAP=LVEDP

The wedge pressure will reflect the left atrial pressure only if the pulmonary capillary pressure is greater than the alveolar pressure (Pc > Pa); otherwise the wedge pressure will reflect the alveolar pressure. Respiratory variations in the wedge pressure suggest that the catheter tip is in a region where alveolar pressure exceeds capillary pressure. In this situation, the wedge pressure should be measured at the end of expiration, when the alveolar pressure is closest to atmospheric (zero) pressure.

In addition to respiratory variations, the CVP and wedge pressures can vary spontaneously, independent of any change in the factors that influence these pressures. In general, a change in wedge pressure should exceed 4 mm Hg to be considered a clinically significant change.


Mean Pulmonary Artery Pressure

CO = (mPAP – mLAP) /PVR

The PVR is a global measure of the relationship between pressure and flow in the lungs. Because the pulmonary artery wedge pressure (PAWP) is equivalent to the left atrial pressure, the formula above could be written as:

CO = (mPAP – PAWP)/PVR


Ventricular End-Diastolic Pressure

Ventricular end-diastolic volume is not easily measured at the bedside, and the end-diastolic pressure (RVEDP and LVEDP) is used as the clinical measure of ventricular preload. Although the end-diastolic pressure is the clinical measure of preload, clinical studies have shown a poor correlation between end-diastolic pressure and end-diastolic volume (preload). Studies indicate that ventricular filling pressures (i.e., CVP and PAWP) are unreliable as surrogate measures of ventricular filling.

The poor correlation between end-diastolic pressures and volume is particularly noteworthy because the subjects were healthy adults with normal cardiac function. When ventricular distensibility is impaired, which is common in critically ill patients, the discrepancy between end-diastolic pressures and volumes will be greater than usual.Screen Shot 2015-10-17 at 12.29.52 PM

Despite the shortcomings of EDP as a measure of ventricular filling, CVP monitoring continues to be a popular practice in ICUs.

The reference ranges for the CVP and wedge pressure are shown in Table 9.1. Note that the very low pressure range for the CVP, which helps to promote venous return to the heart. Note also that the sedge pressure is slightly higher than the CVP; the higher pressure in the left atrium closes the flap over the foramen oval and prevents right-to-left shunting in patients with a patent foramen ovale.

 

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

Screen Shot 2015-09-08 at 9.42.15 PM

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.


Pathophysiology

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

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 http://www.tomhsiung.com/wordpress/2015/06/flow-resistance-of-vessels-in-series-and-vessels-in-parallel/ and http://www.tomhsiung.com/wordpress/2015/07/vascular-resistances-and-compliance-map-and-pulse-pressure/, 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

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 http://www.tomhsiung.com/wordpress/2015/07/arteriolar-tone-and-its-regulation-local-mechanisms/ by Tom Hsiung.

Electrolytes

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.