Physiology and pathophysiology of shock (pediatrics)

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Control of vascular tone[edit | edit source]

Vasomotor vascular tone is affected by several mechanisms: nerve and humoral factors, blood gas composition, local metabolic regulation, endothelial function, and vascular media smooth muscle.

The mechanism that regulates vascular resistance in one region may be completely ineffective in another region. Eg. in case of hypovolemic shock perfusion of heart and brain is maintained and, conversely, reduced in muscles, skin and splanchnic.

Neuromodulation of vascular tone[edit | edit source]

Receptors to which noradrenaline, acetylcholine or neuropeptides bind are present throughout the circulation. However, the distribution of receptors is organ-specific, which allows rapid and coordinated redistribution of blood flow in response to [[hypoxia], posture changes, and hemorrhage. n all organs, the nerve endings of efferent nerves also contain nonadrenergic and noncholinergic peptides, eg neuropeptide Y, VIP (vasoactive intestinal peptide), substance P, calcitonin gene-related peptide (CGRP). Most of these peptides, with the exception of neuropeptide Y, lead to vasodilation and help regulate regional perfusion.

Humoral regulation of vascular tone[edit | edit source]

Humoral factors that regulate vascular tone include renin-angiotensin-aldosterone system (RAAS), ADH, bradykinin, histamine, serotonin, thyroxine, natriuretic peptides and many others. These factors affect vascular tone in both direct and indirect ways. These factors tend to decrease in concentration during hypertension, congestive heart failure or shock and their antagonists are often used in the treatment of these conditions. Some factors such as histamine, serotonin, thyroxine probably affect vascular resistance only in pathological conditions and do not apply in physiological conditions.

Angiotensin plays a special role in homeostasis of blood pressure. Hypovolaemia leads to increased production of renin in the kidney, which converts angiotensinogen to angiotensin I. Angiotensin I is converted to active angiotensin II by angiotensin converting enzyme (ACE) in the endothelium, especially in the pulmonary circulation. However, angiotensin II can be produced directly from renin locally in the heart and vascular wall. Angiotensin II causes generalized vasoconstriction in the systemic and pulmonary circulation, but locally stimulates the release of vasodilators prostaglandins in the kidneys and lungs.

Aldosterone was known primarily for its effect on sodium and potassium balances. Its concentration increases with the release of renin. In patients with congestive heart failure, we find its high concentrations both due to dilution hyponatremia and reduced degradation in the liver. High concentrations, which are a sign of overshoot of the body's compensatory reaction, are harmful to the cardiovascular system. Inhibition of aldosterone by spironolactone appears to be of great benefit in the treatment of heart failure.

ADH (antidiuretic hormone, vasopressin) has an antidiuretic effect and at the same time causes vasoconstriction, low concentrations of ADH lead to vasodilation in the coronary, cerebral and pulmonary arteries. ADH levels decrease in septic shock, while they increase in hypovolemia, congestive heart failure and liver cirrhosis. Selective ADH antagonists allow the excretion of free water without ion excretion and are useful in the treatment of hypervolemia in patients with congestive heart failure, cirrhosis or SIADH.

Bradykinin is a potent vasodilator in the pulmonary and systemic circulation. It is released locally from kallikrein by proteolytic enzymes due to tissue damage.

Histamine it is released from mast cells also in response to tissue damage. It is a potent vasodilator in the systemic circulation, but leads to vasoconstriction in the pulmonary circulation. It also increases vascular permeability.

Natriuretic peptides are released from the heart during its distension in congestive failure. They cause vasodilation and increase natriuresis. NP (atrial natriuretic peptide) is released mainly in the atrial region, BNP (brain natriuretic peptide) from the ventricular region and C-natriopeptide from the cardiac endothelium. Recombinant BNP (nesiritide) is more effective than dobutamine in the treatment of acute severe congestive heart failure.

Serotonin causes vasodilation or vasoconstriction depending on the type of serotonin receptor.

Influence of blood gases on vascular tone[edit | edit source]

Values of paO2 and paCO2 are depended on the quality of the tissue perfusion. The hypoxia and hypercapnia that accompany hypoperfusion are associated with a vasodilatory effect.

Local metabolic regulation of vascular tone[edit | edit source]

Local metabolic regulation of vasomotor tone is an ideal homeostatic mechanism. With its help, the metabolic needs of the tissues directly affect the local perfusion. E.g. adenosine, which accumulates locally during high tissue metabolism and borderline tissue oxygenation, leads to vasodilation in the coronary artery, striated muscle, splanchnic, and cerebral circulation.

Regulation of vascular tone through the endothelium[edit | edit source]

Vascular endothelium plays a prominent role in the regulation of vascular tone. In addition to affecting vasoactive eicosanoids and its role in angiotensin metabolism, the endothelium produces a number of vasoactive substances. One of the most important is nitric oxide (NO; potent vasodilator) and endothelins. Endothelins (ET-1, ET-2, ET-3) represent a family of vasoactive substances. ET-1 is a potent vasoconstrictor, otherwise the effect of endothelins depends on action at two types of receptors: ET-A receptors located in vascular smooth muscle mediate vasoconstriction, ET-B on endothelial cells mediate vasodilation. Endothelin antagonists, such as bosentan, are beginning to be used therapeutically.

Regulation of vascular tone through the smooth muscle of the vascular media[edit | edit source]

Changes in vascular smooth muscle tension are a response to dilation or increase in transmural pressure. Increased vascular flow leads to local vasoconstriction. The opposite reaction is caused by a decrease in vascular flow.

Autoregulation[edit | edit source]

In all organs, if the perfusion pressure suddenly increases or decreases while maintaining constant oxygen consumption, the flow rate increases or decreases temporarily, but then returns to an earlier value. This phenomenon is called autoregulation.

The myogenic tonic response partly explains this phenomenon, but it is not the only mechanism. Some scientists believe that tissues have oxygen sensors that respond to a transient increase or decrease in oxygen supply. Other researchers argue that the process of autoregulation is mediated by increased or decreased release of nitric oxide, which is transferred to tissues via hemoglobin such as S-nitrosohemoglobin, or by the release of ATP from erythrocytes.

Some autoregulatory mechanisms are specific to individual microcirculations (eg renal). Autoregulatory mechanisms vary from one organ to another.

Pulmonary circulation[edit | edit source]

In fetus, the pulmonary circulation has the character of a systemic circulation, the pulmonary arteries have a strongly developed smooth muscle of the media. This is the reason for the high lung resistance in the fetus also early postnatally. After birth within a few weeks, the muscle of the medium involves and the resistance of the pulmonary artery progressively decreases. During the first 24 hours after birth, the pulmonary arterial pressure drops to about 50% mean arterial pressure, and the pulmonary circulation remains low-pressure with low vascular resistance. Due to the intimate relationship between small pulmonary vessels and alveoli, intraalveolar pressure affects pulmonary flow, especially in patients with artificial lung ventilation.

The most important factors that affect pulmonary vascular resistance in the postnatal period are rate of oxygenation and value of pH. When the oxygen tension in the alveoli decreases, hypoxic pulmonary vasoconstriction develops in the given pulmonary segment. The goal is to redistribute blood flow to well-ventilated areas and maintain a favorable ventilation / perfusion (V / Q) ratio. This phenomenon is highly specific for the pulmonary circulation, as the bloodstreams of other organs (including the CNS) respond to hypoxia by vasodilation. Acidosis potentiates hypoxic pulmonary vasoconstriction, Respiratory alkalosis reduces it. The true mechanism of the pH-mediated pulmonary vascular response is not fully elucidated, but occurs independently of pCO2. The mechanism of alveolar hyperoxia and alkalosis is often used to induce pulmonary vasodilation in patients with pulmonary hypertension. Hypocapnia and RAL, in turn, lead to vasoconstriction in the systemic circulation, which can have adverse consequences in CNS and cardiac perfusion.

Selective pulmonary vasodilators are oxygen and nitric oxide administered by inhalation (iNO).

Coronary circulation[edit | edit source]

The right and left coronary arteries emanate from the Valsalva sinus and run across the surface of the heart. Heart perfusion occurs during diastole. In tachycardia, diastole is shortened, myocardial perfusion decreases, and ischemia may occur. Under normal circumstances, the right ventricle is perfused due to low pressures even during systole. Coronary circulation also shows autoregulation. As the pressure rises, vasoconstriction occurs, and the pressure drop leads to vasodilation. When the pressure drops <40 torr, the mechanism of autoregulation is no longer effective and ischemia develops.

Renal circulation[edit | edit source]

Through kidneys flows about 20% of cardiac output, although the weight of the kidneys represents about 0.5% of the total body weight. The reason is to support sufficient glomerular filtration to maintain water and solute homeostasis. At the end of the arterial bed we find afferent arterioles that lead to the capillary network within the glomerulus. The glomerular capillaries form in the effluent part into an efferent arteriole, which then forms a secondary capillary system (peritubular capillaries). The increased hydrostatic pressure inside the glomerular capillaries promotes filtration, while the much lower pressure inside the peritubular capillaries aids reabsorption. Changes in the resistance of afferent and efferent arterioles allow dynamic changes in renal function in response to fluid and solute needs.

Renal flow is determined by the difference between renal arterial pressure (corresponding to systemic arterial pressure) and renal venous pressure. Renal vasomotor activity is influenced by both external factors (sympathoadrenal system, natriuretic peptides, RAAS) and internal factors, which are responsible for renal flow autoregulation in response to changes in renal perfusion pressure (RPP). Glomerular filtration is given by glomerular filtration pressure (GFP). GFP depends on RPP and the balance between arterial tone of afferent and efferent arterioles. Specifically, vasoconstriction of the vas efferens increases glomerular filtration, vasoconstriction of the vas afferens reduces glomerular filtration.

Endothelial functions[edit | edit source]

Endothelium has a number of functions:

  • Endothelial cells play an important role in body defense - they allow adhesion and subsequent extravasation of leukocytes through molecules - selectins, adherins, integrins.
  • The endothelium is intimately associated with the function coagulation system. It has the ability to produce procoagulant factors (platelet activating factor = PAF, von Willebrand factor, fibronectin, ff. V and X) and anticoagulant factors (heparan, dermatan sulfate, thrombomodulin) and inhibits aggregation by producing NO and PGI2 and degranulation of platelets.
  • The endothelium regulates capillary permeability by producing endothelin 1 (ET-1), which increases permeability, and by producing PGE1, which decreases permeability.

Relationship between flow, pressure and vascular resistance[edit | edit source]

From the point of view of the diagnosis of shock syndrome, perfusion efficiency with subsequent manifestations of organ dysfunction is an essential parameter.

Organ perfusion (flow) jis determined by blood flow pressure and vascular resistance. Under normal circumstances, a sufficient pressure gradient is present and vasomotor control regulates individual organ perfusion according to metabolic needs. Only a part of the vascular system is open under resting conditions. The development of shock syndrome is in most cases linked to a drop in pressure and subsequent failure of organ perfusion. However, height of blood pressure is not the only determinant of perfusion. At high blood pressure, but at the same time high vascular resistance, tissue perfusion is also not sufficient.

Thus, the severity of the shock is primarily determined by the depth of the tissue perfusion disorder. Good tissue perfusion ensures an adequate supply of nutrients and oxygen at the cellular level. However, tissue perfusion must always be related to the current needs of the organism. In conditions with hyperkinetic circulation (thyrotoxicosis, high flow phase sepsis, liver failure) even "normal" perfusion may be insufficient, as the tissues show a higher need for oxygen and energy substrates than the body is able to secure at that moment. Simply put, demand for O2 exceeds supply.

Parameters of adequate oxygen supply represent:

The decisive parameter determining regional perfusion Q is the blood flow generating dynamic blood pressure. According to Poiseuill's law, the following applies:

Q = (Pin - Pout) / R

where Q is the tissue flow, Pin is the inlet pressure, Pout is the outlet pressure, R is resistance. In the case of a simple tube, this is determined by the diameter of the tube, its length, is inversely proportional to the square of the radius and directly proportional to the viscosity of the flowing fluid.

A good example: The severity of a shock is determined primarily by the depth of the tissue perfusion disorder.

Thus, regional perfusion is determined by blood pressure and regional resistance. The resistance of the various areas of the systemic circulation and the minute cardiac output determine the value of the systemic arterial pressure. Local factors controlling regional perfusion may have different effects than control mechanisms regulating systemic arterial pressure. For example, hypoxia leads to vasoconstriction by activating central baroreceptors, but vasodilation occurs at the periphery. If we take into account whole body perfusion Qco and we neglect Pout (venous blood pressure is small compared to the value of arterial pressure), we get the equation:

Pa = Qco x Rsv

where Pa is arterial pressure, Qco is minute cardiac output, Rsv is systemic vascular resistance. For a more accurate determination of tissue perfusion, however, we take venous pressure into account (Pout = CVP) namely in the situation when we want to define the parameter perfusion pressure = perfusion pressure PerP. This corresponds to the difference between the mean arterial pressure MAP and the central venous pressure CVP. So:

erP = MAP - CVP
Limiting values for perfusion pressure in cm H2O (mmHg – rounded values)
Children's age Perfusion pressure in cm H2O (mm Hg)
newborns 55 (40)
infants 60 (45)
toddlers 65 (50)
preschoolers 65 (50)
schoolchildren 65 (50)

However, perfusion pressure is not the only important parameter, it is necessary to maintain SvcO2 > 70 % at the same time even with help of transfusion or inotropic support, lactate level < 2 mmol/l, good peripheral perfusion, diuresis > 1 ml/kg/hod.

In conditions with intra-abdominal hypertension (ascites, ileus), the perfusion pressure is equal to the difference of MAP - IAP (intraabdominal pressure). The relationship between flow, pressure and resistance can also be applied to individual organs. In the kidneys, eg renal flow Q = (mean renal arterial pressure - mean renal venous pressure)/renal vascular resistance.

Some organs, as mentioned above, have the ability of vasomotor autoregulation, which maintains blood flow even at low blood pressure. This works up to a certain critical point, when the perfusion pressure is reduced below the value at which a sufficient flow can still be maintained in the given organ. The purpose of shock treatment is therefore to keep the perfusion pressure above a given critical point (but beware - the critical point is not a fixed value, it is strictly individual).

The kidneys are a textbook example: the kidneys need the second highest blood flow. Accurate determination of diuresis and creatinine clearance is very easy and allows us to assess the quality of renal perfusion. And it is the quality of renal perfusion that provides a picture of perfusion in other visceral organs. The kidneys thus represent a kind of "window" to the organ perfusion. Therefore, an accurate assessment of diuresis in each critically ill patient is absolutely essential!

If hypotension occurs, it is the result of low cardiac output or low vascular resistance. From this point of view, shock states can be divided into only two basic categories - shock with low minute cardiac output and shock with low systemic vascular resistance.

Age-specific vital signs and laboratory values (Pediatric Critical Care 2005)
Age Heart rate (beats per minute) Respiratory rate (breaths per minute) Leukocytes (leu x 10/3 v ml) Systolic blood pressure (mm Hg)
0 days - 1 week > 180 x < 100 > 50 > 34 < 65
1 week – 1 month > 180 x < 90 > 40 > 19,5 x < 5 < 75
1 month – 1 year > 180 x < 90 > 35 > 17,5 x < 5 < 100
2 – 5 years > 140 > 22 > 15,5 x < 6 < 94
6 – 12 years > 130 > 18 > 13,5 x < 4,5 < 105
13 – 18 years >110 > 14 > 11 x < 4,5 < 117

Note: these values represent the 5th or 95th percentile for a given age group. Each shock can result in a systemic inflammatory response (SIRS). Undamped cytokine cascades, complement and coagulation lead to impaired vascular wall integrity and increased endothelial adhesiveness. The result is then extravasation, vasodilation, thrombosis, tissue hypoxia. Lactic acidosis is an expression of mitochondrial hypoxia.

Links[edit | edit source]

References[edit | edit source]

  • HAVRÁNEK, Jiří: Šok. (upraveno)

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