STUDY - Technical - New Dacian's Medicine
The
Edema (1)
Translation Draft
Edema is defined as a clinically manifested increase in the volume of interstitial fluid, an increase that may be several liters before the appearance of this symptom. Therefore, a weight gain of a few kilograms usually precedes the onset of edema and a similar weight loss through increased diuresis can be induced in a patient with mild edema, before reaching the "dry weight". Ascita and hydrothorax refer to the accumulation of excess fluid in the peritoneal or pleural cavity and are considered specific forms of edema. Anasarca represents a massive, generalized edema.
Depending on the causes and mechanisms that produce it, edema can be localized or have a generalized distribution, being recognized as a generalized form after the face with a wheezing appearance, being more evident in the periorbital region, and by the presence of the "well sign" after defense, which is known as "soft" edema.
In the small forms, it can only be detected after applying the stethoscope to the chest wall, its edge leaving a dent on the edematized skin, which disappears within minutes. When the ring on a finger fits less comfortably than in the past or when a patient complains of difficulties in shoeing, especially in the evening, edema may be present.
Let's approach the pathogenesis! Around a third of the body's total water is in the extracellular space. Approximately 25% of extracellular water is plasma volume, and the rest is interstitial fluid. The forces that regulate the distribution of liquids between the two components of the extracellular compartment are referred to as Starling forces. Hydrostatic pressure in the vascular system and coloid-osmotic pressure in the interstitial fluid favour the movement of fluid from the vascular space to the extravascular space.
In contrast, the colloid-osmotic pressure given by plasma proteins and the hydrostatic pressure of the interstitial fluid, called tissue tension, favors the passage of fluid into the vascular compartment. Consequently, there is a movement of water and diffusion solutions from vascular space at the arterial end of the capillaries.
The fluid will return from the interstitial space into the vascular system to the venous end of the capillaries and the lymphocytes and, unless these channels are obstructed, the lymphatic flow tends to increase if there is a net displacement of fluids from the vascular compartment into the interstitials. These forces are generally balanced, so that the volumes of the intravascular and interstitial compartments do not change and at the same time allow a permanent exchange between them.
However, if one of the oncotic or hydrostatic forces is significantly altered, a net movement of fluid between the two components of extracellular space will occur. In conclusion, the development of edema depends on changes in Starling forces, so that a net movement of fluid from the vascular system occurs in the interstitials or in a cavity of the body.
An increase in capillary pressure as a possible cause of edema may result from increased venous pressure through a local obstruction in venous drainage. This increase in capillary pressure can be generalized, as occurs in congestive heart failure. The colloid-osmotic pressure of plasma may be reduced as a result of any condition that causes severe hypoalbuminemia, such as malnutrition, liver disease, loss of protein through the urine or gastrointestinal tract, or a severe hypercatabolic condition.
Let's focus now on the capillary damage. Edema can also result from damage to the capillary endothelium, with its increased permeability and the passage of proteins into the interstitial space. Damage to the capillary wall may be the result of the action of a bacterial or chemical agent, as well as mechanical or thermal trauma.
Increased capillary permeability may also be a consequence of a hypersensitivity reaction and is characteristic of immune conditions. Damage to the capillary endothelium is probably responsible for the appearance of inflammatory edema, which is usually rough, localized and accompanied by other signs of inflammation such as local congestion, heat and pain.
To formulate a hypothesis on the physiology of edema, it is important to differentiate between the primary event, such as venous or lymphatic obstruction, reduction of cardiac output, hypoalbuminemia, seizure of fluid in spaces such as peritoneal cavity or an increase in capillary permeability, and secondary consequences of a physiological response, including renal retention of salt and water to restore plasma volume. Both situations, primary and secondary, can contribute to the formation of edema through their consequences.
A first approach would be to reduce the actual arterial volume. In many forms of edema, the actual volume of arterial blood, a still imprecisely defined parameter of arterial tree filling, is reduced and consequently, a number of physiological responses designed to normalize it are put into operation. An essential element of these is increased salt retention and consecutive water, especially in the proximal tube, which in many cases leads to a reduction in the deficit of the actual arterial blood volume (often it occurs without developing edema).
If, for example, salt and water retention is insufficient to restore and maintain the actual arterial blood volume, the stimuli do not disappear, salt and water retention continues, and finally edema occurs. This sequence of events occurs in dehydration and bleeding. Although in these conditions there is a reduction in the volume of arterial blood and activation of the entire sequence presented, including a decrease in salt and water excretion, edema does not occur because the net balance of sodium and water is negative rather than positive.
In most cases of edema, the mechanism responsible for maintaining effective osmolarity of the body's fluids acts effectively, so sodium retention causes thirst and secretion of antidiuretic hormone which, in turn, leads to the ingestion and retention of about 1 liter of water for every 140 nmoles sodium you hold. In the case of edema, the isotonic expansion of extracellular space may be massive, while the volume of intracellular fluid changes very little or not at all.
The next approach is to reduce heart rate. A reduction in heart rate, whatever the cause, is associated with a decrease in the actual arterial blood volume as well as renal blood flow, constriction of efferent renal arterioles and an increase in the filtration fraction, i.e. the ratio between the rate of glomerular filtration and renal plasma flow.
In severe heart failure there is a decrease in the speed of glomerular filtration. Activation of the sympathetic nervous system and the renin-angiotensin system is responsible for renal vasoconstriction. The finding that alpha-adrenergic blockers and/ or angiotensin conversion enzyme (ACE) inhibitors increase renal blood flow and induce diuresis supports the role of the two systems in increasing renal vascular resistance and water and salt retention.
We've reached the kidney stake. Reducing heart rate decreases the volume of arterial blood effectively. There is increased reabsorbtion of the glomerular filtrate through increases in both proximal and distal salt reabsobtion in heart failure. Altering intranal hemodynamics plays an important role. Heart failure and other diseases, such as nephrotic syndrome and cirrhosis, in which the effective arterial volume is reduced, cause vasoconstriction of renal efferent arteriole.
This, in turn, reduces the hydrostatic pressure and increases the colloid-osmotic pressure in the peritubular capillaries, thus increasing the rearborption of water and salt in the proximal tube as well as in the ascending branch of the Henle ansa. In addition, the decrease in renal blood flow characteristic of states in which the actual arterial blood volume is reduced is converted by juxtaglomerular renal cells into a signal to increase the release of renin.
The mechanism responsible for this includes a baroreceptor response, reducing renal infusion leading to incomplete filling of primary arterioles and decreased extent of juxtaglomerular cells, a signal for secretion or release of renin, or both.
A second mechanism for the release of renin involves dense macula, as a result of reduced glomerular filtration, the amount of sodium chloride that reaches the distal renal tube being reduced. This is perceived by the dense macola that signals the cells of the juxtaglomerular apparatus to secrete renina.
A third mechanism involves the sympathetic nervous system and circulating catecholamines. Activation of beta-adrenergic receptors in juxtaglomerular cells stimulates the discharge of renin. These three mechanisms generally work together.
I will complete this post with the presentation of some elements related to the renin-angiotensin-aldosterone system (RAA). Renin, an enzyme with a molecular weight of about 40,000, acts on its substrate, angiotensinogen, an alpha2-globulin synthesized by the liver, to release angiotensin I (AI), a decapeptide that is split into angiotensin II (AII), an octapeptide. It has generalized vasoconstrictor properties, being active especially on efferent arteriola and independently increases sodium rearbsorption in the proximal tube.
The RAA system has long been considered to be a hormonal system, yet it also acting locally. Both circulatory and intrarenal AII contribute to renal vasoconstriction and water and salt retention. These renal effects of AIA are mediated by activating type 1 receptors for IIA, which can be blocked with specific antagonists such as losartan. AII also enters circulation and stimulates the production of aldosterone in the glomerular area of the adrenal cortex.
In patients with heart failure, not only aldosterone production is high, but also the biological half-life of aldosterone is prolonged, which causes an increase in plasma levels of the hormone. A decrease in hepatic blood flow, especially during physical exertion, secondary to the reduction of heart rate, is responsible for reducing hepatic catabolism of aldosterone. Aldosterone, in turn, increases sodium reabsorption and potassium excretion in the collector tube.
Activation of the RAA system is more pronounced in the early stage of severe acute heart failure and is less intense in patients with compensated stable chronic heart failure. Although an increased amount of aldosterone is secreted in heart failure and other edematous states and although blocking the activity of aldosterone by spironolactone (an antagonist of aldosterone) or amylorid (blocker of sodium epithelial channels) often induces moderate diuresis in edematous states, constantly increased levels of aldosterone (or other mineralocorticoid) itself do not always cause the formation of edema , as evidenced by the lack of obvious fluid retention in several situations of primary hyperaldosteronism.
Moreover, although hydrosalin retention is also recorded in normal subjects under the influence of a strong mineralocorticoid, e.g. deoxycorticosterone-acetate or fluorocortisone, this accumulation is self-limiting despite continuous exposure to the steroid, a phenomenon known as mineralocorticoid escape. The inability of normal subjects receiving high doses of mineralocorticoids to accumulate large amounts of fluids and develop edema is likely a consequence of the glomerular filtration rate (pressure natriumuse) and the action of natriumetic substances.
Continuous secretion of aldosterone may be more important for fluid accumulation in edematous states, because patients with edema are generally unable to correct the deficit of the actual arterial volume. As a consequence, they do not develop pressure natriureasis or develop normal amounts of atrial natriuretic peptide.
Blocking the RAA system by blocking AII receptors or inhibiting the angiotensin conversion enzyme (ECA) reduces resistance in the efferent arteriola and increases renal blood flow. This action (combined in patients with heart failure with increased heart rate, secondary to post-pregnancy reduction) as well as reduction of aldosterone secretion, produce diuresis. However, in patients with moderate or severe renal function disorders, interference with the RAA system may cause paradoxical sodium retention due to renal failure.
We'll continue tomorrow...
Edema is defined as a clinically manifested increase in the volume of interstitial fluid, an increase that may be several liters before the appearance of this symptom. Therefore, a weight gain of a few kilograms usually precedes the onset of edema and a similar weight loss through increased diuresis can be induced in a patient with mild edema, before reaching the "dry weight". Ascita and hydrothorax refer to the accumulation of excess fluid in the peritoneal or pleural cavity and are considered specific forms of edema. Anasarca represents a massive, generalized edema.
Depending on the causes and mechanisms that produce it, edema can be localized or have a generalized distribution, being recognized as a generalized form after the face with a wheezing appearance, being more evident in the periorbital region, and by the presence of the "well sign" after defense, which is known as "soft" edema.
In the small forms, it can only be detected after applying the stethoscope to the chest wall, its edge leaving a dent on the edematized skin, which disappears within minutes. When the ring on a finger fits less comfortably than in the past or when a patient complains of difficulties in shoeing, especially in the evening, edema may be present.
Let's approach the pathogenesis! Around a third of the body's total water is in the extracellular space. Approximately 25% of extracellular water is plasma volume, and the rest is interstitial fluid. The forces that regulate the distribution of liquids between the two components of the extracellular compartment are referred to as Starling forces. Hydrostatic pressure in the vascular system and coloid-osmotic pressure in the interstitial fluid favour the movement of fluid from the vascular space to the extravascular space.
In contrast, the colloid-osmotic pressure given by plasma proteins and the hydrostatic pressure of the interstitial fluid, called tissue tension, favors the passage of fluid into the vascular compartment. Consequently, there is a movement of water and diffusion solutions from vascular space at the arterial end of the capillaries.
The fluid will return from the interstitial space into the vascular system to the venous end of the capillaries and the lymphocytes and, unless these channels are obstructed, the lymphatic flow tends to increase if there is a net displacement of fluids from the vascular compartment into the interstitials. These forces are generally balanced, so that the volumes of the intravascular and interstitial compartments do not change and at the same time allow a permanent exchange between them.
However, if one of the oncotic or hydrostatic forces is significantly altered, a net movement of fluid between the two components of extracellular space will occur. In conclusion, the development of edema depends on changes in Starling forces, so that a net movement of fluid from the vascular system occurs in the interstitials or in a cavity of the body.
An increase in capillary pressure as a possible cause of edema may result from increased venous pressure through a local obstruction in venous drainage. This increase in capillary pressure can be generalized, as occurs in congestive heart failure. The colloid-osmotic pressure of plasma may be reduced as a result of any condition that causes severe hypoalbuminemia, such as malnutrition, liver disease, loss of protein through the urine or gastrointestinal tract, or a severe hypercatabolic condition.
Let's focus now on the capillary damage. Edema can also result from damage to the capillary endothelium, with its increased permeability and the passage of proteins into the interstitial space. Damage to the capillary wall may be the result of the action of a bacterial or chemical agent, as well as mechanical or thermal trauma.
Increased capillary permeability may also be a consequence of a hypersensitivity reaction and is characteristic of immune conditions. Damage to the capillary endothelium is probably responsible for the appearance of inflammatory edema, which is usually rough, localized and accompanied by other signs of inflammation such as local congestion, heat and pain.
To formulate a hypothesis on the physiology of edema, it is important to differentiate between the primary event, such as venous or lymphatic obstruction, reduction of cardiac output, hypoalbuminemia, seizure of fluid in spaces such as peritoneal cavity or an increase in capillary permeability, and secondary consequences of a physiological response, including renal retention of salt and water to restore plasma volume. Both situations, primary and secondary, can contribute to the formation of edema through their consequences.
A first approach would be to reduce the actual arterial volume. In many forms of edema, the actual volume of arterial blood, a still imprecisely defined parameter of arterial tree filling, is reduced and consequently, a number of physiological responses designed to normalize it are put into operation. An essential element of these is increased salt retention and consecutive water, especially in the proximal tube, which in many cases leads to a reduction in the deficit of the actual arterial blood volume (often it occurs without developing edema).
If, for example, salt and water retention is insufficient to restore and maintain the actual arterial blood volume, the stimuli do not disappear, salt and water retention continues, and finally edema occurs. This sequence of events occurs in dehydration and bleeding. Although in these conditions there is a reduction in the volume of arterial blood and activation of the entire sequence presented, including a decrease in salt and water excretion, edema does not occur because the net balance of sodium and water is negative rather than positive.
In most cases of edema, the mechanism responsible for maintaining effective osmolarity of the body's fluids acts effectively, so sodium retention causes thirst and secretion of antidiuretic hormone which, in turn, leads to the ingestion and retention of about 1 liter of water for every 140 nmoles sodium you hold. In the case of edema, the isotonic expansion of extracellular space may be massive, while the volume of intracellular fluid changes very little or not at all.
The next approach is to reduce heart rate. A reduction in heart rate, whatever the cause, is associated with a decrease in the actual arterial blood volume as well as renal blood flow, constriction of efferent renal arterioles and an increase in the filtration fraction, i.e. the ratio between the rate of glomerular filtration and renal plasma flow.
In severe heart failure there is a decrease in the speed of glomerular filtration. Activation of the sympathetic nervous system and the renin-angiotensin system is responsible for renal vasoconstriction. The finding that alpha-adrenergic blockers and/ or angiotensin conversion enzyme (ACE) inhibitors increase renal blood flow and induce diuresis supports the role of the two systems in increasing renal vascular resistance and water and salt retention.
We've reached the kidney stake. Reducing heart rate decreases the volume of arterial blood effectively. There is increased reabsorbtion of the glomerular filtrate through increases in both proximal and distal salt reabsobtion in heart failure. Altering intranal hemodynamics plays an important role. Heart failure and other diseases, such as nephrotic syndrome and cirrhosis, in which the effective arterial volume is reduced, cause vasoconstriction of renal efferent arteriole.
This, in turn, reduces the hydrostatic pressure and increases the colloid-osmotic pressure in the peritubular capillaries, thus increasing the rearborption of water and salt in the proximal tube as well as in the ascending branch of the Henle ansa. In addition, the decrease in renal blood flow characteristic of states in which the actual arterial blood volume is reduced is converted by juxtaglomerular renal cells into a signal to increase the release of renin.
The mechanism responsible for this includes a baroreceptor response, reducing renal infusion leading to incomplete filling of primary arterioles and decreased extent of juxtaglomerular cells, a signal for secretion or release of renin, or both.
A second mechanism for the release of renin involves dense macula, as a result of reduced glomerular filtration, the amount of sodium chloride that reaches the distal renal tube being reduced. This is perceived by the dense macola that signals the cells of the juxtaglomerular apparatus to secrete renina.
A third mechanism involves the sympathetic nervous system and circulating catecholamines. Activation of beta-adrenergic receptors in juxtaglomerular cells stimulates the discharge of renin. These three mechanisms generally work together.
I will complete this post with the presentation of some elements related to the renin-angiotensin-aldosterone system (RAA). Renin, an enzyme with a molecular weight of about 40,000, acts on its substrate, angiotensinogen, an alpha2-globulin synthesized by the liver, to release angiotensin I (AI), a decapeptide that is split into angiotensin II (AII), an octapeptide. It has generalized vasoconstrictor properties, being active especially on efferent arteriola and independently increases sodium rearbsorption in the proximal tube.
The RAA system has long been considered to be a hormonal system, yet it also acting locally. Both circulatory and intrarenal AII contribute to renal vasoconstriction and water and salt retention. These renal effects of AIA are mediated by activating type 1 receptors for IIA, which can be blocked with specific antagonists such as losartan. AII also enters circulation and stimulates the production of aldosterone in the glomerular area of the adrenal cortex.
In patients with heart failure, not only aldosterone production is high, but also the biological half-life of aldosterone is prolonged, which causes an increase in plasma levels of the hormone. A decrease in hepatic blood flow, especially during physical exertion, secondary to the reduction of heart rate, is responsible for reducing hepatic catabolism of aldosterone. Aldosterone, in turn, increases sodium reabsorption and potassium excretion in the collector tube.
Activation of the RAA system is more pronounced in the early stage of severe acute heart failure and is less intense in patients with compensated stable chronic heart failure. Although an increased amount of aldosterone is secreted in heart failure and other edematous states and although blocking the activity of aldosterone by spironolactone (an antagonist of aldosterone) or amylorid (blocker of sodium epithelial channels) often induces moderate diuresis in edematous states, constantly increased levels of aldosterone (or other mineralocorticoid) itself do not always cause the formation of edema , as evidenced by the lack of obvious fluid retention in several situations of primary hyperaldosteronism.
Moreover, although hydrosalin retention is also recorded in normal subjects under the influence of a strong mineralocorticoid, e.g. deoxycorticosterone-acetate or fluorocortisone, this accumulation is self-limiting despite continuous exposure to the steroid, a phenomenon known as mineralocorticoid escape. The inability of normal subjects receiving high doses of mineralocorticoids to accumulate large amounts of fluids and develop edema is likely a consequence of the glomerular filtration rate (pressure natriumuse) and the action of natriumetic substances.
Continuous secretion of aldosterone may be more important for fluid accumulation in edematous states, because patients with edema are generally unable to correct the deficit of the actual arterial volume. As a consequence, they do not develop pressure natriureasis or develop normal amounts of atrial natriuretic peptide.
Blocking the RAA system by blocking AII receptors or inhibiting the angiotensin conversion enzyme (ECA) reduces resistance in the efferent arteriola and increases renal blood flow. This action (combined in patients with heart failure with increased heart rate, secondary to post-pregnancy reduction) as well as reduction of aldosterone secretion, produce diuresis. However, in patients with moderate or severe renal function disorders, interference with the RAA system may cause paradoxical sodium retention due to renal failure.
We'll continue tomorrow...
Let us live all the
Hellens and all the Constantines (including vice versa)!
And let my Mary live, my
eldest daughter, who today has become a major, turning 18! Have
a good day, everyone!!!
Dorin, Merticaru