Hemolytic Uremic Syndrome Research Paper
Hemolytic Uremic Syndrome (HUS), is a referred to as a disease characterized by hemolytic anemia, caused by the destruction of red blood cells, acute kidney failure (uremia), and a low platelet count (thrombocytopenia). Although, it mostly affects children, there have been cases of adults with this illness. The destroyed red blood cells block the filtering system in the kidneys, which can lead to a life-threatening kidney failure. HUS usually develops in children after five to 10 days of diarrhea, often bloody and caused by infection with certain strains of Escherichia coli (E. coli) bacteria (O157:H7 Strain). Adults also develop HUS due to E. coli or other types of infection, certain medications, or pregnancy. HUS is a serious condition, but
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timely and appropriate treatment leads to a full recovery for most people, especially young children (Mayo Clinic, 2016). A variety of viruses have also been implicated as a causative agent. It is now the most common cause of acquired acute renal failure in childhood. It is a medical emergency which carries a 5–10% mortality rate; of the remainder, the majority recover without major consequences, approximately 30% suffer residual renal injury. The primary target appears to be the vascular endothelial cell. This may explain the pathogenesis of HUS, in which a characteristic renal lesion is capillary microangiopathy (Mayo Clinic, 2016).
Damage to endothelial cells is the primary event in the pathogenesis of HUS. Damage to the kidney which prevents the filtering of waste and its other functions also follows. The cardinal lesion is composed of arteriolar and capillary microthrombi (thrombotic microangiopathy (TMA) and red blood cell fragmentation (Medscape, 2016). The symptoms that have been associated with the HUS include: prolonged diarrhea, vomiting, abdominal pain, lethargy, bloody stool, unexplained bruises, pallor, and edema, among others. If HUS is not treated, it will lead to death in infancy or early childhood. Common treatments has been found to include blood transfusion, kidney dialysis, fluid replacement and nutritional supplementation given intravenously. In some other cases, a special form of treatment called plasmapheresis may also be necessary. However, early detection and treatment are very important for patients to lead healthy lives.
Discussion
Hemolytic uremic syndrome as described by the National Kidney Foundation, is a “condition that affects the blood and blood vessels. It results in the destruction of blood platelets (cells involved in clotting), a low red blood cell count (anemia) and kidney failure due to damage to the very small blood vessels of the kidneys. Other organs, such as the brain or heart, may also be affected by damage to very small blood vessels” (National Kidney Foundation NKF, 2015). The urinary system plays a large role in this disease especially the kidneys as it is an organ of utmost importance when it comes to cleaning up the body system. The HUS is a complex condition where an immune reaction, most commonly after a gastrointestinal tract infection, causes low red blood cell levels, low platelet levels, and kidney injury. Infections of the gastrointestinal tract are the most common cause of this syndrome. The body’s immune system reacts to toxins released during an intestinal bacterial infection. This causes damage and destruction to blood cells as they circulate through the blood vessels. These include red blood cells (RBC) and platelets, causing them to die prematurely. The kidney is affected in two ways. The immune reaction can cause direct damage to kidney cells resulting in kidney injury. The build-up of damaged red blood cells or platelets can clog up the kidney’s filtering system and cause kidney injury or a build-up of waste products in the body, since the kidney can no longer efficiently eliminate waste from the blood.
HUS from E. coli infections results when bacterial toxins cross from the intestines into the bloodstream and damage the very small blood vessels. The toxic E. coli may come from eating spoiled, undercooked or poorly processed food products, or from exposure to contaminated water. According to Jenssen et.al, in the BioMed Central journal, a common classification of HUS is by clinical presentation which is associated with prodromal diarrhea (D+HUS) or not (D−HUS). Around 90 % of HUS cases in children are D+HUS and most cases of D+HUS are caused by infection with Shiga toxin producing E. coli (STEC-HUS). According to this classification, D−HUS mainly consists of HUS caused by Streptococcus pneumoniae infection (SP-HUS) and HUS associated with familiar or sporadic genetic disorders of complement regulation. It has been suggested that some STEC-HUS cases, especially those with more severe outcome, are genetically predisposed atypical HUS cases triggered by an STEC infection (Jenssen et. al, 2016). In HUS, the Shiga toxins binds to the endothelial cells of the glomeruli, the tubular endothelial cells, the podocytes and other cells in the nephron. After binding, the toxin damages the cells and block protein synthesis which leads to apoptosis which then leads to damage of red blood cells and platelets in the blood stream.
The HUS is usually diagnosed after a series of tests and includes complete blood count, which measures the quality and quantity of the red blood cells and platelets in the blood sample, urine tests for presence of blood or protein which should not be present ion a healthy individual and stool sample tests among other types of tests. The most common markers are presence of red blood cells in urine, low albumin in blood (hypoalbunemia), low platelet count, presence of protein in urine, low Glomerular Filtration Rate (GFR), high percentage of schistocytes, and elevated bilirubin. All these are consequences of the disease’s effect on the kidney which prevents it from performing its functions. The kidney has various structures that helps in accomplishing the filtration of wastes in the body especially its functional unit called the nephron.
Glomerular Filtration Process
This is the first stage in which the kidney filters wastes in the body, it involves the process in which water and some other substances in the blood plasma pass from the capillaries of the glomerulus into the Bowman's capsule.
Very small molecules like water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes, and vitamins can pass through the filtration membrane into the Bowman's capsule. These substances have about the same concentration in the glomerular filtrate as in the blood plasma. Some substances do not pass through the membrane which makes them to be retained in the bloodstream because they are bound to plasma proteins. For example, most calcium, iron, and thyroid hormone in the blood are bound to plasma proteins that does not allow them to be filtered by the kidneys. The small fractions that are not bound to plasma protein, however, passes freely through the filtration membrane and appears in the urine. Kidney infection and trauma can damage the filtration membrane. This allows proteins or blood cells to filter through. The mere presence of these proteins in the urine can be used to detect kidney disease. In the case of HUS, the presence of protein and blood in the urine is used to detect that the kidney has been damages to an extent and treatment must commence immediately to correct it.
Glomerular filtration must be controlled. If it is too high, fluid flows through the renal tubules too rapidly for them to reabsorb the required amount of water …show more content…
and solutes. If it is too low, fluid flows too slowly through the tubules and wastes that should be eliminated are reabsorbed into the bloodstream. Mechanisms employed by the body to control the glomerular filtration rate include, Renal Autoregulation, Sympathetic Control and the Renin-Angiotensin-Aldosterone Mechanism.
Tubular Reabsorption
This is the second stage of the glomerular filtration process and it involves the removal and addition of chemicals, after glomerular filtrate leaves the Bowman's capsule and enters the renal tubule. The renal tubule is very long, which increases its absorptive surface area. It reabsorbs about 65% of the glomerular filtrate, while it removes some substances from the blood. Tubular reabsorption mechanism in the kidneys return the water and solutes that is needed back into the extracellular fluid and circulatory system. Materials that are reabsorbed, are needed by the blood and they include, water, glucose, sodium, potassium, electrolytes among others. This process involves the passive or active movement of water and dissolved substances from the fluid inside the tubule through the tubule wall into the space outside. Water and these substances move through the capillary walls back into the bloodstream again either by passive or active transport.
There are several structures that makes the reabsorption process possible. The proximal convoluted tubule carries out the reabsorption process when pH needs to be maintained and bicarbonate ions are reabsorbed back into the blood stream. glucose, amino acids and potassium ions are actively transported into the blood. sodium and chlorine ions are also moved back into the capillaries so that some salt regulation can occur while substances such as hydrogen ions and toxins are actively secreted from the blood into the tubule. Within the loop of henle, the descending loop allows reabsorption of water through osmosis while the ascending loop allows passive and active transport of salts such as sodium to move out of the tubules for reabsorption. The distal convoluted tubule is where the final adjustments are made to the passing urine within the tubule systems. This is where highly selective reabsorption takes place allowing for small adjustments to be made especially between the presence of Potassium and Sodium (Esterman, 2016).
Tubular Secretion
In addition to reabsorbing the substances that is needed, nephrons are able to secrete unwanted substances from the bloodstream into the filtrate.
Here, acid-base balance and waste removal is achieved. This process is achieved by passive diffusion that involves the movement of molecules from the peritubular capillaries to the interstitial fluid within the nephron. It also involves active transport involving the movement of molecules via ATPase pumps that transport the substance through the renal epithelial cell into the lumen of the nephron (Boundless, 2016). This process differs from the reabsorption process in that it filters and cleans substances form the blood and do not retain them. Some of these substances include, potassium ions, hydrogen ions, urea, hormones, and others. Failure of the kidney to undergo this process allows wastes to be backed up in the system which endangers the organ systems in the
body.
HUS in affected persons therefore increases blood pressure which causes hypertension, hyperkalemia, and other electrolyte abnormalities such as hyponatremia and hypocalcemia, because of the kidney has been damaged. Nearly 40% of patients with STEC–HUS and up to 70% of cases of atypical HUS require renal replacement therapy during the acute episode (Cheung and Trachtman, 2014).
Treatments
The O157:H7 strain of E. coli produces a poison known as Shiga toxin that is absorbed through the intestines. These toxins damages the endothelial cells that line the inner walls of the blood vessels of the glomeruli in the kidneys. Damage to these blood vessels leads to anemia, thrombocytopenia, acute renal failure, and the other symptoms and findings associated with HUS. For example, hemolytic anemia occurs when red blood cells are destroyed or damaged as they pass through the small damaged blood vessels. Circulating platelets are consumed in the small clots in these microscopic blood vessels resulting in thrombocytopenia and the abnormal accumulation of platelets within narrowed blood vessels, causing the formation of small blood clots. As a result, blood flow to organs such as the kidneys, brain, and pancreas variably decreases leading to multiple organ dysfunction or failure (National Organization for Rare Disorders (NORD), 2016).
One of the most viable treatments for HUS that has been discovered overtime is the dialysis process. This process involves a treatment designed to function like normal kidneys. It helps to remove toxic materials that has built up in the system and also helps normalize the body fluid and electrolytes. However, there are different types of dialysis and hemodialysis has been proven to be more time efficient in treating HUS. In this treatment process, there are two compartments separated by a semi-permeable membrane and one compartment which is the body, contains uremic toxins and excess electrolytes and the other dialysate compartment is free of these substances. Toxins and electrolytes will move across the membrane until they are in equal concentrations on both sides. Excess fluid is then removed by creating pressure gradients between the blood and dialysis fluid compartments. Blood access is achieved by surgically attaching a native artery which is usually in the arm to an adjacent vein. The vein enlarges and develops thicker and stronger walls that will accept a dialysis catheter. With this procedure the catheter needle is inserted at the initiation, and removed at the end of each treatment. Blood is circulated from the patient through a cartridge that contains thousands of tiny tubules in dialysis fluid which is free of toxins, and whose concentration of electrolytes and minerals are designed to normalize those of the patient (Marler, 2011). This in turn removes all the toxic wastes in the patient and the kidney’s function is recovered with time.
Conclusion
Most cases and histories or clinical courses of HUS has improved remarkably with the advent of dialysis and intensive care facilities for children. In the 1950s, there was a forty-percent death rate with HUS; however, in developed countries, only 3% to 5% die as a result of HUS (Marler, 2011). Effective therapies had also been adopted to treat this illness and it showed considerable success. Kidneys that have been affected by HUS slowly recovers but it eventually does. After recovery, patients are advised to go for frequent medical follow ups to evaluate their progress and if the kidneys have fully recovered. Evaluations include blood count, urine analysis which can be used to determine filtration rate and blood pressure.
timely and appropriate treatment leads to a full recovery for most people, especially young children (Mayo Clinic, 2016). A variety of viruses have also been implicated as a causative agent. It is now the most common cause of acquired acute renal failure in childhood. It is a medical emergency which carries a 5–10% mortality rate; of the remainder, the majority recover without major consequences, approximately 30% suffer residual renal injury. The primary target appears to be the vascular endothelial cell. This may explain the pathogenesis of HUS, in which a characteristic renal lesion is capillary microangiopathy (Mayo Clinic, 2016).
Damage to endothelial cells is the primary event in the pathogenesis of HUS. Damage to the kidney which prevents the filtering of waste and its other functions also follows. The cardinal lesion is composed of arteriolar and capillary microthrombi (thrombotic microangiopathy (TMA) and red blood cell fragmentation (Medscape, 2016). The symptoms that have been associated with the HUS include: prolonged diarrhea, vomiting, abdominal pain, lethargy, bloody stool, unexplained bruises, pallor, and edema, among others. If HUS is not treated, it will lead to death in infancy or early childhood. Common treatments has been found to include blood transfusion, kidney dialysis, fluid replacement and nutritional supplementation given intravenously. In some other cases, a special form of treatment called plasmapheresis may also be necessary. However, early detection and treatment are very important for patients to lead healthy lives.
Discussion
Hemolytic uremic syndrome as described by the National Kidney Foundation, is a “condition that affects the blood and blood vessels. It results in the destruction of blood platelets (cells involved in clotting), a low red blood cell count (anemia) and kidney failure due to damage to the very small blood vessels of the kidneys. Other organs, such as the brain or heart, may also be affected by damage to very small blood vessels” (National Kidney Foundation NKF, 2015). The urinary system plays a large role in this disease especially the kidneys as it is an organ of utmost importance when it comes to cleaning up the body system. The HUS is a complex condition where an immune reaction, most commonly after a gastrointestinal tract infection, causes low red blood cell levels, low platelet levels, and kidney injury. Infections of the gastrointestinal tract are the most common cause of this syndrome. The body’s immune system reacts to toxins released during an intestinal bacterial infection. This causes damage and destruction to blood cells as they circulate through the blood vessels. These include red blood cells (RBC) and platelets, causing them to die prematurely. The kidney is affected in two ways. The immune reaction can cause direct damage to kidney cells resulting in kidney injury. The build-up of damaged red blood cells or platelets can clog up the kidney’s filtering system and cause kidney injury or a build-up of waste products in the body, since the kidney can no longer efficiently eliminate waste from the blood.
HUS from E. coli infections results when bacterial toxins cross from the intestines into the bloodstream and damage the very small blood vessels. The toxic E. coli may come from eating spoiled, undercooked or poorly processed food products, or from exposure to contaminated water. According to Jenssen et.al, in the BioMed Central journal, a common classification of HUS is by clinical presentation which is associated with prodromal diarrhea (D+HUS) or not (D−HUS). Around 90 % of HUS cases in children are D+HUS and most cases of D+HUS are caused by infection with Shiga toxin producing E. coli (STEC-HUS). According to this classification, D−HUS mainly consists of HUS caused by Streptococcus pneumoniae infection (SP-HUS) and HUS associated with familiar or sporadic genetic disorders of complement regulation. It has been suggested that some STEC-HUS cases, especially those with more severe outcome, are genetically predisposed atypical HUS cases triggered by an STEC infection (Jenssen et. al, 2016). In HUS, the Shiga toxins binds to the endothelial cells of the glomeruli, the tubular endothelial cells, the podocytes and other cells in the nephron. After binding, the toxin damages the cells and block protein synthesis which leads to apoptosis which then leads to damage of red blood cells and platelets in the blood stream.
The HUS is usually diagnosed after a series of tests and includes complete blood count, which measures the quality and quantity of the red blood cells and platelets in the blood sample, urine tests for presence of blood or protein which should not be present ion a healthy individual and stool sample tests among other types of tests. The most common markers are presence of red blood cells in urine, low albumin in blood (hypoalbunemia), low platelet count, presence of protein in urine, low Glomerular Filtration Rate (GFR), high percentage of schistocytes, and elevated bilirubin. All these are consequences of the disease’s effect on the kidney which prevents it from performing its functions. The kidney has various structures that helps in accomplishing the filtration of wastes in the body especially its functional unit called the nephron.
Glomerular Filtration Process
This is the first stage in which the kidney filters wastes in the body, it involves the process in which water and some other substances in the blood plasma pass from the capillaries of the glomerulus into the Bowman's capsule.
Very small molecules like water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes, and vitamins can pass through the filtration membrane into the Bowman's capsule. These substances have about the same concentration in the glomerular filtrate as in the blood plasma. Some substances do not pass through the membrane which makes them to be retained in the bloodstream because they are bound to plasma proteins. For example, most calcium, iron, and thyroid hormone in the blood are bound to plasma proteins that does not allow them to be filtered by the kidneys. The small fractions that are not bound to plasma protein, however, passes freely through the filtration membrane and appears in the urine. Kidney infection and trauma can damage the filtration membrane. This allows proteins or blood cells to filter through. The mere presence of these proteins in the urine can be used to detect kidney disease. In the case of HUS, the presence of protein and blood in the urine is used to detect that the kidney has been damages to an extent and treatment must commence immediately to correct it.
Glomerular filtration must be controlled. If it is too high, fluid flows through the renal tubules too rapidly for them to reabsorb the required amount of water …show more content…
and solutes. If it is too low, fluid flows too slowly through the tubules and wastes that should be eliminated are reabsorbed into the bloodstream. Mechanisms employed by the body to control the glomerular filtration rate include, Renal Autoregulation, Sympathetic Control and the Renin-Angiotensin-Aldosterone Mechanism.
Tubular Reabsorption
This is the second stage of the glomerular filtration process and it involves the removal and addition of chemicals, after glomerular filtrate leaves the Bowman's capsule and enters the renal tubule. The renal tubule is very long, which increases its absorptive surface area. It reabsorbs about 65% of the glomerular filtrate, while it removes some substances from the blood. Tubular reabsorption mechanism in the kidneys return the water and solutes that is needed back into the extracellular fluid and circulatory system. Materials that are reabsorbed, are needed by the blood and they include, water, glucose, sodium, potassium, electrolytes among others. This process involves the passive or active movement of water and dissolved substances from the fluid inside the tubule through the tubule wall into the space outside. Water and these substances move through the capillary walls back into the bloodstream again either by passive or active transport.
There are several structures that makes the reabsorption process possible. The proximal convoluted tubule carries out the reabsorption process when pH needs to be maintained and bicarbonate ions are reabsorbed back into the blood stream. glucose, amino acids and potassium ions are actively transported into the blood. sodium and chlorine ions are also moved back into the capillaries so that some salt regulation can occur while substances such as hydrogen ions and toxins are actively secreted from the blood into the tubule. Within the loop of henle, the descending loop allows reabsorption of water through osmosis while the ascending loop allows passive and active transport of salts such as sodium to move out of the tubules for reabsorption. The distal convoluted tubule is where the final adjustments are made to the passing urine within the tubule systems. This is where highly selective reabsorption takes place allowing for small adjustments to be made especially between the presence of Potassium and Sodium (Esterman, 2016).
Tubular Secretion
In addition to reabsorbing the substances that is needed, nephrons are able to secrete unwanted substances from the bloodstream into the filtrate.
Here, acid-base balance and waste removal is achieved. This process is achieved by passive diffusion that involves the movement of molecules from the peritubular capillaries to the interstitial fluid within the nephron. It also involves active transport involving the movement of molecules via ATPase pumps that transport the substance through the renal epithelial cell into the lumen of the nephron (Boundless, 2016). This process differs from the reabsorption process in that it filters and cleans substances form the blood and do not retain them. Some of these substances include, potassium ions, hydrogen ions, urea, hormones, and others. Failure of the kidney to undergo this process allows wastes to be backed up in the system which endangers the organ systems in the
body.
HUS in affected persons therefore increases blood pressure which causes hypertension, hyperkalemia, and other electrolyte abnormalities such as hyponatremia and hypocalcemia, because of the kidney has been damaged. Nearly 40% of patients with STEC–HUS and up to 70% of cases of atypical HUS require renal replacement therapy during the acute episode (Cheung and Trachtman, 2014).
Treatments
The O157:H7 strain of E. coli produces a poison known as Shiga toxin that is absorbed through the intestines. These toxins damages the endothelial cells that line the inner walls of the blood vessels of the glomeruli in the kidneys. Damage to these blood vessels leads to anemia, thrombocytopenia, acute renal failure, and the other symptoms and findings associated with HUS. For example, hemolytic anemia occurs when red blood cells are destroyed or damaged as they pass through the small damaged blood vessels. Circulating platelets are consumed in the small clots in these microscopic blood vessels resulting in thrombocytopenia and the abnormal accumulation of platelets within narrowed blood vessels, causing the formation of small blood clots. As a result, blood flow to organs such as the kidneys, brain, and pancreas variably decreases leading to multiple organ dysfunction or failure (National Organization for Rare Disorders (NORD), 2016).
One of the most viable treatments for HUS that has been discovered overtime is the dialysis process. This process involves a treatment designed to function like normal kidneys. It helps to remove toxic materials that has built up in the system and also helps normalize the body fluid and electrolytes. However, there are different types of dialysis and hemodialysis has been proven to be more time efficient in treating HUS. In this treatment process, there are two compartments separated by a semi-permeable membrane and one compartment which is the body, contains uremic toxins and excess electrolytes and the other dialysate compartment is free of these substances. Toxins and electrolytes will move across the membrane until they are in equal concentrations on both sides. Excess fluid is then removed by creating pressure gradients between the blood and dialysis fluid compartments. Blood access is achieved by surgically attaching a native artery which is usually in the arm to an adjacent vein. The vein enlarges and develops thicker and stronger walls that will accept a dialysis catheter. With this procedure the catheter needle is inserted at the initiation, and removed at the end of each treatment. Blood is circulated from the patient through a cartridge that contains thousands of tiny tubules in dialysis fluid which is free of toxins, and whose concentration of electrolytes and minerals are designed to normalize those of the patient (Marler, 2011). This in turn removes all the toxic wastes in the patient and the kidney’s function is recovered with time.
Conclusion
Most cases and histories or clinical courses of HUS has improved remarkably with the advent of dialysis and intensive care facilities for children. In the 1950s, there was a forty-percent death rate with HUS; however, in developed countries, only 3% to 5% die as a result of HUS (Marler, 2011). Effective therapies had also been adopted to treat this illness and it showed considerable success. Kidneys that have been affected by HUS slowly recovers but it eventually does. After recovery, patients are advised to go for frequent medical follow ups to evaluate their progress and if the kidneys have fully recovered. Evaluations include blood count, urine analysis which can be used to determine filtration rate and blood pressure.