Physiology of Nephrotic Syndrome Term Paper

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Nephrotic Syndrome is not a disease. It is a condition that is characterized by damaged glomeruli in the kidney. This damage might be caused by one or more disease. These diseases can be related to the kidney as in Familial Focal Segmental Glomerulosclerosis, abbreviated FFGS or membranous nephropathy. Or it can present from relatively distantly related diseases such as heart diseases, hypertension, diabetes and lupus. The types of diseases that cause nephrotic syndrome also vary with age. Some cases can be corrected with properly prescribed medication, despite some side effects. In more serious cases, kidney failure can occur. Regular dialysis and ultimately, transplantation may be required. Nephrotic Syndrome can cause damage to (or arise from damage to) the glomeruli, which affects it's function of filtering out waste matter and excess water that is converted into urine. Nephrotic syndrome is identified from symptoms known as proteinuria, hematuria and edema. The first is an excess of protein in the urine. This condition is paralleled by the loss of protein in the blood. The decrease of protein in the blood is called hypoproteinemia. The second is the presence of blood, or more specifically, red blood cells or erythrocytes in the urine. The loss of glomerular function results in the non-removal of excess fluids, which are retained by the body, especially in the extremities. This retention of fluids and salts is called edema. Additionally, patients suffering from nephrotic syndrome also experience varying levels of discomfort and toxicities due to increasing levels of wastes in the blood due to inefficient filtration in the glomerular layer. (Jennette, 2004)


In order to gain a perspective on understanding the physiology of Nephrotic Syndrome, it is important to understand how critical properly functioning glomeruli are in the execution of normal excretion. The kidneys are bean shaped organs. They are approximately the size of a person's fist and are located in the lower dorsal portion of the body. The function of kidneys is to remove waste from the body in liquid form. This means that the kidneys contain a complex set of filtration devices. Studies and extrapolations show that more than 350 liters of blood flows through the kidneys in a 24-hour period. About two liters of waste material and any excess water is then removed from the body and excreted as urine.

To perform their function, the kidneys receive blood through arteries that branch (on entering the kidneys) into clusters of smaller blood vessels. These clusters are called glomeruli (s. glomerulus). The process of urine creation starts at the glomeruli. Each glomerulus is attached (or ends into) to a tubule. The tubule serves as a collection for the waste and excess water. The nephron, an important part of this process, comprises each glomerulus-tubule unit. There are more than a million such nephrons in a normal human kidney. This explains how complex the process of excretion is. The actual filtration takes place at a membrane called the glomerular membrane. This membrane separates the blood vessel -- glomerulus and the tubule. On the other side, the tubules aggregate to form larger tubes, which further aggregate into the ureters.

The ureters then carry the urine into the bladder for excretion. (Kassirer, 1971)

Causes of Nephrotic Syndrome (EdREN, 2004)

The causes of nephrotic syndrome, as mentioned in the Introduction, are varied and range from disease localized around the kidneys or diseases that affect the entire body and are far removed from the kidneys. Symptoms and effects of nephrotic syndrome can also be due to external factors. These are infections -- bacterial and viral. They can also be due to allergic and toxic reactions due to certain drugs. The immediate non-symptomatic affects on the glomeruli physiologically are inflammation and scarring. Occasionally, symptoms of nephrotic syndrome are idiopathic. This term means that they are not associated with any diseases.

In considering the different reasons how glomerular damage occurs, occasionally it is the body's immune system turning against itself. These are cases of autoimmune diseases. When an antigen -- a bacterium, virus or other foreign body -- attacks the body, the body produces an antibody that acts as a foil to destroy the antigen. The first step in the mechanism of immunity is the formation of an antibody-antigen complex. In autoimmune diseases, due to a perceived attack on the body, whose mechanism is not completely understood, the body produces antibodies called autoantibodies. These antibodies can be systemic or they might attack specific parts of the body. Systemic Lupus erythematosus (SLE), commonly known as lupus attacks the skin, joints and, on occasion, the kidneys. It causes painful inflammations. This is an autoimmune disease. If the kidneys are infected, it is because the body deposits autoantibodies into the glormeruli. This causes inflammation of the glomeruli. Since more women are afflicted by lupus, researchers believe that there is a causative factor with the sex gene for females. Others believe that a virus triggers it.

Goodpasture's syndrome is another autoimmune disorder where autoantibodies attack the kidneys and the lungs. Coughing up blood is how patients of Goodpasture's syndrome first present the condition, however the damage on the kidneys is progressive, permanent and not immediately evident. This illness also affects the glomeruli. As does the consequences of IgA nephropathy. In this case, the immunoglobulin A deposits in the glomeruli. Immunoglobulins are antibody proteins responsible for immunity functions throughout the body. Basically, the molecular structure if Igs consists of four proteins chains, two each of which are identical. Two chains are heavy and two are light. They are connected through sulfide linkages. IgA depositions cause inflammation and eventual kidney scarring. This disease takes several years to develop and is not often found in children. As opposed to lupus, IgA nephropathy affects men more than it does women.

Glomerular diseases and the associated nephrotic syndrome can also be inherited in a small number of patients. This condition is known as Alport syndrome. It is inherited. Men pass it down to their daughters. Women can pass it to their sons or daughters. This condition usually ends up in end stage renal failure by the age of 40. Interestingly, Alport syndrome is often associated with sight and hearing impairment.

Congenital Nephrotic Syndrome can be found in babies of Finnish descent (overwhelmingly) but also in other nationalities and races. This disease is characterized by low birth weight and enlarged placenta. The weight gain within 24 hours followed by swelling (due to edemas) is abnormal. The baby is dangerously ill and immediate steps have to be taken to preserve its life.

Infections or over stimulation of the immune system may also have damaging effects on the renal glomeruli. The condition acute post-streptococcal glomerulonephritis (PSGN) is caused indirectly. In the case of strepthroat or in the rare skin condition impetigo, the streptococcus bacterial infection stimulates the immune system to such an extent that the antibodies to combat the disease will deposit in the glomeruli. Edema, hematuria and oliguria (reduced urination) along with hypertension and elevated levels of creatinine and urea nitrogen in the blood are used to characterize PSGN. PSGN is most common among young children. It is also prevalent in male children. PSGN if left untreated eventually results in ESRD. Bacterial cardiac infections such as endocarditis can also result in kidney lesions associated with damaged glomeruli. Chronic renal failure and ESRD can occur from endocarditis. Mechanistically, it is not known whether there is bacterial infection in the kidneys similar to that of the heart of whether it is the result of an overstimulated immune response. HIV also causes damage to the renal glomeruli. Once again, this is an autoimmune condition. Renal failure is observed in a statistically significant number of patients even when HIV has not escalated to AIDS.

Sclerosis or scaring also results in glomerular damage. This gives rise to the ill effects of nephrotic syndrome. Glomerularsclerosis is a condition caused by lesions and scars in the glomeruli. These might be brought about in two different ways. Research on this is speculative at best. One way is by means of growth factors. The glomerular cells create these themselves. Growth factors are stimulants necessary in the life cycles of all cells. In some cases, overproduction of growth factors leads to sclerosis. It is also possible, that growth factors -- abnormal -- are introduced into the glomeruli through blood transport from remote regions of the body.

One of the biggest drawbacks of the glucose imbalances in diabetes mellitus is association with sometimes-fatal renal failure. This is despite the inherent diabetic problems associated with the rapidly (and dangerously) varying glucose levels in the blood -- that can render a diabetic comatose. Diabetes causes scars and lesions in the kidneys. There is reason to believe that elevated levels of glucose increase the speed of the flow of the blood. This increased force creates a strain on the glomerular layer of a nephron, interfering with the function of filtration. Naturally, moderating diets and increasing physical activity have a salubrious effect on the blood pressure. Angiotensin converting enzymes (ACE) and angiotensin…

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