Dialysis Technology: Application of dialysis in acute renal failure !

Our kidneys are destined to perform excretory as well as regulatory function to maintain a state of homoeostasis in our body. Acute renal failure (ARF) is a syndrome defined as sudden or rapid loss of renal function (kidney function) leading to accumulation of urea and creatinine (nitrogenous waste compounds). If hyperbolic relationship between plasma creatinine or urea and glomerular filtration rate (GFR) is observed after investigations, the diagnosis is established as ARF. The early clinical signs of ARF/uremia are anorexia, nausea, vomiting, and sometimes pericarditis also. The ARF is an implication of loss of more than 50% of renal function. Dialysis should be instituted whenever early signs of uremia (elevated levels of urea in the blood) are present. Cases of metabolic acidosis as well as electrolyte and fluid imbalance also need dialysis for the reversal of hemodyanmics to normal.

Dialysis is a procedure for artificially purifying the blood of a patient through meticulous surgical intervention and electromechanical equipment. No specific elevated value of plasma creatinine or urea could be regarded as critical. The fluid intake and nutritional requirements are taken into consideration for deciding the timing and mode of dialysis. Cases of ARF should be put on dialysis without much delay for the successful recovery of their renal function. However, cases of chronic renal failure (CRF) may be kept in waiting. The dialysis procedure is of two types: i)  Hemodialysis (where patient's blood is passed through artificial kidney in conjunction with dialysis solution) and ii)  Peritoneal dialysis (where dialysis fluid is passed through the abdominal peritoneal cavity of the patient). The technique of dialysis was established long back in USA by Dr. Alan P Kendal, who also patented a 'suitcase kidney' in 1978.

Conventional hemodialysis remains the preferred and the best mode of dialysis. The hemodialysis is ideal for non-hypotensive and hemodynamically stable patients. Peritoneal dialysis is probably less effective in patients with hypercatabolic disorder and/or with undiagnosed abdominal disease. Peritoneal dialysis should be avoided in patients with recent abdominal surgery. The surgical intervention for hemodialysis can be in the following ways: i)  Continuous arteriovenous hemofiltration (CAVH), ii)  Continuous arteriovenous hemofiltration with/without concomitant dialysis (CAVHD), iii)  Continuous veno-venous filtration (CVVHD). These hemodialysis techniques are simpler, safe and very effective. The biochemical recovery is monitored during the dialysis for needful correction of fluid and electrolytes. After successive dialysis sessions the patient would return to normal health.

Urea Synthesis and Clearing: Role of Liver and Kidneys

The proteins we eat contain about 20% nitrogen. A person consuming around 100g proteins daily will excrete about 17g of nitrogen daily in the form of urea. In man and other vertebrate animals the major excretory product of protein metabolism is urea, and they are classified as ureotelic animals. Birds and reptiles excrete the waste nitrogen in the form of relatively insoluble uric acid as the end product of nitrogen metabolism and are called uricotelic animals. Urea is synthesized in liver and is released into the blood and cleared by kidneys in the urine.
Urea synthesis in the liver involves five enzymes: (1) Carbamoyl phosphate synthetase 2) Ornithine carbamoyl transferase (3) Argininosuccinate synthetase (4) Argininosuccinate lyase and (5) Arginase. Deficiency in any of these enzymes may lead to metabolic disorder. The sole function of urea cycle is to convert the ammonia to non-toxic compound urea. All metabolic disorders of urea synthesis cause ammonia intoxication. Catabolism of amino acids in the most of cells produces ammonia. Considerable quantity of ammonia is produced by intestinal bacteria from the dietary proteins and from the urea present in cellular fluids secreted into the gastrointestinal tract. The ammonia produced in the intestine is absorbed into the portal venous blood and is promptly removed by the liver, where urea is synthesized from the ammonia. At first step, carbamoyl phosphate is produced by condensation of one molecule each of ammonia, carbon dioxide and phosphate, under the action of intramitochondrial carbamoyl phosphate synthetase-1 (CPS-1) in the presence of Mg⁺⁺ and N-acetyl glutamate. Now citrulline is formed from the carbamoyl phosphate by union of carbamoyl phosphate and ornithine under the action of another intramitochondrial enzyme called ornithine carbamoyl transferase. The rest of the steps in the urea synthesis take place in cytosol. Citrulline diffuses out from the mitochondrial membrane into the cytosol, where it is linked with aspartate to form argininosuccinate under the action of enzyme argininosuccinate synthetase in the presence of Mg⁺⁺ ions and ATP. There after the cleavage of argininosuccinate to arginine and fumarate is catalyzed by argininosuccinate lyase. The final step in the urea synthesis is the hydrolysis of arginine to urea and ornithine. Ornithine from the cytosol enters the mitochondria and is recycled in urea synthesis. Though other body tissues also exhibit the presence of urea synthesis enzymes but the physiologic contribution of extrahepatic urea synthesis is very low. Urea produced by the hepatic cells enters the blood and is excreted in the urine by the kidneys. Low level of blood/plasma urea and respiratory alkalosis are indicative of urea cycle disorders. Free "Human Body Maps"

Kidney Diseases and Elevated Levels of Blood Urea, Uric Acid and Creatinine

There could be minimal to gross impairment of renal function during the onset and progression of a kidney disease or renal disorder. This impairment of renal function may range from subclinical to complete renal failure. Urine analysis and blood biochemistry have been of great help in the assessment of renal function. Simultaneous increase in the levels of blood urea and uric acid has been observed during a variety of renal disorders. Uric acid is an end product of purine (a component of nucleic acids and nucleoproteins) metabolism. The level of uric acid in the blood depends on its endogenous production through purine metabolism as well as from the exogenously taken purines in the food items. Normal range of uric acid in blood is 2 - 6mg/dl. Elevated level of uric acid is also observed in gout. Urea is an end product of protein metabolism and its normal range in blood is 20 - 40mg/dl.

Formation of Urea: The amino acids derived by the digestion of proteins of the food we eat are absorbed by the villi of the small intestine and brought to the liver through the portal vein. The essential amino acids required for the growth and repair of body tissues are passed on to the blood circulation by the liver and others are used to produce the blood proteins and useful proteins for the body. Useless proteins are broken down in the liver to form bioenergy composed of carbon, hydrogen and oxygen and a waste product urea. Urea is a water soluble substance and carried away buy the blood stream.

The uric acid level may increase earlier than the blood urea level during the course of renal disease. The serum uric acid could be found markedly increased from the normal level of 2 -6mg/dl to 10 - 30mg/dl with minimal impairment of renal function. The creatinine level in blood starts rising after 2 to 4 fold rise in the blood urea level. The level of urea may rise in a variety of conditions, but increased level of creatinine is considered more severe than the increased level of blood urea. The creatinine is derived from the creatine and is a waste product; on the other hand the creatine is necessary for the muscle contraction and is related to the phosphocreatine breakdown. The normal level of creatinine in the blood plasma or serum is 1 - 2mg/dl and its normal daily excretion ranges from 1 to 2 grams. The serum creatinine values of up to and even exceeding occasionally 20mg/dl have been seen in the later stages of renal failure. The major cause of increased levels of serum creatinine and blood urea is the poor clearance of these substances by the kidneys rather than excessive production. In acute glomerulonephritis values from normal to over 300mg/dl are generally observed. In conditions such as malignant hypertension, chronic pyelonephritis and heavy metal poisoning 10 to 15 fold increase in blood urea level may be detected. However, in cases of hypoadrenalism (Addison's disease) blood urea level of about 100mg/dl could be detected. Fifteen to 20 fold increase in the level of blood urea (i.e. a level of 600 - 800mg/dl) may lead to uremic coma in more than 80% cases of cases affected by severe renal disease or renal failure.

Urine Analysis: Physical and Chemical Characteristics of Normal Urine

Urine analysis infers valuable information in a variety of ailments. Physical characteristics of urine have been used as diagnostic and prognostic tool from the time immemorial by the health physicians. We know that the major functions of kidneys are:

1. Removal of water not needed by the body fluids, the amount depending on the balance between glomerular filtrate and he degree of tubular reabsorption;
2. The excretion of certain substances normally present in the plasma when their concentration rises above a certain level;
3. The selective reabsorption of substances such as glucose which are of value to the body;
4. The excretion of useless substances; and
5. Regulation of acid base balance.

Disordered renal function may lead to a change in the volume of the urine excreted per day along with remarkable changes in its physical and chemical properties and microscopic contents. Urine analysis is the very first investigation of diagnostic importance not only in renal disorders but also in other diseases like diabetes, liver disease, jaundice etc. In diagnostic pathology the extent of abnormalities could only be understood in comparison with the reference values obtained from similar investigations in normal individuals. Hence, it is important to have an understanding of normal parameters of physical and chemical characteristics of urine.

Characteristics of normal urine:

1. Quantity: The quantity averages 1500 to 2000 ml in an adult man daily. It may vary with the amount of fluid taken. In fact it is linked with the protein metabolism; higher is the protein intake higher will be the urinary output since the urea produced from the protein needs to be flushed out from the body. Higher is the urea production in the body, the higher is the volume of urine to excrete it.
2. Color: The color should be clear pale amber without any deposits. However, a light flocculent cloud of mucus may sometimes be seen floating in the normal urine.
3. Specific gravity: It varies from 1.010 to 1.025. Specific gravity is determined with urinometer.
4. Odor: The odor is aromatic.
5. Reaction: The reaction of normal urine is slightly acidic with an average pH of 6.0.

Composition of normal urine: Urine is mainly composed of water, urea and sodium chloride. I an adult taking about 100 g protein in 24 hours, the composition of urine is likely to be as follows:

1. Water: Near about 96%
2. Solids: About 4% (urea 2% and other metabolic products 2%. Other metabolic products include: uric acid, creatinine, electrolytes or salts such as sodium chloride, potassium chloride and bicarbonate).

• Urea is one of the end products of protein metabolism. It is prepared from the deaminated amino-acid in the liver and reach the kidneys through blood circulation (The normal blood urea level is 20-40 mg/dl). About 30 gram urea is excreted by the kidneys daily.
• Uric Acid: The normal level of uric acid in blood is 2 to 6 mg/dl and about 1.5 to 2 gram is excreted daily in urine.
• Creatinine: Creatinine is the metabolic waste of creatin in muscle. Purine bodies, oxalates, phosphates, sulphates and urates are the other metabolic products.
• Electrolytes or salts such as sodium chloride and potassium chloride are also excreted in the urine to maintain the normal level in blood. These are the salts which are the part of our daily diet and are always taken in excess and need to be excreted to maintain normal physiological balance.