Urine Glomerular filtration

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Acute renal failure (ARF) is a potentially life-threatening clinical syndrome that occurs primarily in hospitalized patients and frequently complicates the course of the critically ill. It is characterized by a rapid decrease in glomerular filtration rate (GFR) and the resultant accumulation of nitrogenous waste products (e.g., creatinine and urea nitrogen), with or without a decrease in urine output. A recent consensus statement... 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

The first step in the formation of urine is glomerular filtration. The barrier to filtration is designed to facilitate the movement of fluid from the glomerular capillaries into Bowman s capsule without any loss of cellular elements or plasma proteins. Maximizing GFR has two advantages ... 

Under physiological conditions, values for ncc and PBC vary little. In other words, when plasma protein synthesis is normal and in the absence of any urinary obstruction that would cause urine to back up and increase PBC, the primary factor that affects glomerular filtration is PGC. An increase in PGC leads to an increase in GFR and a decrease in PGC leads to a decrease in GFR. 

Acute renal failure (ARF) is broadly defined as a decrease in glomerular filtration rate (GFR) occurring over hours to weeks that is associated with an accumulation of waste products, including urea and creatinine. Clinicians use a combination of the serum creatinine (Scr) value with change in either Scr or urine output (UOP) as the primary criteria for diagnosing ARF. 

In humans, it has been calculated that about 65% of the Ni2+ in the glomerular filtrate is reabsorbed by the renal tubular system [263], and after absorption, urine is the major route for excretion. 

Blood samples were centrifuged at 1000 x g for 20 min at 0-4°. Ionized calcium levels were immediately determined in serum and urine samples using a calcium ion-selective electrode (Ionetics, Inc., Costa Mesa, CA) urine volumes were recorded. The remaining serum and urine were aliquoted for various analyses and stored at -40°. Serum insulin was analysed by radioimmunoassay (Amersham Corp., Arlington Heights, IL). Serum levels of total calcium, phosphorus and creatinine as well as urine creatinine were determined by colorimetric procedures using an automated analyzer (Centrifichem, Baker Instruments Corp., Pleasantville, NY). Glomerular filtration rates (GFR) were calculated from serum and urine creatinine data GFR = urine creatinine/serum creatinine. 

Because the glomerular filtrate contains many important body constituents (e.g., glucose), there are specific active uptake processes for them. Also, lipid-soluble chemicals diffuse back from the tubule into the blood, especially as the urine becomes more concentrated because of water reabsorption. The pH of the urine is generally lower than that of the plasma, and therefore pH partitioning tends to increase the reabsorption of weak acids. The pH of the urine can be altered... 

Kidney Failure, Acute A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH]... 

Except for its lower protein concentration, glomerular filtrate at the top of the nephron is chemically identical to the plasma. The chemical composition of the urine is however quantitatively very different to that of plasma, the difference is due to the actions of the tubules. Cells of the proximal convoluted tubule (PCT) are responsible for bulk transfer and reclamation of most of the filtered water, sodium, amino acids and glucose (for example) whereas the distal convoluted tubule (DCT) and the collecting duct are concerned more with fine tuning the composition to suit the needs of the body. 

Methyixanthines increase urine production. Increases are also seen in renal blood flow and glomerular filtration rate. 

The main filtering units of the kidneys are called nephrons-, about one million nephrons are present in each kidney. Each nephron consists of a renal corpuscle and a unit called a tubule. Blood carrying normal metabolic wastes such as urea and creatine moves through a portion of the corpuscle called the glomerulus, where a filtrate forms that contains water, normal metabolic products, and also waste products the filtrate collects in another unit called Bowman s capsule. Glomerular filtrate then moves into a highly convoluted and multifaceted set of tubes - the tubule - where most useful products (water, vitamins, some minerals, glucose, amino acids) are taken back into the blood, and from which waste products are collected as urine. The relative amounts of water and minerals secreted or returned to the blood are under hormonal control. 

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

In the muscle, phosphocreatine and creatine undergo cyclisation to form creatinine (Figure 8.20(b)). Since creatinine cannot be metabohsed, it is released from muscle and is then excreted in the urine. This biochemical process is useful in clinical practice, since creatinine production is spontaneous and is remarkably constant 1.7% of the phosphocreatine and creatine in muscle cyclises each day, so that its concentration in blood provides an indication of the glomerular filtration rate, and hence provides an indication of the function (i.e. the health) of the kidney. 

In calves and cows, SDM was excreted by glomerular filtration minus tubular reabsorption its renal clearance was urine flow correlated, and amounts to half of the creatinine clearance. The SCH2OH hydroxy metabolite was excreted by glomerular filtration and partly by tubular secretion, whereas both Na-SDM and SOH were excreted predominantly by tubular secretion (15 . The main metabolite in urine SCH2OH was 23 to 55 % of the administered dose (Table III). The urine concentration—time curves for SDM and its metabolites are illustrated in Figure 7 for a high SDM dosage. 

Apart from glomerular filtration (B), drugs present in blood may pass into urine by active secretion. Certain cations and anions are secreted by the epithelium of the proximal tubules into the tubular fluid via special, energyconsuming transport systems. These transport systems have a limited capacity. When several substrates are present simultaneously, competition for the carrier may occur (see p. 268). 

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