1- nephron: structure , anatomy, blood supply, physiology
2- renal disease according to :
a- Glomerular disease
b- tubular disease
c- Renal calculi disease (stone)
d- diabetic nephropathy
3- test of renal functional (biochemistry) laboratory test
references no more than ten
The nephron is the microscopic structure of the kidney, made up of about one million small tubes known as the tubulues. The nephrons confer both the functional as well as structural unit of the kidneys. The nephron consists of two compartments: the malphagian body and the renal tubes. The malphagian body is a double walled cup that surrounds several capillaries. This cup is commonly known as the bowman’s capsule while the network of capillaries is known as the glomerulus. The main parts of the nephron tubule are the proximal convoluted tubule, loop of Henle, distal convoluted tubule and the collecting duct. It is worth noting that a substantial amount of glucose, small proteins and other useful materials are reabsorbed in the proximal convoluted tubule. The afferent arteriole which is a branch of the renal artery finds its way to the glomerulus and ultimately divides into so many capillaries. These capillaries unite again to form the efferent arterioles which leaves the glomerulus once more. The bore is the diameter of the lumen in the afferent arteriole which is bigger than that of the efferent arteriole. Moreover, the walls of the capillaries are made up of the squamous endothelial material which is found on the basement membrane. The cells contain several tiny pores on the capillary walls to facilitate the passage of materials. Moreover, the capillary walls on the Bowman’s capsule consist of the squamous epithelium and rests in the basement membrane to be modified into special cells known as the podocytes (Lasagni et al., 2015).
The renal tubules
This is a very crucial structure of the kidney since it contains the tube fluids which are finally filtered into urine for excretion by the body. These tubules are part of the nephrons and each normal kidney has about one million nephrons with each having the renal tubules. Thus these structures are described as the end of the neuron because after the tubular fluids leave the renal tubules, they end up in the collecting ducts, which empties to the ureter. The tubular fluid starts as the glomerular filtrate which consists of the fluids filtered from the body by the glomerulus. Once the filtrate begins leaving the glomerulus, it enters into the proximal tubule which is the first portion of the renal tubules. In the proximal tubules, there is the regulation of the pH and secretion of organic acids which are not needed by the body into the filtrate. Moreover, there is an increased reabsorption of water and sodium ions back into the body by the capillaries. The midpoint of the renal tubules is known as the tube of Henle and functions to create a concentrate of the sodium and chloride ions, urea and other wastes into the urine while at the same time absorbing more water back to the body. Finally, the distal convoluted tubule is farthest and enables the pH regulation through secretion of protons in form of hydrogen ions into the urine and absorbing back the negatively charged bicarbonate ions (Subramanya & Ellison, 2014). This step is very important in the regulation of various ions in blood such as the calcium, sodium, and potassium. When the filtrate is passing down the descending loop of Henle, it does this in a contrary direction to the fluids inside the ascending limbs. The fluids are highly concentrated when moving down and more dilute when moving upwards. This fashion is known as the countercurrent flow thus allowing the production of the concentrated urine.
Formation of urine and secretion
Formation of urine occurs in three steps which involve various regulatory processes. These are the glomerular filtration, reabsorption in the tubes and secretions. In glomerular filtration, the glomerulus filters low molecular weight materials in blood and retains the high molecular weight substances like proteins. This clearly means that the proteins will be retained in the blood and not lost in urine. If during a test, proteins are found in urine, this is indicative of kidney damage or any other disease which could be affecting the glomerular membrane. In the reabsorption stage, even though the filtrate in the glomerulus has the same concentration of glucose as the plasma, none of it is found in urine (Dantzler, 2016). Therefore, glucose should be completely reabsorbed inside the tubules when the sugar concentrations are normal. Basically, reabsorption of materials is dependent on the renal threshold of the materials inside. Different solid materials get reabsorbed at various sites of the renal tubules. Glucose, amino acids and small proteins can pass through the glomerulus and hence their absorptions occurs in the first portion of the proximal tubules. On the other hand, bicarbonates, sodium and chlorides get absorbed in a uniform manner along all parts of the proximal and distal tubules. However, potassium ions are reabsorbed in the proximal tubules and later get secreted in the distal tubules.
Even though majority of materials are reabsorbed in the tubules, there are others which are actively transported and excreted in the lumen of the tubules. In the tubules of man, majority of the materials which are secreted are creatinine and potassium ions. It is at these sites that the foreign materials such as diagnostic and therapeutic that have been introduced get removed through urine.
Hormonal regulation of the kidneys
For the kidneys to function well, the interplay of three hormones is needed. These hormones include the adrenal cortex hormone, vasopressin and parathormone. The aldosterone hormone is involved in the excretion of sodium ions and potassium ions. The parathormone stimulates the secretion of phosphates while vasopressin is an antidiuretic hormone which facilitates the reabsorption of water. In the vent that the vasopressin hormone is absent, then there will be production of high amounts of dilute hormone.
Diseases of the kidneys
This is a renal disease which is mostly occurs through an immunologic reaction that leads to inflammation and growth of the glomerular tissues. This in turn causes the damage to the basement of the glomerular membranes and the capillary endothelial cells. In this condition, the glomerular lesions result from the deposition or the formation of immune complexes in situ. When viewed, the kidneys are enlarging and some observable histopathological changes include swelling of the glomerular tuts and deposition of immunoglobulins. During acute glomerulonephritis, there are both structural as well as functional changes to the glomerulus. In terms of structural changes, when there is cell proliferation, the number of cells increases in the glomerular tut since the sizes of the endothelium also increases (Chiu et al., 2015). The proliferation of the leukocytes is shown through the presence of neutrophils and monocytes in the capillaries of the glomerulus. Then the thickening of the glomerulus basal membranes begins, it is manifested by the thickening of the capillary walls when viewed under the microscope.
Other causes of glomerulonephritis are the trapping of inflammatory cells such as macrophages and thrombocytes in the glomeruli. These inflammatory cells circulate and accumulate leading to the redness of the glomeruli. Infection like from bacterial agents such as the Streptococci strains can cause proliferative glomerulonephritis. These bacteria target the pharyngeal tissues leading to post infections that make the kidneys inflamed. Majority of the glomerulonephritis is caused by immunologic responses to several agents. The immunological response then activates several biological pathways like the complements and growth factors leading to glomerular injuries and inflammation. During immunological damage, the humoral response involving T helper cells is one of the etiological agents which leads to the depositions of immunoglobulins and complement activation in the glomerulus. On most occasions, the deposition of immune complexes is a result of some binding of antibodies to antigens found within the glomerulus. These antigens could be structural components of the glomerulus like the good pasture antigen which is found in the non-collagen portion of the type IV collagen of the basal membrane of the glomerulus. When the glomerulus becomes damaged, the waste materials accumulate in the body leading to vomiting, lack of sleep, swelling in the ankles, and shortness of breath. In other cases, the damage in the glomerulus may cause loss of blood and proteins through urine.
Glomerulonephritis can be fatal if not treated in time, and can be acute or chronic. In the acute glomerulonephritis, the disease occurs suddenly and may occur especially after a person has had a throat or skin infection. Some of the common symptoms linked with acute glomerulonephritis include hematuria, puffy face in the mornings, and low urination levels. The acute glomerulonephritis may not need medication but in some other cases, medication may be required in order to prevent the infections from moving to other parts of the kidneys (Artinger et al., 2017). The chronic glomerulonephritis takes several years to develop and makes renal symptoms to develop slowly across time. Some common symptoms of chronic glomerulonephritis include high blood pressure, hematuria, edema, and frequent urination during the night.
- The tubular acidosis
This is a disease which develops when the kidneys are unable to excrete acids into the urine. This causes the blood of an individual to become quite acidic, i.e. it has low pH. If there is a lack of proper treatment, chronic tubular acidity develops causing growth retardation, chronic kidney disease, total kidney failure and kidney stones (Santos, Gil-Peña, & Alvarez-Alvare, 2017). These acids are normally formed during the normal metabolism as food is turned into energy. While some level of acidity in the blood is normal, too much acids disturbs the body functions such as the acid base balance.
- Renal calculi disease
Calculi means that there are stones which have developed in the body and they are not only limited to the urinary system but to other body parts as well. They are common in the kidneys, gall bladder, gastrointestinal system and bladder where these stones cause obstruction and inflammation. Renal calculi are a solid mass that develops in the kidneys leading to the aggregation of crystals in the urine. They are considered as the most painful and common disorders of the urinary tract infections. Its formation begins when the urine is so concentrated leading to the crystallization of chemicals that should otherwise be dissolved in urine, thus forming hard mineral deposits (Wirth et al., 2014). These deposits can no longer pass in the urine and hence form kidney stones. Classes of renal calculus are based on the composition of the stones whereby these materials exceed the normal values in urine. The most common form is the calcium stones that form due to the combination between calcium and oxalate, and phosphates probably due to diet imbalance. Another type is the uric acid formed when the concentration of uric acid in urine grows too high (Ding et al., 2015).
Uric acid and calcium stones are the most common forms in men while the struvite stones are found in women. The struvite stones are formed via the combination of calcium, ammonium phosphate and magnesium ions since women have a shorter urethra and hence urinary tract infections. While the struvite stones are big enough to be visualized on x-rays, they can grow bigger and block the ureter, bladder and the kidneys. Another type is the cysteine stones which are formed as a result of a combination between cysteine, arginine and ornithine amino acids where the tubules are unable to reabsorb some amino acids. In the actual pathophysiology of the disease, the chemicals in the body accumulate in the kidneys. This is the opposite in people who have normal kidney functions since these chemicals can easily dissolve in the urine.
- Diabetic nephropathy
This is a group of neural disorders that result from damage in the nerves and arise from either one or more diabetes causes. This condition is also based on the kidney diseases of patients who have initiated the renal replacement therapy who already are type 1 or 2 diabetes (Schena & Gesualdo, 2005). Diabetic nephropathy develops from multigenetic predisposition whereby hyperglycemia in diabetes causes a direct renal damage. It does this by inducing the activation of the protein kinase C and hence increased glycosylated products and manufacture of diacylglycerols. This condition also causes the hemodynamic variations like glomerular hyper filtration, and shear stress to the kidney tissues. This form of alterations causes abnormal stimulation of the kidney cells which produces the tumor growth factor beta-1 which is in turn responsible for upregulation of glucose transporters and thus enhanced glucose transport and uptake by the cells. This growth factor is also responsible for massive deposition of extracellular matrix collagen on the glomerulus (Maezawa Takemoto, & Yokote, et al., 2015). Since the glomerulus is already thickened by the glomerulus, there is low enzymatic activities which would have degraded the collagen and other matrices, leading to their accumulation.
Diabetic nephropathy syndrome is also characterized by persistent microalbuminuria in both insulin and non-insulin dependent diabetes. Since high glucose is the sole cause of these structural changes, the diabetic nephropathy can be treated majorly by controlling glycemic levels. Alternatively, this condition can be treated by the use of transplantation of the pancreas in order to lower down the lesions of the kidneys. Other methods include the control of smoking behaviors, lipids consumption controls and controlling the blood pressure. Early treatment of glucose levels in the young adults who are suffering from diabetes has been found to increase the survival rates (Gale et al., 2005). Concerning the pancreas transplant, in a study involving serial renal biopsies Fioretto, Steffes, Sutherland, Goetz, & Mauer (1998) reported that following pancreas transplant, the thickness of the glomerular membrane base reduced gradually in a period of five to ten years.
Renal function/ biochemistry tests
This tests makes a screening for the possible presence of blood and proteins in the urine. Urinalysis can be used to screen for drug use, pregnancy, monitoring of glucose levels and urinary system disease. Thus urinalysis is a method which is used to test for the physical, chemical as well as microscopic analysis in any sample of urine from a patient. When testing for physical parameters, normal urine is yellow in color because of the presence of uribilin. However, abnormal urine appears dark orange, brown, red in color and has a cloudy appearance (Schroeder, Chang, Shen, Biondi, & Greenhow, 2015). These physical changes could be due to either presence of red or white blood cells. These abnormalities are indicative of abnormalities like infections in the liver or kidneys. Specific gravity is one of the physical parameters, that is the concentration of particles and solutes contained in the urine. High levels of specific gravity in urine could indicate diarrheas, abnormal secretion of ADH hormone and glucose in urine and in other cases renal failure. The chemical parameters in urine are tested using a dipstick which has a plastic coated with some reagent. The dipstick color then changes based on the concentrations of glucose, proteins and pH among many other parameters. The presence of bilirubin and blood cells in urine are another signal for possible infection of the kidneys and hence ineffective ultrafiltration.
- Serum creatinine
Creatinine concentration is maintained through a balance on both production as well as secretion by kidneys. The amounts of creatinine in the serum are affected by the factors that affect its production, filtration as well as eventual secretion (Wong et al., 2017). The secretion of creatinine is affected by individual features of the patients, method of testing and time of the day. Bearing in mind that creatinine is generated by the body in a steady manner, and its easily measured using blood samples, then it gives a proper estimate of the glomerular filtration rate; that is the kidney function. The normal reference ranges in men is 0.7 to 1.2 mg/dl and 0.5 to 1.0 mg/dl in women. Based on the serum creatinine measurements, the glomerular filtration rate equations are used to stage the chronic kidney disease. When high protein food like meat is eaten, it is broken down into wastes in the kidneys and the creatinine as a byproduct is filtered from the blood in urine by kidneys. However, if the kidneys are not functioning well, there could be an increased concentration of creatinine in blood because it cannot be filtered into the urine. Thus, a sample of venous blood from a patient is subjected to creatinine test analysis.
- Blood urea nitrogen
The blood urea nitrogen gives a measure of the amount of nitrogen present in the blood coming from the urea waste. The urea is a waste product which is produced after the proteins are broken whereby, the urea is formed in the liver and later passed out in the urine through the kidneys. The proteins during metabolism are broken down into amino acids which then produce ammonia, a toxic compound (Shimizu et al., 2015). Ammonia is in turn converted to urea, a less toxic compound through urea cycle and later lost in urine. Nitrogen is thus a common component of ammonia and urea and hence the name of this biochemical test. Thus, the blood urea nitrogen is done in order to determine how well the kidneys are functioning in the removal of urea from the blood into urine. In the event that the kidneys are not working well, then blood urea levels will be very high. The normal range values for blood urea nitrogen are 8 to 24 mg/dl in men and 6 to 21 mg/dl in women.
- Glomerular filtration rate
This is a test which is commonly used to measure the level of kidney functions and hence enables the staging of the kidney disease. The glomerular filtration rate test is calculated from the measurement of age, blood creatinine, gender and body size. Once the stage of the kidney disease is determined, the medical practitioners can then be able to make a proper treatment plan (Wesson, Pruszynski, Cai, & Simoni, 2017). In the event that the glomerular filtration rate is low, it means that the kidneys are not functioning well and hence the need for immediate medications. While the normal values of this parameter is estimated as 90, there are other factors like progressive aging which causes a decrease in this value even in the absence of a kidney disease. Common symptoms of this condition are blood in urine, pain in the back near the kidneys, swelling om the wrists and ankles and painful urination.
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