1.

Kidney morphology
The human kidneys:

Fig (1):- Discribe the kidney structure &morphology

Are two bean-shaped organs, one on each side of the backbone.Represent about 0.5% of the total weight of the body,but receive 2025% of the total arterial blood pumped by the heart. Each contains from one to two million nephrons.

Fig(2):-How the kidney work

2.Nephron morphology

Fig(3):-The image shows a cut section of the cortex of a mouse kidney as seen under the scanning electron microscope. Near the top (center) can be seen a Bowman's capsule with its glomerulus. Directly beneath is another Bowman's capsule with its glomerulus removed. The remainder of the field shows the lumens of both proximal and distal tubules as they have been cut at various angles.

The nephron (right) is a tube; closed at one end, open at the other. It consists of:Bowman's capsule. Located at the closed end, the wall of the nephron is pushed in forming a double-walled chamber. Glomerulus. A capillary network within the Bowman's capsule. Blood leaving the glomerulus passes into a second capillary network surrounding the loop of henle. Proximal convoluted tubule. Coiled and lined with cells carpeted with microvilli and stuffed with mitochondria. Loop of Henle. It makes a hairpin turn and returns to the Distal convoluted tubule, which is also highly coiled and surrounded by capillaries. Collecting duct. It leads to the pelvis of the kidney from where urine flows to the bladder and, periodically, on to the outside world. The Bowman's capsules are packed in the cortex of the kidney, the tubules and collecting ducts descend into the medulla.

Formation of urine
The nephron makes urine by -Filtering the blood of its small molecules and ions and then reclaiming the needed amounts of useful materials. -Surplus or waste molecules and ions are left to flow out as urine. In 24 hours the kidneys reclaim ~1,300 g of NaCl ~400 g NaHCO3 ~180 g glucose ,almost all of the 180 liters of water that entered the tubules.

The steps:
Blood enters the glomerulus under pressure. This causes water, small molecules (but not macromolecules like proteins) and ions to filter through the capillary walls into the Bowman's capsule. This fluid is called nephric Filtrate(1)

3.Kidney function

Fig(4):-The function of the kidneys

a. Filtering the blood

The kidneys remove wastes and excess water (fluid) collected by, and carried in, the blood as it flows through the body. About 190 liters (335 pints) of blood enter the kidneys every day via the renal arteries. Millions of tiny filters, called glomeruli, inside the kidneys separate wastes and water from the blood. Most of these unwanted substances come from what we eat and drink.

The kidneys automatically remove the right amount of salt and other minerals from the blood to leave just the quantities the body needs. The cleansed blood returns to the heart and recirculates through the body.Excess wastes and fluid leave the kidneys in the form of urine. Urine is stored in the bladder until it is full and then leaves the body via the urethra. Most people pass about 2 liters (4 pints) of urine every day.

b.Balancing fluid levels

By removing just the right amount of excess fluid, healthy kidneys maintain what is called the body's fluid balance. In women, fluid content stays at about 55% of total weight. In men, it stays at about 60% of total weight. The kidneys maintain these proportions by balancing the amount of fluid that leaves the body against the amount entering the body. Fluid comes into our bodies from what we drink, and from high-liquid foods such as soup. If we drink a lot, healthy kidneys remove the excess fluid and we pass a lot of urine. If we don't drink much, the kidneys retain fluid and we don't pass much urine. Fluid also leaves the body through sweat, breath, and feces. If the weather is hot and we lose a lot of fluid by sweating, then the kidneys will not pass so much urine. As your kidneys fail, maintaining this balance becomes more difficult. You may suffer symptoms of too much fluid. You may need to watch your diet and what you drink to maintain fluid balance.

c. Kidney act as endocrine organ through release hormones

1-Substance effect directly or indirectly on the vascular system One of the important functions of the kidneys is to regulate blood pressure. Healthy kidneys make hormones such as renin and angiotensin. These hormones regulate how much sodium (salt) and fluid the body keeps, and how well the blood vessels can expand and contract. This, in turn, helps control blood pressure. Kidney secret renin in case of: 1. decrease in arterial volume. 2. decrease in presentation of sodium in renal tubule . 3. hypocalemia. They helps control blood pressure by regulating: The amount of water in the body. If there is too much water in the body (fluid overload) blood pressure will go up. If there is too little water in the body (dehydration) the blood pressure will drop. The width of the arteries. The arteries constantly change in width as blood flows through them. The narrower the arteries, the higher the blood pressure. Renin helps control narrowing of the arteries. Failing kidneys often make too much renin. This raises blood pressure. If your blood pressure is high, your heart is working harder than normal to pump blood through your body.High blood pressure (also called hypertension) caused by a breakdown in these functions is common in people with kidney failure. It is also a complication, a secondary condition caused by kidney failure.(2)

2.substance stimulate production of red blood cells Healthy kidneys produce a hormone known as erythropoeitin (EPO), which stimulate erythropiosis(production of RBCs) carried in bone marrow . These cells carry oxygen throughout the body. Without enough healthy red blood cells you develop anemia, a condition which makes you feel weak, cold, tired, and short of breath.

Fig(5):-Stimulate production of red blood cells 3.substance regulate calcium metabolism kidney regulate ca+2 ,where when there is increase of ca+2 in blood and regulat hydroxylation of vit.D3 by 7-dehydrocholesterol(under skin)---------------u.v (sun light)----------cholecalciferol (vit D3)--------liver------ Vit.D3-----kidney-------- 1,25(oH)2 vitD Vit. D Help in: 1. absorbtion of ca+2 in the kidney 2.deposition of ca+2 in bone(3)

Fig(6):-Regulate calcium metabolism

4.Kidney function tests

Blood or urine is commonly collected to test for how the kidneys are functioning. Some kidney function tests include: creatine, creatinine-urine, creatine clearance, and BUN test

1. BUN test
BUN stands for blood urea nitrogen. Urea nitrogen is what forms when protein breaks down. A test can be done to measure the amount of urea nitrogen in the blood.

Normal Results 7 - 20 mg/dL. Note that normal values may vary among different laboratories. What Abnormal Results Mean? Higher-than-normal levels may be due to:

Congestive heart failure Excessive protein levels in the gastrointestinal tract Gastrointestinal bleeding Hypovolemia Heart attack Kidney disease, including glomerulonephritis, , and acute tubular necrosis Kidney failure Shock Urinary tract obstruction

Lower-than-normal levels may be due to:

Liver failure Low protein diet Malnutrition Over-hydration

Considerations For people with liver disease, the BUN level may be low even if the kidneys are normal.

2. Creatinine blood
Creatinine is a breakdown product of creatine, which is an important part of muscle. This article discusses the laboratory test to measure the amount of creatinine in the blood. Creatinine can also be measured with a urine test
Why the Test is Performed?

The test is done to evaluate kidney function. Creatinine is removed from the body entirely by the kidneys. If kidney function is abnormal, creatinine levels will increase in the blood (because less creatinine is released through your urine). Creatinine levels also vary according to a person's size and muscle mass.
Normal Results

A normal value is 0.8 to 1.4 mg/dL. Females usually have a lower creatinine than males, because they usually have less muscle mass. Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.
What Abnormal Results Mean?

Higher-than-normal levels may indicate:

Acute tubular necrosis Dehydration Diabetic nephropathy Glomerulonephritis Kidney failure Muscular dystrophy

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Pyelonephritis Reduced kidney blood flow (shock, congestive heart failure) Urinary tract obstruction

Lower-than-normal levels may indicate:

Muscular dystrophy (late stage) Myasthenia gravis

3. Creatinine clearance
Creatinine tests
A measurement of the serum creatinine level is often used to evaluate kidney function. Urine creatinine levels can be used as a screening test to evaluate kidney function, or can be part of the creatinine clearance test The creatinine clearance test compares the level of creatinine in urine with the creatinine level in the blood. (Creatinine is a breakdown product of creatine, which is an important part of muscle.) The test helps provide information on kidney function. The creatinine clearance appears to decrease with age Why the Test is Performed? The creatinine clearance test is used to estimate the glomerular filtration rate (GFR). However, because a small amount of creatinine is released by the filtering tubes in the kidneys, creatinine clearance is not exactly thto the same as the GFR. In fact, creatinine clearance usually overestimates the GFR. This is particularly true in patients with advanced kidney failure.

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Normal Results Clearance is often measured as milliliters/minute (ml/min). Normal values are:

Male: 97 to 137 ml/min. Female: 88 to 128 ml/min.

Note: Normal values ranges may vary slightly among different laboratories. What Abnormal Results Mean? Abnormal results (lower-than-normal creatinine clearance) may indicate:

Acute tubular necrosis Congestive heart failure Dehydration Glomerulonephritis Renal ischemia (blood deficiency Renal outflow obstruction (usually must affect both kidneys to reduce the creatinine clearance) Shock Acute renal failure Chronic renal failure End-stage renal disease

Considerations Factors that may interfere with the accuracy of the test are as follows:

Incomplete urine collection Pregnancy Vigorous exercise

Drugs that damage the kidneys, such as cephalosporins.

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The creatinine clearance test should only be done for patients who are medically stable. Such patients may have a rapidly changing creatinine clearance, and therefore any result may be inaccurate.(4)

5. Kidney failure
Renal failure (kidney disease) is a disease condition referring to impaired kidney function.

Types
There are 2 types of renal failure: acute and chronic.

1.acute kidney failure

Acute (sudden) kidney failure is the sudden loss of the ability of the kidneys to remove waste and concentrate urine without losing electrolytes.is an express development of decreasing kidney function, usually occurring over a period of days or several weeks. Symptoms include edema of the extremities, weight gain progressing to nausea, vomiting, seizures and coma. Other possible symptoms include fluid accumulation in the lungs (pulmonary edema) and brown cola-colored urine(5). ARF is here defined as an abrupt decline in renal function resulting in retention of nitrogenous end products of metabolism .Such adefinition includes conditions which are

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primarily non renal, such as the rise in blood urea and serum creatinine which accompanies hypovolaemic states and that due to obstruction of the urinary tract, as these conditions must always be considered in the differential diagnosis of the acutely uraemic patient. This definition does not demand that the patient be oligouric or anuric ;this reflect the realization that non-oliguric ARF is relatively common ,and probably becoming more so. The causes of ARF as defined above ,together with the commoner underlying or precipitating factor ,are listed in the table 17.1 in three main categories:pre- renal ,renal and post -renal.

Table 1:- causes of acute renal failure

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Cause

precipitating factor

Pre-renal
Reduced intravascular volume Decreased cardiac output Bleeding,excess gastrointestinal losses hepatic failure, cardiogenic shock

Post-renal
Obstructive uropathy tumors , bleeding , fibrosis and Stone

Renal
Acute tubular necrosis Nephrotoxins Glomerular disease renal ischemia , shock antibiotic , contrast media rapidly progressive Glomerulonephritis ,acute- on chronic renal failure uric acid , myeloma, papillary Necrosis , interstitial nephritis arterial thrombosis

Tubular disease

Vascular disease

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Physical examination:
Physical examination must be equally comprehensive because of the wide range of diseases which may present as ARF. A full review of possible important physical findings relating to all of the possible causes of ARF is unnecessary here, but there are a few important points which should be stressed. In identifying the broad category of ARF (renal, pre-renal or post-renal) an assessment of the state of hydration is critical. The presence of oedema or ascites speaks against the presence of hypovolaemia but does not exclude it, particularly in patients with cardiac, renal or hepatic disease on diuretic therapy. Tachycardia increased by sitting or standing, peripheral vasoconstriction, loss of skin turgor and especially an exaggerated drop in blood pressure on assuming the sitting or standing position from lying all suggest that intravascular volume is decreased. This may be supported by evidence of a recent sudden loss of weight. It should be noted, however, that as most cases of ARF are of a highly complex nature, with multiple organ damage and many contributory factors, and usually further complicated by previous administration of blood, intravenous fluids and drugs, the diagnosis of pre-renal ARF (hypovolaemia, hypoperfusion) is seldom a simple matter of clinical observation. Physical examination may also be helpful in identifying post-renal ARF (obstructive uropathy). Rectal and vaginal examinations may reveal prostatic hypertrophy or pelvic neoplasm, which are the two commonest cases of this syndrome. Evidence of a previous nephrectomy makes urinary tract obstruction more likely, and a distended bladder should be carefully sought. Actue urinary tract obstruction is usually, but not always, associated with some pain, and subacute or chronic obstruction may be quite painless. When ARF is secondary to intrinsic renal disease, the finding of hypertension, particularly if of recent onset or malignant, suggests glomerular disease, while a skin rash with arthralgias may indicate an underlying vasculitis or allergic interstitial nephritis due to drugs.

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While any of the above findings may be helpful, it must be remembered that cases of ARF are often complex, and one must guard against premature acceptance of any diagnosis on the basis of history and physical examination alone the diagnosis usually rests on further biochemical testing and some form of renal imaging.

The complications of Acute Renal Failure (ARF) can affect the entrie body, including the digestive system, heart, lungs, and nervous system. Infection is one of the most common complications of ARF, because the body's immune system may stop working properly. Uremic syndrome (uremia) is a serious complication of severe or prolonged Acuts Renal Failure. It can cause severe nausea, confusion, psychosis, irregular heart beats, and pulmonary edema (fluid in lungs). Increased potassium in the blood due to inability to filter and excrete the electrolytes properly.

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Diagnosis of ARF
Table 2:-Differential diagnosis of renal causes of acuts renal failure. Renal cause Glomerular disease Diagnostic test Red cells; red cell casts in urine: renal biopsy Radionuclide scanning; arteriography Gallium 67 scanning, eosinophilia; renal biopsy Intravenous urography; examination of tissue passed in urine.

Vascular occlusion

Acute interstitial nephritis

Papillary necrosis

2.chronic renal failure

Chronic renal failure, also known as chronic kidney disease (CKD) is characterized by a gradual worsening, or loss of normal kidney function. Developing over a period of many years, it occurs in stages ranging from very mild and moderate to severe and complete failure. It is during the later stages that CKD may progress to end-stage renal disease (ESRD) as the kidneys can no longer function as required for survival, which is below 10% of normal.

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 Note In the mild to moderate stages, those with CKD report no symptoms other than needing to frequently urinate during the night. However, as the disease progresses symptoms of uremia may develop: anorexia, mental confusion, weakness, nausea, vomiting and seizures. Uremia is due to the build up of waste products, namely urea within the blood.

Pathophysiology of chronic renal failure

The hallmark of chronic renal failure is a reduction of glomerular filtration rate. This reflects decreased nephron mass and decreased overall excretory capacity. For substances which are handled predominantly by filtration (e.g.creatinine and, to a lesser extent, urea) metabolic balance is maintained by a compensatory increase in plasma concentration. However, renal tubules have the capacity to adapt to the increased solute load per nephron, and for substance such as sodium, phosphate, potassium and hydrogen ions the rise in plasma concentration is blunted by mobilizing spare capacity of these tubular functions. Thus metabolic balance is maintained but patients are vulnerable to overload if these tubular functions are stressed further, particularly in therapeutic situations. Examples include water intoxication, volume overload (e.g. acute pulmonary oedema from excess sodium retention) and hyperkalaemia.

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Sodium and water:

The kidney retains some regulatory ability with regard to soium and water excretion. Decreased Nephron mass, overperfusion of the remaining nephrons and excessive regulatory demands in patients with chronic renal failure lead to decreased flexibility of response and a tendency to both overload and depletion in certain clinical situations. The changes in sodium reabsorption required to maintain sodium balance in a patient with stable chronic renal failure after a reduction in GFR to 5 litres per day.

Altered renal function in chronic renal failure Reduced excretory capacity Retained metabolites Overperfusion of remaining nephrons Reduced flexibility Tubular adaptation.

Intact nephron hypothesis

The similarity of adaptive processes in kidneys with predominantly glomerular and predominantly tubular damage has given rise to the concept of glomerulotubular balance. Despite considerable structural heteropgeneity there remains a basic orderliness of function so the residual residual nephrons retain a predicatable, definable and organized pattern of response. Thus it was demonstrated that in humans and animals with unilateral kidney damage, kidney functions such as free water and sodium re-absorption remained normal in each kidney if allowance was made for the reduction in GFR.

Potassium 20

Potassium balance is achieved by a marked increase in potassium secretion per nephron, aided by an increase in urine flow rate and in the delivery of sodium and non-reabsorbable anions to the distal nephron which favours potassium ion exchange and excretion. Regulatory mechanisms affecting potassium excretion are probably stimulated by changes in plasma and intracellular potassium and hydrogen ion concentration. In advanced renal failure potassium excretion exceeds filtered potassium but plasma potassium is often normal. However, Hyperkalaemia may occur suddenly if distal mechanisms for potassium excretion are compromised by a reduction in urine flow rate or sodium delivery. Some older patients and diabetics have a defect in aldosterone production and are more prone to hyperkalaemia. The same is true in patients who are given potassium sparing diuretics which block distal potassium transfer and are potentially very dangerous in renal failure.

Hydrogen ions
As GFR falls, metabolic acidosis develops and by providing a stimulus to hydrogen ion secretion enables the diseased kidney to achieve a balance between hydrogen ion production and excretion. Until the GFR falls below 20 ml per minute the defect in hydrogen ion secretion is usually well compensated; after this a progressive fall in plasma bicarbonate becomes apparent. The changes in hydrogen ion excretion occur in the context of an increased solute and phosplate load. The same factors which impair proximal sodium reabsorption may cuse an increased distal delivery of bicarbonate, with some urinary loss of bicarbonate, and failure to fully utilize other urinary buffers and to achieve maximal urinary acidification until a new steady state is reached. Hydrogen ion balance is achieved largely by increased renal ammonia production. The rate at which acidosis develops depends on protein intake (hydrogen ion load), urinary phosphate (buffer) excretion and the rate of nephron loss, which also determines the rate of adaptation. Persistent metabolic acidosis also causes gradual reduction of bone carbonate buffers and loss of calcium from bone.

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Uraemic toxins
The role of uraemic toxins in the pathogenesis of uraemic has been debated for many years. The extrarenal manifestations of uraemia dominate the clinical picture and virtually all organs are affected. It is tempting to attribute such wide spread changes to some or all of numerous metabolic products which accumulate in renal failure.

Anaemia

Fig(7):-Healthy kidneys produce a hormone called erythropoietin, or EPO, which stimulates the bone marrow to make red blood cells needed to carry oxygen throughout the body. Diseased kidneys dont make enough EPO, and bone marrow then makes fewer red blood cells.

In a group of chronic renal failure patients entering our dialysis programme plasma haemoglobin varied from 5.7-12.5g/dl.

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Although anaemia rarely warrants treatment, patient notice improvement in symptoms after renal transplantation. The anaemia is usually normocytic and normochromic, with some variation in shape of the red blood cells and few reticulocytes. The bone marrow is inappropriately normocellular in contrast to the hypercellular marrow of patients with a comparable degree of anaemia and normal renal function. Marrow iron turnover is depressed and plasma erythropoietin levels are appropriately low.the bone marrow response to erythropoietin is also impaired.Red blood cell half life is reduced; since normal cells have a reduced half-life in uraemic plasma this defect is probably due to a circulating toxin. Anemia usually worsens soon after commencement of dialysis, probably due to excessive blood taking for investigation. Predialysis haemoglobin levels are regained after 3-6 months and often rise, particularly in well-nourished patients who continue regular physical activity. Anaemia is much more severe following bilateral nephrectomy. Nowadays, long-term dialysis patients can expect to have a haemoglobin level between 9-12g/dl, particularly those on peritoneal dialysis, who have less blood loss. External source of erythropoietin, such as liver, may play a part in this. Occasional patients who develop hepatitis while on dialysis show a marked rise in haemoglobin. It is rarely necessary to treat the anaemia of chronic renal failure. Patients with incapacitating symptoms often have a correctable cause such as chronic blood loss or another disease such as corony artery disease which focuses attention on their anaemia. Therapy should be directed towards reducing blood loss, uncovering and correcting non-renal causes of anaemia, and encouraging good nutrition and regular activity. Androgen therapy may cause a small rise in haemoglobin in dialysis patients but the benefits rarely justify the use of repeated intramuscular injections. Nausea, virilization and hyperlipidaemia are common and often unacceptable side effect.

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Blood transfusion in the predialysis phase should be reserved for patients who cannot cope without it. Its effect is temporary and there is a danger of aggravating fluid overload or heart failure and further impairing renal function. On the other hand , patient awaiting transplantation are usually transfused ,as this improve the results of transplantation . In advanced renal failure bleeding time may be prolonged because of defective release of platelet factor III. Platelet aggregation, platelet adhesiveness, prothrombin consumption and prostaglandin release may all be reduced, and may contribute to skin and mucosal bleeding and the predisposition to haemorrahagic pericarditis. The prolonged bleeding time may be improved by blood transfusion or dialysis.

Renal bone disease

The major factor contributing to hypocalacemia and renal bone disease is an absolute or relative deficiency of 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D. Vitamin D3in the liver. Regulation of 25-hydroxyvitajin D3 levels is normal in renal failure although patients who hate reduced levels through malnutrition or other reasons are more likely to develop osteomalacia. The kidney regulates the further metabolism of 25-hydroxyvitamin D3 by hydrox ylation either to 1,25 dihydroxyvitamin D3, which is a potent stimulus to calcium absorption, or to other less active metabolites, normally renal hydroxylation of vitamin D is modulated according to the calcium and phosphorus needs of the body, but in renal failure deficiency of 1,25-dihydroxy-vitamin D3 causes impaired intestinal calcium absorption, hypocalcaemia, hypocalciuria, and skeletal resistance to PTH. The dual effects of hyperphosphataemia and lack of 1.25-dihydroxy-vitamin D3 by lowering plasma ionized calcium provides a stimulus or hyperparathyroidism.

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Fig(8):- Renal bone disease

Treatment to renal bone disease

Deficiency of vitamin D metabolites is also an important cause of impaired bone mineralization in renal failure, and most patients with ostcomalacia due to renal failure respond well to vitamin D therapv. However, the incidence of osteompalacial in renal failure patients varies considerably in different parts of the world and is relatively uncommon in Australia. In those patients who develop early and scvee symptomatic osteomalacial it is likely that poor nutrition, lack of other factors also contribute to the mineralization defect. Most patients with chronic renal failure of more than a few year's duration have histological evidence of bone diseae. Those with predominantly hyperparathyroidism show areas of bone resorption, increased number of osteoblasts, marrow fibrosis and increased osteoid.

Diagnosis to bone disease

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The diagnosis of established bone disease is not difficult. Overt hyperparathyroidism is indicated by hypoclacemia, hyperphosphataemia, and elevated alkaline phosphatase level and subperiosteal bone resorption which can be seen on magnified X-rays of the hands. Soft tissue is usually seen in patient with uncontrolled hyperphosphataemia. Calcification in the conjunctiva causes conjunctival irritation and around joints and acute inflammatory response which simulates gout. Vascular calcification in the small vessels of the hand usually indicates severe and prolonged hyperparathyroidism. Extensive soft tissue calcification, pulmonary calcification or ischaemic necrosis of vessels are fortunately very uncommon.

Metabolic and endocrine disturbances

The ready availability of immunossay and its application to renal failure has shown increased plasma levels of a large number of peptide hormones, including insulin, gastrin, glucagon, growth hormone ,prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH) and neutrotensin. Increased levels of hormone may be due to persistent direct stimulation of regulatory mechanism, indirect stimulation through reduced end-organ responsiveness, or decreased hormone catabolism. In many cases all three mechanisms are invoved. Persistently elevated hormone levels may also imply interference with feed-back control loops involving for instance the pituitary gland. Other hormone levels are reduced, for example erythropoietin, 1,25-dihydroxycholecalciferol and testosterone, because of destruction of hormone forming cells or their suppression by uraemic metabolites. The clinical importance of these changes varies. Three hormonal abnormalities which warrant some discussion are abnormalities of thyroid hormone, sex hormones and insulin.

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Thyroid function
Thyroid function is usually normal in patients with chronic renal failure although there may be clinical features and abnormalities of thyroid hormone which mimic hypothyroidism. There is an increased incidence of goiter, levels of protein bound iodine are low, decreased total (and sometimes free) thyroxine (T4), triiodothyronine(T3) and free thyroxin index have been reported. Although variable it appears that the plasma concentration of thyroid hormones (particularly T3) decreases progressively with increased duration of renal failure or dialysis.

Gonadal function
Infertility, menstrual abnormality, decreased libido and impotence are common in chronic renal failure. Gynaecomastia may occur in male patients but is more common in those undergoing dialysis. Many women with chronic renal failure have amenorrhoea or oligomenorrhoea and there is often reduced fertility. Furthermore, patients with advanced uremia who become pregnant have a much higher risk or abortion or premature delivery and contraceptive advice is necessary for women of childbearing age. Estrogen and progesterone levels are often low but the level of gonadotropins varies.

Insulin and glucose intolerance

Mild glucose intolerance is common in renal failure and although it is of little clinical importance this abnormality of carbohydrate metabolism has been extensively studied. Investigation have shown an increased basal insulin level, peripheral resistance to insulin, an impaired hypoglycaemic response to infused insulin and an increased and prolonged insulin response to glucose. Insulin degradation by the kidney and liver is decreased. All these abnormalities improve with dialysis and this may be partly due to improved nutrition and correction of

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potassium depletion and acidosis. Insulin requirements may decrease in diabetic patients as renal failure worsens.

Lipid metabolism
Arteriosclerosis is a common mode of death in chronic renal failure patients but its incidence has not been definitely shown to be increased. Prolonged and persistent hypertension is certainly a predisposing factor but it is questionable whether changes in lipid metabolism play a major role. The main abnormality of lipid metabolism is hypertriglyceridaemia associated with an increase in very low density lipoproteins (VLDL). This has been attributed to reduced clearance of VLDL triglyceride and to suppression of lipase activity. High density lipoproteins. (HDL) are usually low but return to normal after successful renal transplantation. The situation in chronic renal failure resembles type 4 hyperlipoproteinaemia (as seen in diabetes, obesity and patients with an increased alcohol intake ) and may be aggravated by certain drugs, such as androgens, and by excessive dietary carbohydrate. Hypercholesterolaemia is uncommon except in patient with nephritic syndrome. The abnormalities of lipid metabolism may be related to disorders of insulin production and degradation. Treatment is encouraging regular exercise and on avoidance of excess carbohydrate and drugs which may aggravate hypertriglyceridaemia.

Nitrogen metabolism
Changes in nitrogen balance include those due to uraemia, to associated malnutrition, to changes in intestinal nitrogen breakdown and to dialysis. It has been suggested that patients with chronic renal failure can reutilize urea to synthesize protein but the quantities involved are too small to be of practical significane. The normal molar ratio of plasma urea to creatinine is approximately 30: 1.

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Immunological disorders
An increased tendency to infection and reduced ability to heal wounds has been recognized for many years but is of little clinical importance in well-managed patients. There are defects in both antibody production and cellular response to antigen and in various aspects of leucocyte activity. Patients with chronic renal failure have an increased likelihood of becoming virus carriers, particularly of hepaities B and cytomeglaovirus, and have an increased incidence of cancer, both possibly related to immunological incompetence.

Cardiovascular system
Cardiovascular complications in uraemia are moat commonly due to hypertension or extracellular volume expansion. Control of these plays a vital role in conservative management and is associated with a significantly better prognosis. Extracellular volume expansion is important in the pathophysiology of hypertension but is also a compensatory mechanism which depresses proximal tubular solute reabsorption. A prmary objective in treatment is to maintain sodium balance by adjusting sodium intake to excretion and by avoiding sudden changes in extracellular volume, which may compromise renal function. Most hyper ten sive patients with chronic renal failure require antihypertensive drug therapy and blood pressure can be controlled by standard drug regimens.

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Fig(9):-

Cardiovascular system

However, once end-stage chronic renal failure supervenes, antihypertensive drugs can usually be withdrawn and blood pressure controlled by a reduction in extracellular volume. In a small proportion of dialysis patients, usually those presenting with malignant hypertension, blood pressure is more difficult to control both before and after the institution of dialysis. In these cases peripheral resistance and plasma rennin activity are often increased and sodium depletion causes severe postural hypotension. Prior to dialysis it may be necessary to employ newer agents such as angiotensin-converting enzyme inhibitors. After dialysis is started gradual ECV reduction is combined with B-adrenoreceptor blockers or (very rarely) bilateral nephrectomy. Heart failure may be caused by uncontrolled sodium retention and aggravated by anemia, preexisting coronary disease, hypertension and other metabolic derangements associated with uraemia, such as chronic elevation of parathyroid

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hormone and catecholamines. Fluid overload may also cause functional aortic insufficiency. Early diastolic murmurs require careful evaluation but do not often indicate organic valve disease and may disappear after the correction of hypertension and fluid overload. There are occasional patients with gross cardiomegaly which is not explained by the above factors. Most of these are longestablished dialysis patients and the term uraemic cardiomyopathy has been. However, this should not be taken to imply a common cause or recognized aetiology. The term uraemic retinopathy has similarly been used but the changes seen are mostly due to hypertension and arteriosclerosis, with occasional patients showing retinopathy due to cerebral oedema, anaemia, retinal vien thrombosis and other complications. In advanced uraemia, uraemic pericarditis may cause retorsternal pain, fever and a friction rub. Small pericardial effusions are often seen on equated control of extracellular volume. Pericarditis or radiologically detectable effusion is usually an indication for aggressive dialysis with reduction in extracellular volume. Bleeding due to heparin or volume de pletion. If a reduction in ECV is accompanied by hypotension without a corresponding fall in juaular venous pressure, cardiac tamponade should be suspected. The classical signs of pericardial effusion and compression are usually not present but volume repletion and drainage of the pericardium should not be delayed on this account. Although echocardiography and other techniques can be used to define left ventricular function and assess the presence of pericardial fluid, appropriate management still rests on a rapid clinical assessment of their significance. Pericarditis with fever and chest pain. This may be relieved by indomethacin but persistent pericarditis is debilitating and the risk of haemorrhage is always present. Unless there is a rapid and complete response to drugs, partial pericardectomy is advisable and effectively cures the condition.

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Central nervous system

Early treatment has made overt neurological manifestation of uraemia relatively uncommon. However, many patients experience slowing of mental function, poor memory, apathy and a reduced attention span, particularly if renal failure progresses fairly rapidly. A number of studies point to defect in the reticular activating system, which is responsible for maintaining an optimal level of arousal and affects the assimilation and processing of new information. Asterixis and myoclonic jerks are common in advanced uraemia and the latter may be a prelude to generalized convulsions

Conservative management of chronic renal failure

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Despite the success of dialysis and renal transplantation there is no doubt that most patients are better off without these forms of treatment even if renal function is quite markedly impaired. There is every reason to assess such patients thoroughly and to supervise their management with a view to delaying progression of rena failure and treating any reversible complications. Treatment of the underlying condition is of paramount importance and is dealt with under the appropriate headings elsewhere. Practical examples where dramatic changes in prognosis can be made are the treatment of malignant hypertension, cessation of analgesics in patients with analgesic nephropathy, relief of obstruction and the treatment of such conditions as systemic lupus erythematosus, goodpastures syndrome and wegeners granulomatosis. Even after chronic renal failure is established there is still much to be done to preserve renal function and improve the lifestyle of patients nearing end-stage renal failure. The most important aspects of conservative treatment are: 12345supervision and self-care: control of hypertension; maintenance of good nutrition; maintenance of fluid and electrolyte balance; prevention and treatment of bone disease.

Supervision and self

Patients with chronic renal failure should be involved in their own care as soon as possible. They should understand the cause of their disease, the anticipated rate of progression of renal failure and the things they can do to influence this. For patients with a good prognosis it may be sufficient to emphasize the importance of blood pressure control, good nutrition and sodium balance. As renal failure progresses, the need for phosphate control should be explained, as should the importance of reporting any symptoms such as headache, which may indicate or lead to a complication.

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Control of hypertension
Progression of established renal may be delayed by Control of hypertension and hyperphosphataemia. It is also possible that improved nutrition and reduction of protein load may slow the rate of deterioration. With few exceptions, the treatment of hypertension in chronic renal failure is the same as that in non-uraemic hypertensive individuals. Although a number of antihypertensive druge are excreted by the kidney, their use is simplified by the fact that there is a defined therapeutic end- point, i.e. control of blood pressure, which together with the presence of sid-effects determines the does used. Indications and contraindications for individual drugs apply but the aims of blood pressure control should be more stringent in patients with renal impairment.

Nutrition
Good nutrition remains a corner stone in the conservative management of chronic renal failure and the emphasis should be on the positive aspects of nutrition rather than an unnecessarily restricted diet. A reduced protein intake can relive symptoms such as anorexia, nausea and vomiting, and reduce the load of hydrogen ion, sulphate, phospate and potassium which the kidney has to excrete.

Fluid and electrolyte balance

Regular review of blood pressure, weigh and the state of hydration is necessary and should be more frequent as renal failure progresses. It is good practice to establish a routine of daily weighing and to teach patients the importance of maintaining sodium balance and reporting any inter-current illness, fluctuation in weight or unusual symptoms. Temporary electrolyte imbalance may worsen quite if unattended and it often saves time to admit patients to hospital to have this corrected.

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Prevention and treatment of bone disease

Although bone biopsy is necessary to accurately define the type and extent of bone disease it is an unpleasant procedure and the histological techniques are demanding. In practice many patients can be treated without recourse to biopsy. Without treatment, hyperparathyroidism progresses at a variable rate. However, if the plasma phosphate and calcium are maintained in the normal range, this may be prevented. It should be possible to control the plasma phosphate with a combination of protein restriction and phosphate binding agents but frequently these measures are not introduced early enough. If the patient is hypoclacemic, claium carbonate can be given in a dose of 1-2 g three times a day and, if this is not effective , aluminium or magnesium hydroxide may be added.

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6.Management of complications
Patients with chronic renal failure may develop complications with alter the course of the disease but many of these are reversible. Examples include acute urinary infection, septicaemia, urinary tract obstruction, gastrointestinal haemorrhage, dehydration or fluid overload with associated acute electrolyte disturbances and drug toxicity. Some of these are dealt with under the appropriate headings. These complications may be the cause of the patients initial presentation and their correction often leads to improvement which can be maintained over many years. Patients with established chronic renal failure should be encouraged to report any change in health since relatively minor intercurrent illnesses may upset the delicate balance of compensated renal failure. For instance, vomiting may be expected to cause volume depletion but at the same time the patients medications are often not taken and a vicious cycle of events is established which leads to progressive deterioration. If such patients are admitted to hospital this deterioration can be prevented by intravenous fluid replacement, the use of parentral medications and, sometimes, short periods of dialysis. Drug intoxication is a common problem. Almost all drugs or their metabolites are excreted by the kidney and chronic renal failure is a common cause of drug toxicity. No drugs should be given without a definite therapeutic indication and a knowledge of how the drug is handled in renal failure (see Ch. 26). The prescription of anti-nausea drugs is usually unjustified and the patient would be better served by a reduction in protein intake and investigation of other possible causes of nausea, such as water intoxication, drug overdose or ulcer. Similarly, patients should be encouraged to avoid regular use of sedatives. Adding drugrelated symptoms to the symptoms of uraemia does not improve the patients well being.(6)

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7. Renal failure treatment

Dialysis and Transplantation
When the function of the kidneys are no longer adequate for daily survival needs, physicians will deem haemodialysis as a necessary treatment. Haemodialysis is the process by which the blood is cleansed by way of an artificial kidney. Those receiving haemodialysis will undergo minor surgery to construct a fistula in order to obtain access. Fistulas are placed either in the arm or leg of those preparing to begin receiving haemodialysis treatment. It is through these fistulas that the blood can be gradually removed, cleansed and then returned to the body. Haemodialysis may be done in the home, in the hospital or at a haemodialysis center.

1-Heamodialysis
Fig(10):-Haemodialysis requires an artificial kidney, the dialyser, which contains the filtration membrane. Purification is achieved by exchange between the bloodstream and a dialysis bath created and controlled by a generator. This technique requires an accessible, high-flow, vascular outlet. A surgically created arterial-venous fistula on the forearm is the system of choice. The fistula is pierced by two needles for the blood outflow and inflow. 3 sessions per week are necessary. The sessions last 4 hours on average and take place in a specialised Centre, an auto-dialysis Centre, or at home after training.

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2-Peritoneal dialysis
Fig(11):-Peritoneal dialysis is carried out by filling the abdominal cavity with a sterile liquid. After a period of exchange across the peritoneal membrane, the liquid is drained off. Four, 2-litre sachets are required every day. A catheter is inserted through the abdominal wall and the abdomen is filled either manually by gravity or using an automatic machine. Sessions take place at home after training. Around 10% of dialysis is undertaken using this method which is less effective than haemodialysis.

Severe complications associated with dialysis

- Acute oedema of the lungs: excessive weight increase or overestimation of the dry weight may provoke acute oedema of the lungs due to passage of plasma into the alveoli causing progressive asphyxia. Lying down becomes impossible. There is a sensation of gasping for breath. Weight reduction by dialysis is necessary as quickly as possible. - Hyperkalaemias: a potassium restricted diet must be strictly followed when prescribed. An excess of potassium causes hyperkalaemia. This begins with a general feeling of weakness with numbness of the feet, hands and mouth. The pulse rate falls below 50/min. The heart may stop beating. Take two units of Kayexalate and contact the Centre using the numbers shown above who will act quickly

Other major complications

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- Anaemia: this is frequent and generally well controlled by EPO injection. - Accelerated cardiovascular ageing: cardiac follow up is necessary. It is strongly recommended to avoid the use of tobacco. - Hyperparathyroid: responsible for calcium and phosphorus problems. Itching may occur when phosphorus levels are too high. Bones become brittle and the blood vessels calcify.(7)

Reference
1. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/G/GITract.html#intestine 2. http://www.renalinfo.com 3. the kidney book fifth edition edited by barry M.brenner 4. http://www.nlm.nih.gov/medlineplus/ency/article/000500.htm
National Kidney Foundation National Library of Medicine National Library of Medicine

5. http://healthtools.aarp.org/adamcontent/electrolytes 6.Text book of renal disease edited by tudith A.whit worth IR lawrnce.
Adam W R, Dawborn JK, Rosenbaum M 190 Transient early diastolic murmurs in patients with renal failure. Medical Journal of Austaralia 2: 1085 1086 Alvestrand A, Furst P, Bergstrom J 1982 Plasma and muscle free amino acid in uremia. Influence of nutrition with amino acids. Clinical Nephrology 18: 297 305. Nephrology, vol. 7 Chronic renal failure. Churchill Livingstone, New York, Edinburgh, London

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Bricker N S 1972 On the pathogenesis of the uremic state, an exposition of the trade-off hypothesis. New England Journal of Medicine 286 (20): 1093 1099 Briker N S, Klahr S, Lubowitz H, Rieselbach R E 1965 Renal Function in chronic renal disease. Medicine 44 (4): 263- 288

7. www.medindia.net
References And recommended reading
Trauma 15: 1056 1063 DElia J A, Gleason R W, Alday M 1982 Nonoliguric acute renal failure associated with a low fractional excretion of sodium. Annals of internal Medicine 96: 597 600 Kennedy A C, Burton J A, Luke R G 1972 Factors affecting the prognosis in acute renal failur. Quarterly Journal of Medicine 42: 73-86 Kleinknecht D, Jungers P, Chanard J, Barvanel C, Geneval D 1972 Uremic and non-uraemic complications in acute renal failur: evaluations of early and frequent dialysis on prognosis. Kidney International: 1: 190-196 Levinsky N G 1977 Pathophysiology of acute renal failure. Myers B D, Carrie B J, Yee R R, Hilberman M. Michaels A S 1980 Pathophysiology of hemodynamically mediated acute renal failure in man. Kideny International 18: 495-504 Oken D E 1981 On thedifferential diagnosis of acute renal failure. Amercian Journal of Medicine 71: 916-920 Schrier R W 1979 Acute renal failure. Kidney International 15: 205 16 Swann R C, Merrill J P 1953 The clinical course of acute renal failure. Medicine, Baltimore 32: 215 92 Werb R, Linton A L 1979 Aetiology, diagnosis, treatment and prognosis of acute renal failure in an intensive care unit. Resucition 7: 95 - 100

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