the human renal system

8/7/2019 The Human Renal System

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Anatomy and PhysiologyReview of the organ system and its function related to illness of the client.



Blood Supply to the Kidneys



Structure of the Nephron

Renal Corpuscle



DEFI NITIO N:

T RIGO NE- the area on the floor of the urinary bladder between theopening of the urethra in front and the two ureters at the sides.

HILUM - art of an organ where structures such as blood vessels and nerves enter.

T HE H UM AN RE NAL SYSTEM

The human renal system is made up of two kidneys, two ureters, the urinary bladder, and the urethra. Inaddition to the production of urine the renal system has many other functions.

One quarter to one fifth of cardiac output passes through the kidneys at all times. This means that thekidneys filter approximately 1.2 liters of blood every minute. It is therefore not surprising that evenslight abnormalities of renal function quickly lead to electrolyte disturbances. If left untreated death willoccur.

T he KidneysThe kidneys are two bean shaped organs of the renal system located on the posterior wall of theabdomen one on each side of the vertebral column at the level of the twelfth rib. The left kidney isslightly higher than the right. Why do you think that the right kidney is lower than the left? (Q1). Human kidneys are richly supplied with blood vessels which give them their reddish brown color. Thekidneys measure about 10cm in length and, 5cm in breadth and about 2.5 cm in thickness.

The kidneys are protected by three highly specialized layers of protective tissues. The outer layerconsists mainly of connective tissue which protects the kidneys from trauma and infection. This layer isoften called the renal fascia or fibrous membrane . The technical name for this layer is the renalcapsule . The next layer (second layer from the exterior) is called the fascia and it makes a fibrouscapsule around the kidneys. This layer connects the kidneys to the abdominal wall. The inner most layeris made up of adipose tissue and is essentially a layer of fatty tissue which forms a protective cushionsthe kidney; and the renal capsule (fibrous sac) surrounds the kidney and protects it from trauma andinfection.

Blood and Nerve Supply:

The kidneys receive their oxygenated blood supply from the renal arteries which come off theabdominal portion of the aorta. Venous blood from the kidneys drains into the renal veins to join theabdominal portion of the inferior vena cava.

The hilum of the kidneys is located toward the smaller curvature. The opening in the hilum allows for

the entry and exit of blood vessels and nerves. The funnel shaped extension of the kidneys is called therenal pelvis and it connects the kidneys to the two ureters. This structure facilitates the collection of theurine from the kidneys and drainage to the urinary bladder.

The ureters are tubes that are 25-30cm long and lined with smooth muscle. These tubes help carry urineto the bladder. The muscular tissue helps force urine downwards. They enter the bladder at an angle, sourine doesn t flow up the wrong way.

T he NephronThe nephron is a functional part of the kidneys. The G lomerulus is a collection of capillaries which aresurrounded by the Bowman s capsule. The afferent arteriole enters this capsule and the efferent

arteriole leaves it. In the glomerulus the blood pressure is high and it pushes small structured moleculesout (water, salts, glucose and urea). However larger molecules (Proteins and glycogen) stay within thecapillary network. The particles which are pushed out with water (filtrate) enter the proximalconvoluted tubule. This portion is convoluted and broad. The following portion is straight and narrow;hence it is called the straight collecting tubule , also referred to as the Loop of H enle . This portion islocated in the Renal medulla.

The collecting tubule upon re-entry into the renal cortex passes by the efferent arteriole. The maculadensa is the final part of the ascending collecting tubule very closely. The filtrate is selectivelyreabsorbed in the distal broad convoluted and the proximal narrow straight tubules. Water and salts arereabsorbed in the Loop of Henle. Urine concentration occurs here. Proximal tubule is broad andconvoluted. It is located in the renal cortex. Distal tubule is narrow and straight. It forms the Loop of Henle and is located in the renal medulla.



When the filtrate arrives in the distal tubule water is reabsorbed. However, hydrogen ions, ammonia,histamines, and certain antibiotics are excreted into the distal tubule. This process is selectiveand involves the expansion of energy i.e. A TP is used up. It is called tubular excretion .

Question 2. H ow is this process different from osmosis and diffusion?

T he U rinary BladderThe urinary bladder is located midline in the abdominal pelvis. It is a pyramid shaped muscular organ.The main function of the bladder is to collect and store urine. The stored urine will be excreted throughthe urethra when the controlling sphincters are relaxed after receiving signals from the brain. In menthe urethra is much longer, is surrounded by the prostate glandand the enlargement of this gland cancause problems with the excretion of urine. The normal bladder can hold up to 500 mls of urine. Inpatients with urinary retention the bladder may be larger. The bladder has three openings, two ureteralopenings to receive urine from the kidneys, and one urethral opening to drain the urine. These openingsform the trigone of the bladder. This area is smooth and triangular shaped.

The trigone is sensitive to expansion (stretch) which occurs as the bladder fills with urine. Whenstretched to a certain degree, the urinary bladder signals the brain to empty its contents. When thereare problems with the control or sphincter muscles the patient many experience urinary incontinence.As the bladder fills more the signals become more intense.

The smooth muscle of the bladder is called the detrusor muscle . The urethral sphincter at the base of the bladder consists of ring like muscles which facilitate its opening and closing. When the bladder is fullstretch receptors in the bladder send signals to the brain. When the brain receives these signals(indicating that the bladder is full) the sphincter relaxes and urination occurs. For urination to occur thedetrusor muscle must contract and the urethral sphincter muscle must relax at the same time.

The detrusor muscle is unique in the sense that it is capable of distension to accept large quantities orurine without increasing the internal pressure. This allows much larger volumes of fluids to be collected

in the bladder (700 to 1000ml) without causing back pressure and damage to the kidneys.

The urinary bladder is supplied with arteries to supply oxygenated blood vessels. The common arterieswhich supplies the bladder are the vesical, the obturator, uterine, gluteal and vaginal arteries. A venousnetwork drains the blood to the abdominal iliac vein.

The voluntary muscles of the bladder are under the control of the Central Nervous system. The controlsare located in the brain (voluntary) and in the spinal cord (involuntary).

T he U rethraThe urethra is a tube like organ which drains urine from the bladder to the exterior. It is lined withendothelium and surrounded by involuntary muscles. In females it is about 5 to 6 cm long. Generally it is6mm wide in healthy patients. In males it is 15 to 22 cm long. It begins at the base of the bladder andextends to the tip of the penis. Since the female urethra is shorter and located close to the vagina it issubjected to frequent urinary tract infections.

The internal pudendal and vaginal arteries supply arterial blood to the urethra in females. In males theblood supply is slightly different. The inferior vesical and middle rectal arteries supply the bulk or arterialblood. The veinous return follows these blood vessels. Nerve innervation: the pudendal nerve .

Functions of the Renal SystemThe renal system has many functions. The following are the best known. Each is discussed under aseparate subtitle because the functions are varied and complex:

1. Excretion of urea, a byproduct of protein metabolism2. Regulations of the amount of water which stays in the body3. Kidneys maintain the pH balance of the human body4. Produce EPO hormone which has a role in the production of Red blood cells and s like5. Produce the enzyme rennin. This enzyme has a role in the maintenance of blood pressure.

a. U rine production and b. water regulation : These are important functions of the different parts of thenephrons. They filter blood of its small molecules and ions and make urine. During this process itreclaims useful minerals and sugars. In one day (24hrs) the kidneys reclaim 1,300 g of NaCl, 400 g of



NaHCO3 and 180 g of glucose and 180 liters of water. These are the constituents which entered thetubules during the filtration process

c. M aintain p H value of human body: The human body is designed to function optimally at a pH value of 7.35 to 7.45. Death will occur if pH drops below 6.8 or rises above 7.8. It is for this reason that pH valuesare checked frequently during acute illnesses. pH is maintained by buffers dissolved in the blood.However, the kidneys and the lungs play a vital role in removing the H+ ion from the body. MetabolicAcidosis occurs when the kidneys fail to remove the H+ ions. Respiratory acidosis occurs when the lungsfail to remove the excess of CO2 from circulation.

Question 3: Why does exercise generate H+ ?

Question 4: H ow can H+ generated in muscle cells during exercise affect the p H of the bloodthroughout the body?

d. H ormone production : Kidneys produce two hormones known as erythropoietin (EPO), and calcitriol.They also produce the enzyme known as rennin.

Erythropoietin ( EPO ): Is a hormone which is produced by the kidneys. It is needed in the bone marrowfor the formation of red blood cells. Chemically EPO is a glycoprotein with a molecular weight of 34,000.A glycoprotein is a protein with an attached sugar molecule.Highly specialized cells of the kidney which are sensitive to low oxygen levels in the blood produce EPO.The EPO subsequently stimulates the bone marrow to produce RBCs to increase O2 carrying capacity.This also leads to greater production of hb. Hb is the molecule which facilitates the transport of oxygenby the cardiovascular system.

The EPO gene is located on chromosome 7, band 7q21. Some EPO is also produced in the liver. Normallevels of EPO are 0 to 19mU/ml (milliunits per milliliter). Elevated levels of EPO indicate polycythemia.

Lower levels are seen in chronic renal failure. EPO is often prescribed to Renal Failure Patients.

=Kidneys have a role in the manufacture of vitamin D (Calcitriol)=Calcitriol is 1,25[OH]2 = Vitamin D3, the active form of vitamin D.=Vitamin D3 (Cholecalciferol): Is synthesized in skin when it is exposed to sunlight.=Vitamin D2 (Ergocalciferol) is a synthetic vitamid D derivative=Both vitamin D2 and D3 are hydroxylated in the kidneys into Calcitriol.

Vitamin D regulates Calcium and Phosphorus levels in blood by promoting their absorption from thefood in the intestines and promoting re absorption of Calcium in the kidneys.

D eficiency D isorders:Insufficient calcitriol prevents normal deposition of calcium in bone. In childhood, this produces thedeformed bones characteristic of rickets. In adults, it produces weakened bones causing osteomalacia.The commonest causes for vitamin D deficiency are inadequate dietary intake and insufficient exposureto the sun. A rare inherited mutant gene also interferes with the production of the enzyme whichconverts 25[OH] vitamin D3 into calcitriol. Some inherited rickets are also caused by two defective genesfor the calcitriol receptor.

e. Renin : Is an enzyme which is in the juxtaglomerular cells of the juxtaglomerular apparatus of therenal system. This occurs when: a. the circulating blood volume is low or b. or serum NaCl concentrarionis low. Overproduction causes hypertension and underproduction causes hypotension.

Sympathetic stimulation of Beta 1 and Alpha 1 adrenergic receptors on the JGA cells also bring about theproduction of renin. Normal concentration is 1.0 to 2.5 mg/ml.

Answer to Question 1 : This positional difference is due to the presence of the liver in the right side. Theliver pushes the right kidney down.Answer to question 2 : Osmosis and Diffusion are passive processes. There is no expenditure of energybecause the movement of water and particles occurs to balance out the gradient which existed. Once astate of equilibrium is reached there will be no net movement of water or any other particles.Answer to Question 3 : During exercise muscles use the energy stored in glucose. The oxygen is obtainedfrom the oxyhaemoglobin, as the result of this interaction CO2 and H+ ions are produced.Answer to Question 4 : How can H+ generated in muscle cells during exercise affect the pH of the bloodthroughout the body?



Kidneys ultimately remove H+ ions from the body. During exercise H+ ions are produced. If they are notremoved M etabolic Acidosis will occur. The lungs are able to get rid of the H+ ions more quickly so theyare more effective in getting rid of the H+ ions.

IntroductionBackgroundNearly all forms of acute glomerulonephritis have a tendency to progress to chronic glomerulonephritis.The condition is characterized by irreversible and progressive glomerular and tubulointerstitial fibrosis,ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy, the net result is chronic kidney disease (CKD), end-stagerenal disease (ESRD), and cardiovascular disease. The diagnosis of CKD can be made without knowledgeof the specific cause.

The National Kidney Foundation defines CKD as:(1) Evidence of kidney damage based on abnormal urinalysis results (eg, proteinuria, hematuria) orstructural abnormalities observed on ultrasound images or(2) A GFR of less than 60 mL/min for 3 or more months. Based on this definition, the National KidneyFoundation developed guidelines that classify the progression of renal disease into 5 stages, from kidneydisease with a preserved GFR to end-stage kidney failure.This classification includes treatment strategies for each progressive level, as follows:

Stage 1: This stage is characterized by kidney damage with a normal GFR ( 90 mL/min). The action planis diagnosis and treatment, treatment of comorbid conditions, slowing of the progressing of kidneydisease, and reduction of cardiovascular disease risks.

Stage 2: T

his stage is characterized by kidney damage with a mild decrease in the GFR (60-90 mL/min).The action plan is estimation of the progression of kidney disease.Stage 3: This stage is characterized by a moderately decreased GFR (30-59 mL/min). The action plan isevaluation and treatment of complications.Stage 4: This stage is characterized by a severe decrease in the GFR (15-29 mL/min). The action plan ispreparation for renal replacement therapy.Stage 5: This stage is characterized by kidney failure. The action plan is kidney replacement if the patientis uremic.

At the later stages of glomerular injury, biopsy results cannot help distinguish the primary disease.Histology and clues to the etiology are often derived from other systemic diseases, if present.Considerable cause-specific variability is observed in the rate at which acute glomerulonephritisprogresses to chronic glomerulonephritis.

PathophysiologyReduction in nephron mass from the initial injury reduces the GFR. This reduction leads to hypertrophyand hyperfiltration of the remaining nephrons and to the initiation of intraglomerular hypertension.These changes occur in order to increase the GFR of the remaining nephrons, thus minimizing thefunctional consequences of nephron loss. The changes, however, are ultimately detrimental becausethey lead to glomerulosclerosis and further nephron loss.In early renal disease (stages 1-3), a substantial decline in the GFR may lead to only slight increases inserum creatinine levels. Azotemia (ie, a rise in BUN and serum creatinine levels) is apparent when theGFR decreases to less than 60-70 mL/min. In addition to a rise in BUN and creatinine levels, the

substantial reduction in the GFR results in decreased production of:(1) Erythropoietin, thus resulting in anemia;(2) Vitamin D, resulting in hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, andrenal osteodystrophy;(3) Reduction in acid, potassium, salt, and water excretion, resulting in acidosis, hyperkalemia,hypertension, and edema; and(4) Platelet dysfunction, leading to increased bleeding tendencies.

Accumulation of toxic waste products (uremic toxins) affects virtually all organ systems. Azotemiaoccurring with the signs and symptoms listed above is known as uremia. Uremia occurs at a GFR of approximately 10 mL/min. Some of these toxins (eg, BUN, creatinine, phenols, guanidines) have beenidentified, but none has been found to be responsible for all the symptoms.



FrequencyInternationalChronic glomerulonephritis accounted for up to 40% of patients on dialysis in Japan and some Asiancountries. However, more recent data suggest that, in Japan for instance, the rate of chronicglomerulonephritis in patients on dialysis is 28%. The cause of this declining rate is not known.Concurrent with the decline in chronic glomerulonephritis in these countries is an increase in diabeticnephropathy in up to 40% of patients on dialysis.

Mortality/MorbidityESRD and death are common outcomes unless renal replacement therapy is instituted.

ClinicalHistoryThe history should focus on cause-specific symptoms to determine the causes of CKD (if unknown) andon symptoms related to uremia to determine if renal replacement therapy is needed.Cause-specific history: Obtain a cause-specific history so that further workup and management of thedisease (if systemic) can be planned.

Uremia-specific historyThe following symptoms suggest uremia:-Weakness and fatigue-Loss of energy, appetite, and weight-Pruritus-Early morning nausea and vomiting-Change in taste sensation-Reversal in sleep pattern (ie, sleepiness in daytime, wakefulness at night)-Peripheral neuropathy-Seizures

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remors-The presence of edema and hypertension suggests volume retention .-Dyspnea or chest pain that varies with position suggests fluid overload and pericarditis, respectively.-Leg cramps may suggest hypocalcemia or other electrolyte abnormalities.-Weakness, lethargy, and fatigue may be due to anemia.

Uremia-specific findings-Hypertension-Jugular venous distension (if severe volume overload is present)-Pulmonary rales (if pulmonary edema is present)-Pericardial friction rub in pericarditis-Tenderness in the epigastric region or blood in the stool (possible indicators for uremic gastritis or -enteropathy)-Decreased sensation and asterixis (indicators for advanced uremia)

CausesThe progression from acute glomerulonephritis to chronic glomerulonephritis is variable. Whereascomplete recovery of renal function is the rule for patients with poststreptococcal glomerulonephritis,several other glomerulonephritides, such as immunoglobulin A (IgA) nephropathy, often have arelatively benign course and many do not progress to ESRD.

Rapidly progressive glomerulonephritis or crescentic glomerulonephritis: Approximately 90% of patients progress to ESRD within weeks or months.

Focal segmental glomerulosclerosis: Approximately 80% of patients progress to ESRD in 10 years.Patients with the collapsing variant, which is termed malignant focal segmental glomerulosclerosis, havea more rapid progression. This form may be idiopathic or related to HIV infection.M embranous nephropathy: Approximately 20-30% of patients with membranous nephropathy progressto chronic renal failure (CRF) and ESRD in 10 years.M embranoproliferative glomerulonephritis: Approximately 40% of patients withmembranoproliferative glomerulonephritis progress to CRF and ESRD in 10 years.IgA nephropathy: Approximately 10% of patients with IgA nephropathy progress to CRF and ESRD in 10years. 1 Poststreptococcal glomerulonephritis: Approximately 1-2% of patients with poststreptococcalglomerulonephritis progress to CRF and ESRD. Older children who present with crescenticglomerulonephritis are at greatest risk.



Lupus nephritis: Overall, approximately 20% of patients with lupus nephritis progress to CRF and ESRDin 10 years; however, patients with certain histologic variants (e.g., class IV) may have a more rapiddecline.

Other Problems to Be ConsideredMesangial glomerulonephritis

WorkupLaboratory StudiesU rinalysis-The presence of dysmorphic RBCs, albumin, or RBC casts suggests glomerulonephritis as the cause of renal failure.-Waxy or broad casts are observed in all forms of CKD, including chronic glomerulonephritis.-Low urine-specific gravity indicates loss of tubular concentrating ability, an early finding in persons withCDK.-Urinary protein excretion-This can be estimated by calculating the protein-to-creatinine ratio on a spot morning urine sample.

-The ratio of urinary protein concentration (in mg/dL) to urinary creatinine (in mg/dL) reflects 24-hourprotein excretion in grams. For instance, if the spot urine protein value is 300 mg/dL and the creatininevalue is 150 mg/dL, then the ratio is 300 divided by 150, which equals 2. Thus, in this example, the 24-hour urine protein excretion is 2 g.-The estimated creatinine clearance rate is used to assess and monitor the GFR. The 2 formulas availableto calculate the value are the Cockroft-Gault formula, which estimates creatinine clearance, and theModification of Diet in Renal Disease Study (MDRD) formula, which is used to calculate the GFR.-The Cockroft-Gault formula is simple to use but overestimates the GFR by 10-15% becausecreatinine is both filtered and secreted. The MDRD formula is much more complex but is available as aPDA through the National Kidney Foundation or can be calculated online through the Hypertension,Dialysis, and Clinical Nephrology Web site.

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he estimated creatinine clearance rate is also used to monitor response to therapy and to initiate anearly transition to renal replacement therapy (eg, dialysis access placement, transplantation evaluation).-The degree of proteinuria, especially albuminuria, helps predict renal prognosis in patients with chronicglomerulonephritis. Patients with greater than 1 g/d have an increased risk of progression to ESRD.

In a study of 38 patients with chronic glomerulonephritis, Hayakawa et al examined the relationshipbetween plasma adiponectin, leptin, and proteinuria levels; glomerular filtration rate; and metabolic riskfactors. 2 They found that plasma adiponectin levels were much higher in patients with heavy proteinuria(38.8 +/- 27.8 g/mL) than they were in patients who had mild (13.3 +/- 5.1 g/mL, P <0.001) ormoderate proteinuria (18.1 +/- 8.0 g/mL, P <0.01). Serum leptin levels, however, did not differaccording to the degree of proteinuria.

CBC count-Anemia is a significant finding in patients with some decline in the GFR.-Physicians must be aware that anemia can occur even in patients with serum creatinine levels of lessthan 2 mg/dL. Even severe anemia can occur at low serum creatinine levels. Anemia is the result of marked impairment of erythropoietin production.

Serum chemistry-Serum creatinine and urea nitrogen levels are elevated.Impaired excretion of potassium, free water, and acid results in hyperkalemia, hyponatremia, and low-serum bicarbonate levels, respectively.-Impaired vitamin D-3 production results in hypocalcemia, hyperphosphatemia, and high levels of

parathyroid hormone.-Low serum albumin levels may be present if uremia interferes with nutrition or if the patient isnephrotic.-Imaging Studies-Renal ultrasonogram-Obtain a renal ultrasonogram to determine renal size, to assess for the presence of both kidneys, and toexclude structural lesions that may be responsible for azotemia.-Small kidneys often indicate an irreversible process.

PRO CEDU RESKidney biopsy-If the kidney is small, kidney biopsy is usually unnecessary; no specific pattern of disease can bediscerned at this point.



-A kidney biopsy may be considered in the minority of patients who exhibit an acute exacerbation of their chronic disease. This may be particularly pertinent to patients with preserved kidney size and inthose with lupus nephritis.

H istologic F indingsIn early stages, the glomeruli may still show some evidence of the primary disease.In advanced stages, the glomeruli are hyalinized and obsolescent. The tubules are disrupted andatrophic, and marked interstitial fibrosis and arterial and arteriolar sclerosis occur.

T reatmentM edical Care-Progression from CKD to ESRD can be slowed by a variety of measures, including aggressive control of diabetes, hypertension, and proteinuria. Dietary protein restriction, phosphate restriction, andhyperlipidemia control may have significant impact on retarding disease progression. Specific therapiesfor some glomerular diseases (eg, lupus) should be implemented in appropriate settings. Aggressivelymanage anemia and renal osteodystrophy (eg, hyperphosphatemia, hypocalcemia,hyperparathyroidism) before renal replacement therapy. Also, aggressively manage comorbid

conditions, such as heart disease and diabetes.-The target pressure for patients with proteinuria greater than 1 g/d is less than 125/75 mm Hg; forpatients with proteinuria less than 1 g/d, the target pressure is less than 130/80 mm Hg.Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used and are usually the first choice fortreatment of hypertension in patients with CRF. ACEIs are renoprotective agents that have additionalbenefits beyond lowering pressure. ACEIs effectively reduce proteinuria, in part by reducing the efferentarteriolar vascular tone, thereby decreasing intraglomerular hypertension. Particularly, ACEIs have beenshown to be superior to conventional therapy in slowing the decline of the GFR in patients with diabeticand nondiabetic proteinuric nephropathies. Therefore, consider ACEIs for treatment of evennormotensive patients with significant proteinuria. 3 -The role of angiotensin II receptor blockers (ARBs) in renal protection is increasingly being established,

and these medications have been found to retard the progression of CKD in patients with diabetic ornondiabetic nephropathy in a manner similar to that of ACEIs.-Combination therapy with ACEIs and ARBs has been shown to confer superior pressure control andpreservation of renal function than either therapy alone. Therefore, in patients without hyperkalemia oran acute rise in serum creatinine levels following the use of either therapy, combination therapy shouldbe attempted.-Diuretics are often required because of decreased free-water clearance, and high doses may berequired to control edema and hypertension when the GFR falls to less than 25 mL/min. Diuretics arealso useful in counteracting the hyperkalemic potential of ACEIs and ARBs. However, diuretics should beused with caution when given together with ACEIs or ARBs because the decline in intraglomerularpressure induced by ACEIs or ARBs may be exacerbated by volume depletion induced by diuretics,potentially precipitating acute renal failure.-Beta-blockers, calcium channel blockers, central alpha-2 agonists (e.g., clonidine), alpha-1 antagonists,and direct vasodilators (eg, minoxidil, nitrates) may be used to achieve the target pressure.-Because progressive fibrosis is the hallmark of chronic glomerulonephritis , some investigators havefocused their work on finding inhibitors of fibrosis in an attempt to slow progression. Of manycompounds, pirfenidone, an inhibitor of transforming growth factor beta, and hence of collagensynthesis, has emerged as the candidate compound. Cho et al performed an open label study on 21patients with idiopathic and post adaptive focal segmental glomerulosclerosis. 4 They found a median25% improvement in the rate of decline of the estimated GFR (P <0.01). Pirfenidone did not affectproteinuria or blood pressure. Among the adverse events attributed to therapy were dyspepsia,sedation, and photosensitive dermatitis. Pirfenidone offers hope in slowing progressive fibrosis;however, more studies are needed.

-Renal osteodystrophy can be managed early by replacing vitamin D and by administering phosphatebinders. Seek and treat nonuremic causes of anemia, such as iron deficiency, before instituting therapywith erythropoietin.-Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, renaltransplantation). Arrange permanent vascular access when the GFR decreases to less than 20-25mL/min, when the serum creatinine level is greater than 4 mg/dL, or if the rate of rise in the serumcreatinine level indicates the need for dialysis within 1 year. Arteriovenous fistulas are preferred toarteriovenous grafts because of their long-term high-patency rates and should be placed wheneverpossible. Place peritoneal dialysis catheters 2-3 weeks prior to anticipate dialysis therapy.-Treat hyperlipidemia (if present) to reduce overall cardiovascular comorbidity, even though evidencefor renal protection is lacking.-Expose patients to educational programs for early rehabilitation from dialysis or transplantation.



Surgical CareCreate access for dialysis when the GFR decreases to less than 25 mL/min.

ConsultationsNephrologists: Early referral of patients with CRF to a nephrologist is important for the management of complications and the organization of the transition to renal replacement therapy (eg, hemodialysis,peritoneal dialysis, renal transplantation). Some evidence indicates that early referral of a patient withCRF (serum creatinine, 1.5-2 mg/dL) to a nephrologist improves the short-term outcome.Surgeons: When dialysis is imminent, seek consultation for creation of an arteriovenous fistula or graftfor the insertion of a peritoneal dialysis catheter.T ransplantation surgeons: Seek consultations for evaluation for kidney transplantation.

D iet-Protein-restricted diets (0.4-0.6 g/kg/d) are controversial but may be beneficial in slowing the decline inthe GFR and in reducing hyperphosphatemia (serum phosphate, >5.5 mg/dL) in patients with serumcreatinine levels of greater than 4 mg/dL. Monitor these patients for signs of malnutrition, which maycontraindicate protein restriction.

-Educate patients about how diets rich in potassium help control hyperkalemia.-Many dietary restrictions are no longer necessary with the initiation of renal replacement therapy.

ActivityEncourage patients to increase their activity level as tolerated. Increased activity may aid in bloodpressure control.

M edicationThe goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Angiotensin -converting enzyme inhibitorsFor renoprotection. Decrease intraglomerular pressure and, consequently, glomerular protein filtration,by decreasing efferent arteriolar constriction. 3

Enalapril (Vasotec)Competitive inhibitor of ACE. Reduces angiotensin II levels, thus decreases aldosterone secretion.Decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolarconstriction.Adult2.5-10 mg PO qd; not to exceed 40 mg qd

D iureticsTreat edema and hypertension. Increase urine excretion by inhibiting sodium and chloride transporters.Furosemide (Lasix)DOC as a diuretic. Increases excretion of water by interfering with chloride-binding cotransport system,which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renaltubule.Adult1-2 mg/kg PO/IV qd/bid; not to exceed 600 mg/d0.1-0.4 mg/kg/h continuous IV infusion

Pediatric1-2 mg/kg PO/IV qd/bid; not to exceed 6 mg/kg/dose

Metolazone (Mykrox, Zaroxolyn)Treats edema in congestive heart failure. Increases excretion of sodium, water, potassium, andhydrogen ions by inhibiting reabsorption of sodium in distal tubules. May be more effective in impairedrenal function.Adult5-20 mg PO qd

Calcium channel blockersTreat hypertension, angina, and atrial fibrillation.



Amlodipine (Norvasc)Blocks slow calcium channels, causing relaxation of vascular smooth muscles.Adult2.5-10 mg PO qd

Nifedipine (Procardia)Relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improvesmyocardial oxygen delivery. SL administration generally safe, despite theoretical concerns.AdultShort-acting: 10 mg PO tidLong-acting: 30 mg PO qd; not to exceed 120-180 mg qd

Beta -adrenergic blockersCompete with beta-adrenergic agonists for available beta-receptor sites. Propranolol, nadolol, timolol,penbutolol, carteolol, sotalol, and pindolol inhibit both beta-1 receptors (located mainly in cardiacmuscle) and beta-2 receptors (located mainly in bronchial and vascular musculature), thus inhibitingchronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

Metoprolol (Lopressor)Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IVadministration, carefully monitor blood pressure, heart rate, and ECG.

Clonidine (Catapres)Stimulates presynaptic (central) alpha-2 agonist, thereby reducing norepinephrine release andperipheral vasoconstriction.

Follow -up

Further Inpatient CarePatients with CKD admitted to the hospital should have careful monitoring of weight, intake, output, andrenal function so that acute renal failure, if it occurs, can be diagnosed and treated early. All potentiallynephrotoxic agents must be adjusted for the degree of CKD. Furthermore, agents, such as nonsteroidalanti-inflammatory drugs (NSAIDs), aminoglycosides, and intravenous contrast, must be avoided, unlessthe benefits clearly outweigh the risks, because these agents are highly associated with acute renalfailure.Further Outpatient CarePatients with any evidence of kidney disease should be referred to a kidney specialist (nephrologist).Data suggest that early referral to a nephrologist improves the overall outcome. The nephrologist willusually determine the frequency of visits based on the degree of CKD.Complications

The presence of the following complications generally indicates a need for urgent dialysis:

Metabolic acidosisPulmonary edemaPericarditisUremic encephalopathyUremic gastrointestinal bleedingUremic neuropathySevere anemia and hypocalcemiaHyperkalemia

PrognosisThe prognosis depends on the type of chronic glomerulonephritis.

Patient EducationDietary education is paramount in managing patients with CKD. The typical dietary restriction is 2 g of sodium, 2 g of potassium, and 40-60 g of protein a day. Additional restrictions may apply for diabetes,hyperlipidemia, and fluid overload.Patients should be educated regarding the types of ESRD therapy. The specific choices of ESRD therapyinclude hemodialysis, peritoneal dialysis, and renal transplantation.

Patients opting for hemodialysis should be educated on home hemodialysis (ie, patients are trained todo their dialysis at home) and center hemodialysis (ie, patients must come to a center 3 times a week



for 3.5- to 4-hour dialysis sessions). They should also be educated on the types of vascular access.Arteriovenous fistulae should be created when the GFR falls below 25 mL/min or the serum creatininelevel is greater than 4 mg/dL to allow for maturation of the access prior to the initiation of dialysis.Peritoneal dialysis catheters can be placed if dialysis is anticipated within 2-3 weeks.Preemptive transplantation before the initiation of dialysis improves survival as compared withtransplantation after the initiation of dialysis; therefore, preemptive transplantation should be exploredfrom live donors. In patients without live donors, they can be placed on the deceased donor wait listwhen the GFR falls below 20 mL/min to accrue time. Patients who opt for no treatment when it isindicated should be informed of imminent renal failure in a shorter time.In the United States and most developed countries, patients on dialysis can travel. In fact, there are evendialysis cruises. However, patients should inform their social workers to make the necessaryarrangements prior to any travel to ensure that the destination has the right resources to continuedialysis.

Sexual dysfunction and loss of libido is common in patients with kidney disease, especially in men.Patients should be told to seek medical therapy if they experience these symptoms.

M iscellaneousMedicolegal PitfallsNephrotic (urinary protein excretion, >3.5 g/d) patients may have hyperlipidemia. As a part of cardiovascular health care, lipid profile should be checked and lipid-lowering therapy started forpatients with hyperlipidemia.

Steroid therapy may induce or exacerbate diabetes, hypertension, weight gain, fat redistribution in thetrunk (buffalo hump) and face (moon facies), cosmetic problems (eg, hirsutism, acne), and osteoporosis.Monitor fasting blood glucose levels and blood pressure. Obtain baseline bone densitometry values.Repeat bone densitometry for bone pain.

Oral calcium supplements (1 g/d) and vitamin D (400-800 IU/d) are recommended for prophylaxisagainst osteoporosis.

Special ConcernsRenal failure and hypertension worsen during pregnancy in patients with CKD, particularly when theserum creatinine level exceeds 2 mg/dL. The result is decreased fetal viability and increased maternalmorbidity in pregnant women with CKD. Therefore, women with CKD should consult their doctors priorto pregnancy.



ACUTE PYELO NEPH RITI S

Acute pyelonephritis is a potentially organ- and/or life-threatening infection that characteristicallycauses some scarring of the kidney with each infection and may lead to significant damage to the kidney(any given episode), kidney failure, abscess formation (e.g., nephric, perinephric), sepsis, or sepsissyndrome/shock/multi-organ system failure.

Pyelonephritis is an ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney ( nephros in Greek). If the infection is severe, the term " urosepsis " is used interchangeably(sepsis being a systemic inflammatory response syndrome due to infection). It requires antibiotics astherapy, and treatment of any underlying causes to prevent recurrence. It is a form of nephritis. It canalso be called pyelitis .

It presents with dysuria (painful voiding of urine), abdominal pain (radiating to the back on the affectedside) and tenderness of the bladder area and the side of the involved kidney (costovertebral angletenderness) which may be elicited by performing the kidney punch. In many cases there are systemicsymptoms in the form of fever, rigors (violent shivering while the temperature rises), headache,

and vomiting. In severe cases, delirium may be present.

Severe cases of pyelonephritis lead to sepsis, a systemic response to infection characterized by fever,a raised heart rate, rapid breathing and decreased blood pressure (occasionally leading to septic shock).When pyelonephritis or other urinary tract infections lead to sepsis, it is termed urosepsis .

Most cases of "community-acquired" pyelonephritis are due to bowel organisms that enter the urinarytract. Common organisms are E. coli (70-80%) and E ntero coccus fa eca lis. Hospital-acquired infectionsmay be due to coliforms and enterococci, as well as other organisms uncommon in the community(e.g. Klebsiella spp., Pseudomon a s a eruginos a ). Most cases of pyelonephritis start off as lower urinarytract infections, mainly cystitis and prostatitis.

E. coli can invade the superficial umbrella cells of the bladder to form Intracellular BacterialCommunities (IBCs), which can mature into biofilms. These Biofilm-producing e. coli are resistant toantibiotic therapy and immune system responses, and present a possible explanation for the recurrenceof UTIs, including Pyelonephritis. [2]

Risk is increased in the following situations:M echanical: any structural abnormalities to the kidneys and the urinary tract, vesicoureteralreflux (VUR) especially in young children,calculi (kidney stones), urinary tract catheterization, urinarytract stents or drainage procedures (e.g. nephrostomy), pregnancy,neurogenic bladder (e.g. due tospinal cord damage, spina bifida or multiple sclerosis) and prostate disease (e.g. benign prostatichyperplasia) in men.Constitutional: diabetes mellitus, immunocompromised statesBehavioural: change in sexual partner within the last year, spermicide usePositive family history (close family members with frequent urinary tract infections)

Pathology Acute pyelonephritis is an exudative purulent localized inflammation of the renal pelvis (collectingsystem) and kidney. The renal parenchymapresents in the interstitium abscesses (suppurative necrosis),consisting in purulent exudate (pus): neutrophils, fibrin, cell debris and central germ colonies(hematoxylinophils). Tubules are damaged by exudate and may contain neutrophil casts. In the earlystages, the glomerulus and vessels are normal. Gross pathology often reveals pathognomonic radiationsof hemorrhage and suppuration through the renal pelvis to the renal cortex. Chronic infections can

result in fibrosis and scarring.

Xanthogranulomatous pyelonephritis is a form of chronic pyelonephritis associated with granulomatousabscess formation and severe kidney destruction.

T reatment

As practically all cases of pyelonephritis are due to bacterial infections, antibiotics are the mainstay of treatment. Mild cases may be treated with oral therapy, but generally intravenous antibiotics arerequired for the initial stages of treatment. The type of antibiotic depends on local practice, and mayinclude fluoroquinolones (e.g. ciprofloxacin), beta-lactamantibiotics (e.g. amoxicillin or a cephalosporin



), trimethoprim (alone or in combination with sulfamethoxazole). Aminoglycosides are generallyavoided due to their toxicity, but may be added for a short duration.

All acute cases with spiking fevers and leukocytosis should be admitted to the hospital for IV fluidshydration and IV antibiotic treatment immediately. ciprofloxacin IV 400 mg every 12 hours is the firstline treatment of choice. Alternatively, ampicillin IV 2g every 6 hours plusgentamicin IV 1 mg/kg every 8hours also provide excellent coverage. If the patient is pregnant, ampicillin/gentamicin combination isthe treatment of choice, as ciprofloxacin is contraindicated. During the course of antibiotic treatment,serial white blood count and temperature should be closely monitored. Typically, theIV antibiotics should be continued till the patient is afebrile for at least 24 to 48 hours, then equivalentoral antibiotic agents can be given for a total of 2-week duration of treatment.

Intravenous fluids may be administered to compensate for the reduced oral intake, insensible losses(due to the raised temperature) andvasodilation and to maximize urine output. If the patient is septicsecondary to an obstructing stone, percutaneous nephrostomy is indicated for source control.

In recurrent infections, additional investigations may identify an underlying abnormality. Occasionally,

surgical intervention is necessary to reduce chances of recurrence. If no abnormality is identified, somestudies suggest long-term preventative (prophylactic) treatment with antibiotics, either daily orafter sexual intercourse. [5] In children at risk of recurrent U TIs, meta-analysis of the present literatureindicates that not enough studies have been performed to conclude prescription of long-term antibioticshave a net positive benefit. [6] Ingestion of cranberry juice has been studied as a prophylactic measure;while studies are heterogeneous, many suggest a benefit.

Some recommend other nutritional approaches to prevent recurrence of U TIs. Increasing fluid intake,consuming cranberry juice, blueberry juice, and fermented milk products containing probiotic bacteria,have been shown to inhibit adherence of bacteria to the epithelial cells of the urinary tract.

the human renal system

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