PATHOPHYSIOLOGY Name Chapter 29: Alterations of Renal and Urinary Tract Function

I. Urinary Tract Obstruction  Urinary tract obstruction is interference with the flow of urine at any site along the urinary tract. o Could be caused by many factors, including kidney stones, an enlarged prostate gland, or urethral strictures.  Obstructive uropathy - anatomic changes in the caused by obstruction. o Severity is based on location, completeness, and duration of blockage, whether one or both sides of the urinary tract is involved, and the cause. A. Upper Urinary Tract Obstruction  Blockage affecting flow through structures above the bladder.  Causes dilation of the ureter (hydroureter); renal pelvis, calyces, and the proximal renal parenchyma (hydronephrosis); or all of these (ureterohydronephrosis).  Pathophysiology: o Sustained dilation leads to enlargement and fibrosis of portions of the nephron tubule system. o The distal tubules are affected first followed by the proximal tubules. o This decreases the kidney's ability to concentrate urine, causing an increase in urine volume. o The affected kidney is unable to conserve sodium, bicarbonate, and water or to excrete hydrogen or potassium, leading to metabolic acidosis and dehydration. o The glomeruli are damaged later in the process due to increased hydrostatic pressure in the Bowman’s capsule. o This decreases the glomerular filtration rate. o As glomerular damage becomes extreme, urine volume decreases and oligouria occurs. o Irreversible damage occurs after about 4 weeks of obstruction.  Compensatory hypertrophy of the opposite kidney occurs to partially offset loss of function of the obstructed kidney (or if one kidney is removed).  Postobstructive diuresis – high urine output that follows relief of the obstruction. This may cause fluid and electrolyte imbalances. 1. Kidney stones  Nephrolithiasis – disease condition that results in formation of kidney stones, also called calculi, renal stones or urinary stones. o These are masses of crystals, protein, or other substances that form within the urinary tract.  Risk factors - age, gender, race, geographic location, seasonal factors, diet, and occupation. o Dehydration is often a contributing factor.  Kidney stones are classified according to the minerals comprising the stones. 2

 Kidney stone formation: o Kidney stones form when urine becomes supersaturated with the component material. o The component precipitates out of solution and forms a mass. o Most are calcium oxalate or calcium phosphate, but may also be struvite, uric acid or cystine. o Precipitation is most often due to changes in urine pH; may also be caused by a change in body temperature, or increased concentration of components. o Stones may remain in the renal sinus or pass into the ureter, causing obstruction.  Kidney stones are the most common cause of obstructive uropathy.  Clinical manifestation – the most common symptom is . o Renal colic - moderate to severe pain often originating in the flank and radiating to the groin, which usually indicates obstruction of the renal pelvis or proximal ureter.  Treatment - o Increased fluid intake, decreased dietary intake of stone-forming substances, stone removal. o Extracorporeal shock wave lithotripsy (ESWL) - procedure that uses ultrasonic waves to shatter simple stones in the kidney or upper urinary tract so they can pass out of system. ACTIVITY 1: What are the benefits of increased fluid intake for a person with kidney stones?

B. Lower Urinary Tract Obstruction  Blockage involving the bladder, prostate or urethra.  Clinical manifestations – involve alterations in patterns, including: o Frequent daytime voiding or voiding during the night () o Poor force or intermittency of urinary stream o Bothersome urinary urgency, sometimes with hesitancy o Incomplete bladder emptying or 1. Neurogenic bladder  Bladder dysfunction caused by neurologic disorders.  Due to a lesion in the central or peripheral nervous system that interferes with bladder control.  Prevents normal emptying and causes a functional obstruction. 2. Physical obstruction  The neck of the bladder or the urethra by be blocked by: o Kidney stones o Tumors o Prostate enlargement (most common cause of obstruction in males) 3

C. Tumors 1. Renal cell carcinoma  Most common renal neoplasm, arising from glandular or ductal structures.  Risk factors – male gender, tobacco use, obesity, and long-term analgesic use.  Clinical manifestations - hematuria (most common), flank pain, palpable flank mass, weight loss. 2. Bladder tumors  Commonly composed of transitional epithelial cells  High rate of recurrence.  Risk factors - being a man who smokes; exposure to metabolites of aniline-based dyes; and women who take large amounts of phenacetin-containing analgesic drugs. o Most common in males older than 60 years.  Clinical manifestations - gross painless hematuria (blood in urine), possible flank pain, pelvic pain, . II. Urinary Tract Infection (UTI) A. Causes of Urinary Tract Infection  UTI is inflammation of the urinary epithelium caused by retrograde movement of bacteria into the urethra and bladder.  More common in women, because of the shorter length of the urethra.  Most frequently caused by Escherichia coli bacteria (80%) from fecal matter, although other organisms may also be involved including Candida albicans, Klebsiella, Proteus, Pseudomonas, and Staphylococcus.  Defense mechanisms: o Washing out of bacteria during urination. o Acidic pH and bactericidal effects of urine. o Mucus secretion by epithelium traps bacteria. o Closure of ureterovesical junction prevents reflux of urine into the ureters and kidneys.  Recurring urinary tract infections are often the result of bacteria that have developed antibiotic resistance. B. Types of Urinary Tract Infection 1. Acute cystitis  Inflammation of the bladder, usually due to a bacterial infection.  Clinical manifestations – frequent, urgent, or painful urination (), suprapubic and low back pain; more serious cases exhibit hematuria, cloudy urine, and flank pain. 4

2. Acute pyelonephritis  Infection of the ureters, renal pelvis, and renal parenchyma.  Causes: o Most commonly due to urinary tract obstruction. o Infection is usually E. coli if underlying cause is obstruction or vesicoureteral reflux. o Infections of Proteus or Pseudomonas may occur as a result of surgical procedures.  Pathophysiology: o Microorganisms ascending along the ureters or reach kidney through the bloodstream. o Inflammation is usually focal and irregular, primarily in the pelvis, calyces, and medulla. o White blood cells infiltrate the medulla causing renal inflammation, renal edema, and purulent urine. o In severe infections, localized abscesses may extend from the medulla into the cortex. o Renal tubules are primarily affected; the glomeruli usually are spared. o Necrosis of renal papillae can develop. o After the acute phase, healing occurs with deposition of scar tissue and atrophy of affected tubules. The number of bacteria decreases until the urine again becomes sterile. o Acute pyelonephritis rarely causes renal failure.  Clinical manifestations – fever, chills, frequent or painful urination (dysuria), costovertebral angle tenderness; suprapubic, low back, and flank pain.  Treatment – antibiotic therapy. 3. Chronic pyelonephritis  Persistent or recurrent infection of the kidney leading to scarring.  May involve one or both kidneys.  Causes: o Can be due to recurrent bouts of acute pyelonephritis. o More commonly occurs in patients with renal infections associated with some type of obstructive pathologic condition, such as renal stones and vesicoureteral reflux.  Pathophysiology: o Chronic urinary tract obstruction starts a process of progressive inflammation of the renal pelvis and calyces. o Over time destruction of the tubules occurs, with atrophy or dilation and diffuse scarring. o This eventually impairs urine-concentrating ability, leading to chronic renal failure.  Clinical manifestations - early symptoms may include hypertension, urinary frequency, dysuria, and flank pain. Progression leads to renal failure.  Treatment is related to the underlying cause. Obstruction must be relieved. Antibiotics may be given, with prolonged antibiotic therapy for recurrent infection. 5

III. Glomerular Disorders  A group of related diseases of the glomerulus that can be caused by immune responses, toxins or drugs, vascular disorders, and other systemic diseases.  Most glomerular diseases are the result of type II (cell lysis) or type III (immune complex deposition) hypersensitivity reactions directed against the glomerular membrane.  Damage to the glomerulus results in changes in GFR and urinary sediment changes: o Nephrotic sediment - lots of protein, some lipids, limited or no blood (no hematuria) o Nephritic sediment - varying degrees of protein, hematuria with red and white blood cell casts o Sediment of chronic glomerular disease - limited protein and hematuria, waxy & granular casts  Severe glomerular disease may cause , hypertension, and renal failure. A. Acute Glomerulonephritis  Commonly results from damage to the glomerulus as a consequence of immune reactions after a group A beta-hemolytic streptococcal infection (acute poststreptococcal glomerulonephritis). o Often occurs 7 to 10 days after a streptococcal infection of the throat.  Pathophysiology: o Streptococcal antigen-antibody complexes deposit in the glomerular basement membrane. o This activates complement and the release of inflammatory mediators that damage endothelial and epithelial cells lying on the basement membrane. o Thickening of basement membrane results in a decreased glomerular filtration rate (GFR). o Damaged membrane allows RBCs and protein to leak into the urine.  Clinical manifestations - hematuria, RBC casts, proteinuria, decreased GFR, oliguria, hypertension, edema; occasional ascites, or pleural effusions. o Edema occurs due to loss of plasma proteins into the urine, which causes a decrease in plasma osmotic pressure. o Severe glomerulonephritis characteristically exhibits hematuria and protein loss of 3-5 g/day.  Most individuals recover without significant loss of renal function or recurrence of the disease. B. Goodpasture syndrome  A type of rapidly progressive glomerulonephritis.  A rare disease associated with antibody formation against both pulmonary capillary and glomerular basement membranes, and autoimmune destruction of the basement membranes.  Occurs most often in men 20 to 30 years of age.  Often accompanied by pulmonary hemorrhage and renal failure.  Typically, the glomerular injury is accompanied by a rapid decline in glomerular function, progressing to renal failure in a few weeks or months.  Poor prognosis if not diagnosed and treated early.

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ACTIVITY 2: Match the disorder with its cause: 1. Kidney stones a. Autoimmune attack 2. Pyelonephritis b. Bacterial infection 3. Glomerulonephritis c. Supersaturation of urine

C. Nephrotic Syndrome  Excretion of 3.5 g or more of protein in the urine per day.  The protein loss is caused by glomerular injury.  Primary nephrotic syndrome is due to certain types of glomerulonephritis (minimal change disease, focal segmented glomerulosclerosis, and membranous nephropathy).  Secondary nephrotic syndrome is due to systemic diseases, including diabetes mellitus, renal disease, and systemic lupus erythematosus, and indicates a worsening of these conditions.  Pathophysiology of nephrotic syndrome: o As protein is spilled into the urine, the intravascular albumin levels become abnormally low. o This reduces the intravascular osmotic pressure, which reduces amount of fluid pulled out of the interstitial compartment. o Fluid shifts from the vessels and into the interstitial spaces, causing generalized edema. o Hyperlipidemia and lipiduria result from the compensatory increase in synthesis of plasma proteins by the liver. The liver is unable to synthesize one type of plasma protein at a time, so lipoprotein levels increase along with albumin. o Loss of immunoglobulins may increase risk of infection.  Clinical manifestations – proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria, and decreased vitamin D (due to loss of serum transport proteins). o In contrast to acute glomerulonephritis, usually there is NOT hematuria (RBCs in urine).

ACTIVITY 3: Explain why is a frequent symptom of pyelonephritis, while oliguria is a frequent symptom of glomerulnephritis.

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IV. Renal Failure  The kidneys have enough residual capacity to adapt and prevent serious alterations in body chemistry until kidney function reaches 25% of normal.  By this time much damage has occurred to renal tissues.  Renal insufficiency - renal function is impaired to 25% of normal kidney function.  Renal failure - kidney function is significantly less than 25% of normal. A. Acute Renal Failure (ARF)  Usually accompanied by oliguria with an elevated plasma blood urea nitrogen (BUN) and plasma creatinine levels.  Classifications: o Prerenal - caused by impaired renal blood flow. . Most common cause of ARF. . Causes ischemia and necrosis of renal tissue. . GFR declines because of the decrease in filtration pressure. o Intrarenal - most commonly caused by acute tubular necrosis (ATN). . ATN is most often due to ischemia after surgery; also associated with sepsis, severe trauma or burns, and nephrotoxins like radiocontrast media and some antimicrobials. o Postrenal - associated with diseases that obstruct the flow of urine from the kidneys. . ARF occurs with bilateral obstructions (both kidneys affected).  Clinical progression - occurs in three phases: o Oliguria phase - begins within 1day of injury and lasts 1 to 3 weeks. Urine output is usually low (but may vary); BUN and plasma creatinine concentrations increase . o Diuretic phase - as renal function improves, urine volume progressively increases. During the early diuretic phase, the tubules are still damaged and unable to adequately concentrate urine. o Recovery phase – BUN and creatinine return to normal. B. Chronic Renal Failure  Chronic renal failure is a progressive, irreversible loss of renal function.  Develops as a complication of systemic diseases, such as hypertension, diabetes mellitus or system lupus erythematosus, or as a complication of many renal diseases (i.e., chronic glomerulonephritis, chronic pyelonephritis, or chronic obstructive uropathies).  All organs systems are affected by CRF.  Pathophysiology: o Occurs through a complex interaction of factors, including proteinuria and angiotensin II. o Proteinuria contributes to tubulointerstitial injury by accumulating in the interstitial space and triggering inflammation and progressive fibrosis and scarring. o Angiotension II causes vasoconstriction which causes hypertension both in the kidneys and throughout the body. This damages renal vessels, increases filtration and pushes more protein into the filtrate, contributing to the proteinuria. 8

o Over time both the renal tubules and glomeruli are damaged, interfering with normal functions. o Plasma creatinine levels gradually become elevated as GFR declines; sodium is lost in the urine; potassium is retained; acidosis develops; calcium metabolism and phosphate metabolism are altered and erythropoietin production is diminished. o Edema results from loss of protein in urine.  Stages: o Reduced renal reserve - GFR is about 50% of normal, BUN level may be elevated. o Chronic renal insufficiency - GFR is further reduced, levels of serum creatinine and BUN are mildly elevated, but usually there are no systemic symptoms. o Chronic renal failure - significant loss of renal function with systemic manifestations. o End-stage renal failure - less than 10% of renal function remains; dialysis or kidney transplant is required to sustain life.  Azotemia - refers so increased serum urea levels and, often, increased creatinine levels as well.  - a syndrome of renal failure which includes elevated blood urea and creatinine levels accompanied by fatigue, anorexia, nausea, vomiting, pruritus, and neurologic changes. o These are due to the consequences of renal failure and azotemia, including retention of toxic wastes, deficiency states, acid-base imbalance and electrolyte disorders.  Both azotemia and uremia indicate an accumulation of nitrogenous waste products in the blood.  Sequelae - alterations occur in all body systems. A sampling of problems is given below: o Osteomalacia and spontaneous bone fractures due to failure of kidneys to active vitamin D. o Anemia due to failure of kidneys to produce adequate levels of erythropoietin. o Nausea and vomiting due to inability of kidneys to excrete the by-products of protein breakdown (ammonia and urea). o Pruritis (itching) due to accumulation of calcium. o Sodium and water depletion due to kidney’s inability to reabsorb them. o Metabolic acidosis occurs due to loss of renal excretion of hydrogen. o Potassium elevation due to kidney’s inability to excrete it.  Management of Chronic Renal Failure o Life-style changes to maintain homeostasis of fluid and electrolyte balance including: . Protein restriction . Potassium restriction . Nutritional interventions to assure adequate caloric intake . Electrolyte stabilization o Dialysis - initiated based on the patient’s . . Hyperkalemia and its potential cardiac complications often is the most pressing factor in the decision to dialyze. . Typically, when the GFR falls below 15, dialysis is indicated. o Kidney transplant may ultimately be required.