Overview of Kidney Diseases • Classified by site or cause of disease • Organization by site: • Prerenal • Intrarenal (Renal) • Postrenal
Prerenal disease • Results from inadequate blood flow to the kidney • Decreased intravascular volume • Lesions in the renal arteries • Hypotension • Systemic disorders that decrease urine output • Creatinine clearance? Plasma creatine? BUN?
Renal diseases • Result from direct damage to nephron • Glomerular disorders • Tubulointerstitial disorders – disorders of the medullary tubules and interstitial cells
Postrenal diseases • Commonly due to urinary tract obstruction • Kidney stones • Tumors of bladder, ureters or prostate gland
Obstructive Disorders • Interference with urine flow at any point • Anatomic or functional • Impedes flow proximal to blockage • Dilates urinary system • Increases risk for infection • Compromises renal function • Anatomic changes are called obstructive uropathy
Causes of obstruction • Congenital malformations • Stones • Abdominal tumor or inflammation and scarring • Tumor of urinary system or prostate • Severe pelvic organ prolapse in women
Consequences depend on: • Location of lesion • Whether one or both upper urinary tracts are involved • Severity and completeness of blockage • Duration of blockage • Nature of the lesion
Obstruction causes dilation: • Of ureters – hydroureter • Of renal pelvis and calyces – hydronephrosis • Of both - ureterohydronephrosis
There was a large renal calculus (stone) that obstructed the calyces of the lower pole of this kidney, leading to a focal hydronephrosis (dilation of the collecting system). The stasis from the obstruction and dilation led to infection. The infection with inflammation is characterized by the pale yellowish-tan areas next to the dilated calyces with hyperemic mucosal surfaces. The upper pole is normal and shows good corticomedullary demarcations.
Here is a kidney with much more advanced hydronephrosis in which there is only a thin rim of remaining renal cortex. Such a kidney is non-functional and a source for ongoing infection. If this process is unilateral, then the problem originates from the ureteral orifice up to the pelvis. In this case, a large "staghorn" calculus (so named because the prominent projections of the stone into the calyces resemble deer antlers) was present that filled up the pelvis and calyceal system. If this process were bilateral, then the problem would originate in the bladder trigone or urethra (or the prostate around the urethra) or some process (such as a large neoplasm) that could impinge on both ureters
Dilation leads to: • Enlargement and fibrosis of distal nephron in 7 days • Interference with distal and proximal nephron in 14 days • Damage to glomeruli in 28 days, also see reduction in cortex and medulla
Initial tubular damage decreases the ability to concentrate urine, causing an increase in urine volume • Affected kidney cannot conserve water, sodium, or bicarb, or excrete potassium, or hydrogen ions. • Leads to metabolic acidosis and dehydration.
Recovery depends on Completeness of blockage and duration. Complete obstruction →damage to tubules within hours, and irreversible damage within 4 weeks. • Partial recovery if removed within 56-69 days • Partial obstruction can lead to permanent impairment of ability to concentrate urine, reabsorb bicarbonate, excrete ammonia, or regulate acid-base balance.
Body can partially compensate if one kidney is affected by compensatory hypertrophy of other kidney • No increase in number of nephrons • Increase in size of glomerulus and tubules • Ability decreases with age • Is reversible if other kidney recovers
Relief of obstruction of partial obstruction of both kidneys or complete obstruction of one results in postobstructive diuresis. • Usually mild • Restores fluid and electrolyte balance • Occasionally, can result in output of 10L/day • Can cause dehydration and electrolyte imbalance
Obstruction of bladder outlet or urethra affects upper and lower tracts. • Partial obstruction can lead to over active bladder and urine retention • Can back up and cause hydroureter, hydronephrosis and impaired kidney function • Urine can be a microbiological growth medium – infection of obstructed kidney can cause further damage and scarring
Hypertension can result • Renin-angiotensin pathway in acute unilateral obstruction • Due to water and sodium and urea retention in chronic bilateral partial obstruction
Kidney stones or renal calculi • Masses of crystals, protein or other substances • Common cause of obstruction in adults • 2-3 % of U.S. population • Recurrence within 10 years is 50 %
Influenced by age, gender, race, geographic location, season, fluid intake, diet and occupation. • Seen in more men than women • Less risk if physically active and drink adequate water
Type of Stone Frequency Calcium oxalate (or phosphate) 75% Magnesium ammonium phosphate 12% (struvite, or "triple phosphate") Uric acid (Gout) 6% Cystine 1% Other 6%
Get increased concentrations of these molecules in the urine with: • Increased renal excretion of these molecules • Decreased urine volume • Change in pH of urine • Alkaline urine increases risk of calcium phosphate stones • Acid urine increases risk of uric acid stones
Size of stone determines likelihood it will be passed. • < 0.5mm 50 % chance • 1 cm almost no chance ( unless ureter dilated by previous passage) • Develop in renal tubules, calyces, ureter or bladder
Clinical manifestations • Pain (renal colic) – can determine location • Nausea / vomiting • Chills, fever • hematuria
Treatment • Urinalysis and analysis of stones • Removal by surgery/ percutaneous lithotripsy • Drugs to dissolve stones
Prevention of future stones • Treat underlying metabolic disorders • Water intake = urine output of 2 -3 L /day • Reduction in dietary oxalates and animal protein for uric acid stones • Increased dietary fiber • Do NOT decrease calcium intake – increases risk of stones
Urinary Tract infections • Bacteria most common cause • Can also be due to viruses, fungi or parasites • Classified by location in system or by complicating factors
Cystitis – inflammation of the bladder • Urinary frequency • Dysuria – painful or difficult urination • Urgency • Lower abdominal, lower back or suprapubic pain • May be uncomplicated in otherwise healthy individual
Incidence • Young adult women – 0.2/month • Lifetime risk in women 50% • Young adult men prevalence < 1% • High risk groups: • Premature infants • Sexually active women • Women using a diaphragm or spermicide • Diabetics • HIV or immunosuppressive disorders • Obstruction of lower urinary tract
Most UTIs are caused by: gram negative bacteria of the intestinal tract Escherichia coli – 80% of all uncomplicated infections. Can form pili allowing bacterium to adhere to bladder epithelium Cranberry juice decreases bacterial adhesions by epicatechin Staphylococcus saprophyticus 10-20% Other entreobacter species (Klebsiella, Proteus) remaining 5%
Treatment • Antibiotics • Drink normal amounts of water, but avoid bladder irritants, such as caffeine
Nonbacterial cystitis • Same symptoms but without infection • Dysfunction of external sphincter, urethritis, or inflammation of glands near vagina • Tx: antibiotics, drugs to relax urethral sphincter, retraining of voiding habits • Interstitial cystitis – may be due to an autoimmune reaction, mucus deficiency or abnormal mast cells.
Tubulointerstitial disorders • Acute pyelonephritis (pyelo – pelvis) • Urinary obstruction and reflux of urine most common risk factors • One or both kidneys may be involved • Most common in women • Us. E. coli, Proteus or Pseudomonas • Proteus, Pseudomonas are urea splitters • Us. By ascending microorganisms, but can be carried in blood.
Acute pyelonephritis • Inflammation is usually focal, affecting pelvis, calyces, and medulla but glomeruli not usually involved. • Kidney is infiltrated with wbc’s – pyuria • Healing involves scarring and atrophy of affected tubules
Acute pyelonephritis • Clinical manifestations: • Acute onset • Fever or chills • Flank or groin pain • Frequency and dysuria • May be difficult to distinguish from cystitis – look for white cell casts • Treatment: • Microorganism specific antibiotics
Chronic Pyelonephritis • Cause is more difficult to determine • More likely in patients with reflux or renal stones • Scarring can lead to impaired urine-concentrating ability, leading to chronic renal failure • May be due to drug toxicity from analgesics, such as phenacetin, aspirin, acetaminophen • Ischemia, radiation, immune-complex disease
Chronic Pyelonephritis • Manifestations are often minimal- • Hypertension • Frequency and Dysuria • Flank pain • Diagnosis • Urinalysis • Intravenous pyelography, ultrasound • Treatment • Relieve obstruction • antibiotics
Acute pyelonephritis At high magnification, many neutrophils are seen in the tubules and interstitium in a case of acute pyelonephritis.
Ascending bacterial infection This is an ascending bacterial infection leading to acute pyelonephritis. Numerous PMN's are seen filling renal tubules across the center and right of this picture.
Chronic pyelonephritis Both lymphocytes and plasma cells are seen at high magnification in this case of chronic pyelonephritis. It is not uncommon to see lymphocytes accompany just about any chronic renal disease: glomerulonephritis, nephrosclerosis, pyelonephritis. However, the plasma cells are most characteristic for chronic pyelonephritis.
Chronic pyelonephritis The large collection of chronic inflammatory cells here is in a patient with a history of multiple recurrent urinary tract infections. This is chronic pyelonephritis.
Glomerular disorders • Due to a change or dysfunction of the glomerular capillaries • Changes in membrane permeability • Change in GFR • Protein or blood cells in the urine • Systemic changes – hypertension; edema; acid-base and electrolyte imbalances
Glomerulonephritis • Caused by a number of factors, most commonly abnormal immune response • Infection • Toxins • Vascular diseases • Systemic diseases (diabetes mellitus) • Can be diffuse, focal or segmental • Can be membranous, proliferative, sclerotic, or crecentic • Often divided into acute, rapidly progressive and chronic forms.
Acute Glomerulonephritis • Often associated with streptococcal infection • Abrupt onset 7-10 days after strept throat or skin infection (impetigo) • Also staphylococcus or viruses • Strept antigens deposit in glomerular basement membrane and attract neutrophils and macrophages, initiating phagocytosis and release of inflammatory mediators that damage cells on both side of the basement membrane.
Poststreptococcal GN Post-streptococcal glomerulonephritis is immunologically mediated, and the immune deposits are distributed in the capillary loops in a granular, bumpy pattern because of the focal nature of the deposition process.
Proliferative GN- poststretococcal This glomerulus is hypercellular and capillary loops are poorly defined. This is a type of proliferative glomerulonephritis known as post-streptococcal glomerulonephritis.
Acute Glomerulonephritis • Symptoms occur 10-21 days after infection • Hematuria • Proteinuria • Decreased GFR, oliguria • Hypertension • Edema around eyes, feet and ankles • Ascites or pleural effusion • Biopsy – immune complexes and proliferation • Most recover without significant loss of renal function or recurrence