Renal Pathology Chapter 15 Dr. Gary Mumaugh and Dr. Bruce Simat University of Northwestern - St. Paul

Urinary System

Role of Kidneys: primarily regulation or homeostasis (rather than excretion) Regulation of blood plasma and interstitial fluid composition (homeostasis), especially inorganic ions – electrolyte balance 
(e.g. Na+, K+, Cl- , Ca2+) and osmolality Regulation of body fluid volume -- fluid balance 
 Regulation of blood plasma and interstitial fluid pH 


Excretion of (non-volatile) metabolic end products (e. g Excretion of (non-volatile) metabolic end products (e.g. urea, uric acid, creatinine, NH4+) and “foreign” solutes (e.g. some drugs) 
 Note: The above are functions are vital; loss of renal function leads to debilitation beginning in about one day and terminating in death in one-two weeks

Endocrine organ secreting renin, for regulation of Na+, ECF (extracellular fluid volume), vascular resistance, erythropoietin, for regulation of erythrocyte production 
 calcitriol, related to calcium regulation 
 Metabolic functions: e.g. peptide degradation, synthesis of NH3 and H+ 


Mechanisms of Urine Formation Urine formation and adjustment of blood composition involves three major processes Glomerular filtration Tubular reabsorption Tubular secretion Figure 25.8

Urinary Tract Obstruction Urinary tract obstruction is an interference with the flow of urine at any site along the urinary tract The obstruction can be caused by an anatomic or functional defect

Urinary Tract Obstruction Severity based on: Location Completeness Involvement of one or both upper urinary tracts Duration Cause

Urinary Tract Obstruction

Upper Urinary Tract Obstruction Kidney stones Calculi or urinary stones Masses of crystals, protein, or other substances that form within and may obstruct the urinary tract Risk factors Gender, race, geographic location, seasonal factors, fluid intake, diet, and occupation Kidney stones are classified according to the minerals comprising the stones

Pathophysiology 80% of kidney stones are composed of calcium with oxalate or phosphate Kidney stones are the result of crystallization of stone-forming salts that separate from the urine Affects 5% of the population Stones vary in size from microscopic to one-inch

Uteroscopic stone removal Kidney Stones Uteroscopic stone removal

Kidney Stone Formation Supersaturation of one or more salts Presence of a salt in a higher concentration than the volume able to dissolve the salt Precipitation of a salt from liquid to solid state Temperature and pH Growth into a stone via crystallization or aggregation

Kidney Stone Formation Other factors affecting stone formation Crystal growth-inhibiting substances Particle retention Matrix Stones Calcium oxalate or calcium phosphate Struvite stones Uric acid stones

Kidney Stones Manifestation Renal colic Evaluation Stone and urine analysis Intravenous pyelogram (IVP) or kidney, ureter, bladder x-ray (KUB) Spiral abdominal CT Treatment High fluid intake, decreasing dietary intake of stone-forming substances, stone removal

Lower Urinary Tract Obstruction Neurogenic bladder Dyssynergia Detrusor hyperreflexia Detrusor areflexia Obstruction Low bladder wall compliance

Urinary Tract Infection (UTI) UTI is inflammation of the urinary epithelium caused by bacteria Acute cystitis Painful bladder syndrome/interstitial cystitis Interstitial cystitis Acute and chronic pyelonephritis

Urinary Tract Infection (UTI) Most common pathogens Escherichia coli Virulence of uropathogens Host defense mechanisms

Urinary Tract Infection (UTI) Acute cystitis Cystitis is an inflammation of the bladder Manifestations Frequency, dysuria, urgency, and lower abdominal and/or suprapubic pain Treatment Antimicrobial therapy, increased fluid intake, avoidance of bladder irritants, and urinary analgesics

Urinary Tract Infection (UTI) Interstitial cystitis Nonbacterial infectious cystitis Manifestations Most common in women 20 to 30 years old Bladder fullness, frequency, small urine volume, chronic pelvic pain Treatment No single treatment effective, symptom relief

Urinary Tract Infection (UTI) Pyelonephritis Acute pyelonephritis Acute infection of the renal pelvis interstitium Vesicoureteral reflux, E. coli, Proteus, Pseudomonas Chronic pyelonephritis Persistent or recurring episodes of acute pyelonephritis that leads to scarring Risk of chronic pyelonephritis increases in individuals with renal infections and some type of obstructive pathologic condition

Chronic Pyelonephritis

Glomerular Disorders The glomerulopathies are disorders that directly affect the glomerulus Urinary sediment changes Nephrotic sediment Nephritic sediment Sediment of chronic glomerular disease

Glomerular Disorders Glomerular disease demonstrates a sudden or insidious onset of hypertension, edema, and an elevated blood urea nitrogen (BUN) Decreased glomerular filtration rate Elevated plasma creatinine, urea, and reduced creatinine clearance

Glomerular Disorders Glomerular damage causes a decreased glomerular membrane surface area, glomerular capillary blood flow, and blood hydrostatic pressure

Glomerular Disorders Increased glomerular capillary permeability and loss of negative ionic charge barrier result in passage of plasma proteins into the urine Resulting hypoalbuminemia encourages plasma fluid to move into the interstitial spaces Edema

Glomerular Disorders Glomerulonephritis Inflammation of the glomerulus Immunologic abnormalities (most common) Drugs or toxins Vascular disorders Systemic diseases Viral causes Most common cause of end-stage renal failure

Glomerulonephritis Mechanisms of injury Deposition of circulating soluble antigen-antibody complexes, often with complement fragments Formation of antibodies against the glomerular basement membrane

Glomerulonephritis

Nephrotic Syndrome Excretion of 3.5 g or more of protein in the urine per day The protein excretion is caused by glomerular injury Findings Hypoalbuminemia, edema, hyperlipidemia, and lipiduria, and vitamin D deficiency

Nephrotic Syndrome

Acute Renal Failure (ARF) Prerenal acute renal failure Most common cause of ARF Caused by impaired renal blood flow GFR declines because of the decrease in filtration pressure

Acute Renal Failure (ARF) Intrarenal acute renal failure Acute tubular necrosis (ATN) is the most common cause of intrarenal renal failure Postischemic or nephrotoxic Oliguria Postrenal acute renal failure Occurs with urinary tract obstructions that affect the kidneys bilaterally

Acute Renal Failure (ARF) Oliguria phase Diuretic phase Recovery phase

Chronic Renal Failure Chronic renal failure is the irreversible loss of renal function that affects nearly all organ systems Stages Chronic renal insufficiency Chronic renal failure End-stage renal failure

Chronic Renal Failure Proteinuria and uremia Creatinine and urea clearance Fluid and electrolyte balance Sodium and water balance Phosphate and calcium balance Potassium balance Acid-base balance

Chronic Renal Failure Alterations seen in following systems: Musculoskeletal Cardiovascular and pulmonary Hematologic Immune Neurologic

Chronic Renal Failure Gastrointestinal Endocrine and reproduction Alteration in protein, carbohydrate, and lipid metabolism Endocrine and reproduction Integumentary

Renal Dialysis Renal Dialysis- wastes, uremia toxins, excess water are cleared from blood; electrolyte balance is restored Dialysate– dialysis fluid 2 Methods: 1. Hemodialysis–moving the patient’s blood to a hemodialyzer Extracorporeal Dialysis– dialysis outside the body 2. Peritoneal Dialysis– dialysis through the peritoneum dialysate introduced into and removed from cavity

Kidney Transplantation Obstacles Obtaining replacement kidney Working quickly to avoid ischemia damage Implantation Positioned in different area- closer to bladder Nephrectomy– kidney removal Warm Ischemic Time: Tolerate anoxia for up to 1 hr at body temp Cold Ischemic Time: Tolerate anoxia for up to 10 hrs at 4°C Pg. 416

Kidney Transplantation C. Immune Rejection (3 forms) Hyperacute Rejection- due to presence of host antibodies against donor’s red cells or renal antigens Minutes  hours after implantation Acute Rejection- recipient’s immune system attacks both nephron tubules and arteries in donated organ 2nd or 3rd week post-op Chronic Rejection– antibody against graft binds to the implant’s vascular endothelium Develops over several months

Transplant Rejection Donor Kidney rejected after 16 months

Tumors Renal tumors Renal adenomas Renal cell carcinoma (RCC) Bladder tumors Transitional cell carcinoma Gross, painless hematuria Most common in males older than 60 years

Urinary Tract Tumors Renal Cell Carcinoma Dominant, malignant renal tumor in adults Almost 90% of adult kidney cancers Prognosis is usually poor- extensive metastasis Wilms’ Tumor or Nephroblastoma Common tumor among children Prognosis usually good Surgery, radiation, or chemotherapy are usually effective