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

2. Urinary System

4. 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 


5. 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

6. 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+ 


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

9. 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

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

11. Urinary Tract Obstruction

12. 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

13. 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

14. Uteroscopic stone removal
Kidney Stones
Uteroscopic stone removal

15. 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

16. 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

17. 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

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

19. 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

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

21. 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

22. 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

23. 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

24. Chronic Pyelonephritis

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

26. 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

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

28. 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

29. 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

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

31. Glomerulonephritis

32. 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

33. Nephrotic Syndrome

34. 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

35. 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

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

37. 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

38. 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

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

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

41. 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

42. 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

43. 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

46. Transplant Rejection Donor Kidney rejected after 16 months

47. 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

48. 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