1. Altered Renal Function

2. Overview of Kidney Diseases
Classified by site or cause of disease
Organization by site:
Prerenal
Intrarenal (Renal)
Postrenal

3. 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?

4. Renal diseases Result from direct damage to nephron
Glomerular disorders
Tubulointerstitial disorders – disorders of the medullary tubules and interstitial cells

5. Postrenal diseases Commonly due to urinary tract obstruction
Kidney stones
Tumors of bladder, ureters or prostate gland

6. 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

7. Causes of obstruction Congenital malformations Stones
Abdominal tumor or inflammation and scarring
Tumor of urinary system or prostate
Severe pelvic organ prolapse in women

8. 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

9. Obstruction causes dilation:
Of ureters – hydroureter
Of renal pelvis and calyces – hydronephrosis
Of both - ureterohydronephrosis

11. 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.

13. 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

14. 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

15. 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.

16. 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 days
Partial obstruction can lead to permanent impairment of ability to concentrate urine, reabsorb bicarbonate, excrete ammonia, or regulate acid-base balance.

17. 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

18. 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

19. 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

20. Hypertension can result
Renin-angiotensin pathway in acute unilateral obstruction
Due to water and sodium and urea retention in chronic bilateral partial obstruction

21. 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 %

22. 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

23. Type of Stone Frequency
Calcium oxalate (or phosphate) 75%
Magnesium ammonium phosphate 12%
(struvite, or "triple phosphate")
Uric acid (Gout) 6%
Cystine %
Other %

24. 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

25. 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

26. Clinical manifestations
Pain (renal colic) – can determine location
Nausea / vomiting
Chills, fever
hematuria

27. Treatment Urinalysis and analysis of stones
Removal by surgery/ percutaneous lithotripsy
Drugs to dissolve stones

28. 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

29. 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

30. 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

31. 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

32. 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%

33. Treatment Antibiotics
Drink normal amounts of water, but avoid bladder irritants, such as caffeine

34. 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.

35. 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.

36. 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

37. 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

38. 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

39. Chronic Pyelonephritis
Manifestations are often minimal-
Hypertension
Frequency and Dysuria
Flank pain
Diagnosis
Urinalysis
Intravenous pyelography, ultrasound
Treatment
Relieve obstruction
antibiotics

40. Normal glomerulus

41. Acute pyelonephritis
At high magnification, many neutrophils are seen in the tubules and interstitium in a case of acute pyelonephritis.

42. 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.

43. 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.

44. 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.

45. 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

46. 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.

47. 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.

48. 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.

49. 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.

50. Acute Glomerulonephritis
Symptoms occur 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

51. Rapidly Progressive GN
Develops over a period of days or weeks
Primarily adults in 50’s and 60’s
May be idiopathic or assoc. with a proliferative disease
By the time of diagnosis patient has renal insufficiency
Proliferation of cells in Bowman’s space with crescent formation
Progresses to renal failure in a few weeks or months
Hematuria is common, may see proteinuria, edema or hypertension

52. RPGN
Here is another glomerulus with epithelial crescents squashing the glomerular tufts from all sides. RPGN may be idiopathic or may result from SLE, post-infectious GN (as in some cases of post-streptococcal GN), from various types of vasculitis, and from Goodpasture's syndrome.

53. RPGN
Seen here within the glomeruli are crescents composed of proliferating epithelial cells. Crescentic glomerulonephritis is known as rapidly progressive glomerulonephritis (RPGN) because this disease is very progressive. There are several causes, and in this case is due to SLE. Note in the lower left glomerulus that the capillary loops are markedly thickened (the so-called "wire loop" lesion of lupus nephritis).

54. RPGN
This immunofluorescence micrograph of a glomerulus demonstrates positivity with antibody to fibrinogen. With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen leaks into Bowman's space, leading to proliferation of the epithelial cells and formation of a crescent.

55. Goodpasture Syndrome
Antibody formation against pulmonary and glomerular capillary basement membranes
Activation of complement and neutrophils damage glomerular basement membrane
Men years of age
Pulmonary hemorrhage and renal failure

56. Goodpasture Syndrome Treatment must begin early or prognosis is poor
Anticoagulants reduce fibrin content of crescents
Plasmapheresis with steroids and immunosuppression therapy
Dialysis or transplant if kidneys fail

57. Goodpasture’s syndrome
This immunofluorescence micrograph shows positivity with antibody to IgG has a smooth, diffuse, linear pattern that is characteristic for glomerular basement membrane antibody with Goodpasture's syndrome.

58. Chronic Glomerulonephritis
Several diseases with a progressive course leading to chronic renal failure
Two patterns – deposition of antigen-antibody complexes, or antigens specific for GBM.
Complement activation and phagocyte activity damage wall of capillary and cause proliferation of extracellular matrix, affecting GFR

59. Chronic Glomerulonephritis
At first see increased membrane permeability and lose cells (hematuria) or protein into urine (proteinuria)
Fibrin is deposited into Bowman’s space –crescent formation
Renal blood flow and GFR is reduced

60. Chronic Glomerulonephritis
Clinical manifestations:
Hematuria – smoky brown-tinged urine as opposed to pink or red
Proteinuria > 3-5 g/day mostly albumin
↓ GFR leads to fluid retention and hypertension
After 10 – 20 years, renal insufficiency develops and progresses to renal failure

61. Chronic Glomerulonephritis
Treatment:
Treat underlying disease
Steroids do not change the course of the disease
Correct accompanying problems such as volume disorders, blood pressure
Ultimately dialysis or transplant

62. Nephrotic Syndrome
Defined as excretion of 3.5 or more grams of protein / day
Characteristic of glomerular injury
Also see hypoalbuminemia, edema, hyperlipidemia
Loss of immunoglobulins can increase susceptibility to infections
Decrease in vitamin D

63. Nephrotic Syndrome Treatment:
Diet – normal protein, low-fat, salt restricted
Diuretics
Immunosuppression
Protein supplements
Removal of glomerular membrane toxic factor

64. Membranous glomerulonephritis
Here is the light microscopic appearance of membranous glomerulonephritis in which the capillary loops are thickened and prominent, but the cellularity is not increased. Membranous GN is the most common cause for nephrotic syndrome in adults. Some cases of membranous GN can be linked to a chronic infectious disease such as hepatitis B, a carcinoma, or SLE, but many cases are idiopathic.

65. Nephritic Syndrome Alteration of filtration leads to loss of rbc’s
Also decreased GFR
Decreased urine output
Azotemia (increased nitrogenous wastes in the blood)
Renal tubules undergo disuse atrophy and scarring

66. Renal Failure Acute renal failure – abrupt decrease in renal function
Increase in BUN and creatinine
Usually oliguria (output < 30 ml/hour or 400 ml/day)
Most cases are reversible if diagnosed and treated early
Prerenal most common cause – failure to restore blood volume or pressure and oxygen can lead to acute tubular necrosis or acute cortical necrosis

67. Acute tubular necrosis
The tubular vacuolization and dilation here is a result of ethylene glycol poisoning. This is representative of acute tubular necrosis (ATN), which has many causes. ATN resulting from toxins usually has diffuse tubular involvement, whereas ATN resulting from ischemia (as in profound hypotension from cardiac failure) has patchy tubular involvement.

68. Acute Renal Failure Intrarenal acute renal failure
Usually due to acute tubular necrosis
Usually caused by ischemia most often after surgery ( %)
Also sepsis, burns, obstetrical complications, antibiotics, radiocontrast media, other toxic substances
Whatever the cause, get decreased GFR and oliguria

69. Acute Renal Failure Postrenal acute renal failure
Usually due to urinary tract obstruction that affects both kidneys
Characterized by several hours of anuria with flank pain, followed by polyuria

70. Acute Renal Failure
Clinical symptoms of ARF are divided into three stages:
Stage1 Oliguria:
↓urine vol.about 25 % of normal to anuria
can last 1-3 weeks ↑BUN, plasma creatinine
↑ K+ (hyperkalemia) and electrolyte imbalance
fluid retention and edema
congestive heart failure

71. Stage 2 Diuresis:
3-4 L/day of urine
Tubules still damaged, but recovering
Can lose too much Na+ and K+ May see extracellular volume depletion
Stage 3 Recovery
May take 3-12 months for plasma creatinine to return to normal
About 30 % never regain normal kidney function.

72. Acute Renal Failure Treatment Prevention if possible
Maintain individual’s life until renal function is recovered
Correct fluid and electrolyte imbalances
Treat infections
Maintain nutrition and cardiac function
Remember drugs and/or medications are not excreted!

73. Chronic Renal Failure Progressive and irreversible loss of nephrons
Slow development (years)
Alterations in salt and water balance not apparent until renal function is less than 25% of normal.
Common causes:
Chronic glomerulonephritis
Chronic pyelonephritis

74. Chronic Renal Failure
Clinical manifestations are often described using the term uremia –symptoms due to accumulation of toxins in plasma.
hypertension
Anorexia
Nausea
Vomiting
Diarrhea
Weight loss
Pruritis (itching)
Edema
Anemia
Neurologic changes

75. Chronic Renal Failure
Diagnosis is by increased BUN and serum creatinine; imaging will show small kidneys, and can be confirmed by biopsy
Management includes:
Diet control – restrict proteins, potassium
Evaluate fluid and sodium levels
Treat with erythropoietin as needed.

76. End stage kidney
The microscopic appearance of the "end stage kidney" is similar regardless of cause, which is why a biopsy in a patient with chronic renal failure yields little useful information. The cortex is fibrotic, the glomeruli are sclerotic, there are scattered chronic inflammatory cell infiltrates, and the arteries are thickened. Tubules are often dilated and filled with pink casts and give an appearance of "thyroidization."

77. Atrophy
There is a relatively normal kidney at the left with only a few scattered, shallow cortical scars and one fairly large pale tan-yellow scar in the upper pole. The left kidney is atrophic because of renal arterial occlusion. Such a situation can lead to hypertension (Goldblatt kidney).