Renal_Pathology in the human pathology of the kidney

Renal pathology study and diseases

1. Renal
Pathology

2. Renal Pathology Outline
Introductory
Glomerular diseases
Tubular and interstitial diseases
Diseases involving blood vessels
Cystic diseases
Tumors

3. Renal Pathology Outline
Introductory stuff

4. introduction
Functions of the urinary system
Anatomy of the kidney
Urine formation
glomerular filtration
tubular reabsorption
water conservation
Urine and renal function tests
Urine storage and elimination

5. Urinary System
Two kidneys
•Two ureters
•Urethra

6. Kidney Functions
Filters blood plasma, eliminates waste, returns useful
chemicals to blood
Regulates blood volume and pressure
Regulates osmolarity of body fluids
Secretes renin, activates angiotensin, aldosterone
controls BP, electrolyte balance
Secretes erythropoietin, controls RBC count
Regulates P
CO
2
and acid base balance
Detoxifies free radicals and drugs
Gluconeogenesis

7. Nitrogenous Wastes
Urea
proteinsamino acids NH
2removed
forms ammonia, liver converts to urea
Uric acid
nucleic acid catabolism
Creatinine
creatinine phosphate catabolism
Renal failure
azotemia: nitrogenous wastes in blood
uremia: toxic effects as wastes accumulate

8. Excretion
Separation of wastes from body fluids and
eliminating them
respiratorysystem: CO
2
integumentarysystem: water, salts, lactic acid,
urea
digestivesystem: water, salts, CO
2, lipids, bile
pigments, cholesterol
urinarysystem: many metabolic wastes, toxins,
drugs, hormones, salts, H
+
and water

9. Anatomy of Kidney
Position, weight and size
retroperitoneal, level of T12 to L3
about 160 g each
about size of a bar of soap (12x6x3 cm)
Shape
lateral surface -convex; medial -concave
CT coverings
renal fascia: binds to abdominal wall
adipose capsule: cushions kidney
renal capsule: encloses kidney like cellophane wrap

10. Blood Supply Diagram

12. Renal Corpuscle
Glomerular filtrate collects in
capsular space, flows into renal
tubule

13. Filtration Membrane
Fenestrated endothelium
70-90nm pores exclude blood cells
Basement membrane
proteoglycan gel, negative charge
excludes molecules > 8nm
blood plasma 7% protein, glomerular
filtrate 0.03%
Filtration slits
podocyte arms have pedicels with
negatively charged filtration slits, allow
particles < 3nm to pass

15. Introduction
Functions of the kidney:
excretion of waste products
regulation of water/salt
maintenance of acid/base balance
secretion of hormones
Diseases of the kidney
glomeruli
tubules
interstitium
vessels

16. •Azotemia: BUN, creatinine
•Uremia: azotemia + other complications
•Acute renal failure: oliguria
•Chronic renal failure: prolonged uremia
Introduction

17. •Hematuria
•Oliguria
•Azotemia
•Hypertension
•Diffuse edema periorbital
•Encephalophathy
•Smoky urine with
granular casts
Nephritic syndrome
•Massive proteinuria 3-
10g/24hrs
•Hypoalbuminemia
•Edema
•Hyperlipidemia/-uria
•Hypertension*
•Impaired renal function*
Nephrotic syndrome
Presentation of kidney disease

18. Renal failure
Acute and chronic Renal Failure
Acute RF
defined as an abrupt or rapid decline in renal filtration function.
This condition is usually marked by a rise in serum creatinine
concentration or by azotemia (a rise in blood urea nitrogen [BUN]
concentration)
Categories of AKI
AKI may be classified into 3 general categories, as follows:
Prerenal -as an adaptive response to severe volume depletion and
hypotension, with structurally intact nephrons
Intrinsic -in response to cytotoxic, ischemic, or inflammatory insults to
the kidney, with structural and functional damage
Postrenal -from obstruction to the passage of urine

19. conti
Classifying AKI as oliguric or nonoliguric based on daily urine excretion
has prognostic value.
Oliguria is defined as a daily urine volume of less than 400 mL/d and
has a worse prognosis, except in prerenal failure.
Anuria is defined as a urine output of less than 100 mL/d and, if abrupt
in onset, suggests bilateral obstruction or catastrophic injury to both
kidneys. Stratification of renal failure along these lines helps in
diagnosis and decision-making (eg, timing of dialysis) and can be an
important criterion for patient response to therapy.
The driving force for glomerular filtration is the pressure gradient from
the glomerulus to the Bowman space. Glomerular pressure is primarily
dependent on renal blood flow (RBF) and is controlled by combined
resistances of renal afferent and efferent arterioles. Regardless of the
cause of acute kidney injury (AKI), reductions in RBF represent a
common pathologic pathway for decreasing GFR. The etiology of AKI
consists of 3 main mechanisms.

20. Cont…
Prerenal failure -Defined by conditions with normal tubular and
glomerular function; GFR is depressed by compromised renal perfusion
Intrinsic renal failure -Includes diseases of the kidney itself,
predominantly affecting the glomerulus or tubule, which are associated
with release of renal afferent vasoconstrictors; ischemic renal injury is
the most common cause of intrinsic renal failure.
Postobstructive renal failure -Initially causes an increase in tubular
pressure, decreasing the filtration driving force; this pressure gradient
soon equalizes, and maintenance of a depressed GFR is then
dependent on renal efferent vasoconstriction

21. cotni
Pre renal failure:
1. volume depletion
Renal losses (diuretics, polyuria), GI losses (vomiting, diarrhea), Cutaneous
losses (burns, Stevens-Johnson syndrome)
Hemorrhage, Pancreatitis
2. Cardiac
Decreased cardiac output can be caused by the following:
Heart failure
Pulmonary embolus
Acute myocardial infarction
Severe valvular disease
Abdominal compartment syndrome (tense ascites)

22. Conti..
Systemic vasodilation can be caused by the following:
Sepsis, Anaphylaxis, Anesthetics, Drug overdose
Diseases that compromise renal perfusion include the following:
Decreased effective arterial blood volume -Hypovolemia, CHF, liver
failure, sepsis
Renal arterial disease -Renal arterial stenosis (atherosclerotic,
fibromuscular dysplasia), embolic disease (septic, cholesterol)

23. Intrinsic failure
Intrinsic AKI
Structural injury in the kidney is the hallmark of intrinsic AKI, and the
most common form is ATN, either ischemic or cytotoxic.
Frank necrosis is not prominent in most human cases of ATN and tends
to be patchy. Less obvious injury includes loss of brush borders,
flattening of the epithelium, detachment of cells, formation of intratubular
casts, and dilatation of the lumen ( observed in
injury to the distal nephron can also be demonstrated. In addition, the
distal nephron may become obstructed by desquamated cells and
cellular debris.

24. Conti..
causes
Renal artery obstruction (thrombosis, emboli, dissection, vasculitis)
Renal vein obstruction (thrombosis)
Microangiopathy (TTP, HUS, disseminated intravascular coagulation [DIC],
preeclampsia)
Malignant hypertension
Scleroderma renal crisis
Transplant rejection
Atheroembolic disease
Glomerular causes include the following:
Anti-glomerular basement membrane (GBM) disease (Goodpasture syndrome)
Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-
associated GN) (Wegener granulomatosis, Churg-Strauss syndrome,
microscopic polyangiitis)
Immune complex GN (lupus, postinfectious, cryoglobulinemia, primary
membranoproliferative glomerulonephritis)

25. Conti..
Tubular etiologies may include ischemia or cytotoxicity. Cytotoxic etiologies include the following:
Heme pigment (rhabdomyolysis, intravascular hemolysis)
Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C,
acyclovir, indinavir, methotrexate)
Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin, ifosfamide,
radiocontrast agents)
Interstitial causes include the following:
Drugs (penicillins, cephalosporins, NSAIDs, proton-pump inhibitors, allopurinol, rifampin,
indinavir, mesalamine, sulfonamides)
Infection (pyelonephritis, viral nephritides)
Systemic disease (Sjögren syndrome, sarcoid, lupus, lymphoma, leukemia, tubulonephritis,
uveitis)

26. Postrenal AKI
Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters,
bladder, or urethra, results in obstructive uropathy or postrenal AKI.
If the site of obstruction is unilateral, then a rise in the serum creatinine level may not be
apparent due to contralateral renal function.
Causes of obstruction include stone disease; stricture; and intraluminal, extraluminal, or
intramural tumors.
Bilateral obstruction is usually a result of prostate enlargement or tumors in men and urologic or
gynecologic tumors in women.
Patients who develop anuria typically have obstruction at the level of the bladder or downstream
to it.

27. To summarize, causes of postrenal AKI include the following:
Ureteric obstruction (stone disease, tumor, fibrosis, ligation during pelvic surgery)
Bladder neck obstruction (benign prostatic hypertrophy [BPH], cancer of the prostate [CA
prostate or prostatic CA], neurogenic bladder, tricyclic antidepressants, ganglion blockers,
bladder tumor, stone disease, hemorrhage/clot)
Urethral obstruction (strictures, tumor, phimosis)
Intra-abdominal hypertension (tense ascites)
Renal vein thrombosis
Diseases causing urinary obstruction from the level of the renal tubules to the urethra
include the following:
Tubular obstruction from crystals (eg, uric acid, calcium oxalate, acyclovir, sulfonamide,
methotrexate, myeloma light chains)
Ureteral obstruction -Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol,
hydralazine), urolithiasis, or papillary necrosis
Urethral obstruction -Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal
carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder; or
stricture

28. Morphology
Enlarged kidneys with edema
Pale cortex
Congested medulla and dark in colour with
accentuation of the cm junction
Microscopically: tubular necrosis, rapture of
basement membrane, wit variable inflammatory
reaction
Proteinaceous eosinophilic casts
Interstitial oedema

29. Chronic Renal failure
The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney
Foundation (NKF) defines chronic kidney disease as either kidney damage or a
decreased glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m
2
for 3 or
more months
The destruction of renal mass with irreversible sclerosis and loss of nephrons leads to
a progressive decline in GFR. The different stages of chronic kidney disease form a
continuum in time.
In 2002, K/DOQI published its classification of the stages of chronic kidney disease,
as follows:
Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m
2
)
Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m
2
)
Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m
2
)
Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m
2
)
Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m
2
or dialysis)


30. Conti..
Approximately 1 million nephrons are present in each kidney, each contributing to the total
GFR. In the face of renal injury (regardless of the etiology), the kidney has an innate ability to
maintain GFR, despite progressive destruction of nephrons, by hyperfiltration and
compensatory hypertrophy of the remaining healthy nephrons.
This nephron adaptability allows for continued normal clearance of plasma solutes.
Plasma levels of substances such as urea and creatinine start to show significant increases
only after total GFR has decreased to 50%, when the renal reserve has been exhausted.
The plasma creatinine value will approximately double with a 50% reduction in GFR. A rise in
plasma creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still
within the reference range, actually represents a loss of 50% of functioning nephron mass.
The hyperfiltration and hypertrophy of residual nephrons represent a major cause of
progressive renal dysfunction. This is due to increased glomerular capillary pressure, which
damages the capillaries and leads to secondary focal and segmental glomerulosclerosis and
eventually to global glomerulosclerosis.

31. Conti..
Factors other than the underlying disease process and
glomerular hypertension that may cause progressive renal
injury include the following:
Systemic hypertension
Acute insults from nephrotoxins or decreased perfusion
Proteinuria
Increased renal ammoniagenesis with interstitial injury
Hyperlipidemia
Hyperphosphatemia with calcium phosphate deposition
Decreased levels of nitrous oxide
Smoking
Uncontrolled diabetes

32. contiii
Causes of chronic kidney disease include the following:
Diabetic kidney disease
Hypertension
Vascular disease
Glomerular disease (primary or secondary)
Tubulointerstitial disease
Urinary tract obstruction
Vascular diseases that can cause chronic kidney disease include the following:
Renal artery stenosis
Cytoplasmic pattern antineutrophil cytoplasmic antibody (C-ANCA)–positive and perinuclear
pattern antineutrophil cytoplasmic antibody (P-ANCA)–positive vasculitides
Antineutrophil cytoplasmic antibody (ANCA)–negative vasculitides
Atheroemboli
Hypertensive nephrosclerosis
Renal vein thrombosis
Unrecovered acute kidney injury

33. Conti..
Primary glomerular diseases include the following:
Membranous nephropathy
Immunoglobulin A (IgA) nephropathy
Focal and segmental glomerulosclerosis (FSGS)
Minimal change disease
Membranoproliferative glomerulonephritis
Rapidly progressive (crescentic) glomerulonephritis Secondary causes of glomerular
disease include the following:
Diabetes mellitus, Systemic lupus erythematosus, Rheumatoid arthritis, Mixed connective tissue
disease, Scleroderma, Goodpasture syndrome, Wegener granulomatosis, Mixed
cryoglobulinemia, Postinfectious glomerulonephritis, Endocarditis,Hepatitis B and C,Syphilis,
Human immunodeficiency virus (HIV), Parasitic infection, Heroin use, Gold, Penicillamine,
Amyloidosis, Light chain deposition disease,Neoplasia,Thrombotic thrombocytopenic purpura
(TTP),Hemolytic-uremic syndrome (HUS),Henoch-Schönlein purpura, Alport syndrome
Reflux nephropathy

34. Conti..
Urinary tract obstruction may result from any of the following:
Urolithiasis
Benign prostatic hypertrophy
Tumors
Retroperitoneal fibrosis
Urethral stricture
Neurogenic bladder

35. Morphology
Varied with loss of nephrones, fibrosis, vascular
involvement
The kidney is contracted and capsule may be
adherent
Attenuaton of the corticomedullary jc

39. Renal Pathology Outline
Introductory stuff
Glomerular diseases

41. Normal glomerulus

42. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Nephritic syndrome
Postinfectious GN
IgA nephropathy

43. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome

44. Symptoms of Nephrotic Syndrome
Massive proteinuria
Hypoalbuminemia
Edema
Hyperlipidemia, lipiduria

45. Causes of nephrotic syndrome
Glomerular disease: minimal change,
membrane,focal,mesangiocapillary,diffuse
proliferative, focal glomerulonephritis
Systemic disease: Dm, Amyloidosis, sle,infections
malaria, IE, Malignancies; myeloma, lymphoma
Drugs: gold, pencilamine

46. morphology
Kidney enlargement
Pallor due to edema,yellow radial streaking due
to ilipids, accumulation of foamy macrophages
lipid laden, hyaline droplets,
Effacement of foot processes of the epithelial
cells with the cytoplasm closely applied

47. Causes of Nephrotic Syndrome
Adults: systemic disease (diabetes)
Children: minimal change disease
Characterized by loss of foot processes

48. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome
Minimal change disease

49. pathogenesis
Immunological basis:
Deposition of immune complexes at the capillary
walls, trapped,
Directed to the basement membranes
or form intrinsically wit constituents of the
basement membrane. Circulating antibodies

50. Mechanism of injury
activation of the compliment, activating
macrophages to phagocytose
Activation of the coagulation cascade, fibrin is
deposited to the lumina
Cell mediated injury
Manifestation:
hypercellularity,
thickening of the basement membrane,
crescent formation

51. Minimal Change Disease
#1 cause of nephrotic syndrome in children
There is Loss and fusion of foot processes of
the epithelial cells
The glomerulus appear normal, except
dilatation of some capillaries, vacuolation of
epithelial cells and thickening of basement
membrane
Pathogenesis unknown but ass with HD,
NHD,
Good prognosis

52. Minimal change disease

53. Normal glomerulus

54. Minimal change disease

55. Minimal change disease

56. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephroticsyndrome
Minimal change disease
Focal segmental glomerulosclerosis

57. Focal Segmental Glomerulosclerosis
10-20% NS
Non selective proteinuria with hematuria and hypertension
None response to steroids
Primary or secondary
Some (focal) glomeruli show partial (segmental) hyalinization
with sclerosis with obliteration of capillaries with associated
with tubular atrophy
Unknown pathogenesis
Poor prognosis, progressing to RF

58. Focal segmental glomerulosclerosis

59. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephroticsyndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy

60. Membranous Nephropathy
10 yr, reach peak at middle to elderly
Present with NS, ascitis, pleural effusion
Show diffuse hyaline thickening of the walls of all
capillaries resulting to low BF, low GFR, HTN then
uraemia
Autoimmune reaction against unknown renal antigen but
association with malaria, syphillis, malignant lesion,
HBV,drugs such as captopril, pencillamine and gold have
been documented.
Ig G, Immune complexes deposition
Thickened GBM
Subepithelial deposits/spikes

61. Membranous nephropathy

62. Membranous nephropathy

63. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Nephritic syndrome

64. Symptoms of Nephritic Syndrome
Hematuria
Oliguria, azotemia
Hypertension

65. Causes of Nephritic Syndrome
Post-infectious GN, IgA nephropathy
Immunologically-mediated
Characterized by proliferative changes
and inflammation

66. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Nephritic syndrome
Postinfectious GN

67. Post-Infectious Glomerulonephritis
Child after strep throat
Immune complexes
Hypercellular glomeruli
Subepithelialhumps
Things You Must Know

68. Post-Infectious Glomerulonephritis
“Sore throat, face bloat, pee coke”

69. Post-infectious glomerulonephritis

70. Post-infectious glomerulonephritis

71. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Nephritic syndrome
Postinfectious GN
IgA nephropathy

72. IgA Nephropathy
Common!
Child with recurrent hematuria
Occur after infection of mucosal surfaces with ig A URI
IgA with variable G, M and c3 in mesangium
Variable prognosis

73. IgA nephropathy

74. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Inflammatory lesions
pyelonephritis
drug-induced interstitial nephritis
Toxic/ischemic lesions
Acute tubular necrosis

75. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Inflammatory lesions
pyelonephritis

76. Pyelonephritis
Invasive kidney infection
Usually ascends from UTI
Fever, flank pain
Organisms: E. coli, Proteus
Things You Must Know

77. Acute pyelonephritis with abscesses

78. Acute pyelonephritis

79. Acute pyelonephritis

80. Cellular cast

82. Urinary Tract Infection
Women, elderly
Patients with catheters or malformations
Dysuria, frequency
Organisms: E. coli, Proteus

83. E. coli
uncomplicated complicated
UTI: Common Bugs

84. Urinary catheter colonized by Proteus

85. Chronic pyelonephritis

86. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Inflammatory lesions
pyelonephritis
drug-induced interstitial nephritis

87. Drug-Induced Interstitial Nephritis
Antibiotics, NSAIDS
IgE and T-cell-mediated immune
reaction
Fever, eosinophilia, hematuria
Patient usually recovers
Analgesic nephritis is different (bad)
Things You Must Know

88. Drug-induced interstitial nephritis

89. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Inflammatory lesions
pyelonephritis
drug-induced interstitial nephritis
Toxic/ischemic lesions
Acute tubular necrosis

90. Acute Tubular Necrosis
The most common cause of ARF!
Reversible tubular injury
Many causes: ischemic (shock), toxic (drugs)
Most patients recover
Things You Must Know

91. Acute tubular necrosis

92. Acute tubular necrosis

93. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Diseases involving blood vessels
Benign nephrosclerosis
Malignant nephrosclerosis

94. Benign Nephrosclerosis
Found in patients with benign hypertension
Hyaline thickening of arterial walls
Leads to mild functional impairment
Rarely fatal
Things You Must Know

95. Benign nephrosclerosis

96. Malignant Nephrosclerosis
Arises in malignant hypertension
Hyperplastic vessels
Ischemia of kidney
Medical emergency
Things You Must Know

97. Malignant Hypertension
5% of cases of hypertension
Super-high blood pressure, encephalopathy,
heart abnormalities
First sign often headache, scotomas
Decreased blood flow to kidney leads to
increased renin, which leads to increased BP!
5y survival: 50%

98. Malignant nephrosclerosis

99. Malignant nephrosclerosis

100. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Diseases involving blood vessels
Cystic diseases
Adult polycystic kidney disease
Childhood polycystic kidney disease

101. Adult Polycystic Kidney Disease
Autosomal dominant
Huge kidneys full of cysts
Usually no symptoms until 30s
Associated with brain aneurysms
Things You Must Know

102. Adult polycystic kidney disease

103. Childhood Polycystic Kidney Disease
Autosomal recessive
Numerous small cortical cysts
Associated with liver cysts
Patients often die in infancy
Things You Must Know

104. Childhood polycystic kidney disease

105. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Diseases involving blood vessels
Cystic diseases
Tumors
Renal cell carcinoma
Bladder carcinoma

106. Renal Cell Carcinoma
Derived from tubular epithelium
Smoking, hypertension, cadmium
exposure
Hematuria, abdominal mass, flank pain
If metastatic, 5y survival = 5%
Things You Must Know

107. Renal cell carcinoma

108. Renal cell carcinoma

109. Renal cell carcinoma

110. Bladder Carcinoma
Derived from transitional epithelium
Presents with painless hematuria
Prognosis depends on grade and depth of
invasion
Overall 5y survival = 50%
Things You Must Know

112. Bladder carcinoma

113. Renal Pathology Outline
Introductory stuff
Glomerular diseases
Tubular and interstitial diseases
Diseases involving blood vessels
Cystic diseases
Tumors