For medical students

1. KIDNEY
(TUBULES,
INTERSTITIUM
& BLOOD VESSELS)

2. TUBULAR DISEASES
• ACUTE TUBULAR NECROSIS
• TUBULOINTERSTITIAL NEPHRITIS
– PYELONEPHRITIS
• ACUTE
• CHRONIC
– DRUGS
– TOXINS
• URATE NEPHROPATHY
• HYPERCALCEMIA/NEPHROCALCINOSIS
• MULTIPLE MYELOMA

3. ACUTE TUBULAR NECROSIS
• Destruction of renal TUBULAR epithelium
• Loss of renal function
• 50% of ACUTE renal failure
• Two types:
ISCHEMIC
NEPHROTOXIC
-AMINOGLYCOSIDES
-AMPHOTERICIN B
-CONTRAST AGENTS

5. ATN

6. ATN PATHOGENESIS
• BLOOD FLOW
DISTURBANCES (ISCHEMIC)
• TUBULAR INJURY
(NEPHROTOXIC)

10. CLINICAL COURSE
• INITIATION (36 hours)
– Mild OLIGURIA
– Mild AZOTEMIA
• MAINTENANCE
– More OLIGURIA
– More AZOTEMIA
– DIALYSIS NEEDED
• RECOVERY
– HYPOKALEMIA main problem
– BUN, CREATININE return to normal

11. TUBULO/INTERSTITIAL NEPHRITIS
• INFECTIONS, i.e., pyelonephritis
• TOXINS, heavy metals, chemo,
NSAIDS
• METABOLIC, urates, Ca++,
Oxalates
• PHYSICAL, obstruction, radiation
• IMMUNOLOGIC, esp. transplant
rejection

12. PYELONEPHRITIS
• GI Gram NEGATIVES: E. COLI, Proteus,
Klebsiella, Enterobacter, Strep. faecalis,
usually “NORMAL” flora
• ASCENDING, by FAR, the most common,
i.e., reflux, obstruction
• HEMATOGENOUS too
• ACUTE PYELONEPHRITIS, neutrophils
• CHRONIC PYELONEPHRITIS,
lymphocytes, scars

14. ACUTE or CHRONIC PYELONEPHRITIS?

15. MORPHOLOGY
• patchy interstitial suppurative
inflammation, intratubular aggregates
of neutrophils, and tubular necrosis.
• Complication:
– Papillary necrosis
– Pyonephrosis
– Perinephric abscess

16. FACTORS
• OBSTRUCTION: Congenital or Acquired
• INSTRUMENTATION
• VESICOURETERAL REFLUX
• PREGNANCY
• AGE, SEX, why sex? F>>>M
• PREVIOUS LESIONS
• IMMUNOSUPPRESION or
IMMUNODEFICIENCY

18. ACUTE or CHRONIC PYELONEPHRITIS?

19. ACUTE or CHRONIC PYELONEPHRITIS?

20. FORMS OF PYELOPNEPHRITIS
• Chronic pyelonephritis can be divided into two forms:
→REFLUX NEUROPATHY
→CHRONIC OBSTRUCTIVE PYELONEPHRITIS

21. GROSS
• Shrunken , scarred kidneys.
• If both kidneys are involved - involvement is asymmetrical
(in constrast with chronic glomerulonephritis in which the
kidneys are symmetrically involved).
• Coarse , discrete cortico - medullary scarring overlying
blunted deformed calyces.

23. MCIROSCOPY
• Tubules - Atrophy in some and Dilation & Hypertrophy in others.
• Dilated tubules filled with colloid casts – THYROIDIZATON.
• Neutrophils in tubules - if acute reinfection occurs
• Chronic Interstitial Inflammation - cortex and medulla.
• 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.
• Fibrosis - Around calyceal mucosa.

24. … MCIROSCOPY
• Glomeruli - normal except for Periglomerular Fibrosis.
• Secondary Focal Segmental Glomerulosclerosis in patients with
chronic pyelonephritis and reflux nephropathy who develop
proteinuria in advanced stages. The mechanism is adaptive
glomerular alterations secondary to loss of renal mass caused
by pyelonephritic scarring (renal ablation nephropathy).
• Arcuate and interlobular vessels - Obliterative endarteritis.
• Other arteries - Hypertensive Hyaline Arteriolosclerosis.

29. DRUGS/TOXINS causing
INTERSTITIAL NEPHRITIS
• Synthetic penicillins (methicillin,
ampicillin), other synthetic antibiotics
(rifampin), diuretics (thiazides), NSAIDs,
and miscellaneous drugs (allopurinol,
cimetidine).
• 2 weeks later: Fever, eosinophilia, rash,
and an acute renal failure type of picture

31. ANALGESIC NEPHROPATHY
• ASPIRIN, TYLENOL, NSAIDS
–TUBULOINTERSTITIAL NEPHRITIS
–PAPILLARY NECROSIS (also Dm & HbS)

32. URATE NEPHROPATHY
• Precipitation of Uric Acid Crystals in
the TUBULES, especially in a LOWER
than usual PH situation (mini-TOPHUS)
H & E alcohol fixed POLARIZED LIGHT MICROSCOPY

33. • Three forms:
– Acute uric acid nephropathy … chemotherapy
related
– Chronic urate nephropathy … gouty, tophi
– Nephrolithiasis … stones

34. HYPERCALCEMIA
NEPHROCALCINOSIS
PRINCIPLE: In extreme or
uncontrolled or chronic
HYPERCALCEMIA, calcium stones form
in the tubulo-interstitium of the kidney,
which can eventually lead to tubular
obstruction and loss of function

35. MULTIPLE MYELOMA
• Bence Jones proteinuria
(immunoglobulin light chains)
• AMYLOIDOSIS

36. Light Chain Cast Nephropathy
• Bence John Proteinuria and Cast
nephropathy
• Amyloidosis
• Light chain deposition disease
• Hypercalcemia and Hyperuricemia

37. • Acute Phosphate Nephropathy
– No hypercalcemia
– Ca Phosphate stones
• Bile cast Nephropathy
– Hepatorenal syndrome
– Analogous to myeloma protein

38. VASCULAR DISEASES
• BENIGN NEPHROSCLEROSIS
• MALIGNANT NEPHROSCLEROSIS (i.e.,
malignant hypertension)
• RENAL ARTERY STENOSIS
• THROMBOTIC MICROANGIOPATHIES
– Hemolytic-Uremic Syndromes, Child, Adult, TTP
• THROMBI, EMBOLI, INFARCTS
– SICKLE CELL
– DIFFUSE CORTICAL NECROSIS

39. BENIGN NEPHROSCLEROSIS
• Sclerosis, i.e., “hyalinization” of arterioles
and small arteries, i.e., arterio-, arteriolo-
• Is this part of “routine” atherosclerosis????
• VERY VERY VERY common

40. MALIGNANT NEPHROSCLEROSIS
(i.e., malignant hypertension)
• NOT a part of “routine” atherosclerosis
• By definition, associated with rapidly
progressive hypertension (1-2% of HTN)
• VASCULAR DAMAGE
• FIBRINOID NECROSIS
• “ONION SKINNING”
• SIGNIFICANT LUMENAL NARROWING

41. What is “onion-skinning”?
What is an onion?
What is “fibrinoid” necrosis?

42. Renal Artery Stenosis
• Rare cause of HTN
• SMALL Kidney
• 1) Plaque type is usual cause, yes
regular old atherosclerosis
• 2) Fibromuscular “dysplasia” type:
–INTIMAL HYPERPLASIA
–MEDIAL HYPERPLASIA
–ADVENTITIAL HYPERPLASIA
– In younger women

43. PLAQUE, i.e.,
ATHEROSCLEROSIS
FIBROMUSCULAR
DYSPLASIA

44. MICROANGIOPATHIES
(thrombotic)
• Hemolytic-Uremic Syndrome
–Familial
–Childhood
–Adult
• TTP (Thrombotic
Thrombocytopenic Purpura),
IDIOPATHIC

45. MICROANGIOPATHIES
COMMON
PROCESSES
–Hemolysis
–Thromboses in renal
capillaries
–Thrombocytopenia (a
“consumption”
coagulopathy)
–FIBRIN PLUGS

46. • Typicals HUS … Shiga-like toxin by E.
Coli O157:H7
• Atypical HUS … Factor H (C3 convertase
cleaver), Antiphospholipid syndrome, post-
partum, vascular diseases, chemo/radio
therapy
• TTP … ADAMTS13 (vWF cleaver)

47. OTHER VASCULAR
• Atherosclerosis
• Atheroemboli
• Sickle Cell
• Diffuse Cortical
Necrosis

48. • Sickle cell nephropathy … hyperosmolarity
in renal medulla dehydrates RBCs and
increases IC HbS levels
• Diffuse cortical necrosis … obs
emergency, septic shock or extensive
surgery … sharply limited to cortex

49. RENAL INFARCTS
• WEDGE SHAPED
• WELL DELINEATED
• “WHITE” (anemic) INFARCT
• Perhaps a little “YELLOW”
• HEAL WITH A SCAR

51. Kidney is precious.