A tutorial of renal/kidney pathology for 5th year medical students at Cambridge University.

1. Histopath Tutorial 2:
Renal Pathology
Christiane Riedinger 6/3/14

2. Today’s Contents
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organising renal pathology
major symptoms of renal pathology
kidney failure (acute kidney INJURY, chronic renal DISEASE)
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

3. Today’s Contents
●
●
●
●
●
organising renal pathology
major symptoms of renal pathology
kidney failure
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

4. Overview of Renal Pathology
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many different ways of organising this topic
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mnemonic
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hereditary vs. acquired
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structure/anatomy
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outcome: acute vs. chronic

5. Overview of Renal Pathology ctnd.
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mnemonic - surgical sieve: (e.g. A vitamin CDE)
● Acquired: Diabetic kidney disease
● Vascular: Particularly susceptible, renal artery stenosis, arterionephrosclerosis,
hypertension
● Infectious: nephritis (glomeruli vs. tubules, potentially post-infectious), TB,
abscesses
● Trauma: shock
● Autoimmune: Particularly susceptible, SLE, vasculitides, amyloidosis
● Malignant: benign tumours, tubular or transitional cell carcinoma, nephroblastoma
● Idiopathic: many glomerulonephritides, e.g. minimal change
● Neoplastic: renal carcinoma, Wilm’s tumour, multiple myeloma
● Congenital: PKD, Alport’s, Fabry’s, von Hippel-Lindau
● Drugs: toxicity

6. Overview of Renal Pathology ctnd.
●
structure/anatomy
tubule
glomerulus
macroscopic
systemic
collecting
system
vessels
http://www.sclerodermasociety.co.
uk/Theheartandscleroderma1.php
tubulointerstitial
http://www.baileybio.
com/plogger/?
level=picture&id=1486

7. Overview of Renal Pathology ctnd.
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outcome:
acute
vs.
chronic
kidney failure

8. Today’s Contents
●
●
●
●
●
organising renal pathology
major symptoms of renal pathology
kidney failure
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

9. 1* Symptoms of Renal Pathology
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haematuria
○ with or without symptoms
○ microscopic or macroscopic
proteinuria
○ via leakage - glomerular damage
○ defective reabsorption in tubules
■ heavy metal damage
■ Fanconi syndrome
■ Hartnup disease AA absorption disease
○ overflow
■ haemolysis
■ intravascular haemolysis
NEPHRITIC (both) vs NEPHROTIC syndrome (prOtein Only)
oligo/anuria
renal pain
endocrine changes

10. 1* Symptoms of Renal Pathology ctnd.
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always also think about what is happening in the blood, not just the urine!
nephritic syndrome
○ haematuria
○ proteinuria
○ in blood: azotemia
○ oedema, hypertension
nephrotic syndrome
○ proteinuria
○ lipiduria
○ in blood: hypoalbuminuria, hyperlipidaemia
○ oedema
○ increased clotting
○ risk of infection

11. Today’s Contents
●
●
●
●
●
organising renal pathology
major symptoms of renal pathology
kidney failure
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

12. Kidney Failure: Definitions
Acute deterioration in kidney function (over <48h) with
increase in creatinine (>0.3mg/dL) and decrease in
urine output (<0.5mL/kg/h).
Long-term degeneration of kidney function defined by
persistently low or decreasing GFR or abnormal
structural or functional findings.

13. Kidney Failure: Causes (acute)
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pre-renal
○ all vascular + contents of vessels
○ low blood volume
○ low BP
○ CHF
○ renal artery stenosis
○ ischaemia
○ renal vein thrombosis
renal
○ glomerulonephritis (deposition, vasculitis)
○ acute tubular necrosis (toxins, antibiotics, contrast)
○ acute interstitial nephritis (distal obstruction)

14. Kidney Failure: Causes (acute) ctnd.
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post-renal:
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think OBSTRUCTION!
again many ways to organise e.g. extrinsic vs intrinsic, here: structural
parenchyma
■ clot
■ mass
■ papillary necrosis
ureters
■ kidney stones
■ AAA
■ retroperitoneal fibrosis
bladder
■ bladder stone, tumour, clot
■ neurogenic bladder
prostate
■ BPH
■ prostate carcinoma
urethra
■ stone
■ stricture

15. Kidney Failure: Causes (acute) ctnd.
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summary:
80% pre-renal and tubular necrosis
(other statistics: 85% ATN, 10% interstitial nephritis, 5% GN)

16. Kidney Failure: Causes (chronic)
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diabetes mellitus 30%
hypertension 15%
glomerulonephritis 25%
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together 75%!!!!!
vascular: renal artery stenosis, vasculitis, HUS
infectious: HIV nephropathy, parasites
toxins
congenital: Alport’s syndrome, Fabry’s disease, Polycyst. kidney d. (5%)
systemic (see earlier slide)
post-renal obstruction (see earlier slide)

17. Kidney Failure: Causes (chronic) ctnd.
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summary:
75% diabetes, hypertension, GN

18. Kidney Failure: Acute v. chronic
summary

19. Today’s Contents
●
●
●
●
●
organising renal pathology
major symptoms of renal pathology
kidney failure
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

20. Sites of Renal Pathology
The Glomeruli:
Glomerulonephritis

21. Glomerular Pathogenesis
Think DEPOSITION and VASCULAR!

22. Glomerular Pathogenesis: DEPOSITION
● immune complexes
● glycoprotein deposition, glycation
● amyloid deposition
● paraprotein deposition (MM)

23. Glomerular Pathogenesis: IMMUNE COMPLEXES
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whole immune complexes get trapped
○ 3 locations:
■ mesangium
■ between endothelium and GBM
■ between GBM and podocytes
○ (GRANULAR PATTERN)
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in situ reaction
○ ABs attack “planted’ non-glomerular antigens
■ SLE nucleosomal complexes, bact. products, protein
aggregates
○ ABs attack glomerular AGs (LINEAR PATTERN)
■ anti-GBM, anti-podocyte

24. Glomerular Pathogenesis: IMMUNE COMPLEXES

25. Glomerulonephritis: DISTINGUISH
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global vs. segmental
(entire glomerulus or part)
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diffuse vs. focal
(all glomeruli or patches)
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proliferative vs. non-proliferative
(proliferation of endothelial and/or
mesangial cells, often a result of inflammation, but does not have to be. I
don’t think BM thickening counts as proliferative)
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nephrotic, nephritic syndrome or both? (how big are the holes?)
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pathological entity vs. clinical syndrome!

26. Glomerulonephritis
The following slide is the way I have organised GNs to
memorise them more easily - it may not be the best/most
correct way as different books group them differently.
For resources used see my Histopath notes.

28. (post-)
infectious
GN

29. global, diffuse!

30. global, diffuse!

31. global, diffuse!

32. global, diffuse!

33. Histology of Glomerulonephritis
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note: For an excellent overview, also see Wheater’s Basic Pathology Chapter 15 page 180ff
post-infectious GN
membranous GN
membranoprolif. GN
crescenteric GN

34. note: GN can cause ischaemia
which then causes tubular injury!

35. Sites of Renal Pathology
The Tubules:
(Acute) Tubular Necrosis

36. Pathogenesis of Tubular Necrosis
f

37. Sites of Renal Pathology
The Interstitium

38. Tubulointerstitial Pathology

39. Sites of Renal Pathology
The Collecting System:
Kidney Stones

40. Path. of the Collecting System: STONES!
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80% Calcium oxalate
- absorptive hypercalcinuria
10% Magnesium/Ammonium phosphate - alkaline urine from UTIs
<10% uric acid or cystine
- urate from gout
- cystine from defect in transport
all stones contain 2.5% mucoprotein
stone formation around nidus, e.g. bacterial debris or desquamated
epithelium
blockage of urine flow => hydronephrosis:
compression => tubules affected => can’t concentrate urine => even more urine!!
Therefore polyuria if partial obstruction
Anuria if complete and bilateral (80% of stones unilateral)

41. Today’s Contents
●
●
●
●
●
organising renal pathology
major symptoms of renal pathology
kidney failure
○ acute vs. chronic
○ causes, clinical phases
sites of renal pathology
○ glomeruli
○ tubules
○ interstitium
○ collecting system
biochemical abnormalities

42. Biochemistry of Renal Disease
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think about what kidney does and then derive it!
In general potential abnormalities in the following tests
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blood
■ FBC
■ U&E
■ BUN
■ LFTs
■
■
■
ESR/CRP
clotting screen
CK
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urine
■ output
■ urinalysis
■ electrolytes
■ creatinine
■ osmolality
■ Bence-Jones
■ culture
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special
■ GFR
■ tubular function
imaging
■ US, CT, MRI
■ radioisotope scan
pathology
■ biopsy
immunology
ECG!

43. Biochemistry of Renal Disease: prerenal
INADEQUATE PERFUSION = ACCUMULATION/RETENTION
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urea
creatinine
H+
compounds containing N
anuria/oliguria/polyuria
changes in GFR
activation of RAAS
=> uraemia
=> acidosis
=> azothemia
=> Na+ retention
=> U&E’s
=> U&E’s+
=> U&E’s, ABG?
=> BUN, BUN/Cr
=> urine output
=> GFR
=> U&E’s, urine
blood: hi Na+,also hi K+?
urine: low Na+

44. Biochemistry of Renal Disease: renal
REDUCED FUNCTION => ELECTROLYTE IMBALANCE AND LEAKAGE
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=> Hyponatraemia
(Na+ loss)
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opposite of RAAS
hyperkalaemia
retention of H+
=> metabolic acidosis
=> ABG
=> hyperphosphataemia
=> U&E’s
=> hypermagnesaemia
=> U&E’s
=> urinalysis
=> urinalysis
=> urine output
retention of phosphate
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retention of Mg2+
proteinuria
haematuria
anuria/oliguria/polyuria
=> U&E’s

45. Biochemical abnormalities: chronic kidney d.
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initially compensated
one nephron hypothesis of Bricker 1960:
○ as nr of nephrons decrease, remaining nephrons must perform greater
fraction of total renal excretion
disturbances we mentioned in previous slides
starts with polyuria
endocrine effects
○ hyperphosphataemia/hypocalcaemia => renal osteodystrophy
○ decreased calcitriol cynthesis
○ decreased T, Oe
○ thyroid abnormalities
○ disorders of glu metabolism
○ anaemia
○ dyslipidaemia

46. The end.