Pathology of Glomerulonephritis

Pathology of Glomerulonephritis.

1. CPC4.1-2008:
•Miss G.M. is a 37 year old woman with longstanding
Type 1 Diabetes.
•Dysuria (36h), Urinary Frequency, Fatigue,
backache(T11,12) – few months.
•BSL – 9-11, Pedal edema – few weeks.
•Diarrhea, anorexia, bloating – year.
•Microalbuminuria – 1998,
•Urine: nitrate positive; ketones:+; glucose ++ wbc+++;
protein++++; blood : trace;
•Urine MC+S : leucocytes 10^8 ; E Coli Sensitive to
trimethoprim - ?
•Post micturation bladder volume : 180 ml - ?
•Anti tissue transglutaminase antibody: 12(normal < 2) - ?

2. CPC4.4.1 – Clinical Cases
•The patient is a 35y Italian female who works
as a shop assistant, Tired for years, but has
always been able to carry out her work. Over
the past two months, however, her fatigue has
worsened, and she has noted swelling of her
legs and puffiness around eyelids. MGN
•2 year old boy presents with sudden onset
polyuria, proteinuria mild fever. MCD
•8 year old girl presents with fever, oliguria,
smoke coloured urine & hypertension following
upper respiratory tract infection. PGN

3. Investigations: Nephrotic
•Urine: 4+ proteinuria, granular casts, RBC +.
•24h urine: 6g protein in 24h
•Serum: creatinine = 0.14 (slightly elevated)
•LFT, electrolytes, Full blood counts – Normal.
•Serum albumin is 28 g/l (low);
•Cholesterol (6.5mmol/l)
•Triglycerides (2.8mmol/l)
•Antinuclear antibody (SLE) - Negative
•Ultrasound of kidneys: normal
•Renal biopsy – Glomerulonephritis*

4. Investigations: Nephritic
•Urine: Oliguria, 2+ protein, RBC ++++,
RBC & WBC casts.
•24h urine: 0.5 g protein in 24h
•Serum: creatinine = 0.14 (slightly elevated)
•LFT, electrolytes, Full blood counts –
Normal.
•Serum albumin – normal ;
•Antinuclear antibody (SLE) - Negative
•Ultrasound of kidneys: normal
•Renal biopsy – Glomerulonephritis*

5. CPC4.4.1 – Diff. Diag:
•Low serum albumin
–Renal disease – nephrotic syndrome
–Liver disease (cirrhosis)
–Gastrointestinal disease: malabsorption or protein-
losing enteropathy, starvation.
•Normal serum albumin
–Renal disease – Nephritic syndrome
–acute/chronic GN - diabetic, hypertensive.
–Acute/Chronic renal failure.
•Fluid overload
–Congestive cardiac failure
•Endocrine: Hypothyroidism.

6. Pathogenesis of Renal Symptoms / Signs:
Proteinuria GBM Damage – Selective (albumin)-nephrotic, non selective
nephritic syndrome.
Oliguria or anuriaDehydration, GN-Nephritic Sy, renal failure, obstruction.
Polyuria Excessive fluid, Osmotic (DM), GN-Nephrotic Sy, Tubule
dysfunction (D.Insipidus)
Dysuria Inflammation, Obstruction, stone, tumor, stricture.
Renal colic Calculus, blood clot or tumour in ureter
Uraemia (Fatigue, Nausea, vomiting, encephalopathy) Renal failure
Haematuria Infection, stones, tumor, Glomerulonephritis (red cell casts)
Casts: Coagulation of proteins in renal tubules.
• Hyaline/Gr. castscastsProtein loss from glomeruli or necrotic cells
• RBC, WBC, Ep. Protein with cell loss from glomeruli/tubules.
• Waxy casts Degenerated cast following prolonged retention (chronic RF)
Hypertension Renal ischaemia, decreased GFR  Renin  Angiotensin.
Oedema
periorbital*
Hypoalbuminaemia due to albumin loss in urine
(glomerulonephritis) Aldosterone.

7. Pathogenesis of Renal Symptoms / Signs:
Fatigue/MalaiseRenal failure – Azotemia / Uremia.
Headache Fluid retention, acidosis, uremia.
Flank pain Ureteric Colic – stones.
SOB, pallor Anemia – decreased erythropoietin
Nausea / Vom. Renal Osteodystrophy – renal failure.
Pruritis Uremia / neuropathy.
Pigmentation Endocrine abnormality in uremia
Smoky urine Microscopic hematuria at glomerular level – RBC casts.
Nephritic syndrome.
Hematuria UTI, Glomerulonephritis, tumor
Painless Hematu.DM, IgA Nephropathy, TB.

8. Whenever you see someone who is sick,
dispirited, disconsolate, or diseased,
there is a field of service. Every blood
cell, every nerve must tingle with love,
When love fills the heart, it transforms
into Divinity. (Genesis 20:13)
Medicine is the Noble Profession

9. Pathology of
Glomerulonephritis:
Dr. Shashidhar V. Murthy
A/Prof. & Head of Pathology

10. CPC4.4.1 – CLI
Pathology Major CLI:
–Overview & classification Disorders of Kidney.
–Pathogenesis & Clinical features of Nephrotic, Nephritic Syndromes and
Renal Failure.
–Pathology of common types of Glomerulonephritis.
–PGN, MGN, MPGN, FSGS, RPGN, CGN.
–Pathology of Disorders of Tubules, Interstitium & Blood vessels.
–Pathology of Renal failure both acute & Chronic.
Pathology Minor CLI:
–Interpretation of Common Renal function tests.
–Pathogenesis of Renal artery stenosis & other Nephrogenic
Hypertension.
–IgA nephropathy.
–Renal involvement in SLE
–Analgesic nephropathy.
–Amyloid nephropathy.
–Hypertensive nephropathy.
–Acute tubular necrosis.

11. Anatomy-Kidney
LL
RR

12. Normal Kidney
* note: Lobulations are prominent in fetal kidney
Less common in adult kidney.

13. Anatomy of Renal System
Cortex
Medulla - pyramid
Renal Papilla

14. Blood supply of Kidney.
Brödel's 1901 artist rendition of a
human left kidney anterior view,
following celloidin injection with
tissue digestion, demonstrating
details of the lush venous return.
For the sake of clarity, he
omitted the small veins of the
cortex (Brödel M. Johns Hopkins
Hospital Bulletin 1901;118:10–
13).
Arcuate BV
Note arcuate large vessels in medulla, But,
small straight vessels in cortex. (revise
physiology of urine production, counter
current mechansim)

15. Anatomy of Kidney
Note the positions of
Glom, PCT, Loop, DCT, CT

16. Normal Kidney: Histology
DCT
PCT
Gl.Cap
Mesang.
Aff.Art
JGAJGA
* Remember: JGA, Renin, Angiotensin, Blood pressure control….

17. Normal Glomerulus (PAS stain for BM)
DCT
PCT
Gl.Cap
Mesang.

18. Normal Glomerulus
DCT
PCT
Gl.Cap
Mesang.

19. Glomeruli: ScanEM showingScanEM showing
Outside view of GlomOutside view of Glom
Podocyte foot processesPodocyte foot processes
(Epithelium)(Epithelium)
Scan EM showingScan EM showing
View from inside capillaryView from inside capillary
Endothelial FenestrationsEndothelial Fenestrations

20. JGA
GFR  Renin
Aldosterone
Angiotensin
BP, Na/K/H+
AA
BB
CC
DD
EE
FF
FF
Juxta Glomerular
Apparatus

21. Renin
Hypertonic
Review Physiology: Urine, Hormones & Homeostasis

22. Renal Filtration Unit:
•IMPORTANT IN
UNDERSTANDING
GLOMERULONEPHRITIS:
•Permeability to solutes &
water, but Impermeable to
●
Cells (endothelium)
●
larger molecules (BM)
●
small proteins (podocytes).

23. Filtration Membrane:
Endothelium
Basement Mem
Epithelium

24. Glom. Nephritis : Pathogenesis
•Large quantity blood filtration….
–1.2 L/min = 1,728 L/day (25% Cardiac output)
–Glomerular filtrate 180 L / day, Urine 1-2 L / day.
•Trap large proteins – Ag, Ab, Ig.complex, toxins.
•Activation of complement system
•Inflammation – cytokines & inflammatory cells.
•Damage filtration membrane:
–Incomplete/podocyte damage Nephrotic Sy: no swelling,
selective albuminuria.
–Complete filter damage: Nephritic Sy: inflam swelling, ↓ blood
flow, ↓ GFR  Oliguria, hypertension, hematuria.
•Systemic effects:
–JGA  BP, water, electrolyte imbalance.
–Erythropoietin – anemia.
–Vit-D – Bone metabolism.

25. BloodBlood
GBM
Podocyte
Pathogenesis of GN:
GLOM. FILT. MEM:GLOM. FILT. MEM:
1. Endothelium1. Endothelium
2. GBM2. GBM
3. Podocyte Slit membrane3. Podocyte Slit membrane
Endothelium
Cells
Glom.FiltGlom.Filt
Glob.
Alb.
Nephrotic Sy – No Infl. - PolyuriaNephrotic Sy – No Infl. - Polyuria
Nephritic Sy – Inflam - oliguriaNephritic Sy – Inflam - oliguria

26. Glom. Immunoflourescence
Granular Smooth
Circulating Ig. Complexes, C3 Anti GBM Ab. disease/.
Planted antigens & Ab.
Infections, Autoimmune dis.

27. Nephritic
•Oliguria
•Hematuria
•Non selective
Proteinuria.
•GFR¯, Cr­, BUN­
•Edema (salt and
water retention)
•Hypertension
•RBC & Protein casts.
NephroticNephrotic
•Polyuria
•Proteinuria
(“nephrotic range”
>3.5g/24h)
•Edema
(Hypoalbuminemia)
•Hyperlipidemia
•Lipiduria
•Protein casts.
urine
urine

28. Be content with what you have; Be content with what you have;
rejoice in the way things are. When rejoice in the way things are. When
you realize there is nothing lacking, you realize there is nothing lacking,
the whole world belongs to you.the whole world belongs to you.
Lao TzuLao Tzu

29. Causes of Renal Disease:
Hypovolemia
Diarrhoea, vomiting
Bleeding, Burns, CCF
Ascitis, Anasarca
Renal A / V thrombosis
Autoimmune disorders
Vasculitis, anti GBM dis
Diabetes, tubular dis.
Toxins, infections,
metabolic.
Ureteral, urethral
obstruction. Stone,
papillary necrosis,
bladder dis, prostate,
drugs, cancer.

30. Disorders of Kidney:
•Congenital
–Malformations-Horseshoe
–ectopic, cysts, dysplasia.
•Acquired
–Glomerulonephritis – Acute/Chronic
–Tubulointerstitial diseases – toxins, drugs, Infect.
–Vascular diseases. – vasculitis.
–Obstructive uropathy. hydronephrosis…
–Renal calculi.
–Neoplasms – carcinoma.
•End stage renal disease.

31. GN -Clinical Presentations:
1.Asymptomatic Proteinuria:
–Many types of early GN, MCD & FSGS
2.Painless hematuria:
–Bergers (IgA), SLE, SBE,
•Nephritic Syndrome:
–Posts Strep PGN, RPGN, antiGBM, SLE.
•Nephrotic Syndrome:
–Pri: MCD, MPGN, FSGS, MGN, IgA Neph
–Sec: DM, drugs, SLE, Amyloidosis.
•Renal Failure: Acute/Chronic & endstage.
–Common end result, Drugs, infections, ischemic, metabolic.
–ATN-Acute tubular necrosis.
–Sec: Hypertension, DM, GN,
–Pri: CRF.

32. Gross: Acute Nephritis:

33. Glom. Dis. Classification:
•AetiologicalAetiological
–Primary & Secondary
•ImmunologicalImmunological
–Glomerular Ag (anti GBM)
–Non-glomerular Ag.
(immune complex)
•MorphologicalMorphological.
–diffusediffuse: all glomeruli
–focalfocal: some glomeruli.
–globalglobal: whole of glom.
–segmentalsegmental: part of glom.
•Morphologic:Morphologic:
–proliferativeproliferative: increased
cells
–membranousmembranous: thickening
of BM
–membrano-proliferativemembrano-proliferative:
combination
–crescenticcrescentic: epithelial
proliferation, florid /
severe.

34. Morphologic types of GN:
Diffuse
Focal
Global
Segmental
FSGS

35. Casts = Glomerular pathology:
Kidney Biopsy: Showing RBC, protein & mixed casts within tubules
G
lo
m
e
r
u
lu
s

36. Red cell Casts in Urine:

37. Casts in Urine:
WBC Epithelial RBC Mixed
Granular Hyaline
Online Urinalysis tutorial : http://library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html

38. Great achievements can start right
where you stand, by applying the habit
of going the extra mile, by rendering
more service and better service than
you are now being paid for.
Napoleon Hill

39. AGN: Nephrotic Sy:
Polyuria, Proteinuria, hypoalbum hyperlipidemia.
Primary glomerular Primary glomerular
diseases diseases
–minimal change disease
–membranous
glomerulonephritis
–membrano-proliferative GN
(mesangiocapillary GN)
–focal glomerulosclerosis
–mesangial IgA nephropathy
–bacterial endocarditis
–shunt nephritis
Secondary glomerular Secondary glomerular
disease disease
–SLE
–Henoch-Schönlein purpura
–immune complex disease
related to tumours, infections
drugs (gold, penicillamine,
phenytoin etc) etc..
–diabetes mellitus
–amyloidosis
–bee sting allergy
•Inherited diseaseInherited disease
–congenital nephrotic sy.

40. Introduction
Synonyms:
Incidence:
Etiology:
Clinical
Features:
Lab
Features:
Pathology:
Clinical
Course:
Nil disease, lipoid nephrosis, foot
process disease
Idiopathic. Loss of net negative charge
destruction of podocyte foot processes.
Nephrotic syndrome. History of recent
URI in 30%. Association with
Hodgkin’s lymphoma. Overlap with
FSGS patients.
Nephrotic urine (polyuria, Selective
proteinuria. (albuminuria).
Spontaneous remission in 25-40%.
Complete remission in 65-70% of
patients. Steroid resistant patients may
progress to FSGS.
LM - Normal. IF - Negative.
EM - Focal fusion/loss of foot
processes.
80% of nephrotic syndrome in
children (1-8 yrs.), mostly male.
Adults in 2nd-3rd decade.
Minimal Change GN:

41. Minimal Change Disease:
Loss of Foot processes
NormalNormal

42. Focal Segmental GN: Adults
Synonyms:
Incidence:
Etiology:
Clinical
Features:
Lab
Features:
Pathology:
Clinical
Course:
Focal segmental Sclerosis
Idiopathic - ? Auto Immune. No
deposits. (Similar to minimal change).
Nephrotic syndrome. History of recent
URI in 30%. Association with
Hodgkin’s lymphoma. Overlap with
MCD patients.
Nephrotic urine (more, clear)
Selective proteinuria. No specific
laboratory findings.
Spontaneous remission 30% , 50%
progression to chronic renal failure,
20% rapid progression.
Podocyte damage, Segmental collapse
of glom. increase in matrix (pink).
10 - 35% of nephrotic syndrome in
adults.

43. Synonyms:
Incidence:
Etiology:
Clinical:
Lab:
Path:
Clinical
Course:
Epimembranous, extramembranous GN
Immune complex deposition. Idiopathic in
most patients, associated with infections,
drugs, carcinomas, and heavy metals.
Nephrotic syndrome in 80%, asymptomatic
proteinuria in 20%. Microscopic hematuria.
Non-selective proteinuria ± hematuria.
Excellent prognosis in children. Some
adults develop ESRD. Exclusion of other
diseases is required.
Diffuse, uniform BM thickening with
subepithelial projections (“spikes”).
Diffuse, coarsely granular IgG and C3
deposits along basement membranes.
Electron-dense subepithelial deposits.
40-60 Years, 50% of adult nephrotic
syndrome.
Membranous GN:
Wireloop

44. Mem.GN:
Wireloop.
Sub ep. dep.- Spikes
IgG & C3.

45. Etiology:Chronic immune complex GN. Associated with
chronic infections, SLE, cancer, cirrhosis, heroin
abuse, etc.
Clinical:Nephrotic syndrome in 50%, acute nephritic
syndrome in 20%. Recent history of URI in 50%.
Hypertension and/or renal insufficiency.
Lab: Hypocomplementemia of classic and alternate
pathways. C3 nephritic factor (C3NEF). Circulating
immune complexes.
Clinical
Course:
Progressive deterioration of renal function ±
short remissions. ESRD within 10 years in 50%
of children and 80% of adults.
Path: Diffuse proliferative GN with thickening of the
glomerular capillary walls,, and GBM splitting
(“tram-tracking”). Diffuse, coarsely granular C3
and IgG deposits along GBMs. Electron-dense
subendothelial deposits.
Incidence:
Children and young adults (5-25 years).
Membranoproliferative GN:

46. MPGN-Tram tracking
Arrow: Mesangial cell proliferation,
basement membrane thickening, leukocyte
infiltration, and accentuation of lobular
architecture.
Type 1 – Most common 80%
Type 2 – Dense deposit disease (C3)

47. MPGN-Tram tracking
Glomerulus PAS stain to highlight the glomerular basement membranes.
Observe the glomerular capillary loops showing two basements membranes
giving the loops a tram track appearance (arrow).

48. •Commonest form of GN – Nephritic.
•Young 15-30y, males, Asia-Pacific.
•IgA deposits in mesangium, High
serum IgA, varied severity
•Episodic asymptomatic hematuria
•microscopic hematuria (40%)
•Bouts of macro hematuria (40%)
•Nephritic or Nephrotic.
•Renal failure (10%)
•Slowly progressive CRF in 1/3
patients.
IgA Nephropathy (Berger’s)
IgA dep.
Normal
IgA dep.

49. IgA Nephropathy:

50. IgA Nephropathy:

51. IgA Nephropathy:

52. Synonyms:
Incidence:
Etiology:
Clinical:
Lab:
Path:
Clinical
Course:
Acute proliferative glomerulonephritis,
acute post-infectious GN.
Glomerular trapping of circulating immune
complexes. (Group A, Beta-hemolytic
streptococci, type 12).
Acute nephritic following strep. pharyngitis or
pyoderma. (Other infections rare)
Nephritic urine (little, dark, smoky) RBC
casts, non selective proteinuria.
Decreased serum complement. Evidence
of strep inf.
Children - Excellent prognosis. Adults -
Worse prognosis, some develop
progressive disease.
Enlarged, hypercellular glomeruli with
endothelial and mesangial cell
proliferation, neutrophils, IgG and C3 in
very coarsely granular pattern along
GBMs. Discrete, subepithelial “hump-like”
deposits.
children (3-14). Sporatic, mostly winter and
spring.
Acute Post Strept, Diff, Prol GN:

53. Post.Strep Proliferative GN:
NormalNormal PGNPGN
Ig+C3
Ig+C3

54. Post.Strep Proliferative GN:
Hypercellularity, narrow capillary lumen, pleomorphic population of neutrophils,
mesangial cells and granular sub. Epithelial deposits of IgG and C3.
Neutrophils.
Narrow cap.

55. Acute PGN (neutrophils)

56. RPGN / Crescentic GN:
•Acute, Severe Rapidly
progressive.
•Renal failure within weeks.
•Bowman's space – Fibrin,
epithelial & Infl. Cells matrix
 form Crescents.
•Compress Glomerulus.
•End result of many types of
GN
•Progress to CGN  end
stage kidney  renal failure.

57. RPGN (large, pale, edema)

58. RPGN
Epithelial Crescent
Collapsed capillary

59. RPGN
Prot. Cast

60. Progression of GN

61. Diabetic kidney diseases
•Glomerular damage.
–Diffuse global thickening of BM
–Nodular sclerosis (KW lesion)
–Arteriolosclerosis
•Papillary necrosis.
•Interstitial nephritis.
•Pyelonephritis.
Clin: Proteinuria (in 50% diabetics) ESKD (30%)

62. Diabetic Glomerulosclerosis

63. Renal Papillary necrosis in DM:
•Fever and chills, flank
and/or abdominal pain,
and hematuria.
•Also in
–analgesic abuse
–Obstructive uropathy
–Pyelonephritis
–Cirrhosis, alcoholism

64. Acute Nephritis & Papillary necrosis - DM

65. Benign Nephrosclerosis:
•Hyaline artereolosclerosis.
•Intimal fibrosis
•Ischemia
•Glomerular sclerosis
•Scarring
Leathery GranularLeathery Granular
Surface - scarringSurface - scarring

66. Benign Nephrosclerosis: HPTN

67. Arteriosclerosis & Nephrosclerosis in HPTN
Arteriolosclerosis Kidney: Leathery Granularity
Benign Nephrosclerosis

68. Malignant Hypertension:
•Surface petchiae
•Flea bitten kidney
•Fibrinoid necrosis of
arterioles.

69. Recurrent painless haematuria
•Asymptomatic, recurrent:
•IgA nephropathy (Berger's disease)
•systemic lupus erythematosus (SLE)
•vasculitis-polyarteritis.
•Henoch-Schönlein purpura
•bacterial endocarditis
•exercise haematuria

70. •Anti GBM type 4 collagen antibody
•Young men, Rapidly progressive RPGN
•Focal Segmental necrosis with fibrin
deposition.
•Poor prognosis.
Good Pasteur (anti GBM) dis.
Normal
AntiGBM
necrosis

71. Tubulo-Interstitial Diseases:
•Acute Tubular Necrosis
•Pyelonephritis – Acute & Chronic.
•Interstitial Nephritis.

72. Acute Tubular Necrosis:
Sloughing
Ep in PCT
Ep Casts
•Most common
cause of ARF.
•Drugs
(aminoglycosi
des)
•Toxins –
Mercury,
CCL4,
Radiocontrast.

73. Acute Tubular Necrosis:
Glom. Norm
Necrotic PCT
(no nuclei)
Normal DCT
(Pro. cast inside)
PCT early necrosis

74. Pyelonephritis:
Acute / Chronic
•Bacterial, fungal, viral,
Mycobacterial Infection.
•E.coli common.
•Risk factor - Obstruction
•Interstitial inflammation.
•Lymphocytes & plasma
cells in chronic.
•Neutrophils in acute.
•Septicemia – flea bitten
kidney.
•Micro/macro abscesses.

75. Acute
Pyelonephritis
Abscesses
Congestion

76. Pyelonephritis
Inflammatory cells
WBC Cast in DCT
PCT
BV

77. Pyelonephritis - Abscess
WBC Cast in DCT
PCT
Glom.

78. Chronic Renal Failure:
•Uraemia & vague features including
anaemia, nausea, vomiting, gastrointestinal
bleeding and itching; there is often polyuria
and nocturia.
•Two major types:
–End stage of several types of GN.
–De novo presentation.
•Renal osteodystrophy
•Anemia – bleeding, low erythropoietin.

79. Chronic Renal Failure: ESKD
Small atrophic kidney – Irregular pitted surface (due to scarring).
Prominent loss of Cortical tissue.

80. Chronic Renal Failure: ESKD

81. Chronic Glomerulosclerosis:

82. Chronic Glomerulosclerosis:

83. Chronic Glomerulonephritis:
Advanced tubular atrophy
with "thyroidization”
inspisated secretions
within tubules.

84. •General symptoms – weakness, fatigue
•Cardiovascular – hypertension, pericarditis
•G.I. – nausea, vomiting, diarrhea
•CNS – lethargy, confusion, coma
•Muscles – twitching, weakness
•Bones – osteodystrophy
•Metabolic – acidosis, P­K­, BUN­, Cr­.
•Endocrine - parathyroids­
Chronic renal failure (uremia)

85. Chronic Renal Failure:
•Azotemia vs. Uremia ?
•Why anemia in CRF?
–Lack of erythropoietin, chronic blood loss &
haemolysis.
•Renal Osteodystrophy ?
–conversion of the vit D impaired, low intestinal
absorption of calcium, resulting in high PTH –
osteoclast activation – bone resorption. This in turn is
exacerbated by the phosphate retention which
accompanies CRF.

86. Summary:
•Painless haematuria :
–Berger's - IGA nephropathy.
–DM, SLE
–Henoch-Schönlein purpura
–bacterial endocarditis
–vasculitis-polyarteritis.
•Asymptomatic proteinuria:
–SLE
–FSGS
–Henoch-Schönlein purpura
–bacterial endocarditis
–MPGN
•Nephritic Syndrome:
–Post-streptococcal GN
–RPGN
–Goodpasture's
–SLE
–polyarteritis
•Nephrotic syndrome
–minimal change disease
–FSGS
–membranous GN
–membrano-proliferative GN
–IgA nephropathy
–bacterial endocarditis
–shunt nephritis
•Diabetic GN
•Hypertensive Kidney dis.
•Pyelonephritis acute/chronic.
•Acute tubular necrosis.
•Renal Failure Acute/Chronic.
•Endstage renal disease.

87. CPC-4.1– REN–Gn
•Pathology - Core Learning Issues:
–Pathology of Glomerular diseases (primary & Sec).
–Overview of ATN, Pyelonephritis, acute/chronic.
–Pathogenesis of Nephritic & Nephrotic syndrome.
–Pathology of Renal failure both acute & Chronic.
–Interpretation of Common Renal function tests.
•Basic science - Review:
–Anatomy & Histology of Kidney.
–Fluid balance & Renal function.
–Physiology of urine & its production.
–Autoimmunity in the pathogenesis of kidney disease

88. "If you tell the truth, you have
infinite power supporting you; if
not, you have infinite power
against you.
--Charles Gordon

89. 21y Male, hematuria, recovering from an URT infection.
Had similar attack twice in last two years ? diagnosis
1 2 3 4 5
15%
36%
32%
6%
11%
•Diffuse proliferative GN
•Membranous GN
•Nodular Glomerulo sclerosis
•Minimal change GN
•Berger’s Disease

90. 12y Fem, puffy face, Oliguria, smoky urine, hypertension.
Recovering from URTI. Kidney biopsy ? Most likely
diagnosis
1 2 3 4 5
65%
7%
11%
5%
12%
A.Diffuse proliferative GN
B.Membranous GN
C.Minimal change GN
D.Rapidly progressive GN
E.Membranoproliferative GN

91. 2y boy, Severe proteinuria, polyuria, pedal edema.
Kidney biopsy normal. ? Most likely diagnosis
1 2 3 4 5
0%
7%
0%0%
93%
A.Diffuse proliferative GN
B.Membranous GN
C.Minimal change GN
D.Rapidly progressive GN
E.Membranoproliferative GN

92. 48y Male, proteinuria, polyuria, pedal edema. On treatment
for SLE. Kidney biopsy PAS stain ? diagnosis
1 2 3 4 5
2%
74%
17%
6%
0%
A.Diffuse proliferative GN
B.Membranous GN
C.Minimal change GN
D.Rapidly progressive GN
E.Membranoproliferative GN

93. 54y Male, nocturia, polyuria, recurrent infections. Kidney
biopsy ? diagnosis
1 2 3 4 5
2% 2%
77%
19%
0%
A.Diffuse proliferative GN
B.Membranous GN
C.Minimal change GN
D.Rapidly progressive GN
E.Nodular Glomerulo sclerosis

94. 58y Male, Chronic hypertension. Slowly
progressive renal failure. Kidney sp. ? diag
A. B. C. D. E.
92%
4%
0%
2%2%
•Benign nephrosclerosis
•Papillary necrosis
•Pyelonephritis with infarction
•Nodular glomerulosclerosis
•Renal abscesses

95. 14y Male, severe acute renal failure, history of recent throat
infection on treatment. Kidney biopsy ? diagnosis
1 2 3 4 5
18%
4%
11%
65%
2%
A.Diffuse proliferative GN
B.Membranous GN
C.Minimal change GN
D.Rapidly progressive GN
E.Membranoproliferative GN

96. 74y Male, Hypertensive, Oliguria & marked fatigue since 2
months. Left Kidney gross ? diagnosis
1 2 3 4 5
15%
3%
79%
0%
3%
A.Nodular Glomerulo sclerosis.
B.Chronic Pyelonephritis.
C.Polycystic kidney disease.
D.Rapidly progressive GN.
E.Chronic Glomerulonephritis.

97. 46y Male, Hematuria. Urine cytology ? diagnosis
1 2 3 4 5
7%
0%
4%
85%
4%
A.Urinary Tract Infection
B.Bladder cancer
C.Renal stones
D.Glomerulonephritis
E.Schistosomiasis

98. 46y Male, 3wk. lethargy. KFT ? diagnosis
1 2 3 4 5
12%
0% 0%
2%
86%
•Polyuria
•Selective proteinuria
•Hypoalbuminemia
•Hypercholesterolemia
•Serum creatinine normal
A.Nephritic Syndrome
B.Acute renal failure
C.Nephrotic syndrome
D.Chronic Renal failure
E.Renal cell carinoma.

99. 46y Male, 3wk. lethargy. KFT ? diagnosis
1 2 3 4 5
98%
0% 0%0%
2%
•Oliguria
•Hypertension
•Non Selective proteinuria
•Serum creatinine high
•RBC casts present.
A.Nephritic Syndrome
B.Acute renal failure
C.Nephrotic syndrome
D.Chronic Renal failure
E.Rencal cell cancer.

100. 46y Diabetic male. Fever, hematuria? diag
1 2 3 4 5
65%
12%
2%
17%
4%
•Papillary necrosis
•Pyelonephritis
•Nodular glomerulosclerosis
•Renal abscesses
•Chronic Renal failure

101. 44y man, SOB, swelling of his legs and puffiness around his eyes & Ascitis.
Total serum protein is 5.2 g/dL (reference = 5.5–8.0 g/dL), and albumin is 1.9 g/
dL (reference = 3.5–5.5 g/dL). Serum cholesterol is elevated at 530 mg/dL. 5 g
of protein in a 24-hour urine, with many granular casts but no RBCs or WBC.
Image shows renal biopsy stained by direct immunofluorescence for IgG ?
Diagnosis
A. B. C. D. E.
6%
2%
0%
77%
15%
A.Proliferative GN
B.Focal segmental glomerulosclerosis
C.Membranoproliferative GN type I
D.Membranous glomerulopathy
E.Minimal change disease

102. 60y man, chronic back pain and fatigue, excessive urination, and
increased thirst. X-ray - numerous lytic lesions in the lumbar vertebral
bodies. Lab: hypoalbuminemia, 4+ proteinuria & A monoclonal Ig light-
chain peak. A bone marrow biopsy 20% atypical plasma cells. Image
shows kidney biopsy. ? Diagnosis
A. B. C. D. E.
77%
2%
5%
4%
12%
A.Amyloid nephropathy
B.Crescentic glomerulonephritis
C.IgA nephropathy (Berger disease)
D.Membranous glomerulonephritis
E.Nodular glomerulosclerosis.

103. 30y man with h/o drug addiction, 6/12 progressive edema & Ascitis, Marked
proteinuria (>4 g/24 hours) but no WBC or RBCs in urine. Lab: Hyperlipidemia
and hypoalbuminemia. Serum creatinine level is normal. The blood test for
ANCA is negative. Recurrent attacks respond to corticosteroids, Upon the third
recurrence, becomes steroid resistant. A renal biopsy is shown . ? Diagnosis
A. B. C. D. E.
2% 2%
74%
10%
12%
A.Acute glomerulonephritis
B.Amyloidosis
C.Crescentic glomerulonephritis
D.Diffuse proliferative glomerulonephritis
E.Focal segmental glomerulosclerosis

104. A 6-year-old boy complains of swelling of his feet for the past 3 weeks.
He is otherwise healthy, with no known previous illness. Vital signs are
normal. Physical examination reveals pitting edema of the lower legs
and a swollen abdomen. Urinalysis shows 4+ protein but no RBCs or
WBCs. ? Most likely Diagnosis (no image)
A. B. C. D. E.
6%
92%
2%
0%0%
A.Acute glomerulonephritis
B.Minimal change disease
C.Crescentic glomerulonephritis
D.Diffuse proliferative glomerulonephritis
E.Focal segmental glomerulosclerosis

105. 9y boy, episode of hematureia 1wk after flulike illness. One
month later his urine is red again. Urinealysis pH7, SG 1.015,
Proteinuria 1+, 1+ hematuria. No ketones, glucose or
urobilinogen. Serum urea & creat. Normal. Renal biopsy
shows mesangial proliferation & electron dense deposits
within mesangium. Which of the following mechanisms is
most likely to produce his symptoms?
A. B. C. D. E.
35%
7%
49%
7%
2%
A.Deposition of Ig complex with IgA .
B.Ab against type IV collagen
C.Viral injury to GBM.
D.Cytokine injury to Glom. Cap.
E.Anti-streptococcal Ab. dep.
Explanation: Recurrent hematuria following a viral illness in
a child or young adult is typically associated with IgA
nephropathy (Berger’s dis). Defective immune regulation
causes excessive mucosal IgA synthesis in response to
viral or other environmental antigens. IgA complexes are
deposited in the mesangium and initiate glomerular injury.
Antibodies against type IV collagen are formed in
Goodpasture syndrome.

106. 49y male, Ankle & Foot swelling for 2 months.24h urine
yielded 4.1g protein. No DM, SLE or Hyepertension. No
response to steroid therapy. Renal biopsy showed diffusely
thick cap basement membrane with granular C3 deposition.
Two years later he developed chronic renal failure. What is
the most likely pathogenesis?
A. B. C. D. E.
27%
2%
53%
4%
14%
Explanation: This patient has idiopathic MGN & nephrotic syndrome. Diffuse
basement membrane thickening caused by the deposition of immune complexes
on the basement membrane, which activates complement. Antibodies that react
with basement membrane give rise to a linear immunofluorescence pattern.
Membranous glomerulopathy has no association with streptococcal infections.
There is also no evidence of cytokine- or T-cell-mediated damage in this
disease. In 85% of patients is unknown. In the remaining 15%, an associated
systemic disease (e.g., SLE) or some known cause of immune complex
formation (e.g., drug reaction, viral hepatitis) exists.
A.Ab cross reacting with GBM collagen
B.Anti strep. Ab cross-react with GBM
C.Release of cytokines by inflammatory cells
D.Cytotoxic T cells directed against renal
antigens.
E.Deposition of immune complexes on the
GBM

107. “The worst times in your life contain
seeds of the best. When you can see
crisis as an opportunity, your life
becomes not only easier, but more
satisfying.”
–Joe Kogel

108. Video tutorials on Digital Pathology
Slides on
Acknowledgements:
You Tube WashingtonDeceit:
Dedicated to the greatest pathologist of all time -
Martin A. Swerdlow, MD
"Build it and they will come."

109. Links to Digital Histopathology Kidney.
•RPGN - http://www.youtube.com/watch?v=CqSyj4cVZPE
•SLE - http://www.youtube.com/watch?v=Tw07BFaDEo0
•ADPKD - http://www.youtube.com/watch?v=6Ws9cfsjZIk
•CGN: http://www.youtube.com/watch?v=eA1vYarRAWo&feature=related
•ATN- http://www.youtube.com/watch?v=ajCG3sIe2iw
•Pyelonephritis: http://www.youtube.com/watch?v=aZ2il9a63J4
More.. search youtube….!

110. Challenge….!
Jan 2009:
4
th
Year Students at
JCU School of Medicine
set new world record.…!!!
100% Pass & Class Average of over 70%Winners Club is still active….! -
Email me

111. What motivates senior clinicians to teach
Medical students in Australia?
Positive:
•Altruism *
•Intellectual
satisfaction
•Personal skills
•Truth seeking
Negative:
•No strong
involvement (course)
•Heavy work load
•Feeling it was a waste
of time.
Jane Dahlstrom et. al. ANU, Canberra, Australia
BMC Medical Education 2005, 5:27 doi:10.1186/1472-6920-5-27
Be Nice…!
Respect,
Value teaching,
Show concern

112. Altruism……!

113. “To be a great champion you must
believe you are the best. If you’re not,
pretend you are….!”
– Muhammad Ali

114. Urine Analysis:
•clean-catch, midstream sample after the external
genitalia have been cleansed with an antiseptic
solution.
•Delay in testing cause bacterial growth, and in
the process metabolize any glucose present.
The bacteria can also utilize the urea, forming
ammonia and increasing the pH.
•Bilirubin is light sensitive will decompose and will
become un reactive. Casts, red blood cells and
white cells also tend to disintegrate after only a
short time at room temperature.

115. 1. Random clean catch or mid-stream collection
2. First morning specimen
3. Second-voided specimen
4. Post prandial collection
5. Day specimen
6. Night specimen
7. Twenty-four hour collection
8. Catheterized collection
Urine specimens:

116. Normal Urine Crystals
Acid Urine pH Neutral Urine pH Alkaline Urine pH
Calcium Oxalate Ammonium Biurate Triple Phosphates
Uric Acid Calcium Carbonate Ammonium Biurate
Calcium Oxalate Calcium Carbonate
Triple Phosphate Calcium Phosphate
Amorphous urates Amorphous Phosphates

117. •Normal
•Post Strepto GN
•Inflammation
•Proliferation
•Swelling.
•Narrow capillary
•↓GFR-Renin-BP

118. CPC4.4.1 – CLI
•Clinical Core Learning Issues:
–Approach to, History taking & clinical Assessment of
patients with renal disease.
–Clinical features of patient with Renal impairment.
–Over view of Renal dialysis, renal transplantation.
•Population, Rural, Indigenous & tropical:
–Access to specialist nephrologist care from Ingham
–Social / government support for adults who become
unable to work due to illness
•Personal, Professional & Ethical:
–Dealing with resource allocation to chronic diseases.
–Managing patients with renal failure in rural centers.
–Ethical issues in providing Renal
dialysis/transplantation.

119. 35y Male, fatigue.
•A previously healthy 35-year-old man complained of
recent fatigue and swelling of his feet and ankles. He
also noted puffy eyes. Physical exam revealed an
afebrile man with lower extremity edema extending to
the knee, periorbital edema, and a small amount of
ascites.
• Drug history was negative. ANA, HIV, and hepatitis
serologies were negative.
•The patient developed right flank pain the following day.
Ultrasound examination revealed renal vein thrombosis.
A renal biopsy was performed.

120. Laboratory results:
Urinalysis: protein - 4+
glucose - neg
blood - neg
bilirubin - neg
Micro: rare RBCs, no WBCs, many oval fat bodies
Creatinine 0.8 mg/dL
BUN 18 mg/dL
Albumin 1.8 g/dL (3.5-5.1)
Hematocrit 40%
Liver function testsnormal
Triglycerides 400 mg/dL (<150) 0.4-2.29 mmol
Cholesterol 375 mg/dL (<170) 2-4.39 mmol
24-hr urine
protein
11.2 gm/24
hr
•Nephrotic / Nephritic?Nephrotic / Nephritic?
•Where is the pathology?Where is the pathology?
•Why no blood in urine?Why no blood in urine?

121. A 27-year-old white man
•who was previously in good health
presented to his family physician with
increasing fatigue and red urine. There
was no history of previous illness, and
review of systems was negative.
•Physical examination was negative except
for hypertension (165/110).
•Urinalysis revealed 2+ protein and 2+
blood; his serum creatinine was 1.8
mg/dL.

122. A 27-year-old white man
•A week later deteriorated with intermittent
bouts of hematuria and ankle swelling and
generalized malaise, nausea and
vomiting, and decreasing urine output
almost anuric.
•Blood pressure was 170/110.
•An abdominal sonogram showed kidneys
of normal size with no evidence of
hydronephrosis.
•Laboratory exam revealed:

123. A 27-year-old white man
Urinalysis: protein - 2+
blood - 4+
glucose - neg
Micro: > 40 RBCs/HPF (0-2 RBCs/HPF)
10 WBCs/HPF (0-2 WBCs/HPF)
5-10 RBC casts/LPF (0 casts/LPF)
Hematocrit 38%
Creatinine 3.9 mg/dL
BUN 102 mg/dL
Liver serologynormal
ANCA, ANA, HIVnegative

124. Renal Artery stenosis - Atrophy
Leathery Granularity
Benign Nephrosclerosis
Atrophy

125. Septicemia:
pinpoint micro
abscesses with
hyperaemic borders.
(Flea bitten kidney)