2.  Glomerulitis is the exact term of inflammation of
glomeruli but as there is usualy affection of the
adjacent tubules and interstitial tissue, so the term
Glomerulonephritis
 It can refer to a process that is inflammatory or non-
inflammatory, so the term Glomerulopathy

4. Nephritic Glomerulopathies Nephrotic Glomerulopathies
= Active Urinary Sediment = Bland Urinary Sediment
• RBCs (dysmorphic) • Proteinuria
• RBCs casts • Hyaline casts
• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)

5. Nephritic Glomerulopathies Nephrotic Glomerulopathies
= Active Urinary Sediment = Bland Urinary Sediment
• RBCs (dysmorphic) • Proteinuria
• RBCs casts • Hyaline casts
• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)
Parts affected of Glomeruli: Parts affected of Glomeruli:
1. Mesangial cells 1. Podocyte (Epithelial Cells)
2. Endothelial Cells 2. GBM
3. GBM

6.  Situated retroperitoneally on either
side of the vertebral column, at the
level of T12-L3, where they underlie
the costovertebral angles posteriorly.
 The right kidney is about 1.5 cm
lower than the left, and both move up
and down about 3cm during
respiration.

7. 1 renal papilla, 15 interlobular vein,
2 renal column, 16 renal sinus,
3 capsule, 17 arcuate vein,
4 renal pyramid, 18 medulla,
5 calyx, 19 vasa recta,
6 ureter, 20 loop of Henle,
7 renal pelvis, 21 collecting duct,
8 renal vein, 22 arcuate vein,
9 renal artery, 23 arcuate artery,
10 interlobar artery, 24 proximal convoluted
11 arcuate artery, tubule,
12 interlobular artery, 25 glomerulus,
13 interlobar vein,
26 Bowman’s capsule,
14 cortex,
27 distal convoluted tubule

8. 1 renal papilla,
2 renal column,
3 capsule,
4 renal pyramid,
5 calyx,
6 ureter,
7 renal pelvis,
8 renal vein,
9 renal artery, 15 interlobular vein, 21 collecting duct, 26 Bowman’s
10 interlobar artery, 16 renal sinus, 22 arcuate vein, capsule,
11 arcuate artery, 17 arcuate vein, 23 arcuate artery, 27 distal convoluted
12 interlobular artery, 18 medulla, 24 proximal convoluted tubule
13 interlobar vein, 19 vasa recta, tubule,
14 cortex, 20 loop of Henle, 25 glomerulus,

9. 1 renal papilla, 15 interlobular vein,
2 renal column, 16 renal sinus,
3 capsule, 17 arcuate vein, 14
4 renal pyramid, 18 medulla,
5 calyx, 19 vasa recta,
6 ureter, 20 loop of Henle,
7 renal pelvis, 21 collecting duct,
8 renal vein, 22 arcuate vein, 15
9 renal artery, 23 arcuate artery,
10 interlobar artery, 24 proximal convoluted
11 arcuate artery, tubule,
12 interlobular artery, 25 glomerulus,
13 interlobar vein,
26 Bowman’s capsule,
14 cortex,
27 distal convoluted tubule

10. Arteries (down) Veins (up)
Abdominal aorta Vena cava
Renal artery Renal vein
Segmental arteries -
Lobar arteries -
Interlobar artery Interlobar vein
Arcuate arteries Arcuate vein
Interlobular artery Interlobular vein
Afferent arterioles Efferent arterioles
Glomerulus Glomerulus

14. Kidney glomeruli. Coloured scanning electron micrograph (SEM)
The core of a glomerulus is a tightly coiled balls of capillaries. The cast was made by injecting
resin into the blood vessels. The surrounding tissues were then chemically digested.

15. ``
1. 1- Glom. Cap.
2. 2- Bowman`s capsule
3. 3- Afferent a.
4. 4- Efferent a.
5. 5- PCT
6. 6- DCT
7. 7- Collecting tubule
8. 8- Juxtaglomerular app
Affarent a. is wider than
the efferent a.

20. 4 nm
40 nm
Albumin 3.5 nm
RBC 6-8 um

22. Subepithelial space
Subendothelial space

23. Sub-epithelial and sub-endothelial spaces
 The subepithelial space (between GBM and epithelial cells) is
relatively immunologically privileged, compared to the
subendothelial space (between vascular endothelium and GBM).
 Immune deposits in subepithelial region of the glomerulus tend
to result in proteinuria without much in the way of active
inflammation.
 Whereas those in the subendothelial space (as may be seen in
postinfectious GN and mesangiocapillary GN) tend to result in
‘nephritic syndrome’, with haematuria and urinary casts.

25. A - Renal corpuscle
B - Proximal tubule
C - Distal convoluted tubule
D - Juxtaglomerular apparatus
1. Basement membrane (Basal lamina)
2. Bowman's capsule - parietal layer
3. Bowman's capsule - visceral layer
3a. Pedicels (podocytes)
3b. Podocyte or sometimes called
Bowman's cells
4. Bowman's space (urinary space)
5a. Mesangium - Intraglomerular cell
5b. Mesangium - Extraglomerular cell
6. Granular cells (Juxtaglomerular cells)
7. Macula densa
8. Myocytes (smooth muscle)
9. Afferent arteriole
10. Glomerulus Capillaries
11. Efferent arteriole

26. Nephritic Glomerulopathies Nephrotic Glomerulopathies
= Active Urinary Sediment = Bland Urinary Sediment
• RBCs (dysmorphic) • Proteinuria
• RBCs casts • Hyaline casts
• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)
Parts affected of Glomeruli: Parts affected of Glomeruli:
1. Mesangial cells 1. Podocyte (Epithelial Cells)
2. Endothelial Cells 2. GBM
3. GBM

27. Nephritic Glomerulopathies Nephrotic Glomerulopathies
= Active Urinary Sediment = Bland Urinary Sediment
• RBCs (dysmorphic) • Proteinuria
• RBCs casts • Hyaline casts
• +/- Proteinuria (usually non nephrotic) • Lipiduria (oval fat bodies)
Parts affected of Glomeruli: Parts affected of Glomeruli:
1. Mesangial cells 1. Podocyte (Epithelial Cells)
2. Endothelial Cells 2. GBM
3. GBM

28.  Primary: Pathology limited to kidney
 Secondary: kidney involvement as manifestation of systemic disease
 Focal: < 50% of glomeruli involved
 Diffuse: > 50% of glomeruli involved
 Global: Involvement of the whole glomerulus
 Segmental: Involvement of part of the glomerulus
 Proliferative: increased no of glomerular cells ( resident and infiltrative)
 Cresentic GN: Cresent shaped collection of cells in Bowman`s capsule
associated e` RPGN
 Sclerosis: scarred area -acellular - presumed irreversible

31. Normal Proliferative

32. Non Inflammatory Nature
Bland urine sediment Nephrotic
Epithelial Cells + GBM
Circulating Factor or in Situ IC
Inflammatory Nature
Active urine sediment Nephritic
Endothelial + Mesangial+GBM
Circulating IC + Others
 Both 1+2 Nephrotic & Nephritic
2 + Cresent Formation Rapidly Progressive

33. Non Inflammatory Nature
Bland urine sediment Nephrotic
Epithelial Cells + GBM
Circulating Factor or in Situ IC
Inflammatory Nature
Active urine sediment Nephritic
Endothelial + Mesangial+GBM
Circulating IC + Others
 Both 1+2 Nephrotic & Nephritic
2 + Cresent Formation Rapidly Progressive

34. 1. Proteinuria:
• Adult: > 3.5 gm/ day
• Children: > 40 mg/m2/hour
(N: < 4mg/m2/h).
2. Hypoalbuminemia
3. Bland urine sediment
4. Hyperlipedemia
5. Edema

35. Primary causes:
 Minimal Change Disease
 Focal Segmental glomerulosclerosis
 Membranous Nephropathy
Secondary causes:
 Diabetes Mellitus
 Amyloidosis
 Drugs: gold, lithium, penicillamin, NSAIDs

36.  The dipstick  The dipstick results
Dipstick Protein Conc.
results have the Negative the following
have < 150 mg / day
following approximate
Trace 150 mg /day
approximate correlations with
+1
correlations protein mg /day
300
with protein + 2 concentration:
1000 mg /day
concentration: +3 3000-4000 mg /day
+4 > 5000 mg /day

38. MCD Normal

44.  Prednisolone: 60 mg/m2/daily given early in the morning for 6
weeks followed by 40 mg/m2 every other morning for an additional
6 weeks.
 Or slower taper of 60 mg/m2 every other morning for 4 weeks,
tapering further by 10 mg/m2 every 4 weeks for an additional 20
weeks.
 95% will experience complete remission.
 60-75% will develop relapse.
 Relapse treated with another steroid coarse but with slower
tapering.
 Frequent relapse and steroid resistant: cyclosporin, tacrolimus or
MMF.

45.  Prednisolone: single morning dose of 1 mg/kg/day,
maximum of 80 mg, is continued for a minimum of 8
weeks.
 For those patients not in remission at 8 weeks, daily
prednisone may be continued for another 2 months until
remission is attained.
 A gradual taper is then recommended on an every-other-
day schedule until the patient is tapered off over many
months.

46. MINIMAL CHANGE DISEASE

47. NORMAL PODOCYTES

48. Effacement or fusion of podocytes

50. Minimal Change Disease (MCD)
Fused podocytes
Normal glomerulus Minimal changes of glomeruli

51. ???
 An 8-year-old boy complains of nausea and vomiting and fatigue.
On examination, he is oedematous and his blood pressure is 160/100
mmHg. Blood urea and serum creatinine levels are normal.
 Urine microscopy shows oval fat bodies. 24-hour urine protein is 2g.
The doctor plans to start a course of corticosteroids, which he says
will cure the condition.

52. ???
 An 8-year-old boy complains of nausea and vomiting and fatigue.
On examination, he is oedematous and his blood pressure is 160/100
mmHg. Blood urea and serum creatinine levels are normal.
 Urine microscopy shows oval fat bodies. 24-hour urine protein is 2g.
The doctor plans to start a course of corticosteroids, which he says
will cure the condition.

53. ???
 A 6-year-old boy presents with oedema of his face and
ascites.
 The 24-hour urinary protein is 4.0 g, while the serum
albumin concentration is 25 g/l.
 Hypertriglyceridaemia is present.

54. ???
 A 6-year-old boy presents with oedema of his face and
ascites.
 The 24-hour urinary protein is 4.0 g, while the serum
albumin concentration is 25 g/l.
 Hypertriglyceridaemia is present.

55. ???
 A 28-year-old woman presents with painless lymphadenopathy in her
neck region.
 She has had fevers and night sweats intermittently over the past few
weeks, weight loss and generalised malaise.
 She has abandoned her Friday nights out after work due to abdominal
pain after drinking alcohol.
 On examination there is neck lymphadenopathy, abdominal fullness
(which may be ascites) and peripheral oedema.
 Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h
urine collection reveals a protein excretion of 4.5 g over a 24-h period (< 0.2 g/24
h). Initial renal biopsy shows no significant abnormality.

56. ???
 A 28-year-old woman presents with painless lymphadenopathy in her neck region.
 She has had fevers and night sweats intermittently over the past few weeks, weight loss and generalised malaise.
 She has abandoned her Friday nights out after work due to abdominal pain after drinking alcohol.
 On examination there is neck lymphadenopathy, abdominal fullness (which may be ascites) and peripheral oedema.
 Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h urine collection reveals a protein excretion of 4.5 g over
a 24-h period (< 0.2 g/24 h). Initial renal biopsy shows no significant abnormality.

57. ???
 A 28-year-old woman presents with painless lymphadenopathy in her neck region.
 She has had fevers and night sweats intermittently over the past few weeks, weight loss and generalised malaise.
 She has abandoned her Friday nights out after work due to abdominal pain after drinking alcohol.
 On examination there is neck lymphadenopathy, abdominal fullness (which may be ascites) and peripheral oedema.
 Routine initial bloods reveal a decreased serum albumin concentration, and a 24-h urine collection reveals a protein excretion of 4.5 g over
a 24-h period (< 0.2 g/24 h). Initial renal biopsy shows no significant abnormality.

59. Light microscopy (LM): only focally (in some glomeruli – especially juxtamedullar ones) a
segmentally (only in some segments of glomeruli) presence and sclerotisation of glomerular
loops, caused by accumulation of acellular matrix with adhesions to Bowman´s.capsule
(hyalinosis).

60. Normal Glomerulus Prehilar FSGS

61. FSGS – basic histological types
Perihilar FSGS: most common Tip lesion FSGS: more often Collapsing FSGS: rare variant,
corticosensitive ? often secondary (HIV)

62.  It has become the most common diagnosed primary
glomerular disease reported in most published kidney
biopsy series. 30-40% in adult, 10% in children
 It is the fourth most common cause of ESRD,
following diabetes, hypertension, and
glomerulonephritis not otherwise specified.
 Among children it is the second leading cause of
ESRD, following congenital kidney anomalies.

63. FSGS: Clinical
 Full blown picture of NS
 HTN is more common (young adult with HTN)
 RFT is impaired in 60% at presentation
 Spontaneous remission is rare.
 Poor response to steroid (20-30%).

64. Secondary FSGS Secondary FSGS
 Drugs
 Heroin
1. HIV  Analgesics
2. Heroin  Viruses
 HIV
3. Sickle cell  Hepatitis B
 Parvovirus
4. Obesity  Hemodynamic factors - With
5. Reflux nephropathy reduced renal mass
 Solitary kidney
 Renal allograft
 Renal dysplasia
 Renal agenesis
 Vesicoureteric reflux

65. Secondary FSGS Secondary FSGS
 Hemodynamic causes - Without
reduced renal mass
1. HIV  Massive obesity
 Sickle cell nephropathy
2. Heroin  Congenital cyanotic heart disease
3. Sickle cell  Malignancies
 Lymphomas
4. Obesity  Other malignancies
 Scarring - Postinflammatory in
5. Reflux nephropathy postinfectious glomerulonephritis
 Miscellaneous
6. Lymphomas  Hypertensive nephrosclerosis
 Alport syndrome
 Sarcoidosis
 Radiation nephritis

66. Patogenesis of primary FSGS
 Permeability factor: Increased glomerular
permeability and injury to podocytes.

67. FSGS: Pathology
 LM:
 focal segmental glomerular sclerosis (hyalinosis) is seen, especially in
juxtamedullary glomeruli.
 In HIV: Collapsed appearance of glomeruli.
 IF: IgM and C3 in these sclerotic areas.
 EM: Effacement of foot processes + segmental sclerosis (not
immune complexes).
 No immune deposits.
 Histopathology may be normal and confused for MCD.

68. FOCAL SEGMENTAL GLOMERULOSCLEROSIS

69. FOCAL SEGMENTAL GLOMERULOSCLEROSIS

70. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (IF)

72. FSGS: recurrence after Tx
 Recurrence may occur in up to 70% of patients.
 It may occur immediately after transplant, or it
may take months or years to recur.
 Prevention: Plasmapheresis or
immunoadsorption pre and post-transplant.

74. Q 1
 The pathogenesis of focal glomerulosclerosis (FSGS) is unknown.
Increased glomerular permeability and injury to podocytes have
been postulated as possible aetiological factors.

75. Q 1
 The pathogenesis of focal glomerulosclerosis (FSGS) is unknown.
Increased glomerular permeability and injury to podocytes have
been postulated as possible aetiological factors.

76. Q 2
 A 32-year-old Afro–Caribbean man with a 5-year history of HIV infection
presents with swollen ankles. He has been treated with highly active
antiretroviral therapy (HAART) for 2 years, with partial response. His plasma
creatinine concentration is 358 umol/l, albumin is 12 g/dl, CD4 count is 35/u l
and 24-hour urine protein excretion rate is 6.8 g. Renal ultrasound shows
echogenic kidneys 13.5 cm in length.
 What would a renal biopsy show?
 Focal necrotising crescentic nephritis
 Kimmelstiel–Wilson lesions
 Membranous nephropathy
 Microcystic tubular dilatation and collapsing FSGS
 Minimal-change disease

77. Q 2
 A 32-year-old Afro–Caribbean man with a 5-year history of HIV infection
presents with swollen ankles. He has been treated with highly active
antiretroviral therapy (HAART) for 2 years, with partial response. His plasma
creatinine concentration is 358 mmol/l, albumin is 12 g/dl, CD4 count is 35/u l
and 24-hour urine protein excretion rate is 6.8 g. Renal ultrasound shows
echogenic kidneys 13.5 cm in length.
 What would a renal biopsy show?
 Focal necrotising crescentic nephritis
 Kimmelstiel–Wilson lesions
 Membranous nephropathy
 Microcystic tubular dilatation and collapsing FSGS
 Minimal-change disease

78. Q 3
 A 38-year-old man presents with fever, increased symptoms of
asthma, and hypertension. His GP has also noticed that a sample of
faeces was positive for blood.
 On examination he looks pale, his BP Is 155/92 mmHg and he has a
palpable purpuric rash. Auscultation of the chest reveals signs
consistent with asthma.

79. Q 3
 Which of the following are the most likely
findings on renal biopsy?
 Glomerulosclerosis
 Focal segmental glomerulonephritis
 Minimal change disease
 Membranous glomerulonephritis
 Large vessel vasculitis

80. Q 3
 Which of the following are the most likely
findings on renal biopsy?
 Glomerulosclerosis
 Focal segmental glomerulonephritis
 Minimal change disease
 Membranous glomerulonephritis
 Large vessel vasculitis

81. FSGS: Facts
 Focal segmental glomerulonephritis may occur
as a primary disease, but it is also seen in
 Systemic lupus erythematosus,
 Subacute infective endocarditis
 Shunt nephritis (infected atrioventricular shunts)
 Henoch–Schönlein purpura
 IgA nephropathy.
 Vasculitis

84.  Normal Glomerulus
 thin GBM (equivalent to
tubular basement membrane)
 mesangium limited to stalk of
capillary tuft (double arrows)
 Membranous Nephropathy
 thick GBM (in relation to tubular
basement membrane)
 mesangial expansion (asterisks)
images from www.uptodate.com

85.  Immunofluorescence
 diffuse granular IgG deposits
along GBM
 Silver Stain
 spike pattern in GBM
highlights deposits between
new GBM
images from www.uptodate.com

86.  Normal EM
 thin, homogenous GBM
 epithelial cell with foot
processes
 fenestrated endothelial
cell (arrow)
 Membranous EM
 thick GMB, with deposits
(D)
 effacement of foot
processes

87. MN: Facts
 MN is a leading cause of idiopathic nephrotic syndrome in adults
(30–40%) and a rare cause in children (< 5%).
 Peak incidence is between 30 and 50 years of age and
 Male:female ratio is 2:1.
 1/3 of MN is secondary to
 HBV
 SLE
 Drugs: gold, penicillamin, NSAIDs and captopril.
 Malignancy: Solid Tumour (adenocarcinoma of GI and squamous cell ca of lung)

88. Membranous Nephropathy
Rule of
Thirds
1/3 1/3
1/3
Spontaneous Subnephrotic
ESRD
Remission Proteinuria

89. MN:Histopathology
 Light microscopy the glomerular basement membrane is uniformly
thickened.
 IF granular deposits of immunoglobulins and complements are distributed
along the basement membrane.
 EM reveals subepithelial deposits with spike and dome pattern-later
incorporating into GBM, thickening of basement membrane and loss of
foot process of podocytes.

92. MEMBRANOUS GLOMERULONEPHRITIS

93. Lai KN. Kidney Int 2007; 71: 841–843

94. MEMBRANOUS GLOMERULONEPHRITIS

95. MEMBRANOUS GLOMERULONEPHRITIS (IF)

97. MEMBRANOUS GLOMERULONEPHRITIS (EM)

100. MN: Renal Vein Thrombosis
 RVT occurs in 35% of NS patients.
 The most common is MN 20-60%
 The important risk factor: S. Albumin ≤ 25 gm/l
 May be unilateral or bilateral
 Clinical: flank pain + hematuria (gross or microscopic) + enlarged kidney
size + marked ↑ of LDH. If bilateral  AKI will occur.
 Diagnosis: IVC gram with selective renal venography, CT, MR. doppler US may
reveal false +ve and -ve result.
 Therapy: Anticoagulant (Heparin and Warfarin), Thrombolytic tharapy and
rarely surgical removal

101. Q 1
 Membranous glomerulopathy is associated with:
 Idiopathic nephrotic syndrome in children
 Adenocarcinoma of the stomach
 Elevated anti-nuclear antibody levels
 Selective proteinuria
 A progressive course ending in end-stage renal disease (ESRD)

102. Q 1
 Membranous glomerulopathy is associated with:
 Idiopathic nephrotic syndrome in children
 Adenocarcinoma of the stomach
 Elevated anti-nuclear antibody levels
 Selective proteinuria
 A progressive course ending in end-stage renal disease (ESRD)

103. Q 2
 A 65-year-old man with a known history of lung cancer presents with
anorexia, malaise and drowsiness. A CT scan shows metastatic
lesions in the liver.
 Laboratory test results are as follows: Hb, 7.8 g/dl; WCC, 11.5 x 109/l;
Ferritin, 5.0 nmol/l; Urea, 27 mmol/l; Creatinine, 377 µmol/l; 24 hour
urine protein, 3.8g.
 A renal biopsy shows focal subepithelial deposition of IgG and C3.
A probable diagnosis is:
 Focal segmental glomerulosclerosis
 Nodular glomerulosclerosis
 Microcytic hypochromic anaemia
 Minimal change glomerulonephropathy
 Membranous glomerulonephropathy

104. Q 2
 A 65-year-old man with a known history of lung cancer presents with
anorexia, malaise and drowsiness. A CT scan shows metastatic
lesions in the liver.
 Laboratory test results are as follows: Hb, 7.8 g/dl; WCC, 11.5 x 109/l;
Ferritin, 5.0 nmol/l; Urea, 27 mmol/l; Creatinine, 377 µmol/l; 24 hour
urine protein, 3.8g.
 A renal biopsy shows focal subepithelial deposition of IgG and C3.
A probable diagnosis is:
 Focal segmental glomerulosclerosis
 Nodular glomerulosclerosis
 Microcytic hypochromic anaemia
 Minimal change glomerulonephropathy
 Membranous glomerulonephropathy

105. Q 3
 A 47-year-old man attends the outpatient clinic complaining of swelling in
the ankles and lethargy. On examination, his blood pressure is 160/90 and he
is found to have pitting oedema in both legs. Laboratory investigations
reveal: Hb 11.5 g/dl, Urea 35 mmol/l, Creatinine 275 µmol/l , Hepatitis B
antigen Positive ,Anti-nuclear antibodies Negative
What is the probable diagnosis?
 Membranous glomerulonephritis
 Hepatitis B infection
 Acute interstitial nephritis
 Renal tubular acidosis
 Systemic lupus erythematosus

106. Q 3
 A 47-year-old man attends the outpatient clinic complaining of swelling in
the ankles and lethargy. On examination, his blood pressure is 160/90 and he
is found to have pitting oedema in both legs. Laboratory investigations
reveal: Hb 11.5 g/dl, Urea 35 mmol/l, Creatinine 275 µmol/l , Hepatitis B
antigen Positive ,Anti-nuclear antibodies Negative
What is the probable diagnosis?
 Membranous glomerulonephritis
 Hepatitis B infection
 Acute interstitial nephritis
 Renal tubular acidosis
 Systemic lupus erythematosus

107. Q 4
 A 32-year-old woman presents with bilateral flank pain.
 Her GP had diagnosed a urinary tract infection 2 weeks
earlier on the basis of proteinuria, but she returned with
further pain, tiredness and general malaise. He noted a
raised serum creatinine of 285  mol/l at this time.
 Repeat urinalysis revealed blood and protein, but no
bacterial growth and no active urinary sediment.
 Her only past medical history is that she discontinued the
oral contraceptive pill after a DVT.

108. Q 4
 A 32-year-old woman presents with bilateral flank pain.
 Her GP had diagnosed a urinary tract infection 2 weeks earlier on the basis of proteinuria, but she returned with
further pain, tiredness and general malaise. He noted a raised serum creatinine of 285  mol/l at this time.
 Repeat urinalysis revealed blood and protein, but no bacterial growth and no active urinary sediment. Her only past
medical history is that she discontinued the oral contraceptive pill after a DVT.
What diagnosis fits best with this clinical picture?
 Nephrotic syndrome
 Nephritic syndrome
 Inadequately treated UTI with associated renal failure
 Ciprofloxacin-associated nephritis
 Bilateral renal vein thrombosis

109. Q 4
 A 32-year-old woman presents with bilateral flank pain.
 Her GP had diagnosed a urinary tract infection 2 weeks earlier on the basis of proteinuria, but she returned with
further pain, tiredness and general malaise. He noted a raised serum creatinine of 285  mol/l at this time.
 Repeat urinalysis revealed blood and protein, but no bacterial growth and no active urinary sediment. Her only past
medical history is that she discontinued the oral contraceptive pill after a DVT.
What diagnosis fits best with this clinical picture?
 Nephrotic syndrome
 Nephritic syndrome
 Inadequately treated UTI with associated renal failure
 Ciprofloxacin-associated nephritis
 Bilateral renal vein thrombosis

111. Diabetes Diagnostic criteria of DN
 Most common cause of NS In diabetic patient (>10 DM-1,
in adult. may be at diagnosis in DM-2)
development of:
 Most common cause of
 Persistent proteinuria
ESRD worldwide.
>300mg/24h
 In presence of HTN, P.
retinopathy, RF and
absense of other causes

112. Pathology Pathogenesis
 Wide spread thickening of the GBM  Advanced glycosylation end products
accounts for thickening of GBM &
 Diffuse glomerulosclerosis (increase in increased mesangial matrix (seen in
mesangial matrix & mild proliferation of all patients)
mesangial cells)
 Nodular glomerulosclerosis ( hyaline  Hemodynamic effects associated with
mass within mesangial core- glomerular hypertrophy leads to
Kimmelsteil-Wilson disease) glomerulosclerosis
 Hyalinization of arteriolar walls. IF may demonstrate
immunoglobulins and complement in the glomeruli.
EM regularly shows marked thickening of the GBM and
increased mesangial matrix material.

113.  Nodular glomerulosclerosis
(Kimmelstiel-Wilson lesion) of
diabetes mellitus.
 Nodules of pink hyaline material
form in regions of glomerular
capillary loops in the glomerulus.
 This is due to a marked increase in
mesangial matrix from damage as
a result of non-enzymatic
glycosylation of proteins.

114. <30mg/day
30-300mg/day
>300mg/d

116.  Amyloidosis is due to the systemic extracellular deposition
of:
 Antiparallel, β-pleated sheet
 Nonbranching
 8- to 12-nm fibrils
 Stain positive with Congo red (Apple green birefringence with
polarized light).
 Amyloidosis is frequently confirmed by biopsy of the
abdominal fat, kidney, or, in the case of AL amyloidosis
bone marrow

117.  Primary (AL) amyloidosis:
 AL amyloidosis: a single population (or clone) of plasma cells
grows excessively and produces abnormal proteins which are
deposited as amyloid fibrils in tissues and organs.
 AL amyloidosis can occur spontaneously, however, it is often
associated with other blood disorders, such as multiple
myeloma and Waldenström's macroglobulinemia
 kidneys are affected in 50% of patients.
 Patients are typically older than 50 years.
 Common renal manifestations include proteinuria, nephrotic
syndrome (25% of patients), and renal failure.

118.  Primary (AL) amyloidosis:
 Immunofluorescence generally demonstrates λ light chains in
the glomeruli (75% of patients).
 For patients with cardiac involvement, the prognosis is poor,
with a median survival of less than 2 years.
 Treatment with prednisone and melphalan can be beneficial in
some patients. In selected cases, high dose melphalan followed
by bone marrow transplantation has led to resolution of the
disease.

119.  Secondary (AA) amyloidosis
 Most common in patients with rheumatoid arthritis,
inflammatory bowel disease, chronic infection, or familial
Mediterranean fever and in subcutaneous drug users (heroin).
 Treatment of AA amyloidosis is directed at the underlying
inflammatory process. Colchicine is helpful in patients with
familial Mediterranean fever.

120. Amyloid deposits in the lip and tongue are present in this patient. Note the "scalloped"
appearance of the tongue in which indentations are present on both sides (arrows). This
occurs because the enlarged tongue chronically presses against the upper teeth.

121. Pale deposits of amyloid are present in the cortex,
most prominently at the upper center. (arrow)

122. The amorphous pink depositis of amyloid may be found in and around
arteries, in interstitium, or in glomeruli, as seen here with H&E stain.

123. Amyloid deposits are seen in glomeruli at the left and in arteries at the right

124. Glomerulus from renal biopsy stained with congo red and examined by polarization
microscopy. The characteristic "apple-green" birefringence of amyloid is apparent

125. Glomerulus from renal biopsy stained with congo red and examined by polarization
microscopy. The characteristic "apple-green" birefringence of amyloid is apparent

126.  Overwhelming infection
 Loss of opsonising factors in the urine w` is imp against encapsulated bacteria
such as Pneumococcus and Hemophilus influenza.
 Hypogammaglobulinemia
 Thromboembolism
 Children: sagittal sinus thrombosis, pulmonary artery thrombosis, or inferior vena
caval thrombosis
 Adults: deep vein or renal vein thrombosis.
 The hypercoagulable state results from:
 Increased clotting factor synthesis (fibrinogen, II, V, VII, IX, X, XIII)
 Urinary losses of anticoagulants (antithrombin III)
 Platelet abnormalities (thrombocytosis, increased aggregability)
 Hyperlipidemia
 Cardiovascular complications related to hyperlipidemia.
 Acute kidney injury: secondary to decreased renal perfusion and edema of
the renal interstitium.

127. Infection Clinical features Common organisms Antibiotics, duration
Abdominal pain, tenderness,
Cefotaxime or ceftriaxone for
distension; diarrhea, vomiting; ascitic S. pneumoniae, S. pyogenes,
Peritonitis fluid >100 leukocytes/mm3; >50% E. coli
7-10 days; ampicillin and an
aminoglycoside for 7-10 days
neutrophils
Fever, cough, tachypnea, intercostal S. pneumoniae, H. influenzae, Oral: amoxicillin, co-
Pneumonia recessions, crepitations S. aureus amoxiclav, erythromycin
Parenteral: ampicillin and
aminoglycoside; or
cefotaxime/ceftriaxone for 7-
10 days
Cutaneous erythema, induration, Staphylococci, Group A Cloxacillin and ceftriaxone for
Cellulitis tenderness streptococci, H. influenzae 7-10 days co-amoxiclav
Fungal Skin, mucosa: fluconazole for
Pulmonary infiltrates, persistent Candida, Aspergillus spp.
infections 10 days
Fever unresponsive to antibiotics, Systemic: amphotericin for 14-
sputum/urine showing septate hyphae 21 days

128.  Vaccines:
 23-valent pneumococcal vaccine: for all adults and all children older than 2
years.
 Influenza vaccine: yearly
 Childhood vaccines : Children should receive all
 Live virus vaccines (measles-mumps-rubella, varicella) may postponed until they are in
remission off of immunosuppressive medications.
 The administration of live virus vaccine may be associated with a relapse
 Varicella-zoster IgG titer: should be checked in all patients (Varicella infections in
individuals who are immune compromised, may be fatal).
 If the patient does not have a protective titer against varicella, vaccine should be given if
possible.
 If the patient cannot receive vaccine because of continued immunosuppression, varicella-
zoster immune globulin (VZIG) should be administered.
 If a patient who is immunosuppressed develops zoster, he or she should receive
immediate treatment with intravenous acyclovir.

129.  Reduction of thromboembolic complications:
 Protecting the intravascular volume of a critically ill patient in relapse.
 Central venous catheters should be avoided whenever possible.
 If a patient experiences a thromboembolic event, treatment should
include heparin or low molecular weight heparin, followed by warfarin
for 6 months.
 Therapy for chronic hyperlipidemia.
 Hypertension is best treated initially with an ACE inhibitor and/or
an ARB, which should help reduce the risk of cardiovascular
complications later.