1. Evaluation of a child with glomerular disease
DR :Abdulhadi Altalhi .
Department of Pediatrics
Nephrology,Children Hospital, King saud Medical City .

2. GO BACK TO BASICS
Gross Anatomy of the Kidney STRUCTURE OF THE KIDNEY

3. Gross Anatomy of the Kidney

4. Cortical nephron
Juxtamedullary
nephron

5. Electron Micrographs Electron Micrographs
Examine the electron Micrographs so that you understand the ultrastructural equivalents of the structures you have seen under the microscope.
Vascular Arrangement in Glomeruli (SEM)
View larger size
Scanning electron micrograph of arterial blood supply to renal glomeruli (*). The afferent arterioles (aa) that supply the glomeruli (asterisk) receive blood from an interlobular artery (ia). Cormack, D.H. Ham's Histology, 9th ed., Lippincott, Philadelphia, 1987

6. And here we are We are now in Bowman’s space and
here are all the capillaries.

7. Left click anywhere to proceed
Now let’s wind up the magnification even further and look at the outside of one single capillary
Bowman’s space
Tufts of capillaries
Left click anywhere to proceed

8. The next slide will be a scanning electron microscope picture of exactly this - at great magnification
Tufts of capillaries

9. And this is what we would see
The out side of all the capillaries are clothed in epithelial cells that have complicated interdigitating patterns that are traditionally called foot processes.
Bowman’s space

10. The glomerular visceral epithelium consists of podocytes that have primary (1) extensions that branch to form secondary (2) processes from which the podocyte feet (pedicels) extend as side branches and contact the glomerular basement membrane. Arrows indicate interdigitating secondary processes of two neighboring podocytes (Inset). Cormack, D.H. Ham's Histology, 9th ed., Lippincott, Philadelphia, 1987, p. 578

12. And here is the endothelial cell lining of the blood capillary.
Here again is the downstream side of the filter with the interlacing foot processes of the epithelial cells.
Bowman’s space
And here is the endothelial cell lining of the blood capillary.
Look at the 3.5nm pores
in the endothelial cell lining.
These hold back the blood cell but allow plasma access to the basement membrane filter underneath.

13. Portion of glomerulus with three profiles of capillaries (C )
Portion of glomerulus with three profiles of capillaries (C ). Endothelial lining is highly fenestrated (F). Podocytes (P) extend primary processes (P1) that give rise to numerous foot processes (P2) which lie on the thick basement membrane (BM). Adjacent foot processes( aka pedicels),(separated by filtration slits (FS) are derived from different podocytes. The basement membrane is a product of both the endothelial cells and podocytes. Young, B & Heath, JW, Wheater's Functional Histology, 4th ed., Churchill Livingstone, London, 2000

14. INTRODUCTION 
There are many causes of glomerular diseases in children. Many of these conditions vary in their presentation with mild or no symptoms to serious renal disease with life-threatening complications. As a result, the diagnosis of a specific glomerular disease is challenging in children but important so that therapy, if helpful and needed, can be initiated
There are numerous causes of glomerular diseases in children. Many of these conditions vary in their presentation with mild or no symptoms to serious renal disease with life-threatening complications. As a result, the diagnosis of a specific glomerular disease is challenging in children but important so that therapy, if helpful and needed, can be initiated

15. OVERVIEW — 
Glomerular disease either primary (renal disease alone) or secondary (due to systemic autoimmune disorders, vasculitis, or infection) disorders .
Dividing childhood glomerular diseases into two clinical patterns is useful because the evaluation can focus on the most likely underlying disease.
The identified primary pattern of glomerular disease: nephritic or nephrotic presentation.

16. Glomerular disease pattern
The clinical manifestations, urinalysis,and
the rate of protein excretion divide children with glomerular disease into two groups: patients with glomerulonephritis, and those with nephrotic syndrome. In both groups, renal function is assessed by measuring the serum creatinine.

17. Clinical features
  Glomerulonephritis is characterized by edema, hypertension, reddish brown to brown colored urine, and a rising serum creatinine.
Nephrotic syndrome usually present only with edema. In severe cases, nephrotic patients may have anasarca with ascites, and respiratory distress caused by pleural effusions.
Patients with secondary causes of glomerular disease often have nonrenal symptoms and signs (eg, fever, arthralgias, rash, and pulmonary hemorrhage) that are suggestive of a specific underlying systemic disease.

19. Urinalysis
Children with glomerulonephritis typically urinalysis findings include evidence of glomerular bleeding, such as red blood cells and red cell casts .
Patients generally have proteinuria greater than 100 mg/m2 per day, when there is no gross hematuria.
 Testing of the urine is the most important noninvasive test in determining whether or not a child has glomerular disease, and if present, distinguishes between the two patterns of glomerular disease. Children who have evidence of glomerular bleeding are likely to have glomerulonephritis, and those with heavy proteinuria are likely to have nephrotic syndrome.
The following urinalysis findings, if present, are indicative of glomerular bleeding and glomerulonephritis. However, the absence of these findings does not exclude glomerulonephritis (table 2).
Red cell casts (pathognomonic for glomerular bleeding) (picture 1)
Red blood cells that are dysmorphic in appearance (picture 2A-B)
Protein excretion greater than 100 mg/m2 per day at a time when there is no gross bleeding
In contrast, the urinalysis of children with nephrotic syndrome is associated with heavy proteinuria and lipiduria but few cells or cast. Although the urinary dipstick measurement is a qualitative test, a 4+ recording, which corresponds to a concentration of urinary albumin of 1000 mg/dL, is suggestive of nephrotic range proteinuria, defined as a urinary protein excretion greater than 50 mg/kg per day or 40 mg/m2 per hour

24. Differential diagnosis: other diseases which may present with acute
nephritic syndrome.

25. Presenting clinical features of paedriatric glomerular diseases that may mimic APSGN
*Some of these values are estimates, as good epidemiological data are not published.
**Incidence depends upon the histological class lupus nephritis.
***A small number of cases presenting early in the clinical course of the disease may have very transiently depressed C4 levels.
APSGN, acute post-streptococcal glomerulonephritis; MPGN, membranoproliferative (mesangiocapillary) glomerulonephritis; SLE,
Systemic lupus erythematosus; ANCA, anti-neutrophil cytoplasmic antibody; ASOT, antistreptolysin-O titre; ANA, antinuclear antibody;
Anti-dsDNA, anti-double-stranded DNA.
APSGN
Henoch-Schonlein
purpura
IgA
nephropathy
MPGN
SLE
ANCA-positive
vasculitis
Mean age
(years)
5-15
4-14
10-20
8-20
15-20
12-20
Antecedent
Infection
Yes
35%
Concurrent
Common
Rare
Flu-like prodrome
Gross
Haematuria
30%
20%
50-80%
20-50%
<10%
Nephrotic
Syndrome* 5%
5-10%
30-50%
0-50%**
Serum C3
Low
Normal
Serum C4
Normal***
Normal/low
Diagnostic
Serology
ASOT;
streptozyme No
ANA,anti-
dsDNA
ANCA
Extra renal
disease

26. PATTERNS OF CHANGE

27. Biopsy Pathology of Glomerular Disease Patterns of glomerular damage

28. Pathological features of glomerulonephritis Descriptive Terms
Patterns of Damage - 1
One Glomerulus compared with another
All glomeruli normal
= No glomerulonephritis
All glomeruli abnormal
= diffuse glomerulonephritis
Some glomeruli abnormal
= focal glomerulonephritis
(often secondary to
systemic disease)

29. Pathological features of glomerulonephritis Within a single glomerulus
Descriptive Terms
Patterns of Damage - 2
Within a single glomerulus
Normal
= No glomerulonephritis
Damage to part
of glomerulus only
= segmental glomerulonephritis
Damage to all parts
= global glomerulonephritis

30. Pathological features of glomerulonephritis Within a single glomerulus
Descriptive Terms
Patterns of Damage - 2
Within a single glomerulus
There is one further pattern of damage within a single glomerulus that is important because it:
1. Signifies very bad news
2. Picks out a particular group of patients under the collective title of
Left click to reveal

31. Pathological features of glomerulonephritis Descriptive Terms
Patterns of Damage - 2
Within a single glomerulus
There is one further pattern of damage within a single glomerulus that is important because it:
1. Signifies very bad news
2. Picks out a particular group of patients under the collective title of
Rapidly Progressive Glomerulonephritis
Rapidly Progressive Glomerulonephritis is uncommon but very serious.
Click here to learn more about it

32. Press here for one slide about Goodpasture’s disease
Pathological features of glomerulonephritis
Descriptive Terms
Rapidly Progressive Glomerulonephritis
Causes:
1. Bad end of the spectrum of many mechanism but especially -
Anti-basement membrane disease
inluding Goodpasture’s disease
Press here for one slide about
Goodpasture’s disease
Otherwise left click in here

33. Left click to proceed Goodpasture’s Disease Clinical features:
1. Rapidly Progressive Renal Failure
2. Haematuria
3. Haemoptysis
Pathological features:
1. (Cresentic Glomerulonephritis)
2. Deposition of linear IgG and IgM along basement membranes.
Cause:
Specific auto immune immunoglobulin attack on basement membrane’s of 1. Capillaries of the glomeruli in the kidneys and 2. Capillaries in the lung.
Left click to proceed

34. LIGHT MICROSCOPY

35. Pathology of Glomerular Disease
Welcome to a mini-unit on
Light microscopy
This section describes the
central basis for
the pathological classification of Glomerulonephritis
The way in is to start with
the normal components of the Human Glomerulus
Left click to proceed
Left click to proceed

36. Normal Components of the Human Glomerulus
Stuff = non-cellular material
Cells
Normally present
Normally present
Glomerular Basement Membrane
Endothelial cells
Epithelial cells
Mesangial cells

37. A picture of a normal human glomerulus
against which to compare the various diseases.
Tufts of capillaries
Tufts of capillaries
Bowman’s Space
Thin basement membranes
Afferent arteriole
Nuclei of glomerular cells

38. What can change in disease ? Too many cells = proliferation
Stuff (= non-cellular material)
Normally present
Normally present
Endothelial cells
Capillary Basement Membrane
Epithelial cells
Mesangium = stalk
Thickening of the
basement membrane
Too many cells = proliferation
Mesangial cells
First let’s look at changes the previously normal components.
Now click to see changes in normal non-cellular stuff. .
Click to see changes in resident normal cells

39. What can change in disease ? Too many cells = proliferation
Stuff (= non-cellular material)
Normally present
Normally present
Endothelial cells
Capillary Basement Membrane
Epithelial cells
Mesangium = stalk
Thickening of the
basement membrane
Too many cells = proliferation
Mesangial cells
Now we will look at abnormal components that can appear in disease. .

40. What can change in disease ? Too many cells = proliferation
Stuff (= non-cellular material)
Normally present
Normally present
Endothelial cells
Capillary Basement Membrane
Epithelial cells
Mesangium = stalk
Thickening of the
basement membranes
Too many cells = proliferation
Mesangial cells
Only present when abnormal
Amyloid
Collagen scars (glomerulosclerosis)
Myeloma protein
Diabetic deposits
Deposits
Fibrin
Inflammatory cells
Too many cells
= inflammation.
But still called “proliferation”
Now left click to see abnormal non-cellular stuff.
Left first click to see abnormal cells.

41. HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called?
Proliferative glomerulonephritis
Too many cells =
Left click anywhere to find out

42. HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called?
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Left click anywhere to find out

43. HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called?
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Have a guess. It’s easier than you think
Left click anywhere to find out

44. HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called?
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Nephrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Left click anywhere to find out

45. HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called?
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Nephrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Collagen scars in some glomeruli =
Focal Glomerulosclerosis
Left click anywhere to find out

46. Click in each box in turn to explore each type in turn
HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS
Click in each box in turn to explore each type in turn
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Nephrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Collagen scars in some glomeruli =
Focal Glomerulosclerosis .
SECONDARY GLOMERULONEPHRITIS

47. HISTOLOGICAL CLASSIFICATION OF GLOMERULAR DISEASE
Proliferative glomerulonephritis (too many cells)
Endothelial cells
Diffuse Proliferative g/n
Inflammatory cells
Mesangio-proliferative g/n typical of Berger’s disease
Mesangial cells
Epithelial cells (as “Cresents” in Bowman’s space)
Rapidly Progressive g/n

48. HISTOLOGICAL CLASSIFICATION OF GLOMERULAR DISEASE
Proliferative glomerulonephritis (too many cells)
Endothelial cells
Diffuse Proliferative g/n
Inflammatory cells
Left click anywhere to see a picture and to read about the clinical correlations of each
Mesangio-proliferative g/n typical of Berger’s disease
Mesangial cells
Epithelial cells (as “Cresents” in Bowman’s space)
Rapidly Progressive g/n

49. Click in each box in turn to explore each type in turn
HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS
Click in each box in turn to explore each type in turn
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Neohrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Collagen scars in some glomeruli =
Focal Glomerulosclerosis
left click in here to return to “Pathology” page.
SECONDARY GLOMERULONEPHRITIS

50. Click in each box in turn to explore each type in turn
HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS
Click in each box in turn to explore each type in turn
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Neohrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Collagen scars in some glomeruli =
Focal Glomerulosclerosis
left click in here to return to “Pathology” page.
SECONDARY GLOMERULONEPHRITIS

51. Click in each box in turn to explore each type in turn
HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS
Click in each box in turn to explore each type in turn
Proliferative glomerulonephritis
Too many cells =
Thickening of basement membranes =
Membranous glomerulonephritis
Increase number of cells and thickening of basement membranes =
Membrano-proliferative glomerulonephritis
Neohrotic syndrome but thickening of basement membranes =
Minimal Change glomerulonephritis
Collagen scars in some glomeruli =
Focal Glomerulosclerosis
left click in here to return to “Pathology” page.
SECONDARY GLOMERULONEPHRITIS

52. Three types of Membrano-proliferative g/n
Type 1 = Mesangiocapillary g/n
Immune complex mediated
Causes mostly unknown Some associated with infections, drugs, tumours, etc.
Many associated with persistent C3 hypocomplementaemia
Course = progressive deterioration
Type 2 = Dense deposit disease
Related to activation of the alternate complement pathway
Dense deposits in basement membrane are not immune complexes
Type 3
Rare
Left click anywhere to return

53. Click within a box to find out more about each in turn
ELECTRON MICROSCOPY
Here I have selected for you the three topics that I think are most relevant.
Of these the first section is by far the most important.
Normal Appearances
Changes with Proteinuria
Immune Complex Disease
Click within a box to find out more about each in turn
Otherwise click in here to return to Pathology page