CENTRO ESCOLAR UNIVERSITY

School of Medicine

SY 2018-2019

Urinary Tract

Lecture – Glomerulus

October 28, 2018

Urinary tract

1. Kidney
• Glomerulus
• Tubulo-intersititial tissue
• Vascular system

2. Ureter

3. Urinary bladder
Objectives

1. Explain the common diseases of the glomerulus:

• Etiopathogenesis
• Pathology
• Pathophysiology
• Signs and symptoms
• Outcome
Functions of nephron unit

1. Waste elimination

2. Fluid and electrolyte balance control

3. Acid-base balance control

4. Hormone production
GLOMERULUS
Glomerulus

1. Complex capillary tuft

2. Structure

3. Filters and retains impt molecules (e.g.,

proteins)
Structure of glomerulus

1. Endothelial cells

2. Basement membrane

3. Epithelial cells

4. Mesangial cells
Collagen fibrils
Endothelial cells

-- Coagulation factors
-- MHC expression
-- not a major filtration barrier
Basement membrane

1. Does not completely surround capillaries

2. Splays out over the mesangium

3. Potential pathway for substances to enter

mesanjgium without crossing BM

4. Strong negative charge

5. Major charge-selective barrier

Podocytes

1. Synthesize BM

2. Filtration slit diaphragm – thin membrane

bet foot processes

3. Major size-selective filtration barrier

Mesangium

1. Cellular and matrix network

2. Mesangial cells – modified smooth muscle cells

3. Provides mechanical support

4. Endocytosis and processing of plasma proteins

e.g., immune complexes

5. Maintenance of BM

6. Modulates filtration

7. Generates molecular mediators

GLOMERULAR DISEASES
Light microscopic expression of glomerular
injury (glomerulonephritis vs. glomerulopathy)

1. Hypercellularity – increase number of cells

• Endothelial cells
• Mesangial cells
• Epithelial cells (visceral/parietal)
• Leukocytes
• Crescent formation (parietal cells)
Light microscopic expression of glomerular
injury

2. Basement membrane thickening

• Deposition of immune complex
• Increase synthesis of BM components
• Formation of additional BM layers
Light microscopic expression of glomerular
injury

3. Hyalinization and sclerosis – end result of

glomerular damage from various causes
• Hyaline accumulation
• Deposition of extracellular collagenous
matrix e.g., mesangial deposition
Classification of glomerular disease

1. Etiology – immunologic; non-immunologic

2. Immunologic reaction – anti-glomerular

basement membrane; immune complex
deposition derived from various sources

3. Histologic pattern – proliferative;

membranous
Glomerular lesions best grouped into:

1. Primary – kidney prime target

2. Secondary – secondary to events

elsewhere in the body
Mechanisms of glomerular injury

1. Nephrotoxic antibodies – IgG antibodies against

glycoprotein in GBM

2. Immune complex deposition

• Passive entrapment of circulating complexes
• Binding to glomerular component
• Non-glomerular component binding with
glomerular component
Glomerular reaction to injury

1. Immune complex immune reaction

2. Role of glomerular cells

3. Chemical mediators
Primary glomerular disease

1. Anti-glomerular basement membrane

disease
• Autoimmune response against type IV
collagen
• Cross reaction with alveolar BM
• Crescentric glomerulonephritis
• Poor prognosis
• E.g., Goodpasture’s syndrome
Pathogenesis
Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis
e.g., post-streptococcal
Post-streptococcal glomerulonephritis

1. Pathogenesis

2. Histology
Post-streptococcal glomerulonephritis

1. Pathogenesis

2. Histology

3. Immunofluorescence

4. Electron microscopy
C3

IgG
Post-streptococcal glomerulonephritis

1. Pathogenesis

2. Histology

3. Immunofluorescence

4. Electron microscopy

5. Prognosis – good in children

Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis
e.g., post-streptococcal

• IgA nephropathy
IgA nephropathy

1. Most common type of glomerulonephritis

worldwide

2. Excess IgA production due to disturbance

in mucosal immunity

3. IgA and C3 deposition in mesangium

4. Major cause of chronic renal failure

Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis
e.g., post-streptococcal

• IgA nephropathy

• Membranous glomerulopathy
Membranous glomerulopathy

1. Mostly idiopathic

2. Some secondary

3. Pathogenesis ?

4. IgG and C3 deposition in thickened capillary

wall

5. Most common cause of nephrotic syndrome

in adults
Common causes
Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis e.g.,
post-streptococcal

• IgA nephropathy

• Membranous glomerulopathy

• Membrano-proliferative – pattern due to

many causes
Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis e.g.,
post-streptococcal

• IgA nephropathy

• Membranous glomerulopathy

• Membrano-proliferative – pattern due to

many causes

• Crescentric glomerulonephritis
Crescentric glomerulonephritis

1. Manifestation of severe injury

2. May be due to:

• Anti-GBM
• Deposition of immune-complex
• Renal vasculitis (immune diseases)

3. Rapid renal failure

Histology explains rapid
renal failure
Primary glomerular disease

2. Immune-complex-mediated injury
• Diffuse proliferative glomerulonephritis e.g.,
post-streptococcal

• IgA nephropathy

• Membranous glomerulopathy

• Membrano-proliferative – pattern due to

many causes

• Crescentric glomerulonephritis

• Minimal change disease

Chronic glomerulonephritis

1. End-stage renal disease

Nephrotic vs. Nephritic
Syndrome
Common causes
Acute renal failure

1. Sudden fall (oliguria) or total loss (anuria)

of urine production

2. Fluid and electrolyte imbalance

3. Hyperkalemia

4. Metabolic acidosis

5. Uremia
Causes

1. Central perfusion failure - most sensitive component

of the nephron to poor perfusion epithelial cells of
proximal and distal convoluted tubules causing acute
tubular necrosis

2. Glomerular disease – damage to majority of glomeruli

causing occlusion of glomerular capillaries thus
preventing blood flow into the efferent arterioles and
adequate perfusion of the peritubular capillaries

3. Tubulo-interstitial disease – affects absorption and

excretion of substances, e.g., electrolytes
Chronic renal failure

1. Progressive destruction of nephrons over

a prolonged period of time

2. Uremia

3. Sodium and fluid retention

4. Hyperkalemia

5. Metabolic acidosis