RENAL DISEASES

The Nephron
• Consists of the glomerulus and its attached
tubules.
• The functional unit of the kidney.
 Major Renal Syndromes
• Acute Nephritic Syndrome
• The Nephrotic Syndrome
• Rapidly Progressive Glomerulonephritis
• Asymptomatic Hematuria or Proteinuria
 Major Renal Syndromes (cont)
• Acute Renal Failure
• Urinary Tract Infection
• Nephrolithiasis
 Acute Nephritic Syndrome
• Sudden onset of hematuria with RBC casts and
renal failure (days - weeks)
– RBC casts not listed in the book!! But this is critical!!
• Proteinuria (mild to moderate but NOT Nephrotic
Range)
• Hypertension
• Hallmark Disease: Post Streptococcal
Glomerulonephritis
What is an
RBC cast?
 The Nephrotic Syndrome
• Proteinuria (>3.5gm/day)
• Hypoalbuminemia
• Edema
• Hyperlipidema
• Lipiduria
 Rapidly Progressive
Glomerulonephritis

• Nephronal hematuria
• Renal failure developing over weeks to months
• Diffuse glomerular crescent formation.
 Asymptomatic Hematuria or
Proteinuria

• Hematuria with or without RBC casts and/or

• Proteinuria usually <2.0gm/day
• NO RENAL FAILURE
• NO NEPHROTIC SYNDROME
 Acute Renal Failure
• Oliguria (<400ml/day)
• Rarely anuria
• Recent Onset of Azotemia (hours/days)

RENAL CAUSES Post-Renal Causes

RPGN
Acute Neprhitic Syndrome
Pre-Renal Causes
 Chronic Renal Failure
• Uremia
• Final Common Path of All Chronic Renal
Diseases
 Urinary Tract Infection
• Bacteriuria and Pyuria
• Dysuria, Frequency, Urgency
• Pyelonephritis or Cystitis
• WBC casts = Pyelonephritis
– The Book Misses this one!!
• Fever
– The Book Misses this one!!
 Nephrolithiasis
• Renal stones
• Renal colic - OOOUUUCCCHHH!!
– Severe, Crampy Pain in the flank area
• Hematuria (Not RBC casts!)
 Glomerular Diseases
• An important cause of chronic renal failure
• Renal Syndromes related to Glomerular Diseases
– Acute Nephritic Syndrome
– Nephrotic Syndrome
– Rapidly Progressive Glomerulonephritis
– Asymptomatic Hematuria or Proteinuria
 Glomerulus
• Endothelial cells
• Glomerular basement membrane (GBM)
• Podocytes - Visceral Epithelial Cell
• Mesangial cells and matrix
• Parietal epithelium
• Bowman’s Capsule
Normal Glomerulus PAS
Normal Glomerulus Silver Stain
GBM

Mesangium

Normal Glomerulus EM
 Capillary Space
GBM

Endothelium

Podocyte
Urinary Space

Glomerular Basement Membrane

 Glomerular Basement Membrane

Podocytes
 Glomerular Function
• Glomerular filtration
– barrier
– charge
Pathogenesis of Glomerular Diseases

• Immune mechanisms
• Non-immune mechanisms
 Immune Mechanisms of Glomerular
Disease

• Antigen antibody reaction

– Antigen - antibody complex deposition
– Antibodies reacting in-situ within the glomerulus
• Cell mediated immune mechanisms
 Circulating Immune Complex Nephritis

• Glomerulus is “innocent bystander”

• Antigen is either endogenous or exogenous
• Antigen - antibody complexes trapped in
glomeruli.
• Role of complement
Circulating Immune Complex Nephritis:
Histologic Manifestations

• LM - Cellular proliferation and leukocyte

infiltration
• EM - Electron dense deposits
• IF - Granular deposits
 Immune Complex Nephritis
In-Situ

• Antiglomerular basement membrane disease

• Antibodies against fixed antigens in the GBM
• LM - crescents
• IF - linear deposits
Antiglomerular Basement Membrane
Antibodies

• Board Hint:
– Basement membrane antigen in Good Pasture’s -
Alpha 3 chain of collagen type 4
 Heymann’s Nephritis - Membranous
GN

• Antigen - Megalin associated with receptor

associated protein
• Discontinuous distribution
• Granular IF
 Immune Complex Nephritis - “Planted”
Non-glomerular Antigens

• Including: Cationic molecules; DNA; Bacterial

products; etc..
• IF - granular pattern
 Cell Mediated Immune
Glomerulonephritis

• Sensitized T-cells are thought to cause glomerular

injury
• May account for GN without immune deposits
 Mediators of Immune Injury
• Glomerular damage - loss of glomerular barrier
function
• Manifested by proteinuria and sometimes by
reduced GFR
Complement - Leukocyte Mediated
Mechanism
One Well-Established Pathway!!!
• Activation of complement initiates:
– Chemotaxis (C5a)
– Neutrophil and monocyte infiltration
 Neutrophil Activity

• Proteases
• Reactive oxygen metabolites
• Arachidonic acid metabolites
 Other Mediators
• Cytotoxic antibodies
• Macrophages
• Platelets
• Resident glomerular cells
• Fibrin related products
 Other Mechanisms of Glomerular
Injury
• Epithelial cell injury
– “X” - factors
– resulting in epithelial cell detachment
– proteinuria
• Renal ablation glomerulopathy
– fall in GFR
– leads to end stage renal failure