Transcript MGM Medical College Lecture Kidney Part 1 11/06/13

Pathology of Kidney
Dr. Sachin Kale, MD.
Associate Professor, Dept of
Pathology.
Anatomy of Kidney
Note the
positions of
Glomerulus
PCT, DCT, CT
Cortex,
Medulla,
Pelvis.
Glomerular diseases:

Primary
– Acute diffuse post streptococcal
– RPGN
– Membranous GN
– FSGS
– MPGN
– Lipoid nephrosis or minimal change
– IgA nephropathy

Secondary
– SLE, Diabetes, Amyloidosis,
Goodpasture’s syndrome, PAN, WG,
HSP, Hypertension etc.
Clinical Syndromes:

Nephritic syndrome.
– Oliguria, Haematuria, Proteinuria, Oedema,
Azotemmia, Hypertension.

Nephrotic syndrome.
– >3.5 gm proteinuria, Hypoalbuminemia
hyperlipidemia, Lipiduria

RPGN.
– Nephritis, loss of Kidney function - within weeks

Chronic renal failure.
– Azotemia/uremia progressing over months and
years

Asymptomatic Hematuria or proteinuria
CHRONIC RENAL FAILURE
Fluid and Electrolytes: Dehydration, Edema, Hyperkalemia,
Metabolic acidosis
Calcium Phosphate and Bone: Hyperphosphatemia,
Hypocalcemia, Secondary hyperparathyroidism, Renal osteodystrophy
Hematologic: Anemia, Bleeding diathesis
Cardiopulmonary: Hypertension, Congestive heart failure,
Pulmonary edema, Uremic pericarditis
Gastrointestinal: Nausea and vomiting, Bleeding, Esophagitis,
gastritis, colitis
Neuromuscular: Myopathy, Peripheral neuropathy, Encephalopathy
Dermatologic: Sallow (greenish-yellow) color, Pruritus,
Dermatitis
ACUTE TUBULAR NECROSIS
•
•
•
•
Destruction of renal TUBULAR epithelium
Loss of renal function
50% of ACUTE renal failure
Two types:
ISCHEMIC
NEPHROTOXIC
-AMINOGLYCOSIDES
-AMPHOTERICIN B
-CONTRAST AGENTS
NORMAL
ATN
ATN PATHOGENESIS
• BLOOD FLOW
DISTURBANCES (ISCHEMIC)
• TUBULAR INJURY
(NEPHROTOXIC)
CLINICAL COURSE
• INITIATION (36 hours)
– Mild OLIGURIA
– Mild AZOTEMIA
• MAINTENANCE
– More OLIGURIA
– More AZOTEMIA
– DIALYSIS NEEDED
• RECOVERY
– HYPOKALEMIA main problem
– BUN, CREATININE return to normal
Immune Mechanisms of
Glomerular injury:


Antibody mediated:
In-Situ immune complex deposition
– Tissue antigens - Goodpasture anti GBM Ag
– Planted antigens - infections, toxins, drugs.

Circulating immune complex deposition.
– Endogenous - DNA as in SLE
– Exogenous – infections – HBsAg, Syphilis,
Streptococcal, Falciparum,


Cell mediated Immune injury
Activation of alternate complement
pathway
Immune
Glomerulonephritis:
1.
2.
3.
4.
5.
6.
Antigen or Antibody - Immune reaction
Activation of complements,
Neutrophils…
destruction of glomerular structure
Inflammation, exudation  swelling.
↓ blood flow, GFR, Oliguria, Proteinuria, Hematuria,
Hypertension.
Neutrophil Activity



Proteases – GBM degradation
Reactive oxygen metabolites – cell
damage
Arachidonic acid metabolites –
Reduction in GFR
Other Mediators





Cytotoxic antibodies
Macrophages
Platelets
Resident glomerular cells
Fibrin related products
Nephritic Syndromes :

Diffuse Proliferative GN
– Post Streptococcal.

Rapidly Progressive GN (or Crescentic)
– Post Streptococcal, Goodpasture’s,

Focal Glomerulonephritis
– Primary: Bergers disease (IgA Nephritis)
– Secondary IgA nephritis, Henoch
Schonlein purpura, SBE, Coeliac Disease
etc.
Diffuse Proliferative GN:





Post streptococcal* common –
Primary infection - Pharynx, skin, ear
etc..
Kidney damage – 1-4 weeks after
infection.
Malaise, fever, nausea, edema*,
↑ASO, ↓C3
Resolution in 6-8 weeks.
Post Streptococcal GN
(Prol.GN):




1-4 weeks following streptococcal
infection by nephritogenic strains
(time for Ab formation)
Immune mediated
Granular deposits of IgG,IgM & C3 in
GBM, (subepithelial location common)
Humps in GBM on EM or IF Microscopy
•Normal
•Inflammation
•Proliferation
•Swelling.
•Narrow capillary
•↓GFR-Renin-BP
•Post Strepto GN
Diffuse Proliferative GN:




Enlarged hypercellular
glomeruli.
Hyperplasia of
epithelium &
endothelium. Cell
Swelling.
Inflammatory cells.
Collapsed capillaries.
Obstruction to blood
flow.
IF- Diffuse Proliferative
GN
Pathogenesis of Diffuse
PGN:


Streptococcal infection – Antibody attack
GBM - inflammation & proliferation.
Glomerular capillary obstruction:
– J.G.A stimulation – Renin – high blood
pressure
– Reduced filtration – raised blood urea
– Fluid retention – Oedema

Damage to GBM:
– Unselective proteinuria (form Pr. casts in
tubule)
– Haematuria (form RBC casts in tubule)
Progression of DPGN:
Poststreptococ
cal DPGN
Rapidly
Progressive GN
Complete Healing
CGN
Cardiac Failure or
Uremia; death in
acute phase
RPGN




Clinicopathologic syndrome
Glomerular damage
Rapid progressive decline in renal
function
Histology: accumulation of cells in
Bowman’s space in the form of
“Crescents”
RPGN: Classification &
Pathogenesis





Postinfectious
GN associated with systemic diseases
Idiopathic RPGN
Glomerular injury is immunologically
mediated.
Goodpasture’s syndrome – classic antiGBM nephritis
RPGN classification


Post-infectious RPGN
Systemic diseases –
– SLE, Goodpasture’s, Vasculitis (PAN),
Wegener’s granulomatosus, HSP,
Essential cryoglobulinemia

Idiopathic RPGN
RPGN cont..





Idiopathic : ½ the cases,
Linear, Granular or minimal to none
immune deposits
Gross: Enlarged pale kidneys Large
white kidney
Petechial hemorrhages in cortex
M/E: Glomeruli: focal necrosis,
endothelial proliferation
RPGN…




Formation of crescents:
Proliferation of parietal cells, migration
of monocytes and macrophages into
Bowman’s space
Crescents obliterate Bowman’s space,
compression capillary tuft
Crescents undergo sclerosis
RPGN: Clinical features




Goodpasture’s Syndrome: recurrent
hemoptasis & renal manifestations
Hematuria, Red cell casts, Moderate
proteinuria,
Variable HT and edema
Oliguria
Which of the following
presents with hematuria,
proteinuria and
hypertension




Nephrotic syndrome
Nephritic Syndrome
UTI
Renal Tubular Acidosis
All of the following are seen
in renal failure except




Hypercalcemia
Hyperkalemia
Bone lesions
Metobolic Acidosis
Anemia in renal failure is
generally




Microcytic hypochromic
Normocytic normochromic
Dimorphic
megaloblastic
Which of the following is
not a primary GN




Minimal Change disease
Membranous GN
Diabetes mellitus
RPGN
Which of the following is not
part of nephrotic syndrome




Lipiduria
Hypertension
Proteinuria
Edema
True about Post-strepto
GN -




Occurs 1 – 4 months after infection
Occurs 1 – 4 days after infection
Occurs 1 – 4 weeks after infection
Non of the above
False about RPGN..




Formation of crescents
Small contracted kidneys
Hematuria
Oliguria
Spot the diagnosis
RPGN
Spot the diagnosis
ATN
Spot the diagnosis
Post
streptoco
ccal GN
Thought for the day…

Ours is a world where people don't
know
what they want and are willing to go
through hell to get it.
Thanks…

http://sachinkale1.tripod.com