Renal pathology

- DR.AKIF A.B
STEP TO PG-MD/MS/DNB - DR.AKIF A.B

-100% Glucose
-100% amino acids and Proteins
-90% of Bicarbonate
-60-70% of water
-60-70% of all other solutes
-40% of urea
Reabsorption

- Highly permeable to water
-Relatively impermeable to solutes. Hence
concentration of filtrate increases

-Less permeable to water
- But highly permeable to NaCl

-Almost totally impermeable to water
-Na+/K+/2Cl- channel is present here.It reabsorbs
Na,K and Cl.
-Mg and Ca is also reabsorbed
- Loop diuretics acts by inhibiting this channel.

Furosemide Diuretic of choice in patients with
Renal Failure.
Torsemide Longest acting
Ethacrynic acid Most ototoxic Loop Diuretic
-All have weak carbonic anhydrase
activity except Ethacrynic acid.
Bumetanide Most potent loop diuretic
Indacrinone It is used in Gout as it decerases
reabsorption of Uric acid in nephron.

-They have weak Carbonic anhydrase action except Ethacrynic Acid
-Uses :
1) Pulmonary edema

-Similar to Thick Ascending Loop of Henle
-water is less reabsorbed
- 7% of total NaCl is reabsorbed via Na+/Cl- channel

-It has 2 types of cells:
1) Principal cell
2) Intercalated cell
Principal cell is
responsible for
Intercalated cell
- Na+ reabsorption - H+-K+ channel
- K+ secretion Secretes H+
- H20 absorption Reabsorbs K+

PCT Collecting Duct
Brush border present No brush border
Carbonic anhydrase (type4) is present at
luminal membrane
No Carbonic anhydrase (type4) is present
at luminal membrane
Cytoplasmic carbonic anhydrase (type2)
present
Cytoplasmic carbonic anhydrase (type2)
present
Leaky tight junction present Tight tight junctions present
Paracellular transport is possible via leakt
‘TJ’
Paracellular transport is not possible
Gap junctions present at lateral cell
membrane
Gap junctions absent
- Acetazolamide acts on both type2 and type4 cell membrane.

Cortical nephrons Juxtamedullary nephrons
85% of all nephrons 15%
Short Loop of Henle Long loop of henle (Responsible for
counter current multiplier)
Peritubular capillary network is short Peritubular capillary network forms
vasa recta : responsible for counter
current exchanger
Blood flow is large (5ml/gm/min) Less (0.6ml/gm/min)
O2 consumption is high (9ml/gm/min) Low (0.4ml/gm/min)

Total 1250 ml/min
Cortex 5ml/gm/min
Outer medulla 2.5ml/gm/min
Inner medulla 0.6ml/gm/min
-Renal plasma flow = 700ml/min
-Effective Renal Plasma flow = 625ml/min = Measured via Para Amino Hippuric
Acid (PAH) clearance

Total 18ml/gm/min
Cortex 9ml/min/kg
Medulla 0.4ml/min/kg
-Arterio venous O2 difference =14ml/L

Glomerular endothelial cell layer
+
Basement membrane
+
Podocyte (Visceral epithelial layer of Bowman
capsule)

-Slit diaphragm consists of proteins : NPHS-1(Nephrin) , NPHS-2(podocin),actinin etc.

Gene Protein Disease Inheritance
NPHS-1 Nephrin Finnish type of
nephrotic Sx
AR
NPHS-2 Podocin Congenital
nephrotic Sx
AR
LAMB2 Laminin Beta2 Pierson Sx AR
ACTN4 Alpha actinin 4 FSGS AD
COL4A5,3,4 Collagen IV alpha
5
Alport’s Sx XR

-Depends on :
1) Size of particle
2) Charge of particle
Size Charge
<4nm Freely permeable Glomerular basement
membrane is
negatively charged.
>8nm Not permeable So +ve charged
particles are easily
filtrable
4-8nm Depends on charge -ve charge particle are
difficult for filtration

TYPE 2
HYPERSENSITIVITY
TYPE 3
HYPERSENSITIVITY
TYPE 4
HYPERSENSITIVITY
Good-Pasture Sx PSGN Granulomatous
MGN
MPGN
IgA Nephropathy
FSGS
Lupus nephritis

Sub-epithelial Sub
endothelial
Membranous Mesangial
PSGN MPGN-I MPGN-II IgA Nephropathy
MGN
RPGN-II

NEPHRITIC Sx NEPHROTIC Sx
Proteinuria <3.5gm/dl (usually
<1.5gm/dl)
>3.5gm/dl
Edema Mild ( Due to Na+ and
water retention)
Severe ( Due to loss of
Proteins)
Hypertension Severe Mild
Hematuria +++ +
Uremia +++ +
Etiology PSGN ( MC in Children) Minimal Change
Disease( MC in
Children)
MPGN MGN
RPGN FSGS( MC in adults)
IgA Nephropathy( MC
in adults)
MPGN
IgA Nephropathy

Etiology Clinical Features Prognosis
Unknown No prior history Excellent prognosis
99% - Recovers
1% - Progress to chronic
glomerulonephritis

Light Microscopy
(L.M)
Electron
Microscopy (E.M)
Fluorecent
Microscopy (F.M)
No changes Effacement of foot
process
(Podocytopathy)
No changes
- Selective Proteinuria

Effaced foot
Process of
Podocyte
basement membrane
Fenestrated
endothelium

FOCAL SEGMENTAL
GLOMERULOSCLEROSIS (FSGS).
collagenous sclerosis
To focal and segmental
Proliferation of
Visceral epithelial
cells

An area of collagenous sclerosis runs across the middle of this glomerulus.
Focal : <50% of Glomeruli are involved
Segmental : Part of glomerulus involved
In contrast to minimal change disease, patients with FSGS are more likely to
have non-selective proteinuria, hematuria, progression to chronic renal failure, and
poor response to corticosteroid therapy.
FOCAL SEGMENTAL

FOCAL SEGMENTAL
ETIOLOGY
1) Reflux Nephropathy (MC)
2) HIV
3) Sickle cell anemia
4) I.V Drug abuse
5) Massive obesity
6) Congenital Nephrotic Sx

Minimal change disease FSGS
Selective proteinuria Non selective proteinuria
Hematuria –ve +ve
Low chances of progression to
Chronic Glomerulonephritis
(<!%)
High chances of progression
Good response to steroids Poor response
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS (FSGS)

This trichrome stain of a glomerulus in a patient with focal segmental
glomerulosclerosis (FSGS) demonstrates blue collagen deposition.
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS (FSGS)

This glomerulus is hypercellular and capillary loops are poorly defined.
This is a type of proliferative glomerulonephritis known as post-infectious
glomerulonephritis.
This case followed a group A beta hemolytic streptococcal infection of the
pharynx 3 weeks earlier, and thus it could be termed 'post-streptococcal
gomerulonephritis'.

The
hypercellularity
of post-infectious
glomerulonephritis
is due to
increased
numbers of
epithelial,
endothelial, and
mesangial cells
as well as
neutrophils in
and around the
glomerular
capillary loops.

Etiology C/F Prognosis
Beta hemolytic
Streptococci
Nephritic Sx
Hematuria after 7-
21days after Sore
throat/Pyoderma
Very good
95% - Resolves
Antibiotic prophylaxis
has no role in
preventing PSGN
5% -Chronic
glomerulonephritis
<1% - RPGN

L.M F.M E.M
Endo and exo capillary
proliferation
Granular deposit
(Lumpy bumpy
deposit)
Sub epithelial deposits

Question:
What 3 serologic tests have high sensitivity for post-streptococcal
GN?
Answer :
1) The anti-streptolysin O (ASO),
2) anti-hyaluronidase, and
3) anti-DNase B test

Post-infectious
glomerulonephritis is
immunologically mediated,
and the immune deposits are
widely distributed within the
capillary loops.
The deposits are seen here
with bright breen
fluorescence in a granular,
bumpy pattern because of
the focal nature of the
immune complex deposition
process.

Subepithelial
humps
basement
membrane
epithelial cell

Here is the light microscopic appearance of
membranous nephropathy in which the
capillary loops are thickened and prominent,
but the cellularity is not increased.
Membranous GN is the most common cause
for nephrotic syndrome in adults. In most
cases there is no underlying condition
present (idiopathic). However, some cases of
membranous GN can be linked to a chronic
infectious disease such as hepatitis B, a
carcinoma, or SLE.

Etiology
1) Infections : Hepatitis B> C , HIV,Leprosy, Syphilis
2) Autoimmune : SLE, RA
3) Drugs : Gold, Penicillamine, NSAIDs
4) Malignancy : Ca. colon, Melanoma

Light Microscopy F.M E.M
Sub epithelial deposits
On PAS Stain : Spike
and Dome
appearance
Granular deposits Podocytopathy

Spike and Dome
appearance

By electron microscopy in
membranous nephropathy, the
darker electron dense
immune deposits are seen
scattered within the thickened
basement membrane. The
"spikes" seen with the silver
stain represent
the intervening matrix of
basement membrane between
the deposits.
Spike and Dome
appearance

-H/O progression to renal failure within 4 weeks.
-Microscopic Examination = Crescents
-Gross = Flea Bitten Kidney
Type I RPGN Type II RPGN Type III RPGN
Anti Glomerular
Basement membrane
antibodies
Immune complex Pauci Immune or no
immune complex
Good Pasture Sx MGN Wegener’s
Granulomatosis
MPGN Microscopic
Polyangitis
PSGN Churg Strauss Sx
IgA nephropathy ANCA associated
Lupus Nephritis

-Experimentally induced MGN
-Megalin antigen
-Inserted in Rat
-Immune complex deposited
-Biopsy : Similar to MGN

FLEA BITTEN
KIDNEY
More is the no. of
Crescents = Poorer is
the Prognosis

Type I Type II Type III
Linear deposits (Ribbon
like)
Granular deposits No deposits

Seen here within the
glomeruli
are crescents composed of
proliferating epithelial cells.
Crescentic
glomerulonephritis is known
as rapidly progressive
glomerulonephritis (RPGN)
because this disease is very
progressive.
Note in the lower left
glomerulus that the capillary
loops are markedly thickened
(the so-called "wire
loop" lesion of lupus
nephritis).

Here is another
glomerulus with
an epithelial
crescent squashi
ng the glomerular
tufts from all
sides.

This immunofluorescence
micrograph of a glomerulus
demonstrates positivity with
antibody to fibrinogen. With a
rapidly progressive GN, the
glomerular damage is so
severe that fibrinogen leaks
into Bowman's space, leading
to proliferation of the
epithelial cells and formation
of the bright
crescent shown here.

This immunofluorescence
pattern shows positivity with
antibody to IgG and has a
smooth, diffuse, linear
pattern that is
characteristic for deposition
of glomerular basement
membrane antibody with
Goodpasture syndrome.
Serologic testing for anti-
GBM in patient serum is
often positive.

-MC type of Nephritic Sx in adult
-Raised IgA
-IgA deposits in Mesangium,
Hence also known as
Mesangiocapillary
Glomerilonephritis
Secondary IgA
Nephropathy
1) Severe Liver Disease
2) Celiac disease
Poor Prognosis
15-40% : Nephrotic Sx
15% : End stage renal
disease
15% : Recur in post Renal
transplantation

Granular deposits

MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
(MPGN).
ETIOLOGY
1) Infection : Hep.C +/- Cryoglobulinemia, Hep. B, HIV, Kala
Azar
2) Autoimmune
3) Drugs
4) Malignancy : CLL
5) Partial Lipodystrophy

GLOMERULONEPHRITIS
(MPGN).
Type I Type II
Classical complement Alternate complement
All complements : Decreased C1,C2,C4 : Normal
Sub endothelial deposits ( Tram
track appearance)
Membranous deposits
Measngial proliferation + -ve
Poor Prognosis

GLOMERULONEPHRITIS (MPGN).

The pathologic findings shown here
include increased glomerular overall
cellularity, mainly increased mesangial
cellularity.
GLOMERULONEPHRITIS
(MPGN).

This silver stain
demonstrates
a double
contour to many
basement
membranes, or the
"tram-tracking"
that is
characteristic of
membranoprolifera
tive
glomerulonephritis
(MPGN) that
results from
basement
membrane
reduplication.
GLOMERULONEPHRITIS (MPGN).

The bright deposits scattered along
capillary walls and in the mesangium by
immunofluorescence microscopy with
antibody to complement component C3 are
typical for dense deposit disease (formerly
called membranoproliferative
glomerulonephritis, type II).
Dense deposit disease produces a nephritic
syndrome. Most patients have detectable
circulating C3 nephritic factor, an IgG
autoantibody.
GLOMERULONEPHRITIS
(MPGN).

Glomerular disease with systemic lupus
erythematosus (SLE) is common, and
lupus nephritis can have many
morphologic manifestations as seen on
renal biopsy.
In general, the more immune complex
deposition and the more cellular
proliferation, the worse the disease. In this
case, there is extensive immune complex
deposition in the thickened glomerular
capillary loops, giving a so-called wire
loop appearance.

-MC Type = FSGS ( MC : Collapsing variety)
- Collapsing type : Masangial necrosis + Proliferation of visceral epitheluial cells
Collapsing variety

-X-Linked dominant
-Hereditary nephritis
-Defect = collagen 4@5 (MC) > 4@3, 4@4
Hematuria
+
Sensorineural
deafness
+
Eye defects ( Anterior
Lenticonus)

LM FM EM
Diffuse thickening of
Glomerular basement
membrane
Decreased staining with
Col 4@5
Alternate thick and thin
layer
( Basket weave
appearanec)

1) Diabetic nephropathy
2)Analgesic nephropathy
3)Sickle cell anemia
4)Chronic Alcoholism
5)Complication of acute pyelonephritis

SYMMETRIC ASSYMETRIC
Chronic Glomerulonephritis Chronic pyelonephritis
Diabetes
Benign HTN

Renal pathology

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