Cardiovascular Physiology - Regulation of Cardiac Pumping
Interpretation of renal biopsy
1.
2. The kidney is a mysterious organ that makes urine
Has role in-
Excreting wastes
Regulating body fluids
Balancing soluble ions
3. Kidneys-bean shape organs within peritoneum
Each organ weights 125 to 170 gm in males and 115 to 150 gr in females
The renal artery divides into anterior and posterior arteries which in turn give off
segmental arteries
The main renal artery gives off-
Interlobar
Arcuate
Interlobular arteries
On the cut surface-cortex and medulla
medulla is divided to 18 pyramids
Each pyramid base is located at the corticomedullary junction
4.
5. Nephrons-
• Functional and basic unit
• Composed of glomeruli,bowman’s capsule, PCT, DCT & henle’s loop.
• Glomeruli-cortex
• Henle’s loop-medulla
• Nephrons-1 million
Glomeruli-
• Malphigi first described glomerulus
• Glomerulus-glomerular tuft + bowman’s capsule
• Glomerulus-vascular tuft lined by endothelium,supported by mesangium
• 200 μm.
Proximal tubule-
• 14mm long.
• Cells are cuboid/short columnar,eosinophilic cytoplasm,granular,round nucleus in
centre.with brush border
• Reabsorption of majority glomerular ultrafiltrate.
6. Henle’s loop-
• Between proximal and distal tubules
• U-shaped unit
• Cells are flat, attenuated cytoplasm, no brush border
Distal tubule-
• Connects to ascending henle’s loop
• No brush border
Collecting duct-
• Begins near end of DCT in cortex
• Potassium secretion
12. Iverson and Brun (1951)- first renal biopsy description
13. Nephrotic syndrome:
› Adult NS
› Children with atypical features
Acute renal failure:
› Undiagnosed
› Non resolving clinical ATN >3-4
weeks
Systemic diseases with renal dysfunction
Sub-nephrotic proteinuria
› >2g/d in DM, early MGN, FSGS,
IgAN
› <2g/d needs clinicians discretion
Hematuria
› Isolated
› Associated with proteinuria and
abnormal urine sediment
Post transplant
CKD-
generally contraindicated
In moderate dysfunction-potential
reversibility and basic disease
Diabetes Mellitus
Microscopic hematuria
Absence of retinopathy and
neuropathy
Onset of proteinuria <5years from
diagnosis
Acute worsening of renal function
Systemic features
14.
15. Renal biopsies taken by True-cut or biopsy gun under local anesthesia
performed in prone position for native kidneys and in supine position for transplanted
kidneys
It is better to use 16 or 14 guage needle
optimum location for biopsy is juxtamedullary
Other renal biopsy techniques include transjugular retrograde approach by
catheter, laparascopic techniques, and open laparatomic biopsy.
16. Procedure-
Informed consent
Patient in prone position with wedge or pillow below the abdomen
Light sedation
Local anesthesia with 1-2% lignocaine from the skin down to the capsule
Stab incision can be given to ease biopsy gun entry
Advance the biopsy gun, when the capsule is reached, instruct patient to take a deep breath
and fire the gun
2-3 cores can be taken from the lower pole of the left kidney
Press on wound for 2-5 minutes
17. Post procedure-
Bed rest is instructed for 18-24 hours
BP and pulse are monitored in the following way-
Every 15 mins for 1 hour
Every 30 mins for 1 hour
Every hour for 4 hours
4 hourly for next remaining 24 hours
Save aliquots of each voided urine sample in clear specimen jars
Hct monitored 6-8 hours and 18-24 hours after biopsy
Complications-
Hematoma
Hematuria
AV fistula
18. Fixatives-
For light microscopy, neutral buffered formaldehyde is used
suitable for immunohistochemical study and also molecular procedures
For electron microscopy, 2-3% glutaraldehyde fluid is suitable.
Immunofluorescence samples do not need any fixative and should be delivered
and frozen in Michel`s media for frozen sections
Specimen division-
>8mm - LM/IF/EM
4-8mm - EM/IF
<4mm - EM
19. Adequacy of the sample:
› two biopsy cylinders with a minimal length of 1 cm and a diameter of at least
1.2 mm.
› 10–15 glomeruli are optimal; very often 6–10 glomeruli are sufficient
› some cases even one glomerulus is enough
Sectioning and staining-
› After histologic processing and paraffin embedding, the tissues are sectioned
by microtome
› sections are prepared as thin as 3 μm or less for light microscopy. Thicker
sections is needed in congo red and Immunohistochemistry staining.
› Most helpful stains are-HE, PAS, Massons trichrome, JMS and congo red.
20. PAS TRICHROME SILVER
Basement membrane red deep blue black
Mesangial matrix red deep blue black
Interstitial collagen ------ pale blue -------
Cell cytoplasm ------- rust/orange granular ------
Immune complex deposit -/+ bright red
orange,homogenous
-----
Fibrin weakly + Bright red orange,fibrillar ----
amyloid -------- Light blue orange ----
24. A. Injury Localization: Glomerular/Vascular/Tubulointerstitial
B. Category of Injury: Active Versus Fibrosing
1. Active lesions
a. Proliferation
b. Necrosis
c. Crescents
d. Edema
e. Active inflammation (eg, glomerulitis, tubulitis, vasculitis)
2. Fibrosing
a. Glomerulosclerosis
b. Fibrous crescents
c. Tubular atrophy
d. Interstitial fibrosis
e. Vascular sclerosis
C. Types of Lesions
1. Determination of the nature and pathogenesis of lesions: examination by IF, EM and
LM
27. Focal-Involving <50% of glomeruli
Diffuse-Involving 50% or more of glomeruli
Segmental-Involving part of a glomerular tuft
Global-Involving all of a glomerular tuft
Mesangial hypercellularity-4 or more nuclei in a peripheral mesangial segment
Endocapillary hypercellularity-Increased cellularity internal to the GBM composed of
leukocytes, endothelial cells and/or mesangial cells
Extracapillary hypercellularity-Increased cellularity in Bowman’s space, i.e. > one layer of
parietal or visceral epithelial cells, or monocytes/macrophages
Crescent-Extracapillary hypercellularity other than the epithelial hyperplasia of collapsing
variant of FSGS
Fibrinoid necrosis-Lytic destruction of cells and matrix with deposition of acidophilic fibrin-
rich material
Sclerosis-Increased collagenous extracellular matrix that is expanding the
mesangium, obliterating capillary lumens or forming adhesions to Bowman’s capsule
Hyaline-Glassy acidophilic extracellular material
Membranoproliferative-Combined capillary wall thickening and endocapillary
hypercellularity
Lobular -Consolidated expansion of segments that are demarcated by intervening urinary
space
Mesangiolysis-lysis of mesangial matrix
28.
29.
30. No abnormality by light microscopy:
1. No glomerular disease
2. Glomerular disease with no light microscopic changes (e.g. minimal change
glomerulopathy, thin basement membrane nephropathy)
3. Mild or early glomerular disease (e.g. Class I lupus nephritis, IgA nephropathy, C1q
nephropathy, Alport syndrome, etc.)
31. Thick capillary walls without hypercellularity or mesangial expansion:
1. Membranous glomerulopathy (primary or secondary) (>Stage I)
2. Thrombotic microangiopathy with expanded subendothelial zone
3. Preeclampsia/eclampsia with endothelial swelling
3. Fibrillary glomerulonephritis with predominance of capillary wall deposits
32. Thick walls with mesangial expansion but little or no hypercellularity:
1. Diabetic glomerulosclerosis with diffuse rather than nodular sclerosis
2. Secondary membranous glomerulopathy with mesangial immune deposits
3. Amyloidosis
4. Monoclonal immunoglobulin deposition disease
5. Fibrillary glomerulonephritis
6. Dense deposit disease (type II membranoproliferative glomerulonephritis)
33. Focal segmental glomerular sclerosis without hypercellularity:
1. Focal segmental glomerulosclerosis (primary or secondary)
2. Chronic sclerotic phase of a focal glomerulonephritis
3. Hereditary nephritis (Alport syndrome)
34. Mesangial or endocapillary hypercellularity:
1. Focal or diffuse mesangioproliferative glomerulonephritis*
2. Focal or diffuse (endocapillary) proliferative glomerulonephritis*
3. Acute (“exudative”) diffuse proliferative postinfectious glomerulonephritis
4. Membranoproliferative glomerulonephritis (type I, II or III)
35. Extracapillary hypercellularity:
1. ANCA crescentic glomerulonephritis (paucity of immunoglobulin by IFM)
2. Immune complex crescentic glomerulonephritis ((granular immunoglobulin by IFM)
3. Anti-GBM crescentic glomerulonephritis (linear immunoglobulin by IFM)
4. Collapsing variant of focal segmental glomerulosclerosis (including HIV nephropathy)
36. Membranoproliferative, lobular or nodular pattern:
1. Membranoproliferative glomerulonephritis (type I, II/DDD, or IIIB/IIIS)
2. Diabetic glomerulosclerosis with nodular mesangial expansion (KW nodules)
3. Monoclonal immunoglobulin deposition disease with nodular sclerosis
4. Idiopathic (smoking associated) nodular glomerulosclerosis
5. Thrombotic microangiopathy
6. Fibrillary glomerulonephritis
7. Immunotactoid glomerulopathy
37. Advanced diffuse global glomerular sclerosis
1. End stage glomerular disease
2. End stage vascular disease
3. End stage tubulointerstitial disease
38. Directed at identification of pathogenic Ig and complement.
Abs used routinely-IgG, IgA, IgM, Kappa & lambda light chains, C3, C4, C1q,
fibrinogen
Glomerular/extraglomerular location,intensity & pattern of staining
Glomerular staining catagorized as-mesangial, capilary wall or both
Capillary staining –granular,linear,band like
Capillary granularmesangial both
40. Linear cap wall Granular mesangial Granular cap wall Diffuse smudgy mes &
cap wall
•Anti GBM disease(IgG,
C3)
•Monoclonal Ig deposition
disease(mostly kappa
chain)
•Diabetic
nephropathy(IgG,albumin)
•Dense deposit disease(
ribbonlike,thick C3)
•Rarely fibrillary GN (IgG)
•IgA nephropathy
•WHO Class II lupus( full
house)
•C1q nephropathy
•IgM is idiopathic
nephrotic syndrome
•Other
mesangioproliferative GN
•Finely granular
(membranous GN
with/without SLE)
•Coarsely granular
(MPGN, WHO Class III, or
IV lupus)
•Scattered ,coarse granules
(poststreptococcal GN)
•Primary
amyloidosis(usually λ)
•Fibrillary GN(IgG)
•Monoclonal Ig deposition
disease
41. Detailed evaluation of cellular & extracellular contents
Assesment of thickness,contour, & integrity of GBM & mesangial matrix
Fibrillary GN & immunotactoid GP can be diagnosed only on EM
50. Lymphocytes or other inflammatory cells on epithelial side of tubular BM
infiltrating the tubular epithelium
Marker of active tubulointerstitial inflammation.