renal ultrastructural pathology lecture 3 t - v
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Basic Renal EM workshop Southampton September 30 th 2011. Renal Ultrastructural Pathology Lecture 3 T - V. Bart E Wagner BSc CSc FIBMS Dip Ult Path Chief Biomedical Scientist Electron Microscopy Section Histopathology Department Northern General Hospital Sheffield - PowerPoint PPT PresentationTRANSCRIPT
Renal Ultrastructural PathologyRenal Ultrastructural PathologyLecture 3 T - VLecture 3 T - V
Bart E Wagner Bart E Wagner BSc CSc FIBMS Dip Ult PathBSc CSc FIBMS Dip Ult Path
Chief Biomedical ScientistChief Biomedical ScientistElectron Microscopy SectionElectron Microscopy SectionHistopathology DepartmentHistopathology DepartmentNorthern General HospitalNorthern General Hospital
SheffieldSheffieldSouth YorkshireSouth Yorkshire
UKUKS5 7AUS5 7AU
[email protected]+44(0)114-27 14154Tel+44(0)114-27 14154
Basic Renal EM workshop
Southampton
September 30th 2011
Histopathology DepartmentNorthern General Hospital
Renal ultrastructural pathologyRenal ultrastructural pathologyLecture 3 - TopicsLecture 3 - Topics
1.1. Transplant – Hyperacute rejectionTransplant – Hyperacute rejection
2.2. Transplant – Acute cellular rejectionTransplant – Acute cellular rejection
3.3. Transplant – Chronic Humoral rejectionTransplant – Chronic Humoral rejection
4.4. Transplant – Calcineurin inhibitor (CNI) toxicityTransplant – Calcineurin inhibitor (CNI) toxicity
5.5. VasculopathyVasculopathy
6.6. Viral infectionViral infection
TransplantTransplant
Hyperacute rejectionHyperacute rejection
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TransplantTransplant
Hyperacute rejectionHyperacute rejectionCaused by putting a kidney into a person with high titre preformed Caused by putting a kidney into a person with high titre preformed antibodies, such as acquired following a previously rejected kidneyantibodies, such as acquired following a previously rejected kidney
Biopsy taken 30 minutes post vascular anastamosisBiopsy taken 30 minutes post vascular anastamosis
Appearance similar to disseminated intravascular coagulation (DIC)Appearance similar to disseminated intravascular coagulation (DIC)
Numerous intraglomerular platelet and fibrin thrombiNumerous intraglomerular platelet and fibrin thrombi
Haemorrhagic infarcted kidney removed next dayHaemorrhagic infarcted kidney removed next day
Numerous thrombosed capillary loops
Protocol post-perfusion biopsy
Filled with fibrin tactoids
Necrotic endothelial cell nucleus
Aggregate of degranulated and non-degranulated platelets
Transplant Transplant
Acute cellular rejectionAcute cellular rejection
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Glomerulitis
Interstitial oedema
Glomerulitis or intraglomerular endothelialitis
Higher magnification of previous slide Numerous intracapillary mononuclear cells
Apoptotic lymphocyte
Dendritic cell
Filopodia
Antigen in exosomes (endosomal vesicles)
Endothelialitis of peritubular capillary (PTC)
Tubulitis
TubulitisHigher magnification of previous slide
Disruption of tubular basement membrane
TransplantTransplant
Chronic humoral rejection Chronic humoral rejection (CHR)(CHR)
TransplantTransplantChronic Humoral RejectionChronic Humoral Rejection
C4D staining of vessel walls by immunoperoxidase or fluorescenceC4D staining of vessel walls by immunoperoxidase or fluorescence
Basement membrane multilayering in glomerular subendothelial Basement membrane multilayering in glomerular subendothelial zone by endothelial cells producing multiple new basement zone by endothelial cells producing multiple new basement membranesmembranes
In excess of 6 layers of new basement membrane around In excess of 6 layers of new basement membrane around peritubular capillariesperitubular capillaries
New basement membrane laid down by endothelial cells
Mesangial cell interpositioning
Peritubular capillary (PTC) basement membrane multilayering
Peritubular capillary basement membrane multilayering
Transplant cyclosporine toxicityTransplant cyclosporine toxicity
Lung transplant patientLung transplant patient
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Transplant Transplant Cyclosporine A toxicityCyclosporine A toxicity
Lung transplant patientLung transplant patient
Iatrogenic acute renal failureIatrogenic acute renal failure
Biopsied for prognostic reasonsBiopsied for prognostic reasons
Calcineurin inhibitor (CNI) toxicityCalcineurin inhibitor (CNI) toxicity
Arteriolar hyalinosis
Fine isometric vacuolation
Swollen lysosomes in distal convoluted tubule
Fine isometric vacuolation distal convoluted tubular cells
Higher magnification of previous slide
Lysosomal enzymes displaced peripherally These changes can be seen in fibroblast lysosomes in renal transplant biopsies
Proximal convoluted tubular cells
Isometric vaculation
Higher magnification of previous slide
Diffusely swollen lysosomes
Hydropically swollen lysosomes have also Hydropically swollen lysosomes have also been seen in:been seen in:
Muscle biopsy in patient given colloid. Muscle biopsy in patient given colloid. J J
Hepatol 1986;3:223-227Hepatol 1986;3:223-227
Skin biopsy in patient given amphipathic antibiotics. Skin biopsy in patient given amphipathic antibiotics. Personal Personal
observation G Mierau, Denver. observation G Mierau, Denver.
Skin biopsy pre-treated with topical local anaesthetic. Skin biopsy pre-treated with topical local anaesthetic. J J
Inherit Metab 27 (2004) 507-511Inherit Metab 27 (2004) 507-511
On seeing the expanded lysosomes, I initially thought they On seeing the expanded lysosomes, I initially thought they might be cases of unsuspected lysosomal storage might be cases of unsuspected lysosomal storage disorder. disorder.
i.e. Pseudo lysosomal storage.i.e. Pseudo lysosomal storage.
VasculopathyVasculopathy
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Chronic hypertensive elastic reduplication and lumen narrowing
Hypertensive arteriolar hyalinosis
Fibrinoid necrosis of vessel wall
Extravasation of erythrocytes
Malignant phase hypertension
Viral infectionViral infectionBK polyomaBK polyoma
Distal convoluted tubule intranuclear inclusion
Higher magnification of previous slide
Higher magnification of previous slide
Intranuclear inclusion formed of numerous polyoma virus particles
CytomegalovirusCMV
Transplant kidney
Case from Dr Michael Mengel, Greifswald, Germany. With permission.
Nucleus not in plane of section Intracytoplasmic vesicles filled with virions
Case from Dr Michael Mengel, Greifswald, Germany.
CMV CMV
Liver biopsyLiver biopsy
Liver biopsy. CMV in intraportal tract bile duct cholagiocyte
CMV in liver biopsy
‘Owls eye’ intranuclear inclusion
Higher magnification of previous slide
Intracytoplasmic vesicles filled with typical herpes group virions
Final commentsFinal commentsDo toluidine blues on all biopsies and add description to light microscopy Do toluidine blues on all biopsies and add description to light microscopy report.report.
When choosing which block to cut thin sections off, choose the one with When choosing which block to cut thin sections off, choose the one with glomeruli that are neither completely normal nor sclerosed, and has the most glomeruli that are neither completely normal nor sclerosed, and has the most glomeruli, but not one with GBM wrinkling.glomeruli, but not one with GBM wrinkling.
Either, do EM on all renal biopsies, in which case expect to be confirmatory in Either, do EM on all renal biopsies, in which case expect to be confirmatory in 50% of cases, and to change diagnosis partially in 25%, and completely in 50% of cases, and to change diagnosis partially in 25%, and completely in 25%.25%.
Or, if being selective as to which cases should do EM on, should be done on Or, if being selective as to which cases should do EM on, should be done on 60% of cases. 60% of cases.
As for which cases to choose: heavy proteinuria, uncertainly of diagnosis, As for which cases to choose: heavy proteinuria, uncertainly of diagnosis, unexpected findings on light microscopy immunofluorescence or resin sections, unexpected findings on light microscopy immunofluorescence or resin sections, clinicopathological miss-match. clinicopathological miss-match.
If having difficulty in interpreting EM findings:If having difficulty in interpreting EM findings: HAVE A LOOK AT ANOTHER GLOMERULUSHAVE A LOOK AT ANOTHER GLOMERULUS..
If requesting a second opinion, send with clinical details, histology and IF If requesting a second opinion, send with clinical details, histology and IF report, and EM images in step magnificationsreport, and EM images in step magnifications. .
I hope you enjoy these lectures.I hope you enjoy these lectures.
You are more than welcome to use these images for your own lecture purposes, with You are more than welcome to use these images for your own lecture purposes, with acknowledgement – but I’d rather you didn’t use them for publication, in print or on a web site, without acknowledgement – but I’d rather you didn’t use them for publication, in print or on a web site, without
checking with me first.checking with me first.If you have any diagnostic EM related queries do contact me on If you have any diagnostic EM related queries do contact me on [email protected]
and I’d be happy to try to help you out. and I’d be happy to try to help you out.
Bart WagnerBart Wagner
Don’t forget the group photo!
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