The Kidney in Systemic Disease I Flashcards
What are the 4 vascular injury syndromes that cause kidney problems?
- ANCA-associated disease
- Thrombotic Microangiopathy
- Lupus nephritis
- Scleroderma
Other Systemic Diseases in the Kidney • Diabetic Nephropathy • Sickle Cell Nephropathy • Amyloidosis • Light Chain Disease
Other Systemic Diseases in the Kidney • Diabetic Nephropathy • Sickle Cell Nephropathy • Amyloidosis • Light Chain Disease
What are 2 viral associated systemic diseases that affect the kidneys?
- HIV-associated nephropathy
* Cryoglobulinemia
What are two general grouping of vascular disorders that cause kidney damage?
These Diseases either cause:
1. Inflammation of blood vessels as seen in vasculitides
OR
- Loss of thromboresistance as seen in the thrombotic microangiopathies
What should you be worried about when you see cresent formation on a kidney biopsy?
Rapidly Progressive Glomerulonephritis
What is the major Kidney complication of Medium Vessel Disease?
• other factors that may cause reduced kidney function?
• are these people typically ANCA positive?
RENAL INFARCTS
- Distal glomerular ischemia may cause decline in GFR
- NOT associated with glomerular inflammation with RBC casts
NO - these people typically do NOT have ANCA
What small is the major Kidney complication of Small vessel kidney diseases?
• other factors that may cause reduced kidney function?
• are these people typically ANCA positive?
Focal necrotizing lesion with CRESCENT FORMATION
- ACTIVE urinary sediment and RAPID progression of kidney failure
- YES - these people are typically ANCA postitive
Polyarteritis Nodosa (PAN) • vessels affected • ANCA presence? • Epidemiology? • Cause?
Vessels:
• PAN = MEDIUM VESSEL disease (more likely to cause renal infarct)
**ANCA is NEGATIVE in PAN
Epidemiology:
• Mostly Middle-aged or OLDER adults - peak incidence = 60s
Cause:
• Usually Ideopathic, but associated with Hepititis C.
What are some symptoms associated with PAN?
Symptoms = Systemic (b/c its a systemic disease that just happens to affect the kidneys)
• Fatigue, Weight Loss, Weakness, Fever, Arthralgias
May also see:
• Skin lesions, HTN, renal insufficiency, neurologic dysfunction, abdominal pain
PAN
• H and E descriptors?**
• Age of Lesions?
PAN H and E:
• Segmental Transmural Necrotizing Vasculitis
(so it involves only parts of the artery, but affects the full vessel circumference via fibrosis)
Age of Lesions:
• New and Old lesions may exist in the same vessel
What does Pauci-immune glomerulonephritis refer to?
• what is pauci-immune stain often associated with?
Pauci-immune GN => negative immunofluorescence studies often in the setting of CRESCENTRIC Glomerulonephritis.
Association:
• Pauci-immune GN - often associated with ANCAs (anti neutrophil antibodies)
Why is infarction associated with Polyarteritis Nodosa?
Medium Vessel Vasculites are often associated with INFARCTION
caused by: Medial and Intimal proliferation leads to arterial narrowing with Subsequent ischemia and infarction
What do you see grossly in kidneys on autopsy of someone with PAN?
- Large Aneurysms filled with clotted blood
2. Infarcts (in periphery where larger vessels are located)
What how do Kidney Aneurysms in PAN differ from true aneurysms?
• In PAN thse form as a result of erosion of inflammatory cells through the vessel wall into the adjacent parenchyma
In reality this is just erosion through a vessel by an inflammatory process
What are the two distinct kinds of Antineutrophil Cytoplasmic Antibodies?
ANCAs - 2 types
- C-ANCA aka PR3-ANCA
- P-ANCA aka MPO-ANCA
Compare and contrast the following for C-ANCA and P-ANCA:
• Location of Reactivity
• Structure Specificity
• Significance of a Positive test
C-ANCA:
Location - cytoplasmic reactivity
Structure Specificy- Proteinase 3 (serine protease)
Significance of + test: WEGENER’s GRANULOMATOSIS (95% specificity) aka granulomatosis with polyangiitis
P-ANCA:
Location - perinuclear reactivity
Structure Specificity - Lysosomal Peroxidase
Significance of + test: Not that specific
What is the appearance of C-ANCA and P-ANCA in EtOH fixed neutrophils?
C-ANCA:
• Fine Granular Appearance in the cytoplasm
P-ANCA:
• smoother appearance - perinuclear
What happens when ANCAs bind to neutrophils?
- Neutrophil (PMN activation)
* Increased contact and adhesion with endothelial cells and vascular structures
Between Goodpastures and Wegner’s, which is more associated with respiratory problems?
Goodpastures:
• More Renal
Wegner’s (granulomatosis with polyangiitis)
• more Respiratory
Granulomatosis with Polyangiitis
• Vessels affected
• Tissues mostly affected
• Markers?
Vessels - SMALL vessel disorder
Sinopulmonary Renal Syndrome (affects lungs, nose, and kidneys)
markers:
• WeCner’s - C-ANCA (PR3-ANCA) - very sensitive AND specific marker
T or F: you may see patients that have Wegner’s but are ANCA negative
True, this is the case of patients that have been treated with steroids prior to having their biopsy done
some pts. may also be positive for P-ANCA
What is Azotemia?
• does this go with Wegners?
Azotemia = high levels of nitrogen compounds in the blood e.g. Creatinine and Urea
What are you looking for on the H and E of someone’s lung biopsy with Wegner’s?
Overall:
• GEOGRAPHIC NECROSIS with loss of alveoli
Vessels:
• NECROSIS of small to medium-sized vessels (capillaries, venules, arterioles, and arteries)
Cells:
• Giant Cells and lots of infiltration of Neutrophils
T or F: the severity of necrotizing glomerulonephritis in Wegner’s correlates to the severity of clinical presentation.
True,
NOTE:
• this ranges from mild focal and segmental Glomerulonephritis in pts. with asymptomatic hematuria and normal to near-normal renal function.
• all the way to diffuse necrotizing and crescentric glomerulonephritis in pts. with acute kidney injury
T or F: Cresents are seen in patients with Granulomatosis with Polyangiitis (Wegner’s).
True,
How do you treat pts. with Wegners?
• mortality.
• Relapse.
Drugs that suppress the immune system
• Cyclophosphamide
• Steroids
• Plasmapheresis
Mortality:
• 80-90% if left untreated
Relapse:
• 25-50% of pts. relapse with 3 to 5 years of follow up
What are 2 thombotic microangiopathies associated with Renal Disease?
HUS (hemolytic uremic syndrome)
TTP (thrombotic thrombocytopenia purpura)
What clinical Triad and Pentad are associated with HUS and TTP respectively?
HUS:
• Hemolytic Anemia with Schistocytes
• Renal Dysfunction
• Thrombocytopenia (due to platelet consumption)
TTP: • FEVER and NEUROLOGIC dysfunction • Hemolytic Anemia with Schistocytes • Renal Dysfunction • Thrombocytopenia (due to platelet consumption)
What is your first move if you suspect TTP?
TREAT (even if you can’t check off all 5 boxes) these pts will go downhill fast
What is a common neurological defect associated wth TTP?
Siezures
What happens (changes and damages) to vessels in thrombotic microangiopathies?
Changes/Damage to vessel?
• Loss of Thromboresistance by the endothelial cell
- Platelet Activation => Deposition of platelet and fibrin thrombi in the lumen of affected vessels
- Fibrin Deposition may also occur in the Subintima and media of the vessels
- ONIONSKIN appearance is seen
Other than Onion Skinning appearance what are 2 other changes seen on H and E for Thrombotic Microangiopathies?
- Thombi in Glomeruli and Arterioles
- Subendothelial Widening of Glomerular Capillary wall
Note: onion skinning comes from INTIMAL thickening
What are 3 Factors that may cause the endothelial Damage in HUS.
- E. Coli O157 infection
- Chemo Drugs - Cyclosporine, Gemcitabine, Bleomycin/Cisplatinum
- Radiation (bone marrow transplant)
Note: Cancer pts. often recieve the last two of these things
What are the 2 mains types of TTP?
• how do they differ? Pathophysiology?
• other causes?
Familial TTP:
• Low ADAMST13 (less than 10% of cases of TTP)
Autoimmune TTP:
• Antibody binds ADAMST13 making it ineffective
Pathophysiology: ADAMST13 is needed to cleave vWF, it vWF is left in too long of fragments it will cause clotting in small vessels leading to the microangiopathic hemolytic anemia
OTHER CAUSES:
• Like any autoimmune disease (antiphospholipid syndrome)
What 2 major factors differentiate other Thrombotic Microangiopathies from DIC.
- Prothrombin Time (PT) and partial thromboplastin times (PTT) are normal in TMA (aka TTP and HUS) but is prolonged in DIC
- TMAs (TTP and HUS) are more ass’d with THROMBOSIS… DIC is more associated with BLEEDING PROBLEMS
What is the 10 year survival rate of SLE?
10 year survival = 70%
What 9 markers of Lupus?
• which are the most common?
- Malar Rash
- Discoid Rash
- Photosensitivity
- Oral Ulcers
- Serositis - pleural effusion etc.
- Neurologic Disorders
- Hematologic Disorders
- Immunologic Disorders
- Antinuclear Antibody
What are 3 immunologic markers that can be used in SLE?
• how specific are these?
- Anti-dsDNA antibodies
- Anti-Sm Antibodies
- Anti phospholipid Antibody
What are the 6 patterns seen in the kidney in SLE? • KNOW class III, IV and V!
Class I - Minimal Mesangial Lupus Nephritis
Class II - mesangial Proliferative Lupus Nephrtitis
**Class III - Focal Lupus nephritis
**Class IV - Diffuse Lupus Nephritis
***Class V - membranous Lupus Nephritis
Class VI - adv. scelerosing Lupus Nephritis
Class IV lupus nephritis.
• prevalence?
• Key Histological Features
• Severity?
MOST COMMON and MOST SEVERE
Histological Features:
• Wire Loops is what characterize stage IV
Severity:
• Stage IV is the worst it gets
What characterizes Membranous (stage V) lupus nephritis?
Thickening of Glomerular Capillaries
T or F: damage in SLE may be characterized by Crescent formation.
True, crescents may be seen in SLE
T or F: in Lupus Nephritis staining of deposits with antisera to all 3 Igs (IgG, IgM, and IgA), C3 AND C4 is common.
TRUE, this is referred to as Full House Immunofluoresensce.
Note: that type V is not worse than type IV, this is because type V is just a different classification*
Note: that type V is not worse than type IV, this is because type V is just a different classification*
What treatment is generally given to pts. with LUPUS?
Immunosuppressive agents: • GLUCOCORTICOIDS • Cyclophosphamide - this is given IV so its good to give to teens to ensure they are taking their meds. • Mycophenolate mofetil • Hydroxychloroquine
What tissues are affected by Scleroderma?
• different types?
• FIBROSIS of Connective Tissue and Microvasculature
Different Types:
• Limited Cutaneous
• Diffuse Cutaneous
What type of Scleroderma is most often involved in Renal Dysfunction?
• Which type is associated with Constitutional Symptoms (fever, wt. loss)?
• which is most associated with Raynauds?
Renal Dysfunction:
• Diffuse Cutaneous
Constitutional Symptoms:
• Diffuse Cutaneous, NO constitutional symptoms are seen in Limited Cutaneous
Raynauds:
• LIMITED Cutaneous
Scleroderma
• Symptoms of Renal Involvement?
• What part of the kidney is most commonly involved?
• Type most likely involved?
Symptoms:
• Mild Renal Dysfunction
• Proteinuria
• HTN
Part Most commonly involved:
• ARCUATE ARTERIES - INTIMAL and MEDIAL PROLIFERATION
Type:
• Diffuse Cutaneous
What is Scleroderma Renal Crisis?
• how is it treated?
• Risk Factors?
Two main signs:
• Rapid onset Arterial HTN
• Oliuric Renal Failure
Risk Factors: • Early Diffuse Systemic Sclerosis • Rapidly Progressive Skin Disease • anti-RNA pols antibodies • Corticosteriod Therapy
What is commonly seen on the H and E of someone with Scleroderma?
• Fibrinoid Necrosis and Thrombosis common
Sclerodermal Renal Crisis
What features do you expect to see on H and E?
- LUMINAL THROMBOSIS in arterioles with complete occlusion of arteriolar lumina
- Ischemic Glomeruli
- CONCENTRIC FIBROSIS (onion skinning) in SMALL ARTERIES
