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51 Cards in this Set
- Front
- Back
What are the causes of end stage kidney disease?
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*Glomerular disease: 25%!
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Review of glomerular anatomy (xs):
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*Note 3 layers.
*Visceral epithelium = podocytes. |
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Review of the GBM's role in filtration:
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*GBM has strong negative charge due to polyanionic proteoglycans: heparin sulfate as well as other glycoproteins / Sialoglycoproteins (thromboresistance and anionic charge).
*Thus Negative molecules like albumin do not filter. *Structural proteins such as Fibronectin, Entactin, and Laminin contribute to “filter.” *Freely permeable below 2nm, and impermeable above 4 nm. |
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Discuss the role of the Visceral epithelial cell:
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*AKA podocyte (ultrastructural term).
*Maintain structural conformation of tuft. *Largely responsible for synthesis of GBM components. *Foot processes are separated by 20-30 nm filtration slits *Slit diaphragm presents a size-selective distal diffusion barrier to the filtration of proteins. *Proteins located in the slit diaphragm control glomerular permeability. |
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What makes up the slit diaphragm of the podocytes?
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*Podocin and nephrin are most important.
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Discuss the mesangial cells:
What functions do they have? |
*Modified Smooth Muscle Cells embedded in a matrix similar to the GBM.
*Functions: 1) Endocrine (renin production). 2) Contractile (structural integrity). 3) Phagocytic. 4) Synthetic. *Capable of proliferation (2-3 cells per region is normal). *Diagram notes: No GBM between capillary lumen and mesangium; Mesangium is continuous with the Subendothelial space. |
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Identify all the layers based on color shown here:
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What are the 2 major categories of Glomerular Disorders and what characterizes them?
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1) NEPHROTIC Syndrome:
***proteinuria (>3.5 g/24 hr)*** +edema +hypoalbuminemia +hypercholesterolemia +/-hematuria +/-hypertension 2) NEPHRITIC Syndrome: ***hematuria*** +/- casts +hypertension +/-edema +/-proteinuria |
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What is the "spectrum" of glomerular diseases?
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*Diseases in the middle can present as either nephritic or nephrotic.
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What is the "spectrum" of glomerular diseases by looking at inflammation?
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Discuss nephritic syndome in general:
What can it be accompanied by? |
*The nephritic syndrome, or nephritis, refers to inflammatory renal diseases characterized by blood in the urine.
*Nephritis is principally characterized by hematuria and can be accompanied by: 1) Hypertension 2) Edema 3) Reduced GFR 4) Sub-nephrotic proteinuria |
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Discuss Nephrotic Syndrome in general:
What can it be accompanied by? |
*The nephrotic syndrome (or nephrosis) refers to “non-inflammatory” glomerular diseases marked by heavy proteinuria ( > 3.5 g/day in an adult).
*Nephrosis is principally characterized by heavy proteinura and may be accompanied by: 1) Edema. 2) Hyperlipidemia. 3) Lipiduria. 4) Hypercoagulability. |
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What's the pathophysiology of edema in nephritic syndrome?
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What's the pathophysiology of edema in nephrotic syndrome?
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What are the Complications of Nephrosis?
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What are the primary and systemic Nephritic diseases?
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*Primary:
1) IgA nephrohathy. 2) Hereditary (thin b.m.). 3) PSGN. 4) MPGN. 5) RPGN. *Systemic: 1) Vasculitis. 2) Endocarditis. 3) Lupus. 4) Goodpasture’s. 5) Henoch-Schoenlein purpura. |
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What are the primary and systemic Nephrotic diseases?
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*Primary:
1) Minimal change 2) Idiopathic FSGS 3) Membranous 4) MPGN *Systemic: 1) Diabetes 2) “Secondary” FSGS 3) Amyloid 4) SLE (membranous) |
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What is the role of circulating immune complexes in kidney disease?
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*There can be deposition or trapping of pre-formed antigen-Ab (immune) complexes in glomerulus, which can lead to disease.
*Origin of antigens: Endogenous (SLE = DNA). Exogenous (streptococci = postinfectious). *Rarely seen in the epithelial space. |
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Glomerular Pathology: Definitions:
Diffuse-- Focal-- Global-- Segmental-- |
*Diffuse: A lesion involving most (≥50%) of the glomeruli.
*Focal: A lesion involving <50% of the glomeruli. *Global: A lesion involving more than half of the glomerular tuft. *Segmental: A lesion involving less than half of the glomerular tuft (i.e., at least half of the glomerular tuft is spared). |
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Discuss Post-streptococcal or Post-infectious Glomerulonephritis:
When does it occur? What causes it? Symptoms? |
*7-14 days after exposure to nephritogenic (e.g. Group A ß-hemolytic strep) antigen:
*Symptoms: 1) hematuria 2) edema + hypertension 3) renal insufficiency 4) Hypocomplementemia *Usually reversible with spontaneous recovery. *Photos: top shows inflammatory cells. Bottom is EM, showing capillary surrounded by lumpy hump-looking structures that represent ICs. |
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Discuss IgA Nephropathy:
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*Gross or µscopic hematuria; often accompanies URI (hematuria may not lag behind the infection like in post-strep nephritis).
*Associated with abnormalities of IgA (secretory). *May progress to advanced CKD or ESRD (20-50%). *Pic: Green corresponds to the mesangium; lighting up with an IgA antibody. |
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What are the Mechanisms underlying glomerular deposition of IgA and progression of renal disease in IgA nephropathy?
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*Defective glycosylation leads to deposition.
*Cytokines lead to localization of IgA in mesangium. |
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Discuss Rapidly Progressive GN:
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*AKA "Crescentic."
*Rapid onset of renal failure (days-weeks). *LM shows >50% of glomeruli with crescents. *3 types (distinguished by immunofluorescence): 1) Pauci-immune (vasculitis). 2) Anti-GBM disease (e.g. Goodpasture’s; shown in bottom pic. You can tell this is anti-GBM because the green is so complete, as compared the the lumpy fluorescence in IC-mediated). 3) Immune complex (lupus). *May occur as unusual presentation for OTHER diseases, e.g IgAN or PSGN. THIS IS A PATHOLOGICAL PATTERN, NOT A SPECIFIC DISORDER. |
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Describe the 6 classes of lupus:
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Class I: minimal mesangial lupus nephritis.
Class II: mesangial proliferative lupus nephritis. Class III: focal lupus nephritis (a). Class IV: diffuse segmental (IV-S) or global (IV-G) lupus nephritis (b). Class V: membranous lupus nephritis (c). Class VI: advanced sclerosing lupus nephritis. *3, 4, and 5 we try to treat; these may progress to end-stage renal disease. |
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TL: Normal.
TR: Mesangial lupus (class II). BL: Proliferative lupus (class III or IV) BR: Proliferative; IF. Lumpy bumpy appearance of ICs. |
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What are the 4 main types of Nephrotic syndrome?
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Minimal change nephropathy
Focal segmental glomerulosclerosis Membranous glomerulopathy Diabetic nephropathy |
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Discuss Minimal Change Nephropathy:
How common? When does it occur? What do you see on histology? |
*AKA Lipoid Nephrosis.
*Most common form of nephrotic syndrome in childhood. *Often rapid onset. *Spontaneous remission or rapid response to steroids. *Histopathology: -Totally normal light microscopy. -Epithelial foot process loss (effacement) on EM. *Pics: Top is normal; bottom shows minimal change. |
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L: Normal
R: Minimal change disease.. Loss of podocyte foot processes. |
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Loss of podocytes in minimal change? I think yes, but this image was skipped in class.
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Discuss Focal Segmental Glomerulosclerosis:
How does it progress? How common? Who gets it? What are the subtypes? |
*Progressive proteinuria with progression to renal failure.
*Most common NS among adults, particularly young adults and African-Americans. *Steroid dependence or resistance. *Histologic subtypes: 1) Tip lesion. 2) Collapsing (HIV). *May be idiopathic “secondary” to other conditions, such as reflux nephropathy, obesity, HIV. There is high recurrence of idiopathic lesions in transplant recipients. *Pics: Top is normal; bottom is FSGS. |
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What is the Pathogenesis of Secondary FSGS?
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*Multiple pathways of progression to the same end result:
1) Glomerular HTN/Hyperfiltration *Increased body mass (obesity) or decreased renal mass (nephron loss). 2) Glomerular Hypertrophy. 3) Podocyte Injury. |
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What's the pathogenesis of "Podocytopathies"?
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What genetic associations make African-Americans more likely to get certain glomerular diseases?
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*ApoL1 gene is associated with higher risk among African-Americans. Risk may be 20x higher than population at large.
*This mutation ALSO may confer resistance to trypanosomiasis (malaria)! |
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What are the 4 types of Membranous Nephropathy?
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*Idiopathic, or in association with other illnesses:
2) SLE (WHO Class V). 3) Hepatitis B, C. 4) Drugs. *20-30% have spontaneous complete or partial remission. *~50% have progressive renal failure. *Pics: Top is normal; bottom shows thickening of the capillary loop. |
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*Membranous Nephropathy*
TL: Silver stain; black corresponds to GBM. Note pink "holes" where there are subepithelial immune deposits. TR: Immunofluorescence shows granular deposits that array along the capillary loop, not so much in the mesangium. BL: EM in early stage of disease dark deposits (D) subepithelially. BR: Later on in the disease; deposits have degenerated and are absorbed. "Holes" have appeared where they used to be. |
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What is the pathogenesis of subepithelial deposit formation in membranous nephropathy?
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*ICs are not circulating, but FORMED in the subepithelial space (in reaction to the M-type phospholipase A2 receptor).
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Discuss Diabetic Nephropathy:
How common is it? What makes it worse? What symptoms are there? What meds help? |
*Most common cause of kidney disease leading to End-stage renal disease (ESRD).
*Co-existing hypertension is an accelerent. *Usually signified by low grade proteinuria, occasionally by nephrotic range proteinuria. *Ameliorated by ACE-I and ARBs. May be reversed by normalization of glycemic control as with pancreatic transplantation. *Pics: Top is normal, bottom is Diabetic Glomerulosclerosis; note expansion of mesangial matrix. May coalesce into nodules. |
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What is the course of diabetic nephropathy?
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*Best appreciated with DM1, because the DM diagnosis is made early.
*GFR is higher than normal early on; kidney and glomeruli become large. *10-20 years later, you see larger amounts of PRO excretion, accompanied by a drop in GFR. In 2-5 years, patients reach ESRD. |
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Describe the pathogenesis of Diabetic Glomerulosclerosis:
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In evaluating patients with glomerular disorders, what are you looking for in the history?
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*Presence of gross hematuria or “foamy urine” (could mean proteinuria).
*Description of the hematuria (gross, bloody, clots, tea- or coca-cola colored). *Associated symptoms (flank pain, edema). Edema is most common. *Multisystem features (arthritis, upper or lower respiratory tract disease, skin eruption). |
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In evaluating patients with glomerular disorders, what are you looking for on PE?
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*Blood pressure
*CVA or abdominal tenderness *Skin eruptions *Edema *Joint effusions *Pulmonary rales, etc *Other |
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In evaluating patients with glomerular disorders, what are you looking for on labs?
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*Urine analysis.
*Serum creatinine, BUN. *CBC. *May do Serologic tests (ANA, ANCA, C3, C4, Anti-Strep Abs). *May do Imaging studies. Seldomly help. *You should only get serology and imaging if you suspect a specific syndrome! |
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When you see blood in the urine, how do you know if it's glomerular or not?
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*Dysmorphic RBCs. "Mickey Mouse ear" projecting from the RBC.
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FATTY CASTS IN THE URINARY SEDIMENT
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FATTY CASTS IN THE URINARY SEDIMENT, under polarized light. Showing "Maltese cross" sign.
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*A 38 year-old man is referred to you because on pre-employment testing, he is found to have "asymptomatic” microscopic hematuria.
*Further history reveals no manifestations of systemic illness. *Physical Examination: BP 160/90, otherwise normal. *Urine analysis: Numerous rbcs, some dysmorphic and rbc casts. “2+ proteinuria.” *Serum creatinine 1.6 mg/dl. *ANA negative, ANCA negative. *Serum complement levels, normal. *Any further workup? If so, what test? |
*The pt has nephritis (blood in urine, not much protein).
*If you wanted to explore this more, the next step would be a biopsy. |
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What are the general Indications for renal biopsy?
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A renal biopsy is indicated in any parenchymal renal disease in which histopathology is essential for either diagnosis or management.
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What are the specific Indications for renal biopsy? 4
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*Acute or subacute decline in GFR.
*Heavy or nephrotic proteinuria. *Multisystem illness (e.g. pulmonary-renal syndrome). *Assessment of treatment (e.g. lupus nephritis) or prognosis. |
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*Mesangial involvement.
*This is IgA nephropathy. |
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*Mesangial deposits in IgA nephropathy.
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