L5- Renal Pathology Flashcards
list some of the many normal functions of the kidney
- 1700L blood/day –> 1L urine
- fluid / electrolyte / acid-base balance
- excretion of nitrogenous wastes (urea)
- EPO synthesis, renin synthesis, PG synthesis, VitD activation
give the equation for creatinine clearance and what it is used for
CL(Cr) = U(Cr) / P(Cr) * (vol/time)
U = [Cr] in urine; P = [Cr] in plasma
-overestimates GFR up to 15%
what are the common inaccuracies of using creatinine for calculating GFR
- Under collection: false low CrCl in elderly, acute renal disease, chronic renal disease
- Over collection: false high CrCl in pregnancy, diabetic glomerulonephritis
plasma levels of creatinine represent….
function of muscle mass (not a good indicator of renal function)
list the clinical manifestations of Glomerular Renal Diseases (hint- 3 common ones)
- Acute nephritic syndrome: hematuria, proteinuria, HTN
- Nephrotic syndrome: proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia
- Asymptomatic: w/ proteinuria, hematuria
list the clinical manifestations of Tubular Renal Diseases (hint- 3 common ones)
- UTI: bacteria, pyuria
- Nephrolithiasis: colic, hematuria
- Renal tubular defects: polyuria, nocturia, electrolyte disorders
list the clinical manifestations of glomerular/tubular renal diseases (acute and chronic)
- Acute: oliguria, anuria, azotemia (high N levels in blood)
- Chronic: prolonged symptoms of uremia (high blood urea)
list the general causes of renal failure and appropriate related diseases
1) Renal (primary kidney disease): congenital, acquired (glomerular / tubulointerstitial)
2) Pre-Renal (inadequate blood supply): HF (low CO), low perfusion, hypovolemia, sepsis, hemorrhage
3) Post-Renal (bilateral urinary obstruction): tumors, BPH
describe the clinical classification of renal dysfunction in glomerular disorders
- heavy proteinuria
- RBC + RBC casts (microscopic amounts of blood in urine)
- oval fat bodies (lipiduria)
describe the clinical classification of renal dysfunction in tubulointerstitial disorders
- mild proteinuria
- functional tubular defects
- WBCs (pyuria)
list some classic descriptors used to classify types of glomerulonephritis
- Focal (few glomeruli) v Diffuse (all)
- Proliferative (>100 nuclei in glomerulus) v Membranous (thick GBM) v Membranoproliferative
- focal segmental (fibrosis of glomeruli segment)
- crescentic (parietal epithelial cell proliferation)
what are the 2 mechanisms for pathogenesis of primary glomerular diseases
1) immune mechanisms (most common): Ab mediated, cell-mediated, complement activation (alternative pathway)
2) nonimmune mechanisms: reduction in renal mass
in Ab-mediated immune-mediated glomerular disease, how/why are Abs formed/available (in response to……)
Response to Ag type:
- Endogenous: tumor Ags, Ags w/in kidney
- Exogenous: drugs, organisms (viral, fungal)
briefly describe the method Ab-Ag complexes deposit in the kidney and result in glomerular renal disease
- Ab-Ag complex forms either in periphery or in situ => IC (immune complex)
- IC is localized in various parts of glomerulus => complement activation
- complement => influx of inflammatory cells (neutrophils, macrophages) –> injury to glomerular filtration membrane
describe the various types of ICs (immune complexes) in the kidney causing glomerular membrane damage
- In Situ IC: i) fixed Ags (intrinsic), ii) Planted Ags (exo-/endo-genous)
- Circulating IC: endogenous (DNA), exogenous (infectious protein)
- Cytotoxic Abs: direct cell injury w/o IC deposits
immune mechanisms of glomerular kidney disease involves (1) activation and (2) sensitization for its progression
1- alternate complement pathway activation (mostly nephritic syndrome, C3 convertase)
2- T cell sensitization (GBM damage)
list the changes to glomeruli seen on light microscopy in glomerular renal disease caused by nonimmune mechanisms (hint- 7)
- cell proliferation: endothelial, epithelial, mesangial, parietal (crescent) cells
- leukocytic infiltration
- necrosis
- thrombi (fibrin)
- GBM thickening
- hyalinization glomerulosclerosis (segmental, global)
- deposits (amyloidosis)
what are the 4 terms used to describe the distribution of glomerular alterations in glomerular renal disease
- diffuse: all glomeruli
- focal: some glomeruli
- global: entire glomerulus
- segmental: part of glomerulus
list the changes to glomeruli seen on electron microscopy in glomerular renal disease caused by nonimmune mechanisms
- GBM irregularities
- mesangium expansion
- electron dense deposits: i) locations (mesangium, GBM, mixed); ii) pattern (dense granular, fibrillary)
list the 4 ways glomerular deposits are described on electron microscopy
- effacement (absence) of foot processes (minimal change disease)
- subendothelial deposits
- subepithelial deposits
- intramembrane deposits (–> GBM destruction)
list the changes to glomeruli seen on immunofluorescence studies in glomerular renal disease caused by nonimmune mechanisms
(fluorescein isothiocyanate)
- Stains for Ags (IG deposits): Ig-G/A/M, C3, λ/κ chains
- Distribution: i) GBM, mesangium, both; ii) patchy, diffuse
- Pattern: granular, linear (fine, coarse)
Nephritic syndrome is glomerular injury due to (1) with the following clinical presentation: (2)
1- neutrophils
2- HTN; oliguria, hematuria (dysmorphic RBC) + RBC casts, WBC (neutrophils), proteinuria <3.5g
Nephrotic syndrome is glomerular injury due to (1) with the following clinical presentation: (2)
1- CKs –> podocyte damage –> podocyte fusion + lack of negatively charged GBM
2- pitting edema (generalized), proteinuria >3.5g + fatty casts, hypercholesterolemia, hypoalbuminemia, hypercoaguable state (loss of antithrombin III)
what is the purpose of kidney biopsy, and why might it be contraindicated
1) make diagnosis / monitor Tx effects and disease progression
2)
- advanced renal disease (small, echogenic kidney on US)
- young child (nephrotic syndrome)
- associated to systemic findings
- orthostatic proteinuria
- normal complement, creatinine, BP, and limited proteinuria
list the 3 major consequences of reductions in renal mass leading to glomerulosclerosis
i) systemic HTN –> mesangial cell hyperplasia, ECM deposition
ii) intraglomerular HTN –> intraglomerular coagulation
iii) glomerular hypertrophy –> epithelial/endothelial injury
all => glomerulosclerosis
iii) => proteinuria
explain the changes to GBM in intramembranous deposition
- destruction of GBM
- areas of thinning and thickening of GBM
- lamination of lamina densa (it splits into 2 layers)
