PATH: Nephrotic Syndrome I Flashcards
What is nephrotic syndrome?
Insiduous onset of:
1) edema
2) proteinuria
3) hypoalbuminemia
4) hyperlipidemia
What are casts?
cylindrical formations of cells or proteinaceous material
What makes up a hyaline cast?
precipitation of Tamm-Horsfall mucoprotein (which are secreted by renal tubular cells)
What makes up granular casts?
aggregates of plasma proteins or the break-down of cellular casts
What are granular casts characteristic of?
Non-inflammatory tubular interstitial disease (renal disease)
What is contained within a fatty cast?
oval fat bodies with Maltese cross (cholesterol)
When do you see fatty casts?
In nephrotic syndrome (due to associated lipiduria)
When do you see RBC casts?
with glomerular damage
When do you see WBC casts?
inflammation during renal diseases (ex. pyelonephritis, acute post-strep GN, nephritic syndrome)
What characteristics of the glomerulus lead to immune complex entrapment?
1) High plasma flow rate (20% of CO)
2) High intraglomerular pressure
3) High glomerular hydraulic conductivity (permeability)
True or false: nephrotic syndrome has a drop in GFR that will lead to high serum creatinine.
FALSE: the kidney function is normal so you will have normal or mildly elevated creatinine
Which has worse edema: nephrotic or nephritic syndrome?
Nephrotic!
Which has worse proteinuria: nephrotic or nephritic?
Nephrotic (> 3.5g/day)
What cells are targeted with nephrotic syndrome? Nephritic syndrome?
Nephrotic: podocytes (filter leaking; charge barrier gone)
Nephritic: endothelial cells (filter bleeding; big gaps but charge barrier remains)
Why do you see hypocholerterolemia and lipiduria (with potential xanthelasma) in nephrotic syndrome?
Increased hepatic synthesis of cholesterol, TG, and lipoproteins.
What are the 3 purposes of performing a renal biopsy?
1) Make a diagnosis
2) Determine prognosis
3) Guide therapy
What are the relative contraindications for renal biopsy?
single kidney
high pressure hydronephrosis
adult PKD
What are the ABSOLUTE contraindications for renal biopsy?
bleeding diathesis
uncontrolled HTN
Where is the main site of size hindrance in the glomerulus?
Lamina densa of GBM
Slit diaphragm
Where are the main sites of charge hindrance in the glomerulus?
Lamina rara interna
Fenestrated capillary endothelium
Why can albumin not cross the GBM?
it is small enough, but its negative charge excludes it and keeps it in the lumen!
What diameter molecules are restricted?
over 4 nanometer
Where do proteins get reabsorbed?
Most get reabsorbed in the proximal tubule via endocytosis (vesicles fuse with lysosomes, proteins broken down to AAs, cross basolateral membrane and re-enter blood)
What multi-ligand receptors may aid int he receptor-mediated endocytosis of protiens in the PT?
Megalin and Cubulin
What diseases lead to subepithelial deposits?
Membranous Nephropathy
Post-infectious GN (later in disease)
What diseases lead to subendothelial/mesangial deposits?
Focal or Diffuse Proliferative Lupus Nephritis
Early Post-Infectious GN
IgA Nephropathy
Why do you see decreased small proteins and increased larger proteins in the urine of someone with nephrotic syndrome?
You have loss of surface area due to effacement but LARGER gaps between them!
What are the 3 types of proteinuria?
1) Glomerular (albumin dominant)
2) Tubular (low MW proteins)
3) Overflow (production/filtration> reabsorption capacity)
What is an example of an overflow proteinuria?
multiple myeloma
What is the major limitation of the urine dipstick?
The body makes around 150 mg/day of protein AT THE MOST and urine dipsticks only detect > 300-500 mg/day
What is the earliest clinical manifestation of diabetic nephropathy?
microalbuminuria
What is the main goal of managing nephrotic syndrome?
preserving kidney function
What is the main prognostic indicator of nephrotic syndrome?
degree of proteinuria
How can you tell the difference between chronic and rapidly progressive glomerulonephritis?
Chronic will have HTN, renal insufficiency, Proteinuria >3g/day, and shrunken, smooth kidneys
Rapidly progressive will be normotensive, in renal failure, have less proteinuria, and have RBC casts in the urine
