SM 212: Pathophysiology of Nephrotic Syndrome

Question 1

What is the classic tetrad of nephrotic syndrome

Answer 1

1. Proteinuria (>3g)
2. Hypoalbuminemia
3. Hyperlipidemia/Hypercholesterolemia
4. Edema

Question 2

What is the key pathologic mechanism of proteinuria?

Answer 2

Podocyte effacement
Disorganized podocyte cytoskeleton leads to flattening/effacement = decreases surface area = less macromolecule excretion
Effacement also abrogates streaming potential = loss of charge gradient + selectivity = more albumin (negatively charged filtration)

Question 3

What is the mechanism behind edema formation? What two models explain additional edema formation?

Answer 3

1. Starling forces - loss of protein in blood - less blood oncotic pressure - more fluid out to interstitium
2. “Underfilling” model: less oncotic blood = edema + low EABV = less GFR = triggers renin = more thirst, more Na reabsorption = more edema
3. “Overflow” model: when plasma volume too high, serum proteases filtered = activate ENaC = more Na retention = more overflow

Question 4

Why do lipid abnormalities occur in nephrotic syndrome?

Answer 4

Low oncotic signals increased hepatic lipoprotein synthesis
HDL/lipid transport proteins lost in filtration

LPL/LCAT activity down due to albuminuria
(albumin binds products of LCAT rxn - cholesterol ester and lysolecithin - removing them from equilibrium - more cholesterol reacts) albumin lost - less equilibrium shift - cholesterol buildup

Question 5

Why does nephrotic syndrome lead to hypercoagulability?

Answer 5

Renal vein thrombosis due to hemoconcentration in vasa recta, urinary loss of anti-coagulant factors, increased platelet aggregation (without albumin acting as a carrier protein), altered fibrinolysis

Question 6

Why does nephrotic syndrome lead to problems with bone metabolism?

Answer 6

Loss of vitamin D binding protein (megalin) and vitamin D in urine
Low vit D = low Ca absorption = high PTH