Flashcards in Week 3: Clinical Aspects of proteinuria Deck (12):
Describe normal handling of protein by the kidneys.
-Only the smallest plasma proteins are allowed to pass through glomerular basement membrane
-Of the protein excreted in the urine, 50% is plasma proteins (very little albumin, mostly immunoglobulins). Remaining 50% is non-plasma protein. (Tamm-Horsfall glycoprotein-major constituent of casts matrix).
What is microalbuminuria?
-urinary albumin excretion between 30 and 300mg/24 hours or per g of creatinine
-Significance: prognostic indicator for future renal as well as CV disease. May have prognostic implications in patients with essential HTN
What is transglomerular movement of proteins affected by?
1. Properties of protein
-shape: linear, flexible, and round molecules cross GBM more easily than globular and rigid molecules
-charge: + > neutral > -
2. Properties of capillary wall
-RBF, GFR, FF
-Anionic charge of GBM
-integrity of GBM
Describe the mechanisms of proteinuria.
1. Glomerular Proteinuria:
-increased filtration of macromolecules (e.g. albumin) across glomerular capillary wall
-increased glomerular permeability can be from loss of negative charges along the basement membrane or by alteration of normal structure of GBM
2. Tubular Proteinuria
-smaller proteins are filtered and mostly reabsorbed by PT
-diseases affecting tubular functions may result in decreased reabsorption and proteinuria
-e.g. Fanconi, analgesic nephropathy
-characterized by increased excretion of low molecular weight proteins
3. Overflow proteinuria
-due to excessive production, filtration across GBM, and excretion of proteins of low molecular weight and size
-e.g. multiple myeloma: monoclonal light chains of immunoglobulin
-e.g. hemoglobinuria, myoglobinuria
Describe isolated proteinuria.
-discovered on routine examination of an asymptomatic individual, absence of hematuria
-should be evaluated for constant or orthostatic proteinuria
-orthostatic occurs only during the day but not during rest. Usually disappears over time and has no significant histological abnormalities
-constant proteinuria have larger proportion of patients with significant histological alterations and less benign clinical course
-transient proteinuria: appears in connection with an acute illness, e.g. fever, CHF, and resolves with resolution of primary disease
Define nephrotic syndrome.
-syndrome caused by renal diseases that increase permeability
A collection of signs that include
1. Proteinuria >3.5gms/24hrs
Can have the following, but not necessary for diagnosis
5. disturbances of calcium metabolism
7. Thyroid dysfunction
Describe hypoalbuminemia in nephrotic syndrome.
-when disease is characterized by loss of negative charges in the GBM, the primary protein lost is albumin (selective proteinuria)
-when disease is due to alternations in structure, other larger proteins can be loss (non-selective proteinuria)
-the urinary albumin loss stimulates hepatic synthesis of albumin, but compensation is not enough
What causes the edema in nephrotic syndrome?
There are two hypotheses
1. Underfilling: the hypoalbuminemia causes decrease in effecting circulating volume, activating RAAS and causing water and Na retention
-however, 2/3 of patients have normal plasma volume and normal aldosterone levels
2. Overfilling hypothesis
-proteinuria and albuminuria causes increased Na+ reabsorption and decreased renal excretion of Na (EDEMA)-->arterial under filling since fluid is in ISF--> ADH release and RAAS increases
What causes hyperlipidemia in nephrotic syndrome?
-hypoalbuminemia (diminished plasma oncotic pressure) causes increased production of a variety of proteins and lipids
1. proteinuria causes decreased catabolism of VLDL, chylomicrons
2. Lipoprotein lipase (LPL) is reduced because lost in urine
3. Increased HGM-CoA reductase activity
4. LDL receptor deficiency
Describe abnormalities of calcium and Vit D in nephrotic syndrome.
-25-OH-Vit D is bound to alpha globulin in blood
-this globulin and Vit D is lost in urine of patients with nephrotic syndrome
-Lack of Vit D-->reduced intestinal absorption of Ca, skeletal resistance to PTH
-bones: osteomalacia-defective mineralization of osteoid, or enhanced bone resorption (hyperparathyroidism)
Describe hypercoagulability in nephrotic syndrome.
-Alternations in levels of components in coagulation system
-Decreased: Factor XII, VII, IX, ATIII, plasminogen, activated protein C
-increased: Factor XIII, VIII, V, fibrinogen, fibronectin, platelets