Week 3: Clinical Aspects of proteinuria Flashcards Preview

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Flashcards in Week 3: Clinical Aspects of proteinuria Deck (12):
1

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).

2

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

3

What is transglomerular movement of proteins affected by?

1. Properties of protein
-size
-shape: linear, flexible, and round molecules cross GBM more easily than globular and rigid molecules
-charge: + > neutral > -
-deformability
2. Properties of capillary wall
-RBF, GFR, FF
-Anionic charge of GBM
-integrity of GBM

4

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

5

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

6

Define nephrotic syndrome.

-syndrome caused by renal diseases that increase permeability
A collection of signs that include
1. Proteinuria >3.5gms/24hrs
2. Hypoalbuminemia
3. edema
Can have the following, but not necessary for diagnosis
4. Hyperlipidemia
5. disturbances of calcium metabolism
6. hypercoagulability
7. Thyroid dysfunction

7

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

8

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

9

What causes hyperlipidemia in nephrotic syndrome?

Complex mechanisms
-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

10

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)

11

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

12

List the etiologies of nephrotic syndrome.

Secondary causes-most common
-diabetic nephropathy, amyloidosis, multisystem diseases (SLE), neoplasia, drugs, infections (parvo, HIV, syphilis, hep B)
Idiopathic form
-Minimal change disease
-membranous glomerulonephritis
-focal and segmental glomerulosclerosis
-membranoproliferative glomerulonephrits
-IgA nephropathy