Glomerulotubular Disorder

Question 1

Glomerular disease

Answer 1

Breakdown in the normal function of the glomerulus and resultant abnormal leakage of large quantities of protein into the urine (esp. albumin)
- associated with a protein losing nephropathy

Question 2

_____ of plasma entering becomes tubule filtrate

Answer 2

20%

Question 3

Glomerulus is not permeable to _____

Answer 3

Proteins

- passage of substances based on size and charge

Question 4

Albumin

Answer 4

Large quantities only get thru if there is a breakdown in the glomerular membrane

• 69,000 daltons
• negative charge

Question 5

2 causes of glomerular disease

Answer 5

• glomerulonephritis

- amyloidosis

Question 6

Glomerulonephritis

Answer 6

Secondary, deposition of preformed Ag-Ab complexes within the glomeruli

• deposition of Ag in capillary wall with resultant Ab binding and formation of Ag-Ab complexes
• stimulate production of proinflammatory cytokines, vasoactive substances, proteases

Question 7

How the glomerulus responds to glomerulonephritis

Answer 7

Glomerular cell proliferation, basement membrane thickening, eventual fibrosis
- RAAS is activated –> vasoconstriction of efferent glomerular arteriole and intraglomerular hypertension (contributes to protein loss)

Question 8

Amyloidosis

Answer 8

Deposition of excessive amounts of amyloid A protein

• serum amyloid A produced by liver (acute phase protein), result of tissue injury and inflammation
• reactive amyloidosis

Question 9

Amyloidosis - breed disposition

Answer 9

• Shar-pei

- Abyssinian

Question 10

Causes of glomerular disease

Answer 10

• idiopathic

- secondary: infectious, inflammatory, neoplastic

Question 11

Once glomerulus is irreversibly damaged, _______

Answer 11

Entire nephron becomes non-functional

• total GRF decreases –> hypertension
• remaining nephrons increase individual GFR to compensate

Question 12

Hyperfiltration can result in _______

Answer 12

Progressive loss of remaining nephrons and renal failure

Question 13

Hypoalbuminemia

Answer 13

Oncotic pressure is lost and fluid lost from vascular space

• edema
• ascites
• pleural effusion
• hypovolemia

Question 14

Clinical signs of hypoalbuminemia begins at ______

Answer 14

1.4 - 1.6 g/dl

Question 15

Nephrotic syndrome

Answer 15

• hypoalbuminemia
• proteinuria
• hypercholesterolemia
• edema and/or ascites

Question 16

Protein losing nephropathy

Answer 16

Proteinuria!

• excessive amounts of any protein in the urine (albumin is main urine protein
• must be in the absence of active sediment or hemorrhage!

Question 17

Evaluating the magnitude of protein in the urine

Answer 17

• dipstick evaluation
• sulfosalicylic acid test
• urine protein creatinine ratio

Question 18

Dipstick Evaluation

Answer 18

Most common screening test

• concentration of urine can affect protein levels
• can give false negative results! –> low concentration of albumin, dilute urine

Question 19

What causes a false positive for proteinuria via dipstick?

Answer 19

Alkaline urine

Question 20

Other reasons to have proteinuria via dipstick evaluation

Answer 20

• increased SG
• hematuria
• pyuria
• semen

Question 21

Slufosalicylic acid test

Answer 21

SSA reagent added to small volume of urine supernatant

- acidification causes precipitation of protein in the sample (increasing turbidity), subjectively graded as trace

Question 22

SSA reaction will detect _______

Answer 22

Albumin and globulins (more sensitive to albumin)

- considered confirmatory for positive proteinuria rxn on urine dipstick

Question 23

Urine protein: creatinine ratio

Answer 23

Gives better quantitative evaluation of protein loss in the urine

• creatinine is filtered and excreted at a constant rate
• serves as correction factor

Question 24

UPC ratio values

Answer 24

Normal: less than 0.2

• borderline: 0.2-0.5 (dogs), 0.2-0.4 (cats)
• increased: >0.5 (dogs), >0.4 (cats)

Question 25

Diagnosis

Answer 25

- history/PE - blood work/UA/urine culture - bp measurement - aspirate lumps and bumps - serology for suspect infectious dz - imaging

Question 26

Nonspecific management of glomerular dz

Answer 26

- treatment of underlying cause - reduce the proteinuria - management of complications

Question 27

Reduction of proteinuria

Answer 27

Inhibition of RAAS system reduces glomerular capillary bed hydrostatic pressure, thrus reducing proteinuria

Question 28

Reduction of proteinuria

Answer 28

ACE inhibitors help w/ decreasing glomerular capillary hydrostatic pressure - decreased efferent arteriolar resistance - decrease hydrostatic pressure across glomerulus - less protein is forced out into the urine

Question 29

Treatment significantly reduces _________

Answer 29

Proteinuria and delays onset/progression of azotemia | - standard of care w/ glomerular dz in dogs!!

Question 30

Diet changes

Answer 30

Feed high-quality, reduced quantity protein diet | - omega 3 polyunsaturated FAs supplementation

Question 31

Beta pleated sheet conformation resistant to proteolysis

Answer 31

Amyloidosis - colchicine: impair release of serum amyloid A from hepatocytes - DMSO: decrease in interstitial fibrosis and inflammation (may improve renal function)

Question 32

Management of complications

Answer 32

- treatment of renal failure - ascites and edema - systemic hypertension - hypercoagulability and thromboembolism

Question 33

Proteinuria leads to

Answer 33

Abuminuria --> hypoalbuminemia | - albumin between 1.6-1.4 = begin transudation of fluid into interstitial spaces

Question 34

Therapy depends on _____

Answer 34

Severity - mild: cage rest, no salty treats - moderate/severe: consider plasma, synthetic colloids, diuretics

Question 35

Systemic hypertension

Answer 35

Present in 80% of dogs - eyes, heart, kidneys, CNS most susceptible to damage - treat w/ ACE inhibitors, amlodipine

Question 36

Hypercoagulability and thromboemolism

Answer 36

Loss of antithrombin 3, increased platelet activation - antiplatelet therapy used to reduce glomerular inflammation and decrease platelet aggregation, decreasing incidence of thromboembolism

Question 37

Prognosis

Answer 37

Depends on: - underlying disorder - severity and extent of renal insult - response to treatment - glomerulonephritis (variable) - amyloidosis (severe, irreversible)