Glomerulotubular Disorder Flashcards
Glomerular disease
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
_____ of plasma entering becomes tubule filtrate
20%
Glomerulus is not permeable to _____
Proteins
- passage of substances based on size and charge
Albumin
Large quantities only get thru if there is a breakdown in the glomerular membrane
- 69,000 daltons
- negative charge
2 causes of glomerular disease
- glomerulonephritis
- amyloidosis
Glomerulonephritis
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
How the glomerulus responds to glomerulonephritis
Glomerular cell proliferation, basement membrane thickening, eventual fibrosis
- RAAS is activated –> vasoconstriction of efferent glomerular arteriole and intraglomerular hypertension (contributes to protein loss)
Amyloidosis
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
Amyloidosis - breed disposition
- Shar-pei
- Abyssinian
Causes of glomerular disease
- idiopathic
- secondary: infectious, inflammatory, neoplastic
Once glomerulus is irreversibly damaged, _______
Entire nephron becomes non-functional
- total GRF decreases –> hypertension
- remaining nephrons increase individual GFR to compensate
Hyperfiltration can result in _______
Progressive loss of remaining nephrons and renal failure
Hypoalbuminemia
Oncotic pressure is lost and fluid lost from vascular space
- edema
- ascites
- pleural effusion
- hypovolemia
Clinical signs of hypoalbuminemia begins at ______
1.4 - 1.6 g/dl
Nephrotic syndrome
- hypoalbuminemia
- proteinuria
- hypercholesterolemia
- edema and/or ascites
Protein losing nephropathy
Proteinuria!
- excessive amounts of any protein in the urine (albumin is main urine protein
- must be in the absence of active sediment or hemorrhage!
Evaluating the magnitude of protein in the urine
- dipstick evaluation
- sulfosalicylic acid test
- urine protein creatinine ratio
Dipstick Evaluation
Most common screening test
- concentration of urine can affect protein levels
- can give false negative results! –> low concentration of albumin, dilute urine
What causes a false positive for proteinuria via dipstick?
Alkaline urine
Other reasons to have proteinuria via dipstick evaluation
- increased SG
- hematuria
- pyuria
- semen
Slufosalicylic acid test
SSA reagent added to small volume of urine supernatant
- acidification causes precipitation of protein in the sample (increasing turbidity), subjectively graded as trace
SSA reaction will detect _______
Albumin and globulins (more sensitive to albumin)
- considered confirmatory for positive proteinuria rxn on urine dipstick
Urine protein: creatinine ratio
Gives better quantitative evaluation of protein loss in the urine
- creatinine is filtered and excreted at a constant rate
- serves as correction factor
UPC ratio values
Normal: less than 0.2
- borderline: 0.2-0.5 (dogs), 0.2-0.4 (cats)
- increased: >0.5 (dogs), >0.4 (cats)
Diagnosis
- history/PE
- blood work/UA/urine culture
- bp measurement
- aspirate lumps and bumps
- serology for suspect infectious dz
- imaging
Nonspecific management of glomerular dz
- treatment of underlying cause
- reduce the proteinuria
- management of complications
Reduction of proteinuria
Inhibition of RAAS system reduces glomerular capillary bed hydrostatic pressure, thrus reducing proteinuria
Reduction of proteinuria
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
Treatment significantly reduces _________
Proteinuria and delays onset/progression of azotemia
- standard of care w/ glomerular dz in dogs!!
Diet changes
Feed high-quality, reduced quantity protein diet
- omega 3 polyunsaturated FAs supplementation
Beta pleated sheet conformation resistant to proteolysis
Amyloidosis
- colchicine: impair release of serum amyloid A from hepatocytes
- DMSO: decrease in interstitial fibrosis and inflammation (may improve renal function)
Management of complications
- treatment of renal failure
- ascites and edema
- systemic hypertension
- hypercoagulability and thromboembolism
Proteinuria leads to
Abuminuria –> hypoalbuminemia
- albumin between 1.6-1.4 = begin transudation of fluid into interstitial spaces
Therapy depends on _____
Severity
- mild: cage rest, no salty treats
- moderate/severe: consider plasma, synthetic colloids, diuretics
Systemic hypertension
Present in 80% of dogs
- eyes, heart, kidneys, CNS most susceptible to damage
- treat w/ ACE inhibitors, amlodipine
Hypercoagulability and thromboemolism
Loss of antithrombin 3, increased platelet activation
- antiplatelet therapy used to reduce glomerular inflammation and decrease platelet aggregation, decreasing incidence of thromboembolism
Prognosis
Depends on:
- underlying disorder
- severity and extent of renal insult
- response to treatment
- glomerulonephritis (variable)
- amyloidosis (severe, irreversible)
