Nichols - Nephrotic Syndrome 1 Flashcards
Features of nephrotic syndrome
- Edema
- Proteinuria
- Hypoalbuminemia
- Hyperlipidemia
Nephrotic syndrome is a non-inflammatory condition with _____ urinary sediment and ______ or _______ creatinine.
inactive; normal or mildly elevated
What is the key cell in nephrotic syndrome?
Visceral epithelial Cell(podocyte)
Features of nephritic syndrome
- “active” urinary sediment(dysmorphic RBCs and red cell casts)
- Inflammation
- Hypertension
- Elevated creatinine
- Cresents in biopsy
What is the key cell in nephritic syndrome?
Endothelial Cell
What are some other clinical presentations of glomerular disease, other than nephrotic and nephritic syndrome?
- Asymptomatic disease
- Macroscopic hematuria
- rapidly progressive glomerulonephritis
- Chronic glomerulonephritis
When will glomerular disease be without symptoms?
- Proteinuria between 150 mg to 3 g/day
- Mild hematuria
Describe macroscopic hematurea:
Brown, red, or red/brown urine with no clots
Typical presentation of patients with chronic glomeruolnephritis?
- Hypertension
- Renal insufficiency
- Proteinuria
- Shrunken kidney disease
What are casts?
Cylindrical formations of cells or proeinaceous material
What are the most common casts?
Hyaline casts
What are these?
Dysmorphic RBCs
Describe hyaline casts
colorless, homogenous, and transparent
What do the arrows point to?
Hyaline Casts
What forms hyaline casts?
The secretion of Tamm-Horsfall mucoprotein
Tamm-Horsfall mucoprotein is secreted by? Can sometimes contain what in conditions of proteinurea?
Renal Tubule Cells; Albumin
The second most common type of cast?
Granular Casts
What do granular casts result from?
Aggregates of plasma protein, breakdown of cellular casts, or the breakdown of cellular casts
What color are granular casts composed of fine granules? Coarse granules?
Grey or pale yellow;
Darker - often black
Where are granular casts formed?
Renal Tubule
What do granular cast almost always indicate?
Significal renal disease
What type of casts are seen with acute tubular necrosis?
“Muddy brown” granular casts
What is this?
Granular Cast
What are fatty casts?
Yellow-tan hyaline casts with fat globulin inclusions (oval fat bodies)
What forms fatty casts?
Breakdown of lipid-rich epithelial cells
What is the maltese cross pattern seen under polarized light associated with? Indicate what?
cholesterol or cholesterol esters are present.
Lipiduria in Nephrotic Syndrome
What does the mechanism of disease in nephrotic syndrome depend on?
Whether there is inflammation as part of the disease process
Mechanisms of nephrotic syndrome without glomerular inflammation?
- Podocyte injury in minimal change disease and focal segmental glomerulosclerosis
- Subepithelial immune complex formation and complement activation in membranous nephropathy
- Glomerular capillary wall deposition in diabetic nephropathy, amyloidosis, and light chain deposition disease
Mechanism of nephrotic syndrome with glomerular inflammation
- Mesiangial or capillary wall immune complex formation and complement activation in IgA nephropathy and acute post-streptococcal glomerulonephritis
- Antibodies directed against GBM in anti-GBM disease
- Necrotizing injury and inflammation of the glomerular capillaries in disease associated with antineutrophil cytophil autoantibodies (ANCA)
Why are immune complexes formed and trapped in the glomeruli?
- The high plasma flow rate through them
- High intraglomerular pressure
- high glomerular hydraulic conductivity
What does the manifestation of disease depend on?
The nature of the antigen involved and the site of immune complex deposition.
What diseases are subepithelial deposits seen in?
post-infectious glomerulonephritides and membranous nephropathy
What do subepithelial deposits tend to cause?
A nephrotic syndrome picture
Where are subendothelial and mesangial deposits formed?
Either locally or from passive entrapment of circulating immune complexes
What do subendothelial and mesangial deposits tend to cause?
Nephritic syndrome picture - focal or diffuse proliferative lupus nephritis and IgA nephropathy
Clincal features of nephrotic syndrome:
- Urine protein excretion - > 50mg/kg/day or > 3.5 g/day in adults and > 40mg/hr/M2 in children
- Hypoalbumineamia - Serum level < 3.5 g/dL
- Hypercholesterolemia
- Lipiduria
- Can have xanthelasma(subQ lipid deposits)
3 purposes of kidney biopsy?
- Make a dx
- Determine px
- Guide therapy
What 3 types of microscopy do renal biopsies need?
- Light microscopy
- Immunofluorescence
- Electron Microscopy
Absolute contraindications of renal biopsy:
bleeding diathesis, uncontrolled hypertension
Relative controindications of renal biopsies:
single kidney, high pressure hydronephrosis, adult polyscystic kidney disease
What are the main sites of size hindrance for larger molecules in the glomerular filtration barrier?
Lamina densa of the GBM and the slit diaphragm
What is the estimated pore radius for spherical molecules?
42 Angstrom
What are the main sites of charge hindrance in the glomerular filtration barrier?
Anionic charge lamina rara interna and fenestrated capillary endothelium
How much protein is actually excreted in the urine? Why?
Only a tiny amount. Most of the filtered protein is reabsorbed by the renal tubules.
How are proteins taken up in the tubules?
Epithelial cells take them up through endocytosis.
What are the receptors that play a role in the endocytosis of protein?
megalin and cubulin
In glomerulonephritis what is the dominant protein in urine?
Albumin
Tubular disease is associatied with what type of proteinuria?
Low molecular weight proteins
What protein does a urine dipstick measure?
Albumin
How much albumin may health kidneys excrete each day?
30 mg
What is the rate of excretion for Tamm0Horsfall mucoprotein?
30-50 mg/day
What is microaluminuria?
Albumin levels between 30 and 300 mg/day
it is the earliest clinical manisfestation of diabetic nephropathy.
What are some methods of measuring protein urine?
Dipstick, 24-hour urine collection, and spot urine protein/creatinine ratio.
Advantages of dipstick?
Cheap, quick, and semi-quantitative
