Flashcards in Nephrotic Syndromes Deck (60):
What is the key cell of nephrotic syndrome
What is nephrotic syndrome characterized by ?
(1) edema, (2) proteinuria, (3) hypoalbuminemia and (4) hyperlipidemia. It is a non-inflammatory condition with “inactive” urinary sediment (without dysmorphic red cells or red cell casts), and normal or mildly elevated creatinine
What are the characteristics of Niphritis syndrome ?
In contrast, the nephritic syndrome features (1) “active” urinary sediment (with dysmorphic red cells and red cell casts), (2) inflammation, (3) hypertension, (4) elevated creatinine and (5) crescents on biopsy in very severe forms.
What are inactive urinary sediment ?
Without dysmorphic cells or red cell casts
What are the mechanisms of Nephrotic syndrome without glomerular inflammation ?
1. Podocyte Injury
2. Sub-Epithelial Immune Complex Formation
3. Glomerular Capillary Wall Deposition
What are the mechanisms of Nephrotic syndrome that include glomerular inflammation ?
1. Mesangial or capillary wall immune complex formation and deposition including complement deposition.
2. Antibodies directed against GBM
3. Necrotizing Injury of the glomerular capillaries. Inflamation driven by Anti-neutrophil cytoplasmic antibodies.
Where are the immune complexes in Lupus Nephritis ?
In the subepithelial space
What is nephrotic syndrome ?
The insidious onset of Edema, Proteinureia, Hypoalbumemia and Hyperlidemia
What is an active urinary sediment ?
Red Blood Cell casts or dysmorphic red blood cells in urine suggestive of glomerular nephritis with nephritic syndrome
What is microalbuminuria ?
30-300 mg / Day of albumin in the urine, low grade proteinuria
What is nephrotic range proteinuria
> 3.5 grams / day which correlates with a urine protein / creatine ration of > 3.5
How are immune complexes trapped in the glomeruli ?
(1) the high plasma flow rate through them [with about 20% of cardiac output to the kidney], (2) high intraglomerular pressure, and (3) high glomerular hydraulic conductivity (permeability).
What determines the manifestations of the immune complex disease ?
The manifestations of disease depend on the nature of the antigen involved and the site of immune complex deposition
What will a subepithelial deposit mean ?
glomerulonephritides (such as post-streptococcal glomerulonephritis) and membranous nephropathy
What does a subepithelial deposit mean ?
Subepithelial deposits tend to cause a nephrotic syndrome picture, as seen most characteristically with membranous nephropathy.
What does a subendothelial deposit mean ?
Subendothelial and mesangial deposits tend to cause a nephritic syndrome picture as seen in focal or diffuse proliferative lupus nephritis and IgA nephropathy.
Inactive Urinary Sediment ( No dysmorphic RBC's or RBC casts)
What is the most important clinical presentation with glomerular disease ?
Rapidly progressive glomerulonephritis with renal failure over days to weeks
What will you see in patients with renal failure secondary to glomerulonephritis ?
These patients are referred to as rapidly progressive and ggenerally have red blood cell casts in their urine due to large numbers of red blood cells clumping in renal tubules which will form cylindrical casts.
What are the 4 biggest symptons of nephrotic syndrome ?
Edema, Proteinuria, Hypoalbuminemia, and Hyperlipidemia
What are casts ? What are the most common type ?
Cylindrical formations of cells or proteinaceous material. Hyaline Casts are the most common
What will a hylane cast tell you ?
Not a whole lot. They are normal in small amounts and are common to all sorts of renal disease.
What does a granular cast mean ?
Significant renal disease
What are fatty casts associated with ?
The break down of lipid rich epithelial cells. They indicate lipiduria of nephrotic syndrome
What are WBC casts associated with ?
They are indicative of inflammation due to polynephritis, interstitial nephritis, acute post-streptococcal glomerulonephritis
What is the fusion of the foot processes which usually correlates with a large loss of protein in the urine.
Effacement- There is usually a detachment associated with this phenomena that will promote proteins leaking through the capillary
What are the layers of the basement membrane ?
Lamina Lucida Interna, Lamina densa, and Lamina Rara externa
What are the proteins that conrtibure to the slit pore formation ?
Nephrin and podocin, Mutations in these will cause congenital nephrotic syndromes
What molecule gives the charge properties to the basement membrane ?
What causes glomerulonephritis with hematuria ?
A mutation in the NC-1 domain of the alpha 3 (IV) chain
Foot Process Effacement
Minimal change disease
Spike and Dome
Post Infectons Glomerulonephritis
Hypertensive Neuropathy or scleroderma
What is the protein size cutoff that can pass through the glomerulous ?
Under 4 mm can pass through the membrane
Describe the glomerular permeability in nephrotic syndrome
The glomerular permeability will be increased
What protein does the urine spot test look for ?
Production and hence filtration exceeds the reabsorption capacity ( Multiple Myeloma )
Secondary to tubulointerstitial disease- low molecular weight proteins
Seen with any glomerulonephritis, albumin is the dominant protein in the urine.
What is the nnormal albumin / creatine ratio ?
What is the normal kideny excretion rate of protein ?
40 - 80 mg/day but can go up to 150 ( threshold for normal range )
What is the nephrotic range proteinurea ?
Spot urine level will be over 3.5 and 24 hour urine collection will be above 3.5 grams
What is the goal in treating nephrotic syndrome ?
Preserve the kidney function. The disease needs to be modified and supportive measures need to be put in place.
What are the 4 aspects of nephrotic syndrome ?
2. Heavy Proteinurea
Is nephrotic syndrome inflammatory ?
NO it is non-inflammatory injury to the glomerular capillary wall ( Podocytes )
In nephrotic syndrome what is the urinary sediment like ?
It is inactive
What are the 3 layers of the Glomerular capillary ?
2. Glomerular basement membrane
3. Podocyte visceral epithelial cell layer
What are the two podocytopathies ?
Minimial change disease and Focal Segmental Glomerulosclerosis
What disease is a membranous nephropathy ?
It is a form of chronic immune complex glomerulonephritis.
What is soluble urokinase type plasminogen activator receptor (suPAR) ?
Is is a circulating factor that binds to the podocyte anchor beta 3-untegrin and could be a common cause of focal segmental glomerulosclerosis
What is focal segmental glomerulosclerosis ?
It is a disease characterized by deposition of basement membrane like material assocaited with podocyte injury, not affecting all glomeruli ( focal ) and involving only segmnets of each affected glomerulous but progressing to sclerosis
Why is it important to differentiate between focal segmental glomerulosclerosis and minimal change disease ?
Because the prognosis is much worse in focal segmental glomerulosclerosis
What is azotemia ?
Increased concentration of creatine and urea nitrogen
What are apo L1 mutations ?
Mutations causing truncation of apolipoprotein L1 conferring with resistance to trypanosomiasis and susceptibility to focal segmental glomerulosclerosis
What is a soluble Urokinase type plasminogen activator receptor ?
A circulating factor that binds to the podocyte anchor beta3-integrin and could be a common cause of focal segmental glomerulosclerosis