B72, nephrosis syndrome Flashcards
How does nephrosis syndrome cause a hypercoagulable state?
In addition to increased liver synthetic activity, there is selective Antithrombin 3 loss in the urine.
What is the clinical presentation of nephrosis syndrome?
Massive proteinuria, >3.5 g/day
Hypoalbuminuria
Hypogammaglobulinemia (in all except minimal change disease, risk of infection)
Generalized Pitting Edema
Hypercoagulable state (AT3 loss in urine)
Hyperlipidemia hypercholesterolemia
Lipiduria and sometimes adipose casts in urine
*note the absences of azotemia, hematuria, and hypertension.
Describe the pathogenesis of nephrosis syndrome?
Something occurs that increases the permeability of the glomerulus to proteins.
Hypoalbuminemia occurs from the loss.
Generalized Edema develops called anasarca causes more fluid loss from the circulation
Decreased GFR and RAS activation
Vasoconstriction exacerbates edema in a vicious circle.
What are the causes of nephrotic syndrome (6)
Minimal change disease
Focal Segmental Glomerulosclerosis
Membranous Nephropathy
Membranoproliferative Glomerulonephritis
Diabetes Mellitus
Systemic Amyloidosis
What is the pathogenesis of minimal change disease?
Unknown cause, occuring idiopathically, and sometimes in conjunction with Hodkin’s lymphoma
Occurs mostly in children.
Only morphological change is effeacement of the foot processes visible by EM.
Lipid vesicles may be seen in proximal tubule cells
Negative immune deposits
Selective proteinuria, only albumin lost and not immunoglobulin.
What is the clinical presentation and course of minimal change disease?
In young children between ages 1-7 idiopathically or in Hodgkins lymphoma
Slowly developing nephrosis syndrome, without hypertension and with preserved kidney function (no azotemia)
Responds very well to corticosteroids, damage occurs due to cytokine release by T cells.
Over 25 years, about 5% will develop chronic kidney disease, and the prognosis is a little worse in adults than children.
What is the pathogenesis of Focal Segmental Glomerulosclerosis?
idiopathic, and is diagnosed based on histologic description
May be part of continuum of disease with minimal change disease or from transformed minimal change disease.
Podocyte injury is thought to be the initiating event, and foot process effacement is seen on EM.
Develops focal (only some of the glomeruli) segmental (only part of the glom is affected) slcerosis
Affected glomeruli have increased mesangial matrix, obliterated capillary lumins, hyalin deposition, andl ipid droplets.
There is no immune deposition, negative IF.
No response to steroids and progresses to renal failure in 50% of patients within 10 years, worse in adults than children.
What is the etiology and presentation of Focal Segmental Glomerulosclerosis?
Occurs idiopathically in children and adults, is 20-30% of all nephrosis syndromes.
Can occur after both Minimal change disease, and IgA nephropathy.
Also associated with HIV, heroin users, and sickle cell disease. *If a heroin user presents with renal failure, for boards, they definitely have FSGS.
Most common nephrosis syndrome in Hispanic and African Americans.
Will occur often after kidney transplantation, suggesting a circulating factor is involved in pathogenesis.
What is the pathogenesis of membranous nephropathy?
An in-situ reaction of either antibodies against podocyte foot process antigens, or against planted antigens in the sub-epithelial region.
Causes granular staining of IC deposits in the subepithelium
Forming a spike and dome pattern on EM. Some of the se deposits are eventually degraded and may leave cavities in the basement membrane.
The podocytes lay down new baesment membrane because they don’t like being on the IC deposits, causing a diffuse thickening of the capillary walls,
Heyman’s nephritis is the model for membranous nephropathy, because the anti-megalin antibodies have cross reactivity to foot process antigens.
What is the etiology and clinical presentation of membranous nephropathy?
The most common nephrotic syndrome in Caucasian adults
Most are cases are idiopathic, 85%
Others are associated with one of the following:
- Infections: Hepatitis B, syphilis, shistosomiasis, malaria
- Malignant tumors, Lung and Colon carcinoma, and Melanoma
- Systemic Lupus Erythematosus
- Drugs - Penicillamine, NSAIDS
- Gold and Mercury poisoning.
Presents as nephrosis syndrome with non-selective proteinuria.
Is highly variable in its progression.
10-30% will have a partial or complete spontanous recovery
60% will have persistent proteinuria without any other progression to further symptoms
40% will eventually progress to end stage renal failure from between 2 and 20 years.
It does not respond to steroid treatment.
What is the pathogenesis of Membranoproliferative glomerulonephritis?
In Type 1 MPGN: Circulating IC or planted antigens and in situ formation, cause Immune complex deposition in the subendothelial layer.
-type 1 occurs in: SLE, hepatits B and C.
In Type 2 MPGN, now known as a distinct disorder called Dense deposit disease: the lamina densa and subendothelial space are filled with deposited material of unkown composition. It is caused by excessive complement activation. SOME cases but not all, are associated with anti-C3 convertase autoantibodies. Which stabilizes and activates C3 convertase, causeing hyperactivation of the complement pathway. Factor F deficiency also causes hyperactive complement activatio9n
Describe the histology of membranoproliferative GN.
On H&E stain, there is mesangial and endothelial cell proliferation, and there is thickened basement membrane. There is Tram Track splitting of the GBM in both _(but more associated with type 1)_due to extension of the proliferating mesangial cells and their processes extending into the basement membrane to remove the deposits.
Type 1 MPGN and Dense Deposit Disease/Type2 are distinguished by electron microscopy.
Type 1 MPGN: Subendothelial deposits
Type 2/DDD: Intra-GBM deposits.
What are the main types of Renal disease associated with SLE?
most often, a Nephritic syndrome of Diffuse Proliferative Glomerulonephritis
If they have nephrosis syndrome, it is usually Membranous nephropathy, and least commonly, membranoproliferative
How does diabetes mellitus cause nephosis syndrome?
Non enzymatic glycosylation of basement membrane, most heavily in the Efferent artiole –> Damage/increased permeability in efferent arteriole and subsequent Hyaline Arteriolosclerosis of the non-glomerular arteries, both afferent and efferent, but most heavy hyaline arteriolosclerosis is in the efferent arteriole.
Increased glomerular pressure –> hyperfiltration and damge to the filtration barrier –> microalbuminuria and eventual frank nephrosis syndrome.
There is also Mesangial cell proliferation and sclerosis, forming balls of PAS-positive sclerosis and mesangial cells called Kimmelsteil-wilson bodies. (PAS stains glycosylated proteins and lipids)
Capillary basement membrane thickening (hyaline) and tubular basement membrane thickening.
slowed by ace inhibitors: inhibiting AngII decreased pressur in the efferent arteriole, decreasing hyperfiltration
Also due to chronic pyelonephritis from the high glucose in blood and recurrent upper UTIs.
What diseases cause hyaline arteriolosclerosis?
Benign Hypertension and Diabetes Mellitus
