Flashcards in Glomerular Diseases Deck (49)
What is the composition of endothelial cells of the glomerulus? How does this contribute to a selective barrier?
- fenestrated large pores 50-100nm wide which is pretty big considering albumin is 3.6 nm wide
- covered though in a negatively charged glycocalyx which provides a some charge barrier to other negatively charged proteins
What is the composition of the glomerular basement membrane? How does this contribute to the selective barrier?
Network of type 4 collagen and heparan sulphate proteoglycans, the latter of which are negatively charged and contribute the MAJOR charge selectively
What is the slit diaphragm?
A series of proteins that span the filtration slits (between the podocyte processes) by connecting to the actin cytoskeleton of the podocyte?
What is the major function of the slit diaphragm?
provides the major size restriction of protein filtration
Differentiate (briefly) between nephrotic and nephritic syndromes in terms of where the damage occurs and what urine findings you have?
1. Nephrotic syndrome: functional damage to the filtration barrier
- high protein in the urine
- may induce sodium retention and secondary edema and HTN
2. Nephritic syndrome: severe breaks in the glomerular capillary wall
- occur often in the context of significant inflammation in the glomerulus
- RBC, dysphormic RBC, and RBC casts all present
- protein present
broadly, glomerulonephritis refers to ...
autoimmune mediated disorders of the kidney
What is the relationship between GN and ESRD?
there is a high risk of progression from GN to ESRD
- depends on disease type.
- some can be rapid while others take years
What treatment type is used for GN?
What are the 4 clinical classifications of nephrotic syndrome?
1. proteinuria >3.5 g/d
4. peripheral edema
Is GFR abnormal in nephrotic syndrome?
Often normal early on in the disease progression and only decreases later when scarring develops
What are 7 possible complications of nephrotic syndrome?
2. peripheral edema
4. hypergoalgulability and VTE
What is the underlying pathophysiology of the peripheral edema seen in nephrotic syndrome?
- low albumin causing low oncotic pressure
- presence of protein in the urine induces tubular resorption of sodium
What is the underlying pathophysiology of the hypercholesterolemia seen in nephrotic syndrome?
low oncotic pressure induces hepatic production
What is the underlying pathophysiology of the
hypercoaguability seen in nephrotic syndrome?
- urinary losses of anticoagulant proteins
- increased production of procoagulant proteins
What is the underlying pathophysiology of the infection seen in nephrotic syndrome?
hypogammaglobulinemia from the losses of IGs in the urine
What is the underlying pathophysiology of the AKI seen in nephrotic syndrome?
- tubular injury from heavy proteins
- fluid shifts causing intravascular volume depletion
- interstitial edema in the kidney
- bilateral renal vein thrombosis
What is the underlying pathophysiology of the lipiduria seen in nephrotic syndrome?
- high amount of filtered lipid in urine reabsorbed by the tubular cells
- lipid droplets in urine
- oval fat bodies : sloughed tubular cells filled with lipid
- fatty casts: casts containing lipid filled tubular cells or free lipid droplets
What are the 3 most common causes of idiopathic nephrotic syndrome?
1. minimal change disease (MCD)
2. Focal segmental glomerulosclerosis (FSGS)
3. Membranous nephropathy (MN)
What are 3 possible systemic causes of nephrotic syndrome ?
1. Diabetes nephropathy
- most common cause of nephrotic syndrome
How does minimal change disease present?
- sudden onset peripheral edema over several weeks
- younger children and older adults
What is the first line treatment option for MCD
- if they respond well (75% do) it carries a good future prognosis
- steroid resistance or relapses has a worse prognosis
What is the underlying histological change in MCD?
diffuse effacement of the foot process of podocytes leading to disruptions in the slit diaphragm
Describe the histological findings of focal segmental glomerulosclerosis (FSGS)
scarring in <50% of the glomeruli and only involving part of the glomeruli
also has diffuse foot process effacement like MCD
What is the clinical presentation of FSGS
More common presentation in adults
- 35% of nephrotic syndromes
- more common in black patients
- worse prognosis than MCD, more likely to progress to ESRD
What is the most common cause of nephrotic syndrome in caucasians?
What % of patients with membranous nephropathy present with high grade proteinuria?
What is the etiology of primary MN?
organ specific autoimmune disease with Ab againse the phospholiapse A2 receptor
- in 70% of cases
What are the histological findings of MN?
thickened capillary wall due to immune complex deposits under the podocytes and expansion of the GBM
What is the general workup of a patient with nephrotic syndrome?
1. Quantify severity
- creatinine and eGFR
- albumin, cholesterol
- 24hr urine for protein, ACR or PCR
- urinalysis and microscopy
2. R/O secondary causes
- autoimmune disorders -
- hematological malignancy