Nephrotic syndrome Flashcards
The glomerulus is a specialized capillary network which interacts with both (1) cells
- visceral and parietal epithelial
The (1) cells interact with the glomerular capillary (2) to form (3) with specialized foot processes that contribute to the filtration barrier
- visceral epithelial
- basement membrane
- podocytes
The (1) cells line the urinary space which becomes the (2) for each nephron
- parietal epithelial
2. proximal convoluted tubule
Because the glomerulus is designed to filter large quantities of blood, it has a three part filtration barrier. The first is the (1) (essentially holes) within (2) in the glomerular capillaries. Next is the glomerular (3) and the third is the (4)
- fenestrations
- endothelial cytoplasm
- basement membrane
- foot processes/slit diaphragm design of the epithelial podocytes.
This triple barrier is designed for high volume filtration of blood which allows (1) in the filtrate in the urinary space but keeps (2) in the blood stream
- water, ions, and small molecules
2. proteins
Ions, water, and small molecules present in the urinary space can be (1) from the tubular system into the post-glomerular blood stream. Certain ions and small molecules can also be (2) from the post-glomerular blood into the tubules
- reabsorbed
2. secreted
The charge barrier is primarily the (1), which consists of (2) as well as (3)
- basement membrane
- Type IV collagen
- negatively charged glycosaminoglycans such as heparan sulfate.
This strong negative charge prevents negatively charged proteins like (1) from being filtered into the urinary space
- albumin
In constrast to the charge barrier, the size barrier is primarily determined by the (1), which have a complex structure of (2) which may represent an actual pore for entry of certain molecules
- epithelial podocytes
2. foot processes and a slit diaphragm
Specific mutations in genes whose gene products are components of the slit diaphragm (such as (1), can lead to (2), providing some evidence that the slit diaphragm has an important role in maintaining the filtration barrier.
- nephrin or podocin
2. proteinuria
(1) can also increase the size exclusion barrier by allowing some larger molecules to enter the urinary space
- Fenestrations in capillary endothelial cell cytoplasm
Although (1) may not directly contribute to the filtration barrier, they are very important supportive cells (2), which provide both mechanical support and key functions.
- mesangial cells
2. modified smooth muscle cells
The mesangial cells process (1) so they are important for elimination of immune damage. They also provide the (2) functions of the glomeruli and generate (3) and other modulators
- plasma proteins and immune complexes by endocytosis
- contractile
- cytokines
Immunological damage to the glomeruli can either produce predominantly (1) (nephrotic symptoms and signs) or predominantly (2) (nephritic symptoms and signs).
- protein loss
2. bleeding and more severe injury
Clinically, patients with heavy proteinuria have the (1) syndrome which consists of proteinuria (usually 3.5 grams of protein in a 24 hour urine collection), (2)
- nephrotic
2. hypoalbuminemia, edema, hyperliipidemia, and lipiduria
The proteinuria leads directly to the (1) because the kidney is excreting the protein from blood into urine.
- hypoalbuminemia or low serum albumin
The hypoalbuminemia causes (2) because of the decreased plasma oncotic pressure from decreased serum proteins.
- edema (fluid within tissues)
The hyperlipidemia occurs because the (1) produces more (2) in the generalized response to produce more (3).
- liver
- lipoproteins
- albumin
(1) happens because of the increased lipoproteins carrying lipid and because of loss of the filtration barrier.
- Lipiduria (lipid in urine)
There can be extensive (1) in patients without any histopathological changes that can be seen by light microscopy
- proteinuria
However, ultra-structural changes can be seen by electron microscopy generally show (1) in nephrotic syndrome.
- fusion of the epithelial podocyte foot processes
There also can be pathologic changes identified by immune microscopy which identifies whether certain (1) are present in the glomeruli.
- immunoglobulins or complement
Minimal change disease (also called (1) is the most common cause of nephrotic syndrome in children and also can cause nephrotic syndrome in adults. Children who do not develop any complications have a completely normal life span without any later renal disease.
- nil lesion
Examination of a renal biopsy by light microscopy in minimal change disease show no pathologic changes, but (1) can be identified by electron microscopy
- fusion of foot processes in visceral epithelial cells (podocytes)
The epithelial cells in minimal change disease can have some secondary changes such as (1) or the development of (2) on the cell surface
- retraction of the podocyte cytoplasm from the basement membrane
- microvilli
Although the cause of minimal change disease is unknown, it is thought to be the result of (1) occurring within the (2) and the symptoms are rapidly reversed by (3) treatment in children (although (3) can take longer to produce remissions in some adults who can have a more prolonged course).
- antigen-antibody reactions
- podocyte and the basement membrane
- steroid
(1) is a relatively more common cause of nephrotic syndrome in adults than it is in children
- Membranous nephropathy
Membranous nephropathy can be either primary (due to an unknown cause) or secondary from a disease which is producing (2) within the kidney
- antigens or immune complexes
Some of the secondary causes of secondary membranous nephropathy include inflammation disorders like (1)
- SLE, infections (hepatitis B is a classic example although others can as well), drugs, and neoplasms
There has been some controversy in the literature whether membranous nephropathy and other renal diseases which have immune complexes in the kidney are due to (1) or whether the antigen arrives first and the antibodies come later, producing (2) at the site in the kidney.
- circulating immune complexes (type 3 hypersensitivity)
2. immune complexes
Neoplasms can be a fairly common cause of (1) and should be considered in cancer patients with proteinuria
- membranous nephropathy
An experimental animal model called Heymann nephritis suggest that (1) are more often present first in the (2) or surrounding cells before the (3) arrive to form immune complexes.
- antigens
- basement membrane
- antibodies
Light microscopy can show (1) in membranous nephropathy (silver stains show (2) material so they can show immune complexes as areas where the silver stain is lost)
- thickened basement membranes
2. basement membrane
Electron microscopy of membranous nephropathy shows antigen-antibody complexes present in either the (1) or the subepithelial region between the (2)
- basement membrane
2. basement membrane and the podocyte
In (1), the immune complexes can be found in (2) as well, although this is usually not the case in primary membranous nephropathy.
- SLE
2. mesangial cells
The course of membranous nephropathy is variable, and spans from (1)
- resolution to end stage renal disease
Another fairly common cause of nephrotic syndrome is (1) but that will be discussed in the nephritic presentation since it can present either way
- focal segmental glomerulosclerosis (FSGS)
Immune microscopy in membranous nephropathy can show the presence of (1) antibody or (2) components including (3) and the components of the (4) which actually causes the injury
- IgG
- complement
- C3
- membrane attack complex (C5b, C6-C9)
parietal epithelium, situated on the ____, lines the ___, the
cavity in which plasma filtrate first collects
Bowman capsule; urinary space
Stain used to see the glomerular basement membrane (GBM)
Masson trichrome stain
In glomerulus, lumen refers to ____; bowman’s space is where the ___ is; aka Endothelial side: vascular
Epithelial (podocyte) side: urinary
Blood; urine;
Outer BM is covered by foot processes from the
podocyte lining ___
urinary space (Bowman’s)
The glomerular filter:
Molecules pass from capillary lumen to the _____;
Steps:
1. Cross ____ of the endothelial cell;
2. ____
(lamina rara interna, lamina densa, and lamina rara externa),
3. ____ connects podocyte foot processes
urinary space;
fenestrations
trilaminar basement membrane (BM);
Slit pore diaphragm
GBM predominantly of _____
2. Also laminin, fibronectin, and glycosaminoglycans.
Relative exclusion of negatively charged molecules such as albumin due to _____
type IV collagen;
polyanionic glycosaminoglycans, (heparan sulfate).
Glomerular endothelial cells are on the ___ side and _____ by numerous 60- to 100-nm pores
vascular; fenestrated
Podocytes: outer side GBM: cytoplasmic projections (foot processes) onto _____ of GBM
lamina rara externa
central electron-dense zone is ____
___ and ___ are inner and outer electron lucent zone;
Lamina densa of GBM;
Lamina rara interna
Lamina rara externa:
slit diaphragm of podocyte foot processes consist of ____; mutation would lead to ____
nephrin and podocin;
proteinuria
modified smooth muscle cells situated in
the center of the glomerular tuft between capillary loops
Mesangial cells
Mesangial cells
Endocytosis and processing of ___and ____
Generation of ____
plasma proteins; immune complexes;
prostaglandins and cytokines
How is edema caused in nephrotic syndrome: 2 causes
Dec. _____ due to loss of albumin;
- fluid escapes into tissues causing edema;
- Dec. onc. pressure leads to dec. ____ –> dec. ____ –> INC. _____–> fluid retention–> edema
Dec. plasma oncotic pressure due to loss of albumin; 1. fluid escapes into tissues causing edema; 2. Dec. onc. pressure leads to dec. plasma volume –> dec. GFR –> INC. aldosterone–> fluid retention–> edema
Min. change disease aka Nil
Occasional association with ___
and with ____ has led to the
speculation that it is a T lymphocytes disorder
Hodgkin disease; T cell lymphomas
Minimal change disease
Light microscopy:
EM:
Immunofluoresence for immunoglobulins (IF) and complement:
Light microscopy: Normal
Electron microscopy: diffuse obliteration of podocyte foot processes
IF–> negative
In intermediate disease stages, silver stains (which demonstrate basement membrane
material) reveal multiple projections or “spikes” on the epithelial surface of BM
Membranous nephropathy
Membranous nephropathy progression: capillary lumens narrow —–> glomerular sclerosis—> ___
tubular atrophy
and interstitial fibrosis (end stage kidney)
M embranous Nepropathy
Immunofluorescence microscopy reveals ____ staining of capillary walls for IgG and C3. There is intense staining for terminal complement components, including
the _____, which induces glomerular injury
diffuse granular; membrane attack complex;
Membranous glomerulopathy. Caused by the ____ accumulation of immune complexes and the accompanying changes in the ____.
subepithelial; basement membrane (BM)
Membranous glomerulopathy.
Stage I exhibits ____ deposits. The outer contour of the basement membrane remains smooth.
scattered subepithelial
Membranous glomerulopathy.
Stage II disease has ____of basement membrane material adjacent to the deposits
projections (spikes)
Membranous glomerulopathy.
In stage III disease, newly formed basement
membrane has surrounded the deposits.
With stage IV disease, the immunecomplex
deposits lose their electron density, resulting in an _____ with irregular electron-lucent areas.
irregularly thickened basement membrane
