Disorders Of Glomerular Function Flashcards Preview

Renal Course > Disorders Of Glomerular Function > Flashcards

Flashcards in Disorders Of Glomerular Function Deck (40)
Loading flashcards...

Azotemia definition

Elevation of BUN and creatinine levels in blood

**Almost always means decreased GFR**


Prerenal vs postrenal azotemia

Prerenal = usually means hypoperfusion of the kidneys due to reduced ECF (ischemia)

Postrenal = urine outflow is obstructed


Uremia definition

Azotemia + clincial manifestations and biochemical abnormalities
- includes but not limited to: dehydration, edema, metabolic acidosis, anemia, HTN, CHF, N/V, myopathy, bleeding, esophagitis, puritis /dermatitis

**failure of renewal excretory function and metabolic functions**


Classic presentation of nephrotic syndrome

Proteinuria (>3.5g daily protein loss)

Hypoalbuminemia (<3g/dL)

Generalized edema


**numerous causes but all share in a derangement in capillary walls of the glomeruli that results in increased permeability to proteins**


Why does nephrotic syndrome sometimes lead to anasarca (generalized widespread edema)?

Decreased intravascular volume causes renin release in JG cells and triggers the RAAS pathway.
- RAAS pathway results in salt and water retention

Also long standing proteinuria eventually leads to hypoalbuminemia which secondarily casues water to move out of extracellular fluid and into interstitial space = edema/anasarca


Nephritic syndrome classic presentation


Proteinuria (<3.5g/dL)



**may present with or without edema**

***caused by inflammatory lesions of glomeruli which leads to infiltration of leukocytes into the glomerulus. This inflammation allows RBCs to pass through the glomerulus and reduce GFR***


Why does nephritic syndrome show HTN?

A combo of fluid retention and RAAS pathway activation


Rapidly progressing glomerulonephritis

Rapid loss of renal function within a few days- 2 weeks
- almost always accompanied by nephritic syndrome and is not a specific etiology itself.

*histology shows crescentic Glomerulonephritis*

**causes renal failure within months if not treated**


Chronic kidney disease

Results form any process that induces progressive scarring of the kidney

Almost always presents with
- hyperphosphatemia
- dyslipidemia
- metabolic acidosis
- uremia


What two mechanisms of antibody deposition in the glomerulus is known to occur?

1) deposition of circulating Ag-Ab complexes in the glomerular capillary wall

2) antibodies reacting in situ within the glomerulus either with themselves of other extrinsic molecules
- endogenous = SLE
(Shows linear pattern of staining in IF microscopy of the GBM)

- exogenous = Hep B/parasites, spirochete infections
(Shows granular pattern of staining in IF microscopy of the GB)


Mediating immune pathway to glomerular injury

complement activation and recruitment of leukocytes
- complement is activated via the classical pathway and leads to generation of chemotactic agents (C5a) for neutrophils and monocytes


Does primary or secondary glomerular diseases more often cause nephrotic syndrome?

Children = primary

Adults = secondary


Minimal-change disease

Is the most frequent cause of nephrotic syndrome in children
- especially in ages 1-7yrs

**Shows glomeruli that have a normal apperance by light microscopy with only diffuse effacement of the foot processes of the podocytes**

Is relatively benign outside of clinical manifestations of nephrotic syndrome and easily treatable


Minimal change disease treatment and clincial features

Usually only shows selective proteinuria for albumin with abrupt nephrotic syndrome
- NO HTN and decreased renal function

90% if children respond to short course of corticosteroid therapy
- 66% however show recurrence of proteinuria

5% develop CKD after 25 years (believed to be due to hidden underlying focal segmental glomerulosclerosis

**adults respond also to steroids but response is slower and relapses are more common**


Focal segmental glomerulosclerosis (FSGS)

Sclerosis of some but not all glomeruli that involves only a part of each affected glomerulus

Can be primary or secondary
- primary = HIV infections, heroin abuse, IgA nephropathy, inherited disorders

*is the most common primary cause of nephrotic syndrome in adults (35%)*

**is believed that minimal-charge disease can transform into FSGS overtime, but both are still independent entities**


FSGS clinical course and treatment

FSGS and minimal change disease look very identical
- HOWEVER, FSGS has high hematuria and HTN rates with non selective proteinuria

Responds poor to corticosteroid therapy

50% of patients with FSGS develop end-stage renal disease


Membranous nephropathy

Subepithelial immunoglobulin containing deposits along the glomerular basement membrane

Light microscopy shows diffuse thickening of the capillary wall with deposits

**only really shows up in adults between ages 30-60**

***80% of cases are primary and caused by auto-antibodies against podocyte antigens***
- other 20% are secondary to infections, autoimmune diseases, exposure to inorganic salts and medications


Pathogenesis of membranous nephropathy

Chronic immune complex glomerulonephritis induced by antibodies reacting in situ
- most frequent one is podocyte antigen phospholipase A2 receptor

Immune complex leads to spontaneous MAC compliment formation and causes podocyte injury with non selective proteinuria


Membranous nephropathy morphology

Diffuse thickening of the capillary walls with subepithelial deposits in the GBM with spike like protrusions
- forms a “spike and dome” pattern


Membranous nephropathy clincial features

Sudden onset full-blown nephrotic syndrome
- nonselctive proteinuria that is less then 3.5 g/dL

Falls steroid therapy almost always and usually requires treatment of the secondary cause ( if present)


Membranoproliferative glomerulonephritis (MPGN)

Alterations in the GBM and proliferation of the actual glomeruli cells
- accounts for 10% of all nephrotic syndrome cases
- can show non-nephrotic proteinuria or a combined nephrotic-nephritic symptoms

**there are two types, with MPGN type 1 being far more common (80%)**
- type 1 = idiopathic immune complex deposition with unknown antigen

Poor prognosis with 50% of cases a showing nephrotic syndrome


C3 glomerulopathy

Encompasses two conditions, dense deposit disease and C3 glomerulonephritis

Super rare and only differs based on electron microscopy

Can show nephrotic or nephritic syndrome and varying levels of protienuria

Both has very poor prognosis with post-translation rates of up to 85%


Pathogenesis of C3 glomerulopathy

Acquired or hereditary abnormalities of the alternative pathway of complement activation is the cause of both dense deposit disease and C3 glomerulonephritis

**most patients present with an autoantibody against C3 convertase (C3NeF). This causes uncontrolled cleavage of C3 and activation of the alternative complement pathway**


Acute postinfectious glomerulonephritis

Caused by glomerular deposition of immune complexes after an infection. Develops linear IgG and complement immune complexes and damages cells in the glomerulus
- most common is streptococcal species (usually have to be B-hemolytic)
- others include: pneumococcal, mumps/measles/hep B/C

Typical case develops 1-4 weeks after recovering from a group A streptococcal infection


Clincial presentation of acute postinfectious glomerulonephritis

Acute nephritic syndrome is most common
- presents with red cell casts
- mild proteinuria (<1 gm/day)
- low serum compliment levels

- malaise
- fever
- nausea
- oligouria
- hematuria (“cola colored urine”)
- periorbital edema
- mild HTN

**also shows elevated anti-steptolysin O antibodies**


IgA nephropathy

**most common cause of recurrent microscopy or gross hematuria**
- most common glomerular disease revealed in renal biopsy worldwide

Usually affects children and young adults after a nonspecific upper-respiratory tract infection
- begins 1-2 days after the upper-respiratory infection as a episode of gross hematuria
- usually goes away after several days but can recur periodically in the setting of a viral infection

***all mark is deposition of IgA in the mesangium only, henoch-Schonlein purpura is systemic IgA deposition ***


Pathology of IgA nephropathy

Abnormally Glycosylated IgA1 immunoglobulin Elicits autoimmune responses to self cells and forms large immune complexes with circulating IgA

**the presence of C3 complement and the absence of C1q/C4 complement in IgA nephropathy signifies this is a alternative complement pathway**


Clincial features of IgA nephropathy

Gross hematuria after unspecified upper respiratory infection
- sometimes can be UTI or GI infection. But it’s rare

Symptoms: (highly variable amoung patients)
- flank pain
- mild proteinuria
- red blood cell casts


Hereditary nephritis

A group of glomerular diseases caused by mutations in the BGM proteins

Contains alport syndrome and thin basement membrane disease

Most of them affect type 4 collagen


Alport syndrome

When fully developed, shows grooms hematuria with red blood cell casts and progression to chronic renal failure
- also shows deafness and sight disorders (lens dislocation, cataracts, etc.)
- symptoms start to appear at 5-20yrs of age

Is an X-linked disease
- males almost always express fully developed, where as females usually just present with hematuria

**90% of males progress to end stage renal disease before 40 yrs**