Disorders Of Glomerular Function 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
Hyperlipidemia
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
Hematuria
Proteinuria (<3.5g/dL)
Azotemia
Hypertension
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
Symptoms
- 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
Alport syndrome pathogenesis
Manifestations are due to mutations in one of the collagen type 4 genes seen on chromosome 2 or 13
- there are more than 500 different mutations
Always results in defective ensemble and shows loose poorly defined collagen type 4
- defects in GBM, lenses and the cochlea are seen because of this
Shows really irregular basement membranes in GBM (basket-weave appearance)
Thin basement membrane disease
Benign familial hematuria
Very common hereditary issue that presents with asymptomatic hematuria
- can show proteinuria also but renal function is not affected and prognosis is excellent
Shows diffuse thinking of the GBM (150-225nm)
pathology of thin basement membrane disease
Mutations in a3/a4 chains of type 4 collagen
Almost always autosomal inheritance and familial heterozygous is most commonly seen
Rapidly progressing glomerulonephritis
Crescentic glomerulonephritis
always shows crescentic glomerulonephritis
Characterized by rapid loss of renal function, severe oligouria, azotemia and nephritic syndrome
- if untreated rapidly presents to renal failure
- prognosis is based on fraction of involved glomeruli (<80% = good prognosis)
Is associated with:
- good posture syndrome type-1
- immune complex mediated type-2 (IgA nephropathy, poststrep GN, henoch-Schonlein purpura, etc.)
- pauci-immune type-3 (ANCA disorders, idiopathic, Wegener, microscopic polyangitis )
Goodpasture syndrome
Linear deposits of IgG/C3 complexes and development of anti-GBM antibodies
- develops pulmonary hemorrhages w/ hemoptysis and renal failure overtime
Requires plasmapheresis to cure
Chronic glomerulonephritis
End-stage glomerular disease that has a variety of features and reasons it develops
Shows diffuse scarring of glomeruli that stains blue and/or acellular eosinophilic masses on H and E sections
Symptoms:
- proteinuria
- HTN
- azotemia
- non specific symptoms: anemia/vomiting/fatigue
- edema
MUST receive wither dialysis or renal transplant or the patient will die
What are the 6 patterns of glomerular disease seen in SLE?
Class 1 = minimal mesangial lupus nephritis
- least common pattern
Class 2 = mesangial proliferative lupus nephritis
Class 3 = focal lupus nephritis
- ** <50% of glomeruli are in involved
- mild hematuria and proteinuria with red blood cell casts
- often progresses to diffuse without treatment
Class 4 = diffuse lupus nephritis
- most common pattern
- also most severe other than class 6
- > 50% of glomeruli affected
Class 5 = membranous lupus nephritis
- idiopathic immune complexes forms
Class 6 = advanced sclerosing lupus nephritis
- **90% of more glomeruli are sclerotic and begins end stage renal failure
Diabetes mellitus
Group of metabolic disorders that all share hyperglycemia as an effect
- can be defects in insulin secretion ro inability to respond to insulin
Secondary damage is seen in the following organs:
- kidneys
- eyes
- nerves
- blood vessels
is the leading cause of end-stage renal disease, adult-onset blindness and atraumatic lower extremity amputations
What are the 3 lesions in kidneys affected by diabetes nephropathy
1) glomerular lesions
- most important is capillary basement membrane thickening
2) renal vascular lesions via arteriolosclerosis
3) pyelonephritis/ necrotizing papillitis
Diabetes mellitus pathology related to kidney
if glomerulosclerosis is present, often develop nephrotic syndrome
Pathology = almost always shows diffuse GBM thickening and Nodular glomerulosclerosis (kimmelstiel-Wilson lesion)
- both result in scarring of kidneys and ischemia of the kidneys
