Renal Pathology I Flashcards
The 2 most common causes of CRF/ERSD are…
- DM
2. HTN
Prototypical disease process of glomeruli is…
Glomerulonephritis
Prototypical disease process of tubules is…
Bence-Jones proteinuria
Prototypical disease process of interstitium is…
Fibrosis, inflammation or edema
Prototypical disease process of renal vessels is…
Vasculitis, nephrosclerosis
Definition of Azotemia
Biochemical abnormality resulting in elevated BUN and creatinine and is usually associated with decreased GFR
Azotemia is usually a result of renal disorders, but it can also be from pre-renal azotemia and post-renal azotemia, which are…
Pre-renal: occurs after hypoperfusion of kidneys (clood loss, CHF, etc.) and impairs renal function without damage to the renal parenchyma.
Post-renal: seen when whenever urine flow is obstructed. Removing the obstruction will relieve the azotemia.
Definition of Uremia
Azotemia in addition to clinical findings and biochemical abnormalities resulting from renal damage.
What makes a diagnosis of uremia difficult in kids?
The SX are often nonspecific and can become chronic and progressive due to gradual onset of disease.
What metabolic abnormalities may result from uremia?
Anemia
Acidemia
Electrolyte abnormalities
What happens to glycemic control for diabetics as renal function declines?
It improves generally, but they may have more hypoglycemic episodes. This is due to increased insulin secretion and prolongation of its half-life.
Fluid/electrolyte manifestations of uremia
Dehydration
Edema
Hyperkalemia
Metabolic acidosis
Ca++ and PO4- manifestations of uremia
Hyperphosphatemia
Hypocalcemia
Hematologic manifestations of uremia
Anemia
Cardiopulmonary manifestations of uremia
HTN CHF CM Pulmonary edema Pericarditis
GI manifestations of uremia
N/V
GI inflammation
Neuromuscular manifestations of uremia
Myopathy
Peripheral neuropathy
Encephalopathy
Derm manifestations of uremia
Pruritis
Normal GFR
Approx. 100 mL/min
Acute kidney injury (AKI)
Effects on GFR:
Urine production?
What causes it?
What is the progression?
Rapid decline in GFR
Severe forms show oliguria or anuria
May result from glomerular, interstitial, vascular or acute tubular injury
Can be reversible, or may progress to CKD
Chronic kidney disease (CKD)
Mild vs. severe forms:
How is it diagnosed?
What is the progression?
Mild - clinically silent, Severe - uremia
Persistent diminished GFR < 60 mL/min for at least 3 mo. OR persistent albuminemia
CKD is generally irreversible
End-stage renal disease (ESRD)
Effects on GFR:
It is the end-stage of…
GFR < 5% of normal
End stage of uremia
Which diseases/problems are primarily renal interstitial disease?
UTI
UT obstruction
Renal tumors
Nephrolithiasis
Definition of nephrotic syndrome
Glomerular disease characterized by:
Severe proteinuria (more than 3.5 gm/day)
Hypoalbuminemia (<3 gm/dL)
Severe edema
Hyperlipidemia
Lipiduria
What is the mechanism for the hyperlipidemia seen in nephrotic syndrome?
It is a compensatory mechanism from the liver in an effort to increase oncotic pressure, which was reduced due to the proteinuria. Fat can build up in the kidneys as well.
Definition of nephritic syndrome
Glomerular disease dominated by:
Acute onset of grossly visible hematuria
Mild-moderate proteinuria
HTN
*proteinuria and edema is common, but not as severe as nephrotic syndrome
Rapidly progressive glomerulonephritis (RPGN) definition
Signs of nephritic syndrome with rapid decline (days to weeks) in GFR.
Implies severe glomerular injury.
Major pathologic responses of the glomeruli to injury includes…
Hypercellularity: native, inflammatory, crescents
Basement membrane: thickening, deposits
Hyalinosis and sclerosis
Physiologic role of visceral epithelial cells
Provides a diffusion barrier to filtration of proteins and synthesizes GMB components
Prototypical localizations of immune complexes in the glomerulus: Acute glomerulonephritis
Subepithelial humps
Prototypical localizations of immune complexes in the glomerulus: Membranous nephropathy
Epimembranous deposits
Prototypical localizations of immune complexes in the glomerulus: Lupus nephritis, Membranoproliferative glomerulonephritis
Subendothelial deposits
Prototypical localizations of immune complexes in the glomerulus: IgA nephropathy
Mesangial deposits
Antibody-mediated injury to the glomeruli can be from __________ or __________.
Fixed intrinsic tissue Ags or Planted Ags
3 example diseases of fixed intrinsic tissue Ags and its associated Ag
Anti-GBM nephritis: NC1 domain of type IV collagen Ag
Membranous glomerulopathy: PLA2 receptor Ag
Mesangial Ags
What kinds of Ags can become “planted” in the glomerulus and cause an Ab-mediated injury?
Exogenous - DNA and tumor Ags
Exogenous - infectious products
3 immune mechanisms of glomerular injury
Ab-mediated injury
Cell-mediated immune injury
Activation of alternative complement pathway
Describe the following patterns of glomerular disorders:
Diffuse
Focal
Segmental
Global
Diffuse - all glomeruli involved
Focal - involves only a subset of glomeruli
Segmental - of affected glomeruli, only portions are involved
Global - involves entire glomerulus
The principal glomerular manifestation of progressive injury is…
It eventually leads to…
Focal segmental glomerulosclerosis, eventually leading to global glomerular involvement.
Progressive glomerular injury ensues from a…
Progressive glomerular injury is accompanied by…
Glomerular and nephron loss, compensatory changes that worsen the injury and eventually cause ESRD.
Accompanied by chronic injuries to other renal structures, usually manifesting as tubulointerstitial fibrosis.
The most common cause of nephritic syndrome is…
Immunologically mediated glomerular injury, characterized by proliferative effects and leukocyte infiltration.
2 major examples of nephritic syndrome
Acute post-infectious glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN)
Presentation of the nephritic patient includes…
Hematuria Red cell casts in urine Azotemia Oliguria Mild-mod. HTN
Basic pathological difference of nephritic and nephrotic syndromes
Nephritic - inflammation in the glomeruli
Nephrotic - problems with glomerular capillary walls leading to increase permeability to plasma proteins
Acute/Diffuse proliferative glomerulonephritis is caused by…
Immune complex injury resulting from an exogenous bacterial, fungal or viral infection .
Most commonly it is beta-hemolytic Strep.
Acute/Diffuse proliferative glomerulonephritis is characterized by…
- Marked hypercellularity - ranges from simple mesangial to complex endocapillary infiltrate
- Leukocyte infiltration - exudative within glomerular tuft
What is seen on electron microscopy in Acute/Diffuse prolferative glomerulonephritis?
Subepithelial “hump” of immune complex with neutrophils in the lumen
What is seen on immunofluorescence microscopy in Acute/Diffuse prolferative glomerulonephritis?
Granular deposits of IgG, IgM and C3 in the mesangium
Acute/Diffuse prolferative glomerulonephritis (post-streptococcal) clinical picture in kids:
Age?
When does it occur?
What toxin mediates it?
What is the presentation?
Ages 6-10.
Typically from 1-4 wks. following pharyngitis or skin infection.
SpeB (exotoxin B).
Malaise, fever, nausea, oliguria and hematuria for 1-2 wks. after recovery of sore throat.
Dysmorphic red cells, mild proteinuria, periorbital edema and mild/mod. HTN.
^^Nephritic syndrome^^
What is the clinical picture of Acute/Diffuse prolferative glomerulonephritis (post-streptococcal) in adults?
More atypical and aggressive.
May have sudden HTN or edema, often with elevated BUN.
Nephritic syndrome SX.
What is the clinical outcome for kids vs. adults in Acute/Diffuse prolferative glomerulonephritis (post-streptococcal)?
Kids: tends to clear in 6-8 wks., renal BX not usually indicated. 95% recover with conservative care.
Adults: only 60% recover completely.
RPGN - Crescentic Glomerulonephritis appearance on PAS (4)…
Collapsed, compacted glomerular tufts.
Crescent shaped mass of proliferative visceral and parietal epithelial cells.
Obliteration of urinary space.
Infiltration of Mo and leukocytes.
RPGN features on electron microscopy (2)…
Wrinkling of GBM
Fragmentation of GBM
Type I RPGN is…
Disease:
Anti-GBM antbody-mediated and renal limited.
Goodpasture syndrome
Type II RPGN is…
Diseases (3):
Immune complex, idiopathic, post-infectious GN.
Lupus nephritis
Henoch-Schonlein purpura
IgA nephropathy
Type III RPGN is…
Diseases (2):
Pauci-immune, ANCA-associated.
Granulomatosis w/ polyangiitis
Microscopic polyangiitis
Goodpasture syndrome is characterized by…
Effects elsewhere in the body…
High prevalence of patients with…
What unique measure is used as part of a treatment plan?
Linear deposits of IgG (sometimes C3) in the GBM, due to a response to non-collagenous regions on collagen type IV.
Cross-reaction w/ lung alveolus causing pulmonary hemorrhage in addition to renal disease.
Patients with certain HLA subtypes and haplotypes (HLA-DRB1) in RPGN patients (genetic predisposition to autoimmunity).
Plasmapheresis to remove circulating Abs.
4 diseases treated by plasmaphoresis
Goodpasture syndrome
Lupus (cerebritis)
Waldenstrom macroglobinemia
TTP
Type II RPGNs are characterized by (2)…
Cellular proliferation within glomerular tufts
Crescent formation
What is NOT seen in type III RPGN on immunofluorescence or electron microscopy?
No anti-GBM Abs or immune complexes on immunofluorescence or electron microscopy.
Which syndrome has a greater degree of edema?
Where does it start and progress?
Nephrotic syndrome.
Begins periorbitally and progress to generalized edema.
Nephrotic range proteinuria is…
Protein loss of > 3 gm/day
Most common cause of nephrotic syndrome in kids:
Minimal-change disease
Most common causes (2) of nephrotic syndrome in adults:
Focal segmental glomerulosclerosis
Membranous glomerulonephropathy
For most (95%) of kids with nephrotic syndrome, it is ascribable to…
Primary glomerular disease
60% of adults with nephrotic syndrome is due to…
But it is more commonly to be associated with __________ than kids.
Primary glomerular disease.
Associated with systemic disease.
What is the pathogenesis of nephrotic syndrome?
GBM becomes diffusely leaky to protein, especially albumin. It does not usually allow RBCs to transit into the urinary space.
Selective vs. non-selective protein loss
Selective is loss of albumin only.
Non-selective is loss of any proteins.
Primary renal disease vs. secondary renal disease
Primary - kidney pathology in absence of an associated systemic disease.
Secondary - systemic diseases causes renal disease (DM, SLE, etc.) with changes in renal histomorphology.
3 diseases associated with nephrotic syndrome (rarely exhibit hematuria)…
Minimal change disease
Membranous glomerulopathy
Focal segmental glomerulosclerosis
2 diseases “classes” associated with nephritic syndrome (more hematuria, less proteinuria)…
Acute proliferative glomerulonephritis
RPGN (types I,II,III)
2 most common causes of nephrotic syndrome in systemic diseases:
Other causes:
DM
SLE
Amyloid, drugs, infections, malignancies, etc.
Membranous glomerulonephropathy pathology
Approx. 75% due to: AI DZ linked to HLA alleles and Abs to autoAg PLA2 receptor with pathologic involvement of complement (MAC complex) and IgG4.
Remainder is due to drugs, SLE, malignancy, etc.
85% of patients with Membranous glomerulonephropathy have…
What info is vital to get before treating?
What kind of proteinuria is seen?
Nephrotic syndrome manifestations
If there is a systemic component or if it is primary
Nonselective proteinuria
Primary membranous glomerulonephropathy patients respond poorly to…
There is a high reoccurance in…
Respond poorly to steroid therapy.
High reoccurence in transplant pts. (40%).
Women may have more benign course.
Features seen on PAS in membranous glomerulonephropathy include (3)…
- Thickening of capillary walls without increase of cellularity.
- “Spikes” of silver-staining matrix from BM toward urinary space from deposits of IgG.
- Effaced foot processes.
Clinical course of membranous glomerulopathy
Which treatment is NOT effective generally?
Proteinuria persists in 60% of pts., with 40% of them developing renal insufficiency.
10% progress to ESRF.
Corticosteroids are generally not effective.
Presenting clinical sign of MCD
What treatment is highly efficacious?
Edema in child from 2-6 y/o with nephrotic syndrome SX.
90% of kids with MCD respond well to corticosteroid therapy.
MCD has been associated with…
Hodgkin lymphoma
What kind of proteinuria is seen in MCD?
Highly selective proteinuria
What is the postulated pathogenesis of MCD?
Abs against epithelial cell Ags, toxins, cytokines, etc. cause injury resulting in foot process effacement (fusion). These cells can detach and lead to significant protein leakage thru the GBM.
Focal segmental glomerulosclerosis (FSGS) is generally a _____ disease.
It is an adaptive response to…
Inheritance of genes that have what function can cause FSGS?
Primary/idiopathic
Adaptive response to loss of renal mass
Genes that encode proteins localized to the podocyte slit diaphragms
FSGS accounts for what percent of adults and kids with nephrotic syndrome?
Which races have a higher incidence?
Adults - 35% (most common cause of NS in adults in USA)
Kids - 10%
Hispanics and AAs
Prognosis of FSGS if it occurs in other diseases is…
20% of pts. with FSGS follow an…
A DX with a poor prognosis and will lead to progressive renal disease over time.
20% follow an unusually rapid course w/ massive proteinuria and RF within 2 yrs.
How does idiopathic FSGS differ from MCD (and other podocytopathies)? (4)
- More hematuria, reduced GFR and HTN
- Nonselective proteinuria
- Poorer response to steroid therapy
- Significant progression to CKD with at least 50% developing ESRD within 10 yrs.
What kind of syndrome (nephritic/nephrotic) is associated with FSGS?
Can be mixed
What is HIV-associated nephropathy?
FSGS caused by HIV, more commonly in AAs than Caucasians.
Membranoproliferative glomerulonephritis (MPGN) ahs what common presentation?
Combined proteinuria and hematuria
Major histologic findings in MPGN are (3)…
Alterations in GBM
Proliferation of glomerular cells, usually in mesangium
Leukocyte infiltration
Primary Type I MPGN most commonly presents in…
Common presentation:
50% of pts. develop…
Mostly kids and young adults, but can be all ages.
Nephrotic syndrome is common presentation.
CRF over a 10 yr. span.
Secondary Type I MPGN most commonly presents in…
Frequently associated with…
It is seen as a reflection of glomerular disease in patients with (3)…
Prognosis:
Exclusively adults
Chronic antigenemia causing immune complex deposition
Hep C, chronic immune complex disorders (SLE, endocarditis, etc.). and certain malignancies
Same as primary type I MPGN (CRF over a 10 yr. span)
MPGN type II “dense deposit disease” occurs only as…
What is the dominant clinical finding?
Prognosis?
When does occurrence of MGPN II happen frequently?
A primary renal disease in kids (no secondary forms in kids or adults)
Hematuria, 50% have nephritic syndrome
Poorer prognosis due to more severe renal disease
Post kidney transplant
What is the pathogenesis of MPGN II?
C3NeF (nephritic factor) - IgG autoAb that binds C3 convertase causing continuous activation of alternatice complement pathway
IgA nephropathy is the most common type of…
Glomerulonephritis worldwide
Where do IgA deposits occur?
Mesangium
2 eponymic diseases associated with IgA nephropathy
Berger DZ - no systemic DZ
Henoch-Schonlein purpura (HSP) - systemic DZ, with purpura and involvement of the abdominal viscera
Who most often gets IgA nephropathy?
What races are at a greater risk?
Family Hx?
Mostly a DZ of young adults, mostly in 2nd and 3rd decades, but can occur in older pts.
Caucasians and Asians, less in AAs.
Often a 1st degree relative w/ a Hx of the DZ.
What is coincident with the hematuria seen in IgA nephropathy?
Coincdient w/ presence of significant infection (URI, GI, abscess, etc.) and recurrence of infection at same site leads to a flare up.
2 known associations with IgA nephropathy include…
Gluten enteropathy
Liver DZ
Clinical outcomes of igA nephropathy
Recurrent episodes of hematuria without progression of renal DZ in most pts.
CRF occurs in 15-40% as a slowly progressing DZ over 20 yr. period.
Acute nephritic syndrome w/ HTN in 5-10%
Stain for chronic glomerulonephritis
Trichrome stain
