Robbins, Chapter 20, The Kidney Flashcards
Azotemia definition.
Its extra-renal sources (2)
Biochemical abnormality indicating an elevation of blood urea nitrogen (BUN) and serum creatinine levels.
- Prerenal Azotemia
- Postrenal Azotemia
Azotemia associated with increased or decreased GFR?
Decreased
What is prerenal azotemia? Is there parenchymal damage?
Prerenal azotemia occurs after what state of kidney perfusion?
Occurs after HYPOPERFUSION of kidneys in the ABSENCE of parenchymal damage.
**The prostatic hyperplasia could lead to obstructive uropathy with bilateral hydronephrosis, renal cortical atrophy, and eventual chronic renal failure.
Examples of what causes prerenal azotemia.
Due to HEMORRHAGE, SHOCK, VOLUME DEPLETION, CHF.
When is postrenal azotemia seen?
When urine outflow is obstructed distal to calyces and renal pelvis.
What corrects postrenal azotemia?
Removal of obstruction.
What is it called when azotemia becomes associated with a constellation of clinical signs and symptoms and biochemical abnormalities?
Uremia
What are common secondary manifestations that characterize uremia (3)?
GI - uremic gastroenteritis
Peripheral nerves - peripheral neuropathy
Heart - uremic fibrinous pericarditis
Nephritic Syndrome due to?
How do these patients present? (i.e. sick or non-sick)
Associated with what clinical manifestations?
Most common cause?
-Caused by glomerular disease»_space; ACUTE GLOMERULONEPHRITIS.
-Present as sick with acute onset of HEMATURIA, azotemia, oliguria with azotemia, proteinuria, HTN, possible fever
also - with dysmorphic red cells and red casts, mild to moderate proteinuria
-Commonly caused by immunologically mediated glom injury
Nephrotic Syndrome due to?
How do patients present? (i.e. sick or non-sick)
Associated with what clinical?
-Caused by glom disease.
-Present not as sick as nephritic patients.
Characterized by heavy proteinuria of more than 3.5g/day
also - hypoalbuminemia, hyperlipidemia, lipiduria, edema
What is heavy proteinuria level?
More than 3.5g/day
Acute glomerular response to injury
HYPERCELLULARITY with proliferation of mesangial and/or endothelial cells, influx of leukocytes, formation of CRESCENTS
Chronic glomerular response to injury
Basement membrane thickening
Hyalinosis and sclerosis
Diffuse primary glomerulonephropathy
Focal primary glomerulonephropathy
Diffuse - Involve all of a kidney’s gloms, in their entirety.
Focal - Involves a subset of the gloms in the kidney
Global primary glomerulonephropathy
Segmental primary glomerulonephropathy
Global - Involves all of an individual glom.
Segmental - Only a portion of the affected gloms are involved.
Capillary loop or mesangial primary glomerulonephropathy
Affecting predominanty capillary or mesangial regions.
What mechanism underlies most primary glomerulopathy and secondary glomerular disorders?
Immune!
ESRD has GFR of what?
less than 5% of normal
What type of syndrome with clinical manifestations of:
Glomerular syndrome.
Acute nephritic, proteinuria, acute renal failure
Rapidly Progressive Glomerulonephritis (RPGN)
Chronic Renal Failure:
What type of syndrome?
What clinical manifestations?
Time frame.
Glomerular syndrome.
Azotemia, progressing to uremia for months to years.
Isolated Urinary Abnormalities
Glomerular (micro) hematuria and/or subnephrotic proteinuria
Response of glom to injury (3).
Hypercellularity (severe = crescents), BM thickening, hyalinosis and sclerosis
A SUBEPITHELIAL HUMP is found in the glom - what is it indicative of?
Acute glomerulonephritis
An EPIMEMBRANOUS DEPOSIT is found in the glom - what is it indicative of?
Membranous nephropathy or Heymann glomerulonephritis
A SUBENDOTHELIAL DEPOSIT is found in the glom - what is it indicative of?
Lupus nephritis
Membranoproliferative glomerulonephritis
MESANGIAL DEPOSITS are found in the glom - what is it indicative of?
IgA nephropathy
Most common form of antibody mediated glomerulonephritis is caused by what two types of immune complex formation?
What pattern of deposition is seen upon immunofluorescence?
Formation of immune complexes:
- Endogenous antigens - PLA2R in membranous nephropathy
- Exogenous antigens - microbial.
GRANULAR pattern.
Anti-GBM antibody mediated disease PATTERN OF DEPOSITION seen upon immunofluorescent staining.
Where is the deposition in the glom?
LINEAR pattern.
In Situ deposits on the BM.
Heymann glomerulonphritis deposition is where in the glom?
In Situ deposition on foot processes
FSGS and tubulointerstitial fibrosis are two major histological features of what?
PROGRESSIVE renal damage
What is the principal glomerular manifestation of progressive renal injury? What does it eventually lead to?
Focal Segmental GlomerularSclerosis
Leads to global glomerular involvement and glomerular obsolescence. »_space;» ESRD
What accompanies progressive glom injury (FSGS) in other renal structures?
tubulointerstitial fibrosis
What am I?
Diffuse proliferation of glomerular cells with presence of leukocytes.
Acute Proliferative Glomerulonephritis/Post Strep Glomerulonephritis
What am I?
Bug - post-strep A beta-hemolytic Strep, 1-4 weeks after
Antibody forms against M protein Antigen (**ASO titer elevated).
Immune response results in ACUTE NEPHRITIC SYNDROME.
Type III hypersensitivity
Acute Proliferative Glomerulonephritis/Post Strep Glomerulonephritis
What am I? LM - Gloms are enlarged and HYPERCELLULAR, tubules contain RED CELL CASTS IF - GRANULAR deposits of IgM, IgG, C3 EM - "lumpy bumpy" on subepithelial side NEUTS in lumen
Acute Proliferative Glomerulonephritis/Post Strep Glomerulonephritis
What am I and how do you treat?
A young child, 6-10 yo with malaise, fever, nausea, HEMATURIA, periorital edema. Possible facial rash.
1-2 weeks after pharyngeal and/or cutaneous infection. Elevated ASO titer.
Acute Proliferative Glomerulonephritis/Post Strep Glomerulonephritis.
Treat with fluid/electroyte therapy and 95% recover well. 1% develop RPGN
What infections other than group A strep can induce Acute Proliferative Glomerulonephritis?
bacterial (strep pneumo), Viral (Hep B, Hep C, HIV), Parasitic (toxo, malaria)
How does the course of Acute Proliferative Glomerulonephritis differ in ADULTS v. CHILDREN? What may ADULTS (not children) progress to?
Treatment of children?
95% of children recover completely. Adults have more aggressive and atypical - only 60% recover completely. ADULTS may progress to RPGN II
Children - treat with fluid/electrolyte therapy
What am I?
Nephritic Syndrome
Severe glomerular injury associate with formation of crescents in most glom and not necessarily associated with one syndrome.
Rapidly Progressive Glomerulonephritis: Definition
RPGN: Pathogenesis - types (3) and each type’s immunological findings. Which is most common? Which is primary?
Type 1 - anti-GBM (Goodpastures, anti-collagen type 4)
Type 2 - Immune Complex (postinfectious, SLE, Henloch-Schloen)
Most common and PRIMARY: TYPE 3 - Pauci Immune (associated with p- or c-ANCA; Wegner’s)
What am I?
Histo - CRESCENTS within BOWMAN’S SPACE
EM - wrinkled and ruptured BM
Immunofluorescence: T1 = LINEAR IgG, T2 = Granular T3 = no anti-GMB ab or immune complexes but have circulating ANCA Gross - enlarged, pale kidneys
RPGN
What am I? and what tx? What is the prognosis
Present with hematuria, red cell casts, and proteinuria approaching nephrotic ranges, possible HTN and edema. (1) anti-GBM and recurrent hemoptysis (2) immune complex (3) ANCA
RPGN
(1) Goodpastures, Type I Cresentic
(2) SLE, HSP, post infectious
(3) Idiopathic RPGN, Type III Cresentic
Treatment - (1) = plasmapheresis; Type 2, 3=does not respond to plasmapheresis - use anti inflammatory
Prognosis - not good
RPGN I patients found to have HLA subtypes have higher prevalence of what? And recurrent hemoptysis. Rapid progression to renal failure.
Goodpastures
What is the primary renal disease where IgA deposits are found in the mesangium detected by immunofluorescence?
IgA nephropathy
What is the difference between a primary renal disease v. secondary? More frequent in children or adults?
Primary - only kidney affected, no systemic disease. Most common cause of nephrotic syndrome in children.
Secondary - systemic disease that CAUSE renal/nephrotic diseaes (like DM or SLE). Secondary causes of nephritic syndrome more frequent in adults (about 40% of cases)
Nephrotic Syndrome - what causes it, what leaks, what happens to colloid pressure, what are the clinical manifestations?
Initial event causes DERANGEMENT OF GLOMERULAR CAPILLARIES with increased permeability to protein, PROTEINURIA results»_space; hypoalbuminuria and decreased colloid pressure
EDEMA (periorbital and peripheral)
HYPERLIPIDEMIA
Membranous Glomerulopathy - nephritic or nephrotic and in what % of people with membranous glom?
What % are primary and more common in adults of kids?
What genetics - alleles and antibodies are involved?
Nephrotic - 85%
75% primary - most common cause of nephrotic syndrome in adults
HLA alleles and antibodies to renal autoantigen PLA2 receptor with roles for complement (primarily MAC and IgG4
Does Primary Membranous Glomerulopathy respond well to corticosteroid treatment?
Does Secondary MG (secondary to autoimmune disease)?
No
Possibly
What is this the definition of?
Diffuse thickening of glom capillary wall with accumulation of electron dense immunoglobulins with deposits on subepithelial side of BM. Effaced food processes.
Definition of Membranous Glomerulopathy
What has a pathogenesis of chronic immune complex deposition? Most common in adults.
Associated with antibody mediated (THYROIDITIS), penicillamine, lupus, HEPATITIS B/C, gold/mercury, schisto.
Membranous Glomerulopathy
What has:
LM - uniform diffuse THICKENING of BM with thick CAPILLARY LOOPS
EM - dense deposits of IgG in subEPITHELIAL, forming “SPIKES” which form DOMES
IF - GRANULAR IgG and C3
-Effaced Foot processes
membranous glomerulopathy
Is proteinuria selective or non selective in Membranous Glomerulopathy? And it persists in what percentage of patients?
Prognosis: % develop renal insufficiency, % progress to ESRF
Non-selective (large and small proteins). Persists in 60% of patients.
40% renal insuff
10% ESRF
MCD Age range Onset (follows what?) Presenting clinical sign The only thing seen on biopsy
KIDS! 2-6yo
Follows a respiratory infection
Edema
Biopsy - Foot Process Fusion. All other normal LM glom.
Is MCD effectively treated by corticosteroids?
Yes
MCD is associated with what type of cancer?
Hodgkins lymphoma
MCD has what type of proteinuria?
SELECTIVE
MCD has was type of prognosis?
Excellent
Massive proteinuria despite preservation of renal function without hematuria or HTN.
LM and IF = SEE NOTHING
EM = see PODOCYTE FUSION/EFFACEMENT
Clinical course of MCD and findings
What am I?
Sclerosis of some, but not all glomeruli.
Affecting only part of each affected glomeruli.
With nephrotic syndrome.
Adults, even with steroids have a poor prognosis.
Also associated with African-Americans, loss of renal tissue, sickle cell, heroin, AIDS, obesity
Focal Segmental GomeruloSclerosis
Does FSGS respond to corticosteroids?
Does it remit spontaneously?
No
No
Does primary FSGS primarily affect adults or children?
Do children or adults have better prognosis?
What two races have greatest incidence?
Adults (35% of those with Nephrotic Syndrome) > Children (10% of those with Nephrotic Syndrome
Children
Hispanics and Blacks
APOL1 on ch22 strongly associated with resistance to trypanosome infection - associated with what race and increased incidence of what nephrotic syndrome?
Those of African descent.
FSGS
FSGS or MCD?
- Higher incidence of hematuria, reduced GFR, HTN
- Nonselective proteinuria
- Poor response to corticosteroids
- Progression of CKD, at least 50% developing ESRD within 10 years
FSGS
What infection is associated with the collapsing variant of FSGS? What does this mean?
How does this differ from idiopathic FSGS?
HIV associated, esp in African Americans. Complete glom collapse.
EM - This type has large presence of tubuloretucular inclusions within endothelial cells.
NPGS1, NPGS2, TPRC6, alpha-actinin 4 mutations localize to where? what does PPGS2 result in?
Podocyte slit diaphragms.
NPGS’s code for nephrin. NPGS2 results in nephrotic syndrome in children.
What am I?
LM = parts of some glom are eosinophilic(pink) with sclerosis.
EM = effacement of podocytes, as in MCD
IF = IgM and C3 in sclerotic areas
Glomerulosclerosis and increased matrix synthesis are due to genetic defects or circulating cytokines of the slit diaphragm.
FSGS
An adaptive response to loss of renal mass. What is progressive FSGS called - it occurs after removal of diseased or healthy nephrotic segment caused by hypertrophy of remaining segment.
Renal Ablation FSGS
Is Membranoproliferative GN nephrotic or nephritic?
Mixed
What is the difference between type I and type II MPGN?
I=immune complex deposition and activation IgG and complement
II=DDD, a C3 glomerulopathy - autoantibody: alternative complement pathway
If C3 is low in serum, what GN is it? The ONLY glomerular disease with changed serum complement.
MPGN
What am I?
LM=TRAM-TRACK appearance of glom BM
EM=nonspecific, type II has dense deposits
IF = granular C3 pattern
MPGN
What MPGN type has a circulating (C3NeF) C3 NEPHRITIC FACTOR? What does this bind to and what does it do?
MPGN II. IgG autoantibody that binds to the alternative pathway C3 convertase and leads to continuous activation of the pathway» C3 will be low!
What am I?
Basement membrane thickening, increased mesangial matrix, accentuation of lobular architecture, influx of neuts, mesangial cell proliferation.
MPGN
What is “tram-track” in MPGN I and II?
mesangial proliferation and inrceased mesangial matrix that may dissect and split the glom BM
What am I?
Normally in children, with nephrotic syndrome presentation. Microscopic hematuria, with additional nephritic features (HTN, oliguria, edema, renal insufficiency).
50% develop chronic renal failure over 10 years
Tx with steroids is NOT beneficial.
MPGN I, Primary
What else does MPGN Type I resemble with slow progression, crescents, and unremitting course?
RPGN
What am I?
Exclusively adults. Chronic antigenemia association.
Also associated with: Hep C with CRYOGLOBULINEMIA, SLE, hep B, chronic visceral abscesses, HIV, schisto, malignancies (CLL, lymphoma, melanoma).
Dismal prognosis.
MPGN I, Secondary
Although mixed, which MPGN has hematuria as a more dominant clinical finding?
Although mixed, which MPGN has proteinuria as a more dominant clinical finding?
Hematuria in virtually ALL - MPGN II
Proteinuria - MPGN I
Does MPGN I or II have a poorer prognosis/mroe severe renal disease?
Which has a more frequent recurrence following renal transplant?
What has extremely dense deposits?
MPGN II
IgA Nephropathy - nephritic or nephrotic?
nephritic
What am I? LM= MESANGIAL proliferation/WIDENING EM=nonsepcific IF=GRANULAR IgA in mesangium Which MUST be used to diagnose?
IgA nephropathy
IF
What is the most common cause of glomerulonephritis worldwide?
IgA Nephropathy
What do Berger Disease and Henoch Schonlein purpura have in common (immunologically)?
What makes them different?
both are IgA nephropathies
Bergr is a renal localized IgA neph
HSP is a systemic disease, associated with systemic vasculitis
What am I?
Most common nephropathy world wide. Fairly benign/PAINLESS, BRIGHT RED BLEEDING in urine, follows an URI, GI infection, or UTI. RECURRENT episodes of hematuria without progression of renal disease in majority of patients, but CRF in 15-40% as a slowly progressive disease over 20 years (benign, but can progress to renal failure)
IgA nephropathy
What is IgA nephropathy?
primary or secondary, what deposits, detected by what?
Primary renal disease where IgA deposits in mesangium, detected by immunofluorescnence.
What am I?
Most common in children and YA (2nd-3rd decades). Caucasians and Asians, Males>Females. 1st degree relative family hx. Known association with celiac’s/GLUTEN ENTEROPATHY and LIVER DISEASE.
IgA Nephropathy
These lead to what? 90% RPGN (crescentic) 50-80% FSGS 50% MPGN 30-50% IgAN, Membranous nephropathy 1-2% post strep GN
Chronic glomerulonephritis
What is the endpoint of all nephrotic and nephritic syndromes?
Chronic glomerulonephritis
What is characterized by EXTENSIVE HYALINIZATION and FIBROSIS of glom (lg amt of collagen on trichrome stain)?
Kidneys have diffiselu granular surfaces and thinned cortex. Glom completely effaced by hyalinized CT, marked tubular atrophy. Possible changes due to dialysis.
Chronic glomerulonephritis
In chronic glomerulonephritis, HTN is often comcomitant with CRF, so what is often present as well?
arteriole sclerosis
What does CRF inevitably lead to?
UREMIA (pericarditis, uremic gastroenteritis, secondary hyperPTH with nephrocalcinosis and renal osteodystrophy)
with HTN, edema, dialysis, death
