Nephritis Flashcards
Glomerulonephritis (GN) presents with more (1) symptoms and findings (nephritic presentation) than the (2) and associated findings in nephrotic syndrome.
- inflammatory
2. proteinuria
The major pathologic finding in glomerulonephritis is the presence of (1) and (2), which leads to (3) within tubules
- leukocytic infiltration
- bleeding
- red blood cell casts
The clinical presentation of glomerulonephritis thus includes (1), (2), (3)
- hematuria
- proteinuria
- decreased renal function as determined by glomerular filtration rate (GFR).
In decreasing renal function, one sees (1), as well as (2), and (3)
- elevated serum blood urea nitrogen (BUN) and creatinine
- oliguria (decreased urine output)
- salt and water retention which contributes to edema
With continuing renal damage progressing from acute to chronic glomerulonephritis, there is also the development of (1)
- hypertension
Hypertension occurs when the kidney is not delivering as much (1) to the (2), so there is (3) being produced in each nephron.
- sodium
- distal tubules
- increased renin, angiotensin, and aldosterone
(1) are the essential functional unit of the kidney, and consist of the glomerulus and its associated tubules and blood supply. Each kidney has approximately one million (1)
- Nephrons
A distinct presentation known as rapidly progressive glomerulonephritis (RPGN) is associated with the formation of (1) within (2)
- crescents
2. Bowman’s space
One classic example of acute glomerulonephritis is (1) which occurs in children about 1-2 weeks after recovery from (2)
- post-streptococcal glomerulo-nephritis
2. a sore throat
Post-streptococcal glomerulo-nephritis patients develop (1) (from the mild proteinuria), (2) and (3) urine which contains (4)
- periorbital edema
- fever, oliguria
- cola colored
- red blood cell casts
Post-streptococcal glomerulo-nephritis patients can also develop (1) due to the effects of decreased (2) delivery to (3)
- hypertension
- sodium
- distal tubules
Post-streptococcal glomerulo-nephritis causes the nephron to locally produce (1), activating (2), which together increase blood pressure by elevating both total peripheral resistance (3) and stroke volume (4)
- renin
- angiotensin and aldosterone
- vasoconstriction from angiotensin II effects
- increased blood volume from increased sodium and water reabsorption due to aldosterone effects
Adults with post-streptococcal GN have a more atypical presentation and can merely have (1), (2), or (3)
- sudden hypertension
- edema
- increasing BUN (called azotemia).
Lab findings in post-streptococcal GN include evidence of the strep exposure such as increased titers of (1); and evidence of immune response (utilization of complement components as evidenced by (2) or other complement factors).
- antistreptococcal antibodies
2. decreased serum C3
A similar GN to post-streptococcal GN occurs sporadically in association with other infections such as?
bacterial (staph endocarditis, pneumococcal pneumonia, meningococcemia), viral (e.g., hepatitis B, hepatitis C, mumps, HIV infection, varicella, and infectious mononucleosis), and parasitic (malaria, toxoplasmosis).
The classic pathophysiologic findings on electron microscopy for post-streptococcal GN is the (1) or large deposits present between the (2)
- subepithelial “humps”
2. podocytes and the basement membrane.
In post-streptococcal GN, there is also localized proliferation of (1) which occlude the lumen resulting in decreased blood flow.
- capillary endothelial cells
Another type of glomerulonephritis is membranoproliferative GN. In type I, there are prominent (1) and (2) visualized by light microscopy due to the increased number of (3) and increased (4)
- sub endothelial deposits
- lobulated glomeruli
- mesangial cells
- basement membrane and mesangial matrix.
The interposition of (1) between (2) creates a double-contour effect which looks like a double basement membrane.
- mesangial cells and basement membrane
- endothelial cells and basement membrane
refers to type I membranoproliferative GN
The (1) responsible for membranoproliferative GN is not known, but it is known to resolve when patient infections are successfully treated in those rare patients who have an infectious causation.
- antigen
Secondary infectious causes of Type I membranoproliferative GN include ?
subacute bacterial endocarditis (a heart valve infection) or osteomyelitis.
Some patients have secondary membranoproliferative GN due to ?
malignancy.
Type II membranoprolferative GN is also known as (1) because of the electronmicroscopic findings of (2) in the (3)
- dense deposit disease
- very electron dense immune complex deposition
- basement membrane.
Most patients with Type II membranoproliferative GN have a serum (1) autoantibody called (2) which stabilizes the (3) of the alternative complement pathway to produce prolonged cleaving activity
- IgG
- C3 nephritic factor
- C3 convertase enzyme
Stabilization of the C3 nephritic factor results in activation of the alternative complement pathway with (1) deposition in the glomerular (2) and a corresponding (3)
- C3 and properdin
- basement membrane
- decreased serum C3 and factor B.
refers to Type II membranoproliferative GN
However, patients with Type II membranoproliferative GN have normal serum levels of (1) (because (2) are not activated in this alternative pathway).
- C1 and C4
2. immune complexes
Type II MPGN often recurs in (1), suggesting that glomerular injury is mediated through some unknown humoral factor.
- renal transplants
Another renal disease which can produce either a nephritic or a nephrotic presentation is (1). This disease preferentially affects the (2) which have the most concentrating ability
- focal segmental glomerulosclerosis (FSGS)
2. juxtamedullary glomeruli
FSGS produces increased (1) that affects some of the (2) (focal) and initially only a part of an affected (3) (segmental).
- collagenous matrix
- glomeruli
- glomerular tuft
FSGS is seen in conditions where the renal mass can’t meet the renal demands such as decreased renal mass due to congenital (1) or acquired (2) or conditions which overwork the kidney such as (3)
- unilateral agenesis
- reflux nephropathy
- obesity or reduced oxygen conditions (sickle cell disease or congenital heart disease).
During the late 20th century, FSGS was commonly seen in (1) patients although the incidence in both of these populations has decreased and idiopathic FSGS is becoming increasingly common.
- heroin addicts and in black HIV
The lesions observed in FSGS can be either (1)
- sclerosis or hyalinosis
Sclerosis consists of (1) deposition in the (2)
- extracellular collagen
2. mesangium and capillary loops.
Hyalinosis (homogeneous and eosinophilic) is thought to be due to (1) which enter (2) structures as a consequence of (3)
- plasma proteins
- glomerular
- endothelial or capillary injury.
There are a number of different variant types of FSGS including ones in which the sclerosis either affects just the (1) region or collapses due to continuing injury
- perihilar
HIV FSGS can be associated with the (1) variant.
- collapsing
Rapidly progressive GN (RPGN) represents a serious syndrome with multiple causes. The patients present with a sudden onset of ?
oliguria and nephritis.
Renal biopsy in cases of Rapidly progressive GN (RPGN) shows the formation of (1) which are formed by proliferation of the (2) followed by infiltration of (3)
- crescents
- parietal epithelial cells lining Bowman’s capsule
- monocytes and macrophages.
The presence of (1) in (2) is thought to be the initiating factor which leads to crescent formation in RPGN
- fibrin
2. Bowman’s space
RPGN can be due to (1) or the so-called pauci-immune form, which involves (2)
- antibodies or immune complexes
2. antineutrophil cytoplasmic antibodies (ANCA).
Goodpasture Diseases is a type of RPGN caused by (1) antibodies directed against the Goodpasture antigen (a peptide within (2) which cross-reacts with (3) to cause (4)
- anti-glomerular basement membrane
- alpha3 chain of type IV collagen
- pulmonary alveolar basement membrane
- crescentic glomerulonephritis and pulmonary hemorrhage
The anti-glomerular basement membrane antibodies in Goodpasture Disease attract complement producing linear deposits of (1) within the (2)
- IgG and C3
2. glomeular basement membrane.
Other RPGN patients have a granular deposition of (1) within the (2) and associated (3) and have the disorder known as Henoch-Schonlein purpura
- IgA
- glomeruli
- cutaneous bruising
The most common type of RPGN is the pauci-immune type, which is due to circulating (1)
- anti-neutrophil cytoplasmic antibodies (ANCAs).
It is called pauci-immune because few immunoglobulin components are identified in biopsy studies because the disease is mediated more by (1) than by (2)
- neutrophils
2. lymphocytes
ANCAs can either be to the peripheral antigen myeloperoxidase (1) or to the more central PR3 antigen (2).
- p-ANCA
2. c-ANCA
Studies in mice indicate that transferring antibodies against (1) can induce RPGN, suggesting that the antibodies cause the disease.
- myeloperoxidase (target antigen for p-ANCAs)
It is believed that the antibodies in RPGN bind to (1) and cause them to adhere to (2), release toxic oxygen metabolites, de-granulate, and kill the (2)
- neutrophils
2. endothelial cells
Direct injury to capillary walls caused by neutrophil activity on endothelial cells, leads to leakage of (1), and inflammatory mediators into the urinary space including (2). The formation of (2) leads to the proliferation of the (3) and infiltration by (4) which produces the crescent and further damage
- coagulation factors
- fibrin.
- parietal epithelial cells
- macrophages
IgA nephropathy is another type of immune nephritis which can occur and can be either primary or secondary (observed in children with (1) or adults with (2).
- Henoch-Schonlein
2. intestinal or liver disease
IgA nephropathy presents with (1) and there are prominent (2) deposits in (3) on renal biopsy.
- recurrent hematuria or nephritis
- IgA
- mesangial cells
The primary type of IgA nephropathy most commonly occurs in children and younger adults after (1) and can slowly progress to renal failure and even recur in the (2) in some cases.
- infection
2. transplanted graft
Alport syndrome is an inherited disease which is usually (1) with females having (2) and in males exhibiting the entire syndrome.
- X-linked
2. hematuria
However, as is often the case with genetic diseases, autosomal dominant and recessive forms also exist in some families.
Alport syndrome
Maximally affected patients with Alport syndrome have (1) which progresses to chronic renal failure
- nerve deafness, eye disorders, and hematuria
Alport syndrome is caused by inherited mutations in (1)
- type IV collagen.
In contrast to Alport syndrome, patients with Benign familial hematuria (also called (1) present with (2).
- thin basement membrane lesion
2. asymptomatic hematurias and mild proteinuria
Electron microscopy of benign familial hematuria shows (1); they have mutations in (2). However, the patients have normal renal function and an excellent prognosis
- diffuse thinning of the basement membrane
2. certain chains of type IV collagen.
Type I MPGN–> Proliferation of 1) and 2)
Mesangial cells; endothelial cells
Capillary walls are thickened,:silver stains show a doubling or replication of GBMs.
EM shows this is deposition of new BM between the mesangial and endothelial cell
Type I Membranoproliferative Glomerulonephritis
Among these patients, 20% will have crescents, usually only a minority of glomeruli
Type I Membranoproliferative Glomerulonephritis
Immunofluorescence microscopy shows granular deposition of immunoglobulins and
complement in glomerular capillary loops and mesangium
Type I Membranoproliferative Glomerulonephritis
Type I MPGN
IF–> granular staining for C3 in the 1) and 2)
1) capillary walls
2) mesangium
due to Mutations in, alternative pathway complement (factor H)
Type II MPGN
Type II MPGN:
serum IgG autoantibody, termed 1), which stabilizes the activated C3 convertase enzyme (C3bBb) of the 2). The result is prolongation of C3 cleaving activity
1) C3 nephritic factor
2) alternative complement
pathway
Type II MPGN often recurs in 1) , suggesting that glomerular injury is
mediated through some unknown humoral factor
1) renal transplants
EM demonstrates thickening of the basement membrane and intramembranous dense deposits.
Type II MPGN (dense deposit
disease).
IF–>bands of capillary wall staining and
coarsely granular mesangial
staining for C3
Type II MPGN
Hereditary forms (mutations in podocyte genes):
- Podocin
- Alpha-actin-4
- TRPC6 (transient receptor potential cation channel 6)
Focal Segmental Glomerulosclerosis
ANCA glomerulonephritis is an aggressive,1)-mediated disease that is characterized by 2) and 3)
1) neutrophil
2) glomerular necrosis
3) Crescents
