Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Renal 2 Test 1 > Renal Pathology Part 3 > Flashcards

Renal Pathology Part 3 Flashcards

1
Q

Nephrotic syndrome

A
  • caused by a derangement in glomerular capillary walls resulting in increased permeability to plasma proteins
  • massive proteinuria, hypoalbuminemia, generalized edema, hyperlipidemia, lipiduria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Highly selective proteinuria consists mostly of

A

low-molecular-weight proteins (albumin, transferrin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Poorly selective proteinuria consists of

A

-higher-molecular-weight globulins in addition to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Most patients with nephrotic syndrome have

A
  • increased blood levels of cholesterol, triglycerides, very-low-density lipoprotein, low-density lipoprotein, Lp(a) lipoprotein, and apoprotein, and there is a decrease in high-density lipoprotein concentrations in some patients
  • these defects seem to be due to a combination of increased synthesis of lipoproteins in the liver, abnormal transport of circulation lipid particles, and decreased lipid cabalism
  • Lipiduria follows hyperlipidemia, because lipoproteins also leak across glomerular capillary wall
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

In nephrotic syndrome, lipid appears in urine as

A

either free fat or as oval fat bodies, representing lipoprotein resorbed by tubular epithelial cells and then shed along with injured tubular cells that have detached from the basement membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Nephrotic patients are particularly vulnerable to

A

infection, especially staph and pneumococcal infections, probably due to loss of immunoglobulins in the urine

  • thrombotic and thromboembolic complications are also common, due in part to loss of endogenous anticoagulants in the urine
  • Renal vein thrombosis is most often a consequence of the hyper coagulable state, particularly in patients with membranous nephropathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In children younger than 17 years in North America, nephrotic syndrome is

A

almost always caused by a lesion primary to the kidney; among adults, it is often associated with a systemic disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The most frequent systemic causes of the nephrotic syndrome are

A

diabetes, amyloidosis, and SLE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

The most important of the primary glomerular lesions of nephrotic syndrome are

A

minimal-change disease (most common in children in North America), membranous glomerulopathy (most common in older adults), and focal segmental glomerulosclerosis (all ages)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Membranous nephropathy is characterized by

A
  • diffuse thickening of the glomerular capillary wall due to the accumulation of deposits containing Ig along the sub epithelial side of the basement membrane.
  • form of chronic immune complex-mediated disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cases of secondary membranous nephropathy

A
  • drugs (penicillamine, captopril, gold, NSAIDS)
  • underlying malignant tumors
  • SLE
  • infections
  • Other autoimmune disorders
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Primary membranous nephropathy is considerd to be

A
  • an autoimmune disease linked to certain HLA alleles (HLA-DQA1) and caused in most cases by antibodies to a renal auto antigen (phospholipase A2 receptor in adults)
  • lesions ressemble experimental Heymann nephritis (megalin antigenic complex in rat podocyte)
  • C5b-C9 activates glomerular epithelial and mesangial cells, inducing them to liberate proteases and oxidants, which cause capillary wall injury and increased protein leakage.
  • IgG4 is main Ig deposited
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Membranous Nephropathy light microscopy

A

-glomeruli either appear normal in the early stages of the disease or exhibit uniform, diffuse thickening of the glomerular capillary wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

membranous Nephropathy electron microscopy

A
  • the thickening is seen to be caused by irregular electron dense deposits containing immune complexes between the basement membrane and the overlying epithelial cells, with effacement of podocyte foot processes.
  • basement membrane material is laid down between these deposits, appearing as irregular spikes protruding form the GBM
  • These spikes are best seen by silver stains, which color the basement membrane, but not the deposits, black
  • in time the spikes thicken to produce domelike protrusions and eventually close over the immune deposits, burying them within a markedly thickened, irregular membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Membranous Nephropathy Immunfluorescence microscopy

A
  • granular deposits contain both immunoglobulins and complement
  • as the disease advances segmental sclerosis may occur; in the course of time glomeruli may become totally sclerosed
  • the epithelial cells of the proximal tubules contain protein reabsorption droplets, and there may be considerable interstitial mononuclear cell inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Membranous Nephropathy usually presents with

A
  • insidious onset of the nephrotic syndrome or, in about 15% of patients, with nonnephrotic proteinuria
  • hematuria and mild hypertension in 15-35% of patients
  • nonselective proteinuria
  • complete or partial remissions may occur
  • progression is associated with increasing sclerosis of glomeruli, rising serum creatinine reflecting renal insufficiency, and development of hypertension
  • disease recurs in up to 40% of patients who undergo transplantation for ESRD
  • may have circulating antibodies to PLA2 receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Minimal Change Disease

A
  • relatively benign disorder characterized by diffuse effacement of foot processes of visceral epithelial cells (podocytes), detectable only by electron microscopy, in glomeruli that appear virtually normal by light microscopy.
  • most frequent cause of nephrotic syndrome in children, and less common in adults
  • peak incidence between 2 and 6 years of age
  • sometimes follows a respiratory infection or prophylactic immunization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Immunological Basis of Minimal Change Disease

A
  • clinical association with respiratory infection and immunization
  • response to corticosteroids and/or other immunosuppressive therapy
  • association with other atopic disorders (eczema, rhinitis)
  • increased prevalence of certain HLA haplotypes in patients with disease associated with atopy
  • increased incidence of minimal change disease in patients with Hodgkin lymphoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Ultrastructural changes of minimal change disease point to

A

-a primary visceral epithelial cell injury (podocytopathy), and studies in animal models suggest the loss of glomerular polyanions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Minimal Change Disease Electron microscopy

A
  • GBM appear normal, and no electron-dense material is deposited
  • principal lesion is in the visceral epithelial cells, which show a uniform and diffuse effacement of foot processes, these being reduced to a rim of cytoplasm with loss of recognizable intervening slit diaphragms.
  • represents simplification of the epithelial cell architecture with flattening, retraction, and swelling of foot processes
  • only when effacement is associated with normal glomeruli by light microscopy!!
  • reversible after corticosteroid therapy and remission of proteinuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Minimal Change Disease proximal tubules

A

-cells are often laden with lipid and protein, reflecting tubular reabsorption of lipoproteins passing through disease glomeruli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clinical Features of Minimal Change Disease

A
  • massive proteinuria but good renal function
  • NO hypertension or hematuria
  • highly selective proteinuria (albumin)
  • dramatic response to corticosteroid therapy
  • proteinuria may recur though
  • in adults, associated with lymphomas and leukemias
  • secondary disease from NSAID therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Focal Segmental Glomerulosclerosis (FSGS)

A
  • most common cause of nephrotic syndrome in adults in the U.S.
  • sometimes considered to be a primary disorder of podocytes
  • lesion is characterized by sclerosis of some, but not all, glomeruli; and in the affected glomeruli, only a portion of the capillary tuft is involved
  • frequently manifests clinically by the acute or subacute onset of nephrotic syndrome or nonnephrotic proteinuria
  • hypertension, microscopic hematuria, and some degree of azotemia are commonly present when the disease is first clinically recognized
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Focal segmental glomerulosclerosis occurs in the following setting:

A
  • as a primary disease
  • in association with other conditions such as HIV infection, heroin addiction, sickle-cell disease, and massive obesity
  • as a secondary event, reflecting scarring of previously active necrotizing lesions, in cases of focal glomerulonephritis
  • as a component of the adaptive response to loss of renal tissue, whether from congenital anomalies or acquired causes, or in advanced stages of other renal disorders, such as hypertensive nephropathy
  • in uncommon inherited forms of nephrotic syndrome where the disease may be caused by mutations in genes that encode proteins localized to the slit diaphragm, e.g., podocin, alpha-actinin4, and TRPC6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Idiopathic focal segmental glomerulosclerosis accounts for

A

10 and 35% of cases of nephrotic syndrome in children and adults
-has increased in incidence and is not most common cause of nephrotic syndrome in adults in the U.S. (particularly Hispanic and African-American patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Clinical signs of FSGS differ from minimal change disease in the following respects:

A
  • higher incidence of hematuria, reduced GFR and hypertension
  • proteinuria is more often nonselective
  • there is poor response to corticosteroid therapy
  • there is progression to chronic kidney disease, with at least 50% developing ESRD within 10 years
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Hallmark of FSGS

A

epithelial damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Hyalinosis and sclerosis in FSGS stem from

A

entrapment of plasma proteins in extremely hyper permeable foci and increased ECM deposition

29
Q

Several mutations of the NPHS gene have been identified that give rise to

A

congenital nephrotic syndrome of the Finnish type, producing a minimal-change disease like glomerulopathy with extensive foot process effacement

30
Q

A distinctive pattern of autosomal recessive FSGS results from

A

mutations in the NPHS2 gene, which encodes the protein product podocin

31
Q

Mutations in NPHS2 result in a

A

syndrome of steroid-resistant nephrotic syndrome of childhood onset

32
Q

Autosomal dominant FSGS can stem from

A
  • mutations in gene encoding podocyte actin-binding protein alpha-actinin4
  • insidious in onset but high rate of progression to renal insufficiency
33
Q

Adult-onset FSGS can stem from mutations in

A

TRPC6

-may perturb podocyte function by increasing calcium flux in these cells

34
Q

Strongly associate with an increased risk of FSGS and renal failure in individuals of African descent

A
  • 2 sequence variants in the apolipoprotein L1 gene (APOL1) on chromosome 22
  • resistance to trypanosome infection with these polymorphisms
35
Q

Renal ablation FSGS

A
  • secondary form
  • occurs as a complication of glomerular and nonglomerular disease causing reduction in functioning renal failure
  • this occurs in reflux nephropathy and unilateral agenesis
  • may lead to progressive glomerulosclerosis and renal failure
36
Q

FSGS Light Microscopy

A
  • focal and segmental lesions may involve only a minority of the glomeruli and may be missed if the biopsy does not contain enough glomeruli
  • sclerotic segments show collapse of capillary loops, increase in matrix and segmental deposition of plasma proteins along the capillary wall (hyalinosis), which may become so pronounced as to occlude capillary lumens
  • lipid droplets and foam cells often present
  • Glomeruli that do not show segmental lessons usually appear normal on light microscopy but may have increased mesangial matrix
37
Q

FSGS Electron Microscopy

A

-both sclerotic and aonsclerotic areas show diffuse effacement of foot processes, and there may also be focal detachment of the epithelial cells and denudation of the underlying GBM

38
Q

FSGS Immunofluorescence microscopy

A

FSGS Immunofluorescence microscopy -IgM and C3 may be present in the sclerosis areas and/or in the mesangium

  • may be pronounced hyalinosis and thickening of afferent arterioles
  • with progression, there may be total sclerosis of glomeruli,w it pronounced tubular atrophy and interstitial fibrosis
39
Q

Collapsing Glomerulopathy

A
  • morphologic variant of FSGS
  • retraction and/or collapse of the entire glomerular tuft, with or without additional FSGS lesions
  • proliferation and hypertrophy of glomerular visceral epithelial cells
  • lesion may be idiopathic or associated with drug toxicities and HIV-associated nephropathy
  • typically associated with prominent tubular injury with formation of micro cysts
  • poor prognosis
40
Q

HIV Infection can

A

-directly or indirectly cause several renal complications, including acute renal failure or acute interstitial nephritis induced by drugs or the infection, thrombotic microangiopathies, post infectious glomerulonephritis, and, most commonly, a severe form of the collapsing variant of FSGS, termed HIV-associated nephropathy

41
Q

Morphologic features of HIV-associated nephropathy are

A
  • high frequency of the collapsing variant of FSGS
  • striking focal cystic dilation of tubule segments, which are filled with proteinaceous material, and inflammation and fibrosis
  • The presence of large numbers of tubuloreticular inclusions within endothelial cels, detected by electron microscopy.
  • Such inclusions have been shown to be modifications of ER induced by circulating interferon-alpha (may be diagnostic!)
42
Q

Membranoproliferative Glomerulonephritis (MPGN)

A
  • pattern of immune-mediated injury rather than a specific disease
  • Type I and Type II
43
Q

Type I MPGN

A

-deposition of immune complexes containing IgG and complement

44
Q

MPGN characterized histologically by

A
  • alterations i the glomerular basement membrane, proliferation of glomerular cells, leukocyte infiltration, and the presence of deposits in mesangial regions and glomerular capillary walls
  • deposits are made up of immune complexes in Type I and some unknown material in type II
  • in type II, C3 ispresent on the GBM but not in the dense deposits
  • Mesnagiocapillary glomerulnephritis
  • accounts for 10% of cases of nephrotic syndrome in children and young adults
  • some only present with hematuria or proteinuria in the nonnephrotic range, but many others have a combined nephrotic-nephritic picture
45
Q

In most cases of type I MPGN, there is evidence of

A

immune complexes in the glomerulus and activator of both classical and alternative complement pathways

46
Q

MPGN morphology

A
  • glomeruli large and hyper cellular due to proliferation of cells in the mesangium and so-called endocapillary proliferation involving capillary endothelium and infiltrating leukocytes
  • glomeruli have an accentuated lobular appearance due to proliferating mesangial cells and increased mesangial matrix
  • GBM is thickened and shows a double contour appearance caused by duplication of basement membrane
  • between the duplication basement membrane there is inclusion or interposition of cellular elements, which can be mesangial, endothelial, or leukocytic origin
  • crescents are present in many cases
47
Q

Type I MPGN is characterized by

A
  • presence of discrete sub endothelial electron-dense deposits
  • mesangial and occasional sub epithelial deposits may also be presence
48
Q

MPGN immunofluorescence

A

-IgG and C3 are deposited in a granular pattern, and early complement components (C1q and C4) are often present

49
Q

Most patients with primary MPGN present

A

-in adolescence or young adults with nephrotic syndrome and a nephritic component manifested by hematuria or, more insidiously, as mild proteinuria

50
Q

Secondary MPGN

A
  • more common in adults
  • chronic immune complex disorders, endocarditis, infected ventriculatrial shunts, chronic visceral abscesses, HIV infection, and schistosomiasis
  • alpha1-antitrypsin deficiency
  • malignant disease
51
Q

Dense Deposit Disease

A
  • most patients have abnormalities resulting in excessive activation of the alternative complement pathway
  • have a consistently decreased serum C3 but normal C1 and C4, the early components of complement
  • have diminished serum levels of factor B and properdin, components of alternative complement pathway
  • C3 and properdin deposits in the glomeruli
  • in alternative complement pathway, C3 is directly cleaved to C3b leads to C3 convertase
  • More than 70% of patients have a circulating autoantibody C3 nephritic factor (C3NeF) that binds alternative pathway C3 convertase and protects it from inactivation
  • persistent Ce activation and hypocomplementemia
  • decreased C3 synthesis by liver
52
Q

Dense Deposit Disease Morphology

A

Dense Deposit Disease Morphology -many cases have a predominantly mesangial proliferative pattern of injury, while others have an inflammatory and focally crescentic appearance
-in some cases, dense deposits of a cellular material can be seen permeating the glomerular basement membranes in histologic sections

53
Q

Dense Deposit Disease Electron Microscopy

A

-permeation of the lamina densa of the GBM by a ribbon-like, homogenous, extremely electron-dense material of unknown composition

54
Q

Dense Deposit Disease Immunofluorescence

A
  • C3 is present in irregular granular or linear foci in the basement membranes on either side but not within the dense deposits
  • C3 present in the mesangium in characteristic mesangial rings
  • IgG and components of classical pathway absent
55
Q

Dense Deposit Disease Clinical Features

A
  • children and young adults

- poor prognosis

56
Q

IgA nephropathy

A
  • presence of prominent IgA deposits in the mesangial regions and recurrent hematuria
  • most common type of glomerulonephritis worldwide
  • can be suspected by light microscopic exam, but diagnosis is made only by detection of glomerular IgA deposition
  • mild proteinuria; nephrotic syndrome may occasionally develop
  • rarely, patients may present with crescentic MPGN
57
Q

Henoch Schonlein purpura

A

-similar IgA deposits as IgA nephropathy in systemic disorder of children

58
Q

Secondary IgA nephropathy occurs in

A

patients with liver and intestinal diseases

59
Q

In patients with IgA nephropathy,

A

levels of plasma polymeric IgA are increased, but increased production is not sufficient to cause this disease
-the glomerular deposits consist predominantly of polymeric IgA molecules with aberrant glycosylation

60
Q

It is believed that a key facet of IgA nephropathy is

A

a hereditary or acquired defect in the normal formation or attachment of galactose-containing sugar chains called O-linked glycans to the hinge region of the IgA molecule prior to their secretion by B cells

  • aberrantly glycosylated IgA1 is either deposited by itself in glomeruli or it elects an autoimmune response and forms immune complexes in the circulation with IgG autoantibodies directed against the abnormal IgA molecules
  • immune complexes deposited in mesangium; alternatively, abnormal IgA1 is deposited in the mesangium with subsequent formation of immune complexes in situ
61
Q

Mesangial immune deposits in IgA nephropathy

A
  • activate mesangial cells to proliferate, produce increased amounts of ECM, and secrete numerous cytokines and growth factors
  • these secreted mediators may not only participate in further mesangial cell activation but may also recruit inflammatory cells into the glomeruli
  • recruited leukocytes contribute to glomerular injury and also to a reparative response, which can include opsonization and removal of the immune complexes
62
Q

Deposited IgA and IgA-containing immune complexes in IgA nephropathy

A

activate complement system via the alternate pathway, and hence presence of C3 and absence of C1q and C4 in glomeruli are typical

63
Q

Increased synthesis of abnormal IgA in IgA nephropathy may occur in response to

A

respiratory or GI exposure to environmental agents (viruses, bacteria, food proteins)

64
Q

IgA nephropathy occurs with increased frequency in individuals with

A

gluten enteropathy (celiac disease), in whom intestinal mucosal defects are well defined, and in liver disease, in which there is defective hepatobiliary clearance of IgA complexes

65
Q

IgA Nephropathy morphology

A
  • glomeruli may be normal or may show mesangial widening and endocapillary proliferation, segmental proliferation confined to some glomeruli, or rarely, overt crescentic glomerulonephritis
  • presence of leukocytes within capillaries is variable
  • healing of the focal proliferative lesion may lead to secondary focal segmental sclerosis
66
Q

IgA Nephropathy Immunofluorescence

A
  • mesangial deposition of IgA, often with C3 and properdin and lesser amounts of IgG or IgM
  • early complement components usually absent
67
Q

IgA Nephropathy electron microscopy

A

-presence of electron-dense deposits predominantly in the mesangium; capillary wall deposits, if present, usually sparse

68
Q

IgA Nephropathy Clinical Features

A
  • many present with gross hematuria after an infection of the respiratory or GI or urinary tract
  • 30-40% have only microscopic hematuria, with or without proteinuria
  • 5-10% develop acute nephritic syndrome
  • hematuria typically lasts for several days and then subsides, only to return every few months
  • many patients maintain normal renal function for decades
  • slow progression to chronic renal failure occurs in 15-40% of cases over a period of 20 years

Renal 2 Test 1 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions