Renal Flashcards
(146 cards)
1
Q
The study of kidney diseases is facilitated by dividing them into those that affect the four basic
morphologic components:
A
- glomeruli
- tubules,
- interstitium,
- and blood vessels
2
Q
most glomerular diseases are _________________
A
immunologically
mediated
3
Q
whereas tubular and interstitial disorders are frequently caused by ______________
A
toxic or
infectious agents.
4
Q
Disease primarily in the blood vessels, for
example, inevitably affects all the structures that depend on this blood supply.
Severe
glomerular damage impairs the flow through the peritubular vascular system and also delivers
potentially toxic products to tubules; conversely, tubular destruction, by increasing
intraglomerular pressure, may induce glomerular injury. Thus, whatever the origin, there is a
tendency for all forms of chronic kidney disease ultimately to destroy all four components of the
kidney,culminating in chronic renal failure and what has been called____________
A
end-stage kidneys
5
Q
The
functional reserve of the kidney is large, and much damage may occur before there is evident
functional impairment. For these reasons the early signs and symptoms are particularly
important clinically.
A
:)
6
Q
____________ is a biochemical abnormality that refers to an elevation of the blood urea nitrogen
(BUN) and creatinine levels, and is related largely to a decreased glomerular filtration rate
(GFR). Azotemia is a consequence of many renal disorders, but it also arises from extrarenal
disorders.
A
Azotemia
7
Q
____________- is encountered when there is hypoperfusion of the kidneys (e.g.,
in hemorrhage, shock, volume depletion, and congestive heart failure) that impairs renal function in the absence of parenchymal damage.
A
Prerenal azotemia
8
Q
_____________- is seen whenever urine
flow is obstructed beyond the level of the kidney. Relief of the obstruction is followed by
correction of the azotemia.
A
Postrenal azotemia
9
Q
When azotemia becomes associated with a constellation of clinical signs and symptoms and
biochemical abnormalities, it is termed___________ This is characterized not only by failure of
renal excretory functionbut also by ahost of metabolicandendocrine alterations resulting from
renal damage.
These patients frequently manifest secondary involvement of the
gastrointestinal system (e.g., uremic gastroenteritis), peripheral nerves (e.g., peripheral
neuropathy), and heart (e.g., uremic fibrinous pericarditis).
A
uremia.
10
Q
___________________ is due to glomerular disease and is dominated by the acute onset of
usually grossly visible hematuria(red blood cells in urine),mild to moderate proteinuria,
and hypertension; it is the classic presentation of acute poststreptococcal
glomerulonephritis.
A
Nephritic syndrome
11
Q
- *_________________** is characterized as a nephritic syndrome with
- *rapid decline (hours to days) in GFR.**
A
Rapidly progressive glomerulonephritis
12
Q
The _____________also due to glomerular disease, is characterized by heavy
proteinuria(more than 3.5 gm/day),hypoalbuminemia,severe edema,hyperlipidemia,
and lipiduria (lipid in the urine).
A
nephrotic syndrome,
13
Q
______________, or a combination of these two, is usually a
manifestation of subtle or mild glomerular abnormalities.
A
Asymptomatic hematuria or proteinuria
14
Q
_______________ is dominated by oliguria or anuria (reduced or no urine flow), and
recent onset of azotemia. It can result from glomerular, interstitial, or vascular injury or
acute tubular injury.
A
Acute renal failure
15
Q
_____________, characterized by prolonged symptoms and signs of uremia, is the
end result of all chronic renal parenchymal diseases.
A
Chronic renal failure
16
Q
_______________are dominated by polyuria (excessive urine formation), nocturia,
and electrolyte disorders (e.g., metabolic acidosis). They are the result of diseases that
either directly affect tubular structure (e.g., medullary cystic disease) or cause defects in
specific tubular functions.
The latter can be inherited (e.g., familial nephrogenic
diabetes, cystinuria, renal tubular acidosis) or acquired (e.g., lead nephropathy).
A
Renal tubular defects
17
Q
____________ is characterized by bacteriuria and pyuria (bacteria and
leukocytes in the urine). The infection may be symptomatic or asymptomatic, and it may
affect the kidney (pyelonephritis) or the bladder (cystitis).
A
Urinary tract infection
18
Q
_________- is manifested by severe spasms of pain (renal colic) and
hematuria, often with recurrent stone formation.
A
Nephrolithiasis (renal stones)
19
Q
Urinary tract obstruction and renal tumors have varied clinical manifestations based on
the specific anatomic location and nature of the lesion.
A
Urinary tract obstruction
20
Q
renal failure broadly progresses through a series of four stages that merge into one another.
1. In ____________ the GFR is about 50% of normal. Serum BUN and
creatinine values are normal, and the patients areasymptomatic. However, they are
more susceptible to developing azotemia with an additional renal insult.
2. In ______________ the GFR is 20% to 50% of normal. Azotemia appears, usually associated with anemia and hypertension. Polyuria and nocturia can occur as a result
of decreased concentrating ability. Sudden stress (e.g., with nephrotoxins) may
precipitate uremia.
3. In ________ the GFR is less than 20% to 25% of normal. The kidneys cannot
regulate volume and solute composition, and patients develop edema, metabolic
acidosis, and hyperkalemia. Overt uremia may ensue, withneurologic, gastrointestinal,
and cardiovascular complications.
4. In end-stage renal disease the GFR is less than 5% of normal; this is the terminal stage
of uremia. Recent clinical classifications of chronic kidney disease, adopted in part to
better stratify patients in clinical trials, adhere to this schema of progressive injury but
divide patients into five classes based on levels of GFR.
A
diminished renal reserve
renal insufficiency
chronic renal failure
end-stage renal disease
21
Q
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
FLUID AND ELECTROLYTES
______________
A
Dehydration
Edema
Hyperkalemia
Metabolic
acidosis
22
Q
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
CALCIUM PHOSPHATE AND BONE
_________________________________________
A
Hyperphosphatemia
Hypocalcemia
Secondary
hyperparathyroidism
Renal osteodystrophy
23
Q
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
HEMATOLOGIC
__________
A
Anemia
Bleeding
diathesis (unusual susceptibility to bleeding (hemorrhage) mostly due to hypocoagulability, in turn caused by acoagulopathy (a defect in the system of coagulation)
24
Q
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
CARDIOPULMONARY
_____________
A
Hypertension
Congestive heart
failure
Cardiomyopathy
Pulmonary edema
Uremic pericarditis
25
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
GASTROINTESTINAL
Nausea and vomiting
Bleeding
Esophagitis, gastritis,
colitis
Nausea and vomiting
Bleeding
Esophagitis, gastritis,
colitis
26
Clinical Manifestations of Renal Diseases
Myopathy
Peripheral
neuropathy
Encephalopathy
27
Clinical Manifestations of Renal Diseases
DERMATOLOGIC
Sallow color
Pruritus
Dermatitis
Sallow color
Pruritus
Dermatitis
28
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is one of the most common causes of chronic kidney disease in humans.
Glomeruli may be injured by a variety of factors and in the course of several systemic diseases
chronic
glomerulonephritis
29
**Systemic immunological diseases** such as systemic lupus erythematosus (SLE), **vascular
disorders**such as hypertension, metabolic diseases such as diabetes mellitus, and some
**hereditary conditions** such as **Fabry disease** often affect the \_\_\_\_\_\_\_\_\_\_. These are termed
**secondary glomerular diseases** .
glomerulus.
30
**only or predominant organ involved**. The latter constitute the various types of\_\_\_\_\_\_\_\_\_\_\_\_ or, because **some do not have a cellular inflammatory component,
glomerulopathy**. However,**both the clinical manifestations and glomerular histologic changes in
primary and secondary forms can be similar.**
primary
glomerulonephritis
31
**PRIMARY GLOMERULOPATHIES**
Acute proliferative glomerulonephritis
Post-infectious
Other
Rapidly progressive (crescentic)
glomerulonephritis
Membranous glomerulopathy
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis
32
SYSTEMIC DISEASES WITH GLOMERULAR INVOLVEMENT
\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic
polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
33
HEREDITARY DISORDERS GLOMERULUS
Alport syndrome
Thin basement membrane
disease
Fabry disease
34
The clinical manifestations of glomerular disease are clustered into the **five major glomerular syndromes** summarized in Table 20-3 .
**Both the primary** glomerulopathies and the **systemic
disease**s**affecting the glomerulu**s can r**esult in these syndromes**. Because glomerular diseases
are often associated with systemic disorders, mainly **diabetes mellitus, SLE, vasculitis, and
amyloidosis,**in any patient with manifestations of glomerular disease it is**essential to consider
these systemic conditions.**
Nephritic syndrome
Rapidly progressive glomerulonephritis
Nephrotic syndrome
Chronic Renal Failure
Isolated urinary abnormalities
35
\_\_\_\_\_\_\_\_\_\_\_\_ **Hematuria**,
azotemia,
variable proteinuria,
oliguria,
edema, and
hypertension
Nephritic syndrome
36
\_\_\_\_\_\_\_\_\_\_\_\_\_
Acute nephritis, proteinuria, and acute renal failure
Rapidly progressive
glomerulonephritis
37
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\>3.5 gm/day proteinuria, hypoalbuminemia, hyperlipidemia,
lipiduria
Nephrotic syndrome
38
\_\_\_\_\_\_\_\_\_\_\_\_\_\_➙ uremia progressing for months to years
Chronic renal failure Azotemia
39
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Glomerular hematuria and/or subnephrotic proteinuria
Isolated urinary abnormalities
40
Many clinical manifestations of glomerular disease result from **perturbations of specific
components of the glomerular tuft,** so we present key anatomic structures that are subject to
alteration in disease. The \_\_\_\_\_\_\_\_consists of an **anastomosing network of capillaries** lined
by **fenestrated endothelium** invested by two layers of epithelium ( Fig. 20-1 ).
glomerulus
41
The glomerulus consists of an anastomosing network of capillaries lined
by fenestrated endothelium invested by two layers of epithelium ( Fig. 20-1 ).
The\_\_\_\_\_\_\_\_\_\_- is incorporated into and becomes an intrinsic part of the capillary wall, separated
**from endothelial cells** by a **basement membrane**. The \_\_\_\_\_\_\_\_\_\_, situated on the
Bowman capsule, lines the urinary space, the cavity in which plasma filtrate first collects.
visceral epithelium
parietal epithelium
42
The glomerular capillary wall is the filtering membrane and consists of the following
structures:
**endothelial cells**
**glomerular basement membrane (GBM)**
**visceral epithelial cells (podocytes)**
**mesangial cells**
43
A _______________ with a thick electron-dense central layer, the
**lamina densa**, and **thinner electron-lucent peripheral layers,** the **lamina rara interna** and
**lamina rara externa**. The GBM consists of collagen **(mostly type IV)**, laminin, polyanionic
proteoglycans (mostly heparan sulfate), **fibronectin**, **entactin**, and several other
glycoproteins.
**Type IV collagen** forms a network suprastructure to which other
glycoproteins attach. The building block (monomer) of this network is a triple-helical
molecule made up of three α chains, composed of one or more of six types of α chains (
**α1 to α6 or COL4A1 to COL4A6**), the most common consisting of α1, α2, α1. [3,] [5]
Each molecule consists of a 7S domain at the N terminus, a triple-helical domain in the
middle, and a globular noncollagenous domain (NC1) at the C terminus. The NC1
domain is important for helix formation and for assembly of collagen monomers into the
basement membrane suprastructure. Glycoproteins (laminin, entactin) and proteoglycans (heparan sulfate, perlecan) attach to the collagenous suprastructure.
These **biochemical determinants are critical to understanding glomerular diseases**. For
example, as we shall see, the antigens in the NC1 domain are the targets of antibodies
in anti-GBM nephritis; genetic defects in the α-chains underlie some forms of hereditary
nephritis; and the proteoglycan content of the GBM may contribute to its permeability
characteristics.
**glomerular basement membrane (GBM)**
44
The\_\_\_\_\_\_\_\_\_\_\_\_\_ are structurally complex cells that possess
interdigitating processes embedded in and adherent to the **lamina rara externa** of the
basement membrane. Adjacent **foot processes (pedicels)** are separated by 20- to 30-
nm-wide filtration slits, which are bridged by a thin diaphragm (see Fig. 20-2 ).
visceral epithelial cells (podocytes)
45
The entire glomerular tuft is supported by \_\_\_\_\_\_\_\_\_\_\_\_lying between the capillaries.
Basement membrane–like **mesangial matrix** forms a meshwork through which the
mesangial cells are centered (see Fig. 20-1 ). These cells, of mesenchymal origin, are
contractile, phagocytic, and capable o**f proliferation**, of laying down both matrix and
collagen, and of secreting several biologically active mediators. Biologically, they are
most akin to vascular smooth muscle cells and pericytes. They are, as we shall see,
important players in many forms of human glomerulonephritis.
mesangial cells
46
The major characteristics of normal glomerular filtration are an \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_-, because of the **highly fenestrated nature** of the endothelium, and
impermeability to proteins, such as molecules of the size of albumin (∼3.6-nm radius; 70
kilodaltons [kD] molecular weight) or larger.
extraordinarily high permeability
to water and small solutes
47
The latter property of the glomerular filtration
barrier **allows discrimination** among various protein molecules, depending on their **\_\_\_\_\_\_\_\_\_\_\_\_**and** \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**. This size- and
charge-dependent barrier function is accounted for by the **complex structure of the capillary
wall**, the**collagenous porous**and**charged structure of the GBM**, and the many anionic moieties
present within the wall, including the **acidic proteoglycans** of the GBM and the
**sialoglycoproteins of epithelial** and endothelial cell coats (also called **glycocalyx**).
**size** (the
larger, the less permeable)
**charge** (the more cationic, the more permeable)
48
The chargedependent
restriction is important in the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
because albumin is an anionic molecule of a pI 4.5.
virtually complete exclusion of albumin from the filtrate,
49
The\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, also known as a
**podocyte**, is important for the **maintenance of glomerular barrier function**; its ***slit diaphragm*
presents a size-selective distal diffusion barrier**to the filtration of proteins, and it is the**cell type
that is largely responsible for synthesis of GBM components.**
visceral epithelial cell
50
Proteins located in the slit
diaphragm **control glomerular permeability**. Three of the most important slit diaphragm proteins
are depicted in Figure 20-3 .\_\_\_\_\_\_\_\_\_\_\_ is a **transmembrane protein** with a large extracellular
portion made up of immunoglobulin (Ig)-like domains. This molecules extend toward each
other from neighboring foot processes and dimerize across the slit diaphragm. Within the
cytoplasm of the foot processes, **\_\_\_\_\_\_\_\_\_ forms molecular connections with podocin**, CD2-
associated protein, and ultimately the **actin cytoskeleton**. The number of identified slit
diaphragm proteins continues to grow rapidly, and more comprehensive descriptions of their
complex localization and interactions have been published. [6,] [7] The importance of these
proteins in maintaining glomerular permeability is demonstrated by the observation that
**mutations in the genes encoding them give rise to nephrotic syndrome** (discussed later). This
has resulted in renewed appreciation of the importance of the slit diaphragm in glomerular
barrier function and its contribution to protein leakage in disease states. [
1. Nephrin
2. podocin
3. actin cytoskeleton
51
HISTOLOGIC ALTERATIONS
Various types of glomerulopathies are characterized by one or more of four basic tissue
reactions.
Hypercellularity.
Basement Membrane Thickening.
Hyalinosis and Sclerosis.
52
Some inflammatory diseases of the glomerulus are characterized by an **increase in the number
of cells in the glomerular tufts.** This is characterized by one or more
combinations of the following:
Hypercellularity
• Cellular proliferation of **mesangial or endothelial cells**.
• Leukocytic infiltration consisting of **neutrophils, monocytes, and, in some diseases,
lymphocytes.**
• **Formation of crescents**. These are accumulations of cells composed of **proliferating
parietal epithelial cells and infiltrating leukocytes.** The epithelial cell proliferation that
characterizes crescent formation occurs following an **immune/inflammatory injury (see
later).**
**Fibrin,** which leaks into the urinary space, often through ruptured basement
membranes, has been long thought to be the molecule that elicits the crescentic
response.
In support of this, fibrin can be demonstrated **immunohistochemically in the
glomerular tufts**and**urinary spaces of glomeruli that contain crescents**. Mice that are
deficient in fibrinogen are protected to a degree from crescent formation, and mice that
are deficient in molecules important in fibrinolysis (e.g., plasminogen activators) exhibit
enhanced crescent formation in models of anti-GBM antibody–mediated crescentic
glomerulonephritis. [9] Other molecules that have been implicated in crescent formation
and recruitment of leukocytes into crescents include procoagulants such as tissue factor
and cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon-γ.
53
In hypercellularity what type of cells proliferate?
Cellular proliferation of **mesangial or endothelial cells.**
54
These are accumulations of cells composed of **proliferating
parietal epithelial cells**and**infiltrating leukocytes.** The epithelial cell proliferation that
characterizes crescent formation **occurs following an immune/inflammatory injury** (see
later).
Formation of crescents.
55
\_\_\_\_\_\_\_\_\_, which leaks into the urinary space, often through **ruptured basement
membranes**, has been long thought to be the molecule that**elicits the crescentic
response**. In support of this, fibrin can be demonstrated immunohistochemically in the
**glomerular tuft**s and **urinary spaces of glomeruli** that **contain crescents**.
Fibrin
Note : Mice that are
**deficient in fibrinogen** are protected to a degree **from crescent formation**, and mice that
are **deficient in molecules important in fibrinolysis** (e.g., plasminogen activators) exhibit
**enhanced crescent formation in models of anti-GBM antibody–mediated crescentic
glomerulonephritis.** [9]
56
Other molecules that have been implicated in \_\_\_\_\_
and recruitment of leukocytes into crescents include \_\_\_\_\_\_\_\_\_\_
**crescent formation **
**procoagulants such as tissue factor**
and **cytokines such as interleukin-1 (IL-1**), t**umor necrosis factor (TNF**), and **interferon-γ.**
57
\_\_\_\_\_\_\_\_\_\_\_\_\_
By light microscopy, this change appears as **thickening of the capillary walls**, best seen in
sections stained with **periodic acid–Schiff (PAS**).
Basement Membrane Thickening.
58
By electron microscopy such thickening takes
one of two forms:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
• **Deposition** of amorphous electron-dense material, most often **immune complexes**, on
the **endothelial or epithelial side of the basement membrane or within the GBM itself**.
**Fibrin, amyloid, cryoglobulins, and abnormal fibrillary proteins** may also deposit in the
GBM.
• Thickening of the basement membrane due to **increased synthesis of its protein**
**components**, as occurs in **diabetic glomerulosclerosis.**
59
\_\_\_\_\_\_\_\_\_\_\_, as applied to the glomerulus, denotes the **accumulation of material** that is
**homogeneous and eosinophilic by light microscopy**.
Hyalinosis
60
By electron microscopy the \_\_\_\_\_\_\_\_\_\_\_\_- is
**extracellular and amorphous**. It is made up of **plasma proteins** that have insudated from the
circulation into glomerular structures. When extensive, this change contributes to **obliteration of
the capillary lumens of the glomerular tuft**.
hyalin
61
\_\_\_\_\_\_\_\_\_\_\_\_- is usually a consequence of **endothelial or
capillary wall injury**and**typically the end result of various forms of glomerular damage**. It is a
**common feature of focal segmental glomerulosclerosis.**
Hyalinosis
62
Hyalinosis is usually a consequence of **endothelial or
capillary wall injury**and typically the end result of various forms of glomerular damage. It is a
common feature of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
focal segmental glomerulosclerosis.
63
\_\_\_\_\_\_\_\_\_\_\_\_\_- is characterized by **accumulations of extracellular collagenous matrix,** either **confined
to mesangial areas**as is often the case in**diabetic glomerulosclerosis,** or involving the capillary
loops, or both. The sclerosing process may also result in **obliteration of some or all of the
capillary lumens**in affected glomeruli, which in turn**can result in formation of fibrous adhesions**
between the sclerotic portions of glomeruli and the **nearby parietal epithelium and Bowman
capsules.**
Sclerosis
64
Because many of the primary glomerulopathies are of unknown cause, they are often classified
by their histology, as can be seen in Table 20-2 . The histologic changes can be further
subdivided by their distribution into :
diffuse
global
focal
segmental
65
\_\_\_\_\_\_\_\_\_\_\_\_\_, involving all glomeruli;
diffuse
66
\_\_\_\_\_\_\_\_\_\_, involving the entire
glomerulus;
global
67
\_\_\_\_\_\_\_\_\_\_, involving only a proportion of the glomeruli;
focal
68
\_\_\_\_\_\_\_\_\_\_\_, affecting a part of
each glomerulus; and by either capillary loop or mesangial, affecting predominantly capillary or
mesangial regions. These terms are sometimes appended to the histologic classifications.
segmental
Note: \< or \> 50 %
69
Immune Mechanisms of Glomerular Injury
1. ANTIBODY-MEDIATED INJURY IN SITU IMMUNE COMPLEX DEPOSITION
2. CIRCULATING IMMUNE COMPLEX DEPOSITION
3. CYTOTOXIC ANTIBODIES
4. CELL-MEDIATED IMMUNE INJURY
5. ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY
70
WHAT ARE THE ANTIBODY-MEDIATED INJURY
IN SITU IMMUNE COMPLEX DEPOSITION?
1. Fixed intrinsic tissue antigens
* NC1 domain of collagen type IV antigen (anti-GBM
nephritis)
* Heymann antigen (membranous glomerulopathy)
* Mesangial antigens
* Others
2. Planted antigens
* Exogenous (infectious agents, drugs)
* Endogenous (DNA, nuclear proteins, immunoglobulins, immune
complexes, IgA)
71
CIRCULATING IMMUNE COMPLEX DEPOSITION
1. Endogenous antigens (e.g., DNA, tumor
antigens)
2. Exogenous antigens (e.g., infectious products)
72
Two forms of antibody-associated injury have been established:
(1) injury by antibodies
reacting in situ within the glomerulus, either binding to insoluble fixed (intrinsic) glomerular
antigens or to molecules planted within the glomerulus, and (2) injury resulting from deposition
of circulating antigen-antibody complexes in the glomerulus. In addition, there is experimental
evidence that cytotoxic antibodies directed against glomerular cell components may cause
glomerular injury. These pathways are not mutually exclusive, and in humans, all may contribute
to injury.
73
\_\_\_\_\_\_\_\_\_-
In these forms of injury, antibodies react directly with intrinsic tissue antigen, or antigens
**“planted**” in the glomerulus from the circulation. The best established experimental models for
**anti–glomerular antibody–mediated glomerular injury,** for which there are *counterparts in human*
disease, are **anti–glomerular basement membrane (antiGBM) antibody–induced
glomerulonephritis and Heymann nephritis.**
Immune Complex Deposition Involving Intrinsic and in Situ Renal Antigens
74
The study of kidney diseases is facilitated by dividing them into those that affect the four basic
morphologic components:
1. glomeruli
2. tubules,
3. interstitium,
4. and blood vessels
75
most glomerular diseases are \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
immunologically
mediated
76
whereas tubular and interstitial disorders are frequently caused by \_\_\_\_\_\_\_\_\_\_\_\_\_\_
toxic or
infectious agents.
77
Disease primarily in the blood vessels, for
example, inevitably affects all the structures that depend on this blood supply.
Severe
**glomerular damage impairs** the flow through the peritubular vascular system and also delivers
potentially toxic products to tubules; conversely, **tubular destruction**, by increasing
intraglomerular pressure, may induce glomerular injury. Thus, whatever the origin, there is a
t**endency for all forms of chronic kidney disease ultimately to destroy all four components of the
kidney,**culminating in chronic renal failure and what has been called\_\_\_\_\_\_\_\_\_\_\_\_
end-stage kidneys
78
The
functional reserve of the kidney is large, and much damage may occur before there is evident
functional impairment. For these reasons the early signs and symptoms are particularly
important clinically.
:)
79
\_\_\_\_\_\_\_\_\_\_\_\_ is a **biochemical abnormality** that refers to an **elevation of the blood urea nitrogen**
**(BUN) and creatinine levels,** and is related largely to a **decreased glomerular filtration rate**
(GFR). Azotemia is a consequence of many renal disorders, but it **also arises from extrarenal
disorders.**
Azotemia
80
\_\_\_\_\_\_\_\_\_\_\_\_- is encountered when there is **hypoperfusion of the kidneys** (e.g.,
in **hemorrhage,** **shock,** **volume depletion**, and **congestive heart failure)** that **impairs renal function in the absence of parenchymal damage.**
Prerenal azotemia
81
\_\_\_\_\_\_\_\_\_\_\_\_\_- is seen whenever urine
flow is obstructed beyond the level of the kidney. Relief of the obstruction is followed by
**correction of the azotemia.**
Postrenal azotemia
82
When azotemia becomes associated with a constellation of clinical signs and symptoms and
biochemical abnormalities, it is termed\_\_\_\_\_\_\_\_\_\_\_ This is characterized **not only by failure of
renal excretory function**but also by a**host of metabolic**and**endocrine alterations resulting from
renal damage**.
These patients frequently manifest secondary involvement of the
gastrointestinal system **(e.g., uremic gastroenteritis**), peripheral nerves (**e.g., peripheral**
neuropathy), and heart **(e.g., uremic fibrinous pericarditis).**
uremia.
83
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is due to glomerular disease and is dominated by the **acute onset of
usually grossly visible hematuria**(red blood cells in urine),**mild to moderate proteinuria,**
and **hypertension;** it is the **classic presentation of acute poststreptococcal
glomerulonephritis.**
Nephritic syndrome
84
* *\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** is characterized as a nephritic syndrome with
* *rapid decline (hours to days) in GFR.**
**Rapidly progressive glomerulonephritis**
85
The \_\_\_\_\_\_\_\_\_\_\_\_\_also due to **glomerular disease**, is characterized by **heavy
proteinuria**(more than 3.5 gm/day),**hypoalbuminemia**,**severe edema**,**hyperlipidemia,
and lipiduria** (lipid in the urine).
nephrotic syndrome,
86
\_\_\_\_\_\_\_\_\_\_\_\_\_\_, or a combination of these two, is usually a
manifestation of **subtle or mild** glomerular abnormalities.
Asymptomatic hematuria or proteinuria
87
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is dominated by **oliguria or anuria (reduced or no urine flow), and
recent onset of azotemia**. It can result from glomerular, interstitial, or vascular injury or
acute tubular injury.
Acute renal failure
88
\_\_\_\_\_\_\_\_\_\_\_\_\_, characterized by prolonged symptoms and signs of uremia, is the
**end result of all chronic renal parenchymal diseases.**
Chronic renal failure
89
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_are dominated by **polyuria** (excessive urine formation), **nocturia**,
and **electrolyte disorders** (e.g., metabolic acidosis). They are the **result of diseases that
either directly affect tubular structure** (e.g., medullary cystic disease) or cause defects in
**specific tubular functions**.
The **latter can be inherited** (e.g., familial nephrogenic
diabetes, cystinuria, renal tubular acidosis) or acquired (e.g., lead nephropathy).
Renal tubular defects
90
\_\_\_\_\_\_\_\_\_\_\_\_ is characterized by bacteriuria and pyuria (bacteria and
leukocytes in the urine). The infection may be **symptomatic or asymptomatic,** and it may
affect the **kidney (pyelonephritis**) or the **bladder (cystitis).**
Urinary tract infection
91
\_\_\_\_\_\_\_\_\_- is manifested by severe spasms of pain (renal colic) and
**hematuria, often with recurrent stone formation.**
Nephrolithiasis (renal stones)
92
Urinary tract obstruction and renal tumors have varied clinical manifestations based on
the specific anatomic location and nature of the lesion.
Urinary tract obstruction
93
renal failure broadly progresses through a series of four stages that merge into one another.
1. In ____________ the **GFR is about 50% of norma**l. Serum **BUN and
creatinine values are normal**, and the patients are**asymptomatic.** However, they are
more **susceptible to developing azotemia** with an **additional renal insult.**
2. In ______________ the **GFR is 20% to 50%** of normal. **Azotemia** appears, **usually associated with anemia and hypertension**. **Polyuria and nocturia** can occur as a result
of **decreased concentrating ability**. Sudden stress (e.g., with nephrotoxins) may
**precipitate uremia.**
3. In ________ the GFR is **less than 20% to 25%** of normal. The kidneys **cannot
regulate volume and solute composition**, and patients develop e**dema, metabolic
acidosis, and hyperkalemia**. Overt uremia may ensue, with**neurologic, gastrointestinal,
and cardiovascular complications.**
4. In end-stage renal disease the **GFR is less than 5% of normal;** this is the **terminal stage
of uremia.** Recent clinical classifications of chronic kidney disease, adopted in part to
better stratify patients in clinical trials, adhere to this schema of progressive injury but
divide patients into five classes based on levels of GFR.
diminished renal reserve
renal insufficiency
chronic renal failure
end-stage renal disease
94
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
FLUID AND ELECTROLYTES
\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Dehydration
Edema
Hyperkalemia
Metabolic
acidosis
95
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
CALCIUM PHOSPHATE AND BONE
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
**Hyperphosphatemia**
**Hypocalcemia**
Secondary
**hyper**parathyroidism
Renal osteodystrophy
96
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
HEMATOLOGIC
\_\_\_\_\_\_\_\_\_\_
Anemia
Bleeding
diathesis (unusual susceptibility to bleeding (hemorrhage) mostly due to hypocoagulability, in turn caused by acoagulopathy (a defect in the system of coagulation)
97
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
CARDIOPULMONARY
\_\_\_\_\_\_\_\_\_\_\_\_\_
**Hyper**tension
Congestive heart
failure
Cardiomyopathy
Pulmonary edema
**Uremic pericarditis**
98
Principal Systemic Manifestations of Chronic Kidney Disease and Uremia
GASTROINTESTINAL
Nausea and vomiting
Bleeding
Esophagitis, gastritis,
colitis
Nausea and vomiting
Bleeding
Esophagitis, gastritis,
colitis
99
Clinical Manifestations of Renal Diseases
Myopathy
Peripheral
neuropathy
Encephalopathy
100
Clinical Manifestations of Renal Diseases
DERMATOLOGIC
Sallow color
Pruritus
Dermatitis
Sallow color
Pruritus
Dermatitis
101
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is one of the most common causes of chronic kidney disease in humans.
Glomeruli may be injured by a variety of factors and in the course of several systemic diseases
chronic
glomerulonephritis
102
**Systemic immunological diseases** such as systemic lupus erythematosus (SLE), **vascular
disorders**such as hypertension, metabolic diseases such as diabetes mellitus, and some
**hereditary conditions** such as **Fabry disease** often affect the \_\_\_\_\_\_\_\_\_\_. These are termed
**secondary glomerular diseases**.
glomerulus.
103
**only or predominant organ involved**. The latter constitute the various types of\_\_\_\_\_\_\_\_\_\_\_\_ or, because **some do not have a cellular inflammatory component,
glomerulopathy**. However,**both the clinical manifestations and glomerular histologic changes in
primary and secondary forms can be similar.**
primary
glomerulonephritis
104
**PRIMARY GLOMERULOPATHIES**
Acute proliferative glomerulonephritis
Post-infectious
Other
Rapidly progressive (crescentic)
glomerulonephritis
Membranous glomerulopathy
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis
105
SYSTEMIC DISEASES WITH GLOMERULAR INVOLVEMENT
\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic
polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
106
HEREDITARY DISORDERS GLOMERULUS
Alport syndrome
Thin basement membrane
disease
Fabry disease
107
The clinical manifestations of glomerular disease are clustered into the **five major glomerular syndromes** summarized in Table 20-3 .
**Both the primary** glomerulopathies and the **systemic
disease**s**affecting the glomerulu**s can r**esult in these syndromes**. Because glomerular diseases
are often associated with systemic disorders, mainly **diabetes mellitus, SLE, vasculitis, and
amyloidosis,**in any patient with manifestations of glomerular disease it is**essential to consider
these systemic conditions.**
Nephritic syndrome
Rapidly progressive glomerulonephritis
Nephrotic syndrome
Chronic Renal Failure
Isolated urinary abnormalities
108
\_\_\_\_\_\_\_\_\_\_\_\_ **Hematuria**,
azotemia,
variable proteinuria,
oliguria,
edema, and
hypertension
Nephritic syndrome
109
\_\_\_\_\_\_\_\_\_\_\_\_\_
Acute nephritis, proteinuria, and acute renal failure
Rapidly progressive
glomerulonephritis
110
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\>3.5 gm/day proteinuria, hypoalbuminemia, hyperlipidemia,
lipiduria
Nephrotic syndrome
111
\_\_\_\_\_\_\_\_\_\_\_\_\_\_➙ uremia progressing for months to years
Chronic renal failure Azotemia
112
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Glomerular hematuria and/or subnephrotic proteinuria
Isolated urinary abnormalities
113
Many clinical manifestations of glomerular disease result from **perturbations of specific
components of the glomerular tuft,** so we present key anatomic structures that are subject to
alteration in disease. The \_\_\_\_\_\_\_\_consists of an **anastomosing network of capillaries** lined
by **fenestrated endothelium** invested by two layers of epithelium ( Fig. 20-1 ).
glomerulus
114
The glomerulus consists of an anastomosing network of capillaries lined
by fenestrated endothelium invested by two layers of epithelium ( Fig. 20-1 ).
The\_\_\_\_\_\_\_\_\_\_- is incorporated into and becomes an intrinsic part of the capillary wall, separated
**from endothelial cells** by a **basement membrane**. The \_\_\_\_\_\_\_\_\_\_, situated on the
Bowman capsule, lines the urinary space, the cavity in which plasma filtrate first collects.
visceral epithelium
parietal epithelium
115
The glomerular capillary wall is the filtering membrane and consists of the following
structures:
**endothelial cells**
**glomerular basement membrane (GBM)**
**visceral epithelial cells (podocytes)**
**mesangial cells**
116
A _______________ with a thick electron-dense central layer, the
**lamina densa**, and **thinner electron-lucent peripheral layers,** the **lamina rara interna** and
**lamina rara externa**. The GBM consists of collagen **(mostly type IV)**, laminin, polyanionic
proteoglycans (mostly heparan sulfate), **fibronectin**, **entactin**, and several other
glycoproteins.
**Type IV collagen** forms a network suprastructure to which other
glycoproteins attach. The building block (monomer) of this network is a triple-helical
molecule made up of three α chains, composed of one or more of six types of α chains (
**α1 to α6 or COL4A1 to COL4A6**), the most common consisting of α1, α2, α1. [3,] [5]
Each molecule consists of a 7S domain at the N terminus, a triple-helical domain in the
middle, and a globular noncollagenous domain (NC1) at the C terminus. The NC1
domain is important for helix formation and for assembly of collagen monomers into the
basement membrane suprastructure. Glycoproteins (laminin, entactin) and proteoglycans (heparan sulfate, perlecan) attach to the collagenous suprastructure.
These **biochemical determinants are critical to understanding glomerular diseases**. For
example, as we shall see, the antigens in the NC1 domain are the targets of antibodies
in anti-GBM nephritis; genetic defects in the α-chains underlie some forms of hereditary
nephritis; and the proteoglycan content of the GBM may contribute to its permeability
characteristics.
**glomerular basement membrane (GBM)**
117
The\_\_\_\_\_\_\_\_\_\_\_\_\_ are structurally complex cells that possess
interdigitating processes embedded in and adherent to the **lamina rara externa** of the
basement membrane. Adjacent **foot processes (pedicels)** are separated by 20- to 30-
nm-wide filtration slits, which are bridged by a thin diaphragm (see Fig. 20-2 ).
visceral epithelial cells (podocytes)
118
The entire glomerular tuft is supported by \_\_\_\_\_\_\_\_\_\_\_\_lying between the capillaries.
Basement membrane–like **mesangial matrix** forms a meshwork through which the
mesangial cells are centered (see Fig. 20-1 ). These cells, of mesenchymal origin, are
contractile, phagocytic, and capable o**f proliferation**, of laying down both matrix and
collagen, and of secreting several biologically active mediators. Biologically, they are
most akin to vascular smooth muscle cells and pericytes. They are, as we shall see,
important players in many forms of human glomerulonephritis.
mesangial cells
119
The major characteristics of normal glomerular filtration are an \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_-, because of the **highly fenestrated nature** of the endothelium, and
impermeability to proteins, such as molecules of the size of albumin (∼3.6-nm radius; 70
kilodaltons [kD] molecular weight) or larger.
extraordinarily high permeability
to water and small solutes
120
The latter property of the glomerular filtration
barrier **allows discrimination** among various protein molecules, depending on their **\_\_\_\_\_\_\_\_\_\_\_\_**and **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**. This size- and
charge-dependent barrier function is accounted for by the **complex structure of the capillary
wall**, the**collagenous porous**and**charged structure of the GBM**, and the many anionic moieties
present within the wall, including the **acidic proteoglycans** of the GBM and the
**sialoglycoproteins of epithelial** and endothelial cell coats (also called **glycocalyx**).
**size** (the
larger, the less permeable)
**charge** (the more cationic, the more permeable)
121
The chargedependent
restriction is important in the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
because albumin is an anionic molecule of a pI 4.5.
virtually complete exclusion of albumin from the filtrate,
122
The\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, also known as a
**podocyte**, is important for the **maintenance of glomerular barrier function**; its ***slit diaphragm*
presents a size-selective distal diffusion barrier**to the filtration of proteins, and it is the**cell type
that is largely responsible for synthesis of GBM components.**
visceral epithelial cell
123
Proteins located in the slit
diaphragm **control glomerular permeability**. Three of the most important slit diaphragm proteins
are depicted in Figure 20-3 .\_\_\_\_\_\_\_\_\_\_\_ is a **transmembrane protein** with a large extracellular
portion made up of immunoglobulin (Ig)-like domains. This molecules extend toward each
other from neighboring foot processes and dimerize across the slit diaphragm. Within the
cytoplasm of the foot processes, **\_\_\_\_\_\_\_\_\_ forms molecular connections with podocin**, CD2-
associated protein, and ultimately the **actin cytoskeleton**. The number of identified slit
diaphragm proteins continues to grow rapidly, and more comprehensive descriptions of their
complex localization and interactions have been published. [6,] [7] The importance of these
proteins in maintaining glomerular permeability is demonstrated by the observation that
**mutations in the genes encoding them give rise to nephrotic syndrome** (discussed later). This
has resulted in renewed appreciation of the importance of the slit diaphragm in glomerular
barrier function and its contribution to protein leakage in disease states. [
1. Nephrin
2. podocin
3. actin cytoskeleton
124
HISTOLOGIC ALTERATIONS
Various types of glomerulopathies are characterized by one or more of four basic tissue
reactions.
Hypercellularity.
Basement Membrane Thickening.
Hyalinosis and Sclerosis.
125
Some inflammatory diseases of the glomerulus are characterized by an **increase in the number
of cells in the glomerular tufts.** This is characterized by one or more
combinations of the following:
Hypercellularity
• Cellular proliferation of **mesangial or endothelial cells**.
• Leukocytic infiltration consisting of **neutrophils, monocytes, and, in some diseases,
lymphocytes.**
• **Formation of crescents**. These are accumulations of cells composed of **proliferating
parietal epithelial cells and infiltrating leukocytes.** The epithelial cell proliferation that
characterizes crescent formation occurs following an **immune/inflammatory injury (see
later).**
**Fibrin,** which leaks into the urinary space, often through ruptured basement
membranes, has been long thought to be the molecule that elicits the crescentic
response.
In support of this, fibrin can be demonstrated **immunohistochemically in the
glomerular tufts**and**urinary spaces of glomeruli that contain crescents**. Mice that are
deficient in fibrinogen are protected to a degree from crescent formation, and mice that
are deficient in molecules important in fibrinolysis (e.g., plasminogen activators) exhibit
enhanced crescent formation in models of anti-GBM antibody–mediated crescentic
glomerulonephritis. [9] Other molecules that have been implicated in crescent formation
and recruitment of leukocytes into crescents include procoagulants such as tissue factor
and cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon-γ.
126
In hypercellularity what type of cells proliferate?
Cellular proliferation of **mesangial or endothelial cells.**
127
These are accumulations of cells composed of **proliferating
parietal epithelial cells**and**infiltrating leukocytes.** The epithelial cell proliferation that
characterizes crescent formation **occurs following an immune/inflammatory injury** (see
later).
Formation of crescents.
128
\_\_\_\_\_\_\_\_\_, which leaks into the urinary space, often through **ruptured basement
membranes**, has been long thought to be the molecule that**elicits the crescentic
response**. In support of this, fibrin can be demonstrated immunohistochemically in the
**glomerular tuft**s and **urinary spaces of glomeruli** that **contain crescents**.
Fibrin
Note : Mice that are
**deficient in fibrinogen** are protected to a degree **from crescent formation**, and mice that
are **deficient in molecules important in fibrinolysis** (e.g., plasminogen activators) exhibit
**enhanced crescent formation in models of anti-GBM antibody–mediated crescentic
glomerulonephritis.** [9]
129
Other molecules that have been implicated in \_\_\_\_\_
and recruitment of leukocytes into crescents include \_\_\_\_\_\_\_\_\_\_
**crescent formation**
**procoagulants such as tissue factor**
and **cytokines such as interleukin-1 (IL-1**), t**umor necrosis factor (TNF**), and **interferon-γ.**
130
\_\_\_\_\_\_\_\_\_\_\_\_\_
By light microscopy, this change appears as **thickening of the capillary walls**, best seen in
sections stained with **periodic acid–Schiff (PAS**).
Basement Membrane Thickening.
131
By electron microscopy such thickening takes
one of two forms:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
• **Deposition** of amorphous electron-dense material, most often **immune complexes**, on
the **endothelial or epithelial side of the basement membrane or within the GBM itself**.
**Fibrin, amyloid, cryoglobulins, and abnormal fibrillary proteins** may also deposit in the
GBM.
• Thickening of the basement membrane due to **increased synthesis of its protein**
**components**, as occurs in **diabetic glomerulosclerosis.**
132
\_\_\_\_\_\_\_\_\_\_\_, as applied to the glomerulus, denotes the **accumulation of material** that is
**homogeneous and eosinophilic by light microscopy**.
Hyalinosis
133
By electron microscopy the \_\_\_\_\_\_\_\_\_\_\_\_- is
**extracellular and amorphous**. It is made up of **plasma proteins** that have insudated from the
circulation into glomerular structures. When extensive, this change contributes to **obliteration of
the capillary lumens of the glomerular tuft**.
hyalin
134
\_\_\_\_\_\_\_\_\_\_\_\_- is usually a consequence of **endothelial or
capillary wall injury**and**typically the end result of various forms of glomerular damage**. It is a
**common feature of focal segmental glomerulosclerosis.**
Hyalinosis
135
Hyalinosis is usually a consequence of **endothelial or
capillary wall injury**and typically the end result of various forms of glomerular damage. It is a
common feature of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
focal segmental glomerulosclerosis.
136
\_\_\_\_\_\_\_\_\_\_\_\_\_- is characterized by **accumulations of extracellular collagenous matrix,** either **confined
to mesangial areas**as is often the case in**diabetic glomerulosclerosis,** or involving the capillary
loops, or both. The sclerosing process may also result in **obliteration of some or all of the
capillary lumens**in affected glomeruli, which in turn**can result in formation of fibrous adhesions**
between the sclerotic portions of glomeruli and the **nearby parietal epithelium and Bowman
capsules.**
Sclerosis
137
Because many of the primary glomerulopathies are of unknown cause, they are often classified
by their histology, as can be seen in Table 20-2 . The histologic changes can be further
subdivided by their distribution into :
diffuse
global
focal
segmental
138
\_\_\_\_\_\_\_\_\_\_\_\_\_, involving all glomeruli;
diffuse
139
\_\_\_\_\_\_\_\_\_\_, involving the entire
glomerulus;
global
140
\_\_\_\_\_\_\_\_\_\_, involving only a proportion of the glomeruli;
focal
141
\_\_\_\_\_\_\_\_\_\_\_, affecting a part of
each glomerulus; and by either capillary loop or mesangial, affecting predominantly capillary or
mesangial regions. These terms are sometimes appended to the histologic classifications.
segmental
Note: 50 %
142
Immune Mechanisms of Glomerular Injury
1. ANTIBODY-MEDIATED INJURY IN SITU IMMUNE COMPLEX DEPOSITION
2. CIRCULATING IMMUNE COMPLEX DEPOSITION
3. CYTOTOXIC ANTIBODIES
4. CELL-MEDIATED IMMUNE INJURY
5. ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY
143
WHAT ARE THE ANTIBODY-MEDIATED INJURY
IN SITU IMMUNE COMPLEX DEPOSITION?
1. Fixed intrinsic tissue antigens
* NC1 domain of collagen type IV antigen (anti-GBM
nephritis)
* Heymann antigen (membranous glomerulopathy)
* Mesangial antigens
* Others
2. Planted antigens
* Exogenous (infectious agents, drugs)
* Endogenous (DNA, nuclear proteins, immunoglobulins, immune
complexes, IgA)
144
CIRCULATING IMMUNE COMPLEX DEPOSITION
1. Endogenous antigens (e.g., DNA, tumor
antigens)
2. Exogenous antigens (e.g., infectious products)
145
Two forms of antibody-associated injury have been established:
(1) injury by antibodies
reacting in situ within the glomerulus, either binding to insoluble fixed (intrinsic) glomerular
antigens or to molecules planted within the glomerulus, and (2) injury resulting from deposition
of circulating antigen-antibody complexes in the glomerulus. In addition, there is experimental
evidence that cytotoxic antibodies directed against glomerular cell components may cause
glomerular injury. These pathways are not mutually exclusive, and in humans, all may contribute
to injury.
146
\_\_\_\_\_\_\_\_\_-
In these forms of injury, antibodies react directly with intrinsic tissue antigen, or antigens
**“planted**” in the glomerulus from the circulation. The best established experimental models for
**anti–glomerular antibody–mediated glomerular injury,** for which there are *counterparts in human*
disease, are **anti–glomerular basement membrane (antiGBM) antibody–induced
glomerulonephritis and Heymann nephritis.**
Immune Complex Deposition Involving Intrinsic and in Situ Renal Antigens
