1. Differentiate among renal diseases of glomerular, tubular, interstitial and vascular origin.

RENAL DISEASES
Diseases of the kidney are often classified into four types based on the morphologic component initially affected:
glomerular, tubular, interstitial, or vascular. Initially, renal disease may affect only one morphologic component;
however, with disease progression, other components are involved because of their close structural and functional
interdependence. Susceptibility to disease varies with each structural component. Glomerular diseases most often are
immune-mediated, whereas tubular and interstitial diseases result from infectious or toxic substances. In contrast,
vascular diseases cause a reduction in renal perfusion that subsequently induces both morphologic and functional
changes in the kidney.

GLOMERULAR
Diseases that damage glomeruli are varied and include immunologic, metabolic, and hereditary disorders. Systemic
disorders are technically secondary glomerular diseases because they initially and principally involve other organs; the
glomeruli become involved as a consequence as the systemic disease progresses. In contrast, primary glomerular
diseases specifically affect the kidney, which is often the only organ involved. Primary glomerular disorders, collectively
called glomerulonephritides, consist of several different types of glomerulonephritis.

TUBULAR
In addition to diseases of the glomerulus, diseases of the tubules affect urinalysis results. These disorders can be
acquired or inherited. Some tubular diseases result from injury and damage to the tubule and some from metabolic
conditions that damage the tubule.

INTERSTITIAL
This term is used for infections and inflammatory conditions that affect both the interstitium and the tubules, which are
in close proximity. Urinary tract infections can affect both the kidney (a tubulointerstitial disease) and the lower urinary
tract and are the most common urinary tract diseases. Acute interstitial nephritis is an inflammatory tubulointerstitial
disease.

VASCULAR
Because kidney function is directly dependent on receiving 25% of the cardiac output, any disruption in the blood supply
will affect renal function. Likewise, any changes in the vasculature of the kidney directly affect the close interrelationship
and interdependence of the blood vessels with the renal interstitium and tubules. Therefore, disorders that alter the
blood vessels or the blood supply to the kidney can cause renal disease.

REFERENCE: Graff’s Textbook of Urinalysis and Body Fluids

Fundamentals of Urine and Body Fluids by Nancy Brunzel
(Please also refer to Strasinger)

2. Describe the process by which immunologic damage is produced to the glomerular membrane.

With circulating immune complex–mediated disease, the glomerulus may be considered an “innocent bystander”
because it does not incite the reaction. The antigen is not of glomerular origin. It may be endogenous, as in the GN
associated with systemic lupus erythematosus, or it may be exogenous, as is probable in the GN that follows certain
bacterial (streptococcal), viral (hepatitis B), parasitic (Plasmodium falciparum malaria), and spirochetal (Treponema
pallidum) infections. Often the inciting antigen is unknown, as in most cases of membranoproliferative GN (MPGN).

Whatever the antigen may be, antigen–antibody complexes are formed in situ or in the circulation and are then trapped
in the glomeruli, where they produce injury, in large part through the activation of complement and the recruitment of
leukocytes. Injury also may occur through the engagement of Fc receptors on leukocytes independent of complement
activation, as cross-linking of Fc receptors by IgG antibodies also results in leukocyte activation and degranulation.
Regardless of the mechanism, the glomerular lesions usually consist of leukocytic infiltration (exudation) into glomeruli
and variable proliferation of endothelial, mesangial, and parietal epithelial cells.

Once deposited in the kidney, immune complexes may eventually be degraded or phagocytosed, mostly by infiltrating
leukocytes and mesangial cells, and the inflammatory changes may then subside.

A. Caused by In Situ Immune Complexes

-Antibody deposition in the glomerulus is a major pathway of glomerular injury. As noted, antibodies in this form of
injury react directly with fixed or planted antigens in the glomerulus. Immune reactions in situ, trapping of circulating
complexes, interactions between these two events, and local hemodynamic and structural determinants in the
glomerulus all contribute to the morphologic and functional alterations in GN. Antibodies also may react in situ with
previously “planted” nonglomerular antigens, which may localize in the kidney by interacting with various intrinsic
components of the glomerulus.
The following factors affect glomerular localization of antigen, antibody, or immune complexes: the molecular charge
and size of the reactants; glomerular hemodynamics; mesangial function; and the integrity of the chargeselective
glomerular barrier. The localization of antigen, antibody, or immune complexes in turn determines the glomerular injury
response.

B. Anti-Glomerular Basement Membrane Antibody–Mediated

- In this type of injury, antibodies are directed against fixed antigens in the GBM. Antibody–mediated GN in humans
results from the formation of autoantibodies directed against the GBM. Deposition of these antibodies creates a linear
pattern of staining when the bound antibodies are visualized with immunofluorescence microscopy, in contrast with the
granular pattern described for other forms of immune complex–mediated nephritis. This distinction is useful in the
diagnosis of glomerular disease. A conformational change in the α3 chain of the type IV collagen of the GBM appears to
be key in inciting autoimmunity.

C. Other Mechanisms of Glomerular Injury

 Podocyte Injury
Podocyte injury can be induced by antibodies to podocyte antigens; by toxins, as in an experimental model of
proteinuria induced by the ribosome poison puromycin; conceivably by certain cytokines; or by still poorly
characterized circulating factors, as in some cases of focal segmental glomerulosclerosis. Podocyte injury is
reflected by morphologic changes, which include effacement of foot processes, vacuolization, and retraction and
detachment of cells from the GBM, and clinically by proteinuria. In most forms of glomerular injury, loss of
normal slit diaphragms is key in the development of proteinuria. Functional abnormalities of the slit diaphragm
also may result from mutations in its structural components, such as nephrin and the associated podocin. Such
mutations cause rare hereditary forms of the nephrotic syndrome.
 Nephron Loss
Once renal disease, glomerular or otherwise, destroys sufficient nephrons to reduce the GFR to 30% to 50% of
normal, progression to end-stage kidney disease proceeds inexorably at varying rates. Affected persons have
proteinuria, and their kidneys show widespread glomerulosclerosis. Such progressive sclerosis may be initiated,
at least in part, by the adaptive changes that occur in the remaining glomeruli not destroyed by the initial
disease. These remaining glomeruli undergo hypertrophy to maintain renal function. This hypertrophy is
associated with hemodynamic changes, including increases in single-nephron GFR, blood flow, and transcapillary
pressure (capillary hypertension). These alterations ultimately become “maladaptive” and lead to further
endothelial and podocyte injury, increased glomerular permeability to proteins, and accumulation of proteins
and lipids in the mesangial matrix. This is followed by capillary obliteration, increased deposition of mesangial
matrix and plasma proteins, and ultimately by segmental (affecting a portion) or global (complete) sclerosis of
glomeruli. The latter results in further reductions in nephron mass and a vicious circle of progressive
glomerulosclerosis.

REFERENCE: Robbins Basic Pathology, 9 th ed.

3. Define glomerulonephritis

Glomerulonephritis is a sterile, inflammatory condition affecting the glomerulus, resulting in protein, blood, and casts in
the urine. There are multiple types of glomerulonephritis, and one type may change into another type over time, the
condition may become chronic, and glomerulonephritis may also lead to nephrotic syndrome.

REFERENCE: Graff’s Textbook of Urinalysis and Body Fluids

4. Name a significant urinary sediment constituent associated with all of the disorders

(answers, refer to Strasinger and read the objectives. Compare the urinalysis result and make conclusion)

5. Relate laboratory results associated with nephrotic syndrome to the disease process.

The nephrotic syndrome refers to a clinical complex that includes

• Massive proteinuria, with daily protein loss in the urine of 3.5 g or more in adults

• Hypoalbuminemia, with plasma albumin levels less than 3 g/dL

• Generalized edema, the most obvious clinical manifestation

• Hyperlipidemia and lipiduria.

REFERENCE: Robbins Basic Pathology, 9th ed.
The nephrotic syndrome is a group of clinical features that occur simultaneously. Representingnincreased permeability
of the glomeruli to the passage of plasma proteins, most notably albumin, nephrotic syndrome is characterized by heavy
proteinuria (3.5 g/day or more). Additional features include hypoproteinemia, hyperlipidemia, lipiduria, and edema.
Plasma albumin levels are usually less than 3 g/dL because liver synthesis is unable to compensate for the large amounts
of protein being excreted in the urine. Albumin is the predominant protein lost because of its high plasma
concentration. However, proteins of equal or smaller size, such as immunoglobulins, low-molecular-weight complement
components, and anticoagulant cofactors, are also excreted in increased amounts. As a result, patients with the
nephrotic syndrome are more susceptible to infections and thrombotic complications.
REFERENCE: Fundamentals of Urine and Body Fluids by Nancy Brunzel