7. Renal Pathology Flashcards
Introduction
• The study of kidney diseases is facilitated by dividing them into those that affect the four basic morphologic components: ____, tubules, interstitium, and ____
• Most glomerular diseases are ____ mediated
• Whereas tubular and interstitial disorders are frequently caused by
____ or infectious agents
• Whatever the origin, all forms of chronic kidney disease ultimately damage all four components of the kidney, culminating in what has been called ____
glomeruli blood vessels immune toxins end stage kidney disease
Renal disease classification
- Classified based on the presenting ____ syndrome, laboratory investigations, and ____ pattern
- Renal disease is usually manifested by a limited number of symptoms that are commonly grouped in clinical syndromes
- ____
- Nephritic
- ____
- Acute kidney injury
- ____ kidney disease
- End stage renal disease
clinical morpologic azotemia nephrotic chronic
Glomerular disease
- Nephritic syndrome is a clinical entity caused by glomerular disease and is dominated by the ____ onset of either grossly visible ____ (red blood cells in urine) or microscopic hematuria with dysmorphic red cells and red ____ on urinalysis
- Classic presentation of ____
• Nephrotic syndrome, also due to glomerular disease, is characterized
by heavy ____ (more than 3.5 gm/day)
• Damage to the filtration barrier of the glomerulus allows proteins particularly ____ to be filtered into the urine
• The normal glomerulus is highly permeable to water and small solutes, because of the fenestrated nature of the endothelium, and impermeable to proteins of the size of albumin or larger
acute
hematuria
cell casts
acute poststrep glomerulonpehritis
proteinuria
albumin
Renal biopsy
- Renal ____ is an important tool used in the evaluation of patients with renal disease
- Kidney reacts to a variety of injurious agents with a limited number of histopathologic patterns of injury, a given clinical syndrome can be associated with ____ histopathologic patterns, while a single histopathologic pattern may be linked to more than one ____.
- Diagnosis is with routine ____, immunofluorescence and ____.
biopsy several syndrome light microscopy electron microscopy
Pathologic responses of the glomerulus to injury
- Glomeruli may be injured by a variety of factors and in the course of several systemic diseases
- Injuries are characterized by four basic tissue reactions
- ____
- Basement membrane thickening
- ____
- Sclerosis
• Many primary glomerulopathies are classified by their ____
hypercellularity
hyalinosis
histology
Hypercellularity
- Some inflammatory diseases of the glomerulus are characterized by an increase in the number of cells in the ____
- Proliferation of ____ or endothelial cells
- Formation of ____
- These are accumulations of cells composed of proliferating glomerular ____ cells and infiltrating ____ cells
glomerular tufts mesangial crescents epithelial inflam
- Mesangial proliferation based on injuries
- Affliction to glomerulus
- May limit actual ____ of the glomerulus because the capillaries spaces are diminished from their original patency
function
• Section of kidney
○ Do not slice all the way ____
○ Take a rectangular section, and it’s stained with H&E
○ Depending on location > will find more glomerular than tubular structures
• Black is glomerulus
• Yellow is the crescent area of ____
○ There has been ____
hypercellularity
damage
• On the right is a normal glomerulus
○ Tubules surrounding the glomerulus
○ Nicely fenestrated, showing the capillary spaces
• On the left: crescent formation
○ Much more ____
○ Would get “less water ____” if you poured through it
dense
return
Basement membrane thickening
• By light microscopy, this change appears as thickening of the ____
• By electron microscopy the thickening takes one of three forms
• Deposition of ____ on the ____ or epithelial side of the basement membrane or ____ the glomerular basement membrane itself
• Increased synthesis of the ____ components of the basement membrane
Formation of additional ____ of basement membrane matrices
* Increased synthesis of hyaline that thickens the basement membrane (\_\_\_\_) * Basement thickening has different forms, and can be determined on an EM-level; and based on the level, renal pathologists can make a more \_\_\_\_ diagnosis
capillary walls immune complexes endothelial within protein layers sclerosis
Hyalinosis and sclerosis
- Accumulation of hyalin material in the glomerulus
- Hyalin is an ____ amorphous material composed of ____ proteins
- Microscopically can present as pink ____ material as a result of degeneration in certain tissues
- When extensive, these deposits may obliterate the capillary ____
- Sclerosis is characterized by deposition of extracellular ____ matrix
- It may be confined to ____ areas
- The sclerosing process may also result in obliteration of the capillary ____ in affected glomeruli• Extensive hyaline can decrease the function of the kidneys
• Not specific to the kidney; any cell in body will have a ____ response
• Sclerosis - fancy way of saying scar
○ Lose the ability to filter properly
extracellular plasma glassy lumens collagenous mesangial lumens similar
• Within the dotted line you see the hyelnosis occurring in cells
○ Outside of the dotted lines - normal liver parenchyma - these are still ____
• On the right side - you see globs of light ____ areas
functioning
pink
Pathogenesis of glomerular injury
- ____ mechanisms underlie most forms of primary glomerulopathy and many of the secondary glomerular disorders
- Antibody instigated injury takes two forms
- Injury by antibodies reacting in situ within the glomerulus, either binding to ____ glomerular antigens or ____ molecules planted within the glomerulus
- Injury resulting from deposition of circulating ____ in the glomerulus
immune
intrinsic
extrinsinc
antigen-antiobdy complexes
• A - complexes circulating in the body > go to kidneys and get filtrated, but they deposit within the ____ > inflammatory response and damage to the glomerulus
• B - other arm of immune damage > have something within the BM already that is perceived as ____ > immune cells attack that
• The pattern of immune deposition is different
○ In B - it’s ____ - natural structure of glomerulus
○ In A - it’s more ____ - land wherever they land; stochastic
• C - Heymann; one of the classical experiments that helped our understanding of the different arms of immune damage to the kidney; done on rats, antigen found in normal structures in kidneys > induced an inflammatory response similar to the one happening in ____
BM antigen linear granular B
Antibodies against planted antigens
- Antibodies can react in situ with antigens that are not normally present in the glomerulus but are “____” there
- Such antigens may localize in the kidney by interacting with various intrinsic components of the glomerulus.
- Planted antigens include:
- Viral, bacterial, and parasitic ____ ,and drugs
- ____ molecules that bind to anionic components of the glomerulus
- ____, nucleosomes, and other nuclear proteins, which have an affinity for GBM components
- Large aggregated proteins (e.g., aggregated ____), which deposit in the mesangium because of their size
- ____ antigens that become “planted” in the kidneys of infants who have antibodies to bovine albumin. The antibodies bind to planted antigens and infants develop ____
planted products cationic DNA immunoglobulins bovine milk nepropathy
Disease caused by antibodies directed against normal components
- Antibodies bind to intrinsic (normal components) antigens distributed along the entire ____ of the glomerular basement membrane
- The glomerular basement membrane antigen that is responsible for intrinsic antibody-induced glomerulonephritis is a component of type ____ collagen that is critical for maintenance of basement membrane structure
- Although intrinsic antibody-induced glomerulonephritis accounts for fewer than ____% of cases of human glomerulonephritis, it causes severe ____ and crescentic glomerular damage and the clinical syndrome of rapidly ____
length IV 5 necrotizing progressive glomerulonephritis
• With the antigens that attack the normal components > ____ staining of the structure
linear
Circulating immune complexes
- Glomerular injury is caused by the trapping of circulating ____ within glomeruli
- The antibodies have no immunologic ____ for glomerular constituents, and the complexes localize within the glomeruli because of their ____ properties and the hemodynamic factors
- The antigens that trigger the formation of circulating immune complexes may be of endogenous origin such as ____ diseases, or exogenous, such as ____ products
- Some ____ antigens are thought to cause immune complex- mediated nephritis
- More ____ presentation - less of a consistent deposition of immune complexes
- End up in structures through ____ factors
antigen-antibody complexes specificity phhysicochemical autoimmune bacterial tumor granular
Immune complex disease 1. \_\_\_\_: protein antigen triggers immune response, i.e. antibodies 2. \_\_\_\_: Circulating antigen-antibody complexes deposits into various tissues 3. \_\_\_\_: acute inflammatory reaction leads to tissue damage
* Immune complex deposits in glomerulus > \_\_\_\_ released > prolonged, will cause damage to structures * Can result in end-stage renal disease
formatino
deposition
inflammation
complement
- ____ deposition of immune complexes
* End up there via factors of ____ and ____
granular
blood flow
charges
Acute proliferative (poststreptococcal) glomerulonephritis
• This cluster of diseases is characterized histologically by diffuse proliferation of ____ cells associated with influx of ____
• These lesions are typically caused by ____
• The most common underlying infections are ____, but the
disorder may also be associated with other infections
• It usually appears ____ weeks after a streptococcal infection of the pharynx or skin (____)
glomerular leukocytes immune complexes streptococcal 1-4 impetigo
• Seen in \_\_\_\_ children • \_\_\_\_ infection • Crusting around the faces ○ \_\_\_\_ infection on initial diagnosis is not incorrect ○ But with impetigo > poststrep \_\_\_\_
younger
bacterial
herpetic
glomerulonephritis
Clinical
- Poststreptococcal glomerulonephritis occurs most frequently in children 6 to 10 years of age, but children and ____ of any age can also be affected
- Young child abruptly develops malaise, fever, nausea, ____ (smoky or cola colored urine) 1 to 2 weeks after recovery from a sore throat
- More than 95% of affected children eventually ____ renal function with conservative therapy aimed at maintaining ____ and water balance
- Self-____, or conservative therapy is the main mode of treatment
- Most recover from this
adults hematuria recover sodium limiting
• Epithelial ____ (number of nuclei), but intermixed within the nuclei are ____ (acute inflammation)
hypercellularity
neutrophils`
