7. Renal Pathology Flashcards by J L

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

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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

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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

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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

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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

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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

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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

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• 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

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• 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

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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

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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

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• 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

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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

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• 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

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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

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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

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• With the antigens that attack the normal components > ____ staining of the structure

linear

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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

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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

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____ deposition of immune complexes

* End up there via factors of ____ and ____

granular
blood flow
charges

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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

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• Seen in \_\_\_\_ children
	• \_\_\_\_ infection
	• Crusting around the faces
		○ \_\_\_\_ infection on initial diagnosis is not incorrect
		○ But with impetigo > poststrep \_\_\_\_

younger
bacterial
herpetic
glomerulonephritis

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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

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• Epithelial ____ (number of nuclei), but intermixed within the nuclei are ____ (acute inflammation)

hypercellularity

neutrophils`

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Focal segmental glomerulosclerosis • The most frequent systemic causes of nephrotic syndrome are ____, amyloidosis, and ____ • A histological characteristic of nephrotic syndrome is ____, which is progressive fibrosis involving portions of some glomeruli • The ____ of the capillary lumen usually affects one or more lobules of the glomerular tufts • Early lesions may show an increased ____ cellularity • Clinically characterized by massive ____ and associated with a high incidence of renal failure

diabetes SLE focal segmental glomerulosclerosis sclerosis mesangial proteinuria

• Looks similar to poststreptococcal - less epithelial ____, but you see a ____ that has occurred

proliferation | sclerosis

Membranous glomerulopathy * Form of ____ immune complex-mediated disease characterized by basement membrane ____and capillary wall injury associated with protein ____ * Antigens can be ____ or endogenous * Primary (idiopathic) * Considered to be an ____ disease * Most cases autoantigen is the ____ * Secondary * For example, in systemic lupus erythematosus, membranous glomerulopathy is associated with deposition of complexes of self ____ and autoantibodies * Exogenous antigens can include those derived from ____ * Drugs

chronic thickening leakage exogenous autoimmune phospholipase A2 receptor nuclear proteins hepatitis B

Clinical * Membranous glomerulopathy usually presents with onset of the ____ syndrome * ____ and mild hypertension can be present in 15 to 25% of cases * It is necessary in any patient to first rule out the ____ causes described earlier, since treatment of the underlying condition or discontinuance of the offending drug can reverse the injury * Progression is associated with increasing sclerosis of ____, rising serum ____ reflecting renal insufficiency, and development of ____

``` nephrotic hematuria secondary glomeruli creatinine HTN ```

membranous glomerulopathy * Capillary lumen rim has ____ * ____ - thickening of the membrane * Small ____ like projections > rim the capillary lumens, which you can't appreciate from the H&E * Additional stain helps you make the diagnosis

thickened jones silver stain spike

``` Glomerular lesions associated with systemic disease • ____ • Diabetic nephropathy • ____ • Bacterial endocarditis ```

lupus nephritis | amyloidosis

Lupus nephritis • Systemic lupus erythematosus is an ____ disease involving multiple organs characterized by an array of autoantibodies, particularly ____ • Injury is caused mainly by deposition of ____ and binding of antibodies to various cells and tissues • Injury to the skin, joints, kidney are prominent • Up to 50% of systemic lupus patients have clinically significant ____ involvemen

autoimmune antinuclear antibodies immune complexes renal

• Damage manifested with ____ capillary loops as we compare with normal glomerulus ○ Thinner, fenestrated look to it

thickened

Diabetic nephropathy * Diabetes mellitus is a major cause of renal morbidity and mortality, and diabetic nephropathy is the leading cause of ____ in the United States * Advanced or end-stage kidney disease occurs in as many as ____% of both insulin-dependent 1 diabetics and type 2 diabetics * The kidneys are prime ____ of diabetes; renal failure is second only to ____ as a cause of death from this disease * Approximately 15% to 30% of individuals with long-term diabetes develop ____, and in most instances it is associated with renal failure * One of the most consistent morphologic features of diabetes is diffuse thickening of ____

``` CK failure 40 targets MI nodular glomerulosclerosis basement membranes ```

Glomerular lesions in diabetic nephropathy • Capillary ____ thickening occurs in virtually all cases of diabetic nephropathy and is part and parcel of the diabetic microangiopathy • Despite the increase in the thickness of basement membranes, diabetic capillaries are more ____ than normal to plasma proteins • Nodular glomerulosclerosis also known as ____ disease are characteristic findings • Nodules of matrix situated in the ____ of the glomerulus • As the disease advances, the individual nodules enlarge and may eventually compress and engulf capillaries, obliterating the ____ • As a consequence of the glomerular and arteriolar lesions, the kidney suffers from ____, develops tubular atrophy and interstitial fibrosis, and usually undergoes overall ____ in size

``` BM leaky kimmelstiel-wilson periphery glomerular tuft ischemia contraction ```

diabetic nephropathy • Dense, round pink area > ____ > diamond area shows one example

nodules

Amyloidosis • Amyloidosis is a condition associated with deposits of ____ proteins into organs that cause tissue damage and dysfunction • Let’s save the classification of various types of amyloidosis for another day • These abnormal fibrils are produced by the aggregation of improperly ____ proteins that result in a ____ conformation • Normally abnormal fibrils are degraded, but in amyloidosis these quality control mechanisms fail and proteins accumulate ____ of cells • Renal involvement gives rise to proteinuria that can cause ____ • Progressive obliteration of glomeruli in advanced cases ultimately leads to renal failure and uremia

``` fibrillar folded beta pleated sheet outisde nephroti ```

Hemodialysis-associated amyloidosis * Patients on long-term hemodialysis for renal failure can develop amyloid deposits derived from ____ * This protein is present in high concentrations in the serum of individuals with renal disease, and in the past it was retained in the circulation because it could not be ____ through dialysis membranes * With new dialysis filters, the incidence of this complication has ____ substantially * The classical features of this form of amyloidosis are the triad of ____, carpal tunnel syndrome, and ____ of the hand

``` b2-microglobulin filtered decreased scapulohumeral periarthritis flexor tenosynovitis ```

Amyloid diagnosis using Congo red * The diagnosis of amyloidosis depends on the ____ demonstration of amyloid deposits in tissues * Histologically, the amyloid is deposited primarily in the ____, but the interstitial peritubular tissue, arteries, and arterioles are also affected * The glomerular deposits first appear as subtle thickenings of the ____ matrix, accompanied usually by ____ widening of the basement membranes of the glomerular capillaries * The most widely used is the ____ stain, which under ordinary light gives a pink or red color to tissue deposits, but far more striking and specific is the ____ birefringence of the stained amyloid when observed by polarizing microscopy

``` histologic glomeruli mesangial basement membranes congo red green ```

amyloidosis • Under H&E, without Congo red • Pink areas are ____ than others ○ Pink nodularity look: ____

darker | diabetic nephropathy

• Highlighting of amyloid areas within the glomerulus • How to determine what you're looking at isn't hyaline? ○ Staining with ____ and with ____ > answers the question ○ Apple-green birefrigence > confirms the diagnosis for amyloid

congo red | polarized light

Bacterial endocarditis * Glomerular lesions occurring in the course of bacterial endocarditis or other systemic infections, such as infected ____, represent a type of immune complex nephritis initiated by complexes of bacterial antigen and antibody * ____ involvement may be the initial manifestation of subacute bacterial endocarditis in about 20% of patients * Circulating ____ related to infectious endocarditis cause proliferative lesions • Rare cases of glomerular diseases

AV shunts kidney immune complexes

bacterial endocarditis * Glomerulopathy seen in subacute bacterial endocarditis * No empty ____ space

white

Acute tubular injury/necrosis • A clinicopathologic entity characterized clinically by ____ renal failure • Morphologic evidence of tubular injury, in the form of necrosis of tubular ____ cells • Acute tubular injury is a ____ process that arises in a variety of clinical settings • Ischemic shock: have in common a period of inadequate blood flow to the peripheral organs accompanied by marked ____ and shock • Nephrotoxic: caused by a multitude of drugs (____), radiographic contrast dyes, ____, heavy metals (____), and organic solvents

``` acute epithelial reversible hypotension gentamicin poisons mercury ```

ATN • A very circular, nice round structures • Each cell lining the white space are nicely divided and organized • Lose the ____ ○ Vacuolar spaces

organization

Pyelonephritis and urinary tract infection * ____ is one of the most common diseases of the kidney and is defined as inflammation affecting the tubules, interstitium, and renal pelvis * Pyelonephritis is a serious complication of urinary tract infections that affect the bladder (____), the kidneys and their collecting systems (____), or both * ____ infection is the most common cause of clinical pyelonephritis * More than 85% of cases of urinary tract infection are caused by the ____ that are ____ inhabitants of the intestinal tract * For most urinary tract infections, the infecting organisms are derived from the patient's own ____ flora

``` pyelonephritis cystitis pyelonephritis ascending gram-negative bacilli normal fecal ```

* Acute pyelonephritis hallmarks are ____ interstitial suppurative inflammation, intratubular aggregates of ____, neutrophilic tubulitis and tubular ____ * Early stages, the neutrophilic infiltration is limited to the ____. But given time, infection extends to the ____ and produces abscesses that destroy the involved tubules * The suppuration may occur as discrete ____ abscesses or large wedge-like areas and can involve one or ____ kidneys

``` patchy neutrophils necrosis tubules interstitium focal both ```

acute pyeloneprhtiis • Arrow points > little white dots in the red parenchyma > micro ____ ○ Mixture of inflam cells and ____ • May even affect the ____ of the renal parenchyma

abscesses necrosis surface

acute pyelonpehritis • Most of the cells in the yellow are made up of ____ cells ○ Not present in normal kidney tissue • Black: things inside the tubules that makes it look necrotic ○ [???]

acute inflam

Clinical * After the first year of life and up to around age 40 years, infections are much more frequent in ____. * Between 4 to 6% of pregnant women develop bacteriuria during ____, and 20 to 40% eventually develop symptomatic urinary infection, if not treated * With increasing age the incidence in males rises as a result of ____ and instrumentation * Acute pyelonephritis usually presents with a sudden onset of pain at the ____ angle and systemic evidence of infection, such as ____ and malaise * Uncomplicated acute pyelonephritis follows a ____ course, and symptoms disappear within a few days after the institution of appropriate ____ therapy

``` female preganncy prostatic hypertrophy costovertebral fever benign antibiotic ```

Tubulointerstitial nephritis caused by drugs and toxins * ____ most common cause of acute kidney injury * Acute drug induced interstitial nephritis most frequently occurs with synthetic penicillins (____), other synthetic antibiotics (____), diuretics (____), NSAIDs, and miscellaneous drugs (____) * Drug induced acute interstitial nephritis begins about ____ days after drug exposure and is characterized by fever, rash, and renal abnormalities (hematuria, mild proteinuria, and leukocyturia) * ____ of the drug is usually followed by recovery

``` second methicillin rifampin thiazides allopurinol 15 withdrawal ```

Nephropathy associated with NSAIDs • NSAIDs produces several forms of renal injury • Many NSAIDs are nonselective cyclooxygenase inhibitors, and their adverse renal effects are related to their ability to inhibit cyclooxygenase-dependent ____ synthesis • NSAID associated renal syndromes include • Acute kidney injury due to the decreased synthesis of vasodilatory ____ and resultant ____; occurs in setting of other renal disease • ____ • Membranous nephropathy with the ____ syndrome

``` prostaglandin prostaglandins ischemia acute interstitial nephritis nephrotic ```

Autosomal dominant (adult) polycystic kidney disease * Hereditary disorder characterized by multiple expanding cysts of ____ kidneys that ultimately destroy the renal parenchyma and cause renal failure * Affects roughly 1 of every 400 to 1000 live births * Accounts for 5% to10% of end stage renal disease requiring transplantation or dialysis * Individuals with polycystic kidney disease also tend to have ____ congenital anomalies * 40% have one to several cysts in the ____

both extrarenal liver

Autosomal recessive (childhood) polycystic kidney disease * ____ distinct from adult polycystic kidney disease * Perinatal, neonatal, infantile, and juvenile subcategories have been defined, depending on the ____ of presentation and presence of associated hepatic lesions * ____ and ____ are the most common * Serious manifestations are usually present at ____ and the infant might succumb rapidly to renal failure

``` genetically time perinatal neonatal birth ```

Acquired (dialysis-associated) cystic disease * Patients with end-stage renal disease who have undergone prolonged dialysis sometimes show numerous ____ and medullary renal cysts * They probably form as a result of obstruction of tubules by interstitial ____ or by ____ crystals * Most are ____, but sometimes the cysts bleed, causing ____ * There is a 12- to 18-fold increased risk of ____, which develops in 7% of dialyzed patients observed for 10 years.

``` cortical fibrosis oxalatae asymptomatic hematuria renal cell carcinoma ```

• One, solitary cyst will not do anything to affect function • Polycystic > no longer ____ ○ A cut through it > no normal renal ____ ○ Cysts also contain ____ • Will require ____ or have the kidney removed

functioning anatomy fluid transplant

Urolithiasis (renal stones) • Urolithiasis affects 5% to 10% of Americans in their lifetime and the stones may form ____ in the urinary tract, but most arise in the ____ • Stone composition is variable, but suggest increased urinary concentration of ____ that makes up the stone • ____ are affected more often than women, and the peak age at onset is between ____ years • Familial and hereditary ____ to stone formation has long been known • Urolithiasis may be ____, produce severe renal colic and abdominal pain, or may cause significant ____ damage

``` anywhere kidney element men 20-30 predisposition asymptomatic renal ```

renal stones * Can cause renal damage > tissue that's not ____ properly; tissue that's not supposed to be there * [???]

functioning

Nephroblastoma (Wilms tumor) • Seen primarily in ____, 50% of the cases occur before the age of 3 years, and 90% before the age of 6 • Classic location is the ____, and tumor recapitulates (repeats) the embryogenesis of the kidney at the ____ and molecular level • ____ mass is felt when handling the child • Imaging shows ____ intrarenal mass • Grossly, most Wilms are ____ and well-____ • The cut section is solid and ____ or tan and often exhibits areas of cystic change, ____, and hemorrhage

``` infants kidney morphologic abdominal solid solitary circumscribed pale gray necrosis ```

• Metastasis of the ____ is common and regional lymph node metastasis is found in 15% of cases • Most common sites of distant metastases are ____ • Therapy usually involves preoperative chemotherapy followed by ____ resection • Cure rate for unilateral Wilms tumor is ____%

renal vein lungs and liver surgical 80-90

Renal cell carcinoma • Generally a tumor of ____, average age is 55-60 years old • Cigarette smoking and high ____ are said to increase the risk for development • Male to female ratio is about ____:1 • Renal cell carcinoma can be associated with hereditary and non-____ diseases • Acquired cystic disease of the kidney from ____ dialysis • Renal cell carcinoma usually presents with ____, flank pain, or as an abdominal mass

``` blood pressure 2 hereditary long term hematuria ```

* Renal cell carcinoma can be classified into different subtypes each with a varying biologic behavior and genetic component * ____ carcinoma is the most common type * Accounts for ____% of all renal cancers * Most clear cell carcinomas are centered on the ____ * Histologically, the cells of clear cell renal cell carcinoma are optically clear from accumulation of ____ and lipids * Pattern of growth is predominantly ____ * High rate of ____

``` clear cell 65-70 cortex glycogen solid metastasis ```

* Most renal cell carcinomas are found to invade ____ fat and/or regional lymph nodes at time of operation * Most common site of distant metastases are the ____ * Metastases can develop almost at any ____ * Maxillary gingiva (J Oral Max Pathol 2018) * Submandibular gland (JSurgCaseRed2018) * Tongue(JMedCaseRep2017) * Mandible(UrolJ2017) * Lower lip (Oncol Lett 2014) • Therapy is usually ____ excision • No consistent ____ has been demonstrated for administration of adjunctive radiation therapy or chemotherapy • Neoadjuvant therapy is sometimes used to reduce tumor ____ prior to surgery • Overall 5 year survival rate of renal cell carcinoma is approximately ____%

``` perinephric lung and skeleton site surgical excision benefit size 70 ```

7. Renal Pathology Flashcards

(62 cards)