Flashcards in Renal Pathology Deck (109):
What are the four main components of the kidney?
The ______ is a network of capillaries between the afferent and efferent arterioles.
The _____ arteriole brings blood to the capillary bed; whereas, the _______ arteriole drains blood away from the capillary bed.
a = arrives at capillary bed
e = exits from the capillary bed
What are the three layers of the capillary wall in the glomeruli?
epithelium (lining the urinary space)
Epithelial cells have many _______ from the cell body that connect to the basement membrane.
finger-like projections (podocytes)
A membrane, called the _______, connects the adjacent processes and is important in preventing proteinuria.
The capillary wall is permeable to water and small molecules. What is is impermeable to?
albumin and larger proteins
What are the supporting cells within the capillary bed?
mesangial cells (connective tissue)
What is the purpose of the tubules of the kidneys?
the filtrate from the glomeruli travels through the system of tubules and the tubular epithelium which reabsorbs or secretes particular substance = formation of urine
The interstitium is formed by ____ and _____ between the tubules and glomeruli.
collagen and blood vessels
What is "azotemia?"
elevated blood urea nitrogen (BUN) and creatine (breakdown of skeletal muscle) due to a decreased Glomerular Filtration Rate (GFR)
Azotemia PLUS other clinical symptoms (gastroenteritis, peripheral neuropathy, dermatitis, acidosis, pericarditis, hyperkalemia) = _______
What are the three major clinical renal syndromes?
1. Acute Nephritic Syndrome
2. Nephrotic Syndrome
3. Acute Renal Failure
Which renal syndrome is characterized by mild/moderate proteinuria, hematuria, and hypertension?
Acute Nephritic Syndrome
Which renal syndrome is characterized by severe proteinuria? What is "severe?"
>3.5 grams per day
N a+ decrease (hyponatremia)
A lbumin decrease (hypoalbuminemia)
P roteinuria >3.5g per day
R enal vein thrombosis
O rbital edema
I nfection (loss of immunoglobulins in urine)
C oagulability (loss of ATIII in urine)
Severe proteinuria that is characteristic of Nephrotic Syndrome will result in severe ______.
True or False: Nephrotic syndrome is characterized by severe proteinuria and hyperalbuminemia.
False...HYPO-albuminemia (low serum albumin)
What are the clinical signs of "acute renal failure?"
1. acute onset of azotemia (high levels of nitrogen containing compounds)
2. Oliguria (reduced urine) or Anuria (no urine)
Which is more common: Autosomal Dominant Polycystic Kidney Disease or Autosomal Recessive Polycystic Kidney Disease?
Dominant (adult) is more common= 1 in every 500- 1000 people)
Recessive (childhood) is seen in 1 out of every 20,000 live births
What is the clinical presentation of Autosomal Dominant Polycystic Kidney Disease?
MULTIPLE EXPANDING CYSTS in both kidneys
-gradual onset of renal failure (account for 10% of failures)
-Urinary tract hemorrhage (hematuria)
-Urinary Tract Infection
Autosomal Dominant Polycystic Kidney Disease effects the ______ gene on chromosome ______.
What is the defective protein in Adult Polycystic? What is the defective protein in Childhood Polycystic?
Adult : Polycystin-1
_____ of patients of Adult Polycystic Disease will have cysts in the _____. Where might they develop saccular aneurysms (30% of the time)?
1/3 = in the liver
may develop "berry" aneurysms in the Circle of Willis (30%)
With polycystic kidney disease (adult), what is the gross pathology of the kidneys?
VERY LARGE... up to 4 kg (normal is ~0.2kg)
-filled with cysts arising from every part of the tubular system
When do Adult Polycystic patients begin to notice symptoms?
they begin to get "flank pain" around the 4th decade with hypertension, UTI, and hematuria
When does renal failure occur in those patients with Autosomal Recessive Polycystic Kidney Disease?
infancy - several years of age (rare)
True or False: In both the dominant and recessive forms of Polycystic Kidney Disease, the cysts can arise from any part of the tubular system.
dominant = all levels of the nephron
recessive = collecting tubules in cortex/medulla
Which gene is effected in Dominant Polycystic Kidney Disease? Which gene is effected in Recessive Polycystic Kidney Disease?
True or False: Cysts associated with Recessive Polycystic Kidney Disease are all uniform-sized large cysts.
uniform size, SMALL
What are the mechanisms of glomerular injury?
1. Immune Complex deposits in glomerular basement membrane (GBM) or mesangium-- complexes active complements which will cause damage
2. anti-GBM antibody
3. epithelial and endothelial cell injury
What are three mechanisms for pathologic evaluation of kidney biopsies?
1. Light Microscope
3. Electron Microscopy
Which stains are used to detect basement membranes?
Which stain is used to detect collagen?
Which method of evaluation is used to identify immune complexes, epithelial cell changes, basement membrane morphology and other changes?
"changes" is the key word = use electron microscopy
What are the patterns of deposition of immune complexes as seen through immunofluorescence microscopy?
1. Circulating Immune Complex Deposition = granular and spotty
2.anti-GBM = linear
**could have a mix of granular and linear = antibody against glomerular antigen**
What is the most obvious clinical sign of Nephrotic Syndrome?
Severe Edema (from heavy proteinuria)
What are the four causes of Nephrotic Syndrome?
1. Minimal Change Disease (children)
2. Focal Segmental Glomerulosclerosis (adults)
3. Membranous Nephropathy
4. Nodular Glomerulosclerosis (diabetes)
What is the most common cause of nephrotic syndrome in children?
Minimal Change Disease (accounts for 2/3 of cases)
What is the pathology of nephrotic syndrome?
Foot Process Effacement - "busted down" processes diminish the ability to hold epithelium together
-glomerulus appears normal
-no immune complex deposition
True or False: Children with Minimal Change Disease show a poor response to treatment with corticosteroids.
False, GOOD response to corticosteroids (especially children)
What are the most common cause of adult nephrotic syndrome?
Focal Segmental Glomerulosclerosis
Membranous Nephropathy*** (THE most common)
Do adults with Focal Segmental Glomerulsclerosis show a positive response to corticosteroids?
NO! poor response
-renal failure after 10 years in 50% of patients
Focal Segmental Glomerulosclerosis may be ____, _____, or _____.
Secondary (to another disease)
True or False: The idiopathic form of Focal Segmental Glomerulosclerosis shows heavy deposition of immune complexes.
False, NO IMMUNE COMPLEXES with idiopathic (primary) form
Describe the pathology of Focal Segmental Glomerulosclerosis.
Focal = only some glomeruli are effected
Segmental = only part of the glomerulus is effected
Sclerosis = obliteration of capillary loops and increased mesangial matrix collagen
When is Membranous Nephropathy most common?
age 30 to 50
(may effect children, but not as likely as Minimal Change)
True or False: Membranous Nephropathy has immune complex deposition in the epithelial side of the GBM.
Focal Segmental = no immune complexes
Memb. Nephropathy = immune complexes in GBM
Do patients with Membranous Nephropathy show a positive response to corticosteroid treatments?
No, about 40% develop renal failure in 2-20 years
(Focal Segmental = 50% in 10 years)
(Minimal Change = positive response)
In membranous nephropathy, there is a diffuse thicking of the glomerular basement membrane (GBM) and the presences of ______ (of basement membrane material) intertwined between immunoglobulin _____.
The most common cause of death associated with diabetes mellitis is MI. What is the second most common cause of death for these patients?
True or False: Diabetes Mellitis patients have proteinuria.
True, minimally in the beginning but progresses to severe
Which method for evaluating kidney biopsies would be most important for diagnosing Diabetes related Nephrotic syndrome?
LM (light microscopy) **basement membrane**
-visible nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
Which method for evaluating Membranous Nephropathy would be most important for diagnosing Nephrotic Syndrome?
-visible immune complex deposits (IgG)
Which method for evaluating Minimal Change Disease would be most important for diagnosing Nephrotic Disease?
EM (electron Microscopy) **PAS stained glomerulus**
-foot process effacement
Which method for evaluating Focal Segmental Glomerulosclerosis is most important for diagnosing Nephrotic Disease?
LM (light microscopy) **basement membrane**
-focal and segmental glomerular involvement with obliteration of capillary loops
True or False: Kimmelstiel-Wilson lesions are diagnostic for diabetes related nephropathy.
True, its only really seen in diabetes. the mesangial CT displaces normal components of the glomeruli
_____sclerosis, _____sclerosis, and _____sclerosis will affect patients with diabetes in addition to nephrotic syndrome.
(aka: lots of breakdown and scarring throughout the blood vessels and kidney with nodules of mesangial CT tissue- Kimmelstiel Wilson)
Nephritic Syndrome (read carefully-its not nephrotic) is characterized by ACUTE onset of ______, _______, and _______.
oliguria & azotemia
What are two important manifestations of Nephritic Disease (i.e.: symptoms to watch out for)?
-blood passing in the urine with reduced GFR
-inflammatory cells with proliferation into the glomeruli and injury to capillary walls
What are the two CAUSES of nephritic syndrome?
1. Acute Postinfectious Glomerulonephritis
2. IgA nephropathy
Which infection is likely to cause Acute Postinfectious Glomerulonephritis?
(other bacterial and viral infections could cause a problem)
Acute Postinfectious Glomerulonephritis is most common in _____.
children less than 18
(occurs 1 to 4 weeks following infection)
With Acute Postinfectious Glomerulonephritis, there are pathological findings in all three methods for evaluating biopsies (LM, EM, IF). What are the findings?
LM (basement membrane and collagen)
---proliferation of endothelial cells, INFLAMMATORY cells, possible "cellular crescents".... lots and lots of cells
---immune complexes in GBM and mesangium
---GRANULAR immune complex deposition (C3 cross reactive antigens)
_____ Nephropathy is a Nephritic Syndrome that affects both children and young adults.
Following a(n) _____ respiratory tract infection, how quickly will patients with IgA nephropathy show hematuria?
upper (URT infection)
1-2 days following = hematuria (blood in urine)
What is Henoch-Schonlein Purpura?
a cluster of skin, joint, GI, and kidney problems associated with IgA Nephropathy (systemic involvement)
What are the signs of IgA Nephropathy as seen on the biopsy report?
LM (membranes and collage) = mesangial cell proliferation and histiocytes
IF and EM (basement membrane) = IgA complexes within the mesangium
True or False: IgA does not fix "complement" very well and therefore produces less destruction than other Immunoglobulins.
**IgA acts by sterically hindering the attachment of epithelial cells**
In which region does IgA principally deposit in IgA Nephropathy?
What is Rapidly Progressive Glomerulonephritis?
*clinical syndrome, not a specific form of gomerulonephritis*
progressive loss of renal function that could result in death from renal failure (in weeks to months) if left untreated
What is the characteristic finding of Rapidly Progressive Glomerulonephritis?
CRESCENTIC nephritis due to proliferation of epithelial cells with infiltration of histiocytes
Rapidly Progressive Glomerulonephritis could be associated with ______, _______, or _______.
1. Immune Complex Disease (44% of cases)
2. Pauci-Immmune (44% of cases)
3. Anti-GBM antibody disease (12% of cases)
What is Pauci-Immune?
systemic vasculitis associated with the lack of anti-GBM or immune complexes that often results in Glomerulonephritis
Crescentic nephritis is seen with a ______ stain.
PAS (light microscope)
Untreated renal disease will lead to loss of _____ and ______, accompanied by fibrosis.
****LOSS AND FIBROSIS = end-stage renal disease****
True or false: By the time chronic glomerulonephritis is diagnosed, the original renal disease often cannot be identified.
True, because there is too much scar tissue
What are the three clinical signs of Chronic Renal Disease that can be detected through routine exams?
1. proteinuria (do they have foamy urine)
3. azotemia (BUN levels)
Why is a trichome stain used to detect Chronic Renal Disease?
trichrome = collagen stain
Chronic Renal disease = glomeruli are replaced by collagen (scar tissue)
What is Acute Pyelonephritis?
a renal disease affecting tubules, interstitium, and pelvis
--most often secondary to bacterial infection
Acute Pyelonephritis infection may spread from the _______ to the _______ and into the _____.
renal pelvis and kidney
What is another possible route of Acute Pyelonephritis infection (less common than ascending route)?
hematogenous spread of bacteria
Patients with Acute Pyelonephritis will experience a sudden onset of pain at the ________, will show systemic evidence of infection, and will have ______.
dysuria = painful urination with frequency and urgency
Acute Pyelonephritis will appear pathologically as _____ interstitial and tubular ________ inflammation.
What are the predisposing conditions for Acute Pyelonephritis?
-Urinary Tract Obstruction
-vesicoureteral reflux (backflow of urine into kidneys)
-gender and age
Chronic bouts of acute inflammation may lead to chronic pyelonephritis which is characterized by ______ inflammatory infiltration and _______.
Drug-induced interstitial Nephritis could be caused by ____, _____, or other drugs and involves a _____ reaction to the medication.
hypersensitivity (infiltration of neutrophils & eosinophils)
True or False: Drug-induces Interstitial Nephritis involves glomerular inflammation.
False, the glomeruli are not involved (INTERSTITIAL inflammation...its in the name)
In addition to interstitial inflammation, Drug-Induced Nephritis may lead to papillary ______.
necrosis (necrosis of the tips of the medullary pyramids)
Describe Acute Tubular Necrosis.
-Rapid onset of renal failure
-reduced urine output and electrolyte imbalance
-injury to tubular epithelial cells from ischemia or toxins
-dilation of tubules
-necrosis of epithelium
True or False: Acute Tubular Necrosis is reversible over a period of days as the damaged tubular epithelium regenerates.
False, this process takes weeks (not days)
What are three types of Vascular Disease associated with the kidney?
2. Arterionephrosclerosis with malignant hypertension
3. Thrombotic Microangiopathy
Pathology of _______ : kidneys are symmetrically atrophic with moderate size reduction and kidney surfaces have a fine granularity and thin cortex.
(tubular atrophy, interstitial fibrosis, glomerular sclerosis)
What type of arteriosclerosis causes narrowing of arteriole/artery lumen in arterionephrosclerosis?
(with fibroelastic hyperplasia of musclar arteries)
What is malignant hypertension?
hypertension greater than 20/120 mm Hg that occurs in about 5% of patients with essential hypertension
-rapid onset of renal failure due to reduced blood flow and necrosis of glomeruli
-nausea, headache, vomiting, visual impairment
Thrombotic thrombocytopenia purpura (TTP) is an acquired defect in the ________ plasma protease that degrades ____ multimers.
von Willebrand Factor
*remember, vWF activates platelets
Hemolytic-uremic Syndrome (HUS) is ________ injury which is commonly due to a _______ from E. coli that activates platelets.
an endothelial cell
Both TTP and HUS, are disorders that cause ________ formation in capillaries.
Comparing TTP to HUS, which has predominant renal involvement and which is more widespread?
HUS = renal (more common in children)
TTP = widespread involvement of other organs
What is urolithiasis?
---result in tract obstruction, ulceration of the lining, and bleeding
---small stones = migration into ureters = flank pain
---large stones = remain in pelvis = hematuria (pee blood)
Where is the most frequent site for formation of stones?
calyces and pelvis
-could develop in the bladder
Large renal stones are referred to as "_______" because they form a cast of the pelvis and calyceal system.
What are the three types of kidney stones?
2. Magnesium ammonium phosphate
3. uric acid
In ___% of patients, stones are unilateral.
Infection with Proteus, will predispose patients to ____ stones.
Magnesium Ammonium Phosphate
(PP --> Proteus &Phosphate)
Name two tumors associated with the kidneys.
1. Renal Cell Carcinoma
2. Wilm's Tumor
Renal Cell Carcinoma occurs more often in ______.
2 to 1 ratio (Male to Female)
The most common histologic subtype of Renal Cell Carcinoma has cells with ______.
very pale or clear cytoplasm (clear cell carcinoma)
True or False: Risk factors for Renal Cell Carcinoma include hypertension, smoking, obesity, copper exposure, and von Hippel-Lindau Syndrome.
all are true EXCEPT copper... its cadmium exposure that causes problems (involved in zinc processing and stabilizing of plastics, or pigmentation)