Kidney Path Flashcards
nephrotic syndrome
severe proteinuria hypoalbuminemia generalized edema hyperlipidemia lipiduria
nephritic syndrome
hematuria azotemia oliguria hypertension proteinuria
causes of nephrotic syndrome
Minimal Change Disease (MCD) Membranous Glomerulonephritis (MGN) Focal Segmental Glomerulosclerosis (FSGS) Membranoproliferative Glomerulonephritis (MPGN)
Minimal Change Disease (MCD)
n most frequent cause of the nephrotic
syndrome in children
n glomeruli have normal appearance under
the light microscope, but electron
microscopy reveals diffuse loss of visceral
epithelial foot processes
what is universal to nephrotic syndrome
fusion of podocytes
Minimal Change Disease (MCD) path
current evidence points to a disorder of T cells
-elaborate factors (IL-8, TNF, etc.?) that affect
nephrin synthesis
Minimal Change Disease (MCD) gold standard for diagnosis
EM
Minimal Change Disease (MCD) immunofluorescence?
no
Minimal Change Disease (MCD) clinical course
Insidious development of nephrotic syndrome in
otherwise healthy child (peak age, 2-6)
-Usually follows respiratory infection or prophylactic
immunization; assoc. w/atopic disorders
Selective proteinuria (mainly albumin)
Good prognosis
>90% respond to short course of corticosteroids
<5% develop chronic renal failure after 25 years
Membranous Glomerulonephritis
MGN
most common cause of nephrotic syndrome in adults (peak age, 30-50) n glomeruli appear normal early in the disease, but develop diffuse thickening of the capillary walls
Membranous Glomerulonephritis
(MGN) path
form of chronic immune complex nephritis
-idiopathic forms (85% of cases) are mainly autoimmune
*antibodies react to antigens in the glomerulus components, or to
antigens that have become trapped there
-may also be due to circulating complexes of known exogenous
or endogenous antigen
the membrane attack complex of complement (C5b-C9)
activates mesangial and epithelial cells, causing them to
liberate proteases and oxidants that damage glomerular
capillaries
Membranous Glomerulonephritis
(MGN) key to dianosis
silver stain
detects collagen in BM
Membranous Glomerulonephritis
(MGN) clinical course
Insidious development of nephrotic syndrome
Proteinuria is nonselective and does not respond
to corticosteroid therapy
Variable course
40% suffer progressive disease ending in renal failure
after 2-10 years
10-30% follow benign course with partial or complete
remission
Focal Segmental
Glomerulosclerosis (FSGS)
characterized by sclerosis affecting some
but not all glomeruli and involving only
segments of each glomerulus
most well-known association is with HIV
patients and IV drug users, but occurs in
all ages (more common in African-
American populations)
Focal Segmental
Glomerulosclerosis (FSGS) path
unknown (some have suggested it is an
aggressive variant of minimal change
disease)
circulating mediator is likely responsible
-proteinuria recurs soon after renal transplant
Focal Segmental
Glomerulosclerosis (FSGS) diagnosis
IF usually isn’t done, but detects IgM and
C3 in sclerotic segments
Focal Segmental
Glomerulosclerosis (FSGS) clinical course
May be a primary disease or result from other
forms of GN (esp. IgA nephropathy)
Proteinuria is nonselective and has poor
response to corticosteroid therapy
Higher incidence of hematuria and hypertension
(more likely to evolve from nephritic syndromes)
Prognosis is poor, with children faring slightly
better than adults
-50% suffer renal failure after 10 years
Membranoproliferative
Glomerulonephritis (MPGN)
may be nephritic, nephrotic, or mixed
characterized by alterations in the GBM
and mesangium plus proliferation of
glomerular cells
Membranoproliferative
Glomerulonephritis (MPGN) Type I
(2/3rds of cases)
Circulating immune complexes of unknown antigen
-Associated with hepatitis B and C, SLE, infected
atrioventricular shunts, chronic lymphocytic leukemia
Membranoproliferative
Glomerulonephritis (MPGN) Type II
Less clear, but serum of patients has a factor called C3
nephritic factor (C3NeF)
Activates the alternative complement pathway by stabilizing
C3 convertase
hypocomplementemia, but normal C1, C2, C4
Membranoproliferative
Glomerulonephritis (MPGN) key to diagnosis
“doubled” GBM on silver stain
Membranoproliferative Glomerulonephritis (MPGN) EM varies by type
Type I: subendothelial deposits Type II: dense deposits in center of GBM and under endothelium
Causes of Nephritic Syndrome
Acute Proliferative (Poststreptococcal) Glomerulonephritis (PGN) Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN) IgA Nephropathy (Berger Disease)
Acute Proliferative (Poststreptococcal) Glomerulonephritis (PGN)
Typically caused by immune complexes of
exogenous or endogenous antigens
-Prototype exogenous pattern = 1-4 weeks after a
streptococcal infection
*Only “nephritogenic” strains of group A β-hemolytic
streptococci associated
*Most cases follow skin or pharynx infection
Children affected more frequently than adults
Acute Proliferative (Poststreptococcal) Glomerulonephritis (PGN) path
Immune complex formation, but unclear if complexes are simply trapped as they pass through the glomerulus, or if C3 is deposited on GBM before IgG subepithelial humps
Acute Proliferative (Poststreptococcal) Glomerulonephritis (PGN) Clinical Course
Abrupt onset, with malaise, slight fever, nausea, and
nephritic syndrome
Hematuria: urine appears smoky brown
Hypocomplementemia; elevated serum antistreptolysin
O titers in poststreptococcal cases
Children: complete recovery in most (95%)
Adults: complete recovery (60%); many develop RPGN
or chronic GN
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN)
Clinical syndrome (not a specific etiologic form of
GN)
Characterized by rapid and progressive loss of
renal function associated with severe oliguria
and (if untreated) death from renal failure in
weeks to months
All types demonstrate crescents (proliferation of
parietal cells/migration of monocytes into
Bowman’s space)
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN) type I
anti-GBM disease
Type IV collagen is target
Linear deposits of IgG (sometimes C3 also) on GBM
In some patients, anti-GBM antibodies also bind to pulmonary
alveolar capillary basement membranes = GOODPASTURE
SYNDROME
-Goodpasture antigen is noncollagenous component of Type IV
collagen
-Males > females; peak age is 20-40 y.o.
-Pulmonary involvement precedes renal disease
*Pulmonary hemorrhage and recurrent hemoptysis
-Plasmapheresis is beneficial (removes pathogenic antibodies)
Least common of all CrGN types
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN) Type II CrGN
Complication of any immune complex nephritides
(PGN, SLE, IgA nephropathy)
Granular IF pattern
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN) Type III GrGN (pauci-immune type CrGN)
Component of a systemic vasculitis, like microscopic
polyangiitis or Wegener granulomatosis, or idiopathic
Most have serum ANCAs
No anti-GBM antibodies or immune complexes
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN)
Crescents obliterate the Bowman’s space
and compress the glomeruli
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN or CrGN) clinical course
Typical nephritic syndrome, but oliguria and
azotemia more pronounced
Rapid progression to severe renal failure; longterm
dialysis or transplantation required
Prognosis roughly related to crescent number
(<80% crescents means better prognosis) and
type
IgA Nephropathy (Berger Disease)
Most common glomerular disease, and one of
most common causes of recurrent hematuria
Usually affects children and young adults (mostly
males)
Typical presentation = gross hematuria that
occurs 1-2 days after a nonspecific respiratory
tract infection; disappears, but recurs every few
months
IgA Nephropathy (Berger Disease) path
Genetic or acquired abnormality of IgA
production and clearance
-IgA synthesis is increased in response to respiratory
or GI exposure to antigen
*IgA nephropathy occurs with increased frequency in patients
with celiac sprue and liver disease
-IgA and IgA complexes are entrapped in the
mesangium, where they activate the alternative
complement pathway and cause glomerular injury
Proposed to be a variant of Henoch-Schönlein purpura
IgA Nephropathy (Berger Disease) clinical course
Typically presents with loin pain, gross hematuria; usually after respiratory, gastrointestinal, or urinary infection Some develop slow progression to chronic renal failure in 20 years
Hereditary Nephritis
Group of hereditary familial renal diseases
Best studied is Alport syndrome
-GBM defect due to mutation in type IV collagen components
-Nephritis accompanied by nerve deafness and eye disorders,
including lens dislocation, posterior cataracts, and corneal
dystrophy
-Males affected more frequently, more severely
Patients present at age 5-20 y.o., and develop renal
failure by 20-50 yoa
Heterogenous inheritance (X-linked, autosomal
recessive, or autosomal dominant)
Chronic Glomerulonephritis
The final stage of many forms of glomerular disease; characterized by progressive renal failure, uremia, and untimely death Usually from rapidly progressive GN, focal glomeulosclerosis, membranoproliferative GN
signs & symptoms of Chronic Glomerulonephritis
decreased renal acuity cramps restless leg sleep disturbances bone disease itching anemia
Chronic Glomerulonephritis morphology
Kidneys small with
granular surface
Chronic Glomerulonephritis clinical course
Usually undiscovered until late in its course, when symptoms of renal insufficiency develop (proteinuria, hypertension, azotemia, anasarca, anemia, anorexia) Urinalysis: broad waxy casts Dialysis and renal transplantation required
Chronic Diabetic Glomerulopathy risk factors
Poor glycemic control
hypertension
diabetic retinopathy (high
correlation)
Diabetic Glomerulopathy path
Nonenzymatic glycosylation (NEG) -glomerular and tubular BMs -arterioles (efferent 1st) osmotic damage to glomerular capillary endothelial cells - glucose → osmotically active sorbitol hyperfiltration damage to mesangium diabetic microangiopathy
Diabetic Glomerulopathy clinical features
Microalbuminuria
-first lab manifestation (usually after ~10 y of poor
glycemic control)
-microalbuminuria dipsticks detect albumin levels 1.5-8
mg/dL
increased susceptibility to acute and chronic
pyelonephritis
infarction of renal papillae = papillary necrosis
most common cause of chronic renal failure in
U.S.
Renal amyloidosis
B-2 microglobulin
Acute Pyelonephritis
if obstruction prevents draining, the renal pelvis, calyces, and ureter may fill with exudate = pyonephrosis -pus under pressure may develop ischemic and suppurative necrosis of the renal pyramid tips = papillary necrosis -more common in diabetics papillary necrosis
Acute Pyelonephritis clinical course
Fever, chills, malaise
Dysuria, frequency, and urgency
Costovertebral angle (CVA) tenderness
Urinalysis shows WBC casts and pyuria
Chronic Pyelonephritis
Due to recurrent infections promoted by chronic obstruction or reflux -Chronic Obstructive Pyelonephritis -Chronic Reflux-Associated Pyelonephritis Important cause of chronic renal failure
Chronic Pyelonephritis morphology
Uneven scarring of the pelvis and/or calyces -Leads to blunted calyces
Chronic Pyelonephritis clinical course
Unnoticed until renal insufficiency begins;
may cause hypertension
n Some develop FSGS
Acute Drug-Induced Interstitial
Nephritis (aka, Acute TIN)
Adverse reaction to drugs that begins ~15 days (range,
2-40 days) after exposure
-Synthetic antibiotics, especially penicillins
-Diuretics (thiazides)
-Nonsteroidal anti-inflammatory agents (phenylbutazone)
Acute Drug-Induced Interstitial
Nephritis (aka, Acute TIN) path
Drugs acts as haptens that covalently bind to
cytoplasmic or extracellular component of tubular cells
and become immunogenic
eosinophils in the urine help support the
diagnosis
Acute Drug-Induced Interstitial
Nephritis (aka, Acute TIN) Clinical Course
Fever
Eosinophilia (may be transient)
Rash (only ~25% of patients)
Renal abnormalities: hematuria, minimal or no
proteinuria, leukocytouria
A rising serum creatinine level or acute renal failure with
oliguria develops in about 50% of cases (esp. elderly)
Withdrawal of offending drug results in recovery (may
take months)
Analgesic Nephropathy
Seen in patients consuming large quantities of analgesics -Most consume mixtures containing some combination of phenacetin, aspirin, acetaminophen, caffeine, and codeine for long periods papillary necrosis
Analgesic Nephropathy clinical course
Chronic renal failure (more common in those with preexisting renal disease), hypertension, anemia Increased incidence of transitional cell carcinoma
Acute Tubular Necrosis
The most common cause of acute renal failure
Characterized by destruction of tubular epithelial
cells
Generally a reversible lesion that arises in a
variety of clinical settings:
Ischemic Type = due to decreased blood flow (e.g.,
severe hemorrhage, shock, dehydration)
Nephrotoxic Type = death of tubular cells due to
poisons, drugs
Acute Tubular Necrosis: Nephrotoxic Type
Aminoglycosides (#1 cause) and other drugs
IV radiographic contrast agents (#2 cause)
Heavy metals (e.g., mercury, gold, lead)
Organic solvents (e.g., carbon tetrachloride)
Ethylene glycol
Mushroom poisoning
Pesticides
Myoglobin (from crushing injuries)
Acute Tubular Necrosis Clinical Course
Oliguria and elevation of blood urea nitrogen and
creatinine
Metabolic acidosis and hyperkalemia
Urinalysis: dirty brown granular casts and
epithelial casts
Prognosis is excellent in nephrotoxic ATN if
patient survives the disease responsible
normal BUN & creatinine
BUN: 7-18 mg/dL
creatinine = 0.6-1.2 mg/dL
Ratio should be ~15:1
Pre-renal azotemia
caused by a decrease in cardiac output to kidneys (e.g., blood loss,
CHF) that ↓GFR
BUN:Cr > 15
Renal (intrinsic) azotemia
caused by damage to the kidneys (e.g., ATN, chronic renal failure)
BUN:Cr ≤ 15
Post-renal azotemia
↓GFR due to obstruction and increased tubular pressure causes backdiffusion
of urea into blood
BUN:Cr > 15
**persistent obstruction will lead to renal azotemia
Benign Nephrosclerosis
term for the renal changes observed in benign hypertension -always associated with hyaline arteriolosclerosis * homogeneous, pink hyaline thickening of the vessel lumen
Benign Nephrosclerosis morphology
kidneys atrophy --> grain leather appearance does not cause severe damage to kidneys -↓ GFR -loss of concentrating ability
Malignant nephrosclerosis
associated with malignant hypertension
-always associated with hyperplastic
arteriolosclerosis
Malignant nephrosclerosis morphology
small, pinpoint petechial hemorrhages
cover the kidney surface
-“flea-bitten kidney”
Malignant nephrosclerosis clinical course
Diastolic pressure >120 mm Hg, papilledema,
encephalopathy, cardiovascular abnormalities, renal
failure
At onset, there is marked proteinuria and hematuria, but
no significant alteration in renal function
-quickly progresses to renal failure, so treat as medical
emergency
~50% survive 5 years; 90% of deaths caused by uremia
Simple Cysts
occur as multiple or single cystic spaces in renal cortex -~1-5 cm in diameter; filled with clear fluid no clinical significance; common postmortem finding main importance is differentiation from tumors (usually simply via ultrasound)
Dialysis-associated cystic change
occur in patients with end-stage renal disease that
have undergone prolonged dialysis
present in both cortex and medulla, and may bleed,
causing hematuria
increase risk for adenomas and adenocarcinomas
Autosomal Dominant (Adult) Polycystic Kidney Disease
multiple expanding cysts of both kidneys that destroy underlying parenchyma important cause of chronic renal failure (~10% of cases)
Autosomal Dominant (Adult) Polycystic Kidney Disease path
caused by inheritance of an autosomal dominant
polycystin (PKD) gene, either PKD1 (90% of
families) or PKD2
-both genes encode proteins of unknown function, but
have homology to those involved in cell-cell or cellmatrix adhesion
pressure of expanding cysts leads to
ischemic atrophy of renal parenchyma
Autosomal Dominant (Adult) Polycystic Kidney Disease clinical course
usually does not produce symptoms until the 4th decade -flank pain; "heavy, dragging sensation" -intermittent gross hematuria -superimposed hypertension and urinary infection are most important complications Berry aneurysms of the circle of Willis present in 10-30% of patients - high incidence of subarachnoid hemorrhage Asymptomatic liver cysts in 1/3rd of patients
Autosomal Dominant (Adult) Polycystic Kidney Disease prognosis
better than other most chronic renal diseases -slow progression; renal failure occurs, on average, at 50 yoa, but variable - treat with renal transplantation
Autosomal Recessive (Childhood) Polycystic Kidney Disease path
rare polycystic kidney disease with perinatal,
neonatal, infantile, and juvenile categories
caused by inheritance of two mutated copies of
the fibrocystin gene (PKHD1)
- unknown function, but may be a receptor with role in
collecting-duct and biliary differentiation
Autosomal Recessive (Childhood) Polycystic Kidney Disease presentation
numerous small cysts in the cortex and medulla;
give kidney sponge-like appearance
- all cysts derive from collecting tubules
Autosomal Recessive (Childhood) Polycystic Kidney Disease clinical course
perinatal and neonatal forms are most common - cysts present at birth - may die quickly from pulmonary or renal failure - patients surviving infancy develop liver cirrhosis
Urolithiasis
Renal Calculi, Stones
stones may arise at any level in the urinary
tract, but the kidney is the most common site
affect 5-10% of Americans in their lifetime
- men > women; peak age: 20-30s
-most commonly contain calcium oxalate (70%),
followed by magnesium ammonium phosphate
(struvite), uric acid, and cystine
Urolithiasis
(Renal Calculi, Stones) path
increased urine concentration of the
stone’s constituents so that it exceeds
their solubility in urine (supersaturation)
e.g., hypercalciuria associated with calcium
oxalate stones
Magnesium ammonium
phosphate (struvite)
stones
associated with UTIs caused by urea-splitting bacteria (e.g., Proteus sp.) bacteria also serve as nidus for stone formation
Uric acid stones
predisposition with gout, diseases involving
rapid cell turnover (leukemias), and low urine
pH (<5.5)
Cystine stones
genetic defect in renal transport of amino acids
Urolithiasis
(Renal Calculi, Stones) clinical course
renal or ureteral colic - flank pain radiating toward the groin gross hematuria predispose to bacterial infection; large stone may cause hydronephrosis
Hydronephrosis
dilation of the renal pelvis and calyces, with
atrophy of the parenchyma, caused by
obstruction to urine outflow
Hydronephrosis morphology
kidney may be massively enlarged
renal parenchyma is compressed and atrophied;
papillae are obliterated and pyramids are flattened
Hydronephrosis clinical course
complete bilateral obstruction (below ureters) causes anuridia, but partial bilateral obstruction causes polyuria (due to defects in tubular concentrating mechanism) unilateral obstruction often remains silent for long period reversible if obstruction is removed within a few weeks
