Kidney Path Flashcards Preview

Pathology > Kidney Path > Flashcards

Flashcards in Kidney Path Deck (84):
1

nephrotic syndrome

severe proteinuria
hypoalbuminemia
generalized edema
hyperlipidemia
lipiduria

2

nephritic syndrome

hematuria
azotemia
oliguria
hypertension
proteinuria

3

causes of nephrotic syndrome

Minimal Change Disease (MCD)
Membranous Glomerulonephritis
(MGN)
Focal Segmental
Glomerulosclerosis (FSGS)
Membranoproliferative
Glomerulonephritis (MPGN)

4

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

5

what is universal to nephrotic syndrome

fusion of podocytes

6

Minimal Change Disease (MCD) path

current evidence points to a disorder of T cells
-elaborate factors (IL-8, TNF, etc.?) that affect
nephrin synthesis

7

Minimal Change Disease (MCD) gold standard for diagnosis

EM

8

Minimal Change Disease (MCD) immunofluorescence?

no

9

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

10

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

11

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

12

Membranous Glomerulonephritis
(MGN) key to dianosis

silver stain
detects collagen in BM

13

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

14

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)

15

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

16

Focal Segmental
Glomerulosclerosis (FSGS) diagnosis

IF usually isn’t done, but detects IgM and
C3 in sclerotic segments

17

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

18

Membranoproliferative
Glomerulonephritis (MPGN)

may be nephritic, nephrotic, or mixed
characterized by alterations in the GBM
and mesangium plus proliferation of
glomerular cells

19

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

20

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

21

Membranoproliferative
Glomerulonephritis (MPGN) key to diagnosis

"doubled" GBM on silver stain

22

Membranoproliferative
Glomerulonephritis (MPGN) EM varies by type

Type I: subendothelial
deposits
Type II: dense
deposits in center of
GBM and under
endothelium

23

Causes of Nephritic Syndrome

Acute Proliferative (Poststreptococcal)
Glomerulonephritis (PGN)
Rapidly Progressive (Crescentic)
Glomerulonephritis (RPGN or CrGN)
IgA Nephropathy (Berger Disease)

24

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

25

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

26

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

27

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)

28

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

29

Rapidly Progressive (Crescentic)
Glomerulonephritis (RPGN or CrGN) Type II CrGN

Complication of any immune complex nephritides
(PGN, SLE, IgA nephropathy)
Granular IF pattern

30

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

31

Rapidly Progressive (Crescentic)
Glomerulonephritis (RPGN or CrGN)

Crescents obliterate the Bowman's space
and compress the glomeruli

32

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

33

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

34

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

35

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

36

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)

37

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

38

signs & symptoms of Chronic Glomerulonephritis

decreased renal acuity
cramps
restless leg
sleep disturbances
bone disease
itching
anemia

39

Chronic Glomerulonephritis morphology

Kidneys small with
granular surface

40

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

41

Chronic Diabetic Glomerulopathy risk factors

Poor glycemic control
hypertension
diabetic retinopathy (high
correlation)

42

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

43

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.

44

Renal amyloidosis

B-2 microglobulin

45

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

46

Acute Pyelonephritis clinical course

Fever, chills, malaise
Dysuria, frequency, and urgency
Costovertebral angle (CVA) tenderness
Urinalysis shows WBC casts and pyuria

47

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

48

Chronic Pyelonephritis morphology

Uneven scarring of
the pelvis and/or
calyces
-Leads to blunted
calyces

49

Chronic Pyelonephritis clinical course

Unnoticed until renal insufficiency begins;
may cause hypertension
n Some develop FSGS

50

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)

51

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

52

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)

53

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

54

Analgesic Nephropathy clinical course

Chronic renal failure (more common in
those with preexisting renal disease),
hypertension, anemia
Increased incidence of transitional cell
carcinoma

55

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

56

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)

57

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

58

normal BUN & creatinine

BUN: 7-18 mg/dL
creatinine = 0.6-1.2 mg/dL
Ratio should be ~15:1

59

Pre-renal azotemia

caused by a decrease in cardiac output to kidneys (e.g., blood loss,
CHF) that ↓GFR
BUN:Cr > 15

60

Renal (intrinsic) azotemia

caused by damage to the kidneys (e.g., ATN, chronic renal failure)
BUN:Cr ≤ 15

61

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

62

Benign Nephrosclerosis

term for the renal
changes observed in
benign hypertension
-always associated with
hyaline
arteriolosclerosis
* homogeneous, pink
hyaline thickening of
the vessel lumen

63

Benign Nephrosclerosis morphology

kidneys atrophy --> grain
leather appearance
does not cause severe
damage to kidneys
-↓ GFR
-loss of concentrating
ability

64

Malignant nephrosclerosis

associated with malignant hypertension
-always associated with hyperplastic
arteriolosclerosis

65

Malignant nephrosclerosis morphology

small, pinpoint petechial hemorrhages
cover the kidney surface
-“flea-bitten kidney"

66

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

67

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)

68

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

69

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)

70

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

71

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

72

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

73

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

74

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

75

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

76

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

77

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

78

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

79

Uric acid stones

predisposition with gout, diseases involving
rapid cell turnover (leukemias), and low urine
pH (<5.5)

80

Cystine stones

genetic defect in renal transport of amino acids

81

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

82

Hydronephrosis

dilation of the renal pelvis and calyces, with
atrophy of the parenchyma, caused by
obstruction to urine outflow

83

Hydronephrosis morphology

kidney may be massively enlarged
renal parenchyma is compressed and atrophied;
papillae are obliterated and pyramids are flattened

84

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