Renal 04: Pathology 1

Front 1

How thick is the cortex of the kidney?

Back 1

~1 cm

Front 2

What imaging tools can be used to view the kidney?

Back 2

Ultrasound or CT

Front 3

How does a kidney show up on an ultrasound?

Back 3

- Cortex = darker
- Medulla = lighter

Front 4

How many distal tubules combine and enter medulla to form Collecting Duct?

Back 4

~6 distal tubules - form ducts of Bellini which drain into calyx

Front 5

What is the organization of the glomerulus and mesangial cells?

Back 5

- Mesangium in center w/ 3 capillary loops of glomerular basement membrane
- Endothelial cells lines the inside of GBM
- Epithelial cells on outside w/ podocytes

Front 6

What are the features of the glomerular endothelial cells as part of the filtration barrier?

Back 6

- Fenestrations: 70-100 nm
- Negatively charged surface
- Form initial filtration barrier
- Synthesize and maintain GBM

Front 7

What are the features of the glomerular basement membrane as part of the filtration barrier?

Back 7

- Composed of type IV collagen
- Size and charge are main determinants of filtration
- Heparan sulfate provides negative charge
- Water and cationic proteins of LMW (<70,000) are permeable
- Albumin permeability is limited by negative charge

Front 8

What are the features of the visceral epithelial cells (podocytes) as part of the filtration barrier?

Back 8

- Also synthesize and maintain GBM
- Cytoplasmic foot processes form filtration slit (slit pore)
- Podocytes are negatively charged

Front 9

What is in the cell cytoplasm of mesangial cells?

Back 9

Myosin filaments

Front 10

What surrounds the mesangial cells?

Back 10

Glomerular Basement Membrane like matrix

Front 11

What are the functions of mesangial cells?

Back 11

- Provides structural support
- Modulates glomerular filtration

Front 12

What are the congenital abnormalities associated with the kidneys?

Back 12

- Aplasia, hypoplasia, dysplasia
- Ectropic kidneys
- Fusion abnormalities
- Duplication of ureters

Front 13

What is the most common congenital kidney disorder?

Back 13

Horseshoe kidney

Front 14

What percentage of horseshoe kidneys are fused at the lower poles?

Back 14

90%

Front 15

What genetic issue is Horseshoe kidney associated with?

Back 15

Turner's Syndrome

Front 16

What are the complications of a horseshoe kidney anomaly?

Back 16

- Increased risk of infection
- Kidney stones

Front 17

What cystic diseases are associated with the kidney?

Back 17

- Renal dysplasia
- Autosomal recessive polycystic kidney disease (ARPKD)
- Autosomal dominant polycystic kidney disease (ADPKD)
- Medullary sponge kidney
- Acquired cystic disease

Front 18

What is the most common cystic disease of the kidneys?

Back 18

Autosomal dominant polycystic kidney disease (ADPKD)

Front 19

What are the types of Renal Dysplasia?

Back 19

- Unilateral Multicystic Renal Dysplasia
- Bilateral Multicystic Renal Dysplasia (fatal)

Front 20

How do you detect Renal Dysplasia?

Back 20

- Prenatal ultrasound
- Palpable mass
- Asymptomatic (undetected into adulthood)

Front 21

What gene mutation / chromosome is responsible for Autosomal Recessive Polycystic Kidney Disease?

Back 21

PKHD1 gene located on chromosome 6p21

Front 22

How can you diagnose Autosomal Recessive Polycystic Kidney Disease?

Back 22

- In utero by ultrasound
- Large, hyperechoic kidneys
- Oligohydramnios - decreased urine in fetal bladder

Front 23

How frequent is Autosomal Recessive Polycystic Kidney Disease? Who is it more common in?

Back 23

- 1:20,000
- More frequent in caucasians

Front 24

What features are associated with Autosomal Recessive Polycystic Kidney Disease?

Back 24

- Enlarged kidneys at birth
- Maternal oligohydramnios
- Potter's facies
- Pulmonary hypoplasia

Front 25

What is the prognosis for Autosomal Recessive Polycystic Kidney Disease?

Back 25

- Serious cases are incompatible with life
- Perinatal mortality 30-50%

Front 26

What are the extra-renal manifestations of Autosomal Recessive Polycystic Kidney Disease?

Back 26

- Hepatic fibrosis
- Cholangitis (infection of the bile duct, usually caused by bacteria)
- Portal HTN (esophageal varices, GI bleeding)

Front 27

What are the morphological features of Autosomal Recessive Polycystic Kidney Disease?

Back 27

- Smooth kidney w/ numerous small cysts (cortical and medullary cysts)
- Cylindrical cysts extending radially through cortex
- Microscopically cysts lined by cuboidal epithelium (may see epithelial hyperplasia)
- Normal glomeruli

Front 28

What does this histologically represent?

Back 28

Autosomal Recessive Polycystic Kidney Disease

Front 29

How frequent is Autosomal Dominant Polycystic Kidney Disease? Who is it more common in?

Back 29

- 1:400 - 1:1000 Americans
- Most common cystic disease of the kidneys

Front 30

How common is a LACK of family history in Autosomal Dominant Polycystic Kidney Disease?

Back 30

- Absent in 25-40%
- New mutations
- Late onset renal failure

Front 31

What mutations commonly cause Autosomal Dominant Polycystic Kidney Disease? What chromosomes?

Back 31

- 90% have mutation of PKD1 gene on chromosome 16
- Others have mutation of PKD2 gene on chromosome 4

Front 32

How does the mutation you have for Autosomal Dominant Polycystic Kidney Disease affect when you progress to renal failure?

Back 32

- PKD1 (chr 16) progress to renal failure earlier (but in adulthood usually)
- PKD2 (chr 4) progress to renal failure at later age

Front 33

What are the possible causes of cyst formation in Autosomal Dominant Polycystic Kidney Disease?

Back 33

- Abnormal differentiation of epithelial cells
- High proliferation rate
- Secretion of fluid into cysts w/ loss of connection to functioning nephrons
- Abnormal ECM

Front 34

What are the renal symptoms of Autosomal Dominant Polycystic Kidney Disease?

Back 34

- Hematuria
- Mild proteinuria
- Hypertension
- Progressive renal failure (50% reach ESRD by age 57-73)
- Infections
- Stones
- Pain

Front 35

When do patients with Autosomal Dominant Polycystic Kidney Disease get progressive renal failure? Implications?

Back 35

- 50% reach ESRD by age 57-73
- They need to be on dialysis or kidney transplant to live

Front 36

What are the extra-renal symptoms of Autosomal Dominant Polycystic Kidney Disease?

Back 36

- Hepatic cysts (40%)
- Intracranial aneurysms (10-30%)
- Cardiac valvular abnormalities
- Arterial aneurysms (aorta, coronaries)
- IVC thombosis
- Inguinal and umbilical hernias
- Pancreatic cysts

Front 37

What do 40% of patients with Autosomal Dominant Polycystic Kidney Disease get?

Back 37

Hepatic cysts

Front 38

What do 10-30% of patients with Autosomal Dominant Polycystic Kidney Disease get?

Back 38

Intracranial Aneurysms

Front 39

In what kidney disease do 40% get hepatic cysts and 10-30% get intracranial aneurysms?

Back 39

Autosomal Dominant Polycystic Kidney Disease

Front 40

How do you diagnose Autosomal Dominant Polycystic Kidney Disease?

Back 40

Patients present in several ways:
- Symptomatic: flank pain and hematuria
- Multiple bilateral cysts noted incidentally on imaging
- Screening d/t family hx w/ ultrasound

Front 41

What are the diagnostic criteria for Autosomal Dominant Polycystic Kidney Disease when a patient has a family history?

Back 41

With ultrasound find:
- Age <30: at least 2 cysts
- Age 30-59: at least 2 cysts on each kidney
- Age >60: at least 4 cysts bilaterally

Front 42

What are the treatment goals of Autosomal Dominant Polycystic Kidney Disease?

Back 42

- Slow progression to ESRD (control BP and treat infections)
- Identify and manage extra-renal manifestations
- Control pain
- Dialysis / kidney transplant

Front 43

What are the common causes of acquired cystic disease?

Back 43

Develops in 50% of patients on dialysis and depends on duration of dialysis (the more years on dialysis, the more likely)

Front 44

What symptoms are noticed with Acquired Cystic Disease?

Back 44

- Usually asymptomatic
- May present w/ bleeding or pain

Front 45

What are the morphological features of Acquired Cystic Disease?

Back 45

- Clear, fluid-filled cysts
- Uni- or multi-locular cysts
- Cortex (usually)
- May involve corticomedullary junction and medulla

Front 46

What type of cancer is Acquired Cystic Disease associated with an increased risk of?

Back 46

Papillary Renal Cell Carcinoma

Front 47

When is a renal biopsy indicated?

Back 47

- Persistent glomerular hematuria (need to rule out other causes of hematuria like cancer or kidney stone)
- Persistent nephrotic range proteinuria
- Unexplained renal failure
- Renal transplant rejection

Front 48

What are the contraindications for a renal biopsy?

Back 48

- Bleeding disorders
- Anatomic abnormalities (eg, solitary kidney)

Front 49

What are the potential complications after a renal biopsy? How common?

Back 49

- Self-limited gross hematuria (10%)
- Hematoma formation (80%)
- Hemorrhage (1-2%) - surgery requiring (0.3%)
- Death (1/8000)

Front 50

How do you do a renal biopsy?

Back 50

- Use long needle / instrument
- Real time guided by ultrasound (enter on side to avoid vessels)
- Take 3 samples

Front 51

What tests are done to the tissue obtained from a renal biopsy?

Back 51

- Light microscopy
- Direct immunofluorescence microscopy
- Electron microscopy

Front 52

What do you do for light microscopy to study renal biopsy samples?

Back 52

Silver, trichrome, PAS, and/or H&E stains

Front 53

What do you do for direct immunofluorescence microscopy to study renal biopsy samples?

Back 53

IgA, IgG, IgM, C3, C1q, albumin, fibrinogen, kappa, lambda (identifies patterns of immune-complex deposition)

Front 54

What do you do for electron microscopy to study renal biopsy samples?

Back 54

Identifies submicroscopic defects and sites of damage in glomerulus