Warren- Diseases of Tubules and Interstitium

Question 1

What does ischemic or toxic inury to tubules lead to?

Answer 1

ATN (acute tubular necrosis)

or

ATI (acute tubular injury)

Question 2

What does INFLAMMATORY rxt of the tubules and interstitium lead to?

Answer 2

TIN (tubulointerstitial nephritis)

Question 3

What is acute tubular necrosis?

Answer 3

Destruction of TUBULAR EPITHELIAL CELLS which presents as acute loss of renal function

Question 4

What is the MCC of acute renal failure?

Answer 4

ATN

50% of ARF in hospitalized pts

Question 5

What causes ischemic ATN?

Answer 5

hypotension/shock>

Inadequate blood flow to kidneys

Question 6

What causes nephrotoxic ATN?

Answer 6

drugs
heavy metals
organic solvents
contrast dye

Question 7

What is the pathogenesis of ATN?

Answer 7

1. tubular epithelial cell injury (reverisble: cell swelling, loss of polarity; lethal: necrosis and apoptosis)
2. Disturbances in blood flow (intrarenal vsoconstriction)

Question 8

What causes tubule cell injury?

Answer 8

1. DEPLETION OF ATP>
increased intracellular Ca>
redistribution of membrane proteins>
abnormal ion transport>
increased Na/Cl to DT>
tubuloglomerular feedback and vasoconstriction

2. INJURED CELLS RECRUIT WBCS
3. LUMINAL TUBULE OBSTRUCTION BY DETACHED CELLS> increased intratubular pressure and decreased GFR

Question 9

How do disturbances in renal blood flow relate to tubular injury?

Answer 9

1. intrarenal vsoconstriction> decreased glomerular plasma flow/oxygen to TAL and the PT
2. Vasoconstrictor pathways>
   RAS>
   endothelin released by damaged endothelial cells decreases NO

Question 10

Can you recover from ATN?

Answer 10

Yes!

Reversibly injured epithelial cells proliferate and differentiate d/t GFs like EGF

Question 11

What is the pathology of ATN?

Answer 11

1. Tubular epithelial necrosis
2. SLOUGHING of tubular cells into lumen
3. Hyaline/granular CASTS
4. interstitial edema and increased lymphocytes

Question 12

What specific changes are associated w/ toxic ATN specifically ethylene glycol poisoning?

Answer 12

Ca oxalate crystals in the tubular lumen

Question 13

Describe the clinical course of ATN.

Answer 13

1. initiation- decreased urine output and increased BUN (36 hrs)
2. Maintenance- oliguria, increased BUN, hyperkalemia, met. acidosis (requires dialysis)
3. Recovery (steady increase in urine volume), hypokalemia d/t loss of K

Question 14

HOw do you differentiate acute and chronic forms of tubulointersitital nephritis?

Answer 14

acute PMN/Eos, edema

Chronic- fibrosis/tubular atrophy

Question 15

What are the clinical sxs of tubulointerstitial nephritis?

Answer 15

Polyuria
nocturia
metabolic acidosis

Question 16

What are causes of TIN?

Answer 16

Infections
toxins
Metabolic disease
Neoplasms- MM
Physical factors
Immunologic rxns

Question 17

What causes acute pyelonephritis?

Answer 17

bacterial infection

Question 18

What causes chronic pyelonephritis?

Answer 18

Bacterial infection
reflux
obstruction

Question 19

What accounts for >85% of casses of pyelonephritis?

Answer 19

Gram - bacilli from GI tract

E. COLI
proteus
klebsiella

Question 20

What is the pathogenesis of pyelonephritis?

Answer 20

Colonization of urethra>
organisms into bladder>
multiplication d/t decreased urine flow (obstruction/neurogenic bladder)

Question 21

What is vesicoureteral reflux? What commonly causes it?

Answer 21

INCOMPETENCE of the vesicoureteral valve>
allows bacteria to enter ureter/renal pelvis

Congenital shortening of intravesicle portion of the ureter

Question 22

What is intrarenal reflux?

Answer 22

Occurs via the ducts at the tips of papillae

another cause of pyelonephritis

Question 23

What is the morphology of Acute Pyelonephritis?

Answer 23

Intersitital inflammation by PMN

Intratubular aggregates of NEUTROPHILS>
tubular necrosis>
heals by scarring>
tubular atrophy w/ interstitial fibrosis w/ lymphocytes

Question 24

What part of the kidney is most commonly affect with acute pyelonephritis?

Answer 24

Upper and lower poles

easier to have reflux through these papillae

Question 25

What are complications of acute pyelonephritis?

Answer 25

1. papillary necrosis--> yellow necrosis of papillary tips seen in pts w/ obstruction (diabetics) 2. pyonephrosis (kidney full of pus) 3. Perinephric abscess (suppurative inflammation extends through capsule to adjacent tissue

Question 26

What is seen in chronic pyelonephritis?

Answer 26

chronic reflux/chronic obstruction> Pelvocalyceal damage > important cause of END STAGE RENAL DISEASE

Question 27

What morphology it typical of chronic pyelonephritis?

Answer 27

Irregular scarred kidney surface Blunt calyces cortex filled w/ THYROIDIZATION- tubules w/ colloid casts May see glomeruli normal or secondarily affected by FSGS

Question 28

Describe the onset of chronic pyelonephritis.

Answer 28

SILENT or associated w/ recurrent acute pyelonephritis

Question 29

How do pts with chronic pyelonephritis present?

Answer 29

Late in disease w/ HTN or renal insufficiency FSGS and proteinuria

Question 30

What are three ways that drugs can induce injury?

Answer 30

1. Interstitial immunologic rxn (methicillin) 2. Cause acute tubular injury/ARF 3. Slow injury to tubules over many years (analgesic abuse nephropathy)

Question 31

Describe the course of acute DRUG induced interstitial nephritis.

Answer 31

``` Take drug> onset 15 d after exposure> fever, rash, renal abnormalities (hematuria, proteinuria, white cells)> EOSINOPHILIA> Stop the offending drug> full recovery ``` *50% develop ARF (elderly)

Question 32

What do you see microscopically with Acute Drug induced interstitial nephritis?

Answer 32

1. Eosinophils and PMNs 2. Granulomas and giant cells 3. Lymphocytes infiltrate tubular epithelium> tubular necrosis 4. Gomeruli NORMAL 5. Interstitial edema, MACROPHAGES AND LYMPHOCYTES *NO neutrohpils in lumen of tubules just inflammation in interstitium

Question 33

What is the pathogenesis of Acute Drug induced interstitial nephritis? How long does it take to progress to sxs?

Answer 33

Idiosyncratic IR ``` Drug (hapten)> covalently bind to cytoplasmic/extracellular component of tubular cells> Mix: Type I (IgE- eosinophilia) Type IV (delayed) ``` 2 wks

Question 34

How can NSAIDS effect the kidney?

Answer 34

1. ARF 2. Acute hypersensitivity 3. Acute interstitial nephritis and MCD 4. Membranous glomerulonephritis

Question 35

How do NSAIDS cause ARF?

Answer 35

Nsaid> inhibition of PG> lose vasodilation/local vasoconstriction> decreased blood volume

Question 36

What causes tubulointerstitial disease?

Answer 36

Urate nephropathy Hypercalcemia and nephrocalcinosis (Ca stones and deposition of Ca)

Question 37

What is Urate nephropathy?

Answer 37

ACUTE UA nephropathy> precipitation of UA crystals in tubules> obstruction> ARF Chronic UA nephropathy> gout

Question 38

What is acute UA nephropathy associated with?

Answer 38

CHEMO ``` Chemo> tumor cells killed> release urate> clogs up kidney tubules> obstructs flow> ARF ```

Question 39

What is Multiple myeloma?

Answer 39

plasma cell neoplasm

Question 40

What causes MM?

Answer 40

Occurs in HALF of all MM pts Bence jones proteins (kappa/lambda light chains)> combine w/ Tamm horsfall protein> large tubular casts> obstruction/peritubular inflammation