Tubulointerstitial Disease

Question 1

causes of acute renal failure

Answer 1

pre-renal
renal (tubular, glomerular, vascular)
post-renal

Question 2

causes of tubular ARF

Answer 2

1. acute tubular injury (ischemic or toxic)
2. inflammatory

Question 3

what nephron segments are the most susceptible to acute tubular injury

Answer 3

PCT and thick ascending loop of Henle

due to HIGH O2 demand

Question 4

ischemic ATI

Answer 4

decreased perfusion of renal parenchyma caused by vasoconstriction

segmental distribution

Question 5

what part of the kidney is most susceptible to ischemic ATI

Answer 5

outer medulla

LOW O2 availability

Question 6

toxic ATI

Answer 6

nephron exposure to endogenous/exogenous toxins

diffuse distribution

Question 7

what part of the kidney is most susceptible to toxic ATI

Answer 7

renal tubules

high surface area, active transport systems, high O2/energy demands, high toxin exposure

Question 8

what is the maladaptive response to injury in the nephron

Answer 8

1. tubular activation
2. histologic cell changes
3. cell swelling
4. cell detachment
5. de-differentiation
6. proliferation
7. differentiation

Question 9

tubular activation

Answer 9

increased demand on tubular cells –> release of cytokines –> recruitment of inflammatory cells and fibroblasts –> fibrosis + necrosis –> tubule loss

occurs in response to ischemia/hypoxia, glomerular injury, and tubular injury

Question 10

what is the main sign of glomerular dysfunction

Answer 10

proteinuria

Question 11

how is glomerular dysfunction related to tubular injury

Answer 11

glomerular dysfunction causes proteinuria

proteins in urine cause tubular damage –> tubular activation

Question 12

what histologic changes occur to tubular epithelial cells during maladaptive response to injury

Answer 12

loss of polarity
loss of microvilli/brush border –> decreased absorptive capacity –> high Na in filtrate reaching DCT –> increased vasoconstriction

Question 13

why do cells start to swell in maladaptive response to injury

Answer 13

leukocyte infiltrate and vesiculation –> increased intracellular pressure

Question 14

what happens when cells detach from basement membrane

Answer 14

dead tubular cells slough off into lumen –> increase intratubular pressure and decreased GFR –> wrinkled basement membrane (tubular atrophy)

formation of casts –> can obstruct distal tubules

Question 15

what is de-differentiation

Answer 15

simplification (stretching out) of surviving epithelial cells to cover the exposed segments of the basement membrane; causes cells to become undifferentiated

Question 16

what is required in order for cells to regenerate

Answer 16

INTACT basement membrane

Question 17

what happens if the basement membrane is not intact OR cells don’t regenerate

Answer 17

chronic nephron loss –> CKD

Question 18

what happens once cells completely cover the basement membrane

Answer 18

cells proliferate across the basement membrane and re-differentiation (reestablish polarity)

Question 19

what are the classes of inflammatory diseases

Answer 19

1. tubulointerstitial nephritis
2. interstitial nephritis (acute and chronic)
3. pyelonephritis (acute and chronic)

Question 20

what is the pathogenesis of tubulointerstitial nephritis

Answer 20

infectious
sterile (glomerular disease)
idiopathic
chronic

Question 21

pathogenesis of leptospirosis

Answer 21

• bacteria is shed in urine
• enters through MM or abraded skin
• moves through the blood to the kidney, liver, uterus, and eye and migrates through endothelium

Question 22

what kind of disease does leptospirosis cause

Answer 22

1. interstitial nephritis
2. tubulitis

Question 23

interstitial nephritis

Answer 23

lymphocyte and plasma cell infiltrate/inflammation

Question 24

tubulitis

Answer 24

neutrophil infiltrate in renal tubules

Question 25

what is chronic nephritis

Answer 25

loss of nephrons that get replaced by fibrosis

Question 26

gross and histologic lesion of chronic nephritis

Answer 26

scalloped edges interstitial inflammation, fibrosis, tubular atrophy w/ intact glomeruli

Question 27

what is the sign of tubular atrophy

Answer 27

wrinkled basement membrane

Question 28

what histologic lesion does FIP cause

Answer 28

perivascular pyogranulomatous interstitial nephritis/vasculitis (neutrophils + lymphocytic infiltrate) causes pressure necrosis --> tubule loss

Question 29

pyelonephritis

Answer 29

ascending infection from lower urinary tract to kidneys ONLY infectious etiologies neutrophilic infiltrate

Question 30

chronic pyelonephritis gross lesion

Answer 30

pale, fibrotic, irregular margins, irregular renal crest linear scars from ascending necrosis

Question 31

mechanism of NSAID toxicity

Answer 31

- NSAIDs inhibit COX 1 and 2 - decreased production of prostaglandins - decreased vasodilation --> increased vasoconstriction - vasoconstriction --> medullary ischemia --> renal papillary necrosis

Question 32

renal papillary necrosis

Answer 32

death of renal parenchyma in the region of the renal papilla caused by ischemia due to low perfusion of papillary vessels

Question 33

mechanism of copper toxicity

Answer 33

chronic low-level copper exposure --> massive hepatic copper storage --> stressful event triggers hepatocellular necrosis --> copper releases into the blood --> damages RBCs (intravascular hemolysis) --> anemia + hemoglobinuria --> ischemia + tubular necrosis occurs in sheep

Question 34

gross lesion of copper toxicity

Answer 34

gun metal blue kidneys