(LEC) Toxic Response of the Kidney

Question 1

The kidney releases _________ and ______________

Answer 1

Renin, Erythropoietin

Question 2

Principal role: Excretion of
metabolic wastes

Answer 2

Kidney

Question 3

(T/F) The kidney metabolizes VIT A into 1,25 dihydroxyvitamin D

Answer 3

False. it metabolizes VITAMIN D3

Question 4

(T/F) The kidney plays a role on acid-base balance and electrolyte composition

Answer 4

True

Question 5

(T/F) The kidneys ensure the regulation of extracellular fluid volume

Answer 5

True

Question 6

Anatomical areas of the kidney (CMP)

Answer 6

• Cortex (90%)
• Medulla (~6-10%),
• Papilla (1-2%)

Question 7

Functional units of the kidney

NVGT

Answer 7

• Nephron
• Vascular element
• Glomerulus
• Tubular element

Question 8

A complex, specialized capillary bed composed primarily of endothelial cells.

Answer 8

Glomerulus

Question 9

Interlobar, arcuate, interlobular arteries and afferent arterioles that supply the glomerulus

Answer 9

Renal artery

Question 10

(T/F) BOTH afferent and efferent arterioles control glomerular capillary pressure and glomerular plasma flow rate.

Answer 10

True

Question 11

Carry the blood away from the glomerulus

Answer 11

Afferent arteriole

Question 12

Deliver the blood to the glomerulus

Answer 12

Efferent arteriole

Question 13

The glomerulus is a complex, specialized capillary bed composed primarily of __________________ cells.

Answer 13

Endothelial

Question 14

Three discrete segments of the proximal tubule

CTR 123

Answer 14

S1 (pars convolute)
S2 (transition between pars convolute and pars recta)
S3 (pars recta)

Question 15

Workhorse of the nephron that reabsorbs 60-80% of solute and water filtered at the glomerulus

Answer 15

Proximal tubule

Question 16

(T/F) The proximal tubule reabsorbs virtually all the filtered high MW proteins by specific exocytotic protein reabsorption processes.

Answer 16

False. It reabsorbs virtually all the filtered LOW MW proteins by specific ENDOCYTOTIC protein reabsorption processes.

Question 17

This is characterized by an attenuated and fenestrated cytoplasm & visceral epithelial cells

Answer 17

Renal Vasculature/Glomerulus

Question 18

Reabsorbs 25% Na and K and 20% of filtered water

Answer 18

Loop of Henle

Question 19

Iso-osmotic to the renal interstitium (water is freely permeable)

Answer 19

Tubular fluid entering the Thin descending limb

Question 20

Impermeable to water, and electrolytes are reabsorbed by the active Na+/K+/2Cl- cotransport mechanism

Answer 20

Thin ascending limb

Question 21

________ distal tubule reabsorbs most of the remaining impermeable to water.

Answer 21

Early distal tubule

Question 22

(T/F) The late distal tubule, cortical collecting tubule, and medullary collecting duct perform the final regulation and finetuning of urinary volume and composition.

Answer 22

True

Question 23

Build up of Nitrogenous waste in blood caused by decrease in GFR (AKI)

Answer 23

Azotemia

Question 24

Abrupt decline in GFR with resulting azotemia

Answer 24

Acute Kidney Injury

Question 25

A complex disorder that comprises multiple causative factors with clinical manifestations ranging from minimal **elevation in serum creatinine to anuric renal failure.**

Answer 25

Acute Kidney Injury

Question 26

Decline in GFR result from?

Answer 26

Prerenal, postrenal, intrarenal factors

Question 27

# Cause of GFR decline renal vasoconstriction, intravascular volume depletion, insufficient cardiac output

Answer 27

Prerenal factors | Afferent arteriolar constriction so dec. blood flow

Question 28

# Cause of GFR decline ureteral or bladder obstruction

Answer 28

Postrenal factors | Obstruction inc. tubular pressure = dec. GFR

Question 29

# Cause of GFR decline glomerulonephritis, tubular cell injury, death and loss resulting in back leak

Answer 29

Intrarenal | Back leak in intracellular space/bloodstream

Question 30

# Mechanisms of chemically-induced acute kidney injury NSAID, Radiocontrast agents, Cyclosporine, Ampho B, Tacrolimus

Answer 30

Vasoconstriction ## Footnote Never Run Cats After tacos (NRCAT)

Question 31

# Mechanisms of chemically-induced acute kidney injury Sulfonamides, Methotrexate, Acyclovir, Triamterene, Ethylene glycol, Protease inhibitors

Answer 31

Crystalluria ## Footnote Silly Monkeys Are Trying Extra Potions (SMATEP)

Question 32

# Mechanisms of chemically-induced acute kidney injury Cyclosporine, Mitomycin C, Tacrolimus, Cocaine, Conjugated estrogens, Quinine

Answer 32

Endothelial Injury

Question 33

# Mechanisms of chemically-induced acute kidney injury Gold, Penicillamine, NSAID

Answer 33

Glomerulopathy ## Footnote Gold Pigs Nibble (GPN)

Question 34

# Mechanisms of chemically-induced acute kidney injury Antibiotics, NSAID, Diuretics

Answer 34

Interstitial Nephritis ## Footnote Anti Naughty Dog (AND)

Question 35

# Mechanisms of chemically-induced acute kidney injury Aminoglyco, Cisplatin, Vancomycin, Pentamidine, Radioconstrast agents, Heavy metals, Halo-alkane

Answer 35

Tubular Toxicity

Question 36

# Mechanisms of chemically-induced acute kidney injury Diuretics, ARa, ACEi, Anti-htn

Answer 36

Prerenal ## Footnote Something to do with htn + diuretics

Question 37

# Nephrotoxic Insult Path of Uninjured Cells

Answer 37

Compensatory hypertrophy, Cellular adaptation, Cellular proliferation

Question 38

# Nephrotoxic Insult Path of Injured Cells

Answer 38

Cellular repair, Cell death

Question 39

# Nephrotoxic Insult _________________> Re-epithelialization > Differentiation

Answer 39

Cellular proliferation

Question 40

Endpoint after toxic insult

Answer 40

**Structural** and **functional** recovery of nephron

Question 41

Chemicals that induce renal deterioration

Answer 41

Analgesics, Lithium, Cyclosporine (ALC)

Question 42

Progressive deterioration of renal function may occur with longterm exposure to various chemicals

Answer 42

Chronic Kidney Disease | longterm exposure = chronic

Question 43

Leads to tubular atrophy and interstitial fibrosis

Answer 43

CKD

Question 44

(T/F) A nontoxic concentration of a chemical in the plasma may reach toxic concentrations in the kidney and its tubules.

Answer 44

True

Question 45

The kidneys receive ____% to ____% of resting cardiac output

Answer 45

20% to 25%

Question 46

NSAID toxicity mechanism

Answer 46

prostaglandin synthesis suppressor → ↓renal blood flow → AKI

Question 47

ACEi toxicity mechanism

Answer 47

block vasoconstriction → precipitous decline in filtration pressure and AKI

Question 48

Site selective injury can be attributed to:

Answer 48

- site-specific differences in blood flow - transport and accumulation of chemicals - physicochemical properties of the epithelium - reactivity of cellular/ molecular targets - balance of bioactivation/ detoxification reactions - cellular energetics - regenerative/ repair mechanisms

Question 49

Initial site of chemical exposure within the nephron

Answer 49

Glomerulus

Question 50

# Glomerular Injury **Impair glomerular ultrafiltration without significant loss of structural integrity and decrease GFR** | Drugs

Answer 50

Cyclosporine, Amphotericin B, Gentamicin

Question 51

# Glomerular injury ↓GFR by renal vasoconstriction and ↓glomerular capillary ultrafiltration coefficient (Kf) | Specific Drug

Answer 51

Amphotericin B

Question 52

# Glomerular injury interacts with anionic sites on the endothelial cells → ↓GFR and Kf | Specific Drug

Answer 52

Gentamicin

Question 53

# Glomerular injury Renal vasoconstriction and vascular damage, injurious to the glomerular endothelial cell | Specific drug

Answer 53

Cyclosporine

Question 54

# Proximal Tubular Injury Most common site of toxicant-induced renal injury

Answer 54

Proximal tubule

Question 55

# Proximal Tubular Injury (T/F) The proximal tubule has a **tight** epithelium, favoring the **outflow** of compounds **outside** proximal tubular cells

Answer 55

False. The proximal tubule has a ***leaky*** epithelium, favoring the ***flux*** of compounds ***into*** proximal tubular cells

Question 56

# Proximal Tubular Injury Localized primarily in proximal tubule

Answer 56

Organic anions, cations, low MW proteins and peptides, GSH conjugates, and heavy metals

Question 57

# Loop of Henle / Distal Tubule / Collecting Duct Injury These drugs induce an ADH resistant polyuria occurs at the level of the medullary thick ascending limb and /or the collecting duct.

Answer 57

Amphotericin B, Cisplatin, Methoxyflurane

Question 58

# Loop of Henle / Distal Tubule / Collecting Duct Injury Manifestation of functional abnormalities in distal nephron sites

Answer 58

Impaired **concentrating** ability and/or **acidification** defects

Question 59

# Papillary injury Susceptible to the chronic injurious effects of abusive consumption of analgesics

Answer 59

Renal papilla

Question 60

# Papillary injury Initial target of abusive consumption of analgesics

Answer 60

Medullary interstitial cells > Degenerative changes in capillary > Loops of Henle > Collecting ducts

Question 61

# Site specific biomarkers Thrombotic microangiopathy

Answer 61

Glomerulus/Kidney

Question 62

# Site specific biomarkers Collagen IV, Cystatin C, Total protein

Answer 62

Glomerular markers

Question 63

# Site specific biomarkers Calbindin d28, RPA-1

Answer 63

Collecting duct markers

Question 64

# Site specific biomarkers NHE3, Osteopontin

Answer 64

Loop of Henle markers

Question 65

# Site specific biomarkers Clusterin, H-FABP, NGAL, Osteopontin, pi-GST

Answer 65

Distal tubule markers

Question 66

# Specific Nephrotoxicants Heavy metals

Answer 66

Mercury, Cadmium

Question 67

# Specific Nephrotoxicants Characterized by proximal tubular necrosis and AKI within 24 to 48 hours after administration.

Answer 67

Mercury | HgCl2

Question 68

# Specific Nephrotoxicants Induce **proximal tubule dysfunction** (S1 and S2 segments) and injury that *may progress to chronic interstitial nephritis*

Answer 68

Cadmium

Question 69

# Specific Nephrotoxicants Proteinuria, glucosuria, ↑BUN levels | Inc. BUN = Chloroform induced nephrotoxicity

Answer 69

Chloroform

Question 70

# Specific nephrotoxicants Primary cellular target of chloroform

Answer 70

Proximal tubule

Question 71

# Specific Nephrotoxicants The products of the reaction are ammonia, pyruvate, and a reactive thiol that is capable of binding covalently to cellular macromolecules, causing cellular damage.

Answer 71

Tetrafluoroethylene

Question 72

# Specific Nephrotoxicants Penultimate nephrotoxicant (under TFE)

Answer 72

Cysteine S-conjugate

Question 73

# Specific Nephrotoxicants (T/F) Chloroform poses no primary damage to the glomerulus or distal tubule.

Answer 73

True

Question 74

# Specific Nephrotoxicants (T/F) Biotransformation of bromobenzene and other halogenated benzenes is critical for their nephrotoxicity.

Answer 74

True

Question 75

# Specific Nephrotoxicants Metabolizes bromobenzene and conjugates it to glutathione

Answer 75

Hepatic cytochrome P450 | It is released it as a form that can cause nephrotoxicity

Question 76

# Specific Nephrotoxicants 1000-fold more potent than bromobenzene

Answer 76

diglutathione conjugate of the hydroquinone

Question 77

# Specific Nephrotoxicants (T/F) Mycotoxins are products of bacteria and fungi

Answer 77

False. Molds and fungi. | Mycotoxins produce nephrotoxicity.

Question 78

# Specific Nephrotoxicants ↓urine osmolality, GFR and RBF, glycosuria, ↑urinary enzyme exretion

Answer 78

Citrinin nephrotox

Question 79

# Specific Nephrotoxicants - Found on corn and corn products - Nephrotoxicity in rats and rabbits (↑ urine volume, ↓osmolality, ↑ low and high MW proteins)

Answer 79

Fumonisins B1 and B2

Question 80

# Specific Nephrotoxicants Aristolachia and I genera

Answer 80

Aristolochic acids and aristolactams | (tubular dysfunction, proteinuria, interstitial fibrosis)

Question 81

# Specific Nephrotoxicants Upon a large dose of (answer), AKI may occur within hours; but reversible on withdrawal | Chronic consumption >3 years – ***irreversible*** nephrotoxicity (Analge

Answer 81

NSAIDs | such as Aspirin, Ibuprofen, Naproxen, Indomethacin, celecoxib

Question 82

# Specific Nephrotoxicants Proximal tubular necrosis with increases in BUN and plasma creatinine, ↓ GFR, and clearance of para-aminohippurate

Answer 82

Acetaminophen

Question 83

# Specific Nephrotoxicants Characterized by non oliguric renal failure with ↓ GFR, ↑serum creatinine, and proteinuria

Answer 83

Aminoglycosides

Question 84

(T/F) The process that concentrates urine also serves to concentrate potential toxicants in the tubular fluid.

Answer 84

True

Question 85

(T/F) Toxicants may also cause mitochondrial dysfunction via compromised respiration and ATP prod; leading to apoptosis or necrosis

Answer 85

True