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Phar 303 > Renal Toxicology > Flashcards

Renal Toxicology Flashcards

1
Q

What is the key step of ADME that is relevant to kidneys?

A

Metabolism - occurs in kidneys

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2
Q

How can you measure kidney function?

A

Blood Urea Nitrogen (BUN)

and Creatinine levels in blood

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3
Q

Why is the kidney vulnerable?

A 
High blood flow (entire blood volume passes through kidneys once every 6 mins)
Excretory function (concentrates toxins)
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4
Q

What are the excretion risks of the nephron?

A

High concentrations
Immune complex deposition
Intratubular pH may induce precipitation

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5
Q

How does the kidney protect itself from toxins?

A

Large functional reserve

Ability to hypertrophy itself

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6
Q

What is the difference between filtration, reabsorption, and secretion?

A

Filtration: filters liquid out of blood
Reabsorption: reabsorbs most of the liquid BACK INTO BLOOD
Secretion: of metabolites INTO TUBULE

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7
Q

What is the net pressure at the glomerular capillary

A

Glomerular capillary: 55 mmHg
Capsule: -15 mmHg
Osmotic pressure of glomerular cap: -30
Net: 10 mmHg out of capillary into tubule

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8
Q

How does the distal convoluted tubule autoregulate itself?

A

Juxtaglomerular apparatus
Loops back on glomerulus, senses sodium concs in distal tubule and regulates blood flow according to ensure blood flow is appropriate

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9
Q

What division of the Autonomic Nervous system controls the juxtaglomerular autoregulation of blood flow?

A

Sympathetic

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10
Q

Describe the glomerular filtration membrane

A

Fenestrated capillaries, podicytes (with pedicel projections)
Pressure forces liquid through “pasta strainer”

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11
Q

Plasma concentrations are, on average, ______ than glomeular filtrate concentrations

A

the same*

Proteins to big to get through glomerulus stay in blood (this maintians osmotic force

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12
Q

What enzyme(s) is/are found in the proximal tubule of the kidney? What is a consequence of this?

A

Renal P450s are located here, and this makes the proximal tubule of the kidney a major site of nephrotoxicity

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13
Q

What can toxins do to kidneys?

A

Block ATP production (big nono for proximal tubule)
Block enzymes/transporters
Impair blood flow (ischemia)

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14
Q

Renal medulla and papillae have ____ luminal concentration of toxins

A

Higher

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15
Q

Slower blood flow will ____ toxicant exposure

A

Increase

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16
Q

What causes glomerulonephritis?

A

many causes, usually due to toxicant exposure (eg immune complexes)

17
Q

What are immune complexes? Name two

A

Hydralazine/mercury
Antigen-Antibody complexes, many types
Causes Podocyte injury

18
Q

What is the most common site of injury?

A

Proximal confoluted tubule

19
Q

How does Mycotoxin Orellanine cause renal tubular necrosis?

A

Production of free radicals in proximal tubule
Symptoms take days/weeks (earlier the symptoms, the worse you’ll be)
Kidney failure

20
Q

What toxic substances are concentrated at the Proximal Convoluted Tubule? How do those toxins work?

A 
Like everything
Heavy metals (Mercury, Cadmium)
Mycins (streptomycin, gentamycin)
Aminoglycosides
Ethylene glycol (antifreeze)
21
Q

How do mycins cause kidney damage?

A

FIltered in glomerulus, binds lipids in tubular cells, taken into lysosomes and causes rupture in cells –> cell injury

22
Q

How do aminoglycosides cause kidney damage?

A

AGs are uptaken by proximal tubular cells (absorptive pinocytosis)
Transport and accumulation in lysosomes,
Rupture of lysosomes, cell necrosis
Phospholipiduria is common symptom
Non-Oligouric renal failure (loss of function but not completely dysfuncitonal)

23
Q

How do ethylene glycol and rhubarb leaves cause kidney damage?

A

Directly toxic to tubular epithelial cells
Metabolized into oxalic acid (found in rhubarb) which + calcium –> calcium oxalate
CaOxalate -> obstruction

End result is injury of proximal tubule, obstruction of rest

24
Q

What toxins damage distal tubule?

A

Melamine

Cisplatin

25
Q

How is melamine nephrotoxic?

A

(whiteboard material, found in pet food)
Specifically damages distal tubule
Water gets pumped out at DT, melamine concentrates and forms crystals (nephrolithiasis) - chronic/acute kidney disease

26
Q

How is cisplain, an anticancer agent, nephrotoxic?

A

Affects distal AND proximal tubule
Causes vascular injury/injury through many pathways
Tubular cell death -> decrease in GFR -> acute renal failure
Triggers Apoptosis (ER stress, death receptor pathway, mitochondrial pathway)

27
Q

How can toxicants affect The Loop of Henle/collecting ducts?

A

Xenobiotics can precipitate during concentration of Loop

e.g. Fluoride can compete with Sodium and decrease reabsorption

28
Q

Where do NSAIDs produce nephrotoxic effects?

A

Renal Medulla

29
Q

How are Chronic NSAIDs nephrotoxic?

A

(recall NSAIDs block COX 1/2 which make prostaglandins responsable for inflammation)
Prostaglandins also regulate diameter of proximal tubule

Inhibition of COX lowers PGs, which causes vasoconstriction
NORMALLY, not a problem unless:
- Chronic use
- Megadose
- Underlying problem

Can cause necrosis from papilla to inner medulla

30
Q

How can you evaluate renal toxins?

A

Animal models
Histopathology (main)
Urinalysis
Blood electrolytes/BUN/creatinine

31
Q

What can cause chronic renal failure?

A

Analgesics
Lithium
Cyclosporine

32
Q

What is the recommended course of action for temporary kidney failure? Permanent kidney failure?

A

Temporary - Dialysis

Permanent - Transplantation

33
Q

Describe the mechansim of acute mercury toxicity

A

Mercuric chloride formation (HgCl2) or Elemental Hg vapor

Rapid transport to proximal tubule –> injury to MT - necrosis

34
Q

Describe the mechanism of chronic mercury toxicity

A 
Nephrotic syndrome
Increased glomerular permeability (proteins in blood)
Loss of coagulation factors
Loss of albumin
Infection
Malnutrition
Edema

Glomerular injury, proteins leaking out
Plasma Volume goes down
CO goes down (RAAS)

Phar 303 (19 decks)

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