Renal Toxicology Flashcards
What is the key step of ADME that is relevant to kidneys?
Metabolism - occurs in kidneys
How can you measure kidney function?
Blood Urea Nitrogen (BUN)
and Creatinine levels in blood
Why is the kidney vulnerable?
High blood flow (entire blood volume passes through kidneys once every 6 mins) Excretory function (concentrates toxins)
What are the excretion risks of the nephron?
High concentrations
Immune complex deposition
Intratubular pH may induce precipitation
How does the kidney protect itself from toxins?
Large functional reserve
Ability to hypertrophy itself
What is the difference between filtration, reabsorption, and secretion?
Filtration: filters liquid out of blood
Reabsorption: reabsorbs most of the liquid BACK INTO BLOOD
Secretion: of metabolites INTO TUBULE
What is the net pressure at the glomerular capillary
Glomerular capillary: 55 mmHg
Capsule: -15 mmHg
Osmotic pressure of glomerular cap: -30
Net: 10 mmHg out of capillary into tubule
How does the distal convoluted tubule autoregulate itself?
Juxtaglomerular apparatus
Loops back on glomerulus, senses sodium concs in distal tubule and regulates blood flow according to ensure blood flow is appropriate
What division of the Autonomic Nervous system controls the juxtaglomerular autoregulation of blood flow?
Sympathetic
Describe the glomerular filtration membrane
Fenestrated capillaries, podicytes (with pedicel projections)
Pressure forces liquid through “pasta strainer”
Plasma concentrations are, on average, ______ than glomeular filtrate concentrations
the same*
Proteins to big to get through glomerulus stay in blood (this maintians osmotic force
What enzyme(s) is/are found in the proximal tubule of the kidney? What is a consequence of this?
Renal P450s are located here, and this makes the proximal tubule of the kidney a major site of nephrotoxicity
What can toxins do to kidneys?
Block ATP production (big nono for proximal tubule)
Block enzymes/transporters
Impair blood flow (ischemia)
Renal medulla and papillae have ____ luminal concentration of toxins
Higher
Slower blood flow will ____ toxicant exposure
Increase
What causes glomerulonephritis?
many causes, usually due to toxicant exposure (eg immune complexes)
What are immune complexes? Name two
Hydralazine/mercury
Antigen-Antibody complexes, many types
Causes Podocyte injury
What is the most common site of injury?
Proximal confoluted tubule
How does Mycotoxin Orellanine cause renal tubular necrosis?
Production of free radicals in proximal tubule
Symptoms take days/weeks (earlier the symptoms, the worse you’ll be)
Kidney failure
What toxic substances are concentrated at the Proximal Convoluted Tubule? How do those toxins work?
Like everything Heavy metals (Mercury, Cadmium) Mycins (streptomycin, gentamycin) Aminoglycosides Ethylene glycol (antifreeze)
How do mycins cause kidney damage?
FIltered in glomerulus, binds lipids in tubular cells, taken into lysosomes and causes rupture in cells –> cell injury
How do aminoglycosides cause kidney damage?
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)
How do ethylene glycol and rhubarb leaves cause kidney damage?
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
What toxins damage distal tubule?
Melamine
Cisplatin
