Kidney toxicity Flashcards
Acute kidney injury definition
abrupt decrease in kidney function including acute renal failure
GFR formula
Kf (glomerular surface area x glomerular capillary) x net filtration pressure
3 GFR reduction causes
- afferent arteriole constriction
- tubular obstruction
- filtrate leakage
how does afferent arteriole cause GFR reduction
constriction in the afferent artery decreases the blood that enters, decreasing the hydrostatic pressure in the glomerulus, reducing GFR
how does tubular obstruction reduce GFR
increases hydrostatic pressure in the Bowman’s capsule, decreasing GFR
changes to uninjured cells after nephron injury
- hypertrophy
- adaptation
- proliferation
Chronic kidney disease measurement parameters
measured by GFR and albumin-creatinine ratio
3 reasons why kidneys are susceptible to toxicity
- 20-25% of cardiac output, therefore receives higher amounts of drugs and chemicals
- concentrated urine leading to more concentrated toxicants within tubular fluid. therefore, may be non-toxic in plasma but toxic in kidney
- precipitation of insoluble compounds in the kidney leads to tubular obstruction which may cause acute kidney injury
Most common form of mercury
elemental mercury
elemental mercury targets
crosses BBB and affects CNS
inorganic mercury target
kidney
organic mercury target
brain
3 sources of mercury
- natural degassing of earth crust
- sediment leaching
- industrial release
mechanism of action of mercury
interacts with SH group -> inactivate enzymes, structural proteins and permeability
effects of mercury
oxidative stress
disrupt microtubule formation
interfere protein synthesis
interfere DNA synthesis
interfere calcium homeostasis
Halogenated hydrocarbons such as chloroform targets
- proximal tubule
- liver
effects of chloroform
increased proteinuria, glucosuria and blood urea
carcinogen
mechanism of chloroform
metabolised by P450 to tri-chloromethanol, which breaks down to phosgene. phosgene binds to nucleophillic groups on cellular macromolecules
acetaminophen toxic effects (list 5)
- proximal tubular necrosis
- increase blood urea nitrogen
- decrease GFR and para-aminohippurate clearance
- increase water, sodium and potassium excretion
- increase urinary glucose, protein, and brush border enzymes
acetaminophen mechanism in kidney
metabolised by P450 to NAPQI which is a reactive compound.
an overdose of acetaminophen leads to insufficient glutathione to conjugate NAPQI.
NAPQI will bind with proteins in kidney and lead to necrosis
NSAID effects
constriction of blood vessels
NSAID mechanism
inhibit COX enzyme which decreases the production of inflammatory agents and constricts blood vessels.
this reduces renal blood flow, causing ischemia
symptoms of NSAIDS and acetominophen for more than 3 years
irreversible nephrotoxicity.
urinary concentration and acidification is impaired
forms primary lesion
usage of NSAIDs for more than 5 months leads to
interstitial nephritis
aminoglycosides act as
antibiotics against gram negative bacteria
aminoglycosides cause decreased GFR, increased serum creatinine and blood urea nitrogen because of
acute proximal tubular necrosis and renal failure
mechanism of aminoglycosides (gentamycine)
filtered from the glomerulus and enters the proximal tubule. It is uptaken by cells and fuses with lysosomes. It will break down the vesicle to release hydrolytic enzymes and damage cells.
it also deals direct mitochondria damage which decreases ATP production
