Nephrotoxicology Flashcards
5 functions of the kidney
waste excretion regulation of fluid volume electrolyte composition acid-base balance hormone production
there are three distinct regions of the kidney
cortex, medulla, papilla
when toxicants are delivered to the kidney through the blood they will cause toxic effects more often in which part of the kidney
cortex
functional unit of the kidney
nephron
five parts of the nephron
glomerulus proximal tubule loop of henle distal tubule collecting duct
a complex specialized capillary bed composed primarily of endothelial cells
glomerulus
the glomerulus is a good barrier against what
macromolecules
regulates the pressure in the nephron
macula densa
the proximal tubule consists of three discrete segments
S1
S2
S3
what is the job of the proximal tubule
to reabsorb approximately 60% to 80% of solute and water filtered at the glomerulus
four characteristics of ultrafiltration
driven by blood pressure
filtrate free of cells and large proteins
20% of blood is filtered in the glomerulus
filtration rate can be regulated
facilitate filtration
large enough for fluids not white and red blood cells
fenestrae
how is the glomerulus filtration rate regulated functionally
dilation or constriction of blood vessels
what regulates the filtration rate chemically
direct nervous system angiotensin vasopressin adenosine norepinephrin
molecule to look for when checking for impaired kidney function
creatine
how are molecule reabsorbed in the proximal tubule
active transport through Na-K-ATPase
passive diffusion for water along osmotic gradient
facilitated diffusion for glucose
what is excreted from the proximal tubule and how
p-glycoproteins by active transport
what is reabsorbed at the loop of henle
25% of filtered Na and K
20% of water
what are two things that occur in the distal tubule
macula densa regulates filtration rate
further concentration of urine
one of the most common manifestations of nephrotoxic damage is
acute renal failure
what happens during acute renal failure
sudden drop in filtration rate
causes for prerenal acute failure
renal vasoconstriction
loss of blood pressure
causes for post renal acute failure
blockage of ureter
causes for intrarenal acute failure
tubular cell death
tubular blockage
what can cause tubular obstruction
toxicant enters tubular cells
los of polarity, tight junction integrity and brush border
cell death by apoptosis or necrosis
sloughing off of viable cells into the intraluminal cavity where they can become lodged and form obstruction
what is the kidneys first adaptation to damage
increase in GFR for unaffected nephrons
what does the kidney do about damaged cells
induction of MT and HSP
cell repair or apoptosis
how can kidney cells regenerate
no renal stem cells
some cells can go through dedifferentiation, proliferation, migration, and differentiation
chronic renal disease has been postulated to be a consequence of
glomerular hemodynamic response to renal injury
three characteristics of chronic renal failure
long term compensatory activity of healthy nephrons
mechanical damage in overworked nephrons
development of sclerosis
four reasons for the susceptibility of the kidney
large blood supply needed
deliver and concentration of waste material containing potential toxicants
high biotransformation activity
high mitochondrial activity
site specific injury to glomerulus
change of membrane charge
vasoconstriction
reasons for injury to glomerulus
antibiotics impair filtration
interference by immune cells
local release of cytokines and ROS
most susceptible portion of the nephron to injury
proximal tubule
why is the proximal tubule the most susceptible
place of reabsorption concentration and biotransformation
general parameters to check for renal damage
volume, pH, osmolality
specific parameters to check for renal damage
glucose, proteins, creatine, enzymes
what can be tested in the blood to check for renal damage
urea nitrogen
creatine
inulin clearance
types of nephrotoxicity
cardiovascular
direct tubular effects
nephritis
causes of cardiovascular nephrotoxicity
diuretics
beta-blockers
vasodilators
reasons for proximal tubular effects
certain antibiotics, cisplatin (chemotherapy)
reasons for distal tubular toxicity
NSAIDs, cyclosporin (immunosuppressant)
What causes acute nephritis
70-90% of cases caused by medications
What causes chronic nephritis
lithium, cyclopsorin
bind strongly to sylfhydryl groups
important for transport and protein damage
heavy metals
bound to albumin, glutathione, and cysteine that mediates reuptake
mercury
what does mercury toxicity do
reduce GFR
damage to tubular cells
mitochondrial damage
ROS production
bind to MT in liver and intestine
transport to kidney were reuptake can occur in the proximal tubule
cadmium
what does cadmium toxicity do
lysosomal degradation
interference with cell signaling pathways
halogenated hydrocarbons cause
proximal tubule cell damage
inhibit prostaglandin production, causes acute vasoconstriction from overdose
NSAIDs
from wild plants, used in Chinese herbal medicine, also potent mutagen
aristolochic acid
