PSL301: Water 8 Flashcards
Excretion of waste products; endocrine function
UREMIA
a raised level in the blood of urea and other nitrogenous waste compounds that are normally eliminated by the kidneys
= advanced kidney failure
clinical symptoms of uremia
- severe fatigue & weakness
- poor appetite, nausea, vomiting
- edema in feet, ankles
- itchy skin
- disturbed mental functions
Telltale biochemical marker of uremia
very high serum creatinine & urea levels (GFR < 10%)
What are the waste products excreted by urine?
mainly products of protein metabolism
- urea
- creatinine
- uric acid (urate)
many other small molecules excreted in small amounts
most abundant waste in urine
urea
amount of waste found in urine depends on…
how much protein is eaten
each urea has __ nitrogens
2
Waste products in urine are readily ____ and minimally ___
filtered;
reabsorbed
___ is generated from AA breakdown
ammonia
ammonia is highly…
toxic
to combat toxic effects of ammonia, it is converted to ___ in the ____. This is then excreted in the urine.
urea;
liver
steps of urea generation from ammonia
- ammonia + CO2 -> carbamoyl phosphate
- L-ornithene -> citrulline
- L-aspartate -> arginosuccinate
- -> L-Fumarate + L-Arginine
- L-Arginine + H2O -> Urea + L-ornithene
enzyme: CO2 + NH3 -> carbamoyl phosphate
carbamoyl phosphate synthase
enzyme: carbamoyl phosphate + L-ornithene -> citrulline
ornithine carbamoyltransferase
enzyme: citrulline + L-aspartate -> arginosuccinate
arginosuccinate synthase
enzyme: arginosuccinate -> L-Fumarate + L-Arginine
argininosuccinate lysase
enzyme: L-Arginine + H2O -> Urea + L-ornithene
arginase
creatinine is generated from…
phosphocreatine -> creatine -> creatinine
PHOSPHOCREATINE
storage compound for energy in muscle
how many molecules of nitrogen does each creatinine molecule have?
2
enzyme: phosphocreatine -> creatine
creatine kinase
Uric acid is generated from…
nucleic acid break down
- uric acid = nitrogenous metabolite of purines
high concentrations of uric acid causes…
gout (type of arthritis)
gout typically occurs in the ___. It is caused by…
foot/ankles;
urate crystal deposition in joint fluids -> inflammation -> joint becomes swollen/tender/painful
enzyme: xanthine -> uric acid
xanthine oxidase
what is used to treat gout? why?
xathine oxidase inhibitors;
xathine oxidase is the enzyme that produces uric acid
some human studies suggest that a 60% GFR may be associated with…
increased risk of death from cardiovascular disease
___ and ___ are not toxic. The toxicity of low GFR is due to…
urea;
creatinine;
the small molecules that builds up in blood
endocrine functions of the kidney
- renin
- erythropoietin
- vitamine D metabolism
renin is synthesized & secreted by…
cells of afferent arteriole
effect of renin on Na
increase Na reabsorption
- ANG II (directly)
- aldosterone (indirectly)
effect of renin on water
keeps water inside body
- thirst
- vasopressin
effect of renin on GFR
- constricts efferent arteriole to increase glomerular capillary pressure
- increase GFR
- balances out decreased GFR from hypotension
___ is synthesized by ___ at border of medulla and cortex where O levels are low
glycoprotein;
pericytes
where are pericytes located, and what are they used for?
located at border of kidney medulla & cortex, used to make glycoprotein
Why are pericytes located at the border of the medulla and cortex?
- O2 are low there
- very sensitive to O levels
- decreased O stimulates secretion of EPO
2 conditions which cause secretion of EPO
- anemia
2. hypoxemia
function of EPO
increase RBC production in bone marrow
EPO is a popular drug for…
long-distance athletes, where O2 is a limiting factor to success
function of vit D
increase absorption of dietary calcium from gut
how to activate vit D from diet or skin?
1) 25-hydroxylation in liver (can be stored here)
2) 1-hydroxlation in kidney
what is the final active hormone of vit D?
1,25-(OH)2 vit D3
= calcitriol
which vitamin D activation step is regulated? Which isn’t?
regulated: 1-OHase in kidney
unregulated: 25-OHase in liver
effect of PTH on calcium
Increase serum Ca
- break down bone
- reabsorption by kidney
- increase rate at which vit D is converted to calcitriol (activity of 1-OHase)
what happens to vit D conversion if the kidney is damaged?
- no 1-OHase
- low Ca absorption from gut
- low serum Ca
- stimulate high PTH
most common causes of uremia
- diabetes (30-40%)
2. high BP
uremia: why fatigue & weakness?
Low EPO secretion by kidneys
- less RBC
- reduced O carrying capacity of blood
Waste products reduce muscle function
uremia: why hypertension?
kidney can’t excrete Na+ as well (damage, reduced GFR)
- Na+ retained in blood
- pull water into blood as well
uremia: why edema?
kidney can’t excrete Na+ as well (damage, reduced GFR)
- Na+ in ECF
- expanded ECF = edema
uremia: why high levels of urea, creatinine, urate?
low GFR can’t process all the waste fast enough
what allows us to rule in chronic kidney disease / severe kidney failure?
high levels of urea & creatinine in serum
- if this is not present, we can rule out CKD
uremia: why hyperkalemia?
- impaired excretion of K by damaged kidney
- low GFR
How to treat hyperkalemia?
IV insulin
- moves K+ into cells
uremia: why metabolic acidosis?
impaired ammonium excretion by damaged kidney
- can’t buffer H+
low GFR = metabolic ___
acidosis
uremia: why loss of appetite?
Low GFR => metabolic acidosis
- continued food (protein) intake -> acid
- acid binds to all available bicarb
- kidney can’t make ammonium to keep up with acid from diet
- feels sick & unwell
- negative effects on bone health
uremia: why low Ca, high PTH?
- kidney can’t make calcitriol
- reduced absorption from gut -> hypocalcemia
- parathyroid responds to low Ca
- lots of PTH
- excess reabsorption of bone -> fragile
increased PTH secretion due to low low calcitriol is ____ hyperparathyroidism
secondary
untreated uremia leads to..
coma, death
treatment for uremia
- kidney dialysis
- kidney transplant
hypernatremia implies an decrease in ___ volume
intracellular
hyponatremia implies an increase in ____ volume
intracellular
urine concentration requires…
- thick ascending limb function
2. vasopressin action on collecting duct
