Flashcards in PSL301: Water 8 Deck (63):
1
UREMIA
a raised level in the blood of urea and other nitrogenous waste compounds that are normally eliminated by the kidneys
= advanced kidney failure
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clinical symptoms of uremia
- severe fatigue & weakness
- poor appetite, nausea, vomiting
- edema in feet, ankles
- itchy skin
- disturbed mental functions
3
Telltale biochemical marker of uremia
very high serum creatinine & urea levels (GFR < 10%)
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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
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most abundant waste in urine
urea
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amount of waste found in urine depends on...
how much protein is eaten
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each urea has __ nitrogens
2
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Waste products in urine are readily ____ and minimally ___
filtered;
reabsorbed
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___ is generated from AA breakdown
ammonia
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ammonia is highly...
toxic
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to combat toxic effects of ammonia, it is converted to ___ in the ____. This is then excreted in the urine.
urea;
liver
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steps of urea generation from ammonia
1. ammonia + CO2 -> carbamoyl phosphate
2. + L-ornithene -> citrulline
3. + L-aspartate -> arginosuccinate
4. -> L-Fumarate + L-Arginine
5. L-Arginine + H2O -> Urea + L-ornithene
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enzyme: CO2 + NH3 -> carbamoyl phosphate
carbamoyl phosphate synthase
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enzyme: carbamoyl phosphate + L-ornithene -> citrulline
ornithine carbamoyltransferase
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enzyme: citrulline + L-aspartate -> arginosuccinate
arginosuccinate synthase
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enzyme: arginosuccinate -> L-Fumarate + L-Arginine
argininosuccinate lysase
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enzyme: L-Arginine + H2O -> Urea + L-ornithene
arginase
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creatinine is generated from...
phosphocreatine -> creatine -> creatinine
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PHOSPHOCREATINE
storage compound for energy in muscle
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how many molecules of nitrogen does each creatinine molecule have?
2
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enzyme: phosphocreatine -> creatine
creatine kinase
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Uric acid is generated from...
nucleic acid break down
- uric acid = nitrogenous metabolite of purines
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high concentrations of uric acid causes...
gout (type of arthritis)
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gout typically occurs in the ___. It is caused by...
foot/ankles;
urate crystal deposition in joint fluids -> inflammation -> joint becomes swollen/tender/painful
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enzyme: xanthine -> uric acid
xanthine oxidase
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what is used to treat gout? why?
xathine oxidase inhibitors;
xathine oxidase is the enzyme that produces uric acid
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some human studies suggest that a 60% GFR may be associated with...
increased risk of death from cardiovascular disease
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___ and ___ are not toxic. The toxicity of low GFR is due to...
urea;
creatinine;
the small molecules that builds up in blood
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endocrine functions of the kidney
1. renin
2. erythropoietin
3. vitamine D metabolism
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renin is synthesized & secreted by...
cells of afferent arteriole
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effect of renin on Na
increase Na reabsorption
- ANG II (directly)
- aldosterone (indirectly)
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effect of renin on water
keeps water inside body
- thirst
- vasopressin
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effect of renin on GFR
- constricts efferent arteriole to increase glomerular capillary pressure
- increase GFR
- balances out decreased GFR from hypotension
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___ is synthesized by ___ at border of medulla and cortex where O levels are low
glycoprotein;
pericytes
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where are pericytes located, and what are they used for?
located at border of kidney medulla & cortex, used to make glycoprotein
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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
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2 conditions which cause secretion of EPO
1. anemia
2. hypoxemia
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function of EPO
increase RBC production in bone marrow
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EPO is a popular drug for...
long-distance athletes, where O2 is a limiting factor to success
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function of vit D
increase absorption of dietary calcium from gut
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how to activate vit D from diet or skin?
1) 25-hydroxylation in liver (can be stored here)
2) 1-hydroxlation in kidney
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what is the final active hormone of vit D?
1,25-(OH)2 vit D3
= calcitriol
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which vitamin D activation step is regulated? Which isn't?
regulated: 1-OHase in kidney
unregulated: 25-OHase in liver
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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)
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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
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most common causes of uremia
1. diabetes (30-40%)
2. high BP
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uremia: why fatigue & weakness?
Low EPO secretion by kidneys
- less RBC
- reduced O carrying capacity of blood
Waste products reduce muscle function
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uremia: why hypertension?
kidney can't excrete Na+ as well (damage, reduced GFR)
- Na+ retained in blood
- pull water into blood as well
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uremia: why edema?
kidney can't excrete Na+ as well (damage, reduced GFR)
- Na+ in ECF
- expanded ECF = edema
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uremia: why high levels of urea, creatinine, urate?
low GFR can't process all the waste fast enough
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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
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uremia: why hyperkalemia?
- impaired excretion of K by damaged kidney
- low GFR
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How to treat hyperkalemia?
IV insulin
- moves K+ into cells
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uremia: why metabolic acidosis?
impaired ammonium excretion by damaged kidney
- can't buffer H+
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low GFR = metabolic ___
acidosis
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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
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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
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increased PTH secretion due to low low calcitriol is ____ hyperparathyroidism
secondary
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untreated uremia leads to..
coma, death
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treatment for uremia
- kidney dialysis
- kidney transplant
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hypernatremia implies an decrease in ___ volume
intracellular
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hyponatremia implies an increase in ____ volume
intracellular
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