PSL301: Water 8 Flashcards by Airi -

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

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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

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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

ammonia + CO2 -> carbamoyl phosphate
- L-ornithene -> citrulline
- L-aspartate -> arginosuccinate
-> L-Fumarate + L-Arginine
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?

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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

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

1. renin 2. erythropoietin 3. 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

1. 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

1. 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...

1. thick ascending limb function | 2. vasopressin action on collecting duct

PSL301: Water 8 Flashcards

Excretion of waste products; endocrine function (63 cards)