Skildum: Electrolytes Flashcards
What is EAR?
Estimated Average Requirement. The average daily nutrient intake level estimated to meet the requirements of half of the healthy members of a particular life stage and gender group.
What is RDA?
Recommended Daily Allowance. The average daily dietary nutrient intake level sufficient to meet the nutritional requirements of nearly all (97-98%) healthy persons in a particular life stage and gender group
What are the major minerals in the body?
Ca phosphorus K Na, Cl Mg
What are the major trace elements in the body?
Iron
Zinc
Copper
Manganese
What are the ultratrace elements in the body?
Selenium
Molybdenum
Iodine
Chromium
Molybdenum
four human enzymes require it sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase
Chromium
Role in insulin sensitivity, binds chromodulin, an insulin receptor binding protein
Selenium
Role in antioxidant proteins; de-iodinases in the thyroid: Selenocysteine
Iodine
thyroid hormone
What is the major extracellular cation?
Na
What is the major intracellular cation?
K
What is hte most abundant metal ion in the body?
Ca (mostly in bone)
What are the dietary sources of Ca?
dairy seafood turnip broccoli kale supplements
What are the fxns of Ca?
bone mineralization
blood clotting
muscle contraction
metabolism regulator
How is Ca absorbed?
- Saturable carrier mediated transport (TRPV6 transports Ca across the brush border membrane> calbindin chaperones Ca in the cell> Ca/ATPase transports Ca across the basolateral membrane)
- Pericellular transport around tight jxns (claudin)
What regulates Ca absorption?
calcitrol
What increases Ca absorption?
Vit D
sugars; sugar alcohols
protein
what decreases Ca absorption?
fiber
phytic, oxalic acids
divalent cations (Mg, Zn)
unabsorbed fatty acids
How much Ca is in the blood?
8.5-10 mg/dL
40% bound to protein (albumin)
50% free ionized Ca
10% complexed w/ sulfate, phosphate, citrate
What is the cytosolic conc of Ca in cells?
LOW 100nmol
How does the extracellular conc of Ca differ from the intracellular?
10,000x higher (2.3 mmol)
Where is Ca stored?
intracellular compartments (mitochondria, ER)
How is Ca exported from cells?
Ca/2Na exchanger- low affinity, high capacity transporter
Ca/2H exchanger is a high affinity, low capacity transporter
What is is the affect of the Ca -calmodulin complex?
Stimulates:
- Calcineurin> inhibits Ca channels
- MLCK> muscle contraction
- Ca/calmodulin kinase> inhibits glycogen synthase
- phosphorylase kinase> phosphorylase
What happens to glycogen synthase and glycogen phosphorylase when intracelluar Ca increases?
Glycogen synthase> inactivated
glycogen phosphorylase> activated
How does Ca affect phosphorus uptake?
blocks it
How do you treat hyperphosphatemia secondary to kidney failure?
high doses of Ca
How does Ca affect Fe uptake?
transiently blocks it
Ca can trap fatty acids and bile salts in soaps that are not digestable. This can cause…
- bile salts not recycled
- cholesterol diverted to bile acid synthesis
- LDL decreases
What does hydroxylation at the #12 carbon do when Ca is present?
Re-uptake tag
Chenodeoxycholate in bile decreaes and the ratio of deoxycholate to lithocholate in feces decreases
What much Ca is excreted daily?
100-240 mg/day urinary
45-100 feces
60 sweat
What controls resorption of Ca in the proximal tubule?
calcitrol
How does caffeine affect urinary excretion of Ca?
increases it
How does a high Na content affect Ca?
inhibits Ca reuptake and increases excretion
How is at risk for Ca deficiency?
fat malabsorption disorders
imobilized patients
What causes Ca def?
rickets
tetany
osteoporosis
What is Ca def associated wtih?
colorectal cancer
HTN
Type II diabetes
What is the TUL for Ca?
2,500 mg/day
What are clinical signs of acute Ca toxicity?
constipation and bloating
What are clinical signs of chronic Ca toxicity?
hypercalcemia that can cause calcification of soft tissue that can lead to hypercalciuria and kidney stones
How do you assess Ca status?
Tightly regulated–bone density scan is most useful
Where is most Mg in the body stored?
bone
What food are rich in Mg?
Nuts, legumes, whole grains, chlorophyll, chocolate, hard water
How is Mg transported across the brush border?
- Saturable transport (TRPM6)>
basolateral transport (2Na/Mg antiporter and 2K/3Na/ATPase)
- Non-saturable paracellular diffusion through tight junctions
In the bone, where is Mg located?
70% of bone magnesium is associated with phosphorous and calcium in crystal lattice.
30% of bone magnesium is in amorphous form on the surface; this is available for exchange with serum to maintain magnesium homeostasis.
Intracellularly, what percent of Mg is associated w/ ATP?
> 90%
What is Mg essential for?
kinases and polymerases that use NTPs
Activation of vitamin D requires what cofactor?
25-hydroxylase requires Mg to make circulating vitamin D
What are the three things that Mg can interact with?
- Vitamin D
- Compete w/ Ca for resorption in the kidney
- Inhibit phosphorus absorption by forming a Mg (PO4) precipitate
How do you assess Mg levels?
- Renal Mg excretion before and after a loading dose is best!
- Erythrocyte Mg
Mg def rarely occurs but can be experimentally induced. What are the sxs of Mg def?
nausea, vomiting, headache, anorexia; progresses to seizures, ataxia, fibrilation.
Chronic Mg def is associated with what conditions?
Type II diabetes
HTN
What is Gitelman syndrome?
Autosomal recessive
Mut in SLC12A3–> thiazide sensitivie Na/Cl transporter
What is gitelman syndrome characterized by?
hypomagnesemia
hypokalemia
hypocalciuria
Mg toxicity is usually associated with…
epsom salts
What are the sxs of Mg toxicity?
diarrhea, dehydration, flushing, slurred speech, muscle weakness, loss of deep tendon reflex.
High concentrations can cause CARDIAC ARREST
Is most Cl intracellular or extracellular?
extracellular
How is Cl absorbed?
paracellularly or through a Na/Cl electroneutral transporter
What is teh only anion secreted by GI cells?
Cl
What is the fxn of Cl when cells deliver O2 to tissues?
Cl ENTERS RBC in exchange for bicarb
What is the fxn of Cl when cells take oxygen from the lugns?
Cl LEAVES RBC in exchange for bicarb
How do neutrophils use Cl?
Neutrophils combine Cl w/ ROS to make hypochlorous acid that is secreted during phagocytosis to neutralize pathogens.
Parietal sells secrete…
hydrochloric acid
Where does K come from in the diet?
fruit, leafy green veggies, milk
How is K absorbed?
paracellular diffusion
K/H ATPase
basolateral K channel
What is the major intracellular cation?
K (maintains electrical potential across cell membranes)
How is K accumulated w/in cells?
Na/K ATPase consumes energy to accumulate K which is then released through channels resulting in a positive charge.
What is the major fxn of K?
muscle contractility (smth, skieletal, cardiac)
What increases urinary K excretion?
vasopressin and aldosterone
What does K do to Ca excretion?
Decreases it
Na INCREASES Ca excretion
What causes hypokalemia?
fluid loss, thiazide or loop diuretics, refeeding syndrome
What are the sxs of K def?
Cardiac arrythmias, muscular weakness, hypercalciuria, glucose intolerance, mental disorientation
Moderate K def is associated with…
elevated blood pressure
decreased bone density (increased urinary Ca++ excretion)
Hyperkalemia caused by renal failure can cause…
cardiac arrythmia/arrest
Where is most phosphorus in the body stored?
bone
Where do we get phosphorus in the diet?
meat poultry fish eggs dairy cola
How does phosphorus cross the brush border?
- Saturable carrier mediated active transport when phosphate intake is LOW. Activated by calcitrol.
- Diffusion in the proximal duodenum (slightly acidic)
What inhibits phosphorus absorption?
Mg
Aluminum
Ca
What is used to treat hyperphosphatemia?
antacids (mg, Al, Ca)
What are the functions of phosphorus?
- bone mineralization–amorphous and crystalline
- molecules w/ high E bonds–nucleotides, RNA, DNA, proteins, phospholipids, vitamins
- Acid base balance–impt buffer in the kidney
- Availability of O2–helps Hb deliver O2 under low O2 conc
What is hte difference between calcitonin and calcitrol?
calcitonin–phosphorus deposition in bone
calcitriol–phosphorus desorption in bone
How is phosphorus regulated?
through renal clearance
What promotes the excretion of phosphorus?
elevated dietary phosphorous
parathyroid hormone (PTH) (calcitonin acts in oppos. To this)
acidosis
phosphotonins (e.g. FGF-23; secreted by osteoblasts and osteocytes)
What inhibits the excretion of phosphorus?
low dietary phosphorous calcitriol alkalosis estrogen thyroid hormone growth hormone
What can cause phosphorus def?
- extereme use of antacids
- malnourishment
- refeeding syndrome
- inherited disorders
What inherited disorders are associated w/ phosphorus def?
dents
x-linked hypophosphatemic rickets
autosomal dominant hypophosphatemic rickets
What is dents disease?
X-linked, mutation in renal chloride channel (interferes w/ P clearance in the kidney)
What is X linked hyphosphatemic rickets?
Mutation in PHEX gene causes elevated FGF-23
What is autosomal dominant hypophosphatemic rickets?
Mutation in the gene encoding FGF-23, prevents its degradation. (FRF-23 is a phosphatonin that promotes phosphorous excretion)
What are sxs of phosphorus def?
anorexia, reduced cardiac output, decreased diaphragmatic contractility, myopathy, death
How do we get Fe in the diet?
half heme, half non heme–meat, fish, poultry
non heme–nuts, fruits, vegetables, grains
How is Fe absorbed?
at the brush border of an enterocyte, REDUCTASE reduces ferric iron to ferrous iron>
ferrous iron is transported through DMT1>
Fe is stored as FERRITIN>
Ferrous iron is then transported out of the cell through FPN>
HEPHAESTIN uses COPPER to oxidize ferrous iron to ferric iron>
Ferric iron binds TRANSFERRITIN for transport to tissues
Where is Fe primarily stored?
in the liver as hemosiderin that can be liberated when Fe is low.
What regulates Fe upatake?
When Fe stores in the liver are high (increased hemosiderin)>
liver produces HEPCIDIN>
binds ferroportin (FPN)>
causes its degradation
What are the fxns of Fe?
- heme synthesis
- Iron-sulfur clusters (electron transfer groups)
- Non-heme iron (dioxygenase)
How does Vit C affect Fe?
Vit C maintains Fe in the REDUCED state
What is required for export of Fe from enterocytes?
Cu
What inhibits Zinc absorption?
Fe
Fe def is commonly observed in what populations?
infants (low iron in diets)
adolescents (rapid growth rate)
pregnant women (rapid growth rate, blood loss at delivery)
absorption disorders
What are sxs of Fe def?
Microcytic hypochromic anemia, listlessness, fatigue
What happens if Fe intake exceeds the livers ferritin storage capacity?
it can accumulate in tissues and act as free radical causing oxidative damage
What is chronic hemochromotosis?
inherited mutations in hepcidin (or other iron metabolism genes). It causes organ failure due to iron accumulation.
Where is Cu found in the diet?
meat
shellfish
nuts
How is Cu absorbed in the enterocyte at the brush border?
A brush border REDUCTASE reduces Cu2+ to Cu+.
Cu+ then is transported through CTR1.
Cu+ can then enter the blood through ATP7A, a basolateral transporter, and circulate bound to proteins e.g. ALBUMIN
What causes Menkes Kinky hair syndrome?
Mut in ATP7A
Hypothermia, hypotonia, poor feeding, FTT and seizures is characteristic of…
menkes kinky hair syndrome
*pts have normal hair at birth but it becomes brittle and sparse as they age b/c Cu requiring enzymes in hair follicles
What are the functions of Cu?
- Cofactor for Ceruloplasmin
- Cytochrome C oxidase
- Cofactor for lysyl oxidase (collagen synthesis)
How does Cu fxn in antioxidant defense?
Cofactor for superoxide dismutase (an antioxidant enzyme)
How does Cu fxn in NT synthesis?
Copper is a cofactor for dopamine b-hydroxylase, required for catecholamine synthesis.
What are the fxns of Fe?
- Heme for Hb and ETC complexes
2. Fe-S centers for ETC complexes
What are the functions of Cu?
Superoxide dismutase Cytochrome C oxidase Ceruloplasmin (a.k.a. hephaestin) Oxidizes iron for transport in blood Dopamine b-hydroxylase
Cu def commonly occurs in…
people who consume a lot of zinc or take PPI
A pt presents w/ anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism. What do they have?
Cu def
What sxs are associated with actue Cu toxicity?
epigastric pain, N/V, diarrhea
What sxs are associated with chronic Cu toxicity?
hematuria, liver damage, kidney damage
What causes Wilson disease?
mut in the liver specific Cu transporter ATP7B–> accumulation of Cu in the liver–> toxic
What is the role of ATP7B and what happens when its defective?
ATP7B normally transports excess copper into the bile for excretion. When it is defective, copper accumulates and ‘leaks out’ unbound to ceruloplasmin
How do you tx Wilson disease?
avoid high CU foods, chelation therapy
What might be seen on physical exam of a pt with wilson disease?
kayser fleisher ring
