Minerals and Electrolytes Flashcards
1
Q
Major minerals in order of abundance in the body
A
Calcium Phosphorous Potassium Sodium, Chloride Magnesium
2
Q
Trace elements (require < 100 mg/day)
A
Iron
Zinc
Copper
Manganese
3
Q
Ultratrace elements (require < 1 mg/day)
A
Selenium
Molybdenum
Iodine
Chromium
4
Q
Functions of minerals in the body
A
Osmotic balance Maintaining charge / concentration gradients across membranes Enzyme cofactors Structure Taste
5
Q
Major extracellular cation
A
sodium
6
Q
major intracellular cation
A
potassium
7
Q
Most abundant metal ion in body
A
Calcium
8
Q
Dietary sources calcium
A
Dairy, seafood, turnip, broccoli, kale, dietary supplements
9
Q
major functions calcium
A
Bone mineralization
Blood clotting
Muscle contraction
Metabolism regulator
10
Q
Calcium absorption
A
Saturable carrier mediated transport
paracellular transport around tight junctions (claudins)
11
Q
saturable carrier mediated transport of calcium
A
TRPv6 transports Ca2+ across the brush border membrane
Calbindin chaperones Ca2+ within the cell
Ca2+ /ATPase transports Ca2+ across the basolateral membrane
12
Q
ca absorption regulated by
A
calcitriol (vitamin D)
13
Q
what increases Ca absorption
A
Vitamin D
sugars, sugar alcohols
protein
14
Q
what decreases ca absorption
A
Fiber
Phytic, oxalic acids
Other divalent cations, e.g. Mg2+ & Zn2+
Unabsorbed fatty acids
15
Q
what inhibits PTH
A
calcitonin (peptide hormone made by thyroid)
16
Q
what form is calcium in blood
A
40% bound to protein
50% free
10% w/ sulfate, phosphate, citrate, etc
17
Q
where is calcium in cells
A
The cytosolic concentration of Ca2+ is very low (100 nmol).
The extracellular concentration of Ca2+ is 10,000x higher (2.3 mmol).
Ca2+ is stored in intracellular compartments, e.g. mitchondria, ER
18
Q
export of ca from cells
A
Ca2+ /3Na+ exchanger is a low affinity, high capacity transporter
Ca2+ /2H+ exchanger is a high affinity, low capacity transporter
19
Q
Intracellular signaling by calcium is mediated by
A
Intracellular signaling by calcium is mediated by calmodulin, a protein whose association with other proteins is regulated by calcium binding.
20
Q
ca/calmodulin w/ calcineurin
A
inhibit ca channels
21
Q
ca/calmodulin w/ MLCK
A
muscle contraction
22
Q
ca/calmodulin w/ ca/calmodulin kinase
A
inhibit glycogen synthase
When intracellular calcium increases, glycogen synthase is inactivated and glycogen phosphorylase is activated.
23
Q
ca/calmodulin w/ phosphorylase kinase
A
phosphorylase
When intracellular calcium increases, glycogen synthase is inactivated and glycogen phosphorylase is activated.
24
Q
calcium interactions with other dietary components
A
Calcium blocks phosphorous uptake
Calcium transiently blocks iron uptake
Calcium can trap fatty acids and bile salts in ‘soaps’ that are not digestable. (LDL decreases)
25
calcium excretion
Urinary 100-240 mg/day
Feces 45 – 100 mg/day
Sweat 60 mg/day
26
urinary excetion calcium impacted by
Resorption in the proximal tubule is controlled by calcitriol.
Caffeine increases urinary excretion of calcium.
Sodium and calcium share common resorption mechanism in the proximal tubule. Very high sodium inhibits calcium reuptake and increases excretion.
27
those at risk of calcium deficiency
```
fat malabsorption disorders
immobilized patients (bone calcium stores depleted)
```
28
calcium deficiency causes
Rickets
Tetany (intermittant muscle contractions)
Osteoporosis
29
calcium deficiency associated with
Colorectal cancer
Hypertension
Type II diabetes
30
calcium toxicity TUL
2500 mg/day
31
calcium toxicity acute and chronic
Acute toxicity:
constipation, bloating
Chronic toxicity:
hypercalcemia can cause calcification of soft tissue
may lead to hypercalciuria and kidney stones
cardiovascular disease (?)
32
assessment of calcium status
Serum levels of Ca2+ are tightly regulated; measuring serum levels doesn’t tell much.
Bone density scan is more clinically useful.
33
magnesium in the body
25 grams
50-60% in bone
40-50% in soft tissues
1% in extracellular fluid
34
RDA magnesium
400 mg
35
magnesium foods
nuts, legumes, whole grains, chlorophyll, chocolate, and ‘hard’ water.
36
transport of magnesium
Saturable transport across brush border: TRPM6
Basolateral transport:
2Na+/Mg2+ antiporter
2K+/3Na+/ATPase
Non-saturable paracellular diffusion.
37
mg in the blood
50% free Mg2+
13% salts
37% bound to protein
38
functions of magnesium on bone
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
39
actions of mg intracellularly
Intracellularly, >90% of magenesium is associated with ATP.
| Magnesium is essential for kinases and polymerases that use nucleotide triphosphates.
40
activation of ______ requires magnesium
vitamin D
| 25-hydroxylase in liver
41
mg interactions in diet
Vitamin D
Mg2+ may mimic Ca2+ and compete for resorption in the kidney.
Mg2+ inhibits phosphorous absorption by forming Mg3(PO4)2 precipitate
42
Mg assessment
Normal serum [Mg2+] ~ 1.7 mg/dL
Assessment:
Serum is a minor store of magnesium, so concentrations are not reliable.
Erythrocyte magensium is not turned over as rapidly, and can be a better measure.
Renal Mg2+ excretion before and after a loading dose is the best measure of magnesium status.
43
Mg deficiency
Not described. Experimentally induced, chronic or gitelman syndrome.
44
Mg deficiency symptoms, chronic
Symptoms include nausea, vomiting, headache, anorexia; progresses to seizures, ataxia, fibrilation.
Chronic magnesium deficiency is associated with hypertension and type II diabetes.
45
Gitelman syndrome
is an autosomal recessive mutation of SLC12A3, a thiazide sensitive Na/Cl transporter characterized by hypomagnesemia, hypokalemia, hypocalciuria.
46
Magnesium toxicity
TUL = 350 mg/day
Toxicity associated with use of epsom salts (MgSO4).
Symptoms are diarrhea, dehydration, flushing, slurred speech, muscle weakness, loss of deep tendon reflex.
At concentrations higher than 15 mg/dL, can cause cardiac arrest.
47
Chloride locations in body
88% ec
| 12% intracellular
48
chloride absorption
Chloride is absorbed paracellularly, or through a Na+/Cl- electroneutral transporter.
49
chloride secretion
GI cells
50
chloride functions (bicarb)
cl/bicard exchanger
Chloride enters red blood cells in exchange for bicarbonate when cells deliver oxygen to tissues.
Chloride leaves red blood cells in exchange for bicarbonate when cells take in oxygen from lungs.
51
chloride functions (immune system)
Hypochlorous acid (~ bleach) is secreted by neutrophils during phagocytosis to neutralize pathogens.
52
chloride functions (stomach)
Gastric hydrochloric acid secretion by parietal cells.
53
Potassium in the diet
fruit, leafy green vegetables, milk
54
potassium absorption
Paracellular diffusion
K+/H+ ATPase
Basolateral: K+ channel
55
K function
It functions to generate and maintain electrical potential across cell membranes.
Na+/K+ ATPases consume energy to accumulate potassium within cells.
Channels then allow potassium to flow out of the cell, resulting in a loss of positive charge.
Muscle contractility
56
K regulation
Vasopresin and aldosterone increase urinary potassium excretion.
Opposite of sodium.
57
K interactions
decreases calcium excretion (opposite of sodium)
58
normal K levels
3.5-5 mEq/L
59
K deficiency
< 3.5 mEq/L = hypokalemia
60
causes hypokalemia
Caused by fluid loss, thiazide or loop diuretics, or refeeding syndrome
61
symtpoms hypokalemia
Cardiac arrythmias, muscular weakness, hypercalciuria, glucose intolerance, mental disorientation
Moderate deficiency associated with:
elevated blood pressure
decreased bone density (increased urinary Ca++ excretion)
62
toxicity potassium
Hyperkalemia can be caused by renal failure and can cause cardiac arrythmia / arrest.
63
phosphorus locations
85% in bone
1% in fluids
14% in soft tissue, esp. muscle
64
diet phosphorus
widely distributed in the diet: Meat, poultry, fish, eggs, dairy, cola (phosporic acid).
65
kinds of phosphates
Inorganic (phosphates)
Organic: associated with protein, sugar, lipids, nucleic acids
Phytic acid: limited bioavailability
66
absorption phosphorus
Saturable carrier mediated active transport is used when phosphate intake is low. It is activated by calcitriol.
Diffusion occurs in the proximal duodenum (slightly acidic and phosphate is in the H2PO4- form).
67
phosphorus absorption inhibited by
Magnesium ( Mg3(PO4)2 is un-absorbable.)
Aluminum
Calcium
68
Functions of phosphorus
bone mineralization
molecules with high energy bonds
acid base balance
availability of oxygne
69
phos and bone mineralization
amorphous: Ca3(PO4)2, CaHPO4-2H2O, Ca3(PO4)2-3H2O
crystalline: hydroxyapatite: Ca10(PO4)6(OH)2
calcitonin phosphorous deposition in bone
calcitriol phosphorous desorption from bone
70
phos and high energy bonds
```
Nucleotides
Nucleic acids: DNA, RNA
Proteins: Serine, Threonine, Tyrosine
Phospholipids
Vitamins cofactors
thiamin thiamine pyrophosphate (TPP)
pryidoxine pyridoxal phosphate (PLP)
```
71
phos and acid-base balance
Na2HPO4 + H+ NaH2PO4 + Na+
| Phosphorous is an important buffer in the kidney.
72
phos and oxygen availability
2,3-bisphosphoglycerate
73
regulation of phos is at the level of
renal clearance
74
excretion of phos promoted by
elevated dietary phosphorous
parathyroid hormone (PTH)
acidosis
phosphotonins (e.g. FGF-23; secreted by osteoblasts and osteocytes)
75
excretion of phos inhibited by
```
low dietary phosphorous
calcitriol
alkalosis
estrogen
thyroid hormone
growth hormone
```
76
phos deficiency is rare but can occur in
Extreme use of antacids containing magnesium, calcium, aluminum
Malnourishment
Refeeding syndrome
Inherited disorders
77
Inherited disorders with phos def
Dents disease: X-linked, mutation in renal chloride channel
X-linked hyphosphatemic Rickets: Mutation in PHEX gene causes elevated FGF-23
Autosomal dominant hypophosphatemic Rickets: Mutation in the gene encoding FGF-23, prevents its degradation. (FGF-23 is a phosphatonin; promotes phosphorous excretion)
78
phos def symptoms
anorexia, reduced cardiac output, decreased diaphragmatic contractility, myopathy, death
79
Iron in diet
meat, fish, poultry (half heme iron, half non-heme)
| nuts, fruits, vegetables, grains (mostly non-heme; conjugated with phenols)
80
ferrous iron
Fe 2+ (reduced)
81
Ferric iron
fe 3+ (oxidized)
82
low pH prefers ___ iron
ferrous iron (Fe2)
83
ceruloplasmin prefers ___ iron
ferric iron (Fe3)
84
Iron absorption into enterocytes
brush border: reductase makes ferric --> ferrous
| Fe2+ transported through DMT-1
85
iron in enterocyte
iron bound to ferritin
86
iron transport in blood requires
oxidation to Fe 3+ by hephaestin (HP; ceruloplasmin), this enzyme also requires copper
87
Fe 3+ binds ____ for transport to tissues
transferritin
88
regulation of iron uptake through
hepcidin
| When iron stores in the liver are high, hepcidin is produced. It binds ferroportin (FPN) and causes its degradation
89
protein for export from enterocyte
ferroportin
90
funtion of iron
heme synthesis
iron-sulfur clusters
non-heme iron
91
iron and heme synthesis
```
Glycine + succinyl CoA + Iron heme
Heme is used in:
cytochrome B, cytochrome C
hemoglobin, myoglobin
monooxygenases, e.g. phenylalanine dehdrogenase
```
92
iron-sulfur clusters
Electron transfer groups in, e.g. NADH dehydrogenase
93
non-heme iron
Dioxygenase, e.g. homogentisate dioxygenase
94
iron interactions
Vitamin C enhances absorption and maintains iron in the reduced state.
Copper is required for export from enterocytes.
Iron inhibits zinc absorption.
95
iron deficiency observed in
infants (low iron in diets)
adolescents (rapid growth rate)
pregnant women (rapid growth rate, blood loss at delivery)
absorption disorders
96
iron def sxs
Microcytic hypochromic anemia, listlessness, fatigue
97
iron toxicity, TUL
45 mg/day
98
iron toxicity pathology
If intake exceeds the livers ferritin storage capacity, it can accumulate in tissues and act as a free radical, causing oxidative damage.
99
chronic hemochromatosis
caused by inherited mutations in hepcidin (or other iron metabolism genes). It causes organ failure due to iron accumulation.
100
copper diet
meat. shellfish, nuts
101
copper absorbtion
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.
102
Menkes kinky hair syndrome
caused by mutations in ATP7A. It is characterized by hypothermia, hypotonia, poor feeding, failure to thrive, and seizures.
Patients have normal hair at birth, but it becomes brittle and sparse as they age.
103
function of copper
Cofactor for ceruloplasmin; see iron.
Cytochrome C oxidase has 3 Cu+ per enzyme
Cofactor for lysyl oxidase (collagen synthesis; also requires ascorbate)
Copper is a cofactor for superoxide dismutase, an antioxidant enzyme.
Copper is a cofactor for dopamine b-hydroxylase, required for catecholamine synthesis.
104
copper deficiency
May occur in people who consume a lot of zinc, or a lot of proton pump inhibitors.
Symptoms: anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism.
105
copper TUL
10 mg/day
106
copper toxicity acute, chronic, cong. disease
acute: epigastric pain, nausea, vomiting, diarrhea
chronic: hematuria, liver damage, kidney damage
Wilson disease
107
wilson disease
is caused by mutation in the liver specific copper transporter ATP7B.
108
normal ATP7B
ATP7B normally transports excess copper into the bile for excretion. When it is defective, copper accumulates and ‘leaks out’ unbound to ceruloplasmin.
109
tx wilson diease
Treatment is to avoid high copper foods, and chelation therapy.
110
sx wilson disease (hallmark)
Kayser-Fleischer ring
