Minerals Flashcards
1
Q
Fluid compartments in the body
A
- intracellular
- extracellular
- interstitial
- plasma
- transcellular
2
Q
Intracellular volume
A
24 L (60%)
3
Q
Extracellular volume
A
16 L (40%)
4
Q
Interstitial volume
A
11.2 L (28%)
5
Q
Plasma volume
A
3.2 L (8%)
6
Q
Transcellular volume
A
1.6 L (4%)
7
Q
Osmolality
A
- The particle (solute) concentration of a fluid
- units are millosmoles per kg (mos-mol/kg)
- ECF solutes (or osmoles) are very different from the ICF, due to the action of transporters and active pumps, and different permeability of different membranes
8
Q
Major ECF solutes
A
- Na+
- Cl-
- HCO3-
9
Q
Major ICF solutes
A
- K+
- organic phosphate esters (ATP, creatine phosphate, phospholipids)
10
Q
Albumin
A
- responsible for about 80% of the osmotic pressure of blood
11
Q
Main macrominerals
A
- sodium
- potassium
12
Q
Sodium RDA
A
- 2400 mg/day
- adults ~500 mg/day (estimated requirement)
13
Q
Potassium RDA
A
- 3,500 mg/day
- adults 2,000 mg/day (estimated requirement)
14
Q
Causes of electrolyte imbalances
A
- vomit
- Ingested food/water becomes isotonic
- Diarrhea
- close to isotonic and can lose liters
- urine
- very variable; depends many factors
15
Q
Macrominerals
A
- Sodium
- Potassium
- Calcium
- Phosphorous
- Sulfur
- Magnesium
16
Q
Excess Sodium effects
A
- 20% population Na-sensitive, can lead to hypertension (ECF expansion)
- K:Na ratio linked to hypertension
17
Q
Excess Potassium effects
A
- cardiac arrest
- K:Na ratio linked to hypertension
18
Q
Potassium deficiency
A
- heart arrhythmia
- muscle weakness
- increased blood pH (alkalosis)
19
Q
Functions of Calcium Ca ++
A
- Regulation of intracellular enzyme activities
- Second –messenger functions
- Hormone-receptor interactions; epinephrine ‘fight or flight’ hormone released from adrenal medulla. Binds to α-receptors in liver, activates glycogenolysis and inhibits glycogen synthesis mainly by raising Ca++ levels in liver
- Secretory processes (nerve conductance, pancreatic enzymes, milk protein release)
- Blood clotting
- Muscle contraction
- Structure/growth of bones and teeth
- Binds to many proteins, affecting their function
- Intracellular [Ca] can be ~ 0.1 uM (~ 10,000x lower than ECF)
- Calmodulin binding (regulates MANY proteins and processes such as muscle contraction, inflammation – you name it)
20
Q
Absorption of Calcium Ca ++ promoters
A
- vitamin D
- gastric acid
- lactose
- citrate, malate
- protein and phosphorous
- exercise
21
Q
Absorption of Calcium Ca ++ inhibitors
A
- oxalic acid
- phytic acid
- dietary fiber
- phosphate
- steatorrhea
- increased rate of passage
22
Q
Calcium Ca ++ deficiencies
A
- rickets, osteomalacia (adult rickets)
- Vitamin D prevents rickets (poor intestinal absorption / poor kidney reabsorption of Ca and Phosphate)
- Osteoporosis
- Adult males should consume 1000 mg/day, adolescents, women need slightly more
- Excessive intake increases risk of renal stone formation in some people
23
Q
Phosphorous
A
- Second most abundant mineral in body
- 85% in bones and teeth, 15% elsewhere (e.g. nucleic acids)
- Also regulated by vitamin D
- Functions in structure of nucleic acids, phospholipids, activation of enzymes by phosphorylation, ENERGY (ATP)
- Also acid-base balance
24
Q
Phosphorous RDA
A
- 700-1250 mg/day
25
Magnesium Mg ++ Functions
* Bone strength
* ATP hydrolysis
* Enzyme cofactors (also for structural reasons)
* Binds nucleic acids
* Muscle relaxation after contractions
* Intake is well distributed in US food
* about 30-50% of intake is absorbed
* [Intracellular] > [Extracellular]
26
Magnesium Mg ++ deficiency
- relatively rare except with alcoholics (DTs – hallucination) – extent is not really known
- hypertension
- vascular disease
- preeclampsia
- osteoporosis
27
Magnesium Mg++ toxicity
- anaesthetic effects
| - diarrhea
28
Sulfur S
* Sulfate in tissues, and sulfur containing amino acids methionine and cysteine
* Key role in protein structure (Cys-S-S-Cys) disulfide bonds
* Key role in transfer groups (Acetyl CoA!) – things are easily attached and removed to and from S
29
Key metals involved in enzymatic activities and protein structure
• Iron (Fe)
* some metals like Fe tend to be very insoluble (hard to mobilize). Also, they can be very toxic in excess
• Zinc (Zn)
* Iron and zinc may be the ‘most important’ or at least most common
• Iodine (I)
• Selenium (Se)
30
Iron function
- key role in MANY enzymes – catalysis and electron transfer, oxygen transport
* Despite critical functional role, only about 8 mg Fe in all the different enzymes
- Highly toxic (and insoluble) in presence of oxygen – catalyzes the Haber-Weiss-Fenton Reactions
* creates HIGHLY reactive hydroxyl radical that attacks proteins, lipids, EVERYTHING! and damages these molecules
- Fe proteins create these toxins (by accident) and also defend against them (e.g. superoxide dismutase)
31
Iron stored in:
- ferritin and hemosiderin, mostly in liver
- spleen
- muscle myoglobin
- bone marrow
32
Iron stores
~ 3-4 grams Fe. Most (~2g) is in blood with hemoglobin
- Avg male stores 500-1500 mg, avg female 300-1000 mg
- iron overload disorders, body iron can reach 40-50 grams! Mainly in liver, spleen and bone marrow
- Iron is VERY strictly regulated by the body to maintain a constant store
33
Iron uptake
- requires copper
* presumably for a ferroxidase
activity
- uptake by Transferrin
• Specific cell membrane receptors on target cells
• Tf-receptor complex is internalized by receptor-mediated endocytosis
• Fe is released by acidification*
• Transferrin and receptor are recycled by exocytosis
• There is another poorly characterized pathway for taking up Fe bound to heme
* Note – many metals are very insoluble at pH 7, but most are very soluble in acid
34
Iron RDA
- at least 8 mg per day to maintain stores with a mixed diet
- ages 11-18 require 12M and 15F mg/day
- ages 19-50 require 10M and 18F mg/day
- >50 years require 10M and 10F mg/day
- pregnancy requires 30mg/day
- lactating requires 15mg/day
35
Iron uptake inhibited by
- phytate
| - polyphenols
36
Iron uptake promoters
- vitamin C
- organic acids
- heme
37
Iron excess
* Hemochromatosis (hereditary defect)
* Hemosiderosis – dietary overload (still genetic component)
* Alcohol (particularly red wines) in excess
* Children ingesting Fe supplements
* Possible roles in etiology of heart disease
* Oxidative stress
* Decreases absorption of thyroxine, tetracycline, ciprofaloxacin, and others
* Hereditary ataxias (Freidreich ataxia – defective frataxin –Fe can’t be exported from mitochondria)
* Overall, the evidence is not yet clear on the role of moderately elevated Fe levels and chronic diseases
* Again, the body maintains iron levels very vigorously
38
Iron deficiency
• At least 1 billion people are anemic (abnormally low blood hemoglobin) to some extent, mainly due to dietary Fe deficiency
• Other causes
* Infection (Helicobacter pylori – ulcers)
* vitamin deficiencies, inflammation
• Fe deficiency can exacerbate other problems – e.g. lead poisoning, possibly b/c of increased expression of the DMT divalent metal transporter in response to low Fe
39
Zinc Zn ++ function
- key role in MANY enzymes – catalysis and structure, particularly proteins interacting with DNA (Zinc fingers), and thus gene regulation
- Note that unlike Fe, zinc is NOT redox active (though it still may act in catalysis)
40
Zinc uptake promoters
binding to:
- Histine
- Cysteine
* Metallothioneins – key Cys rich proteins bind many metals at high capacity (12 atoms per protein)- liver, stomach, brain, tongue
* Metallothioneins regulate Zn transfer into blood
- nucleotides
41
Zinc stores
* Men store about 2.5g, women 1.5 g, mainly in muscle and bone
* Turnover very slow, about 300 days
* Turnover in liver Zn-Mth is fast, about 2 weeks – can be mobilized for dietary deficiency – but this is a small pool, only good for a week or so
* You lose about 1 mg/day – depends on many things
* Like Fe, homeostasis rigorously regulates Zn levels in body over wide range of intake levels
* However, Zn levels are not clinically well-established yet
42
Zinc Zn ++ deficiency
* Specifics are not clear, but there are so many key enzymes which require Zn, that it is no surprise it affects almost everything
* Tissue damage, (oxidative stress, apoptosis), immune deficiencies, developmental changes
* Skin lesions, growth reduction, late onset secondary sex char
* Poor appetite
* Genetic deficiencies
* Malabsorption disorders – inflammatory bowel disease
43
Zinc RDA
- ~11 mg/day (Males)
| - ~8 mg/day (Females)
44
Zinc Zn ++ excess
* Gastric distress, dizziness, nausea
* Emetic effect at doses as low as 50 mg
* Can reduce Cu absorption (Cu and Zn uptake are related)
* Implicated in Alzheimer’s disease
* Can affect cholesterol and lower HDLs
45
Copper functions
• Involved in iron uptake (copper deficiency → anemia)
46
Copper excess
- weakness
- tremors
- anorexia
- organ damage
- nausea
- diarrhea
47
Wilson’s disease
- rare hereditary disorder where liver does not excrete excess copper into bile as normal; released into blood and accumulates
- Begins after age 5 – brain damage, involuntary movements, even psychosis (~ ½ affected people)
- In the other half, first symptoms are liver damage → hepatitis and cirrhosis. See gold or greenish gold rings in corneas
- Requires lifelong treatment with Cu-binding drugs. Liver transplant can cure it
48
Iodine functions
- Essential to thyroid hormones affecting development, growth
and metabolism
- Typically bound to tyrosine residues of proteins – regulates metabolic rates in cells (glycolysis) among other functions
49
Iodine RDA
- 150 micrograms μg/day
50
Iodine uptake
- Taken up in gut, concentrates in thyroid
51
Iodine deficiency
- spontaneous abortion
- birth defects
- irreversible impairment of brain and physical development
- In adults, deficiency stimulates enlargement of thyroid (goiter)
52
Iodine excess
- Mild excess (up to 2 mg/day) no apparent effects
| – chronic excess can disrupt thyroid function (added to table Salt)
53
Selenium functions
- Enzyme cofactor for antioxidant defense, thyroid hormone and
insulin function, regulation of cell growth, fertility
54
Selenium RDA
- Adults require about 55 μg/day
55
Selenium deficiency
- cardiac failure
- liver disease
- cancer
- atherosclerosis
- hair loss
- skin changes
- infertility
56
Selenium excess
```
>400 μg/day
– peripheral neuropathy
- nausea
- diarrhea
- dermatitis
- hair loss
- nail deformities
```
57
Manganese, molybdenum, chromium, cobalt, nickel functions
- These have been shown to have roles with some specific enzymes (though not always in humans), or shown to be essential for reasons not yet understood
58
Other metals Probably required – functions unknown:
- Boron
- silicon
- arsenic
- tin
- rubidium
- germanium, etc
