3.02 Minerals Flashcards
What is the daily amount needed for macro minerals?
> 100 mg per day
Most abundant mineral in the body?
Calcium
Where is calcium in the body?
98% bone
The rest is free in cells (signal, muscle contraction, etc.)
What form does calcium need to be for absorption?
Ionized
(freed from slats)
Major sources of calcium in diet?
Dairy product, leafy greens, fortified orange juice (30-35% at a time)
Common causes of hypercalcemia?
Primary hyperparathyroidism
Cancer metastasis to bone
Vit D toxicity
Soft tissue calcification, EKG abnormalities, nausea, vomiting, anorexia can be clinical indication of?
Hypercalcemia
What happens when Ca2+ binds avidly to cell membrane phospholipids?
Reduces membrane fluidity
How many Ca2+ can bind to calmoduline to create the calcium-calmodulin complex?
4
When does Ca2+ become free/dissociated from salt it was bound to in order to be absorbed in intestine?
Low pH of stomach
What is the channel that uptakes the Ca2+ into the intestinal cell ?
TRPV5 < TRPV6*
What binds to the free Ca2+ immediately when it enters into an intestinal cell?
Calbindin-D
What BL proteins are responsible for pumping calcium into portal blood?
NCX1 - antiporter (Ca + 3Na+)
PMCA1b - active
How does Vitamin D increase Ca2+ absorption?
It promotes the activity and proliferation of calcium binding proteins, protein synthesis, and activating BL pumps
What is the unregulated way that ca2+ can go from the lumen to circulation (unable to be saturable)?
Paracellular transport
Where is the majority of calcium clearance?
Urine (free, 2%) and feces (most non absorbed)
What hormones tightly control serum levels of calcium?
PTH (Parathyroid hormone) and Vitamin D
How does PTH increase serum Ca2+ ?
increased bone resorption
Kidney calcium reabsorption
What does PTH do to serum phosphate?
It decreases it by reducing its absorption at the kidneys
What hormone is solely responsible for intestinal Ca2+ absorption?
Vit D
What reduces serum levels of calcium in the blood by inhibiting bone resorption and kidney reabsorption?
Calcitonin
What is calcitriol?
Active form of vitamin D
What does calcitriol do to promote increased serum calcium?
Increase bone resorption
Increase gut absorption
Increase kidney reabsorption
Where does the PTH act in order to increase serum calcium?
Bone and Kidney
(NO GUT INVOLVEMENT)
What are common causes of hypocalcemia?
Hypoparathyroidism
(Wilson’s Disease, thyroidectomy, primary PTH def, autoimmune)
Low Vit D
(Low sunlight, low diet, malabsorption diseases)
Bone density disorders (Rickets, osetomalacia, osteoporosis) and neuromuscular tetany, spasms, and cramping, cardiomyopathy (prolong QT), and laryngopharyngeal spams are indicative of?
Hypocalcemia
What is the most abundant intracellular ion in humans?
Phosphorus
Where is 85% of phosphorus in body found?
Bone and teeth (hydroxyapatite)
What the issue in drinking a lot of colas despite it being a good source of phosphorus?
It can form tight complexes with free calcium becoming insoluble and prevent both from being absorbed at gut
At physiologic pH, what is the form of free phosphate?
HPO4 2-
(Make it a good buffer)
What are the roles of phosphorus in our bodies?
Energy storage (ATP bonds)
Structural (phospholipids/nucleotides)
Metabolic charging
Protein modification and covalent regulation
Cell signaling
PH buffer
How is most of the phosphorus we need absorbed?
Diet as chylomicrons
How is free phosphate absorbed?
Na+/P symporter regulated by Vit D and estrogen
What are hormones that regulate serum phosphate?
Calcitriol - Increase
(bone + intestinal)
PTH - Decrease
(Kidney)
What are common causes of hypophospahatemia?
Vitamin D def
Antacid Aluminum overuse
Liver or kidney Dx
Malnutrition
Refeeding syndrome
Hyperparathyroidism
Chronic alcoholism
Fanconi Syndrome
How can phosphorus depletion happen in Refeeding syndrome?
After long period of fasting/stravation the cells are flooded with carbs, insulin pushes glucose into cell, cells depletes phosphorus (cell then blood) to phosphorylate the glucose “sugar trap”
Lethargy (CNS depression, irritability, seizures), anemia, and myopathy are common presentations of what?
Hypophosphatemia
Common causes of hyperphosphatemia?
Decreased PTH production
Renal insufficiency - dehydration
Hyperlipidemia (impaired kidneys, insulin resistance, diet, inflamm)
Tetany, diarrhea, soft tissue calcifications, and kidney stones are presentations of?
Hyperphosphatemia
What should be noted about free iron, especially Fe2+?
Highly toxic b/c Fenton Reaction (free iron + hydrogen peroxide —> hydroxyl radical)
Major sources of iron?
Diet
Heme = meat, poultry, shellfish
Ferric = cereals, lentils, molasses
Major function of iron in body?
Oxygen transport
Cell respiration (Fe-S mito)
Drug & xenobiotic metabolism
Oxidative burst macrophages
Key transport proteins for iron at enterocytes?
DMT-1 (free Fe2+)
Dcytb (Fe3+—> Fe2+)
HCP (heme)
What oxidizes intracell Fe2+ (free) back to Fe3+ (ferretin)?
Heme oxygenase
What happens to the remaining free iron inside a cell that is not stored in ferritin?
Ferroportin moves them out into circulation
What happens when Fe2+ is released from enetrocyte into circulation?
Hephaeston (Heph) oxidizes Fe2+ —> Fe3+
Then Fe3+ able to bind to transferrin to move in blood to other organs
Hormone secreted by liver that binds to ferroportin to internalize/destroy it in response to high serum iron levels?
Hepcidin
Protein found in blood stream that oxidizes any free Fe2+ (ferrous) back to Fe3+ (ferric) ?
Ceruloplasmin
What cofactor is necessary for ceruplasmin to do its job?
Copper
What are factors that can inhibit iron absorption by acting as chelators?
Oxalates
Tannins
Polyphenols
What allows infants to additionally absorb iron?
Lactoferrin mediated endocytosis (breast milk)
And Pinocytosis
Main effect of iron deficiency?
Microcytic hypo chromic anemia
(Lethargy + neuro/physical delay)
An overload of what can affect/inhibit iron absorption?
Excess Copper and Zinc absorption (competition)
What is a downside to iron supplementation in terms of correcting the deficiency?
It can take week to months to correct
What are signs of iron overload?
Nausea, headaches, neuroimpairment
Hyperpigmentation with hyperglycemia and damage to the pancreas, liver, kidneys, and heart are signs of?
Hereditary hemochromatosis (iron overload)
What is the most common cause of iron overload?
Over supplementation
What is the role of copper in the body?
Required cofactor for ferroxidase enzymes in iron oxidation
Immune system signaling
Cell differentiation
Bone formation pathway
Oxidation defenses
Although copper deficiency via diet is rare since it is in meat, shellfish, nut, and whole grains, the first sign of a deficiency is?
Anemia (iron metabolism impairment)
What are the main copper transporters into enterocytes (entire length of small intestine)?
DMT1
Ctr1 (but needs Dcytb to reduce it to Cu1+ first)
What copper transporter is seen in the BL?
ATP7A - Copper ATPase (active)
How is copper transported in body?
Mostly through albumin
(But can also bind transferrin or ceruloplasmin)
What is the main way that copper is excreted?
Biles salts allows it to be expelled from feces
(Also sloughed off intestinal cells)
Copper and/or Zinc overload can cause iron deficiency because it displaces Fe3+ from what?
Transferrin
Anemia, changes to hair, skeletal defects, and connective tissue disturbances, progressive neuro degeneration, altered pigmentation, nuetropenia are signs of?
Copper deficiency
What are risk factors of copper deficiency?
MENKES SYNDROME
Diets rich in phytates/oxalates or low meat
Where is the mutation in Menke’s Syndrome?
ATP7A
Copper toxicity can lead to what?
Liver failure with chronic intakes >30mg/day
Most ADSE from iron absorption disruption
What is the genetic deficiency of Wilsons disease?
ATP7B*
What happens in Wilsons Disease?
Protein responsible for copper efflux (ATP7B) is shot, so it accumulates in liver, eyes, brain, kidneys, and skin
What is a diagnostic test you can do for Wilsons Disease?
Urine Copper Levels (elevated)
Why would urine copper be high in Wilsons disease?
Liver damage to hepatocytes causes them to burst and spill into circulation
Cognitive impairment, loss of motor function, and liver failure are signs of?
Copper toxicity
Treatments for copper toxicity?
Zinc supplementation and chelation
Roles of zinc in the body?
Structure of transcription factors (Zinc fingers) = gene expression
Insulin store/secrete
Immune signaling and diff
Cofactors (LOTS)
Zinc dependent hormone involved in T cell differentiation?
Thymulin
Sources of ZInc in diet?
Meat, fish, eggs, diary
Who should consider Zinc supplementation?
Strict vegans
What protein is for zinc uptake into enterocyte?
ZIP4
What proteins allow zinc to move from enterocyte into circulation?
ZIP5 or ZnT1
How does zinc mostly move through the body?
Bound to albumin
How is zinc mostly excreted?
Feces (bile salts + metallothionien)
Appetite loss, alopecia, hyperkeratinization of skin, slow growth in children, low T/B cells, loss of taste and smell, low sperm count are signs of?
Zinc deficiency
What are some risk factors of zinc deficiency?
Phytate rich food
Low meat diets
Metal chelating drugs
Acrodermatitis enteropathica (defined of SLC39A4 - encodes ZIP4)
Vision problems
Most common cause of zinc toxicity?
Excess long term supplementation, excess cold Lozenges, and Neutropenia (secondary to Cu def)
