1. Essential Micronutrients Flashcards
• Basis of hematopoiesis and neuro growth and development
○ Array of essential micro nutrients: ____
○ Macro: proteins, carbs, fat
• Micro nutrients are the small molecules that are used as cofactors
for a variety of enzymatic rxns
• Or a component of an essential substance
○ Example: Iron Hg
○ Example: Zn synthesize DNA
vitamins and minerals
Vitamin A • Comes in two dietary forms • Vitamin A from \_\_\_\_ sources • Provitamin A carotenoid from \_\_\_\_ – α-carotene – β-carotene – β-cryptoxanthin • Other carotenoids not converted to vitamin A
• Comes in two main dietary forms
○ Animal sources ‐ vegans and vegetarians are fucked
• ____ is the most common organ that provide this source, very rich source
○ Plants
• Comes to us from animals as vitamin A
• Plant source comes as a precursor called carotenoids
○ ____ is most well recognized
• One of the primarily used that can be a precursor to vitamin A
• High abundance in ____ colored fruits and vegetables
animal plant liver b-carotene red/orange
Vitamin A • \_\_\_\_ soluble retinoid • Solubilized into \_\_\_\_ in intestine • Absorbed in \_\_\_\_ • Vitamin A > retinol > retinal > \_\_\_\_ • Most Vitamin A stored in liver \_\_\_\_ cells
• All B vitamins are ____ soluble
• All the other lettered are fat soluble (including vitamin A)
○ Similar pattern of absorption
○ Once digested and converted to vitamin A they are incorporated into
micelles
○ ____ are used to cross plasma membranes
• Different parts of the intestine absorb different nutrients
○ Most absorbed in the duodenum, some in ileum, few in the jejunum
• Most fat soluble absorbed in the ____
• Once absorbed they get converted eventually to an end product called
retinoic acid
○ This is what works within the cell as the ____ form
○ Array of enzymatic actions most importantly ____
• Cofactor for promoting DNA transcription
Drug: for ____
○ Retinoic acid
○ Topically potent
○ Pro ____ function
Storage:
○ Stored in the body, we don’t ____ it
○ Stored in the liver in Ito cells (BS1 last year, first lecture)
fat micelles duodenum retinoic acid Ito
water micelles duodenum biologic DNA transcription acne transcrption synthesize
Vitamin A deficiency • Most common cause of \_\_\_\_ in 3rd world • \_\_\_\_ blindness • Dry \_\_\_\_, eyes and hair • Hyperkeratosis of skin and mucosa – \_\_\_\_ • Angular \_\_\_\_ • Immune dysfunction – Increased infection
Vitamin toxicity is not as commonly seen as deficiency
In this part of the world it is not commonly seen
○ Most common cause of third world blindness
Night blindness / ocular and vision problems
Dry skin, eyes, hair
○ Hair might fall out
○ Retinoic acid plays a roll in transcription, the cells that are rapidly turning over give rise to these
____ of the oral mucosa
○ Hyperkeratosis reflective Hyerkeratosis of the ____
○ can cause blindness as well
○ Damage to conjunctiva
○ Keratomalacia
Angular cheilitis is common to all ____
○ Fungal infection at the commissures of the lips
Immune dysfunction
○ Many immune states
○ Roll in immune development ‐ development of ____
blindness night skin keratomalacia chelitis
leukoplakias
oral mucosa
defieincies
lymphocytes
Hypervitaminosis A • \_\_\_\_ • Bone pain and fracture • \_\_\_\_ complications • Liver damage • Disrupts \_\_\_\_ of other vitamins
Hypercarotenemia
• Non-____
• Excessive ____
• Pigmentation of ____ NOT mucosa > differentiates from jaundice
Excessive vitamin A, not a big problem in this part of the world
○ Happens if you eat foods only excessively rich in vitamin A Too much causes an array of systemic problems
○ Complications are common to many excessive toxicity so just learn it for all the vitamins
Hypercarotenemia ‐ what is more common
○ Non‐toxic state
• Not real complications beyond the change in skin color
○ High b‐carotene ingestion
• Lots of carrots
○ Become orange (see picture)
○ Ddx: ____
• Difference: even mucosal tissues turn yellow in jaundice • Here only the skin
toxic
neurologic
metabolism
toxic
b-carotene
skin
jaundice
B complex vitamins • B1 = \_\_\_\_ • B2 = Riboflavin • B3 = \_\_\_\_ • B5 = Pantothenic acid • B6 = \_\_\_\_ • B7 = Biotin • B9 = \_\_\_\_ • B12 = Cobalamin All water soluble vitamins absorbed in intestine via \_\_\_\_ transport
All water soluble absorbed in intestine via passive transport (except food level active transport)
○ Caveat: if you are taking multivitamins with ____ doses that is how you absorb them through passive transport
○ Small quantities in the diet is through ____ transport
• Nutrient level sources
• Food level sources digested absorbed through active transport Need to know the B number and names
thiamin niacin pyridoxine folate passive
high
active
B complex vitamins
____: high doses absorbed ____: nutritional doses into the food
○ Requires energy
passive
active
Thiamin (B1)
- Required for ____ metabolism
- Nutritional sources (low dose) absorbed via ____ transport
- Pharmacologic (high) dose absorbed by ____ transport
- Minimal storage
All the vitamins are required for metabolism ○ Many are in the ____ cycle pathway
This does not get stored in the body
○ taken up converted to ____: functionally active form of thiamine
• cofactor to biologic pathways
• ____ required for conversion Abs, converted, little stored
○ Once it is used its used
energy active passive krebs thiamine pyrophosphate ATP
Know where it is used
Functional form: thiamine pyrophosphate is used in four places
○ ____: Converts ribose 5 phosphate to glyceraldehyde 3 phosphate (precursor to the Kreb cycle)
○ Catabolize ____
• This catabolism helps synthesis ____ in the citric acid
Citric acid cycle thiamine pyrophosphate comes in twice
○ ____: Converting pyruvate to acetly coa (decarboxylate)
○ ____: Alpha‐ketogluterate to succinyl coA
pentose phosphate AA acetyl CoA pyruvate dehydrogenase alpha-ketoglutarate dehydrogenase
Thiamin (B1) Deficiency state called \_\_\_\_ – \_\_\_\_ manifestations – \_\_\_\_ complications – \_\_\_\_ syndrome
Risk factors – Insufficient \_\_\_\_ intake – Chronic alcoholism – \_\_\_\_ / AIDS – Diabetes mellitus – Medications eg \_\_\_\_
Deficiency for one of two reasons
○ From a third world country in a deficient state
○ ____
Phenotype is the same: Berberi
○ Body wide rash
○ ____: Stays depressed in the skin
These patients are at risk for Wernicke‐Korsakoff syndrome
○ Two phenotypes that occur in the same context
○ Wernicke: ____
• Neurologic complications much like patients with menigitis, or prion disease
• Gate changes, ____
○ Korsakoff: ____ over time
• Start forgetting
• Confabulating: makes up ____ stories out of the blue
Unique: alcoholism can cause Berberi
○ Alcoholism does not typically cause the other disease states Medication ‐ Furosimide:
○ ____
○ Usage can cause B1 deficiency is used excessively Tx: replenishing the B1
○ ____ usage
No real complications associated with excessive B1 because it is not stored
beriberi
mucocutaneous
cardiovascular
wernicke korsakoff
dietary
HIV
furosemide
alcoholism
peddle edema
encephalopathy
tremors amnesia bizarre diuretic multivitamin
Riboflavin (B2) • Essential component of two coenzymes – Flavin \_\_\_\_ – Flavin \_\_\_\_ • Required for \_\_\_\_ production • \_\_\_\_ / drug / steroid metabolism • Regulates metabolism of other \_\_\_\_ vitamins
Component of two important coenzymes
○ FMN: Flavin mononucleotide
○ FAD: flavin adenine dinucleotide
○ Need to recall both of these from the ____ cycle
○ Beyond that these are used in other pathways including ____
Required for energy production
○ Macromolecules metabolism (fat and steroids)
○ Metabolism steroid
B2 plays a role in regulating other vitamins
○ A, folic acid, and B 12
○ synergistic
• Some of the phenotypes are common to most of the vitamins Know where they come in the pathway
○ FAD: converts ____ to a byproduct needed to synthesize DNA
○ FMN: together to convert ____ to excretable form in the
urine
○ Work ____ with one another
mononucleotide adenine dinucleotide energy fat B
kreb
DNA synthesis
folic acid
synergistically
Riboflavin (B2)
• Absorbed in \_\_\_\_ • \_\_\_\_ storage • \_\_\_\_ molecule – Fluoresces when exposed to \_\_\_\_ light • \_\_\_\_ = deficiency
Not stored to any great extent
At high levels this molecule is fluorescent
If you suspect toxicity state, test the urine and it will phosphoresce ____ under UV light
Toxicity does not cause too many problems, neurologic, cardiovascular but no ____ complications associated with excessive B2
Deficiency state is pretty rare because so many sources
○ Ariboflavinosis
○ Manifestations are no different than B12, foliac acid cholitis
• Angular cheilitis, oral lesions, burning mouth
• Common to most of the vitamins
proximal small intestine minimal photosensitive UV ariboflavinosis
yellow-green
long-term
Riboflavin (B2) • Mucocutaneous lesions – \_\_\_\_ tongue • Anemia • Degeneration of \_\_\_\_ and CNS • Risk factors – \_\_\_\_ athletes – Vegan diet and/or minimal dairy – Treatment of neonatal \_\_\_\_
Deficiency tongue might turn magenta
○ Not pathognomonic but highly characteristics
The rest are all things we see in other deficiency states as well
○ Vegetarian or vegan you run the risk
○ B2 is primarily found in the ____
○ Fortified foods do have a good source of B2
○ Metabolized in the liver
magenta liver vegetarian jaundice liver
Niacin (B3) • Essential component of two coenzymes – Nicotinamide \_\_\_\_ – Nicotinamide \_\_\_\_ • Critical in most \_\_\_\_ pathways • Tissues with high \_\_\_\_ or high energy demands most susceptible to deficiency
Component of two coenzymes ○ NAD ○ NADP ○ \_\_\_\_ and \_\_\_\_ synthesis ‐ close to our heart • Only know the major: Kreb and DNA • But in a lot others
adenine dinucleotide dinucleotide phosphate turnover kreb DNA
Niacin (B3)
Mild deficiency
– Slows ____
Severe deficiency = \_\_\_\_ – Diarrhea – \_\_\_\_ – Dementia – \_\_\_\_
Deficiency is not common, we get B3 through an array of sources When it does happen it is very severe
○ Mild: minimal complications
• Lethargic
• Ddx: ____
• But no ____
○ Severe: pellagra
• Only used to describe severe niacin deficiency
• Experience four very commonly occurring manifestations D
• Diarrhea, dermatitis, dementia, death Get it from fortified foods like cereal
metabolism
pellagra
dermatitis
death
Pantothenic acid (B5)
• Required for biosynthesis of \_\_\_\_ • Synthesis and metabolism of – \_\_\_\_ – Fat – \_\_\_\_ • Deficiency state very rare
Critical cofactor of ____
○ Linked to yield: ____ used in the kreb cycle
Needed for synthesis of macromolecules, fat, carbs, proteins
○ Plus ____
Many sources we get this from, not a common deficiencies
coenzyme A
protein
carbohydrate
coenzyme A
acetyl CoA
DNA
Pyridoxine (B6) • Required for numerous enzymatic reactions • \_\_\_\_ metabolism • Gluconeogenesis and \_\_\_\_ • Hemoglobin formation • \_\_\_\_ function • Immunity
Unique vitamin, required for an entire array of enzymatic rxns
○ Producing ____: gluconeogenesis and glycogenolysis
○ Metabolizing protein
• ____ are lower on B6
○ Problems, additive beyond the diabetes
○ Diabetics metabolize ____ to yield energy to survive and sustain function
○ So if this is low in these patients it a double whammy
○ Required for gluconeogenesis and glycogenolysis
• Hemoglobin formation: At risk for ____
• Critical cofactor in brain development and function
protein
glycogenolysis
brain
glucose
diabetics
protein
anemia
Pyridoxine (B6) • Deficiency state is rare – \_\_\_\_ – Mucocutaneous lesions – \_\_\_\_ dysfunction – Seizures
• Risk factors – \_\_\_\_ disease – Inflammatory bowel disease – \_\_\_\_ – Chronic alcoholism
Rare, third world countries primarily speaking
• None of the features are unique to B6,
○ Common to B6, iron, B12, and folic acid
○ ____ Is the most severe manifestation
• Microcytic anemia
microcytic anemia
immune
chronic renal
rheumatoid arthritis
anemia
Biotin (B7)
- Coenzyme for ____ enzymes
- Synthesis of ____ acids
- Synthesis of ____ and valine
- ____
Coenzyme for carboxylase enzymes
○ Ex: left picture
○ ____ is used in the krebs cycle for glycolysis
• Fatty acid synthesis
• Synthesis of isoleucine and valine
○ Only vitamin that is used in ____ synthesis directly
carboxylase
fatty
isoleucine
gluconeogenesis
oxaloacetate
amino acid
Biotin (B7) • Deficiency very rare – \_\_\_\_ – Hair loss – \_\_\_\_ – Conjunctivitis – \_\_\_\_ complications • Risk factors – \_\_\_\_ – Inherited disease
Array of plant based sources
○ Do not see many deficiency states
• Not unique to this deficiency only
• Too much: not bad just passes through
brittle nails
dermatitis
neurological
pregnancy
Folate (B9)
- Essential coenzyme for ____ synthesis
- Converts homocysteine to ____
- Required for ____ and neural tube formation
- Nutritional sources absorbed via ____ transport
- Pharmacologic doses absorbed by ____ diffusion
The first six are important and have an array of important functions but this part of the world their deficiency is not commonly seen
○ Eat enough cereal, yogurt, granola all fortified foods
• Folic acid and B12 the two of the most common we will see in practice, along with ____
○ Most common we see and most common we test for
○ These do not get directly passed on but a pregnant women who is folic acid deficient will likely result in a fetal malformation where the spinal cord doesn’t develop in the fetus: ____
• B9, folate, folic acid, is a critical cofactor for nucleic acid synthesis
○ Helps convert homocysteine to methionine
• Methionine the first AA in protein translation, so also critical for ____ synthesis
• B9 is critical for erythropoiesis and neural development
• Nutritional doses are actively pumped into the cells
• Pharmacologic doses is passively diffused
• Need to know this pathway
○ ____ in the same pathway
• One of the shared pathways between these
○ Folic acid is taken in, digested absorbed, and is converted to ____
○ TH4 folate version is used during met synthesis and nucleic acid
synthesis
• Converted to ____ which is used in nucleic acid synthesis
5 methly tetra in converted back to tH4 in the formation of ____
• B12
• Three critical vitamins that play a roll in this
nucleic acid methionine erythropoiesis active passive
iron spina bifida protein B12 tetra-hydrolate (TH4) folate 5-methyl THF methionine
Folate (B9) • \_\_\_\_ > Tetra-hydrofolate > 5-methyl-THF (enters plasma) • How to assess folate status – \_\_\_\_ levels – Erythrocyte folate concentration – \_\_\_\_ concentration
Beyond the use in cells, the 5 methyl‐THF enters plasma
○ One of the way we measure folic acid in serum ____
• One of the most common deficiency serum states we need an easy
mechanism to measure this
• Measure it directly in serum
○ Don’t indicate the true availability
○ Homocysteine is the better measure even though its indirect because it
implies the ____ usage
• ____ but more accurate because they are used by blood in their synthesis
and create homocysteine as a byproduct of this pathway
• Used to convert homocysteine to methionine
○ If homo is high it means the conversion pathway may not be ____ (____ is low)
folate
serum
homocysteine
directly actual indirect functioning folate
Folate (B9)
Deficiency state – \_\_\_\_ anemia – Spina bifida – \_\_\_\_ – Cardiovascular disease
Risk factors – \_\_\_\_ – Pregnancy – \_\_\_\_ disease – Medications eg antiepileptics, \_\_\_\_, sulfasalazine
Unlike B6, unlike iron deficiency, B9 and B12 are macrocytic or megaloblastic anemia • \_\_\_\_ is unique to B9 deficiency • Same risk factors • Oral manifestations are not unique to the deficiency state • Liver not functioning array of issues ○ Vitamin A, vitamin K ○ Alcoholism • Most important for \_\_\_\_
megaloblastic depression alcoholism inflammatory bowel methotrexate
spina bifida
beriberi
Cobalamin (B12)
• \_\_\_\_ and 5-deoxyadenosylcobalamin • Essential cofactor for \_\_\_\_ – Converts homocysteine to \_\_\_\_ • Essential cofactor for \_\_\_\_ – Converts L-methylmalonyl-CoA to \_\_\_\_ • Required for – \_\_\_\_ synthesis – Fat / protein metabolism – \_\_\_\_ synthesis and erythropoiesis
Critical vitamin
• ____ soluble
• Used in the same pathway in conversion of homocysteine to methionine
• Better measure of b12 is not homocysteine but methylmalonic acid
○ B12 here is used to convert homocysteine to methionine
• But the availability in this context is not easily measurable
• Better measure for B12 is the second pathway where it converts
methylmalonyl co A to ____
methylcobalamin
methionine synthase
methionine
L-methylmalonyl-CoA mutase
succinyl CoA
DNA
hemoglobin
water
succinyl CoA
Cobalamin (B12)
The second pathway used to converts methylmalonyl‐CoA to succinyl CoA
○ This is how we measure indirect B12 ‐ ____
○ Much more reliable measure for B12
• Folic acid and b12 are required for same pathways
○ ____ synthesis
○ ____
methylmalonic acid
DNA
hematopoiesis
Cobalamin (B12)
• Found in \_\_\_\_ products and fortified foods • Dietary supplementation with \_\_\_\_ • How to assess B12 status – \_\_\_\_ or plasma – \_\_\_\_ level
B12 is found only in animal products ○ Unless fortified foods • Deficiency: Most common in a \_\_\_\_, \_\_\_\_ second most common - make sure taking multivitamins • Assessed
○ Serum direct
○ Indirect: ____
• B12 is used to convert Methylmalonyl‐CoA to ____
• If its accumulated implies its not being converted ____
animal
cyanocobalmin
serum
methylmalonic acid
vegan folic acid methylmalonic acid succinyl CoA properly
Absorption of B12 from food Binds to \_\_\_\_ in stomach Travels to duodenum – \_\_\_\_ digest HC to release B12 – B12 then binds to \_\_\_\_ IF-B12 binds to receptor and internalized within \_\_\_\_ – Released from lysosomes and transported to blood HC and \_\_\_\_ bind B12 in blood
Intricate absorption pathway
• When you first absorb from food it first binds to haptocorrin protein found
in the stomach and the saliva
○ Mostly bound in the stomach via haptocorrin
• Takes the complex to the duodenum
Pancreatic digest haptocorrin and release B12 to the duodenum
○ Binds to intrinsic factor in the duodenum
○ Passes through the intestine
• IF‐B12 is internalized in the ileum via IF receptors
○ Absorbed into cells, B12 released in to the plasma / serum
○ As it is released binds to the transcobalamin carrier protein
throughout the blood
○ Measuring this ____ in the blood
• Which cells produce IF?
○ ____ cells found in the stomach
○ Protein goes to the intestine where it sits till it binds to b12
• ____, ileectomy are at risk for this type of anemia because they loss the ability to bind B12 efficiently
○ Intestinal surgery pts are at risk
• Pernicious anemia characterized by ____ to intrinsic factor
○ Synonymous with b12 anemia but it is autoimmune in nature
○ Target in autoimmune is parietal cells, so no production of IF
haptocorrin (HC) pancreatic enzymes intrinsic factor (IF) distal ileum transcobalamin (TC)
transcobalamin (B12)
parietal
colectomy
autoimmune
Cobalamin (B12) • Deficiency state – \_\_\_\_ – Neurologic complications – \_\_\_\_ disease – Mucocutaneous lesions
Like folic acid the anemic state is macrocytic / megaloblastic anemia
○ Red cells are ____ than what they should be • Manifestations are not different from ____
○ Except no risk for fetal ____
megaloblastic anemia cardiovascular larger folic acid spina bifida
Cobalamin (B12)
• Risk factors – \_\_\_\_ or vegan – Elderly – \_\_\_\_ – Inflammatory bowel disease – \_\_\_\_ surgery – Medications • \_\_\_\_ inhibitors (eg Prilosec, Nexium) • H2 receptor antagonists (eg Pepsid, Zantac) • \_\_\_\_
If you are vegan or vegetarian you run the risk
vegetarian pernicious anemia gastric bypass proton pump metformin
Vitamin C (L-Ascorbic acid)
• \_\_\_\_-soluble vitamin • Required for – \_\_\_\_ biosynthesis – L-carnitine – \_\_\_\_ – Protein metabolism – \_\_\_\_ – Immunity
Water soluble vitamin that is also known as ascorbic acid
• Found in the same pathways as the B vitamins
• Critical nutrient
• Found in primarily ____, can also get it in meat
• Critical for collagen biosynthesis
• ____ is common manifestation of vitamin c deficiency
○ ____ disease = manifestations
○ ____ collagen fibers are not sufficiently produced and not an attachment of the teeth to the alveolar bone
• Do not memorize these pathways
water
collagen
neurotransmitters
antioxidant
citrus
scurvy
periodontal
sharpey
Vitamin C (L-ascorbic acid)
• Deficiency = Scurvy acid – \_\_\_\_ and periodontal inflammation – Loss of teeth – \_\_\_\_ – Impaired wound healing – \_\_\_\_
• Risk factors
– ____
– Inadequate diet
– Intestinal ____
When you are deficient = Scurvy • Anything collagen is needed for: wound healing, tooth maintenance, eyeball structure ○ All regulated by collagen ○ Lines \_\_\_\_ ‐ at risk for bleeding • High in guava
gingival
bleeding
infections
smoking
malabsorption
blood vessels
Vitamin D (Cholecalciferol)
• \_\_\_\_-soluble vitamin • From food or UV-B activity on skin • Vitamin D > 25-hydroxyvitamin D (calcidiol) > \_\_\_\_ (calcitriol) • To assess vitamin D status – Measure \_\_\_\_ levels NOT 1,25(OH)D
Fat soluble vitamin
• Primarily get it from food
○ We don’t ____ these, they are all food based
• Produce by going out in the ____
○ Critical for mental health ‐ seasonal ____
• Vitamin d is what we start with converted to functional form 25‐hydroxyvitmain d calcidiol
Converted to 1,25‐dihydroxyvitamin D calcitriol
• Calcitriol is the ____ form of vitamin D
Measuring 25OHD not 1,25D
○ Used at 1,25 so not measuring this
○ You are measuring the 25OHd (true measure of the vitamin d levels)
Calcium regulator, and parathyroid indirectly through calcium
Acts on the bone, kidney (converted to the useable 1,25 form)
fat 1,25-dihydroxyvitamin D 25(OH)D synthesize sunlight depression functional
Know this pathway: synergy between ____ and ____ hormone
They regulatory output is in the ____ way to control calcium levels
vitamin D
PTH
synergistic
Vitamin D
• Required for – \_\_\_\_ absorption from intestine – Regulation of calcium and phosphate homeostasis – \_\_\_\_ growth and remodeling – Neuromuscular and immune function
• Deficiency due to – Insufficient \_\_\_\_ intake – Vegan diet – Impaired \_\_\_\_ – Increased excretion – \_\_\_\_ disease
Overall it is required for... ○ \_\_\_\_ absorption ‐ most important ○ Regulating serum calcium and phosphate ○ Regulates \_\_\_\_ ○ Neuromuscular and immune Low vitamin d: \_\_\_\_ ○ Endogenously low vitamin D levels ○ Genetic‐ cannot convert vitamin d properly ○ Bones are weak and malformed Vegans
calcium bone dietary absorption kidney
calcium
bone
rickets
Vitamin D • Deficiency results in – \_\_\_\_ – Rickets (failure of bone to properly mineralize) – \_\_\_\_ (weak bones) – Osteoporosis
• Risk factors – \_\_\_\_ – Age – Limited \_\_\_\_ – Dark-colored skin – Intestinal \_\_\_\_
Early in life deficiency: Debilitating and forming ____
Later: weak bones ____
Secondary Hyperparathyroidism
These are unique to vitamin d because the only vitamin that regulates calcium
Dentition
○ Born with low calcium ‐ calcium is used in hydroxyapatite so the teeth do not mineralize properly
○ Poorly ____ tooth structure
secondary hyperparathyroidism
osteomalacia
breastfeeding
sun exposure
malabsorption
rickets
osteoporosis
mineralized
Vitamin D
• Excessive levels are toxic • May induce – \_\_\_\_ – Anorexia – \_\_\_\_ complications
This vitamin does have a risk for toxicity if ingested at high levels Excessive vitamin d \_\_\_\_ is life threatening ○ May result from vitamin d toxicity Paradoxically ‐ ○ Risk for \_\_\_\_ ○ Tissues are not responding properly to vitamin d or calcium so they are \_\_\_\_ ○ Similar phenotypes Life threatening
hypercalcemia cardiovascular hypercalcemia anorexia wasting
Vitamin E
- ____-soluble vitamin
- ____ chemical forms
- Only ____ is needed for humans
- Storage and secretion via liver
Fat soluble Different chemical forms ○ We only need \_\_\_\_ found in food ○ Only version we use biologically Stored vitamin • Secreted from the \_\_\_\_ • Many non meat sources provide enough ‐ vegans are good
fat eight alpha-tocopherol alpha-tocopheorl liver
Vitamin E
• Required for – \_\_\_\_ activity – Immune function – Regulates \_\_\_\_ function and red cell formation – Homeostasis of vitamins \_\_\_\_ – Cardiovascular health
• Deficiency state very ____
Anti‐oxidant
○ Same with vitamin c (lesser extent)
○ Help scavenge ____ from damaging tissues
• ____ metabolize each other and control each other (see picture)
• See this through an entire array of sources
○ Deficiencies are rare and unheard of
• ____ homeostasis
• Critical in the liver for regulating vitamin k
antioxidant
platelet
A, C and K
rare
free radicals
synergistically
A C and K
Vitamin K
• ____-soluble vitamin
• ____ (vitamin K1)
– Main dietary form found in green leafy veges
• ____ (vitamin K2)
– Mostly of bacterial origin
• Adds carboxylic group to ____ residues
– ____ modification = ____ protein
Mostly from plant sources
• Leafy greens
• K1 and K2 mechanistically and functionally the same
○ K1 Phylloquinone (leafy greens)
○ K2 Menaquionens (yogurt)
• Molecularly slightly different but functionally they serve the same purpose
• Adds carboxylic group to glutatmate
○ Critically to array of function
○ Most important in the liver for our clotting factors
• See next slide
• ____
fat phylloquinone menaquinones glutamate gamma carboxylglutamate GIa
prothrombin, 7, 9, 10
Vitamin K
• Essential coenzyme for
– ____
– Matrix Gla-protein
– ____
• Required for
– Synthesis of ____ factors
– Bone metabolism
• How to assess vitamin K status
– Plasma levels of ____
– Prothrombin time
Know this pathway • How do you assess? ○ \_\_\_\_ primarily • \_\_\_\_ • PTT ‐ more severe cases ○ Not as easy to measure: pylloquinone = the plant version of vitamin k • Do not measure directl
Different cartoon but do know this pathway
• ____ is back in this pathway so fun to note
vitamin K dependent carboxylase osteocalcin clotting phylloquinone indirectly PT prothrombin time
NADPH
Vitamin K • Deficiency leads to – Increased \_\_\_\_ time – Spontaneous bleeding – \_\_\_\_ and osteoporosis – Coronary heart disease
• Risk factors
– Newborn ____ not treated with vitamin K
– Intestinal ____
Deficient
○ Bleed
• Alcoholics ‐ alcoholic ____ or cirrhosis will also experience deficiency because the liver is not functioning and more over develop clotting dysfunctions / deficiencies
○ They will bleed
prothrombin osteopenia infants malabsorption hep
____ and ____ are most common mineral deficiency we see in practice (folic b12)
• Not as common zn but important
• Array of minerals one might be deficiency in
____: in salt so most of us are not deficient
○ Good for ____ gland
• Most foods are supplemented with calcium, phosphorous, mg
• But Zn and iron the two most common
zinc iron
iodine
thyroid
Zinc
• Essential for – \_\_\_\_ synthesis – Cell division – \_\_\_\_ healing – Immunity – \_\_\_\_ and development – Taste and smell
Element that is essential in DNA and protein synthesis
• Cofactor for a class of enzymes called ____
○ Transcription factors
• Needed as a cofactor for these
• Also a requirement for proteins in ____ synthesis
• Because both are byproduct (DNA and protein synthesis) of Zn functionality
○ So is ____ read list every broad biologic function regulated
• N the absence you can have very severe deficiencies
DNA and protein
wound
growth
zinc finger proteins
protein
cell division
Zinc • Deficiency – Impaired \_\_\_\_ function – Growth retardation – Loss of \_\_\_\_ – Hair loss – Oral \_\_\_\_ and angular cheilitis
• Risk factors – Intestinal \_\_\_\_ – Vegetarians and vegans – \_\_\_\_ – Sickle cell disease – \_\_\_\_ supplementation – Diuretic medications
Small list of things
• Not unique to zinc per say
• Critical mineral in an array of critical biologic functions
• Vegans and vegs are fucked
immune
appetite
ulcers
malabsorption
pregnancy
iron
Iron
• Essential component of
– ____
– Myoglobin
• Required for
– ____
– Muscle function
– ____ and development
Deficiency is not inconsequential • \_\_\_\_ don’t have a risk • \_\_\_\_ constant risk ○ Especially with heavy menstrual cycles • Rectal bleeding form diseases • Iron is a critical component of two critical proteins ○ Hb ○ Myoglobin • If you are iron deficiency at risk for not just anemia but \_\_\_\_ problems • Required for: erythropoiesis, muscle function, growth and development • Heme iron: \_\_\_\_ • Non heme: \_\_\_\_ ○ Not as plentiful as the meat
hemoglobin erythropoiesis growth meat eaters women
muscle
meat and fish
veggies
Iron
• Dietary iron
– Non-heme found in ____
– Heme (= iron + ____) in meat and seafood
• Most found within hemoglobin or stored in ____
• Iron lost through shedding of ____ cells or blood loss
Heme is iron+protophoryrin complex ○ How we get it from meat • Iron metabolism cycle we need to know • Most of the iron in the body is found within Hb ○ Stored with \_\_\_\_ ‐ physically attached • How do you lose? ○ Blood loss ○ Shedding of epithelium • Losing your \_\_\_\_ losing your iron • Skin shedding is another way you lose iron
plants
protoporphyrin
ferritin
Iron homeostasis • Ferritin – Stores iron in \_\_\_\_ • Ferroportin – \_\_\_\_ iron from cells to blood • Transferrin – Binds and transports iron in \_\_\_\_ • Transferrin receptor – Enables uptake of iron-bound transferrin from \_\_\_\_ • Hepcidin – Hormone produced by \_\_\_\_ that reduces dietary iron \_\_\_\_ and blocks \_\_\_\_ of recycled iron from macrophages
Need to know this pathway
• Comes from the food
• Converted to ____
• Escorbic acid (____) plays a role in this
• Fe3+ to ____ via vitamin C (Iron‐>Fe3+‐>Fe2+)
○ This is internalized into the cell via transporter transporter
• Once in the cells back to ____
• Ferric iron is bound to ____
○ This is how it is bound in the cell ____
• Stays there as long as it needs to stay there
• Liver is rich source where it is mostly bound
• Once it needs to get used converted back to ____ to go in the
blood stream
○ Leaves the cell through ____ transport
In the blood stream it is ferris ion 2+, converted to ferric 3+ bound to transferrin, circles through the blood and carried on the transferrin molecule
In the cell its stored as ferritin
In the blood is carried as transferrin
○ Goes wherever it needs to go as this conjugate Re‐initiation of the pathway one internalized into the cell
cells and tissues exports blood plasma hepatocytes absorption release
ferric iron Fe3+ vitamin C Fe2+ (ferris) ferric iron Fe3+ apoferritin ferritin ferric iron Fe3+ ferroportin
Iron homeostasis
Another circuit to illustrate how iron is used and released into the serum Most of the iron that our blood cells used or carries are released after the blood cells are destroyed in the spleen
○ ____ back to liver
○ Liver stored or released back in the ____
○ Or sent to ____ for use in hemopoiesis
RBC half life 120 days
○ Iron taken out in the spleen and goes back for storage or to liver for storage purposes
spleen
blood stream
bone marrow
• How to measure iron
• Total iron binding capacity = blood’s capacity to bind iron via ____
• Transferrin saturation = s____
– eg Value of 25% means 25% of transferrin’s iron binding sites carry iron
How do you measure iron? Serum free iron Iron as \_\_\_\_ Iron as \_\_\_\_ Iron as \_\_\_\_ \_\_\_\_ used specifically when trying to determine if the patient has anemia \_\_\_\_ is the easiest most common ○ \_\_\_\_ measure
transferrin
serum iron / total iron binding capacity
ferritin transferrin hemoglobin saturation percentage and total iron binding capacity hemoglobin indirect
Deficiency state relatively common – Hypochromic microcytic anemia
• Risk factors – \_\_\_\_ – Heavy menstrual bleeding – \_\_\_\_ bleeding – Heart failure – \_\_\_\_ – Frequent blood donors
-B12/folic -> ____ anemia
Most common cause of ____ anemia
○ RBC are smaller and paler than normal
○ Not as richly red as normal red blood cells
B folic and Cobalmin B12 is megablastic
Any mechanism that causes ____ bleeding may result in anemia
pregnancy
rectal
cancer
megaloblastic
microcytic
excessive
Iron and medication interactions
• Iron may reduce bioavailability of medications
– ____
– ____
• ____inhibitors may reduce iron absorption
Drugs can reduce availability
Synthroid? Higher levels are often given iron to go with it
Levodopa ‐ parkinsons may result
Proton pump inhibitors can reduce iron absorption
○ Reflux disease commonly used for
levothyroxine > ____ iron
PPIs are used commonly in ____
levodopa
levothyroxine
proton pump
chelates reflux dx (GERD)
Excessive iron • Acute toxicity – Usually \_\_\_\_ signs and symptoms – May reduce \_\_\_\_ absorption – Can cause \_\_\_\_, multisystem organ failure and death
• Hereditary hemochromatosis
– ____ disease
– Requires chelation or ____
– May cause liver ____, heart disease, pancreatic insufficiency
• Acquired hemosiderosis
– Anemic patients dependent upon ____
– Treated by ____ therapy
High levels ‐ hemochromatosis
○ Caused by excessive high levels
○ Hereditary
Bone with the inability to regulate iron
• Iron accumulates ‐ to treat they have to go to the ____ to
get blood removed to reduce the iron levels
• High levels cause array of life threatening complications
• Can be a life threatening disease
• May occur as consequence of other event
• May be a genetic disease
• High iron may have inability to effectively absorb low zinc
○ Can be life threatening for variety of disease
high iron can affect ability to absorb ____ (high Fe -> low Zn)
non-specific
zinc
coma
genetic phlebotomy cirrhosis blood transfusions chelation
phlebotomy
zinc
