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Molecules to Organs > Exam 2: Nutrition > Flashcards

Exam 2: Nutrition Flashcards

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1
Q

Nutrients

A

Nutrients provides structural or functional components or energy to the body.

Essential nutrients must be obtained from the diet.

Body unable to produce sufficient quantity to meet needs.

Important compounds which do not participate in metabolic pathways include antioxidants and dietary fiber.

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2
Q

Food Regulation

A

Limited primarily to labeling and purity.

US Department of Agriculture (USDA) regulates safety, quality, and labeling of meat, poultry, and eggs.

Food and Drug Adminsitration (FDA) regulates all other foods.

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3
Q

Nutrient Recommendations

A

Made by the Food and Nutrition Board of the Institute of Medicine.

Dietary Reference Intakes (DRI) value for any given nutrient is continually reevaluated.

Goal to determine the amount high enough to prevent impairment of health even if intake is inadequate for a short period.

There are four seperate recommendations:

  1. Estimated average requirement (EAR)
  2. Recommended dietary allowance (RDA)
  3. Adequate Intake (AI)
  4. Tolerable Upper Intake Level (TUL)
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4
Q

Nutritional Supplements

A

Labeling and advertising limited to structural claims and cannot make disease claims.

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5
Q

Estimated Average Requirement

(EAR)

A

Average daily intake level needed to meet the requirement of half of healthy individuals in a particular life stage and gender group.

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6
Q

Recommended Dietary Allowance

(RDA)

A

Average daily intake level needed to meet the requirement of 97.5% of healthy individuals (mean ± 2 SD) in a particular life stage and gender group.

Applies to most micronutrients (vitamins and minerals).

RDA values have been set for carbohydrates and proteins but not most fats except for n-6 and n-3 polyunsaturated fatty acids.

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7
Q

Adequate Intake (AI)

A

Recommended average daily intake level based on observed or experimentally determined approximations by groups of healthy people that are assumed to be adequate.

Used when RDA cannot be determined.

Most commonly seen for young infants.

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8
Q

Tolerable Upper Intake Level

(UL or TUL)

A

Highest average daily intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population.

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9
Q

Nutrition Facts Label

A

Required on most types of packaged foods.

Contains 2 types of information in the US:

Nutrient content and list of ingredients

Based on serving size and number of servings per container

  • Items above the heavy line:
    • Macronutrients
      • 100% daily value (%DV) represents an upper limit (DRV)
      • No RDA for these nutrients
      • Fiber
        • 100% daily value (%DV) based on recommendation of 25 g/day
      • ​Sugars ⇒ mono- and disaccharides
      • Remainder of carbs are complex carbs = total less sugars and fibers
    • Sodium
    • Cholesterol
  • Items below the heavy line:
    • %DV is the mininum value for any individual
      • Based upon the highest RDA among age groups for micronutrients
      • Denominator used is RDI
      • Would be higher for someone with a lower RDA
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10
Q

Food Label Revisions

A
  1. Newer values for daily requirements used to calculate %DV
  2. Added sugars now included
  3. Vit D & potassium added. Vit A & C removed
  4. Calories from fat removed ⇒ type more important than amount
  5. Serving sizes revised to reflect what is actually eaten
    • Things usually consumed in one sitting now reported as single serving per container
    • Larger packages should clearly indicate “per serving” vs “per package”
  6. Calories and serving sizes more prominent
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11
Q

Reference Daily Intake

(RDI)

A

The highest RDA value among the different age and gender groups.

Used to determine the micronutrient amount per serving for food labels.

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12
Q

Basal Metabolic Rate

(BMR)

A

The energy needed to carry out fundamental metabolic functions.

  • Measured with subject fasted, laying quietly in a room of comfortable temperature
  • Varies with age and sex
  • Lean body mass major determinant (men with less body fat)
  • Values normalized for surface area
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13
Q

Acceptable Macronutrient Distribution Range

(AMDR)

A

The breakdown of the % of total calories provided by fat, carbohydrate, and protein.

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14
Q

Healthy Eating Index

(HEI)

A

Used to assess whether individuals or populations are compliant with recommendations.

If they are, does this translate to getting enough nutrients.

Score on 0-100 scale.

All components of the nation’s intake inadequate (20% to 82%) except for proteins.

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15
Q

Allergy vs Intolerance

A

Food allergies are immune responses which can be life threatening.

Most common are eggs, peanuts, and milk.

Food intolerances are non-immune responses.

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16
Q

Nutrition in Infancy

A

Ideal infant nutrition based on human milk.

Must provide for the greater metabolic needs and growth rates.

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17
Q

Nutrition in 1 to 10 y/o Child

A
  • Most children with access to a varied diet will choose adequate amounts of all nutrients.
  • Major concerns:
    • iron deficiency anemia in 1-3 y/o
    • inadequate calcium intake for good bone development
    • inadequate protein intake in vegan children and those with allergies
    • over-nutrition (obesity)
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18
Q

Nutrition in Adolescence

A
  • Adolescence associated with intense anabolism
  • Food habits can produce deficiencies in some nutrients:
    • Vit A & B6
    • Calcium
    • Iron
    • Zinc
    • Folate
  • Excess fats and sodium common
  • Eating disorders a concern
  • Obesity can be a significant problem
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19
Q

Effects of Health on Nutrition

A
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20
Q

Nutrition in the Elderly

A

Nutritional requirements unchanged or even increased (e.g. protein) at a time when total food consumption decreases resulting in unmet needs.

  • High probability of malnutrition
  • Decreased appetite ⇒ insufficient essential nutrient content in calorically adequate meals
  • Changes in vitamin and mineral absorption ⇒ changes dietary requirements
  • Greatest risk for inadequacy:
    • Proteins
    • Vit B12
    • Calcium & Vit D
    • Vit C
    • Zinc
  • Age-related achlorhydria ⇒ reduced output of stomach acid
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21
Q

Nutritional Problems With Aging

A
  • Sensory change: loss of smell, taste may make foods less appealing.
  • Physical limitations can affect nutrition by affecting ease of obtaining and preparing foods.
  • Social factors: Social isolation, loneliness, depression may result in inadequate diet, problems with transportation, financial problems.
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22
Q

Vegetarianism

A
  • Subject to individual preference and varies in strictness
    • vegan ⇒ no meat or dairy
    • lacto-ovo-vegetarianism ⇒ allows eggs and dairy
  • Nutritional benefits:
    • lower saturated fats
    • higher fiber intake
    • higher antioxidants
    • lower body weight
    • lower incidence of heart disease
  • Nutritional concerns:
    • deficient in some amino acids
    • may be deficient in Vit B12, calcium, Vit D, iron, zinc
  • Compensation for any deficiencies important in infants and children
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23
Q

Drug-Nutrient Interactions

A

Drugs may interact with foods favorably or unfavorably.

Many drugs can cause nutritional problems.

Foods can interfere with or potentiate the actions of some drugs.

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24
Q

Tyramine and MAO inhibitors

A
  • Tyramine = monoamine that can induce the release of norepi from SNS terminals
    • Leads to ↑ BP and HR
    • Derived from tyrosine in foods via fermentation or decay
  • Tyramine metabolized by monoamine oxidase
  • Patients taking MAO inhibitors may have elevated tyramine levels
  • Results in risk for increased BP ⇒ hypertensive crisis
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25
Q

Energy Measurement

A

1 Calorie = 1,000 calories

Often labeled as kcal.

Becoming common to replace kcal with kilojoules

1 Cal = 4.184 kJ

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26
Q

Metabolic Rate

A

The rate per hour that we expend calories by merely subsisting i.e. just sleeping.

Expenditure proportionally higher if awake and active.

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27
Q

Protein Oxidation

A

RQ = 63/77 = 0.82

Protein oxidation is not evaluated with RQ but rather through measurement of urea excretion.

Test called urinary urea nitrogen or UUN.

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28
Q

Total Energy Expenditure

(TEE)

A

The total of all calories expended over the course of a 24-hour day.

~ 60% of TEE is due to basal metabolism aka basal energy expenditure (BEE).

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29
Q

BMR

vs

RMR

A

Basal metabolic rate (BMR) refers to a very specific set of conditions ⇒ at rest, fasted, not subject to stimuli, etc.

Not always practical to measure.

Resting metabolic rate (RMR) measured under more realistic conditions and regarded as “close enough” to BMR.

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30
Q

Metabolic Rate

Determination

A

Metabolic rates can be estimated based on crude estimates or using emperical equations.

Estimated BMR for a man is 1 kcal/kg/hr and that of a woman is slightly less.

  • Empirical equations are based on population averages.
    • Harris-Benedict equations most common
    • Uses height, weight, age, and set of constants.
    • Different equations used for men and women.
  • Can be determined by measuring the oxygen consumed or carbon dioxide produced.
    • Factors exist that relate liters of gas respired to Calories expended
    • Normalized to Cal/hr or Cal/kg-hr
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31
Q

Indirect Calorimetry

A

Amount of O2 consumed and CO2 produced used to estimate the number of kcal expended over time.

Used to estimate RMR or BMR.

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32
Q

Respiratory Quotient

A

Ratio of CO2/O2​​

Determines what proportion of calories used comes from fats vs carbs.

RQ ≈ 0.85 in a typical american diet.

Typically get 50% of non-protein-derived energy from carbs and 50% from fats.

Patients with severe dyspnea/hypercapnia may benefit from burning fats d/t lower RQ.

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33
Q

Macronutrient Caloric Content

A
  • Carbohydrates
    • Max 4.1 Cal/g possible
    • 98% efficiency of digestion/absorption
    • Corrects to 4 Cal/g
  • Fats
    • Max 9.4 Cal/g
    • 95% absorbed
    • Corrects to 9 Cal/g
  • Proteins
    • Max 5.6 Cal/g
    • Only 92% absorbed
    • Only 75% of absorbed protein catabolized to CO2
    • Corrects to 4 Cal/g
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34
Q

Weight Loss

A

1 lb of body weight translates to a deficit of ~ 3,500 Cal

35
Q

Physical Activity Ratio

(PAR)

A

PAR divided into 3 activity levels:

Light (1-1.8)

Moderate (2-4)

Heavy (>4)

Each activity level then multiplied by BMR to calculate the energy expended performing that activity.

36
Q

Metabolic Equivalent of Task

(MET)

A

Similar to PAR.

Also refers to the increase in energy expenditure relative to basal.

37
Q

Total Energy Expenditure (TEE)

Calculation

A

In healthy individuals:

  • Requires
    • BMR/RMR
    • energy expenditure due to physical activity
    • thermic effect
      • amount of energy above BMR used for processing of food for use and storage
      • estimated as additional 10% added to energy expenditure
38
Q

Injury Factor

A

Sick or injured patients enter a hypercatabolic state.

Counterregulatory hormones rise.

(glucocorticoids, epi, norepi)

Results in increased protein breakdown, gluconeogenesis, and glycogenolysis.

Increased catabolism termed the “injury factor”

39
Q

Hospitalized Patient

TEE Calculation

A

Requires:

  • BMR
  • Injury factor
  • Physical activity factor (PAR)
    • simplified to 1.20 if bed riden
    • simplified to 1.30 if allowed out of bed
  • Thermic effect
    • if they are digesting and absorbing food
40
Q

Risks for Nutritional Deficiencies

A
  1. Inadequate Intake
  2. Inadequate Absorption
  3. Decreased Utilization
  4. Increased Losses
  5. Increased Requirements
    • due to various stresses such as fever, burns, trauma, etc
    • hypercatabolic state caused by elevated counterregulatory hormones
    • increased need for calories, proteins, and some vitamins
41
Q

Anthropometric Measures

A

The physical measures of weight or body dimensions.

  • For children:
    • most commonly involve height and weight
    • mid-arm circumference common in developing countries
    • comparison to growth charts
  • For adults:
    • BMI most common criterion
    • waist size measurement also used
    • skin-fold thickness provides a measure of sub-Q fat
42
Q

Hamwi Method

A

Most common method for calculating ideal body weight.

Comparison of ideal weight & weight at which people have the greatest longevity found them in close agreement.

43
Q

Body Mass Index

(BMI)

A

Proxy for body fat percentage.

Used to classify individuals as obese or non-obese in order to evaluate for potential risk factors.

44
Q

Weight Classifications

A

BMI ranges associated with weight classifications.

45
Q

Malnutrition

A

An involuntary weight loss of 10% or more over a 6-month period.

46
Q

Biochemical Measures

A
  1. Serum albumin
    • most common visceral protein evaluated as part of nutrition assessment
    • useful for free-living populations or upon hospital admission
    • gives an integrated picture of nutritional intake over a period of several weeks
  2. Serum prealbumin (aka transthyretin)
    • half-life of 2-3 days
    • measure of choice for monitoring progress of hospitalized patients
    • gives information about short-term changes in nutritional status
  3. Transferrin
    • intermediate half-life of 8-9 days
    • useful in establishing cumulative nutrition status over an intermediate time interval
  4. Hemoglobin and hematocrit
    • likely the first detected sign of severe protein malnutrition
  5. Creatine-height index (CHI)
    • sometimes used to estimate skeletal muscle mass
47
Q

Dietary Assessment

A
  1. Twenty-four hour recall
    • all food & beverages consumed over the past 24 hours
    • usually starts with meal immediately preceding interview and working backwards
  2. Food frequency questionnaire
    • retrospective review of intake frequency
    • how much of each category consumed per day, week, or month
  3. Typical day history
    • patient orally reports all foods and beverages consumed on a typical day
  4. Food diary
    • only prospective approach
    • patient records specific types and exact amounts of food & beverages eaten as soon as possible after consumption
48
Q

Mini Nutritional Assessment

A

Typically used with the elderly.

Evaluates areas such as:

  • anthropomorphic measures
  • dietary measures
  • “global assessment”
    • mobility
    • lifestyle
    • medications
    • etc
  • subjective measures
    • self-perception of health and nutritional status
49
Q

ROS Associated Diseases

A
  • Cancer development through oxidative DNA damage leading to mutagenesis
  • Atherosclerosis due to oxidation of LDL and uptake by macrophages ⇒ foam cells
  • Alzheimer’s disease due to neuronal death from elevated NO and/or mitochondrial dysfunction
  • Aging attributed to progressive decline in mitochondrial function
50
Q

Alimentation

Methods

A

Routes for feeding of a patient incapable of taking food by mouth:

  1. Enteral
    • liquid diet fed directly into stomach or intestine via tube
    • preferred method
      • preserves gut integrity
      • less expense
  2. Parenteral (IV) aka hyperalimentation or “hyperal” nutrition
    • formulas require glucose, AAs, vitamins, minerals, and triglyceride emulsions
      • components in the form normally encountered in blood
    • no fiber
    • must be sterile
51
Q

Reactive Oxygen Species

(ROS)

Production

A

ROS are by-products of oxygen metabolism.

Typically generated in the mitochondria.

  • Add 1 e- ⇒ superoxide (O2-)
  • Add 2 e- ⇒ hydrogen peroxide (H2O2)
  • Add 3 e- ⇒ extremely reactive hydroxyl radical (OH・)
  • Concerted addition of 4 electrons generates the desired H2O product

Nitric oxide (NO・) is another physiological free radical.

52
Q

Effects of ROS

A
  • In membranes and lipoproteins, hydroxyl radical acts on unsaturated fatty acid groups to form lipid carbon-centered radicals
    • Can initiate a chain reaction
    • Lipid carbon-centered radicals seen as foreign
  • Oxidative stress occurs when production of ROS faster than antioxidant defenses can consume them
    • Ex. respiratory burst
    • Can lead to cell damage and death
  • With ischemia-reperfusion injury, most tissue damage occurs on re-exposure to oxygen
    • Tissue undergoes necrosis and death
53
Q

Vitamin E

Sources and Absorption

A

Lipophilic Antioxidant

  • Synthesized in plants
    • High levels in grains and vegetable oils
    • wheat germ, whole grain bread and cereals, egg yoke, nuts and sunflower seeds
  • Absorbed in intestines and transported to liver in chylomicrons
  • May include a variety of tocopherols (saturated side-chains) and tocotrienols (3 double bonds in side-chain)
    • 𝛼-tocopherol with highest activity ⇒ “natural” vitamin E
  • RDA is 15 mg/day
  • TUL is 1,000 mg/day
    • Vit E supplementation at high doses can compete with Vit K
54
Q

Vitamin E

Functions

A

Lipophilic Antioxidant

  • Can function as a chain-breaking antioxidant
  • Prevents propagation of lipid carbon-centered radicals of FA residues of membranes
  • Able to cross BBB and protect lipids in CNS from oxidative damage
    • Deficiency can result in neurological sx
  • Important at blocking formation of atherogenic lipoprotein species
    • Concomitant reduction in CAD not yet adequately demonstrated
  • Antioxidant supplements are not currently recommended
55
Q

Vit E Deficiency

in

Celiac Disease

A

Celiac’s results in autoimmune damage of intestinal villous.

Prevents absorption of lipid-containing mixed micelles which would normally deliver fat-soluble vitamins to enterocytes.

Results in malabsorption of many nutrients including iron, calcium, Vit D, and less frequently Vit E.

Causes progressive systemic degeneration of large-caliber myelinated sensory axons in spinal cord and peripheral nerves.

Presenting symptoms:

Neuromyopathy, Sensory neuropathy, Optic atrophy, Cerebellar syndrome

Hemolytic anemia, myopathy, weakness, ataxia, impaired reflexes, ophthalmoplegia, retinopathy, damage to nervous tissue

Treatment includes Vit E replacement with 𝛼-tocopherol.

56
Q

Vitamin C

A

Major hydrophilic antioxidant vitamin.

Many important physiological roles:

  1. Returns Vit E back to reduced state
    • Indirectly impacts oxidation of membrane components
  2. Important for collagen synthesis
    • Coenzyme for several hydroxylases
    • Vit C deficiency results in scurvy
      • loose teeth, bleeding gums, ecchymoses, slow wound healing
  3. Dietary Vit C reduces ferric iron to ferrous iron (absorbed form)
    • Results in improved absorption of dietary iron

Beneficial effects of ascorbate seen in lowered markers of DNA oxidation (8-oxoguanine) and lowered markers for membrane oxidation (malondialdehyde)

57
Q

Antioxidant Enzymes

A

ROS are enzymatically inactivated.

  • Superoxide dismutase
    • superoxide → hydrogen peroxide
    • mammals with at least 2 isozymes
  • Catalase
    • hydrogen peroxide → water and oxygen
    • heme protein
    • located in peroxisomes
  • Glutathione peroxidases
    • Catalyzes reduction of H2O2 by glutathione (GSH)
    • Oxidized GSSG returned to GSH by glutathione reductase utilizing NADPH
    • Found in cytosol
    • Selenium is an important prosthetic group in these enzymes and is therefore essential.
58
Q

Flavonoids & Flavones

A

Plant-derived hydrophilic antioxidants.

Found in blueberries, green tea, red wine, and cocoa.

Possible role in reduction of CAD and cancer.

59
Q

Carotenoids

A

Have also been suggested to act as antioxidants.

Ex. beta-carotene

60
Q

Antioxidant Supplementation

A

Studies unable to prove health benefits of antioxidant supplements.

Balanced diet rather than supplementation is the most consistent health recommendation.

Many antioxidants advertised without significant scientific validation e.g. lipoic acid, CoQ, grape seed extract.

61
Q

Essential B Vitamins

Nomenclature

A

Thiamine = Vit B1

Riboflavin = Vit B2

Niacin = Vit B3

Pantothenic Acid = Vit B5

Pyridoxine = Vit B6

Biotin = Vit B7

Folic acid = Vit B9

Cobalamin = Vit B12

62
Q

Thiamine

Characteristics

A

Vitamin B1

  • Sources:
    • Lean pork, whole-grain cereals, legumes, and yeast
    • Chronic ethanol ingestion strongly favors thiamine deficiency
    • Absorbed primarily in the jejunum
  • Functions:
    • Phosphorylated form ⇒ thiamine pyrophosphate (TPP)
      • Cofactor for formation or degradation of 𝛼-ketols by transketolase
      • Cofactor in oxidative decarboxylation of 𝛼-keto acids
        • conversion of pyruvate to acetyl-CoA by pyruvate dehydrogenase
    • ​Important for
      • carbohydrate catabolism
      • proper heart and brain function
      • structural component of nervous system membranes
63
Q

Wernicke-Karsakoff Syndrome

A

Caused by weak TPP binding.

Becomes manifested if thiamine intake is compromised ⇒ alcoholism, poor diet, malabsorption.

Similar symptoms to beri-beri but also memory problems, disorientation, confabulation, and coma.

64
Q

Beri-beri

A

Caused by a thiamine (Vit B1) deficiency.

Two forms: “wet” (edematous) and “dry” (non-edematous).

  • Causes:
    • Most commonly seen with alcoholic patients
      • ​due to interference by alcohol on B vitamin absorption
    • Associated with bariatric surgery when Vit B supplementation inadequate
      • absorbed primarily in the jejunum
      • restrictive reconstruction results in mild malabsorptive state
      • B1 level can be depleted after PO or IV carb intake
      • Sx can occur within 6 months of surgery in adolescent cases
  • Considered a medical emergency
    • can progress to cardiac failure
    • can result in permanent neurological deficits
  • Symptoms include:
    • muscle weakness
    • ataxia
    • foot drop
    • ophthalmoplegia
    • nystagmus
    • neuropathy
    • cardiac abnormalities
    • GI manifestations
65
Q

Niacin

Characteristics

A

Vitamin B3

  • Substituted pyridine derivatives
    • Niacin (nicotinic acid)
    • Niacinamide (nicotinamide)
  • Sources:
    • Dietary:
      • Mostly as physiologically active forms: NAD+ or NADP+
      • Legumes, cereals, lean meat, poultry, and fish
      • Absorption impeded by alcohol
    • Synthesized from tryptophan
      • Requires sufficient dietary tryptophan and pyridoxal (Vit B6) cofactor
        • B6 deficiency or inadequate tryptophan absorption can result in pellagra-like symptoms
66
Q

Niacin

Physiological Functions

A
  • Pyridine nucleotide functions:
    • Essential co-substrates/co-enzymes for most dehydrogenase reactions
    • Substrates for ADP-ribosylation reactions
    • Precursors of cyclic ADP-ribose
      • Role in intracellular Ca2+ handling
    • Important for:
      • cellular repair
      • DNA repair
67
Q

Niacin

Pharmacological Uses

A

Niacin (but not nicotinamide) used at high doses for treatment of hypercholesterolemia.

High doses of niacin only in excess of 1 g/day causes acute flushing.

Chronic intake at these levels can cause biochemical abnormalities.

Abnormal liver function, hyperglycemia, increased plasma uric acid, vasodilation.

68
Q

Pellagra

A

Caused by a niacin deficiency.

  • Clinical signs are the three Ds:
    • Diarrhea
    • Dementia
    • Dermatitis
      • ​glossitis
      • angular cheilitis
      • characteristic Casal’s necklace
    • Can result in death if untreated
  • Serious disease in Africa, Europe, and Southeastern US
    • Diet consisting mainly of corn which is low in niacin and tryptophan
69
Q

Secondary Niacin Deficiency

A

Pellagra due to frank malnutrition rare in the US.

Pellagra-like symptoms can result from:

  1. Bariatric surgery
    • can result in vitamin malabsorption
    • ↓ plasma pyridoxine and niacin levels can be seen
    • treat with supplements of pyridoxine, nicotinamide, zinc sulfate, and riboflavin
  2. Drug-nutrient interaction
    • ​​Ex. isoniazid (commonly prescribed anti-Tb drug)
      • mimics niacin deficiency
      • competetively inhibits conversion of nicotinamide acid to NAD+ and NADP+
      • coenzyme deficiency inhibits repair of cell damage
      • affects tissues of high turnover i.e. skin and GI tract
    • Other agents known to cause pellagra-like sx
      • 6-mercaptopurine, 5-fluorouracil, and chloramphenicol
  3. Abnormalities of tryptophan metabolism
    1. Carcinoid syndrome
    2. Hartnup’s disease
70
Q

Folic Acid

Characteristics

A

Vitamin B9

  • Sources:
    • Derived from leafy green vegetables, legumes, and some fruits
    • Grains fortified with folate
    • Most dietary folate with chain of glutamate residues
  • ​​Folate masks a B12 deficiency
    • TUL is set at 1 mg/day
  • Absorption and transport:
    • Involves specific enzyme systems:
    • Dietary folate taken up by a saturable transport system
    • Absorbed mostly in jejunum
    • Reduced and some methylated to 5-methyl-THF before entering blood
  • Functions:
    • One-carbon donor in many biochemical reactions
    • Tetrahydrofolate (THF) ⇒ reduced coenzyme form of folate
      • Role in biosynthesis of purines, TMP, and methionine
71
Q

Folate Pool

A

Reversion of 5-methyl-THF → THF requires Vit B12.

B12 deficiency “traps” folate in the 5-methyl-THF form preventing re-entry into the folate pool.

72
Q

Folate Deficiency

A

Common, particularly among the poor.

  • Forms of folate required for purine and pyrimidine synthesis & DNA synthesis
  • Folate deficiency inhibits synthesis of new cells resulting in:
    • macrocytic anemia
      • ​hypochromic, macrocytic RBCs on blood smear
      • hypersegmented neutrophils possible
    • villous atrophy
    • depapillation of the tongue
    • increased risk for serious diseases
    • weakness and fatigue
    • palpitations
    • shortness of breath
    • increased neural tube defects in fetuses
      • 400 mcg/day supplement recommended for pregnant women
  • Hyperhomocysteinemia commonly accompanies folate deficiency
    • linked to increased risk of CAD
    • folate supplementation lowers homocysteine levels
      • not consistently shown to reduce risk of CAD
73
Q

Inadequate Folate

Time Course

A
  1. Serum folate ↓
  2. RBC folate ↓
  3. Hypersegmented neutrophils appear
  4. Mean Corpuscular Volume (MCV) ↑
    • months before anemia is apparent
  5. Hb levels ↓
74
Q

Cobalamin

Sources and Absorption

A

Vitamin B12

  • Sources:
    • Synthesized by microorganisms
    • Found primarily in animal sources
    • Meats, fish, dairy, eggs
  • Absorption: requires gastric acid (to release the vitamin from food) and Intrinsic Factor (IF) secreted by the stomach
    1. B12 initially bound to “R-proteins” in acidic conditions of stomach
    2. released by proteases in duodenum
    3. binds to intrinsic factor
    4. very efficiently absorbed (or reabsorbed) in ileum by receptor-mediated process
    5. remaining 1% taken up by diffusion
  • If absorption mechanisms are intact, B12 stores can last 10-20 years due to recapture
  • If absorption mechanisms damaged, anemia can appear within 3-6 months
  • Vegetarians, elderly, and bariatric sx patients at risk for deficiency
75
Q

Cobalamin

Functions

A

Involved in only two metabolic pathways:

  1. Conversion of 5-methyl-THF → THF
    • B12 deficiency traps folate in methyl form
    • folate can no longer be used in purine and TMP synthesis
  2. Conversion of methylmalonic acid → succinyl CoA
    • prolonged B12 deficiency results in neuropathy
      • due to inability to catabolize odd # FAs
76
Q

Vit B12 Deficiencies

A
  • Common disorder among older adults and vegetarians
    • ~ 5-15% in people > 65 y/o
  • Folate can mask a B12 deficiency
  • Causes:
    • food-cobalamin malabsorption
      • achlorhydria
      • atrophic gastritis
      • prolonged PPI use
      • bariatric surgery
    • pernicious anemia
      • due to IF deficiency
    • inadequate intake of animal sources
  • Symptoms:
    • megaloblastic anemia
    • neuropathy
    • cognitive impairment
    • psychopathology
    • elevated levels of methylmalonic acid (MMA) and homocysteine (HCYS)
      • Only hyperhomocystemia seen with folate deficiency
  • Clinical Course:
    • monitoring of Vit B12 concentrations in asymptomatic patients taking PPI for > 4 years
    • immediate screening for Vit B12 deficiency if symptoms manifest
      • given irreversible nature of neurologic changes
  • Treatment:
    • Supplementation with non-protein-bound B12
      • ↓ in MMA and HCYS levels after replacement suggestive of food-cobalamin malabsorption
      • R/O renal dysfunction as cause of elevated MMA/HCYS
    • B12 injections may be neccessary
      • used for treatment of pernicious anemia
77
Q

Pernicious Anemia

A

B12 deficiency due to inability of parietal cells to synthesize Intrinsic Factor (IF), resulting in malabsorption.

  • Results in similar sx as folate deficiency
    • megaloblastic anemia and hyperhomocysteinemia
  • Neuropathy due to failure to metabolize odd # FAs
  • Usually treated with B12 injections
78
Q

Schillings Test

A

Used for the assessment of B12 absorption.

79
Q

Pyridoxine

Characteristics

A

Vitamin B6

  • Widely distributed in foods
    • Poultry, fish, pork, liver, kidney
    • Whole grains, carrots, cabbage, peas, potatoes and tomatoes
  • Deficiency is rare
  • Large doses of B6 > 500 mg/day can cause irreversible peripheral toxic sensory neuropathy
    • Abnormal for a soluble vitamin
80
Q

Pyridoxine

Functions and Deficiencies

A
  • Pyridoxine, pyridoxal, and pyridoxamine are precursors to biologically active coenzyme pyridoxal phosphate (PLP)
  • PLP functions:
    • Associated with amino acid metabolism
    • Conversion of tryptophan → niacin
      • ​Deficiency produces pellagra-like sx
    • Involved in glycogen breakdown
    • Factor in conversion of homocysteine → cysteine
      • role in reducing elevated homocysteine
81
Q

Riboflavin

A

Vitamin B2

  • Widely found in a variety of foods
    • Dairy products, yogurt, cheese, meat, eggs, broccoli,asparagus, and whole grain foods.
  • Component of enzyme prosthetic groups
    • Flavin mononucleotide (FMN)
    • Flavin adenine dinucleotide (FAD)
  • FAD and FMN are part of oxidation-reduction enzymes
    • NADH dehydrogenase
    • Succinate dehydrogenase
    • Riboflavin-containing enzymes critical to life
  • Uncomplicated riboflavin deficiency uncommon
  • Deficiency usually seen with multiple vitamin deficiencies
    • Has surprisingly mild symptoms
      • ​dermatitis, cheliosis (fissures at corners of mouth), and glossitis (smooth and dark appearing tongue)
      • corneal vascularization
      • anemia
82
Q

Biotin

A

Vitamin B7

  • Widely distributed in foods
  • Deficiency is ordinarily not seen
    • Egg whites contain avidin which has very strong affinity for biotin
    • Consumption of raw egg whites can lead to biotin deficiency
  • Functions as coenzyme in carboxylation reactions
    • serves as carrier of activated CO2
    • binds to specific lysine residues in enzymes
      • ex. pyruvate carboxylase
83
Q

Pantothenic Acid

A

Vitamin B5

  • Sources are common
    • eggs, liver, and yeast are major sources
  • Deficiency is rare
    • cooking may destroy some B5 in foods
    • deficiency only suspected in recorded cases
    • No RDA established
  • Toxicity is rare
    • No TUL established
  • Functions:
    • Pantothenic acid itself is a component of the acyl carrier domain of fatty acid synthase
    • Component of CoA
      • Functions in the transfer of acyl groups in numerous reactions

Molecules to Organs (12 decks)

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