nutrition exam 3

WATER AND ELECTROLYTES

• ECF - ⅓ of body water

  • 20% of body weight

  • interstitial is 75% 

  • plasma is other 25%

• ICF - ⅔ of body water

  • 40% of body weight

• NaCl

  • isotonic: 0.9% NaCl

• water follows movement of electrolytes by diffusion

• +/- charges same in each compartment

• Na and K constantly using energy to exchange with ATPase

  • 30% of total energy for cells

• fluid pH - bicarbonate and proteins are pH buffers for body

  • affected by lung respiration and excretion of bicarbonate in kidney

• plasma-interstitial space exchange

  • cardiovascular system is closed 

    • hydrostatic pressure

  • capillaries

    • fluid and solute exchange

    • large surface area

• capillary hydrostatic pressure - blood pressure

  • pressure high when leaving heart

  • drops going through arteries => capillaries => veins

  • arterial side - hydrostatic pressure > oncotic pressure

  • venous side - oncotic pressure > hydrostatic pressure

• plasma oncotic pressure

  • liver disease, low serum albumin - oncotic pressure reduced

  • pregnancy - hydrostatic pressure increased

  • hemorrhage blood loss - hydrostatic pressure decreased

• edema - fluid buildup in interstitial space

  • due to elevation in capillary hydrostatic pressure (heart failure)

• regulation of water

  • partially regulated by kidneys

  • insensible water loss

    • skin, respiration, 

    • kidneys compensate for these

  • sweat

WATER AND ELECTROLYTES 2

• water intake should be about 1 mL water/kcal expended 

  • must excrete at least 500 mL or urine to eliminate waste products

  • consistently concentrated urine is a risk for kidney stones 

• water loss

  • insensible - respiration and skin (not sweat

  • sensible

• GI Tract

  • handles about 9L of water per day

• dehydration

  • thirst sensation - excessive loss of body water leads to increase ECF osmolarity (hyperosmolarity)

    • hyperosmolarity - water intoxication

      • occurs following rapid fall is osmolarity

      • water from ECF moves into cells

      • brain cells swell causing nausea, malaise, headache, confusion, seizures, coma

  • increases as small as 2% will activate neural centers in the hypothalamus to produce strong desire to drink

  • some individuals impaired to this response - infants, elderly, diseased/vigorous states

• kidneys

  • regulate body fluid osmolarity and volume and electrolyte balance

  • regulate acid/base balance

  • excrete metabolic waste products 

  • produce and secrete hormones 

  • principles of the nephron - functional unit of kidney

    • filtration

      • initial removal of solutes and water from blood

      • doesn’t include large proteins or blood cells

      • solutes in filtrate include some vitamins, minerals, and nutrients

    • reabsorption

      • selective removal of water and solutes from the glomerular filtrate back into blood 

      • regulated by hormones (Ca²⁺ and PTH)

        • PTH induces kidney to activate more Vitamin D

        • increases Calcium reabsorption and lowers excretion

    • secretion

      • selective removal of certain solutes from the plasma into the tubules 

      • occurs after blood has passed through the glomerulus

    • excretion

      • removal or final urine to bladder

    • tubular system involved in urine production

    • glomerulus - part of nephron

      • rich in capillaries and site of plasma filtration into the renal tubes 

    • tubules - site of processing of the plasma filtrate to create urine 

• hormonal control of water/electrolytes

  • antidiuretic hormone (ADH)

    • arginine vasopressin

    • released by pituitary in response to increases in ECF osmolarity or decreased blood volume

    • predominantly acts on kidneys to increase water reabsorption

    • alcohol inhibits ADH secretion and causes dehydration

• Renin

  • enzymes released from kidneys in response to decreased blood pressure

  • acts in blood on angiotensinogen to produce angiotensin 1

  • angiotensinogen made in liver

    • angiotensin 1 - converted to angiotensin 2 in lungs

      • angiotensin 2

        • most powerful vasoconstrictor in body

        • constricts blood vessels to increase blood pressure

        • increases vasopressin production

        • also causes release of the hormone aldosterone from adrenal glands 

      • ACE inhibitors - angiotensin-converting-enzyme inhibitors

        • treat high blood pressure

        • inhibit ACE enzymes that convert angiotensin 1 to angiotensin 2

        • inhibit hydrolysis of bradykinin, which is a vasodilator

        • net effect: lower blood pressure

        • side effects: cough and angioedema

• Sodium (Na⁺)

  • Major ECF cation

  • critically important for regulating body water and electrolyte balance 

  • aids in nutrient absorption

  • very important for neural and muscular function

  • efficiently absorbed throughout the entire small intestine and colon 

  • plasma Na+ levels are closely regulated by the kidney (intake = output)

  • excess amounts filtered and excreted

  • tubules regulate reabsorption to precisely maintain 145 mEq/L

  • dietary requirements

    • NO RDA

    • minimum ~ 500 mg/day

    • depending on physical activity and climate suggested to consume 3000mg

    • table salt is 40% sodium 

      • 1 g salt = 400 mg sodium

  • food sources 

    • processed food contain high amounts

    • not always in NaCl form; sodium bicarbonate and sodium saccharin are also possible and do not taste salty

  • sodium sensitivity 

    • occurs in 10% of the population

    • associated with chronic renal disease, diabetes, hypertension

    • african american over 50 are prone

  • sodium deficiency

    • vomiting, diarrhea, heavy sweating

    • muscle cramps, mental apathy, loss of appetite 

  • sodium toxicity

    • acute toxicity causes edema and hypertension 

• Potassium (K⁺)

  • principal cation inside cells

  • plays major role in fluid and electrolyte balance

  • nerve and muscle function and fundamental cell processes and growth

  • 90% of absorption in small and large intestine 

  • renal excretion closely matched to intake

  • hormonal regulation

    • epinephrine regulates K+ uptake may be important after exercise to prevent hypokalemia

    • insulin increases uptake by cells after a meal

    • aldosterone increases K⁺ uptake into cells and increases urinary excretion

  • dietary requirements/sources

    • NO RDA

    • minimum = 2000 mg/day

    • DRV = 3500 mg/day

    • fresh unprocessed foods

      • fruits and veggies in particular

    • coffee, tea, milk, potatoes, OJ, animal products major sources in American diet

  • deficiency

    • low blood K+ termed hypokalemia

      • occurs because of diarrhea, vomiting, and severe dehydration

    • associated with use of certain diuretics, steroids, or abuse of laxatives

    • causes muscle weakness, paralysis, confusion, cardiac arrhythmias

    • Low K⁺ diets may cause hypertension

  • toxicity

    • hyperkalemia

    • mostly from overuse of potassium supplements 

    • hard to induce from diet as kidney will accelerate excretion of excess from dietary intake 

    • results in muscle weakness, vomiting, and heart failure in severe cases 

NUTRITIONAL SCIENCES

• epidemiological studies - to generate hypothesis

  • cross-sectional studies - measures various exposures and outcomes simultaneously

  • retrospective studies

  • prospective cohort studies

  • limitations

    • confounding factors - unmeasured variables may skew associations

    • selection bias - non-random exposure allocation can distort results

    • causal ambiguity - associations may reflect reverse causation or latent factors

• interventional studies - to test hypothesis 

• experimental studies exhibit strengths in establishing causation

  • control over confounding factors

  • direct manipulation of variables

  • randomization of subjects to reduce selection bias 

  • temporal sequences 

• association vs causation

  • association - refers to a relationship or correlation between two variables where they tend to occur together 

    • doesn’t imply one variable causes the other

  • causation - implies that one event directly results in another event 

  • epidemiological studies can identify complex associations/correlations

  • experimental studies can establish causation 

• three types of causation

  • necessary - if cause is not there, outcome won’t occur 

  • sufficient - if the cause is there, the outcome will too

  • conditional or contributory - cause is necessary and/or sufficient only under certain circumstances

7 key challenges in human nutrition research: validity of measurements

• assessment of exposures

  • lack of reliable measurements

  • potential confounding factors and biases

• assessment of health outcomes of interest

  • indexes/biomarkers of diseases are used

  • nutritional assessments are often not specific 

• randomized human clinical trials

  • ideal design to address human nutritional needs: large-scale, placebo controlled, double blinded, intervention studies

  • RCTs are at the top of evidence based hierarchies for biomedical intervention because they directly test hypothesis by manipulating variables under controlled conditions 

  • strengths

    • well-designed interventions can prove causality

    • can be directly applied to humans 

  • weaknesses

    • limited generalizability

    • limited reproducibility

    • ethical constraints 

    • difficult to control all confounding factors

    • limited duration

    • cost and resources

    • varabilabites 

NUTRIENTS AND DIETARY REFERENCES

• organismal level - nutrients promote growth, maintain tissues, regulate physiological processes like reproduction

• cellular level - nutrients provide energy, structural materials, regulatory agents needed for cellular processes and functions 

• lipids are highest energy yielding macro, proteins and carbs are tied 

• phytochemicals - natural compounds found in plants that contribute to their color, flavor, and disease resistance. In nutrition, they are recognized for their potential health benefits, though they are not considered essential nutrients like vitamins or minerals. These compounds have antioxidant, anti-inflammatory, and immune-boosting properties, and they may help reduce the risk of chronic diseases such as cancer, heart disease, and diabetes

• nutrient requirement - lowest intake level of a nutrient that maintains basic physiological functions and supports optimal health

  • nutrient requirements differ among individuals 

• history of nutrient recommendations - distribution of nutrient requirements within a population; sex and life stage groups; promotion of optimal health; chronic disease prevention; toxicity risk 

• Estimated average requirement (EAR) - for a nutrient is the amount that covers half of the population 

• RDA - set well above the EAR, covering about 98% of the population 

• nutrient density - the amount of micronutrients and protein of a food item relative to its energy content 

  • nutrient dense foods - high in nutrients but relatively low in calories

    • contain vitamins, minerals, complex carbs, lean protein, and healthy fats

• energy density - the energy content (kcal) of a food item relative to its weight (g)

Systemic Energy Balance, Body Weight, and Body Composition

• glycogen - 4 kcal/g dry weight; one gram of glycogen binds 3 grams of water 

• triglycerol - 9 kcal/g, hydrophobic 

  • main storage molecule of metabolic energy

  • adipose tissue triglyceride being the heaviest 

• bomb calorimeter - direct measure of gross chemical energy 

• more metabolizable energy in highly processed foods 

• neuroendocrine signals regulate food intake 

• leptin - peptide secreted by adipose tissue

  • transmits signal through cell-surface leptin receptors on certain neurons in the hypothalamus

• discovery 

  • Ob/Ob Mice

    • mutation in gene that encodes leptin

  • Db/Db Mice

    • mutation in gene responsible for encoding leptin receptor 

  • +/+

    • wildtype mouse

  • parabiosis studies

    • db/db with +/+

      • diabetes

        • body weight up

        • adipose tissue mass up

      • lean

        • food intake down

        • insulinemia down

        • blood sugar down

        • death by starvation

    • db/db with ob/ob

      • diabetes

        • body weight up

        • adipose tissue mass up

      • obese

        • food intake down

        • adipose tissue mass

        • insulinemia down

        • blood sugar down

        • death by starvation

    • ob/ob with +/+

      • obese

        • food intake down

        • insulinemia down

        • blood sugar down

      • lean

        • no change 

    • +/+ with +/+

      • lean

        • normal insulin

        • normal blood sugar

        • decreased pad size

• energy expenditure can be estimated by indirect calorimetry, based on gas exchanges

• basal metabolism

  • lean body mass and temperature affect BMR

• thermic effect of food

  • increases of energy expenditure above the resting metabolic rate after consuming a meal

  • representing energy cost of processing food for use and storage 

  • associated with heat production

  • vary by the amount and composition of meals 

• adaptive thermogenesis

• Estimated Energy Needs for Growth

  • body stores is small ... in healthy adults

  • – 1 m old infant

    • • 5.8g/kg/d x 4.1kcal/g= 100kcal/d (25% of Ein)

  • – 6 m old infant

    • • 1.8g/kg/d x 3.2 kcal/g = 45kcal/d (7% of Ein)

  • – 14 y old male

    • • 0.5g/kg/d x 2kcal/g = 50kcal/d (2% of Ein)

  • – Pregnant women

    • • 1g/kg/d x 4.1kcal/g = 220kcal/d (9% of Ein)

  • – Nonpregnant adult

    • • 0g/kg/d = 0kcal/d (0% of Ein)

• BMI = weight (kg) / height² (m²)

  • > 25 = overweight

• skinfold measures

  • estimate body fat by using a caliper to gauge the thickness of a fold of skin on the back of the arm (over the triceps), below the shoulder blade (subscapular), and in other places (including lower body sites), then comparing these measurements with standards 

• hydrodensitometry 

  • measures body density by weighing person on land then again while submerged in water 

  • difference in body weight provides measure of body volume

• air displacement plethysmography

  • estimates body composition by having a person sit inside a chamber while computerized sensors determine the amount of air displaced by the person’s body

• bioelectrical impedance

  • measures body fat by using a low intensity electrical current

  • measurement of electrical resistance is used in an equation to estimate the percentage of body fat 

• DEXA

  • uses two low dose X rays that differentiate among fat-free soft tissues (lean body mass), fat tissue, and bone tissue, providing a precise measurement of total fat and its distribution in all but extremely obese subjects 

• waist circumference - measures central obesity 

CELLULAR ENERGY METABOLISM

• metabolism - the sum of life-sustaining chemical reactions which convert nutrients to energy driving cellular processes, to building blocks for cellular components, and to wastes for excretion 

• metabolic pathways

  • metabolic pathway 1

    • products formed before a metabolic pathway reaches completion are called intermediate products 

  • metabolic pathway 2

    • product of each chemical reaction becomes the substrate in the reaction that follows 

    • end products can enter new metabolic pathways 

• catabolism

  • proteins, carbs, fats =====> CO₂, H₂O, NH₃

• anabolism

  • amino acids, sugars, fatty acids, glycerol ====> proteins, glycogen, TGs, other lipids

• enzymes

1. substrate binds to active site of enzyme, forming enzyme-substrate complex

2. shape of active site alters the chemical structure of the substrate, transforming it into the product

3. product is released freeing the enzyme to bind another substrate 

• PKU - inherited error in metabolism 

  • toxic levels of phenylalanine due to inability of body to convert 

  • causes retardation, convulsions, behavior problems, skin rash

• coenzymes/cofactors of enzymes

1. inactive enzyme combines with the cofactor to form an active enzyme 

2. substrate binds to the active enzyme 

3. active enzyme catalyzes its specific reaction

4. products are released

5. cofactor is released from the enzyme, thereby inactivating the enzyme

• ATP

1. energy released from high-energy phosphate bond in ATP is broken

   1. becomes ADP + P

2. ADP needs energy to make ATP

• metabolic pathways

1. catabolic pathways - generates ATP

   1. breaking down energy yielding macronutrients

   2. consume O2, generate ATP, CO2, and H₂O

   3. generating ATP

      1. energy yielding nutrients broken down into Acetyl Coa which enters the TCA cycle

      2. most of the reactions above release H with electrons which are carried by coenzymes to ETC

      3. ATP synthesized

      4. H atoms reaction with O to produce water

2. anabolic pathways - store excess energy substrates 

   1. glycogenesis

   2. lipogenesis

3. anabolic reactions during catabolic physiological states

   1. gluconeogenesis, ketogenesis

• pyruvate to acetyl-CoA is IRREVERSIBLE

• lipolysis - breaking down fat

1. glycerol enters the glycolysis pathway about midway between glucose and pyruvate 

2. fatty acids are broken down into 2-carbon fragments that combine with CoA to form acetyl CoA

• mitochondria

  • outer membrane - site of fatty acid activation

  • cytosol - site of glycolysis

  • inner membrane - site of ETC

  • inner compartment - site of pyruvate to acetyl CoA, fatty acid oxidation, TCA cycle

• fatty acid oxidation : beta oxidation

1. fatty acid is activated by the addition of coenzyme A to its carboxylic acid end

   1. fatty acid is then transported across the mitochondrial membrane by carnitine

2. process involves B-oxidation involves enzymes that cleave off 2-carbon units from the fatty acid chain, forming acetyl-CoA

   1. entire fatty acid has been broken down

   2. each cleavage generates 1 NADH + H⁺ and FADH₂

3. B-oxidation of an 18 carbon fatty acid generates (8) NADH + H+ and (8) FADH2

4. total of 40 ATP are subsequently produced via the ETC

• breaking down amino acids

  • most amino acids can be used to synthesize glucose, they are glucogenic

  • some amino acids are converted directly to acetyl CoA, they are ketogenic

  • some amino acids can enter the TCA cycle directly, they are glucogenic

  • transamination and denomination

    • Transamination: This is the first major step in amino acid breakdown. In this process, the amino group (–NH₂) from an amino acid is transferred to a keto acid (usually α-ketoglutarate), forming a new amino acid (often glutamate) and a new keto acid. This allows the body to funnel nitrogen from many amino acids into just a few forms for easier processing.
      
      

    • Deamination: After transamination, glutamate can undergo oxidative deamination, where the amino group is removed entirely, releasing free ammonia (NH₃). This happens mostly in the liver. The enzyme glutamate dehydrogenase plays a big role here.

  • elimination of Nitrogen

    • Free ammonia is toxic, so the body quickly converts it into urea through the urea cycle (also in the liver). Urea is then safely excreted in the urine via the kidneys. This process is essential for maintaining nitrogen balance and preventing toxicity

• coenzymes delivers H and high energy electrons to the ETC from the TCA cycle, glycolysis, and fatty acid oxidation

• oxidation of energy yielding nutrients

  • all can be broken down into acetyl CoA

    • acetyl CoA enters the TCA or makes fat

  • in the end, oxygen is consumed, water and CO2 are produced, and energy is captured in ATP

  • some amino acids, pyruvate, and glycerol can be used to make glucose 

  • fatty acids cannot be used to make glucose 

• gluconeogenesis

1. rather than forming acetyl-CoA, pyruvate is converted to oxaloacetate

   1. some amino acids can be converted to oxaloacetate 

2. this then exits the TCA and is converted to phosphoenolpyruvate

3. two molecules of PEP are combined to form glucose 

• ketogenesis

1. oxaloacetate is diverted from the TCA and used for glucose synthesis via gluconeogenesis 

2. fatty acids are oxidized to acetyl-CoA via Beta oxidation

   1. ketogenic amino acids are also converted 

3. when acetyl CoA cannot enter the citric acid cycle, it takes another metabolic route called ketogenesis resulting in the production of ketones 

4. ketones are then released into the blood where they are taken up by some tissues and metabolized for energy 

• ketoacidosis - severe ketosis

  • lowered blood pH

  • results in nausea, coma, and death

  • occurs in people with uncontrolled type 1 diabetes 

• insulin

  • in response to elevated blood glucose levels, the pancreas increases its release of this hormone 

  • glucagon is released in response to low blood glucose levels

• fed state

  • concentration of insulin is higher than glucagon favoring energy storage 

  • blood glucose elevated

  • glycogen storage increased 

• postabsorptive state 

  • insulin levels decrease, and glucagon increases

  • blood glucose decreases

  • increased liver glycogen broken down for a source of glucose 

  • increase use of fatty acids for energy 

• fasting state

  • relative concentration of glucagon is higher than insulin

  • liver glycogen stores are depleted

  • glucose is supplied mainly by gluconeogenesis

  • stores TGs are broken down with an increase in the use of fatty acids for energy

  • ketone formation increases

• glucose polymers that resist digestion (inaccessible to digestive enzymes) in the small intestine but can be fermented by gut microbiota 

• type 1 vs 2

  • type 1 - pancreas fails to produce insulin

  • type 2 - cells fail to respond to insulin properly