Energy Balance and Temperature Regulation

What does the first law of thermodynamics state?

Energy cannot be created or destroyed.

What are the two main components of energy output?

External work and internal work.

What is external work?

Energy spent when skeletal muscles are contracted to move external objects or to move the body

What is internal work?

All other forms of biological energy expenditure that do not accomplish mechanical work outside the body

Example of internal work

Skeletal muscle use for purposes other than external work (maintaining posture, shivering). Basically all energy-spending activities that go on throughout our life.

What is the primary fuel for carbohydrate metabolism?

Glucose which converts to pyruvate through glycolysis.

What is the ATP yield from aerobic glycolysis?

Approximately 36-38 ATP per glucose molecule.

What is the ATP yield from anaerobic glycolysis?

2 ATP per glucose

What is the process of lipid metabolism that produces acetyl-CoA?

β-oxidation of fatty acids.

What is the ATP yield from the complete oxidation of palmitate?

Approximately 129 ATP.

What is the role of amino acids during starvation?

They are catabolized to produce glucose and ketones.

What percentage of ATP is produced by oxidative phosphorylation?

About 90%.

What occurs during the fed state?

Carbohydrates are the primary energy source

What occurs during the fasting state?

Lipids become dominant, ketone bodies supplement glucose.

What occurs during starvation state?

Proteins become catabolized into glucose (via gluconeogenesis) and ketones

What is the function of insulin?

Promotes glucose uptake, glycogenesis, lipogenesis, protein synthesis

What is the function of glucagon/epi?

Glycogenolysis, lipolysis, gluconeogenesis

What is the function of cortisol?

Protein catabolism, gluconeogenesis

What is the clinical implication of diabetes? (in regards to energy and breakdown)

Impaired carb utilization leads to increased lipid/protein catabolism, which leads to ketoacidosis

What is the clinical implication of starvation/cachexia?

Protein catabolism leads to muscle wasting

What is the clinical implication of ischemia?

Glycolysis dominates leading to lactate accumulation which leads to acidosis

What is the Basal Metabolic Rate (BMR)?

The energy expended at rest in a post-absorptive state at neutral temperature.

What does BMR represent?

About 60-70% of daily energy output

What is the normal adult average of BMR?

~25-30 kcal/kg/day

What is the total energy expenditure of thermic effect of food?

~10%

What is the total energy expenditure of physical activity?

~20%

What factors can affect Basal Metabolic Rate (BMR)?

Age, sex, body size/composition, thyroid hormones, sympathetic activity, and temperature.

How does age affect BMR?

Decreases with age

How does sex affect BMR?

Males have a higher BMR than females, due to muscle mass

How does body size/composition affect BMR?

Lean body mass increases BMR

How does thyroid hormone affect BMR?

It's the most important regulator, T3/T4 increase metabolism

How does sympathetic activity affect BMR?

Increased energy output via B-adrenergic stimulation

How does temperature/fever affect BMR?

Increases metabolic rate

How do hormones affect BMR?

GH, testosterone and cortisol lead to increased protein turnover, increasing metabolism.

What is the normal caloric requirement for a sedentary adult?

Approximately 2000-2500 kcal/day.

What is the normal caloric requirement for a moderate activity adult?

2500-3000 kcal/day

What is the normal caloric requirement for a high activity adult/athlete?

>4000 kcal/day

What determines weight gain/loss?

Energy balance, intake vs expenditure

What is the clinical implication of hyperthyroidism (with regards to BMR)?

Increases BMR, leads to weight loss, heat intolerance, tachycardia

What is the clinical implication of hypothyroidism (with regards to BMR)?

Decreases BMR, leads to weight gain, cold intolerance, lethargy

What is the clinical implication of starvation (with regards to BMR)?

Decreases BMR as an adaptive response

What is the clinical implication of obesity (with regards to BMR)?

Alters BMR, usually due to caloric imbalance.

What is the clinical implication of fever/sepsis (with regards to BMR)?

It's a hypermetabolic state with increased energy demands.

What are the hypothalamic centers?

Arcuate nucleus, orexigenic neurons, and anorexigenic neurons

What is the arcuate nucleus?

It integrates peripheral signals

What are the orexigenic neurons?

NPY and AgRP, which stimulate appetite

What are anorexigenic neurons?

POMC and CART, which suppress appetite

What are the key centers?

Leptin, ghrelin and insulin

What is the role of leptin in energy regulation?

Exists in adipocytes. It signals energy sufficiency, decreasing appetite and increasing energy expenditure.

What hormone is known as the hunger hormone?

Ghrelin.

How does ghrelin affect NPY/AgRP?

Increases these hormones, leading to increase food intake.

What is the primary role of insulin in energy storage?

It promotes satiety and facilitates glucose uptake and storage.

What kind of regulator is leptin?

A long term regulator, reflecting fat stores.

When and where is ghrelin released?

In the stomach before meals to signal hunger.

What does insulin promote?

Glycogenesis, lipogenesis and protein synthesis

What other signals promote satiety and are gut derived?

CCK, GLP-1 and PYY

What other signal promotes appetite and fat storage?

Cortisol

What is the clinical implication of obesity (with regards to key centers)?

Causes leptin resistance, leading to persistent appetite despite high leptin

What is the clinical implication of Prader-Willi syndrome (with regards to key centers)?

Causes increased ghrelin, leading to insatiable appetite

What is the clinical implication of DM2 (with regards to key centers)?

Insulin resistance impairs satiety and energy storage regulation

What is the clinical implication of starvation/cachexia (with regards to key centers)?

Decreases leptin, stimulating appetite, conserving energy.

What is the clinical implication of bariatric surgery (with regards to key centers)?

Decreases ghrelin levels, increases PYY and GLP-1, leading to appetite suppression which contributes to weight loss

What controls satiety signals?

Gut hormones and stretch

How does CCK affect satiety signals and where is it released?

It slows gastric emptying and increases satiety. Released in duodenum

How does GLP-1 and PPY affect satiety signals and where are they released?

They suppress appetite post-meal. Released in ileum/colon.

How does gastric distension affect satiety signals?

Stretch caused by vagal afferents, leading to satiety.

How does leptin affect long-term regulation?

Signals fat stores, decreases appetite, increases energy expenditure.

How does insulin affect long-term regulation?

Reflects carb/fat storage. Plays a role in satiety.

What are short-term regulatory mechanisms of food intake?

Hunger and satiety signals that influence meal timing and size.

What is the difference between short-term and long-term regulation of food intake?

Short-term signals determine meal timing/size, while long-term signals maintain body weight set-point.

What is obesity defined as?

Excess body fat accumulation impairing health.

What is the normal BMI range?

18.5-24.9 kg/m²

What BMI is considered overweight?

25-29.9

What BMI indicates obesity?

≥30 kg/m²

What waist circumference indicates increased cardiometabolic risk for men?

>102 cm

What waist circumference indicates increased cardiometabolic risk for women?

>88 cm

What are the three main factors contributing to obesity?

Genetic factors, behavioral factors, environmental factors.

What genetic mutation can lead to severe early obesity?

Mutations in leptin or leptin receptor

What lifestyle factors contribute to obesity?

Sedentary lifestyle and caloric-dense, high-fat/high-sugar diet.

What environmental factors contribute to obesity?

Food availability and marketing, urbanization which decreases activity, socioeconomic status.

What is leptin resistance?

A condition common in obesity that impairs satiety signaling.

What is the role of insulin resistance in obesity?

Hyperinsulinemia promotes fat storage.

How do reward pathways, specifically dopamine, affect obesity?

Override satiety, promoting hedonic eating.

What hormones are affected during obesity?

GLP-1, PYY, ghrelin dynamics.

Which cause of obesity is rare?

Genetic obesity. Treatable with leptin therapy.

Which causes of obesity are common?

Polygenic and environmental factors, comprising 95% of cases.

What are some complications of obesity?

Type 2 diabetes mellitus, hypertension, coronary artery disease, non-alcoholic fatty liver disease, obstructive sleep apnea, osteoarthritis, certain cancers.

What is the Respiratory Quotient (RQ)?

RQ = CO₂ produced ÷ O₂ consumed.

How is RQ measured?

Via indirect calorimetry (gas exchange analysis)

What is the normal range for RQ?

0.7-1.0.

What is the RQ value of carbs?

About 1.0, glucose oxidation produces equal CO2 and O2 consumed.

What is the RQ value of fats?

0.7, requires more O2 relative to CO2 produced.

What is the RQ value of proteins?

0.8, involves deamination and mixed metabolic pathways.

What is the average RQ of a mixed diet?

0.8-0.85

What does a high RQ indicate?

Predominance of carbohydrate metabolism.

What does a low RQ indicate?

Predominance of fat metabolism.

What is the clinical implication of indirect calorimetry in the ICU?

Monitors energy needs to avoid overfeeding.

What is the clinical implication of DM (in regards to RQ)?

High RQ may reflect reliance on glucose oxidation (if insulin present) or altered balance in insulin resistance.

What is the clinical implication of COPD/respiratory failure (in regards to RQ)?

High carb feeding raises RQ, leading to increased CO2 load, and causing worsening hypercapnia.

What is the clinical implications of athletic physiology (in regards to RQ)?

Training alters RQ since endurance athletes use fat longer, sparing glycogen.