Therapeutic Interventions Week 1 - Intro, Energy, Review of Inflammation (Hard)

• Function is influenced by balance, stability, neuromuscular control/coordination, muscle performance, cardiopulmonary endurance, and mobility/flexibility.
• Mobility refers to the ability to move freely without restriction, which is dependent on soft tissue extensibility (passive) and neuromuscular activation (active).
• Therapeutic interventions are systematic and planned to remediate impairments, improve function, reduce health risks, and optimize well-being.

Bioenergetics and ATP

• ATP powers muscular activity, with adenosine composed of a nitrogen base and ribose.
• Hydrolysis breaks down ATP, requiring water and releasing energy for biological work.
• ATP is a high-energy molecule storing energy in its two terminal phosphate groups.
• ATP must constantly be produced during activity.
• Hydrolysis of ATP is catalyzed by ATPase, yielding ADP, and further hydrolysis yields AMP.

ATP Replenishment

• Three basic energy systems replenish ATP in muscle: phosphagen, glycolysis, and oxidative.
• Phosphagen and the first phase of glycolysis are anaerobic and occur in the sarcoplasm.
• The Krebs Cycle and electron transport system are aerobic and occur in the mitochondria.
• Carbohydrates are the only macronutrient metabolized for energy without direct oxygen involvement and are critical during anaerobic metabolism.
• All three energy systems are active at any given time. Contributions depend on the intensity and duration of the activity.

Phosphagen System

• The phosphagen system provides ATP for short-term, high-intensity activities and is active at the start of all exercise.
• It is the fastest method of producing ATP involving the donation of a phosphate group from phosphocreatine (PC or CP) to ADP, using creatine kinase.
• The body stores about 80-100g of ATP.
• Creatine phosphate concentrations in skeletal muscle are four to six times higher than ATP concentrations.
• Type II muscle fibers contain higher concentrations of creatine phosphate than type I.

Glycolysis

• Glycolysis involves the breakdown of carbohydrates to resynthesize ATP and occurs in the sarcoplasm.
• ATP resynthesis isn't as rapid but is higher capacity due to larger glycogen and glucose supplies than creatine phosphate.
• The glycolytic system has a much higher capacity for storing energy and is considered anaerobic, dominating activities lasting 30 seconds to 2-3 minutes.
• Glycolysis breaks down glucose or glycogen into two molecules of pyruvate or lactate, yielding a net gain of two ATP molecules.

Glycolysis Phases

• Glycolysis has two phases: energy investment and energy generation.
• The energy investment phase requires ATP to form sugar phosphates, priming glycolysis with two ATP (or one if starting with glycogen).
• The energy generation phase produces four ATP, resulting in a net gain of 2 ATP (or 3 if starting with glycogen).

Lactate Production

• Pyruvate can be converted into lactate or shuttled into the mitochondria for the Krebs Cycle.
• Aerobic glycolysis (slow glycolysis) occurs when pyruvate is shuttled into the mitochondria, providing a slower but longer duration of ATP resynthesis if exercise intensity is low enough.
• Lactate, not lactic acid, is the product of the reaction due to the consumption of protons in earlier steps, even though muscle fatigue correlates with high lactate concentrations, lactate doesn't cause fatigue.

Krebs Cycle

• If oxygen is present, pyruvate is transported into the mitochondria instead of being converted to lactate, along with two molecules of reduced NADH.
• Substrate-level phosphorylation and oxidative phosphorylation are primary mechanisms for ATP resynthesis during metabolism, yielding a net gain of 2 ATP.
• Glycolysis is considered anaerobic because oxygen isn't directly involved, but pyruvate can participate in aerobic ATP production if oxygen is present in the mitochondria.

Regulation of Glycolysis

• Glycolysis rate increases with high concentrations of ADP, Pi, ammonia, and a slight decrease in pH and AMP.
• Glycolysis rate is inhibited by markedly lower pH, ATP, CP, citrate, and free fatty acids.
• Phosphofructokinase is the most important regulator as it proceeds at a rate-limiting step.
• Hexokinase and pyruvate kinase concentrations also play a role in the regulation of glycolysis.
• Regulatory enzymes like phosphofructokinase have allosteric binding sites, contributing to allosteric regulation.

Lactate Threshold

• Lactate threshold (LT) occurs when blood lactate abruptly increases above baseline concentration, typically at 50-60% of maximal oxygen uptake in untrained individuals and 70-80% in aerobically trained athletes.
• It represents a greater reliance on anaerobic mechanisms for energy production.
• Ventilatory threshold corresponds well with lactate threshold. It is a marker of anaerobic threshold.
• The onset of blood lactate accumulation (OBLA) occurs when blood lactate reaches 4 millimoles per liter.
• The break in the lactate accumulation curve may correspond to the recruitment of intermediate and larger motor units during high-intensity exercise, which are typically type 2 fibers suited for anaerobic metabolism and lactate production.

Oxidative System

• The main function is to generate energy carriers (NADH and FADH2) through the oxidation of acetyl-CoA.
• The oxidative system is aerobic, deriving energy from carbs, then shifting to proteins and fats for prolonged submaximal exercise.
• Dominant for low-intensity activities lasting longer than 3 minutes.
• Protein use increases during long starvation and exercise bouts, greater than 90 minutes.
• At rest, the body primarily uses fats and carbs as substrates.
• During high-intensity aerobic exercise, most energy is derived from carbs, but there's a gradual shift back to fats during submaximal steady-state work

Aerobic ATP Production

• Aerobic production of ATP occurs inside the mitochondria.
• Involves the citric acid cycle (Krebs Cycle) and electron transport chain.
• The Krebs Cycle completes oxidation (electron removal) from acetyl CoA, using NAD+ and FAD+ as electron energy carriers.
• Electrons contain potential energy to be used in the electron transport chain to combine ADP to phosphate to reform ATP.
• Oxygen is the final electron and hydrogen acceptor at the end of the electron transport chain.
• The material Acetyl CoA starts the process of aerobic ATP production.

Krebs Cycle Details

• The Krebs Cycle generates energy carriers like NADH and FADH2 through the oxidization of Acetyl CoA.
• One cycle produces two molecules of carbon, three molecules of NADH, one molecule of NADH2, and one molecule of GTP.
• Each glucose molecule produces two molecules of acetyl CoA, so the cycle occurs twice.
• Most energy yield is from NADH and FADH2.
• GTP is a high energy compound that can transfer its terminal phosphate group to ADP to form ATP which accounts for a small amount of total energy conversion.

Electron Transport Chain

• Electrons removed from hydrogen atoms supported by NADH and FADH are passed down a series of electron carriers called cytochromes.
• During the passage, energy is released to dephosphorylate ADP to form ATP.
• One molecule of NADH can produce three molecules of ATP, while one molecule of FADH2 can produce two molecules of ATP.

Oxidative System Summary

• Through the oxidization of substrates and the formation of NADH and FADH in the Krebs cycle, the electron transport chain results in the formation of ATP and water.
• The oxidative system (glycolysis, Krebs cycle, and electron transport chain) produces about 38 ATP from the degradation of one molecule of blood glucose.
• If glycolysis initiates with muscle glycogen, the net ATP is 39 since the hexokinase reaction is not necessary with muscle glycogenolysis.

Fat Oxidation

• Triglycerides stored in fat cells are broken down to produce free fatty acids and glycerol.
• Free fatty acids enter the mitochondria and go through beta-oxidation.
• A series of reactions in which free fatty acids are broken down resulting in acetyl CoA and hydrogen protons.
• Acetyl CoA enters the Krebs Cycle directly, and hydrogen atoms are carried by NADH and FADH2 to the electron transport chain, resulting in hundreds of ATP molecules.

Protein Oxidation

• Protein is broken down into amino acids and then converted into glucose via gluconeogenesis.
• Branched-chain amino acids are the major amino acids oxidized in skeletal muscle.
• Nitrogenous waste products of amino acid degradation are eliminated through urea and small amounts of ammonia.

Energy Production and Capacity

• Exercise intensity defines muscular activity.
• High-power output activities require a rapid energy supply, relying almost entirely on the phosphagen system.
• Low-intensity, long-duration activities rely on the oxidative system.
• Short, high intensity activities rely largely on phosphagen energy and fast glycolysis.
• As intensity decreases and duration increases, the emphasis shifts to slow glycolysis and the oxidative system.

Substrate Depletion and Repletion

• Energy substrates are molecules that provide starting materials for bioenergetic reactions.
• Fatigue is associated with the depletion of phosphagens and glycogen.
• Dynamic muscle actions deplete phosphagens to a greater extent than isometric muscle actions.
• Complete ATP resynthesis occurs within three to five minutes, and creatine phosphate resynthesis occurs within eight minutes.
• Repletion of phosphagens is largely accomplished through aerobic metabolism
• Resting concentrations of liver and muscle glycogen can be influenced by training and diet; Muscle glycogen is more important energy source than liver during moderate and high intensity exercise.
• Liver glycogen is more important during low intensity exercise and its contribution to metabolic processes increases with duration of exercise.
• Muscle glycogen may be replenished within 24 hours, provided carbs are ingested.

Limiting Factors in Exercise Performance

• Glycogen depletion can limit long-duration, low-intensity exercise and repeated high-intensity exercise.
• Metabolic acidosis can limit contractile force during resistance training.

Oxygen Uptake

• Oxygen uptake measures a person's ability to take in oxygen. Send it to the tissue and then able to use the oxygen
• During low-intensity exercise, oxygen uptake increases until a steady state is reached.
• Anaerobic mechanisms supply energy at the start of exercise due to the slow response of the aerobic system, known as the oxygen deficit.
• Post exercise oxygen uptake, or EPOC, remains above pre exercise levels according to intensity and length of exercise.

Acute Inflammation

• Acute inflammation is characterized by redness, warmth, pain, swelling, and loss of function.
• Redness is caused by blood vessel dilation.
• Warmth is often due to blood vessel dilation.
• Pain is from inflammatory mediators, increased pressure from swelling on nerves.
• Swelling is due to exudation.
• Loss of function depends on several of the above factors.

Inflammatory Response

• Includes homeostasis which occurs first, with platelets responding to the injured area to stop bleeding by adhering to exposed collagen and forming a clot.
• Platelets also produce growth factors in later healing stages.
• Swelling continues due to extravasation, or fluid movement from blood vessels which results in redness and elevated local temperature.
• Neutrophils and macrophages clean the wounded area of non-viable material to begin the proliferative phase.

Sequence of Inflammatory Response

• Injury to cell
• Vascular reaction (vasoconstriction, vasodilation, exudate creates stasis)
• Platelets and leukocytes adhere to vascular wall
• Chemical mediators liberated (histamine, leukotrienes, cytokines)
• Phagocytosis
• Clot formation
• Hemostasis is the vascular reaction that involves the vascular spasm or vasoconstriction that contributes to the platelet plug
• The immediate response is the vasoconstriction in which the vessel is leading away from the site of injury that lasts for about 5-10 minutes
• Disruption to the endothelium exposes collagen fibers, which platelets adhere to and creates a sticky matrix
• The initial event that precipitates clot formation is a conversion of fibrogen to fibrin

Fibroblastic-Repair and Proliferative Phase

• The function of this phase is to repair the defect and replace damaged tissue.
• It can lasts several weeks depending on the injury.
• Fibroblasts are attracted to the wound by the macrophages from the inflammatory phase and laying down collagen and elastin between 48 to 72 hours after injury
• Keratinocytes becomes importan when injury results in a break in the skin and covers the wound with a new layer of epithelium.
• Scar formation occurs or fibroplasia is within the first few hours following the injury and may last for as long as four to six weeks
• Growth of endothelial capillary buds into the wound or angiogenesis
• Increase oxygen in the area = increased blood flow which delivers nutrients essential for tissue regeneration in the area
• Number of fibroblasts diminishes to signal the beginning of the maturation phase
• A mature scar will still have less tensile strength than the original tissue and not as vascularized.

Maturation – Remodeling Phase

• During this phase, newly formed collagen matrix is rearranged and continues to gain strength and can last over a year
• Ongoing breakdown and synthesis of collagen occur with a steady increase in the strength of the scar
• Collagen fibers realign in a position of maximum efficiency parallel to the lines of tension with increased stress and strain

Acute to Chronic Inflammation

• Acute involves neutrophils with exudation of fluid, and increased permeability and cardinal signs.
• Chronic involves macrophages and lymphocytes. There may be blood vessel proliferation, fibrosis, and necrosis.
• Chronic inflammation occurs when the acute inflammatory response is insufficient, with neutrophils replaced by cells that are more likely to cause connective tissue damage.
• Insufficient acute inflammatory response is related to overuse or overload with cumulative microtrauma.
• Chronic inflammation is resistant to both physical and pharmacologic treatments.
• There can be inflammation without healing but there cannot be healing without inflammation.
• Repeated episodes of acute inflammation can contribute to chronic inflammation, resulting in abnormal function.

Factors that Impede Healing

• Extent of injury determines the inflammatory response, with macro tears causing more tissue destruction and functional alterations.
• Hemorrhage occurs with smallest amount of damage to capillaries, exacerbating the negative effects of healing
• Poor vascular supply inhibits delivery of cells necessary for scar tissue formation.
• Mechanical separation of tissue increases scarring. Muscle spasm can do this.
• Strength and mobilization helps stop muscle atrophy that begins quickly with injury.
• Corticosteroids in early stages can inhibit fibroplasia, capillary growth, collagen synthesis and increase the strength of healing scar
• Keloids and hypertrophic scars occur when collagen production exceeds the rate of collagen breakdown during the maturation phase of healing
• A moist environment is ideal, and Oxygen tension is preferrable.
• Vitamins C, K, A, E, zinc, and amino acids or proteins play a role in the healing process
• Diabetes or atherosclerosis can be a major concern to healing

Stages of Healing and PT Intervention

• Acute Stage: Inflammation presents as pain before tissue resistance. Physical therapy goals include controlling inflammation, protecting the site, and preventing deleterious effects of rest. Interventions include protection, rest, ice, compression, elevation, passive range of motion, and muscle setting.
• Subacute Stage: Proliferation, Repair and Healing presents as pain synchronous with tissue resistance. Physical therapy goals involve developing mobile scar tissue and promoting healing through selective stretching and nondestructive exercises to improve endurance and balance
• Chronic Stage: Maturation and Remodeling presents as pain after tissue resistance Physical therapy intends to increase the tensile quality of scar by improving strength, balance, and endurance with functional and job-specific exercises to return to high-demand activities.

Energy Systems Summary

• Phosphagen system is quick and high intensity and is dominant for 5-6 seconds
• Glycolysis is high to moderate intensity and is dominant for 2-3 minutes
• The Oxidative system is low intensity and is dominant for over 3 minutes

Result of Malfunctioning Systems

• Phosphagen system impairments result in reduced high-intensity performance, strength, and hypertrophy development, leading to increased reliance on glycolysis, which can cause early lactate accumulation and exhaustion.
• Glycolysis genetic disorders can result in disrupted muscle contraction, exercise intolerance, and neurocognitive symptoms
• Oxidative System disorders lead to severe ATP deficiency, fatigue, neurological impairments, and oxidative stress. This leads to cellular damage.

Inflammatory Timeline

• Hemostasis brings platelets to the area in 5-10 min
• Inflammation brings fluid and WBC lasting up to 48-72 hours
• Proliferation fibroblastic cells create new scar tissue, lasting for several weeks
• Remodeling realigns collagen fibers over years

This quiz explores the critical roles of oxygen, electron transport chains, and the Krebs cycle in aerobic ATP production. It also examines the impact of exercise on blood glucose regulation and cardiovascular physiology, particularly concerning cardiac output and stroke volume.