JW

D3.3 Comprehensive Notes

D3.3.1 Homeostasis as maintenance of the internal environment

  • Definition: Homeostasis is the maintenance of a constant internal environment within preset limits, despite fluctuations in the external environment.
  • Key homeostatic variables in humans include:
    • body temperature
    • blood pH
    • blood glucose concentration
    • blood osmotic concentration
  • Function: Maintains stable internal conditions by monitoring variables and making corrections via negative feedback mechanisms.
  • Set points: Each variable has a preset value (set point) that the system works to maintain.
  • Concept to remember: Homeostasis works through monitoring levels of variables and performing corrections to keep them within narrow limits.
  • Connections to broader ideas: Links to the idea of a steady state in physiology, where multiple systems coordinate to keep core conditions stable (e.g., temperature, pH, ion balance, and hydration).
  • Practical relevance: Essential for normal cell function, enzyme activity, and metabolic processes; deviations can lead to disease states (e.g., diabetes when glucose regulation fails).
  • Related questions to consider: Which factors must stay the same inside the body to maintain a steady state? (See next section for details.)

D3.3.2 Negative feedback loops in homeostasis

  • Core concept: Negative feedback loops counteract changes by driving a system back toward its set point.
  • Why negative rather than positive feedback is used in homeostasis:
    • Negative feedback restores variables to the set point after a deviation above or below it.
    • Positive feedback amplifies a stimulus and moves the system away from the starting state; it is less common in maintaining steady conditions.
  • Example of negative feedback in homeostasis: Noting that many body systems function to stabilize variables around a set point (e.g., temperature, glucose). Positive feedback examples (less common) might include certain phases of the menstrual cycle where a stimulus leads to further release (FSH stimulates follicle growth which then stimulates more FSH in the provided material).
  • Key takeaway: Negative feedback is the main mechanism maintaining internal stability; it requires energy to operate but keeps the body within narrow limits.
  • Visual references: Diagrams showing feedback loops (negative) returning variables toward the set point.

D3.3.3 Regulation of blood glucose as an example of the role of hormones in homeostasis

  • Pancreatic endocrine cells regulate blood glucose via insulin and glucagon.
  • Cells involved:
    • Langerhans islets in the pancreas contain α cells (glucagon) and β cells (insulin).
  • Hormones in circulation:
    • Insulin and glucagon are secreted into the bloodstream and travel to target cells.
  • Target tissues and responses:
    • Insulin promotes uptake of glucose into muscle and adipose tissue; stimulates storage of glucose as glycogen in liver and muscle; promotes lipogenesis; overall lowers blood glucose levels.
    • Glucagon promotes glycogenolysis and gluconeogenesis in the liver; increases blood glucose levels.
  • Negative feedback loop: High blood glucose triggers insulin release; low blood glucose triggers glucagon release; the loop helps maintain glucose around the set point.
  • Important distinctions:
    • Endocrine function (hormone secretion into blood) vs exocrine function (ductal secretions, e.g., digestive enzymes).
    • The pancreas has multiple roles, hence the need to distinguish endocrine vs exocrine glands.
  • Note on transport and action:
    • Hormones are transported in blood to reach specific receptor-bearing target cells.
  • Basic numeric reference (from the material): a typical normal fasting blood glucose level is around 90 mg/100 mL of blood.
  • LaTeX note: The regulatory relationship can be summarized with a simple set-point model:
    • Let G(t) be blood glucose, G_set the set point. The negative feedback adjustment can be represented as a small-signal dynamic:
    • rac{dG}{dt} = -k\,(G - G_{set}) where k > 0.

D3.3.4 Physiological changes that form the basis of type 1 and type 2 diabetes

  • Diabetes definition: A condition where blood glucose remains consistently elevated, including presence of glucose in urine during fasting.
  • Type I diabetes (early onset):
    • Cause: Autoimmune destruction of pancreatic β cells, leading to insufficient insulin production.
    • Age: Typically affects children and young people.
    • Symptoms: Increased thirst, urination, constant hunger, weight loss, blurred vision, nerve damage; may lead to kidney failure if untreated.
    • Risk factors: Autoimmune factors, genetics; environmental influences are not fully understood.
  • Type II diabetes (late onset):
    • Cause: Insulin resistance due to defective insulin receptors or glucose transporters on target cells; may also include insufficient insulin production.
    • Age: Typically affects older people but increasingly seen in younger individuals with lifestyle factors.
    • Symptoms: Fatigue, slow healing, sometimes mild; glucose in blood remains high due to impaired uptake.
    • Risk factors: Lifestyle (high-sugar/fat diet, obesity, sedentary behavior), genetics, aging.
  • Common consequences: Chronic hyperglycemia can lead to complications such as cardiovascular problems, kidney issues, neuropathy, and vision problems if not managed.
  • Practical implications: Prevention and management focus on diet, exercise, weight control, and blood glucose monitoring; treatment for Type I requires insulin therapy; Type II may require lifestyle changes, oral medications, and sometimes insulin.
  • Thematic connections: Both types illustrate the central role of insulin and glucose regulation in homeostasis and the consequences when the system fails.

D3.3.5 Thermoregulation as an example of negative feedback control

  • Core idea: Thermoregulation uses negative feedback to maintain core body temperature near a set point.
  • Key components:
    • Peripheral thermoreceptors in the skin detect external temperature changes.
    • Central thermoreceptors in the body's core monitor internal temperature.
    • The hypothalamus acts as the regulatory center, integrating information from thermoreceptors.
    • The pituitary gland and thyroid axis (thyroxin/T4) are involved in adjusting metabolic heat production via hormonal pathways.
  • Effectors and responses:
    • Skeletal muscles (including shivering) generate heat when needed.
    • Adipose tissue (including brown adipose tissue) contributes to heat production via uncoupled respiration; brown adipose tissue is more abundant in newborns and small mammals.
    • Hair erection (piloerection) reduces heat loss.
  • Behavioral aspects: Humans employ behavioral adjustments (e.g., clothing, seeking shade, hydration) to help regulate temperature.
  • Set-point and variability:
    • The body may adjust the set point with time of day, season, or organismal state; thermoregulation integrates both physiological and behavioral strategies.

D3.3.6 Thermoregulation mechanisms in humans

  • Humans regulate body temperature through physiological (internal) and behavioral means; birds and mammals share the general approach of maintaining a stable core temperature.
  • Physiological mechanisms include:
    • Vasodilation: widening of blood vessels to increase heat loss through the skin when overheating.
    • Vasoconstriction: narrowing of blood vessels to reduce heat loss and conserve heat when cold.
    • Shivering: muscle activity generates heat when core temperature drops.
    • Sweating: evaporative cooling when body temperature rises.
    • Uncoupled respiration in brown adipose tissue (BAT): produces heat rather than ATP, contributing to heat generation, especially in newborns and small mammals.
    • Hair erection (piloerection): raises the insulating layer of hair to reduce heat loss in cold conditions.
  • Hormonal regulation related to temperature:
    • Thyroxin (T4) increases metabolic rate and heat production.
    • The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the pituitary to release thyroid-stimulating hormone (TSH), which then stimulates T4 production by the thyroid.
    • Increased metabolic activity in target tissues (muscle, brain, liver) raises heat production; adipose tissue acts as insulation.
  • Role of heat distribution: Blood circulation distributes heat generated by metabolism to the skin and periphery for dissipation or retention.
  • Key point: Thermoregulation relies on negative feedback to maintain core temperature near the set point, with adjustments in both heat production and heat loss.

Factors that must stay constant for a steady state (overview)

  • The internal environment requires steady values for multiple variables to maintain homeostasis:
    • Concentration of respiratory gases in blood: pCO2, ext{ } pO2
    • Body temperature
    • Glucose level in blood
    • Blood pressure (arterial)
    • Water content of blood
    • Heart rate
    • Blood pH
    • Concentration of essential ions
  • These variables are monitored and adjusted through various feedback mechanisms to keep the organism within tolerable limits.

Blood glucose regulation: overview and physiology

  • Blood glucose transport and homeostasis depend on two key hormones: insulin and glucagon.
  • Normal fasting blood glucose level: around G_{ ext{normal}} \approx 90\;\frac{mg}{100\,mL}
  • Hyperglycemia and regulation: High blood glucose is linked to higher blood pressure in some contexts; the feedback system aims to prevent persistent high glucose levels.
  • Hormone sources:
    • Pancreatic islets (Langerhans): alpha cells secrete glucagon; beta cells secrete insulin.
  • Hormone actions:
    • Insulin: promotes glucose uptake into cells (muscle and adipose tissue) and storage as glycogen; lowers blood glucose.
    • Glucagon: promotes glycogen breakdown and glucose production in the liver; raises blood glucose.
  • Target cell responses differ by tissue type:
    • Insulin signals cells to insert glucose transporters into membranes, increasing glucose uptake.
    • Glucagon signals hepatic cells to mobilize glucose stores and generate new glucose.
  • Negative feedback in glucose regulation is achieved by the rise/fall of insulin and glucagon depending on current glucose levels.
  • Contextual notes:
    • Endocrine vs exocrine: The pancreas has both endocrine (islets) and exocrine (ductal) functions; insulin and glucagon are endocrine products.
    • The glucose tolerance test (GTT) is used to diagnose diabetes by measuring blood glucose response after a glucose challenge; diabetics typically show slower clearance and higher peak levels than unaffected individuals.

Diabetes: types, risk factors, prevention, and treatment (summary)

  • Type I diabetes (early-onset):
    • Causes: Autoimmune destruction of pancreatic β cells; little to no insulin produced.
    • Onset: Usually in children or young people.
    • Symptoms: Thirst, frequent urination, weight loss, fatigue, blurred vision, possible nerve damage.
    • Risk factors: Genetic predisposition and autoimmune factors; not fully understood; not easily preventable.
    • Treatment: Insulin injections, diet and exercise, regular glucose monitoring; education on injection timing and dose management.
  • Type II diabetes (late-onset):
    • Causes: Insulin resistance due to defective insulin receptors or glucose transporters; sometimes reduced insulin production.
    • Onset: Often in older individuals but increasingly seen in younger populations due to lifestyle factors.
    • Symptoms: Fatigue, slow healing, mild symptoms; higher fasting glucose may be present.
    • Risk factors: Obesity, unhealthy diet, physical inactivity, genetics, aging.
    • Treatment: Diet and exercise, glucose monitoring; sometimes oral medications; sometimes insulin if needed; emphasis on reducing glycemic load and maintaining a healthy weight.
  • Common treatment themes: Diet with low glycemic index foods, exercise, weight management, and monitoring of blood glucose levels; adherence reduces risk of complications.
  • Practical relevance: Understanding these diabetes types highlights the importance of the glucose regulatory axis and its implications for long-term health outcomes.

Glucose tolerance test (GTT) – data-based questions (example and interpretation)

  • Purpose: Diagnose diabetes by assessing how quickly blood glucose is cleared after a glucose load.
  • Procedure outline: Involves drinking a concentrated glucose solution and monitoring blood glucose concentration over time to produce a glucose response curve.
  • Comparative interpretation (diabetic vs normal):
    • Fasting glucose level (time zero): Diabetic often higher than normal.
    • Time to return to baseline: Diabetic typically takes longer to return to baseline (i.e., higher and delayed peak).
    • Peak glucose level: Diabetic often has a higher peak.
    • Time to begin fall: Diabetic may show a delayed onset of decline.
  • Practical note: Fasting blood glucose measurement (without glucose challenge) is another diagnostic method and is often used in combination with GTT results.

Thermoregulation: mechanisms and response to heat stress (summary)

  • Overview: Thermoregulation is controlled by the hypothalamic thermoregulatory center, integrating input from peripheral and central thermoreceptors.
  • Core processes:
    • Heat gain from metabolic activity and environmental exposure is balanced by heat loss through various mechanisms.
    • Negative feedback governs the adjustment processes to maintain core temperature near a set point.
  • Heat generation and distribution:
    • Metabolic heat is produced by cells and distributed by the blood.
    • Thyroxin (T4) increases metabolic rate and heat production; its production is regulated via the hypothalamus-pituitary-thyroid axis (TRH -> TSH -> thyroxine).
  • Role of adipose tissue:
    • Adipose tissue acts as insulation; brown adipose tissue (BAT) can generate heat rapidly via non-shivering thermogenesis (uncoupled respiration, UCP1).
  • Behavioral and hormonal responses:
    • Behavioral: clothing adjustments, seeking shade, hydration.
    • Hormonal: adjustments in thyroid hormone levels to regulate metabolic rate and heat production.
  • Non-thermal considerations: Evaporative cooling via sweating involves energy absorption to break hydrogen bonds in water; this energy loss reduces body temperature.
  • Vascular adjustments:
    • Vasodilation increases heat loss by bringing blood closer to the skin.
    • Vasoconstriction reduces heat loss by keeping blood away from the skin surface and conserving heat.
  • Practical implications: In hot conditions, the body prioritizes heat loss (sweating, vasodilation); in cold conditions, heat conservation is prioritized (vasoconstriction, shivering, BAT activation).
  • Connections to broader biology: Thermoregulation is a classic example of a negative feedback loop operating across physiology, endocrinology, and behavior to maintain homeostasis.

Quick reference: key terms and concepts

  • Set point: The target value around which a homeostatic variable is maintained.
  • Negative feedback: A control system that reduces deviation from the set point.
  • Positive feedback: A control system that amplifies deviations from the set point; less common in maintaining homeostasis.
  • Endocrine vs exocrine: Endocrine glands secrete hormones directly into the bloodstream; exocrine glands secrete through ducts.
  • Langerhans islets: Clusters in the pancreas containing α and β cells that secrete glucagon and insulin, respectively.
  • Glycemic control: Regulation of blood glucose through hormones and organ responses (primarily liver, muscle, adipose tissue).
  • Glycemic index: A measure of how quickly a carbohydrate-containing food raises blood glucose.
  • Thyroxin (T4): Thyroid hormone that increases metabolic rate and heat production.
  • TRH/TSH axis: Hormonal pathway controlling thyroid hormone production.
  • Brown adipose tissue (BAT): A fat tissue type capable of non-shivering heat production via uncoupled respiration.
  • Hypothalamus: Brain region that acts as the regulatory center for many autonomic and endocrine processes, including temperature and energy balance.
  • Insulin vs glucagon: Hormones with opposing actions regulating blood glucose.
  • pCO2 and pO2: Partial pressures of carbon dioxide and oxygen in blood, important for respiratory and acid-base balance.

Connections to broader concepts and real-world relevance

  • Diabetes management is a direct application of understanding glucose regulation, hormone action, and feedback loops to prevent long-term complications.
  • Thermoregulation demonstrates integration of nervous, endocrine, and behavioral responses to maintain homeostasis in changing environments.
  • The balance between energy intake, metabolic rate, and heat production is tied to thyroid hormone regulation and adipose tissue dynamics.
  • These principles underpin many clinical conditions (e.g., thyroid disorders, obesity, metabolic syndrome) and inform public health strategies for lifestyle interventions.