BIO303 Topic 4.3 Integrative Physiology Notes

Atoms to Organisms

• Levels of Organization:

  • Atoms: Basic units of matter that form all chemical substances (e.g., Oxygen, Carbon, Hydrogen). Atoms combine to form molecules.

  • Small Molecules: Simple combinations of atoms (e.g., Methane, Water, Carbon Dioxide). These molecules are crucial for various cellular processes.

  • Large Molecules: Complex polymers like proteins, nucleic acids (DNA, RNA), carbohydrates, and lipids. These are essential for structure and function of cells.

  • Cells: Basic unit of life, capable of carrying out all life processes. Cells can be prokaryotic or eukaryotic, each with distinct structures and functions.

  • Tissues: Groups of similar cells performing a specific function (e.g., muscle tissue, nervous tissue, epithelial tissue). Different tissues work together to form organs.

  • Organs: Structures composed of different tissues that perform specific functions in the body (e.g., heart, brain, liver). Each organ contributes to the overall function of an organ system.

  • Organ Systems: Groups of organs working together to perform complex functions necessary for life (e.g., digestive system, circulatory system, nervous system).

  • Organism: An individual living being, which can be unicellular (e.g., bacteria), colonial (e.g., Volvox), or multicellular (e.g., animals, plants).

Organisms to Ecosystems

• Ecological Levels:

  • Population: A group of individuals of the same species living in the same area and interacting (e.g., a flock of birds, a school of fish).

  • Community: All the populations of different species living and interacting in a particular area (e.g., a forest community including trees, animals, and microorganisms).

  • Ecosystem: A community of living organisms (biotic factors) interacting with their physical environment (abiotic factors), such as climate, soil, and water (e.g., a lake, a desert).

  • Biosphere: The sum of all ecosystems on Earth, including all living organisms and their environments. It represents the broadest level of ecological organization.

Integrative Physiology

• Integrative physiology focuses on the study of how different organ systems interact and coordinate to maintain overall physiological functions and homeostasis within an organism.

• Example: The Renin-Angiotensin-Aldosterone System (RAAS) illustrates integrative physiology by involving the kidneys, blood vessels, adrenal glands, and brain to regulate blood pressure, fluid balance, and electrolyte balance.

Homeostasis: Maintaining Blood Pressure

• Blood pressure in large arteries fluctuates between 120 mmHg (systole) and 80 mmHg (diastole). Systole represents the pressure during heart contraction, while diastole is the pressure during heart relaxation.

• Maintaining adequate blood pressure, and therefore blood flow, is critical for:

  • Transporting oxygen and CO_2: Ensures that oxygen is delivered to tissues and carbon dioxide is removed.

  • Filtration of blood at the kidney to control the composition and volume of blood: Essential for removing waste products and regulating fluid and electrolyte balance.

  • Transporting nutrients from the digestive system, e.g., glucose: Delivers essential nutrients to cells throughout the body.

• Blood flow through vessels:

  • Artery → Arterioles → Capillaries → Venules → Vein: This sequence ensures efficient delivery of blood to tissues and return to the heart.

  • Blood pressure drives blood flow through vessels: Pressure gradients are essential for ensuring blood circulates properly.

Factors Affecting Blood Pressure

• Mean Arterial (Blood) Pressure (MAP) is determined by:
  Blood\ pressure = Cardiac\ Output \times Peripheral\ Resistance

• Cardiac Output (CO) is determined by:
  Cardiac\ Output = Stroke\ Volume \times Heart\ Rate

• Peripheral Resistance (PR) is affected by:

  • Vessel Radius: Smaller radius increases resistance, larger radius decreases it.

  • Vessel Length: Longer vessels increase resistance.

  • Blood Viscosity: Higher viscosity increases resistance.

Control and Regulation of Blood Pressure

• Baroreceptor Reflex Arc:

  • Stimulus: Change in blood pressure (MAP).

  • Sensory Receptor: Carotid and aortic baroreceptors (mechanoreceptors) detect changes in arterial pressure.

  • Afferent Sensory Neurons: Transmit signals to the integrating center in the brainstem.

  • Integrating Center: Medullary cardiovascular control center processes sensory input and coordinates an appropriate response.

  • Efferent Path: Parasympathetic and sympathetic neurons.

  • Effectors:

  • SA node (change heart rate).

  • Ventricles (change stroke volume).

  • Arterioles (change vessel radius).

  • Veins (affect venous return and preload).

  • Neurotransmitters:

  • ACh (acetylcholine): Released by parasympathetic neurons to decrease heart rate.

  • NE (norepinephrine): Released by sympathetic neurons to increase heart rate and cause vasoconstriction.

Chemical Communication

• Types of Signaling:

  • Autocrine: Acts on the same cell that secreted it, often regulating its own function.

  • Paracrine: Affects nearby cells by diffusion through the interstitial fluid.

  • Neural: Fast, short duration signaling via neurotransmitters across synapses.

  • Endocrine: Slow, long duration signaling via hormones in the blood, affecting distant target cells.

Endocrine Regulation of Blood Pressure

• Slow response, but long-lasting effects on blood pressure regulation!

• Mediated by the Renin-Angiotensin-Aldosterone System (RAAS), involving several hormones and organ systems.

• Response begins in the kidney, specifically with the juxtaglomerular apparatus.

Juxtaglomerular Apparatus

• Consists of macula densa cells (distal tubule) and granular cells (afferent arteriole).

• Granular cells: Produce and store renin, which can be released into the blood at the afferent arterioles in response to various stimuli.

• Stimuli for renin release:

  • Low blood pressure in afferent arterioles detected by granular cells.

  • Paracrine signaling from macula densa cells if filtrate flow through renal tubules is low (because GFR is reduced), or has an abnormal [Na^+].

• Release of renin is a rate-limiting step in the activation of the renin-angiotensin-aldosterone system.

Renin-Angiotensin-Aldosterone System (RAAS)

• Process:

  • Liver constantly secretes angiotensinogen into the bloodstream.

  • ↓BP stimulates granular cells in the kidney to release renin enzyme.

  • Renin converts angiotensinogen (inactive in plasma) to angiotensin I (ANG1).

  • ACE (angiotensin-converting enzyme), found in cells lining blood vessels and especially concentrated in the lungs, converts ANG1 to angiotensin II (ANGII).

  • Angiotensin II is the primary hormone responsible for raising blood pressure through multiple mechanisms.

• Targets of Angiotensin II:

  • Smooth muscle lining systemic arteries and arterioles.

  • Adrenal gland (zona glomerulosa).

  • Hypothalamus and posterior pituitary.

• Responses to Angiotensin II:

  • Vasoconstriction: Constricts systemic arteries and arterioles, reducing vessel radius and increasing peripheral resistance.

  • Aldosterone release: Stimulates the adrenal gland to release aldosterone, increasing Na^+ and H_2O reabsorption from the kidney.

  • ADH release & Thirst: Stimulates the hypothalamus to release ADH (antidiuretic hormone), increasing H_2O reabsorption from the kidney, and stimulates thirst, increasing fluid intake.

• Increases blood pressure both directly through vasoconstriction and indirectly by increasing blood volume.

Integrative Physiology: Acid-Base Balance

• Acid-Base balance (pH homeostasis) is maintained by the cooperative actions of the renal system and respiratory system.

• [H^+] must be carefully controlled within a narrow range to ensure proper cellular function. Typical pH of ECF and ICF = 7.4

• pH is critical for protein folding and function; deviations can disrupt protein structure and enzymatic activity.

• Acidosis: Elevated H^+, resulting in a reduced pH (<7.38).

• Alkalosis: Reduced H^+, leading to an elevated pH (>7.42).

• pH <7.0 or >7.7 can be fatal due to severe disruption of cellular processes.

Acid-Base Balance Mechanisms

• The body controls constant changes in pH using three primary mechanisms to regulate CO2, H^+, and HCO3^-:

  • Buffers: Chemical systems that resist changes in pH by binding or releasing H^+.

  • Ventilation/respiratory system: Adjusts the rate and depth of breathing to alter CO_2 levels in the blood.

  • Renal system: Regulates the excretion or reabsorption of H^+ and HCO_3^- to maintain acid-base balance.

• The biggest source of acid on a daily basis is CO_2 production from aerobic respiration, which generates metabolic acids.

• Buffers:

  • HCO_3^- in ECF: Bicarbonate is a major buffer in extracellular fluid, neutralizing excess acid.

  • Proteins, hemoglobin, phosphates in ICF: Act as buffers within cells, counteracting pH changes.

  • Phosphates & ammonia in urine: Help to buffer urine, facilitating the excretion of excess acid by the kidneys.

Acid-Base Balance: Respiratory System

• The body uses ventilation as a homeostatic mechanism for adjusting pH by altering CO2 levels: CO2 + H2O \rightleftharpoons H2CO3 \rightleftharpoons H^+ + HCO3^-

• Changes in ventilation can both correct and cause acid-base imbalances:

• Hypoventilation:

  \uparrow CO2 + H2O \rightleftharpoons H2CO3 \rightleftharpoons H^+ + HCO_3^-

• Hyperventilation:

  \downarrow CO2 + H2O \rightleftharpoons H2CO3 \rightleftharpoons H^+ + HCO_3^-

Acid-Base Balance: Renal System

• Two types of intercalated cells (A and B) line the collecting ducts of the kidneys and control the excretion/reabsorption of H^+ and HCO_3^- to maintain acid-base balance.

• Both cell types have high levels of carbonic anhydrase (CA) in the cytoplasm and K^+ - H^+ antiporters on the cell membrane.

• Type A cells secrete acid, while type B cells secrete base, allowing for precise regulation of pH.

• Type A cells: Excrete H^+ into the urine and reabsorb HCO_3^- into the blood to correct acidosis.

• Type B cells: Excrete HCO_3^- into the urine and reabsorb H^+ into the blood to correct alkalosis.