Physio 1: Homeostasis and Body Regulation

Medical Homeostasis

• Body temperature, blood sugar, fluid pH, and electrolyte balance (K+, Cl-, HCO3-, Na+, Mg2+, Ca2+) are regulated through negative feedback components of homeostasis.

Set Point

• Target value of the control system, which is set to maintain homeostasis.
• Examples: O2 for respiration and ATP production, blood glucose levels.

Negative Feedback Components

• Sensors: Continuously monitor a controlled variable.
• Comparator: Interprets sensory input to determine deviations from the set point and initiates a counter response.
• Effectors: Organs that bring about change to restore the set point to normal levels.

Glucose Control

• Insulin is secreted by beta cells in the pancreas to regulate blood glucose levels.
• Insulin stimulates the insertion of GLUT transporters to facilitate glucose uptake.
• Glycogen is stored in the liver and broken down to glucose when needed.

Blood Pressure Control

• Controlled variable: Mean arterial blood pressure (MAP).
• Set point: MAP = 95 mm Hg.
• Sensor: Intravascular pressure sensor located in the carotid sinus.
• Comparator: CNS site in the medulla oblongata.
• Effectors: Cardiac rate and contractility, vascular tone, and urinary fluid excretion.

Osmosis

• Water movement driven by a water concentration gradient across a membrane.
• Hypertonic IVF: promotes osmosis of fluid out of the cell, causing it to shrink.
• Isotonic IVF: does not promote osmosis, increasing extracellular volume without changing cell size or concentration.
• Hypotonic IVF: promotes osmosis of extracellular fluid into the cell, causing it to swell.

Electrical Potentials

• Movement of ions across the cell membrane creates a charge imbalance between the intracellular fluid (ICF) and extracellular fluid (ECF).
• This charge imbalance creates a voltage difference across the cell membrane, known as the membrane potential (Vm).
• Typical nerve cell has a resting Vm = -70 mV.

Diffusion and Equilibrium Potentials

• More sodium outside the cell than inside, and more potassium inside the cell than outside.
• Sodium pump maintains the balance of sodium and potassium ions.
• Most cells at rest have minimal permeability to Na+ or Ca2+, and significant permeability to K+.

Cellular Bioenergetics

• Energy is stored in molecular bonds between phosphoric acid molecules and other organic compounds.
• High-energy phosphate compounds contain phosphate bonds that release energy when hydrolyzed.
• Compounds such as ATP, NAD, and NADP are used to store energy.

Cellular Respiration

• Glycolysis: breakdown of glucose to pyruvate or lactate, producing ATP.
• Fatty acid oxidation: metabolized to acetyl-CoA.
• Amino acid catabolism: from proteins can be ketogenic or glucogenic.
• Gluconeogenesis: non-carbohydrate source of energy.
• Citric acid cycle: acetyl-CoA metabolized to CO2 and H+, while consuming O2 and producing ATP and H2O.

Hydrolysis of ATP

• ATP is hydrolyzed to ADP and Pi, releasing energy.

Oxidation of Acetyl-CoA

• Produces ATP, CO2, and H2O while consuming H2O.### Cellular Stress and Hypertrophy
• Cellular stress leads to changes in morphology and hypertrophy, increasing tissue mass by increasing cell size
• Enlargement of the nucleolus indicates increased contractile protein synthesis and cell growth, an early indicator of cardiac hypertrophy
• Mature cardiac cells (myocites) lose the ability to undergo mitosis, leading to heart failure, cardiovascular disease, and anemia

Chromosomal DNA Abnormalities

• Turner syndrome: affects only females, resulting from a missing or partially missing X chromosome (XO)
• Klinefelter syndrome: one extra copy of the X chromosome is present in males (XXY), resulting in phenotypic abnormalities (tall stature, gynecomastia, and a more gynecoid pelvis structure)
• Sickle cell anemia: mutation of the Hb-beta gene on chromosome 11, causing an inability of Hb to carry oxygen and resulting in abnormal RBC shape

Rough Endoplasmic Reticulum (RER)

• Involved in protein synthesis
• Alterations in RER homeostasis (cellular stress) lead to abnormal increased protein synthesis, accumulation of misfolded proteins, and alterations in calcium balance, associated with:
  • Alzheimer's disease
  • Parkinson's disease
  • Amyotrophic lateral sclerosis (Lou Gehrig's disease)
  • Type 2 diabetes
  • Atherosclerosis
  • Nonalcoholic fatty liver disease
  • Alcoholic liver disease
  • Cancer

Smooth Endoplasmic Reticulum (SER)

• No ribosomes
• Involved in steroid hormone production (more prominent in testes, adrenal cortex, and ovaries)
• Involved in lipid and carbohydrate synthesis
• Liver has more SER for metabolic and detoxification processes
• Stress on SER can interfere with signaling, leading to:
  • Type 2 diabetes
  • Atherosclerosis
  • Alcoholic and nonalcoholic fatty liver disease
  • Endocrine disorders
  • Cancer

Golgi Body

• Functions, modifies, and segregates proteins for secretion
• Synthesizes lysosomes
• Associated with neurodegenerative diseases:
  • Parkinson's disease: broken ribbon formation of Golgi causes malfunction in intracellular functions and alters cytoskeleton
  • Alzheimer's disease: degenerative brain disease causing dementia
  • Amyotrophic lateral sclerosis: progressive disease atrophying motor neurons in the spinal cord and brain

Lysosomes

• Malfunctioning protein packaging and breakdown, associated with:
  • ALS and Parkinson's: buildup of unusable proteins becomes toxic
• Tay-Sachs disease: deficiency in the enzyme that metabolizes fatty substances, inherited and progressively destroys nerve cells in the brain and spinal cord
• Fabry disease: deficiency in alpha-galactosidase
• Gaucher disease: deficiency in galactocerebrosidase

Mitochondria

• Converts chemical energy in food to ATP
• Regulates immunity, Ca2+ homeostasis, and apoptosis
• Associated with:
  • Cyanide: disrupts ETC, preventing ATP formation using oxygen
  • Leigh syndrome: genetic disorder causing CNS degeneration due to abnormal mitochondrial energy production
  • Epilepsy and encephalopathy: certain types

Centriole

• Duplication necessary for cell division
• Organizes mitotic spindles during mitosis
• Abnormalities linked to neurodegeneration, autoimmune disorders, and solid breast tumors
• Increase in centrioles: hallmark of cancer
• Structural defects linked to changes in gene expression

Microtubules

• Long, hollow structures forming part of the cytoskeleton
• Give shape to cells
• Protein subunits alpha tubulin and beta tubulin
• In cytoplasm
• Assist movement of proteins and organelles within cells
• Form spindles that transport chromosomes during mitosis
• Partially compose cilia and flagella of sperm
• Primary ciliary dyskinesia: inherited problem with cilia formation, leading to abnormal movement of cilia

Microfilaments

• Smaller version of microtubules
• Actin filaments wound in a spiral
• Allow for intra-cell movements and support cell structure
• Keep cell organelles bound in one place
• Allow for muscle contraction by binding to myosin (thicker filament, contractile protein)
• Associated with:
  • Giant axonal neuropathy: rare genetic disorder affecting both CNS and PNS

Cytoplasm

• Within cell membrane
• 85% water
• Maintains cell shape, intracellular movement, and material exchange
• Dehydration: loss of cellular water causes cell collapse, affecting cell function

Cell (Plasma) Membrane

• Outer membrane surrounding cell cytoplasm and intracellular structures
• Physical barrier, selective permeability, endo- and exocytosis, and cell signaling
• Cell growth, metabolism, and regulation
• Defects associated with:
  • Cancer
  • Hemolytic disease
  • Cystic fibrosis

Membrane Protein

• May be embedded (integral) or peripheral
• Provides passage or selective permeability
• Contributes to preservation of electrochemical gradients
• Associated with:
  • Cystic fibrosis: transmembrane conductance regulator protein (CFTR) regulates flow of chloride and sodium across cell membrane in lungs and GI tract

Skeletal Muscle

• Develops force by contraction
• Muscle columns (fascicles) contain bundles of muscle cells (fibers)
• Each multi-nucleated cell behaves as a single unit, containing many myofibrils
• Sarcomere: fundamental unit of skeletal muscle, with repeated striated pattern segments### Motor Neurons and Muscle Fibers
• Small motor units: motor neurons branch to only a few muscle fibers, allowing for fine control (e.g., hand and eye muscles)
• Large motor units: motor neurons branch to many muscle fibers, resulting in coarse control (e.g., postural trunk muscles)

Sliding Filament Theory (Skeletal Muscle Contraction)

• Thin filaments (actin) slide over thick filaments (myosin) to cause muscle contraction
• Mechanism of skeletal muscle contraction:
  • Relaxed: tropomyosin-troponin complexes block myosin attachment sites on actin
  • Stimulation: Ca2+ binds to troponin, exposing myosin attachment sites on actin
  • Contraction: myosin cross-bridges bind to actin, using energy from ATP hydrolysis and cycling through structural changes
  • Rigor mortis: no ATP, myosin heads can't be released from actin binding, and no muscle relaxation occurs

Force of Skeletal Muscular Contraction

• Controlled by frequency of action potentials (temporal summation):
  • Low frequency: brief contraction and relaxation
  • High frequency: tetanic contraction, maximal cross-bridge attachments
• Controlled by number of active motor neurons (spatial summation):
  • Small motor units: easily excitable, reach few muscle fibers
  • Large motor units: require stronger CNS stimulation, reach many muscle fibers

Skeletal Muscle Diversity

• Slow and fast twitch fibers:
  • Different myosin and protein types, resulting in varying contraction speeds
  • Different proportions of slow and fast twitch fibers in different muscles (e.g., postural muscles: more slow twitch, extraocular muscles: more fast twitch)
  • Genetic differences affecting muscle fiber types and training-induced changes

Tetanus Toxin and Duchenne Muscular Dystrophy

• Tetanus toxin: produced by Clostridium tetani, blocks inhibitory nerves, causing rapid fire of excitatory motor neurons and uncontrolled muscular contraction
• Duchenne Muscular Dystrophy:
  • Lack of dystrophin, a protein linking sarcolemma to myofilaments
  • X-linked inheritance, more common in genetic males
  • Progressive muscle inheritance and eventual death from respiratory failure