Electrical and Chemical Signals

Types of Communication

• Electrical signals generate a fast, rapid response with short-lived effects.
• Chemical signals generate a slower response, but their effects are long-lived.

Electrical Signals

• Cell membrane potentials change, triggering cellular responses such as action potentials or graded potentials.
• Resting potential is -70mV, relative to the inside of the cell.
• Depolarization occurs when sodium or calcium enters the cell, raising the potential above -70mV.
• Action potentials are reversals of polarity and travel long distances without fading; they are self-propagating and operate on an all-or-none principle.
• Repolarization involves potassium exiting the cell, returning it to -70mV.
• Hyperpolarization occurs when chloride enters the cell, dropping the potential below -70mV, inhibiting the cell.
• Glycine and Gamma-aminobutyric acid (GABA) cause inhibition of cells.
• Graded potentials can be depolarizing or hyperpolarizing, but fade with time and distance.
• Depolarizing graded potentials (EPSPs) may lead to muscle contraction or secretion of insulin.
• Hyperpolarizing graded potentials (IPSPs) inhibit muscle contraction or neuron activation.

Chemical Signals

• Hormones travel via the blood and neurotransmitters are secreted by neurons.
• Endocrine glands secrete hormones to target sites of action, binding to receptors to cause a response.
• Neurotransmitters secreted by neurons also bind to specific receptors for a cellular response.
• Neurohormones are hormones secreted by neurons

Endocrine Glands

• Endocrine glands involves hormones such as growth hormone, insulin, calcitonin, parathyroid hormone, estrogen and androgen.
• Chemical messengers bind to receptors on or in target cells.
• Neurotransmitters includes, ACH, epinephrine, norepinephrine, dopamine, serotonin, histamine, glutamic acid, glycine, GABA, ATP, Adenosine, nitric oxide, carbon monoxide
• Catecholamines: are epinephrine, norepinephrine, dopamine.
• Neurohormones include ADH (antidiuretic hormone) and oxytocin.
• ADH causes water reabsorption in the kidneys, preventing diuresis, and synthesized in the hypothalamus
• Presence of ADH leads to concentrated urine with less volume.
• Absence of ADH leads to water loss, diluted urine, and excessive thirst causing diuresis.
• Prolonged ADH absence can lead to diabetes insipidus.
• Oxytocin causes uterine contractions or milk ejection.

Hypothalamus

• Neurohormones from the hypothalamus regulate pituitary functions: releasing factors and inhibiting factors.
• TRH (thyrotropin-releasing hormone), which is the smallest known hormone (3 amino acids).
• Other releasing hormones are CRH (corticotropin-releasing hormone) and GnRH (gonadotropin-releasing hormone), GHRH (growth hormone release hormone).
• Inhibiting factors block secretion of hormones; SRIF (somatotropin release-inhibiting factor) or somatostatin (SST), and PIF (prolactin-inhibiting factor).

Neurohormones from the GI Tract

• Ghrelin comes from the stomach and increases appetite.
• Secretin causes secretion of pancreatic juice rich in bicarbonate to neutralize stomach acid.
• Cholecystokinin (CCK) causes contraction of gallbladder, bile secretion, and pancreatic enzyme-rich secretion and regulates eating.
• Motilin controls peristalsis.
• Glucagon-like peptide-1 (GLP-1) inhibits appetite.
• Gastric Inhibitory Peptide (GIP) inhibits gastrin secretion and stimulates insulin release.
• Somatostatin (SST) is also produced by the hypothalamus (where it is called SRIF).
• Vasoactive intestinal polypeptide (VIP) acts on smooth muscles of sphincters causing relaxation when sphincter opens and allows food to move forward.
• Achalasia is a condition where the lower esophageal sphincter does not open, due to lack of VIP.

Homeostasis

• Balance between internal and external environments which involves sensors detecting changes from a set point.
• Sensors include glucoreceptors, osmoreceptors, chemoreceptors, and baroreceptors.
• Negative feedback is constantly active to maintain homeostasis.
• Hyperglycemia triggers insulin secretion to restore normal glucose levels.
• Positive feedback is only active as needed causing an increase in response.
• Suckling stimulates oxytocin release causing milk ejection.
• Parturition: Uterine contractions during childbirth cause stretch receptors to fire, sending signals to the hypothalamus to secrete oxytocin

Homeostasis History

• Claude Bernard in the 18th century proposed concept of internal/external environments that depend on each other.
• Walter Canon in 1930 founded and named Homeostasis.

Functions of the Endocrine System

• Osmoregulation maintains water and electrolyte balance using ADH, which elevates BP and retains water.
• Aldosterone regulates sodium reabsorption and water retention in kidney tubules.
• Metabolism is controlled by basal metabolic rate, which is affected by height, weight, age, and body surface area.
• T3 and T4 control metabolic rate and physical growth; deficiency leads to cretinism in children.
• Insulin and glucagon maintain blood glucose level.
• Reproduction: Hormones are essential for embryonic development, fertilization, gametogenesis, reproductive cycle, sex differentiation, pregnancy, and lactation.

Reproduction

• Dihydrotestosterone (DHT) is necessary for male genitalia development during the 7-8 weeks of embryonic life.
• GnRH from the hypothalamus causes the pituitary to secrete gonadotropins (FSH and LH).
• FSH causes follicular maturation in females.
• LH causes ovulation.
• Primary follicles produce estradiol-17 Beta.
• After ovulation, the discharged follicle (need LH) creates the corpus luteum that secretes progesterone.
• Fertilization: The corpus luteum remains for 3 months vs 2 weeks, during pregnancy.
• Human chorionic gonadotropin (HCG) maintains placenta during pregnancy.
• In males, FSH acts on testes for spermatogenesis and affects Sertoli cells to secrete Anti-Mullerian hormone (AMH).
• LH acts on testes for testosterone production by Leydig cells.

Physical Growth and Development

• Growth hormone (somatotropin) from the pituitary gland increases height.
• Growth hormone causes the liver to make somatomedins (IGF 1&2) which goes to the epiphysis causing bone elongation.

Hormones of the GI Tract

• Play a crucial role in digestive physiology.

Classification of Hormones

• Protein hormones: origin is the pituitary, pancreas, hypothalamus, parathyroid gland, thymus, kidneys, heart.
• Steroid hormones: origin is the adrenal cortex, testes, ovaries, skin, bile.
• Biogenic Amines: Tyrosine can be converted to catecholamines and histamine, serotonin, and melatonin.
• Tyrosine gives T3 and T4 they make melanin
• Eicosanoids: Prostaglandins.

Transport, Synthesis, and Elimination of Hormones

• Peptide hormones start as pre-pro-insulin → pro-insulin → insulin.
• Free hormones circulate unbound such as insulin, glucagon, PTH, and calcitonin.
• Bound State: T3 and T4 circulate with transthyretin, cortisol circulates with transcortin and testosterone and DHT circulate with androgen-binding protein.
• Hormones are eliminated by kidneys, degradation or enzymes.
• Enzymes: insulinase degrades insulin and monoamine oxidase (MAO) degrades epinephrine/ norepinephrine.
• Hormones have a half-life: time it takes for a hormone to reduce by 50%.

Mode of Action of Hormones

• The hormone exits the source, travels through blood to the target, binds with receptors and causes a response and all receptors are proteins.
• Up-regulation is receptors increase in numbers.
• Down regulation is receptors decrease in number.

Receptors

• Cell surface receptors act on protein hormones such as insulin, glucagon, PTH, epinephrine, FSH, LH, TSH, ACTH, ADH, oxytocin.
• Nuclear or Cytosolic Receptors act on steroids such as T3/T4 , testosterone, estradiol-17beta, cortisol, aldosterone.

Surface Receptors

• Ion channels such as ACH.
• G-Protein coupled receptors where g-protein changes to GTP and is active and GDP is inactive.
• Adrenergic receptors bind epinephrine and norepinephrine
• Beta 1 - speeds up the heart
• Beta 2 - vasodilation
• Alpha 1 - vasoconstriction

Hormones that act via 2nd messenger

• Catecholamines, ACTH, FSH, LH, Glucagon, PTH, TSH, and Calcitonin.

Glands Secretions

• Pineal Gland: Melatonin secretion.
• Hypothalamus: TRH, CRH, GnRH, SRIF, ADH, Oxytocin secretion.
• Pituitary Gland:
  • Anterior Pit: Prolactin, somatotropin, corticotropin (ACTH), thyrotropin (TSH), Gonadotropin (FSH, LH), Melanocortin (MSH) secretion.
  • Posterior Pituitary: Releases ADH and oxytocin into the blood.
• Parathyroid Glands: PTH (parathyroid hormone increases calcium levels).
• Pancreas: Insulin, Glucagon, Somatostatin secretion.
• Gonads: Androgens, estrogens secretion.
• Adrenal Glands: 2 portions
  • Adrenal medulla: Epinephrine, Norepinephrine, dopamine:Catecholamines leads to a rise in BP and blood Glucose levels- they prepare the body for fight/flight. Catecholamines bind to adrenergic receptors.
  • Adrenal Cortex: secretes cortisol, aldosterone:Steroid hormones - Zona glomerulosa: produces aldosterone causing Na+, Zona fasciculata: secretes cortisol anti-inflammatory, , Zona Reticularis: secretes dehydroepiandrosterone (DHEA) which can change into testosterone.

Hypothalamus and Pituitary Gland

• Originates as 2 portions
• Anterior: : Somatropinne cells make somatotropin (growth hormone), Corticotrope cells make corticotropin (ACTH), Gonadotropes make gonadotropins (FSH, LH), Thyrotropes: Thyrotropin (TSH), Melantropes: Melanocyte-stimulatinhormone MSHSH, Lactrotropes: (prolactin).
• Posterior: : Releaes ADH and oxytocin into blood.

Somatotropin

• Somatotropin activates the Liver which makes somatomedins (insulin-like growth factors IGF 1 AND 2 which travels to the Epiphyseal plate causing Bone Elongation.
• Dwarfism is the lack of growth hormone and Gigantism is the excess of Growth hormone in children.
• Acromegaly is adult excess growth hormone.

Negative Feedback

• TSH(thyrotropin) to the thyroid produces T3/T4, if levels are too high TSH secretion is blocked for homeostasis, at the pituitary and hypothalamus level.
• ACTH to the adrenal cortex to secrete cortisol and dehydroepiandrosterone (DHEA), too much blocks ACTH

Hypothalamus Factors

• TRH, pituitary, Thyrotropin, thyroid, T3/T4.
• CRH, pituitary, ACTH , adrenal cortex, cortisol and DHEA.
• GnRH, pituitary, FSH (Follicular Maturation), Ovary/testes.
• GnRH, pituitary, LH, ovary/testis, ovulation/testosterone.
• GHRH, pituitary, growth hormone.
• SRIF (somatostatin), pituitary, inhibits somatotropin.
• PIF =dopamine, pituitary, inhibits prolactin

Thyroid

• Largest, purely endocrine gland is made up of thyroid follicles which are single layer of cuboidal epithelium: thyrocytes, colloid center-protein with tyrosine amino acids-iodination from T3/T4 in circulation.
• Basolateral (blood side) and apical side (colloid side).
• Parafollicular cells secrete calcitonin (causes hypocalcemia).
• Basolateral side (blood side) and apical side (colloid side).

Thyroid Process

• Iodine enters cells with Na+ via Na+/I- symporter (Secondary active transport).
• Na+ exits K+ enters via Na+/K+ ATPase pump (Primary active transport).
• Iodine oxidation by TPO (thyroid peroxidase).
• T3/T4 releases into the blood and into the basolateral side.
• T3 is the most potent while T4 is the most abundant.
• Thyroid is necessary for neuronal, physical, and gonadal growth.
• Hypothyroidism leads to cold, lethargic symptoms.
• Hyperthyroidism leads to warm and sweating symptoms and Graves disease.

Parathyroid Glands

• PTH causes hypercalcemia and is responsible for regulation of plasma Ca2+ because calcium is need for muscle contraction
• PTH bone Ca2+ can be put into the blood causing hypercalcemia

Calcitonin Causes

• Hypocalcemia causes blood calcium to go to bone.
• Vitamin D3 helps absorb calcium in the intestine.

Pancreas

• Acinar cells are the source of pancreatic enzymes.
• Alpha cells and hyperglycemia breakdown glycogen (glycogenolysis) and create sugar (gluconeogenesis) from proteins, lipids (lipolysis).
• Beta cells causes hypoglycemia glucose oxidation→ ATP production.
• Delta cells are a source of somatostatin (SRIF): inhibits insulin and glucagon.

Diabetes Mellitus

• Type 1: no beta cells=no insulin, has to be given insulin for the whole life, type 1 is called insulin-dependent diabetes mellitus (IDDM) blood glucose level high.
• Type 2: insulin is present but insulin receptors are not working and also called noninsulin-dependent diabetes mellitus (NIDDM), Perhaps (insulin resistance b/c there is down-regulation of insulin receptors → receptor desensitization)
• Gestational diabetes can occur during pregnancy.

Thymus

• T-cell maturation- immunological memory-remembers what belongs to the body and what does not.

Pineal

• Makes melatonin - anti-aging, anti-oxidant, anti-gonadal, induces sleep, secreted in darkness.

Respiratory System

• Ventilation or mechanics of breathing is how air goes in and out of the lungs with the diaphragm contraction.
• Uptake and transport of gases is to load O2 in lungs and unload in tissues and control is by CO2 more than O2.

Anatomical Structure

• Upper respiratory tract: nose → nasal cavity or passage → nasopharynx or oropharynx
• Lower respiratory tract: laryngopharynx → trachea → divides into 2 bronchi or bronchial tree → bronchioles → terminal bronchioles → respiratory bronchioles → alveolar ducts → alveoli air sacs
• Conducting zone: nose to terminal bronchioles and the respiratory zone is respiratory bronchioles to alveoli.
• Epithelium is non-keratinized, the right lung has 3 lobes and the left has 2 lobes

Upper Respiratory Tract

• Superior, middle, and inferior nasal conchae are paper-thin bones lined with mucus membrane that help equilibrate air temp
• Cilia: traps bacteria, dust particles.
• Paranasal sinuses: frontal, sphenoidal, ethmoidal, and maxillary.

Structures of the Pharynx

• Nasopharynx: behind the nose, unpaired pharyngeal tonsils.
• Oropharynx: behind the mouth, paired palatine tonsils.
• Laryngopharynx: Sound box, common path for air and food.

Larynx

• Sound box
• Paired cartilages: arytenoid, cuneiform, corniculate and unpaired: thyroid, cricoid, and epiglottis.
• Vestibular folds and vocal folds vibrations determine frequency and amplitude.

Trachea/Bronchioles

• 13 CM long and 2.5 cm wide and has pseudostratified ciliated columnar epithelium.
• Carina is the last ring division which is the Trachea divided into the left and right bronchus.
• Right bronchus is wider and more vertical and left bronchus is narrower and more horizontal
• Alveoli: lined with a single layer of simple squamous epithelium and where gases are picked up via simple diffusion.
• Bronchioles only 1 mm in diameter and collapsed
• Bronchodilation is when bronchioles too wide with smooth muscles relaxed versus Bronchoconstriction.
  • Pneumocytes: Two type 1: gas exchange and type 2: secrete surfactant.

Lungs

• Surrounded by pleural cavity has pleural pressure - cavity has negative pressure.
• When one has an injury, there is a loss of negative pressure and the lung collapses = pneumothorax (loss of the lungs being completely surrounded by the 2 mucous membranes.

Ventilation or Mechanics

• Normal breathing is quiet breathing aka Eupnea.
• Forced breathing is different.
• Inspiration is an active process, and expiration is a passive process.
• Inspiration is diaphragm contracted and Expiration: diaphragm released.
• Inspiration, external intercostals muscles contract vs Expiration: external intercostal muscles relax