Lecture 1 – Homeostasis and Second Messenger Physiology (Online Slide 1) Anatomy 1. Form and structure – heart, kidney tubules, brain 2. Connections – nervous circulatory Chemistry 1. Molecular structure a. Proteins – hemoglobin, contractile, hormone receptors b. Membrane lipids 2. Chemical reactions – enzymes Physical Forces 1. Electrical – nerve impulses, muscle potentials 2. Mechanical – blood pressure, muscle contraction 3. Molecular diffusion Major Cell Types In The Body (Fig 1.2 a,b) 1. Neurons – long and thin; conduct neural potentials 2. Muscle cells – contractile proteins; skeletal, smooth or cardiac muscle cell types 3. Epithelial cells 4. Connective tissue cells Epithelial Cells (Fig 1.2 c, 4.23) 1. Cells designed to form sheets 2. Serve as a barrier between the lumen and the interstitial fluid 3. Form protective barrier from the external world 4. Form tight junctions which serve as fusion such as glue; do not allow for transport 5. Specialized for transport into and out of the body (transmembrane proteins) Connective Tissue (Fig 1.2 d) 1. Contain a scattering of cells immersed in an extracellular matrix a. Blood cells in plasma make up blood b. Cartilage cells in collage make up cartilage c. Fat cells in globules make up fat d. Osteocytes in calcium deposits make up bone Organ Systems (Table 1.1) System Organs/tissues within the system Function Endocrine Hypothalamus, pituitary, adrenal, thyroid, parathyroid, thymus, pancreas Provide communication between cells of the body through the release of hormones into the bloodstream Nervous Brain, spinal cord, peripheral nerves Provide communication between cells of the body through electrical signals and the release of neurotransmitters into small gaps between certain cells Musculoskeletal Skeletal muscle, bones, tendons, ligaments Support the body; allow voluntary movement of the body & facial expressions Cardiovascular Heart, blood vessels, blood Transport molecules throughout body in bloodstream Respiratory Lungs, pharynx, trachea, bronchi Bring oxygen into the body and eliminate carbon dioxide from the body Urinary Kidneys, ureters, bladder, urethra Filter blood to regulate acidity, volume and ion concentrations; eliminate waste Gastrointestinal Mouth, esophagus, stomach, small intestine, large intestine, liver, pancreas, gallbladder Break down food and absorb it into the body Reproduction Gonads, reproductive tracts and glands Generate offspring Immune White blood cells, thymus, lymph nodes, spleen, tonsils, adenoids Defend the body against pathogens and abnormal cells Integumentary Skin Protect the body from the external environment Negative Feedback Control (Online Slides 2,3) Homeostasis: Constancy of Internal Environment (Fig 1.4) 1. There must be a consistency of the internal environment in the body. 2. Only a small degree of variation is allowed. 3. Homeostasis is maintained between the blood/interstitial fluid and the various organs of the body. 4. This ensures the optimal functioning of the cells in the body. Thermoregulation (Fig 1.9) 1. Thermoreceptors on the body sense the external environment relative to the internal. 2. That information is sent to the brain. 3. Let’s say the body temperature needs to be raised. Three events can occur. 4. First, the opening of sweat glands causes body temperature to drop, so sweat glands close. 5. Second, an increased constriction of blood vessels close to the skin’s surface will reduce blood flow and reduce heat loss. 6. Third, the rapid contraction of skeletal muscles will cause shivering, increasing heat generation and increasing body temperature. Reflex Arc: Stretch Reflex (Fig 10.19) 1. The knee jerk reflex is an example of negative feedback control. 2. A stimulus strikes the knee. 3. The signal is sent to the spinal cord via an afferent neuron. 4. The signal is registered and a response is sent out via an efferent neuron. 5. The signal tells the leg to move forward, shortening the muscle. 6. The shortening is registered in the brain, and homeostasis is maintained by lengthening it again. Positive Feedback 1. The pituitary gland releases LH hormone. This tells the ovaries to increase estrogen production. Increased estrogen production tells the pituitary gland to release more LH until a follicle bursts and releases an egg. 2. A neural membrane becomes slightly positive, causing some sodium ion channels to open. This allows a few sodium ions to flow in, making the membrane more positive. This opens more ion channels, allowing more sodium ions to flow in, making the membrane more positive. This chain reaction continues until the action potential is reached. Intercellular Communication (Fig 5.1) 1. May have direct communication via gap junctions. a. Made up of proteins called connexons (6 units on each cell, 12 units in one junction) b. Allows for free flow of small molecules or ions from cell to cell. 2. Chemical messenger a. One cell releases a messenger, such as a hormone b. Target cell has a receptor for the messenger c. Triggers a series of biochemical reactions Chemical Messengers (Fig 5.2 a,b) 1. Paracrines – secreted by one cell and diffuse to a nearby target cell 2. Autocrines – bind to receptors on the cell that secreated them Paracrine Communication (Online Slide 4) 1. Histamine – Production of hives a. Antigen is applied locally to skin and binds to IgE antibodies attached to Mast cells b. Mast cells release histamine c. Stimulates nerve endings and increases permeability of capillary walls d. Fluid movement into interstitial space swells tissue 2. Nitric Oxide – Control Blood Flow a. Low blood O2 in tissue b. Endothelial cells lining walls of small blood vessels release nitric oxide c. Nitric oxide relaxes smooth muscle in blood vessel walls d. Blood vessels dilate e. Increased blood flow raises tissue O2 levels Chemical Messengers (Fig 5.2 c,d,e) 1. Neurotransmitters – secreted from neuron at functionally specialized structures called synapses; axon terminal of a presynaptic cell releases the neurotransmitter, which then diffuses a very short distance to bind to receptors on a specific target cell, called the postsynaptic cell 2. Hormones – secreted by endocrine cells into the interstitial fluid; then diffuse into the bloodstream for transport to target cells in the body; target cells identified by the presence of receptors for the specific hormone; cells without receptors for the hormone cannot respond to its signal 3. Neurohormone – special class of hormones secreted by neurons into interstitial fluid; then diffuse into the blood for transport to target cells throughout the body G Protein Regulation (Fig 5.16) 1. A messenger (hormone) binds to a receptor in the cell membrane in a lock + key type fit. 2. The receptor is connected to G proteins. The alpha subunit breaks off and GDP is converted into GTP. 3. GTP binds to the alpha subunit, which then binds to an amplifier enzyme called adenylate cyclase, which catalyzes the synthesis of a second messenger (could be cyclic AMP or cAMP). 4. The second messenger activates the enzyme protein kinase. 5. Protein kinase’s job is to phosphorylate a protein using a phosphate from ATP, changing it into ADP. 6. This can either activate or deactivate a protein. Epinephrine Triggers Glucose Release From Liver Cell (Online Slide 5) 1. Glycogen ( n glucose a. Epinephrine binds to receptor, triggering production of cAMP b. cAMP activates Protein Kinase A, which phosphorylates hydrolytic and synthetic enzymes. c. Hydrolytic enzymes become activated, breaking glycogen into n glucose d. Synthetic enzymes become deactivated, stopping n glucose becoming glycogen 2. n glucose ( Glycogen 1. Epinephrine binds to receptor, triggering production of cAMP 2. cAMP activates phosphatase, which dephosphorylates hydrolytic and synthetic enzymes. 3. Hydrolytic enzymes become deactivated, stopping glycogen breaking down into n glucose 4. Synthetic enzymes become activated, turning n glucose into glycogen Signal Amplification (Fig 5.18) 1. One messenger binds to one receptor. 2. One receptor activates several G proteins. 3. Each G protein activates one adenylate cyclase. 4. Each adenylate cyclase generates hundreds of cAMP molecules. 5. Each cAMP molecule activates one protein kinase. 6. Each protein kinase phosphorylates hundreds of proteins. 7. So one messenger molecule leads to the phosphorylation of millions of proteins.