Integrative Cellular Physiology 303B EXAM 2 NOTESSignal Transduction Pathways that Alter Gene Expression—This process involves the binding of an extracellular signal to amembrane receptor, which then transduces a signal intracellularly to the nucleus in order to create a change in gene expression. These long-term changes move on a slower time scale and Red Blood Cells are an example of a cell that contains no nucleus.Hereditary Hemorrhagic Telangiectasia (HHT)—This disease occurs in about one to every 5000-8000 people and 1.2 million people are affected with this disease worldwide. This is a vascular disorder that affects multiple systems in the body and it leads to the production of focal vascular lesions known as talengiectasias and arteriovenous malformations. - Inheritance Genetics—This is an autosomal dominant disease, meaning it is not located on sex chromosomes (menand women have it) and you need only mutated copy of the gene to show the disease.o Haploinsufficiency is the probable cause in most cases, which involves a loss of function of the mutated gene (no activity) and the one gene that functions properly is not sufficient because it doesn’t produce enough mRNA and protein in order to function properly.o Some mutations can also be dominant negative, which is not a loss of function problem, but rather the generation of bad proteins that can inhibit normal protein function. - There is also marked intrafamilial variation associated with this disease—o Incomplete Penetrance—This refers to the percentage of people with the disease that display symptoms of the disease.o Variable Expressivity—This term refers to the range of the severity of the disease symptoms that patients with the disease are facing. - Diagnosis of HHT—Diagnosis is definite if three of the following criteria are met:o Spontaneous and recurrent epistaxis (nosebleeds)o Multiple telangiectasias at characteristic siteso Visceral vascular lesions (gastrointestinal telangiectasias and proven arteriovenous malformations on lung, liver, brain, or spine) o Family history of HHT (first-degree relative) - Clinical Presentation of HHT—Defects may appear in childhood but they ten to get worse with age, many patients experience only nosebleeds and telangiectasia, 1/3 of patients have chronic anemia due to the GI bleeding, and a majority of the patients will have arteriovenous malformations that are usually silent—pulmonary (50%), hepatic (30 %), cerebral (10 %) and spinal (1%). - Potential Complications of HHT—Anemia due to severe nosebleeds or GI bleeding, complications that may be life-threatening due to large arterivenous malformations in lungs, brain, liver and GI tract, including hemorrhage, stroke, or brain infection; rarer complications include congestive high output heart failure.- Treatment and Management of HHT—Stop or prevent the bleeding, increase clotting ability, replenish lost blood, monitor for more serious complications and potentially block off local sites where there is a blood vessel defect. The Underlying Disorder in HHT has to do with Abnormal Vascular Architecture—1. Telangiectias—a. These are focal dilations of microvessels, such as arterioles and venules in the dermal vasculature.b. There is an overall decrease in the number of lack of capillaries and the vessels may become convoluted in larger lesions in later stages of HHT.c. These are commonly found on skin and mucous membranesd. In the skin, over time, capillaries disappear and arterioles connect directly into venules and there is also a large increase in smooth muscle cells in the veins. 2. Arteriovenous Malformations (AVMs)—a. This occurs when there is direct connection between much larger vessels such as arteries and veins due to adecrease or lack of capillaries. b. These are bigger than telangiectasias and can be up to several centimeters in diameter. c. AVMs can present as a big, fragile tangle (called a nidus) of arteries and veins. A nidus is a very serious issue in the brain because it can lead to clotting and a stroke occurring. d. AVMs have the ability to develop in different parts of the vasculature, for example between the pulmonary arteries and the pulmonary veins and between the systemic arteries and veins in the nose, brain, pancreas, gut, and the liver.Cardiovascular System—This is required as a mechanical pump in order to send blood and nutrients throughout the body,we cannot rely on diffusion for the transport of nutrients and gases over long distances. - Without a blood supply, tumors would only be able to grow to a couple millimeters in diameter because with the inhibition of blood vessel growth through tumors, they would not receive proper oxygen. - Typical cells are no more than 100 microns away from a capillary to allow for proper diffusion and there are over 60,000 miles of capillaries in your body. - Functions of the CV System—Transport and exchange (Lungs: oxygen and CO2, Excretory organs: wastes (kidneys), Gut: nutrients, Tissues: oxygen, CO2, hormones, wastes, nutrients, electrolytes), fluid balance, dissipationof excess heat, and pH homeostasis (buffers) - Homeostasis: The CV system helps to maintain a relatively constant environment around cells (pH and temperature)- William Harvey was the first to explain the motion of blood in the heart and throughout the body of it being a circular flow with ceaseless motion. - Vertebrates (including humans) and a few invertebrates contain a closed circulatory system in which blood is contained within vessels of varying size and thickness at all times. With out high metabolic rate, a closed system allows for imparting pressure to move materials. - Components of the cardiovascular system include the heart (a driving force that pumps blood throughout the circulation), blood vessels (allow for the deliverance of blood), and blood (which carries oxygen and carbon dioxide). - Total Cross-Sectional Area—The capillaries (all together) have the greatest total cross-sectional area of about 4,500cm2. The total cross-sectional area is an important determinant of the velocity of blood flow because blood moves through the capillaries at a slower linear velocity due to the time required for the exchange of materials. o The velocity of blood flow begins to decrease in the arterioles and becomes very slow in the capillaries, where is then increases again throughout the venules in a parabolic shape. The total-cross sectional