Download NURS 8022 – Patho –Exam 1 Study Guide [100% CORRECT] and more Exams Nursing in PDF only on Docsity! /Exam one study guide Membrane Physiology and Action Potentials Outcome 1. Explain the structure of the cell membrane and the organization of it’s polar and non-polar components, including lipids and proteins. Cell membrane has a phospholipid bilayer (1 molecule thick), heads LIKE the water (polar/charge attached) making it hydrophilic, and tails do NOT like the water (nonpolar/uncharged) making it hydrophobic so they face each other. Cholesterol is in the middle amongst the phospholipid tails. Proteins are what makes the cell function. Some go through the entire cell membrane (integral) and some are found only at the edges of the membrane (peripheral). All of these parts are not fixed and can move about the cell membrane. Remember the bilayer is insoluble to most water soluble particles because the middle (tails) are “oily”. This is why the proteins are important as they allow substances in and out of the cell when the cell membrane doesn’t. Oxygen and carbon dioxide move freely through it as they are fat-soluble. Glycoproteins on the membrane tell other cells what type it is (McCance & Huether, 2014). Proteins are the workhorse of the cell (transport, enzyme, receptors, markers) Club bouncers. The fatty acids and glycerol form NONPOLAR, hydrophobic tails. The phosphate forms the hydrophilic head which is POLAR. (amy) Referenc es McCance, K. L., Huether, S. E. (2014). Pathophysiology: The biologic basis for disease in adults and children (7th Ed.). St. Louis MO: Elsevier. 4 major functions of Carbohydrates: 1. Most Carbs are negatively charged 2. Can form cell to cell attachments (sticking to other things) cells stick to other cells 3. Can act as receptors for binding with hormones (like insulin) 4. Play important role in immune response Outcome 2. Describe transport across the cell membrane by various means including diffusion, active transport and cotransport, as well as the significance of the Na*-K* pump and other ion channel proteins and their role in membrane electrical processes. | picture simple/passive diffusion oxygen crossing the cell membrane. It does not have to go through a special protein channel, just goes from high to low concentration (I envision someone just sledding down a hill). (Fat soluble substances - O2 & CO2) Simple/Passive Diffusion will not occur if the membrane is non-permeable to the molecule. Facilitated diffusion is similar but it requires another particle (cell membrane protein) to carry an ion across the membrane through a channel. Neither type of diffusion requires energy so they are both passive transport. Note: Hall ch 4- simple diffusion is through the membrane itself (ex A fat soluble substance) and facilitated diffusion requires interaction with a cell membrane protein. Primary active transport requires energy (best example is the sodium potassium pump). As | have been reading, | have pictured this as a pump that is keeping more sodium OUTSIDE the cell and more potassium INSIDE the cell. The outside is more positive so the sodium, if left to its own devices, wants to get inside the cell. This pump is keeping things unequal and establishes what they call the resting membrane potential or concentration gradient. Primary active transport- molecules are pumped (uphill) against a concentration gradient at the expense of energy (ATP)- direct use of energy Secondary active transport is only different because glucose is coming into the cell WITH the sodium molecule (Khan Academy, 2007). The glucose doesn’t normally want to do this (because there is already more glucose inside the cell) so it needs help from the sodium to get in. This is co- transporting. Secondary Active- transport driven by a stored energy created by primary active transport- indirect use of energy References Khan Academy (2007). Uniporters, symporters and antiporters. Biology. Retrieved from sym porters- -and- a ntiporters Cells are more positive outside, more negative inside. In order to reach a state in which there is more positivity outside than inside, they must use the Na-K pump, which uses ATP. There is a higher concentration of Na outside the cell than inside and a higher concentration of K inside than outside. This creates the electrical potential gradient, because the ions are wanting to move to an area that is less crowded. The positive up the opposite direction, releasing the K into the cell. EACH time the Na-K is u ions want to move to a less positive area, and negative ions want to move to a less negative area. The Na-K pump actually moves things outside of the cell. When the pump is inactivated, if there is no ATP, then the ions or Na would just sit there, doing nothing. ATP then pays the pump a fee of one phosphate, and then ATP becomes ADP = energy. Once this energy has been absorbed, the pump releases the Na to the outside of the cell. This requires energy because there is already a lot of Na outside the cell, but you’re pumping more to the outside, which requires energy. So, once this Na is released, the K wants inside the cell even more, and it hitches a ride on the pump, back into the cell. Once the K binds into the pump to catch its ride, it opens back sed, 3 Nais exchanged for 2 K. So there is a plus 1 charge to outside, versus inside ALWAYS keeping the outside MORE charged than the inside. This is what causes the electrical potential difference. -70milivolts is the resting voltage difference across the membrane in a neuron. Outcome 3. Explain the ionic basis of the resting membrane potential (RMP) including how differences in resting K* and Na* permeability influence the RMP. 4. Overshoot: Portion of the AP where the membrane potential is positive (cell interior is positive) 5. Undershoot: aka hyperpolarizing afterpotential a. The portion of the AP, following repolarization where the membrane potential is actually more negative than at rest. 6. Inward Current: positive charge entering cell 7. Outward Current: positive charge exiting cell Outcome 6. Describe the molecular basis of the refractory period immediately following an action potential. The refractory period happens when the potassium channels SLOWLY are closing the doors so the potassium is still leaving the cell for a little bit longer than needed. During most of the action potential the membrane CANNOT respond to additional stimulus. The refractory period is after an action potential during which a new stimulus CANNOT be elicited. The only condition that will allow them to reopen is for the membrane potential to return to or near the original resting potential. The membrane is more permeable to Na and cannot respond to other stimuli until it is no longer more permeable to Na. Outcome 7. Describe the components necessary for skeletal and smooth muscle contraction. In skeletal muscle there is actin and myosin that work together to create muscle contraction. Actin has tropomyosin coiled around it and troponin that seals it down in certain areas. When the intracellular calcium is high enough, the troponin “seal” is broken, tropomyosin moves out of the way and myosin is able to latch onto actin to move along the fiber (Khan Academy, 2007). Smooth muscle: contains both myosin and actin filaments, no striations and more actin is present than myosin. No troponin complex, contraction is activated by Ca ions and ATP that are broken down to ADP. Actin and myosin are controlled and restricted by binding Ca to a protein called Calmodulin. References Khan Academy (2007). How tropomyosin and troponin regulate muscle contraction. Retrieved from https://www. khanacademy.org/science/biology/human-biology/muscles/v/myosin-and- actin Outcome 8. Describe the nervous and hormonal controls of smooth muscle contraction. Smooth muscles are stimulated by nervous, hormonal, and stretching signals. Multiple receptors may facilitate the contraction. Neurotransmitters are ACH and norepinephrine, excitatory and inhibitory. Skeletal Muscle Physiology: 1. Explain the difference between muscle fiber and myofibril - Each muscle fiber is a single muscle cell. This long cell is cylindrical and surrounded by a membrane capable of excitation and important use propagation. - Myofibril is the muscle fibers functional subunit, in a parallel arrangement along the longitudinal axis of the muscle. - Myofibrils are the most abundant subcellular muscle components and are the functional units of muscle contraction - Muscle fibers are created from precursor cells call myoblasts 2. Explain the structure of the sarcomere and how thick and thin filaments are arranged - Sarcomere - The sarcomere is the fundamental unit of muscle structure. Its capacity for contraction is the essential trait that makes muscles work. It has two primary compghfonents (1) thin filaments (each of which contains two strands of actin and a single strand of regulatory protein); and (2) thick filaments made of myosin - Asarcomere is defined between 2 z-disks - Thick filaments = myosin - Thin filaments = actin, tropomyosin, and troponin 3. Explain the process of excitation and contraction coupling and the source and role of Ca?* in this process (skeletal muscle contraction) -Excitation- contraction coupling is the process by which an action potential in the plasma membrane of the muscle fiber tiggers the cycle of events leading to cross- bridge activity and contraction. Activation of this cycle depends on the availability of calcium. -calcium is stored in the tubule system and the sarcoplasmic reticulum. It enters the myocardial cell from the interstitial fluid after electrical excitation (increase intracellular calcium concentration). The released Ca2+ binds to troponin C, which causes tropomyosin to move off of the receptors on the actin. This allows the actin to bind with the myosin and the actin slides over the myosin (this is the muscle contraction) this is what is known as cross-bridge cycling. In relaxation the Ca2+ is reaccumulated into the sarcoplasmic reticulum by the Ca2+ ATPase pump. Ca2+ is released from troponin C and tropomyosin returns to its resting position blocking the binding sites (the actin and myosin release and the muscle cell relaxes). As long as intracellular Ca2+ is low cross-bridge cycling cannot occur and muscle relaxes. (LaToya) 4. Describe the structure of cardiac/smooth muscle and explain differences between skeletal and smooth muscle -Cardiac/smooth muscle is found in walls of hollow organs, vasculature, ureters, bronchioles and muscles of the eye - smooth muscle main function- produce motility and maintain tension - smooth muscle does not have striated arrangements of actin and myosin filaments. There is more actin than myosin. NO troponin complex! Smooth muscle can be stimulated by multiple types of signals= hormones or neurotransmitters (acetylcholine and norepinephrine), stretch of the muscle and others. -Ca2+ binding to calmodulin creates the interaction between actin and myosin -Ca2+-calmodulin regulates myosin- light-chain-kinase, which regulates cross bridge cycling=tension McCance, K. L., Huether, S. E. (2014). Pathophysiology: The biologic basis for disease in adults and children (7th Ed.). St. Louis MO: Elsevier. -Contractile process in smooth muscle is activated by Ca2+ ions and ATP that is broken down to ADP (which is different from skeletal muscle contraction). -Smooth muscles have dense bodies instead of z discs (which equals the same role of z discs in skeletal muscle). -Important difference is that smooth muscle contains “sidepolar” cross-bridges. -Does not have highly structured neuromuscular junction like in skeletal muscle -2 neurotransmitters: Ach and norepinephrine (both excitatory and inhibitory). (LaToya) McCance, K. L., Huether, S. E. (2014). Pathophysiology: The biologic basis for disease in adults and children (7th Ed.). St. Louis MO: Elsevier. Altered Cell and Tissue Biology 1. Describe the cellular adaptations that occur during atrophy, hypertrophy, hyperplasia, occur. dysplasia, and metaplasia and identify conditions under which each can 2 Classifications of Cellular Adaptations: Physiological (occurs in early development). Pathological (occurs in result of decreases in workload, use, pressure, blood supply, nutrition, hormonal stimulation or nervous stimulation.) Atrophy is a decrease or shrinkage in the size of a cell; cellular atrophy most commonly affects the skeletal muscle, heart, secondary sex organs and the brain. Prolonged immobilization can lead to skeletal muscle atrophy. Aging causes brain cells to become atrophic, endocrine dependent organs, such as gonads, begin to shrink as hormonal stimulation decreases. Hypertrophy is the increase in the cell size and consequently in the size of the affected organ, caused by increased workload or hormones; the cells of the heart and kidneys are particularly responsive to enlargement. After the removal of one kidney, the other kidney adapts to an increased demand for work with an increase in both the size and the number of cells. The major contribution to renal enlargement is hypertrophy. Pathological hypertrophy in the heart is secondary to hypertension or valvular dysfunction, advanced hypertrophy can lead to myocardial failure. Another example is larger muscle fibers in result of heavy lifting. Physiological hypertrophy is caused by preservation of myocardial structure characterizes postnatal development, moderate endurance exercise training, pregnancy, and early phases of increased pressure and volume loading of the adult human heart; the physiological response is temporary. Hyperplasia is an increase in the number of cells resulting from an increased rate of cellular division. Hyperplasia is a response to injury when the injury has been severe or prolonged. (Hyperplasia and Hypertrophy often occur together; Both adaptations take place if the cells are capable of synthesizing DNA.) 2 types of physiological hyperplasia are compensatory hyperplasia and hormonal hyperplasia. Compensatory hyperplasia is an adaptive mechanism that enables certain organs to regenerate- jie.: removal of part of the liver leads to hyperplasia of the remaining liver cells to compensate for the loss. Hormonal hyperplasia occurs chiefly in estrogen dependent organs, ie.: Breast and uterus. After ovulation, for example, estrogen stimulates the endometrium to grow and thicken for reception of the fertilized ovum. If pregnancy occurs, hormonal hyperplasia and hypertrophy occur, enabling the uterus to enlarge. Pathologic hyperplasia is abnormal proliferation of normal cells and can occur as a response to excessive hormonal stimulation or the effect of growth factors on target cells. Most common example is hyperplasia of the endometrium is caused by an imbalance in 3. Ethanol - nutritional deficiencies, especially folate. Acute alcoholism affects CNS. Chronic affects the liver (fatty liver, alcoholic hepatitis, cirrhosis) and stomach (acute gastritis). 4. mercury, drug use d. Physical injury - unintentional or intentional. Ex: falls, poisonings, MVAs, homicide, suicide, gunshot, medication errors a. Infectious injury - pathogenicity or virulence of microorganism i. Invasion and destruction, toxin production, and causes hypersensitivity reaction b. Immunologic and inflammation - key to remember that inflammation can cause cellular injury. c. Genetics - nuclear alterations, sickle cell anemia d. Nutritional imbalances - you MUST have proteins, carbs, lipids, and vitamins. Can have deficient or excessive intake. e. Temps - hypothermic slows metabolic process & produces reactive oxygen species. Hyperthermia ex: heat stroke, malignant hyperthermia, burns f. Atmospheric pressure - high-altitude illness, diver disease, blast injury (soldiers) g. lonizing radiation i. Bystander is horizontal. (cells affected that are not in the direct field of radiation) ii. Genomic is vertical (cells derived from an irradiated cell appear normal but over time lethal and nonlethal mutations appear) 3. Identify the various cellular accumulations that occur in response to injury and the subsequent manifestation of cellular damage A. Water - cellular swelling (oncosis). The most common degenerative change, shift of water in ECF into cells, reversible, occurs in almost all cellular injury. Assoc. w/ high fever, hypokalemia and some infections. Lipids and carbs - fatty liver Glycogen - seen in genetic disorders. Accumulation of glycogen causes excessive vacuolation of the cytoplasm Proteins - accumulates in renal tubules & immune B lymphocytes Pigments - melanin, hemoproteins, bilirubin Calcium - dystrophic or metastatic calcification Urate - uric acid and gout attacks 4. Identity systemic manifestations and causes of cellular injury a. Fever - acute inflammatory response, release of pyrogens from bacteria or macrophages b. Tachycardia - increased need for oxygen resulting from fever c. Leukocytosis (inc. WBC) - infection d. Pain - various causes, release of bradykinins, obstructions, pressure 5. Identify the major types of cellular necrosis a. Necrosis - inflammatory changes, pathological i. Injury, swelling, breakdown of membrane, organelles, and nucleus, leakage of contents b. Apoptosis - NO inflammatory changes OB ,O MMO i. Programmed cell death ii. Dropping off of cellular fragments iii. Active process of cellular destruction iv. Can be normal or pathological c. Autophagy i. Recycle center, eats itself, self-destructive, survival mechanism 6. Characterize somatic death and its manifestations. . Death of entire person . NO inflammatory response . Algor mortis - reduced temp . Livor mortis - purple skin . Rigor mortis - muscle stiffening Postmortem autolysis - putrefactive changes associated with release of enzymes and lytic dissolution 24-48 hour after death ->oa0o0D Module 1 Cellular biology, Membrane physiology, action potentials, skeletal/smooth muscle contraction, and Altered cellular tissue Positive and negative feedback - what are they? Understand basics of what they do and how they affect physiology-Positive feedback promotes a change (not considered a positive/good thing). Positive feedback is when there is a stimulus that gets exaggerated. She mentioned in the lecture the example of labor contractions... start off mild and spread out... the positive feedback is they become more intense and closer together. Negative feedback promotes stability and is considered a good thing. Negative feedback is when the body senses a change and tries to fix it. (Sabrina Wilson) An example she provided for negative feedback is when a patient has high blood glucose. It causes the pancreas to release more insulin. Insulin moves glucose into the cell, brings down the glucose in the serum. This causes a lower serum blood glucose level (Heather) Transport of molecules through the membrane; diffusion and what affects it; facilitated diffusion, active transport; and osmosis and what it is Transport of molecules through the membrane can be completed via diffusion (simple and facilitated), active transport, and endocytosis. Passive diffusion does not utilize additional energy, does not require a carrier, and occurs down a concentration gradient, whether it be dft it’s concentration difference, electrical potential, or pressure difference. These 3 factors also affects it net rate of diffusion, the greater the potential, the faster the rate of net diffusion. Facilitated diffusion has similar characters as simple diffusion except the molecule needs to attach to carrier to facilitate the passage down its concentration gradient. Active transport is broken into 2 different types, Primary Active Transport and Secondary Active Transport which both require energy and attachment of a carrier protein to pump molecules against or uphill a concentration gradient (Na/K pump). The major difference is that primary active transport uses direct energy (ATP) while secondary active transport uses indirect energy. It’s transport is driven from the stored energy in the concentration gradient formed by another ion, usually Sodium. Therefore movement of a molecule occurs d/t movement of another molecule. Secondary active transport can be further broken down into A. co-transport and B. counter-transport. A- substance is transported in the same direction as the driver ion. For example, the Na/K pump in primary active transport causes Na+ to have a high concentration and electrochemical gradient to want to come into the cell. The build-up of energy from Na+ wanting into the cell so bad allows a molecule like glucose to hitch a ride & enter into the cell against its concentration gradient (indirect energy use). Although both molecules are moving in different concentration gradients, they are both traveling in the same direction. (the KHAN video is really helpful in understanding this) B- substance is transported in the opposite direction of the driver ion. The same concept of how it uses the indirect energy from the Na/K pump to transport another molecule from a carrier protein applies. The difference is as Na is going in to the cell, a substance is moving to the outside of the cell. Osmosis is a type of PASSIVE TRANSPORT of fluid across a membrane from an area of lower solute concentration (hypotonic) to a higher one (hypertonic), NOT a diffusion of fluid/water. Water moves down its concentration gradient by a difference in solute concentrations across the membrane, resulting osmotic pressure as it’s driving force for the water’s movement. Membrane permeability and ion permeability Simple diffusion is greatly dependent on the permeability of the membrane. A molecule will not be able to pass if the membrane is non-permeable to ie. Lipid soluble molecules move more easily. This is why protein plays such a major role as they are what helps ions or substances pass through the membrane to help maintain homeostasis. Diffusion potentials A diffusion potential is the potential difference generated across a membrane because of a concentration difference of an ion. It can be generated only if the membrane is permeable to the ion. The size of the diffusion potential depends on the size of the concentration gradient. The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively charged. Diffusion potentials are created by the diffusion of very few ions and, therefore, do not result in changes in concentration of the diffusing ions. Diffusion potential depends on the 3 factors if it involves more than one ion 1. Polarity of the electrical charge 2. Permeability of the membrane 3. Concentration difference inside and outside the cell Resting membrane potential Defined as the difference in electrical charge between the extracellular fluid (ECF) and the intracellular fluid (ICF) in mV. Each permeable ion will attempt to drive the membrane potential towards its equilibrium potential. lons with the highest permeability will make the greatest contributions.The resting potential is approximately -70mvV to -90mV. The equilibrium potential of K+ is -94. The equilibrium potential of Na+ is +61. The resting potential is closest in value to the ion that is most permeable to the membrane (K+). At the resting potential, there are more K+ ions inside the cell via exocytosis into the synapse. If enough ACh binds to the specific binding sites of the junctional folds of the postsynaptic membrane, nicotinic ACh receptor channels open on the muscle fiber membranes (Na, K, and Ca) the binding of ACh to its receptor causes the sodium/potassium channels to open (sodium moves in “depolarization” bringing positive charge and potassium leaks out with positive charge. The movement of ions across the membrane particularly depolarization produces an end plate potential that initiates an AP to be generalized to the adjacent muscle tissue causing muscle contraction. AChE breaks down the ACH into choline and acetate. Choline is taken back into the presynaptic terminal via co-transport to be used again. (LaToya) Neuromuscular junction physiology; know basic process in order Action potential travels down the motor neuron to the presynaptic terminal Depolarization of presynaptic terminal opens Ca channels, Ca flows IN Ach is extruded into the synapse by exocytosis Ach binds to its receptor on motor end plate Channels for Na and K are opened at motor end plate Depolarization of motor end plate causes AP to be generated in adjacent muscle Ach is degraded to choline and acetate by AchE and choline is taken back into the presynaptic terminal on an Na-Choline co-transporter Calcium role in skeletal muscle contraction; tropomyosin function and Troponin- Tropomysin is a filamentous protein that runs along the groove of each twisted actin filament. During rest the function is to block the myosin-binding sites on actin. In contraction, the tropomyosin must be moved out of the way so that actin and myosin can interact. Troponin is a complex of 3 globular proteins. Located at regular intervals along the tropomyosin filaments. Troponin T attaches the troponin to tropomyosin. Troponin | along with tropomyosin inhibits the interaction of actin and myosin by covering myosin binding site of actin. Troponin C is a Ca2+ binding protein that plays a central role in the initiation of contraction. Excitation and contraction of smooth muscle, calcium, and calmodulin- Smooth muscle contains both myosin and actin filaments. No striated arrangement of actin and myosin filaments. More actin than myosin. No troponin complex. Contractile process activated by Ca2+ ions and ATP that is broken down to ADP.Dense bodies instead of Z discs. Important difference is that smooth muscle contains “sidepolar” crossbridges.Can be stimulated by multiple types of signals. Nervous, hormonal, stretch of muscle, and others. Smooth muscle membrane contains many types of receptor proteins that can initiate the contractile process. Both excitatory and inhibitory. Calcium binds to calmodulin which increases myosin light chain kinase which then phosphorylation of myosin light chains then increases myosin atpase then myosin atpase + actin does the cross bridge cycling which then causes the tension. So easier said the binding of calcium to calmodulin regulates myosin light chain kinase, which regulates cross bridge cycling. Atrophy, hypertrophy, dysplasia- Atrophy - decrease in cell size. The atrophic muscle contains less endoplasmic reticulum and fewer mitochondria and myofilaments(which controls contraction). Disuse immobilization for extended period of time. Decreased protein synthesis, increased protein catabolism or both. Results from decrease in workload, pressure, blood supply, nutrition, hormonal and nervous stimulation. Common place heart, brain. Hypertrophy- increase in cell size and leads to increase in size of organ (ex. Heart and Kidney) caused by increase work demand or hormones. Response to heavy work.ex enlarged heart- dilatation, muscle fibers work harder. Dysplasia- refers to abnormal changes in size, shape, and organization of mature cells (deranged cellular growth). Can be called atypical hyperplasia. Does not indicate cancer. Cervix, respiratory tract. Reperfusion injury physiology- when additional injury occurs when oxygen is restored you get influx of oxygen that is metabolized and it leads to production of oxygen free radicals. Results from generation of highly reactive oxygen intermediates (oxidative stress), including hydroxyl radical, superoxide o2 and hydrogen peroxide. These radicals can cause further membrane damage and mitochondrial calcium overload. Apoptosis vs. necrosis - These are two types of cell death. Apoptosis is when there is no inflammation. It is shrinkage of the cell, no leakage of the cell, and is eventually eaten up by WBC. This process is considered to be normal and is a “self-destructive process.” (Apoptosis is Patho) Necrosis is inflammation of the cell, there is leakage of the cell, and then pus. (Necrosis is Physiology) (Sabrina Wilson) Cellular aging, frailty, somatic death-Cellular aging is normal, just like we age, so do our cells. With cellular aging the cells have less function ability, we lose cells as we get older. Frailty is “wasting syndrome of aging” It means that the cell is frail, like humans bodies as we get older. Everything just slows down in the body, same thing with our cells. Somatic death- this means the whole person is now dead. This involves different changes in the body (Postmortem changes). These include Rigor Mortis and how the body becomes stiff after death. Livor mortis, the discoloration of the skin and Algor Mortis-when the body becomes cold. (Sabrina Wilson) Postmortem autolysis release of enzymes and lytic dissolution (occurs 24-48 hrs after death when body starts to decay and smell. Fink, S. L, & Cookson, B. T. (2005). Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells . Infection and Immunity, 73(4), 1907- 1916. http://doi.org/10.1128/IAI.73.4.1907-1916.2005 Cellular injury basic patho hypoxia; infiltrations, etc -Four biochemical themes- 1) adenosine triphosphate (ATP) depletion- changes that all contribute to the loss of integrity of the cell membrane. 2) oxygen and oxygen derived free radicals- free radicals cause destruction of cell membranes. 3) Intracellular calcium increases- causes this by activating enzymes 4) defects in membrane permeability- found in all forms of cell injury. Hypoxic injury- ischemia - arteriosclerosis and thrombosis common causes and anoxia- total lack of oxygen- cellular response- decrease in ATP, causing failure of the sodium/potassium pump and sodium calcium exchange, cellular swelling and reperfusion injury-when oxygen is restored. Understand basics of common toxins and the path behind how they cause cellular alterations (lead/radiationicarbon monoxide) “Sense” of the codon produced after transcription of the mutant gene is altered. May or may not cause disease or problems Frameshift: insertion or deletion of one or more base pairs to a DNA molecule. This can significantly change the DNA molecule and therefore the protein. Silent - mutations in the DNA that do NOT significantly alter the phenotype (physical appearance) Aneuploidy, polyploidy Aneuploidy can be described as numerical or structural, depending on whether whole chromosomes or portions of chromosomes are gained or lost. Both of these are distinct from polyploidy, in which cells contain more than two complete sets of chromosomes, but always contain an exact multiple of the haploid number, so the chromosomes remain balanced. Zasadil, L. M., Britigan, E. M. C., & Weaver, B. A. (2013). 2n or not 2n: Aneuploidy, polyploidy and chromosomal instability in primary and tumor cells. Seminars in Cell & Developmental Biology, 24(4), 370-379. http://doi.org/10.1016/j.semcdb.2013.02.001 Polyploidy - euploid cell has more than the diploid number, is always a multiple of 23. Ex: triploidy (3 copies of each chromosome = 69 chromosomes), tetraploidy (4 copies = 92). These fetuses do not survive and result in miscarriage or stillbirth. Aneuploidy - somatic cell does NOT contain a multiple of 23 chromosomes, ex: 45 or 47 In sex chromosomes - less serious Y usually causes no problems; contains little genetic material X inactivation of extra chromosomes largely diminishes their effect Ex: Trisomy: a cell that contains three copies of 1 chromosome (infants can survive with trisomy of certain chromosomes); monosomy: is the presence of only one copy of any chromosome (often fatal or lethal) Non-disjunction Autosomal aneuploidy - Down Syndrome Trisomy 21 (a cell that contains 3 copies of 1 chromosome in a cell; protruding tongue, mental challenges, low nasal bridge, epicanthal folds, poor muscle tone, and low set ears); risk increase with maternal age; cause leukemia, infections and heart diseases. Turner’s - 45X Only females, sterile (no ovaries)-gonadal streaks(gonadal streaks susceptible to cancer), short stature, webbing of neck, widely spaced nipples high number of aborted fetuses. Females have only 1X Chromosome Caused by mother Kleinfelter’s - XXY, XXXY, or XXXXY (must have at least 2 X and 1 Y) Only males, sterile small testes, female like breast (gynecomastia), sparse body hair, male appearance, mental impairment, and high pitched voice) May also have additional Y . Increases with mother’s age ° Metafemale - XXX, 47XXX or 47XXY Trisomy X (female have 3 X chromosomes); symptoms worsen with each additional X chromosome, sterility, menstrual irregularity and congenital deficits. Nondisjunction and typical diseases associated with it - failure to separate normally ° Aneuploidy Trisomy 21 for example (Down Syndrome) o ~=Nondisjunction- usually the cause of aneuploidy § Failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis § Down syndrome Sex chromosome abnormalities; understand the patho basics with: ° Turner syndrome - females only have one X, 45X Absence of ovaries, short stature, webbing of neck, widely spaced nipples X is usually inherited by MOTHER ° Kleinfelter’s syndrome - males have XXY Male appearance, female-like breasts, small testes, sparse body hair May even be XXXY or XXXXY ° Fragile X syndrome Chromosomes develop and then break Site is on long arm of X chromosome Elevated number of repeated sequences Mentally challenged Recurrence risk for dominant and recessive inheritance ° Autosomal dominant - union of normal person with heterozygous affected person 50% chance of passing altered gene; 50% normal Equally in males and females, no skipping ° Autosomal recessive - abnormal allele is recessive and person must be HOMOZYGOUS to express the disease; trait appears in children and not the parents; often skips generation; equally in males and females 25% chance of passing altered gene; 50% carrier; 25% normal ° X-Linked - Males, if inherited the defected X gene hemizygous, then he will express the disease, females could be homo for normal, homo for disease, or hetero More likely in males than females Females must have TWO recessive, affected genes to express the disease, males just need ONE from the mother NEVER transmitted from father to son Fathers will transmit to ALL daughters, generation skipping noted 100% of daughters who will transmit it to 50% of their sons . Penetrance, Expressivity ° penetrance - percentage of individuals with a specific genotype who also express the expected phenotype incomplete - has the gene, but does not express the disease age-dependent penetrance - does not express disease until certain age is reached, such as Huntington’s (40 or later) ° expressivity - variation in a phenotype associated with a particular genotype caused by modifier genes, environment, mutations Recklinghausen disease . Autosomal dominant . Mutation in tumor suppressor gene - leads to tumor development Brown spots that are fine all the way to cancer . Benign vs. Malignant tumors ° Benign Grows slowly Encapsulat ed Not invasive Well differentiated Low Mitotic Index Do not mets Malignant Tumors Grows rapidly NOT encapsulated Invasive Poorly differentiated CAN mets . Anaplasia, metaplasia ° Anaplasia - loss of cellular differentiation, irregularities of size and shape of nucleus and loss of normal tissue structure (without form) ° Metaplasia - abnormal change in nature of tissue . Carcinoma in situ ° PREinvasive epithelial malignant tumor of glandular or epithelial origin that have NOT broken through the basement membrane or invaded surrounding stroma ° Growing in its normal location Can be stable, regress, or advance Carcinogenesis; understand basic patho behind development of cancer Process during which a normal cell becomes a cancer cell Autonomy is the cancer cell’s independence from normal cellular control Lacks contact inhibition Immortal Anaplasia occurs - cellular misshape, irregular Anchorage independent, does NOT need to be anchored to divide ALWAYS uses glycolysis - can thrive in hypoxic environments (anaerobic metabolism) Mutations and cancer Disease of aging Multiple mutations are required before cancer forms eoo0oo00000 80 oo . Cancer epidemiology, basics and common risk factors ° Cancer occurs in genes, but 2/3 of cancer is caused by environment and lifestyle factors interacting with genes ° Risk factors Tobacco Diet (Fats, fried foods, Grilled/Blackened Foods) Alcohol Lack of fruits/veggies Meat Lack of fiber Overweight Lack of exercise Post-menopause Infection lonizing radiation/UV radiation Chemical hazards Air pollution (Outdoor and Indoor) Occupational hazards Reproduction Sun exposure, tanning (module 2 - amy meadors) (LaToya) Take Test: Exam #1 Test Information Descriptio n Instructio ns Timed Test This test has a time limit of 1 hour and 27 minutes. You will be notified when time expires, and you may continue or submit. Warnings appear when half the time, 5 minutes, 1 minute, and 30 seconds remain. Multiple Force Completion Attempts Not allowed. This test can only be taken once. Th is te st ca n be sa ve d an d re su m ed lat er. Th e ti m er wil co nti Remaining Time: 1 hour, 26 minutes, OO seconds. Question Completion Status: QUESTION 1 A biologist is explaining how RNA directs the synthesis of protein. Which process is the biologist describing? ¢ ATermination ¢ B Transcriptio .n © C Translation ¢ DTranslocati on 1 points QUESTION 2 What is the sequence of steps in the development of a digestive enzyme by the pancreas cells from the initial transcription to the release from the cell? cA The enzyme is transcribed from DNA by RNA in the nucleus, proceeds to the ribosome for synthesis, and is . transported in a secretory vesicle to the cell membrane. ¢~ _B The enzyme is transcribed from RNA by DNA in the nucleus, proceeds to the lysosome for synthesis, and is . transported in an encapsulated membrane to the cell membrane. ¢ C The enzyme is transcribed from DNA by RNA in the nucleus, proceeds to the Golgi complex for synthesis, and is . transported in a cytosol to the cell membrane. cD The enzyme is transcribed by the mitochondria in the nucleus, proceeds to the ribosome for synthesis, and is . transported in a cytoskeleton to the cell membrane. 1 points QUESTION 3 A 20-year-old pregnant female gives birth to a stillborn child. Autopsy reveals that the fetus has 92 chromosomes. What term may be on the autopsy reort to describe this condition? cA Biploidy rc B Triploidy cf Tetraploid cy cP Aneuploid cy 1 points QUESTION 11 Which of the following is an example of positive feedback in the body? © A Return of blood pressure toward normal after a hemorrhage B Clotting of blood % c © Increased respiration rate caused by accumulation of carbon dioxide in the blood c © Decreased sympathetic nervous system activity that occurs in response to * increased blood pressure 1 points QUESTION 12 When a child inherits a disease that is autosomal recessive, it is inherited from: ¢ A Father ¢ B Mother c C Both parent 7 c ? Neither * parent 1 points QUESTION 13 Skeletal muscle relaxation occurs when. is. by the sarcoplasmic reticulum. cA Sodium; released © sodium; * accumulated © © Calcium; released c DP Calcium; * accumulated 1 points QUESTION 14 A patient is seen in the clinic, and is obese. The NP is discussing the patients weight and cancer risk. The NP will explain that the patient is at risk for what type of cancer because of obesity specifically? c A Lung Cancer © B stomach * Cancer © pancreatic * cancer D Esophageal * cancer 1 points QUESTION 15 During a chemical synapse what process occurs at the presynaptic terminal? A Na channels open and cause the action potential 8 Neurotransmitters bind to receptors on the terminal © Calcium channels open and cause the release of the neurotransmitter D Sodium channels open and cause the release of the neurotransmitter 1 points QUESTION 16 A student has been researching telomere caps. Which statement indicates the student has a good understanding? The presence of telomere caps gives cancer cells: c¢ AThe ability to divide over . and over again © B Clonal distribution @ C Limited mitosis @ D Mutation abilities 1 points QUESTION 17 A middle aged patient is diagnosed with a small cell lung cancer. Small cell lung cancer is a neuroendocrine tumor that can release biological substances. The NP knows that this puts the patient at risk for which complication of cancer? A pain B cachexia c Paraneoplastic * syndrome > anemia 1 points QUESTION 18 Skeletal muscle contracts when calcium binds to which structure or molecule? © AActive site s c 8 calmoduli on ¢ CTropomysi .n cD Troponin- Cc 1 points QUESTION 19 In hypoxic injury, sodium enters the cell and causes swelling because: c AATP is insufficient to maintain the pump that keeps sodium . out of the cell ¢ B The cell membrane permeability increases @ C Lactic acid produced in hypoxia binds with sodium in the cell ¢ D Sodium cannot be transported to the cell membrane during . hypoxia 1 points QUESTION 20 It has been determined that a tumor is in stage 2. What is the meaning of this finding? ¢ ACancer is confined to the organ of . origin cB Cancer has spread to regional . structures « C Cancer has spread to distant sites ¢ D Cancer is locally invasive 1 points QUESTION 21 Which statement concerning benign tumors is true? c A Benign tumors are not * encapsulated. c B Benign tumors are fast * growing. Cc co er Cc Down D Fragile X 1 points QUESTION 29 A practitioner is caring for a patient diagnosed with a malignant sarcoma. The practitioner recalls that what is true of malignant tumors? ¢ AMalignant tumors grow slowly ¢ B Malignant tumors are non-invasive @ C Malignant tumors are . poorly differentiated ¢ D Malignant tumors . do not metastasize 1 points QUESTION 30 A student remembers that a diploid cell, with the normal number of chromosomes, is a type of. cell and has_chromosomes. c A triploid; 46 ce B Aneuploid; “26 ce © Euploid; 46 cP Haploid; 46 1 points QUESTION 31 Smooth muscle contraction is controlled by. cA Binding of actin and myosin c B Binding of calcium to * troponin T cf Binding of calcium to + calmodulin cP Binding of calmodulin to * myosin 1 points QUESTION 32 Cancer causing mutations. c¢ A Promote apotosis c¢ B Activate anti-growth path . Ways © C Deactivate telomerase ¢ D Promote angiogenesis 1 points QUESTION 33 A patient presents with an enlarged heart seen on echocardiogram, the NP knows that hypertrophy of the heart is MOST likely do to what effect on the heart? c A Disuse c increased cellular * division roe Physiologic changes cP Increased workload 1 points QUESTION 34 When ATP is generated in the absence of oxygen (anaerobic metabolism) there is ATP per molecule of glucose in comparison to oxidative phosphyloration (aerobic metabolism). c A Mor ‘e © Bless 1 points QUESTION 35 The process of translation takes place: c Ainthe cytosol and on the surface of the “rough” * endoplasmic reticulum ¢ 8 In the nucleus and on the surface of the “rough” * endoplasmic reticulum ec In the cytosol and the trans-Golgi network (TGN) ¢ Inthe nucleus and on the outer mitochondrial membrane 1 points QUESTION 36 An elderly patient presents to their general practitioner with issues with mobility and balance issues, and has had multiple recent falls with functional decline. The NP believes the MOST likely diagnosis is what? c A Frailty c B Dysplasia c © Disuse * Atrophy c Plead * poisoning 1 points QUESTION 37 While reading a textbook, the student reads the term, “apoptosis”. The student recall that apoptosis is: c ACellular aging © B Cellular programmed d . eath c C Cellular swelling c¢ D Cellular regeneration 1 points QUESTION 38 The sodium-potassium pump maintains the sodium-potassium balance thereby regulating: @ A The initiation of action potentials ¢ B Osmotic balance ¢ C Oxidative phosphorylation c Pa positive voltage inside * the cell 1 points QUESTION 39 A oncologist is giving a speech about the transformation in terms of cancer. The student knows that one factor contributing to carcinogenesis is that cancer cells_. c A Have contact inhibition c Buavea lifespan © CFill the space and cause normal cells to stop c 8 chloride c © Potassiu “m o > Magnesiu “m 1 points QUESTION 47 Why is it possible for potassium to diffuse easily into and out of cells? ¢ A Potassium has a greater concentration in ECF ¢ B Sodium has greater concentration in ECF ¢ C The membrane potential of potassium . is closer to the resting membrane potential ¢@ D An excess of anions are inside the cell 1 points QUESTION 48 Oncogenes are genes that are capable of: © Undergoing mutation that directs the synthesis of proteins to accelerate the rate of * tissue proliferation c 8 Directing synthesis of proteins to regulate growth and to provide necessary * replacement of tissue © © Encoding proteins that negatively regulate the synthesis of proteins to slow or halt * the replacement of tissue © Undergoing mutation that directs malignant tissue toward blood vessels and lymph * nodes for metastasis 1 points QUESTION 49 Which of the following best describes the correct (temporal) order of events when considering the neuromuscular junction: a. opening of nicotinic acetylcholine (nACh) channels on the muscle membrane; the opening of b. voltage-gated sodium channels on the muscle membrane; c. and initiation of presynaptic action potentials (AP). ¢ A opening of nACh channels, Presynaptic AP, opening of voltage . gated Na channels ¢ B opening of nACh channels, opening voltage gated Na . channels, presynaptic AP ¢@ C presynaptic AP, opening of nACh channels, opening of voltage . gated Na channels c Dpresyaptic AP, opening of voltage gated Na channels, opening . of nACh channels 1 points QUESTION 50 During an action potential the process of making the membrane potential more negative is known as_. cA Depolarization c ® Threshold * potential c © Overshoot co D yperpolarizatio on 1 points QUESTION 51 Duchenne muscular dystrophy is an example of which type of genetic disorder? c AxX-linked * recessive c 8 X-linked * dominant © © Autosomal * recessive c > atuosomal * dominant 1 points QUESTION 52 A 52-year-old male suffered a myocardial infarction secondary to atherosclerosis and ischemia. Once oxygen returned to the damaged heart, reperfusion injury occurred as a result of: ¢ A Free radical formatio .n c BVaculoation c C Increased metabolic . State ¢@ D Lipid acceptor protei -ns 1 points QUESTION 53 Cri du chat syndrome is an example of a chromosomal alteration as the result of which abnormality in chromosomal structure? c co 4y A inversions B Duplication “Ss © Deletions > Translocati ‘on 1 points QUESTION 54 What organic compound facilitates transportation across cell membranes by acting as receptors, transport channels for electrolytes, and enzymes to drive active pumps? co A Lipids B Proteases C Carbohydrat es D proteins 1 points QUESTION 55 A patient presents to the ED with tinnitus, n/v, and weakness. The practitioner suspects carbon monoxide poisoning. The NP remembers that the basic pathophysiology of carbon monoxide poisoning is a hypoxic injury as a result of what? c c c c A Carbon monoxide causes release of oxygen : free radicals 8 Carbon monoxide has increased affinity for * hemoglobin © Carbon monoxide causes lysis of red blood cells > Carbon monoxide causes mitochondrial * damage 1 points