NUR 565 UNIT 1

TRUE - When the body senses a change out of the norm, it activates mechanisms that oppose that change (vasodilation and sweating with increased temperatures; vasoconstriction and shivering with decreased temperatures). This is known as negative feedback. Positive feedback, on the other hand, senses a change but activates a mechanism that exaggerates the change. - Thermostatic set point: level at which body temperature is regulated so that core temperature is maintained within the normal range.

(T/F) Body temperature is controlled through negative feedback loops.

Numeric Disorders Involving Autosomes

*Aneuploidy*: a change in chromosome number Common cause: failure of chromosomes to separate during oogenesis or spermatogenesis; can occur in autosomes or sex chromosomes and is called *nondisjunction* Monosomy: presence of only one member of chromosome pair - Turner syndrome (X chromosome) Polysomy: presence of more than two chromosomes in a set; occurs when germ cell containing more than 23 chromosomes is involved in conception - Klinefelter syndrome (polysomy of X chromosome in males) Trisomy - Down syndrome (trisomy 21; most common of autosomal chromosomes)

Keloids

- A raised scar (overgrowth of scar tissue) after an injury has healed Kara's Notes - Abnormality in scar tissue repair; tend to develop in genetically predisposed persons an are more common in African Americans and other dark skinned people

Dependent Edema

- Accumulation of fluid in lower parts of the body - Typically seen with edema resulting from increased capillary pressure - Impacted by gravity - Edema of feet and legs often more prominent after standing

Pitting Edema

- Accumulation of interstitial fluid exceeds absorptive capacity of tissue gel - Tissue water can be moved with pressure exerted by a finger (leaves a dent) How is the severity of pitting edema noted? The impact edema exerts on the body function is determined by its location. Edema of the brain, lungs, and/or larynx is an acute medical problem and can be life-threatening.

Coagulation (Necrotic Cell Death)

- Acidosis develops and denatures the enzymatic and structural proteins of the cell - Caseous: form of coagulation necrosis; dead cells persist indefinitely as soft, cheese-like debris; commonly found in center of TB granulomas or tubercles

Nitric Oxide (NO)

- Antagonism of platelet adhesion, aggregation, and degranulation - Regulator of leukocyte recruitment - Production of NO appears to be an endogenous compensatory mechanism that reduces the cellular phase of inflammation - Impaired production of NO by vascular endothelial cells is implicated in the inflammatory changes that occur with atherosclerosis

Cell Injury mechanisms: Free Radicals

- Are highly reactive chemical species with an unpaired electron in the outer orbit (valence shell) of the molecule - Extremely unstable and reactive due to unpaired electron - React nonspecifically with nearby molecules - Can establish chain reactions that generate new free radicals - In cells and tissues: free radicals react with proteins, lipids, and carbohydrates thereby damaging cell membranes, inactivating enzymes, and damaging nucleic acids that make up DNA - Normally removed from body by antioxidants: enzymatic and nonenzymatic Circumstances involving the production of free radicals: - Ischemia-reperfusion injury - Chemical and radiation injury - Toxicity from oxygen and other gases - Cellular aging - Responses to microbial infections - Tissue injury cause by inflammation

Infarction (Necrotic Cell Death)

- Artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists

Intermittent Fever (fever pattern)

- Associated with gram-negative or gram-positive sepsis, abscesses, and acute bacterial endocarditis - Temperature returns to normal at least once every 24 hours

Marfan Syndrome

- Autosomal dominant disorder - 75% familial with rest from new mutations in germ cells of parents - Mutation in gene on chromosome 15 - Wide range in variation of expression (not everyone with this disease has the exact same symptoms)

Phenylketonuria

- Autosomal recessive disorder; metabolic disorder - Caused by elevated levels of phenylalanine that are toxic to brain - 1 per 10,000 in white and Asian populations; varies widely geographically - Require dietary restrictions - Routinely screened for in newborns

Complement System (Plasma-Derived Inflammatory Mediators)

- Cascade of plasma proteins that play important roles in both immunity and inflammation - They cause vasodilation and increase vascular permeability, promote leukocyte activation, adhesion, and chemotaxis, and augment phagocytosis

Necrotic Cell Death

- Cell death in an organ or tissue that is still part of a living person - Unregulated death caused by injuries to cells - Cells swell and rupture inflammation - Infarction: artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists - *Necrosis differs from apoptosis because it involves unregulated enzymatic digestion of cell components, loss of cell membrane integrity with uncontrolled release of products of cell death into the extracellular space, and initiation of the inflammatory response; usually interferes with cell replacement and tissue regeneration* - Liquefaction: occurs when some of the cells die but their catalytic enzymes are not destroyed - Coagulation: acidosis develops and denatures the enzymatic and structural proteins of the cell - Infarction: artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists - Caseous: form of coagulation necrosis; dead cells persist indefinitely as soft, cheese-like debris; commonly found in center of TB granulomas or tubercles

Endothelial Cells

- Cell of inflammation lining of blood vessels - Single cell thickness - Help separate intravascular and extravacular spaces - Smooth surface - Non-thrombogenic (does not promote things clumping to it) - Produces agents that maintain vessel patency - Produces vasodilators and vasoconstrictors (regulate blood flow) - Selective permeability barrier to exogenous and endogenous inflammatory stimuli - Impact leukocyte expression - Synthesize and release inflammatory mediators

Impaired Calcium Homeostasis

- Cell usually maintains low cytosolic calcium (low amount of calcium in the aqueous portion of the cytoplasm). Normally, more calcium outside the cell than inside the cell - Ischemia and some toxins result in increased cytosolic calcium because of influx across cell membrane and release of calcium from intracellular stores - Calcium acts as a "second messenger." It May inappropriately activate intracellular enzymes which can damage the cell (Phospholipids can damage cell membrane, protease that damage cytoskeleton and membrane proteins, ATPases that break down ATP and quicken its depletion, and endonucleases that fragment chromatin (chromatin=material comprising chromosomes=protein, RNA, DNA))

Reversible Cell Injury

- Cellular swelling: usually due to hypoxic injury - Fatty change-linked to intracellular accumulation of fat (May occur in obese persons -- more ominous than swelling -- while reversible, it usually indicates severe injury) - Fatty changes may occur because normal cells are presented with an increased fat load or because injured cells are unable to metabolize the fat properly

Gas Gangrene

- Clostridium infection - Hydrogen sulfide bubbles in muscle - More common in trauma/compound fractures - Treatment: antibiotics, surgery - Potentially fatal The only type of gangrene that causes crepitus (bubbles that can be felt under the skin) -- the bubbles are the result of gas produced by the Clostridium infection

Eicosanoid

- Cyclooxygenase pathway culminates in synthesis of prostaglandins - Lipoxygenase pathway culminates in synthesis of leukotrienes - Corticosteroid drugs block both pathways by inhibiting phosphodiesterase activity and thus preventing release of arachidonic acid

Atrophy

- Decrease in cell size - Occurs when cells have a decrease in work demand or adverse environmental conditions; adapt to survive - Atrophied cells use less oxygen and reduce other cellular functions by decreasing the number and size of organelles an other structures - When enough cells experience atrophy, the entire tissue atrophies. - Five groups of causes: 1. disuse 2. denervation 3. loss of endocrine stimulation, 4. inadequate nutrition, and 5. ischemia or decreased blood flow

Dyplasia

- Deranged cell growth resulting in cells that vary In size, shape, and organization - Minor _______ associated with chronic irritation or inflammation. Usually respiratory tract or uterine cervix - Is abnormal but is considered adaptive because it can be reversible if irritating factor is removed. Highly associated with cancer but does not always lead to cancer - Can be reversed - Pap test: cervical cancer develops in incremental epithelial changes

Cellular Adaptation

- Diseases begin with cellular alterations - Extent of injury depends on: *Type, state, adaptive processes of cell *Type, severity, and duration of injurious stimulus - Can be reversible - All diseases exert their effects on the smallest living unit: the cell - Cells adapt to changes in the internal environment just as the total organism adapts to changes in the external environment - When the stress is overwhelming or adaptation is ineffective: injury, maladaptive changes, and cell death occur - Pathological: abnormal, disease - Physiological: normal

Water and Sodium Balance

- Distribution of body fluids between ICF and ECF compartments relies on concentration of ECF water and sodium - Sodium salts make up about 90% to 95% of ECF solutes - Normal serum sodium level is 135 to 145 mEq/L - Sodium usually enters the body through the GI tract and is lost through the kidneys - Regulates ECF volume and osmolarity (Most sodium losses occur through the kidneys. Kidneys are very good at regulating sodium output. With limited or conservative sodium intake, the kidneys are able to absorb almost all of the sodium that has been filtered in the glomerulus (a tiny ball-shaped structure composed of capillary blood vessels actively involved in the filtration of the blood to form urine). The result is essentially sodium-free urine.)

Acute Inflammation

- Early/almost immediate reaction of local tissues and blood vessels to injury Primary objectives: - Remove injurious agent - Limit tissue damage - Five cardinal signs: redness (erythema), swelling (edema), heat, pain, and loss of function - Acute-phase response: constellation of systemic manifestations and increase in serum proteins that occur during acute inflammation Two Stages: Vascular and Cellular Goal: remove the harmful agent limit extent of tissue damage Triggers: infections, immune reactions, blunt and penetrating trauma, physical or chemical agents, tissue necrosis. - Vascular Stage: involves arterioles, capillaries, and venules of the microcirculation

Genetic Imprinting

- Expression of disease phenotype depends on whether the mutant allele was inherited from the father or the mother - Both Angelman (from mother) and Prader-Willi syndromes (from father) involve the same deletion on chromosome 15 - Gene expression can also be entirely "turned off" or "turned on" during spermatogenesis or oogenesis

Granulomas

- Form of chronic inflammation - Characterized by aggregates of macrophages that "wall off" the causal agent - Granulomatous inflammation is associated with: 1. Foreign bodies such as splinters, sutures, silica, and asbestos 2. Microorganisms that cause TB, syphilis, sarcoidosis, deep fungal infections, and brucellosis

Angiogenesis & Granulation Tissue (Stage 1 of Repair)

- Glistening red, moist connective tissue fills injured area while necrotic debris is removed - Composed of newly formed capillaries (angiogenesis), proliferating fibroblasts, & residual inflammatory cells (Angiogenesis is a tightly regulated process that includes migration of endothelial cells to the site of injury, formation of capillary buds, and proliferation of endothelial cells, followed by fusion and remodeling of the endothelial cells into capillary tubes. Most important growth factors in this process are VEGF and FGF-2. New blood vessels are leaky = accounts for edematous appearance of granulation tissue and accounts in part for swelling that may persist in healing wounds long after acute inflammation has resolved.)

Mast Cells

- Granulocytes - Come from same stem cells as basophils but do not develop until they leave the circulation and lodge in tissue sites - More prominent along mucosal surfaces of the lung, GI tract, & dermis of skin-good position for environmental allergens, activation results in release of histamine, proteases, cytokines, growth factors, & synthesis of lipid mediators. Release of mast cell contents stimulates cytokine and chemokine synthesis by monocytes and macrophages

Hypoxic Cell Injury

- Hypoxia deprives the cell of oxygen and interrupts oxidative metabolism and the generation of ATP - Time necessary to cause irreversible cell damage depends on degree of oxygen deprivation and metabolic needs of the cell (cells of heart, brain, kidney require large amounts of oxygen to function) - Brain cells undergo permanent damage after 4 to 6 minutes of oxygen deprivation (thin margin between reversible and irreversible damage) Causes of hypoxia: - Inadequate amount of oxygen in the air - Respiratory disease - Ischemia (decreased blood flow due to vasoconstriction or vascular obstruction): characterized by impaired oxygen delivery and impaired removal of metabolic end products such as lactic acid - Anemia - Edema - Inability of cells to use oxygen - Hypoxia Causes ATP Depletion or "Power Failure" (aerobic metabolism stops and less ATP is produced = Na+/K+ ATPase decreases then increased intracellular sodium then cell swells with water) - Anaerobic (absence of oxygen) metabolism used = lactic acid produced: *Cellular pH falls as lactic acid accumulates in the cell *Acid damages cell membranes, intracellular structures, and DNA *Leakage of intracellular enzymes into extracellular fluid provides important clinical indicator of cell membrane and death (these enzymes enter the blood and can be measured by laboratory tests)

Hypertrophy

- Increase in cell size - Increased cell size results in increased amount of functioning tissue mass -- involves an increase in the functional components of the cell that allows equilibrium between demand and functional capacity -- can result from normal physiologic or abnormal pathologic conditions - Physiologic (normal functioning): increased muscle mass with exercise - Pathologic (abnormality/disease state): result of disease -- Can be adaptive or compensatory: *Adaptive: myocardial hypertrophy from valvular heart disease or HTN *Compensatory: enlargement of remaining kidney after one is surgically removed-compensation.

Hyperplasia

- Increase in number of cells - Occurs in tissues with cells capable of mitotic division (epidermis, intestinal epithelium, glandular tissue) Physiologic (2) types: - Hormonal: Uterus during pregnancy - Compensatory: Liver regeneration after partial hepatectomy - Also important in wound healing (fibroblasts and blood vessels) Nonphysiologic: Results from excessive hormonal stimulation or effects of growth factors on target tissues (Ex. Skin warts secondary to HPV)

Prostaglandins

- Induce inflammation and potentiate the effects of histamine and other inflammatory mediators - Aspirin and NSAIDs reduce inflammation by inactivating the first enzyme in the cyclooxygenase pathway for prostaglandin synthesis

Translation

- Involves taking the instructions transcribed from DNA to mRNA and transferring them to the rRNA of ribosomes so proteins can be built - Proteins are made from a standard set of amino acids, which are joined end-to-end to form the long polypeptide chains of protein molecules - The process of protein synthesis is called translation because the genetic code is translated into the language of this polypeptide assembly - mRNA acts as a pattern instructing ribosomes how to sequence amino acids - Amino acids are carried into position by tRNA - Ribosomes containing rRNA link amino acids together to make a protein (The process of translation involves taking the instructions transcribed from DNA to mRNA and transferring them to the rRNA of ribosomes located in the cytoplasm. It is the recognition of the mRNA codon by the tRNA anticodon that ensures the proper sequence of amino acids in a synthesized protein. In order to be functional, the newly synthesized protein must be folded into it functional form, modified further, and then routed to its final position in the cell)

Dry Gangrene

- Lack of arterial blood supply but venous flow can carry fluid out of tissue - Dry, shrinks, skin wrinkles, dark brown/black - Line of inflammatory reaction is present - Confined to extremities

Wet Gangrene

- Lack of venous flow lets fluid accumulate in tissue - Cold, swollen, pulseless, moist, black, odor - No line of demarcation between normal and diseased tissue; spreads rapidly - Can affect internal organs

Calcium, Phosphorus, and Magnesium

- Major divalent ions (++ charge) of the body - Directly or indirectly regulated by a number of factors including Vitamin D and PTH (parathyroid hormone)

Wound Healing and Nutritional Status

- Malnutrition slows healing process Proteins, carbohydrates, fats are needed - Protein deficiencies prolong inflammatory phase of healing and impair other healing processes - Carbohydrates are energy source for WBCs and have protein-sparing effect - Fats are important component of cell membranes and needed for synthesis of new cells Vitamins - Vitamin C for collagen synthesis - Vitamin A for epithelialization, capillary formation, and collagen synthesis - B vitamins for enzymatic reactions - Vitamin K to prevent bleeding Minerals - Must be present for normal cell function - Zinc is important for cell proliferation

Reactive O2 Species

- Many harmful free radicals are derived from oxygen which are called __________ - Free radicals: uperoxide anion (o2-), Hydroxyl radical (oh.) - Non-free radicals: Hydrogen peroxide (h2o2) - ROS are normal products of mitochondrial respiration and energy metabolism that usually removed by cellular antioxidative systems but ROS production can also be from exogenous sources (ionizing and UV radiation) - Oxidative stress: generation of ros exceeds the ability of body to neutralize and eliminate Ros. Can eventually lead to dna damage and changes in gene expression and might also cause mitochondrial dysfunction - Oxidative damage implicated in many diseases including cancer and cardiovascular disease

Acute Inflammation—Cellular Stage

- Marked by changes in endothelial cells of blood vessels and movement of phagocytic leukocytes into area of injury or infection - Sequence of events of cellular response to inflammation include leukocyte: margination and adhesion, transmigration, chemotaxis, and activation and phagocytosis Margination - Results in leukocyte accumulation - Cytokines Tethering - Leukocytes slow down and come to rest along endothelial surface - Adhere to intercellular adhesion molecules - Adhesion followed by endothelial cell separation - Leukocytes extend pseudopodia and transmigrate to tissue Chemotaxis - Movement of leukocytes into the tissue guided by chemoattractants Phagocytosis - Phagocytes (neutrophils, monocytes, and tissue macrophages) activated to engulf and degrade bacteria and cellular debris - Opsonization is the enhanced binding of an antigen to a coated microbe or particle - Agent is engulfed after determination is made that it is foreign. - Phagosome fuses with a cytoplasmic lysosome containing antibacterial molecules and enzymes that kill and digest the microbe

Liquefaction (Necrotic Cell Death)

- Occurs when some of the cells die but their catalytic enzymes are not destroyed

Recurrent/Relapsing (fever pattern)

- One or more episodes of fever, each as long as several days, with one or more days of normal temperature between episodes - Can be seen in several different infectious diseases including TB, fungal infections, Lyme disease, and malaria

Gene Interactions

- Polygenic: many genes could affect one trait - Multifactorial: both multiple genes and the environment could affect one trait - Epistasis: one gene could mask the phenotypic effect of another - Complementary: one gene might depend on another - Collaborative: two genes together might create a new phenotype

Wound Healing

- Poor blood flow and hypoxia may negatively impact wound healing Wounds must have adequate blood flow to supply necessary nutrients and to remove waste, toxins, and other debris - Poorly oxygenated wounds more likely to become infected - Oxygen can be given systemically or locally using a topical device - Hyperbaric oxygen - Inflammation is important beginning step of wound healing - Diabetes and administration of corticosteroid drugs can impair healing (neutrophils less effective in hyperglycemic environment) Kara's Notes - Causes of delayed wound healing include: malnutrition; impaired inflammatory and immune responses; infection, wound separation, and foreign bodies; and age effects - Neutrophils and macrophages require oxygen for destruction of microorganisms

Klinefelter Syndrome

- Presence of one or more extra X chromosomes (usually 47,XXY) - Abnormal development of testes - Characterized by enlarged breasts, sparse facial and body hair, small testes, inability to produce sperm - Usually undetected at birth - As mature, low testosterone causes lower part of body to be longer than upper part - Voice may remain high pitched with sparse beard and pubic hair - Normal intellect but some degree of language impairment - One of the most common genetic abnormalities occurring in 500 to 1,000 male births

Healing by Connective Tissue Repair

- Primary objective of healing process: fill gap created by tissue destruction and restore structural continuity of injured part - Tissue regeneration is restoration of injured tissue to its normal structure and function by proliferation of adjacent surviving cells - Regeneration can only occur in parenchymal organs with stable cell populations, but, with exception of liver, is usually a limited process Kara's Notes - Fibrosis = extensive deposition of collagen that occurs in organs that are incapable of regeneration - Organization is the process by which fibrous tissue grows into the area of damage converting it to a mass of fibrous tissue -- this can also occur in serous cavities such as the pleura and peritoneum when excessive exudate accumulates and cannot be cleared - Adhesions are strands of fibrous tissue

Histamine

- Produces dilation of arterioles and increases the permeability of venules, binds to H1 receptors on endothelial cells - Antihistamine drugs bind to H1 receptors and antagonize (work against) many effects of the immediate inflammatory response - Leukotrienes and histamine function similarly, however, histamine is produced rapidly and transiently while leukotrienes are being synthesized - Leukotriene (LT) C4, LTD4, and LTE4, collectively known as the slow-reacting substance of anaphylaxis (SRS-A), cause slow and sustained constriction of bronchioles and play an important role in asthma and anaphylaxis

Apoptosis

- Programmed cellular death ("Cell suicide") which is different from necrosis - Active process of cellular self-destruction - Found in normal and pathological tissue changes - Cells need to die to prevent endless proliferation, if there is a screw up in this mechanism it may cause cancer - Normally create 10 billion new cells daily and destroy same number of cells daily Two basic pathways: Extrinsic (death receptor) or intrinsic ~ Extrinsic: death receptor dependent ~ Intrinsic: death receptor independent - Execution phase of both pathways carried out by proteolytic enzymes call *caspases* which leads to DNA and cellular fragmentation More info from kara's notes Extrinsic Pathway: - Death receptors: extracellular signaling proteins bind to cell surface molecules - Prototype death receptors: tumor necrosis factor (TNF) receptor and Fas ligand receptor - Others include: TNF-related apoptosis-inducing ligand (TRAIL); cytokine interleukikn-1(IL-1); lipopolysaccharide (LPS)-endotoxin found in outer cell membrane of gram-negative bacteria - When Fas ligand binds to a receptor, proteins congregate at the cytoplasmic end of the Fas receptor to form a death-initiating complex. The complex then converts procaspase-8 to caspase-8. Caspase-8 then activates a cascade of caspases that execute the process of apoptosis The end result induces activation of endonucleases that cause fragmentation of DNA and cell death. Intrinsic Pathway: - Activated by conditions such as DNA damage, ROS, hypoxia, decreased ATP levels, cellular senescence, and activation of the p53 protein by DNA damage - Tightly regulated to ensure cells only kill themselves when appropriate. Involves protein release from mitochondria into cytoplasm. Proteins bind to procaspase-activating protein, activates caspases. Steps: - Shrinking and condensation of the nucleus and cytoplasm occur - Chromatin aggregates at the nuclear envelope, and DNA fragmentation occurs - Cell becomes fragmented into multiple apoptotic bodies in a manner that maintains the integrity of the plasma membrane and does not initiate inflammation - Changes in plasma membrane induce phagocytosis of the apoptotic bodies by macrophages and other cells - Degradation is compete Physiologic examples: separation of webbed fingers and toes in embryo, hormone-dependent involution of tissues, death of immune cells (see pg. 42) - Pathologic examples: possibly linked to neurodegenerative disorders such as ALS, Alzheimer's, and Parkinson...still being researched

Fever

- Prominent manifestation of the acute-phase response - Nearly all biochemical processes in the body are affected by changes in temperature (metabolic processes speed up or slow down based on body temperature) - Thermoregulatory center regulates core body temperature, not surface temp. (this occurs by integration of input from cold and warmth receptors located throughout the body and participating in negative feedback mechanisms) - Some pyrogens act directly and immediately on the hypothalamic thermoregulatory center to increase its set point - Purpose of fever is not completely understood - Can get a fever without having an infection

Cyclins

- Proteins that control the entry and progression of cells through the cell cycle by binding to and activating proteins called cyclin-dependent kinases (CDKs) - Different arrangements of _________ and CDKs are associated with each stage of the cell cycle

Respiratory Control Mechanisms

- Provides for elimination of CO2 into the air and plays major role in acid-base regulation - Increased pulmonary ventilation increases carbon dioxide elimination, producing a decrease in arterial PCO2 - Decreased ventilation decreases carbon dioxide elimination, producing an increase in arterial PCO2 - Chemoreceptors in the brain stem and peripheral chemoreceptors in the carotid and aortic bodies sense changes in the PCO2 and pH of the blood and alter the ventilatory rate - The respiratory control of pH is rapid (occurring within minutes, maximal within 12 to 24 hours) - Although the respiratory response is rapid, it does not completely return the pH to normal (only about 50% to 75% effective as a buffer system)

Ischemia-Reperfusion Injury

- Reestablishment of blood flow following loss of perfusion is associated with oxidative injury to vital organs (Endothelial dysfunction)

Maturation and Remodeling of Fibrous Tissue (Phase 3 of Repair)

- Remodeling of ECM - Rate of collagen synthesis decreases until reaches equilibrium with collagen degradation

Gene Mutations

- Represent accidental errors in duplication, rearrangement, or deletion of parts of the genetic code - Most are corrected by DNA repair mechanisms in the cell - Mutations can result from the substitution of one base pair for another, the loss or addition of one or more base pairs, or rearrangements of base pairs -Some occur spontaneously while others occur because of exogenous or environmental agents such as chemical and radiation.

Metaplasia

- Reversible change in which one adult cell type is replaced by another adult cell type (always within boundary of primary tissue type) - Thought to involve the reprogramming of undifferentiated stem cells. Usually in response to chronic irritation and inflammation. Cells better able to survive than more fragile cells they are replacing. (Ex. Tracheal changes in long-term cigarette smokers). - Continued exposure to the causes for metaplasia could result in cancer

Emigration of Fibroblasts & Deposition of ECM (Stage 2 of Repair)

- Scar formation builds on the granulation tissue framework of new vessels and loose ECM - Two phases: 1. emigration and proliferation of fibroblasts into the site injury and 2. deposition of extracellular matrix by these cells. - Mediated by growth factors - As healing progresses: collagen deposition takes place - Gives strength to healing area - Eventually turns into a scar

Stem Cells

- Self-renewal: stem cells can undergo numerous mitotic divisions while maintaining an undifferentiated state - Asymmetric replication: after each cell division, some progeny of the stem cell enter a differentiation pathway, while others remain undifferentiated, retaining their self-renewal capacity - Differentiating cells undergo multiple mitotic divisions becoming more mature cell type on way to specialization - Progeny of progenitor cell follows more restricted genetic program - Result: Single stem cell can produce many cells needed for normal tissue repair or blood cell production Potency: differentiation potential of stem cells - Totipotent: produced by a fertilized ovum, give rise to pluripotent stem cells - Pluripotent: can differentiate into the three germ layers of the embryo (ectoderm, mesoderm, and endoderm) - Multipotent: cells such as hematopoietic stem cells that give rise to a family of cells, including RBCs and all various types of leukocytes (WBCs). - Unipotent: produce only one cell type but retain the property of self-renewal (ex: skin cell)

Gene

- Sequence of DNA that contains the instructions for making a RNA molecule (the assembly of proteins), fundamental unit of info storage - Codon: Each set of three bases on the mRNA codes for a specific amino acid (used for protein synthesis in humans) - The amino acids are linked together in the order specified to make a protein - Genetic information carried in DNA can survive the many stages of cell division involved in the day-to-day process of cell renewal and tissue growth

X-Linked Recessive Inheritance

- Simple pedigree for inheritance of an X-linked recessive trait. - X-linked recessive traits are expressed phenotypically in the male offspring - A small blue-colored circle represents the X chromosome with the defective gene in the female and the larger blue-colored square represents the affected male - The affected male passes the mutant gene to all of his daughters, who become carriers of the trait and have a 50% chance of passing the gene to their sons and daughters, who in turn have a 50% chance of being carriers of the gene

Autosomal Dominant Inheritance

- Simple pedigree for inheritance of an autosomal dominant trait - The black-colored square (male) or circle (female) represents an affected person with a mutant gene - An affected parent with an autosomal dominant trait has a 50% chance of passing the mutant gene on to each child regardless of sex - In many conditions, the onset of disease is delayed so signs and symptoms do not appear until later in life (ex: Hungtinton's) - Sometimes, a person with an autosomal dominant disorder does not have an affected parent

DNA

- Stores genetic information in nucleus - Long, double-stranded, helical structure - Composed of nucleotides (phosphoric acid, a five-carbon sugar (deoxyribose), and one of four nitrogenous bases) - Nitrogenous bases carry genetic info (divided into two groups: pyrimidine bases and purine bases) - RNA is what moves genetic material out of nucleus DNA Helix and Base Pairing - Four bases: guanine, adenine cytosine, and thymine - Precise base pairing *A is paired with T *G is paired with C [A-T; G-C] - Each nucleotide in a pair is on one strand of the DNA molecule, with the bases on opposite DNA strands bound together by hydrogen bonds (this pairing allows for efficient and correct repair of damaged DNA molecules) DNA Packaging - Genome consists of chromosomes * Chromosomes: discrete bundles of one continuous, linear DNA helix * Each human somatic cells (non-gamete) has 23 pairs of different chromosomes * One from mother and other from father - Due to length, DNA double helices are coiled in a complex called chromatin which consist of histones and other proteins * Histones: ensure normal chromosome behavior and appropriate gene expression - Each complex of DNA with histone core is called a nucleosome, which is the basic structural unit of chromatin. - Each chromosome contains several hundred to over a million nucleosomes - DNA contains within its structure the basic information needed to direct the function of our cells, influence our appearance and how we respond to our environment, and serve as the unit of inheritance that is passed on from generation to generation - Genes transmit information contained in the DNA molecule as a triplet code consisting of an arrangement of the nitrogenous bases of the four nucleotides - The parental strands separate at the replication fork. Each parental strand serves as a template for the production of a new strand. The backbone of DNA consists of a sugar-phosphate backbone with paired pyrimidine bases (thymine [T] and cytosine [C] with their one nitrogen ring) and purine bases (adenine [A] and guanine [G] with their two nitrogen rings) projecting inward. During mitotic cell division, the newly duplicated double-stranded molecules are separated and placed in each daughter cell by the mechanics of mitosis. Each daughter cell again contains the meaningful strand and the complementary strand joined together as a double helix.

Stress cells may fill up with these (intracellular accumulations)

- Substances may accumulate in the cytoplasm or nucleus - Normal body substances: Lipids, proteins, pigments. produced faster than metabolism or removal (ex: fatty liver) - Abnormal endogenous substances: Metabolic products—glycogen, lipids, May result from genetic disorders hindering degradation of a substance or interrupting transfer of a substance to another site (ex: Tay sachs) - Abnormal exogenous substances: Pigments -May be transient or permanent, might be harmless or toxic. The significance of intracellular accumulations depends on the cause and severity of the condition. For example: hyperbilirubinemia is reversible but glycogen storage diseases result in organ dysfunction. **Endogenous: Icterus/jaundice secondary to retention of bilirubin **Exogenous: Coal dust

Nonpitting Edema

- Swollen area becomes firm and discolored - Occurs when plasma proteins have accumulated in the tissue spaces and coagulated - More common in infection or trauma

Cytokines and Chemokines

- TNF-a and IL-1 are responsible for directing both local and systemic inflammatory responses - Can be stimulated by bacterial toxins, immune cells, injury, and a variety of inflammatory stimuli - Mediators of acute-phase response associated with injury or infection include: fever, hypotension, increased heart rate, anorexia, release of neutrophils, and increased levels of corticosteroid hormones

Gene Expression

- The degree to which a gene or particular group of genes is active - Genes "turn on" and "turn off" - *Induction*: something turns a gene on - *Repression*: something turns a gene off - Gene expression involves a set of complex interrelationships among different levels of control including RNA transcription and posttranslational processing. Whenever product levels decrease, gene transcription is increased, and when product levels increase, gene transcription is repressed.

Cell Cycle

- The periodic biochemical and structural events occurring during cell proliferation are called the cell cycle Four phases: - G1(Gap 1) : post-mitotic (mature cell no longer capable of mitosis (cell division)) DNA synthesis ceases while RNA and protein synthesis and cell growth take place (longest phase- make organelles and proteins) - S: DNA synthesis occurs resulting in two sets of chromosomes, one for each daughter cell - G2: Pre-mitotic phase, similar to G1 (preparing for mitosis- making microtubules used to pull chromatids apart) - M (mitosis): Phase of nuclear division and cytokinesis (active cell division) Kara's Notes: G0: when environmental conditions are adverse (lack nutrients or growth factor) or cells become terminally differentiated (highly specialized), cells may exit the cell cycle and rest in this state -- cells in this state may reenter the cell cycle when nutrients or growth factor become available, in response to hormones or other signals such as blood loss or tissue injury that trigger the need for cell renewal -- some highly specialized and terminally differentiated cells may remain in G0 - Within cell cycle: checkpoints for specific events of the cell cycle (may need to pause) and also checkpoints to ensure DNA accuracy -- DNA damage checkpoints allow for any defects to be corrected so each daughter cell has full complement of genetic information identical to parent cell - The transition from G2 to M is thought to be one of the most important checkpoints in the cell cycle (All phases besides mitosis are considered interphase and most cells live there with the exception of cancer cells that are wanting to divide a lot)

Inflammation

- The reaction of vascularized tissues to cell injury or death - Characterized by the production and release of inflammatory mediators and the movement of fluid and leukocytes (WBC) from the vasculature into the extravascular tissues

Sustained/Continuous (fever pattern)

- The temperature remains above normal with minimal variations (usually less than 1 degree F) - Seen in drug-induced fever in which a drug causes a hypermetabolic fever-inducing state

Down Syndrome

- Trisomy 21 - Causes combination of birth defects including some degree of intellectual dysfunction, characteristic facial features, and other health problems - Growth delay; small head; flatter facial profile; small nose; depressed nasal bridge; small folds on inner corners of eyes (epicanthal folds); upward slanting of eyes; small, low-set and malformed ears; fat pad at back of neck; open mouth; larger, protruding tongue; single palmar crease; hypotonia and joint laxity - Often accompanied by congenital heart defects and increased risk of GI malformations - Most common chromosomal disorder (1: 691 births) - Risk increases with advancing maternal age (usually worried 30-35+ bc eggs have been there for so long). Reason for correlation in maternal age and chromosomal nondisjunction is unknown; thought perhaps to have something to do with the aging oocyte (egg). Women are born with all of the eggs they will ever have, oocytes may change as part of aging process. - Down syndrome due to translocation (think Robertsonian) show no relation to maternal age - Several prenatal screening tests can help determine the risk of having a child with Down syndrome -- Most commonly used are blood tests that measure maternal serum levels of alpha fetoprotein, human chorionic gonadotropin (HCG), unconjugated estriol, inhibin A, and pregnancy-associated plasma protein A. Ultrasound can show fetal nuchal translucency between 10 and 13 weeks gestation; fetus with Down syndrome tends to have a greater area of translucency compared with a chromosomally normal fetus. Standard for determining presence of Down syndrome in fetus is through chromosome analysis using chorionic villus sampling, amniocentesis, or percutaneous umbilical blood sampling.

Fever Mechanism

1. Release of PGE2 or fever-producing cytokines from inflammatory cells 2. Resetting thermostatic set point 3. Temperature-raising responses: vasoconstriction, shivering, piloerection, increased metabolism (causes FEVER) 4. Core body temp. reaches new set point 5. Temperature-reducing responses: vasodilation, sweating, increased ventilation - Febrile response is caused by a cytokine-induced upward displacement of the set point of they hypothalamic thermoregulatory center; resolves when factor causing the increased set point is removed (max is typically 105 degrees F) - Neurogenic fever: characterized by high temperature that is resistant to antipyretic therapy and is not associated with sweating; usually caused by damage to the hypothalamus

Progeria

A disease where children age uncontrollably, normal aging but it occurs earlier

Gene Silencing

A newer strategy for management of genetic disorders focuses on ______________ by using ribonucleic acid interference (RNAi) technology to stop genes from making unwanted disease proteins

Antidiuretic Hormone (ADH) Disorders

ADH (vasopressin) controls reabsorption of water by kidneys Two important conditions alter ADH levels *(know these)*: Diabetes insipidus (DI) - Neurogenic: occurs because of a defect in synthesis or release of ADH (ADH deficiency) - Nephrogenic: occurs because kidneys do not respond to ADH - Manifestations of DI: intense thirst, craving for ice water, and large urine output - Dangerous in someone who cannot communicate need for water or is unable to get water - Treated with access to water, ADH in medication form Syndrome of inappropriate ADH (SIADH) - Failure of the negative feedback system that regulates the release and inhibition of ADH - ADH secretion continues despite decreased serum osmolality causing water retention - Results in marked water retention and dilutional hyponatremia - Manifestations of SIADH: decreased urine output, high urine osmolality and low serum osmolality - Mild cases treated with fluid restriction

Turner Syndrome

Absence of all ( 45, X/0) or part of one of the female's two X chromosomes 1 in 5,000 live births Manifestations include: - Short stature - Absent ovaries - Congenital heart defects - Kidney problems - Typically normal intelligence - May have ADD

Local Manifestations of Inflammation

Acute inflammatory response usually involves production of exudates of various substances according to fluid type, plasma protein content, and presence or absence of cells Kinds of Exudate: - Serous: watery fluids low in protein content; result from plasma entering the inflammatory site - Hemorrhagic: result of severe tissue injury with damage to blood vessels - Fibrinous: contain large amount of fibrinogen and form a thick and sticky meshwork, much like fibers of a blood clot - Membranous, pseudomembranous: develop on mucous membrane surfaces and are composed of necrotic cells enmeshed in a fibropurulent exudate - Purulent, suppurative: Contains pus-composed of degraded WBCs, proteins, and tissue debris

Adipocytokines

Adipose tissue is an endocrine organ Produces several hormones including leptin and adiponectin - Leptin: involved in satiety and appetite -- involvement in obesity is uncertain - Adiponectin: decreases with increased adipose -- regulates insulin sensitivity (decreased) -- proinflammatory Adipose tissue integrally involved in coordinating a variety of physiologic processes including energy metabolism, neuroendocrine function, and immune function. It is the dysfunctional aspects of these processes that are implicated in the pathogenesis and adverse effects of adipose tissue excess or obesity. Abnormal cytokine production results in chronic inflammatory response

Wound healing in the Elderly

Age-related changes: - Decreased dermal thickness - Decline in collagen content - Loss of elasticity Elderly are more vulnerable to chronic wounds, such as pressure, diabetic, and ischemic ulcers as compared to younger persons

Teratogens

An environmental agent that produces abnormalities during embryonic or fetal development Theoretically, environmental agents can cause birth defects in three ways: - Direct exposure of the pregnant woman and the embryo or fetus to the agent - Exposure of soon-to-be-pregnant woman with agent that has a slow clearance rate - Effects of an environmental agent that occur before pregnancy causing permanent damage to a woman's or man's reproductive cells Stage of development of embryo determines susceptibility to teratogens Embryo is most susceptible to teratogenic agents during rapid differentiation and development of body organs and tissues Prenatal Screening: Prenatal diagnosis includes the use of ultrasonography, maternal blood sampling, and percutaneous umbilical fetal blood sampling - Ultrasonography is used for determination of fetal size and position and for the presence of structural anomalies - Maternal blood sampling, which measures alpha-fetoprotein (AFP), unconjugated estriol, and chorionic gonadotropin (hCG), is used to assess for neural tube defects (AFP) and Down syndrome (AFP, unconjugated estriol, and hCG) - Amniocentesis, chorionic villus sampling, and percutaneous umbilical blood sampling are used to obtain specimens for cytogenetic and biochemical studies

Laboratory Test in Acid-Base Balance

Arterial blood gases (ABG), serum electrolytes, base excess or deficit, and anion gap Serum pH measurement determines acidosis or alkalosis - Does not provide information about the cause of acid-base imbalance Base excess indicates metabolic alkalosis whereas base deficit indicates metabolic acidosis Anion gap - Difference between the serum concentration of the major measured cation (sodium) and the sum of the measured anions (chloride and bicarbonate) * Normal is 8 to 12 mEq/L. - Anion gap is increased in conditions such as lactic acidosis and ketoacidosis that result in a decrease of bicarbonate (Base excess or deficit is a measure of the bicarbonate excess or deficit. It describes the amount of a fixed acid or base that must be added to a blood sample to achieve a pH of 7.4 (normal))

Chromosomal Damage

Balanced reciprocal translocation - No genetic information is lost; therefore, persons with translocations usually are normal. However, these persons are translocation carriers and may have normal and abnormal children. Robertsonian translocation occurs most commonly in chromosomes 13 and 14 or 14 and 21: carriers of a Robertsonian translocation involving chromosome 21 are at risk for producing a child with Down syndrome Structural abnormalities in the human chromosome: - Deletion of part of a chromosome leads to loss of genetic material and shortening of the chromosome. - A reciprocal translocation involves two nonhomologous chromosomes, with exchange of the acentric segment. - Inversion requires two breaks in a single chromosome, with inversion to the opposite side of the centromere (pericentric) or with the fragment inverting but remaining on the same arm (paracentric). - In Robertsonian translocation, two nonhomologous acrocentric chromosomes break near their centromeres, after which the long arms fuse to form one large metacentric chromosome - Isochromosomes arise from faulty centromere division, which leads to duplication of the long arm and deletion of the short arm, or the reverse - A ring chromosome with breaks in both telomeric portions of a chromosome, deletion of acentric fragments, and fusion of the remaining centric portion Alterations in chromosome structure occur when there is a break in one or more of the chromosomes followed by rearrangement or deletion of the chromosome parts. Among factors believed to cause chromosome breakage are exposure to radiation sourced such as X-rays; including certain chemicals; extreme changes in the cellular environment; and viral infections.

Kinins (Plasma-Derived Inflammatory Mediators)

Bradykinin causes increased capillary permeability and pain

No, necrotic tissue is already dead, so it cannot be restored to functional tissue

Can necrotic tissue be reversed using high concentrations of oxygen?

Multifactorial Inheritance Disorders

Caused by multiple genes and, in many cases, environmental factors Cleft lip and cleft palate are common examples - Other congenital examples include clubfoot, congenital dislocation of the hip, congenital heart disease, and urinary tract malformation *Environmental factors are thought to play a greater role in disorder of multifactorial inheritance that develop in adult life*

Chronic Inflammation

Characterized by: - Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells) - Attempted connective tissue repair involving angiogenesis and fibrosis May increase susceptibility to cancer - Causes DNA damage which incites tissue proliferation as an attempt to repair the damage - May create an environment full of cytokines and growth factors = tumor development and growth Causes of chronic inflammation: - Persistent infections or irritants that do not penetrate deeply or spread rapidly - Disease causing excessive and inappropriate activation of immune system - People can be asymptomatic for a long time - May result from recurrent or progressive acute inflammatory situation or from a smoldering response that fails to cause an acute inflammatory response -- is often asymptomatic for a long time -- often causes tissue damage in atherosclerosis, chronic lung disease, RA, an inflammatory bowel disease. - Obesity is thought to cause chronic inflammation. White adipose tissue was recognized to be an active endocrine organ and a source of inflammation. Adipose tissue is a source of proinflammatory cytokine TNF-a = insulin resistance- Type 2 DM. Research is ongoing. - Granulomas are a form of chronic inflammation characterized by aggregates of epithelioid macrophages that "wall off" the causal agent. Granulomatous inflammation is associated with foreign bodies such as splinters, sutures, silica, and asbestos and with microorganisms that cause TB, syphilis, sarcoidosis, deep fungal infections, and brucellosis.

Meiosis

Chromosomes duplicate --> one pair goes to each daughter cell in first division --> one chromosome of each pair goes to the daughter cell in second division --> produces daughter cells (gametes (eggs or sperm)) with only one copy of each 23 chromosome - Limited to replicating germ cells and takes place only once in a cell line Two phases - In meiosis I: homologous chromosomes approach each other and pair forming a double-structured chromosome containing four chromatids (four strands). After cell division 1 each of the two daughter cells contains one member of each homologous pair of chromosomes and a sex chromosome (23 double-stranded chromosomes). No DNA synthesis occursin this phase . - During meosis II, the 23 double-stranded chromosome (two chromatids) of each of the two daughter cells from meiosis I divide at their centromeres (central regions where the chromatids meet). Each subsequent daughter cell receives 23 single-stranded chromatids (single set of 23 chromosomes). A total of four daughter cell is formed by meiotic division of one cell.

Nutritional Status

Condition of the body related to availability and use of nutrients - Nutrients provide energy and materials necessary for performing activities of daily living and for growth and repair of body tissues Can be assessed by evaluation of dietary intake; anthropometric measurements, and laboratory tests

Binge Eating

Consumption of unusually large quantities of food in a short period of time that is not followed by compensatory behaviors

Coagulation and Fibrinolysis Proteins (Plasma-Derived Inflammatory Mediators)

Contributes through formation of fibrin mesh formed during final steps of clotting process

Allele

Copies of a gene If all your copies of a gene are alike, you are homozygous (example: BB (homozygous dominant) or bb (homozygous recessive)) If they differ, you are heterozygous (example: Bb) - If you are heterozygous for a recessive trait and do not show it, you are a carrier Capital letter = dominant traits Lowercase letters = recessive traits Pedigree: graphic method for portraying a family history of an inherited trait

Transcription

DNA never leaves the nucleus (RNA is our mover) The step from DNA to messenger RNA (mRNA) is called transcription Transcription occurs in cell nucleus - Copying the genetic code containing the instructions for protein synthesis from DNA to complementary strand of mRNA Involves synthesis of RNA from a DNA template - Replication process is started when RNA binds to the double-stranded DNA at the promotor region (see picture next slide) - Weak hydrogen bonds of DNA are broken so free RNA nucleotides can pair with exposed DNA counter parts - Continues until reaches stop codon Messenger RNA (mRNA) is sent to ribosomes in the cytoplasm - Protein synthesis occurs (Involves attachment of RNA at the thymine-adenosine-thymine-adenosine region on the promotor region of DNA; terminates at the stop codon -- transcription creates a complementary copy of mRNA from one of the DNA strands in the double helix)

Systemic Manifestations of Inflammation

Damaged cells release inflammatory mediators. Local responses- in ideal conditions it is just a local response ~ Vascular stage ~ Cellular stage Systemic (whole-body) responses ~ White blood cell response (normal value 4,000 to 10,000. WBC response causes increase to 15,000 to 20,000) ~Acute-phase response

true Normal BMI = 18.5−24.9. BMI >25 places individuals at increased risk for type II diabetes, cardiovascular disease, and hypertension. The higher the BMI above normal, the greater the risk of health problems. Obesity is also associated with gallbladder disease, infertility, osteoarthritis, sleep apnea, complications of pregnancy, menstrual irregularities, nonalcoholic fatty liver disease, thromboembolic disorders, and poor wound healing. Childhood obesity is becoming an increasingly prevalent nutritional disorder that predisposes children and adolescents to hypertension, dyslipidemia, type2 DM, and psychosocial stigma.

Does a BMI that is greater than normal increases an individual's risk of developing type II diabetes mellitus?

Dissociation (Seperation) of Electrolytes

Electrolytes dissociate (disconnect or separate) in solution to form charged particles (ions) - Sodium chloride (NaCl) dissociates to form positively charged Na+ and negatively charged Cl- Nonelectrolytes do not dissociate into ions - Glucose and urea Cation - Positively charged ion Anion - Negatively charged ion Positive attracts negative - Result: ICF and ECF contain equal amounts of anions and cations Ions may exchange (pos. for pos. and neg. for neg.)

Upper Versus Lower Body Obesity

Fat distribution may be more important factor for morbidity and mortality than overweight or obesity

Proliferative phase During this phase, fibroblasts and vascular endothelial cells proliferate to form granulation tissue. Epithelial cells at the wound edges migrate, proliferate, and differentiate to form a new surface layer similar to that destroyed by the injury.

Fibroblasts, endothelial cells, and epithelial cells divide during which phase of wound healing?

- Gene - Genetics (Genetics plays an important role in disease development -- advances have lead to earlier detection of disease and new treatments)

Genetic control definitions (2): - Segment of DNA sequence that encodes a set of functional products, typically proteins - Study of genes

Genetics

Genetic disorders can be caused by single gene (mendelian) or multiple gene (polygenic) inheritance Single gene disorders - Defective gene may be present on an autosome (one of the 22 pairs) or on the X chromosome (sex chromosome) - May be expressed as a dominant or recessive trait

Chromosomes

Genetic information is stored as discrete bundles of DNA called _________ 46 chromosomes arranged in 23 pairs (one is from the mother and the other is inherited from the father, together the pair is a homologous chromosome) - 22 are alike for males and females (autosomes) - 1 pair of sex chromosomes (XX pairing in females, XY pairing in males - Y chromosome contains male-specific region that determines sex)

- Expressivity - Penetrance - Locus

Genetic-related Definitions (3): - Gene expression in the phenotype - The ability of a gene to express its function (75% penetrance means 75% of persons of a particular genotype present with a recognizable phenotype. Syndactyly (webbed fingers or toes) and blue sclera are genetic mutations that often do not exhibit 100% penetrance) - Position of a gene on a chromosome (two copies of a gene at the same locus are called alleles)

Eosinophils

Granulocyte: 2% to 3% of circulating leukocytes (WBCs), appear at site of acute inflammation 2 to 3 hours after neutrophils, granules toxic against worms that cannot be phagocytized, play important role in allergic reactions, longer life so present in chronic inflammation, too

Basophils

Granulocyte: < 1% of circulating WBCs, most prominent in allergic reactions mediated by IgE-binding of IgE triggers release of histamine and vasoactive agents from basophil granules

Neutrophils

Granulocyte: Most numerous leukocyte, first cells to appear at site of acute inflammation, capable of phagocytizing bacteria and debris, disappear within 24 to 48 hours via apoptosis (multi-lobed nucleus)

Potassium (K)

High ___________ content in ICF necessary for many cell functions, second most abundent cation in the body - Maintenance of osmotic integrity of cells and acid-base balance, chemical reactions that transform carbohydrates into energy, changing glucose into glycogen, and converting amino acids to proteins - Conducting nerve impulses and controlling the excitability of skeletal, cardiac, and smooth muscles Normal level is 3.5 to 5.0 mEq/L Maintains intracellular osmolarity Controls cell resting potential Needed for Na+/K+ pump Exchanged for H+ to buffer changes in blood pH Regulation - Ingested through foods - Eliminated in the urine - ICF and ECF levels regulated by * Compartmental shifts and adjustments in renal excretion with dietary ingestion of potassium

Hyperkalemia

High serum potassium >5.5 mEq/L Causes: - Most common cause is decreased renal function/chronic kidney disease - Decreased elimination of potassium by the kidney - Shift from ICF to ECF - Excessive rapid IV administration of potassium Symptoms: - Intestinal cramping, diarrhea, muscle weakness, paresthesia, paralysis - EKG changes, risk of cardiac arrest with severe ___________ - Can cause brady dysrhythmias which can result in ventricular fibrillation or cardiac arrest

Genotype: a person's genetic material - Genetic information stored in the base sequence triplet code Phenotype: a person's physical characteristics Genotype usually not evident by available detection methods More than one genotype may have the same phenotype - Some brown-eyed persons carry one copy of the gene that codes for blue eyes and other brown-eyed persons do not. - Phenotypically, these two types of brown-eyed persons are the same, but genotypically they are different.

How are genotype and phenotype different?

- Leukocytes (WBC) are the major cellular components of the inflammatory response - Two types: granulocytes and agranulocytes *Granulocytes: contain specific cytoplasmic granules and a nucleus with multiple lobes *Agranulocytes: lack cytoplasmic granules and have a single nucleus - Granulocytes Neutrophils Eosinophils Basophils - Agranulocytes Monocytes/macrophages Lymphocytes

How do WBC's participate in inflammation?

One gene in the nucleus may produce: - Many different mRNAs - Many different proteins *Splicing* permits a cell to produce a variety of mRNA molecules from a single gene and thus a variety of different proteins from a single gene

How do we process mRNA?

Moment-by-moment regulation of pH depends on chemical buffer systems in ICF and ECF 3 major systems - Chemical buffer system in body fluids- immediately combine with excess acids or bases to prevent large changes in pH - Transcellular hydrogen- potassium exchange system - Body proteins- largest buffer system in the body, can function as acids or bases pH is threatened by the production of strong acids resulting from protein metabolism These strong acids are buffered in the body by chemical buffer bases such as ECF bicarbonate The kidney eliminates hydrogen ions combined with urinary buffers and anions in the urine At the same time, they add new bicarbonate to the ECF to replace the bicarbonate consumed in buffering strong acids The respiratory system disposes of carbon dioxide

How do we regulate pH?

- Diminishes ATP production - Oxygen is a key reactant for the majority of ATP production. With less oxygen, less ATP is produced, and the cell cannot function at the same level. If hypoxia is severe or prolonged, the cell will die.

How does hypoxia cause cell damage?

- Determine cause of fever - Fever of Unknown Origin (FUO) - Modify environment so heat is transferred away from body - Avoid vasoconstriction/shivering - Lots of fluids and adequate intake of simple carbs - Antipyretic drugs work by resetting the hypothalamic temperature control center to a lower level (likely by blocking the activity of cyclooxygenase (required for conversion of arachidonic acid to prostaglandin E2)

How is a fever managed?

Renal Control Mechanisms

Hydrogen (acid)/bicarbonate (base) exchange system Regulates pH through the secretion of excess H+ and reabsorption of HCO3- (bicarb) by renal tubules Chloride/bicarbonate anion exchange - Occurs in association with Na+ reabsorption. Chloride is absorbed along with sodium throughout the tubules Potassium/hydrogen exchange system - Occurs in collecting tubules, functions in hydrogen secretion by substituting the reabsorption of potassium for excretion of hydrogen (Both reabsorption of bicarb and excretion of acid are accomplished through hydrogen secretion as the urine filtrate moves through the tubular structure of the kidney) (Generation of new bicarb: Ammonia buffer system Phosphate buffer system: Utilized because elimination of extremely acidic urine would be damaging to the urinary tract)

B. 50% Rationale: Because a son receives the X sex chromosome from his mother (who has one normal and one mutant allele), there is a 50% chance that the mutant allele will be inherited.

If an unaffected mother carries one normal and one mutant allele on her X chromosome, what are the chances that she will transmit the defective gene to her sons? A. 25% B. 50% C. 75% D. 100%

- No: It is recessive - Yes: It is dominant - Sometimes: It has intermediate penetrance

If you have the allele for a trait, do you display the trait?

Intermediate and Long-Term Regulation of Hunger

Increased blood glucose Adipose cells secrete hormones - Leptin Increased blood ketoacids --> Hypothalamus satiety center--> Feeling of "fullness"

ROS

Influence of ROS in any inflammatory process depends on a balance between the generation and inactivation of metabolites

The Human Genome Project

International project - Goal is sequencing and identifying all genes in human genome Any two individuals share 99.9% of their DNA sequence, indicating that the remarkable diversity among individuals is vested in about 0.1% of our DNA The genome is the gene complement of an organism.

Fluid Distribution

Intracellular fluid compartment (ICF) - Contains about 2/3 of the body water in healthy adults - ICF composition: * Almost no calcium * Small amounts of sodium, chloride, bicarbonate, and phosphate * Moderate amounts of magnesium * Large amounts of potassium Extracellular fluid compartment (ECF) - Remaining 1/3 of body water (interstitial (tissue) spaces AND plasma in blood vessels) - The extracellular space includes the vascular compartment and the interstitial spaces - ECF composition: * Large amounts of sodium and chloride * Moderate amounts of bicarbonate * Small amounts of potassium, magnesium, calcium, and phosphate

Isotonic Fluid Disorders

Isotonic fluid volume deficit (hypovolemia) - Deficit in ECF volume - Almost always caused by loss of body fluids & often accompanied by decrease in fluid intake - Results in weight loss, thirst, signs of dehydration, and decreased urine output along with an increase in urine specific gravity - Treated with fluid replacement Isotonic fluid volume excess (hypervolemia) - Expansion of ECF compartment with increases in both interstitial and vascular volumes - Usually results from an increase in total body sodium that is accompanied by a proportionate increase in body water * Can occur due to excessive sodium intake, usually caused by decrease in sodium and water elimination by kidney * Circulatory overload: IV fluid infusion or transfusion of blood - Characterized by an increase in ECF volume and is manifested by signs of increased vascular volume and edema - Treated with sodium restriction and diuretics

The Punnett square showing all possible combinations for transmission of a single gene trait (dimpled cheeks). The example shown is when both parents are heterozygous (Aa) for the trait. The alleles carried by the mother are on the left and those carried by the father are on the top. The A allele is dominant and the a allele is recessive. The AA and Aa offspring have dimples and the aa offspring does not.

Know punnett squares for test!! (not in depth)

RNA

Large molecule made up of long string of nucleotides Differs from DNA in three aspects: - RNA is single-stranded - Sugar in each nucleotide is ribose instead of deoxyribose - Pyrimidine base thymine [T] in DNA is replaced by uracil [U] in RNA DNA determines what is needed by the cell and directs production RNA, through transcription and translation, is responsible for actual assembly of the products (proteins) Cells contain three types of RNA: 1. Messenger RNA (mRNA) - Template for protein synthesis - Each group of three nucleotides forms a codon that is exactly complementary to a nucleotide triplet of the DNA molecule. - mRNA is formed by transcription: the weak hydrogen bonds of DNA are broken so that free RNA nucleotides can pair with their exposed DNA counterparts - As with base pairing of DNA strands, complementary RNA bases pair with the DNA bases 2. Ribosomal RNA (rRNA) - rRNA forms 60% of the ribosomes - Produced in nucleolus, rRNA synthesizes proteins - The formed rRNA combines with ribosomal proteins in the nucleus to produce the ribosome, which is then transported into the cytoplasm. In the cytoplasm, most ribosomes become attached to the endoplasmic reticulum and begin the task of protein synthesis 3. Transfer RNA (tRNA) - Translates mRNA - Delivers the activated form of an amino acid to the protein being synthesized in ribosome - Smallest RNA molecule

Hypokalemia

Low serum potassium < 3.5 mEq/L Causes: - Inadequate intake - Excessive losses - Redistribution from ECF to ICF - Some medications can cause intracellular shifts including beta-agonists and insulin Symptoms: - Increased thirst, nausea, vomiting, constipation (due to reduced function of GI muscles), muscle weakness, flabbiness, fatigue, paresthesia, muscle cramps and tenderness, confusion, depression - Impact on heart: decreased resting membrane potential which can cause changes on EKG

Metabolic

Metabolic acidosis (serum pH<7.35 & bicarb < 24 meq/dL): decrease in pH/increase in H+ due to a decease in bicarb (HCO3-) - Caused by excessive production and accumulation of metabolic acids or excessive loss of bicarb - Increased levels of ketoacids, lactic acid (cardiac arrest), etc. - Decreased bicarbonate levels - Heavier breathing causes decreased PCO2. -Treatment focuses on correcting underlying cause and restoring fluids and electrolytes that have been lost from the body. Metabolic alkalosis (serum pH>7.45, bicarb>29, & base excess above 3): an increase in pH/decrease in H+ due to an increase in bicarb, is caused by conditions that produce a gain in bicarb or a decrease in hydrogen (H+) - Decreased H+ levels - Increased bicarbonate levels - Lighter breathing causes increased PCO2 -Treatment focuses on correcting the cause

Mitochondrial DNA

Mitochondria have their own DNA distinct from DNA in cell nucleus Codes for the proteins needed for aerobic metabolism Mitochondria come from the mother (disorders typically inherited from mom) Interferes with production of cellular energy Generally affects tissues with high energy needs - Nervous system - Heart muscle - Skeletal muscle

Agranulocytes

Monocytes -> macrophages - Monocytes account for 3% to 8% of circulating WBCs - Half-life of monocytes is about 24 hours after which they migrate to site of injury and mature into larger macrophages to become more phagocytic - Linked to atherosclerosis - Produce vasoactive mediators including prostaglandins and leukotrienes, platelet-activating factor (PAF), cytokines, and growth factors to help regenerate tissue - Help start healing process, play a role in chronic inflammation Lymphocytes - T lymphocytes: activated T cells produce cytokines that activate macrophages furthering cytokine production = chronic inflammation - B lymphocytes -> plasma cells: in the inflammatory site, they produce antibodies directed at antigens

Triplet Repeat Mutations

Mutation characterized by long repeating sequence of three nucleotides 40 diseases associated with neurodegenerative changes have been classified as triplet repeat mutations including - Fragile X syndrome (most common after down syndrome for disabilities) - Huntington disease - Myotonic dystrophy Fragile X: fragile site on the long arm of the X chromosome Other features of Fragile X: - Large face; large mandible; large, everted ears; hyperextensible joints; high-arched palate; mitral valve prolapse; large testes

Magnesium

Normal level 1.3 to 2.1 mg/dL Ingested in diet, absorbed from the intestine, and excreted by the kidneys Mainly regulated by kidneys; renal absorption stimulated by PTH Cofactor in enzymatic reactions: - ATP generation - DNA replication - mRNA production and translation Blocks K+ exit from cardiac cells Smooth muscle relaxant

Phosphorus

Normal level is 2.5 to 4.5 mg/dL More in ICF (14%) than ECF, more in bone (85%) Ingested in diet and eliminated in urine Many dietary sources including red meats and milk Renal elimination directly related to amount of phosphate in blood Functions: - Bone and ATP formation - Glucose, fat, protein metabolism - In DNA, RNA, phospholipids - Acid-base buffer - RBC, WBC, platelet function

Calcium

Normal level is 8.5 to 10.5 mg/dL 99% located in bone; most of remainder in ICF Functions: - Bone strength and stability - Membrane potentials and excitability - Contraction of all muscle types - Clotting - Second messenger in many hormone and neurotransmitter pathways

Acid-Base Balance

Normal metabolic body function depends on the precise regulation of acid-base balance - Normally maintained in very narrow range of 7.35 to 7.45 Acid - Compound that can dissociate and release a hydrogen (H+) ion Base - Compound that can accept or combine with H+

pH

Normal value is 7.35 to 7.45 Regulated by - Chemical buffer systems - Lungs: eliminate CO2 Kidneys: eliminate H+, reabsorb/generate HCO3− Lungs quicker and kidney better for regulating pH

Short-Term Regulation of Hunger

Oral receptors detect tasting, chewing, swallowing GI tract secretes hormones - Cholecystokinin, glucagon-like peptide 1, ghrelin, insulin, glucagon Stomach stretches --> Hypothalamus satiety center --> Feeling of "fullness"

Osmolarity

Osmolarity/osmolality - Osmotic activity of a solution Serum osmolality usually determined by Na+ and associated anions Tonicity - Tension or effect osmotic pressure of a solution with nondiffusible solutes exerts on cell size - Due to water movement across the cell membrane * Isotonic * Hypertonic solution (cell shrinks) * Hypotonic solution (cell swells)

Edema

Palpable swelling produced by increase in interstitial fluid volume Physiologic mechanisms: - Factors that increase capillary filtration pressure (increased vascular volume (CHF), venous obstruction) - Factors that decrease capillary colloidal osmotic pressure (increased loss of plasma proteins (extensive burns), decreased production of plasma proteins (liver disease)) - Factors that increase capillary permeability (inflammation, allergic reactions) - Factors that produce obstruction to lymph flow (surgical removal of lymph nodes (biopsy, mastectomy))

Acid

Physiologically, ________'s fall into two groups: - Volatile: carbonic acid [H2CO3] (derived from CO2)- leave body by way of lungs - Nonvolatile: nonvolatile acids- generated by metabolism of dietary proteins -- leave body by kidney after buffering Other sources of acid generation: - Energy metabolism (lactic acid) - "Food" for brain (ketoacids) - Most of the body's acids and bases are weak; the most important are H2CO3, (carbonic acid), which is a weak acid derived from carbon dioxide (CO2) and HCO3- (bicarbonate), which is a weak base - pH represents the negative logarithm of the hydrogen concentration, thus a low pH indicates a high concentration of hydrogen and a high pH a low concentration of hydrogen

Plasma vs Cell

Plasma-derived mediators are synthesized in the liver. Plasma is the source of inflammatory mediators that are products of three major protein cascades or systems: the kallikrein-kininogen system which generates kinins, the coagulation system which includes the fibrin end product, and the complement system that includes various complement proteins. Cell-derived mediators are released from cells that are present at sites of inflammation. Tissue macrophages, mast cells, endothelial cells, as well as leukocytes that are recruited to the site from the blood are all capable of releasing different mediators of inflammation, as are platelets.

Inflammatory Mediators

Plasma-derived mediators are synthesized in the liver. They are present in plasma in precursor form that must be activated ~ Acute phase proteins ~ Coagulation factors ~ Complement proteins Cell-derived mediators are released from cells that are present at the site of inflamation ~ Platlets ~ Neutrophils ~ Monocyte/macrophages ~ Mast cells

Pyogenic

Pus forming

Environmental Causes for Congenital Disorders

Radiation and environmental pollutants such as mercury, medications and illicit dugs, alcohol, and infectious agents Women of childbearing age avoid all unnecessary use of drugs and abstain from alcohol Infectious agents most frequently implicated in fetal anomalies - TORCH: toxoplasmosis, other, rubella, cytomegalovirus, herpes Maternal folic acid deficiency - Can cause neural tube defects Iodine deficiency - Can cause congenital hypothyroidism and impaired neurological development

Anorexia Nervosa

Refusal to maintain a minimally normal body weight

Respiratory

Respiratory acidosis (serum pH<7.35 and arterial PCO2 above 50 mm Hg) : reflects a decrease in pH due to an increase in PCO2 levels - Caused by conditions that cause hypoventilation (decreased ventilatory drive, lung disease, disorder of chest wall) - Increased bicarbonate Respiratory alkalosis (serum pH>7.45, arterial PCO2<35, and serum bicarb levels usually below 24): reflects an increase in pH due to a decrease in PCO2 levels - Caused by conditions that cause hyperventilation (anxiety, pain, fever, encephalitis) - Decreased bicarbonate

Chromosomal Disorders

Result from a change in chromosome structure or number Reflect events that occur at the time of meiosis - Defective movement of an entire chromosome - Breakage of a chromosome with loss, gain, or translocation of genetic material Commonly identified according to the shorthand description of the karyotype - Total number of chromosomes is given first, followed by the sex chromosome complement, and then the description of any abnormality - Male with trisomy 21 (Down's syndrome) - 47,XY, +21 (has third copy of 21st chromosome)

Mechanisms of Water and Sodium Regulation

SYMPATHETIC NERVOUS SYSTEM Two major players of water regulation: thirst and antidiuretic hormone (ADH) Two major players of sodium regulation: sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAS) SNS responds to changes in arterial pressure and blood volume - Adjusts the glomerular filtration rate (GFR) and rate of sodium filtration from the blood - Regulates reabsorption of sodium in kidneys and renin release The RAS system works through angiotensin II and aldosterone - Angiotensin II works on the renal tubules to increase sodium reabsorption - Angiotensin II also causes constriction of renal blood vessels which decreases the glomerular filtration rate and slows renal blood flow so that less sodium is filtered and more is reabsorbed - Angiotensin II also regulates aldosterone which is a hormone secreted by the adrenal cortex - Aldosterone increases sodium reabsorption by kidneys while increasing potassium elimination

Brugada syndrome has only a 12.5% penetrance What does this mean for the young man whose father died of it? - When a person inherits a dominant mutant gene but fails to express it, the trait is described as having reduced penetrance - Penetrance is expressed in mathematical terms: a 50% penetrance indicates that a person who inherits the defective gene has a 50% chance of expressing the disorder. The person who has a mutant gene but does not express it is an important exception to the rule that unaffected persons do not transmit an autosomal dominant trait. These persons can transmit the gene to their descendants and so produce a skipped generation. - Autosomal dominant disorder also can display variable expressivity, meaning that they can be expressed differently among individuals. For example, polydactyly can happen in fingers or toes.

Scenario: - A young man's father died of Brugada syndrome (don't have to know what this disease is but its a cardiac issue) - Unexplained sudden death (due to gene mutation for cardiac muscle Na+ channel) - Autosomal dominant trait - His mother and both grandmothers are alive and healthy Question: What is the son's chance of having the disease?

Bulimia nervosa: secretive episodes of binging

Secretive episodes of binging followed by compensatory behaviors such as self-induced vomiting

Hypocalcemia

Serum calcium < 8.5 mg/dL Result: nerves fire more easily Other symptoms: paresthesia, tetany (muscle spasms of face, hands, feet), seizures (severely low calcium) Causes: - Lost through kidneys in renal failure - Abnormal PTH levels (hypoparathyroidism) - Impaired mobilization of calcium from bone - Acute pancreatitis - Medications (antiepileptics, loop diuretics) Manifestations: - Asymptomatic in mild cases - Increased neuromuscular excitability leading to paresthesias, tetany, and possibly laryngeal spasm and seizures - Cardiovascular effects include hypotension, cardiac insufficiency, cardiac arrhythmias (heart block and v-fib) Treatment depends on severity/duration: IV calcium, oral calcium

Hypercalcemia

Serum calcium > 10.5 mg/dL Result: nerves less able to fire Causes: - Hyperparathyroidism resulting in increased resorption from bone - Neoplasms - Medications Manifestations - Alterations in cardiac and smooth muscle function, dulled consciousness, weakness, muscle flaccidity, ventricular arrhythmia, constipation, N/V, bone pain, kidney stones Treatment: - Rehydration, loop diuretics, bisphosphonates

Autosomal Recessive Inheritance

Simple pedigree for inheritance of an autosomal recessive trait The half blue-colored square (male) and circle (female) represent a mutant gene When both parents are carriers of a mutant gene - 25% chance of having an affected child (full blue-colored circle or square) - 50% chance of a carrier child - 25% chance of an unaffected or noncarrier child, regardless of sex

Platelets (Cells of Inflammation)

Small, membrane-bound disks circulating in the blood that play an active role in normal homeostasis -- when a _______ undergoes activation, over 300 proteins are released, many of which play a role in the inflammatory process

False: The surface epithelial cells of the skin are most likely to be damaged in this instance. Surface epithelial tissue has the ability to regenerate, replacing the damaged tissue with the same type (epithelial).

T/F: If you get a paper cut, epithelial tissue will be replaced with connective tissue.

Remittent Fever (fever pattern)

Temperature does not return to normal

Gangrene

Term applied when considerable mass of tissue undergoes necrosis

Sex-Linked Traits

The gene is usually on the X chromosome An unaffected mother carries one normal and one mutant allele on the X chromosome - She has a 50% chance of transmitting the defective gene to her sons, who are affected bc they only have one X, and her daughters, who are carriers - Because one of the paired genes is normal, female heterozygotes rarely experience the effects of a defective gene Examples - Red-green colorblindness - Male Pattern baldness - Hemophilia - Duchenne Muscular Dystrophy

Extracellular Matrix (ECM)

The process of tissue growth and repair involves proliferation of functioning parenchymal cells of an organ or body part and its supporting connective tissue and ECM ECM Properties: - Provides turgor to soft tissue and rigidity to bone - Supplies substratum for cell adhesion involved in regulation of growth, movement, and differentiation of cells surrounding it - Provides for the storage and presentation of regulatory molecules that control the repair process - Provides scaffolding for tissue renewal (Transitions in the ECM are critical components of wound healing. ECM components are degraded by proteases, some of which are highly specific. For example, collagenases are highly specific and cause cleaving of particular proteins at a small number of sites which allows for the structural integrity of the ECM to be retained while healing occurs)

- Hypodipsia - Polydipsia

Thirst Definitions (2) Decrease in ability to sense thirst - Associated with lesions near hypothalamus - Elderly persons - May lead to dehydration Excessive thirst - Normal during water deficit - Abnormal when results in excessive water intake - Psychogenic form can be seen in some mental health disorders

Thirst and Control of Blood Osmolarity

Thirst controlled by thirst center in hypothalamus Two stimuli for true thirst based on water need - Cellular dehydration caused by increase in ECF osmolality - Decreased circulating volume Osmoreceptors (sensory neurons)near thirst center respond to changes in ECF osmolality by swelling or shrinking - Thirst normally develops when there is as little as a 1% to 2% change in serum osmolality Third stimulus responding to low blood volume and low BP - Production of angiotensin II from kidneys - Considered backup system; may lead to thirst in persons with CHF or chronic kidney disease where renal blood flow is decreased *(High osmolarity = more concentrated)*

B. Increased proliferation and decreased apoptosis Rationale: Proliferation, or cell division, increases the number of cells in a tissue. Apoptosis, or programmed cell death, decreases the number of cells in a tissue. If proliferation is increased, tissue size increases. If apoptosis decreases, cell death decreases; cell numbers and tissue size increase. Kara's Notes: In normal tissues, the size of the cell population is determined by a balance of cell proliferation, death by apoptosis, and emergence of newly differentiated cells from stem cells

Tissue size will increase with: A. Increased proliferation and increased apoptosis B. Increased proliferation and decreased apoptosis C. Decreased proliferation and increased apoptosis D. Decreased proliferation and decreased apoptosis

Capillary/Interstitial Fluid Exchange

Transfer of water between vascular and interstitial compartments occurs at capillaries Four main forces: 1. Capillary filtration pressure: pushes water out of capillary into interstitial spaces 2. Capillary colloidal osmotic pressure: pulls water back into the capillary 3. Interstitial or tissue hydrostatic pressure: opposes the movement of water out of the capillary 4. Interstitial colloidal osmotic pressure: pulls water out of the capillary into the interstitial spaces

True Rationale: ADH prevents diuresis by causing more water to be reabsorbed in the kidney tubules. If more water is reabsorbed, there is less water left to eliminate as waste, decreasing urine output.

True or False? Increased levels of ADH decrease urine output.

False Rationale: A calorie is simply energy measured in heat units (the amount of heat or energy required to raise the temperature of 1 g of water 1°C). Metabolism is the breakdown of nutrients.

True or false? A calorie is energy that measures the breakdown of nutrients.

False Rationale: Hyperkalemia causes cells to fire more easily by moving RMP closer to the threshold, making them more likely to fire. In hypercalcemia, cells are less likely to fire. In hypocalcemia, cells are more likely to fire.

True or false? Both hyperkalemia and hypercalcemia cause cells to fire more easily.

True Rationale: While each chromosome contains the same genetic material, the same genes are not activated in every cell. For example, if a gene responsible for a digestive enzyme were to be induced in the lung, the result would be digestion of lung tissue, which would result in significant tissue/organ damage.

True or false? If a gene is induced where it should be repressed, the result can be injury to the tissue.

False Rationale: Mitosis replicates nongerm cells, like red blood cells and epithelial cells. It occurs during growth, replacement, or repair. Cell division that forms gametes is termed meiosis and occurs only once in a cell line. Mitosis provides a way for the body to replace cells that have a limited life span; increase tissue mass during periods of growth; and repair tissue, such as in wound healing.

True or false? Mitosis results in the formation of gametes (reproductive cells).

False Rationale: As blood levels of CO2 increase, pH becomes more acidic (decreases).

True or false? Serum levels of pH and CO2 levels are directly proportional.

False Rationale: bb represents a genotype (the two alleles). The physical trait that results from a certain genotype is termed phenotype. An easy way to remember this is the first two letters of the term and its description: phenotype/physical trait.

True or false? bb represents the phenotype for blue eyes.

Malnutrition

Two functional compartments involved in the distribution of proteins within the body: - Somatic compartment represented by skeletal muscles - Visceral compartment represented by protein stores in body organs, principally the liver Protein-energy Malnutrition: Marasmus - Too few calories and too little protein in diet - Affects the somatic compartment (skeletal muscle) more severely Kwashiorkor: - Adequate calories but too little protein in diet - Affects the visceral compartment more severely (especially liver) - Also common during illness, recovery from trauma, and hospitalization - In industrialized societies, protein-energy malnutrition most often occurs secondary to trauma or illness - Kwashiorkor-like secondary protein - energy malnutrition typically results from chronic illnesses such as COPD, CHF, cancer, and HIV The effects of malnutrition and starvation on body function are widespread - Loss of muscle mass - Impaired immunologic function and wound healing - Decreased appetite - Loss of calcium and phosphate from bone - Anovulation and amenorrhea in women - Decreased testicular function in men

Disorders of Acid-Base Balance

Two types: - Metabolic - Respiratory Metabolic disorders produce an alteration in the serum bicarbonate concentration and results from the addition or loss of nonvolatile acid or alkali to or from the ECF. - A reduction in pH due to a decrease in bicarbonate is called metabolic acidosis - An elevation in pH due to increased bicarbonate levels is called metabolic alkalosis Respiratory disorders involve an alteration in the arterial PCO2, reflecting an increase or decrease in alveolar ventilation *Respiratory acidosis* is characterized by a decrease in pH, reflecting a decrease in ventilation and an increase in PCO2 *Respiratory alkalosis* involves an increase in pH, resulting from an increase in alveolar ventilation and a decrease in PCO2

Cutaneous Wound Healing: Primary and Secondary Intention

Type of intention (primary vs secondary) depends on extent of tissue loss - Primary intention = sutured surgical incision - Secondary intention = larger wounds such as burns and large surface wounds with greater tissue loss and contamination Healing by secondary intention is slower and results in formation of larger amounts of scar tissue Infection might make a wound normally healed via primary intention require healing through secondary intention

Third- Spacing

Use from Kara's notes

Cell-Derived Mediators

Vasoactive amines: histamine (produces dilation of arterioles and increases the permeability of venules, binds to H1 receptors on endothelial cells. Antihistamine drugs bind to H1 receptors and antagonize (work against) many effects of the immediate inflammatory response), serotonin ~ Derived from amino acids and produce changes in blood vessel tone Eicosanoid family: prostaglandins, leukotrienes - Cyclooxygenase pathway - Lipoxygenase pathway Omega-3 polyunsaturated fatty acids - Dietary modification of the inflammatory response - Potentially reduces arachidonic acid-derived inflammatory mediators Platelet-activating factor (PAF): activates a variety of cell types - Induces platelet aggregation and degranulation at the site of injury enhances leukocyte adhesion among other properties Cytokines and chemokines: TNF-a, IL-1 Produced by many cell types, major source is activated macrophages Nitric oxide (NO): relaxes vascular smooth muscle among other roles Reactive oxygen species (ROS): Released from leukocytes in phagocytosis

Acute Inflammation—Vascular Stage

Vasodilation ~ Increasing blood flow to the injured area ~ Induced by mediators include histamine and nitric oxide ~ Redness and warmth result Increased permeability of microvasculature ~ Allows protein-rich exudate into extravasculature ~ Mediators include histamine, bradykinin, and leukotrienes ~ Loss of plasma proteins leads to: - Lowers osmotic pressure of interstitial fluid - Fluid movement into the tissue space from the vasculature - Results in swelling, pain, and impaired function

- Embryonic - Adult

What are the 2 basic categories of stem cells?

- Basement membrane: surrounds epithelial, endothelial and smooth muscle cells - Interstitial matrix: present in spaces between cells in connective tissue and between the epithelium and supporting cells of blood vessels

What are the 2 basic forms of ECM?

- Fibrous structural proteins (collagen and elastin fibers) - Water-hydrated gels (proteoglycans and hyaluronic acid)-permit resilience and lubrication - Adhesive glycoproteins (fibronectin and laminin)-connect matrix elements to one another and to cells

What are the 3 basic components of the ECM?

- Caused by upward displacement of the set point of the thermoregulatory center in the hypothalamus Causes of fever: - Many microorganisms - Proteins such as lipopolysaccharide toxins released from bacterial cell membranes can raise the set point of the hypothalamic thermostat - Noninfectious but secrete pyrogens: myocardial infarction and pulmonary emboli, some malignant cells

What are the causes of a fever?

Disorders impact calcium and phosphate homeostasis Acute hypoparathyroidism causes hypocalcemia - Manifested by signs of increased neuromuscular excitability such as tetany Chronic hypoparathyroidism is manifested by lethargy and fatigue Hyperparathyroidism - Primary disorder causing elevated serum calcium levels and increased urinary excretion of both calcium and phosphorus. - Increased chance for kidney stones - Secondary hyperparathyroidism, which is associated with chronic kidney disease, exerts it effects on bone = osteodystrophy = increased fracture risk

What are the disorders of parathyroid hormone (PTH)?

Causes water to move in or out of cells Hyponatremia - Serum sodium less than 135 mEq/L - Increase in ICF water causing cells to swell - Symptoms: muscle cramps, weakness, fatigue, N/V, lethargy, headache, confusion, seizures, coma Hypernatremia - Serum sodium more than 145 mEq/L - ICF water deficit and cellular dehydration - Symptoms: weight loss, thirst, decreased urine output, dry mucous membranes and skin

What are the effects of hypernatremia and hyponatremia?

Results in one of three processes: - Resolution: replacement of any irreversibly injured cells and return of tissues to normal structure and function (minimal injury; inflammatory processes are ceased) (involves neutralization or degradation of inflammatory mediators, normalization of vascular permeability, and cessation of leukocyte infiltration) - Progression to chronic inflammation (may occur if offending agent is not removed; restoration may still be possible) - Substantial scarring and fibrosis (occurs after substantial injury or when inflammation occurs in tissues that do no regenerate) Outcome determined by nature and intensity of injury, tissue affected, an person's ability to mount a response Recent research shows that resolution begins soon after inflammatory process has started. Neutrophils trigger a switch from proinflammatory eicosanoids (prostaglandins and leukotrienes) to other anti-inflammatory classes of eicosanoids which initiate the termination sequence during which neutrophil recruitment ceases and programmed cell death by apoptosis commences. The apoptotic neutrophil then undergo phagocytosis by macrophages, leading to their clearance and release of anti-inflammatory and reparative cytokines. Research is ongoing.

What are the outcomes of acute inflammation?

The mechanisms of cell injury can produce sub-lethal and reversible cellular damage or lead to irreversible injury with cell destruction or death. - Reversible cell injury - Apoptosis - Necrotic cell death

What are the outcomes of cell injury?

Inflammatory phase: begins at time of injury - Prepares wound environment for healing - Includes homeostasis and the vascular and cellular phases of inflammation Proliferative phase: focus is on building new tissue to fill wound space - Begins 2 to 3 days post-injury and may last 3 weeks - Key cell is fibroblast (produce growth factors and induce angiogenesis and endothelial cell proliferation and migration) - Final phase component is epithelialization = migration, proliferation, and differentiation of the epithelial cells at the wound edges to form new surface layer similar to that destroyed by the injury Remodeling Phase: begins about 3 weeks after injury and can lost six months or longer depending on extent of wound - Continued remodeling of the scar tissue by simultaneous synthesis of collagen by fibroblasts and lysis by collagenase enzymes - Tensile strength is increased

What are the phases of cutaneous healing?

1. Free radical formation 2. Hypoxia & ATP depletion 3. Disruption of intracellular homeostasis

What are the three mechanisms by which injurious agents cause cell injury and death and complex?

1.) Hemostasis, angiogenesis, and ingrowth of granulation tissue 2.) Emigration of fibroblasts and deposition of the extracellular matrix 3.) Maturation and reorganization of the fibrous tissue (remodeling) - Usually begins within 24 hours of injury - Evidenced by the migration of fibroblasts and the induction of fibroblast and epithelial cell proliferation - By 3 to 5 days, granulation tissue is apparent - Granulation tissue then progressively accumulates connective tissue --> scar formation --> remodeled

What are the three phases of repair?

White fat - Predominant in adults - Endocrine and adipocytokine secretion, insulation, cushioning - Located in: * Greater omentum * Mesentery & retroperitoneal space * Around kidneys * Behind the eyeballs * Bone marrow * Between other tissues Brown fat - Brown due to presence of iron in mitochondria - Abundant in newborns - Thermogenic

What are the types of adipose tissue?

- Physical: trauma, heat and cold, electricity - Radiation: ionizing, ultraviolet, non-ionizing - Chemical: drugs, lead, mercury - Biologic agents: bacteria, viruses, parasites - Nutritional imbalances: fats, minerals, vitamins, amino acids In health, cell injury and death are balanced by cell renewal (ongoing process). . Extra notes from kara's powerpoint - Physical: -Extreme temperatures cause damage to cells including the organelles & enzyme systems - Low-intensity heat: causes vascular injury, accelerated cell metabolism, enzyme and cell membrane disruption -- with increasing heat comes coagulation of blood and tissue proteins - Cold: increased blood viscosity and induces vasoconstriction by direct action on blood vessels and through sympathetic nervous system. Decreased blood flow may lead to hypoxic tissue injury, depending on the degree and duration of cold exposure Electrical Forces: - Can cause massive tissue injury and/or disruption of neural and cardiac impulses. - AC is more dangerous than DC d/t causing muscle contractions preventing release of electrical source - Pathway current takes through the body is critical -- energy alters function of excitable tissues (think of using shock during cardiac arrest-opposite effect) - Passes through path of least resistance in body - nerves and blood/body fluids = extensive muscle and deep tissue injury Radiation: - Ionizing: photons have enough energy to knock electrons off atoms and molecules - Affects cells by causing ionization of molecules and atoms in the cell, by directly hitting the target molecules in the cell, or by producing free radicals that destabilize molecules in critical cell components. - Most injury caused by irradiation associated with cancer treatment; usually localized - Immediately after exposure: only vessel dilation is apparent = skin erythema -- later, or with higher levels of radiation, destructive changes occur in small blood vessels: acute reversible necrosis causing radiation cystitis, dermatitis, and diarrhea from enteritis -- damage can be persistent with acute necrosis of tissue cells incapable of regeneration or from chronic ischemia. Chronic effects include fibrosis and scarring of tissues and organs in the irradiated area. Injury is dose-dependent and also depends on differential sensitivity of exposed tissue - Due to impact on DNA synthesis and mitosis; rapidly dividing cells more vulnerable to injury (bone, intestine) - Radiation dermatitis is common - Nonionizing: radiation energy at frequencies below those of visible light - Infrared light, microwaves, ultrasound, laser energy - Causes vibration and rotation of atoms and molecules; eventually converts to thermal energy - Injury typically thermal: dermis and subcutaneous tissue - UV: electromagnetic radiation just above the visible range - Contains increasingly energetic rays powerful enough to:disrupt cellular bonds, cause sunburn, increase chance for skin cancer - Damages DNA resulting in formation of pyrimidine dimers, single-stranded breaks, and DNA-protein cross-links - Xeroderma pigmentosum-autosomal recessive, 2000-fold increase risk skin cancer Chemical: can injure cell membrane and other cell structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic and ionic balance of the cell. Some may destroy on contact while others cause issues in cells in the process of metabolism or elimination. Lead: Accumulates to become toxic Many environmental sources Absorbed through GI tract or lungs into the blood; absorption greater in children than adults; children more susceptible d/t more permeable blood-brain barrier. Major targets of lead toxicity: RBCs, GI tract kidneys & nervous system Anemia is cardinal sign Mercury: Modern-day sources include some fish, dental fillings, and vaccines Extra info from the powerpoint: Biologic: Able to replicate and thus can continue to produce injurious effects. Viruses: Enter the cell and incorporate its genetic material into their cellular DNA Certain bacteria: Produce exotoxins that may interfere with cellular protein synthesis Other bacteria: esp. gram-negative bacilli, release endotoxins causing cell injury and increased capillary permeability. Nutritional: Excesses and deficiencies predispose cells to injury (Ex: obesity and atherosclerosis; iron-deficiency and anemia)

What are the types of injurious agents?

Macronutrients - Proteins—contain nitrogen, broken down into amino acids (4kcal/g) * Main role is in building functional and structural body proteins - Fats—triglycerides, cholesterol * Concentrated water-free energy source (9kcal/g) * Stored in fat cells as triglycerides - Carbohydrates—sugars, starches, fiber * Primary source of energy (4kcal/g) * Stored in limited quantities as glycogen, can be converted to fatty acids Micronutrients - Vitamins—fat (A, D, E, K) and water (Bs, C) soluble - Minerals—major (Na, Cl, K, Mg, S) and trace Water

What are the types of nutrients?

Hypophosphatemia (< 2.5 mg/dL in serum) - Causes: intestinal absorption issues, renal losses, transcompartmental shifts - Manifestations: hematologic issues, altered musculoskeletal function. Serious but uncommon-tremors, paresthesia, hyporeflexia, coma, seizures, bone abnormality - Treatment: Prevention-dietary intake, can be given IV Hyperphosphatemia (>4.5 mg/dL in serum) - Causes: High phosphate intake, transcompartmental shifts due to heat stroke or massive tissue injury, kidney issues, PTH deficit - Manifestations: same as hypocalcemia-tetany - Treatment: treat the cause; dietary restriction

What do abnormal phosphate levels look like?

- Small signaling proteins that increase cell size and cell division, cell proliferation - Also assist in regulating the inflammatory process; serve as chemoattractants for neutrophils, monocytes, fibroblasts, keratinocytes and epithelial cells; stimulate angiogenesis (development of new blood vessels); and contribute to the generation of extracellular matrix (ECM) - Named for their tissue of origin, biologic activity, or cells on which they act (ex: platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF)) Kara's Notes - Cell proliferation can be triggered by chemical mediators including growth factors, hormones, and cytokines - Signaling pathways for GFs are similar to those of other cellular receptors -- the binding of growth factor to its receptor triggers signals transmitted into the cell, leading to stimulation or inhibition of gene expression -- functions: might relieve blocks on cell cycle progression (promoting cell proliferation), prevent apoptosis, and enhance synthesis of cellular proteins in preparation for mitosis

What do growth factors do?

Hypomagnesemia (< 1.3 mg/dL in serum): - Causes: Starvation, diarrhea, prolonged NG suction, chronic alcoholism - Manifestations: decrease in serum calcium due to suppression of PTH release & decrease in serum potassium due to renal wasting (result in increased neuromuscular excitability) Hypermagnesemia (> 2.5 mg/dL in serum): RARE - Causes: Renal disease, overuse of magnesium-containing medications such as antacids - Manifestations: Neuromuscular dysfunction with hyporeflexia, muscle weakness and confusion

What do magnesium imbalances look like?

Four successive stages: - Prodrome (early stage of disease, first symptoms appearing, nonspecific complaints such as mild headache and fatigue, general malaise, fleeting aches and pains. Think of this stage as "I think I might be getting sick...") - Chill (usually associated with pyrogen entering circulation, Uncomfortable sensation of being cold and the onset of generalized shaking , although the temperature is rising. Vasoconstriction and piloerection usually precede the onset of shivering. Skin is pale and covered with goose bumps. There is an urge to cover up. When shivering has caused the body temperature to reach the new set point of the temperature control center, the shivering stops and the patient feels warm ) - Flush (skin is warm and red, Cutaneous vasodilation occurs ) - Defervescence (initiation of sweating) - Febrile persons often have reduced desire to eat, have muscle and joint aches (myalgia and arthralgia) and fatigue - Febrile persons have increased respirations and heart rate - During fever, body switches from using glucose to metabolism based on protein and fat breakdown - Note: not all persons proceed through all four stages of fever development (for ex: people don't always chill or sweat) - Symptoms associated with fever are worse when temperature rises quickly or exceeds 103.1 degrees F - Headaches usually caused by vasodilation of cerebral vessels - Delirium may develop at temperatures exceeding 104 F (can develop at lower temperature in elderly)

What do the manifestations of fever look like?

Leukocytes release interleukins and tumor necrosis factor - Affect thermoregulatory center -> fever - Affect the central nervous system -> lethargy - Skeletal muscle breakdown - The liver makes fibrinogen, C-reactive protein, serum amyloid A protein - Stimulated by cytokines including TNF-a, IL-1, and IL-6 - Acute-phase response usually begins within hours or days of onset of inflammation. - Acute-phase response includes changes in the concentrations of plasma proteins, skeletal muscle catabolism, negative nitrogen balance, elevated erythrocyte sedimentation rate, and increased number of leukocyte. Other manifestations include fever, increased heart rate, anorexia, somnolence and malaise.

What does the acute-phase response look like?

- Inflammatory mediators cause WBC production, especially those caused by bacterial infection - WBC count rises → leukocytosis (circulating neutrophil life span approx. 10 hours so must be constantly replaced) - Immature neutrophils (bands) released into blood (when cant release enough WBC) ("Shift to Left": Refers to increase in immature neutrophils-sign of severe infection) - Bacterial infections cause increase in neutrophils, parasitic and allergic responses cause increase in eosinophils in bloodstream, viral infections cause a reduction in neutrophils (neutropenia) and an increase in lymphocytes (lymphocytosis). WBCs may be decreased (leukopenia) in persons with overwhelming infections or impaired ability to produce WBCs.

What does the white blood cell response look like?

Karyotype: Picture of chromosomes arranged in pairs in descending order of size Chromosomes form an "X" or wishbone pattern Chromosomes divided into three types depending on position of centromere - Metacentric: Centromere is in the center and the arms are about the same length - Submetacentric: Centromere is not centered and the arms are clearly different lengths - Acrocentric: the centromere is near one end Short arm called "p" for petite Long arm called "q" - Arms of chromosome are indicated by the chromosome number followed by p or q designation - Useful when communicating the location of genes involved in genetic diseases (Essentially, to examine the karyotype, a chromosome spread is prepared by fixing and spreading the chromosomes on a slide. Stain is applied which reveal the chromosomal banding patterns so. The chromosomes are photographed and the photoimages are arranged in 23 pairs.)

What is a chromosomes structure?

An innate (part of innate immune system), automatic response to cell injury that: - Neutralizes harmful agents - Removes damaged and dead tissue - Generates new tissue - Promotes healing - Dilutes, destroys, and gets rid of damaged or necrotic tissue and foreign agents

What is inflammation?

Recombinant DNA

What is it? vector DNA is combined with chromosomal DNA fragment for cloning using DNA ligase which is then introduced into bacterium _____ ___ studies involve the extraction of specific types of mRNA used in the synthesis of complementary DNA strands. The complementary DNA strands, labeled with a radioisotope, bind with the genes for which they are complementary and are used as gene probes. ______ ___ technology has made it possible to produce proteins that have therapeutic properties. One of the first products to be produced was human insulin. Genetic engineering has provided the methods for manipulating nucleic acids and recombining genes (recombinant DNA) into hybrid molecules that can be inserted into unicellular organisms and reproduced many times over. As a result, proteins that formerly were available only in small amounts (such as human insulin) can now be made in large quantities once their respective genes have been isolated. DNA fingerprinting, which relies on recombinant DNA technologies and those of genetic mapping, is often used in forensic investigations.

- Proliferation: increases cell numbers through mitotic division - Differentiation: cells becomes more specialized in structure and function - Repair process largely driven by proteins called growth factors - All cells originate from a single cell - Most then differentiate to develop different cells and organs of the body - Differentiation occurs in orderly steps - Some cells (usually highly specialized) lose ability to proliferate - Less-specialized cells often renew continuously (rely on parent (progenitor) cells-daughter cells are limited to same cell line but haven't reached point of differentiation that precludes proliferation)

What is the difference between cell proliferation and cell differentiation?

- Parenchymal tissue: functioning cells of an organ or body part - Stromal tissue: contain supporting connective tissues, blood vessels, fibroblasts nerve fibers, and extracellular matrix

What is the difference between parenchymal tissue and stromal tissue?

- Both may contribute to wound healing - Regeneration: injured cells replaced with cells of same type leaving no trace of previous injury - Replacement: connective (fibrous) tissue leads to scar formation or fibrosis in organs such as liver or lung

What is the difference between regeneration and replacement?

- PTH works by stimulating release of calcium and phosphorus from bone into ECF which increases renal reabsorption of calcium and excretion of phosphorus; and enhancing GI absorption of calcium and phosphorus through its effects on Vitamin D synthesis. Vitamin D is synthesized by the skin and converted to its active form, calcitriol, in the kidney. - This active form has several effects on intestines, kidneys, and bone that increase serum levels of calcium and phosphorus and contribute to their feedback regulation. Calcitriol stimulates absorption of calcium, and to lesser degree phosphorus, from the intestine, it increase calcium and phosphorus reabsorption by the renal tubules, and it inhibits PTH synthesis by the parathyroid glands.

What is the main function of PTH?

Continuously dividing or labile tissues: destroyed cells are continuously replaced - Cells continue to divide & replicate throughout life - Tissues can readily regenerate after injury Stable tissues: stop dividing when growth ceases - Remain dormant in G0 - Capable of undergoing regeneration when confronted with certain stimulus and thus can reconstitute the tissue of origin Permanent tissues: do not proliferate - Considered terminally differentiated

What is the proliferative capacity of tissues?

Multipotent stem cells (they give rise to red blood cells and leukocytes)

What produces white blood cells?

Crossing-Over

When chromosome pairs line up during meiosis, they can exchange ends

Prostaglandins and Luekotrienes (Prostaglandins and leukotrienes cause vasodilation, which brings more blood to the injured/affected area -- the symptoms caused by this vasodilation are redness/erythema and warmth)

Which causes the redness (erythema) associated with the inflammatory process?

Eosinophils Monocytes Neutrophils (Granulocytes and monocytes play a role in the acute phase of the immune response -- eosinophils and neutrophils are granulocytes, so all of the leukocytes listed participate)

Which leukocytes participate in the acute inflammatory response?

D. Heterozygous; does not suffer from CF Rationale: If an individual is a carrier, he or she is heterozygous for the recessive trait (in this case, CF), but he or she does not display the trait (because the trait is recessive).

Which of the following statements is true about an individual who is a carrier for the cystic fibrosis (CF) gene? A. Homozygous; suffers from CF B. Homozygous; does not suffer from CF C. Heterozygous; suffers from CF D. Heterozygous; does not suffer from CF

B. Hypothalamus Rationale: The feeding center for hunger and satiety is contained in the hypothalamus. The hypothalamus takes in information from the GI tract, blood, and cerebral cortex in order to determine when to begin eating and when to stop.

Which part of the brain controls both hunger and the feeling of fullness? A. Cerebral cortex B. Hypothalamus C. Reticular formation D. Thalamus

A. Messenger RNA (mRNA). Rationale: messenger RNA is the only RNA that moves between the nucleus and the cytoplasm. Both tRNA and rRNA are relegated to the cytoplasm, *while DNA never leaves the nucleus* ON THE TEST

Which type of RNA moves from the nucleus into the cytoplasm, carrying the genetic code? A. Messenger RNA (mRNA). B. Transfer RNA (tRNA). C. Ribosomal RNA (rRNA). D. All of the above can move between the nucleus and the cytoplasm.

C. Translocation Rationale: Translocation is the only chromosomal alteration where no genetic material is actually lost (chromosome parts are exchanged), so the offspring are usually normal. Offspring are translocation carriers, so their children may or may not be normal.

Which type of chromosome alteration generally results in normal offspring? A. Deletion B. Inversion C. Translocation D. Ring formation

Is it programmed into the cells (programmed theory)? - Replicative senescence implies cells have limited capacity for replication - Possibly due to telomeres become too short the cell can no longer divide Is it the result of accumulated damage (damage or error theory) - Changes result from an accumulation of random events or environmental agents or influences that are associated with DNA damage *DNA damage *Free radicals *Glycation Aging: even in absence of disease, beginning in fourth decade of life, there is progressive decline in muscle strength, cardiac reserve, vital capacity, nerve conduction time, and glomerular filtration rate. Many cell functions decline with age. Programmed Theories or Damage or Error Theories: Animal studies show genetics account for less than 35% of the effects of aging and environmental 65%. In humans, long life appears to have a stronger genetic basis, which explains why longevity seems to be familial.

Why do our cells change with aging?

During the synthesis (S) phase of the cell cycle, DNA synthesis occurs, giving rise to two separate sets of chromosomes.

Within which phase of the cell cycle is DNA replicated?

Genes are found on chromosomes

X or Y chromosome: sex-linked Other chromosomes: autosomal (not sex-linked) Autosomal dominant disorders: - Single mutant allele from an affected parent is transmitted to an offspring regardless of sex - Affected parent has a 50% change of transmitting the disorder to each offspring Autosomal recessive disorders: - Manifested only when both members of the gene pair are affected - Usually, both parents are unaffected but are carriers of the defective gene. - Chance of having an affected child is one in four - Ex: cystic fibrosis