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ADVANCED PATHO EXAM 1 STUDY GUIDE Prokaryotes No Nucleus Single Circular chromosome = nucleoid No membrane-bound organelles Cyanobacteria, bacteria, & riskettsiae Eukaryotes Complex cellular organization Membrane-bound organelles Well-defined nucleus Higher animals, plants, fungi, &...

ADVANCED PATHO EXAM 1 STUDY GUIDE Prokaryotes No Nucleus Single Circular chromosome = nucleoid No membrane-bound organelles Cyanobacteria, bacteria, & riskettsiae Eukaryotes Complex cellular organization Membrane-bound organelles Well-defined nucleus Higher animals, plants, fungi, & protozoa EUKARYOTIC CELL Nucleus largest membrane bound organelle Nuclear envelope allows molecules to move between the nucleus & the cytosol Nucleolus composed of RNA, DNA, & DNA binding proteins (histones) Histone proteins DNA binding proteins Cell division *primary function of nucleus* along w/ control of genetic info Cytoplasm Cytoplasmic matrix Cytosol aqueous solution; main site for protein synthesis & degradation Function synthesis of proteins & hormones, & their transport out of the cell, breakdown & disposal of cellular debris & foreign proteins & maintenance of cellular structure & motility EUKARYOTIC ORGANELLES Ribosomes function is to provide sites for protein synthesis Endoplasmic reticulum binding site for protein synthesis Site of protein synthesis Smooth vs. rough endoplasmic reticulum smooth doesn’t contain ribosomes Golgi complex processes and packages proteins for delivery 1 Secretory vesicles Proteins from the endoplasmic reticulum are packaged in the Golgi complex Lysosomes remove toxic cell components, useless organelles, terminate signal transduction, & maintain homeostasis Originate from the Golgi Hydrolases, lipids, nucleic acids, & carbohydrates Role in auto-digestion Peroxisomes detoxify compounds & fatty acids Contain oxidative enzymes Break down substances into harmless products Mitochondria powerhouse of the cell Participate in oxidative phosphorylation which generates ATP Cytoskeleton “Bones and muscles” of the cell Maintains the cell’s shape & internal organization Permits movement of substances w/in the cell & movement of external projections Microtubules support & move organelles from one part of the cytoplasm to another CELLULAR METABOLISM Anabolism Energy using Catabolism Energy releasing CELLULAR ENERGY Digestion Glycolysis splitting of glycogen Occurs in the cytoplasm Anaerobic vs. aerobic anaerobic= without oxygen ; aerobic= with oxygen - anaerobic metabolism synthesizes ATP, through substrate phosphorylation, causing glycolysis (the break down of carbohydrates) ▪ Atrophy shrinking – Decrease or shrinkage in cellular size – Physiologic vs. pathologic physiologic= occurs w/ early development; pathologic= result of decreases in workload, use, pressure, blood supply, nutrition, hormonal stimulation, & nervous stimulation 2 ▪ Hypertrophy overgrowth – Increase in the size of cells & affected organ – Physiologic vs. pathologic physiologic= increased demand, stimulation by hormones, and growth factors; pathologic= chronic hemodynamic overload ▪ Hyperplasia overgrowth of tissue – Increase in number of cells resulting from an increased rate – Compensatory vs. hormonal compensatory= adaptive organism that enables organs to regenerate; hormonal= occurs in estrogen dependent organs ▪ Dysplasia deranged cell growth – Abnormal changes ▪ Metaplasia associated with tissue damage, repair, & regeneration – Reversible replacement of one mature cell by another Cellular Death ▪ Necrosis – Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis) lysosomes “eat” them & they get reabsorbed Necrosis ▪ Coagulative necrosis results from hypoxia caused by severe ischemia or chemical injury – Kidneys, heart, & adrenal glands – Protein denaturation ▪ Liquefactive necrosis – Neurons and glial cells of the brain – Hydrolytic enzymes ▪ Caseous necrosis – results from Tuberculous pulmonary infection – Combination of coagulative and liquefactive necrosis ▪ Fat necrosis cellular dissolution caused by lipases – Breast, pancreas, & other abdominal organs – Action of lipases 3 ▪ Gangrenous necrosis soft tissue damage death of tissue & results from severe hypoxic injury, commonly occurring bc of arteriosclerosis, or blockage of major arteries esp in the lower leg) – Clinical term – Dry vs. wet gangrene dry: usually result of coagulative necrosis; skin becomes very dry and shrinks; wet: develops when neutrophils invaded the site, causing liquefactive necrosis; site becomes cold, swollen, black (usually occurs in internal organs) – Gas gangrene gets under skin & causes putrefaction of tissue, releasing gas Apoptosis ▪ Programmed cellular death active process of cell self destruction ▪ Mechanisms severe cell injury, accumulation of misfolded proteins, infections (particularly viral), obstruction in tissue ducts ▪ Necrosis vs. apoptosis apoptosis: release chemical factors that recruit phagocytes to quickly engulf remains of dead cell, reducing chances of inflammation; necrosis: cells died as a result of acute injury swell, burst, and spill their contents al over, causing damaging inflammatory response Somatic Death ▪ Death of an entire person ▪ Postmortem changes complete cessation of respiration and circulation – Algor mortis postmortem reduction of body temp – Livor mortis blood settles in most dependent/lowest tissue, causing purple discoloration – Rigor mortis muscle stiffening – Postmortem autolysis release of enzymes & lytic dissolution causing putrefactive changes Osmosis vs. Diffusion - Both passive transport - diffusion: movement of solute molecule from area of higher concentration to lower concentration - Passive moment of particles down a concentration gradient - ** osmosis: movement of water “down” a concentration gradient, across a semipermeable membrane, from a region of high water concentration to lower water concentration - A membrane must be more permeable to water than solutes and the concentration of solutes must be greater so water moves more easily 4 Sodum Potassium Pump - transports sodium (3) outward and potassium (1) inward - Active transport - Causes action potential What prevents water soluble molecules from leaking out? - phospholipid bilayer - Is part hydrophobic and part hydrophilic - The hydrophobic tail is protected from water leaking out, and the hydrophilic head is immersed in it - This makes the plasma membrane impermeable to water soluble molecules bc they are insoluble in the oily core region Acute vs. Chronic Inflammation Acute Response – Short, 8-10 days; chronic inflammation is 2 weeks – Begins after injury or infection – Involves vascular response, activation of plasma proteins & activation of a variety of cells Chronic Inflammation Continuation of acute inflammation lasting 2 weeks or longer Often related to an unsuccessful acute inflammatory response Distinct process without acute inflammatory Other causes – High lipid and wax content of microorganism – Ability to survive inside the macrophage – Toxins – Chemicals, particulate matter, or physical irritants Characteristics – Dense infiltration of lymphocytes and macrophages – Granuloma formation = wall off and isolate infection for protection against tissue damage – Epithelioid cell formation – Giant cell formation What is RNA synthesized from? - RNA is synthesized from DNA by an enzyme known as RNA polymerase during transcription - RNA sequences compliment the DNA sequences 5 - RNA is then translated into proteins by ribosomes Hypokalemia Potassium level 5.5 mEq/L can be treated w/ insulin Hyperkalemia is rare due to efficient renal excretion Caused by increased intake, shift of K+ from ICF, decreased renal excretion, insulin deficiency, or cell trauma Mild attacks Hypopolarized membrane, causing neuromuscular irritability Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea Severe attacks The cell is unable to repolarize, resulting in muscle weakness, loss of muscle tone, flaccid paralysis, cardiac arrest Hyponatremia can cause confusion Serum sodium level 147 mEq/L Related to sodium gain or water loss Water movement from the ICF to the ECF Intracellular dehydration 6 Manifestations: intracellular dehydration, convulsions, pulmonary edema, hypotension, tachycardia Inflammatory Response Characteristics – “Cardinal signs of inflammation” – Redness, heat, swelling, and pain Goals – Limit and control the inflammatory process – Prevent and limit infection and further damage – Control bleeding – Interact with components of the adaptive immune system – Prepare the area of injury for healing Chemical Mediators of Inflammation Mast Cells – Central to inflammation – Release histamine, chemotactic factors, cytokines, leukotrienes, prostaglandins, growth factor & other mediators – Cellular bags of granules located in loose connective tissues close to blood vessels – Skin, digestive lining, respiratory tract – Activation – Physical injury, chemical agents, immunologic processes, Toll-like receptors (TLRs) – Chemical release in 2 ways – Degranulation and synthesis of lipid-derived chemical mediator Systemic Manifestations of Acute Inflammation Fever – Caused by exogenous and endogenous pyrogens – Act directly on the hypothalamus Leukocytosis – Increased numbers of circulating leukocytes – Left shift, increase in immature cells (bands) Increased plasma protein synthesis – Acute-phase reactants 7 – C-reactive protein, fibrinogen, haptoglobin, amyloid A, ceruloplasmin, and alpha-1 antitrypsin produced by liver Resolution and Repair Resolution (regeneration) ex: broken bone – Returning injured tissue to the original structure and function Repair ex: scars (has healed as a repair) – Replacement of destroyed tissue with scar tissue – Healing by scar tissue formation – Scar tissue composed primarily of collagen to restore the tensile strength of the tissue Debridement – Cleaning up dissolved clots, microorganisms, erythrocytes, and dead tissue cells Healing – Filling in the wound – Sealing the wound (epithelialization) – Shrinking the wound (contraction) Healing Primary intention regular stitches – Wounds that heal under conditions of minimal tissue loss Secondary intention dehisced wound; heals from bottom up – Wounds that require a great deal more tissue replacement – Open wound – Scar formation Resolution and Repair 2 phases: Reconstructive – Wound healing begins Maturation – Remodeling of healed wound Dysfunctional Wound Healing Dysfunction during inflammatory response – Hemorrhage – Fibrous adhesion – Infection 8 – Excess scar formation keloids (overgrowth of collagen matrix) – Wound sepsis – Hypovolemia – Hypoproteinemia – Anti-inflammatory steroids steroids slow down would healing Dysfunction during reconstructive phase – Impaired collagen matrix assembly – Keloid scar hypertrophy; too much collagen matrix – Hypertrophic scar – Impaired epithelialization – Anti-inflammatory steroids, hypoxemia, and nutritional deficiencies – Impaired contraction – Contracture Wound disruption – Dehiscence – Wound pulls apart at the suture line – Excessive strain and obesity are causes – Increased risk of wound sepsis What causes a callus to form? - compensatory hyperplasia - Thickening of the skin as a result of hyperplasia of epidermal cells in response to a mechanical stimulus Metabolic acidosis - depression of HCO3– or an increase in noncarbonic acids occurs in poor perfusion, hypoxemia, renal failure (can’t excrete acid), starvation or DKA; respiratory system causes hyperventilation, which transfers the excess acid to the blood, later to be excreted by the kidneys - Confusion, hyperventilation Alterations in Water Movement: Edema Accumulation of fluid within the interstitial spaces Causes Increase in capillary hydrostatic pressure venous obstruction or sodium water retention; ex: venous blood clots, hepatic obstruction, right heart failure, tight clothing around extremities, prolonged standing Losses or diminished production of plasma albumin ex: liver disease, protein malnutrition, kidney diseases, hemorrhage, & serous draining from open wounds or burns 9 Increases in capillary permeability ex: inflammation & the immune response; burns, crushing injuries, neoplastic diseases, allergic reactions, & infection Lymph obstruction (lymphedema) lymphatic channels blocked bc of infection or tumor Prostaglandins – Similar effects to leukotrienes; they also induce pain prostaglandins cause pain and inflammation Down syndrome – Best-known example of aneuploidy › Trisomy 21 (47, XX or 47, XY karyotype) – 1:800 live births – Mentally retarded, low nasal bridge, epicanthal folds, protruding tongue, poor muscle tone, short stature, flat low set ears – Risk increases with maternal age – Increased risk of congenital heart disease, gastrointestinal disease, and leukemia, early onset Alzheimers - most cases are caused by nondisjunction during formation of one of the patent’s gametes during early embryonic development Autosomal Recessive Disorders › Characteristics – Condition expressed equally in males and females – Affected individuals most often the offspring of asymptomatic heterozygous carrier parents › Approximately 1/4 of offspring will be affected; 1/2 will be asymptomatic carriers; and 1/4 will be unaffected › Individuals must be homozygous for the condition to be expressed – Generational skipping may be present – Consanguinity may be present Autosomal Dominant Disorders › Characteristics of autosomal dominant disorders – Condition is expressed equally in males and females – Approximately half of children of an affected heterozygous individual will express the condition › Homozygous affected individuals are rare – No generational skipping 10 Sex-Linked Disorders › Disorders involve X and Y chromosomes › X-linked disorders usually expressed by males because females have another X chromosome to mask the abnormal allele – Most are recessive › Y-linked disorders uncommon because Y chromosome contains relatively few genes – Father-son transmission present – No father-daughter transmission Genetics › Homozygous – Loci on a pair of chromosomes have identical alleles – Example › O blood type (OO) › Heterozygous – Loci on a pair of chromosomes have different alleles – Example › AB blood type (A and B alleles on pair of loci)› Genotype (“what they have”) – The genetic makeup of an organism › Phenotype (“what they demonstrate”) – The observable, detectable, or outward appearance of the genetics of an organism › Example – A person with the A blood type could be AA or AO › A is the phenotype › AA or AO is the genotype › If two alleles are found together, the allele that is observable is dominant, and the one whose effects are hidden is recessive › In genetics, the dominant allele is represented by a capital letter, and the recessive by a lowercase letter › Alleles can be codominant ex: A blood type & B blood type, forming AB › Carrier – A carrier is one that has a disease gene but is phenotypically normal – For a person to demonstrate a recessive disease, the pair of recessive genes must be inherited – Example 11 › Ss = sickle cell anemia carrier › ss = demonstrates sickle cell disease Single-Gene Disorders › 1 risk – The probability that parents of a child with a genetic disease will have yet another child with the same disease – Recurrence risk of an autosomal dominant trait › When one parent is affected by an autosomal dominant disease and the other is normal, the occurrence and recurrence risks for each child are one half › Autosomal recessive disorder – Abnormal allele is recessive and a person must be homozygous for the abnormal trait to express the disease – The trait usually appears in the children, not the parents, and it affects the genders equally because it is present on a pair of autosomes › Autosomal recessive disorder recurrence risk – Recurrence risk of an autosomal dominant trait › When two parents are carriers of an autosomal recessive disease, the occurrence and recurrence risks for each child are 25% X-Linked Recessive Disorders › Characteristics – Males most commonly affected › Affected males cannot transmit the genes to sons, but they can to all daughters – Unaffected carrier females › Sons of female carriers have a 50% risk of being affected – Pedigree analysis › Generational skipping often present › No father-to-son transmission › Fragile X syndrome – Site on the long arm of the X chromosome – Associated with mental retardation; second in occurrence to Down syndrome – Higher incidence in males because they have only one X chromosome 12 trisomy X. This is a female that has three X chromosomes. › Termed “metafemale” – Symptoms are variable: sterility, menstrual irregularity, and/or mental retardation – Symptoms worsen with each additional X Turner syndrome – 45, X karyotype – Females with only one X chromosome › Absence of ovaries (sterile) gonadal streaks › Short stature (~ 4'7") › Webbing of the neck › Edema of feet in newborns Sparse body hair › Underdeveloped breasts; wide nipples › High number of aborted fetuses › X is usually inherited from mother most cases caused by loss of paternally transmitted x chromosome * treated w/ estrogen to promote development of secondary sex characteristics Klinefelter syndrome – Individuals with at least two X and one Y chromosome – 47, XXY karyotype – Characteristics › Male appearance › Develop female-like breasts gynecomastia › Small testes › Sparse body hair › Long limbs – Some individuals can be XXXY and XXXXY – The abnormalities will increase with each X RECURRENCE RISKS Recurrence risks of multifactorial diseases can change substantially because gene frequencies as well as environment and lifestyle factors can differ among populations Recurrence risk becomes higher if more than one family member is affected 13 If the expression of the disease in the proband is more severe, recurrence risk is higher Recurrence risk is higher if the proband is of the less commonly affected sex Recurrence risk for the disease usually decreases rapidly in remotely related relatives IgG Most abundant Igs-80-85% Provide most protection against infections Crosses placenta Found in fetus & newborn Four classes-IgG1, IgG2, IgG3, & IgG4 Cellular Injury Mechanisms ▪ Chemical injury – Lead toxic metal; found in old paint – Carbon monoxide most common chemical asphyxiant Lead poisoning - one of the most common overexposures found in industry - Still primary hazard to children - Alters intracellular concentrations of calcium - Disrupts zinc, magnesium leading to altered neurotransmitter function, decreasing cellular energy - Affects nervous, immune, & reproductive system & has developmental effects Carbon monoxide poisoning - reduces oxygen carrying capacity of blood - Headache, confusion, weakness, loss of consciousness Active versus Passive Immunity Active immunity Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Passive immunity Preformed antibodies or T lymphocytes are transferred from a donor to a recipient 14

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