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8th Edition Pathophysiology Chapter Summaries
Advanced Pathophysiology (NURS-6501N)
Walden University
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McCance/Huether: Pathophysiology: The Biologic Basis of Disease in Adults
and Children, 8th Edition
Chapter 01: Cellular Biology
Chapter Summary Review
Cellular Functions
- Cells become specialized through the process of differentiation, or maturation.
- The eight specialized cellular functions are movement, conductivity, metabolic absorption, secretion, excretion, respiration, reproduction, and communication.
Structure and Function of Cellular Components
The eukaryotic cell consists of three general components: the plasma membrane, the cytoplasm, and the intracellular organelles.
The nucleus is the largest membrane-bound organelle and is usually found in the cell’s center. The chief functions of the nucleus are cell division and control of genetic information.
Cytoplasm, or the cytoplasmic matrix, is an aqueous solution (cytosol) that fills the space between the nucleus and the plasma membrane.
The organelles are suspended in the cytoplasm and are enclosed in biologic membranes.
The endoplasmic reticulum (ER) is a network of tubular channels (cisternae) that extends throughout the outer nuclear membrane. It specializes in the synthesis and transport of protein and lipid components of most of the organelles. Importantly, the ER is responsible for protein folding and sensing cell stress.
The Golgi complex is a network of smooth membranes and vesicles located near the nucleus. The Golgi complex is responsible for processing and packaging proteins into secretory vesicles that break away from the Golgi complex and migrate to a variety of intracellular and extracellular destinations, including the plasma membrane.
Lysosomes are saclike structures that originate from the Golgi complex and contain digestive enzymes. These enzymes are responsible for digesting most cellular substances completely to their basic components, such as amino acids, fatty acids, and carbohydrates. A newly understood role of lysosomes is nutrient-dependent signal transduction. The signaling function cooperates with the known degradative role to mediate basic cell functions, such as nutrient sensing, metabolic adaptation, and quality control of proteins and organelles.
Four pathways of degradation in lysosomes include endocytosis, phagocytosis, macropinocytosis, and autophagy.
Peroxisomes are similar to lysosomes but contain several oxidative enzymes, such as catalase and urate oxidase.
Mitochondria are found in great numbers in most cells and are responsible for cellular respiration and energy production. The enzymes of the respiratory chain (electron- transport chain), found in the inner membrane of the mitochondria, generate most of the cell’s ATP.
The cytosol or liquid portion of the cytoplasm has several functions including intermediary metabolism involving enzymatic biochemical reactions; ribosomal protein synthesis; and storage of carbohydrates, fat, and secretory vesicles.
The cytoskeleton is the “bone and muscle” of the cell. The internal skeleton is composed of a network of protein filaments including microtubules and actin filaments (microfilaments).
The plasma membrane encloses the cell and, by controlling the movement of substances across it, exerts a powerful influence on metabolic pathways.
The plasma membrane is a bilayer of lipids and proteins. The basic structure of the cell membrane is the lipid bilayer.
Membrane functions are determined largely by proteins. These functions include (a) recognition and binding units (receptors) for substances moving in and out of the cell; (b) pores or transport channels; (c) enzymes that drive active pumps; (d) cell surface markers, such as glycoproteins; (e) cell adhesion molecules; and (f) catalysts of chemical reactions.
The information regarding concepts of biologic membranes has changed markedly in the last two decades.
A protein is made from a chain of amino acids known as polypeptides. Proteins are the major workhorses of the cell. Proteins move from one compartment to another by gated tr ansport, protein translocation, or vesicular transport.
Proteostasis is a state of cell balance of the processes of protein synthesis, folding, and degradation. Proteostasis is vital to cellular health.
Cellular receptors are protein molecules on the plasma membrane, in the cytoplasm, or in the nucleus that are capable of recognizing and binding smaller molecules, called ligands.
The ligand-receptor complex initiates a series of protein interactions, causing adenylyl cyclase to catalyze the transformation of cellular ATP to messenger molecules that stimulate specific responses within the cell.
The carbohydrate contained within the plasma membrane is generally bound to membrane proteins.
Cell-to -Cell Adhesions
- Cell-to -cell adhesions are formed on plasma membranes, thereby allowing the formation of tissues and organs. Cells are held together by three different means: (a) the extracellular membrane, (b) cell adhesion molecules in the cell’s plasma membrane, and (c) specialized cell junctions.
- The extracellular matrix includes three types of protein fibers: collagen, elastin, and fibronectin. The matrix helps regulate cell growth and differentiation.
- The basement membrane is a thin layer of connective tissue underlying the epithelium of many organs. It is also called the basal lamina.
- Cell adhesion molecules (CAMs) are cell surface proteins that bind to an adjacent cell and to components of the extracellular matrix. CAMs include four main protein families: the integrins, the cadherins, the selectins, and the immunoglobulin (Ig) superfamily.
- The three main types of cell junctions are desmosomes, tight junctions, and gap junctions.
Cellular Communication and Signal Transduction
- Diffusion is the passive movement of a solute from an area of higher solute concentration to an area of lower solute concentration.
- Hydrostatic pressure is the mechanical force of water pushing against cellular membranes.
- Osmosis is the movement of water across a semipermeable membrane from a region of lower solute concentration to a region of higher solute concentration.
- The amount of hydrostatic pressure required to oppose the osmotic movement of water is called the osmotic pressure of the solution.
- The overall osmotic effect of colloids, such as plasma proteins, is called the oncotic pressure or colloid osmotic pressure.
- Mediated transport can be passive or active. Mediated transport includes the movement of two molecules simultaneously in one direction (symport) or in opposite directions (antiport), or the movement of a single molecule in one direction (uniport).
- Endocytosis is a cellular-internalizing process where a section of the plasma membrane enfolds substances from outside the cell, invaginates, and separates from the plasma membrane forming a vesicle that moves inside the cell.
- Endocytosis can be subdivided into four categories: (1) clathrin-mediated endocytosis, (2) caveolae-mediated endocytosis, (3) macropinocytosis, and (4) phagocytosis. Over time, however, these categories may change.
- A new advancement in cellular biology is the role of exosomes in understanding the biology of vesicles and their role in disease. Exosomes are small-membrane vesicles of endocytic origin containing lipid, protein, and RNA species in a single biologic unit. They are secreted by nearly all mammalian cell types and confer messages between cells.
- Exocytosis is the discharge of secretion of material from the intracellular vesicles at the cell surface. Exocytosis has two main functions: replacement of portions of the plasma membrane that have been removed by endocytosis and release of molecules synthesized by the cells into the extracellular matrix.
- Pinocytosis is a type of endocytosis in which fluids and solute molecules are ingested through formation of small vesicles.
- Phagocytosis is a type of endocytosis in which large particles, such as bacteria, are ingested through formation of large vesicles, called vacuoles.
- All body cells are electrically polarized, with the inside of the cell more negatively charged than the outside. The difference in voltage across the plasma membrane is the resting membrane potential.
- When an excitable (nerve or muscle) cell receives an electrochemical stimulus, cations enter the cell, causing a rapid change in the resting membrane potential known as the action potential. The action potential “moves” along the cell’s plasma membrane and is transmitted to an adjacent cell. This is how electrochemical signals convey information from cell to cell.
Cellular Reproduction: The Cell Cycle
The continuity of life depends on constant rounds of cell growth and division.
Cellular reproduction in body tissues involves mitosis (nuclear division) and cytokinesis (cytoplasmic division).
Only mature cells are capable of division. Maturation occurs during a stage of cellular life called interphase (growth phase).
The cell cycle is the reproductive process that begins after interphase in all tissues with cellular turnover. The four phases of the cell cycle are (1) the G1 phase (G = gap), which is the period between the M phase and the start of DNA synthesis; (2) the S phase (S = synthesis), in which DNA is synthesized in the cell nucleus; (3) the G2 phase , in which RNA and protein synthesis occurs, the period between the completion of DNA synthesis and the next phase (M); and (4) the M phase (M = mitosis), which includes both nuclear and cytoplasmic division.
The M phase (mitosis) involves four stages: prophase, metaphase, anaphase, and telophase.
The mechanisms that control cell division depend on the integrity of genetic, epigenetic, and protein growth factors.
Two classes of switches or regulatory molecules that determine a cell’s progress through the cell cycle are cyclin-dependent kinases (Cdks) and cyclins.
Organ size and body size depend on cell growth, cell division, and cell survival.
A mitogen is a substance that induces or stimulates mitosis.
Growth factors stimulate an increase in cell mass or cell growth by promoting the synthesis of proteins and other macromolecules and inhibiting their degradation.
The DNA damage response occurs when DNA is damaged and several protein kinases are recruited to the site of damage and start a signaling pathway that stops the progression of the cell cycle called cell cycle arrest.
Tissues
- Cells of one or more types are organized into tissues, and different types of tissues compose organs. Organs are organized to function as tracts or systems.
- To form tissue, cells must exhibit intercellular recognition and communication, adhesion, and memory.
- The four basic types of tissues are epithelial, muscle, neural, and connective tissues.
- Stem cells are cells with the potential to develop into many different cell types during early development and growth. Stem cells serve as an internal repair and maintenance system dividing indefinitely. Tissue repair and renewal does not always depend on stem cells.
- Epithelial tissue covers most internal and external surfaces of the body. The functions of epithelial tissue include protection, absorption, secretion, and excretion.
- Connective tissue binds various tissues and organs together, supporting them in their locations and serving as storage sites for excess nutrients.
- Muscle tissue is composed of long, thin, highly contractile cells or fibers called myocytes. Muscle tissue that is attached to bones enables voluntary movement. Muscle tissues in internal organs enable involuntary movement, such as the heartbeat.
- Neural tissue is composed of highly specialized cells called neurons that receive and transmit electrical impulses very rapidly across junctions called synapses.
immune responses, genetic factors, insufficient nutrients, or physical trauma from many causes. Injurious stimuli cause cell stress. 3. Cell injury can be acute or chronic, and it can be reversible or irreversible. It can involve necrosis, apoptosis, autophagy, accumulation, or pathologic calcification. 4. Four biochemical themes are important to cell injury: (a) depletion of ATP, (b) decreased levels of oxygen and increased levels of oxygen-derived free radicals, (c) increased concentration of intracellular calcium and loss of calcium steady-state, and (d) defects in membrane permeability. 5. The sequence of events leading to cell death is commonly decreased ATP production, failure of active transport mechanisms (the Na+-K+ pump), cellular swelling, detachment of ribosomes from the endoplasmic reticulum, cessation of protein synthesis, mitochondrial swelling as a result of calcium accumulation, vacuolation, leakage of digestive enzymes from lysosomes, autodigestion of intracellular structures, lysis of the plasma membrane, and death. 6. The initial insult in hypoxic injury is usually ischemia—the cessation of blood flow into vessels that supply the cell with oxygen and nutrients. Hypoxia can induce inflammation, and inflamed lesions can become hypoxic. 7. Restoration of oxygen after ischemic injury can result in reperfusion (reoxygenation) injury. Reperfusion injury results from the generation of highly reactive oxygen intermediates or radicals. 8. Inherent reactive oxygen species (ROS) from aerobic metabolism play a crucial biologic role, not just in various diseases but also from cellular communication and cell function. ROS reversibly modulates many intracellular signaling pathways. ROS can affect protein functions through several mechanisms, including regulation of protein expression, posttranslational modifications, and alteration of protein stability. 9. Reduction-oxidation- (redox) dependent regulation and the roles of ROS include both normal physiologic and pathologic roles. These expanding roles include proliferation and differentiation, immune function, stem cell self-renewal, tumor progression, autoimmunity, stem cell exhaustion, senescence, and longevity. 10. Cell injury produced by free radicals, particularly ROS, is an important mechanism of cell damage in many conditions including chemical and radiation injury, ischemia- reperfusion injury, microbial killing by phagocytes, and cellular aging. 11. A significant mechanism of membrane damage is injury caused by free radicals, including oxidative stress. Oxidative stress can activate several intracellular signaling pathways because ROS can modulate enzymes and transcription factors. Free radicals are difficult to control and initiate chain reactions. 12. Free radicals can cause (a) lipid peroxidation or the destruction of unsaturated fatty acids, (b) alterations of proteins, protein loss, and protein misfolding, and (c) mutations in DNA. 13. Mitochondria contain their own DNA, called mitochondrial DNA (mtDNA), and can encode proteins involved in energy production. mtDNA encodes enzymes involved in oxidative phosphorylation, and mutations affecting these genes exert their damaging effects on organs most dependent on oxidative phosphorylation, such as the CNS, skeletal muscle, cardiac muscle, liver, and kidneys. Emerging is the role mitochondria has in mediating environmental changes and genomic responses.
- Humans are exposed to thousands of chemicals that have inadequate toxicologic data. Toxicity pathways or cellular response pathways result in adverse health effects when disturbed. Components of these pathways include oxidative stress, heat shock response, DNA damage response, hypoxia, ER stress, mental stress, inflammation, and osmotic stress.
- The initial insult in chemical and toxic injury is damage or destruction of the plasma membrane. Two general mechanisms include direct toxicity and conversion to toxic intermediates or metabolites. Examples of chemical agents that cause cellular injury include air pollutants, insecticides, herbicides, alcohol, lead, carbon monoxide, ethanol, mercury, opioids (heroin, morphine, prescription drugs for pain), and social or street drugs.
- Under investigation are the beneficial effects of chemical compounds called phytochemicals. Examples of these products include certain fruits and plants, chamomile, silymarin, carrot, ginger root, milk thistle seed, rosemary leaf, turmeric, and others.
- The world’s largest single environmental health risk is air pollution. From WHO data, every year 4 million deaths occur from exposure to indoor air pollution and 3 million deaths to outdoor air pollution. Air pollution is contamination of the environment by any chemical, physical, or biologic agent that modifies natural characteristics of the atmosphere.
- By reducing air pollution levels, countries can lower the burden of diseases from stroke, heart disease, lung cancer, and chronic and acute respiratory diseases, including asthma. Prompt and sustained health benefits can come from improved air quality.
- Heavy metals commonly associated with harmful effects in humans include lead, mercury, arsenic, and cadmium. Studies of the involvement of metals in pathophysiology include DNA repair mechanisms, tumor suppressor functions, and interference with signal transduction pathways.
- Unintentional and intentional injuries are an important health problem in the United States. Injuries include motor vehicle crashes, opioid overdoses, poisonings, sports and recreation-related injuries, firearms, falls, blunt force (tearing, shearing, crushing of tissues), asphyxia (suffocation, strangulation, chemical asphyxiants, drowning), and others including injury from medical care itself.
- Injury from microorganisms lies in their ability to survive and proliferate in the human body. Injury depends on the microorganisms’ ability to invade and destroy cells, produce toxins, and produce damaging hypersensitivity reactions.
- Activation of inflammation and immunity, which occurs after cellular injury or infection, involves powerful biochemicals and proteins capable of damaging normal (uninjured and uninfected) cells.
- Genetic disorders injure cells by altering the nucleus and the plasma membrane’s structure, shape, receptors, or transport mechanisms.
- Deprivation of essential nutrients (proteins, carbohydrates, lipids, vitamins) can cause cellular injury by altering cellular structure and function, particularly of transport mechanisms, chromosomes, the nucleus, and DNA. Excessive amounts of other nutrients, for example, carbohydrates, can lead to obesity, changes with insulin utilization, and diabetes.
Aging
- Aging is the progressive loss of tissues and organs over time. It is difficult to determine the physiologic (normal) from the pathologic changes of aging. One of the hallmarks of aging is the accumulation of damaged macromolecules.
- Investigators are focused on genetic, epigenetic, inflammatory, oxidative stress, cell renewal by adult stem cells, and metabolic and endocrine origins of aging.
- Senescence is a process of permanent proliferative arrest on cells in response to various stressors and may be an important contributor to aging and age-related diseases.
- Aging is associated with increased levels of circulating cytokines and proinflammatory markers. There are changes in the immune system with aging known as inflammaging. The microbiota plays a fundamental role in the induction and function of the immune system. Diet is believed to have a major influence on both the development and the prevention of age-related diseases.
- Humans have an inherent maximal life span (80 to 100 years) that is dictated by currently unknown intrinsic mechanisms.
- Although the maximal life span has not changed significantly over time, the average life span, or life expectancy, has decreased for the first time in 20 years in the United States.
- Frailty is a common clinical syndrome in older adults, leaving a person vulnerable to falls, functional decline, disability, disease, and death. The syndrome is complex, involving oxidative stress, dysregulation of inflammatory cytokines and hormones, malnutrition, physical inactivity, and muscle changes. Women have a higher risk of frailty than men.
Somatic Death
- Somatic death is death of the entire organism. Postmortem change is diffuse and does not involve the inflammatory response.
- Manifestations of somatic death include cessation of respiration and circulation, gradual lowering of body temperature, dilation of pupils, loss of elasticity and transparency in the skin, stiffening of muscles (rigor mortis), and discoloration of the skin (livor mortis). Signs of putrefaction are obvious about 24 to 48 hours after death.
McCance/Huether: Pathophysiology: The Biologic Basis of Disease in Adults
and Children, 8th Edition
Chapter 03: The Cellular Environment: Fluids and Electrolytes, Acids, and Bases
Chapter Summary Review
Distribution of Body Fluids
- Body fluids are distributed among functional compartments and are classified as ICF or ECF.
- The sum of all fluids is the TBW, which varies with age and amount of body fat and is higher in infants because they have less body fat.
- Water moves between the ICF and ECF compartments principally by osmosis.
- Water moves between the plasma and interstitial fluid by osmosis and hydrostatic pressure, which occur across the capillary membrane.
- Movement across the capillary wall is called net filtration and is described according to the Starling law (forces favoring filtration minus forces opposing filtration).
Alterations in Water Movement
- Edema is a problem of fluid distribution that results in accumulation of fluid within the interstitial spaces.
- Edema is caused by venous or lymphatic obstruction (increases hydrostatic pressure), plasma protein losses (decreases plasma oncotic pressure), increased capillary permeability, and increased vascular volume.
- The pathophysiologic process that leads to edema is related to an increase in forces favoring fluid filtration from the capillaries into the tissues.
- Edema may be localized or generalized and usually is associated with swelling and puffiness, tighter-fitting clothes and shoes, limited movement of the affected area, and, in severe cases, weight gain.
Sodium, Chloride, and Water Balance
Sodium balance and water balance are intimately related; chloride levels are generally proportional to changes in sodium levels.
Sodium balance is regulated by aldosterone, which increases reabsorption of sodium by the distal tubule of the kidney.
Renin and angiotensin are enzymes that promote or inhibit secretion of aldosterone and thus regulate sodium and water balance.
Atrial natriuretic hormone is also involved in decreasing renal tubular resorption and promoting urinary excretion of sodium.
Water balance is regulated by the sensation of thirst and by the level of antidiuretic hormone, which is initiated by an increase in plasma osmolality or a decrease in circulating blood volume.
Hypocalcemia (total serum calcium concentration <9 mg/dL) is related to inadequate intestinal absorption, deposition of ionized calcium into bone or soft tissue, blood administration, or decreased PTH and vitamin D levels.
Hypercalcemia (serum calcium concentration >10 mg/dL) can be caused by a number of diseases, including hyperparathyroidism, bone metastases, sarcoidosis, and excess vitamin D.
Hypophosphatemia is a serum phosphate level less than 2 mg/dL and is usually caused by intestinal malabsorption and increased renal excretion of phosphate.
Hyperphosphatemia is a serum phosphate level more than 4 mg/dL and develops with acute or chronic renal failure with significant loss of glomerular filtration.
Magnesium is a major intracellular cation and is principally regulated by PTH.
Magnesium functions in enzymatic reactions and often interacts with calcium at the cellular level.
Hypomagnesemia (serum magnesium concentrations <1 mEq/L) may be caused by malabsorption syndromes.
Hypermagnesemia (serum magnesium concentrations >3 mEq/L) is rare and is usually caused by renal failure.
Acid-Base Balance
Hydrogen ions, which maintain membrane integrity and the speed of enzymatic reactions, must be concentrated within a narrow range if the body is to function normally.
Hydrogen ion concentration is expressed as pH, which represents the negative logarithm of hydrogen ions in solution.
Different body fluids have different pH values.
The renal and respiratory systems, together with the body’s buffer systems, are the principal regulators of acid-base balance.
Buffers are substances that can absorb excessive acid or base to minimize fluctuations in pH.
Buffers exist as acid-base pairs; the principal plasma buffers are bicarbonate, protein (hemoglobin), and phosphate.
Buffer pairs can associate and dissociate; the pK value is the pH at which a buffer pair is half dissociated.
The lungs and kidneys act to compensate for changes in pH by increasing or decreasing ventilation and by producing more acidic or more alkaline urine.
Correction is a process different from compensation; correction occurs when the values for both components of the buffer pair are returned to normal.
Acid-base imbalances are caused by changes in the concentration of H+ in the blood; an increase causes acidosis, and a decrease causes alkalosis.
An abnormal increase or decrease in bicarbonate concentration causes metabolic acidosis or metabolic alkalosis; changes in the rate of alveolar ventilation produce respiratory acidosis or respiratory alkalosis.
Metabolic acidosis is caused by an increase in the concentrations of non–carbonic acids or by loss of bicarbonate from the extracellular fluid.
Metabolic alkalosis occurs with an increase in bicarbonate concentration usually caused by loss of metabolic acids from conditions such as vomiting, gastrointestinal suctioning, excessive bicarbonate intake, hyperaldosteronism, and diuretic therapy.
Respiratory acidosis occurs with a decrease of alveolar ventilation and an increase in levels of carbon dioxide, or hypercapnia.
Respiratory alkalosis occurs with alveolar hyperventilation and excessive reduction of carbon dioxide concentration, or hypocapnia.
Human cells consist of diploid somatic cells (body cells) and haploid gametes (sperm and egg cells).
Humans have 23 pairs of chromosomes: 22 of these pairs are autosomes. The remaining pair consists of the sex chromosomes. Females have two homologous X chromosomes as their sex chromosomes; males have an X and a Y chromosome.
A karyotype is an ordered display of chromosomes arranged according to length and the location of the centromere.
Various types of stains can be used to make chromosome bands more visible.
About 1 in 150 live births has a major diagnosable chromosome abnormality. Chromosome abnormalities are the leading known cause of mental retardation and miscarriage.
Polyploidy is a condition in which a euploid cell has some multiple of the normal number of chromosomes. Humans have been observed to have triploidy (three copies of each chromosome) and tetraploidy (four copies of each chromosome); both conditions are lethal.
Somatic cells that do not have a multiple of 23 chromosomes are aneuploid. Aneuploidy is usually the result of nondisjunction.
Trisomy is a type of aneuploidy in which one chromosome is present in three copies in somatic cells. A partial trisomy is one in which only part of a chromosome is present in three copies.
Monosomy is a type of aneuploidy in which one chromosome is present in only one copy in somatic cells.
In general, monosomies cause more severe physical defects than do trisomies, illustrating the principle that the loss of chromosome material has more severe consequences than the duplication of chromosome material.
Down syndrome, a trisomy of chromosome 21, is the most well-known disease caused by a chromosome aberration. It affects 1 in 800 live births and is much more likely to occur in the offspring of women older than 35 years of age.
Most aneuploidies of the sex chromosomes have less severe consequences than those of the autosomes.
The most commonly observed sex chromosome aneuploidies are the 47,XXX karyotype; 45,X karyotype (Turner syndrome); 47,XXY karyotype (Klinefelter syndrome); and 47,XYY karyotype.
Abnormalities of chromosome structure include deletions, duplications, inversions, and translocations.
Elements of Formal Genetics
Mendelian traits are caused by single genes, each of which occupies a position, or locus, on a chromosome.
Alleles are different forms of genes located at the same locus on the chromosome.
At any given locus in a somatic cell, an individual has two genes, one from each parent. An individual may be homozygous or heterozygous for a locus.
An individual’s genotype is the person’s genetic makeup, and the phenotype reflects the interaction of genotype and environment.
At a heterozygous locus, a dominant gene’s effects mask those of a recessive gene. The recessive gene is expressed only when it is present in two copies.
Transmission of Genetic Diseases
- Genetic diseases caused by single genes usually follow autosomal dominant, autosomal recessive, or X-linked recessive modes of inheritance.
- Pedigree charts are an important tool in the analysis of modes of inheritance.
- Recurrence risks specify the probability that future offspring will inherit a genetic disease. For single-gene diseases, recurrence risks remain the same for each offspring, regardless of the number of affected or unaffected offspring.
- The recurrence risk for autosomal dominant diseases is usually 50%.
- Germline mosaicism can alter recurrence risks for genetic diseases because unaffected parents can produce multiple affected offspring. This situation occurs because the germline of one parent is affected by a mutation but the parent’s somatic cells are unaffected.
- Skipped generations are not seen in classic autosomal dominant pedigrees.
- Males and females are equally likely to exhibit autosomal dominant diseases and to pass them on to their offspring.
- A gene that is not always expressed phenotypically is said to have incomplete penetrance.
- Penetrance may be age-dependent, as in Huntington disease and familial breast cancer.
- Variable expressivity is a characteristic of many genetic diseases.
- Most commonly, parents of children with autosomal recessive diseases are both heterozygous carriers of the disease gene. In this case, the recurrence risk for autosomal recessive diseases is 25%.
- Males and females are equally likely to be affected by autosomal recessive diseases.
- Consanguinity is sometimes present in families with autosomal recessive diseases, and it becomes more prevalent with rarer recessive diseases.
- Carrier detection tests for an increasing number of autosomal recessive diseases are available.
- The frequency of genetic diseases approximately doubles in the offspring of first-cousin matings.
- In each normal female somatic cell, one of the two X chromosomes is inactivated early in embryogenesis.
- X-inactivation is random, fixed, and incomplete (i., only part of the chromosome is actually inactivated). It may involve methylation.
- Gender is determined embryonically by the presence of the SRY gene on the Y chromosome. Embryos that have a Y chromosome (and thus the SRY gene) become males, whereas those lacking the Y chromosome become females. When the Y chromosome lacks the SRY gene, an XY female can be produced. Similarly, an X chromosome that contains the SRY gene can produce an XX male.
- X-linked genes are those that are located on the X chromosome. Nearly all known X- linked diseases are caused by X-linked recessive genes.
- Males are hemizygous for genes on the X chromosome.
- X-linked recessive diseases are seen much more often in males than in females because males need only one copy of the gene to express the disease.
McCance/Huether: Pathophysiology: The Biologic Basis of Disease in Adults
and Children, 8th Edition
Chapter 05: Genes, Environment-Lifestyle, and Common Diseases
Chapter Summary Review
Factors Influencing Incidence of Disease in Populations
- The incidence rate is the number of new cases of a disease reported during a specific period (typically 1 year) divided by the number of individuals in the population.
- The prevalence rate is the proportion of the population affected by a disease at a specific point in time. This rate, and the incidence rate, can be used to compare population variations in disease frequency.
- Relative risk is a common measure of the effect of a specific risk factor. It is expressed as a ratio of the incidence rate of the disease among individuals exposed to a risk factor divided by the incidence of the disease among individuals not exposed to a risk factor.
- Many factors can influence the risk of acquiring a common disease, such as cancer, diabetes, or hypertension. The factors can include age, gender, diet, exercise, and family history of the disease.
Principles of Multifactorial Inheritance
- Traits in which variation is thought to be caused by the combined effects of multiple genes are polygenic.
- The term multifactorial is used when environmental factors also are believed to cause variation in the trait.
- Many quantitative traits (e., blood pressure) are multifactorial.
- Because traits are caused by the additive effects of many genetic and environmental factors, they tend to follow a normal or bell-shaped distribution in populations.
- Those diseases, however, that do not follow a bell-shaped distribution appear to be either present or absent in individuals. They do not follow the inheritance patterns of single- gene disease. Instead, such diseases may follow an underlying liability distribution. It is thought that a threshold of liability must be crossed before the disease is expressed.
- Examples of diseases that correspond to the liability model include pyloric stenosis, neural tube defects, CL/P, and some forms of congenital heart disease.
- Many of the common adult diseases, such as hypertension, coronary heart disease, stroke, diabetes mellitus (types 1 and 2), and some cancers, are caused by complex genetic and environmental factors and are thus multifactorial diseases.
- For most multifactorial diseases, empirical risks (risks based on direct observation of data) have been derived.
- In contrast to most single-gene diseases, recurrence risks for multifactorial diseases can change significantly from one population to another because gene frequencies, as well as environmental factors, can differ among populations.
- Several criteria are used to define multifactorial inheritance: (a) the recurrence risk becomes higher if more than one family member is affected; (b) if the expression of the
disease in a proband is more severe, the recurrence risk is higher; (c) the recurrence risk is higher if the proband is of the less commonly affected sex; (d) the recurrence risk for the disease usually decreases rapidly in more remotely related relatives; and (e) if the prevalence of the disease in a population is f , the risk for offspring and siblings of probands is approximately √ f.
Nature and Nurture: Disentangling the Effects of Genes and Environment
- Family members share genes and a common environment; therefore, resemblance in traits, such as high blood pressure, reflects both genetic and environmental factors (nature and nurture, respectively).
- Few traits are influenced only by genes or only by environment. Most are influenced by both.
- When a disease has a relatively larger genetic component, as in breast cancer, examination of family history should be emphasized in addition to lifestyle modification.
- Two research strategies often are used to estimate the relative influence of genes and environment-lifestyle: twin studies and adoption studies.
- Monozygotic twins originate when the developing embryo divides to form two separate but identical embryos.
- Dizygotic twins are the result of a double ovulation followed by the fertilization of each egg by a different sperm.
- If both members of a twin pair share a trait, they are said to be concordant. If they do not share the same trait, they are discordant.
- Studies of adopted children also are used to estimate the genetic contribution to a multifactorial trait.
- A genetic predisposition may interact with an environmental-lifestyle factor to increase the risk of disease; this is called a gene-environment interaction.
Genetics of Common Diseases
- Congenital diseases are those present at birth. Most of these diseases are multifactorial in etiology.
- Multifactorial diseases in adults include coronary heart disease, hypertension, breast cancer, colon cancer, diabetes mellitus, obesity, AD, alcoholism, schizophrenia, and bipolar affective disorder.
- It is incorrect to assume that the presence of a genetic component means that the course of a disease cannot be altered—most diseases have both genetic and environmental aspects.
8th Edition Pathophysiology Chapter Summaries
Course: Advanced Pathophysiology (NURS-6501N)
University: Walden University
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