Module 1 Highlights & Notes PDF

6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology Definitions 5/12/2024 Side Notes...

6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology Definitions 5/12/2024 Side Notes the World Health Organization (WHO) defined health as a “state of complete physical, mental, and social well-being and not merely the absence of disease and infirmity,” Definitions 5/12/2024 five key environments of social determinants of health (U.S. Department of Health and Human Services, 2021): 1. Economic Stability, 2. education access and quality, 3. healcare access and quality, 4. neighborhood and built environment, 5. social and community context Definitions 5/12/2024 Disease A disease is considered an acute or chronic illness that one acquires or is born with that causes physiologic dysfunction in one or more body system. CO Attention! 5/14/2024 Etiology The causes of disease are known as etiologic factors. Among the recognized etiologic agents are biologic agents (e.g., bacteria, viruses), physical forces (e.g., trauma, burns, radiation), chemical agents (e.g., poisons, alcohol), one’s genetic inheritance, and nutritional excesses or deficits. Definitions 6/7/2024 pathogenesis explains how the disease process evolves. Definitions 6/7/2024 Morphology refers to the fundamental structure or form of cells or tissues. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 1/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology Definitions 6/7/2024 deals with the study of the cells and extracellular matrix of body tissues. CO Attention! 5/13/2024 Clinical Manifestations Diseases can manifest in a number of ways. Sometimes, the condition produces manifestations, such as fever, that make it evident that the person is sick. In other cases, the condition is silent at the onset and is detected during examination for other purposes or after the disease is far advanced. Signs and symptoms are terms used to describe the structural and functional changes that accompany a disease. A symptom is a subjective complaint that is noted by the person with a disorder, whereas a sign is a manifestation that is noted by an observer. Pain, difficulty in breathing, and dizziness are symptoms of a disease. An elevated temperature, a swollen extremity, and changes in pupil size are objective signs that can be observed by someone other than the person with the disease. Signs and symptoms may be related to the primary disorder, or they may represent the body’s attempt to compensate for the altered function caused by the pathologic condition. Many pathologic states are not observed directly. For example, one cannot see that a person is hemorrhaging or that they have decreased pulmonary gas exchange. Instead, what can be observed is the body’s attempt to compensate for changes in function brought about by the disease, such as the tachycardia that accompanies blood loss or the increased respiratory rate that occurs with pneumonia. A syndrome is a compilation of signs and symptoms (e.g., chronic fatigue syndrome) that are characteristic of a specific disease state. Complications are possible adverse extensions of a disease or outcomes from treatment. Sequelae are lesions or impairments that follow or are caused by a disease. Definitions 6/7/2024 A diagnosis is the designation as to the nature or cause of a health problem Definitions 6/7/2024 The clinical course describes the evolution of a disease. Definitions 6/7/2024 A diagnosis is the designation as to the nature and cause of a health PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes problem. created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 2/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/13/2024 The term clinical expertise implies the proficiency and judgment that individual clinicians gain through clinical experience and clinical practice. The best external clinical evidence relies on the identification of clinically relevant research, often from the basic sciences, but especially from patient-centered clinical studies that focus on the accuracy and precision of diagnostic tests and methods, the power of prognostic indicators, and the effectiveness and safety of therapeutic, rehabilitative, and preventive regimens. CO Attention! 5/13/2024 Clinical practice guidelines are systematically developed statements intended to inform practitioners and people in making decisions about healthcare for specific clinical circumstances (Duke University Medical Center, 2021). CO Attention! 5/13/2024 Individuals age because their cells age. Age is one of the strongest independent risk factors for many chronic diseases. Cellular aging is not acute; rather, it is progressive in nature as a result of environmental damage such as free radical damage, fixed cellular senescence, genetic influences, culture, diet, and decline in function ( CO Attention! 5/14/2024 Adaptive cellular responses also include intracellular accumulations and storage of products in abnormal amounts (Strayer et al., 2020). Compare the pathogenesis and effects of dystrophic and metastaticcalcifications. CO Attention! 5/14/2024 The general causes of atrophy can be grouped into five categories: Disuse Denervation Loss of endocrine stimulation Inadequate nutrition Ischemia or decreased blood flow Disuse atrophy occurs when there is a reduction in skeletal muscle use PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 3/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 For example, athletes may develop “exercise-induced cardiac remodeling” or “athlete’s heart” that is asymptomatic (McKelvie, 2020). This is in contrast to the hypertrophy that develops in dilated cardiomyopathy, in which the hypertrophied cells have a relatively greater increase in length than width. In pressure overload, as occurs with hypertension, the hypertrophied cells have greater width than length (Colucci, 2022). It is anticipated that further elucidation of the signal pathways that determine the adaptive and nonadaptive features of cardiac hypertrophy will lead to new targets for treatment. CO Attention! 5/14/2024 Although people with BE are at a much higher risk than people without this condition to develop adenocarcinoma of the esophagus, most (American Cancer Society, 2020) do not get esophageal cancer. CO Attention! 5/14/2024 Icterus, also called jaundice, is characterized by a yellow discoloration of tissue due to the retention of bilirubin, an endogenous bile pigment. This condition may result from increased bilirubin production from red blood cell destruction, obstruction of bile passage into the intestine, or toxic diseases that affect the liver’s ability to remove bilirubin from the blood. CO Attention! 5/14/2024 Metastatic Calcification In contrast to dystrophic calcification, which occurs in injured tissues, metastatic calcification occurs in normal tissues as the result of increased serum calcium levels (hypercalcemia ). Almost any condition that increases the serum calcium level can lead to calcification in inappropriate sites such as the lung, renal tubules, and blood vessels. The major causes of hypercalcemia are hyperparathyroidism, chronic renal failure, and primary bone disease such as mobilization of calcium from the bone in Paget disease. Malignant causes include multiple myeloma, small cell lung carcinoma, and leukemia (Broaddus, 2022). PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 4/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Causes of Cell Injury Although most of this section is not on the midterm blueprint werecommend that NP students review the highlighted information.Especially on how these forces affect the body. If you plan to work in urgent care or the ER you may see these types of injuries. CO Attention! 5/14/2024 Injury From Physical Agents These types of injuries split and tear tissue, fracture bones, injureblood vessels, and disrupt blood flow. CO Attention! 5/14/2024 Mechanical Forces. Injury or trauma due to mechanical forces occurs as the result of body impact with another object. The body or the mass can be in motion, or, as sometimes happens, both can be in motion at the time of impact. These types of injuries split and tear tissue, fracture bones, injure blood vessels, and disrupt blood flow. CO Attention! 5/14/2024 Extremes of Temperature. CO Attention! 5/14/2024 Exposure to cold increases blood viscosity and induces vasoconstriction by direct action on blood vessels and through reflex activity of the sympathetic nervous system. The resultant decrease in blood flow may lead to hypoxic tissue injury, depending on the degree and duration of cold exposure. Injury from freezing probably results from a combination of ice crystal formation and vasoconstriction. The decreased blood flow leads to capillary stasis and arteriolar and capillary thrombosis. Edema results from increased capillary permeability. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 5/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Electrical Injuries. Electrical injuries can affect the body through extensive tissue injury and disruption of neural and cardiac impulses. CO Attention! 5/14/2024 Alternating current is usually more dangerous than direct current because it causes violent muscle contractions, preventing the person from releasing the electrical source and sometimes resulting in fractures and dislocations. In electrical injuries, the body acts as a conductor of the electrical current (Zemaitis et al., 2023). CO Attention! 5/14/2024 The current enters the body from an electrical source, such as an exposed wire, and passes through the body and exits to another conductor, such as the moisture on the ground or a piece of metal the person is holding. The pathway that a current takes is critical because the electrical energy disrupts impulses in excitable tissues. Current flow through the brain may interrupt impulses from respiratory centers in the brain stem, and current flow through the chest may cause fatal cardiac arrhythmias. CO Attention! 5/14/2024 Radiation Injury CO Attention! 5/14/2024 Ionizing Radiation. Ionizing radiation impacts cells by causing ionization of molecules and atoms in the cell. This is accomplished by releasing free radicals that destroy cells and by directly hitting the target molecules in the cell. It can immediately kill cells, interrupt cell replication, or cause a variety of genetic mutations, which may or may not be lethal. Most radiation injury is caused by localized irradiation that is used in the treatment of cancer. Except for unusual circumstances such as the use of high-dose irradiation that precedes bone marrow transplantation, exposure to whole-body irradiation is rare. Rapidly dividing cells of the bone marrow and intestine are much morevulnerable to radiation injury than tissues such as bone and skeletalmuscle. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 6/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 The injurious effects of ionizing radiation vary with the dose, dose rate (a single dose can cause greater injury than divided or fractionated doses), and the differential sensitivity of the exposed tissue to radiation injury. CO Attention! 5/14/2024 Chemical Injury Chemicals capable of damaging cells are everywhere around us. Air and water pollution contains chemicals capable of tissue injury, as does tobacco smoke and some processed or preserved foods. Some of the most damaging chemicals exist in our environment, including gases such as carbon monoxide, insecticides, and trace metals such as lead. CO Attention! 5/14/2024 Chemical agents can injure the cell membrane and other cell structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic and ionic balance of the cell. Corrosive substances such as strong acids and bases destroy cells as the substances come into contact with the body. Other chemicals may injure cells in the process of metabolism or elimination. Carbon tetrachloride (CCl4), for example, causes little damage until it is metabolized by liver enzymes to a highly reactive free radical (CCl3 ). Carbon tetrachloride is extremely toxic to liver cells (Al Amin & Menezes, 2022). Carbon tetrachloride (CCl4), for example, causes little damage until it ismetabolized by liver enzymes to a highly reactive free radical (CCl3 ).Carbon tetrachloride is extremely toxic to liver cells.17 CO Attention! 5/14/2024 Drugs. Many drugs—alcohol, prescription drugs, over-the-counter drugs, and street drugs—are capable of directly or indirectly damaging tissues. Ethyl alcohol can harm the gastric mucosa, liver, developing fetus, and other organs. Antineoplastic and immunosuppressant drugs can directly injure cells CO Attention! 5/14/2024 This is characterized by “lead colic,” a severe and poorly localized PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes form of acute abdominal pain. A lead line formed by precipitated lead created by user are not part of publisher content. No part of sulfide may appear along the gingival margins. this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 7/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Mercury Toxicity. Mercury has been used for industrial and medical purposes for hundreds of years. Mercury is toxic, and the hazards of mercury-associated occupational and accidental exposures are well known. Currently, mercury and lead are the most toxic metals. Mercury is toxic in four primary forms: mercury vapor, inorganic divalent mercury, methyl mercury, and ethyl mercury (Centers for Disease Control and Prevention, 2022). Depending on the form of mercury exposure, toxicity involving the central nervous system and kidney can occur (Centers for Disease Control and Prevention, 2022). CO Attention! 5/14/2024 Injury From Biologic Agents CO Attention! 5/14/2024 Injury From Nutritional Imbalances Nutritional excesses and nutritional deficiencies predispose cells to injury. Obesity and diets high in saturated fats are thought to predispose people to atherosclerosis. The body requires more than 60 organic and inorganic substances in amounts ranging from micrograms to grams. These nutrients include minerals, vitamins, certain fatty acids, and specific amino acids. Dietary deficiencies can occur in the form of starvation, in which there is a deficiency of all nutrients and vitamins, or because of a selective deficiency of a single nutrient or vitamin. Iron-deficiency anemia, scurvy, beriberi, and pellagra are examples of injury caused by the lack of specific vitamins or minerals. The protein and calorie deficiencies that occur with starvation cause widespread tissue damage. CO Attention! 5/14/2024 Free radical formation Hypoxia and ATP depletion Disruption of intracellular calcium homeostasis ( CO Attention! 5/14/2024 Free radicals are highly reactive chemical species with an unpaired electron in the outer orbit (valence shell) of the molecule (Zemaitis et al., 2023). In the literature, the unpaired electron is denoted by a dot, for example, NO. The unpaired electron causes free radicals to be unstable and highly reactive, so they react nonspecifically with molecules in the vicinity. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 8/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Oxidative damage has been implicated in many diseases (Mavondo- Nyajena Mukuwa Greanious et al., 2021). Oxidative stress is thought to play an important role in the development of cancer (Arfin et al., 2021). Reestablishment of blood flow after loss of perfusion, as occurs during heart attack and stroke, is associated with oxidative injury to vital organs CO Attention! 5/14/2024 Antioxidants are natural and synthetic molecules that inhibit the reactions of ROS with biologic structures or prevent the uncontrolled formation of ROS. Antioxidants include enzymatic and nonenzymatic compound CO Attention! 5/14/2024 Nonenzymatic antioxidants include carotenes (e.g., vitamin A), tocopherols (e.g., vitamin E), ascorbate (vitamin C), glutathione, flavonoids, selenium, and zinc (Shah & Gupta, 2021). CO Attention! 5/14/2024 n hypermetabolic states, cells may require more oxygen than that can be supplied by normal respiratory function and oxygen transport. CO Attention! 5/14/2024 Hypoxia causes a power failure in the cell, with widespread effects on the cell’s structural and functional components CO Attention! 5/14/2024 mpaired Calcium Homeostasis Calcium functions as an important second messenger and cytosolic signal for many cell responses. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 9/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Reversible Cell Injury Reversible cell injury, although impairing cell function, does not result in cell death. Two patterns of reversible cell injury can be observed under the microscope: cellular swelling and fatty change. CO Attention! 5/14/2024 Apoptosis is a highly selective process that eliminates injured and aged cells, thereby controlling tissue regeneration. Cells undergoing apoptosis have characteristic morphologic features as well as biochemical changes. CO Attention! 5/14/2024 Apoptosis is linked to many pathologic processes and diseases. For example, interference with apoptosis is known to be a mechanism that contributes to carcinogenesis. Apoptosis may also be implicated in neurodegenerative disorders such as Parkinson disease (Gupta, 2022). However, the exact mechanisms involved in these diseases remain under investigation. Two basic pathways for apoptosis have been described (Fig. 3.10). These are the extrinsic pathway, which is death receptor dependent, and the intrinsic pathway, which is death receptor-independent. CO Attention! 5/14/2024 An example of liquefaction necrosis is the softening of the center of an abscess with discharge of its contents. During coagulation necrosis, acidosis develops and denatures the enzymatic and structural proteins of the cell. This type of necrosis is characteristic of hypoxic injury and is seen in infarcted areas (Strayer et al., 2020). Infarction (i.e., tissue death) occurs when an artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists. As a rule, the shape of the infarction is conical and corresponds to the distribution of the artery and its branches. An artery may be occluded by an embolus, a thrombus, disease of the arterial wall, or pressure from outside the vessel. CO Attention! 5/14/2024 Caseous necrosis is a distinctive form of coagulation necrosis in which the dead cells persist indefinitely (Strayer et al., 2020). It is most commonly found in the center of tuberculous granulomas or tubercles PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 10/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Age-related sarcopenia, the loss of muscle mass, is due to loss of type II fibers. This is different from cachexia, which is associated with loss of type I fibers CO Attention! 5/14/2024 Otitis media is associated with upper respiratory and adenoid hypertrophy, causing eustachian tube dysfunction and potential loss of hearing (Kyle & Carman, 2021). Epididymitis in young boys is often caused by urinary tract infections, resulting in pain and inflammation (Stanford Medicine, 2022). Children taking phenytoin, an anticonvulsant, are at risk for gingival hyperplasia, which can be treated with vitamin D (Kyle & Carman, 2021). Puberty is associated with cellular hypertrophy due to rapid increases in androgens and growth hormones (Strayer et al., 2020). CO Attention! 5/14/2024 GENETIC CONTROL OF CELL FUNCTION A pedigree is a graphic method (see Figs. 4.11 and 4.12) forportraying a family history for an inherited trait. It is constructed froma carefully obtained family history and is useful for tracing the patternof inheritance for a particular trait. CO Attention! 5/14/2024 Messenger RNA is formed from DNA by a process called transcription. In this process, the weak hydrogen bonds of the DNA nucleotides are temporarily broken so that free RNA nucleotides can pair with their exposed DNA counterparts of the DNA molecule (see Fig. 4.4). As with the base pairing of the DNA strands, complementary RNA bases pair with the DNA bases. As with DNA, guanine pairs with cytosine. But in RNA, uracil (U) replaces thymine to pair with adenine. I recommend reading over the part about mRNA since it is used to develop some vaccine, the COVID vaccine for example. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 11/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 IN SUMMARY The summary can provide a general overview of this topic. This knowledge benefits the FNP in the process of educationg patients regarding vaccines and other treatments. CO Attention! 5/14/2024 Genes DNA is organized into 23 pairs of chromosomes. There are 22 pairsof autosomes, which are alike for males and females, and one pair ofsex chromosomes, with XX pairing in females and XY pairing inmales. CO Attention! 5/14/2024 Translation Translation begins when the mRNA carrying the instructions for a particular protein comes in contact with a ribosome and binds to a small subunit of the rRNA. It then travels through the ribosome while the tRNA delivers and transfers the correct amino acid to its proper position on the growing peptide chain. The tRNA binds to a three-base section of the mRNA called a codon. There are 20 types of tRNA, one for each of the 20 different types of amino acid. In order to be functional, the newly synthesized protein must be folded into its functional form, modified further, and then routed to its final position in the cell. See mRNA and examine its role. CO Attention! 5/14/2024 In the human, 46 chromosomes are present, and these are arranged into 23 pairs. Of the 23 pairs of human chromosomes, 22 are called autosomes, and each has been given a numeric designation for classification purposes (Fig. 4.6). The pairs of autosomal chromosomes are called homologous chromosomes. They are not identical, however, because one comes from the biological father and one comes from the biological mother. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 12/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 he sex chromosomes, which make up the 23rd pair of chromosomes, determine the sex of a person. Human males have an X and Y chromosome (i.e., an X chromosome from the biological mother and a Y chromosome from the biological father); human females have two X chromosomes (i.e., one X chromosome was inherited from each biological parent). The much smaller Y chromosome contains genes necessary for the development of male sex CO Attention! 5/14/2024 Mitosis is the process by which DNA is replicated to duplicate somatic cells in the body CO Attention! 5/14/2024 Meiosis also replicates DNA, but the end product is the formation of gametes or reproductive cells (i.e., ovum and sperm) (Fig. 4.8). Each cell undergoing meiosis only has a single set of 23 chromosomes. Meiosis is divided into two distinct phases, meiosis I and meiosis II. As in mitosis, the first step of meiosis I is to replicate the DNA during interphase. During metaphase I, all homologous autosomal chromosomes pair up, forming a tetrad of bivalents. CO Attention! 5/14/2024 KEY POINTS CHROMOSOMES DNA is organized into 23 pairs of chromosomes. There are 22 pairs of autosomes, which are alike for males and females, and one pair of sex chromosomes, with XX pairing in females and XY pairing in males. Cell division requires the duplication of chromosomes. Duplication of chromosomes in a somatic cell line is completed by the process of mitosis, in which each daughter cell receives 46 total chromosomes, arranged in 23 pairs. Meiosis is limited to replicating germ cells and results in daughter cells that each has 23 total chromosomes. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 13/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Cytogenetics is the study of the structure and numeric characteristics of the cell’s chromosomes. Chromosome studies can be done on any tissue or cell that grows and divides in culture, but white blood cells or buccal (cheek) samples are frequently used for this purpose. After the cells have been cultured, a drug called colchicine is used to arrest mitosis in metaphase so that the chromosomes can be easily seen. Note the terms and definitions. These are not in the blueprint or exam but you may want to familiarize yourself with these if your work in a practice that routinely sees patients with genetic issues. CO Attention! 5/14/2024 Definitions CO Attention! 5/14/2024 genotype of a person is the genetic information stored in the sequence of base pairs. The phenotype refers to the recognizable traits, physical or biochemical, that are associated with a specific genotype. CO Attention! 5/14/2024 he position of a gene on a chromosome is called its locus, and alternate forms of a gene at the same locus are called alleles CO Attention! 5/14/2024 These include epistasis, in which one gene masks the phenotypic effects of another gene; multiple alleles, in which more than one allele affects the same trait ( CO Attention! 5/14/2024 Certain genes exhibit a “parent of origin” type of transmission in which the parental genomes do not always contribute equally in the development of a person PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 14/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Well-known examples of genomic imprinting are the transmission of the mutations in Prader-Willi and Angelman syndromes (Butler & Duis, 2020). Both syndromes result in intellectual disability as a common feature, and both disorders are created by the same deletion mutation in chromosome 15. When the deletion is inherited from the biological mother, the infant presents with Angelman syndrome, but when the same deletion is inherited from the biological father, Prader- Willi syndrome results. This is astounding when you think about it! CO Attention! 5/14/2024 A related chromosomal disorder is uniparental disomy. This occurs when two chromosomes of the same number are inherited from one biological parent. CO Attention! 5/14/2024 Punnett square using capital and lowercase letters CO Attention! 5/14/2024 The Human Genome Project CO Attention! 5/14/2024 Linkage Studies. CO Attention! 5/14/2024 Hybridization Studies. CO Attention! 5/14/2024 The term recombinant DNA refers to a combination of DNA molecules that are not found together in nature. Recombinant DNA technology PRINTED BY: [email protected]. Printing of Notes makes it possible to identify the DNA sequence in a gene and and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of produce the protein product encoded by a gene. T this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 15/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 DNA Fingerprinting The technique of DNA fingerprinting also uses recombinant DNA technology, as well as basic principles of medical genetics. CO Attention! 5/14/2024 This can be done with even very small samples of DNA (a single hair or a drop of blood or saliva) using amplification by polymerase chain reaction. CO Attention! 5/14/2024 Gene Therapy CO Attention! 5/14/2024 Two main approaches are used in gene therapy: transferred genes can replace defective genes, or they can selectively inhibit the expression of deleterious genes. Cloned DNA sequences are usually the compounds used in gene therapy. CO Attention! 5/14/2024 Another potential therapeutic has been found in the advent of CRISPR-Cas9 technology CO Attention! 5/14/2024 RNA Interference Technology RNA technology is a fast-growing area of research. CO Attention! 5/14/2024 Genetic influences on aging are evident by a substantially longer life (up to 65%) when single-gene mutations occur in specific signaling pathways (Singh et al., 2019). The shortening or erosion of telomeres PRINTED BY: [email protected]. Printing of Notes contributes to organismal aging (Singh et al., 2019). and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 16/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 1 in 150 live births has a chromosomal anomaly causing cognitive impairment and birth defects. Chromosomal abnormalities are even more prevalent among stillbirths and spontaneous abortions. Inborn errors of metabolism, caused by gene mutations, may be lethal if not treated, thus prompting many states to require mandatory newborn screening. Creation of a family pedigree can help to identify genetic disorders and is useful when going for genetic counseling. CO Attention! 5/14/2024 TABLE 5.1 SOME DISORDERS OF MENDELIAN OR SINGLE-GENE INHERITANCE AND THEIR SIGNIFICANCE CO Attention! 5/14/2024 utosomal dominant disorders also may manifest as a new mutation. Whether the mutation is passed on to the next generation depends on the affected person’s reproductive capacity. Many autosomal dominant mutations are accompanied by reduced reproductive capacity; therefore, the defect is not perpetuated in future generations. I CO Attention! 5/14/2024 Although there is a 50% chance of inheriting a dominant genetic disorder from an affected biological parent, there can be wide variation in gene penetrance and expression. When a person inherits a dominant mutant allele but fails to exhibit the associated phenotype, the trait is described as having reduced penetranc CO Attention! 5/14/2024 wo relatively common disorders of autosomal inheritance, Marfan syndrome and neurofibromatosis (NF), are described here. CO Attention! 5/14/2024 eurofibromatosis. NF is a condition that causes tumors to develop from the Schwann cells of the neurologic system. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 17/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Autosomal Recessive Disorders CO Attention! 5/14/2024 Consanguineous mating (mating of two related people), or inbreeding, increases the chance that two people who mate will be carriers of an autosomal recessive disorder. CO Attention! 5/14/2024 utosomal recessive disorders include almost all inborn errors of metabolism. CO Attention! 5/14/2024 X-Linked Recessive Disorders CO Attention! 5/14/2024 When the affected son procreates, he only has his mutant X or a normal Y to pass on to the next generation. In order to have a daughter, the biological father donates his only X chromosome, which combines with one of the biological mother’s two X chromosomes, resulting in a XX child. Because his X is mutated, he transmits the mutant gene to 100% of his daughters, who then become carriers. Because the genes of the Y chromosome are unaffected, the affected male does not transmit the defect to any of his sons, and they will not be carriers or transmit the disorder to their children. Although rare, females can be affected with an X-linked recessive disorder. CO Attention! 5/14/2024 Fragile X Syndrome Fragile X syndrome is a single-gene disorder that causes intellectual disability. CO Attention! 5/14/2024 The deletion of a portion of a chromosome leads to the loss of genetic PRINTED BY: [email protected]. Printing of Notes material and a shortened chromosome. and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 18/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 special form of translocation called a centric fusion or Robertsonian translocation involves two acrocentric chromosomes in which the centromere is near the end, most commonly chromosomes 13 and 14, or 14 and 21. CO Attention! 5/14/2024 Having an abnormal number of chromosomes is referred to as aneuploidy. CO Attention! 5/14/2024 Approximately 95% of cases of Down syndrome are caused by nondisjunction or an error in cell division during meiosis, resulting in a trisomy of chromosome 21. A rare form of Down syndrome can occur in the offspring of people in whom there has been a Robertsonian translocation CO Attention! 5/14/2024 But the definitive diagnosis of Down syndrome in the fetus is through chromosome analysis using chorionic villus sampling, amniocentesis, or percutaneous umbilical blood sampling, CO Attention! 5/14/2024 Turner Syndrome. Turner syndrome describes an absence of all (45, X/0) or part of the X chromosome. CO Attention! 5/14/2024 Characteristically Turner's syndrome is associated with coarctation of the aortat and bicuspid aortic valve. These conditions interfere with sufficient blood flow in the CV system. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 19/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Klinefelter Syndrome. Klinefelter syndrome is a condition of testicular dysgenesis accompanied by the presence of one or more extra X chromosomes in excess of the usual male XY complement. Most males with Klinefelter syndrome have one extra X chromosome (47, XXY). In rare cases, there may be more than one extra X chromosome (48, XXXY). CO Attention! 5/14/2024 Males with Klinefelter syndrome have congenital hypogonadism, which results in an inability to produce normal amounts of testosterone accompanied by an increase in hypothalamic gonadotrophic hormones. CO Attention! 5/14/2024 Mitochondrial Gene Disorders The mitochondria contain their own DNA, which is distinct from the DNA contained in the cell nucleus. Although the majority of inherited disorders come from nuclear DNA abnormalities, there are multiple disease-causing rearrangements and mutations that can occur in mitochondrial DNA (mtDNA). This DNA is packaged in a double-stranded circular chromosome and contains 37 genes: 2 ribosomal RNA genes, 22 transfer RNA genes, and 13 structural genes encoding subunits of the mitochondrial respiratory chain enzymes, which participate in oxidative phosphorylation and generation of adenosine triphosphate. CO Attention! 5/14/2024 mtDNA mutations frequently affect the neuromuscular system and produce disorders such as encephalopathies, myopathies, retinal degeneration, loss of extraocular muscle function, and deafness. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 20/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 DIAGNOSIS AND COUNSELING The birth of a child with a congenital defect is a traumatic event. Usually, two issues must be resolved. The first deals with the immediate and future care of the affected child and the second with the possibility of future children in the family having a similar defect. Genetic assessment and counseling can help to determine whether the defect was inherited and the risk of recurrence. Prenatal diagnosis provides a means of determining whether an unborn child has certain types of abnormalities. It is important that the biological parents are aware of the potential complications of acquiring more information from these genetic tests. The purpose of prenatal screening and diagnosis is not just to detectfetal abnormalities but also to allay anxiety and provide assistance toprepare for a child with a specific disability. CO Attention! 5/14/2024 Effective genetic counseling requires accurate diagnosis and communication of the findings and of the risks of recurrence to the biological parents and other family members who need such information. CO Attention! 5/14/2024 c ultrasonography, maternal serum (blood) screening tests,amniocentesis, chorionic villus sampling, and percutaneous umbilicalfetal blood sampling CO Attention! 5/14/2024 Prenatal Screening and Diagnosis The purpose of prenatal screening and diagnosis is not just to detect fetal abnormalities but also to allay anxiety and provide assistance to prepare for a child with a specific disability. Prenatal screening cannot be used to rule out all possible fetal abnormalities. It is limited to determining whether the fetus has (or probably has) predesignated conditions as indicated by late maternal age, family history, or well-defined risk factors. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 21/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Ultrasonography Ultrasonography is a noninvasive diagnostic method that uses reflections of high-frequency sound waves to visualize soft- tissue structures. CO Attention! 5/14/2024 Maternal Serum Markers Maternal blood testing began in the early 1980s. Since that time, a number of serum factors have been studied as screening tests for fetal anomalies. CO Attention! 5/14/2024 AFP is a major fetal plasma protein and has a structure similar to the albumin found in postnatal life. AFP is made initially by the yolk sac, gastrointestinal tract, and liver. Fetal plasma levels of AFP peak at approximately 10 to 13 weeks’ gestation and decrease until the third trimester when the level peaks again. Maternal and amniotic fluid levels of AFP are elevated in pregnancies where the fetus has an NTD (i.e., anencephaly and open spina bifida) or certain other malformations such as an anterior abdominal wall defect in which the fetal integument is not intact CO Attention! 5/14/2024 A complex glycoprotein, hCG, is produced exclusively by the outer layer of the trophoblast shortly after implantation in the uterine wall. It increases rapidly in the first 8 weeks of gestation, declines steadily until 20 weeks, and then plateaus. The single maternal serum marker that yields the highest detection rate for Down syndrome is an elevated level of hCG. Inhibin A, which is secreted by the corpus luteum and fetoplacental unit, is also a maternal serum marker for fetal Down syndrome. Unconjugated estriol is produced by the placenta from precursors provided by the fetal adrenal glands and liver. CO Attention! 5/14/2024 Amniocentesis is an invasive diagnostic procedure that involves the withdrawal of a sample of amniotic fluid from the pregnant uterus usually using a transabdominal approac PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 22/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Chorionic villus sampling is an invasive diagnostic procedure that obtains tissue that can be used for fetal chromosome studies, CO Attention! 5/14/2024 PUBS is an invasive diagnostic procedure that involves the transcutaneous insertion of a needle through the uterine wall and into the umbilical artery. CO Attention! 5/14/2024 Amniocentesis and chorionic villus sampling yield cells that can be used for cytogenetic and DNA analyses. Cytogenetic studies are used for fetal karyotyping to detect abnormalities of chromosome number and structure in the fetus. Karyotyping also reveals the sex of the fetus. This may be useful when an inherited defect is known to affect only one sex. CO Attention! 5/14/2024 Aging is an important risk factor for development of Parkinson disease and Alzheimer disease. Parkinson disease has been found to have a genetic component. Mutations in certain genes (such as LRRK2, PARK7, PINK1, PRKN, SNCA) are strongly associated with the development of Parkinson disease; whereas alterations in other genes (GBA, UCHL1) only increase the risk for developing the condition (Blauwendraat et al., 2020). More than 40 susceptibility loci have been found for Alzheimer disease (Andrews et al., 2020). CO Attention! 5/14/2024 While many birth defects are characterized by only genetic changes, others exhibit gene–environment interactions (Beames & Lipinski, 2020). Mitochondrial disorders are passed from the biological mother to all her children due to mutations in the mitochondrial DNA. Prognosis depends on the number of organ systems involved. Prenatal screening is available for early detection of many birth defects and congenital disorders. CO Attention! 5/14/2024 PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes TABLE 6.2 CHARACTERISTICS OF BENIGN AND MALIGNANT created by user are not part of publisher content. No part of NEOPLASMS this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 23/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 The characteristics of altered proliferation and differentiation are associated with several other cell characteristics and functional changes that distinguish cancer cells from their normally differentiated counterparts. These changes are listed in Table 6.3. Benign neoplasms are well-differentiated tumors that resemble thetissues of origin but have lost the ability to control cell proliferation CO Attention! 5/14/2024 TABLE 6.3 COMPARISON OF NORMAL CELL CHARACTERISTICS WITH THOSE OF CANCER CELLS Comparision of normal vs cancer cells CO Attention! 5/14/2024 Genetic Instability. Malignant neoplasms are less well-differentiated tumors that have lostthe ability to control both cell proliferation and differentiation. Theygrow in a disorganized and uncontrolled manner to invadesurrounding tissues, CO Attention! 5/14/2024 ETIOLOGY OF CANCER An important role of stem cells in the pathogenesis of cancer hasbeen identified, and it continues to be studied.11 Cancer stem cells(called tumor-initiating cells [TICs]) have been identified in breast,prostate, acute myeloid leukemia (AML), and other cancers. CO Attention! 5/14/2024 CLINICAL MANIFESTATIONS PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 24/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 ABLE 6.4 COMMON PARANEOPLASTIC SYNDROMES CO Attention! 5/14/2024 TABLE 6.5 TUMOR MARKERS Recommended review CO Attention! 5/14/2024 Cancer Treatment Compare the different screening mechanisms for cancer. Differentiateamong the three types of cancer treatment (curative, control, andpalliative), considering the risks and benefits of each approach. FYI, for future clinical practice, review the different screeningmechanisms for cancer. Review the three approaches to cancertreatment: curative, control, palliative. CO Attention! 5/14/2024 Treatment and Research of Stress Disorders The following are examples of research that has been done on stress: CO Attention! 5/14/2024 Geriatric Considerations CO Attention! 5/14/2024 PEDIATRIC Considerations CO Attention! 5/14/2024 Water crosses the cell membrane by osmosis, using special protein channels called aquaporins. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 25/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Inappropriate or excessive thirst may persist despite adequate hydration. It is a common complaint in people with congestive heart failure, diabetes mellitus, and chronic kidney disease CO Attention! 5/14/2024 Without ADH, the luminal membranes of the tubular epithelial cells of the collecting ducts are almost impermeable to water. In the presence of ADH, pores or water channels, called aquaporins, are stimulated to move into the membrane of these tubular cells, making them permeable to water. The specific water channel that is controlled by ADH is aquaporin-2 CO Attention! 5/14/2024 TABLE 8.3 DRUGS THAT AFFECT ANTIDIURETIC HORMONE LEVELSA CO Attention! 5/14/2024 Hypernatremia represents a deficit of water in relation to the body’s sodium stores. It can be caused by net loss of water or sodium gain. Net water loss can occur through the urine, gastrointestinal tract, lungs, or skin. A defect in thirst or inability to obtain or drink water can interfere with water replacement. Rapid ingestion or infusion of sodium with insufficient time or opportunity for water ingestion can produce a disproportionate gain in sodium (Table 8.7). This can occur with critically ill people who present with multiple needs for fluid resuscitation and electrolyte balance. In fact, hypernatremia is an independent risk factor linked highly with increased mortality (Sterns, 2019a). CO Attention! 5/14/2024 Manifestations The clinical manifestations of hypernatremia look similar to dehydration. CO Attention! 5/14/2024 PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of Figure 8.8 Mechanisms regulating transcellular shifts in potassium. this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 26/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/14/2024 Disorders of Potassium Balance The kidneys are the main source of potassium loss. CO Attention! 5/14/2024 Potassium also plays a critical role in conducting nerve impulses and the excitability of skeletal, cardiac, and smooth muscle. It does this by regulating the following: The resting membrane potential The opening of the sodium channels that control the flow of current during the action potential The rate of membrane repolarization CO Attention! 5/14/2024 nadequate Intake. Inadequate intake is a frequent cause of hypokalemia. A potassium intake of at least 40 to 50 mEq/day is needed daily. Insufficient dietary intake may result from the inability to obtain or ingest food or from a diet that is low in potassium-containing foods. Potassium intake is often inadequate in people on fad diets and those who have eating disorders. Older adults are particularly likely to have potassium deficits. Many have poor eating habits as a consequence of living alone; they may have limited income, which makes buying foods high in potassium difficult; they may have difficulty chewing many foods that have high potassium content because of dental problems; or they may have problems with swallowing. CO Attention! 5/14/2024 Magnesium depletion causes renal potassium wasting. Magnesium deficiency often coexists with potassium depletion because of diuretic therapy or disease processes such as diarrhea. CO Attention! 5/14/2024 Renal losses of potassium are accentuated by aldosterone and cortisol. Increased potassium losses occur in situations such as trauma and surgery that produce a stress-related increase in these hormones. Primary aldosteronism, caused by either a tumor or hyperplasia of the cells of the adrenal cortex that secrete aldosterone, produces severe potassium losses and a decrease in plasma potassium levels (Hall & Hall, 2021). Cortisol binds to aldosterone receptors and exerts aldosterone-like effects on potassium PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes elimination. created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 27/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/15/2024 IN SUMMARY CO Attention! 5/15/2024 Normal body function depends on the precise regulation of acid–base balance. The pH of the ECF is normally maintained within the narrow physiologic range of 7.35 to 7.45. Metabolic processes produce volatile and fixed or nonvolatile metabolic acids that must be buffered and eliminated from the body. The volatile acid, H2CO3, is in equilibrium with dissolved CO2, which is eliminated through the lungs. The nonvolatile metabolic acids, which are derived mainly from protein metabolism and incomplete carbohydrate and fat metabolism, are excreted by the kidneys. It is the ratio of the HCO3 − concentration to dissolved CO2 (H2CO3 concentration) that determines the pH of the ECFs. When this ratio is 20:1, the pH is 7.4. The ability of the body to maintain pH within the normal physiologic range depends on respiratory and renal mechanisms and on chemical buffers in the ICF and ECF, the most important of which is the HCO3 − buffer system. The respiratory regulation of pH is rapid but does not return the pH completely to normal. The kidneys aid in regulation of pH by eliminating H+ ions, conserving HCO3 − ions, and producing new HCO3 − ions. In the process of eliminating H+, it uses the phosphate and ammonia buffer systems. Body pH is also affected by the distribution of exchangeable cations (K+ and H+) and anions (Cl− and HCO3 −). Laboratory tests used in assessing acid–base balance include arterial blood gas measurements, CO2 content and HCO3 − levels, base excess or deficit, and the AG. The base excess or deficit describes the amount of a fixed acid or base that must be added to a blood sample to achieve a pH of 7.4. The AG describes the difference between the plasma concentration of the major measured cations (Na+ and K+) and the sum of the anions (Cl− and HCO3 −). This difference represents the concentration of unmeasured anions, such as phosphates, sulfates, and organic acids, which are present. The urine AG uses the difference between the measurable cations (Na+ and K+) and anions (Cl−) to provide an estimate of ammonium (NH4 +) excretion and the ability of the kidney to rid the body of excess H+. Good summary PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 28/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/15/2024 Understanding Acute Inflammation Acute inflammation is the early response to an injurious agent and is highly coordinated to control and eliminate altered cells, microorganisms, and antigens. This response occurs in two phases: (1) the vascular phase, which leads to an increase in blood flow and changes in the small blood vessels of the microcirculation, and (2) the cellular phase, which leads to the migration of leukocytes from the circulation and their activation to eliminate the injurious agent. The primary function of inflammatory response is to limit the injurious effect of the pathologic agent and remove the injured tissue components, thereby allowing tissue repair to take place. CO Attention! 5/15/2024 Local Manifestations Although all acute inflammatory reactions are characterized by vascular changes and leukocyte infiltration, the severity of the reaction, its specific cause, and the site of involvement introduce variations in its manifestations and clinical correlates. These manifestations can range from swelling and the formation of exudates to abscess formation or ulceration. CO Attention! 5/15/2024 Chronic Inflammation In contrast to acute inflammation, which is usually self-limited and of short duration, chronic inflammation is self- perpetuating and may last for weeks, months, or even years. Chronically inflamed tissues signal immune cells, which amplify the inflammatory response, resulting in the destruction of healthy tissue and leading to maladaptive remodeling (Aghasafari et al., 2019 CO Attention! 5/15/2024 Nonspecific Chronic Inflammation Nonspecific chronic inflammation involves a diffuse accumulation of macrophages and lymphocytes at the site of injury. Ongoing chemotaxis causes macrophages to infiltrate the inflamed site, where they accumulate owing to prolonged survival and immobilization. CO Attention! 5/15/2024 Granulomatous Inflammation A granulomatous lesion is a distinctive form of chronic inflammation. A granuloma typically is a small, 1- to 2- mm lesion in which there is a massing of macrophages surrounded by lymphocytes. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 29/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/15/2024 Systemic Manifestations of Inflammation CO Attention! 5/15/2024 Acute-Phase Response Along with the cellular responses that occur during the inflammatory response, a constellation of systemic effects called the acute-phase response occurs. The acute-phase response, which usually begins within hours or days of the onset of inflammation or infection, includes changes in the concentrations of plasma proteins (i.e., acute-phase proteins), skeletal muscle catabolism, negative nitrogen balance, elevated erythrocyte sedimentation rate (ESR), and increased numbers of leukocytes. CO Attention! 5/15/2024 In severe bacterial infections (sepsis), the large quantities of microorganisms in the blood result in an uncontrolled inflammatory response with the production and release of enormous quantities of inflammatory cytokines (most notably IL-1 and TNF-α) and development of what is referred to as the systemic inflammatory response syndrome (Chakraborty & Burns, 2022; Masi et al., 2020). These cytokines cause generalized vasodilation, increased vascular permeability, intravascular fluid loss, myocardial depression, and circulatory shock. CO Attention! 5/15/2024 CRP is an acute-phase protein and an important inflammatory biomarker in various clinical conditions like acute myocardial infarction, malignancies, autoimmune disorders, and surgical interventions. CRP was named because of its ability to react with C fraction (C-polysaccharide) isolated from the cell wall of pneumococci (Koozi et al., 2020). The function of CRP is thought to be protective, in that it binds to the surface of invading microorganisms and targets them for destruction by complement and phagocytosis (Koozi et al., 2020). CO Attention! 5/15/2024 White Blood Cell Response Leukocytosis, or increased white blood cells, is a frequent sign of an inflammatory response, especially one caused by bacterial infection. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 30/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/15/2024 Bacterial infections produce a relatively selective increase in neutrophils (neutrophilia), whereas parasitic and allergic responses induce eosinophilia. Viral infections tend to produce a decrease in neutrophils (neutropenia ) and an increase in lymphocytes (lymphocytosis). A decrease in white blood cells (leukopenia) may occur with overwhelming infections or an impaired ability to produce white blood cells. CO Attention! 5/15/2024 Lymphadenitis Lymphadenitis is caused by an infection in one or more than one lymph nodes, causing enlarged lymph nodes. Localized acute and chronic inflammation may lead to a reaction in the lymph nodes that drain the affected area. CO Attention! 5/15/2024 Wound Healing CO Attention! 5/15/2024 Healing by Primary and Secondary Intention Depending on the extent of tissue loss, wound closure and healing occur by primary or secondary intention (Fig. 9.7). A sutured surgical incision is an example of healing by primary intention. Larger wounds (e.g., burns and large surface wounds) that have a greater loss of tissue and contamination heal by secondary intention (Armstrong & Meyer, 2022). Healing by secondary intention is slower than healing by primary intention and results in the formation of larger amounts of scar tissue. A wound that might otherwise have healed by primary intention may become infected and healed by secondary intention. CO Attention! 5/15/2024 Phases of Wound Healing Wound healing is commonly divided into three phases: (1) the inflammatory phase, (2) the proliferative phase, and (3) the maturational or remodeling phase (El Ayadi et al., 2020). The duration of the phases is fairly predictable in wound healing by primary intention. In wound healing by secondary intention, the process depends on the extent of injury and the healing environment. Inflammatory Phase. The inflammatory phase of wound healing begins at the time of injury and is a critical perio PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 31/60 6/7/24, 2:46 PM Highlights & Notes: Porth's Pathophysiology CO Attention! 5/15/2024 Factors That Affect Wound Healing CO Attention! 5/15/2024 Malnutrition. CO Attention! 5/15/2024 Blood Flow and Oxygen Delivery CO Attention! 5/15/2024 Impaired Inflammatory and Immune Responses. CO Attention! 5/15/2024 Infection, Wound Separation, and Foreign Bodies. CO Attention! 5/15/2024 Bite Wounds. CO Attention! 5/15/2024 The Effect of Age on Wound Healing Wound Healing in Neonates and Children. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes