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Pathophysiology Cellular Function Presenter: V. Alexander, DNP., ARNP General Concepts • Must understand cellular processes to understand disease • Pathophysiology ? • Disease occurs when there is a disruption in homeostasis or deviation from normal Homeostasis • Dynamic process • The relative consistency of the body’s internal processes • Give and take system • Equilibrium is necessary for all cells • Self-regulating • Compensatory • Negative feedbackmost common; eg. temp regulation • Positive feedback- eg: blood clot • May use many means to correct one imbalance Factors that Determine Normality • • • • • • • Age Gender Genetic and ethnic background Geographic area Time of day Environment-altitude, temp, etc Remember findings are only relevant to the individual’s “normal” Pathophysiology • Etiology May include agents, age, gender, health, nutritional status, genetics, etc Idiopathic Iatrogenic May be intrinsic or extrinsic Pathophysiology • Pathogenesis Affected by time, quantity, location, and morphologic changes • Clinical manifestations Includes S/S of the disease, stages of the disease, acute v/s chronic Disease • Epidemiology • Levels of prevention Primary Secondary Tertiary Question • Which of the following are sigs of infection in a patient? 1. Bradycardia 2. Hypothermia 3. Increased body temperature 5. Increased neutrophils 6. Increased RBC 7. Increased WBC 8. Localized edema 9. Localized pain Answer • 3; 4; 6; 7; 8. • 3. Increased body temp – inflammatory process to fight infection • 4. increased neutrophils – through phagocytosis these specialized WBC ingest and destroy microorganisms • 6. Increased WBC – WBC leaves blood vessels • 7. localized edema – occurs when injury causes necrosis • 8. localized pain – swelling or inflamed tissues increases pressure on nerve endings Cellular Attributes • Ability to: exchange material with their environment obtain energy from organic nutrients manufacture complex molecules replicate themselves Functional Cell Components • Three major components of eukaryotic cells: Nucleus Cytoplasm Cell Membrane Functional Cell Components • Nucleus Contains chromatin and nucleolus At least one per cell Control Center Genetic Code Nucleoli Functional Cell Components • Cytoplasm Place for cell work Contains water, electrolytes, suspended protein, neutral fats, and glycogen Contains the organelles Organelles Functional Cell Components • Ribosomes Site for protein synthesis Small particles of nucleoproteins May be attached to Endoplasmic Reticulum (ER) or free • Endoplasmic Reticulum (ER) Matrix of paired membranes and vesicles Tubular communication system Place where metabolic activity occurs Organelles Functional Cell Components • Two Forms of Endoplasmic Reticulum (ER): Rough-Produce proteins for membranes and lysosomal enzymes Smooth-lipid, lipoprotein, and steroid synthesis: Regulation of intracellular Ca+, metabolism, and detoxification of hormones and drugs Functional Cell Components • Golgi Apparatus Organelles Site for carb production • Lysosomes Breakdown cell products and foreign bodies to be used again Requires acidic environment Functional Cell Components Organelles • Peroxisomes Controls free radicals • Mitochondria Power plants Aerobic metabolism-ATP Number in a given cell varies depending on the cell’s energy needs Contains own DNA and ribosomes Functional Cell Components Cytoskeleton • Microtubules Cilia and Flagella • Hair like processes • Aid in movement Centrioles • Barrel-shaped bodies • Aid in chromosomal division • Microfilament Threadlike structure Functional Cell Components • Cell Membrane Semi-permeable Contains receptors Involved in electrical conduction Regulates cell growth and proliferation Lipid bilayer Proteins Functional Cell Components • Membrane receptors Open and close ion channels Activates G protein-linked signals Activates enzyme-linked cell function Cellular Transportation • Passive 1. Diffusion 2. Osmosis 3. Facilitated diffusion • Active transport • Endocytosis Pinocytosis Phagocytosis • Exocytosis Na+ K+ ATP pump Na+ K+ ADP ATP Cell Cycle • Cell proliferation Cells divide and reproduce Mitosis • Prophase • Metaphase • Anaphase • Telophase Meiosis Cell Cycle • Cell differentiation Proliferated cells become different and specialized Begins after fertilization Generalized to specific Atrophy Workload (or disease state) Functionality Efficiency in disease -OR- state Size Size organelles of oforganelles Energy Usage Hypertrophy Workload (or disease state) ability to Functionality meet demands! in disease state -OR- Size Size # oforganelles organelles # of contractility Hyperplasia Workload Physiological state types:to 2ability Compensatory meet demands!& Hormonal tissue rate ofsize cell # division by of cells functionality Metaplasia Ex: Cigarette Smoking Pathological Normal Cells Abnormal Cells Replacement Dysplasia Epithelial Tissue Pathological Mutation Normal Cells Abnormal Shape & Size Cell Injury • Most disease start with cell injury • Can be reversible to a point • Normal states - balanced with cell renewal Physiological Cell Death Apoptosis ‘Programmed Suicide’ Normal process of cell replacement & development Ex:Ex: endometrial induced apoptosis sloughing during during Balance between death and regeneration Immune menstruation response Causes of Cell Injury • Physical agents • • • • Mechanical forces Extreme temp. Electrical Radiation • • • Ionizing Ultraviolet Non-ionizing • Chemical • • • • Pollution Lead Poisonings Drugs • Biological Agents • Bacteria • Viruses • Parasites • Nutritional Imbalances Mechanism of Injury • Ischemia • Necrosis • Free Radical Necrotic Cell Death Necrotic Cell Death Coagulative Gelatinous, Firm transparent & opaque protein Liquefactive Walled-Off Brain & neurons Liquid Goo Caseous Mycobacterium ‘Cased’-Off Cheese tuberculosis Globules Fatty Opaque, Chalky Breast, pancreas Soapy Gangrene Caused by severe hypoxic injury Dry Coagulative Wet Liquefactive Gas Release Tissues Clostridium gas not into just cells! tissue Alterations in Cell Growth and Replication • Neoplasia = “new growth” • Lacks normal controls and regulation • Can originate in one organ Prostate most common in men Breast most common in women Lung leading cause of death in men and women • Can also spread from another site Carcinogenesis • • Cancer development Steps in Carcinogenesis: Initiation Promotion Progression • Heredity • Oncogenes • Carcinogens Benign v/s Malignant • Benign Slow, progressive, localized, well defined, resembles host (more differentiated), grow by expansion, does not usually cause death • Malignant Rapid growing, spreads (metastasis) quickly, fatal, highly undifferentiated Clinical Manifestations Change in bowel or bladder habits A sore that doesn’t heal Unusual bleeding or discharge Thickening or lump in the breast or elsewhere Indigestion or difficulty swallowing Obvious change in a wart or mole Nagging cough or hoarseness Complications • • • • • • • Anemia Cachexia Fatigue Infection Leukopenia Thrombocytopenia Pain Diagnosis • Biopsy Can be done through needle aspiration, endoscopy, laproscopy, or excision • Tumor Markers Antigens on the surface of tumor cells Used for screening, diagnosing, monitoring, treatment, and establishing remission • Miscellaneous procedures X-rays, radioactive isotope scanning, CT scans, endoscopies, US, MRI, positron emission tomography scanning (PET scan) Classification • Staging -TNM (Tumor; Node; Metastasis): based on spread of the disease • Grading-according to histology I, II, III, and IV-as it increases, the tumor is less differentiated Treatment • • • • • • 3 goals: Curative Palliative Prophylactic Surgery Radiation Chemotherapy Hormone and antihormone therapy Biotherapy Chromosomes • • • • • • Contains genetic information 23 pairs Sex chromosome Karyotype Phenotype Patterns of inheritance Homozygous Heterozygous Dominant Recessive Genetic and Congenital Disorders • Caused by a mutation • >800 disorders • Characterized by the patterns of transmission Autosomal Dominant Disorders • Transmitted from an affected parent to offspring regardless of gender • 50% chance of transmission • Unaffected do not pass on the disorder • Delayed onset • Examples: Marfan Syndrome and neurofibromatosis Autosomal Dominant Disorders • Marfan Syndrome Disorder of connective tissue Mutation on chromosome 15 Results in elastin and collagen defects Affects the eyes, skeleton, and cardiovascular system Diagnosis History, physical examination, skin biopsy (presence of fibrillin), genetic testing Treatment • None, palliative Autosomal Dominant Disorders • Neurofibromatosis Neurogenic tumors A defect on chromosome 17 or 22 Two forms: • Type 1 - subcutaneous lesions, café-aulait spots (at least 6 at birth), freckles, scoliosis, erosive bone defects, and nervous system tumors • Type 2 - Tumors of the acoustic nerve Treatment • Palliative removal of tumors Autosomal Recessive Disorders • • • • • • • • Rare Both members of gene pair are affected Affects both genders One out of four will be affected Two out of four will be carriers Onset early Usually caused be a deficient enzyme Examples: PKU and Tay-Sachs Autosomal Recessive Disorders• PKU (phenylketonuria) Mutation on chromosome 12 leads to an error in converting phenylalanine to tyrosine Appear normal at birth then fails to meet developmental milestones Progressive neurological decline If untreated, can lead to mental retardation Diagnosis- serum phenylalanine at 3 days old Treatment: • • • • Avoid high protein foods Limited amounts of starches Phenylalanine lowering agents Gene therapy Autosomal Recessive Disorders • Tay-sachs A deficiency or absence of hexosaminidase A • Necessary to metabolize certain lipids • Lipids accumulate, destroying and demyelinating nerve cells • Leads to a progressive mental and motor deterioration Most are of Jewish decent Autosomal Recessive Disorders • Tay-sachs Appears normal at birth, then the infant begins to miss milestones Progresses to seizures, muscular rigidity, and blindness Usually fatal by 5 years of age Diagnosis: history, physical examination, and low serum and amniotic hexosaminidase A levels No cure Genetic counseling suggested X-linked Disorders • Sex-linked disorders are almost always X linked • Males have 50% chance of getting disorder from their mother • Females have a 50% chance of being carriers • All daughters of affected males will be carriers, but none of their sons • Example: Fragile X syndrome X-Linked Disorders • Fragile X syndrome Associated with a single tri-nucleotide gene sequence on the X chromosome Lack of a protein necessary for neural tube development Manifestations: long face with large mandible, large ears, large testicles, mental retardation, learning disabilities, speech delays, connective tissue disorders, and behavioral issues Diagnosis: history, physical examination, genetic testing Treatment: supportative Multifactorial Inheritance Disorders • Results from an interaction between environmental and genetic factors • Less predictable • Extremely common • May be expressed at birth or later • Examples: cleft lip or palate, clubfoot, congenital dislocation of the hips, congenital heart defects, pyloric stenosis, urinary tract malformations, diabetes mellitus, hypertension, cancer, and psychiatric disorders Chromosomal Disorders • May be related to abnormality in chromosomal number and/or structure that occurs in meiosis • Accounts for most of early abortions • More than 60 syndromes Trisomy 21 (Down’s syndrome) • Risk increases with maternal age • Caused from nondisjunction during meiosis • Manifestations: small square head, upward slant of the eyes, small low set ears, fat pad on the back of the neck, open mouth with protruding tongue, Simian crease, and varying degrees of mental retardation Trisomy 21 (Down’s syndrome) • Also associated with congenital heart defects, ocular issues, leukemia, respiratory complications • Diagnosis: parental screening including amniocentesis, hormone levels, four-dimensional ultrasound • Treatment: symptomatic and supportative Monosomy X (Turner’s Syndrome)• Deletion of all or part of an X chromosome • No Y chromosome - no female • Manifestations: gonadal streaks instead of ovaries, short stature, increased weight, webbing of the neck, small lower jaw, drooping eyelids, small fingernails, and widely spaced nipples • Also associated with coarctation of the aorta, vision issues, hearing loss, renal abnormalities, infertility, and increased risk for infections • No mental retardation present Monosomy X (Turner’s Syndrome)• Diagnosis: history, physical examination, and chromosomal testing • Treatment: estrogen and growth hormones Trisomy X (Klinefelter’s Syndrome) • One or more extra X chromosomes with the presence of the Y • Male appearance • Often undetected • Manifestations: gynecomastia, small testes and penis, tall stature, increased weight, and sparse body hair • Also associated with learning disabilities, behavioral problems, sexual dysfunction, pulmonary disease, varicose veins, osteoporosis, and breast cancer • Treatment: testosterone The End ???????? 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