Lecture 3: Neoplasia & Genetics PDF

pathophysiology PATH200 & 310/MACHS Lecture-3 :Neoplasia & Genetics 1  Outlines Adaptive changes and causes of cellular adaption. Genetic control of cell function and inheritance. Mechanisms of inheritance Genetic and congenital disorders...

pathophysiology PATH200 & 310/MACHS Lecture-3 :Neoplasia & Genetics 1  Outlines Adaptive changes and causes of cellular adaption. Genetic control of cell function and inheritance. Mechanisms of inheritance Genetic and congenital disorders Neoplasm – terminology Differentiating between benign and malignant tumors. Cancer and carcinogenesis process Pathophysiology of the malignant process Tumor staging and grading 2  LEARNING OBJECTIVES By the end of this lecture each student will be able to : ◼ Describe the Cell injury and Cellular Adaptive Changes. ◼ Discuss the common congenital disorders ◼ Explain the definition of neoplasia ◼ Differentiate between benign tumor and malignant tumor ◼ Describe the TNM system. 3  INTRODUCTION ◼ The life cycle of a cell exists on continuum that includes normal activities and adaptation, injury or lethal changes. ◼ Adaptive changes- Prevention of disease by the body depends on the capacity of the affected cells to undergo self-repair and regeneration 4  CAUSES OF CELLULAR ADAPTION When cells are confronted to one of the following stimulus, they may undergo adaptive changes a) Physical agents - Trauma, Burn, pressure, irradiation, etc b) Chemical agents - Poisons, drugs, simple compounds, etc. c) Micro organisms – Bacteria, Virus, Fungus, Parasites d) Hypoxia - most common cause. Is because of inadequate oxygen in the blood or decreased tissue perfusion. e) Genetic defects - Can affect cellular metabolism through inborn errors of metabolism or gross malformation f) Nutritional imbalances g) Immunologic reaction E.g. - Hypersensitivity reaction. 5 Refers to prevention of disease by the body depends on the capacity of the affected cells to undergo self-repair and regeneration. a. Physiological changes b. Biological changes c. Adaptive changes d. Chemical changes 6 Which of the following adaptive changes occurs due to inadequate oxygen in the blood or decreased tissue perfusion? a. Physical agents b. Chemical agents c. Micro organisms d. Hypoxia 7  TYPES OF CELLULAR ADAPTIVE-CHANGES When cells are exposed to one of the above noxious stimulus, they will undergo one or more of the following types of adaptive changes:- I. Abnormal accumulation of intracellular substances II. Changes to cellular size or numbers III. Cellular injury and lethal changes 8  I. Abnormal Accumulation Of Intracellular Substances Due to environmental changes or an inability of the cell to process materials (substances) that cannot be metabolized by the cells, these substances may accumulate in the cytoplasm. As a result, common changes include:- ◼ Cellular swelling ◼ Lipid accumulation ◼ Glycogen depositions. ◼ Calcification This can lead to stiffness and dysfunction in affected areas,due to calcium build up in tissue ◼ Hyaline infiltration protein buildup that gives tissues a glassy appearance 9 II.Changes To Cellular Size Or Numbers Result of response to adaptation to harmful agents I) Atrophy: refers to a decrease in cell size. II) Dysplasia:- Dysplasia refers to the appearance of cells that have undergone some atypical changes in response to chronic irritation. III) Hyperplasia: increase of tissue mass due to an increase in the number of cells. IV) Hypertrophy: increase in the size of individual cells, resulting in increased tissue mass with out an increase in the number of cells. V) Metaplasia: one type of adult cell is replaced by another type. 10 11 Refers to the appearance of cells that have undergone some atypical changes in response to chronic irritation a. Atrophy b. Dysplasia c. Hyperplasia d. Hypertrophy 12  Sublethal injury changes how a cell functions but doesn’t kill it, and these changes can often be reversed if the harmful cause is removed III. Cellular Injury And Lethal Changes Cell injury can be sub lethal or lethal. Sub lethal injury alters functions with out causing cell death. The changes caused by this type of injury are potentially reversible if the injuring stimuli are removed. Causes of Cell Injury ◼ Hypoxia and ischemia less-than-normal amount of blood flow to part of your body ◼ Toxins ◼ Infectious agents ◼ Immunologic reactions ◼ Nutritional imbalances ◼ Genetic abnormalities ◼ Physical agents ◼ Aging 13 TYPES OF CELLULAR INJURY 14 REVERSIBLE CELL INJURY ◼ Cell injury which can be reversed when the stimulus or the cause of injury is removed. Causes ◼ Ischemia: critical lack of blood supply to a localized area. 15  Irreversible Cell Injury ◼ It is cellular injury that can not be corrected (reversed) after the stimulus or cause has been removed. a. Infarction:- Is localized area of tissue death due to lack of blood supply. It is due to occlusion of blood vessels by thrombus or embolus. b. Necrosis: cell or tissue death characterized by structural evidence of this death. c. Apoptosis : programmed cell death or “clean” form of cell suicide occurring in pathologic situations When a cell's DNA or proteins are damaged beyond repair or cells destined to die activate their own enzymes to degrade their own nuclear DNA and proteins 16 Genetic Control Of Cell Function And Inheritance Nucleus contains the chromosomes Chromosomes: Discrete bundles of DNA containing genetic information, Arranged in pairs; one from the mother and one from the father Humans have 23 pairs of chromosomes,22 are autosomes , 23rd pair are the sex chromosomes (determine the sex of an individual) DNA -Long, double-stranded helical structure composed of nucleotides, which consist of phosphoric acid, deoxyribose, and one of four nitrogenous bases (Thymine (T),Cytosine (C),Adenine (A),Guanine (G)) Gene -a part of the DNA molecule that contains the information needed to code for the types of proteins and enzymes needed for the day-to-day function of the cells in the body. A gene is the unit of heredity passed from generation to generation 17  Nucleus and Chromosomes What part of the cell contains chromosomes? 1. What is the function of the nucleus in a cell? A) Mitochondria A) Energy production B) Nucleus B) Storage of genetic material C) Cytoplasm C) Protein synthesis Answer: B) Nucleus Answer: B) Storage of genetic material 2. How many pairs of chromosomes do humans have? 2. What are chromosomes made of? A) 22 A) Proteins B) 23 B) RNA C) 46 C) DNA Answer: B) 23 Answer: C) DNA 3. What are autosomes? 2. Chromosomes A) Sex chromosomes 1. How are chromosomes arranged in humans? B) Non-sex chromosomes A) In single strands C) Chromosomes that determine height B) In pairs Answer: B) Non-sex chromosomes C) In groups of three 4. What does DNA stand for? Answer: B) In pairs A) Deoxyribonucleic acid 2. From whom do you inherit your chromosomes? B) Dioxyribonucleic acid A) Only from your mother C) Deoxyribose nucleic acid B) Only from your father Answer: A) Deoxyribonucleic acid C) From both parents 5. What do genes provide instructions for? Answer: C) From both parents A) Making energy 3. Autosomes and Sex Chromosomes B) Making proteins 1. What is the total number of autosomes in humans? C) Making fats A) 22 pairs Answer: B) Making proteins B) 23 pairs 6. What is heredity? C) 46 pairs A) The process of aging Answer: A) 22 pairs B) The passing of genes from parents to offspring 2. What determines a person’s sex? C) The development of new cells A) Autosomes Answer: B) The passing of genes from parents to offspring B) Sex chromosomes C) Mitochondria Answer: B) Sex chromosomes 4. DNA Structure 1. What shape does DNA have? 18 A) Linear B) Circular C) Double helix Answer: C) Double helix  Mechanisms Of Inheritance: Cell Division ◼ Cells form two groups based on function: ◼ Body (somatic)cells: form the structures of the body ◼ Reproduce by mitosis: Forming two identical cells, each equipped with 23 pairs of chromosomes ◼ Germ cells: form the reproductive cells ◼ Reproduce by meiosis: forming four cells with each cell containing only 23 chromosomes ◼ These cells are the gametes: ova or sperm ◼ During conception, a sperm merges with an ovum to form a new cell containing 23 pairs of PATH200/MACHS chromosomes 19 What are body (somatic) cells? A) Cells that form reproductive organs B) Cells that make up the structures of the body C) Cells that only exist in embryos Answer: B) Cells that make up the structures of the body 2. How do body cells reproduce? A) Through meiosis B) Through mitosis C) By splitting randomly Answer: B) Through mitosis GENETIC DISORDERS 3. How many chromosomes do body cells have after mitosis? A) 23 B) 46 C) 92 Answer: B) 46 4. What are germ cells? A) Cells that make up muscles B) Reproductive cells that form gametes C) Cells found only in plants 20 Answer: B) Reproductive cells that form gametes 5. How do germ cells reproduce? A) Through mitosis B) Through meiosis C) By fusing with other cells Answer: B) Through meiosis 6. What are gametes? A) Body cells B) Reproductive cells like sperm and ova C) Cells involved in healing wounds Answer: B) Reproductive cells like sperm and ova 7. What happens during conception? A) Two body cells combine B) A sperm merges with an ovum to form a zygote C) Germ cells stop functioning Answer: B) A sperm merges with an ovum to form a zygote 8. How many chromosomes does a zygote contain? A) 23 B) 46 C) 92  Genetic and Congenital Disorders Congenital conditions are those present from birth. Birth defects are described as being congenital. They can be caused by ◼ Genetic Factors -chromosomal aberrations ◼ Environmental Factors (Fetal Development)-Maternal disease, infections, or drugs taken during pregnancy ◼ Intrauterine Factors (Rare)-Fetal crowding, positioning 21  Genetic and Chromosomal Disorders ◼ Genetic disorders represent changes (or mutations) in gene function or changes in chromosomal structure. ◼ The effects of an abnormal genetic trait may present at birth or may not become apparent until later in life. 1. Single gene Disorders -Caused by a single defective or mutant gene 2. Disorders of Autosomal Inheritance -Autosomal Dominant Eg: Marfan Syndrome, Autosomal Recessive Eg: Sickle cell disease The key difference between autosomal dominant and autosomal recessive disorders is that, in autosomal dominant disorders, one altered copy of a gene is enough to cause the disease while, in autosomal recessive disorders, both altered copies of the gene are needed to cause the disease. 3. Disorders of Sex- Linked Inheritance - Always associated with the X chromosome 4. Chromosome disorders 22  MCQs on Genetic and Chromosomal Disorders Autosomal Dominant: Only one mutated copy of the 1. What causes genetic disorders? gene is necessary for the disorder to manifest. Each A) Environmental factors B) Changes in gene function or chromosomal structure child of an affected parent has a 50% chance of C) Lifestyle choices inheriting the condition. Examples include Marfan D) All of the above Genetic and Chromosomal Disorders Answer: B) Changes in gene function or chromosomal structure syndrome and neurofibromatosis. 2. Which of the following is a characteristic of single gene disorders? Autosomal Recessive: Two copies of the A) They are always inherited from parents. B) They are caused by mutations in a single gene. mutated gene are required for the disorder to C) They affect multiple genes at once. Genetic disorders represent changes (or mutations) in gene function or changes in ◼ are often carriers without develop. Parents symptoms. Examples include sickle cell disease D) They cannot be detected until adulthood. Answer: B) They are caused by mutations in a single gene. chromosomal structure. 3. In autosomal dominant disorders, how many copies of the mutated gene are needed for the disease to manifest? and cystic fibrosis. A) One B) Two C) Three The effects of an abnormal genetic trait may present at birth or may not D) None ◼ Answer: A) One 4. Which of the following is an example of an autosomal recessive disorder? become apparent until later in life. A) Marfan Syndrome B) Huntington’s Disease C) Sickle Cell Disease D) Hemophilia 1. Single gene Disorders -Caused by a single defective or mutant gene Answer: C) Sickle Cell Disease 5. What is a common feature of sex-linked inheritance disorders? A) They are associated with the Y chromosome. B) They can affect both males and females equally. 2. Disorders of Autosomal Inheritance -Autosomal Dominant Eg: Marfan C) They are always linked to the X chromosome. D) They only occur in females. Answer: C) They are always linked to the X chromosome. Syndrome, Autosomal Recessive Eg: Sickle cell disease 6. Which of the following is an example of a chromosomal disorder? A) Cystic Fibrosis B) Down Syndrome C) Tay-Sachs Disease The key difference between autosomal dominant and autosomal recessive disorders is D) Marfan Syndrome Answer: B) Down Syndrome 7. What is required for a person to develop an autosomal recessive disorder? that, in autosomal dominant disorders, one altered copy of a gene is enough to cause A) One mutated gene from either parent B) Two mutated genes, one from each parent the disease while, in autosomal recessive disorders, both altered copies of the gene are C) A single environmental trigger D) None of the above Answer: B) Two mutated genes, one from each parent needed to cause the disease. 8. Which disorder is characterized by an extra copy of chromosome 21? A) Turner Syndrome B) Down Syndrome C) Klinefelter Syndrome 3. Disorders of Sex- Linked Inheritance - Always associated with the X chromosome D) Sickle Cell Disease Answer: B) Down Syndrome 9. Hemophilia is primarily associated with which type of inheritance? A) Autosomal Dominant 4. Chromosome disorders B) Autosomal Recessive C) Sex-Linked Inheritance 22 D) Chromosomal Disorders Answer: C) Sex-Linked Inheritance 10. What is Marfan Syndrome primarily known for affecting? A) Blood clotting ability B) Connective tissue and skeletal structure Autosomal Dominant Disorders Marfan Syndrome: A connective tissue disorder manifested by changes in the skeleton, eyes, and cardiovascular system ◼ Tall and slender build. ◼ Disproportionately long arms, legs and fingers. ◼ A breastbone that protrudes outward or dips inward. ◼ A high, arched palate and crowded teeth. ◼ Heart murmurs. ◼ Extreme nearsightedness. ◼ An abnormally curved spine. ◼ Flat feet 23 Autosomal dominant disorders ◼ Neurofibromatosis (NF) A condition involving neurogenic tumors that arise from Schwann cells and other elements of the peripheral nervous system 24  Autosomal recessive disorders ◼ Phenylketonuria (PKU) ◼ A rare metabolic disorder caused by a deficiency of the liver enzyme phenylalanine hydroxylase. ◼ PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. 25 26  X-linked Disorder Hemophilia A Disorder where the blood cannot clot properly due to a deficiency of a clotting factor called Factor VIII. This results in abnormally heavy bleeding that will not stop, even from a small cut 27  What is the primary characteristic of Turner’s syndrome? A) Extra chromosome 21 B) Only one X chromosome C) Extra Y chromosome Chromosome Disorders D) Three copies of chromosome 18 Answer: B) Only one X chromosome 2. Which of the following describes Klinefelter’s syndrome? A) Missing a chromosome Chromosome disorders involve a change in B) Extra X chromosome in males C) Extra Y chromosome in females chromosome number or structure that results in D) Three copies of chromosome 21 Answer: B) Extra X chromosome in males damage to sensitive genetic mechanism or in 3. What condition is associated with an extra copy of chromosome 21? reproductive disorders. A) Turner’s syndrome B) Klinefelter’s syndrome ◼ Monosomy X (Turner’s syndrome) C) Down syndrome D) Fragile X syndrome Answer: C) Down syndrome ◼ Poly somy X (Klinefelter’s syndrome) 4. Individuals with Turner’s syndrome often experience which of the following? A) Tall stature B) Delayed puberty C) Increased muscle mass ◼ Trisiomy 21 (Down’s syndrome) - Presence of all D) Enhanced cognitive abilities Answer: B) Delayed puberty or part of a third copy of chromosome 21, 5. Which characteristic is commonly seen in individuals with Down syndrome? associated with physical growth delays, mild to A) Long limbs B) Distinctive facial features moderate intellectual disability, and characteristic C) High intelligence D) Normal growth rates facial features Answer: B) Distinctive facial features 28  NEOPLASIA PATH200/MACHS 29  NEOPLASM - TERMINOLOGY ◼ Neoplasm: - New abnormal growth because of abnormal cellular- reproduction. It is synonymously used with tumor. ◼ Tumor: - A growth of Neoplastic cells clustered together to form a mass. It can be benign or malignant. ◼ Benign tumor: - Is characterized by abnormal cell division but no metastasis or invasion of the surrounding tissues. ◼ Malignant tumor: - Abnormal cell division characterized by ability to invade locally, metastasize and reoccur. It is cancer cells. ◼ Carcinogenesis: - production or origination of cancer cells. ◼ Metastasis: - Ability to establish secondary tumor growth at a new location away from the primary tumor. 30 31  Factors Differentiating Benign and Malignant Tumors Benign Malignant ◼ Similar to cell of origin ◼ Dissimilar from cell of origin ◼ Edges move out word smoothly ◼ Edges move outward irregularly. ◼ Compress locally ◼ Invade locally ◼ Slow growth rate ◼ Rapid to very rapid growth rate. ◼ Seldom Recur after removal by surgery ◼ Frequently recur after removal ◼ Necrosis and ulceration is uncommon ◼ Necrosis and ulceration common. ◼ Systemic effect is uncommon ◼ Systemic effect is common ◼ No metastasis ◼ Metastasis is common 32 https://www.youtube.com/watch?v=ZcVSHYl_THE 33  CANCER ◼ Disease process that begins when a cell is transformed by genetic mutation of cellular DNA ◼ Growth is uncoordinated and relatively autonomous. ◼ Lacks normal regulatory controls over cell growth and division ◼ Tends to increase in size and grow after stimulus ceases or needs of the organism are met Causes: Heredity, Hormones, Immunologic mechanisms, carcinogens like Chemicals, Radiation, Oncogenic viruses 34  CARCINOGENESIS Malignant transformation, or carcinogenesis, is thought to be at least a three-step cellular process: ◼ Initiation : Initiators (carcinogens), such as chemicals, physical factors, and biologic agents, alter the genetic structure of the cellular DNA. ◼ Promotion: Repeated exposure to promoting agents (co-carcinogens) causes the expression of abnormal or mutant genetic information ◼ Progression: The cellular changes formed during initiation and promotion now exhibit increased malignant behavior. These cells now show a propensity to invade adjacent tissues and to metastasize.. 35  Pathophysiology of The Malignant Process ◼ Cancer is a disease process that begins when an abnormal cell is transformed by the genetic mutation of the cellular DNA. ◼ This abnormal cell begins to proliferate abnormally ◼ The cells acquire invasive characteristics, and changes occur in surrounding tissues. ◼ The cells infiltrate these tissues and gain access to lymph and blood vessels, which carry the cells to other areas of the body.This phenomenon is called metastasis (cancer spread to other parts of the body). 36 Methods By Which Cancer Spreads ◼ Direct invasion and extension ◼ Seeding of cancer cells in body cavities ◼ Metastatic spread through the blood or lymph pathways 37  Tumor Staging And Grading ◼ Staging determines the size of the tumor and the existence of metastasis. The TNM system is frequently used. ◼ T -the extent of the primary tumor ◼ N -lymph node involvement ◼ M -the extent of metastasis 38  TNM Classification System T The extent of primary tumor N The absence or presence and extent of regional lymphnode metastasis M The absence or presence of distant metastasis Primary Tumor(T) Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1,T2,T3,T4 Increasing size and/ or local extent of the primary tumor Regional Lymph Nodes(N) Nx Regional lymphnodes cannot be assessed N0 No regional lymph node metastasis N1,N2,N3 Increasing involvement of regional lymph nodes Distant Metastasis (M) Mx Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis 39 Clinical Manifestations of Cancer ◼ Tissue Integrity -Compressed and eroded blood vessels; ulceration and necrosis; frank bleeding and hemorrhage ◼ Cancer Cachexia -Weightloss and wasting of body fat and muscle tissue; profound weakness, anorexia, and anemia ◼ Paraneoplastic Syndromes -Inappropriate hormone release, circulating hematopoietic, neurological, and dermatological factors Diagnostic Measures for Cancer Detection Screening for early detection Lab tests, Biopsy, Endoscopic examinations, Ultrasound, X-ray studies, MRI, CT and PET ,Tumor markers Treatment Surgery, Chemotherapy, radiotherapy, Hormone therapy , Immunotherapy, Palliative treatment 40  REFERENCES  NORRIS, T. (2019). Porth’s Pathophysiology Concepts of Altered Health States. 10th ed. Wolters Kluwer  Ian Peate, (2021) Fundamentals of applied pathophysiology: an essential guide for nursing & healthcare students. 4th ed.  Hoboken, NJ : Wiley-Blackwell Dignle, M., Mulvihill, M., Zelman, M. & Tompary, E. (2011). Introductory pathophysiology for nursing & healthcare professionals. |Pearson  Nair, M., & Peate, I. (2015). Pathophysiology for nurses at a glance (nursing and healthcare). Publisher: West Sussex, England: John Wiley & Sons, Inc 41