Cell Injury and Cellular Adaptation in Pathology (PDF)

11/8/2024 Cell injury and Cellular adaptation in pathology Liam Mannion HS1934 – Introduction to the Diagnostic and Therapeutic Radiography Professions Learning outcomes ▪ Describe the functions of a eukaryotic...

11/8/2024 Cell injury and Cellular adaptation in pathology Liam Mannion HS1934 – Introduction to the Diagnostic and Therapeutic Radiography Professions Learning outcomes ▪ Describe the functions of a eukaryotic cell ▪ Describe normal and abnormal cellular growth, including definitions for types of abnormal growth ▪ Define a range of cellular changes e.g., Hypertrophy, Hyperplasia, Atrophy, Metaplasia and Dysplasia. ▪ Explain direct and indirect effects of ionising radiation on DNA ▪ Explain the five distinct ways in which DNA damage can occur due to ionising radiation Human (animal) cells ▪ How many (estimated) cells are there in the human body? ▪ 20-30 trillion ▪ How many different types? ▪ 200 ▪ Can you name some types? ▪ Red/white blood, muscle, nerve, skin, bone, fat, stem… ▪ Name some ways cells can become injured ▪ Physical, chemical, biological, radiation ▪ Can they repair themselves? ▪ Yes, in certain situations repair enzymes can reverse damage and repair DNA damage to restore cellular function. However, some injuries are not repairable 1  11/8/2024 Eukaryotic cells are complex and highly organised, containing various specialised structures called organelles, each with specific functions. Nucleus: 1. Function: Acts as the control centre of the cell, housing the cell’s DNA and coordinating activities like growth, metabolism, and reproduction. 2. Key Features: Surrounded by a nuclear envelope with pores that regulate the exchange of materials between the nucleus and the cytoplasm. 1.Mitochondria: 1. Function: Known as the powerhouse of the cell, they generate ATP through cellular respiration, providing energy for the cell’s activities. 2. Key Features: Contain their own DNA and are involved in energy production. 2  11/8/2024 Endoplasmic Reticulum (ER): 1. Rough ER: Studded with ribosomes and involved in protein synthesis and modification. 2. Smooth ER: Lacks ribosomes and is involved in lipid synthesis and detoxification processes. Golgi Apparatus: 1. Function: Modifies, sorts, and packages proteins and lipids for secretion or delivery to other organelles. 2. Key Features: Consists of flattened membrane-bound sacs. Lysosomes: 1. Function: Contain digestive enzymes that break down waste materials and cellular debris. 2. Key Features: Act as the cell’s waste disposal system. Ribosomes: 1. Function: Sites of protein synthesis, translating genetic information into proteins. 2. Key Features: Can be found floating in the cytoplasm or attached to the rough ER. Cytoskeleton: 1. Function: Provides structural support, maintains cell shape, and facilitates cell movement and division. 2. Key Features: Composed of microtubules, microfilaments, and intermediate filaments. Plasma Membrane: 1. Function: Regulates the movement of substances in and out of the cell, providing protection and support. 2. Key Features: Composed of a lipid bilayer with embedded proteins. Vacuoles: 1. Function: Storage of nutrients, waste products, and other materials; in plant cells, they also maintain turgor pressure. 2. Key Features: Large central vacuole in plant cells, smaller vacuoles in animal cells. These organelles work together to ensure the cell functions efficiently and responds to its environment. 3  11/8/2024 Cell Growth Cell populations go through a phase of exponential growth – doubling Cell cycle controls the rate of cell division Under “normal” circumstances – balance between rates of new cell growth and old cell death once maturity has been reached Extent of cell replacement depends on: – normal rate of turn-over – tissue type Cell Growth Differentiation Process by which unspecialised cells become specialised for a particular function (stem cells) Control mechanism determines degree of differentiation, cell size and size of each organ Mechanism controls balance between normal destruction of cells and their replacement Control mechanism may go wrong → abnormal growth ▪ When cells are injured, they may undergo several responses: Adaptation: Cells may adapt to mild stress by changing their structure or function. Reversible Injury: If the injury is not severe, cells can recover once the harmful stimulus is removed. Irreversible Injury: Severe or prolonged injury can lead to cell death through processes like necrosis or apoptosis. Understanding the causes and mechanisms of cellular injury is crucial for diagnosing and treating various medical conditions. 4  11/8/2024 Abnormal cell growth can occur in various forms, often categorised based on their potential to cause harm. Here are the main types: 1.Benign Tumours: These are non-cancerous growths that typically grow slowly and do not spread to other parts of the body. Examples include lipomas (fatty tissue growths) and fibroids (muscle tissue growths) 2.Precancerous (Premalignant) Growths: These cells are not yet cancerous but have the potential to become malignant over time. Examples include dysplasia (abnormal cells that can develop into cancer) and certain types of polyps in the colon 3.Malignant Tumours (Cancer): These are cancerous growths that can invade nearby tissues and spread to other parts of the body (metastasise). Types of malignant tumours include: 1. Carcinomas: Cancers that arise in epithelial cells, such as those in the skin, lungs, and glands 2. Sarcomas: Cancers that originate in connective tissues like bone, muscle, and fat 3. Leukaemias: Cancers of the blood and bone marrow, characterised by the overproduction of abnormal white blood cells Lack of ability to invade adjacent tissue Potential to metastasis Types of Abnormal Growth Aplasia - an absence or defective development of an organ or tissue. It can occur in various parts of the body and can be congenital (present at birth) or acquired later in life. Bone marrow aplasia: This is a condition where the bone marrow fails to produce sufficient blood cells, leading to aplastic anaemia. 5  11/8/2024 ▪ Hypertrophy refers to the increase in the size of an organ or tissue due to the enlargement of its cells. It is a common physiological response to increased demand or stress. Muscle hypertrophy: This occurs when muscle fibrer increase in size, typically as a result of strength training or resistance exercises. Image source: https://ladder.sport/pages/arnolds- workout-routine/ Hypoplasia - underdevelopment or incomplete development of a tissue or organ due to an inadequate (or below normal) number of cells. It can affect various parts of the body and is often congenital (present at birth). Optic nerve hypoplasia: This involves the underdevelopment of the optic nerve, leading to vision problems or blindness. Image source: https://aapos.org/glossary/optic-nerve-hypoplasia Metaplasia involves the replacement of one differentiated cell type with another differentiated cell type. This change can be a normal response to environmental stressors or an abnormal adaptation Squamous Metaplasia: Commonly occurs in the respiratory tract due to chronic irritation from smoking, where Image source: https://www.osmosis.org/answers/metaplasia the normal columnar epithelium is replaced by squamous epithelium. 6  11/8/2024 Dysplasia refers to the abnormal growth or development of cells within tissues or organs. It is not cancer, but it can be a precursor to cancer, indicating early changes that might lead to malignancy if left untreated. Definition: Dysplasia involves the presence of abnormal cells within a tissue or organ. These cells look different under a microscope compared to normal cells. Types: Cervical Dysplasia: Abnormal changes in the cells on the surface of the cervix, often caused by human papillomavirus (HPV) Image source: https://drnickleroy.com/case-studies-hpv- infection. cervical-dysplasia/#iLightbox[0674498dac7fc29077f]/0 So, what happens if IR interacts with a cell? ▪ Radiation damage can affect cells in two primary ways: directly and indirectly. Direct Effects ▪ Direct effects occur when radiation interacts directly with DNA molecule (or other critical cellular components e.g., plasma membrane). ▪ There is a low probability this occurring with IR used for medical procedures Indirect Effects ▪ Indirect effects are more common and occur when radiation interacts with water (plasma component of cell). Highly reactive molecules are firmed and damage the DNA helix. 7  11/8/2024 Deletion “Point Mutation” Chromosome Section deleted Start Process End Duplication Section duplicated Chromosome Start Process End Inversion Chromosome Start Process End 8  11/8/2024 Insertion Chromosome Start Process End Translocation Chromosome 3 2 non homologous chromosomes Start Process End Summary Human body is made of many complex eukaryotic cells that contain various organelles, each with specific functions. Cells grow and divide in a controlled manner to replace old or damaged cells and differentiate to perform specific functions. Abnormal cellular growth can occur as a result to damage to a cell and if not repaired can cause unregulated cell growth. Ionising radiation can directly or indirectly damage DNA within a cell There are five distinct ways in which DNA damage can occur. Suggested reading Cancer and its management - Jeffrey S. Tobias; Daniel Hochhauser; Robert L. Souhami / 2015 /Seventh edition Pgs. 25-43 9  11/8/2024 End of presentation School of Health & Psychological Sciences City St George’s, University of London Northampton Square London EC1V 0HB United Kingdom T: +44 (0)20 7040 5060 E: [email protected] www.city.ac.uk/department 10