Pathology Lecture Notes PDF

# KAAF UNIVERSITY COLLEGE ## SCHOOL OF NURSING ### Lecturer: Richmond Rwakye # PATHOLOGY - **Normal Gastric Mucosa:** This is a microscopic image of a normal stomach lining. The cells are arranged in a regular, organized pattern. - **Gastric Intestinal Metaplasia:** This image shows the stomach l...

# KAAF UNIVERSITY COLLEGE ## SCHOOL OF NURSING ### Lecturer: Richmond Rwakye # PATHOLOGY - **Normal Gastric Mucosa:** This is a microscopic image of a normal stomach lining. The cells are arranged in a regular, organized pattern. - **Gastric Intestinal Metaplasia:** This image shows the stomach lining has undergone metaplasia. This is a change in the type of cells that make up the lining. The cells in this image are more like those found in the intestine. - **Gastric Adenocarcinoma:** This image shows a gastric adenocarcinoma, which is a type of cancer that affects the stomach lining. The cancer cells are abnormal and grow in a disorganized manner. - **Atrophic Gastritis:** This image shows atrophic gastritis, which is a condition in which the stomach lining is thinned. This can happen due to chronic inflammation or other factors. # Historical Concept of Pathology - **The early days of Pathology - Descriptions and Humoral Theory (body fluids)** - In the early days of pathology, unsystematic, general descriptions of the diseases are observed, accompanied by their manifestations and numerous theories related to the causes and development of these observed diseases. - Still deprived from any technological tools, the physicians and thinkers of that time used empiricism and the observations of dissections to understand the workings of the body and its diseases. - **HC.PATH.** - The first records of the presence and manifestation of diseases date back to the 16th and 17th centuries BC. - The Edwin Smith Papyrus, which depicts skin ulcerations in patients in the Valley of the Nile, still with no causal relationship or clear development mechanism, is a testament to this. - It was only in the 4th century BC, during the heyday of Greek civilization, that more detailed descriptions of diseases emerged, which led to the formation of the first theory of disease development, **The Humoral Theory**. This theory, suggested by Empedocles and applied to Medicine by Hippocrates, posited that an imbalance of humors (fluids) resulted in diseases. - Moreover, Hippocrates was one of the first physicians to make clear descriptions of the inflammatory process and of tumors. - These detailed and objective reports gave Cornelius Celsius the foundation to publish, more than 400 years later, his "De Re Medicina", presenting **the four phlogistic signs of inflammation (heat, tumor, redness and pain)**, supplemented a century later by Galen (loss of function). - Another interesting description of this stage attributed to Galen refers to **the "crab-shaped" aspect of tumor growth**, a description that is the basis for the term used to this day for malignant neoplasms (cancer). - The isolated descriptions of diseases or their groups, together with the strengthening of **the humoral theory**. This was the foundation for everything that is considered closest to "Pathology" for that time until much of the Middle Ages. - **HC.PATH.** - The first age of Pathology - Autopsies and Macroscopy - Anatomical and organic bases of diseases (physicians was Antonio Benivieni (1443 - 1502) - The second age of Pathology - Microscopy, tissues and the Cellular Basis of Diseases - The third age of Pathology - Immunology and Molecular Biology at the service of the study of the physio-pathological and molecular bases of disease - Pathology at the University of Sao Paulo (USP) Faculty of Medicine, # pathology - **pathology:** “patho” (disease) & "logy" (study). - **Pathology:** scientific study of changes in the structure and function of the body in disease. - Diseases may, in turn, be defined as an abnormal variation in structure or function of any part of the body. - **Pathology helps to understand disease in four aspects:** - Etiology - Pathogenesis - Morphologic changes - Functional derangement and clinical manifestation # etiology - **Etiology:** The cause of the disease. - **Types:** - **primary etiology:** when the cause of the disease is known. - **idiopathic:** cause of the disease is unknown - Knowledge or discovery of the primary cause remains the backbone on which a diagnosis can be made, a disease understood, & a treatment developed. - There are two major classes of etiologic factors: - genetic and acquired (infectious, nutritional, chemical, physical, etc). # pathogenesis - **Pathogenesis:** the mechanism through which the cause operates to produce the pathological and clinical manifestations. - The pathogenetic mechanisms could take place in the latent or incubation period. Pathogenesis leads to morphologic changes. # Morphologic changes - **Morphologic changes:** The morphologic changes refer to the structural alterations in cells or tissues that occur following the patho-genetic mechanisms. - The structural changes in the organ can be **gross morphologic** (seen with the naked eye) or **microscopic** (only be seen) under the microscope. - Both the gross & the microscopic morphologic changes are specific to a disease. - Morphologic changes can be used by the pathologist to identify (i.e. to diagnose) the disease. - In addition, the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease # Functional derangements and clinical significance - The morphologic changes in the organ influence the normal function of the organ. By doing so, they determine the clinical features (symptoms and signs), course, and prognosis of the disease. # Pathology in summary - Pathology studies: - Etiology - Pathogenesis - Morphologic changes - Clinical features & Prognosis of all diseases # Disease? - abnormal variation in structure or function of any part of the body. Or - A disturbance of the normal function of an organ, a part or the whole of the body. # Causes? - **Environmental factors** - Physical agents (noise, radiation, extreme of temperature) - Chemicals (cyanide, strong acid, drugs) - Nutritional deficiencies & excesses (interference with absorption and transport, dietary excess leading to obesity, HBP or heart diseases - **biological** (viruses, bacteria, fungi, protozoa) - **Immunological factors** (Hypersensitivity reaction - eg. bronchial asthma can occur due to exaggerated immune response to the harmless pollen, Immunodeficiency, Autoimmunity: eg. type 1 diabetes mellitus is caused by autoimmune destruction of the beta cells of the islets of Langerhans of the pancreas.) - **Psychogenic factors** (mental stress) - **genetic factors** (hereditary) or - a combination of the two. # The Course of a disease - The 'Course of Disease' refers to the progression and development of a medical condition over time, including factors influencing its trajectory, such as etiological and risk factors, social responses, and adaptations. - The course of a disease in the absence of any intervention is called the **natural history of the disease**. The different stages in the natural history of disease # Natural history of disease - **STAGES:** - Exposure - Latency - Biological onset (disease initiation process, asymptomatic) - Incubation (no clinical signs) - Clinical onset - Permanent damage - Death - **The course flow chart:** - Exposure - Biological onset - Clinical onset - Permanent damage - Death - NB: the latent period is the time interval between when an individual or host is infected by a pathogen and when that individual becomes infectious. - An incubation period is the span of time between exposure to an infectious disease/agent and the start of symptoms # Outcome and consequences of disease - Following clinical onset, disease may follow any of the following trends: - Resolution can occur leaving no sequelae, - The disease can settle down, but sequelae are left, or - It may result in death. # Diagnostic techniques used in pathology - The pathologist uses the following techniques to the diagnose diseases: - a. Histopathology (studies tissues under the microscope using biopsy) - b. Cytopathology (the study of cells from various body sites to determine the cause or nature of disease. - c. Hematopathology # Techniques - d. Immunohistochemistry (detect a specific antigen in the tissue in order to identify the type of disease) - Microbiological examination - f. Biochemical examination - g. Cytogenetics - h. Molecular techniques - i. Autopsy # Cell Injury, Adaptation and Death - Cell injury underlies all diseases. When a cell is exposed to an injurious agent - 1. The cell may adapt to the situation or - 2. They cell may acquire a reversible injury or 3. The cell may obtain an irreversible injury & may die. The cell may die via one of two ways: either by necrosis or by apoptosis. - Which of these outcomes occur depends on both the injurious agent & on cellular factors. In other words, the result depends on the type, severity, & duration of the injury & on the type of the cell. - **NB: causes of cell injury is same as discussed for causes of disease** # Cellular adaptation - Cellular adaptations refer to the changes cells make in response to various stimuli or changes in their local environment. - This can involve changing the number of cells or their morphological appearance. It can be physiological, which occurs in normal tissues or organs, or pathological, i.e., in disease states. # Cellular adaptation types - **Hypertrophy:** - Hypertrophy is an increase in the **size** of cells. Increased workload leads to increased protein synthesis & increased size & number of intracellular organelles which, in turn, leads to increased cell size. - The increased **cell size** leads to increased size **of the organ.** Examples: the enlargement of the left ventricle in hypertensive heart disease & the increase in skeletal muscle during strenuous exercise. # Hypertrophy: - This is a diagram illustrating the distinction between a normal heart, a hypertrophied heart, and a heart with cardiomyopathy. The hypertrophied heart is larger than a normal heart. # Hyperplasia - **Hyperplasia:** Hyperplasia is an increase in the **number** of cells. It can lead to an increase in the size of the organ. It is usually caused by hormonal stimulation. - It can be physiological as in enlargement of the breast during pregnancy or - it can be pathological as in endometrial hyperplasia. # Hyperplasia - This shows a diagram of the normal uterus and a uterus with excessive growth (endometrial hyperplasia). This is considered to be pathological. # Atrophy - **Atrophy:** Atrophy is a **decrease** in the size of a cell. This can lead to decreased size of the organ. - Atrophy can be caused by: - 1. Disuse - 2. Undernutrition - 3. Decreased endocrine stimulation - 4. Denervation - 5. Old age # Atrophy - This is showing two pictures, one, a arm muscle, the second is a diagram of a healthy testicle and an atrophied testicle, making the point that atrophy can happen to muscles and organs. # Metaplasia - **Metaplasia:** Metaplasia is the replacement of one differentiated tissue by another differentiated tissue. - **Types:** - 1. Squamous metaplasia: This is replacement of another type of epithelium by squamous epithelium. For example, the columnar epithelium of the bronchus can be replaced by squamous epithelium in cigarette smokers - 2. Osseous metaplasia: This replacement of a connective tissue by bone, for example at sites of injury. # Metaplasia - This shows a diagram of the bronchus lined with the normal columnar epithelial cells (purple) being replaced by flattened squamous epithelial cells (pink) # Cell death - Cells can die via one of the following two ways: - 1. Necrosis - 2. Apoptosis - Necrosis occurs by the following mechanisms: - A. Hypoxia - B. Free radical-induced cell injury - C. Cell membrane damage - D. Increased intracellular calcium level # Necrosis and apoptosis - **NECROSIS:** In necrosis, excess fluid enters the cell, swells it, & ruptures its membrane which kills it. After the cell has died, intracellular degradative reactions occur within a living organism. - Necrosis does not occur in dead organisms. In dead organisms, autolysis and heterolysis take place. # Necrosis and apoptosis - **Apoptosis:** Apoptosis is the death of single cells within clusters of other cells. (Note that necrosis causes the death of clusters of cells.) - In apoptosis **the cell shows shrinkage** which is followed by fragmentation of the cells. These fragments are called apoptotic bodies. - Apoptosis usually occurs as a physiologic process for removal of cells during embryogenesis, menstruation, etc. It can also be seen in pathological conditions caused by mild injurious agents. # Necrosis and apoptosis - This is a diagram illustrating the differences between necrosis and apoptosis. - On the left is necrosis where the cell swells and then disintegrates as it dies. - On the right is apoptosis which illustrates the cell shrinking with compaction and fragmentation, a more organized process than necrosis. On the bottom of the diagram, it shows a phagocytic cell ingesting a dead apoptotic body. # PRESENTATION/ ASSIGNMENT - NECROSIS MECHANISMS - TPYES OF NECROSIS