Pathophysiology Reference Notes PDF

Unit -- 1.2 Pathophysiology - Study of functional changes in cells, tissues, and organs affected by injury or disease Cellular Adaptations - Changes made by body cells in response to stimuli or environmental changes Adaptation - Adaptations help organism to survive and thrive in i...

Unit -- 1.2 Pathophysiology - Study of functional changes in cells, tissues, and organs affected by injury or disease Cellular Adaptations - Changes made by body cells in response to stimuli or environmental changes Adaptation - Adaptations help organism to survive and thrive in its environment - It can be reversible, structural or behavioral to the conditions - Severe or long-term stressors to cells can lead to: - In a condition where cells start to withdraw from normal functioning of the body - Which eventually leads to cell death. - What would happen if cells did not adapt to stressors? How does this affect health & disease? - If cells did not adapt to stressors, it would have significant negative impacts on health and could lead to various diseases. The ability of cells to adapt to stressors is crucial for maintaining homeostasis and overall cellular function. - Without adaptation, cells cannot adequately respond to harmful conditions like oxidative stress, heat shock, or toxic substances. This can lead to damage of cellular components such as DNA, proteins, and membranes. - Persistent damage without adaptation mechanisms can trigger cell death through apoptosis (programmed cell death) or necrosis (uncontrolled cell death), contributing to tissue damage. - **Loss of Cellular Function**: - Cells under stress may lose their ability to perform normal functions, such as energy production, detoxification, or cell signaling. This dysfunction can impair the overall function of tissues and organs. For example, if heart cells cannot adapt to stress, it can lead to heart failure, while failure of neurons to adapt may contribute to neurodegenerative diseases. - Chronic Inflammation\*\*: Failure to adapt to stress can lead to chronic inflammation, contributing to diseases like cardiovascular disease, diabetes, and cancer. - Accelerated Aging\*\*: Cells would age faster without proper stress responses, leading to tissue degeneration and age-related diseases. Overall, the inability to adapt to stressors would result in a higher likelihood of diseases and disorders, and the body's ability to recover from injury or maintain health would be compromised. Define Atrophy: decrease/shrinkage in cell size Physiologic effects of Atrophy: - Reduction in Organ or Tissue Size: For example, muscle atrophy reduces muscle mass and strength, while brain atrophy decreases brain volume, affecting cognitive function. - Decreased Functionality: For instance, muscle atrophy leads to weaker muscle contractions, making physical activity and mobility more difficult. Similarly, atrophy of the brain in aging or neurodegenerative conditions can impair memory, thinking, and coordination. - Reduced Metabolic Activity: there is a reduction in the number and activity of organelles such as mitochondria. This can lead to decreased energy production and overall efficiency of the affected tissue. - Loss of Specific Cellular Functions: For example, the atrophy of glandular tissues like the thymus or adrenal glands leads to decreased hormone production, impacting immune function or stress response. - Impaired Blood Supply: Reduced vascularization further limits nutrient and oxygen supply, exacerbating tissue shrinkage and functional decline. - Altered Cellular Structure: altered protein composition. This can impair cellular processes like protein synthesis, repair, and cellular signaling. - Increased Susceptibility to Injury: For example, atrophied muscles are more prone to strains and tears, while thinning skin is more susceptible to bruising and wounds. - Compromised Immune Function: In cases like thymic atrophy (common with aging), there is a reduction in immune cell production, particularly T-cells, which can compromise the body\'s ability to respond to infections. - Impact on Overall Body Function: For example, muscle atrophy can lead to reduced physical endurance and greater fatigue, while atrophy of the kidneys can impair fluid and electrolyte balance. - Altered Hormonal Balance: When endocrine organs atrophy, it can disrupt hormone production and balance, affecting various body systems. For example, adrenal gland atrophy reduces cortisol production, which can impair stress responses and metabolism. Define Hypertropy: Increase in cell size. There is increased demand or workload. **Physiologic Hypertrophy**: This is a healthy and adaptive response to normal physiological demands. It is usually beneficial and does not lead to tissue damage. Physiologic hypertrophy refers to the enlargement of cells, tissues, or organs due to an increase in the size (but not number) of the individual cells. This type of hypertrophy is a normal, adaptive response to increased demand or workload and is typically reversible once the stimulus is removed. Physiologic hypertrophy is generally beneficial, enhancing the function of the affected tissues or organs. Here are some key aspects of physiologic hypertrophy: **Causes of Physiologic Hypertrophy** 1. **Increased Physical Demand**: - **Skeletal Muscle Hypertrophy**: This occurs in response to resistance training or weightlifting, where muscle fibers increase in size to handle the added load. This adaptation improves muscle strength and endurance. 2. **Hormonal Stimulation**: - **Pregnancy**: The uterus undergoes hypertrophy to accommodate the growing fetus. This is stimulated by increased levels of estrogen and other pregnancy-related hormones. - **Breast Tissue Enlargement**: During puberty and pregnancy, breast tissue hypertrophies in response to hormonal changes to prepare for potential lactation. 3. **Increased Functional Demand**: - **Cardiac Hypertrophy**: In athletes, the heart muscle (myocardium) can enlarge in response to increased demand from prolonged endurance training. This type of hypertrophy improves cardiac output and efficiency, allowing the heart to pump more blood per beat. **Characteristics of Physiologic Hypertrophy** - **Symmetrical Growth**: In physiologic hypertrophy, the growth is typically proportional and symmetrical, enhancing the overall function of the tissue or organ. - **Reversibility**: This form of hypertrophy is usually reversible when the stimulus (like exercise or pregnancy) is removed. - **Improved Function**: The primary goal of physiologic hypertrophy is to enhance the performance and capacity of the affected tissue. For example, muscle hypertrophy leads to increased strength and endurance, while cardiac hypertrophy improves the heart\'s ability to pump blood. **Physiologic vs. Pathologic Hypertrophy** - **Physiologic Hypertrophy**: This is a healthy and adaptive response to normal physiological demands. It is usually beneficial and does not lead to tissue damage. - **Pathologic Hypertrophy**: In contrast, pathologic hypertrophy occurs in response to abnormal conditions, such as high blood pressure or heart valve disease, and can lead to detrimental effects, including heart failure. **Examples of Physiologic Hypertrophy** 1. **Athlete\'s Heart**: In endurance athletes, the heart enlarges to increase stroke volume and cardiac output, enhancing the delivery of oxygen and nutrients during prolonged physical activity. 2. **Skeletal Muscle Hypertrophy**: Resistance training induces hypertrophy in skeletal muscles by increasing the size of muscle fibers through protein synthesis, leading to greater muscle mass and strength. 3. **Uterine Hypertrophy**: During pregnancy, the smooth muscle cells of the uterus grow larger to support the developing fetus, and the uterine wall thickens. 4. **Left Ventricular Hypertrophy in Athletes**: This type of hypertrophy involves the thickening of the heart\'s left ventricle in response to increased physical demands, allowing for greater cardiac output during exercise. **Physiologic Effects of Hypertrophy** - **Enhanced Performance**: For muscles, hypertrophy increases strength and endurance, while for the heart, it improves blood flow and oxygen delivery during physical activity. - **Increased Functional Capacity**: Hypertrophy allows tissues and organs to meet higher functional demands without experiencing damage or failure. **Pathologic Hypertrophy**: In contrast, pathologic hypertrophy occurs in response to abnormal conditions, such as high blood pressure or heart valve disease, and can lead to detrimental effects, including heart failure. High blood pressure heart valve blockageheart failure **Hyperplasia** is the increase in the number of cells in a tissue or organ, leading to its enlargement. Unlike hypertrophy, which is an increase in cell size, hyperplasia involves cell proliferation, where cells divide and multiply. Hyperplasia is typically a controlled process that occurs in response to a specific stimulus and usually stops when the stimulus is removed. Hyperplasia is a normal and often beneficial process that supports growth, repair, and adaptation. However, when dysregulated, it can contribute to pathologic conditions and potentially lead to neoplastic changes if cell growth becomes uncontrolled. **Pathologic hyperplasia - Abnormal proliferation from excessive hormonal stimulation** **Types of Hyperplasia** 1. **Physiologic Hyperplasia**: A normal, adaptive response to a physiological need. - **Hormonal Hyperplasia**: Occurs in response to hormonal stimulation, such as the proliferation of the endometrium (lining of the uterus) during the menstrual cycle or the enlargement of breast tissue during pregnancy and lactation. - **Compensatory Hyperplasia**: Occurs when a portion of an organ is removed or damaged, such as liver regeneration after partial hepatectomy or the proliferation of skin cells during wound healing. 2. **Pathologic Hyperplasia**: An abnormal increase in cell number due to excessive hormonal stimulation or other factors, which can potentially lead to disease. - **Endometrial Hyperplasia:** Excessive proliferation of the cells lining the uterus, often due to prolonged estrogen stimulation without progesterone balance, which can increase the risk of developing endometrial cancer. - **Benign Prostatic Hyperplasia (BPH):** An enlargement of the prostate gland due to increased cell proliferation, commonly seen in older men, which can cause urinary obstruction. **Key Characteristics of Metaplasia** 1. **Cellular Reprogramming**: Metaplasia involves the change in cell type due to reprogramming of precursor cells, usually directed by altered gene expression. 2. **Reversible Process**: Metaplasia is generally reversible if the underlying cause or stressor is removed. However, prolonged exposure can make this adaptation persistent and possibly lead to irreversible changes. 3. **Adaptive Response**: It is a protective mechanism that replaces a sensitive or vulnerable cell type with another that can better tolerate the stress or injury. 4. **Predisposition to Malignancy**: While metaplasia itself is not cancer, the change can increase the risk of developing dysplasia and subsequent malignancy if the injurious stimulus continues. **Common Examples of Metaplasia** 1. **Squamous Metaplasia**: - **Respiratory Tract**: In chronic smokers, the normal ciliated columnar epithelium of the bronchial lining can transform into stratified squamous epithelium, which is more resistant to the harmful effects of smoke. However, this squamous epithelium lacks cilia and mucus production, impairing normal respiratory function and increasing the risk of lung cancer. 2. **Intestinal Metaplasia**: - **Barrett's Esophagus**: In response to chronic gastroesophageal reflux disease (GERD), the normal squamous epithelium of the lower esophagus can transform into columnar epithelium with goblet cells, resembling the intestinal lining. This change increases the risk of esophageal adenocarcinoma. 3. **Osseous Metaplasia**: - In some cases, soft tissues like muscle or connective tissue can transform into bone tissue, often seen in areas of chronic inflammation, injury, or mechanical stress. 4. **Connective Tissue Metaplasia**: - **Myositis Ossificans**: Following muscle injury, there may be a metaplastic transformation where fibroblasts turn into bone-forming cells, leading to abnormal bone formation within the muscle. **Pathologic metaplasia - chronic irritation and inflammation.** **E.g.) smoking produces changes to the lung's cells.** **Dysplasia** is an abnormal and disordered growth or development of cells within a tissue or organ. It is characterized by changes in the size, shape, and organization of cells, as well as alterations in the cellular architecture. Dysplasia is considered a precancerous condition, as it often represents an intermediate stage between normal tissue and cancer. However, dysplasia is still reversible if the underlying cause is removed or treated, distinguishing it from neoplasia (true cancer). **Causes:** Pathologic dysplasia - persistent severe injury or irritation - Can occur in epithelial tissue of cervix (eg. HPV) **Classified as mild, moderate or severe** - **Mild:** it is associated with lower third of the epithelial layer - **Moderate:** Abnormal changes occur now in the middle third of the epithelial layer - **Severe:** which involves more than 2-3^rd^ of the epithelial layer, almost reaching to the full thickness of the layer. **Dysplasia serves as an important early warning signal in clinical medicine, prompting interventions aimed at preventing the development of invasive cancer.** **HPV Dysplasia** - The cervix is made up of two distinct cells types squamous epithelium and columnar epithelium - Transformation zone- merging site of the 2 types of cells (common site for HPV changes) Virus enters cell in the transformation zone ↓ Becomes integrated in cell genome ↓ Changes in DNA ↓ Mutations ↓ Maligancy if left untreated **Key Points about HPV-Related Dysplasia** 1. **High-Risk HPV Types**: - Types 16 and 18 are considered high-risk for causing dysplasia and are most commonly associated with cervical cancer. Other high-risk types include 31, 33, 45, 52, and 58. 2. **Mechanism of Dysplasia**: - HPV infection leads to the expression of viral oncoproteins (E6 and E7) that interfere with host cell regulatory mechanisms. These oncoproteins inactivate tumor suppressor proteins like p53 and Rb, leading to uncontrolled cell proliferation and abnormal cell differentiation. 3. **Types of Dysplasia**: - **Cervical Dysplasia**: - **Low-Grade Squamous Intraepithelial Lesion (LSIL)**: Represents mild dysplasia where abnormal cells are present in the lower third of the cervical epithelium. Often associated with transient HPV infections and may regress spontaneously. - **High-Grade Squamous Intraepithelial Lesion (HSIL)**: Represents moderate to severe dysplasia involving more than two-thirds of the epithelium. Higher risk for progression to cervical cancer if not treated. - **Other Dysplasias**: - HPV-related dysplasia can also affect other anogenital areas such as the vulva, vagina, and penis, leading to similar grading systems and potential for progression to cancer. Human papillomavirus (HPV) is a common sexually transmitted infection, and certain strains of the virus, particularly HPV-16 and HPV-18, are linked to the development of dysplasia in various tissues, most notably the cervix. Dysplasia refers to the abnormal growth and development of cells within a tissue, often resulting in disorganized structure and function. **How HPV Leads to Dysplasia:** 1. **Infection**: HPV infects epithelial cells, usually in areas like the cervix, throat, or genital regions. The virus integrates its DNA into the host cells, disrupting normal cellular function. 2. **Cellular Changes**: HPV causes changes in the infected cells by interfering with tumor suppressor proteins, such as p53 and Rb. This leads to uncontrolled cell division and growth, which can result in the formation of abnormal cells. 3. **Development of Dysplasia**: Over time, the abnormal proliferation of cells can lead to dysplasia, a precancerous condition characterized by disorganized and atypical cells. Cervical dysplasia is often detected through Pap smears and is graded as: - **CIN 1 (Mild dysplasia)**: Abnormal cells are limited to the lower third of the cervical lining. - **CIN 2 (Moderate dysplasia)**: Abnormal cells extend to the middle third. - **CIN 3 (Severe dysplasia)**: Abnormal cells affect more than two-thirds of the cervical lining, potentially becoming carcinoma in situ (localized cancer). 4. **Potential for Progression**: If HPV infection and dysplasia persist over time, the condition may progress to invasive cancer, especially if high-risk HPV strains are involved. Cervical cancer is the most common cancer linked to HPV, but the virus can also cause dysplasia and cancer in other areas, such as the throat and anus. **Cellular Injury and Death** - Cell injury occurs if cell cannot maintain homeostasis - Cell injury can be reversible or irreversible - If changes occur to the cell nucleus & membranes are altered irreversible injury & death Causes of cell injury & death - Hypoxic injury - ROS & free radicals - Chemical injury - Infectious agents - Immunologic & inflammatory injury **Insufficient oxygen supply (hypoxia) or reduced blood flow (ischemia) deprives cells of necessary nutrients and oxygen, causing injury.** **Understanding cellular injury and death is crucial for diagnosing and treating diseases, as well as for developing therapeutic strategies to prevent or mitigate cellular damage.** - **Causes of hypoxic injury:** - ↓ O~2~ in air - Loss of hemoglobin - ↓ RBC production - Respiratory or CV disease - Asphyxial injury **This results in ischemia.** **Reperfusion (restoration of blood flow)** **Ischemic-reperfusion injury:** Ischemic-reperfusion injury represents a complex interplay of oxidative stress, inflammation, and cellular dysfunction that can exacerbate tissue damage after the restoration of blood flow. Understanding these mechanisms is crucial for developing strategies to protect tissues during critical situations such as heart attacks, strokes, and organ transplantation. **Definition: Free radicals are molecules or atoms that have one or more unpaired electrons in their outer shell. This makes them highly reactive and unstable, as they seek to pair their unpaired electrons by reacting with other molecules.** **Understanding free radicals and ROS is essential for developing strategies to combat oxidative stress and its associated diseases. Managing oxidative stress through lifestyle changes, antioxidants, and medical interventions can help mitigate the damage caused by these reactive species.** Chemical Injury: Interaction between a toxic substance & cells plasma membrane Includes: - Drugs (medical & street) - Pollutants - Herbicides/ insecticides - ETOH - Poisons- lead/ CO Infectious Injury: Injury from pathogens such as bacteria, viruses, fungi - Virulence of pathogen determines the degree of injury Immunologic & Inflammatory Injury: Components of the immune system & inflammatory system can injure cells - Include: - Histamine - Antibodies - Complement system - Phagocytic cells - Infiltrates (cellular accumulations) - Accumulation of normal cellular substances: - water, proteins, lipids, carbohydrates or - Accumulation of abnormal substances - Infectious agents - Inflammatory mediators - Water accumulation - Shifting of ECF into cells - May cause organ to in ↑ size & become pale Progressive Changes in cells: When faced with a stressor a cell can use adaptation - If stressor is too harmful cell may have irreversible injury Cell Injury & Death: Once a cell is affected by injury the following processes occur: - ATP depletion - Free radicals - Increased cellular calcium - Non-selective membrane permeability Irreversible Injury: - Irreversible injury results in either: Apoptosis (describe) - Causes: - damaged genetics/ old age - Hormone changes - Severe injury to cell - Infections **Mechanism of Ischemic-Reperfusion Injury:** 1. **Initial Ischemia**: - During the ischemic phase, tissues experience a lack of oxygen and nutrients, leading to reduced ATP production and the build-up of harmful metabolites (e.g., lactate, reactive oxygen species). - Cellular processes dependent on oxygen, such as aerobic respiration, shut down. Cells switch to anaerobic metabolism, which generates minimal ATP and acidifies the cellular environment. - Sodium-potassium pumps fail due to lack of ATP, leading to cellular swelling and potential cell death. 2. **Reperfusion (Restoration of Blood Flow)**: - Upon reperfusion, oxygen returns to the tissue, which should theoretically halt damage, but instead, it initiates a series of damaging events. 3. **Excessive Production of Reactive Oxygen Species (ROS)**: - Oxygen reintroduction leads to a burst in the production of reactive oxygen species (ROS), including free radicals like superoxide and hydroxyl radicals. These highly reactive molecules damage cellular proteins, lipids, and DNA, leading to oxidative stress. 4. **Calcium Overload**: - Ischemia impairs calcium regulation, causing calcium to accumulate inside cells. When blood flow is restored, calcium floods the cells, activating enzymes like proteases, phospholipases, and endonucleases, which can break down cellular structures and induce cell death. 5. **Inflammatory Response**: - The return of blood flow brings immune cells (e.g., neutrophils) that release inflammatory cytokines and more ROS, exacerbating tissue injury. The inflammation can spread to surrounding tissues, creating a broader area of damage than originally caused by ischemia. 6. **Mitochondrial Damage**: - Mitochondria, the cell\'s energy producers, are particularly sensitive to ischemic injury. During reperfusion, dysfunctional mitochondria generate even more ROS, amplifying the damage and leading to cell death through apoptosis or necrosis. **Consequences of Ischemic-Reperfusion Injury:** - **Necrosis**: Irreversible cell death due to overwhelming damage to the cell membranes and organelles. - **Apoptosis**: Programmed cell death, which may be triggered by mitochondrial damage and oxidative stress. - **Endothelial Dysfunction**: Damage to the inner lining of blood vessels, which can impair vascular function and lead to problems such as thrombosis (clot formation). - **Organ Failure**: Depending on the tissue or organ affected, reperfusion injury can contribute to conditions like heart failure (after a myocardial infarction), kidney failure, or brain injury (following a stroke). **Clinical Examples:** - **Myocardial Infarction (Heart Attack)**: Restoring blood flow to the heart after a coronary artery blockage (via procedures like angioplasty or thrombolysis) can result in reperfusion injury, causing additional damage to heart muscle cells. - **Stroke**: In ischemic stroke, restoring blood flow to the brain (e.g., using clot-busting drugs) can sometimes exacerbate injury to neurons. - **Organ Transplantation**: When organs are harvested and transplanted, they experience a period of ischemia. Reperfusion injury is a major concern when the organ is reconnected to the recipient\'s blood supply. **Prevention and Management of Ischemic-Reperfusion Injury:** - **Antioxidants**: Therapies using antioxidants (e.g., superoxide dismutase) aim to neutralize ROS and reduce oxidative stress. - **Ischemic Preconditioning**: Exposing tissues to short, controlled periods of ischemia before the main ischemic event can condition them to be more resistant to reperfusion injury. - **Calcium Channel Blockers**: These drugs may help prevent calcium overload during reperfusion. - **Anti-inflammatory Agents**: Medications that reduce inflammation (e.g., corticosteroids or anti-cytokine drugs) can minimize damage during reperfusion. In summary, ischemic-reperfusion injury occurs when the return of blood flow paradoxically worsens damage after ischemia, largely due to oxidative stress, calcium overload, and inflammation. It is a major concern in conditions like heart attacks, strokes, and organ transplantation. Unit -- 2.1 Infection Despite advances in antibiotics and vaccinations, infectious diseases continue to be a significant healthcare challenge for several reasons: **1. Antibiotic Resistance** **Challenge**: Development of new antibiotics is slow as compared to the rapid evolution of resistant strains, leading to infections that are harder to treat and more likely to spread. 2\. **Viral Mutations** **3. Emerging and Re-emerging Infectious Diseases** **Challenge**: Some diseases emerge faster than vaccines or treatments can be developed, leading to widespread outbreaks and pandemics. **4.Globalization and Travel** **Infection - Infection refers to the invasion and multiplication of pathogens (such as bacteria, viruses, fungi, or parasites) in the body. These foreign organisms can disrupt normal bodily functions, leading to disease or illness. Infections can occur in different parts of the body and can range from mild to life-threatening, depending on the type of pathogen and the body\'s immune response.** **Symptoms of Infection:** **Local Symptoms:** Redness, swelling, pain, and heat at the site of infection (e.g., a skin wound). **Systemic Symptoms:** Fever, fatigue, malaise, and generalized weakness, indicating that the infection has spread through the body. Infections can be spread through various means, such as direct contact, contaminated food or water, airborne transmission, or insect bites, and they can sometimes be prevented or managed with treatments like antibiotics, antivirals, and vaccines. **Antibiotic Resistance** **Antibiotic resistance** refers to the ability of bacteria (and other microorganisms) to **resist the effects of antibiotics** that were once effective against them. This means that the bacteria survive and continue to multiply despite the presence of the antibiotic, leading to infections that are harder to treat. **Causes of Antibiotic resistance:** - Genetic mutations - Ability to inactivate the antibiotic - Alteration of metabolic pathway - Preventing the entrance of an antibiotic - Overuse - Lack of compliance **Infectious Process Cycle** - The cycle involves the transmission of an infectious disease from a human/ animal/ environment to a susceptible host - Six components are needed: 1. **Infectious agent (can be opportunistic):** The **pathogen** (microorganism) that causes the infection. This can be bacteria, viruses, fungi, or parasites. 2. **Reservoir:** The **place** where the infectious agent normally lives, grows, and multiplies. 3. **Portal of exit:** The path by which the infectious agent leaves its host. 4. **Mode of transmission:** The **means by which the infectious agent is spread** to a new host. **Examples**: - **Direct Contact**: Physical contact with an infected person (e.g., touching, kissing). - **Indirect Contact**: Contact with contaminated surfaces (fomites) or objects. - **Droplet Transmission**: Pathogens spread via large respiratory droplets (e.g., coughing, sneezing). - **Airborne Transmission**: Small particles or droplets remain suspended in the air and can be inhaled (e.g., tuberculosis, measles). - **Vector-Borne Transmission**: Spread by insects like mosquitoes or ticks (e.g., malaria, Lyme disease). - **Water/Foodborne Transmission**: Ingesting contaminated food or water (e.g., salmonella, cholera). 5. **Portal of entry:** The site through which the infectious agent enters a new host. 6. **Susceptible host:** The person or animal who is vulnerable to infection, often due to factors that impair the body\'s immune system or defense mechanisms. **Pathogens Infectivity -** The capacity of the pathogen to cause disease is determined by: 1. **Communicability:** - **Definition**: The ability of a disease to **spread from one individual to another**. - **Explanation**: This refers to how easily a pathogen can be transmitted between hosts. Some diseases, like measles, have high communicability, while others are less easily spread. - **Example**: **Measles** is highly communicable because it can spread easily through respiratory droplets. 2. **Infectivity:** - **Definition:** The ability of a pathogen to **enter, survive, and multiply** in a host. - **Explanation:** This describes the capacity of an organism to infect a host and establish infection. Higher infectivity means it takes a smaller number of organisms to cause infection. - **Example:** Norovirus has high infectivity, as it only requires a small number of viral particles to cause an infection. 3. **Pathogenicity:** - **Definition**: The ability of a pathogen to **cause disease** in the host. - **Explanation**: This is a measure of the pathogen\'s ability to cause symptoms or illness after infecting a host. High pathogenicity means the organism is more likely to cause disease. - **Example**: **Rabies virus** has high pathogenicity because it almost always causes disease once a person is infected. 4. **Portal of entry:** - **Definition**: The route by which a pathogen **enters the body** of the host. - **Explanation**: Different pathogens use different portals of entry, such as through the respiratory tract, gastrointestinal tract, skin, or mucous membranes. - **Example**: The **respiratory tract** is the portal of entry for influenza viruses. 5. **Toxigenicity:** - **Definition**: The ability of a pathogen to **produce toxins** that contribute to disease. - **Explanation**: Some pathogens produce toxins that cause damage to the host, which can lead to illness. These toxins can disrupt normal cellular functions or kill cells directly. - **Example**: **Clostridium botulinum**, the bacterium that causes botulism, produces a potent neurotoxin that can lead to paralysis. 6. **Virulence:** - **Definition**: The degree of **severity of disease** caused by a pathogen. - **Explanation**: Virulence refers to how harmful or deadly a pathogen is once it infects a host. Highly virulent pathogens cause more severe illness or death, while less virulent organisms may result in mild or asymptomatic infections. - **Example**: **Ebola virus** is highly virulent, often causing severe hemorrhagic fever and a high mortality rate. **Pathogens mechanism of action to resist immune system** 1. **Destroy or block components of immune system:** - Production of toxins - Production of antioxidants - Production of surface molecules that can bind antibodies 2. **Mimic self-antigens** - When a pathogen or foreign substance mimics self-antigens by producing antigens that are similar to the body's own, this can lead to molecular mimicry, a phenomenon where the immune system mistakenly attacks the body's tissues. This misrecognition results in autoimmune reactions because the immune system can\'t distinguish between the pathogen\'s antigens and the body\'s own self-antigens. - When pathogens produce antigens that mimic self-antigens, it can trick the immune system into attacking the body\'s own cells. This leads to **autoimmune disorders** where the body's tissues are mistakenly targeted, causing inflammation, tissue damage, and various disease manifestations. Molecular mimicry is a critical factor in the development of many autoimmune conditions. 3. **Change antigenic profile** - When pathogens mutate their antigens and alter surface molecules, they can delay or escape immune recognition, leading to a prolonged or incomplete immune response. This mechanism helps pathogens evade immune surveillance, making it harder to develop long-term immunity or effective vaccines against them. This is why diseases like influenza, HIV, and malaria are particularly challenging to control. **Pathogens employ a variety of sophisticated strategies to avoid detection, destruction, or elimination by the immune system, enabling them to persist, replicate, and cause disease.** **Bacteria** - **One celled with a cell wall** - **Reproduce by cell division** - **Some are part of normal flora** - **Can survive outside of a host** - **Overgrowth can be harmful** - **Produce endotoxins and release exotoxins** - **Use adhesion through pili to attach to cells** - **Classified as:** - **Gram -- or gram +** - **Shape (morphology)** - **aerobic or anaerobic** - **Gram +** - Retains the gram stain - Cell wall contains certain amino acids - Wall gives strength & structure - Antibiotics target the cell wall - **Gram --** - Does not retain gram stain - Cell wall contains limited amino acids - Cell wall has a endotoxin layer protects bacteria from certain antibiotics **Exotoxins vs Endotoxins** - Produced by the bacteria to kill cells and disrupt tissue - Exotoxins: - Toxic molecules - Proteins released during bacterial growth - Damage cell membranes & inhibit cell protein synthesis - Specific to sites in the body ie) neurotoxins, enterotoxins - **Endotoxins** - Contained in the cell wall of gram -- bacteria - Released from the bacteria cell membrane during growth or when being treated with antibiotics causing lysis of the bacteria - Produce pyrogens stimulate the release of inflammatory mediators - **Produce fever and local and systemic effects of inflammation** - **Can cause septic shock and damage organs** **Bacteremia** is the presence of **bacteria in the bloodstream.** While the bloodstream is normally sterile, bacteria can enter it from infections in other parts of the body, such as the skin, lungs, urinary tract, or gastrointestinal system. Bacteremia can occur transiently (for a short period) or lead to more serious conditions if not cleared by the immune system. **Treatment:** - Antibiotics are typically used to treat bacteremia and prevent complications such as sepsis. Bacteremia can become serious if left untreated, so timely diagnosis and management are critical. **Septicemia**, often referred to as **blood poisoning**, is a serious and potentially life-threatening condition where **bacteria or their toxins** are present and multiplying in the bloodstream. It can result from infections that spread from other parts of the body, such as the lungs, urinary tract, or abdomen, and is a precursor to **sepsis**, a systemic inflammatory response that can lead to organ failure. **Treatment:** - Immediate treatment with broad-spectrum antibiotics, fluids, and other supportive care (like oxygen or vasopressors) is crucial to prevent the progression to sepsis and septic shock. Septicemia is a medical emergency requiring prompt attention to prevent severe complications and death. **Antimicrobial Mechanism of Action** - Inhibits production of bacterial cell wall or membrane - Inhibits protein synthesis - Blocking of DNA replication - Interferes with folic acid metabolism **Virus:** - Intracellular parasites containing DNA or RNA - Can be single-stranded or double stranded - Require a host to live - Can proliferate to tumors - Can directly kill the cell or modify cell functions - Produce virions - May be present and dormant - Attaches to target cell - Penetrates cell membrane - Uncoating to release nucleic acids - Replicating of viral RNA - Assembly of virions - Releasing of virions by lysis or budding - Host cell is destroyed in the process (cytopathic) **Viral Invasion & Evasion** - Successful viruses bypass the immune system through: - Rapid division - Intracellular survival - Antigenic variation - Neutralization - Complement evasion - Immune suppression **Outcome of virus on host cell** Viruses have a cytopathic effect on cells including: - inducing apoptosis - directly killing the cell - changing cell to a cancerous cell - changes cell so immune system sees it as foreign and attacks it **HIV** Blood borne pathogen transmitted via: - Blood or blood products - Sexual activity - IV drug use - Prenatal transfer **Acute HIV** Viral replication occurs - Primary infection flu like symptoms (non-specific) - Fever, night sweats - Swollen, tender lymph nodes (lymphadenopathy) - Headache - Joint pain - Sore throat - Fatigue