Pathophysiology Part 1 Lecture Notes PDF

Pathophysiology Part 1 Prof. George S. Shehatou  Lecture 1 Mechanisms of Pathogenesis How, when and why do body systems fail?  Pathophysiology Patho = Abnormal; disease Physiology = Function Science that study mechanisms of development of diseases  Factors that Con...

Pathophysiology Part 1 Prof. George S. Shehatou  Lecture 1 Mechanisms of Pathogenesis How, when and why do body systems fail?  Pathophysiology Patho = Abnormal; disease Physiology = Function Science that study mechanisms of development of diseases  Factors that Contribute to Disease Genes Nutrition Infection Injury and Toxicity Immune Dysfunction Neoplasia (cancer)  1- Genes A. Genetic diseases B. Genetic risk factors C. Gene – environment interactions 6  Remember! Shape of proteins gives rise to function. Small errors can result in dysfunctional proteins  In healthy cells, physiologic changes (inside your body) or environmental changes (outside your body) cause changes in gene expression to adapt to changing conditions. Example: When you have an infection, the genes for proteins that help you fight the infection are turned on.  What can go wrong? A- Genetic diseases Example: Sickle cell anemia caused by a mutation in hemoglobin gene A mutation is an error in the genetic code → incorrect form of the protein  Hemoglobin Protein in the RBC’s that contain iron and transport oxygen The change of a single base-pair causes one change in the amino acid sequence of the hemoglobin molecule Normal vs. Sickle Cell Hemoglobin  What else can go wrong? B. Genetic risk factors Certain genes increase risk of disease Eg: breast cancer runs in some families Some people are at high genetic risk for breast cancer. Environment and lifestyle may not make much difference in these cases. Genes may increase breast cancer risk but other factors are also involved  Breast Cancer Genes 35-85% of women With BRCA1 or BRCA2 mutations will have breast cancer  What else can go wrong? C- Gene-environment interactions Some genes can cause disease, but only under certain environmental conditions. Eg: Obesity and type II diabetes  Insulin is necessary to transport glucose from the blood into cells Type 1 diabetics: lack insulin Type 2 diabetics: are insulin resistant  Certain ethnic groups are at greater risk of type II diabetes. Eg: Pima Indians of North America Pima Indians appear to have genes that cause obesity, but only become obese in certain environments Pima Indians living in the US – Most are obese – 50% have type II diabetes, a common consequence of obesity. Pima Indians living a more traditional lifestyle in Mexico – Most are not obese – About 10% have diabetes  2- Malnutrition A diet too low or too high in calories. A diet deficient in essential nutrients. - Iron → needed for production of hemoglobin. - Iodine → needed for production of thyroid hormone. - Vitamins → act as co-factors in metabolic reactions Malnutrition weakens defenses against many kinds of diseases. 3- Inflammation 22  The inflammatory response Damaged tissue release histamine → dilate capillaries & ↑ permeability → leak fluid → swelling, redness, and heat. Increase blood supply → o WBCs (fight bacteria) o Platelets & clotting factors (clot formation). 23  Inflammation is characterized by swelling, redness, heat and pain due to: ↑ blood flow to affected area ↑ capillary permeability Movement of phagocytic cells into site of injury  Is inflammation a good thing or a bad thing? ▪ Good: Protect against infection Helps with tissue repair ▪ Bad: Causes pain Can damage healthy tissue Sometimes occurs in disease eg: allergy, autoimmune disease  Lecture 2 Mechanisms of Pathogenesis  Factors that Contribute to Disease ✓ Genes ✓ Nutrition Injury and Toxicity Infection Immune Dysfunction Neoplasia (cancer)  Injury and Toxicity Causes of Cell Injury 1- Trauma (e.g. car accidents) 2- Extremes of heat and cold 3- Electrical forces 4- Radiation 5- Exposure to toxic chemicals e.g. Air pollutants & smoking → lung injury e.g. Carbon tetrachloride → very toxic to liver cells. 4  Organs and tissues differ in their ability to stand/repair damage - Liver cells continue to divide all life (regenerate) → can repair mild to moderate damage - Nerve cells can not divide so nerve damage is usually permanent. 5  Biological Safety Factors (ratio of capacity to load) Organs differ in their capacity to deal with damage/load Pancreas (enzyme secretion) – About 10 Kidney (plasma filtration) – About 4 Lungs (aerobic capacity) – About 1.25 - 2  Cell Adaptation Cells adapt to change in their environment to protect themselves from injury and/or death Cells can adapt to stress to maintain normal function If adaptation is not effective → maladaptive changes, injury and cell death occur How do cells and tissues respond to injury, toxicity and stress? Adaptive Changes Normal Cell Injury or Tissue Maladaptive Changes (generally reversible) Irreversible Damage (cell death by necrosis)) Adaptive cell changes to stress may include change in cell size (hypertrophy and atrophy), number (hyperplasia) or cell type (metaplasia) 9  Atrophy ↓ in cell size due to ↓ in workload Atrophy can be caused by: 1- Disuse/ ↓ in skeletal muscle use e.g. Muscles encased in plaster casts. 2- Denervation atrophy e.g. muscles of paralyzed limbs. 3- ↓ endocrine stimulation e.g. Loss of estrogen stimulation during menopause  Hypertrophy ↑ in cell size due to ↑ in workload e.g. Cardiac and skeletal muscle cells → don’t divide → respond to ↑ load by hypertrophy Adaptive changes e.g. ↑ in muscle mass in response to exercise e.g. Weight-bearing exercise ↑ bone density  Maladaptive changes e.g. Cardiac hypertrophy Hypertension → hypertrophy of the heart → the heart become less effective in pumping blood. 12  Hyperplasia ↑ in cell numbers due to ↑ workload It occurs in cells that can divide such as the epidermis and glandular tissue e.g. Breast and uterine enlargement during pregnancy results from estrogen stimulation (the pregnant uterus undergoes both hypertrophy and hyperplasia) Maladaptive changes: Excessive estrogen production can cause endometrial hyperplasia and abnormal menstrual bleeding  Metaplasia Reversible conversion of one type of epithelial cell into another type of epithelial cell e.g. Cigarette smoking → Respiratory tract replacing damaged ciliated columnar epithelium with stratified squamous epithelium (lack cilia)  Cilia on the respiratory epithelium When exposed to cigarette smoke, this tissue adapts by producing epithelial cells that lack cilia. The cells are more likely to survive smoke exposure, but the person loses function (cilia helps carry mucus and trapped inhaled particles) out of the lungs.  Cellular Death Occurs when cells no longer adapt to the agents that injured them.  Apoptosis Programmed cell death (Cellular Suicide) It occurs as a part of normal development and maintenance of tissues, but can also occur during disease The processes of disposal of the cellular fragments occurs by phagocytosis of apoptoptic bodies→ does not cause inflammation  e.g. Developing human hand apoptosis During the formation of the digits, the tissue between the fingers and toes dies off by apoptosis  Necrosis Unregulated death of cells and living tissue due to injury or toxicity Unlike apoptosis, cells that die by necrosis may release harmful chemicals that damage other cells and causes inflammation How Cells Die Necrosis vs. Apoptosis  Necrosis vs Apoptosis Necrosis o Generally a pathological process o Causes inflammation Apoptosis o Often part of normal development o Does not cause inflammation Apoptosis can help in control of tissue damage e.g. Apoptosis of Irreversible Injured Cells during Ischemic Stroke.. Area of necrotic (dead) tissue Cells in the surrounding area are irreversibly damaged → Cells in this region often undergo apoptosis in the hours after the stroke. 24  Infection There are many kinds of infections (bacteria, fungi, viruses and parasites such as protozoa & helminths) The presence of these pathogens in our body activate the immune response to eliminate them There are 2 types of immune response 1-Non-specific immune response: rapid response o Local → inflammation o Systemic → fever 2-Specific immune response: slower response but more effective o B-lymphocytes produce antibodies which bind specifically to the pathogens moving in blood & facilitate phagocytosis o If the pathogen is intracellular (inside the cell), T-lymphocytes identify and kill infected body cells The damage from infection can result from: 1- Direct injury at site of infection 2- Toxins released by pathogens can enter circulation and cause systemic disease 3- They can stimulate a strong immune response in our body, that itself causes illness e.g. sepetic shock 4- Viruses insert their genes into host DNA→ changes in genes → development of cancer 26  Immune Dysfunction Autoimmune diseases The body is attacked by its own immune system Allergy The immune system of a susceptible person produce a specific immune response to a substance that is harmless to most people. 27  Autoimmune Diseases the body is attacked by its own immune system Common Allergens Allergen binds to IgE, which links to mast cells, triggering release of histamine.  Neoplasia New and abnormal growth of cells in a tissue or organ. Tumor May be benign or malignant ❑ A benign neoplasm grows slowly, and does not spread to distant sites. ❑ A malignant neoplasm (cancer) grows rapidly, and travels to surrounding tissue (metastasis)  The Development of Cancer Cancer starts by an event that causes genetic damage in a single cell e.g. Mutations in genes that regulate cell growth The development of cancer from a genetically damaged cell can be stimulated by various environmental and physiological conditions, including exposure to reproductive hormones. Some tumor cells have the ability to separate from the initial (primary) tumor, travels in the blood stream to distant tissues → produce new tumors (secondary tumors). This process is called metastasis.