OCC 2005 Lecture 2 Cell & Infections - Essential Pathophysiology for OT

School of Medical and Health Sciences By Michael KUO, PhD │ Essential Pathophysiology for OT│ Cell, Homeostasis, and Disease Infection & Immunity Prepared by Michael KUO AP/MHS/TWC A...

School of Medical and Health Sciences By Michael KUO, PhD │ Essential Pathophysiology for OT│ Cell, Homeostasis, and Disease Infection & Immunity Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 1  OCC 2005 Essential Pathophysiology for OT Learning outcomes To understand cell parts and their functions, tissues types, and cell changes. To describe body’s mechanisms to keep the cells in a constant environment. To understand the pathogens and processes of infections and its relationships with immunity. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 2  OCC 2005 Essential Pathophysiology for OT Overview Cells Tissues Homeostasis Infection/immunity Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 4  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 5  OCC 2005 Essential Pathophysiology for OT Boundary – Cell membrane Composed of lipid molecules in bilayer Also contains embedded proteins important for cell-cell communication: receptors for hormones & cell recognition also important for metabolic processes inside the cell: channels, pumps, enzymes Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 6  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 7  OCC 2005 Essential Pathophysiology for OT Cytoplasm Cytosol – aqueous gel-like medium Organelles – membrane bound structures Membranes provide compartments for separation of chemical reactions Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 8  OCC 2005 Essential Pathophysiology for OT Nucleus DNA codes for proteins Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 9  OCC 2005 Essential Pathophysiology for OT Mitochondria Smooth ER synthesizes The cell’s power plant phospholipids detoxifies Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 10  OCC 2005 Essential Pathophysiology for OT Rough Endoplasmic Reticulum Contains ribosomes – make proteins Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 11  OCC 2005 Essential Pathophysiology for OT Golgi Apparatus Packages protein for export Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 13  OCC 2005 Essential Pathophysiology for OT Inclusions filaments – cytoskeleton – protein strands other molecules without membranes: melanin lipids Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 14  OCC 2005 Essential Pathophysiology for OT Tissues Made up of cells with common function Four major tissue types: 1. Epithelial covering and lining interacts with the body’s environment glandular tissue Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 15  OCC 2005 Essential Pathophysiology for OT 2. Connective tissue Important to structure, support and protection 3. Nervous tissue Made up of neurons and supporting (glial) cells receives info from outside (or inside) the body processes information acts on the information through muscles, glands, etc. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 16  OCC 2005 Essential Pathophysiology for OT 4. Muscle Important to movement Three types Skeletal Smooth Cardiac Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 17  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 18  OCC 2005 Essential Pathophysiology for OT Cells change to adapt to their environment A_____= shrinkage = decrease in cell size. Due to : decreased use decreased blood supply decreased nutrition H_____= increase in cell size We'll see this in heart, kidney (and others) w/ pathology NOT due to increased cell volume or fluid Due to increased protein synthesis within the cell, or decreased protein breakdown Result is increased protein in organelles Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 19  OCC 2005 Essential Pathophysiology for OT H_____= increase in cell number Due to increased cell division Parathyroid gland in kidney failure Liver M_____= replacement of one cell type with another Reversible example: ciliated columnar epithelium replaced by stratified squamous epithelium Dysplasia = change in cell resulting in abnormal cell size, shape or organization We'll see this in respiratory tract, cervix w/ pathology In mature cells only Immature cells would be expected to change in size, shape as they grow and mature Considered a reversible change Neoplasia = associated with a malignant tumor Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 20  OCC 2005 Essential Pathophysiology for OT Cellular injury cell unable to maintain homeostasis Causes of cell injury: Deficiency – lack of a substance necessary to the cell Intoxication or poisoning – presence of a toxin or substance that interferes with cell functioning Trauma – physical injury and loss of cell’s structural integrity Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 21  OCC 2005 Essential Pathophysiology for OT Deficiencies Deficiency in oxygen most important Hypoxia = deficiency in oxygen at cell Due to decreased: oxygen in air hemoglobin oxygen transported to cells or diseases of the respiratory and/or cardiovascular system Why is this important? Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 22  OCC 2005 Essential Pathophysiology for OT Ischemia is inadequate blood supply to a cell or tissue. Ischemia can cause hypoxia. Intoxication Effect on cell depends on toxin and on cell Lead -- injures nervous system CO -- deprives body of oxygen Ethanol -- effects central nervous system Trauma -- physical disruption of cells abrasion, cutting, burns, microorganisms etc. Cell injury can have effects on the entire body fever, pain, increased heart rate Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 23  OCC 2005 Essential Pathophysiology for OT Apoptosis 細胞自毀 “fallen apart” Regulated cell death Worn out cells Diseased cells Necrosis 壞死 Messy cell death Gangrene – large mass of tissue undergoes necrosis Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 24  OCC 2005 Essential Pathophysiology for OT What is Homeostasis? Body cells work best if they have the correct Temperature Water levels Glucose concentration Your body has mechanisms to keep the cells in a constant environment. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 26  OCC 2005 Essential Pathophysiology for OT Controlling body temperature All mammals maintain a constant body temperature. Human beings have a body temperature of about 37ºC. Sweating Vasodilation Vasoconstriction Piloerection Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 27  OCC 2005 Essential Pathophysiology for OT Controlling Glucose levels Your cells also need an exact level of glucose in the blood. Excess glucose gets turned into glycogen in the liver. This is regulated by 2 hormones (chemicals) from the pancreas called: Insulin Glucagon Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 37  OCC 2005 Essential Pathophysiology for OT Diabetes Some people do not produce enough insulin. When they eat food, the glucose levels in their blood cannot be reduced. This condition is known as DIABETES. Diabetics sometimes have to inject insulin into their blood. They have to be careful of their diet. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 40  OCC 2005 Essential Pathophysiology for OT Controlling water levels The control of water levels is carried out by the KIDNEYS. It is closely linked to the excretion of urea. Urea is a waste product that is made when the LIVER breaks down proteins that are not needed by the body. Urea contains the element Nitrogen. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 43  OCC 2005 Essential Pathophysiology for OT The kidneys The kidneys “clean” the blood of waste Glucose: products and control how much water Ions: is kept in the body. The waste Water: Urea: products and water make up urine which is excreted via the ureter. “Dirty” blood enters the kidney through the renal artery. Then, several things happen to clean the blood... Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 45  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 46  OCC 2005 Essential Pathophysiology for OT Reabsorbing water If you have too If you have too little water in your much water in your blood, you will blood, you will produce very produce very dilute concentrated urine. urine. (very little water in (lots of water in it) it) Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 53  OCC 2005 Essential Pathophysiology for OT Assessment of Renal Function Glomerular Filtration Rate (GFR) = the volume of water filtered from the plasma per unit of time. Gives a rough measure of the number of functioning nephrons Normal GFR: Men: 130 mL/min./1.73m2 Women: 120 mL/min./1.73m2 Cannot be measured directly, so we use creatinine and creatinine clearance to estimate. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 56  OCC 2005 Essential Pathophysiology for OT Acute vs Chronic kidney disease Acute sudden onset rapid reduction in urine output usually reversible tubular cell death and regeneration Chronic progressive not reversible nephron loss 75% of function can be lost before its noticeable Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 59  OCC 2005 Essential Pathophysiology for OT Chronic Kidney Disease = a GFR of < 60 for 3 months or more. Most common causes: Diabetes Mellitus Hypertension Symptoms: Malaise, weakness, fatigue, CHF, anorexia, nausea, vomiting Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 60  OCC 2005 Essential Pathophysiology for OT ½ of patients with Management CRF eventually Blood pressure require dialysis control! Diffuse harmful Diabetic control! waste out of body Smoking cessation Control BP Dietary protein Keep safe level of restriction chemicals in body Dialysis? Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 61  OCC 2005 Essential Pathophysiology for OT Temporary Catheter, AV Fistula & Graft Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 62  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 63  OCC 2005 Essential Pathophysiology for OT INFECTION AND IMMUNITY Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 64  OCC 2005 Essential Pathophysiology for OT What is an Infection? A harmful invasion and spread of foreign species, or pathogen, in a host. VIRUS Small pox, measles, influenza, Ebola PRIONS Cow’s disease BACTERIA Tuberculosis, pneumonia, salmonella, anthrax FUNGUS Athlete’s foot, ring worm PROTISTS Malaria, toxoplasmosis, Algae Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 65  OCC 2005 Essential Pathophysiology for OT Pathogens are microorganisms that cause disease. A host is any organism that is capable of supporting the nutritional and physical growth requirements of another organism. Infection is the presence and multiplication of a parasitic organism in the host. Treatment depends on the microorganism Prokaryote vs. eukaryote vs. virus Resistance to antibiotics Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 66  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 67  OCC 2005 Essential Pathophysiology for OT No. of Notifications for Notifiable Infectious Diseases https://www.chp.gov.hk/en/statistics/data/10/26/43/6940.html Cholera 38 Meningococcal infections 10 Plague 0 Mumps 76 Yellow fever 0 Paratyphoid fever 21 Acute poliomyelitis 0 Rabies (Human) 1 Amoebic dysentery 7 Relapsing fever 0 Bacillary dysentery 389 Rubella 57 Chickenpox 16,501 Scarlet fever 147 Dengue fever 17 Tetanus 4 Diphtheria 0 Tuberculosis 7,262 Food poisoning (outbreaks) 672 Typhoid fever 67 Food poisoning (affected) 2,709 Typhus fever 7 Legionnaires’ Disease 3 Viral hepatitis A 482 Leprosy 10 Viral hepatitis B 125 Malaria 47 Non-A, non-B hepatitis 39 Measles 182 Unclassified hepatitis 33 Total 26,212 Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 68  OCC 2005 Essential Pathophysiology for OT A couple of points to note Not all interactions between bacteria and humans are harmful – normal microbiota prevents the growth of pathogens. Most microorganisms can be opportunistic pathogens which can cause disease if the host is immunocompromised or if they can enter the body in a place where they are not normally found. ( E. coli UTI) Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 69  OCC 2005 Essential Pathophysiology for OT Prions Infectious proteins Improperly folded proteins that cause other proteins to take on that shape Extremely difficult to destroy Transmissible spongiform encephalopathies Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 70  OCC 2005 Essential Pathophysiology for OT Bacteria Prokaryotes Lack a nucleus and membrane-bound organelles Structurally simple but metabolically complex Contain both DNA and RNA Single circular chromosome Plasmids : extrachromosomal DNA that provides information (antibiotic resistance) that can be shared with other bacteria. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 71  OCC 2005 Essential Pathophysiology for OT Virulence factors Exotoxins proteins released from a bacterial cell enzymes that lead to cell death or dysfunction Endotoxins complex molecules made of lipid and polysaccharides found in the cell wall. Usually released when the cell is killed. can cause clotting, bleeding, inflammation, hypotension and fever. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 72  OCC 2005 Essential Pathophysiology for OT Viral Infection Viruses extremely small – can infect bacteria Usually just composed of DNA (or RNA) + protein “coat” or capsid Can’t reproduce on their own – need to use a host cell Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 73  OCC 2005 Essential Pathophysiology for OT Infection Adsorbed to host cell receptor Penetration Coat removal Uses host enzymes to replicate nucleic acid and proteins New viruses are assembled Virus is released Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 74  OCC 2005 Essential Pathophysiology for OT Spread of Disease & Transmission Infection in one person can be transmitted to others T S Susceptible P S Immune S T Sub-clinical Clinical Cases ❖ Patient “Zero” – the first case identified ❖ Primary – the case that brings the infection into a population ❖ Secondary – infected by a primary case ❖ Tertiary – infected by a secondary case Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 77  OCC 2005 Essential Pathophysiology for OT Transmission of Pathogens Direct contact Indirect contacts Air Objects Vectors Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 78  OCC 2005 Essential Pathophysiology for OT Routes of transmission Direct Indirect ❖ Skin-skin ❖ Food-borne ❖ Herpes type 1 ❖ Salmonella ❖ Mucous-mucous ❖ Water-borne ❖ Sexually transmitted infections ❖ Hepatitis A ❖ Across placenta ❖ Air-borne ❖ toxoplasmosis ❖ Chickenpox ❖ Through breast milk ❖ HIV ❖ Sneeze-cough (droplet) ❖ Influenza Vector ❖ A carrier of an infectious agent ❖Ex. Malaria parasite carried by Mosquito Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 79  OCC 2005 Essential Pathophysiology for OT Diagnosis Medical history and physical examination Detailed identification techniques involve the culture of infectious agents isolated from a patient. X-rays, CAT scans, PET scans or MRI are used to produce images of internal abnormalities resulting from the growth of an infectious agent. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 80  OCC 2005 Essential Pathophysiology for OT Disease: Fighting it IMMUNE RESPONSE NON-SPECIFIC SPECIFIC ACTIVE IMMUNITY Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 81  OCC 2005 Essential Pathophysiology for OT Immunity: Non-specific defenses FIRST LINE OF DEFENSE SKIN - MOST IMPORTANT PATHOGENS CANNOT PENETRATE WHEN BROKEN, OPENS BODY TO INFECTION MUCUS TRAP BACTERIA IN NOSE AND MOUTH DIGESTIVE SECRETIONS ACID AND ENZYMES CAN DESTROY PATHOGENS Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 82  OCC 2005 Essential Pathophysiology for OT Immunity: Non-Specific Defenses SECOND LINE OF DEFENSE (INFLAMMATION) BLOOD VESSELS AROUND WOUND SWELL AND RELEASE WBC’S (PHAGOCYTES) FEVERS ARE ALSO PART OF THIS RESPONSE Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 83  OCC 2005 Essential Pathophysiology for OT Immunity: Specific Defense RESPONSE TRIGGERED BY AN ANTIGEN: ORGANIC MATERIALS ON SURFACE OF PATHOGENS THAT BODY DOES NOT RECOGNIZE 3 Types of Specific Defense: Humoral Immunity Cell Mediated Immunity Permanent Immunity Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 84  OCC 2005 Essential Pathophysiology for OT Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 85  OCC 2005 Essential Pathophysiology for OT If body defense fails, ANTIBIOTICS KILL BACTERIA WITHOUT HARMING THE CELLS OF ANIMALS SOME CAN DESTROY THE CELL WALLS OF BACTERIA SO THEY DIE. EXAMPLE IS PENICILLIN ANTIVIRALS PREVENT VIRUSES FROM INVADING CELLS AND THEN MULTIPLYING (Tamiflu) Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 89  OCC 2005 Essential Pathophysiology for OT Allergies IS AN OVERREACTION OF THE IMMUNE SYSTEM OCCURS WHEN ANTIGENS FROM ALLERGENS (POLLEN, PET DANDER, ETC) ATTACH TO MAST CELLS THIS IN TURN TRIGGERS HISTAMINES THESE PRODUCE SNEEZING, RUNNY NOSE AND EYES ETC…. Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 90  OCC 2005 Essential Pathophysiology for OT Autoimmune Disorders WHEN THE IMMUNE SYSTEM MAKES A MISTAKE AND ATTACKS ITS OWN BODY CELLS CAN BE THE RESULT OF AN INFECTION EXAMPLES OF AUTOIMMUNE DISEASES JUVENILE DIABETES (Type 1) MULTIPLE SCLEROSIS (MS) Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 91  OCC 2005 Essential Pathophysiology for OT AIDS ACQUIRED IMMUNE DEFICIENCY SYNDROME WHAT CAUSES AIDS? CAUSED BY THE HIV VIRUS (Human Immunodificiency Virus) HIV INFECTS HELPER T-CELLS OF IMMUNE SYSTEM AND DESTROYS THEM PERSON CAN BE INFECTED W/ HIV FOR YEARS AND NOT KNOW IT WHEN T-CELL COUNT IS LOW ENOUGH, FULL-BLOWN AIDS IS DECLARED Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 92  OCC 2005 Essential Pathophysiology for OT ABCESS 膿腫 IT IS A LOCALISED COLLECTION OF SUPPURATIVE INFECTION CAUSING SWELLING AND INFLAMMATION MRSA: methicillin-resistant Staphylococcus aureus MAY PRESENT AS SUPERFICIAL OR DEEP MANAGEMENT: ANTIBIOTICS, DRAINAGE UNDER GUIDANCE (U/S, MRI,CT) Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 93  OCC 2005 Essential Pathophysiology for OT CELLULITIS CELLULITIS IS NON SUPPURATIVE INVASIVE INFECTION OF TISSUES Beta HAEMOLYTIC STREPTOCOCCI CLINICAL FEATURES: FEVER, CHILLS, TACHYCARDIA, TACHYPNOEA MANAGEMENT: BROAD SPECTRUM ANTIBOTICS Prepared by Michael KUO AP/MHS/TWC All Rights Reserved 94