module 1 review questions Flashcards
- What is meant by “disease”?
An organ/system no longer works properly
What three characteristics are associated with disease?
An associated cause, characteristic signs and symptoms, characteristic changes in the anatomy of the organ/system
Define cell injury.
When the cell can no longer maintain homeostasis
List and be familiar with examples of the 5 main categories by which cells can be injured.
- Physical agents: mechanical trauma
- Radiation: UV radiation
- Chemical agents: drugs
- Biological agents: viruses
- Nutritional imbalances: calorie malnutrition
Describe reactive oxygen species, how they are generated, what they can damage, and be familiar with examples of ROS’s.
Free radical injury can be induced by reactive oxygen species and reactive oxygen species are very reactive chemicals that contain oxygen. Generated: during ordinary reactions in metabolism, absorption of X-ray or UV, metabolism of drugs or released by phagocytosis. Damage: cell membranes and DNA. Examples: hydrogen peroxide
How does the body protect itself from ROS (2 ways)?
Enzymes that destroy these compounds (catalase) and antioxidants (vitamin E) also act to decrease effect
Describe the importance of calcium to cellular metabolism, how changes in intracellular calcium levels can injure a cell and one example of this effect.
Very important as a messenger within the cell, as it is used to initiate various important chemical reactions (muscle contraction; also plays part in cell movement, cell division & metabolism). Some conditions can lead to an increase in intracellular calcium, which may inappropriately activate some reactions within the cell, leading to injury. Example: proteases may destroy cell proteins
Outline two main categories of theory for the aging process (not required in depth).
- Programmed theories: changes that occur with aging are programmed genetically
- Damage theories: changes result from an accumulation of random events associated with damage to DNA
Describe the purposes of inflammation (3).
Limit damage, prevent infection, initiate and promote healing
Describe the classic characteristics of inflammation (5)
Redness, heat, swelling, pain and loss of function
Differentiate between acute and chronic inflammation (3 ways)
Acute: relatively short duration, has exudate, WBC present are mainly neutrophils
Chronic: long duration, has fibrosis instead of instead of exudate, WBC present are mainly lymphocytes and macrophages
Describe the cells involved in inflammation (7) (name and what they do).
- Endothelial: produce antiplatelet and antithrombotic agents
- Neutrophils: phagocytosis, produce ROS & proteases to kill bacteria, produce potent vasoactive mediators, cytokines & chemokines
- Macrophages: produce cytokines and chemokines to control inflammation, ingest larger volumes and more numerously than neutrophils, initiates and controls later healing
- Eosinophil: killing of antibody-coated parasites, important in hypersensitivity responses
- Basophils: release of histamine and other vasoactive cytokines
- Mast cell: granules immediately release histamine, synthesize & release compounds active in the inflammatory responses
- Platelets: produce numerous inflammatory mediators: chemokines, cytokines, vasoactive substances
Define PRR’s, PAMP’s and DAMP’s
Pattern recognition receptors: proteins capable of recognizing molecules frequently found in pathogens
PAMPs: general structures that typical pathogens have, that we don’t (flagella) and cells of the non-specific immune system become activated when these are detected
DAMPs: PRRs can recognize molecular patterns that wouldn’t normally be present in significant amounts outside of cells. If these are encountered outside of cells, there must de damage to cells
List, define, and describe the general action of the 3 key plasma protein systems of the chemical portion of inflammation.
Clotting proteins: cascade reactions that activate proteins already present in the blood, producing fibrin net that traps pathogens and forms a clot
Complement system: cascade reactions that activate proteins already present in the blood, which then either kill pathogens directly or intensify reactions of the inflammatory response (opsonization, cause mast cells to release histamine) = very potent defenders against bacterial infection
Kinin system: cascade reactions that activate proteins already present in the blood, which assist with inflammatory response (also dilate blood vessels, increase vessel permeability) major kinin is bradykinin, causes increased permeability later in inflammatory response and acts with other compounds to produce pain
What are 3 characteristics that make cytokines very complicated
Multiple sources – the same cytokine can be produced by many different types of cells (IL-1 can be produced by WBC, endothelial cells and fibroblasts)
Pleotrophic – the same cytokine can affect more than one type of cell (IL-2 can affect growth of T cells, B cells and natural killer cells)
Redundant – different cytokines can have the same effect (both IL-1 & TNF can induce fever)
Know one source and main effects of the following cell-produced chemicals: cytokines (specifically IL-1, TNF, IL-6, IL-8, TGF-beta), histamine, and prostaglandins and leukotrienes (are the PGs and LTs on the slide all bronchoconstrictors? Know that various PGs and LTs cause vasodilation, vasoconstriction and smooth muscle contraction – but you don’t have to know which ones do which),
IL-1: produced by tissue macrophages & helps neutrophils migrate to site of inflammation (promotes cell adhesion molecules on endothelial cells & causes increased permeability)
TNF: produced by macrophages & helps neutrophils migrate to site of inflammation (promotes cell adhesion molecules on endothelial cells & causes increased permeability)
IL-6: produced by macrophages & stimulates the liver to produce chemicals that induce the acute phase response
IL-8: produced by macrophages & potent neutrophil chemokine
TGF-beta: released by macrophages & platelets & attracts phagocytes and fibroblasts, very important in healing process
Histamine: premade and stored in mast cells, basophils, platelets & increases vascular dilation and permeability & bronchoconstriction
Arachidonic acid altered through reactions to produce prostaglandins and leukotrienes. Leukotrienes (LTC4, LTD4, LTE4): induces smooth muscle contraction & vasoconstriction in lungs. Prostaglandins (PDl2, PGF2a): induces vasodilation & bronchoconstriction
What is a chemokine? Name one chemokine.
A type of cytokine that functions mainly to induce WBC chemotaxis (e.g. IL-8
Define chemotaxis.
The movement of cells along a chemical gradient (biological molecules secreted by cells that act as attractants, to guide the migration of cells)
Describe the vascular response of acute inflammation and relate this to the classic characteristics.
Damage to tissue cells releases cytokines (e.g. IL-1, TNF) & chemokines (IL-8) into interstitial fluid
Mast cells become activated: by cytokines, bacterial PAMPs, other antigens, physical stress
Mast cells release histamine (vasodilation of blood vessels & increased permeability of capillaries (endothelial cells contract))
Fluid and blood proteins leak into interstitial fluid of tissues = edema
Edema and vasodilation = heat, swelling, redness, loss of function
Define exudates and describe the 3 functions of exudates.
The fluid that moves from the vessels into the tissues, combined with neutrophils and the debris from phagocytosis
Functions: transport of leukocytes & antibodies, dilution of toxins & irritating substances, transport of the nutrients necessary for tissue repair
Describe four types of exudate.
Serous: low protein content (blood vessels only slightly more permeable), similar to fluid under a blister (mild inflammation)
Fibrinous: greater injury, more inflammation and the vessels become more permeable, letting more proteins out into tissue. Fluid is sticky and thick and may have to be removed for healing
Purulent: “pus” - severe inflammation accompanied by infection = neutrophils, protein and tissue debris. Large pockets, abscesses, must usually be removed for healing to occur
Hemorrhagic: contains large amount of RBC. Occurs with severe inflammation (severe leakage or necrosis)
Describe the cellular phase of acute inflammation: invasion of tissues by leukocytes, including the terms “margination”, “chemotaxis” and “transmigration”
Leukocytes come into contact with inflammatory chemicals in the bloodstream at site of injury
They move to the periphery of the blood vessels (margination)
Endothelial cells develop adhesion molecules (e.g. selectins) on cell surface that bind to the leukocytes (tethering)
Meanwhile, the vessel walls have become more permeable as part of the inflammatory response
This allows the leukocytes to migrate out of the blood vessel in a process called transmigration
Chemicals released by cells in the injured area attract leukocytes (chemotaxis)
Leukocytes migrate over and phagocytose (ingest) foreign material (if damage is due to bacterial infection, a large number of leukocytes are involved; leukocytes + debris = pus)
Describe three causes for chronic inflammation.
Low grade, persistent infection (viral, tubercle bacillus)
Irritants that the body is unable to dispose of (talc, silica, asbestos)
Autoimmune in origin (rheumatoid arthritis)
Describe the development of general and granulomatous inflammation, and give an example of each.
General: because chemotaxis continues due to extended process, macrophages continue to arrive and they accumulate, this causes the arrival of fibroblasts, which then form scar tissue, scar tissue may replace normal tissue (e.g. chronic inflammation of the bowel)
Granulomatous:
Particles that are not easily removed by the immune response become surrounded by mass of macrophages and lymphocytes
Macrophages alter shape, resembling epithelial cells (“epithelioid cells”) that specialize in taking up debris
Macrophages also may coalesce into multinucleate “giant cells” that can engulf very large particles
Eventually that mass of cells is surrounded by connective tissue, and is called a granuloma
e.g. crohn’s disease
Describe the acute phase response and leukocytosis as systemic characteristics of inflammation.
Acute phase: release of IL-1, IL-6 & TNF-alpha can cause fever, increase in number of immature neutrophils, anorexia, malaise, increased production of “acute phase proteins”
Increase in neutrophils, increase in eosinophils, increase in lymphocytes
Describe two detrimental effects of inflammation.
Excessive swelling: with edema, blood flow to the area can decrease, and less fluid leave the vessels. If this is excessive, the nutrient supply to, and waste removal form, the cells may be decreased, harming cells
Phagocytes release lysozymes & ROS, which can harm nearby tissue cells (causing much of the damage associated with inflammation). The destructive effect of lysozymes can be minimized by natural inhibitors found in the blood
What is alpha1-antitrypsin and what is its effect?
A plasma protein produced by the liver & protects the body’s tissues from being damaged by infection-fighting agents released by its immune system
Describe the 3 phases of healing.
Phase I: inflammation:
Acute inflammation & last 1-2 days
Includes coagulation, and infiltration of cells that are involved in healing process:
Platelets are involved in producing blood clot, of which the fibrin net acts as a scaffold for cells that take part in healing process
Platelets also release growth factors
Macrophages release growth factors
Phase II: proliferation & new tissue formation
Begins 3-4 days after & continues as long as 2 weeks
Wound initially plugged by blood clot, which is broken down by enzymes either in clot or released by dead neutrophils
Macrophages clean up dissolved clot and release cytokines that attract fibroblasts to the area. Fibroblasts secrete collagen, growth factors that induce angiogenesis
Granulation tissue grows in from healthy connective tissue at the edges of the wound. Granulation tissue is red in colour, delicate, easily broken down
Epithelial tissue grows over the granulation tissue from all sides of the wound, eventually reaching the middle. The cells then begin to differentiate, forming the layers of the epidermis
Granulation tissue also contains myofibroblasts, which are responsible for wound contraction
Ends about 2 weeks after injury
Phase III: remodelling and maturation
Before the reconstructive phase ends, the maturation phase begins
During this phase, scar tissue is remodelled (the original collagen is broken down and a stronger type of collagen is built along the lines of stress to increase the strength of the scar), and capillaries shrink
Normally complete within 2 years
Distinguish between open and closed wounds.
Open: skin has been broken (cut, torn), underlying tissue is exposed
Closed: skin is intact (caused by blunt trauma), there is injury below the surface (producing a contusion, hematoma or crush injury)
Describe the differences in the wounds that require healing by primary vs. secondary intention (what is a clean incision?).
Primary intention: occurs with a clean incision (e.g. paper cut, stitched surgical incision), not much sealing is required (edges are either naturally close together or are held together by stitches
Secondary intention: greater loss of tissue and perhaps contamination (burns), requires a lot of sealing, filling in and contraction, slower and results in larger scar
Describe local problems of healing due to ischemia, blood clots, excessive fibrin, excessive collagen, excessive wound contraction and wound disruption. Know definitions of the terms: adhesion, keloid scarring, contracture, dehiscence.
Ischemia: decreased ATP & protein synthesis (e.g. collagen), this decreases wound strength, increases susceptibility to infection
Large blood clots: impedes formation of granulation tissue, decreases O2 diffusion, provides a culture medium for bacteria
Excessive fibrin: adhesions: fibrous bands of tissue that attach to internal organs. Typically occur with healing after surgery. May restrict normal movement
Excessive collagen: surface over healing, leading to keloid scarring (excessive scar that extends beyond wound boundaries)
Excessive contraction of wound: causing deformity, restricted movement (I.e. joints) = contracture
Wound disruption: in a sutured wound (dehiscence) in which the wound is pulled apart along the suture line
Describe common systemic problems of healing resulting from in particular: inadequate nutrition, diabetes mellitus (at this point, only know decreased circulation – we will cover the other reasons later, in the endocrine disorder module), medications and age.
Inadequate nutrients: chemotaxis, phagocytosis and protein production all require energy ATP and building materials (I.e. carbohydrates, proteins)
Diabetes mellitus: decreases capillary circulation, glycosylated hemoglobin occurs which decreases O2 release at tissues, decreases macrophage activation
Medications: corticosteroids, NSAIDs, anticancer drugs: all can delay healing process
Age: elderly – impaired immunity, decreases powers of tissue regeneration. Childrens: underdeveloped inflammatory/immune response
Define the terms: fistula and stricture.
Fistula: abnormal passageway between 2 structures that does not normally exist – through disease or surgery
Strictures: narrowing of passageway
Define the following terms: etiology, pathogenesis, prognosis, communicable disease, degenerative disease, idiopathic, iatrogenic, congenital, genetic, signs, symptoms, syndrome, local, systemic, acute, chronic, remission, exacerbation.
Etiology: the causation of the disease
Pathogenesis: manner of development of a disease
Prognosis: the course of the disease
Communicable disease: disease that can be passed from one individual to another
Degenerative disease: a disease where the function of the structure that is affected gets worse over time.
Idiopathic: disease of unknown origin.
Iatrogenic disease from receiving some sort of medical treatment.
Congenital: disease that is present from birth
Genetic: a disease that is passed through genes
Signs: manifestation of disease that the physician perceives
Symptoms: manifestation of disease that is perceived by the patient themselves
Syndrome: a group of symptoms that occur together
Local: changes within a limited area of host tissue (spots on leaf)
Systemic: changes within a larger area, most likely everywhere (plant wilting)
Acute: severe and sudden symptoms
Chronic: long developing syndrome
Remission: a temporary recovery
Exacerbation: acute increase in severity in syndrome
List, describe, and be familiar with examples of each of the 7 types of cell adaptation (atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, intracellular accumulations, calcification)
Atrophy: decrease in size, normal (thymus) or pathological (brain)
Hypertrophy: increase in size, normal or pathological (heart muscle doesn’t do mitosis so increase in size to be able to keep up with workload)
Hyperplasia: increase in the number of cells, found in cells that go through mitosis (normal - wound healing & pathological – warts)
Metaplasia: a change of cells to a form that does not normally occur in the tissue it is found (replacement of columnar ciliated cells along respiratory tract with stratified squamous epithelial cells, as a result of cigarette smoking.)
Dysplasia: the presence of abnormal cells in tissues, abnormal changes in size, shape and organization of mature cells. Rtae of mitosis often increased. Often found associated with cancerous cells in cervix, respiratory tract.
Intracellular accumulations: build up of material that the cells can’t metabolise, can be endogenous (normally produced substance produced faster than it is used, can be pigments as well: lipofuscin)
Calcification: build up of calcium salts in tissues (can happen in damaged tissue (Calcium comes from damaged/dead cells, as well as circulation. Serum levels of calcium are normal) and normal tissue due to excess serum calcium levels
List three mechanisms of cell injury. Then in more detail: a. Describe hypoxia and its causes. b. Differentiate between hypoxia and ischemia. c. Describe the mechanism whereby hypoxia leads to changes in cell membrane permeability
3 mechanisms of cell injury are hypoxia, reactive oxygen species, impaired calcium hemostasis
lack of sufficient oxygen delivery to cells due to loss of oxygen in air, loss of hemoglobin/RBC, some of the causes are heart conditions, and lung conditions like asthma and bronchitis
Ischemia is insufficient blood flow to a specific area due to narrowing arteries or sudden acute anoxia whereas hypoxia usually happens after ischemia, which is a lack of sufficient oxygen being delivered to cells
Hypoxia decreases amount of ATP that can be made. With less ATP, the sodium-potassium pump slows or ceases to function, the intracellular ion concentrations are altered, water enters the cell, the cell swells, and chemical changes occur that change permeability of the membrane
Differentiate between apoptosis and necrosis on the basis of number of cells affected, presence of inflammation, pathogenicity, energy requirement and overall process.
Necrosis: group of cells affected, inflammation is present, always pathogenic, no energy required, process: swelling of organelles, loss of functioning mitochondria, nucleus may shrink or fragment, rapid loss of plasma membrane structure
Apoptosis: programmed cell death, no inflammation, could be normal or pathogenic, energy required, process: nucleus self-destructs, cell shrinks, then fragments into membrane bound sacs, which are engulfed by macrophages
List and describe (causes, locations and appearance) of 7 types of necrosis (coagulative, liquefactive, caseous, fatty, and dry, wet and gas gangrene).
Coagulative necrosis: caused by hypoxia, location: kidneys, heart and adrenal glands, appearance: tissue becomes firm and opaque
Liquefactive necrosis: caused by ischemic injury, location: brain & infections, appearance: tissue soft and liquid
Caseous necrosis: caused by coagulative & liquefactive, location: lungs, appearance: tissues aren’t fully digested and appear soft and granular
Fatty necrosis: cause: Released lipases digest fat into glycerol and fatty acids which combine with ions like calcium in the tissue to make soap, location: breasts & pancreas, appearance: opaque and white
Dry gangrene: appearance: skin becomes dry, wrinkled and dark, with clear boundary, location: extremities, causes: Usually due to interference with arterial blood supply, coagulative necrosis
Wet gangrene: location: usually in internal organs, appearance: where area becomes cold, swollen and black, with a foul odour due to bacterial action, causes: liquefactive necrosis
Gas gangrene: specific condition caused by infection with a species of bacteria (Clostridium species); bacteria produce enzymes that destroy connective tissue and cause bubbles of gas to form
Differentiate between regeneration and replacement of tissues in the healing process.
Regeneration: injured tissues are returned to almost original structure and function (possible if damage is minor, no complications or infection occurs and tissue is capable of regeneration)
Replacement: replacement of destroyed tissue with scar tissue (occurs if damage is large, tissues are not capable of regeneration, infection or other complication occurs)
Define labile, stable and fixed tissues, and be familiar with the examples of each.
Labile: continually dividing. Epithelial tissue and bone marrow cells
Stable: normally stop dividing when growth ceases, but can regenerate if simulated. Liver, kidney, smooth muscle cells and vascular endothelial cells
Fixed: cannot regenerate – will be replaced with scar tissue, nerve cells, skeletal muscle cells, cardiac muscle cells
