HSS3305 Lecture 1-5 midterm 1 review

disease

disturbance of structure or function of the body; may be associated with defined, characteristic structural changes, lesions, present in organs and tissues

pathology

study of disease, pathologist- physician diagnoses and classifies diseases by examining morphology of cells and tissues

pathophysiology

Deranged function in an individual or an organ that is due to a disease. A pathophysiologic alteration is a change in function as distinguished from a structural defect.

pathogenesis

manner by which disease develops, pathogen - microorganism causes disease ie. Bacteria, virus

disease mechanisms

Underlying disease is specific pathophysiological mechanism(s). Can be identified by examining cells/cellular processes, may be a criteria to group or classify diseases

disease of cells

Concept that disease can be diagnosed by examining changes at cellular level.
Involves morphological changes (morphology -- Structure or architecture of a tissue or organ.) Cells attempt to adapt to stressors, become injured and die as disease progresses

Congential & Hereditary diseases

congenital: present since birth & hereditary: genetic, inherited but not necessarily congenital

inflammatory disease

inappropriate inflammatory reactions, autoimmune disease & infection (cell injury produces inflammatory response)

metabolic disease

dysregulation of metabolism & impaired energy production

neoplasm disease

irregular cell growth proliferation

degenerative disease

may be associated with aging process (joints, lumbar disc issues), abnormal degeneration occurs in advance of aging process

endocrine disease

inappropriate inflammatory relation & autoimmune disease

malnutrition disease

caused by deficiencies in nutrients/vitamins, or obesity

leading causes of death in Canada

-cancer
-heart disease
-stroke
-chronic lower resp. disease
-accidents
-diabetes

determinants of health

-Income & social status
-Social support networks
-Education & literacy
-Employment/working conditions
-Social environments
-Physical environments
-Personal health practices & coping skills
-Healthy child development
-Biology & genetic endowment
-Health services
-Gender
-Culture

disease manifestations

Symptoms (eg. weakness, pain) is subjective, where as signs/physical findings (eg. abnormal blood test) is objective

history of current illness

Severity, time of onset, and character of patient's symptoms

past medical history

other significant past illnesses, like high blood pressure, asthma, or diabetes

social history

a record of habits like smoking, drinking, drug abuse, and sexual practices that can impact health

invasive test

tests that invades body, may involve pain, discomfort, Example: endoscope, needles, catheters

non-invasive test

test with no risk or minimal risk to patient, Example: urinalysis, chest x-ray

clincal laboratory tests

tests used to evaluate constituents and concentrations of substances in blood, urine. Examples: urea, white blood cells, enzymes; Also used to evaluate organ function Example- urea, creatinine clearance- renal function; CO2, O2-pulmonary function, uptake/excretion of substances - liver function

microbiological tests

tests to detect presence of pathogens in urine, blood, feces

serologic tests

test to detect & measure the presence of antibodies

Tests of electrical activity

Test used to measure electrical impulses associated with bodily functions and activities; electrodes used to measure activity. Examples- electrocardiogram (ECG), electroencephalogram (EEG), electromyogram (EMG)

ultrasound

technique for mapping echoes produced by high-frequency sound waves transmitted into the body; echoes are reflected where there is a change in tissue density Examples: fetal development, structure, function of heart

x-ray

x-rays are passed through body, dense structures (bone) absorb rays=white. Structures containing air= black. Fat, muscle= shades of gray Examples: mammogram, angiogram/arteriogram

compute tomography (CT)

scan is performed by x-ray machine images of the body in cross- section by rotating the x-ray tube around the patient at various levels data is transmitted to a computer which reconstructs data into cross-sectional images useful for detection of abnormalities of internal organs

Magnetic resonance imaging (MRI)

Used to produce computer-constructed images of organs/tissues; device consists of strong magnet capable of developing a powerful magnetic field.
Advantages over CT: X-ray absorption from bone creates background, MRI- water content in bone is low, no background, grey/white matter of brain/spinal cord very different water content, good contrast

positron emission tomography (PET)

used to study body functions, a biochemical compound (glucose) labeled with positron-emitting isotope is injected distribution and metabolism of compound assessed by measuring radiation produced in the body by the labeled compound radiation output fed into computer that constructs images.

Cytologic & histologic examinations

examination of cells identified in fluid or secretions. Example: Papanicolaou smear "Pap smear" used to detect cervical cancer

biopsy

histologic examination of a small sample of tissue removed from affected tissue or organ, examination of tissue structure/cellular pattern

mammogram

an x-ray test that produces an image of the inner breast tissue on film. The American Cancer Society recommends women obtain first baseline mammogram between 35 to 40. After age 50, a mammogram should be repeated yearly.

effective screening

A significant number of persons must be at risk for the disease in the group being screened & a relatively inexpensive noninvasive test must be available to screen for the disease.

genetic screening

Tests to detect gene carriers of heritable genetic diseases are used to counsel prospective parents on the risk of transmitting the disease gene/allele to their offspring. Examples: cystic fibrosis, sickle cell anemia

amniocentesis

A diagnostic procedure performed by inserting a hollow needle through the abdominal wall into the uterus and withdrawing a small amount of fluid from the sac surrounding the fetus. Detect chromosomal disorders -- Down's syndrome, spina bifida, anencephaly and many rare, inherited metabolic disorders

phenotype

Biological trait not secondarily acquired. If transmissible between different generations, this is heritable, & likely to have a genetic basis called genotype

genotype

Genetic basis for a hereditary phenotype. Environment-gene interactions -- virus, ionizing radiation, epigenetics

Proteins

Macromolecules; constructed form one or more unbranched chains of amino acids. Every function in the living cell depend on these.

cell injury

appears to be the common denominator in almost all diseases. It is the change in cell structure or functioning in response to a stressor, cell is unable to compensate through normal physiological adaptive mechanism

cells response to stress

1. alter their structure &/or biochem processes in order to achieve a homeostasis (adaptation through changes in gene expression, metabolism & protein function)
2. or/if no adaptation, critical cell functions may be impaired & the cell is said to be injured
-determined by the severity of a stress & the duration of the cell's exposure to it

hypoxia

(a pathological stress) Depriving tissues of oxygen is a common mechanisms for cellular injury. Causes:
interrupted blood supply (ischemia), pulmonary disease or hypoventilation
heart failure, impaired oxygen carrying capacity of the blood (anemia, carbon monoxide poisoning, etc.).
It depletes cellular ATP and generates oxygen-derived free radicals

chemical injury

(a pathological stress) Number of chemicals, drugs (inorganic & organic) including byproducts of normal metabolism & toxins synthesized by microorganisms.
Two basic mechanisms:
(1) Direct injury from chemical;
(2) Parent compound is harmless, but metabolites are toxic; eg. Acetaminophen overdose is toxic to the liver

physical agents

(a pathological stress); common examples include:
Mechanical injury (crush injury, fractures, lacerations, hemorrhage), extremes of heat or cold, ionizing or non-ionizing radiation (x-rays, radioactive elements, ultraviolet radiation), electric shock, sudden changes in atmospheric pressure & noise trauma

infection

(a pathological stress); Exposure to pathogenic viruses, bacteria, fungi. Can cause injury by:
1. replicating inside host cells and disrupting the structural integrity of the cell (eg. herpes virus)
2. producing a toxin that is harmful to host cells (e.g., clostridia and diphtheria)
3. triggering an inflammatory or immune response that inadvertently injures host cells caught in the "cross fire" between the immune system and invading microorganism (e.g., TB)

immune reactions

(a pathological stress) Exaggerated immune reactions (anaphylaxis, allergy), or the inappropriate targeting of the body's own cells by the immune system (autoimmunity) can result in acute or chronic inflammation and cell injury.
Abnormal suppression of the immune system (drugs) can increase vulnerability to microbial invasion

nutritional imbalance

(a pathological stress) Deficiencies or excesses in normal cellular substrates (e.g., proteins, carbs, minerals, vitamins) can produce problems such as obesity, malnutrition, scurvy, iron deficiency anemia, etc.

genetic abnormalities

(a pathological stress); Inherited or acquired mutations in important genes can alter the synthesis of crucial cellular proteins leading to developmental defects, or abnormal metabolic functioning.
Acquired mutations to somatic cells during life can affect cell differentiation and replication leading to diseases such as cancer.

atrophy

A decrease in individual cell size due to lower rates of metabolism and decreased protein synthesis. May also involve a reduction in cell number (involution) via apoptosis. These cells have less structural proteins, fewer mitochondria & less ER. May occur due to pathological (eg. immobilization, loss of blood supply, etc.) or physiological conditions (eg. with age)

hypertrophy

An increase in tissue mass resulting from an increase in cell size rather than cell numbers due to accelerated synthesis of proteins and other structural components of the cell. May be caused by physiological (eg. increased functional demand) or pathological conditions (increased heart size due to hypertension).

hyperplasia

Increase in tissue mass due to an increased rate of cell division and cellular proliferation. Increase cell number, no change in cell size. Happens due to an increase in local production of growth factors and growth factor receptors on target cells, activation of intra-cellular signaling pathways, transcription factors turn on genes. May be caused by physiological (eg. hormone stimulation) or pathological conditions (eg. repetitive trauma)

metaplasia

Change from one type of cell to another type that is better able to tolerate adverse environmental condition; form of 'transdifferentiation', reversible. Abnormalities in morphology, cell #, cell maturity; considered a misalignment condition.

dysplasia

Disordered cellular morphology (size, shape, nuclear structure), organization, and function, loss of cellular differentiation. Always associated with a pathologic process & is considered a premalignant change, may arise subsequent to metaplasia. Mild/mod. may be reversible if removal of pathologic stimuli

genetic modulation

involves direct interaction of transcription factors & transcriptional co-activators with DNA

Epigenetic Modulation

involves the chemical modification of histones or methyl groups to facilitate or black access of transcriptional machinery to DNA

necrosis

The ultimate consequence of irreversible injury is cell death, is accompanied by inflammation and secondary injury to surrounding normal tissues. The structural changes that accompany result from two processes:
1.Enzymatic digestion of the cell by its own hydrolytic lysosomal enzymes
2.Denaturation and precipitation of cellular proteins (coagulation necrosis). Eg. gangrene

apoptosis

A normal physiologic process designed to eliminate unwanted, functionally abnormal, or senescent cells. Does not induce inflammation because: 1) absence of membrane lysis; 2) emission of signals at the surface allowing the phagocytosis of the apoptotic bodies. The key morphological changes are: 1)the formation of membrane blebs, 2)compaction and nuclear fragmentation, 3) permeabilization of mitochondrial membranes, 4) the formation of apoptotic bodies

autophagy

Typically induced by nutrient deprivation, the cell degrades its cellular constituents to provide essential elements for its survival (amino acids, nucleic acids, etc.). This process involves the formation of autophagosomes and their fusion with lysosomes. Can degrade small molecules or whole organelles. More of a "quality control" mechanism rather than a mechanism of cell death

non specific immunity

Inflammatory reaction, innate immunity & barrier immunity. Not antigen dependent, immediate response.

inflammatory reaction

nonspecific response to any harmful agent and includes phagocytosis of material by neutrophils and other macrophage

innate immunity

non-specific immunity, genetic basis

barrier immunity

non-specific immunity physical/chemical barriers to infection; tears, saliva, coughing, normal flora, skin oil residue, low ph of urine

specific immunity

Acquired immunity- immunity that develops after exposure to a specific agent (infection with pathogen). Response is antigen dependent, there is a lag time between exposure & response.

white blood cells (leukocytes)

-Monocytes/macrophages -phagocyte
-Neutrophils -both phagocyte/granulocyte
-Eosinophils -granulocyte (some phagocytic activity)
-Basophils-granulocyte
-Mast cells-granulocyte

phagocytes

The cells capable of ingesting particles larger than 1 μm. They include polynuclear leukocytes (Neutrophils, & eosinophils (weakly)) and macrophages. (the roombas of the immune system)

neutrophils

Constitute about 50% of the white blood cells in humans. Quickly recruited to areas of infection or inflammation. They phagocytose and destroy pathogens. In order to destroy foreign bodies, they use two routes: one associated with the release of granules (proteinase, cathepsin, elastase, lysosomes, etc.), the other dependent on the release of reactive oxygen species

monocytes

represent ~ 5% of the white blood cells. They migrate into tissues where they differentiate into macrophages & form a network of cells capable of phagocytosing pathogens.
Depending on the environment and the presence of particular cytokines, may acquire different phenotypes (M1 or M2). They will produce different cytokines and will be involved in distinct phases of inflammation.

eosinophils

Represent 1-3% of leukocytes. They pass from the blood into the tissues, especially the intestine and lung. They are an important source of leukotrienes and their numbers are increased in diseases such as allergy, asthma, in which they play a pro-inflammatory role.

basophils

Represent less than 1% of the white blood cells. They express the receptor for IgE and can therefore be activated by the allergens.

natural killer cells

Approximately 15% of lymphocytes. Kill by secretion of granzymes / perforin and interferon-gamma (IFN-γ) tumor or infected cells that no longer express MHC class I.

cytokines

Families of small proteins/lipids, generic term to refer to these signaling ligands. Bind to specific cytokine receptors on target cells. Key Functions; stimulate cell growth/ proliferation/ differentiation,
promote cell activation, recruit cells (chemotaxis) &
destroy target cells (trigger apoptosis)

Inferons

signals neighboring infected cells to destroy RNS & reduce protein synthesis, signals neighboring infected cells to undergo apoptosis, activates immune cells

cytokine receptor families

-Ig (Immunoglobulin) Type
single-pass transmembrane protein (Ligands: IL-1a, IL-18)
-TNFR Type; single-pass transmembrane proteins
(Ligands: TNFa, TNFb, TRAIL)
-CytokineR Type I; single-pass transmembrane proteins (Ligands: IL-2, IL-6, G-CSF, LIF)
-CytokineR Type II
single-pass transmembrane proteins (Ligands: IFNa, IFNb, IL-10)
-Chemokine R Type
Seven transmembrane domain proteins, G-protein coupled receptors
(Ligands: all known chemokines)

danger signal receptors

(Pattern Recognition Receptors); These are alarm receptors that will detect the presence of pathogens. They are also sensitive to cell damage indicators. Play a role in the activation of cells that have encountered a pathogen, induce the expression of several genes of the innate immune response. They are expressed almost quasi-ubiquitously in the body.
Ligand is the signal that is binding to the receptor
Properties of the PRR Families

complement

Series of proteins that work to "complement" the work of antibodies in destroying bacteria. At least 9 different proteins circulating in the blood in an inactive form (C1-C9). Small complement by-products (fragments) increase vascular permeability & participate in attracting WBCs into a site of inflammation.

granulocytes

WBC that contain granules filled with cytokines

inflammation

Essentially refer to the same phenomenon of the accumulation of fluid in the interstitial space, resulting in enlarged or engorged tissues. Inflammation as a physiological process, symptoms/signs: Pain, Redness, Swelling & Heat.
Can caused by things that are non penetrative, (eg. punch in the arm)

inflammation process

-immediate vasoconstriction of damaged vessels
-mediated release of thromboxane A2 & serotonin
-hemeostasis (clotting) at the site of vessel injury
-histamine release (vasodialator)
-dilation of blood vessels
-increased capillary permeability
-decreased velocity of blood flow
-[ ]of cells in the blood increases, RBC pack small vessels (RBC stasis) makes neutrophils stick to endothelium

leukocyte adhesion cascade

Sequence of adhesion and activation events that ends with extravasation of the leukocyte (from blood vessel to interstitial space). At least five steps of the cascade:
1.Capture
2.Rolling
3.Slow rolling
4.Firm adhesion
5.Transmigration

chemotaxis

directed migration through the tissue to the site of the inflammatory response

histamine

chemical mediator of inflammation with two major functions:
-Dilation of arterioles (vasodilation)
-Increased permeability in venules and capillaries.

serotonin

chemical mediator of inflammation; increases vascular permeability, vasoconstriction

prostaglandins

chemical mediator of inflammation; produce vasodilation and increased permeability.

leukotrienes

chemical mediator of inflammation; increase permeability & chemotactic activity (attracts leukocytes and other cells by chemical signal).

mast cells

granulocytes in connective tissue, contain histamine and other chemical mediators
Mast cells degranulate in response to:
1. Physical injury
2. Certain chemical agents
3. Immunological process - immune complexes, fragments of the complement system.

bradykinins

"Kinins"- group of mediators activated during inflammatory response.
Four functions:
1.Arteriolar dilatation,
2. Increased capillary/venule permeability,
3. Increased migration of white blood cells to site of injury, (chemotaxis),
4. Produce pain.

exudate

Fluid mixture of protein, leukocytes & debris that forms during inflammatory process

serous

primarily composed of fluid, large amount of fluid accumulation in injured skin may result in blisters (eg. burn)

fibrinous

consists of fibrinogen (sticky film). Adhesions: exudate between 2 surfaces in close proximity may cause surfaces to adhere

purulent

consists largely of inflammatory cells (pus)

hemorrhagic

inflammatory process ruptured small capillaries, producing bloody exudate

wound repair

Dead cellular material & debris are removed by phagocytosis (mainly by macrophages/monocytes). Regeneration (Endothelial cells grow into the damaged area form new capillary network). Repair (fibroblasts migrate to damaged area & form granulation tissue. Epitheliazation (covering of a surface by the development of epithelial tissue). Wound contraction & remodeling

angiogenesis

Formation of new blood vessels. Mediated by VEGF (vascular endothelial growth factor)

Contracture Scar

burns; skin retracts & shrinks

hypertrophic scar

scar with too much collagen; stays within wound boundary

keloid scar

scar that is raised, with too much collagen; extend beyond wound boundary

antigen

any substance capable of triggering an immune response; Examples: Pathogens (whole organism or parts), pathogenic products (toxins), foreign cells (tissue transplant, blood transfusion) & altered host cells (cancer cells, virus infected cells)

epitopes

also called antigenic determinant. Characteristic, unique part of antigen; usually few amino acids or carbohydrate residues
Specialized section of the antigen which will interact with immune system components (B cells, T cells & antibodies)

cell mediated immunity

Specific immunity produced by t-cells (helper, cytotoxic, memory); characterized by formation of population of lymphocytes that can attack and destroy foreign material
main defense against viruses, fungi, parasites and some bacteria. Also mechanism by which body rejects transplanted organs& eliminate abnormal cells within body.

humoral immunity

Specific immunity produced by B cells that produce antibodies that circulate in body fluids. Major defense against many bacteria and bacterial toxins.