pathophysiology class 1 cellular adaptation

Describe the mechanisms whereby physical agents such as mechanical forces, extremes of temperature, and electrical forces produce cell injury.

- Physical agents - disruption of the cell (Mechanical Forces, Motor vehicle accident, Temperature Extremes, Burns, frost bite, Heat stroke, Electrical Forces) - Radiation (Interferes with DNA synthesis and mitosis +Ionizing - Photons have enough energy to knock electrons off atoms and molecules +Ultraviolet (just above visible range) - Sunburns, microwaves +Nonionizing (just below visible range) -Chemical Injury - block enzyme pathways, disrupt osmotic pressure, Drugs Alcohol, prescription, OTC, +Lead (Example: Paint, dust, soil, pottery glazes, cosmetics) Via GI tract or lungs. More permeable BBB of infants and children make them more susceptible Preschool, before 1960, Interferes with enzymes necessary for hemoglobin formation. Damages nerves and neurotransmitters +Mercury - Fish, amalgams, vaccines, Can harm the nervous system -Biologic agents- Able to replicate and continue to produce injury , Human immune deficient disease, Viruses, Bacteria, Parasites -Nutritional imbalance - Dietary deficiency, Under nutrition, over nutrition, malnutrition, Dietary excess

Define neoplasm

- a new and abnormal growth of tissue in some part of the body, especially as a characteristic of cancer. - Disorder of altered cell differentiation & growth (neoplasia) - Growth is uncoordinated & relatively autonomous - Lack normal regulatory controls over cell growth and division - Tends to increase in size and growth after stimulus ceases or needs of the organism are met

Define intracellular accumulations Stressed cells may fill up with:

-Body substances (CHO, proteins, lipids, glycogen Pigments (bilirubin=icterus) Normal - lipids, proteins, carb, melanin, and bilirubin Abnormal - endogenous products - inborn errors of metabolism Exogenous - env, pigments not broken down by cells) -Exogenous products - some can be harmful and some cannot (Tattoos, lead, coal dust)

Describe the mechanisms of heat production

-Shivering (Hypothalamus impulse. General increase in muscle tone. Oscillating rhythmic tremor. Results in heat) -Physical exertion

Pyrexia (fever) stages

1- Prodromal Stage: Mild headache, fatique, aches, pains, malaise 2- Chill Stage: chilled, v/c, AV shunts close, sutis anserine, pale skin, shivering 3- Flush Stage: Vasodilation, AV shunts open 4- Defervescence Stage: Subsiding of the fever and sweating providing heat loss

Characterize the physiology of fever: Pathogenesis of Pyrexia (summary)

1-Exogenous pyrogen enters body 2-Interleukins released and travel to hypothalamus 3-Cyclooxygenase 2 (COX-2) converts arachidonic acid in wall of brain to prostaglandin E2 (PGE2) 4-Epinephrine release

State the five cardinal signs of acute inflammation, and describe the physiologic mechanisms involved in the production of these signs

5 signs - Redness (Rubor) and Heat (Calor) - Due to vasodilatation and increase rate of blood flow to the micro circulation - Swelling (Tumor) - due to vascular permeability that is increase and plasma fluids that will leak into the injured tissue - Pain (Dolor) - brought about by the pressure of fluids or swelling through the nerve endings. - Loss of function/ movement - brought by the swelling and pain.

When calcium is released into the cell, it:

Acts as a (troponin, calmdulin) transducers for cytosolic calcium signaling Acts as a second messenger inside the cell Turns on intercellular enzymes, some of which can damage the cell Can open more calcium "gates" in the cell membrane Letting in more calcium Calcium cascade

Contrast acute and chronic inflammation

Acute Phase Response onset: Fast - minutes or hours cellular response: mostly neutrophils tissue injury, fibrosis: usually mild and self-limited local and systemic signs: prominent 1-Leukocytes release interleukins and tumor necrosis factor and Affect thermoregulatory centre fever and Affect central nervous system lethargy 2-Liver makes fibrinogen and C-reactive protein (CRP) and Immediate and early response to an injurious agent and facilitate clotting - Binds to pathogens - Moderate inflammatory response Chronic onset: Slow- days cellular response: monocytes/macrophages and lymphoctes tissue injury, fibrosis: often severe and progressive local and systemic signs: less prominent may be subtle 1- Often begins insidiously, often asymptomatic (atherosclerosis, RA, inflammatory bowel disease) -Macrophages accumulate & release inflammatory mediators -Fibroblasts proliferate -Scar tissue forms --Macrophages mass around foreign bodies -Connective tissue surrounds & isolates the mass Causes -Foreign bodies - Eg. Asbestos, talc, surgical sutures -Viruses, bacteria, fungi, parasites Injured tissue -Eg. Around a healing fracture -Obesity - Adipose tissue source of inflammatory mediators (unclear)

State ways benign and malignant neoplasms differ in regards to their characteristics

Benign Neoplasm -Enclosed in a fibrous capsule -Grow by expansion (of capsule) Slow, progressive -Lost ability to control cell proliferation -Well-differentiated cells that resemble normal cells -Inability to metastasize to distant sites -Named by adding "oma" Malignant Neoplasm -No well-define capsule or margin -Lost ability to control both proliferation & differentiation -Better differentiation of the neoplasm = slower rate of growth -Invading/extension surrounding tissues -Crablike -Cause a release of toxins and enzymes -Ability to break loose -Solid tumors (confined to area or than spread) hematologic cancers (cells found in blood or lymph system)

Etiology

Cause of disease -Biological agents, bacteria, physical forces, chemical agents, nutritional excesses/deficits

Components of Tissue Renewal & Repair • Cell Proliferation • Cell Differentiation • Apoptosis

Cell Proliferation -Process of division -Adaptation mechanism for cell replacement Cell Differentiation -Process of specialization -Normal process whereby new cells acquire structure/function of cells they replace o Well-differentiated cells are benign Apoptosis -A form of programmed cell death to eliminate unwanted cells

Distinguish between cell proliferation and differentiation

Cell Proliferation Process of cell division is the process that results in an increase of the number of cells, and is defined by the balance between cell divisions and cell loss through cell death or differentiation. Cell proliferation is increased in tumours. Cell Differentiation Process specialization - new cells acquire the structural, microscopic, and functional characteristics of the cells they replace Normal process whereby new cells acquire structure/function of cells they replace Well-differentiated cells are benign or malignant

Conduction

Direct transfer of heat from one molecule to another Blood carries or conducts heat from the inner core of the body to the skin surface

Manifestations of Pyrexia

Fatigue Anorexia - Not eating Arthralgia -Joint pain or stiffness Myalgia -Pain in muscles

Describe the three major mechanisms whereby most injurious agents exert their effects.

Free radical formation - oxidation of cell structures and nuclear and mitochondrial DNA Hypoxia/ischemia - Blood flow to cells and organs that is not sufficient to maintain their normal function, combined with a lower-than-normal concentration of oxygen in arterial blood. High intracellular Ca - inappropriate activation of enzymes that damage cell organelles, cytoskeleton and cell membranes, hasten ATP depletion and fragment chromatin

Discuss the grading and staging of cancers

Grading (level of differentiation) 1-4 -Microscopic examination of cancer cells -Grade I: well differentiated -Grade IV: poorly differentiated with marked anaplasia Staging (extent and spread) 1-4 -Vary with organ, size of primary tumor, lymph node involvement, and metastasis I to IV

what kind of cells fall under each category Granulocytes and Agranulocytes

Granulocytes Neutrophils - response to bacteria Eosinophils - response to allergen, parasite, neoplasia Basophils - response to allergen, stress Mast cells - response to allergen Agranulocytes - Monocytes/Macrophages- a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection. Lymphocytes/Plasma cells (response to viral) - a form of small leukocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system.

what are the 2 sub categories of Leukocytes

Granulocytes - a white blood cell with secretory granules in its cytoplasm, e.g., an eosinophil or a basophil. Agranulocytes- white blood cells with a one-lobed nucleus. They are characterized by the absence of granules in their cytoplasm, which distinguishes them from granulocytes.

Describe the mechanisms of heat retention

Heat retention implies an artificial elevation of surface (skin) temperature and an elevation of the temperature of the deeper soft tissue of the body. At the same time heat retention relies on the prevention of vasoconstriction (or narrowing of the blood vessels) within the skin and deeper tissues, and the promotion of vasodilation (or opening) of the blood vessels within these tissues.

Convection

Heat transfer through the circulation of air currents Layer of warm air tends to remain near the bodys surface - continual removal of the warm layer and replacement with air from the surrounding env.

Explain how host factors such as heredity, levels of endogenous hormones, obesity, and immune system function increase the risk for development of selected cancers

Heredity -Basic inheritance - genetic predisposition for development of cancer = cancerous and precancerous lesions -Associated with ovarian, prostate, pancreatic, colon, and other cancers -One mutant gene and one normal gene - normal needs to be inactivate to develop cancer Hormones -For breast cancer, ovary, and endometrium in women and prostate and testis in men Obesity -Risk of breast, endometrial and prostate -Linked to insulin resistance and increase production of pancreatic insulin -Chronic inflammation and cytokines Immunologic mechanisms -Immune system plays a role against development of tumors -Development of cancer associated with impairment or decline in the surveillance capacity of the immune system

what is the outcome Increased intracellular calcium?

Increased ICF Ca+2 results from failure of energy dependent Ca+2-Mg+2 ATPase pump and is also related to increased membrane permeability. Sustained rise in intracellular Ca2+ This event is considered the initial step of irreversible injury. Sustained increased ICF Ca+2 leads to activation of intracellular self-destructive lysosomal enzymes that destroy the mitochondrial membrane, cellular membrane and other organelle membranes.

Describe the phases of the cell cycle

Cell cycle - Normally the number of cells produced = the number of cells that die The total number of cells in the body remains constant In cancer, growth fraction increase & doubling time decreases more on separate section in patho notes

what is intracellular calcium levels usually at?

Cell usually maintains low intracellular calcium

Describe cell changes that occur with dysplasia, and state general conditions under which these changes occur.

deranged cell growth of a specific cell tissue that vary in size, shape and organization chronic irritation and inflammation - Precursor of cancer

All mechanisms of cell injury (hypoxia, mechanical forces, extremes of temperature, electrical injuries, etc.) lead to irreversible cellular damage with cell destruction or death

false

Apoptic cell death and necrotic cell death are both pathologic forms of cell death that is unregulated and invariably injurious to the cell organism

false

Benign neoplasms are less differentiated tumors that grow in a crab-like manner to invade surrounding tissues, have cells that break loose and travel to distant sites to form metastases, and inevitably cause suffering and death unless their growth can be controlled through treatment

false

Erythrocytes (RBC) play a central role in the physiology of inflammation

false

Fever is a pathologic response to bacterial and viral infection and has no positive outcome on illness

false

Vasoconstriction occurs during the vascular stage of inflammation

false

Differentiate between the effects of ionizing and nonionizing radiation in terms of their ability to cause cell injury.

nonionizing radiation - cannot directly break chemical bonds bu exerts its effects by causing vibration and rotational energy = converted to thermal energy infrared light, ultrasound, mircowaves and laser energy eg. Microwave ionizing - directly break chemical bonds immediately kill cells, interrupt cell rep, of cause genetic mutations used for treating cancer

Rate of growth three factors:

number of cells that are actively dividing or moving through the cell cycle the duration of the cell cycle the number of cells that are being lost relative to the number of new cells being produced - C-cells cycle time is not ness

Use the concepts of growth fraction and doubling time to explain the growth of cancerous tissue.

the ratio of dividing cells to resting cells in a tissue mass is called the growth factor. the doubling time is the length of time it takes for the total mass of cells in a tumor to double. As the growth blood increases the doubling time decrease. when the normal tissues reach their adult size, and equilibrium between cell birth and cell death is reached. cancer cells continue to divide until limitations in blood supply and nutrients inhibit their growth - when this occurs the doubling time for cancer cells decrease

Acute inflammation is the immediate and early response to an injurious agent and occurs in two phases; the vascular phase and the cellular phase.

true

Cancer is a disorder of altered cell differentiation and growth

true

Cell differentiation is the process whereby proliferating cells are transformed into different and more specialized cell types.

true

Cells are able to adapt to changes in work demands or threats to survival by changing their size, number, and type

true

Chronic inflammation is self-perpetuating and may last for weeks, months, or even years

true

Prolonged exposure to cold increases blood viscosity and induces vasoconstriction

true

The Papanicolaou test is a cytologic method used to detect cancer cells

true

Describe cell changes that occur with atrophy and state general conditions under which these changes occur.

• Atrophy - decreased cell size - reduce oxygen consumption and other cellular functions by decrease number and size of organelles and other structures o Disuse o Denervation (Paralysis) o Loss of endocrine stimulation (Metaposil women) o Inadequate nutrition o Ischemia

Describe cell changes that occur with hypertrophy and state general conditions under which these changes occur.

• Hypertrophy - increase cell size = increase amount of functioning mass - increased work load Physiologic (Exercise) Non-physiologic (pathologic) -Adaptation : hypertension -Compensatory : enlargement to a organ of tissue to compensate for the loss

pathogenesis

• Sequence of cellular & tissue events from time of contact with etiological event until expression of disease

syndrome

• Symptoms (subjective information example pain, dizzy) & Signs (noted by the observer - increased temp, change in pupil size)

Define and describe typical clinical manifestation of cancer

Anemia - lack of RBC - May be related to blood loss, iron deficiency, hemolysis, impaired red cell production or treatment effects -Pt need transfusions -Reduce performance in life and in healing Anorexia & Cachexia -Weight loss and wasting of body fat and muscle tissue accompanied by weakness, anorexia and anemia -Persistent inflammation -Common except for some ca (eg. breast) Fatigue & Sleep disorders -Feelings of tiredness, weakness and lack of energy and is distinct from the normal tiredness -May be early symptom of malignant disease - 40% of pt. Related to anemia, hormonal changes Specific to area affected Paraneoplastic Syndromes -When cancer can produce manifestations in sites that are not directly affected by the disease -Caused by elaboration of hormones by cancer cells or because of circulating factors that produce hematopoietic, neurologic and dermatologic syndromes -Mostly w/ lungs, breasts and hematologic malignancies -Disease process (Cushings) or symptoms (hypercalcemia)

State the importance of angiogenesis in cancer growth and metastasis

Angiogenesis -Normal physiological process of growth, wound healing -New blood vessels form from pre-existing vessels -Also transition of benign state to malignant in tumor -Process is triggered and regulated by tumor-secreted growth factors

sequaelae

Are lesions or impairments that follow or that are caused by the disease

Relate the effects of environmental factors such as chemical carcinogens, radiation, and oncogenic viruses to the risk for cancer development

Chemical carcinogens -Direct - reacting agents - do not require activation in the body to become carcinogenic -Indirect - reacting agents called procarcinogens or initiators - Eg. cigs Radiation Ionizing radiation w/ atomic bombs - malignant epithliomas of skin and leukemia Sunlight & cancer - ultraviolet radiation emits relatively low-energy rays that do not deeply penetrate the skin Viral/Microbial Agents -Oncogenic virus = induce cancer -4 DNA virus implicated in human cancers 1- human papilloma virus (HPV) 2- espstein-barr virus (EBV) 3- hepatitis B virus (HBV) 4- human herpesvirus 8 (HHV-8)

Differentiate between body core temperature and skin temperature

Core body deep tissues of the body (36-37.5) -Reflection of the balance between heat gain and heat loss by the body -Intracranial, intraabdominal, intrathoracic -Time of the day (Highest in late afternoon and evening, Lowest in early morning) Skin (thermal control centre) Hypothalamus -Receives information from peripheral and central thermoreceptors and compares it with its temperature set point -Directs cooling or warming mechanisms -Body heat is generated in the tissues of the body, transferred to the skin surface by the blood, and then released into the environment surrounding the body

Tumour Cell Transformation

Initiation Cells exposed to doses of carcinogenic agent Promotion Unregulated accelerated growth in already initiated cells caused by various chemicals & growth factors Progression Tumor cells acquire malignant phenotypic changes Growth properties Proliferation and differentiation are associated with a number of growth and behavioral changes Normal cell = density-dependent inhibition (stop dividing when cell reaches right density) - malignant cells don't Cancer cells can have unlimited life span

Disease

Interruption, cessation, or disorder of a body system or organ structure that is characterized usually by a recognized etiologic agent or agents, an identifiable group of signs and symptoms, or consistent anatomic alterations

describe Hypoxia & ATP depletion/ Hypoxic Cell Injury

Interrupts metabolism and generation of ATP Depends on the body and where it happens in the body Damage in 4-6 minutes Atmospheric, respiratory disease, vasoconstriction, anemia, edema, etc. Causes a "power failure" in cell Cell "power failure" results in: -aerobic metabolism ceases -Cell reverts to anaerobic metabolism, using glycogen stores to maintain cell function -Lactic acid accumulates and cellular pH falls -Reduced ATP leaves Na in cell and less K = sodium and water accumulate in the cell (SWELLING) K higher in the cell and less outside = Na in the cell = swelling Reversed with oxygen inside the patient

state the mechanisms and manifestations of cell injury associated with lead poisoning.

Manifestations Acute encephalopathy Manifested by persistent vomiting, ataxia, seizures, papilledema, impaired consciousness, and coma Anemia is a cardinal sign of lead T Mechanisms of cell injury Env,(flaking paint, lead contaminated dust, soil, pottery, glazes, cosmetics, wild game) Ability to inactivate enzymes, complete with calcium for incorporation into bone and interfere with nerve transmission and brain development Major targets: RBC, GI, kidneys, and nervous system

Trace the pathway for the hematologic spread of a metastatic cancer cell

Metastasis is used to describe the development of a secondary tumor in a location distant from the primary location Maintain microscopic characteristics of the primary tumor Hematogenous spread Cancer cells commonly invade capillaries and venules - arterioles and arteries are usually resistant Venous invasion -C-cells follow the venous flow draining the site of the neoplasm & often stopping at the first cap bed -B/C venous blood from GI, spleen and pancreas goes to portal vein to liver and all vena caval to lungs... liver and lungs are freg metastatic sites for spread Distant & unrelated sites -Eg. Preostatic cancer goes to bone Tumour Growth - Direct invasion & extension and aided by enzyme secretion Seeding in body cavities Metastatic spread thru lymphatic or vascular pathways Metastatic tumors retain microscopic characteristics of primary tumor "Sentinel node" -is initial lymph node draining cancer cells

Sustained/Continuous fever

Never returns to normal but has minimal variations With persons with drug-induced fever typhoid fever

Remittent fever

Never returns to normal but varies

Intermittent fever

Normal temp at least once every 24 hours Associated with gram negative/positive sepsis, abscesses and acute bacterial endocarditis

Recurrent/Relapsing fever

One of more Episodes of fever with episodes of lasting long as several days with one or more days of normal temperature between episodes

All tumours (benign and malignant) are made up of:

Parenchymal Tissue: Cells of tumour, determining its growth Supporting Tissue: Connective tissue, extracellular matrix and blood vessels, essential to tumour growth as carries blood supply & provide support for parenchymal cells

Describe cell changes that occur with hyperplasia and state general conditions under which these changes occur.

Physiologic -Hormonal - hormonal enlargment -Compensatory-regeneration of the liver Non-physiologic (pathologic) -Excessive hormonal stimulation of growth factors

State how nutritional imbalances contribute to cell injury.

Predisposition cells to injury Obesity and diets high in sat fats are thought to predispose persons to atherosclerosis Lack of selective nutrient (amino acid, minerals, V, certain fatty acids) Iron-deficiency anemia, scurvy, beriberi, and pellagra = lack of specific V or M Protein and cal deficiencies occur in starvation = tissue damage

Differentiate reversible cell injury and cell death associated with apoptosis and necrosis.

Reversible Cell Injury -Cellular edema- Reversible when ATP pump reactivated -Fat accumulations -Usually d/t a disease process, Can be partially reversible in most cases Programmed Cell Death -Apoptosis (cell suicide)- Controlled cell destruction to remove/replace cells:In excess, Improperly development, Genetically damaged, Worn out, Damaged -Necrosis - Cell death and degradation, unregulated +Cells may undergo: Liquefaction, +Coagulation, infarction +Cell contents often released Inflammation often results

Name and describe the types of inflammatory exudates - 6

Serous - Watery fluid low on protien content Hemorrhagic - Serves tissue injury to blood vessels RBCs - Significant leakage of BC from the capillaries Fibrinous - Mesh work, Fibrinogen Membranous - Neurotic cells in fibropurulent exudate Purulent - Puss - white blood cells, tissue debris Sanguineous- red with fresh blood, thin sero-sangunieous - pink to light red, watery, thin

Pyrogen

Substance that produces a fever -Exogenous pyrogens: From outside the body, Bacterial products, bacterial toxins or whole MO, virus - Endogenous pyrogens: Phagocytosis or cell necrosis release fever-producing mediators

Cite the terminology for naming benign and malignant neoplasms

The origin of cancerous cells, where the disease of cancer begins, is called the primary tumor. Metastasis is the spread of cancer cells from one part of the body to another. The metastatic tumor contains cells that are like those in the original (primary) tumor and are therefore named accordingly. Those tumors that grow locally without invading adjacent tissues are classified as benign and those tumors that invade nearby tissues and result in metastasis are classified as malignant, and are again named accordingly.

Radiation

Transfer of heat through the air or a vacuum Heat loss varies with the temperature of the env.

Describe the mechanisms of heat loss

Transference of body core heat to surface Radiation - opening of AV shunts Allow the move of heat - open = lost - closed = contained Conduction - cooling blankets Move the heat to the surface Convection - air currents Evaporation - sweat, insensible perspiration Exhalation Urine/feces Heat edema Increased HR

Free radical injury - what is happening and how do you reverse it

Unpaired electron on outer orbit of molecule resulting in them being highly reactive React with proteins, lipids, CHO Damaging cell membranes Inactivating enzymes Damaging nucleic acids in DNA (Antioxidants neutralize free radicals) Vitamins A, C, E can reverse free radical injury

Evaporation

Use of body heat to convert water on the skin to vapor

Compare the vascular and cellular stages of the inflammatory response

Vascular Vasodilation causing increased blood flow Release of inflammatory mediators increase vascular permeability allowing plasma proteins to leave the circulation Causing redness and warmth Protein rich fluids - fluid from vascular to extravascular = cardinal signs Cellular Leukocytes (neutrophils) accumulate at injury/inflammation site 1-Margination and adhesion - Adhere to endothelium - Cytokines released 2-Transmigration - Move through the vessel wall to tissue 3-Chemotaxis - Are carried to site 4-Activation and phagocytosis - Recognition & adherence- Engulfment - Intracellular killing 5-White Blood Cell Response Inflammatory mediators cause WBC production, WBC count rises leading to leukocytosis Immature neutrophils released into blood- Bone marrow cant keep up with the neutrophils needed

Paraneoplastic Syndromes and explain its pathogenesis and manifestations

When cancer can produce manifestations in sites that are not directly affected by the disease -Caused by elaboration of hormones by cancer cells or because of circulating factors that produce hematopoietic, neurologic and dermatologic syndromes -Mostly w/ lungs, breasts and hematologic malignancies -Disease process (Cushings) or symptoms (hypercalcemia) Manifestations in sites not directly affected by cancer Often as a result of inappropriate hormone/cytokine release

Describe cell changes that occur with metaplasia and state general conditions under which these changes occur.

• reversible change in one adult cell (epithelial or mesenchymal) is replaced by another adult cell o Occurs in response to chronic irritation and inflammation and allows for substitution of cells that are better to survive under those circumstances o Chronic irritation -GERD - lower esophageal is weakend and the stomach acid comes up - squamus o Chronic inflammation

clinical manifestations

• signs and symptoms