Cell Injury Mechanisms

Introduction to Pathophysiology

• Pathophysiology studies the functional and physiological changes in the body due to disease processes.
• Disease is a deviation from the normal structure or function of a body part, organ, or system, or a deviation from a state of well-being that develops when homeostasis cannot be maintained without intervention.

Implications for Licensed Practical Nurses (LPNs)

• Need to stay informed about new information, research, diagnostic tests, and therapies.
• Understanding pathology aids in informed clinical decision-making, assessment, planning, and promptly implementing care.
• Patient education on treatment options, managing conditions, and lifestyle modifications is important

Terms to Characterize a Disease

• Pathogenesis: development sequence of events involved in the tissue changes associated with the disease process.
• Onset of disease:
  • Acute: sudden and obvious onset.
  • Insidious: gradual progression with vague and mild signs.
• Acute disease: short-term illness that develops quickly with marked signs such as fever or severe pain.
• Chronic disease: persists over a longer time, often milder, and gradually develops, and often causes permanent tissue damage.
• Subclinical state: pathological changes occur without obvious signs or manifestations due to reserve capacities of some organs.
• Latent stage: "silent" stage; clinical signs are evident, and may be referred to as the "incubation period" in infectious diseases.
• Incubation period: time between exposure to the microorganism and the first appearance of signs and symptoms; can last for one day or prolonged for days or weeks; disease may be communicable (infectious) during this period.
• Prodromal period: early development of disease; changes are occurring in the body, but the signs are non-specific
• Manifestations of disease: clinical evidence/effects, signs and symptoms of disease; may be local or systemic.
• Signs: objective indicators of disease that are obvious and observable; may be local or systemic.
• Symptoms: subjective feelings or statements made by the affected individual.
• Lesion: describes a specific local change in the tissue; microscopic or highly visible.
• Syndrome: collection of signs and symptoms often affecting more than one organ, and occurs together in response to a certain condition.
• Diagnostic tests: lab tests that assist in diagnosing a specific disease; may be used for monitoring the response to treatment or disease progression.
• Remission: period or condition in which the manifestations of the disease subside (permanently or temporarily).
• Exacerbation: worsening in the severity of the disease, or in its signs and symptoms.
• Precipitating factor: conditions that trigger an acute episode.
• Therapy: therapeutic interventions; treatment measures are used to promote recovery or slow the progress of the disease.
• Sequelae: potential unwanted outcomes of the primary condition.
• Convalescence/rehabilitation: the period of recovery and return to a normal healthy state; may last for several days or months.

Disease Prognosis

• Prognosis: probability or likelihood for recovery or other outcomes.
• Morbidity: disease rates within a group.
• Mortality: relative number of deaths resulting from a disease.
• Autopsy: a post-mortem examination to determine the cause of death.
• Epidemiology: the study of tracking patterns and the occurrence of disease is tracked by two factors.
  • Incidence: # of new cases in given population within given time period.
  • Prevalence: # of new, old, existing cases within a given population + time period.
• Epidemics: a higher number of expected cases of infectious disease within an area.
• Pandemic: a higher number of infectious diseases in many regions globally.
• Communicable disease: infectious disease that can spread from person to person.
• Notifiable/reportable disease: must be reported by a physician to designated authorities; intended to prevent the further spread of the disease.

Predisposing Risk Factors for Disease

• Characteristics make an individual more susceptible to developing a disease, disorder or health condition, indicating a high risk for the disease but not certain development:
  • Age: older adults are more susceptible to osteoporosis due to age-related bone density loss.
  • Gender: men have a higher risk for heart disease; women have a higher risk for lupus.
  • Genetics: a family history of breast cancer.
  • Lifestyle: smoking, drinking, poor nutritional habits, poor oral hygiene, a sedentary lifestyle.
  • Medical conditions: people with diabetes have a higher risk of developing infections and delayed wound healing.
  • Environmental factors: exposure to air pollution can cause respiratory complications and asthma.
  • Socioeconomic factors: low income and limited access to healthcare services = untreated, poor health outcomes.
  • Stress: can predispose individuals to mental health disorders and hypertension.

Cellular Adaptations to Health Disruption

• Cells adapt their growth + differentiation to altered conditions in the body:
  • Increase in breast and uterine tissue during pregnancy (normal adaptations).
  • Tissues may be modified due to hormonal stimulation (pregnancy) or environmental stimuli (irritation).
  • Disease develops when cell structure/function change + cannot maintain homeostasis.
  • Irreversible changes in a cell signal a change in DNA structure or function.
• Atrophy: a decrease in the size of cells; e.g., muscle atrophy = immobility issues.
• Hypertrophy: an increase in the size of cells; e.g., pregnancy.
• Hyperplasia: an increase in the number of cells.
• Metaplasia: one mature cell is replaced by a different mature cell type.
• Dysplasia: an increase in abnormal cell growth; a precancerous state.
• Anaplasia: a loss of differentiation + structure in cells; often seen in most malignant tumors.
• Neoplasia (malignancy): "New growth"; neoplasm AKA tumor.
  • Benign: does not typically become cancerous; non-life-threatening unless found in certain areas.
  • Malignant: cancerous.

Causes of Cell Injury

• Ischemia: decreased supply of oxygenated blood to tissues or organs (insufficient blood flow) leads to cell death.
• Hypoxia: reduced oxygen in the tissue interferes with ATP production.
  • The brain, heart, and kidneys are in high demand + easily affected.
• Physical damage: excessive heat, cold, and radiation.
• Mechanical damage: pressure or tearing of tissue.
• Chemical toxins:
  • Exogenous: from the environment.
  • Endogenous: is from inside the body
• Microorganisms: bacteria and viruses.
• Abnormal metabolites: genetic disorders, inborn errors of metabolism, and altered metabolism.
• Nutritional deficits.
• Imbalance of fluids or electrolytes.

Process of Cell Damage and Necrosis

• Apoptosis: programmed cell death and normal occurrence in the body (may not affect surrounding cells).
• Pyroptosis: results in lysis, releasing lysosomal enzymes into the tissue, causing nearby inflammation, damage, and reduced function of cell.
• Necrosis: AKA CELL DEATH, a group of cells dies + causing further damage due to cell disintegration.
• Liquefaction necrosis: dead cells liquefy due to the release of certain enzymes and occurs when the brain tissue dies, or certain bacterial infections.
• Coagulative necrosis: cell proteins are altered or denatured.
  • Typically occurs in heart attacks (cell death caused by ischemia)
• Fat necrosis: Fatty tissue is broken down into fatty acids in the presence of infection or certain enzymes and may cause inflammation.
• Caseous necrosis: a form of coagulation necrosis.
  • Thick, yellowish, "cheesy" substance that is likely developed in tuberculosis (TB).
• Infarction: an area of dead cells that results from a lack of oxygen = significant loss of function.
  • Less than 10 minutes before brain death and myocardial infarction AKA heart attack.
• Gangrene: an area of necrotic tissue that has been invaded by bacteria.
  • Wet gangrene is the result of liquefaction causing tissue to be cold, swollen, and black.
  • Dry gangrene is caused by coagulative necrosis where tissue dries, shrinks, and blackens.
• Two Stages of Cell Damage:
  • Initial cell damage (ischemia, mechanical, physical, and chemical).
  • Irreversible cell damage resulting in cell death (necrosis, gangrene, etc.).

Acute vs Chronic Illnesses

Acute Illness

• Short-term illness that develops quickly.
• Marked signs: high fever + severe pain.
• Sudden + obvious onset/Vomiting, cramps, and diarrhea.
• Ex Acute appendicitis

Chronic Illness

• Develops gradually + persists for a longer period of time. Typically milder. Can cause more permanent tissue damage. May involve intermittent acute episodes. Ex. Rheumatoid arthritis

Impact of Stress on Health

• Stress: occurs when an individual's status is altered by their reaction to a stressor and is considered a precipitating + exacerbating factor for many chronic disorders.
• Distress: results from harmful effects if a person cannot adapt/cope.
• Stress Response: generalized or systemic response to a change (stressor) that is internal or external.
• Homeostasis: the body's compensation for minor changes in needs or the environment.
• GAS = General Adaptive System = fight/flight response.
• Stressor: a factor that creates a significant change in body function.

Three Stages in STRESS RESPONSE (GAS/ General Adaptive System)

1. Alarm stage: the body's defenses are mobilized by the activation of the hypothalamus, sympathetic nervous system, and adrenal glands.
2. Resistance stage: elevation of hormonal levels with peak operation of essential body systems.
3. Exhaustion stage: occurs when the body is unable to respond further or is damaged by increased demands.

Significant Effects of Stress Response

• Bronchodilation and increased ventilation.
• Elevated and increased heart rate.
• Arousal of CNS
• Decreased inflammatory and immune responses.
• Increased blood glucose levels through glycogenolysis, gluconeogenesis (liver), protein catabolism (muscle), and lipolysis.
• Potential Effects of Prolonged Stress:
  • Renal failure: prolonged severe vasoconstriction + ischemia causes cell damage.
  • Stress ulcers: vasoconstriction + glucocorticoids decrease mucosal regeneration and production.
  • Infection: depression of inflammatory + immune responses. Delayed healing: after trauma or surgeries PTSD:
  • Is a serious consequence of major disaster or personal threat.
  • High risk of developing drug or alcohol dependence.

Interventions/Coping with Stress (p. 619)

• Adequate rest and healthy diet.
• Changing lifestyle habits and goals.
• Using creative solutions to minimize and adapt quickly to stressors.
• Regular and moderate exercise to release muscle tension.
• Engaging in activities
• Counselling, therapies, support services.
• Relaxation techniques.

Body Defenses for Disease Prevention

• Phagocytosis: neutrophils (leukocytes) + macrophages randomly engulf and destroy bacteria, cell debris, or a foreign matter - final process in acute inflammation.
• First Line of Defence:
  • Non Specific defense
  • Physical barrier includes unbroken skin.
  • Mucous membranes.
  • Secretions consist of tears, gastric juices, sweat, normal flora, and pH changes.
• Second Line of Defense:
  • Non Specific defense
  • Phagocytosis and consists of neutrophils and macrophages.
  • Inflammation.
  • Fever.
• Third Line of Defense:
  • Specific defense
  • Production of antibodies or cell mediated immunity
  • B + T cells
  • Memory cells
  • Vaccinations

Physiology of Inflammation

• Inflammation/Inflammatory Response.
• Protective mechanism is an important basic concept in pathophysiology
• Disorters ending in it is = inflammation
• It is intended to localize and remove injurious agents
• Signs and symptoms of inflammation are signs of a problem
• It is NOT the SAME AS infection because infection is a cause of it.
• Causes of Inflammation:
  • Physical damage(cuts, sprains)
  • Caustic chemicals(acids), Alkali
  • Ischemia, heart attack
  • Allergic reactions
  • Extreme heat or cold
  • Foreign Matter, Splinters, Glass
  • Infection

Steps of Inflammation

1. Injury to Tissue Cells: bradykinin (triggers nociceptors) and histamine (vasodilation) release from injured cells.
2. Activation of Pain Receptors: triggered by the release of bradykinin.
3. Sensation of Pain: stimulates mast cells + basophils to release histamine.
4. Capillary Dilation: caused by histamine and bradykinin.

• increased blood flow.
• increased capillary permeability.
• formation of exudate.

5. Bacteria Enter Tissue: an original injury or break in the skin allows for bacteria to enter the tissue; migration of neutrophils + monocytes to the site of injury.
6. Neutrophils: phagocytize the bacteria.
7. Macrophages: mature monocytes leave the bloodstream + phagocytize microbes.

Characteristics of Acute Inflammation

• Local Effects of Inflammation:
  • Cardinal Signs:
    • Redness (erythema): an increased blood flow to injury by vasodilation.
    • Swelling (edema): increased capillary permeability, shifts protein and fluid into the interstitial space.
    • Pain: increased pressure of fluid on nerves and release of chemical mediators (bradykinin + histamine).
    • Loss of function.
• Exudate: collection of interstitial fluid formed in the inflamed area, varying with the cause of trauma.
  • Serous: Watery, fluid with small proteins + WBC e.
  • Fibrinous: Thick + sticky, high cell and fibrin content is an increased risk of scar tissue.
  • Purulent: Thick, yellow-green, more leukocytes, cell debris + microorganisms = Infection
  • Abscess: Localized pocket of purulent exudate or pus in solid tissue.
  • Hemorrhagic: May be present if blood vessels are damaged
• Systemic Effects of Inflammation:
  • Fever (pyrexia): is common if inflammation is extensive and results from the release of pyrogens.
  • Malaise is feeling unwell.
  • Fatigue
  • Headache
  • Anorexia is the loss of appetite

Comparison - Chronic and Actual Inflammation

• Acute Inflammation:
  • The process of inflammation is the same, regardless of cause and timing.
  • Chemical mediators: histamine + bradykinin. -Injury + Affects the blood vessels + nerves in the damaged area:
    • Vasodilation of smooth muscles.
    • Hyperemia or Increased blood flow to injured area.
    • 3. Increased capillary permeability -4. Diluting toxic material Chemotaxis: attracts cells of the immune system. -Leukocytes -Neutrophilis An example is infection, chemical irritants, allergy, or trauma and burns.
• Chronic Inflammation:
  • Follows the acute episode.
  • Less swelling and less exudate.
  • Presence of Lymphocytes and Macrophages.
  • Fibrous scar tissue develops due to increased collagen in area.
  • Granuloma covers around a foreign object. An example is cardiovascular diseases neurological diseases and autoimmune.

Diagnostic Tests for Inflammation

• Diagnostic Test Purpose:
  • C-Reactive protein is the Marker of acute inflammation made in the liver
  • Erythrocyte Sediment Rate (ESR) measures the Inflammation
  • WBC count detects an Elevates the inflammation
  • Procalcitonin Elevates in Bacterial Infection Interleukin-6 (IL).
• Imaging Studies that measure a X-ray and Ultrasound.

Medical Treatments for Inflammation

• Types of Drugs
  • Antipyretic Effects
  • Analgesic Effects
  • Analgesia Effects
• First Aid and the rice approach Ice, compress, elevate
• The types of healing Replace Damaged one and Function Through Mitios
• Cell is capable in Myotosos
• In the terms of Burns Damages has cells

Types of Healing

• Resolution: cells recover and return to normal.
• Regeneration: damaged tissue replaced with functional cells through mitosis.
• Replacement: damaged tissue is replaced by scar tissue and the cells lose function.
• First intention: the wound is clean and free of debris/necrotic tissue and edges are well approximated (close together).
• Second intention: large break in tissue, more inflammation, that requires a more scar and longer healing time.
• Tertiary intention: the wound is intentionally left open with no approximation requiring longer healing, time for and an infectedabdominal wound.

Complications of Scar Formation

• Loss of function: impact to hair follicles, nerves, and receptors.
• Contractures and obstruction: a restrictive range of movement.
• Adhesions: occurs when bands of scar tissue join two surfaces that are normally separated.
• Hypertrophic Scar Tissue: Overgrowth of tissues results in hard ridges of scar tissues.
• Ulcer ations: Results in further tissue break down with scar tissue.

Classifications/Effects of Burns

• Superficial Burns damages Epimermis and involve part dermis :red and painful.
• 2nd Degree Burns cause damgage the epinmis and cause Sensitive touch
• 1st degree and they are destroyed with tissue damage; require skins.

Effects of Burns Includes

• Burns are Effects includes local and systemic Damages tissues.
• There are 3 type: shock is 80% of total

Treatment

• Burns need lots of healing time
• Can be severe

Pain and Neoplasms

• Infection
• Ischemia
• Necrosis
• Stretching tissues
• Chemicals and burns
• Characteristics of Pain May be periced a site

Phantom Pains

• Pains can be caused by trauma or damages

Activation

• Temperature
• Chemica:Bradykinin, Histamine, Prostoglandin
• Chemical:Physical or Mechanical Presure

Afferent Pain Fibers

• Sensory Nuerons, carrying Nerver Inpulses brain
• 1.MYLNIATED A DELTA Fibers A: Sudden and localize.

A PATH WAY (P54)

Over View of PATHS

1. Stimulas
2. Nocireptor
3. Synapse spinal cord discarison Last 4 pain, spinthalamic

GATE control theory of Pain

A. Pain has a gate, that build into normal pathways B. The modifiers include C. The pain impules transmilled from perihery

Factor to influence pain

A response B. May be induced:Endorphin releases fatigue C. Pain is more subective with more individuals D. Factor: Stress E.Identify purpose of analgesics in mangment.

ANalgestics

Reduces the amount of pain

• Oral parnetely
• classified by modifiy- moderate mild- sever pain.

List of anasthesies

LocAL: INjection SPINAL REGiONEAL- Bloocks PAin. GENRAL: GENERAL surgy Neuoplethesisa Patients can

• Relarivey unmare
• Discomfort
• terms to know

Tumor

cells go no inger

PATHOLOGICAL PROGRESS

1. Inmmations
3. vresselss
4. Maligment

Spread

• 1.local 2.Seeding is fuilds along

3. Spredasnt sites of bodys

• grading/staging stagey used to estimate A. proogis B. no clinical signes of cancers reate several renissions. c. systems.

systemics

• tumor and metastasis d. genetic factors that grow

Local Effecs

a. Obstunction: tumors and d. systemic effects

#Cancer Sines:

• Unusual bleeding

Risk of devloping

a. Factors genetis B.Radiation C. Chemical

screeaning Method For Early Dection:

a. blood tests b Routine Screenings c. Routine Scrrenings

Diagnostic tests for cancers lab tests blood tests mediccal images

common treatments for cancers a. Surgry b. Radation therapy chemotherpay

Mod 4 flid and lyte

a. a) water + b)lyte fluid with the body

Flid Componds

• a) intercular compartment (ICF) : INSode CELLS extra cellur compaertmet (ECF) : outside

MOVOVEN OF WATER

A.depends + permiable. water mvoes from B. Hydrostatic pressure:Pushh amount of intake = amount out

MOVOVEN OF fluids

• A, Filtatrion, asmotis,difsua, A trnasport osmosis pasies transport passive trangr

the trerm - hyptontic,iso B. bALEANE

Flidly and lytes

THIRST: ADH,ALDONORENES + ANTIPIC- SODIUM. RENIAL and serveum

Renl panel

evaluate fluir+ electroltes Serum osmoarly Urinaray: utine osmosis

#Cause Sings and smps treat: a. edma

• Excress aount : enlgrement
• in tersitular: swelling: A. capillar hyrostaica B. los os plasma/ c, obstructiion

4. Increase capillary permeabilily

De hydrations

causes

1. imsuficent 2.vomi, diaress DIABETIS

simgnd somps Dry mou,th, reduce the fluiod level , headahc, lowered bpo

Lyet Imbalnace

A. hyponatermia B. hyporematmia C. HYpokalmea D.

Imbanches

CALUM B. Hypescalcma

Maguesium Imabalces acid base balance

Buffrer

a. Chemical budder syse. repsonmd to ph levls

baases Phosphaes to monerlati.

#######TYPES OF AB

Acidodsis:

a. Metatolic acidois deceeases incccreses acide

alkalinosis - metrabic highee ph

• a - decrease the pph
• increases co decreases base

moduler

is micro.

• micobolgy
• microbioy study.

A. non pthageniswusally b. pthagenis capalbe

cell wall yes virus no - and fundi yes and pro no

yes a rewuire - to lvi

ANTIBERCIl - anticiral , antugal Antifugual eurkotes

Difreance between infectious and infection

a. pathogens: micro capable of causing disease

A - transmissoin form orne eprosn

Indentidy a Location

a. Normal floas b. commin in c. Stileo

a. NOsimicall Inflection: accures withi withtin the care facilities

Explore cell injury mechanisms including necrosis types (liquefactive, coagulative). Differentiate apoptosis from pyroptosis. Understand infarcts, gangrene, and the effects of toxins and hypoxia on cell injury.