Oxygen is restored to cells creating a ROS leading to cell membrane damage.

How do you know hypoxia is occurring?

Ischemia causes increase in extra cellular calcium. Na Ca pump fails. Water and Ca moves into the cell and swells and damages nucleic acids, proteins, cell membrane. Ca activates enzymes lead to cell death.

Mitochondria can’t make ATP. Electrolyte pump fails and cell swells. ER can’t work to make proteins. Looses membrane potential and structure fails.

Activated as part of stress response leading to lysozymes breaking down Cellular components in order to salvage primarily ATP.

Not a true cellular adaptation. Disordered cell growth with a changes in cell size, shape, and organization associated with chronic irritation, inflammation, pre-cancerous and cancerous growths.

Cellular adaptation that may be reversible in which one cell type is replaced by another.

Pseudostratified columnar epithelium replaced with squamous epithelium.

Squamous epithelium replaced with Columnar epithelium (Barrett’s Esophagus).

Achondroplasia

Cervical Cancer

Cellular adaption by increasing number of cells leads to increased tissue and organ size.

Endometrium during menses

Bone marrow in anemia

Benign prostatic hypertrophy

Cellular adaptation increasing cell size leading to increased protein synthesis and tissue and organ size.

Weightlifting and Pregnancy

Cardiac muscle response to hypertension

Cellular adaption decreasing cell size and metabolic demand leads to increased cellular efficiency.

Thymus in infant

Tonsils in adolescents

Skin and brain in aging

Disuse of muscle (leg in cast)

Denervation

hydroxyl radicals, superoxide, hydrogen peroxide, nitric oxide

must give up or gain electron binding to lipids (cell membrane)

causes inflammation implicated in many diseases (CV disease, DMII, aging, cancer, autoimmune) as a result of damage to cell membrane, DNA, and mitochondria.

Can damage cell membrane directly or creating ROS that does the damage, leads to calcium influx injury.

Drugs, metals, ethanol, carbon monoxide

Tylenol, Vancomycin, Cephalosporins, Quinolones.

Arsenic and Cyanide

Occurs naturally, treats leukemia, replaces phosphate in ATP to damage mitochondria

Slow accumulation over time deadly

Blocks intercellular use of oxygen

Single exposure deadly

Disrupts calcium homeostasis and substitutes for other substances (iron, Vit D, Mag, Zinc) in metabolism

Found in paint dust soil, builds up over time causing neurological, musculoskeletal, endocrine, reproductive, and dental problems.

Metabolized to Acetaldehyde

Replaces nutrients causing deficiencies in magnesium, Vit B6, phosphorus, folic acid and alters protein synthesis.

Hepatotoxicity and Cirrhosis caused by.

Wernicke Encephalopathy and Peripheral Neuropathy

colorless, odorless, created from burning wood, gas, propane, charcoal.

Has a stronger affinity for hemoglobin than oxygen causing ischemia and cell injury

Slows metabolism and ATPase pump for therapeutic effect

Non-Therapeutic Hypothermia

Dose related effects with a “safe” threshold

Effect is not dose related, there is no “safe” threshold

Physiologic programmed cell death requiring ATP with no negative effects

Pathophysiologic cell destruction, breaking down cell membrane leak into extracellular space resulting in inflammation.

Cell destruction for survival activated in stress response leading to lysosomes to catabolize cellular components.

Cell recycling to salvage cellular components, primarily ATP. Implicated in cancer and dementia.

Thymus, Lymph Nodes, and Mucosal associated with Lymph Tissue

Nonspecific Response

Specific Response

Non-specific response to foreign substance in phases, no memory

First line of defense with layers of protection (skin, low PH stomach urine, ciliary action).

Second line of defense. Respond immediately that includes stages of protection (vascular, plasma protein, and cell mediator responses).

Vasodilation increases vascular permeability cause WBC to migrate causes redness, swelling, heat, and pain.

Complement, Clotting,and Kinin Cascades.

Found in connective tissue close to blood vessels and lungs and GI tract.

Release Histamine I and Histamine S. Chemotaxic factors - neutrophils and eosinophils.

Synthesize leukotrines, prostaglandins, platelet-activating factors.

Proteins that produce factors that destroy pathogens activating innate and adaptive responses.

Antigen-Ab complex, complements activated, mast cell degranulation, histamine release, leukocyte chemotaxis, opsonization, cell lysis.

Prevents spread, traps antigen, stops bleeding, creates fibrin mesh

Short acting, rapidly degrade, primary protein is bradykinin

Local effects: vasodilation (common), vascular permeability, smooth muscle contraction, nerve cell stimulation, leukocyte chemotaxis (common).

Post injury facilitates blood clotting and passage of cells (RBC, PLT, WBC) and fluid to site.

Recognize patterns and cell damage, and activates complement cascade.

Send messages and coordinate the inflammatory response.

In early inflammation, engulf bacteria dead cells and debris.

initiate cellular inflammatory response, long term clean up and healing.

Engulf parasites and regulate mast cell response, associated with allergic reactions.

Associated with allergic response, important for Ab response in B-Cells.

Not a true leukocyte, engulf viruses and some cancer cells.

complement brings leukocyte to inflammation site to recognize, engulf, fuse, and destroy antigen.

Phagocytes use oxygen to generate ROS, what turns off this destructive mechanism?

Messenger cells that create chemical communication network and mediate ramping up or slowing down immune system.

IL, TNF-a, Interferons, Chemokines

Produced by Macrophages and Leukocytes, alter adhesion molecule expression, stimulate leukocyte production in bone marrow and bring them to inflammation site to enhance and suppress inflammation.

Pro-Inflammatory

Anti-Inflammatory

Pro-Inflammatory

Enhances endothelial cell molecules, starts chemokine production, leads to fever, septic shock, and cachexia.

produced my cells infected by viruses. functions to attach to cells not affected by virus to stimulate proteins that prevent viral replication enhancing acquired immunity.

Produced by macrophages, fibroblasts, endothelial cells in response to PRO-inflammatory cytokines. induces leukocyte chemotaxis and involved in cancer growth.

IL-1 act on hypothalamus causing fever, leukocytosis (left shift), synthesize plasma proteins (acute phase reactants, C reactive protein, fibrinogen, ferritin).

Too many cytokines released too quickly at once (PRO-inflammatory ILs). Fever is hallmark symptom. COVID and CAR-T cells.

Damages cells and weakens immune system seen in: periodontitis, DMII, obesity, CV disease, Alzheimer’s, insulin resistance, frailty.

Always ready to respond, general response, short duration.

Must be induced, specific response, generates long term protection and memory.

Antigen that induces an immune response.

Presents the antigen to the lymphocytes.

too small to be Immunogenic so binds with larger proteins.

Cellular immunity, stimulate cytokine response to activate leukocyte response or kill target directly. Do not produce Abs. Slow to respond. When impaired likely to have opportunistic infections.

Humoral Immunity, work outside cells binding to and neutralizing antigens, secretes Abs, responds quickly, when impaired cause systemic responses and more susceptible to encapsulated organisms.

Presenting and packaging known antigen.

Presenting and packaging naive antigen

Occurs in Thymus, has two chains

On cell surface working as markers for T-cells