Class 2 Flashcards
Causes of Cellular injury
Hypoxia Free Radicals Chemical Injury Intentional & Unintentional injuries Cellular swelling Excess lipids & carbohydrates Calcium excess & hardening
Hypoxia
Lack of oxygen (most common cause of cellular injury)
4 cellular disruptions
- ATP depletion
- Oxygen & oxygen-derived free radicals
- Intracellular calcium & loss of calcium steady state
- Defects in membrane permeability.
Apoptosis
active process of cell death (programmed)
Ischemia
reduced blood supply to tissues caused by arterioscelrosis & thrombosis
- a decrease in ATP levels causes Na+ & K+ pump & Na+ & Ca2+ exchange to fail which accumulates ions intracellularly,.
- If O2 is not restored, lysosomes swell and irreversible damage occurs
- Acute: clot suddenly obstructs vessel
- Chronic: body compensates for collateral circulation around blockage
Myocardial Infarction
Cell death & obstruction in coronary artery (heart attack)
Reperfusion Injury
Generation of reactive O2 intermediates & cause further membrane damage & mitochondrial calcium overload
Complement
Destroy pathogens directly & activate other components of inflammatory response
Dehiscence
Wound pulls apart at suture site & is associated with infection (worse with obesity)
Evisceration
Sutures open and abdominal organs protrude.
Keloid
Excess scar tissue formation
Contracture
Excessive contraction that shrinks the wound further than needed, (common in burns)
Stenosis
Narrowing of blood vessel or organs
Primary Intention
Damage is not extensive & heal is under minimal loss Ex: suture surgical wound
Secondary Intention
Extensive damage & takes longer to heal and contract Ex: Open wound
Debridement
Cleaning of the wound
Gangrene
Death of tissue caused by severe hypoxic injury (lack of O2) most commonly via arteriosclerosis
Atrophy
Shrinking in cellular size
Physiologic: early development
Pathologic: decreased workload, blood supply, nutrition (Autophagic vacuoles due to malnutrition)
Proteosomes
Protein catabolic complex & ubiquitin-proteosome pathway –> both involved in protein catabolism
Proteins –> ubiquitin
Hypertrophy
Increased size of cells & therefore the affected organ
- Kidneys & heart are prone to it
- Increases accumulation of protein
- Triggered via mechanical or hormones
- Only occurs in non-dividing cells
- Can be physiologic or pathologic
Hyperplasia
Increased number of cells due to increased rate of cellular division
- Compensatory (regeneration)
- Hormonal (estrogen)
- Pathologic (abnormal proliferation, menses)
Dysplasia
Abnormal changes in size, shape & organization of cells
-Involved in breast cancer development
Metaplasia
Reversible replacement of one mature cell type by another less differentiated type
5 signs of inflammation
Redness (due to increased RBC at site)
Warmth (due to RBC)
Loss of Function (decreased tissue strength)
Swelling (Increased movement of fluid outside vessels)
Pain (prostaglandins activate nerve receptors)
Cellular injury
Cell no longer is able to maintain homeostasis, possible recovery if stressor is removed in time
5 types of Necrosis (Cell Death)
Liquifaction –> ischemic damage to nerve cells
Coagulative (clotting) –> hypoxia cause by severe ischemia kidneys/heart
Fat Necrosis –> caused by lipases (opaque/chalky) livers, breast & abdominal
Caseous Necrosis –> due to tuberculosis pulmonary infection (clumped cheese)
Gangrenous Necrosis –> associated with diabetes mellitus, lack of bl. flow. (Gas, wet or dry)
– Dry is due to coagulative necrosis
– Wet is due to liquifactive necrosis
Gas Gangrene –> caused by the Clostridium species, results in bubbles of gas to form in muscle cells
Anoxia
total lack of O2 caused by sudden obstruction
Free Radicals & Reaction O2 Species
Electrically uncharged atom having an unpaired election (unstable)
- Can cause damage to DNA (fragmenting) decreasing protein synthesis
- Damage vital proteins that affect ion pumps & transport mechanisms
- Destroy membranes & cell wall
- Lipid peroxidation (destruction of polyunsaturated lipids)
- Damaging mitochondria causing liberation of Ca2+ into cytosol
Chemical Injury Types
Carbon tetrachloride Lead Carbon Monoxide (higher affinity to hemoglobin than O2) Ethanol (Alcohol( Mercury Street drugs
Physical Injury Types
Blunt Force –> mechanical energy application resulting in tearing, shearing or crushing
Contusions (bruises)
Abrasions (scrape)
Phenylketonuria (PKU)
newborn disease caused by genetic defect of not having certain enzymes required for protein degeneration resulting in nervous damage.
ATP Depletion (Cellular Injury Disruption)
Lack of ATP = Na-K pump stops working = accumulation of Na+ inside the cell (swelling)
Decrease of protein synthesis = ER dilation = ribosome detachment
Fats, pigments & glycogen inflitrates
Free Radicals Activation (Cellular Injury Disruption)
Damage cell membrane & structures within cell
Calcium Homeostasis Disruption (Cellular Injury)
Lack of Ca decreases activation of enzyme in cell therefore no breakdown & Ca accumulates in mitochondria
Free Ca2+ results in the activation of
- Protein kinases (phosphorlyation of protein)
- Phospholipases (Membrane damage)
- Proteases (Cytoskeletal damage)
- Endonuclease (Nucleus chromatin damage)
Defects in Membrane Permeability
Imbalance of electrolytes and can lead to shrinking or swelling of cell and therefore necrosis
Systemic Manifestations of Cellular Injury
Fatigue Malaise Fever Loss of appetite Elevated plasma enzymes Inflammatory Response
Inflammatory Response
Second line of defense, innate immunity
Activated by cellular injury or death
Inflammation Goals
Limit & control injury process
Prevent & limit infection & further damage
Initiate adaptive immune response
Initiate health
Inflammatory Vascular Response
- Brief vasoconstriction (dunno why?)
- Vasodilation (slower blood velocity & increased bl. flow)
- Increased vascular permeability (allow leakage out of vessel causing swelling, allows increased movement of RBC)
- White blood cell adherence to inner walls
Inflammatory Response Order
- Neutrophils
- Monocytes
- Macrophages
- Mast cells
- Platelets
- Lymphocytes
Neutrophils
Arrive 1st & battle with injurious agent
Present in exudate (die off within 6-12 hrs)
Monocytes
Immature macrophages that travels to inflammation site to mature.
Macrophages
Surround bacteria and replace neutrophils for a longterm dense phagocytozing the bacteria
Mast Cells
Release histamine to increase permeability to encourage leakage of white blood cells
Platelets
Cause clotting of wound and injury
Lymphocytes
Debride & repair
Histamine/Leukotrienes
Cause vasoconstriction
Increased vascular permeability
Released by mast cells
Prostaglandins
Sets of pain
Increased permeability
Sets off inflammatory response
Bradykinin
Dilation of blood vessels
Induces pain
Smooth muscle contraction
Increased vascular permeability
Complement system proteins
Destroy pathogens directly or activate other components of inflammatory response
Fever
Systemic Inflammatory Mechanism
Caused by pyrogens (act directly on hypothalamus & therefore temperature) & interleukin-1
Leukocytosis
Increased number of circulating WBC’s
Causes fatigue, loss of appetite, lymphadenitis (swollen lymphnodes)
Elevated erythrocyte sedimentation rate
Chronic Inflammation
Arthritis** Inflammation last longer than 2 weeks due to failed acute inflammation (microbes didn't undergo phagocytosis b/c of good cell wall because of high lipid/wax content in microbe, toxins, chemicals) Granuloma (isolated infected area) --> dense infiltration of lymphocytes & macrophages (can differentiate into epithelioid cells & fuse together) Limits prostaglandin (increases inflammatory response)
Causes of Inflammatory Injury
Macrophages & Lymphocytes arrive first rather than neutrophils
Histamine, antibodies, lymphokines, complement & proteases can further delay healing
Fibroblast infiltration & keloid formation (scar tissue) leads to loss of function
Manifestations of Chronic Inflammation
- Hyperplasia of spleen or lymphnodes
- Leukocytosis & increased antibody production
- Elevates erythrocyte sedimentation rate
- Low grade fever
- Anemia
- Pain
- Activity Intolerance
- Depression
- Fatigue
- Insomnia
- Anorexia
Resolution
Returning injured tissue to original structure & function
Tissues must be able to undergo regeneration (extensive injury but no infection)
Repair
Replace old tissue with scar tissue (keloid) which is consistent of collagen to restore tensile strength but no full function
Healing Process
Debride (clean) -> Seal (epithelialization)-> Fill in -> Shrink (contraction)
Factors Affecting Tissue Repair
Age (metabolism)
Temperature (cool skin slows rate of cell division)
Moisture (dry, cells can’t divide or migrate well)
Nutrition (proteins & vitamin C for collagen & carbs for nrg)
Blood supply **
Tension on tissue (obesity)
Drugs & stress hormones
Chronic diseases
Phases of Healing
- Inflammation (debride)
- Proliferation/New Tissue Formation (Reconstructive phase)
- Remodelling & Maturation Phase
Reconstructive Phase
Begins 3-4 days after injury, and goes for 2 weeks
Seal & fill**
Fibroblast proliferation (secreting collagen)
Epithelialization (Epithelial cells divide to seal top of wound)
Contraction (Pulling of muscles to decrease wound size)
Cellular differentiation
Remodelling Phase
Takes up to 2 years depending on damage extent
Continuation of cellular differentiation
Scar tissue formation
Scar remodelling
Complications of Wound Healing
Hemorrhage (provides accumulated bl for bacteria to grow)
Fibrous adhesion (overactive fibroblasts cause surface cells to stick together and bind organs)
Infection
Excess scar formation –> Keloids
Strictures & Contractures (too much collagen or scar tissue, cell malfunction)
Dehiscence
