Mod 1: cell injury Flashcards
Cell injury: hypoxia
Causes
Clinical manifestation
Cause: decreased O2 or blood,rbc,hgb dysfunction
Sickle cell, hemorrhage, iron deficiency, asphyxiation
Ischemia triggers inflammation
Cell injury: Hypoxia patho
Cell swelling caused by
Ca causes-
Protein synthesis affected by
vO2=vmitochondrial function = v ATP production and ^anaerobic metabolism (eventually stops)
vATP=impair and fail K and Na pumps = ^Na+Ca in cell=water swells into cell
Ribosomes detach from ER + malfunction= no protein synthesis
Intracellular Ca= cytoskeleton, membrane, DNA,chromatin damage, vAtp, inflammation
Cell injury markers: CK LDH AST/ALT Trop
CK-found in muscle cells
LDH- muscle, liver, lungs, heart, rbc, brain
AST/ALT-liver
Trop-heart
Cell injury: ischemic reperfusion
Free radicals created by
Apoptosis caused by
effects
o2 restored= xanthine dehydrogenase -> xanthine oxidate -> metabolizes purine catabolites (hypoxanthine +xanthine)
Purine catabolites accumulated bc of vATP = large amt of free radicals (superoxide, H2O2) when metabolized=membrane damage + mitochondrial Ca overload
Ph alterations, osmotic changes, inflammation, mitochondrial Ca overload==open mitochondrial permeability transition pore= ATP escapes=apoptosis
Free radical injury:
causes death by
Stealing electrons= cell injury/death
Can overwhelm mitochondria+ exhaust antioxidants=oxidative stress=injury, aging, disease
Cause lipid peroxidation
Reactive oxygen species cause what kind of injury
Cause endothelial injury= inflammation, hypertrophy, proliferation, apoptosis, fibrosis, angiogenesis vascular remodeling~atherosclerosis
Ethanol injury
deficiencies
dysfunction of _, effects
vFolic acid, magnesium, B6, thiamine, Phosphorus
Brain+peripheral nerve dysfunction~wernikes enceph, neuropathy, korsakaff phychosis
Head/neck CA d/t acetalhyde
Alters cell signaling, neuro inflammation, ox stress, brain development
Apoptosis (Normal programmed death) triggered by (3)
Severe cell injury
misfolded proteins (d/t mutation/free rad damage) accumulate on ER=ER stress
Infections (viral)
Obstruction in organ ducts
Autophagy
2 types
triggered by
provides
Autodigestion of cell
Catabolic-degradation of cell components
Anabolic-preserves metabolites=metabolic +nutrition homeostasis
Triggered when cells lack nutrition
Provides ATP for survival during metabolic stress, eventually leads to death
aging effects (4) senescence activation of increase of morbidity risk ^ d/t:
Telomere erosion,ER stress, DNA damage, epigenetic stress
Senescence=loss of tissue repair abilities, release proinflammatory molecules
Activation of clotting cascade=hypercoag
Increase of cytokines=inflammation
Rise in IL-6, Timor necrosis factor alpha, c reactive protein=morbidity risk
Body changes w aging
rise in:
skin changes:
structural changes:
Crp , IL6 rise seen in high visceral tissue/fatty diey
Less collagen=wrinkly and dry
Increased free radical damage
Structural changes in bones, fascia, tendons, ligaments, joints
More body changes w age
Thymus atrophy, less ova/sperm, decreased response to hormones, vGastric emptying, atrophy, sarcopenia, shorter, thinning limbs, ^fat 70/50, insulin resistance,
Cv disease risk
Altered cell metabolism: Ethanol
rise in :
NAD/NADH ratio rise caused by
effects (4)
Ethanol metabolizes
to acetalhyde in cytoplasm
In mitochondria-Acetalhyde->acetate by ADH
Oxidized niacin -> NADH during ethanol-acetate conversion=^^^NAD/NADH ratio in liver=
Pyruvate->lactic acid=Lactic acidosis
Oxaloacetate->malate=prevents gluconeogenesis=fasting hypoglycemia
Glyceraldehyde3phosphate->glycerol3phosphate-combines with fatty acids= triglycerides in liver =hepatosteatosis
decreases citric acid cycle production of NADH=acetylcoa used for ketogenesis+lipogenesis =ketoacidosis + hepatoseatosis
Ketogenesis Triggers Role of acetylcoA Effect on oxaloacetate Hepatocytes role Mitochondria
Starvation/DM (no energy) =^B.oxidation cycle=^amt of acetylcoa-used in citric acid cycle, combines w oxaloacetate to =citrate
Oxaloacetate used in gluconeogenesis
when oxaloacetate depleted=^acetylcoa->ketone bodies (acetoacetate, acetone, B-Hydroxybutyrate)
forms ketones in mitochondria of hepatocytes
Atrophy
Body cause
Cellular cause (2)
Decrease in cell and eventually organ size
Body cause: decreased-workload,pressure, blood supply/nutrition, hormonal stimulation
Cellular cause: increased catabolism-less organelles, imbalance between protein synthesis and degradation Includes autophagy (self eating)
Hypertrophic
Body cause
Cellular cause
Caused by increased workload
Cell:
hormonal stimulation, ^protein in ER/membrane/myofilaments/myochondrium NOT cell fluid
Hyperplasia
Cause
Example
Results from growth factors stimulating cells to divide
Resection/damage of liver= regeneration
Hormonal: mammary glands/uterus while pregnant
Endometrial CA dt GH
Metaplasia
Cause
Example
Pre-CA, reversible
Chronic irritation/injury/stress signal stem cells-new cellular pathway (bc cytokines/GFs)=new cell better able to handle stressor/injury
Columnar->squamous in smokers, most common
Squamous->columnar in gerd (CA may arise) (Barrets esophagus)
Dysplasia
Cause
Example
From severe persistent injury
Spreads to basement membrane in epithelial cells-preinvasive neoplasm
Pre-ca “carcinoma in situ”/not truly adaptive
Cervical dysplasia
Oxidative stress=what diseases (4)+death how
affects pregnancy how
heart disease(sclerosis), alzheimers, parkinsinons, amyotropic lateral sclerosis, arrythmias~death preeclampsia, intrauterine growth retardation, miscarriage
lipid peroxidation effects (damage 4, v1,^1)
damage Chromatin, mitochondria, DNA, proteins that maintain ion pumps + cellular transport, + vProtein synthesis, increased cell membrane permeability
Antioxidants
C,E, cysteine, glutathione, albumin, ceruloplasmin, transferrin
Free radicals created by
ROS deactivated by
cell metabolism, radiation/uv light, chemicals/drugs/pesticide metab, metal transition, nitric oxide(chem mediator/free rad)
deactivated by superoxide dismutase
ROS play role in (5)
CV (ischemic/HF) disease, htn, hld, dm, sleep apnea
Ethanol cellular injury metabolism effects (5)
ethanol->acetalhyde by alcohol dehydrogenase
======NAD->NADH
===
Pyruvate->Lactic acid =lactic acidosis
Oxaloacetate (used in gluconeogenesis)->malate= fasting hypoglycemia
Glyceraldehyde3phospate->glycerol3phosphate= combines w fatty acids=triglycerides=hepatosteatosis
Decreases citric acid cycle production of nadh=acetyl-CoA for ketogenesis and lipogenesis =hepatosteatosis+ketoacidosis
Ethanol effects on the developing brain (FAS)
neuroinflammation (vCell signaling) =ox stress vThiamine alters autophagy prevents brain from developing/malformation
Necrosis
rapid loss of membrane organelle swelling mitochondrial dysfunction =local cell death+autolysis (autodigestion) infarct=area of necrosis
Autophagy key component in
cellular proliferation, development, remodeling
aging, CA
Neurodegen./CV disease
antigen presentation, inflammation, infection,
metabolic disease
cell death
Cellular aging =5
telomere erosion, dna damage, epigenetic stress, ROS accumulation, endoplasmic reticular stress
Starvation
glucose levels maintained by hepatic glycogenolysis and release of fatty acids,
hepatic gluconeogenesis occurs from lactate +alanine
3+days-adipose stores used for brain until gone, protein degradation=organ failure/death