Altered Cellular Function and Cancer Flashcards
How is the Action Potential altered by a potassium imbalance?
Hyperkalemia will cause in increase in cell excitability and increase a cells ability to produce action potentials this is because the cell is more positive and closer to the threshold potential.
Hypokalemia will cause a decrease in cell excitability and decrease a cells ability to produce action potentials this is because the cell is more negative and further from the threshold potential.
How is the action potential altered by a calcium imbalance?
Calcium decreases the cells affinity to Sodium (Na) (less sodium can go into the cell)
Hypercalcemia causes the cell to be less excitable as it decrease Na affinity, this makes the cell more negative and resistant against action potentials.
Hypocalcemia causes the cell to be more excitable as it increases Na affinity, this makes the cell more positive and decreases the RMP.
Atrophy
A decrease in cellular size (organ shrinks)
Results from a decrease in protein synthesis, protein degradation and autophagy
Can be caused by: a decrease in work load, pressure, use, blood supply, nutrition, hormonal stimulation or nervous stimulation.
Physiologic example of cellular atrophy
Shrinking of thymus gland in childhood
Hypertrophy
Increase in cell size causing increase in organ size
Caused by hormonal stimulation or increase in functional demand ie: increasing protein synthesis (done in the ER, myofilaments, and mitocondria)
Physiologic ex: wt lifting exercise, kidney compensation
Pathologic ex: cardiomegaly (HTN)
Hyperplasia
Increase in the number of cells
Caused by: increased rate of cellular division, caused by the secretion of GF
Physiologic ex: liver regeneration, uterine and mammary glands in pregnancy
Pathologic ex: endometriosis (increased estrogen secretion)
Metaplasia
Reversible change in which one adult cell is replaced by another cell, results from chronic stress, injury or irritation. New cell is better adapted to handle the chronic stressor.
Caused by reprogramming of stem cells influenced by cytokines and GF
Ex: columnar cells —> squamous cells in the bronchial lining when exposed to chronic smokers
Squamous cells —> columnar cells in the esophageal epithelium when exposed to GERD Barrett Esophagus’s (HCL)
Dysplasia
Abnormal changes in size, shape and organization of mature cells due to persistent, severe cell injury or irritation.
Disordered cellular growth in the epithelium.
If abnormal cells spread to the basement membrane —> pre-invasive neoplasm, carcinoma in situ
Mechanism of cellular injury
ATP depletion
Loss of mitochondrial production of ATP —> cellular swelling, decreased protein synthesis, and impaired cellular membrane transport system. (Cellular membrane Integrity loss)
Oxygen and Oxygen Free Radicals
Decreased O2 delivery —> O2 free radicals H2O2, NO —> destroy cell membranes and structures
Intracellular Calcium and loss of calcium steady state
Cellular injury triggers and increase intracellular Ca —> destroys cells
Hypoxic injury
Decreased amount of O2 in the air which is common in high altitudes, asphyxiation, or drowning.
Loss of Hbg or Hbg fx: hemorrhage or sickle cell anemia
Decreased RBC production: iron deficiency anemia and leukemia
Disease of heart or lungs
Ischemia
Acute: stroke/ PE
Chronic: cholesterol/plaque build up
Inflammation.
Reperfusion injury
Oxidative stress
Oxygen supply rapidly restored to ischemic tissues triggers O2 free radicals which causes cell damage and increased calcium in the mitochondria and WBC fx is impaired
Lack of O2 (lack of ATP)
Increased in cellular purine catabolites (hypoxanthine and xanthine)
Xanthine dehydrogenase — O2—> Xanthine oxidate
= free radical production
Free radicals / ROS
Unstable molecules that steal electrons to become stable
Targets of free radicals
Cell membranes, DNA, RNA, cellular proteins, and lipids.
Example free radical: reactive oxygen species (ROS) by-product of ATP production
ROS can overwhelm the mitochondria —> oxidative stress —> cellular injury, aging and disease.
ROS absorbs high energy sources radiation and UV light
ROS linked to the developments of heart disease, Alzheimer’s disease, Parkinson’s disease, and AML.
ROS causes: lipid peroxidation & damage proteins
Antioxidants are bodies defense against ROS
Antioxidants
Vitamin E, Vitamin C, Cysteine, Glutathione, Albumin, Ceruloplasmin, and transferrin.
Ethanol (ETOH)
Chronic ETOH liver damage and nutritional deficiencies: folic acid, magnesium, vitamin B6, thiamine, and phosphate.
Can cause brain and peripheral nerve dysfunction
Wernicke’s encephalopathy (wet brain) caused by Vitamin B6 deficiency and thiamine (AMS)
Korsakoff’s psychosis CNS amnesia and decrease in memory decrease in thiamine (blacking out)
Folic acid deficiency—> Fetal ETOH syndrome
-smooth Philtrum, thin vermilion and small palpebral fissures
ETOH Metabolism in the body
ETOH —ADH—> Acetaldehyde —Mito—> Acetaldehyde dehydrogenase —> acetate and
(Niacin) NAD+ —>NADH
NAD+ —> NADH
NADH/NAD+ ratio is increased causing
Pyruvate to change to lactic acid
Oxaloacetate to change to malate (decreases in glucose)
Triglycerides formation —> fatty liver
Necrosis
Cell death in irreversible cellular injury
Rapid loss of plasma membrane, organelle swelling, and mitochondria dysfunction
Infarct
Area of necrosis resulting from sudden insufficient arterial blood flow
Apoptosis
Programmed cell death, expected cellular process
Caused by severe cell injury, misfolded proteins in the ER, infection and obstruction.
Autophagy
Eating of self, autodigestion, and recycles cellular contents
In times of starvation this can create ATP for survival
Aging
Progressive tissue and organ loss over time
Accumulation of damaged macromolecules
Senescence permanent cessation of proliferation
Increased secretion of cytokines and pro inflammatory substances —> chronic inflammation
Increased CRP, IL-1, IL-6 and TNF-alpha, increase inflammation—> coag cascade
Increase disease risk
Ketogenesis
Ketone bodies formed in mito of hepatocytes due to no blood glucose, inability to use glucose or decrease carb intake
Fat for energy—> acetyl-CoA —> metabolized by the liver —> ketone bodies: acetoacetate, acetone, and B-hydroxybutyrate
Starvation
Glucose & FFA
Fats (3 days)
Protein
Oxaloacetate
Used in glucose production, activates brain mito, increases insulin pathway, decreases inflammation and increase neurogenesis
Binds with acetyl-CoA —> citrate
Decreased oxaloacetate, more free acetyl-CoA -> more free ketone bodies
Cancer cell characteristics
Anaplasia (loss of cell differentiation)
Pleomorphic (variable size and shape)
Cell life cycle unregulated
Ignore signals to stop mitosis
Undetected by the immune system
