Lectures 2 and 3 - Cell Injury and Necrosis I and II Flashcards
(42 cards)
What can cause cell injury?
- Lack of oxygen
- Lack of nutrients
- Extreme pH
- Electrolyte imbalances
- Toxins
- Free radical damage
- Physical disruption
Reversible changes:
- Cellular swelling
- Cell membrane blebs
- Detached ribosomes
- Chromatin clumping
- Lipid deposition
- Vacuole formation
Irreversible changes:
- Lysosomes rupture
- Dense bodies in mitochondria
- Cell membrane rupture
- Karyolysis, karyorrhexis, pyknosis
Karyolysis:
Karyorrhexis:
Pyknosis:
- Chromatin dissolves
- Chromatin breaks
- Condensation of chromatin (followed by karyorrhexis)
Neurons are damaged in…
Myocardium, hepatocytes, renal epithelium in…
Fibroblasts, epidermis, skeletal muscle in…
- 3-4 min
- 30 min - 2hr
- Many hours
3 ways to move from cell injury to cell death:
- Require continuous ATP, so irreparable damage to mitochondria
- Holes in membranes (ion transport, can’t exclude Ca2+ and Na+)
- Activation of self-digestion (proteinases, lipases, endonucleases)
List 6 pathways of cell injury:
- ATP depletion
- Irreversible mitochondrial damage
- Disrupted Ca2+ homoeostasis
- Free radical formation
- Defects in cell membrane permeability
- Accumulated DNA and protein damage
What can cause ATP depletion?
Lack of O2, lack of substrates, decrease in mitochondrial function
What does ATP depletion do exactly?
- Can’t pump out Na+ or maintain Ca2+ homeostasis –> swelling issues
- Switch to anaerobic glycolysis (lactic acid build-up) –> chromatin clumping
- Damage to protein synthesis (ribosomes detach RER…lack of O2 leads to misfolded proteins) –> lipid deposition
What produces free radicals?
Normal metabolism and neutrophils (superoxide anion), hydrogen peroxide, toxins and environmental agents
What do free radicals do?
Cause lipid peroxidation of membranes and formation of thymidine dimers and single-stranded DNA breaks (cancer)
also, chain breakage in proteins
What protects from oxygen free radicals?
Catalase, superoxide dismutase, antioxidants and scavengers (Vitamins E and A, ascorbic acid), glutathione peroxidase, binding of metals such as copper and iron
Membrane damage can be caused by a host of things, such as…
ROS, decreased O2, increase in cytosolic Ca2+
What is the “point of no return”?
Damage to mitochondria and inability to make ATP
…also loss of structural integrity; leakage
List causes of hypoxia:
- ischemia
- low oxygen tension (hypoxia)
- CO poisoning
- severe anemia
Ischemia tends to be more damaging than simple hypoxia (added decrease in delivery of metabolic requirements, and accumulation of metabolic waste)
Hypoxia causes:
- Anaerobic metabolism
- Impaired Na+ pump
- Disaggregation of ribosomes
Cancer associated with chronic inflammation examples (ROS):
- chronic hepatitis C
- smoking
- gastric reflux, chronic gastritis
What is hemochromatosis?
Hereditary disease that leads to deposition of iron in many tissues (liver, heart, pancreas, etc.)
- Chronic tissue damage
- “Bronze diabetes” - cirrhosis, diabetes, skin pigmentation, heart failure, maybe liver cancer
What is reperfusion injury?
Re-establishing blood flow to ischemic area may enhance damage initially (ultimately saves tissue)
- O2 converted to ROS, re-establish metabolic pathways that make ROS
Antioxidants help
What causes contraction bands?
Reperfusion injury, cocaine, chronic catecholamines
Carbon tetrachloride yields ROS CCl3- and…
Fulminant liver damage and necrosis
- Lipoprotein synthesis damage –> fatty liver
- Lipid peroxidation
What is the timeline of cell injury?
- Biochemical and functional changes (minutes)
- Ultrastructural changes (hours)
- Microscopic changes (hours to days…at least 4 hrs.)
- Gross tissue changes (days)
What is “ballooning degradation” indicative of?
Viral illness. Swollen eosinophilic cytoplasm w/o vacuoles
Lymphocytic infiltration.
Fatty changes are _______.
Reversible! From damage to lipoprotein synthesis. Cells are still intact.
But eventually will die. Alcoholism.
