Cellular Injury Flashcards
Cellular Injury
Stress > Ability to Adapt
Factors Determining Adaptation vs. Injury
Type of Stress (Inflammation → Adaptive)
Severity of Stress (Renal Stenosis → Adaptive Atrophy vs. Renal Artery Thrombosis → Injurious Infarct)
Type of Cell Affected (Neurons vulnerable to hypoxia, skeletal muscle resistant to hypoxia)
Common Causes of Injury
Inflammation (Acute or Chronic) Nutritional Deficiency/Excess Hypoxia Trauma Genetic Mutations
Hypoxia
Low O2 delivery to tissue → Decreased ATP → Cellular Injury
Causes of Hypoxia
Ischemia
Hypoxemia
Decreased O2-Carrying Capacity of Blood
Ischemia
Decreased blood flow through organ
Arterial Blockage
Venous Blockage
Shock
Example of Ischemia from Venous Blockage
Budd Chiari (Hepatic Vein Thrombosis → Congestive Hepatopathy → Infarct)
Most commonly caused by Polycythemia Vera
Can be caused by Lupus Anticoagulant too
Hypoxemia
Low Partial Pressure of O2 in Blood
PaO2 < 60mmHg → SaO2 < 90%
Causes of Hypoxemia
Altitude can affect FiO2
Increasd PACO2 → Decreased PAO2 (Hypoventilation, COPD)
Alveolar thickening (Interstitial Fibrosis) → A-a Gradient
Gas Exchange
FiO2 (Atmosphere) ↓ PAO2 (Alveoli) ↓ PaO2 (Arterioles) ↓ SaO2 (Hemoglobin)
Decreased O2-Carrying Capacity
From Hb Loss or Dysfunction
Anemia
CO Poisoning
Methemoglobinemia
Decreased O2-Carrying Capacity - Anemia
RBC Mass ↓
PaO2 Normal
SaO2 Normal
Decreased O2-Carrying Capacity - CO Poisoning
CO Binds Hb more avidly than O2 (100x more)
PaO2 normal
SaO2 decreased
CO Poisoning Exposures
Smoke (Fires)
Exhaust (Cars)
Gas Heaters
CO Poisoning Classic Finding
Cherry Red Skin
CO Poisoning Early Exposure Sign
Headache
CO Poisoning Significant Exposure Complications
Coma
Death
Decreased O2-Carrying Capacity - Methemoglobinemia
Heme iron oxidized to Fe3+
Fe3+ can’t bind O2 (Fe2+ normally binds O2)
PaO2 normal
SaO2 decreased
Seen with Oxidant Stress (Sulfa & Nitrate Drugs) or in Newborns
Methemoglobinemia Classic Findings
Chocolate-Colored Blood
Cyanosis
Methemoglobinemia Treatment
IV Methylene Blue
Helps reduce Fe3+ to Fe2+
Final e- Receiver in ETC
Oxygen
O2 is necessary for the formation of ATP
Consequences of Hypoxia
Impaired Oxidative Phosphorylation
ATP ↓ → Disrupts Na+/K+ Pump, Ca2+ Pump, Aerobic Glycolysis
Hypoxic Disruption of Na+/K+ Pump Leads To
Increased Na+ in the cell → H2O Influx → Cellular Swelling
Hypoxic Disruption of Ca2+ Pump Leads To
High cytosolic calcium
Enzymes inappropriately activated
Hypoxic Disruption of Aerobic Glycolysis Leads To
Anaerobic Glycolysis → Poor ATP Production & Lactic Acid Formation → Decreased pH → Precipitation of DNA & Protein
Calcium in Cytosol is normally
Kept low using ATP-dependent Pump
Initial Phase of Cellular Injury
Reversible
Hallmark: Cellular Swelling
Loss of Microvilli (eg Small Bowel & Proximal Renal Tubule)
Membrane Blebbing
RER Swelling → Ribosomes Dissociate → Decreased Protein Synthesis
Late Phase of Cellular Injury
Irreversible
Hallmark: Membrane Damage
Plasma Membrane Compromise → Enzymes leak into bloodstream (ex Troponin) & Ca2+ Rushes Into Cell
Mitochondrial Membrane Dysfunction → ETC Broken & Cytochrome C leaks into cytoplasm → Apoptosis Activation
Lysosomes Compromised → Enzymes leaked into Cytosol (which then get activated by Ca2+)
Ultimately: Cell Death
Which Mitochondrial Membrane holds the ETC
Inner
