Cellular Injury

Question 1

Cellular Injury

Answer 1

Stress > Ability to Adapt

Question 2

Factors Determining Adaptation vs. Injury

Answer 2

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)

Question 3

Common Causes of Injury

Answer 3

Inflammation (Acute or Chronic)
Nutritional Deficiency/Excess
Hypoxia
Trauma
Genetic Mutations

Question 4

Hypoxia

Answer 4

Low O2 delivery to tissue → Decreased ATP → Cellular Injury

Question 5

Causes of Hypoxia

Answer 5

Ischemia
Hypoxemia
Decreased O2-Carrying Capacity of Blood

Question 6

Ischemia

Answer 6

Decreased blood flow through organ

Arterial Blockage
Venous Blockage
Shock

Question 7

Example of Ischemia from Venous Blockage

Answer 7

Budd Chiari (Hepatic Vein Thrombosis → Congestive Hepatopathy → Infarct)

Most commonly caused by Polycythemia Vera
Can be caused by Lupus Anticoagulant too

Question 8

Hypoxemia

Answer 8

Low Partial Pressure of O2 in Blood

PaO2 < 60mmHg → SaO2 < 90%

Question 9

Causes of Hypoxemia

Answer 9

Altitude can affect FiO2
Increasd PACO2 → Decreased PAO2 (Hypoventilation, COPD)
Alveolar thickening (Interstitial Fibrosis) → A-a Gradient

Question 10

Gas Exchange

Answer 10

FiO2 (Atmosphere)
↓
PAO2 (Alveoli)
↓
PaO2 (Arterioles)
↓
SaO2 (Hemoglobin)

Question 11

Decreased O2-Carrying Capacity

Answer 11

From Hb Loss or Dysfunction

Anemia
CO Poisoning
Methemoglobinemia

Question 12

Decreased O2-Carrying Capacity - Anemia

Answer 12

RBC Mass ↓
PaO2 Normal
SaO2 Normal

Question 13

Decreased O2-Carrying Capacity - CO Poisoning

Answer 13

CO Binds Hb more avidly than O2 (100x more)
PaO2 normal
SaO2 decreased

Question 14

CO Poisoning Exposures

Answer 14

Smoke (Fires)
Exhaust (Cars)
Gas Heaters

Question 15

CO Poisoning Classic Finding

Answer 15

Cherry Red Skin

Question 16

CO Poisoning Early Exposure Sign

Answer 16

Headache

Question 17

CO Poisoning Significant Exposure Complications

Answer 17

Coma

Death

Question 18

Decreased O2-Carrying Capacity - Methemoglobinemia

Answer 18

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

Question 19

Methemoglobinemia Classic Findings

Answer 19

Chocolate-Colored Blood

Cyanosis

Question 20

Methemoglobinemia Treatment

Answer 20

IV Methylene Blue

Helps reduce Fe3+ to Fe2+

Question 21

Final e- Receiver in ETC

Answer 21

Oxygen

O2 is necessary for the formation of ATP

Question 22

Consequences of Hypoxia

Answer 22

Impaired Oxidative Phosphorylation

ATP ↓ → Disrupts Na+/K+ Pump, Ca2+ Pump, Aerobic Glycolysis

Question 23

Hypoxic Disruption of Na+/K+ Pump Leads To

Answer 23

Increased Na+ in the cell → H2O Influx → Cellular Swelling

Question 24

Hypoxic Disruption of Ca2+ Pump Leads To

Answer 24

High cytosolic calcium

Enzymes inappropriately activated

Question 25

Hypoxic Disruption of Aerobic Glycolysis Leads To

Answer 25

Anaerobic Glycolysis → Poor ATP Production & Lactic Acid Formation → Decreased pH → Precipitation of DNA & Protein

Question 26

Calcium in Cytosol is normally

Answer 26

Kept low using ATP-dependent Pump

Question 27

Initial Phase of Cellular Injury

Answer 27

Reversible

Hallmark: Cellular Swelling
Loss of Microvilli (eg Small Bowel & Proximal Renal Tubule)
Membrane Blebbing
RER Swelling → Ribosomes Dissociate → Decreased Protein Synthesis

Question 28

Late Phase of Cellular Injury

Answer 28

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

Question 29

Which Mitochondrial Membrane holds the ETC

Answer 29

Inner