Chapter 1 Introduction to Pathophysiology; Cellular Responses to Stress, Injury, and Aging
Section 11 Infarction, Clinical Death, Amputation and Gangrene Case Application
Zoë Soon
Infarction
Infarction refers to an area of dead cells resulting from oxygen deprivation caused by stoppage of blood flow – i.e., ischemia leading to coagulative necrosis. You are likely already familiar with the term myocardial infarction (heart attack). Other examples of infarction include ischemic stroke (brain infarction), and necrosis of extremities in severe frostbite or peripheral vascular disease.
Defining Death
What constitutes death has evolved over the last century, particularly with the advent of artificial ventilators and life-support systems. Today a person is typically declared clinically dead when the following criteria are met:
- No electrical activity in the brain.
- No response to painful stimuli.
- Absence of cranial reflexes
The brain and heart are the organs most critical to this determination, as both require continuous oxygen supply and cannot survive even brief periods of ischemia without permanent damage.
* Case Application: Diabetes, Ischemia, and Foot Amputation
The most common cause of limb amputation in Canada is diabetes. This case study traces the full cellular pathway from disease to amputation:
| Step 1 | Diabetes causes progressive blood vessel damage.
As vessel walls are damaged, they narrow, reducing blood flow to peripheral tissues – particularly the feet. |
| Step 2 | Reduced blood flow causes ischemia of foot tissue: reduced oxygen (hypoxia), reduced nutrient and glucose, and accumulation of waste products. |
| Step 3 | First sign of ischemia: cyanosis – a blue discolouration of the skin resulting from low hemoglobin oxygen saturation (below ~75%). |
| Step 4 | Ischemia causes low ATP → Na+/K+ and Na+/Ca2+ pump failure → intracellular calcium accumulation → phospholipase and protease activation → cell membrane breakdown → cell swelling and lysis.
Simultaneously, anaerobic metabolism generates lactic acid, lowering intracellular pH and further impairing of enzyme function. |
| Step 5 | Sensory neurons in the foot die (neuronal death).
The patient loses sensation in the foot – they may injure themselves (e.g., step on something sharp) without noticing. |
| Step 6 | An undetected wound becomes infected.
The immune response is compromised by the same ischemia, so infection can spread unchecked. |
| Step 7 | Dead tissue undergoes coagulative necrosis.
If gangrene develops (black discolouration from iron sulfide which forms as hemoglobin is degrade and iron binds to hydrogen sulfide release by colonizing bacteria) |
| Step 8 | If revascularization surgery is not possible, preventative amputation of the affected tissue is performed to stop infection from spreading into healthy tissue. |
Vascular ischemia of the toes with the characteristic cyanosis (bluish-purple hue to skin).
Regenerative Capacity of Different Organs
The ability to recover from ischemic injury, infection, or other causes of damage depends heavily on the regenerative capacity of the affected tissue:
- Skin: High regenerative capacity. New cells replace damaged tissue through mitosis.
- Bone: Good regenerative capacity. Fractures once set properly often heal within months.
- Kidney: Limited regenerative capacity. Can increase in size modestly to compensate, but significant damage is largely permanent.
- Heart: Very limited regenerative capacity. Cardiomyocytes (heart muscle cells) lost to infarction are largely replaced by scar tissue, reducing contractile function.
- Brain and Spinal Cord: Minimal regenerative capacity. Neuronal loss is generally permanent, making strokes, traumatic brain and spinal cord injuries so consequential.
This chapter has examined common terms used in pathophysiology as well as the full spectrum of cellular deterioration – from the quiet accumulation of materials inside aging cells, through two pathways of cell death (planned and unplanned), to the tissue-level consequences of four types of necrosis. These cellular events underlie virtually every disease process you will encounter throughout this course.
Media Attributions
- Private: Ischemia © James Heilman is licensed under a CC BY-SA (Attribution ShareAlike) license
- Private: GangreneFoot © James Heilman is licensed under a CC BY-SA (Attribution ShareAlike) license
