CELL INJURY & CELL DEATH


Multicellular organisms are dependent on the integrity and functioning of the cells that make up their tissues, organs, and organ systems. Cellular injury and/or cellular death inevitably impairs function at some level. While complex organisms have means to overcome much of it, constituting a physiological "reserve capacity," the impairment or loss of individual cells or groups of cells can become too great; when this happens disease or even death ensues. Age, environmental factors, infectious organisms, physical insult, nutrition, and many other influences can affect this reserve and expose the individual to illness as a result.

Cell death is a state in which cells are incapable of sustaining essential cellular functions. It can occur under normal physiologic conditions as part of a process by which cells and tissues maintain their cell numbers and vitality. A common example of physiologic cell death is red blood cells: after circulating for about 120 days, the erythrocytes wear out and undergo destruction by the spleen. They are constantly replenished by stem cells in the bone marrow. Cell death can also be the ultimate result of cell injury. In this case cell death has a fundamental role in the development of various diseases.

We can distinguish these two modes of cell death as APOPTOSIS (a part of normal physiology) and NECROSIS (the result of some injury or disease process), respectively. Since ultimately it's at the cellular level that organisms die, in a very real sense, understanding the mechanisms and appearance of cell injury and death is the foundation stone of the study of pathology. Students must understand the mechanisms of cellular injury and death, and be able to recognize their morphological hallmarks.

Goal

Resources

Case 1: Myocardial Infarct

1.    Autopsy Results: Gross Pathology
2.   Autopsy Results: Microscopic View
3.   Etiology of Cell Death: Ischemia, Hypoxia, and Anoxia
4.   Etiology of Cell Death: Free Radical Damage
5.   Free Radicals and "Reperfusion Injury"
6.   Causes of Hypoxia: Ischemia
7.   Causes of Hypoxia: Hemoglobin Abnormalities
8.   Causes of Hypoxia: Carbon Monoxide Poisoning
9.   Causes of Hypoxia: Respiratory Disorders
10.  Defective Oxidative Phosphorylation
11.  Morphologic Expression Of Hypoxia: Reversible Cell Injury
12.  Morphologic Expression Of Hypoxia: Irreversible Cell Injury
13.  Can Chemicals Or Ionizing Radiation Cause Cell Injury?
14.  How Do Infections Result In Cell Injury And Death?
15.  What Influence Do Genetic Factors Have On This Process?

Case 2: Cerebral Infarction

1.   Autopsy Findings In Similar Cases: Gross View
2.   Autopsy Findings In Similar Caes: Microscopic View
3.   Why Does This Patient Have Gait And Cognitive Deficits?

Case 3: Acetaminophen Poisoning

1.   Lab Test Results
2.   What Is The Mechanism Of Acetaminophen Toxicity?
3.   What Other Common Toxic Materials Act By Generating Free Radicals?
4.   Common Pathways

Case 4: Pulmonary Tuberculosis

1.   Autopsy Results: Gross View
2.   What Is Meant By "Caseous" Necrosis?
3.   How Has Necrosis Produced These Clinical Symptoms?
4.   Morphologic Variants of Necrosis: Coagulative Necrosis
5.   Liquefactive Necrosis
6.   Gangrenous Necrosis
7.   Fibrinoid Necrosis
8.   Another Form Of Cell Death: Apoptosis
9.   How Does Apoptosis Differ From Necrosis?
10.  How Can You Tell A Cell Is Dead?

Case 5: Pancreatitis

1. Acute Pancreatitis: Gross View
2. Acute Pancreatitis: Microscopic View
3. What Is Fat Necrosis?

The Role Of Subcellular Components In Cell Death

1.   The Membrane Skeleton
2.   Lysosomes
3.   Lysosomal Storage Diseases
4.   Smooth Endoplasmic Reticulum
5.   Cytoskeletal Elements: Thin Filaments
6.   Intermediate Filaments
7.   Microtubules