Cell Injury and Death: Intro Concepts

Cell Injury and Cell Death: Introductory Concepts

• The current series is an updated version (2.1) of the previous year's series on general pathology.

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• New 5-minute videos with updated information for 2023 will be regularly uploaded.

Chapter Focus: Cell Injury and Adaptation

• The initial videos cover cell injury and adaptation mechanisms within Chapter 1.
• Necrosis, apoptosis, and cellular morphological changes from cell injury are emphasized.

Cellular Alterations in Response to Injury

• Cell injury leads to cellular swelling, hydropic changes (water accumulation), and altered fat metabolism.

Solid Organs

• Cells are tightly packed in solid organs, maintaining a structured architecture.
• Necrosis initially preserves tissue architecture, gradually losing details over time.
• Early necrosis retains basic outlines, losing internal cellular details.
• Later necrosis involves complete loss of internal cellular details.

Liquefactive Necrosis

• Liquefactive necrosis transforms solid tissue into a liquid mass.
• Cell lysis and enzymatic digestion break down tissue architecture.
• Tissue architecture may be entirely lost or retain some remnants.
• Transformation of tissue into a liquid state is a key feature.

Purulent Exudate (Pus)

• Purulent exudate, or pus, has a creamy, yellowish-white appearance.
• Pus is associated with infections and contains neutrophils, cellular debris, and bacteria.
• "Choqi White" describes the creamy white appearance of pus.
• Pus indicates severe acute inflammation.

Hemorrhage and Blood Vessels

• Hemorrhages involve blood vessel rupture and blood leakage into surrounding tissues.
• Identifying blood vessels is crucial for diagnosing hemorrhages.
• Blood vessels are round structures with a defined lumen and endothelial lining.
• Red blood cells outside vessels indicate hemorrhage.
• Hemosiderin, a hemoglobin breakdown product, is found within macrophages at hemorrhage sites.
• Macrophages containing hemosiderin indicate previous hemorrhage.
• The Bremen stain identifies intracellular and extracellular iron.

Microscopic Characteristics of Hemorrhage

• Old hemorrhage appears as golden brown deposits in tissue.
• Hemosiderin deposits within cells are a hallmark of previous bleeding.
• Blood vessels can be identified histologically, even in areas of hemorrhage.
• Extravasated red blood cells indicate bleeding in tissues.

Tissue Changes After Cell Death

• After cell death, nuclei undergo pyknosis (shrinkage), karyorrhexis (fragmentation), and karyolysis (dissolution).
• Pyknosis involves nucleus shrinkage, becoming smaller and darker.
• Karyorrhexis is nuclear fragmentation.
• Karyolysis is nuclear dissolution or fading.
• These nuclear changes are important markers of cell death and necrosis.

Apoptosis and Tissue Changes

• Apoptosis causes cell shrinkage, cytoplasmic changes, and alterations to the nucleus.
• Cell shrinkage is a key change in apoptosis.

Microscopic Findings

• Apoptotic bodies resembling Councilor bodies may be present in liver pathologies like viral hepatitis.
• Councilor bodies are small, round eosinophilic bodies in the liver.
• Civatte bodies are commonly seen in skin disorders like lichen planus.
• Civatte bodies represent apoptotic keratinocytes in the epidermis.
• Acidophilic bodies are indicative of apoptosis.

Patterns of Cell Death

• Single-cell necrosis and apoptosis may occur with scattered individual dead cells.
• Patterns of necrosis and apoptosis vary depending on the underlying pathology.

Microscopic Evaluation of Cell Death

• Apoptosis is characterized by cell shrinkage and is difficult to observe under microscope, due to cells being removed rapidly.
• Apoptotic cells feature cell shrinkage, chromatin condensation, and formation of apoptotic bodies.
• Apoptosis is a controlled process and typically doesn't cause inflammation.

Apoptosis vs. Mitosis

• Apoptosis and mitosis are opposing processes in tissues; one removes cells, the other divides cells.
• Apoptosis maintains tissue homeostasis by removing damaged or unnecessary cells, while mitosis ensures cell turnover.

DNA Fragmentation in Apoptosis

• DNA is cleaved at regular intervals, resulting in a "ladder pattern".

TUNEL Assay

• The TUNEL assay detects DNA fragmentation in apoptotic cells.
• The TUNEL assay labels fragmented DNA ends to visualize apoptotic cells.
• The TUNEL assay helps distinguish apoptosis from other forms of cell death, but is non-specific to apoptosis.

Nobel Prize Recognition

• Yoshinori Ohsumi received the Nobel Prize in 2016 for discovering mechanisms for autophagy.
• Emmanuelle Charpentier and Jennifer Doudna won the Nobel Prize in Chemistry for developing CRISPR-Cas9 gene editing.
• David Julius and Ardem Patapoutian received the Nobel Prize for discoveries of receptors for temperature and touch.

Cellular Pigments and Staining

• Melanin provides skin its color.

Melanin Pigmentation

• Melanin is responsible for brown-black pigmentation in skin and other tissues.
• Melanin pigment is produced by melanocytes in the skin.

Identifying Melanin

• Melanin appears as fine, brown granules under H&E stain.
• Melanin can be identified using special stains like Masson-Fontana.
• Masson-Fontana stain uses argentaffin reaction and is more specific for melanin.

Melanin Origins

• Melanocytes in the skin produce melanin, and its presence is determined through melanocyte activity.
• It’s located in the nucleolus, so there is no need for special stains.

Lipofuscin Pigment

• Lipofuscin is a "wear and tear" pigment that accumulates in cells over time.
• Lipofuscin is often found in older individuals and increases around the heart.

Lipofuscin Characteristics

• Lipofuscin appears as brown-yellow granules.
• Lipofuscin indicates the accumulation of cellular damage, resulting in aging.

Bile Pigment

• Bile has a greenish-brown color and is a product of heme breakdown.

Identifying Bile

• Bile identification involves hallistine, and has to be the classical one.
• Bile pigment is produced by heme breakdown.

Calcium Deposits

• Calcium stains dark black to black-blue color.
• Key stains for identifying calcium deposits are Von Kossa or Alizarin red.

Hemosiderin Pigment

• Hemosiderin appears as golden brown granules.
• Indicates iron accumulation.

Pigment

• Detecting iron accumulation is unclear without Berlin Prussian blue stain.
• Lipofuscin is positive under PAS.
• Melanin stains positive with Masson-Fontana stain.
• Hemosiderin stains positive under Prussian blue.

Amyloid Deposits General

• Amyloid deposits are extracellular.
• Congo-red stain is needed.
• Green birefringence is observed.

Differentiating Amyloid Deposits and Collagen

• Amyloid is not the only thing that can stain red.
• It will show apple green color.
• Use Polarizing lenses.

Case Study: Ewing Sarcoma

• A 13-year-old boy experiencing knee pain may have Ewing Sarcoma.
• Confirm diagnoses using PAS which stains positive and is sensitive to diastase.
• Patient’s symptoms match Ewing Sarcoma and it is sensitive to PAS.

Call to Action

• The next video focuses on neoplasms.

Introduction to cell injury, adaptation, necrosis, and apoptosis. Overview of cellular morphological changes resulting from injury specifically cellular swelling, hydropic changes, and altered fat metabolism. Discussion of necrosis in solid organs and tissue architecture.