Lecture 3 -- Cell death

This set of flashcards covers critical concepts related to cellular adaptation, degeneration, and death, focusing on amyloidosis, calcification types, necrosis, and apoptosis.

What is necrosis?

Necrosis = irreversible cell death characterized by:

• Denaturation of cellular proteins

• Damage to cell membranes

• Leakage of cellular contents

• Often associated with inflammation

Why is necrosis irreversible?

• Inability to reverse mitochondrial dysfunction → ATP depletion

• Irreversible damage to cell membranes

What type of necrosis commonly occurs in the pancreas?

Autolysis

• Pancreatic cells release digestive enzymes

• Enzymes digest their own tissue

• Leads to auto-digestion of pancreatic tissue

What type of necrosis commonly occurs in body cells apart from pancreas?

Heterolysis 

• Digestion of dead cells by enzymes from inflammatory cells, especially neutrophils and macrophages

What processes occur after cell membrane damage in necrosis?

1. Protein denaturation

   • ↑ intracellular Ca²⁺ → Activates proteases → Protein denature

2. Inflammation

   • Release of damage-associated molecular patterns (DAMPs)

3. Enzymatic digestion

   • Necrotic cells broken down by enzymes

What are the cellular changes or morphological features in necrosis?

• Increased cellular eosinophilia

• Nuclear shrinkage

• Fragmentation of nucleus

• Loss of nuclear basophilia = Loss of nuclear staining

• Pale tan discolouration

Name the types of necrosis.

• Coagulative necrosis

• Lytic necrosis

• Caseous necrosis

• Liquefactive necrosis

• Gangrenous necrosis

• Fibrinoid necrosis

• Steatonecrosis = Necrosis of adipose tissue

What types of necrosis are shown in this picture? What are the clinical features of this type of necrosis?

Coagulative necrosis

• Dominant feature: protein denaturation

• Characteristics:

  • Cell borders remain visible

  • Cellular architecture preserved

Under what circumstances does this type of necrosis usually occur?

Ischemia except brain tissue

What types of necrosis are shown in this picture? What are the clinical features of this type of necrosis?

Lytic necrosis

• Dominant feature: enzymatic digestion

• Characteristics:

  • Loss of cell borders

Under what circumstances does this type of necrosis usually occur?

• Neutrophil-rich inflammation e.g. bacteria

What is caseous necrosis? Under what circumstances does caseous necrosis usually occur?

Subtype of lytic necrosis

Characteristics:

• Cheese-like appearance

• Associated with granulomatous inflammation

What is liquefactive necrosis? Under what circumstances does liquefactive necrosis usually occur?

Subtype of lytic necrosis

Characteristics:

• Formation of fluid-filled lesion

• End stages of necrosis in brain

What is steatonecrosis ?

Necrosis of adipose tissue

What is the morphology of steatonecrosis?

Somewhat in between a coagulative and lytic necrosis

• No nuclei with well defined cell borders

• Basophilic = Mineral, including calcium or nucleic acid deposition

What is gangrenous necrosis? Under what circumstances does gangrenous necrosis usually occur?

Subtype of lytic necrosis

Characteristics:

• Occurs in distal limbs or dependent organs

• Can be dry gangrene (mainly vascular damage) or wet gangrene (bacterial proliferation)

What is fibrinoid necrosis? Under what circumstances does fibrinoid necrosis usually occur?

Specific type of lytic necrosis

Characteristic:

• Occurs in vessels during vascular damage or vasculitis

• Accumulation of fibrin, blood proteins and immunocomplexes

What is apoptosis?

Regulated (programmed) cell death

Which enzyme mediate the process of apoptosis?

Caspases

• Aspartic acid is one specific amino acid → Caspases are enzymes that recognise aspartic acid in a protein chain → They cleave the peptide bond immediately after the aspartic acid residue

What are the physiological roles of apoptosis (homeostasis)?

• Embryogenesis – shapes tissues/organs by removing unnecessary cells

• Cell turnover in proliferating tissues – e.g., intestinal epithelium

• Tumor suppression – eliminates potentially malignant cells

• Immune system maturation – removes excess or self-reactive lymphocytes

What are the causes of apoptosis?

Normal homeostasis (No inflammation)

Intrinsic:

• DNA damage

• Accumulation of misfolded proteins

Extrinsic:

• Pathogen infection via cytotoxic T cells

• TNF-1 receptor (death domain)

What is the morphology of apoptosis?

• Cellular shrinkage and eosinophilia

• Chromatin condensation

• Formation of apoptotic bodies → Engulfed by macrophages

What distinguishes apoptosis from necrosis?

Apoptosis is a regulated form of cell death that avoids inflammation, while necrosis often triggers inflammation due to cell lysis.