Altered Cells & Tissues: Cellular Injury, Adaptation, and Disease

Chapter 2: Altered Cells & Tissues

Overview

This chapter explores the mechanisms by which cells and tissues respond to injury and stress, including cellular components, types of injury, adaptive responses, and clinical examples. Understanding these processes is fundamental to cell biology and pathology.

• Cellular injury: deficit, toxins, trauma

• Response to injury: adaptation, reversible injury, permanent damage, cell death

• Clinical modules: cerebral atrophy, acromegaly

Cellular Components & Functions

Major Cellular Structures

Cells contain specialized structures (organelles) that perform essential functions for survival and adaptation.

• Plasma membrane: regulates transport and communication

• Organelles:

  • Endoplasmic reticulum: protein and lipid synthesis

  • Golgi apparatus: protein modification and sorting

  • Lysosomes: intracellular digestion

  • Peroxisomes: lipid metabolism and detoxification

  • Proteasomes: protein degradation

  • Mitochondria: energy production (ATP synthesis)

• Cytoplasm: site of metabolic activity

• Nucleus: genetic material storage and regulation

• Cytoskeleton: structural support and cell movement

Cellular Functions

• Transportation: active/passive transport, diffusion, osmosis

• Ingestion: uptake of nutrients

• Secretion: release of substances

• Respiration: energy production

• Communication: signaling between cells

• Reproduction: cell division

Cellular Injury

Types of Cellular Injury

Cells can be injured by various mechanisms, leading to functional impairment or death.

1. Deficit Injury: Lack of essential substances (e.g., oxygen, nutrients)

   • Example: Ischemic stroke—reduced blood supply causes hypoxia and cell death

2. Toxins: Presence of harmful substances

   • Exogenous: bacteria, drugs, chemicals

   • Endogenous: metabolic byproducts, free radicals

   • Example: Phenylketonuria (PKU)—mutation leads to accumulation of phenylpyruvic acid, damaging brain cells

3. Trauma: Physical injury (e.g., car crash, cold, heat, radiation)

Cellular Injury Mechanisms

• Deficit injury: Disrupts metabolic pathways, can be caused by genetic diseases or infections

• Toxins:

  • Reactive oxygen species (ROS) from mitochondrial respiration can cause free radical injury

  • Antioxidants (e.g., Vitamin E) help inactivate free radicals

• Trauma: Can result in tissue damage, necrosis, or altered cell structure

Cellular Responses to Stress

Compensatory Responses

Cells respond to stress or injury by activating adaptive or pathological processes.

1. Adaptation

2. Reversible injury and recovery

3. Permanent dysfunction

4. Cell death

Five Adaptive States

• Hyperplasia: Increase in cell number

• Hypertrophy: Increase in cell size

• Atrophy: Decrease in cell size

• Metaplasia: Change in cell type

• Dysplasia: Change in cell size, shape, uniformity, structure, arrangement

Reversible Injury

Cellular Accumulations

Injury can disrupt metabolism or protein synthesis, leading to accumulation of substances within cells.

• Water: Most common; cells appear swollen and pale due to water-filled vacuoles

• Lipids: Fat accumulation can damage organs (e.g., fatty liver disease)

• Glycogen: Excess leads to vacuolation, often seen in diabetes mellitus

• Proteins: Excess proteins can damage organelles or disrupt function

Structural Changes

• Distorted cell membranes and organelles

• Vacuolated cytoplasm

• Clumping in nucleus

• Cells can reorganize if normal conditions are restored

Permanent Dysfunction and Cell Death

Irreversible Injury

• Breakdown of organelles

• Cell membrane defects increase permeability

• Altered nucleus—irreversible damage if nucleus fails

Types of Cell Death

• Apoptosis: Programmed, orderly cell death (can be normal or pathologic)

• Necrosis: Disorderly process due to cell injury

Clinical Example: Cerebral Atrophy

Features and Causes

• Common in many diseases, not a disease itself

• Reduction in size of brain cells (neurons)

• Leads to functional deficits

• Causes: low B vitamins (deficit), bacterial infection (toxin), car crash (trauma)

• Manifestations can be focal (localized) or global (entire cerebrum)

Treatment

• Supportive care

• Physical, speech, occupational therapy

• Pharmacologic treatment (depends on pathology)

Clinical Example: Acromegaly

Pathophysiology

• Condition of cellular hyperplasia due to excessive hormonal stimulation

• Caused by increased pituitary growth hormone (GH) and liver insulin-like growth factor 1 (IGF-1)

• Feedback mechanism: IGF-1 normally inhibits GH via somatostatin

• Most cases due to pituitary adenoma (tumor)

Clinical Manifestations

• Soft tissue swelling

• Enlarged hands and feet

• Altered facial features

• Pain and numbness in hands

• Voice deepening, snoring

• Skin changes

• Enlarged organs

• Altered reproductive function

Treatment

• Reduce release of IGF-1 and GH (can reverse or decrease effects)

• Drug therapy, radiation therapy, surgical removal of adenoma

• If identified early, chronic effects can be eliminated

Summary Table: Types of Cellular Injury

Type of Injury	Cause	Example
Deficit	Lack of essential substances	Ischemic stroke
Toxins	Presence of harmful substances	PKU, ROS/free radicals
Trauma	Physical injury	Car crash, frostbite

Key Equations

• ATP production (cellular respiration): $C_6H_{12}O_6 + 6O_2 ightarrow 6CO_2 + 6H_2O + ATP$

• Phenylalanine metabolism (PKU): $\text{Phenylalanine} \xrightarrow{\text{Phenylalanine hydroxylase}} \text{Tyrosine}$ In PKU, this enzyme is deficient, leading to accumulation of phenylpyruvic acid.

Additional info:

• Cellular adaptation and injury are central to understanding disease mechanisms in cell biology and pathology.

• Clinical examples illustrate how cellular changes manifest as disease symptoms and guide treatment strategies.