Ch. 2

Chapter 2: Altered Cells & Tissues

Overview

  • Normal brain of a young adult.

  • Atrophy of the brain in an 82-year-old male with atherosclerotic disease.

  • Key areas to cover:

    • Cell review

    • Cellular injury

    • Deficit

    • Toxins

    • Trauma

    • Response to injury

    • Adaptation

    • Reversible injury

    • Permanent damage

    • Cell death

  • Clinical modules implications on pathology.

Cellular Components & Functions

  • Important components to understand:

    • Plasma Membrane: The barrier that separates the interior of the cell from its external environment.

    • Organelles: Specialized structures within cells that perform specific functions.

    • Endoplasmic Reticulum: Involved in the synthesis of proteins and lipids.

    • Golgi Apparatus: Modifies, sorts, and packages proteins and lipids for secretion or delivery.

    • Lysosomes: Contains enzymes for digestion of cellular waste and macromolecules.

    • Peroxisomes: Breaks down fatty acids and detoxifies harmful substances.

    • Proteasomes: Complexes that degrade unneeded or damaged proteins by proteolysis.

    • Mitochondria: The powerhouse of the cell, generating ATP through respiration.

    • Cytoplasm: The gel-like substance where cell components are suspended.

    • Nucleus: Contains genetic material (DNA), responsible for cell regulation and replication.

    • Cytoskeleton: Provides structural support, helps with intracellular transport and cell division.

  • Transportation mechanisms:

    • Active Transport: Movement against a concentration gradient, requiring energy.

    • Passive Transport: Movement along a concentration gradient, does not require energy.

    • Diffusion: Movement of molecules from an area of high concentration to low concentration.

    • Facilitated Diffusion: Movement of molecules across a cell membrane via transport proteins.

    • Osmosis: The diffusion of water across a semipermeable membrane.

    • Primary and Secondary Active Transport: Primary uses ATP directly, whereas secondary relies on the gradient established by primary transport.

  • Cellular processes:

    • Ingestion: Taking in substances necessary for cell function.

    • Secretion: Release of substances from a cell.

    • Respiration: Process of breaking down nutrients to generate energy.

    • Communication: Intercellular signaling and response to external stimuli.

    • Reproduction: Cell division and replication processes.

  • Reference additional materials: Anatomy & Physiology text and Module 1 in Chapter 2 of Pathological text for review of structures & functions.

Cellular Injury

  • Cellular injury can occur through various mechanisms:

    • Deficit Injury: Lack of essential substances for cell function such as:

    • Oxygen (O2)

    • Nutrients

    • Toxins: Substances that interfere with cellular functions include:

    • Exogenous Toxins: Originating externally, e.g., bacteria, drugs.

    • Endogenous Toxins: Originating internally, e.g., metabolic byproducts such as free radicals.

    • Trauma: Physical injuries resulting from:

    • Car crashes

    • Exposure to cold, heat, radiation

    • Enzymatic action of bacteria.

Types of Cellular Injury

1. Deficit Injury: Stroke

  • Lack of oxygen (hypoxia) to the brain can lead to stroke.

  • Often caused by reduced blood supply (ischemia) due to:

    • Narrowing of arteries (arteriosclerosis)

    • Blood clots (thrombosis)

  • Other causes of deficit injuries include:

    • Disruptions of metabolic pathways due to genetic diseases or viruses.

    • Infection agents utilizing nutrients necessary for normal cellular function.

2. Toxins: Phenylketonuria (PKU)

  • PKU is a genetic defect resulting in an endogenous toxin.

  • A mutation alters the metabolic pathway leading to:

    • Accumulation of an abnormal metabolite, phenylpyruvic acid.

    • Damage to brain cells, potentially resulting in cognitive disabilities.

  • Other Endogenous Toxins:

    • Reactive Oxygen Species (ROS): Generated during mitochondrial respiration.

    • Excessive ROS or insufficient detoxifying enzymes lead to free radical injury.

    • Implications of free radical injury in diseases such as heart disease, diabetes, and cancer.

    • Role of antioxidants (e.g., Vitamin E) in inactivating free radicals.

3. Trauma

  • Physical injury can occur from:

    • Trauma from accidents (car crash)

    • Effects of extreme temperatures (cold/heat)

    • Radiation exposure

    • Enzymatic actions of bacteria.

Cellular Responses to Injury or Stress

  • Cells can respond to injury or stress through various compensatory mechanisms:

    • Adaptation: Cells adjust to changing conditions.

    • Reversible Injury: Potential for recovery if conditions return to normal.

    • Permanent Dysfunction: Could lead to irreversible changes in function.

    • Cell Death: Can result from severe damage or cumulative stress.

Adaptive States of Cells

  • Hyperplasia: Increase in cell number.

  • Hypertrophy: Increase in cell size.

  • Atrophy: Decrease in cell size.

  • Metaplasia: Change from one differentiated cell type to another.

  • Dysplasia: Abnormal change in size, shape, uniformity, and arrangement of cells.

Reversible Injury: Cellular Accumulations

  • Cellular injury may disrupt metabolism or protein synthesis, leading to:

    • Accumulation of substances within cells, which can be either normal or abnormal.

    • Examples of accumulations include:

    • Water

    • Lipids

    • Glycogen

    • Proteins

Specific Types of Reversible Injury Accumulation

  • Water Accumulation:

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

    • Cell rupture is possible, but not common.

  • Lipid Accumulation:

    • Fat can accumulate in cells due to injury.

    • The cytoplasm and nucleus may be pushed to the periphery, leading to possible damage.

    • Cells can rupture, causing fat to coalesce and damage organs.

    • Tissues that utilize fat for energy or synthesize lipids are more susceptible to damage (e.g., alcoholic fatty liver disease).

  • Glycogen Accumulation:

    • Excess glycogen can cause vacuolation of the cytoplasm, often linked with diabetes mellitus.

  • Protein Accumulation:

    • Can damage cells in two ways:

    • Cells digest excess proteins, leading to excess breakdown products and damage to organelles.

    • Congested excess proteins can exert physical pressure on organelles, disrupting their function.

Structural Changes in Reversible Injury

  • Influx of water or other accumulations can cause:

    • Distortion of cell membranes

    • Distortion of organelles

    • Vacuolation of cytoplasm

    • Clumping of the nucleus

  • Cells may reorganize if normal conditions are restored.

Permanent Dysfunction: Irreversible Injury

  • Irreversible injuries typically lead to cell death characterized by:

    • Breakdown of organelles.

    • Defects in cell membranes increase permeability.

    • Altered nuclear structure.

    • Dysfunction of the nucleus leads to irreversible damage.

Types of Cell Death

  • Apoptosis: Programmed cell death; an orderly process that can be either normal or pathological.

  • Necrosis: Disorderly process resulting from cellular injury.

Cerebral Atrophy

  • Atrophy can occur due to multiple sclerosis progression:

    • Common feature of various diseases rather than a singular disease.

    • Represents a reduction in the size of cells within the cerebrum of the brain.

    • Progressive neuron size reduction leads to functional deficits.

Causes of Cerebral Atrophy

  • Potential causes include:

    • Low levels of B vitamins.

    • Bacterial infections.

    • Car crashes.

  • Atrophy effects may be focal (localized) or global (affecting entire cerebrum).

Treatment Strategies for Atrophy

  • Focus on maximizing function and minimizing ongoing damage through:

    • Supportive care.

    • Physical, speech, and occupational therapy.

    • Pharmacological interventions (vary depending on pathology).

  • Question for Reflection: Can neurologic function be completely restored after it is lost due to cerebral atrophy? Discuss the reasons why or why not.

Acromegaly

  • Condition characterized by cellular hyperplasia due to excessive hormonal stimulation:

    • Influenced by Pituitary Growth Hormone and Liver Insulin-like Growth Factor 1 (IGF-1).

Feedback Mechanism in Growth Regulation

  • Growth Hormone (GH) stimulates cellular proliferation leading to hyperplasia.

  • GH induces the release of IGF-1, promoting growth in bones, cartilage, soft tissues, and organs.

  • IGF-1 normally signals back to the hypothalamus, leading to the release of somatostatin (GH-inhibiting hormone).

Causes of Acromegaly

  • The majority of acromegaly cases arise from adenomas that do not respond to feedback from somatostatin, incessantly producing GH, which leads to increased IGF-1 levels.

  • An adenoma developing in childhood can result in gigantism (excessive height).

Clinical Manifestations of Acromegaly

  • Symptoms may include:

    • Soft tissue swelling.

    • Enlarged hands and feet.

    • Altered facial features.

    • Pain and numbness in the extremities.

    • Deepening of voice and snoring.

    • Skin changes.

    • Enlargement of organs.

    • Altered reproductive functions.

Treatment for Acromegaly

  • Goals include reducing releases of IGF-1 and GH to reverse or decrease effects of acromegaly through:

    • Drug therapy.

    • Radiation therapy.

    • Surgical removal of adenomas.

  • Early identification can potentially eliminate chronic effects.