1) Introduction to General Pathology & Tissue Reaction to Injury

INTRODUCTION TO GENERAL PATHOLOGY & TISSUE REACTION TO INJURY

Dr Huzlinda Hussin

MD (USM), MPath (UM)

Pathologist

Department of Pathology

FMHS, UPM

Pathology teaching & Problem Based approach

• Use modular approach- is one of the SCL methods that emphasizes on compact self-contained teaching/learning module to encourage students’ participation and engagement towards learning

• Module format:

1. Module title

2. Module code

3. Learning resources- list of references

4. Terminologies- list of important terms in the topics eg: pathogenesis

5. Learning outcomes (LO)

6. Course contents & learning activities -lists of topics that will be covered in the lectures; other activities eg: practicals and tutorial

7. Summary

8. Assignment

9. Evaluation- final exam

What is pathology?

• Pathology is literally the study (logos) of suffering (pathos)

• More specific- a bridging discipline involving both basic science and clinical practice and is devoted to the study of the structural and functional changes in the cells, tissues and organs that underlie disease.

• The study of pathology- general pathology (GP) and systemic pathology (SP).

• GP-basic reactions of cells and tissues to abnormal stimuli that underlie all diseases.

• SP-examines the specific responses of specialized organs and tissues to more or less well defined stimuli.

• 4 aspects of disease process that form the core of pathology are:

1.Etiology: cause of disease

2.Pathogenesis: mechanisms of disease development

3.Morphologic changes: structural alterations induced in cells and organs of the body

4.Clinical significance: functional consequences of the morphologic changes

1. Etiology or Cause• 2 major classes of etiologic factors:

1. Intrinsic/ genetic- developmental, cytogenetic defects.

2. Acquired- a) Hypoxia and ischemia

b) Physical agents- trauma (mechanical/thermal), radiation

c) Chemicals & drugs

d) Microbial agents- eg bacteria, virus,fungus, etc

e) Immunologic agents- eg: hypersensitivity reactions, autoimmune disease, etc

f) Nuritional derangements (excess or deficiency) -eg: marasmus (protein def), vit def , iron def anaemia, obesity, etc.

mnemonic for remembering the 8 causes of cellular injury:

• 1. Causes = Chemicals2. Of = Oxygen deprivation3. Injury = Infectious agents4. Give= Genetic5. A = Aging6. Physician = Physical agents7. Necessary = Nutritional Imbalances8. Information = Immunologic

Knowledge of etiology remains the backbone:Knowledge of etiology remains the backbone:

Disease diagnosesDisease diagnoses

Understanding the nature of diseasesUnderstanding the nature of diseases

Treatment of diseases.Treatment of diseases.

2. Pathogenesis

• Refers to the sequence of events in the response of cells of tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the dz.

Eg: to understand cystic fibrosis- need to know not only the defective gene and gene products but also the biochemical, immunologic and morphologic events leading to the formation of cysts and fibrosis in the lung, pancreas and other organs

3. Morphologic changes

• Refer to the structural alterations in cells or tissues that are either characteristic of the disease or diagnostic of the etiologic process- tissue reaction to injury

• Characteristic of the disease

• Diagnostic of the etiologic process

TISSUE REACTION TO INJURY

– lethal and sublethal injury (reversible and irreversible damages)

– cellular changes due to sublethal injury:• hydropic degeneration

• fatty change

– outcome of injury

What are 3 events that can result in cell injury?

1) cells are stressed beyond ability to adapt

2) cells exposed to damaging agents

3) cells suffer from intrinsic abnormalities

Sequential development of biochemical and morphologic changes in cell injury. Cells may become rapidly non-functional after the onset of

injury, although they are still viable, with potentially reversible damage. A longer duration of injury may lead to irreversible injury & cell death and typically this precedes ultrastructural, light microscopic & grossly

visible morphologic changes.

What happens intracellularly in reversible cell injury?

1. reduced oxidative phosphorylation, ATP

2. cellular swelling caused by Na+ & H2O influx 

3. intracellular organelles (mitochondria & cytoskeleton) show changes

At the EM level, what organelle changes are seen in reversible injury?

• 1. PM alterations- blebbing, bunting2. Mito changes- swelling, small amorphous densities3. Dilation of ER4. Nuclear alterations

What two cellular changes are seen at the light microscope level in reversible

cell injury?

1. Cellular swelling (hydropic change/ degeneration)

2. Fatty change

Hydropic change- kidney tubules

Hydropic change- hepatocytes

At the LM level, what cellular changes are seen in cellular swelling (hydropic)?

1. Small clear vacuoles (pinched off ER)

2. Hydropic change or vacuolar degeneration

Fatty change- hepatocytes (nucleus is squeezed into the periphery of the

cytoplasm by fat vacuoles)

What are two examples of cells that are involved in and dependent on fat

metabolism?

• Hepatocytes

• myocardial cells

**Other occurs in muscle and kidney

In reversible cell injury, what induces fatty change in cells involved in and

dependent on fat metabolism?

• Hypoxic, toxic or metabolic injury

What is the cause of irreversible cell injury and what does it lead

to?• 1. Continued exposure to damaging stimulus

2. Leads to cell death

What are the two main types of cell death?

1. Necrosis

2. Apoptosis