Chapter 1

Introduction to Pathology
Zhao Guoqiang

Introduction to Pathology
• Definition of Pathology • Evolution of Pathology • Subdivision of Pathology • Methods for the study of pathology

Definition of Pathology
The word “Pathology” is derived from two Greek word ---pathos meaning suffering logos meaning study

Definition of Pathology
Pathology is scientific study of structure and function of the body in disease. It deals with causes, effects, mechanisms and nature of disease.

The knowledge and understanding of pathology is essential for all would-be doctors as well as general practitioners and specialists since unless they know the causes and mechanisms of disease and understand the language spoken by the pathologist in the form of laboratory reports, they would not be able to institute appropriate treatment or suggest preventive measures to the patient.

For the medical student, the discipline of pathology forms a vital bridge between initial learning phase of preclinical science and the final phase of clinical subjects.

Evolution of Pathology
• From religious beliefs to rational approach (Antiquity to AD 1500) • Era of gross pathology (AD 1500 to 1800) • Era of technology development and cellular pathology (AD 1800 to 1950s) • Modern pathology (1950s to dawn of 21st century)

From religious beliefs to rational approach (Antiquity to AD 1500)
• Hippocrates (Greece) 460-377 BC
Permanently dissociated medicine from religious mysticism. Started study of patient’s symptoms as method of diagnosis.

• Cornelius Celsus (Rome) 53 BC-7 AD
Described 4 cardinal signs of inflammation (redness, heat, swelling, pain)

Hippocrates (Greece) 460-377 BC

Era of gross pathology (AD 1500 to 1800)
• Giovanni B Morgagni (Italy) 1682-1771
Introduced clinicopathologic correlation (CPC) in the study of disease

• John Hunter (Scotland) 1728-1793
Introduced pathology museum in the study of disease.

• R.T.H. Laennec (France) 1781-1826
Described several lung diseases such as various tuberculous lesions of lungs, bronchiectasis. Described cirrhosis of liver (later called Laennec’s cirrhosis). Invented stethoscope.

John Hunter (Scotland) 1728-1793

R.T.H. Laennec (France) 1781-1826

Era of technology development and cellular pathology (AD 1800 to 1950s)
• Rudolf Virchow (Germany) 1821-1905
Father of cellular pathology Introduced histopathology as a diagnostic branch by his cellular theory

• George N. Papanicolaou (USA) 1883-1962
Father of exfoliative cytology Developed Pap smear for detection of cervical cancer in 1930s

Rudolf Virchow (Germany) 1821-1905

George N. Papanicolaou (USA) 1883-1962

Modern pathology (1950s to dawn of 21st century)
• Watson and Crick 1953
Described the structure of DNA

• Nowell and Hagerford 1960
Philadelphia chromosome in CML i.e. t(9;22)

• Gall and Pardue 1969
In Situ Hybridization

• Kary Mullis 1983
Introduced polymerase chain reaction (PCR)

Prof. Liang Boqiang 1899-1968

Prof. Qin Guangyu 1902-1969

Subdivision of Pathology
• General Pathology --- dealing with general principles of disease • Systemic Pathology --- includes study of diseases pertaining to the specific organs and body systems

Subdivision of Pathology
• • • • • • • • Histo-Pathology Experimental Pathology Molecular Pathology Chemical Pathology Geographic Pathology Immunology Haematology Medical Genetics

Methods for the study of Pathology • Autopsy • Biopsy • Cytology

What is Autoposy?
Autopsy means "see for yourself". It is a special surgical operation, performed by specially-trained physicians, on a dead body. Its purpose is to learn the truth about the person's health during life, and how the person really died.

What is Bioposy?
A biopsy is the removal of a sample of tissue from the body for examination. The tissue will be examined under a microscope to assist in diagnosis. Therefore, only very small samples are needed.

What is Cytology?
Cytology can also refer to cytopathology, which analyzes cell structure to diagnose disease .

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Chapter 2
Cellular Adaptations and Cell Injury

Cellular Adaptations and Cell Injury
• Cellular adaptations • Causes of cell injury • Mechanisms of cell injury • Morphology of cell injury

• Cellular Responses to Stress and Noxious Sti

Human body is quite complex and is made of 70,000 billion cells. In health, these cells remain in accord with each other. However, most forms of diseases begin with cell injury and consequent loss of cellular function .

Injury is defined as an alteration in cell structure or function resulting from some stress that exceeds the ability of the cell to compensate through normal physiologic adaptive mechanisms.

Cells typically respond to potentially injurious stress in one of two ways: Adaptation - Cells can alter their structure and/or biochemical processes in order to achieve a new "steady state" and maintain near-normal physiologic functions (homeostasis). Injury - If stressed cells cannot adequately adapt, critical cell functions may be impaired, and the cell is said to be injured.

Reversible and irreversible injury
If injured cells recover their normal functions when the stress is removed, the injury is said to be reversible. If the injury is severe enough, however, a “Point of no return” is reached and the cell suffers irreversible injury and dies.

Cellular Responses to Stress and Noxious Stimuli

Adaptation, Reversible injury, Irreversible injury (Cell death)
may be considered as different stages of a progressive impairment of the cell’s normal function and structure.

Cellular adaptations
• Atrophy • Hypertrophy • Hyperplasia • Metaplasia

Atrophy
Reduction of the number and size of parenchymal cells of an organ or its parts which was once normal is called atrophy. It may occur from physiologic or pathologic causes.

Physiologic Atrophy
• Atrophy of thymus after puberty • Atrophy of gonads after menopause • Atrophy of brain with aging

Pathologic Atrophy
• • • • • • Malnutrition atrophy Denervation atrophy Disuse atrophy Pressure atrophy Endocrine atrophy Ischaemic atrophy

Atrophy of one kidney, gross

Atrophy, muscle fibers, microscopic

Hypertrophy
Hypertrophy is an increase in the size of parenchymal cells resulting in enlargement of the organ or tissue, without any change in the number of cells. It may be physiologic or pathologic.

Physiologic Hypertrophy

Pathologic Hypertrophy
• Hypertrophy of cardiac muscle • Hypertrophy of smooth muscle • Hypertrophy of skeletal muscle • Compensatory hypertrophy

. Hypertrophy, heart, gross

Hyperplasia
Hyperplasia is an increase in the number of parenchymal cells resulting in enlargement of the organ or tissue. Hyperplasia occurs due to increased recruitment of cells from C0 (resting) phase of the cell cycle to undergo mitosis,when stimulated.

Hyperplasia, prostate, gross

Metaplasia
Metaplasia is defined as a reversible change of one type of epithelial or mesenchymal adult cells to another type of adult epithelial or mesenchymal cells, usually in response to abnormal stimuli, and often reverts back to normal on removal of stimulus.

Metaplasia
• Epithelial metaplasia 1. Squamous metaplasia 2. Columnar metaplasia • Mesenchymal metaplasia 1. Osseous metaplasia 2. Cartilaginous metaplasia

Metaplasia, squamous, larynx, microscopic

Metaplasia , gastric columnar mucosa in esophagus, microsc

Causes of cell injury
• • • • • • • Hypoxia and ischaemia Physical agents Chemical agents and drugs Infection agents Immunologic reactions Genetic derangements Nutritional imbalances

Hypoxia and ischaemia
Hypoxia is the most common causes of cell injury. The causes of hypoxia are as under: • The most common mechanism of hypoxic cell injury is by reduced supply of blood to cell i.e. ischaemia. • Oxygen deprivation of tissues may result from other causes as well e.g. in anaemia, CO poisoning, cardiorespiratory insufficiency, and increased demand of tissues.

Physical agents
Physical agents in causation of disease are:
• • • • • Mechanical trauma (e.g. road accidents); Thermal trauma (e.g. by heat and cold); Electricity; Radiation (e.g. ultraviolet and ionising); Rapid changes in atmospheric pressure.

Chemicals and Druges
Important example include:
• • • • • • • • Chemical poisons such as cyanide, arsenic, mercury; Strong acids and alkalis; Environmental pollutants; Insecticides and pesticides; Oxygen at high concentration; Hypertonic glucose and salt; Social agents such as alcohol and narcotic drugs; Therapeutic administration of drugs.

Infection agents
Injuries by microbes include infections caused by :
• • • • • • • Bacteria; Rickettsiae; Viruses; Fungi; Protozoa; Metazoa; Other parasites.

Immunologic reactions
Immunity is a “double-edged sword” --- it protects the host against various injurious agents but it may also turn lethal and cause cell injury e.g.
• Hypersensitivity reactions; • Anaphylactic reactions; • Autoimmune reactions.

Genetic derangements
Genetic defects as causes of cell injury are of major interest to scientists and physicians today. • The genetic injury may result in a defect caused by a chromosomal abnormality (e.g. the congenital malformations associated with Down syndrome). • Variations in the genetic makeup can also influence the susceptibility of cells to injury by chemicals and other environmental insults.

Nutritional imbalances
A deficiency or an excess of nutrients may result in nutritional imbalances. • Nutritional deficiency diseases may be due to overall deficiency of nutrients (e.g. starvation), of protein calorie (e.g. marasmus, kwashiorkor), of minerals (e.g. anaemia), or of trace elements. • Nutritional excess is a problem of affluent societies resulting in obesity, atherosclerosis, heart disease and hypertension.

Mechanisms of cell injury
• Depletion of ATP • Membrane damage • Influx of intracellular calcium and loss of calcium homeostasis • Accumulation of oxygen-derived free radicals (oxidative stress)

Cellular and biochemical sites of damage in cell injury

Morphology of cell injury
• Degeneration/Intracellular Accumulations • Cell death

Degeneration and Intracellular Accumulations
• In conventional description of morphologic change, the term degeneration has been used to denote morphology of reversible cell injury. • Currently, more acceptable terms of reversible cell injury are applied to non-lethal cell injury.

• One of the manifestations of metabolic derangements in cells is the intracellular accumulation of abnormal amounts of various substances.

The stockpiled substances fall into three categories: 1. A normal cellular constituent accumulated in excess, such as water, lipids, proteins, and carbohydrates; 2. An abnormal substance, either exogenous, such as a mineral or products of infectious agents, or endogenous, such as a product of abnormal synthesis or metabolism; 3. A pigment.

Degeneration and Intracellular Accumulations
• Cellular swelling • Fatty change • Hyaline change • Amyloidosis • Pigments • Pathologic calcification

Cellular Swelling
• • Cellular swelling is the first manifestation of almost all forms of injury to cells. Other synonyms of cellular swelling used in the past are: cloudy swelling (for gross appearance of the affected organ) hydropic change (accumulation of water within the cell) vacuolar degeneration (due to cytoplasmic vacuolation)

Cellular Swelling
• Grossly, the affected organ such as kidney, liver or heart muscle is enlarged due to swelling. The cut surface bulges outwards and is slightly opaque.

Cellular Swelling
• Microscopically, it is characterised by the following features: 1. The cells are swollen and the microvasculature compressed. 2. Small clear vacuoles are seen in the cells and hence the term vacuolar degeneration.

Fatty change (Steatosis)
• The terms fatty change and steatosis describe abnormal accumulations of triglycerides within parenchymal cells. • Fatty change is often seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart, muscle, and kidney.

Fatty metamorphosis of liver, gross

. Fatty metamorphosis of liver, microscopic

Fatty change, liver, microscopic

Hyaline Change
• • The word “Hyaline” means glassy (hyalos = glass). Hyaline is a descriptive histologic term for glassy, homogeneous, eosinophilic appearance of material in H.E stained sections and does not refer to any specific substance. Hyaline change is associated with heterogeneous pathologic conditions and may be intracellular or extracellular.

Intracellular Hyaline
• Intracellular hyaline is mainly seen in epithelial cells. For example: 1. Hyaline droplets in the proximal tubular epithelial cells in cases of excessive reabsorption of plasma. 2. Mallory’s hyaline represents aggregates of intermediate filaments in the hepatocytes in alcoholic liver cell injury.

Intracellular Hyaline
3. Nuclear or cytoplasmic hyaline inclusions seen in some viral infections. 4. Russel’s bodies representing excessive immunoglobulins in the RER of the plasma cells.

Hyaline droplets in the renal tubular epithelium

Mallory's hyaline, liver, microscopic

Extracellular Hyaline
• Extracellular hyaline is seen in connective tissues. A few examples of extracellular hyaline change are: 1. Hyaline degeneration in leiomyomas of the uterus. 2. Hyalinised old scar of fibrocollagenous tissues. 3. Hyaline arteriosclerosis is renal vessels in hypertension and diabetes mellitus. 4. Hyalinised glomeruli in chronic glomerulonephritis.

Uterus, leiomyoma, microscopic

Renal hyaline arteriolosclerosis with diabetes melli

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