RAD 204 Pathology Basic Terminology Week of 15.Septmeber.2013 College of Medical Sciences/ Radiological Sciences Department Dr. Shai’ Lecture 2

I. INTRODUCTION

A. Objectives 1. Define pathology 2. Discuss the core aspects of disease in pathology 3. Know pathological manifestations of disease 3. Know pathological manifestations of disease 4. Know the diagnostic techniques used in pathology 4. Know the diagnostic techniques used in pathology

B. Definitions Latin, Patho: disease, Logy: study of Diseases: Abnormal Variations in Structure or Function of Any Part of the Body WE study the aetiology, pathogenesis, morphologic changes & functional derangements and clinical significance

1. Aetiology Cause Known: primary aetiology {key to diagnosis and treatment development} Unknown: Idiopathic ClassesGeneticAcquired Infectious, Nutritional, Chemical, etc

2. Pathogenesis Mechanism through which the cause operates to produce the pathological and clinical manifestations Occurs in latent or incubation period Leads to morphological changes: visible by naked eye, microscopes and diagnostic visualization

3. Morphology Cell and Tissue Structure Changes: structural alterations subsequent to pathogenesis Allows pathologist to identify (diagnose) disease And will lead to understanding of clinical signs and symptoms of disease

4. Functional derangements and clinical significance AetiologyPathogenesis Clinical Features Prognosis There are different diagnostic modalities used in pathology. Most of these diagnostic techniques are based on morphologic changes.

5. Diagnostic techniques used in pathology HistopathologyCytopathology Haematopathology ImmunohistochemistryMicrobiological Exam Biochemical ExamCytogenetics Molecular TechniquesAutopsy

II. CELLULAR INJURY

A. Objectives 1. Define hyperplasia, hypertrophy, atrophy, hyperplasia, metaplasia & list some of their causes. 2. Know the differences between reversible & irreversible forms of cell injury. 3. Oncology Terminology 4. Molecular Basis of Cancer

B. Definitions Cellular injury underlies ALL DISEASE INJURIOUS AGENT > CELL > OUTCOMES: Cell adapts to situation Cell acquires a reversible injury Cell acquires IRREVERSIBLE injury and dies by: Necrosis (unprogrammed) Apoptosis (programmed) Outcome depends on type of injurious agent & on cellular factors It depends on the Type, Severity, Duration of Injury & Type of cell

1. Cellular Adaptation HYPERTROPHYATROPHYHYPERPLASIAMETAPLASIA

A. HYPERTROPHY Increase in size of cells Increased workload leads to increased protein synthesis Leads to increased size and number of intra cellular organelles Leads to increased cell size > increased ORGAN size Eg. LV enlargement in hypertensive heart dz Eg. Increased skeletal muscle during strenuous exercise

B. ATROPHY Atrophy is a decrease in the size of a cell. This can lead to decreased size of the organ. The atrophic cell shows autophagic vacuoles which contain cellular debris from degraded organelles. Atrophy can be caused by: 1. Disuse 2. Undernutrition 3. Decreased endocrine stimulation 4. Denervation 5. Old age

C. HYPERPLASIA Hyperplasia is an increase in the number of cells. It can lead to an increase in the size of the organ. It is usually caused by hormonal stimulation. It can be physiological as in enlargement of the breast during pregnancy or it can pathological as in endometrial hyperplasia. It is usually caused by hormonal stimulation. It can be physiological as in enlargement of the breast during pregnancy or it can pathological as in endometrial hyperplasia.

D. METAPLASIA Replacement of one differentiated tissue by another differentiated tissue. Examples include: 1. Squamous metaplasia: replacement of another type of epithelium by squamous epithelium. Eg. columnar epithelium of bronchus replaced by squamous epithelium in cigarette smokers 2. Osseous metaplasia: replacement of a connective tissue by bone, for example at sites of injury.

3. Oncology Terminology Tumour An abnormal mass of tissue, resulting from autonomous disordered growth that persists after the initiating stimulus has been removed. Results from genetic alteration and deregulated growth control mechanisms -oma: means swelling Anaplastic: poorly differentiated Benign: localized cancers that do NOT invade other organs Malignant: capable of invasion and spread to distant organs Dysplasia: Disordered development of cells resulting in an alteration in size, shape and organization

Carcinoma in situ: Epithelial neoplasm with cellular features associated with malignancy, but not yet invaded through epithelial basement membrane DID YOU KNOW? Japan: gastric carcinoma is 30 times more common than UK ? Why do you think this is?

4. Molecular Basis of Cancer Proto Oncogenes Tumour Suppressor Genes

Cell proliferation and division regulated by 2 opposing functions Proto oncogenes: genes expressed in normal cells Code for onco proteins, which positively regulate cell growth differentiation {growth factors, transcription factors, receptor molecules} Healthy cells: tightly controlled Unhealthy cells: mutation produce onco protein which is functionally altered eg hyperactive mutant ras protein affects intracellular pathway signalling Or normal protein overproduced eg myc oncogene in neuroblastomas Includes: Nuclear binding proteins (eg c-myc) Tyrosine kinase proetins (eg src) Growth factors (eg platelet derived growth factor) Receptors for growth ( eg c-erb, HER 2), GTP binding proetins (eg ras)

Tumour Suppressor Genes (TSG) Encode proteins that prevent or suppress tumour growth If inactivated>>increased susceptibility to cancer Eg. BRCA1 in breast cancer & ovarian cancer, located on chromosome 17q P53 protein on 17p (implicated in many cancers) RB1 in retinoblastoma, 17q TSGs lose normal function by: Mutations (hereditary / acquired) Binding of TSG protein to viral gene proteins (HPV E6/7) Complexing TSG protein to mutatnt TSG protein If DNA damaged, TSG will promote cell apoptosis

5. Definitions … Apoptosis: PROGRAMMED CELL DEATH Active process Single cell initiates own death under normal physiological conditions Occurs in tissue modelling, embryogenesis, immune regulation, and deregulated in tumours

ZisZ0&list=PL88EDB2A96ED033AE ZisZ0&list=PL88EDB2A96ED033AE OVERVIEW (25 MIN)