1. INTRODUCTION TO PATHOLOGY SUFIA HUSAIN ASSIT. PROF & CONSULTANT PATHOLOGY KKUH, RIYADH

2. DEFINITION OF PATHOLOGY Pathology is the study of disease by scientific methods. It is the study of changes which occur in cells and tissues as a result of any injury to the cell or tissue. It originates from 2 Latin words “patho” & “logy”. ‘Patho’ means disease and ‘logy’ means study. Diseases is defined as an abnormality in structure or function of any part of the body.

3. The following are the four major aspects studied as part of pathology of any disease. 1. Etiology, 2. Pathogenesis, 3. Morphologic changes and 4. Functional alteration and clinical features (signs and symptoms)

4. 1. E TIOLOGY Etiology of a disease means the cause of the disease. Knowledge of the primary cause is important in order to diagnosis understood, & treat any disease. If the cause of the disease is unknown it is called idiopathic/ cryptogenic/ essential etc. There are two major classes of etiologic factors: Genetic e.g. Down’s syndrome(extra chromosome 21), it is a chromosomal abnormality Acquired Infectious: bacterial, viral, fungal. Nutritional: e.g. protein energy malnutrition Chemical: e.g. alcohol cause liver disease Radiation: e.g. thyroid cancer after radiation to neck. Post radiation skin cancer etc. Mechanical: e.g. road traffic accident

5. 2. P ATHOGENESIS Pathogenesis is the mechanism through which the cause leads to the pathological and clinical manifestations. The pathogenetic mechanisms could take place in the latent or incubation period. Pathogenesis leads to morphologic changes. The four basic pathogenetic mechanisms are as follows: Inflammation Degenerative Carcinogenesis Immunological All these will be dealt with in later chapters

6. 3. M ORPHOLOGIC CHANGES The morphologic changes are the structural changes that take place in cells or tissues after any pathogenic mechanisms. These morphological changes can be seen grossly with the naked eye or sometimes they can only be seen under the light microscope. Changes that are seen with the naked eye are called gross morphologic changes & those that are seen under the microscope are called microscopic changes. In many cases a particular gross or microscopic change is seen only in a particular disease, i.e. they may be specific to that disease. And such morphologic features are used by the pathologist to diagnose the disease.

7. 4. F UNCTIONAL ALTERATIONS AND CLINICAL FEATURES The altered morphology will affect the normal function of the affected organ and this will lead to the development clinical features (signs & symptoms) of a disease. Symptoms: is something experienced and reported by the patient e.g. ‘I am feeling tired’, ‘I have a headache’ etc. Signs: are findings discovered by the physician during examination of the patient e.g. doctor finds a lymph node when he/she examines the neck of patient or doctor find a liver or spleen enlargement while palpating the abdomen etc.

8. PATHOLOGY Etiology Pathogenesis Morphological or chemical alteration Clinical features (signs and symptoms)

9. EPIDEMIOLOGY Epidemiology : Study of the occurrence and distribution of health-related diseases or events in specified populations, including the study of the determinants influencing such states, and the application of this knowledge to control the health problem (Porta M, Last J, Greenland S. A Dictionary of Epidemiology, 2008). It is the study of the patterns, causes, and effects of health and disease conditions in defined populations.

10. EPIDEMIOLOGY Epidemiology studies the various data and statistics of diseases to provide information regarding the following titles in any disease in a particular population or race: 1. Sex: certain disease are more common in men and certain in women 2. Age: various conditions are seen in various age groups 3. Race: some race are more predisposed to certain disease 4. Occupation: e.g. people working in asbestos industry can have asbetosis or mesotheliomas. People working in aniline dye industry can have urinary bladder cancer etc. 5. Geographic location: e.g. Under-developed countries has more malnutrition and infection like tuberculosis. Developed countries have more cardiac problems, obesity related diseases etc.

11. EPIDEMIOLOGY 6. Socioeconomic strata: also affects the type of disease 7. Prevalence: is the total number of cases of a particular disease in a particular defined population in a particular period of time. 8. Incidence: is the number of new cases of a particular disease in a defined population in a defined period of time. It measures the rate of occurrence of new cases. 9. Sequalea: it is the complication or the consequence of a disease. 10. Prognosis: it is the expected outcome of the disease. It is the clinician’s estimate of the severity and possible results of the disease. 11. Morbidity: is the presence and extent of illness 12. Mortality rate is a measure of the number of deaths (in general, or due to a specific cause) in a defined population, during a defined period of time. It is expressed in units of deaths per 1000 individuals per year.

12. P URPOSES AND IMPORTANCE OF E PIDEMIOLOGY 1. To investigate the extent of a disease in a community. 2. To study natural history and prognosis of disease 3. To identify causes and risk factors 4. To provide good health care based on the findings. 5. To recommend and assist in various interventions done to prevent or treat disease (preventive and therapeutic measures), e.g. immunizations, to develop screening programs for different disease etc. 6. To evaluate all health care facilities and programs. 7. It is the cornerstone of public health, and informs policy decisions. To provide foundation for public policy.

13. THEREFORE IN MEDICINE DISEASE IS STUDIED UNDER THE FOLLOWING HEADINGS : Definition Epidemiology of disease Clinical features/presentation: signs and symptoms Pathogenesis Morphology: it is divided into  Gross/ macroscopic- visible to the naked eye  Microscopic- visble under a microscope Differential diagnosis: is there any other alternative diagnosis/diagnoses Treatment and management Prognosis

14. CLASSIFICATION OF DISEASE BASED ON ETIOLOGY AND PATHOGENESIS I. CONGENITAL DISEASE: is a condition existing at birth and often before birth, or that develops during the first month of life, regardless of causation. They can be: Genetic/ chromosomal: e.g. hemophilia which is an x-chromosome linked disorder), Down syndrome, inborn error of metabolism etc Non-genetic: e.g. a birth defect like cleft lip/palate or spina bifida.

15. CLASSIFICATION OF DISEASE BASED ON ETIOLOGY AND PATHOGENESIS II. ACQUIRED DISEASES: They can be: Inflammatory e.g. rhematoid arthiritis, dermatitis Infective e.g. bacterial, viral, fungal Vascular or Immune mediated e.g. atherosclerosis (causes stroke and heart attack), vasculitis etc. Degenerative e.g. Alzheimer’s disease Neoplastic (growth disorder) e.g. cancer Drug related e.g. liver or kidney failure secondary to certain drugs Metabolic e.g. gout, diabetes mellitus etc. Nutritional deficiency diseases may arise as a result of poor supply, interference with absorption, inefficient transport within the body, or defective utilization. It may take the form of deficiency either of major classes of food, usually protein and energy, or vitamins or elements essential for specific metabolic processes, e.g. iron for haemoglobin production.

16. C OURSE OF DISEASE The course of a disease in the absence of any intervention is called the natural history of the disease. The different stages in the natural history of disease especially infectious include: a) Exposure to various risk factors (causative agents) b) Latent period between exposure and onset of disease. Incubation (induction) period refers to variable period of time without any obvious signs or symptoms from the time of exposure c) Onset of disease : the disease may remain asymptomatic or subclinical (i.e. without any clinical manifestations), or may lead to overt clinical disease. d) Outcome and consequences of disease: Following clinical onset, disease may follow any of the following trends:  resolution or recovery with or without complication or sequalae can occur or,  The disease can settle down, but sequelae are left or,  Natural recovery i.e. recovery without any intervention, can occur at any stage in the progression disease or,  It may result in death.

17. S IGNIFICANCE OF PATHOLOGY Understanding pathology will help to understand how the clinical features of different diseases occur & how to treat them. It will teach the health care workers how to handle & help their patients in a better & scientific way. It is for these reasons that it is essential to study pathology. In addition, the pathologist can use the morphologic changes seen in diseases to diagnose different diseases. There are different diagnostic modalities/instruments used in pathology. Some of the instruments used in pathology are light microscope, immunofluorescent microscope electron microscope.

18. LIGHT MICROSCOPY

19. IMMUNOFLUORESCENCE MICROSCOPY Immunofluorescence is a common technique using a fluorescence microscope With special blue filter. This technique uses antibodies chemically linked to a fluorescent dye to identify or quantify various antigens in a tissue sample. This method of study focuses on the immune response that occurs within a diseased tissue or its cells. It helps in diagnosing various diseases.

20. ELECTRON MICROSCOPE The electron microscope is a type of microscope that uses electrons to create an image of the target. It has more magnification power than a normal light microscope. Modern electron microscopes can magnify objects up to two million times. It enables us to see cell structure like mitochondria, endoplasmic reticulum, viral particles etc. It is also called as ultra structural studies.

21. This is a hydrothermal worm. It is so tiny it requires a electron microscope to see it. The organism, only slightly larger than a bacterium, lives in deep sea near or beneath the Earth's hot crust (This striking image, captured by Phillippe Crassous taken using scanning electron microscope).

22. A tardigrade, or "water bear" is seen through an electron microscope. Less than 1 mm in length, they can withstand harsh environmments and still thrive. They're known as "extremophiles". These life forms thrive under the most extreme conditions e.g. under thousand-years-old layers of ice, extreme heat, volacano. They withstand radiation bombardment and still reproduce. They bathe in acid and keep on going. The can be dried, dehydrated and desiccated, yet still go about their business. (And you thought your days were challenging!) Extremophiles, are life forms that inhabit what human beings consider "hostile" environments.

23. D IAGNOSTIC TECHNIQUES USED IN PATHOLOGY OR THE VARIOUS SUBDIVISIONS IN PATHOLOGY 1) Histopathology 2) Cytopathology 3) Immunohistochemistry 4) Hematopathology 5) Chemical pathology/ clinical biochemistry 6) Microbiology 7) Immunology 8) Toxicology 9) Cytogenetics 10) Molecular techniques 11) Autopsy

24. 1) HISTOPATHYOLOGY Histopathology studies tissues under the microscope. Tissues for histopathological examination are obtained by biopsy. Biopsy is a tissue sample from a living person to identify the disease. Biopsy can be either incisional or excisional. Once the tissue is removed from the patient, it has to be immediately fixed by putting it into adequate amount of 10% Formaldehyde (10% formalin) before sending it to the pathologist. The purpose of fixation is to prevent autolysis and bacterial decomposition and putrefaction. When the tissue reaches the lab the pathologist examines it macroscopically (i.e. naked-eye examination of tissues). They then either put the entire tissue for processing or choose parts of tissue for processing depending on the requirment.

25. 1) H ISTOPATHYOLOGY CONTD … The tissue is processed is special way resulting in very thin tissue slices (i.e. 4 to 6 microns) and the slices are then placed on a slide with the help of an adhesive. The end result is thin slices of tissue on a slide tissue ready for staining with various kinds of stains ( e.g. H&E stain or other special stains such as PAS, Immunohistochemistry, etc...) The Hematoxylin/Eosin (H&E) stain is routinely used to stain the selected tissue part. It gives the nucleus a blue color & the cytoplasm & the extracellular matrix a pinkish color. Then the pathologist will look at the tissue structures under the microscope. And based on this abnormal morphology he/she will make the diagnosis. Histopathology is usually the gold standard for pathologic diagnosis.

26. H ISTOPATHOLOGY SLIDES READY TO BE EXAMINED UNDER A LIGHT MICROSCOPE

28. 2) CYTOPATHOLOGY Cytopathology is the study of cells from various body sites to determine the cause or nature of disease. It is used for the purpose of: Screening for cancer e.g. cervical cytology is used in the screening of carcinoma of cervix. Diagnosis of disease especially cancer The advantage of cytologic technique when compared to histopathological techniques is that the procedure is cheap, takes less time and requires no anesthesia.

29. a) Histology b) Cytology b a

30. 2) C YTOPATHOLOGIC METHODS There are different cytopathologic methods including: a) Fine-needle aspiration cytology (FNAC): It is the suction of cells from diseased organ. In FNAC, cells are obtained by aspirating the diseased organ or a suspicious mass using a thin bore needle under negative pressure. The cells thus obtained are stained and examined under a microscope. Most of the organs can be sampled by fine-needle aspiration.  When the mass lesion is superficial and grossly papable then the FNA is done directly e.g. organs like thyroid, breast, lymph nodes, skin and soft tissues.  In deep seated organs e.g. lung, mediastinum, liver etc. the mass lesion is detected with the help of radiology, then an ultrasound guided or CT Scan guided FNA is performed.

33. 2) C YTOPATHOLOGIC METHODS CONTD… b) Exfoliative cytology: In this case the cells are scraped of the mucosa using a spatula (e.g. cervix and oral cavity) or the cells exfoliate themselves and collect in a particular type of secretion (e.g. the cells lining the bronchus of the respiratory tract that collect in the sputum or in case of a urinary tract disease the cells which exfoliate collect in the urine). The material obtained is smeared (spread) on a glass slide, fixed and stained and then studied under a light microscope. Examples of exfoliative cytology include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.

34. P AP SMEAR ( STEPS 1,2,3 AND 4 (1) (2) (3) (4)

35. 3. Hematology It is a study of abnormalities of the cells of the blood and their precursors in the bone marrow. It is used in the diagnosis various types of anemia & leukemia. 4. Immunohistochemistry This is a specialized staining procedure is used to detect a specific antigen in the tissue in order to identify the type of disease.

36. 5. Biochemical examination It is the analysis of bodily fluids and biochemical tests are used for diagnosis and management. It is used to detect and quantitate various normal and abnormal compounds in the blood, urine, etc. 6. Microbiology It is the study and diagnosis of organisms responsible for various infectious diseases 7. Immunology It is the analysis of the immune system of the body. 8. Toxicology It is the study and identification of various poisons and toxic substances. 9. Cytogenetics (clinical genetics) it is a study of chromosomal abnormalities. 10. Molecular techniques various molecular techniques such as fluorescent in situ hybridization, Southern blot are used to detect genetic diseases.

37. 11. AUTOPSY It is a sub-specialty that focuses on determining the cause of death by examining a dead body. The autopsy informs about the pathologic process, the injury, or the disease that directly results in or initiates a series of events that lead to a person's death. It can be homicidal, suicidal, accidental, some active pathologic disease (like cancer, cardiovascular disease) natural etc. The pathologist can perform the autopsy. It also provides useful information about various disease. It can be used in research. Also it can be used as a tool to educate students, surgeons etc

38. ROLE OF DIAGNOSITIC PATHOLOGY IN DISEASE MANAGMENT Any patient presenting to a clinic is generally subjected to history taking, clinical, radiological and pathological examination in order to come to a diagnosis. Among the pathological examinations the are almost always asked to do various blood and urine tests. Sometimes they are asked to undergo a cytological or histopathological test (or any of the other pathological techniques mentioned before) in order to obtain an accurate diagnosis. This way pathology plays an essential role in the management of the patient and diagnosis of their disease and therefore their treatment.