Introduction to Pathology

1. Introduction to Pathology By Gandi Li Department of Pathology West China Medical School Feb,2003

2. Where there is love of medicine, there is love of humankind. -- Hippocrates (460-377 BC)

3. The most common diseases in developing countries • Infectious diseases (viral hepatitis, tuberculosis, bacterial pneumonia, bacterial diarrheas, AIDS, et al) • Atherosclerosis and hypertension • Cancer • Emphysema and chronic bronchitis • What happens in Nepal?

4. Disease could reasonably be defined as internal problems that cause pain and/or interfere with a person's ability to work, play, and/or love others. • Pathology is the scientific study of disease. • Now more and more people know many diseases are lifestyle-related. • Pathology is a bridge between medicine and basic sciences formedical students. • Pathology is also one of the most important methods to diagnose disease in clinical practice.

5. Pathology involves • Etiology (causes of diseases,Why?) • Pathogenesis (mechanisms, How?) • Pathological changes (lesions, What?) • Morphological changes (anatomical pathology) • Functional changes (pathophysiology) • Clinical manifestations (signs and symptoms) • Sequelae (healing, complications, death)

6. General pathology cell injury tissue repair hemodynamic disorders inflammation tumor Systemic pathology the blood vessels and the heart the respiratory system the digestive system the urinary system the male and female genital system the nervous system the endocrine system Branchs of pathology

7. GOAL of PATHOLOGY for MEDICAL STUDENTS • Be able to understand and analyze the relationship between pathologic changes and clinical manifestations. • Be able to take a clinical history and order tests logically. • Be able to develop a correct diagnosis. • Be able to communicate with professionals and patients. • Does become a physician or a pathologist? Physician or surgeon mostly.

8. What does a PATHOLOGIST do? • SURGICAL PATHOLOGY • Interpret biopsies (e.g., skin, breast, gastrointestinal tract) • Evaluate surgical resection specimens (e.g., colectomy, nephrectomy, mastectomy) • Frozen sections (intra-operational rapid diagnosis)

9. What does a PATHOLOGIST do? • CYTOPATHOLOGY(e.g., Pap smears, FNA - Fine Needle Aspiration) • CLINICAL PATHOLOGY • Hematology (Peripheral blood smear, bone marrow, coagulation disorders). • Chemistry (Blood, urine, cerebrospinal fluid, effusions). • Microbiology. • Blood bank. • AUTOPSY PATHOLOGY • Final diagnosis, forensic pathology--criminal investigation

10. How to study pathology? Background: • Basic medical sciences (anatomy, histology, physiology, biochemistry, immunology, microbiology, parasitology,et al) • Medical terms (e.g. hyperplasia, et al) • Clinical knowledge (physical examination, laboratory tests, X-ray, CT, et al)

11. How to study pathology? • The key for studying pathology: Characteristic morphologic lesions (lesions) Functional Changes (Pathophysiology) Pathogenesis Etiology Clinical manifestations

12. How to study pathology? Approach to good result: • Lectures and textbooks • Laboratory practice: gross specimen and glass slides • Clinicopathologic conference (CPC) • Autopsy demonstration (real or video) • Recommend internet web sites: http://www-medlib.med.utah.edu/webPath/webpath.html

13. Observation of gross specimen: a hypertrophic heart (left) and a normal heart (right)

14. Gross observation of a nutmeg liver and mircoscopic changes

15. Cancer cells in ascites of a patient with gastric carcinoma

16. Summary of introduction • The terms • disease pathology general pathology • lesion pathologist surgical pathology • The roles of pathology in medical education and clinical practice • How to study pathology • Uebung machts Master. (Practice trains master) • Arbeit machts Spass! (Work brings happy!)

17. A famous painting about autopsy by Rhunbrant in 18 century

20. “As is our pathology, so is our medicine” • “Ask not what disease the patient has, but rather what patient the disease has.” Sir William Osler (Canadian Physician)

21. Cell Injury, Adaptation and Death • Overview of cell injury • Causes of cell injury • Mechanisms of cell injury • Cellular adaptation to injury • Reversible and irreversible cell injury • Programmed cell death---- apoptosis • Cellular aging

22. Overview of cell injury • Homeostasis requires functional cooperation in widely distributed cells.

23. Normal cells homeostasis Lethal Reversible Reversible Cell death Adaptative cells necrosis apoptosis atrophy, hypertrophy hyperplasia metapllasia Reversible Reversible injured cells Lethal intracellular accumulations, degeneration A summary of the relationship between normal cells, adaptative cells, reversible injured cells and cell death

24. The relationship between cellular function, cell death and the morphologic changes of cell injury.

25. Causes of cell injury • Ischemia/hypoxia (e.g. heart attack) • Chemical agents (toxins, acid, drugs) • Active oxygen species: free radicals, oxidants, electrophiles • Infectious agents (bacterial, virus, parasite) • Immunologic reactions (hypersensitivity) • Genetic defects (Down’s syndrome) • Nutritional imbalances (protein insufficiency) • Physical agents (trauma, temperature) • Aging

26. Mechanisms of cell injury • ATP depletion • Oxygen deprivation or generation of reactive oxygen species • Loss of calcium homeostasis • Defects in plasma membrane permeability • Mitochondria damage

27. Mechanism of ischemic and hypoxic injury

28. Cell mechanisms of injury Free radicals/ reactive chemicals O2 OH• H2O2 NO Cell membrane Mitochondria Endo. Retic. DNA Normal metabolisms Detoxification SOD/Catalase Glutathiole peroxidase/GSSG Vitamin E, C

29. Neutralization of free radicals SOD • 2O2 + 2H+ H2O 2 + O2 catalase • 2H2O2 2H2O + O2 glutathione peroxidase • 2OH• + 2GSH GSSH + 2H2O glutathione reductase

33. Summary • Any stimuli and stresses can result in cell injuries. • The injurious consequences depend on not only the type of injury, its duration, its severity, and also the type, status, adaptability and genetic makeup of the injured cell. • Cell injury can be divided into reversible and irreversible. • The loss of cell function is far before the cell death, but the morphological visible changes appear far behind the cell death.

34. Cellular adaptation to injury • Concept of Adaptation: When cells encounter physiologic stresses or pathologic stimuli from outside and inside of body, they can alter themselves to achieve a new steady state and preserve viability. • All kinds of adaptation may be considered as disorders of growth and/or differentiation • Cellular adaptation can be considered as a state between the normal, unstressed cell and injured, overstressed cell.

35. Atrophy • Definition: (briefly, decrease in cell size) Shrinkage in the size of the parenchymal cells by loss of cell substances in a well developed organ or tissue is known as atrophy. Or: acquired shrinkage of cells, tissues or organs. • Simple atrophy (loss of cell size only) • Numerous atrophy (loss of cell size and number through apoptosis) • Differentiation: aplasia, hypoplasia

36. Testis: Right: Atrophied Left: Normal

37. There are kidneys and ureters of a one-year-old boy. The right Kidney is hypoplastic and the left one with a three-ureters abnormality.

38. Atrophy • The reasons of atrophy: • Decreased workload disuse atrophy • Loss of innervation neuropathic atrophy • Diminished blood supply ischemic atrophy press atrophy • Absence of nutrition undernourished atrophy • Loss of hormone stimuli endocrine atrophy • Aging senile atrophy

39. Brain atrophy in an old patient with arteriosclerosis. Note the widened sulci and narrow convolutions.

40. Brain atrophy in a patient with Alzheimer’s disease. The gyri are narrowed and the sulci widened toward to frontal pole.

41. Hydrocephalus (left) and nephrohydrosis (right) Note the dilated ventricles and thinner grey and whine matter. The renal calyces and renal pelvis are dilated too.

42. There are some skeletal muscle fibers. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. In this case, innervation of the small fibers in the center was lost. This is a trichrome stain.

43. Atrophy • The atrophied cells, tissue and organ have • Reduction of physiologic functions • Decreased synthesis • Increased catabolism—increased protein degradation through Lysosomes digest the senescent organelles (autolysis) • If the number of cells decrease, there is apoptosis (cell suicide), or programmed cell death

44. Hypertrophy • Definition: (briefly: increase in cell size) • an increase in the size of parenchymal cells and consequently an increase in the size of the organ. No increase of cell number in a purified hypertrophy!

45. Hypertrophy • Compensatory hypertrophy • Mechanical stimuli---skeletal muscle of a sportsman • Increased workload---left ventricle hypertrophy of systemic hypertension • Decompensation---heart failure • Endocrine hypertrophy • Hormonal stimuli---pregnant uterus ---Cushing’s syndrome

46. Hypertrophy of left ventricle (centripetal hypertrophy) in a patient with essential hypertension.Note the marked thickened wall of ventricle.

47. Hypertrophy of the left ventricle • Normal myocardial fibers • Hypertrophic myocardial fibers

48. A pregnant uterus (right) and normal uterus (left)

49. Physiologic hypertrophy of the uterus during pregnancy. Left: gross appearance of a normal uterus and a gravid uterus. Middle: small spindle-shaped uterine smooth muscle cells from A normal uterus. Right: large, plump hypertrophied smooth muscle cells from a gravid uterus.

50. Cushing’s syndrome resulted from adenoma of adrenal cortex