Surgical Pathology Fundamentals

1. Surgical Pathology Fundamentals Concorde Career College, Portland ST120 Adapted from “Pathology” by Kansas State University

2. Terminology • Pathology: • The study of the structural and functional changes leading to disease in: • Cell • Tissue • Organs • Pathophysiology: • Is the abnormal function of organs or systems due to disease

3. Cell structure

4. Terminology • Pathology is divided • General • Special or systemic • General pathology: • Basic reaction of cells and tissue to normal stimuli • Specific pathology: • Specific response special organs to well defined stimuli

5. Four aspects of disease process • Etiology • Pathogenesis • Morphological changes • Clinical significance

6. 1.Etiology • A) Determining cause • Specifically known to be the soul cause of disease, such as a pathogenic organism, e.g., HIV • B) Predisposing causes • Leading indirectly to disease such as genetic predisposition

7. 2.Pathogenesis • Is the mechanism by which a certain etiological factor causes disease (In Greek: pathos = disease, genesis = development). • Some forms of pathogenesis are: • Inflammation • Malignancy • Tissue breakdown

8. 2.Pathogenesis • The pathogenesis process leads to the formation of a lesion • Lesion is derived from the Latin word "laesio" which means "injury." • Lesions are a result of damage to tissues. For example: • A cancerous tumor is an example of a lesion • The surrounding tissue damaged by a tumor is also termed a lesion.

9. 3.Morphological changes • Are the changes that occur in the cell tissue or organ as a result of the pathological process • These changes can be Morbid: • Macroscopic appearance visible to the naked eye

10. 3.Morphological changes • Are the changes that occur in the cell tissue or organ as a result of the pathological process • Or Histological: • Microscopic appearance only visible under the microscope

11. 4.Clinical significance • What impact do these changes have on the patient?

12. Progression of a disease • Complete cure • Death • Complication • Additional pathological changes which may occur during or after the course of any disease

13. Pathological investigation • During life • Surgical biopsy • Fine needle aspiration biopsy (FNAB) • Cytopathology • Molecular techniques • After death • Autopsy

14. Exposure to stress (irritant) • Mild irritant A) inflammation • Moderate B) Degeneration • Severe irritant Necrosis

15. Necrosis

16. Types of irritants • Non-living irritant: • Physical • Trauma, Burns, Radiation • Chemical • Acids, Alkalies • Immunological • Ag-Ab reaction • Hypersensitivity reaction • Living irritant: • Bacteria • Pathogenic fungi • Parasite • Virus • Helminths

17. Chemical burns

18. Inflammation • It is the response of the living tissue to mild to moderate irritant • The response is directed to defend the tissue for foreign irritants and to prevent further damage • The aim is to bring more blood to the damaged area by acceleration of the blood stream • It is denoted by the suffix “itis”

19. Inflammation • Examples of inflammation • Tonsillitis • Appendicitis • Tendonitis ,………etc. • Lung?

20. Tonsillitis

21. Inflammation

22. Exudate • An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation • Its composition varies but generally includes water and the dissolved solutes of the blood, some or all plasma proteins, white blood cells, platelets and RBC

23. Transudate • A fluid that passes through a membrane which filters out much of the protein and cellular elements to yield a watery solution. • A transudate is due to increased pressure in the veins and capillaries pressure forcing fluid through the vessel walls or low levels of protein the blood serum • The transudated fluid accumulates in tissues outside the blood vessels and can cause edema

24. Types of Exudate • Serous exudate is usually seen in mild inflammation, with little protein content; seen in certain disease states like tuberculosis • Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells; referred to as pus. • Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic carditis, but is seen in all severe injuries such as strep throat and bacterial pneumonia • Hemorrhagic exudate is seen in injury that causes rupture of blood vessels. • Pleural • Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.

25. Purulent Exudate

26. Inflammation • Effects of inflammation • Vascular phenomena • Transient vasoconstriction rapidly followed by • Vasodilatation • Stasis • Migration of leucocytes

27. Inflammation • Composition and function of inflammatory fluid exudates • Fluid exudates • Dilution of bacterial toxins • fibrin threads : help the movement of leucocytes and limit the spread of infection • Also contain antibodies

28. Inflammation • Composition and function of inflammatory fluid exudates • Cellular part • Phagocytosis: engulfing of and destruction of bacteria and necrotic tissue by phagocytes and PNL

29. Inflammation • Chemotaxis: the movment of WBCs in the area of inflammation towards the irritant • Emigration of leukocytes: the migration of WBC from within the blood vessel towards the inflammation site • Diapedesis: the passage and movement of RBCs from within the blood vessel towards the inflamed area

30. Cardinal signs of inflammation • Redness (rubor) • Hotness (calor) • Edema (tumor) swelling due to inflammatory exudate • Pain (dolor) due to pressure of edema on nerves and irritation of nerve endings by metabolites • Loss of function (functio laesa) this is to make the inflamed part of tissue rest and heal

31. Types of inflammation • Acute inflammation • Acute non-suppurative inflammation: acute without the formation of pus • Acute suppurative inflammation: with pus • Localized : Abscess, Furuncle, Carbuncle • Diffused : cellulitis, septic meningitis • Chronic inflammation • Chronic specific : TB • Chronic non-specific: follows acute or chronic from the beginning

32. Cells of inflammation Acute inflammation cells: 1- RBC 2- PNL (leukocyte) Eosinophils Basophils Neutrophils Chronic inflammation cells 1- lymphocytes 2- Plasma cells 3- Histocytes 4- fibroblasts

33. Leukocyte review http://en.wikipedia.org/wiki/White_blood_cell Neutrophil engulfing anthrax bacteria

34. Cells of inflammation Fate of acute inflammation 1- Regression: by resolution, for example when the body (immune system) overcomes bacterial infection 2- Progression: can lead to chronic inflammation and spread; the bacteria overcome the immune system and can spread by: Blood: septicemia, bacteremia, toxemia pyemia Lymphatyic: lymphangitis, lymphadenitis Direct: to other surrounding tissue

35. Type of cells Labile cells: epithelium, haematopoietic (blood) Quiescent (Stable): hepatic, kidney and pancreas Non-dividing (Permanent): nerve cells and skeletal muscle cells

36. Cell development • Proliferation: increased number • Differentiation: development through stages

37. Healing Tissue repairinvolves replacement of damaged tissue with new healthy living tissue when resolution cannot occur Types Usually involves two separate but coordinated components A) Regeneration: healing by the same type of tissue cells from surrounding healthy living cells; this occurs following damage to labile cells and stable cells, for example, liver cirrhosis and bone fractures B) Fibrous (scar tissue): healing by granulation tissue (fibroblast with new capillaries formed) which mature into vascular fibrous tissue (scar); this occurs in the healing process of permanent cells and stable cells with extensive damage, for example, myocardial infraction and open wounds

38. Introduction to wound healing • Healing is a complex and dynamic process of restoring cellular structures and tissue layers. • The adult wound healing process can be divided into 4 distinct phases: • Hemostasis phase • Inflammatory phase • Proliferative phase • Remodeling phase

39. Sequence of events in healing Initial phase - Hemostasis • Following vasoconstriction, platelets adhere to damaged endothelium and discharge adenosine diphosphate (ADP), promoting thrombocyte clumping, which dams the wound. • The inflammatory phase is initiated by the release of numerous cytokines by platelets. • Fibrinogen is cleaved into fibrin and the framework for completion of the coagulation process is formed. Fibrin provides the structural support for cellular constituents of inflammation. • This process starts immediately after the insult and may continue for a few days.

40. Sequence of events in healing Second phase - Inflammation • Within the first 6-8 hours, the next phase of the healing process is underway, with polymorphonuclear leukocytes (PMNs) or PNLs engorging the wound • These cells “cleanse” the wound, clearing it of debris. The PMNs attain their maximal numbers in 24-48 hours and commence their departure by hour 72. • As the process continues, monocytes also exude from the vessels. These are termed macrophages. The macrophages continue the cleansing process and manufacture various growth factors during days 3-4. • Many factors influencing the wound healing process are secreted by macrophages.

41. Sequence of events in healing Third phase – Proliferation This phase consists of different subphases. • Fibroplasia • Matrix deposition • Angiogenesis • Reepithelialization • During days 5-7, fibroblasts have migrated into the wound, laying down new collagen. • The wound is suffused with GAGs and fibronectin that are bonded to a protein core and contribute to matrix deposition. • Angiogenesis is the product of parent vessel offshoots. The formation of new vasculature requires extracellular matrix and basement membrane degradation followed by migration, mitosis, and maturation of endothelial cells. • Re-epithelization occurs with the migration of cells from the periphery of the wound and adnexal structures. This process commences with the spreading of cells within 24 hours. Division of peripheral cells occurs in hours 48-72, resulting in a thin epithelial cell layer, which bridges the wound. This succession of subphases can last up to 4 weeks in the clean and uncontaminated wound.

42. Sequence of events in healing Fourth phase - Remodeling After the third week, the wound undergoes constant alterations, known as remodeling. • This can last for years after the initial injury occurred. Collagen is degraded and deposited in an equilibrium-producing fashion. • The collagen deposition in normal wound healing reaches a peak by the third week after the wound is created. • Contraction of the wound is an ongoing process resulting in part from the proliferation of the specialized fibroblasts termed myofibroblasts, which resemble contractile smooth muscle cells.

43. Stages of wound healing Resolution/ Remodeling Vessel regression, Collagen remodeling Proliferation Reepithelialization, Angiogenesis, Fibrogenesis, Inflammation PMNs, Macrophages, Lymphocytes Hemostasis Fibrin clot, platelet deposition 1D 3D 1wk 6wk 8wk Time after injury

44. Types of healing

45. Primary vs. secondary healing

46. Complications of the healing process • This process can go wrong and produce an increase of fibroblastic proliferation with a resultant hypertrophic scar • Further exuberance can result in keloid formation where scar production extends beyond the area of the original insult. Conversely, insufficient healing can result in atrophic scar formation.

47. Hypertrophic scar

48. Keloid

49. Complications of the healing process • Weak scar: this may lead to hernia • Cicatrisation: contracture of the size of the scar • Implantation epidermoid cyst • Stump neuroma: following amputation causing a painful coiled mass of nerves • Sinus: is a track of septic granulation tissue connecting a cavity to the outside and has one blind end, e.g. pilonidal sinus • Fistula: is a tract of septic granulation tissue connecting 2 epithelial surfaces • Infection : leading to delayed healing • Rarely scars may develop squamous cell carcinoma • Ulcers: discontinuity of cover epithelium or muscle membrane

50. Anal fistula