1. Pathology

2. 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 Tools : Molecular Microbiological Immunological Morphological Terminology

3. 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 Terminology

4. 1. Aetiology 2. Pathogenesis 3. Morphological changes 4. Clinical significance Four aspects of disease process

5. A) Determining cause Specifically known to be the soul cause of disease such pathogenic organism e.g. HIV B) Predisposing causes Leading indirectly to disease such as genetic predisposition 1.Aetiology(Cause )

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

7. 2.Pathogenesis The pathogenesis process leads to the formation of 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 tumour is also termed a lesion.

8. 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

9. 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

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

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

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

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

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

15. 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”

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

17. Inflammation

18. Exudate An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammationfluidcirculatory systemlesionsinflammation Its composition varies but generally includes water and the dissolved solutes of the blood, some or all plasma proteins, white blood cells, platelets and RBCsolutesplasma proteinswhite blood cellsplatelets

19. 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

20. Difference between exudates and transudate Exudatetransudate inflammation venous congestion High above 4gm/m3normal increasednormal high above 1018normal turbid due to pnlsclear +ve-ve Cause Protein Fibrin SG Appearance Fibrin clot on standing

21. Types of Exudate 1. Serous exudate is usually seen in mild inflammation, with little protein content. seen in certain disease states like tuberculosistuberculosis 2. Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells. referred to as pus. neutrophilsfibrinogenpus 3. 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 pneumoniafibrin 4. Hemorrhagic exudate is seen in injury that causes rupture of blood vessels. 5. Pleural. 6. Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.

22. Inflammation Effects of inflammation 1. Vascular phenomena 1. Transient vasoconstriction rapidly followed 2. Vasodilatation 3. Stasis 4. Migration of leucocytes

23. Inflammation Effects of inflammation 2- Exudative stress Emigration of leukocytes Inflammation fluid exudate

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

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

26. Inflammation Chemotaxis: the movment of WBC 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 movment of RBC from within the blood vessel towards the inflamed area

27. Cardinal signs of inflammation Redness Hotness Swelling (edema) due to inflammatory exudate Pain: due to pressure of edema on nerves and irritation of nerve ends by metabolites Loss of function: this is to make the inflamed part of tissue rest and heal.

28. 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

29. 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

30. Cells of inflammation Fate of acute inflammation 1- Regretion: by resolution for example when the body (immunsystem) overcomes the bacterial infection 2- Progression which can lead to chronic inflammation and spread: the bacteria overcome the immunsystem and can spread by : Blood: septeciemia, bacterimea, toximia pyaemia Lymphatyic: lyphangitis, lyphadenites Direct to other surrounding tissue

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

32. Cell development Proliferation: increased number Differentiation: development through stages

33. healing Tissue repair involves 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 with in small damages of labile cells and stable cells for examples liver cirrhosis and bone fractures B) Fibros (scar tissue): healing by granulation tissue (fibroblast with new capillaries formed) which mature a vascular fibrous tissue (scar), this occurs in the healing process of permanent cells and stable cells with high damage. for example myocardial infraction and wounds

34. Introduction to wond 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: The homeostasis phase the inflammatory phase the proliferative phase the remodeling phase.

35. 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

36. 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. These include TGFs, cytokines and interleukin-1 (IL-1), tumor necrosis factor (TNF)

37. Sequence of events in healing Third phase - Granulation This phase consists of different subphases. These subphases do not happen in discrete time frames but constitute an overall and ongoing process. The subphases are: fibroplasia matrix deposition angiogenesis and re-epithelialization In days 5-7, fibroblasts have migrated into the wound, laying down new collagen of the subtypes I and III The wound is suffused with GAGs and fibronectin that are bonded covalently 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.

38. 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.

39. Types of healing

42. 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. Complications of the healing process

43. Week scar: this may lead to hernia Cicatrisation: contracture of the size of the scar Implantation epidermiod 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

44. Introduction: Bone: Introduction: Bone is a dynamic tissue Osteoblasts - osteoid (type 1 collagen) Calcium and phosphate (calcium hydroxyapatite) Osteoclasts are multi-nucleated cells which resorb bone (PTH).

45. Osteogenic cells:

46. Bone Anatomy Diaphysis Metaphysis Epiphysis – Prox/Dist Epiphyseal line Periosteum Compact cortical bone Spongy bone Articular Cartilage Medullary cavity Marrow Nutrient artery

47. The Histologic Types: Compact bone Spongy bone Lamellar bone Woven bone Osteoid Callus

48. The matrix of bone : Contains inorganic salt Calcium Hydroxyapatite in collagen framework. Osteoblasts - Calcification - Mineralization Minerals  hardness Collagen fibres  Tensile strength. Collagen is necessary for Calcification.

49. Fractures: Break in the bone. Simple / Compound – infection. Single - Horizontal, oblique, spiral, Comminuted – multiple. Greenstick – partial children. Torus – compression of cortex – children.

50. Types of Fracture:

51. Bone Remodeling Vitamin D Nutrition Physical activity Age, hormones PTH, PHRP IL1, TNF,TGF-β 5-10% bone / year.

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

53. Healing in Bone: 1D - Hematoma formation (fibrin mesh) 3D - Inflammation 1W - Soft callus – granulation, matrix. 3-6W - Callus – ossification, woven bone 8+W - Re-modeling – absorb/deposit, strength, lamellate.

54. Healing in Bone:

59. Factors affecting Healing: Systemic & Local factors Immobilization * Improper reduction – abnormal position Infection. Debris, dead tissue in wound Joint involvement

60. Complications: Delayed healing. Non healing. Joint involvement - ankylosis Abnormal position – arthritis. Bone necrosis – nutrient artery Involucrum formation. Pseudoarthrosis