b.pharma introduction to pathology.ppttx

D The figure shows a dark red hemorrhagic infarction extending to the pleura, a typical finding when a
medium-sized thromboembolus lodges in a peripheral pulmonary artery branch. The infarct is hemorrhagic because
the bronchial arterial circulation in the lung (derived from
the systemic arterial circulation and separate from the pulmonary arterial circulation) continues to supply a small
amount of blood to the interstitium in the affected area of
infarction. Persons with underlying heart or lung disease
are at greater risk for pulmonary infarction. Passive congestion, whether acute or chronic, is a diffuse process, as
is edema, which does not impart a red color. Pulmonary
venous thrombosis is rare.
PBD9 129–130 BP9 92–93 PBD8 128 BP8 101
33 B The figure shows a pale ischemic infarction of the
renal cortex extending nearly to the renal capsule, a typical finding when a medium-sized arterial thromboembolus
lodges in a peripheral renal artery branch. The infarct is
wedge-shaped, typical for many parenchymal organs,
because there is minimal collateral circulation. An abscess is
a form of liquefactive necrosis from a localized collection of
neutrophils in association with infection, and though it could
be yellowish, it is likely to be round. Liquefactive necrosis
from arterial occlusion and infarction occurs in the brain.
Multiorgan failure occurs with shock, and whole organs are
affected by ischemia. Venous thrombosis tends to produce
hemorrhagic lesions.
PBD9 129–130 BP9 92–93 PBD8 128 BP8 101
34 D The liver has a dual blood supply, with a hepatic
arterial circulation and a portal venous circulation. Infarction
of the liver caused by occlusion of hepatic artery is uncommon. Cerebral infarction typically produces liquefactive
necrosis. Infarcts of most solid parenchymal organs such as
the kidney, heart, and spleen exhibit coagulative necrosis,
and emboli from the left heart often go to these organs.
PBD9 130 BP9 93 PBD8 129 BP8 101
35 B The patient has septic shock from infection with
gram-negative organisms that have lipopolysaccharide,
which binds along with other microbe-derived substances containing pathogen-associated molecular patterns
(PAMPs) to cells via Toll-like receptors (TLRs). Binding initiates release of various cytokines such as tumor necrosis
factor (TNF) and interleukin-1 (IL-1) that produce fever.
Macrophages are stimulated to destroy the organisms.
Nitric oxide is released, promoting vasodilation and circulatory collapse. Complement C3b generated by bacteria
via the alternative pathway acts as an opsonin. Plateletactivating factor mediates many features of acute inflammation and in large quantities can cause vasoconstriction
and bronchoconstriction. Toxic shock syndrome toxin-1 is
a superantigen released by staphylococcal organisms that
is a potent activator of T lymphocytes, inducing cytokine evidenced by the high lactate level. Vasodilation is a feature of septic shock, typically as a result of

1. B.PHARM LECTURE

2. Welcome to Pathology lets introduce Path2054 Course ECTS-5(135hrs) lecture -48 Course Methodology= active method (STUDENT CENTERED) Assessment –continuous and summative attendance , quiz,assignment,final exam(40) Learning material-handout and text book Michael Z ewdu M.D,MSC PM(candidate)&Assistant professor(MPH)

3. Basic/ground rules phone should be silent during class Active participation = must speak when asked Attendance --- quiz

4. Materials

5. 6 contents Introduction Definition Discuss the core of pathology Etiology Pathogenesis Morphological changes Functional derangements & clinical manifestations Diagnostic modalities Disease & it’s outcomes Introduction…

6. Introduction… 7 1. Introduction Pathology – study of diseases Patho – suffering Logos – study It is devoted to the study of the structural & functional changes in cells, tissues, organs & systems underlying diseases.

7. Introduction… 8 Definition of pathology… It is the “ Scientific study of disease" "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents.“ Pathology serves as a "bridge" or "link" between the preclinical sciences ( anatomy, physiology, …… etc .) and the courses in clinical medicine.

8. Introduction… 9 Pathology is divided in to : General pathology – deals with basic reactions of cells & tissues to abnormal stimuli that underlie all diseases. Systemic pathology – specific responses of specific systems, organs & tissues to more or less well defined stimuli.

9. Introduction… 10 The core of pathology Pathology gives explanation of a disease by studying the four aspects of the disease 1. Etiology 2. Pathogenesis 3. Morphological changes 4. Functional derangement & clinical significance

10. Introduction… 11 1. Etiology Cause of the disease If the cause of the disease is known it is called primary etiology If the cause of the disease is unknown it is called idiopathic Knowledge or discovery of the primary cause remains the back bone on which a diagnosis can be made, a disease understood & a treatment developed

11. Introduction… 12 Two factors:- Intrinsic or genetic Acquired ( infectious, nutritional, chemical, physical…)

12. Introduction… 13 Disease Disease Disease Disease Disease One etiologic agent- one disease, as Malaria Several etiologic agents - one disease, as diabetes . One etiologic agent - several diseases, as smoking.

13. Introduction… 14 2. Pathogenesis Mechanisms of disease development It refers to the sequence of events in the response of the cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease It means the mechanism through which the cause operates to produce the pathological & clinical manifestations The pathogenic mechanism could take place in the latent or the incubation period It will lead to morphological changes

14. Introduction… 15 3. Morphological changes Structural alterations induced in the cells & organs of the body Characteristic to the disease or diagnostic to the etiologic process Seen with naked eye or under the microscope

15. Introduction… 16 Both the gross & the microscopic morphologic changes may only be seen in that disease, i.e. they may be specific to that disease ( pathognomonic ). Therefore, such morphologic changes can be used by the pathologist to diagnose the disease In addition, the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease

16. Introduction… 17 4. Functional derangement & Clinical significance Functional consequence of the morphologic change The morphologic changes influence the normal function → determine the clinical feature Also the course & prognosis of the disease

17. Introduction… 18 Diagnostic modalities Most are based on morphologic changes(microscopic) Diagnostic techniques: 1. Histopathology 2. Cytopathology 3. Hematopathology 4. Immunohistochemistry 5. Microbiological examination 6. Biochemical examination 7. Cytogenetics 8. Molecular techniques 9. Autopsy

18. Introduction… 19 Histopathology Studies the tissue under the microscope Tissues are obtained by biopsy Biopsy – tissue sample from living person Biopsy – Incisional - Excisional Tissue examined grossly (macroscopically) & microscopically It is usually the gold standard for pathologic diagnosis

19. Introduction… 20 Once the tissue is removed from the pt, it has to be immediately fixed by putting it into adequate amount of 10% formalin before sending it to the pathologist Once the tissue arrives at the pathology department, the pathologist will examine macroscopically

20. Introduction… 21 Then the tissue is processed to make it ready for microscopic examination. The whole purpose of the tissue processing is to prepare a very thin tissue which can be clearly seen under the microscope The tissue is processed by putting it into different chemicals. It is then impregnated (embedded) in paraffin, sectioned (cut) into thin slices, & is finally stained. The stains can be Hematoxylin/Eosin stain or special stains such as PAS, immunohistochemistry, etc…

21. Introduction… 22 The Hematoxylin/Eosin stain is usually abbreviated as H & E stain. It is routinely used. It gives the nucleus a blue color , the cytoplasm & the extracellular matrix a pinkish color

22. Introduction… 23 Then the pathologist will look for abnormal structures in the tissue & based on this abnormal morphology s/he will make the diagnosis.

23. Introduction… 24 Cytopathology Study the cells Used in: Screening for early detection of cancer Diagnosis of symptomatic cancer Diagnosis of inflammatory condition, infectious/others Surveillance of pts treated with cancer

24. Introduction… 25 Its advantage: Cheap Takes less time Needs no anesthesia Cytopathological methods: 1. FNAC 2. Exfoliative cytology 3. Abrasive cytology

25. Introduction… 26 1. FNAC Easy in superficial organs May need guidance in deep seated mass 2. Exfoliative cytology From cells that are shed spontaneously into body fluids or secretion 3. Abrasive cytology Cells are dislodged from skin or mucous membrane by various tools

26. Introduction… 27 Hematological examination This is a method by which abnormalities of the cells of the blood & their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia .

27. Introduction… 28 Immunohistochemistry This is a method used to detect a specific antigen & antibody in the tissue in order to identify the type of the disease. For example , ANA, ACA in pt with SLE.

28. Introduction… 29 Microbiological examination This is a method by which body fluids, excised tissue, etc… are examined by microscopically, culture , serological techniques to identify microorganisms responsible for many diseases Assignment1: microbiological examinations for TB & HIV infections

29. Introduction… 30 Biochemical examination This is a method by which the metabolic disturbances of disease are investigated by assay of various normal & abnormal compounds in the blood, urine, or any other body fluids. E.g.. High serum HCG level – choriocarcinoma AFP …..in hepatoma /????

30. Introduction… 31 Clinical genetics ( Cytogenetics ) This is a method in which inherited/acquired chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology

31. Introduction… 32 Molecular techniques Different molecular techniques such as fluorescent in situ hybridization, southern blot, etc… can be used to detect genetic diseases.

32. Introduction… 33 Autopsy Autopsy is an examination of the dead body to identify the cause of death This can be for -- forensic or -- clinical purposes

33. Introduction… 34 Diseases Disease is defined as an abnormal variation in structure or function of any part of the body Causes of disease Environmental Genetic or Both

34. Introduction… 35 Environmental factors Are many & are classified into:- Physical agents Chemicals Nutritional deficiencies & excesses Infections & infestations Immunological factors Psychogenic factors

35. Introduction… 36 Genetic factors These are hereditary factors that are inherited genetically from parents.

36. Introduction… 37 Course of disease The course of disease in the absence of any intervention is called the natural history of the disease. Stages 1. Exposure 2. Latency period 3. Biological onset 4. Incubation period 5. Clinical onset 6. Permanent damage 7. Death

37. Introduction… a) Exposure to various risk factors (causative agents) b) Latency period between exposure and biological onset of disease c) Biological onset of disease ; this marks the initiation of the disease process, without any sign or symptom. d) Incubation (induction) period refers to period of time without any obvious signs or symptoms from the time of exposure. e) The clinical onset of the disease , when the signs and symptoms of the disease become apparent. f) The onset of permanent damage, and g) Death 38

38. Introduction… 39 -The course of disease is shown with a simplified diagram as follows Exposure → biological onset → clinical onset ↑ ↓ Latency period permanent damage ↓ incubation p death

39. Introduction… 40 Out come of diseases Resolution can occur leaving no sequelae The disease can settle down, but sequelae are left, or It may result in death

40. Introduction… 41 Clinical & biological death Clinical death is the reversible transmission between life & biological death. Clinical death is defined as the period of respiratory, circulatory & brain arrest during which initiation of resuscitation can lead to recovery

41. Introduction… 42 Signs indicating clinical death The pt is with out pulse or blood pressure & is completely unresponsive to the most painful stimulus. The pupils are widely dilated Some reflex reactions to external stimulation are preserved. For example, during intubations, respiration may be restored in response to stimulation of the receptors of the superior laryngeal nerve, the nucleus of which is located in the medulla oblongata near the respiratory center. Recovery can occur with resuscitation

42. Introduction… 43 Biological death Biological death (sure signs of death), which sets in after clinical death , is an irreversible state of cellular destruction It manifests with irreversible cessation of circulatory & respiratory functions, or irreversible cessation of all functions of the entire brain, including brain stem

43. Introduction… 44 Postmortem changes Rigor mortis – contraction of muscle Livor mortis – bluish discoloration on dependent part of the body Algor mortis – cooling of the body Autolysis – degradation of the body

44. Introduction… Summery Definition the four core aspects of disease to be studied by pathology Diagnostic investigation Course of diseases 45

45. 46 contents Introduction Definition Discuss the core of pathology Etiology Pathogenesis Morphological changes Functional derangements & clinical manifestations Diagnostic modalities Disease & it’s outcomes Introduction…

46. Introduction… 47 1. Introduction Pathology – study of diseases Patho – suffering Logos – study It is devoted to the study of the structural & functional changes in cells, tissues, organs & systems underlying diseases.

47. Introduction… 48 Definition of pathology… It is the “ Scientific study of disease" "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents.“ Pathology serves as a "bridge" or "link" between the preclinical sciences ( anatomy, physiology, …… etc .) and the courses in clinical medicine.

48. Introduction… 49 Pathology is divided in to : General pathology – deals with basic reactions of cells & tissues to abnormal stimuli that underlie all diseases. Systemic pathology – specific responses of specific systems, organs & tissues to more or less well defined stimuli.

49. Introduction… 50 The core of pathology Pathology gives explanation of a disease by studying the four aspects of the disease 1. Etiology 2. Pathogenesis 3. Morphological changes 4. Functional derangement & clinical significance

50. Introduction… 51 1. Etiology Cause of the disease If the cause of the disease is known it is called primary etiology If the cause of the disease is unknown it is called idiopathic Knowledge or discovery of the primary cause remains the back bone on which a diagnosis can be made, a disease understood & a treatment developed

51. Introduction… 52 Two factors:- Intrinsic or genetic Acquired ( infectious, nutritional, chemical, physical…)

52. Introduction… 53 Disease Disease Disease Disease Disease One etiologic agent- one disease, as Malaria Several etiologic agents - one disease, as diabetes . One etiologic agent - several diseases, as smoking.

53. Introduction… 54 2. Pathogenesis Mechanisms of disease development It refers to the sequence of events in the response of the cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease It means the mechanism through which the cause operates to produce the pathological & clinical manifestations The pathogenic mechanism could take place in the latent or the incubation period It will lead to morphological changes

54. Introduction… 55 3. Morphological changes Structural alterations induced in the cells & organs of the body Characteristic to the disease or diagnostic to the etiologic process Seen with naked eye or under the microscope

55. Introduction… 56 Both the gross & the microscopic morphologic changes may only be seen in that disease, i.e. they may be specific to that disease ( pathognomonic ). Therefore, such morphologic changes can be used by the pathologist to diagnose the disease In addition, the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease

56. Introduction… 57 4. Functional derangement & Clinical significance Functional consequence of the morphologic change The morphologic changes influence the normal function → determine the clinical feature Also the course & prognosis of the disease

57. Introduction… 58 Diagnostic modalities Most are based on morphologic changes(microscopic) Diagnostic techniques: 1. Histopathology 2. Cytopathology 3. Hematopathology 4. Immunohistochemistry 5. Microbiological examination 6. Biochemical examination 7. Cytogenetics 8. Molecular techniques 9. Autopsy

58. Introduction… 59 Histopathology Studies the tissue under the microscope Tissues are obtained by biopsy Biopsy – tissue sample from living person Biopsy – Incisional - Excisional Tissue examined grossly (macroscopically) & microscopically It is usually the gold standard for pathologic diagnosis

59. Introduction… 60 Once the tissue is removed from the pt, it has to be immediately fixed by putting it into adequate amount of 10% formalin before sending it to the pathologist Once the tissue arrives at the pathology department, the pathologist will examine macroscopically

60. Introduction… 61 Then the tissue is processed to make it ready for microscopic examination. The whole purpose of the tissue processing is to prepare a very thin tissue which can be clearly seen under the microscope The tissue is processed by putting it into different chemicals. It is then impregnated (embedded) in paraffin, sectioned (cut) into thin slices, & is finally stained. The stains can be Hematoxylin/Eosin stain or special stains such as PAS, immunohistochemistry, etc…

61. Introduction… 62 The Hematoxylin/Eosin stain is usually abbreviated as H & E stain. It is routinely used. It gives the nucleus a blue color , the cytoplasm & the extracellular matrix a pinkish color

62. Introduction… 63 Then the pathologist will look for abnormal structures in the tissue & based on this abnormal morphology s/he will make the diagnosis.

63. Introduction… 64 Cytopathology Study the cells Used in: Screening for early detection of cancer Diagnosis of symptomatic cancer Diagnosis of inflammatory condition, infectious/others Surveillance of pts treated with cancer

64. Introduction… 65 Its advantage: Cheap Takes less time Needs no anesthesia Cytopathological methods: 1. FNAC 2. Exfoliative cytology 3. Abrasive cytology

65. Introduction… 66 1. FNAC Easy in superficial organs May need guidance in deep seated mass 2. Exfoliative cytology From cells that are shed spontaneously into body fluids or secretion 3. Abrasive cytology Cells are dislodged from skin or mucous membrane by various tools

66. Introduction… 67 Hematological examination This is a method by which abnormalities of the cells of the blood & their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia .

67. Introduction… 68 Immunohistochemistry This is a method used to detect a specific antigen & antibody in the tissue in order to identify the type of the disease. For example , ANA, ACA in pt with SLE.

68. Introduction… 69 Microbiological examination This is a method by which body fluids, excised tissue, etc… are examined by microscopically, culture , serological techniques to identify microorganisms responsible for many diseases Assignment1: microbiological examinations for TB & HIV infections

69. Introduction… 70 Biochemical examination This is a method by which the metabolic disturbances of disease are investigated by assay of various normal & abnormal compounds in the blood, urine, or any other body fluids. E.g.. High serum HCG level – choriocarcinoma AFP …..in hepatoma /????

70. Introduction… 71 Clinical genetics ( Cytogenetics ) This is a method in which inherited/acquired chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology

71. Introduction… 72 Molecular techniques Different molecular techniques such as fluorescent in situ hybridization, southern blot, etc… can be used to detect genetic diseases.

72. Introduction… 73 Autopsy Autopsy is an examination of the dead body to identify the cause of death This can be for -- forensic or -- clinical purposes

73. Introduction… 74 Diseases Disease is defined as an abnormal variation in structure or function of any part of the body Causes of disease Environmental Genetic or Both

74. Introduction… 75 Environmental factors Are many & are classified into:- Physical agents Chemicals Nutritional deficiencies & excesses Infections & infestations Immunological factors Psychogenic factors

75. Introduction… 76 Genetic factors These are hereditary factors that are inherited genetically from parents.

76. Introduction… 77 Course of disease The course of disease in the absence of any intervention is called the natural history of the disease. Stages 1. Exposure 2. Latency period 3. Biological onset 4. Incubation period 5. Clinical onset 6. Permanent damage 7. Death

77. Introduction… a) Exposure to various risk factors (causative agents) b) Latency period between exposure and biological onset of disease c) Biological onset of disease ; this marks the initiation of the disease process, without any sign or symptom. d) Incubation (induction) period refers to period of time without any obvious signs or symptoms from the time of exposure. e) The clinical onset of the disease , when the signs and symptoms of the disease become apparent. f) The onset of permanent damage, and g) Death 78

78. Introduction… 79 -The course of disease is shown with a simplified diagram as follows Exposure → biological onset → clinical onset ↑ ↓ Latency period permanent damage ↓ incubation p death

79. Introduction… 80 Out come of diseases Resolution can occur leaving no sequelae The disease can settle down, but sequelae are left, or It may result in death

80. Introduction… 81 Clinical & biological death Clinical death is the reversible transmission between life & biological death. Clinical death is defined as the period of respiratory, circulatory & brain arrest during which initiation of resuscitation can lead to recovery

81. Introduction… 82 Signs indicating clinical death The pt is with out pulse or blood pressure & is completely unresponsive to the most painful stimulus. The pupils are widely dilated Some reflex reactions to external stimulation are preserved. For example, during intubations, respiration may be restored in response to stimulation of the receptors of the superior laryngeal nerve, the nucleus of which is located in the medulla oblongata near the respiratory center. Recovery can occur with resuscitation

82. Introduction… 83 Biological death Biological death (sure signs of death), which sets in after clinical death , is an irreversible state of cellular destruction It manifests with irreversible cessation of circulatory & respiratory functions, or irreversible cessation of all functions of the entire brain, including brain stem

83. Introduction… 84 Postmortem changes Rigor mortis – contraction of muscle Livor mortis – bluish discoloration on dependent part of the body Algor mortis – cooling of the body Autolysis – degradation of the body

84. Introduction… Summery Definition the four core aspects of disease to be studied by pathology Diagnostic investigation Course of diseases 85