1. Pathophysiology: Introduction to Basic Pathology Lecture 1 Dr. Karen Ronquillo Premed 2

2. Basic Pathophysiology Basic Pathology Basic Pathology Basic Microbiology Basic MicrobiologyBacteriologyVirologyMycologyImmunology Basic Pharmacology Basic Pharmacology

3. What is Pathology?

4. Pathology Branch of Medicine Branch of Medicine “suffering’ “suffering’ Studies the underlying causes of diseases Studies the underlying causes of diseases“etiology” Mechanisms that result in the signs and symptoms of the patient Mechanisms that result in the signs and symptoms of the patient“pathogenesis”

5. Pathology Bridge between basic science and clinical practice Bridge between basic science and clinical practice Divisions: Divisions: General Pathology Systemic Pathology

6. The Cell

7. How do cells react to environmental stress? Hypertrophy Hypertrophy Hyperplasia Hyperplasia Aplasia Aplasia Hypoplasia Hypoplasia Atrophy Atrophy Metaplasia Metaplasia

8. Hypertrophy Increase in protein synthesis/ organelles Increase in protein synthesis/ organelles Increase in size of cells Increase in size of cells Increase in organ/tissue size Increase in organ/tissue size

9. Hypertrophy

10. Hyperplasia Increase in NUMBER of cells Increase in NUMBER of cells Increase in size of organ/tissue Increase in size of organ/tissue Similar end result as hypertrophy Similar end result as hypertrophy May occur with hypertrophy May occur with hypertrophy

11. Hyperplasia

12. Aplasia Failure of cell production Failure of cell production Agenesis or absence of an organ:fetus Agenesis or absence of an organ:fetus Loss of precursor cells:adults Loss of precursor cells:adults

13. Technetium: scintigraphy

14. Aplasia

15. Hypoplasia Decrease in cell production Decrease in cell production

16. Atrophy Decrease in mass of preexisting cells Decrease in mass of preexisting cells Smaller tissue/organ Smaller tissue/organ Most common causes: Most common causes:disuse poor nutrition lack of oxygen lack of endocrine stimulation aging injury of the nerves

17. Atrophy

18. Metaplasia Replacement of one tissue by another tissue Replacement of one tissue by another tissue Several forms: Several forms: Squamous metaplasia Cartilaginous metaplasia osseous metaplasia myeloid metaplasia

19. Metaplasia Squamous to columnar change in cells

20. Barrett’s esophagus

21. What are the causes of injury/stress? Hypoxic cell injury Hypoxic cell injury Free radical injury Free radical injury Chemical cell injury Chemical cell injury

22. Hypoxic cell injury Complete lack of oxygen/ decreased oxygen Complete lack of oxygen/ decreased oxygen Anoxia or hypoxia Anoxia or hypoxia Causes: Causes:ischemiaanemia carbon monoxide poisoning decrease tissue perfusion poorly-oxygenated blood

23. Hypoxic cell injury

24. Early stage Hypoxic cell injury Decrease in production of ATP Decrease in production of ATP Changes in cell membrane Changes in cell membrane Cellular swelling Cellular swelling endoplasmic reticulum mitochondria Ribosomes disaggregate Ribosomes disaggregate Failure of protein synthesis Failure of protein synthesis Clumping of chromatin Clumping of chromatin

25. Late stage Cell membrane damage Cell membrane damage myelin blebs cell blebs

26. Cell Death Irreversible damage to the cell membranes Irreversible damage to the cell membranes Calcium influx Calcium influx Mitochondria calcifies Mitochondria calcifies Release of cellular enzymes Release of cellular enzymes lab exams for AST, ALT, CKMB, LDH Most vulnerable cells: Most vulnerable cells:neurons

27. Cardiac enzymes

28. CKMB kit

29. Free radicals: superoxide and hydroxyl radicals Seen in: Seen in: normal metabolism oxygen toxicity ionizing radiation UV light drugs/chemicalsischemia

30. What will neutralize free radicals?

31. Mechanisms to detoxify free radicals Glutathione Glutathione Catalase Catalase Superoxide dismutase Superoxide dismutase Vitamin A, C, E Vitamin A, C, E Cysteine, selenium, ceruloplasmin Cysteine, selenium, ceruloplasmin Spontaneous decay Spontaneous decay

32. Chemical Injury Carbon tetrachloride and liver damage Carbon tetrachloride and liver damage

33. Morphologic patterns of cell death: NECROSIS AND APOPTOSIS Necrosis Necrosis sum of all the reactions seen in an injured tissue, leads to cell death autolysis – cell’s enzymes autolysis – cell’s enzymes Heterolysis – extrinsic factors Heterolysis – extrinsic factors

34. Types of necrosis Coagulative necrosis Coagulative necrosis Liquefactive necrosis Liquefactive necrosis Caseous necrosis Caseous necrosis Gangrenous necrosis Gangrenous necrosis Fibrinoid necrosis Fibrinoid necrosis Fat necrosis Fat necrosis

35. Coagulative necrosis Interruption of the blood supply Interruption of the blood supply Poor collateral circulation Poor collateral circulationheartkidney

36. Characteristic nuclear changes

37. Coagulative necrosis

38. Coagulative Necrosis

39. Liquefactive necrosis Interruption of blood supply Interruption of blood supply Enzymes liquefy the tissue Enzymes liquefy the tissueBrain Suppurative infections Suppurative infectionsBacteria

40. Liquefactive necrosis

41. Caseous necrosis Coagulative + liquefactive Coagulative + liquefactive “cheese - like” “cheese - like” Part of granulomatous inflammation Part of granulomatous inflammation Classic picture: Classic picture:Tuberculosis

42. Caseous necrosis

43. Gangrenous necrosis Interuption of the blood supply to the lower extremities or bowels Interuption of the blood supply to the lower extremities or bowels 2 types: 2 types: 1. Wet type: complicated by liquefactive necrosis 2. Dry type: complicated by coagulative necrosis

44. Gangrenous necrosis types

45. Fibrinoid necrosis Immune-mediated vascular damage Immune-mediated vascular damage Protein – like material in the blood vessel walls Protein – like material in the blood vessel walls

46. Fat necrosis Traumatic fat necrosis: after injury Traumatic fat necrosis: after injury Breast Breast

47. ENZYMATIC FAT NECROSIS: PANCREAS

48. APOPTOSIS “falling away from” “falling away from” Another cell death pattern Another cell death pattern “Programmed cell death” “Programmed cell death” Removal of cells Removal of cells Prevents neoplastic transformation Prevents neoplastic transformation

49. Necrosis versus apoptosis Gross irreversible cell injury Gross irreversible cell injury Passive form of cell death Passive form of cell death Does not require genes, protein synthesis Does not require genes, protein synthesis Marked inflammatory reaction Marked inflammatory reaction Physiologic programmed cell removal Physiologic programmed cell removal Active form of cell death Active form of cell death Requires genes, proteins, energy Requires genes, proteins, energy No inflammatory reaction No inflammatory reaction

50. Genes affecting apoptosis Inhibits: Inhibits:bcl-2 Facilitates: Facilitates:baxp53

51. Morphological features in apoptosis Involves small clusters of cells only Involves small clusters of cells only No inflammatory cells No inflammatory cells Cell membrane blebs Cell membrane blebs Cytoplasmic shrinkage Cytoplasmic shrinkage Chromatin condensation Chromatin condensation Phagocytosis of apoptotic bodies Phagocytosis of apoptotic bodies

53. Reversible Cellular changes Fatty change Fatty change Hyaline change Hyaline change Accumulation of exogenous pigments Accumulation of exogenous pigments Accumulation of endogenous pigments Accumulation of endogenous pigments Pathologic calcifications Pathologic calcifications

54. Fatty change Liver, heart, kidney Liver, heart, kidney Accumulation of intracellular parenchymal triglycerides Accumulation of intracellular parenchymal triglycerides -increased transport -decrease mobilization -decreased use -overproduction

55. Fatty change: LIVER

56. Hyaline change Accumulation of hyaline Accumulation of hyaline HYPERTENSION; DIABETES MELLITUS HYPERTENSION; DIABETES MELLITUS “glassy” appearance “glassy” appearance

57. Exogenous pigments Lungs Lungscarbonsilica iron dust Lead – Plumbism Lead – Plumbism Silver - Argyria Silver - Argyria

58. Endogenous pigments BilirubinHemosiderin

59. Lipofuscin Lipofuscin “wear and tear” pigment “wear and tear” pigment Elderly patients Elderly patients Liver, heart Liver, heart Brown atrophy Brown atrophy

60. Pathologic calcifications Previously damages tissues Previously damages tissues “dystrophic calcification” scarred heart valves

61. Pathologic calcifications Hypercalcemia Hypercalcemia “metastatic calcification”

62. Question: A young woman was admitted due to a bacterial infection. CT scan showed an abscess in her brain. What type of necrosis would you expect to see? A young woman was admitted due to a bacterial infection. CT scan showed an abscess in her brain. What type of necrosis would you expect to see? A.coagulative A.coagulative B.Caseous B.Caseous C.Liquefactive C.Liquefactive

63. Question: A 15 year old girl was brought into your clinic due to painful menses. She also said that her menstrual blood flow was heavy and had clumps of blood clots and tissues.Menstruation is classified as: A 15 year old girl was brought into your clinic due to painful menses. She also said that her menstrual blood flow was heavy and had clumps of blood clots and tissues.Menstruation is classified as: A. Apoptosis A. Apoptosis B. Coagulative Necrosis B. Coagulative Necrosis C. Liquifactive Necrosis C. Liquifactive Necrosis