med 2 lecture file

1. Introduction to Pathology
Cell Adaptation, Injury and Death
By Noel C. Santos, M.D.

2. LEARNING OBJECTIVES

3. Introduction to Pathology
• Define Pathology
• Give the two main divisions of
Pathology
• Give the four aspects of
disease process

4. Cell Adaptation
• Define and review the concept
of normal homeostasis
• Define cellular adaptation
• Give the six types of adaptive
response that may occur in a
cell

5. Cell Injury
• Define cell injury
• Enumerate the general categories of the cause of cell injury
• Give the two main phase of cell injury
• Give the basic principles of cell injury
• Give the general biochemical mechanisms of cell injury
• Discuss the events that occur during ischemia with hypoxia
• Discuss the events that occur during ischemia with
reperfusion
• Discuss the events that occur in free radical-induced cell injury
• Discuss the mechanisms of chemical injury
• Give the morphologic changes that occur during reversible cell
injury
• Enumerate and discuss each of the subcellular responses to
cell injury

6. Cell Death
• Define cell death
• Give the principal patterns of cell death in response to
lethal and/or acute cell injury
• Discuss the causes, biochemical features and
mechanisms of apoptosis
• Give examples of apoptosis
• Give the morphologic changes of cells that undergo
apoptosis
• Give the morphologic changes that occur during
irreversible cell injury and cell death
• Enumerate the morphologic types of necrosis, and give
examples
• Give the morphologic cellular alterations in response to
sublethal and/or chronic cell injury

7. Pathology
Definition:
“pathos” = “suffering” or “disease”
“logos” = “study”
“study of diseases”
- study of the structural and
functional causes of human
disease.

8. Main Divisions of Pathology
1. BASIC or GENERAL PATHOLOGY
2. SYSTEMIC PATHOLOGY
- CLINICAL PATHOLOGY
- ANATOMIC PATHOLOGY
- PATHOPHYSIOLOGY
- SURGICAL PATHOLOGY

9. Four Aspects of Disease Process
1. ETIOLOGY – cause of a disease
2. PATHOGENESIS – mechanism/s of
disease development
3. MORPHOLOGIC CHANGE –
structural alterations induced in cells,
tissues, organs, systems, body
4. FUNCTIONAL DERANGEMENT and
CLINICAL SIGNIFICANCE –
functional consequences of the
morphologic changes

10. PATHOLOGY……..

11. HOMEOSTASIS
“steady state – normal function where
there is a balance between
physiologic demands and the
constraints of cell structure and
metabolic capacity.”
MAINTAINED STATE OF VIABILITY
OR VITALITY

12. THE CELL
- Can alter their functional state in
response to modest stress, maintain
the steady state
- More excessive physiologic stresses
or adverse pathologic stimuli
- ADAPTATION
- INJURY: Reversible or Irreversible
- DEATH

13. Normal
Cell
Cell
Adaptation
Cell Injury
Reversible Irreversible
Cell Death
Hypoxia
Infectious
Chemical
Physical
Immunologic
Genetic
Nutritional Imbalance

15. ADAPTATION
- Stressful stimuli induce a new state
that changes the cell
- Preserves the cell’s viability
- HYPERPLASIA
- HYPERTROPHY
- ATROPHY
- INVOLUTION
- METAPLASIA
- DYSPLASIA

18. Muscle - ischemic atrophy:

20. LVH - Heart in
Hypertension:
Left Ventricular Hypertrophy

21. Goitre – Iodine Deficiency

22. Renal Artery stenosis - Atrophy
Nephrosclerosis Atrophic Kidney

23. CELL INJURY
- REVERSIBLE
- Pathologic cell changes that can be
restored to normal state
- IRREVERSIBLE
- Stress exceeds the capacity to adapt
- “point of no return”
- Permanent changes – DEATH

33. CELL DEATH
- 2 patterns
- NECROSIS
- Always pathologic
- Severe cell swelling
- Denaturation and coagulation of proteins
- Breakdown of cellular organelles
- Cell rupture
- Large number cells in the adjoining tissue are
affected
- APOPTOSIS
- May be physiologic
- Activation of internal “suicide” program
- Orchestrated disassembly of cell components
- Minimal disruption of the surrounding tissue
- Chromatin condensation/fragmentation

35. Morphologic Types of Necrosis
• Coagulation
• Liquefaction
• Caseation
• Enzymatic Fat

39. Cerebral Infarction (Stroke) :
Haemorrhagic
Necrosis

40. Normal & Ischemic - kidney tubule
Microvilli

41. Renal Infarction - Coagulative

42. Infarct Adrenal gland:

43. Caseous necrosis
Tuberculosis
hilar lymphnode

44. Extensive
Caseous necrosis
Tuberculosis

45. Splenic Infarction - Coagulative necrosis

46. Stroke- Liquifactive necrosis

47. Liver abscess: Liquifactive necrosis

48. Gangrene Intestine - Thrombosis.

49. Gangrene - Diabetic foot

50. Gangrene - Amputated Diabetic foot

51. Ageing

52. Ageing:
“Progressive time related loss of
structural and functional capacity of
cells leading to death”
• Senescence, Senility, Senile changes.
• Ageing of a person is intimately related
to cellular ageing.
• Countdown starts with birth…!

53. Factors affecting Ageing:
• Genetic – Clock genes,
(fibroblasts)
• Diet – malnutrition, obesity etc.
• Social conditions -
• Diseases – Atherosclerosis,
diabetes etc.
• Genetic disease - Werner’s
syndrome.

54. Telomerase in ageing:
Germ
Cells
Somatic
Cells

55. Cellular ageing mechanisms:
• Nuclear:
– Reduced synthesis of nucleic acids
– Telomere shortening
– Clock genes
• Metabolic:
– Reduced Mitochondrial oxidative reactions
– Reduced protein synthesis, Protein cross
linking.
– Decreased cell receptors, transcription factors.
– Oxidative peroxidation of organelles.

56. Ageing – Morphologic
changes:
• Loss of skin elasticity
• Easy bruising – fragile capillaries.
• Glycosylation of lens proteins –
• Accumulation of Lipofuscin pigment
– Brown atrophy.

57. Normal Brain surface:

58. Cerebral atrophy - Alzheimers:

59. Elastosis of skin:

60. Pathology
of Ageing

61. Conclusions:
• Cellular Injury - Various causes
• Reversible Injury - Adaptations
– Hypertrophy, Hyperplasia, Atrophy
– Accumulations - Hydropic, hyaline, fat..
• Irreversible Injury - Necrosis
– Coagulative, Liquifactive, Caseous, fat…
• Ageing: Physiological & pathological.
– Time related, several theories.

62. Thank You