1. Cell injury:necrosis, apoptosis
Cell injury:necrosis, apoptosis. Adaptations:atrophy, hypertrophy,hyperplasia. Metaplasia.
2011

2. DEFINITIONS OF BASIC ASPECTS OF DISEASE PROCESS
epidemiology (occurrence and incidence of d.)
etiology (causes of disease)
pathogenesis (mechanisms of disease)
morphology of the tissue changes
clinical significance and consequences

3. classification of diseases
congenital- present at birth, even though they are sometimes recognized later
acquired- occur only later after births (infectious, nutritional, chemical, physical, radiation injury etc.)

4. CELL INJURY
Causes of cell injury heterogeneous, range from gross mechanical external causes to mild endogenous causes as genetic lack of enzymes etc.
Normal cell is confined to relatively narrow range of functions and structure by its genetic program to handle normal physiologic demands
homeostastatic „steady„ state
Cells react to adverse influence by
adapting
sustaining reversible injury
suffering irreversible cellular injury- cell death

5. cellular adaptation
More excessive stimuli (either physiologic or pathologic)
Cellular adaptation
altered steady state
excessive work stress causes the increase in muscle mass that reflects the increase in size of the individual muscle fiber - higher level of metabolic activity -new equilibrium
hypertrophy
adaptive response, in which there is a decrease in the size and function of the cells
vascular atrophy- results from slow long-lasting decrease of blood supply
If the limits of adaptive mechanisms are exceeded or when no adaptive response is possible- cell injury

6. Cell injury
Reversible cell injury denotes pathologic changes that can be reversed when the stimulus is removed and the cellular injury has been mild. Cell injury is reversible- up to certain point.
Irreversible cell injury denotes pathologic changes that are permanent and cause cell death, cannot be reversed to normal state

7. Cell death

8. Cell death

9. Cell death

10. Necrosis
defined as the morphologic changes that following the cell death in a living tissue or organ resulting from the progressive degradative activity of catalytic enzymes on lethally injured cells
These enzymes are derived either from dying cells themselves-autolysis
or from lysosomal enzymes of leukocytes -heterolysis

11. COAGULATIVE NECROSIS most common pattern
hypoxic death- results from sudden severe ischemia
Coagulative necrosis implies preservation of the basic outline of coagulated cells for several days
nucleus usually disappears, but the shape of cell is preserved
best example of coagulative necrosis- myocardial infarction

12. Coagulative necrosis
Myocardial infarct

13. Histological hallmarks of myocardial infarction:
Thin, wavy and hypereosinophilic cardiomyocytes lacking nuclei and inflammatory infiltration of the interstitium

14. Coagulative necrosis
Kidney infarct

15. Necrotic tissue
Viable tissue
necrosis
Demarcation line

16. Coagulative necrosis
Infarct of the spleen

17. LIQUEFACTIVE NECROSIS
results from rapid action of hydrolytic enzymes
autolysis and heterolysis prevail over denaturation of proteins
characteristic of ischemic necrosis of brain, pancreas
also common in bacterial lesions
-due to activity of enzymes of bacterial and leukocytic origin good example of liquefactive necrosis is brain infarction
gross morphology
very soft and fluidly, tissue liquefaction
results in subsequent pseudocystic degeneration
no fibrous scar is formed, necrotic area changes into postmalatic pseudocyst (postnecrotic)

18. Liquefactive necrosis
Encephalomalacia (liquefactive necrosis of the brain) and the resulting postmalatic pseudocyst

19. FAT NECROSIS due to action of activated lipases
acute pancreatic necrosis,
in which active pancreatic enzymes cause focal necrosis of the pancreas and the adipose tissue throughout the abdomen
lipases are activated and released and destroy not only pancreatic tissue itself but also fat cells in the pancreas and also fat cells throughout the peritoneal cavity
Balser necrosis
sharply circumscribed foci of enzymatic necroses of fat tissue with shadowy outlines surrounded by a zone of inflammation

20. Liquefactive necrosis
So-called Balser´s necrosis of pancreatic and peripancreatic fat

21. Viable pancreatic glandular tissue
Shadows of dead fat cell that have undergone enzymatic necrosis

22. CASEOUS NECROSIS in tuberculosis Gross morphology
it appears grossly as soft, friable, whitish-gray debris resembling cheesy material -caseous necrosis
Histologically, caseous necrosis appears as amorphous eosinophilic material with cell debris
specific granulomatous inflammatory reaction
Composed of epithelioid histiocytes
giant cells of Langhans type
lymphocytes

23. Yellow „cheesy“ areas of caseous necrosis in TBC lymphadenitis

24. GANGRENOUS NECROSIS
dry gangrene- black and dry and is sharply demarcated from viable tissue
in extremities as a result of ischemic coagulative necrosis doe to arterial obstruction
wet gangrene- results from severe bacterial infection
extremities due to arterial obstruction,
in acute suppurative appendicitis
tissue is swollen, reddish-black with extensive liquefaction
wet gangrene is severe complication associated with high mortality rate
gas gangrene- is a wound infection caused by Clostridium perfringens
extensive necrosis, tissue destruction, and production of gas by fermentative action of bacteria
presence of gas in tissues -crepitus
associated with a high mortality rate

25. Healing of necrosis
regeneration
necrosis
scar
postnecrotic
pseudocyst

26. Cellular adaptation and repair

27. Atrophy Reduction in size of a previously normal organ As opposed to:
Hypoplasia: insufficient growth of the organ during its development
Aplasia: inborn lack of the organ
Agenesis: inborn lack of the primordium of the organ

28. Atrophy under pathologic conditions-pathologic adaptation
There are four main adaptive states:
atrophy- shrinkage of the organ as a result of decreased cell size or/and the cell number
hypertrophy - enlargement of the organ as a result of increased cell size
hyperplasia - enlargement of the organ as a result of increased cell number
metaplasia -the replacement of one cell type by another cell type in a tissue or organ

29. Vascular atrophy of the kidney
is caused by a long standing gradual incomplete narrowing of the renal artery

30. Brown atrophy of the liver
is an example of senile atrophy
Aging
Diminution of cells
during their aging
Accumulation
of lipofuscin
in cells due to its
poor solubility
Brown atrophy

31. Hydronephrosis
is an example of mechanical atrophy due to compression of the renal parenchyma by dilated pelvis (e. g. in the setting of urolithiasis)

32. Dilated calyces in moderate hydronephrosis
Normal kidney
Severe hydronephrosis

33. Renal parenchyma
Flattened papilla
Dilated calyx
Histological hallmark of hydronephrosis is flattening of the renal papilla. On higher power you can see glomerular and tubular atrophy

34. Hypertrophy and hyperplasia
Hypertrophy: enlargement of an organ due to enlargement of its cells
Hyperplasia: enlargement of an organ due to increase in number of cells

35. Myocardial hypertrophy
Normal Hypertrophy
Myocardial hypertrophy
is characterized by increased thickness of cardiac walls and increased weight of the heart

36. Myocardial hypertrophy
Normal myocardium

37. Enlargement of prostate may be due to:
Hyperplasia
Adenocarcinoma

38. Hyperplasia
Adenocarcinoma

39. Imunohistochemical staining for HMW cytokeratin 34βE12
Hyperplasia
Adenocarcinoma
Imunohistochemical staining for HMW cytokeratin 34βE12

40. Hyperplasia
Adenocarcinoma
+ orchiectomy?
TURP

41. Other possible but usually not used differentiation lines
Metaplasia
Reversible change in which one adult cell type is replaced by another adult cell type
Other possible but usually not used differentiation lines
Injury
New line of
differentiation
Normal line of
differentiation
Stem cell
Stem cell

42. Metaplasia
is an abnormality of cell differentiation in which one type of mature cell is replaced by a different type of adult cell
squamous metaplasia n
nonsquamous columnar or pseudostratified epithelium is replaced by stratified squamous epithelium
in uterine cervix, in bronchial mucosa, in nasal cavity and paranasal sinuses
glandular metaplasia
occurs in the oesophagus, where the normal epithelium is replaced by glandular mucus secreting epithelium Barret oesophagus
Clinical significance: risk of development of peptic ulcer in metaplastic gastric mucosa
intestinal metaplasia - occurs often in chronic gastritis
Metaplasia only rarely occurs in mesenchymal tissue:
osseous metaplasia - in scars