This document discusses various types of cell injury and growth disturbances. It describes reversible cell injury known as degeneration, which includes cloudy swelling and hydropic change caused by mild injury and accumulation of water in cells. Prolonged or severe injury can lead to irreversible necrosis or programmed cell death known as apoptosis. Fatty change is also a type of reversible degeneration caused by accumulation of lipids in cells. Different types of necrosis like coagulative, liquefactive, and caseous are outlined. The document also discusses cellular changes seen in apoptosis. Various growth disturbances like atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, and neoplasia are defined and examples provided.

1. Reversible cell injury
(degeneration)
1

2. Effects of cell injury:
• Reversible injury (degeneration):
– Morphological changes due to disturbance of
cellular metabolism caused by mild injury.
– Reversible if remove the irritant.
– Necrosis (irreversible) injury occure: if prolonged
or intensity.
– Parynchemal cells > vulnerable while mesenchymal
cells > resistant.
2

3. Reversible injury (degeneration):(cont.)
– Cell swelling due to accumulation of IC water
or fat:
• Water: mild form of cell injury with 2 subtypes:
–Cloudy swelling: small amount of water cell
swelling + granular cytoplasm.
–Hydropic swelling: larger amount of water
swollen , pale with clear cytoplasmic vacules.
• Fatty change.
3

4. Effects of cell injury (cont.):
• Irreversible injury (cell death): 2 types:
– Necrosis: severe or prolonged cell injury.
– Apoptosis: cell suicide in certain
circumstances unrelated to tissue irritation.
4

5. Cloudy swelling
Hydropic change kidney. The tubular
epithelial cells are distended with
cytoplasmic vacuoles while the
interstitial vasculature is compressed.
The nuclei of affected tubules are pale.
Cell swelling due to accumulation of water:
5

6. Cell swelling due to accumulation of water:
• Pathogenesis: mild injury (hypoxia) inhibit
oxidative phosphorelation ATP production:
– Disturbed memb. Transport influx of Na (+ water) &
efflux of K.
– Anaerobic metabolism accumulation of inorganic
Phosphate, lactate, purine nucleosides IC OP.
• E.g:
– Ballooning of epid cells with viral infection & mild burn.
– Balloning B cells of islets of langerhans in DM.
6

7. Pahtology:
Gross :swollen & pale affected tissue.
Microscopic:
Cloudy: swollen + pale esinophilic granular
cytoplasm.
Hydropic: swollen + single large or multible
clear vacules.
Cloudy swelling
7

8. Hydropic change kidney. The tubular epithelial cells are distended with cytoplasmic
vacuoles while the interstitial vasculature is compressed. The nuclei of affected tubules
are pale. 8

9. Fatty change (steatosis):
• Accumulation of lipids inside parynchemal cells, can
affect many organs but common in liver (hepatic
steatosis).
• Causes & pathogenesis:
– Fatty change of liver:
• Hypoxia or bact. toxins mitochondrial lipid metabolism
enzymes IC accumulation of fat.
• HC specific causes (as fat metabolism organ):
– > fat carried to liver (obesity, starvation & DM).
– liptropic factors.
– Hepatotoxins: alcohol ( FA synthesis , FA oxidation & peripheral
lipolysis
– Liver cell ds. E.g HCV.
– Fatty change of other organs : mainly toxic or hypoxic
depression of mitochondrial enzymes. 9

10. Fatty change (steatosis) (cont.):
• Gross:
– Organ: enlarged with tense capsule, soft, greasy, cut surface
is bulging with rounded boarders, diffuse or patchy yellow
color.
– Liver & Heart: diffuse (toxic) or patchy (hypoxic) affection.
– Kidney: mainly cortical &patchy or rarely diffuse.
• Microscopic:
– Ordinary stains: small clear vacules or single vacule signet
ring appearance.
– Special stains: orange (Sudan III)or black (osmic a.)
• Clinical significance:
– It is sever form of cell injury, may progress to necrosis:
• diffuse heart affection HF
• Liver affection may progress to cirrhosis. 10

11. Fatty change, liver(Steatosis)
Yellow cut section
rounded border
Vacuolated hepatocyte
(signet ring appearance)
Portal tract
High power
11

12. LM of connective tissue spread stained with
Sudan III stain to demonstrate fat cells
(orange colour). Hx stain used as counter
stain to demonstrate nuclei (optional)
Note the absence of use of fat solvents
12

13. 13

14. 14

15. Necrosis
• Death of group of cells within a living
body caused by irritant.
• Gross:
–necrotic tissue : opaque yellow, may be
swollen.
–Surrounding tissue: hyperemic
(inflammation).
15

16. Necrosis
• Microscopic:
–Cellular changes:
• Nuclear: pyknosis, karyorrhexis, karyolysis
• cytoplasmic: cytomegally, indistinct memb.,
esinophilic cytoplasm (denatured ptns).
–Architectural changes:
• Structureless due to cell lysis (auto +/-
heterolysis).
• Structural ghosts finally Structureless .
16

17. Cellular features of necrosis
17

18. 18

19. Fate of necrotic tissue:
• Inflammation surrounds it (due to mediators).
• Healing (regeneration or fibrosis).
• Dystrophic calcification.
19

20. Types of necrosis:
• Coagulative:
• Infarcts (ischaemic necrosis): all except CNS.
• Structural ghosts for some days.
20

21. Coagulative necrosis. A, A wedge-shaped kidney infarct (yellow). B,
Microscopic view of the edge of the infarct, with normal kidney (N) and
necrotic cells in the infarct (I) showing preserved cellular outlines with loss
of nuclei and an inflammatory infiltrate (seen as nuclei of inflammatory cells
21

22. Coagulative necrosis. A. Normal heart. All myocytes are
nucleated, and striations are clear. B. Myocardial infarction.
The heart from a patient following acute myocardial infarction.
Thenecrotic cells are deeply eosinophilic and most have lost 22

23. Types of necrosis:
• Liquefactive:
– Infarcts of CNS & pus.
– Cell lysis > ptn
denaturation (as >
proteolytic enzyms in
pus)
23

24. 24

25. Types of necrosis:
• Gangrenous:
– Necrosis followed by putrifaction.
• Caseous:
– Typical for TB.
– Necrotic tissue : cheesy (as casein) due to:
• Ischaemic coagulative necrosis due to endarteritis
obleterans.
• Partial liquefaction (cell fragmentation) due to coexisting
hypersensitivity release cytotoxins & proteolytic
enzymes.
• Fat librated from dead TB bacilli.
– M/P: granular esinophilic structureless material (fragmented
necrotic cells).
25

26. 26

27. 27

28. Types of necrosis (cont.):
• Fat necrosis: 2 subtypes
– Enzymatic:
• Cause: acute hrgic pancreatitis.
• Michanism: rupture pancreatic ducts lipase & protease
digestion (necrosis) of surrounding peritoneal fat cells.
• Gross:may show chalky white hard calcified patches (Ca
soaps).
• M/P:swollen necrotic fat cells surrounded by chronic inflam.
Celss (including FBGC) & fibrosis, sometimes with
calcifications.
– Traumatic:
• Cause: trauma (may be surgical), common in SC fat & breast.
• Michanism:rupture of fat cells autodigestion release FA
bind to Ca.
• Gross: hard, sometimes chalky white mass (mistaken with 28

29. 29

30. Fat necrosis, notice the signet
ring appearance (arrow)
30

31. Types of necrosis (cont.):
• Fibrinoid:
– Not true necrosis (not
affecting living cells).
– Autoantibodies against
collagen.
– Affects Muscle fibers &
collagen.
– Collagen Fragmented to finer
particles (rsemble fibrin).
– In autoimmune ds (as RA &
LE).
31

32. Apoptosis
• Type of cell death that considered as Cell
suicide or programmed cell death to remove
un-necessary or diseased cells.
• Affects single or few cells.
• Occur in physiological & pathological
conditions.
• Without tissue injury (or with mild injury not
causing necrosis) so, no healing or
calcification.
• No chemical mediators not excite inflamm.
32

33. Morphological features of
apoptosis:
• Shrinkage of cell size.
• Condensation of nuclear
chromatin then fragmentation
of DNA.
• Membrane blebs formation
separation apoptotic
bodies (dark nuclear fragment
surrounded by eosinophilic
cytoplasm) engulfed by
phagocytes.
33

34. 34

35. Examples of apoptosis:
• Physiological state:
– During embryogenesis.
– Normal turnover of cells
to maintain constant
no.
– Cells after achieving
purpose e.g PMN in
acute inflam.
– Hr. dependent tissue
involution e.g
endometrium.
35

36. • Pathological states:
– Malignant tumor cells.
– T lymph. Induced cytotoxicity e.g organ rejection.
– Some cases of atrophy.
– Mild radiation & mild thermal injury.
– Liver cells in viral hepatitis (councilman bodies).
36

37. Growth disturbances
• Congenital:
– Agenesis: failure of development of an organ.
– Hypoplasia: undersized organ.
– Aplasia: failure of cell growth (severe hypoplasia).
– Others: supernumerary organ, organ duplication,
ectopic tissue, fused organs.
• Aquired:
– Atrophy, hypertrophy, hyperplasia, metaplasia,
dysplasia, neoplasia.
37

38. Supernumerary teeth in the premaxillary area
38

39. Atrophy
• Cellular : acquired shrinkage of cell size
( anabolism &/or catabolism), remain alive
with organelles
• Tissue or organ: size & weight after it’s full
development (due to cell atrophy or death).
The atrophic part replaced by fibrous or
adipose tissue.
39

40. Atrophy
aetiology & types
• Physiological:
–Localized:e.g mammary & ovaries atrophy with
menopause.
–Generalized (aging):
• Physiological aging of cells: age related (senile
atrophy) due to oxidative phosphorelation by aged
mitochondria energy nutrients uptake.
• Pathological premature aging (progeria): aging in
young individuals due to error in DNA replication
cell viability. 40

41. Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old man with
atherosclerotic cerebrovascular disease, resulting in reduced blood supply. Note that loss of brain
substance narrows the gyri and widens the sulci. The meninges have been stripped from the right
half of each specimen to reveal the surface of the brain.
41

42. Atrophy
aetiology & types
• Pathological:
– Generalized:
• affects all tissues & organs.
• Due to : anabolism (starvation), catabolism (cachexia), progeria.
– Localized:
• Disuse: workload (limb ms. After fracture).
• Neuropathic: due to loss of innervation (poliomyelitis).
• Hormonal:loss of endocrine stimulation (breast after oophorectomy)
• blood supply:
– Pressure atrophy : of cells & feeding vs from outside.
– Vascular atrophy: of tissue or organ due to blood supply by
vascular disease causing luminal narrowing (atherosclerosis).
• Acquired aplasia: idiopathic cell loss e.g BM aplasia (aplastic a.) 42

43. Progeria
Atrophy of the left side of the tongue and deviation of the tongue to the
left on protrusion. Arrow shows the atrophy of the left side of the
tongue.
43

44. Unilateral Tongue Atrophy
Denervation Atrophy of the Tongue after
Hypoglossal-Nerve Injury
44

45. Figure 1: (a and b) Left hemifacial
atrophy involving cheek, masseter, and
temple (arrow) Figure 2: Atrophy of left half of
tongue (arrow)
Parry-Romberg syndrome with hemimasticatory spasm in pregnancy;
A dystonia mimic
45

46. Hypertrophy
• size of the cell size of tissue or organ.
• Protien synthesis due to functional demands.
• Pure in muscles but in others associated with
hyperplasia.
• Aetiology & types:
– Physiological: e.g pregnant uterus & striated ms.
– Pathological:
• Adaptive: ms coat of hollow organ due to intralumenal
pressure, e.g LV hypertrophy with HTN or AS.
• Compensatory: if 1 of paired organs is out of function or
surgically removed the other undergoes compensatory
hypertrophy e.g kidney enlargement.
46

47. Calcium channel blocker induced gum
hypertrophy: no class distinction .
gum hypertrophy - phenytoin,ciclosporin
nifedipine
This man in his twenties with epilepsy has
gum hypertrophy (enlargement) as a result
of being massively overdosed on his
antiepileptic treatment for the past ten
years. 47

48. Normal heart
48

49. Physiologic hypertrophy of the uterus during pregnancy. Gross
appearance of a normal uterus (right) and a gravid uterus (left)
that was removed for postpartum bleeding. 49

50. Physiologic hypertrophy of the uterus during pregnancy. B, Small spindle-shaped
uterine smooth muscle cells from a normal uterus. C, Large, plump hypertrophied
smooth muscle cells from a gravid uterus; compare with B. (B and C, Same
magnification.) 50

51. Hyperplasia
• Number of cells size of tissue or organ.
• Usually accompanied by some degree of hypertrophy.
• Occures in all cells capable of division i.e all cells except
nerve cells, skeletal & cardiac ms. Cells
• Aetiology & types:
– Physiological: e.g mammary glands & genitalia at
puperty (physiological hormonal hyperplasia).
– Pathological: (in pathological states)
• Hormonal :endometria & mammary due to estrogen stim.
• Irritation: lymphoid tissue with Ag stim.
• Compensatory (considered physiological or pathological): BM
hyperplasia after hemorrhage or hemolysis. 51

52. hyperplasia
• Excited by stimulus.
• Reversible.
• Normal shaped cells.
• May be useful as
compensatory hyperplasia.
neoplasia
• Stimulous may not be detected.
• Irreversible (unlimited
progressive proliferation even if
any stim. Stopped).
• Abnormal shaped (in malignant
neoplasia).
• Harmful.
Although it is different from neoplasia but it may be precancerous
i.e pathological hyperplasia may lead to malignant neoplasia.
52

53. Metaplasia
• Transformation of 1 mature differentiated cell
type into another of the same category.
• Reversible.
• Adaptive substitution of cells > sensitive to
stress by cells > resistant that can better
withstand the adverse environment.
• Precancerous.
53

54. Aetiology & types
• Epithelial:
– Squamous: columner or transitional stratified squamous that
sometimes followed by leukoplakia.
– Intestinal: of gastric mucosa at edges of peptic ulcer.
• Mesenchymal:
– fibroblasts chondro & osteoblasts bone & cartilage in
abnormal sites (soft tissue ossification in foci of injury).
– Localized myositis Ossificans : ms necrosis followed by infiltration
by granulation tissue in which fibroblasts undergo osteoblastic
metaplasia ossification.
– Old fibrotic TB lesion.
• Serosal: mesothelial cells Stratified, glandular or other epithelial
types
• Tumor metaplasia: epithelial metaplasia e.g adenocarcinoma
(glandular) show areas of adenoacanthoma (squamous). 54

55. 55

56. Leukoplakia
• Related to chronic irritation.
• Precancerous SCC.
• Gross:Thick irregular white mucosal patches.
• Represent: Squamous metaplasia with
keratinization (as urinary bladder) or hyperplasia
with keratin formation (if arise on mm composed
of stratified sq.epith. As tongue & vulva).
• M/P: thick hyperkeratotic SSE & chronic
inflammation in subepithelial layer.
56

57. 57

58. Dysplasia
• Non-neoplastic disordered proliferation of cells,
usually induced by prolonged irritation.
• Microscopic with no specific gross change.
• Chiefly affect epithelial cells.
• Microscopically:
– Loss of uniformity of individual cells with loss of
archetecture (polarity).
– Cells: atypical looking, pleomorphism, hyperchromatic &
mitotic activity.
– Degree (degree of cell atypia & etent of involvement):
mild (lower 1/3), moderate (lower 2/3), sever (CIS). 58

59. 59

60. 60

61. • Prognosis:
– Mild & moderate: reversible when cause is removed but
may progress to sever form.
– Sever (CIS): highly precancerous invasive cancer
• Examples:
– Cervical dysplasia in females with ch. Cervisitis.
– Urothelial dysplasia with bilharzial cystitis.
Dysplasia (cont.)
61

62. Carcinoma In Situ (CIS)
• Preinvasive stage of cancer with sever
dysplasia (cellular atypia) without BM
invasion.
• It is a microscopic change.
• It ends once BM invaded and become actual
invasive malignant tumor.
• E.g: skin, GIT, cervix & endometrium.
62

63. Carcinoma In Situ (CIS)
pathological features
• Gross:
– Difficult to detect.
– May cause thick indurated patch.
– Rarely cause a mass e.g CIS of mammary duct.
• M/P:( essentially microscopic change)
– Diffuse cellular atypia in the whole epith.
Thickness.
– NO BM INVASION.
• Fate : progress to invasive carcinoma after
time (usually years). 63

64. 64

65. Histology: squamous cell carcinoma in situ,
high power 65

66. Squamous cell carcinoma in situ (SCCS)/Bowen's disease. (a) There
is prominent dyskeratosis and aberrant mitoses at all levels of the
epidermis, along with marked parakeratosis (100x). (b) Note,
however, that the basement membrane remains intact (400x).
66