intro to cytology intro cytopathology Cellular Adaptations Cellular Injuries Necrosis Apoptosis

1. Pathology of the Cell
Dr. Sami

2. “All organ injuries start with
structural or molecular alterations in
cells”
 Virchow in 1800's

3. “you cannot appreciate the
abnormal before you
understand”

4. What is Cell?
 The cell (from Latin cellula 'small room') is the basic structural, functional,
and biological unit of all known organisms.
 A cell is the smallest unit of life. Therefore, cells are often described as the
"building blocks of life".
 Cell biology (also called cellular biology or cytology) is the study of cells.
 The human body is composed of trillions of cells.
 They provide structure for the body, take in nutrients from food, convert
those nutrients into energy, and carry out specialized functions. ...
 Cells have many parts, each with a different function.

6. Structure of the Cell
 A cell consists of three parts: the cell membrane, the nucleus, and,
between the two, the cytoplasm.
 Within the cytoplasm lie intricate arrangements of fine fibers and hundreds or
even thousands of miniscule but distinct structures called organelles.

7. Cell Membrane:
 Every cell in the body is enclosed by a cell (Plasma) membrane.
 The cell membrane separates the material outside the cell, extracellular,
from the material inside the cell, intracellular. It maintains the integrity of a
cell and controls passage of materials into and out of the cell.
 It is semi-permeable which means it allows certain things to pass in and out of
the cell.

9. Cytoplasm:
 Cytoplasm is a thick gel-like fluid inside the cell and is enclosed by the cell
membrane. It is mainly composed of water, salts, and proteins.
 It is the medium for chemical reaction.
 It provides a platform upon which other organelles can operate within the
cell.
 All of the functions for cell expansion, growth and replication are carried out
in the cytoplasm of a cell.

11. Nucleus:
 The nucleus, formed by a nuclear membrane around a fluid nucleoplasm, is
the control center of the cell.
 Threads of chromatin in the nucleus contain deoxyribonucleic acid (DNA),
the genetic material of the cell.
 The nucleolus is a dense region of ribonucleic acid (RNA) in the nucleus and
is the site of ribosome formation.
 The nucleus determines how the cell will function, as well as the basic
structure of that cell.

13. Cytoskeleton:
 The cytoskeleton of a cell is made up of microtubules, actin filaments, and
intermediate filaments.
 The cytoskeleton is a network of long fibers that make up the cell’s structural
framework.
 The cytoskeleton has several critical functions, including determining cell
shape, participating in cell division, and allowing cells to move.
 It also provides a track-like system that directs the movement of organelles
and other substances within cells.

14. Endoplasmic reticulum (ER)
 Another membrane organelle that associates with the nuclear membrane
 The ER consists of the nuclear envelope and the peripheral ER, which
includes smooth tubules and rough sheets.
 While the ER is defined as an interconnected network with a continuous
membrane,
 the different structures that make up the ER perform a variety of functions,
the most important being protein synthesis and folding.
 Some proteins move on to the Golgi for more modification and final
packaging.

16. Ribosomes
 Ribosomes are made of proteins and ribonucleic acid (abbreviated as RNA),
in almost equal amounts
 Ribosomes are organelles that process the cell’s genetic instructions to create
proteins.
 These organelles can float freely in the cytoplasm or be connected to the
endoplasmic reticulum

18. Golgi apparatus
 The Golgi apparatus, also called Golgi complex or Golgi body, is a membrane-
bound organelle that is made up of a series of flattened stacked pouches
called cisternae.
 It is located in the cytoplasm next to the endoplasmic reticulum and near the
cell nucleus.
 The Golgi apparatus packages molecules processed by the endoplasmic
reticulum to be transported out of the cell.

19. Lysosomes and peroxisomes
 These organelles are the recycling center of the cell.
 They digest foreign bacteria that invade the cell, rid the cell of toxic
substances, and recycle worn-out cell components.
 break down food molecules, old or unwanted organelles and even invading
pathogens

20. Mitochondria
 Power House of the Cell.
 Respiration of the Cell.
 Mitochondria are complex organelles that convert energy from food into a
form that the cell can use.
 They have their own genetic material and can make copies of themselves.

21.  Mitochondria have an inner and outer membrane, with an intermembrane
space between them.
 The outer membrane contains proteins known as porins, which allow
movement of ions into and out of the mitochondrion.
 The inner membrane contains a variety of enzymes. It contains ATP synthase
which generates ATP in the matrix, and transport proteins that regulate the
movement of metabolites into and out of the matrix.
 The inner membrane is arranged into cristae in order to increase the surface
area available for energy production via oxidative phosphorylation

23. Cell Pathology;
Cell Adaptations:
Cell Injury:
Cell Death

25. Homeostasis:
 Definition:
 a self-regulating process by which biological systems maintain
stability while adjusting to changing external conditions.
 Homeostasis in the cell is maintained by regulation and by the
exchange of materials and energy with its surroundings.

26. Cell Adaptations:

27. Cell Adaptations:
 Cellular Adaptation • Cell can adapt themselves by undergoing 5 different
conditions
 1. Hyperplasia
 2. Hypertrophy
 3. Atrophy
 4. Metaplasia
 5. Dysplasia

28. Hyperplasia:

29. Hyperplasia:
 Hyperplasia is an increase in the tissue or organ size due to increased cell
number, without an increase in cell size. It can only occur in labile or stable
cell populations.
 The cell proliferation in hyperplasia remains under physiological control and
is reversible, unlike in neoplasia (cancer) which is irreversible.

30. Types
 Physiologic Hyperplasia:
 Pathologic Hyperplasia:

31. Physiologic Hyperplasia:
 The two most common types follows:
 1.Hormonal hyperplasia
 2. Compensatory hyperplasia

32. Hormonal Hyperplasia:
 Influence of hormonal stimulation •
 Hyperplasia of female breast at puberty, during pregnancy and lactation
 normal endometrium after a normal menstrual cycle. (The lining of the uterus
(endometrium) becomes unusually thick because of having too many cells
(hyperplasia) )

33. Compensatory hyperplasia
 Hyperplasia occurring following removal of part of an organ or a
contralateral organ in paired organ •
 Regeneration of the liver following partial hepatectomy •
 Regeneration of epidermis after skin abrasion •
 Following nephrectomy on one side, there is hyperplasia of nephrons of the
other kidney.

34. Pathological Hyperplasia:
 Occurs due to an abnormal stressor.
 skin warts from hyperplasia of epidermis due to human papilloma virus. –
 Pseudo carcinomatous hyperplasia of the skin

35. Hypertrophy:

36. Hypertrophy:
 Hypertrophy is an increase in cell or organ size and results from an increase
in the amount of cytoplasm and an increase in the number and size of
cytoplasmic organelles.

37.  Hypertrophy may be
 Physiologic
 Pathologic.

38. Physiologic hypertrophy.
 Physiologic hypertrophy.
 Enlarged size of the uterus in pregnancy is an excellent example of
physiologic hypertrophy as well as hyperplasia

39. Pathologic hypertrophy
 Pathologic hypertrophy: •
 Hypertrophy of cardiac muscle may occur in a number of cardiovascular
diseases Ex: Systemic hypertension •
 Hypertrophy of smooth muscle Ex: Pyloric stenosis (in stomach) • (pylorus, a
muscle at the end of the stomach. When the pylorus thickens, food can't pass
through. Premature birth. Family history. Smoking during pregnancy )
 Hypertrophy of skeletal muscle Ex: hypertrophied muscles in athletes and
manual labourers

40. Atrophy:

41. Atrophy:
 Definition:
 Atrophy is defined as a decrease in the size of a tissue or organ due to
cellular shrinkage; the decrease in cell size is caused by the loss of
organelles, cytoplasm and proteins.

42. Types:
Physiological.
Pathological.

43. Physiological Atrophy:
 Physiologic atrophy is caused by not using the muscles enough.
 This type of atrophy can often be reversed with exercise and better nutrition.
 People who are most affected are those who:
 Have seated jobs,
 health problems that limit movement,
 decreased activity levels.
 Are bedridden.
 Atrophy of brain with aging.
 Atrophy of gonads after menopause.

44. Pathological Atrophy:
 Pathologic atrophy of muscles can occur with diseases of the motor nerves
or diseases of the muscle tissue itself.
 Starvation atrophy. •
 Ischemic atrophy •
 Disuse atrophy. •
 Neuropathic atrophy. •
 Endocrine atrophy •
 Pressure atrophy. •
 Idiopathic atrophy

45.  Starvation Atrophy:
 generalized atrophy (wasting away) of body tissues either because food is
unavailable or because it cannot be taken in or properly absorbed.
 Ischemic atrophy:
 Atrophy of a Tissue Organ or muscle resulting from injury to its blood supply;
 Atrophy of brain in cerebral atherosclerosis, CVA

46.  Disuse atrophy
 Disuse atrophy is a type of muscle atrophy, or muscle wasting, which refer
to a decrease in the size of muscles in the body.
 Disuse atrophy occurs when a muscle is no longer as active as usual.
 When muscles are no longer in use, they slowly become weaker.
 Eventually, they begin to shrink.

47.  Neurogenic atrophy
 the most severe type of muscle atrophy. It can be from an injury to, or
disease of a nerve that connects to the muscle.
 This type of muscle atrophy tends to occur more suddenly than physiologic
atrophy
 Poliomylitis

48.  Endocrine Atrophy:
 Failure of a gland to stimulate another gland to release hormones
 Hypopituitarism may lead to atrophy of thyroid, adrenal and gonads.
 Hypopituitarism is a rare disorder in which your pituitary gland fails to
produce one or more hormones, or doesn't produce enough hormones.

49.  Pressure Atrophy:
 the wasting of hard or soft tissue resulting from excessive pressure applied
to tissue by a denture base.
 Erosion of spine by tumor in nerve root
 Idiopathic Atrophy:
 Testicular atrophy.

50. Metaplasia:

51. Definition:
 A reversible change of one type of epithelial or mesenchymal adult cells to
another type of adult epithelial or mesenchymal cells, usually in response
to abnormal stimuli, and often reverts back to normal on removal of
stimulus.
 Epithelial cells are a type of cell that lines the surfaces of your body.
 Mesenchymal stem cells are multipotent adult stem cells that are present
in multiple tissues, including umbilical cord, bone marrow and fat tissue

52. Types:
 Epithelial Metaplasia
 Mesenchymal Metaplasia.

53. Epithelial Metaplasia
 Two types of epithelial metaplasia are seen
 Squamous and Columnar
 Squamous metaplasia: squamous metaplastic change due to chronic irritation
that may be mechanical, chemical or infective in origin.
 Ex: Smokers often exhibit squamous metaplasia in the linings of their airways.
 2. Columnar metaplasia: There are some conditions in which there is
transformation to columnar epithelium.
 Ex: Intestinal metaplasia in healed chronic gastric ulcer

54. Mesenchymal Metaplasia.
 Transformation of one adult type of mesenchymal tissue to another.
 • 1. Osseous metaplasia:
 Ex-In cartilage of larynx and bronchi in elderly people •
 2. Cartilaginous metaplasia.
 In healing of fractures, cartilaginous metaplasia may occur where there is
undue mobility

55. Dysplasia:

56. Definition:
 The presence of cells of an abnormal type within a tissue, which may
signify a stage preceding the development of cancer.
 The abnormal growth or development of a tissue or organ.
 Fibrous dysplasia of bone.
 Hip dysplasia.
 Multicystic dysplastic kidney.

57. Aplasia:

58. Definition:
 Failure of cell Reproduction during Embryogenesis.
 Absence of organ or tissues

59. Hypoplasia:

60. Definition:
 Decrease in cell production during Embrogenesis.
 Small Organ or tissues

61. Cell Injuries:

62. Definition:
 Cellular injury occurs when a stress exceeds the cell’s ability to adapt.
 Cells cannot adapt, or the maximum adaptive response to physiologic or
pathologic stimuli is exceeded.

63. Factors:
 Factors affecting cell injury:
 Nature,
 duration, and severity
 Type and adaptability of the cell

64. Etiology:
 Injurious stimuli
 Physical agents:
 Mechanical trauma
 Temperature and atmospheric pressure changes
 Radiation
 Electric shock
 Chemical agents and drugs:
 Chemicals causing electrolyte derangements (e.g., glucose)
 Poisons (e.g., cyanide, arsenic)
 Environmental pollutants
 Industrial hazards (e.g., asbestos)
 Medications (toxic effects)

65.  Oxygen deprivation:
 Ischemia
 ↓ oxygen-carrying capacity of the blood (anemia)
 Infections: viruses, bacteria, parasites, other biological agents
 Immunologic reactions:
 Immune reactions to external agents
 Autoimmune diseases

66.  Genetic abnormalities:
 Congenital malformations
 Deficient protein function from enzyme defects
 Misfolded proteins
 Nutritional deficiencies and excess:
 Nutritional deficiencies (vitamin deficiency)
 Nutritional excess (obesity, increased lipids)

67. Target:
 The most notable components of the cell that are targets of cell damage are
the DNA and the cell membrane.
 DNA damage: In human cells, both normal metabolic activities and
environmental factors such as ultraviolet light and other radiations can
cause DNA damage, resulting in as many as one million individual molecular
lesions per cell per day.
 Membrane damage: Damage to the cell membrane disturbs the state of cell
electrolytes, e.g. calcium, which when constantly increased, induces
apoptosis.

68.  Mitochondrial damage: May occur due to ATP decrease or change in
mitochondrial permeability.
 Ribosome damage: Damage to ribosomal and cellular proteins such as protein
misfolding, Leading to apoptotic enzyme activation.

69. Types of cell injury
 Reversible Cell Injury.
 Irreversible Cell Injury.

70. Reversible Cell Injury.
 if the injured cell can regain homeostasis and return to a morphologically
(and functionally) normal state.
 Effect of mild or transient damage
 Elimination of the pathologic stimuli or restoration of critical supply leads to
cell returning to steady state.

71. Cellular swelling
 Cellular swelling (or cloudy swelling) may occur due to cellular hypoxia(Low
Oxygen),
 which damages the sodium-potassium membrane pump; it is reversible when
the cause is eliminated.
 Cellular swelling is the first manifestation of almost all forms of injury to
cells.
 When it affects many cells in an organ, it causes some pallor, increased
turgor, and increase in weight of the organ.
 On microscopic examination, small clear vacuoles may be seen within the
cytoplasm; these represent distended and pinched-off segments of the
endoplasmic reticulum.

72.  Blebbing
 Blunting
 distortion of microvilli
 loosening of intercellular attachments
 mitochondrial changes
 dilation of the endoplasmic reticulum

73. Fatty change
 The cell has been damaged and is unable to adequately metabolize fat.
 Small vacuoles of fat accumulate and become dispersed within cytoplasm.
 Mild fatty change may have no effect on cell function; however, more
severe fatty change can impair cellular function.
 In the liver, the enlargement of hepatocytes due to fatty change may
compress adjacent bile canaliculi, leading to cholestasis.
 fatty change is generally reversible.
 Fatty Change is also known as fatty degeneration, fatty metamorphosis, or
fatty steatosis.

74. Irreversible Cell Injury:
 “Point of no return”: cell cannot be restored → cell death
 Injurious stimulus is severe and/or persistent.

75. Necrosis

76. Necrosis:
 Necrosis (from Ancient Greek νέκρωσις, nékrōsis, "death") is a form of cell
injury which results in the premature death of cells in living tissue by
autolysis
 Autolysis is the enzymatic digestion of cells by the action of its own
enzymes, and it mostly occurs in dying or dead cells
 It is an uncontrolled type of cell death that happens before the end of the
natural life span of the cell.
 Pathologists use the word necrotic to describe a large area of tissue that has
died of necrosis.
 Another common type of cell death is called apoptosis.

77.  Necrosis is caused by factors external to the cell or tissue, such as infection,
or trauma which result in the unregulated digestion of cell components.
 Cellular death due to necrosis does not follow the apoptotic signal
transduction pathway, but rather various receptors are activated and result in
the loss of cell membrane integrity
 and an uncontrolled release of products of cell death into the extracellular
space.
 This initiates in the surrounding tissue an inflammatory response, which
attracts leukocytes and nearby phagocytes which eliminate the dead cells
by phagocytosis.
 However, microbial damaging substances released by leukocytes would create
collateral damage to surrounding tissues.
 This excess collateral damage inhibits the healing process..

78.  Thus, untreated necrosis results in a build-up of decomposing dead tissue and
cell debris at or near the site of the cell death.
 A classic example is gangrene.
 For this reason, it is often necessary to remove necrotic tissue surgically, a
procedure known as debridement
 Phagocytosis is a cellular process for ingesting and eliminating particles larger
than 0.5 μm in diameter, including microorganisms, foreign substances, and
apoptotic cells.

79. Types:
 There are six types of necrosis:
 Coagulative necrosis
 Liquefactive necrosis
 Caseous necrosis
 Fat necrosis
 Fibroid necrosis
 Gangrenous necrosis

80.  Coagulative necrosis
 is characterized by the formation of a gelatinous (gel-like) substance in dead
tissues in which the architecture of the tissue is maintained, and can be
observed by light microscopy.
 Coagulation occurs as a result of protein denaturation

81.  Liquefactive necrosis (or colliquative necrosis),
 in contrast to coagulative necrosis, is characterized by the digestion of dead
cells to form a viscous liquid mass.
 This is typical of bacterial, or sometimes fungal, infections because of their
ability to stimulate an inflammatory response.

82.  Gangrenous necrosis can be considered a type of coagulative necrosis that
resembles mummified tissue.
 Caseous necrosis can be considered a combination of coagulative and
liquefactive necrosis, typically caused by mycobacteria (e.g. tuberculosis),
fungi and some foreign substances.
 Fat necrosis is specialized necrosis of fat tissue
 Fibrinoid necrosis is a special form of necrosis usually caused by immune-
mediated vascular damage. It is marked by complexes of antigen and
antibodies, referred to as immune complexes deposited within arterial walls
together with fibrin.

83. Apoptosis

84.  Apoptosis (from Ancient Greek ἀπόπτωσις, apóptōsis, "falling off") is a form of
programmed cell death that occurs in multicellular organisms.
 Biochemical events lead to characteristic cell changes (morphology) and
death. These changes include blebbing, cell shrinkage, nuclear
fragmentation, chromatin condensation, DNA fragmentation, and mRNA
decay
 The average adult human loses between 50 and 70 billion cells each day due
to apoptosis.
 For an average human child between the ages of 8 and 14, approximately
20–30 billion cells die per day

85.  In contrast to necrosis, which is a form of traumatic cell death that results
from acute cellular injury,
 apoptosis is a highly regulated and controlled process that confers
advantages during an organism's life cycle.
 For example, the separation of fingers and toes in a developing human
embryo occurs because cells between the digits undergo apoptosis.
 Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies
that phagocytes are able to engulf and remove before the contents of the cell
can spill out onto surrounding cells and cause damage to them.

86.  Because apoptosis cannot stop once it has begun, it is a highly regulated
process.
 Apoptosis can be initiated through one of two pathways.
 In the intrinsic pathway the cell kills itself because it senses cell stress,
 in the extrinsic pathway the cell kills itself because of signals from other
cells.
 Weak external signals may also activate the intrinsic pathway of apoptosis.
 Both pathways induce cell death by activating caspases (Dismantle Cellular
Structure), which are proteases (Enzyme that break Protein), or enzymes that
degrade proteins.
 The two pathways both activate initiator caspases, which then activate
executioner caspases, which then kill the cell by degrading proteins
indiscriminately.

87. Necrosis vs Apoptosis