Altered Cellular and Tissue Biology

1
Altered Cellular and Tissue Biology

• Cellular adaptation
• Atrophy
• Hypertrophy
• Hyperplasia
• Dysplasia
• Metaplasia

2
Atrophy

• Decrease in cell size
• Causes of atrophy include
• Decrease use or load- for example cause muscle
  atrophy
• Decrease in blood supply, decrease in nervous and
  hormonal stimulation
• Decrease in nutrition

3
Atrophy

• Disuse atrophy- as in muscles in a polio patient
• Autophagic vacuoles appear in tissues affected by
  malnutrition
• Lipofuscin granules are often found in atrophy

4
Hypertrophy

• Increase in cell size
• Often leads to increase size of organ
• Examples - enlarged heart or kidney
• Enlargement is due to an increase in organelles
  not in the increase of intracellular fluid

5
organelle change in hypertrophy-

• liver cells have increase amounts of endoplasmic
  reticulum
• Hypertrophy in skeletal muscles in weight lifters
  have increase amounts of myofibrils

6
Note

• In atrophy and hypertrophy there is no increase
  in number of cells and cells are normal in
  structure
• The condition may or may not be reversible

7
Hyperplasia

• increase in the number of cells caused by
  increase in mitosis
• the two types of physiological hyperplasia are
  compensatory and hormonal

8
Compensatory hyperplasia

• is adaptive allowing regeneration to occur
• For example- liver regenerates due to hepatocyte
  growth factor
• Some cells do not regenerate, for example lens
  cells

9
Hormonal hyperplasia

• Stimulation of endometrial estrogen

10
Pathologic hyperplasia

• Endometrial hyperplasia

11
Dysplasia

• Abnormal changes in size, shape, organization of
  mature cells
• Cells still retain their tissue identity however
  (epithelial, muscle, nervous, connective)
• Often these cells can become malignant
• Cause is persistent injury and or irritation

12
Metaplasia

• Reversible replacement of one mature cell type by
  another
• Columnar epithelial being replaced by stratified
  squamous is an example (stratified squamous is
  more protective when abrasion, or irritation is
  present
• In the respiratory tract the irritant that most
  often causes this response is cigarette smoking

13
Cell injury

• Cells adapt then develop injury which is usually
  reversible
• If irritation, trauma persists than irreversible
  cell injury occurs and then cell dies

14
Necrosis

• Tissue death caused by extensive cell death in
  one location

15
Mechanisms of cell injury
16
Hypoxic injury

• Hypoxia- lack of oxygen
• Ischemia- reduced blood supply to the tissue
  causes hypoxia

17
Causes of ischemia

• arteriosclerosis
• thrombosis
• obstruction- causing anoxia (total lack of oxygen)

18
Cellular events in hypoxia

• Membranes become damaged
• cytoplasm develops vacuoles
• Mitochondria swell because of Ca ion
  accumulation
• ATP levels decrease because mitochondria are
  damaged

19
Cellular events in hypoxia, cont.

• Dilation of endoplasmic reticulum
• Anaerobic respiration- lactic acid is produced
• Lysosomes- swell and release hydrolytic enzymes
• Cell death occurs

20
Free radicals, reactive oxygen injury

• a free radical is electrically uncharged atom
  having an unpaired electron. Oxygen is converted
  to superoxide, also hydroxyl radical and hydrogen
  peroxide can cause damage

21
Vitamin E

• Acts as antioxidant by attracting and
  neutralizing free radials in cell membranes

22
Formation of free radicals

• Absorption of extreme energy ( UV and radiation)
• Endogenous reactions (redox reactions)
• Metabolism of exogenous chemicals

23
Mechanism of damage of free radicals

• Lipid peroxidation
• See figure 3-7

24
Causes of cell injury

• Toxins and chemicals
• Infection and immunological
• Physical agents and trauma
• Deficit (lack of water, oxygen, nutrients, etc.)
• memory jogger (TIPD)

25
Toxin and Chemical injury

• Exogenous (outside sources
• highly toxic substances are called poisons
• poisons can kill in very small amounts
• Heavy metals bind to DNA and proteins
• examples are lead, mercury, arsenic

26
Toxin and Chemical injury

• Chronic exposure causes damage
• air pollinates
• insecticides
• herbicides

27
organic compounds cause damage

• carbon tetrachloride
• benzenes and derivatives of benzene
• tar and nicotine

28
Example- lead poisoning

• At risk- inner city youths in areas where there
  were previous industrial activity- for example
  East St. Louis
• Systems affected- nervous system- slow
  development, hyperactivity, hematopoietic tissue(
  anemia), urinary system (kidney diseases), GI
  tract (loss of weight, abdominal cramps, GI
  distress)

29
Lead poisoning

• Detection- blood tests
• Treatment- chelating agents
• Prevention- detoxification of soil, removal of
  lead paint in homes and schools
• Mechanism of cell injury-binds to DNA and
  enzymatic proteins

30
Ethanol

• at risk- fetus, persons with addictive behavior,
  persons with deficiencies in enzymes needed to
  metabolize ethanol either acquired or genetic)
• Systems affected- nervous system, digestive
  system (liver)
• Acute alcoholism, chronic alcoholism, fetal
  alcohol syndrome

31
Fetal alcohol syndrome

• Low birth weight
• Congenital heart defects
• Microcephaly and mental retardation

32
Chronic alcoholism

• Deficiencies of alcohol dehydrogenase, and or
  acetaldehyde dehydrogenase has been implicated in
  some cases
• Linked to tolerance is MEOS or microsomal ethanol
  oxidizing system
• MEOS is dependant on cytochrome P-450

33
Chronic alcoholism, cont.

• Cirrhosis of the liver, chronic and acute
  pancreatitis is associated with chronic
  alcoholism
• Accumulation of ferritin (liver) is associated
  with over consumption of red wine
• Excess acetaldehyde is toxic and causes tissue
  damage

34
Trauma

• Unintentional and intentional injuries
• Blunt force injuries include car accidents and
  falls
• Types are contusion, abrasion, laceration,
  incised wound, gunshot wounds
• Asphyxial injuries include suffocation,
  strangulation, chemical poisons (carbon
  monoxide), drowning

35
Infectious, immunological and inflammation

• Pathogens cause damage when they invade cells
  (entry and exit damage
• Pathogens produce toxins (endotoxin produced by
  gram negative bacteria for example)
• Hypersensitivity reactions can cause tissue damage

36
Infectious, Immunological and inflammation

• Phagocytic cells cause peripheral damage
• Complement and proteases can cause damage also
• Antibodies can cause membrane damage and destroy
  cell junctions

37
Mechanisms of Cellular Injury
38
Genetic factors
39
Nutritional imbalances

• Protein deficiency
• Protein-calorie malnutrition
• Glucose deficiency
• Lipid deficiency
• Hyperlipidemia
• Vitamin deficiencies

40
Physical agents of cellular injury

• Temperature extremes
• Atmospheric pressure
• Ionizing radiation
• Illumination
• Mechanical stresses
• Noise

41
Manifestations of cellular injury

• Cellular accumulation (infiltrations)

42
Process of hydropic degeneration

• Hypoxia?ATP decreases
• Na and water move into cell
• K moves out of cells
• More water moves into cell (excess cell
  hydration)
• Extensive vacuolation occurs

43
Accumulation of organic substances

• are manifestations of cellular injury
• Accumulation of lipids, glycogen, proteins,
  pigments can occur
• The problem is sometimes uptake is greater than
  the ability to catabolize
• Or cellular anabolism exceeds the cells capacity
  to use or secret the compound

44
Dystrophic calcification is a sign of damage

• Metastatic calcification can occur in persons
  with hypercalcemia

45
Fatty change in the liver

• (accumulation of fats in the liver)
• Increased movement of free fatty acids to the
  liver
• Failure of conversion of fatty acids to
  phospholipids, or triglycerides
• Increased synthesis of triglycerides from fatty
  acids
• failure of transport(exit mechanisms) system (
  apoproteins, binding, export)

46
Urate (uric acid)

• by product of purine metabolism
• excess leads to gout (uric acid crystals in
  joints)

47
Blood chemistries can reveal cellular damage

• (Systemic manifestations include fever and
  elevated cellular enzymes found in plasma)

48
Examples of enzymes found when there is cell
damage

• LDH lactate dehydrogenase
• Creatine kinase's CK (different isoenzyme for
  each muscle type)
• AST/SGOT aspartate aminotransferase
• ALT/SGOT Alanine aminotransferase
• Alkaline phosphatase
• Amylase
• Aldolase

49
Necrosis

• Cellular and tissue death
• Autolysis- lysosomes rupture
• Pyknosis- nucleus shrinks and chromatin clumps
• Karyolysis- nuclear dissolves, plasma membrane
  ruptures

50
major types of necrosis

• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fat necrosis
• Gangrenous necrosis

51
Coagulative necrosis

• Protein denaturation causes albumin to become
  firm
• Occurs in kidneys, heart, adrenal glands most
  often
• Causes- hypoxia, chemical ingestion such as
  mercuric chloride

52
Liquefactive necrosis

• Hydrolases cause tissue to become soft, often
  cyst form
• Occurs in brain
• Causes- bacterial infection such as
  staphylococci, streptococci and E. coli

53
Caseous necrosis

• Hydrolases do not completely digest tissue,
  pockets form looks like clumped cheese (caseous)
• Occurs in lung
• Cause- often infection with Mycobacterium
  tuberculosis

54
Fat necrosis

• Lipases break down triglycerides and release free
  fatty acids which form soaps when they combine
  with cations such as Ca, Na
• Occurs in breast and pancreas, other abdominal
  organs

55
Gangrenous necrosis

• Severe hypoxia
• Occurs in lower leg
• precipitated by arteriosclerosis, and in diabetes
  
• Foul smell, black color is caused by the gangrene
  organisms

56
Gangrenous necrosis

• Clostridium which are anaerobic and produce
  hydrolytic enzymes and toxins that destroy
  connective tissue and cells

57
Dry gangrene

• Is coagulative necrosis
• Skin black and wrinkled

58
Wet gangrene

• Neutrophils invade and cause liquefactive
  necrosis
• Occurs internally

59
Gas gangrene

• Bubbles form from infection of Clostridium
  organism
• Death can occur

60
Apoptosis

• 'Programmed' cell death
• Scattered cells are affected
• Nucleus and cytoplasm shrinks and then cell
  divides into membrane bound vesicles
• Occurs naturally in the tail of an embryo as it
  disappears
• Neurons in a neural pathway sometimes do this

61
Aging of cells

• Limitations on mitosis
• Accumulations of toxins and waste
• Slowing of repair mechanism
• Telomerase and telomers on chromosomes