Unit 1 Chapter 2 Altered Cellular and Tissue Biology (Weber State)

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1

Pluripotent

A term describing a cell that has the potential to specialize into many different types of cell
Cells can adapt to a new environment
Cells can escape
Cells can protect themselves

2

Totipotent

Describing a cell that can give rise to all parts of the embryo and adult, as well as extra embryonic membranes in species that have them.
A fertilized egg
Muscle vs Epithelial
Nerves
Connective tissue

3

Unipotent

Ability to give rise to only one other type of cell.

4

Terminally Differentiated Cell

A cell has become all it can be and cannot change anymore

5

Can cellular adaptation be a pathological response, functional response or both?

Cellular adaptation can be both.
A cell has 2 choices of change
1. it changes in TROPHY (size)
2. it changes in PLASTICITY (cell shape) [plasty = plasia]

6

Hypertrophy

Increase in SIZE and MASS of cells but not the number of cells
Common tissues - cardiac muscle, skeletal muscle, kidneys
EG: A body builder

7

Hyperplasia

The increased production and growth of normal cells in a tissue or organ, resulting in an abnormal increase in size of the tissue or organ
Cause - an increased rate of cell division

8

Is it possible to experience both hypertrophy and hyperplasia?

Yes
the uterine muscle enlargement during pregnancy (hypertrophy) and hyperplasia of the uterine endometrium during pregnancy (and also during every menstrual cycle)

9

Metaplasia

The reversible replacement of one adult cell type with another adult cell type
Allows for the replacement with cells that are better able to tolerate the environmental stresses
EG replacement of ciliated columnar epithelial with stratified squamous epithelium in the respiratory tract of a smoker.
EG A callous due to ill fitted shoes

10

Dysplasia

AKA - atypical hyperplasia
A deranged cell growth that results in cells that vary in size, shape and appearance at maturity.
The growth of abnormal cells; a precancerous condition that may or may not develop into cancer
-characterized by atypical changes in the size, shape, and appearance and the cells (atypical hyperplasia)
-caused by persistent injury or irritation progressing towards neoplasia (abnormal proliferation of cells)
EG cervical dysplasia from human papilloma virus (HPV) or bronchial dysplasia from smoking- both are precancerous - colon pullups

11

Cellular Injury

[1] quiescence (ignore), [2] adapt, [3] divide and differentiate, and [4] die (necrosis/apoptosis).
Cells become injured in many different ways
-membrane permeability changes
-Interruption of oxidative metabolism (ATP production)
-diminished protein synthesis
-leakage of digestive enzymes

12

If two people are exposed to the same stimulus, will they incur the same degree of cellular damage?

No because the pathos of individuals is different.

13

Free Radicals

Chemicals that harm the bodies tissues by starting destructive chain reactions in the molecules of the bodies cells, such reactions are believed to trigger or worsen some diseases
-free radicals is an atom or molecule that has an unpaired electron. This radical makes the atom very unstable and active.
-to gain stability, the radical gives up or steals an electron.
EG
Superoxide ion (O2-) [most common]
Hydroxl (OH)
Peroxinitrite ion (ONOO-)

14

Free Radical Formation

Normal metabolism
Ionizing radiation (exposure to radioactivity)
Drug metabolism

15

Mechanisms of injury

-Lipid peroxidation - the destruction of unsaturated fatty acids by free radicals
-Protein destruction - Fragmentation of polypeptide chains and denaturation (alteration of amino acid structure)
-DNA Alteration - the breakage of DNA strands or repair mechanisms

16

Antioxidants

Molecules that neutralize free radicals, thereby preventing them from causing damage to cells
-Block the synthesis of inactive free radicals
-Vitamin E, Vitamin C, albumin, ceruloplasmin, and transferrin, Licopenes in diet.

17

Enzymes

Molecules, usually proteins or nucleic acids, that act as catalysts in biochemical reactions. Used in Free Radical Inactivation
EG
Superoxide dismutase (SOD) - usually inactivated by the enzyme SOD converts Superoxide to H2O2 [this can be a problem because of hydrogen peroxide]
Catalase
-SOD makes H2O2
-Catalase then converts 2H2O2 to O2 + 2H2O
-Glutathione peroxidase (GPx)

18

Lead Poisoning

A heavy metal; poorly absorbed by the body and slowly excreted; it replaces calcium in the bones; acts like calcium, iron and zinc; interferes with hemoglobin synthesis; increases the permeability of CNS membranes; most common poisoning amongst children under 6 years old; major sources(inhalation exposure or ingestion of particles, lead based paint, lead contaminated dust, lead contaminated bare soil, lead pipes)
--Likely acts on the CNS by interferring with neurotransmitters

19

Toxic Chemical Agents

Cellular injury is caused by direct contact with chemical agents, with the molecular components of the cell, formation of free radicals or lipid peroxidation.
EG carbon monoxide (CO) has a high affinity for Hgb
CO is colorless, odorless and causes nausea, vomiting, headache, weakness and tinnitus (ringing in the ears)

20

Ethanol (Alcohol)

A specific alcohol compound formed from the fermentation of dietary carbohydrates and used in a variety of alcoholic beverages
-In the liver, ethanol is converted to acetaldehyde which is toxic to the liver (free radical damage)
This toxicity leads to deposition of fat, hepatomegaly [enlarged liver], interruption of protein transport, decreased fatty acid oxidation, increased membrane rigidity [due to the inability to make cholesterol] and liver cell necrosis
-- In the CNS alcohol is a depressant that initially affects subcortical structures.
--Motor and intellectual activities become disoriented
--At high alcohol levels medullary centers become depressed.
--Fetal alcohol can lead to growth retardation, cognitive impairment, facial anomalies & ocular disturbances.

21

Blunt Force Trauma

Injuries are mechanical injuries resulting in tearing, shearing, or crushing of tissues.
The most common are caused by falls and auto accidents

22

Contusion

An injury that doesn't break the skin but results in some discoloration - a bruise

23

Hematoma

The collection of blood under the skin as the result of blood escaping into the tissue from damaged blood vessels. bruise
EG Subdural Hematoma
Epidural Hematoma

24

Abrasion

Removal of the superficial layers of the skin caused by contact between the skin and the injuring object (a rock or the cement after a bike fall)
EG a skinned knee - the top layer of skin is removed

25

Laceration

A rip or tear when the elasticity of the skin or tissue will not hold up to the pressure applied by injuring object.
EG A paper cut - longer than deep or wide

26

Incised Wound

A cut that is longer than it is deep

27

Stab Wound

Penetrating, sharp, cutting injury that is deeper than wide or long

28

Gunshot Wound (GSW)

Penetrating bullet remains in the body
or
Perforating bullet exits the body

29

Asphyxia

A condition in which insufficient or no oxygen and carbon dioxide are exchanged on a ventilatory basis
-A means of Hypoxia
-Suffocation
-Strangulation
-Chemical (CO2 fills lungs and prevents O2 from moving through the blood stream
-Drowning - H2O doesn't allow O2 to diffuse to the air

30

Nutritional Imbalances

For adequate cellular function and integrity, adequate amounts of proteins, lipids and carbohydrates are required.
-low levels of plasma proteins like albumin, encourages movement of water into the tissues thereby causing edema
-Hyperglycemia (high blood sugar) or Hypoglycemia (low blood sugar)
-Vitamin deficiencies
Vitamins B, E, D, K, A and folic acid are the most deficient.

31

Physical Agents

-Extreme Temperatures (hypothermia, hyperthermia)
-Atmospheric Pressure
-Water Pressure
-Radiation Illumination
-Mechanical Factors
-Noise
-Prolonged Vibration
-Physical injury is often environmental.

32

Hypothermia

Below normal body temperature
vasoconstriction
ice crystal formation causing cellular swelling

33

Hyperthermia

Exceptionally high fever; when the body temperature grows too hot
Loss of fluids and plasma proteins

34

Blast Injuries

Caused by atmospheric pressure
Compressed waves of air
Thorax collapses; organs hemorrhage and rupture

35

Water Pressure

-Causes nitrogen to dissolve in the blood
-When pressure is removed, nitrogen is released and forms gas emboli
-Commonly known as "The Benz" when surfacing from under water at rapid speeds.

36

Ionizing Radiation

-Any form of radiation that is capable of removing orbital electrons from atoms
-Emitted by x-rays, gamma rays, and the process of radioactive decay.

37

Noise

Acute loud noise or the cumulative effect of loud noise over a period of time or by the cumulative effects of various intensities, frequencies and durations of noise.

38

Cellular Accumulations

Unwanted materials build - can be intracellular(more severe) or interstitial (less severe)
-Can be created by disease or can themselves cause disease or dysfunction
-Classic example -water -ie as an exudate in inflammation
-Imbalance in water forces in water can create local tissue fluid - transduate not due to inflammation
-Water
-Lipids
-Carbohydrates
-Protein
-Pigments
-Calcium
-Urate (Uric Acid)

39

Reversibility of Cellular Injury

-Necrosis is local cell death and is irreversible
-Necrosis involves the process of self/auto digestion and lysis

40

5 types of Necrosis

1. Coagulative
2. Liquefactive
3. Caseous
4. Fat Necrosis
5. Gangrenous

41

Coagulative Necrosis

-Common in kidneys, heart and adrenal glands
-Coagulation is caused by protein denaturation
--Albumin is changed from a gelatinous, transparent state to a firm, opaque state.
--Compare what happens to an egg when cooked.
-It is suspected that high levels of intracellular calcium play a role in coagulative necrosis.

42

Liquefactive Necrosis

Fungal/Bacterial infection leads to mushy liquid; Brain tissue normally dies by this as brain enzymes are released from dead cells causing tissue breakdown and liquefaction
Can occur in certain infections: - Hydrolytic enzymes are released from neutrophils to fight an invading pathogen. Basil ganglia become liquified.

43

Caseous Necrosis

Conversion of necrotic cells to an amorphous mass grossly resembling cottage cheese.
Histologically, appears as amorphous granular debris composed of fragmented coagulated cells. Most often seen in Tuberculosis

44

Fat Necrosis

Soap Former
Occurs in breast, pancreas & other abdominal structures. Cellular dissolution caused by lipases (enzymes), which are found at very high levels and appears opaque and chalky white
Lipases break down triglycerides, releasing free fatty acids
The fatty acids combine with Ca++, Mg and Na+ to form soaps.

45

Gangrenous Necrosis

Strictly speaking this is not a different type of necrosis; it is used to describe variants of coagulation necrosis. It is usually localized to the soft tissue of the lower limbs that have been compromised by protracted hypoxia and ischemia (inadequate blood supply).
If there is great vascular occlusion, leukocytes cannot migrate to the areas of cell death, so the dead tissue is not digested and removed and becomes desiccated and mummified (dry gangrene).
If the overlying skin is devitalized, bacteria and/or leukocytes will enter and extensive liquefaction may ensure (wet gangrene).
-Infection caused by many species of Clostridium bacteria (anerobic)
-The enzymes and toxins released by these bacteria cause bubbles of gas to form.

46

Apoptosis

Programmed cell death involving a cascade of specific cellular events leading to death and destruction of the cell
-Cell death involved in normal & pathologic conditions
-Depends on cellular signals
-These signals cause protein cleavage (proteases) within the cell, causing cell death
--Different from necrosis because it affects scattered, individual cells and results in cell shrinkage, not lysis and swelling.

47

Aging and Cellular Death Theories

Aging is caused by the accumulation of injurious events (environment)
Aging is the result of genetically-controlled developmental programming.

48

Aging and Cellular Death Mechanisms

Genetic, environmental and behavioral
Changes in regulatory mechanisms
Degenerative alterations

49

Somatic Death

Death of an entire organism.
Cessation of respiration and circulation
Skin surface becomes pale and yellowish
Body temperature falls gradually until after 24 hours body temperature equals that of the environment.

50

Algor Mortis

Decreased body temperature resulting in a lack of skin elasticity
Skin becomes pale

51

Livor Mortis

A coloration of the skin of the lower parts of a corpse caused by the settling of the red blood cells as the blood ceases to circulate (peripheral tissues)

52

Rigor Mortis

A condition associated with death results from the depletion of ATP and the progressive accumulation of cross bridges formed during muscle contraction
Within 12-14 hours, rigor mortis usually affects the whole body.
After this time, rigor mortis diminishes gradually and the body becomes flaccid because of the release of enzymes and lytic dissolution.

53

Postmortem autolysis

Swelling or bloating of the body and liquefactive changes occur sometimes opening body cavities
Breaks down muscle and other tissues

54

Homeostasis

--The concept of a dynamic steady state and a turnover of bodily substances that maintains physiologic parameters within narrow limits.
--Stressors cause reactions that alter this dynamic state.
--Deviations from normal values, which are normally maintained by homeostasis cause disease.

55

Hypoxia

--Deprives the cell of O2 and interrupts oxidative metabolism and the generation of ATP.
--As ATP declines there is
**1. A decreased sodium pump activity which leads to a decreased intracellular potasium level and an increase in sodium and H2O in the cell which leads to dilation of the endoplasmic reticulum, increased membrane permeability and decreased mitochondrial function and eventually cell lysis
**2. Increased glycolysis
Because of the lack of O2 there is a continued loss of essential enzymes, proteins and ribonucleic acid through the permeable membrane of the cell. This leads to a decreas in pH, which leads to protein denaturation, nuclear chromatin clumping and lysosomal swelling with enzyme release and cellular digestion.

56

What can hypoxia result in?

--inadequate oxygen in the air
--respiratory disease
--decreased blood flow due to circulatory disease
--anemia
--inability of the cells to use oxygen.

57

Cellular Atrophy

--Decreases cell substance and results in cell shrinkage.
--Causes of atrophy
**1. disuse (seen in muscles that are not used)
**2. denervation (seen in paralyzed limbs)
**3. lack of endocrine stimulation (seen in changes that may occur in reproductive structures during menopause)
**4. decreased nutrition (seen as generalized wasting of tissues from rapid weight loss)
**5. ischemia (seen in reduced blood flow and delivery of oxygen and nutrients to tissues)

58

Reperfusion (reoxygenation) injury

Reperfusion is a cause of injury in tissue transplantations and in myocardial, hepatic, intestinal, cerebral, renal and other ischemic syndromes.
During reperfusion with oxygen, xanthine oxidase is produced which makes massive amounts of superoxide hydrogen peroxide and the free radical nitric oxide.

59

Infectious Agents

--Produce injury by invading and destroying cells
--Producing toxins
--Inducing hypersensitivity reactions

60

Immunologic and Inflammatory Injury

--causes cellular injury
--Cellular membranes are in direct contact with cellular and chemical components of the immune and inflammatory responses.
--Mediators include lymphocytes and macrophages, chemicals such as histamine, antibodies and lymphokines, complement and proteases

61

Mechanical Injury

--Caused by physical impact or irritation
EG a head injury when a worker is struck by a falling object.
--Most mechanical stresses are stubtle and can cause accumulative injuries and disorders over time.

62

Theories of Aging

--Aging is caused by accumulations of injurious events which are sometimes called damage-accumulation theories.
--Aging is a result of a genetically controlled developmental program
--Some believe that each cell may have finite life span during which it can replicate

63

Mechanisms of Aging

1) Genetic, environmental, and behavioral factors produce cellular aging change
2) Changes in regulatory mechanisms especially in the cells of the endocrine, immune and CNS are responsible for aging.
3) Degenerative extracellular and vascular alterations cause aging.

64

Alterations of cellular control mechanisms

include
--increased hormonal degradations,
--decreased hormonal synthesis and secretion
--decreased receptors for hormones and neuromodulators.
This suggests that a genetic program for aging is encoded in the brain and relayed through hormonal and neural agents because of shared, common receptors within these systems.

65

Collagen Cross-Linking

A degenerative extracellular change which makes collagen more rigid and results in decreased cell permeability to nutrients.

66

Frailty

A wasting syndrome of aging.
Invokes decreased protein synthesis, muscular mass and strength decline and neuroendocrine and immune dysfunction.