1. Chapter 4. Tissue Response to Injury: Inflammation, Swelling, and Edema

2. Inflammation The local response of the body to an irritant Purpose
Defend the body against alien substances
Dispose of dead and dying tissue so repair can take place

3. Cardinal Signs of Inflammation
Rubor: redness
Calor: heat
Edema: swelling
Dolor: pain
Funca laesa: functional loss
Each of these signs will occur to some degree when tissue is injured and the body responds with the inflammatory process.

4. Common Misconceptions of Inflammation
Do you need to limit or eliminate inflammation?
No. Inflammation is necessary.
Repair will not occur without inflammation.
You cannot eliminate inflammation.
You can only minimize the signs of inflammation.

5. Common Misconceptions of Inflammation (cont.)
Swelling, edema, and inflammation are synonymous
Swelling and edema occur during inflammation.
Edema and swelling are not the same.
All edema causes swelling, but not all swelling is caused by edema.

6. Phases of Inflammation
Inflammation consists of sequential and overlapping events.
Primary injury
Ultrastructural changes
Chemical mediation
Hemodynamic changes
Metabolic changes
Permeability changes
Leukocyte migration
Phagocytosis

7. Primary Injury
Any occurrence that impairs tissue structure or function
Most sports injuries are caused by
Macrotrauma (impact or contact)
Microtrauma (overuse, cyclic loading, or friction)
There are many other types of injury, each of which results in the same basic inflammatory reaction.
Other examples?

8. Primary Injury (cont.) Other causes of injury include
Physical agents (trauma, burns, radiation)
Metabolic processes (hypoxia)
Biological agents (bacteria, viral, parasitic, infection)
Chemical agents (acids, gasses, organic solvents, endogenous chemicals)
Endogenous chemicals
Normal secretions
In abnormal locations (gout)
In increased quantity in a normal location (stomach ulcers)
The magnitude after each phase varies according to the causative agent

9. Ultrastructural Changes
Cellular membrane is disrupted and eventually breaks down.
Contents spill out into the extracellular spaces, thereby killing the damaged cell.
Two causes
Direct
Trauma (primary injury)
Indirect
Hypoxia (oxygen deficiency)
Enzymes (chemicals)
In cells adjacent to the primary injury

10. Ultrastructural Changes (cont.)
Occur as a direct result of trauma (primary injury) and indirectly as a result of hypoxia (secondary injury)
We will discuss this in more detail later in this chapter (see “Orthopedic Injury Model”).

11. Ultrastructural Changes (cont.)
Lysosome
Supplies chemicals that digest foreign material within the cell and gets rid of it.
If the membrane of the lysosome ruptures, its contents will attack and digest other material.

12. Chemical Mediation Histamine, bradykinin, and other chemicals
Modify and regulate the rest of the inflammatory response to:
Neutralize the cause of the injury
Remove cellular debris so repair can take place

13. Hemodynamic Changes
Arteries dilate, increasing blood flow to the injured area.
However, blood vessels that were previously inactive open, so blood flow through individual vessels decreases.
Slowing of blood flow is necessary, so WBCs can move to the margins.

14. Hemodynamic Changes (cont.)
Leukocytes
Marginate
Tumble along the vessel wall
Adhere to the vessel wall near an opening

15. Hemodynamic Changes (cont).
Leukocytes begin passing though the vessel wall.

16. Metabolic Changes ↓ Energy
↓ Oxygen, causes cell to switch to anaerobic metabolism
Membrane functions slow down.
Sodium pump maintains the concentration of intracellular sodium at a very low level.

17. Metabolic Changes (cont.)
↑ Sodium concentration in cell and organelles
↑ Water in cell
Cells swell and burst
↑ Intracellular acidosis (lactic acid)
Membrane attacked
Lysosome digests cell.

18. Permeability Changes
Histamine and bradykinin increase the permeability of small blood vessels.
The endothelial cells contract, pulling away from each other.
Gaps are left, through which the WBCs can move out of the vessel and to the injury site.

19. Leukocyte Migration
WBCs adhere to the endothelium (vessel wall) and/or to other white blood cells.
(Reprinted with permission from McLeod I. Inflammation. Kalamazoo, MI: Upjohn, 1973.)

20. Leukocyte Migration (cont.)
WBCs move out of the vessel by squeezing through the endothelial gaps.
Neutrophils first, then larger macrophages
(Reprinted with permission from McLeod I. Inflammation. Kalamazoo, MI: Upjohn, 1973.)

21. Leukocyte Migration (cont.)
Neutrophils
Macrophages

22. Leukocyte Migration (cont.)
Neutrophils
Travel fast and arrive at the injury site first
Provide the first line of defense
When they die, they release chemical mediators that attract macrophages.
Death of neutrophils results in a large concentration of chemical mediators released by the cells.

23. Leukocyte Migration (cont.)
Macrophages
Live for months
Long-lasting second line of defense
Release potent enzymes that may destroy connective tissue, thus adding to the injury
Release chemical mediators that may prolong inflammation
Release factors that aid in healing
Secrete proteins that are important in defense mechanisms

24. Phagocytosis
Digestion of cellular debris and other foreign material into pieces small enough to be removed from the injury site

25. Chronic Inflammation
Results from microtrauma but does not necessarily involve an inflammatory reaction
Example: clinically diagnosed Achilles tendinitis and patellar tendinitis in which there is no evidence of an inflammatory reaction
Structural disruption and microvascular damage may occur (causing pain and other symptoms) before the classic inflammatory process is set into action.

26. Orthopedic Injury Model
What happens when a muscle is pulled or an ankle is sprained?
Just put an ice bag on it, right?
WRONG.
This is overly simplistic.
Techniques must be based on sound theory if they are to be developed and improved.
It is essential to understand the body’s response to injury.

27. Orthopedic Injury Model (cont.)
Example: typical tissue undergoing a typical muscular injury
Used to illustrate inflammation in relation to orthopedic injuries

28. Orthopedic Injury Model (cont.)
Normal tissue
Cells
Two blood vessels (A, B)
Two nerves (1, 2)

29. Orthopedic Injury Model (cont.)
Contusion with injury to:
Three cells
Nerve 1
Blood vessel B

30. Orthopedic Injury Model (cont.)
Immediate ultrastructural change
Local nerves and blood vessels may be disrupted or broken.
This damage is called primary traumatic damage.

31. Orthopedic Injury Model (cont.)
Hemorrhage
Few minutes only (usually)
Clot forms, stopping hemorrhage.
Pain, from damaged nerve
Hematoma forms.

32. Orthopedic Injury Model (cont.)
Pain, from damaged nerve
Muscle spasm and more pain
Inhibition of muscular strength, range of motion, etc.
Body attempts to protect itself by splinting the area, thus preventing aggravation of injury.

33. Orthopedic Injury Model (cont.)
The damaged cells release chemical mediators as a signal to the body that an injury has taken place.
Extravascular hemorrhage occurs from broken blood vessels.
Swelling occurs.
Injury site

34. Orthopedic Injury Model (cont.)
Fibrin forms into strands, creating a network somewhat like a fishnet.
This net captures circulating platelets.
A plug forms to seal the damaged vessel.

35. Orthopedic Injury Model (cont.)
Chemical mediators released from dying cells cause
Hemodynamic changes
Permeability changes
Leukocyte (white cell) migration

36. Orthopedic Injury Model (cont.)
Secondary enzymatic injury begins.

37. Orthopedic Injury Model (cont.)
Hemodynamic changes
Blood flow slows down OR
Blood flow ceases
Tissue oxygen decreases
Hypoxia
Metabolic changes
Secondary hypoxic injury soon seen
No flow

38. Orthopedic Injury Model (cont.)
Phagocytosis
Free protein
Causes edema

39. Orthopedic Injury Model (cont.)
Secondary hypoxic injury begins.
Secondary enzymatic injury continues.

40. Orthopedic Injury Model (cont.)
Phagocytosis and secondary injury continue.

41. Orthopedic Injury Model (cont.)
Pressure on undamaged nearby pain fibers cause additional
Pain
Muscle spasm and inhibition

42. Orthopedic Injury Model (cont.)
Total injury:
Primary injury (yellow)
Secondary injury

43. Secondary Injury Model in Review

44. Orthopedic Injury Model (cont.)
The inflammatory response is not all positive.
Example
Slowed blood flow in the vessels on the periphery of an injury and decreased blood flow from the damaged vasculature result in less oxygen to the cells.
If prolonged, secondary hypoxic injury occurs.
The total amount of damaged tissue is increased, and more debris is added to the hematoma.

45. Secondary Injury Model
Body’s response to tissue damaged by trauma (primary injury) leads to further tissue damage, known as secondary injury.
Two separate mechanisms result in secondary injury:
Enzymatic
Hypoxia

46. Decreased Metabolism Theory
In normal tissue O2
needed O2
available

47. Decreased Metabolism Theory (cont.)
After injury O2
needed
available

48. Decreased Metabolism Theory (cont.)

49. Decreased Metabolism Theory (cont.)
After injury and cryotherapy O2
needed O2
available

50. Secondary Injury Model in Review

51. Swelling, Edema, and Vessel Fluid Pressures

52. What Is Edema? Accumulation of fluid in the tissue What causes it?
Must first understand normal fluid dynamics

53. Fluid Filtration in Normal Tissue
Fluid out
Fluid in

54. Fluid Filtration in Normal Tissue (cont.)
All fluid leaving the capillary is returned
Two-thirds via capillary
One-third via lymphatic system

55. Fluid Filtration in Normal Tissue (cont.)
Occurs constantly between capillary and tissue
Sum of multiple forces
In capillary and tissue
Oncotic (osmotic) pulls
Hydrostatic pushes O H

56. Hydrostatic Pressure Pressure exerted by a column of water
The higher the column of water, the greater the pressure.
Example: swimming
The deeper you go, the higher the column of water above you and the greater the pressure.
The depth of the water, not the amount of water, is important.
Hydrostatic pressure is exerted by the water portion of the blood.

57. Hydrostatic Pressure (cont.)
Hydrostatic pressure pushes water.
Capillary hydrostatic pressure pushes fluid out of the capillary.
Tissue hydrostatic pressure pushes fluid into the capillary.
capillary
CHP
tissue
THP

58. Oncotic Pressure capillary tissue COP TOP
Also called colloid osmotic pressure
Results from the attraction of fluid by free protein
Tissue oncotic pressure pulls fluid out of the capillary.
Capillary oncotic fluid pulls fluid into the capillary.
tissue
capillary
COP
TOP

59. Fluid Filtration in Normal Tissues, Revisited
Sum of all forces

60. Capillary Filtration Pressure Components
CFP = (CHP + TOP) − (THP + COP + EFP)
CFP: Capillary filtration pressure
CHP: Capillary hydrostatic pressure
TOP: Tissue oncotic pressure
COP: Capillary oncotic pressure
THP: Tissue hydrostatic pressure
EFP: External force pressures

61. Normal Capillary Filtration Pressure Forces

62. Fluid Filtration in Normal Tissue, Revisited

63. What Causes Edema?
Imbalance of fluid filtration caused by an injury

64. Capillary Filtration Pressure Changes after Injury
Hematoma (tissue debris and hemorrhage) dumps large amounts of free protein into tissue spaces.
Increased tissue oncotic pressure

65. Fluid Filtration in Injured Tissue
Injury results in a great increase in the tissue oncotic pressure.
TOP

66. Fluid Filtration in Injured Tissue (cont.)
Fluid out
Fluid in
>

67. Fluid Filtration in Injured Tissue (cont.)
Fluid accumulates in tissue.

68. Fluid Filtration in Injured Tissue (cont.)
More fluid accumulates in tissue.

69. Fluid Filtration in Injured Tissue (cont.)
Even more fluid accumulates in tissue.

70. What Is Swelling? Hemorrhaging and edema
Can do nothing about hemorrhaging
Can minimize edema

71. What Causes Swelling?
Capillary
Tissue spaces
Lymphatic

72. How Do You Prevent Swelling?
Capillary
Tissue spaces
Lymphatic

73. How Do You Prevent Swelling? (cont.)
Capillary
Tissue spaces
Lymphatic

74. How Do You Prevent Swelling? (cont.)
Capillary
Tissue spaces
Lymphatic

75. How Does Cold Decrease Swelling?
As cold decreases secondary hypoxic injury, the amount of free protein in tissues decreases.
This causes less tissue oncotic pressure (the major factor for edema).
Cold can prevent edema from occurring only if applied soon after injury.
Once edema develops, cold application cannot decrease that edema.

76. Decreased Metabolism Theory, Revisited
Secondary hypoxic injury
Normal tissue
Injured tissue
Injured
and with cryotherapy
O2 needed
O2 available

77. Time Course of Swelling
Swelling immediately after injury is the result of direct hemorrhaging.
Edema begins minutes to hours after injury and continues to develop over many hours.
Accounts for the delayed nature of most swelling.

78. Secondary Injury and Edema
Secondary injury results in increased edema, and increased edema can contribute to increased secondary injury.
Two mechanisms
As edema develops, the distance between blood vessel and tissue cells increases.
More difficult for oxygen and other substances to diffuse from the circulatory system to the tissue
Edema can compress the blood vessel, thus decreasing circulation to the area.

79. Capillary Filtration Pressure Changes after Injury, Revisited
If swelling is the result of edema, why does the area turn black and blue?
Isn't this caused by oxidized blood?
Some is, but most discoloration in the muscle is caused by oxidized myoglobin from the damaged musculature.

80. Common Misconceptions Concerning Ice and Inflammation
Many think the purpose of ice is to decrease inflammation.
However, inflammation is necessary to prepare for healing.
Healing cannot take place until much of the cellular debris is removed from the area.
So decreasing inflammation is not helpful.

81. Common Misconceptions Concerning Ice and Inflammation (cont.)
Misconception results from confusing inflammation with swelling.
The more the swelling is contained, the quicker the injury can heal.

82. Common Misconceptions Concerning Ice and Inflammation (cont.)
Another misconception concerning ice is that it should be used until the swelling is gone.
Ice is effective for preventing swelling but not for removing swelling.
Swelling reduction occurs as free protein is removed from the area.

83. Summary Inflammation is the body’s response to any injury.
Protects the body against invasion by foreign bodies and prepares the injured tissue for repair.
After understanding inflammation, hemorrhaging, and edema, you will be qualified to educate your athletes and coaching staff, who commonly apply ice to decrease inflammation after an injury.
You can explain that swelling is one of the signs of inflammation but is not the process itself; they are separate but related processes.