WOUND HEALING- Complications, Factors & Strength
Wound healing is affected by:
| A |
Age |
|
| B |
Nutrition |
|
| C |
Dryness or wetness of wound |
|
| D |
a and b |
Wound healing is affected by:
| A |
Age |
|
| B |
Nutrition |
|
| C |
Dryness or wetness of wound |
|
| D |
a and b |
Ans. is ‘ a ‘ , ‘ b ‘
|
Factors that adversely affect wound healing |
|
• Local |
|
• Abnormal blood supply (ischemia due to arterial disease or impaired venous drainage, e.g. |
|
arteriosclerosis, varicose veins) |
|
• Infection |
|
• Presence of foreign material, necrotic tissue or excessive blood (hematoma) |
|
• Movement in injured area |
|
• Tension in injured area |
|
• Irradiation (decreases the viability of cells) |
|
• Denervation |
|
• Systemic |
|
• Advanced age |
|
• Failure of collagen synthesis d/t |
|
– vitamin C deficiency |
|
– protein deficiency |
|
– zinc deficiency |
|
– Ehlers-Danlos syndrome (disorder characterized by defective collagen formation, |
|
hyperextensible joints, fragile tissues and impaired wound healing) |
|
• Diabetes mellitus |
|
• Corticosteroid excess (administration of exogenous corticosteroids or Cushing’s syndrome) |
|
• Malnutrition |
|
• Anemia |
|
• Obesity |
|
• Drugs (steroids, cytotoxic medication, intensive antibiotic therapy) |
|
• Genetic disorders (osteogenesis imperfecta, Ehler-Danlos syndrome, Marfan syndrome) |
|
• Systemic infection |
|
• Malignant disease |
|
• Temperature |
|
• Trauma, hypovolemia and hypoxia |
|
• Uremia |
|
• Bleeding disorder |
The Vitamin which has inhibitory effect on wound healing is –
| A |
Vitamin -A |
|
| B |
Vitamin – E |
|
| C |
Vitamin -C |
|
| D |
Vitamin B-complex |
The Vitamin which has inhibitory effect on wound healing is –
| A |
Vitamin -A |
|
| B |
Vitamin – E |
|
| C |
Vitamin -C |
|
| D |
Vitamin B-complex |
Ans. is ‘b’ i.e., Vitamin-E.
Fibroblasts in healing wound are derived from –
| A |
Local mesenchyme |
|
| B |
Epithelium |
|
| C |
Endothelium |
|
| D |
Vascular fibrosis |
Fibroblasts in healing wound are derived from –
| A |
Local mesenchyme |
|
| B |
Epithelium |
|
| C |
Endothelium |
|
| D |
Vascular fibrosis |
Ans. is ‘a’ i.e. Local mesenchyme
Fibroblasts are specialized cells that differentiate from resting mesenchyme cells in connective tissue. They do not arrive in the wound cleft by diapedesis from circulating cells.
A patient of total parenteral nutrition develops delayed wound healing, loss of taste, deficient immunity and diarrhea. Most probably it could be due to deficiency of: September 2008
| A |
Selenium |
|
| B |
Copper |
|
| C |
Zinc |
|
| D |
Iron |
A patient of total parenteral nutrition develops delayed wound healing, loss of taste, deficient immunity and diarrhea. Most probably it could be due to deficiency of: September 2008
| A |
Selenium |
|
| B |
Copper |
|
| C |
Zinc |
|
| D |
Iron |
Ans. C: Zinc
Symptoms of Zinc Deficiency
- Poor Immune system
- Weight loss
- Intercurrent infections
- Hypogonadism in males
- Lack of sexual development in females
- Growth retardation
- Dwarfism
- Delayed puberty in adolescents
- Rough skin
- Poor appetite
- Mental lethargy
- Delayed wound healing
- Short stature
- Diarrhea
Congenital abnormalities causing zinc deficiency may lead to a disease called acrodermatitis enteropathica.
Most important vitamin, which promotes wound healing ?
| A |
Vitamin C |
|
| B |
Vitamin D |
|
| C |
Vitamin A |
|
| D |
Niacin |
Most important vitamin, which promotes wound healing ?
| A |
Vitamin C |
|
| B |
Vitamin D |
|
| C |
Vitamin A |
|
| D |
Niacin |
- Vitamin C is required for collagen synthesis.
- Due to its important role in collagen synthesis, vitamin C is required for adequate wound healing.
False about wound healing ‑
| A |
Inhibited by infection |
|
| B |
Inhibited by DM |
|
| C |
Inhibited by hematoma |
|
| D |
Inhibited by foreign body |
False about wound healing ‑
| A |
Inhibited by infection |
|
| B |
Inhibited by DM |
|
| C |
Inhibited by hematoma |
|
| D |
Inhibited by foreign body |
Ans. is ‘c’ i.e., Inhibited by hematoma
Factors causing impairment of wound healing
A. Systemic factors
- Poor nutrition (protein deficiency, vitamin C deficiency).
- Metabolic abnormalities (Diabetes mellitus).
- Poor circulatory status (Inadequate blood supply).
- Hormones, e.g. glucocorticoids.
B. Local factors
- Infection is the single most important factor.
- Mechanical factors, e.g. early mobilization.
- Foreign bodies (unnecessary sutures, fragments of steel or glass).
- Wound in poorly vacularized area, e.g. foot.
WOUND HEALING- Complications, Factors & Strength
WOUND HEALING- Complication, Factors & Strength
Complications of Wound Healing-
- Infections
- Epidermal cyst
- Deficient scar formation
- Incisional hernia
- Hypertrophied scar
- Keloid formation
- Excessive contraction
Wound Strength-
- Wound contraction- completed by 14th day
- At the end of 3rd month 70- 80% of normal skin (maximum strength)
Extracellular Matrix-
- It has 5 major components
- Collagen
- Glycoproteins
- Basement membrane
- Elastic fibres
- Proteoglycan
- Fibroblasts in healing wound are derived from local mesenchyme.
- Vitamin C promotes wound healing.
- Vitamin E inhibits wound healing
Exam Important
Complications of Wound Healing-
- Infection
- Deficient scar formation
- Hypertrophied scar
- Keloid formation
Wound Strength-
- Wound contraction- completed by 14th day
- At the end of 3rd month 70- 80% of normal skin (maximum strength)
- Fibroblasts in healing wound are derived from local mesenchyme.
- Vitamin C promotes wound healing.
- Vitamin E inhibits wound healing
Healing of Skin wounds
Maximum collagen in wound healing is seen at –
| A |
End of first week |
|
| B |
End of second week |
|
| C |
End of third week |
|
| D |
End of 2 months |
Maximum collagen in wound healing is seen at –
| A |
End of first week |
|
| B |
End of second week |
|
| C |
End of third week |
|
| D |
End of 2 months |
Ans. is ‘b’ i.e., End of second week
o During second week there is continued accumulation of collagen and proliferation of fibroblast. Maximum collagen is seen in second week.
Which occurs first in wound healing –
| A |
Thin continuous epithelial cover appears |
|
| B |
Fibroblasts lay down collagen fiber |
|
| C |
Granulation tissue fills the wound |
|
| D |
Neutrophils line the wound edge |
Which occurs first in wound healing –
| A |
Thin continuous epithelial cover appears |
|
| B |
Fibroblasts lay down collagen fiber |
|
| C |
Granulation tissue fills the wound |
|
| D |
Neutrophils line the wound edge |
Ans. is ‘d’ i.e., Neutrophils line the wound edge
Wound healing is the summation of following processes except –
| A |
Coagulation |
|
| B |
Matrix synthesis |
|
| C |
Angiogenesis |
|
| D |
Fibrolysis |
Wound healing is the summation of following processes except –
| A |
Coagulation |
|
| B |
Matrix synthesis |
|
| C |
Angiogenesis |
|
| D |
Fibrolysis |
Ans. is ‘d’ i.e., Fibrolysis
Primary intentional healing which is true ‑
| A |
Neovascularization is maximum by day 5 |
|
| B |
Neovascularization is maximum by day 3 |
|
| C |
Neutrophils appear at wound margins on day 3 |
|
| D |
The epidermis recovers its maximum thickness by day 7 |
Primary intentional healing which is true ‑
| A |
Neovascularization is maximum by day 5 |
|
| B |
Neovascularization is maximum by day 3 |
|
| C |
Neutrophils appear at wound margins on day 3 |
|
| D |
The epidermis recovers its maximum thickness by day 7 |
Ans. is ‘a’ i.e., Neovascularization is maximum by day 5
Skin wound healing
- Skin wounds are classically described to heal by primary or secondary intention.
A. Healing by primary intention
- It occurs in wounds with opposed edges, e.g., surgical incision.
- The healing process follows a series of sequantial steps : ‑
Immediate after incision
- Incisional space filled with blood containing .fibrin and blood cells.
- Dehydration of the surface clot forms scab that covers the wound.
Within 24 hours
- Neutrophils appear at the margins of wound.
In 24-48 hours
- Epithelial cells move from the wound edges along the cut margin of dermis, depositing basement membrane components as they move.
- They fuse in the midline beneath the surface scab, producing a continuous but thin epithelium layer that closes the wound.
By day 3
- Neutrophils are largely replaced by macrophages.
- Granulation tissue progressively invades the incision space.
- Collegen fibers now present in the margin but do not bridge the incision.
By day 5
- Incisional space is largely filled with granulation tissue.
- Neovascularization is maximum.
- Collegen fibrils become more abundant and begin to bridge the incision.
- The epidermis recovers its normal thickness.
During second week
- Leukocytes and edema have disappeared.
- There is continued accumulation of collegen and proliferation of fibroblast.
- By the end offirst month
- Scar is made up of a cellular connective tissue devoid of inflammatory infiltrate covered now by intact epidermis.
B. Healing by secondary intention
- It occurs in wounds with seperated edges in which there is more extensive loss of cells and tissue.
- Regeneration of parenchymal cells cannot completely restore the original architecture, and hence abundant granulation tissue grows.
Healingby secondary from primary intention in several respects :
- Inflammatory reaction is more intense.
- Much larger amounts of granulation tissue are formed.
- Wound contraction occurs → Feature that most clearly differentiate secondary from primary healing.
- Permanent wound contraction requires the action of myolifibroblasts – Fibroblasts that have the ultrastructural characteristic of smooth muscle cells.
Two types of Healing of wounds are shown in the image.The characteristics of ‘A’ type of wound healing as compared to ‘B’ type of wound healing are all except:
| A |
Wound is clean |
|
| B |
Scanty granulation tissue |
|
| C |
Sutures are not used |
|
| D |
Outcome is neat linear scar |
Two types of Healing of wounds are shown in the image.The characteristics of ‘A’ type of wound healing as compared to ‘B’ type of wound healing are all except:
| A |
Wound is clean |
|
| B |
Scanty granulation tissue |
|
| C |
Sutures are not used |
|
| D |
Outcome is neat linear scar |
Ans:C.)Sutures are not used
Image shows:’A’:Healing by primary intention,’B’:Healing by secondary intention.
Healing of Skin wounds
HEALING OF SKIN WOUNDS (CUTANEOUS WOUND HEALING)
- Healing of skin wounds is a classical example of combination of regeneration & repair.
Wound healing in two ways-
- Healing by first intention (primary union)
- Healing by second intention (secondary union)
a) Healing by first intention-
Sequence in primary union are-
- Initial hemorrhage
- Acute inflammatory response
- Epithelial changes
- Organization
- Suture tracks
b) Healing by second intention (secondary union)-
Characterised by-
- Open with large tissue defect
- Having extensive loss of tissue & cells
- Wound left open
Sequence of secondary intention is-
- Initial hemorrhage
- Inflammatory phase
- Epithelial changes
- Granulation tissue
- Wound contraction- is most prominent seen in wound healing.
- Presence of infection
Exam Important
Secondary intention-
- Initial hemorrhage
- Inflammatory phase
- Epithelial changes
- Granulation tissue
- Wound contraction- is most prominent seen in wound healing.
- Presence of infection
Wound healing & repair
Which are not labile cells‑
| A |
Bone marrow |
|
| B |
Epithelium of skin |
|
| C |
Intestitial mucosa |
|
| D |
Hepatocytes |
Which are not labile cells‑
| A |
Bone marrow |
|
| B |
Epithelium of skin |
|
| C |
Intestitial mucosa |
|
| D |
Hepatocytes |
Ans. is ‘d’ i.e., Hepatocytes
When a cell proliferates, it pass through a cell cycle
Early granulation tissue
| A |
Type I collagen |
|
| B |
Type IV collagen |
|
| C |
Type I & IV collagen |
|
| D |
None |
Early granulation tissue
| A |
Type I collagen |
|
| B |
Type IV collagen |
|
| C |
Type I & IV collagen |
|
| D |
None |
- Early granulation tissue- Type I & III collagen
Wound healing & repair
Healing involves 2 processes-
1. Regeneration- results in complete restoration of original tissues.
2. Repair- results in fibrosis & scarring.
- 2 processes in repair include-
A. Granulation tissue formation-
i) Phase of inflammation-
- Acute inflammatory response which exudation of plasma, neutrophils within 24hours.
ii) Phase of clearance-
- Autolytic enzymes & phagocytes clears off necrotic tissue.
iii) Granulation tissue growth consist of triad-
- Neovascularization (angiogenesis)
- Fibrogenesis
- Non specific inflammation
B. Contraction of wounds
- Scar tissue & adult skin – Type I collagen
- Early granulation tissue- Type I & III collagen
Types of cells-
Exam Important
Repair- results in fibrosis & scarring.
Granulation tissue growth consist of triad-
- Neovascularization (angiogenesis)
- Fibrogenesis
- Non specific inflammation
- Scar tissue & adult skin – Type I collagen
- Early granulation tissue- Type I & III collagen
Types of cells-
Granulomatous inflammation
A sarcoidosis patient developed non caseating granulomas. Which type of hypersensitivity is responsible for developing granulomatous inflammation in this patient?
| A |
Type I |
|
| B |
Type II |
|
| C |
Type III |
|
| D |
Type IV |
A sarcoidosis patient developed non caseating granulomas. Which type of hypersensitivity is responsible for developing granulomatous inflammation in this patient?
| A |
Type I |
|
| B |
Type II |
|
| C |
Type III |
|
| D |
Type IV |
Delayed-type hypersensitivity or or type IV hypersensitivity is a T-cell mediated or inflammatory response in which the stimulation of antigen-specific effector T cells leads to macrophage activation and localized inflammation and edema within tissues.
Three variants of type IV hypersensitivity reaction are recognized, contact, tuberculin type and granulomatous.
Contact hypersensitivity and tuberculin-type hypersensitivity both occur within 72 hours of antigen challenge.
Granulomatous hypersensitivity reactions develop over a period of 21-28 days – the granulomas are formed by the aggregation of macrophages and lymphocytes and may persist for weeks.
This is the most important type of hypersensitivity response for producing clinical consequences.
Examples of chronic diseases which manifest type IV granulomatous hypersensitivity are leprosy, tuberculosis, schistosomiasis, sarcoidosis, Crohn’s disease.
Ref: Immunology By David K. Male, 2006, Page 477, 486 ; Immunology by David K. Male, Jonathan Brostoff, Ivan Maurice Roitt, David B. Roth, Page 477-478
A 49 year old female with shortness of breath is found to have hilar lymphadenopathy on chest x-ray. Biopsy of one of the lymph nodes reveals granulomas, and is highly suggestive of sarcoidosis. Which of the following histological findings must have been present in the biopsy material to support the diagnosis of granulomatous inflammation?
| A |
Asteroid bodies |
|
| B |
Caseous necrosis |
|
| C |
Epithelioid histiocytes |
|
| D |
Fibroblast proliferation |
A 49 year old female with shortness of breath is found to have hilar lymphadenopathy on chest x-ray. Biopsy of one of the lymph nodes reveals granulomas, and is highly suggestive of sarcoidosis. Which of the following histological findings must have been present in the biopsy material to support the diagnosis of granulomatous inflammation?
| A |
Asteroid bodies |
|
| B |
Caseous necrosis |
|
| C |
Epithelioid histiocytes |
|
| D |
Fibroblast proliferation |
The epitheloid cell and multinucleated gaint cells of Granulomatous inflammation are derived from ‑
| A |
Basophils |
|
| B |
Eosinophils |
|
| C |
CD 4 – T lymphocytes |
|
| D |
Monocytes – Macrophages |
The epitheloid cell and multinucleated gaint cells of Granulomatous inflammation are derived from ‑
| A |
Basophils |
|
| B |
Eosinophils |
|
| C |
CD 4 – T lymphocytes |
|
| D |
Monocytes – Macrophages |
Ans. is ‘d’ i.e., Monocyte macrophages
In granulomatous inflammation
o Main cells involved —-> Macrophages, CD-4 helper T cells.
- Epitheloid cells – Macrophages that develop epithelial like appearance.
- Multinucleated giant cells -4 Due to fusion of epitheloid cells.
Which of the following is not a cyclin dependent kinase (CDK) inhibitor?
| A |
p21 |
|
| B |
p27 |
|
| C |
p53 |
|
| D |
P57 |
Which of the following is not a cyclin dependent kinase (CDK) inhibitor?
| A |
p21 |
|
| B |
p27 |
|
| C |
p53 |
|
| D |
P57 |
p53 is a tumor supressor gene, that control some CDK inhibitors like p21, but p53 itself is not a CDK inhibitor.
Cell cycle Inhibitors
o The activity of cyclin – CDK complexes is tightly regulated by inhibitors, called CDK inhibitors.
o By inhibiting CDK they inhibit cell cycle and replication –> Act as tumor suppressors.
o There are two main classes of CDK inhibitors ‑
- The Cip/kip family
- The INK4/ARF family
o The Cip / kip family
It has 3 components, p21, p27 and p57.
This binds and inactivate cyclin – CDK complexes.
Transcriptional activation of p21 is under the control of p53, a tumor suppressor gene that is mutated in a large proportion of human cancers.
o INK 4a/ARF family
It consists p16INK4a and p14 ARF
p16 INK4a competes with cyclin D for binding with CDK4, so it inhibits cyclin D-CDK4 complex.
p14 ARF acts through p53 by preventing its degradation. p53 then activate p21 that inturn inhibit cyclin D-CDK4 complex.
Granulomatous inflammation
GRANULOMATOUS INFLAMMATION
- Granuloma is circumscribed tiny lesion composed of macrophages and lymphoid cells.
- Formation of granuloma is a Type IV granulomatous hypersensitivity reaction.
Pathogenesis-
Composition of granuloma-
- Epitheloid cells
- Multinucelated giant cells
- Lymphoid cells
Types of granuloma-
- Immunological granuloma
- Non- immunological granuloma- silicosis, foreign body pneumonia
Special forms of granuloma-
- Stellate granuloma- Cat scratch disease
2. Durck’s granuloma- celebral malaria
3. Eosinophillic granuloma- Churg- strauss syndrome
4. Naked granuloma- Sarcoidosis
Systemic effects-
- Fever- IL-1 (most important pyrogens)
- Most important cytokine for synthesis of acute phase protein is IL-6.
Examples of granulomatous chronic inflammation-
Wound healing & Repair-
3 processes-
- Resolution
- Regeneration
- Repair-
- Formation of granulation tissue is the hallmark of repair.
- Wound contraction by myofibroblast.
Exam Important
- Formation of granuloma is a Type IV granulomatous hypersensitivity reaction.
Pathogenesis-
Composition of granuloma-
- Epitheloid cells
- Multinucelated giant cells
- Lymphoid cells
Types of granuloma-
- Immunological granuloma
- Non- immunological granuloma- silicosis, foreign body pneumonia
Special forms of granuloma-
- Stellate granuloma- Cat scratch disease
2. Durck’s granuloma- celebral malaria
3. Eosinophillic granuloma- Churg- strauss syndrome
4. Naked granuloma- Sarcoidosis
Systemic effects-
- Fever- IL-1 (most important pyrogens)
- Most important cytokine for synthesis of acute phase protein is IL-6.
Examples of granulomatous chronic inflammation-
Chronic inflammation
All occurs in chronic inflammation except –
| A |
Infiltration of macrophages |
|
| B |
Fibrosis |
|
| C |
Infiltration of neutrophils |
|
| D |
Angiogenesis |
All occurs in chronic inflammation except –
| A |
Infiltration of macrophages |
|
| B |
Fibrosis |
|
| C |
Infiltration of neutrophils |
|
| D |
Angiogenesis |
Ans. is ‘c’ i.e., Infiltration of neutrophils
Chronic inflammation
- Chronic inflammation is of prolonged duration in which active inflammation, tissue destruction and attempts of repair are proceeding simultaneously.
- It may : ‑
- Begins insdiously without acute inflammation (more common). or
- Follows acute inflammation, when the injurious stimulus is persistent.
- Chronic inflammation is characterized by
A. Mononuclear cell infiltration
- The macrophages are the major cells involved in chronic inflammation.
- Macrophages are derived from monocytes i.e., when these cell circulate in the blood, they are known as monocytes and when they come out from the circulation and become part of the tissue, they are called macrophages.
- Macrophage accumulation persists in chronic inflammation by following mechanisms.
- Recruitment of monocyte from the circulation (most common).
- Local proliferation of the macrophages.
- Immobilization of macrophages at the site of inflammation.
- Other cells involved in chronic inflammation are plasma cells, lymphocytes, eosinophils, mast cells.
B. Tissue destruction
- The products of activated macrophages serve to eliminate injurious agents such as microbes and to initiate the process of repair.
- These mediators also cause tissue injury because some of these are toxic to host cells, (reactive oxygen species) or extracellular matrix (proteases) and a variety of other substances may contribute to tissue damage in chronic inflammation.
- So, tissue destruction is one of the hallmark of chronic inflammation.
C. Healing and Fibrosis
- Attempt at healing by connective tissue replacement of damaged tissue is accomponied by proliferation of new small vessels (angiogenesis) and fibrosis.
Sign of chronic inflammation ‑
| A |
Angiogenesis |
|
| B |
Purulent exudate |
|
| C |
Induration |
|
| D |
Edema |
Sign of chronic inflammation ‑
| A |
Angiogenesis |
|
| B |
Purulent exudate |
|
| C |
Induration |
|
| D |
Edema |
Ans. is ‘a’ i.e. Angiogenesis
Chronic inflammation is characterized by :‑
- Infiltration with mononuclear cells, which include → macrophages, lymphocytes, and plasma cells
- Tissue destruction, induced → the persistent offending agent or by the inflammatory cells
- Attempts at healing → connective tissue replacement of damaged tissue, accomplished by angiogenesis (proliferation of small blood vessels) and, in particular, fibrosis.
Chronic inflammation
CHRONIC INFLAMMATION
- Chronic inflammation is the inflammation of prolonged duration with tissue destruction.
Characteristics of Chronic inflammation-
- Infiltration with mononuclear cells includes- macrophages (most important), lymphocytes and plasma cells.
- Tissue destruction or necrosis- Hallmark of chronic inflammation by activated macrophages.
- Repair- healing takes place by angiogenisis and fibrous collagen.
Types of Chronic inflammation-
It is of 2 types-
- Chronic non specific inflammation
- Granulomatous inflammation
System effects of chronic inflammation-
- Fever
- Leucocytosis
- ESR increased
- Amyloidosis
Exam Important
Characteristics of Chronic inflammation-
- Infiltration with mononuclear cells includes- macrophages (most important), lymphocytes and plasma cells.
- Tissue destruction or necrosis- Hallmark of chronic inflammation by activated macrophages.
- Repair- healing by fibrous & collagen takes place.
System effects of chronic inflammation-
- Fever
- Leucocytosis
