Tissue repair & response to injury Flashcards
With regard to healing by first intention, which of the following options is correct?
A Neutrophils accumulate at the wound margins with 24 hrs
B Collagen deposited early in granulation tissue is type I
C Myofibrils account for the majority of wound strength
D Neovascularisation is maximal by day three
A
Explanation
Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. They release proteolytic enzymes that clean out debris and invading bacteria. The epidermis at its cut edges thickens as a result of mitotic activity and within 24-48 hours, spurs of epithelial cells from the edges both migrate and grow along the cut margins of the dermis. Neovascularisation is maximal by the 5th day. Collagen type III is initially laid down and then replaced by the stronger collagen type 1. Wound strength at one week is 10% and at 3 months 80% but in never reaches 100% of pre-injury levels. Type 1 collagen accounts for most of the wound strength.
Which of the following statements is NOT characteristic of platelets?
A They are biconvex discs
B hey contain a nucleus
C They contain alpha and delta granules
D They are found in the plasma at levels of 200-500 thousand per microlitre
B
Explanation
Platelets have membrane-bound smooth biconvex discs and do not have a nucleus. They are shed from megakaryocytes in the bone marrow into the blood. Platelets play a critical role in haemostasis. They contain alpha granules (containing: fibrinogen, fibronectin, factors V and VIII, platelet factor 4, PDGF and transforming growth factor B) and delta granules (containing: ADP and ATP, ionised calcium, histamine, serotonin and adrenaline). They are found in the plasma at levels of 200-500 thousand per microlitre. Some texts say 300 thousand per microlitre. The average lifespan of a platelet is normally 5 to 9 days. After vascular injury, platelets encounter extracellular matrix substances such as collagen and glycoprotein vWF. On contact with these proteins, platelets undergo adhesion (shape change), secretion (release reaction) and aggregation.
Note:
RBC: BICONCAVE shape
PLT: round, oval BICONVEX disc shaped cells
Macrophages secrete all of the following except?
A Oxygen free radicals
B Coagulation factors
C Prostaglandins
D Histamine
D
Explanation
Macrophages are the dominant cellular player in chronic inflammation. The products of activated macrophages serve to eliminate injurious agents such as microbes, and to initiate the process of repair. They are responsible for much of the tissue injury in chronic inflammation. The products produced by macrophages, which cause tissue injury and fibrosis, are: arachidonic metabolites, reactive oxygen species, reactive nitrogen species, proteases, cytokines and coagulation factors. The factors they release which cause repair include; growth factor, fibrogenic cytokines, angiogenic factors and remodeling collagenesis.
Which of the following cells cannot phagocytose?
A T-cells
B Eosinophils
C Macrophages
D Neutrophils
A
Explanation
Phagocytes are divided into “professional” and “non-professional” groups based on the efficiency with which they participate in phagocytosis. The professional phagocytes are the monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells. One litre of human blood contains about six billion phagocytes.
Concerning the repair of a well opposed, clean, surgical incision, which of the following statements is correct?
A 20% of original tissue strength is attained after 1 week
B New collagen begins to accumulate after the first week
C There is an initial inflammatory response
D Dermal appendages destroyed by the incision usually recover
C
Explanation
Dermal appendages destroyed by the incision do not recover. New collagen deposition occurs by day 3 of wound healing. Granulation tissue progressively invades the wound space by day 3 of healing. Wound strength is usually 10% by the end of the first week.
Question 6
Which of the following occurs first in fracture healing?
A Collagen deposition
B Procallus formation
C Woven bone ossification
D Neutrophil invasion
D
Explanation
The clot provides a mesh which creates a framework for the influx of inflammatory cells
Extra:
Haematoma formation – immediately after fracture occurs. Fills the fracture gap. This provides a fibrin mesh.
Inflammation via degranulation of platelets and migration of inflammatory cells e.g.Neutrophils–> release of PDGF, TGF B which activate osteoprogenitor cells in periosteum and medullary cavity. –> osteoclastic and osteoblastic activity.
Haematoma Organising by end of first week – Macrophages.
Procallus – provides anchorage between the ends but offers no structural integrity for weight bearing.
Callus formation – subperiosteal deposition of trabecular woven bone. Maximal girth at week 2-3. Endochondral calcification.
Tissue remodelling after weight bearing. Excesses are resorbed
In bone fracture healing, which of the following statements is correct?
A In the remodelling phase, osteoblasts first resorb the lamellar bone before they replace it with compact bone
B Haematoma at the fracture site plays little role in the development of procallus
C Endochondral ossification refers to the replacement of hyaline cartilage with lamellar bone
D All fractures contain cartilage as a component of the callus
C
Explanation
There are 3 phases of fracture healing: reactive phase, reparative phase and remodelling phase
In the reactivephase, the haematoma that forms immediately after a fracture is essential as it surrounds the area of injury, and provides a fibrin mesh, which helps seal off the fracture site and at the same time serves as a framework for the influx of inflammatory cells and ingrowth of fibroblasts and new capillary cells. This sets up the framework for the formation of procallus.
Fracture callus is most often made up of hyaline cartilage and woven bone. However, not all fractures contain cartilage as a component of callus
In the reparative stage there is replacement of the hyaline cartilage and woven bone with lamellar bone. The replacement process is known as endochondral ossification with respect to hyaline cartilage and bony substitution with respect to woven bone.
In the remodelling phase, the trabecular bone (which replaced the lamellar bone) is resorbed by osteoclasts, creating a shallow pit- Howship’s lacuna”- into which osteoblasts deposit compact bone which is remodelled into shape which closely resembles the bone’s original shape and strength
In healing by primary intention, which of the following statements is correct?
A An epithelial spur forms in 24-48hrs
B The tissue defect cannot be reconstituted
C It involves excessive granulation tissue
D There is a large tissue defect
A
Explanation
Healing by first intension-primary union, the wound is a clean, uninfected surgical incision approximated by surgical sutures. The incision involves a limited number of epithelial cells and connective tissue cells as well as disruption of epithelial basement membrane continuity.
Following the incision, the space fills with a clot immediately.
Within 24hrs neutrophils appear at the wound margins, and the epidermis at its cut edges thickens because of mitotic activity.
24-48hrs, epithelial spurs develop fusing in the midline beneath the surface scab producing a thin epithelial layer.
Day3, granulation tissues invades the space, collagen appears.
Day 5 neovascularization is maximal (granulation tissues completely fills the space). Collagen fibres bridge the incision. The epidermis recovers.
Week two, accumulation of collagen and fibroblasts, decrease of vascularity and inflammatory cells and almost disappeared.
One month, the scar compromises a cellular connective tissue devoid of inflammatory infiltrate covered now by intact epidermis
Secondary intension: Extensive loss of cells and tissues, as occurs in infection, ulceration, abscess results in a large tissue defect that must be filled. Regeneration of parenchyma cells cannot completely reconstitute the original architecture. Abundant granulation tissue grows in from the margin to complete the repair.
The feature that most clearly differentiates primary form secondary healing is the phenomenon of wound contraction, which occurs in large wounds
Which of the following statements regarding mast cells is correct?
A They are involved in acute but not chronic inflammation
B They release lysosymes
C Adenosine diphosphate is a stimulator of mast cell degranulation
D They may discharge independent of IgE
D
Explanation
Mast cells participate in both acute and chronic inflammatory reactions. Mast cells release multiple primary and secondary mediators but not lysosomes. Adenosine triphosphate provides the energy for mast cell degranulation. Non IgE dependent discharge is called anaphylactoid for instance with drugs (including x-ray contrast material), bacterial toxins, during surgery and with exposure to heat or cold.
Which of the following does NOT impair wound healing?
A Vitamin A deficiency
B Glucocorticoid excess
C Vitamin C deficiency
D Lack of insulin
A
Explanation
I have chosen to keep this question as is.
If you look in the current TB, it states that infection, diabetes, nutritional –vit C deficiency, mechanical factors, glucocorticoids, poor perfusion, FB, type and extent of injury and the location of injury are all factors impairing wound healing.
Vitamin A deficiency: night blindness, epithelial metaplasia and keratinization-of the eyes: xeropthalmia. Upper respiratory and urinary tract undergo squamous metaplasia. Hyperplasia and keratinization of the epidermis leading to follicular or popular dermatosis. Another serious consequence is immune deficiency.
It does not speak about wound healing directly. I have therefore chosen vit A as the most likely answer. Please see extensive note about vitamin A form a new resource
It’s not news that diet plays an important role in the body’s capacity for wound healing. Many people are aware that fats, protein, carbohydrates and zinc are necessary for the development of new tissue. However, one often overlooked nutrient is vitamin A. According to the University of Maryland Medical Centre, vitamin A aids cells in the reproduction process, known as cellular differentiation. This is an integral part of wound healing, as cellular reproduction must occur for new tissue to grow. Vitamin A also helps reduce the risk of wound infection, as it is essential to proper immune system function, and the nutrient helps manage inflammation that occurs after a wound is sustained.
Factors Affecting Wound Healing:
Local Factors
Systemic Factors
Oxygenation
Infection
Foreign body
Venous sufficiency
Age and gender
Sex hormones
Stress Ischemia
Diseases: diabetes, keloids, fibrosis, hereditary healing disorders, jaundice, uraemia Obesity Medications: glucocorticoid steroids, non-steroidal anti-inflammatory drugs, chemotherapy Alcoholism and smoking Immunocompromised conditions: cancer, radiation therapy, AIDS Nutrition
The classical complement pathway is activated by:
A Complex polysaccharides
B Bacterial endotoxin
C Leucocytes
D Antigen-Antibody complexes
D
Explanation
Activation of the C3 component of complement occurs via 3 mechanisms. The classical pathway is triggered by C1 binding to immune complexes, the alternative pathway via microbial surface molecules e.g. endotoxin, and the lectin pathway via lectin binding to mannose groups in bacteria
In a patient of the same age with widespread burns who develops shock, what is the underlying mechanism?
A Loss of plasma volume
B Increased intravascular osmotic pressure
C Increased vascular permeability
D Decreased tone
C
Explanation
Burns causes hypovolaemia as a result of rapid fluid mobilization, due to both local fluid shifts and SIRS.
With burns of more than 20% of body surface area, there is a rapid shift of body fluids into the interstitial compartments, both at the burn site and systemically, which can result in hypovolaemic shift.
Mechanisms include an increase in local interstitial osmotic pressure (from release of osmotically active constituents of dying cells) and both neurogenic and mediator-induced increases in vascular permeability. Because protein from the blood is lost into the interstitial tissue, generalized oedema, including pulmonary oedema, may become severe if fluids used for volume replacement are not osmotically active
At the end of the inflammatory process, neutrophils that have completed their role are removed by which physiological process?
A Antibody-dependent cell cytotoxicity
B Atrophy
C Necrosis
D Apoptosis
D
Explanation
Physiological situations where apoptosis occurs include embryogenesis, endometrial breakdown, and removal of neutrophils in acute inflammation, self-reactive lymphocytes, and cytotoxic T cells
Following a partial hepatectomy, the liver regenerates due to:
A Compensatory hyperplasia
B Limited hyperplasia
C Hepatic stem cells
D Hypertrophy
A
Which of the following adaptations results in a change of a cell type
A Anaplasia
B Hyperplasia
C Metaplasia
D Hypertrophy
C
Explanation
Metaplasia is a reversible, replacement of one normal cell type with another normal cell type. It can be adaptive in response to increased stress.
Anaplasia is a lack of differentiation often seen in malignant neoplasms.
Hypertrophy: increase in size of cells, resulting in the increase in size of the organ
Hyperplasia: increase in the number of cells in an organ.
Which of the following influences wound healing?
A Serum calcium level
B Insulin excess
C Estrogen excess
D Glucocorticoid excess
D
Explanation
Glucocorticoids delay wound healing.
Other system factors impacting wound healing including nutrition (protein, vitamin C deficiency), diabetes mellitus, blood flow (CCF/PVD)
What occurs at the same time as epithelial cell proliferation in wound healing by first intention?
A Formation of granulation tissue
B Release of proteolytic enzymes
C Deposition of basement membrane
D Neutrophil invasion
A
Explanation
I have tried to provide a new update answer. Some users have said BM deposition is the correct answer, but I am leaving it as formation of granulation tissue
In the context of healing by first intention, both epithelial proliferation and granulation tissue formation occur simultaneously, but if we compare their visibility and contribution to the healing process, the formation of epithelial and granulation tissue occurs more prominently and earlier than the specific process of epithelial proliferation and basement membrane formation.
Granulation Tissue Formation:
Granulation tissue is a crucial component that forms rapidly at the wound site. It is characterized by new capillaries (angiogenesis), fibroblast proliferation, and inflammatory cells. The presence of granulation tissue is essential for providing the scaffold and nutrients necessary for healing.
Epithelial Proliferation:
Epithelial cells proliferate and migrate across the wound bed, which is supported by the underlying granulation tissue. The proliferation of epithelial cells is necessary for re-establishing the epithelial barrier.
Basement Membrane Formation:
While epithelial proliferation occurs, the formation of the basement membrane happens as part of the re-establishment of the epithelial layer. This process is crucial, but it follows the earlier stages of granulation tissue formation and epithelial migration.
Conclusion:
Given these aspects, in the healing by first intention, epithelial and granulation tissue formation occurs more prominently and simultaneously, as granulation tissue provides a critical support structure for migratory epithelial cells. The basement membrane formation, while important, is a more nuanced process that takes place concurrently but is secondary to the initial events of granulation tissue formation and epithelial migration. Thus, the overall focus on healing by first intention emphasizes the role of granulation tissue and epithelial proliferation over basement membrane formation in terms of immediacy and visibility in the healing process.
Wound healing by first intenion: OLD answers
Blood clot: stops bleeding, scaffold for migrating cells
24 hours: neutrophils arrive
24-48 hours: epithelial proliferation and formation of granulation tissue (fibroblasts and vascular endothelial tissue). Increased vascular permeability and protein/fluid leakage into extravascular space
Day 3: ECM deposition, neutrophils replaced by macrophages
Day 5: neovascularisation reaches peak
2nd week: continued collagen accumulation. Leukocytes etc. are diminished
4 weeks: scar with few inflammatory cells
Extra: This is an old question from an old TB edition. Robbins Pathology 11th edition reads. I have kept the question in its orignal form
Epithelial proliferation and formation of granulation tissues occurs on separate days.
Success of the inflammatory phase results in a shift toward tissue repair and the recruitment of keratinocytes, fibroblasts, and endothelial cells. The proliferation phase starts on the third day, lasts about 2 weeks, and consists of reepithelialization, formation of granulation tissue, and wound contraction.
Reepithelialization
Reepithelialization attempts to restore the protective barrier of the skin; it begins within hours of injury and is the result of keratinocyte migration and proliferation. Keratinocyte proliferation begins 1 to 2 days after injury.
Keratinocytes are guided into the wound and migrate between the fibrin clot and the collagenous dermis through the interaction of the integrin receptors and the ECM proteins.
Once the wound is epithelialized, the proliferation signals cease and the deactivated keratinocytes return to their normal differentiation pathway and epithelial stratification process.
Formation of Granulation Tissue
At approximately 3 to 4 days following injury, a new stromal framework—known as granulation tissue— begins to enter the wound and replace the fibrin clot. Granulation tissue consists of a dermal matrix that provides a framework for cell migration, which is enhanced by angiogenesis. The initial wound matrix is primarily composed of fibrin and fibronectin. Fibrin is gradually replaced by collagen and other proteins such as glycoproteins, which are a key component of the mature matrix and are actively synthesized during this part of healing. Collagen imparts integrity and strength to tissues and plays an important role in the proliferative and remodelling phases.
The fibroblast is critical to the production of the dermal matrix and produces type I and III collagens, fibronectin, elastin, and proteoglycans. After the first week, abundant ECM further supports cell migration.
In healing by first intention, when is neovascularisation at its peak?
A Day 7
B Day 3
C Day 5
D Day 1
C
Explanation
By day 5, neovascularization reaches its peak as granulation tissue fills the incisional space
