Session 5 Flashcards

Question

Apart from collagen, what are the other key components of the Extracellular Matrix?

Answer 1

Matrix glycoproteins (e.g. fibronectin, Iaminin, Tenscin) organise and orientate cells, support cell migration Proteoglycans (e.g. Heparan sulphate proteoglycan) are involved in matrix organisation, cell support, regulate availability of growth factors Elastin provides tissue elasticity

Answer 2

1. Inflammatory cell infiltrate 2. Clot replaced by granulation tissue 3. Maturation

Answer 3

Blood vessels get damaged and blood clot forms. Acute inflammation around the edges - neutrophils infiltrate and digest clot Chronic inflammation - macrophages and lymphocytes migrate into the clot.

Answer 4

Angiogenesis: capillaries and lymphatics sprout and infiltrate (ingress of new cells into the site of injury) Myo/fibroblasts migrate and differentiate, Extracellular matrix such as glycoproteins are produced by myo/fibroblasts. There is now a vascular network; collagen synthesised; macrophages reduced

Answer 5

Comparatively long lasting Cell population falls Collagen increases, matures, contracts and remodels Myofibroblasts contract - reduces volume of defect (pulls the edges close together) Vessels differentiate and are reduced Left with a fibrous scar.

Answer 6

Complex and poorly understood: Inflammatory cells recruited by chemotaxis Angiogenesis is due to angiogenic cytokines produced by platelets, extracellular matrix and others in response to hypoxia e,g, VEGF, bFGF Fibrosis is due to macrophages releasing pro-fibrotic cytokines e.g. IL1, TNF alpha, TNF beta) causing fibroblast proliferation and production of extracellular matrix.

Answer 7

Healing by primary intention: Incised wound (very localised tissue damage) Apposed edges (as close together as possible) Minimal clot and granulation tissue formation Epidermis regenerates Dermis undergoes fibrous repair Sutures out at 5-10 days: approximately 10% normal strength. A clean sutured wound - transition from granulation tissue to scar tissue. Maturation of scar continues up to 2 years, minimal contraction and scarring, good strength Risk of trapping infection - abscess

Answer 8

Healing by Secondary Infection - infarct, ulcer, abscess or any large wound (including most burns). Quantitative differences: Unapposed wound edges Large clot dries to form a scab (ESHAR) Epidermis regenerates from the base up Repair process produces much more GRANULATION TISSUE

Answer 9

Produces much more contraction to reduce volume of defect Produces a larger scar; not necessarily weaker Takes longer

Answer 10

Haematoma forms from ruptured vessels within marrow cavity and periosteum. Organising haematoma provides a framework for ingress of macrophages, endothelial cells, fibroblasts and osteoblasts. Endothelial cells start to produce new blood vessels. Necrotic tissue removed Capillaries develop Angiogenesis occurs Callus formation - initially soft Bone is laid down in an irregular woven pattern, sometimes with Islands of cartilage External callus provides sprint-like support Woven bone gradually replaced by more organised lamellar bone. Lamellar bone gradually remodelled to the direction of mechanical stress.

Answer 11

Type, size, location of wound Apposition, lack of movement - skin wounds, bone fractures, severed nerves Blood supply: arterial, venous Infection: suppurations (pus areas), gangrene, systemic Foreign material: dirt, glass, sutures, necrotic tissue Radiation damage: cancer patients undergoing radiotherapy which could impact their endothelial regeneration and cause inactivation of fibroblasts.

Answer 12

Age (elderly may have impaired ability) Drugs (steroids can impair) and hormones General dietary deficiencies e.g. Protein Specific dietary deficiencies e.g. Vitamin C (alpha chain hydroxylation) and essential amino acids General state of health - chronic diseases e.g. Diabetes, rheumatoid arthritis Chronic cardiovascular status

Answer 13

Insufficient fibrosis: wound dehiscence; hernia, ulceration. High risk in obesity (particularly with abdominal wounds), elderly, malnutrition, steroids etc Excessive fibrosis: cosmetic scarring, keloid (abnormal collagen in skin); cirrhosis; lung fibrosis (affects gas exchange) Excessive contraction: obstruction of tubes and channels (strictures) Excessive contraction: limitation of joint movement (contractures).

Answer 14

Hepatocytes have excellent regenerative capacity. In some circumstances, hepatic regeneration comes from liver progenitor cells rather than hepatocytes; bone marrow-derived stem cells are a third option. The hepatic architecture however cannot be satisfactorily reconstructed if severely damaged. Consequently, conditions that result only in hepatocytes loss may be followed by complete restitution, whereas damage destroying both the hepatocytes and architecture may not. In the latter situation the imbalance between hepatocytes regeneration and failure to reconstruct the architecture may proceed to cirrhosis. However following partial surgical resection of the liver, there can be substantial regeneration of functioning liver Loss of only scattered liver cells or even small groups can be stored without architectural disturbance. However if there is confluent loss of liver cells and architectural damage the liver heals by scarring (fibrosis - chronic) and nodular regenerations of liver cells, resulting in cirrhosis

Answer 15

Similar to the liver with respect to tissue injury, in that it has an epithelium that can be regenerated and an architecture that cannot. Loss of tubular epithelium following an ischaemic episode or exposure to toxins may result in renal failures but in general there is sufficient surviving epithelium to repopulate the tubules and enable normal renal function to return. Inflammatory or other damaging resulting in destruction of the glomerulus is likely to be permanent or result in glomerular scarring, with loss of filtration capacity. Similarly, interstitial inflammation is likely to proceed to fibrosis and thus, impaired reabsorption from tubules

Answer 16

Cardiac muscle fibres and smooth muscle cells are permanent cells (fibrosis - scarring will occur); vascular smooth muscle may be different in that new vessels can be formed so it has some limited regeneration capability. This means that damaged muscle is replaced by scar tissue. However if contractile proteins only are lost, then it is possible to synthesise new ones within the old endomysium. Voluntary skeletal muscle has a limited capacity for regeneration from satellite cells

Answer 17

There is no effective regeneration of neurones in the CNSbut glial cells however may proliferate in response to injury, a process referred to as gliosis. Peripheral nerve damage affects axons and their supporting structures such as Schwann cells. If there is transection of the nerve, axons degenerate proximally for a distance of about one or two nodes; distal of there is Wallerian degeneration followed by proliferation of Schwann cells in anticipation of Axonal regrowth. If there is good realignment of the cut ends, the axons may regrow down their previous channels (now occupied by proliferated Schwann cells); however full functional recovery is unusual. When there is poor alignment or amputation of the nerve, the cut ends of the axons still proliferate but in a disordered manner to produce a tangled mass of axons and stroma called an amputation neuroma. Sometimes these are painful and require removal

Answer 18

Degeneration of nerve fibres that occurs following injury or disease and that progresses from the place of injury along the axon away from the cell body while the part of the axon between the place of injury and the cell body remains intact

Answer 19

Myocardial cells are permanent cells so cannot divide in a regenerative response to tissue injury. In myocardial infarction, a segment of muscle dies and if the pstient survives, it is replaced by scar tissue (fibrosis). As the remainder of the myocardium must work harder for a given cardiac output, it undergoes compensatory hypertrophy (without cell division). Occasionally there may be right ventricular hypertrophy as a result of left ventricular failure and consequent pulmonary hypertension

Answer 20

Cartilage is avascular. Articular cartilage does not usually regenerate after injury or disease leading to loss of tissue and formation of a defect. Small damage does not repair itself, as cartilage is also aneural (lack of nerve supply) so shallow damage often does not trigger pain. When the damage increases and the chondral defect reaches the subchondral bone, the blood supply in the bone starts a healing process in the defect. Scar tissue made up of a type of cartilage called Fibrocartilage is then formed. although Fibrocartilage is able to fill in articular cartilage defects, its structure is slightly different to hyaline cartilage. It is much denser and doesn't withstand the demands of everyday activites as much as hyaline cartilages. It is therefore at a higher risk of breaking down. Defects may also progress to osteoarthritis over time if left untreated. An articular cartilage defect that initially may be small still has the potential to have a physical and chemical domino effect in the surrounding normal articular cartilage

Answer 21

* Also known as decubitus ulcers or bedsores. * This occurs when tissues are compressed by either exogenous agents (atrophy of skin and soft tissues overlying the sacrum in bedriiden patients) or endogenous factors (atrophy of a blood vessel wall compressed by a tumour). * In both of these circumstances, a major facotr is actually local tissue hypoxia - pressure applied to soft tissue resulting in completely or partially obstructed tissue, usually over a bony promience. Shear is also a cause as it can pull on blood vessels feeding the skin. * Most commonly develop in people who are not moving about or confined to wheelchairs.

Answer 22

Although often prevented and treatable if detected early, pressure ulcers can be very difficult to prevent in critically ill patients, frail elders, wheelchair users (especially where spinal injury is involved) and terminally ill patients. Primary prevention is to redistribute pressure by turning the patient regularly. In addition to turning and repositioning the patient in bed or wheelchair, eating a balnced diet with adequate protein and keeping the skin free from exposure to urine and stool is very important.

Answer 23

Guiding: collagen fibres serve to guide fibroblasts. Fibroblasts migrate along a connective tissue matrix. Chemotactic properties: the large surface area available on collagen fibres can attract fibrogenic cells which help in healing Nucleation: collagen in the presence of certain neutral salt molecules can act as a nucleation agent, causing formation of fibrillar structure. A collagen wound dressing might serve as a guide for orienting new collagen deposition and capillary growth. Haemostatic properties: blood platelets interact with the collagen to make a haemostatic plug.