Lecture 2- Cell Damage, Change, Necrosis & Wound Healing Flashcards

Question

What is Gangrene?

Answer 1

Complication of necrosis. Tissues are invaded by bacteria which release proteolytic enzymes. The enzymes degrade the necrotic tissue releasing foul smelling gas. The tissue becomes green or black due to breakdown of heamoglobin. Examples: - Obstruction of blood supply in the bowel, is almost inevitably followed by gangrene. - Diabetic foot

Answer 2

Cardiac Arrest Example- cessation of oxygen (hypoxia) to the whole body follows. Most sensitive cells are the large neurons of the hippocampus & cerebellum which die after 2-5mins without oxygen. Prolonged hypoxia causes damage to the majority of the pyramidal cells The most robust cells are fibroblasts. These can remain even after all the parenchymal cells have been destroyed. (It all comes down to the varying metabolic capacities of the different cells types to survive ATP depletion and calcium influx!)

Answer 3

Damaged proteins are removed by a cell stress response & autophagy. (this is called sublethal cell damage and is associated with recognisable structural changes).

Answer 4

The cell is killed immediately without passing through the stages of apoptosis or necrosis. Examples of this include: Severe heat – burns Strong acids

Answer 5

Proliferative ability Type and Severity of the damage Most Importantly, regeneration is NOT possible if the STEM CELLS are destroyed.

Answer 6

1. Proliferation of surviving cells to replace lost tissue 2. Migration of surviving cells Into the vacant space. The factors which control healing & repair are complex; they include the production of a large variety of growth factors.

Answer 7

Epithelial regeneration (healing of the epidermis) Repair by scarring (healing of the dermis)

Answer 8

(coagulation / Inflammation) Pre-existing capillaries in the undamaged tissue form new capillaries by budding into the damaged area. The damaged area is also infiltrated by macrophages, fibroblasts, and myofibroblasts. Macrophages phagocytose inflammatory exudate and dead tissue Vascular granulation a fragile complex of interconnecting capillaries, macrophages and support cells replace the area of tissue damage.

Answer 9

(tissue formation) There is progressive growth of fibroblasts and myofibroblast. the tissue is filled with: complex capillary network proliferating fibroblasts & a few residual macrophages (fibrovascular granulation tissue). With continued proliferation of the fibroblasts and active collagen synthesis, many of the newly formed capillaries regress until a comparatively small number of vascular channels remain, connecting the damaged area of tissue to the normal undamaged area around it – providing nutrients for the fibroblasts.

Answer 10

(remodelling) The intervening spaces between the vessels become progressively filled with fibroblasts synthesizing collagen (FIBROUS GRANULATION TISSUE). The fibroblasts align themselves so that they deposit collagen in a mainly uniform pattern- running in a direction that provides maximum strength (for the physical stresses encountered). Contraction of the area of granulation tissue frequently occurs, partly through the contractile effects of the myofibroblasts; the size of the damaged area is therefore reduced.

Answer 11

(remodelling) Production of dense collagen by the fibroblasts forms a collagenous scar Once the fibroblasts have synthesized sufficient collagen to fill the defect, they assume a resting status – known as fibrocytes.

Answer 12

The process whereby the inflammatory exudate is replaced by granulation tissue is called organisation of the exudate The process where the granulation tissue is subsequently replaced by fibrous scar is called fibrous repair.

Answer 13

When there has been substantial structural damage to the tissue stroma, healing does not occur through resolution of the exudate, but by a process known as organisation and repair. This eventually leads to the formation of a scar.

Answer 14

HEALING BY FIRST INTENTION (Primary Union) HEALING BY SECOND INTENTION (Secondary union)

Answer 15

Occurs in clean, incises wounds. An example is a planned surgical incision

Answer 16

Occurs in open wounds, particularly where there has been significant loss of tissue, necrosis or infection

Answer 17

In secondary intention healing, there is a higher amount of tissue loss and separation of edges or infected wounds. These wounds are filled by an abundance of granulation tissue which forms the margins of the wound. The same process occurs as in healing by primary intention, but there is a more intense inflammatory process & considerable more wound contraction - This means the scar takes on the shape of the original wound

Answer 18

Keloid scar – overproduction of collagen.

Answer 19

Inadequate Nutrition – Protein is required for collagen synthesis, as are Vit. C & Zinc Ischemia Infection Foreign Material (continued infection / inflammation) Steroids – hinder the formation of granulation tissue and their immunosuppressive effects may predispose to local infection. Diabetes – Poor wound healing for several reasons.

Answer 20

Following acute inflammation if the causal agent is not removed Or “Primary” - there is no acute inflammation. Examples – Tuberculosis, leprosy, auto-immune diseases, Crohn’s

Answer 21

Lymphoid cells and macrophages are the key effector cells in chronic inflammation. Macrophages not only act as phagocytic cells but they become activated to fulfil immunological and secretory functions. Once activated they secrete: Platelet activating factor & arachidonic acid metabolites (mediators of acute inflammation) Cytokines, IL-1 TNFalpha (stimulate fibroblast proliferation and collagen synthesis) Growth Factors (growth of blood vessels, division & migration of fibroblasts) Proteases & hydrolytic enzymes (dissolution of extracellular material) Plus a lot of other chemical processes which are involved in specific chronic diseases..!

Answer 22

A special type of chronic inflammation In certain diseases, the acute inflammatory response, dominated by neutrophils is quickly replaced by an immune based cellular response It is characterized by aggregation of macrophages & lymphocytes The macrophages form clusters called granulomas. Examples include - Tuberculosis Sarcoidosis Crohn’s Disease

Answer 23

1 - initial infection and replication of Mtb in macrophages 2 - Infected Macrophages 3 - Recruitment of innate and adaptive immune cells 4 - Solid granuloma, containment of Mtb 5 - Infected cells undergo necrosis resulting in the formation of the caseum 6 - Caseating granuloma 7 - Granuloma cavitation and dissemination of Mtb in the lung