Week 7 Quiz (Wound healing and alt. of Hematologic fx) Flashcards
Resolution definition
- injured tissue is replaced by cells of the same type
- restoration of the original structure and function
Repair definition
- destroyed tissue is replaced by connective tissue (scar)
- fills in lesion and restores tensile strength but can not carry out physiologic functions of the destroyed tissue
when do resolution/repair occur?
they begin early during the inflammatory process
Regenerative capacity of different cell types
- Labile cells
- Quiescent cells
- Permanent cells
Labile cells and examples
- continuously dividing (proliferate thought life)
- skin, oral cavity, GI tract lining, urinary tract, bone marrow
Quiescent cells and examples
- stable cells
- usually demonstrate low level of replication, but stimulation can lead to rapid increases in division
- bone, kidney, pancreas, fibroblasts, liver
Permanent cells and examples
- nondividing cells
- stopped dividing during prenatal life
- nerve cells, cardiac m., skeletal m.
Skeletal muscle fiber repair
- multinucleated, provide multiple copies of genes to speed up production of enzymes and structural proteins
- myoblasts: embryonic cells which fuse to create the muscle fibers
- satellite cells: assist with repair of damaged fibers = left-over myoblasts
Other factors which influence wound healing
- site of the wound
- mechanical factors
- size of wound
- infection (won’t heal until get rid of infection)
- circulatory status (cartilage example)
- nutritional and metabolic factors
- age
Tension lines
- most collagen and elastin fibers are in parallel bundles
- their orientation depends on the stress placed on the skin during normal movement
- clinical significance in surgery
Debridement
- the first, absolutely essential step in wound healing is debridement
- “clean-up” of particulate matter in the inflammatory exudate by phagocytosis
- dissolution of fibrin clots by fibrinolytic enzymes
- natural debridement occurs, but is slow (inflammation and phagocytosis)
- surgical debridement speeds up healing
First intention healing
- primary union
- wounds with minimal tissue loss
- example: sutured surgical wound
- always preferred if possible
- more likely to lead to resolution
Second intention healing
- large, open defects and infected wounds
- examples: degloving injuries, burns
- formation of granulation tissue
- more likely to lead to repair
Healing by second intention involves
- formation of a healthy granulation bed (happy pink)
- filling in the wound defect
- covering or sealing the wound (epithelialization)
- shrinking the wound (contraction)
- wound maturation
- remodeled (scars)
granulation tissue
- has a soft, pink, granular appearance
- represents a temporary scaffolding that changes over time
- contains angioblasts and fibroblasts
- angioblasts are cells that form new blood vessels
- fibroblasts form collagen fibers for strong scar tissue
Repair involves and occurs in what two phases?
- filling in the wound defect
- epithelialization (covering or sealing the wound)
- contraction (shrinking the wound)
- reconstruction phase
- maturation phase (think about us remodeling)
Epithelialization
- epithelial cells from the surrounding healthy tissue migrate onto the granulation bed
- use proteolytic enzymes to sever the connection between the clot and the wound surface and slide in between
- make contact with similar cells from all sides of the wound and seal it (contact inhibition allows the cells to meet up and say they are done sealing)
- epithelialization can be aided by keeping the wound moist
Phases of wound healing
- inflammation
- granulation tissue
- wound contraction
- collagen accumulation remodeling starts near the end of granulation tissue phase
Reconstructive phase
- wound is initially sealed off by a blood clot containing fibrin and trapped cells
- debridement by macrophages and neutrophils (or by a surgeon)
- chemical mediators of inflammation are secreted by macrophages and promote growth and activity of angioblasts, and fibroblasts
- granulation tissue forms in 2-5 days
Angiogenesis
- capillary buds sprout out of vascular endothelial cells on wound margins
- new endothelial cells migrate into the scaffolding and organize into vessels
- allows influx of blood with oxygen, nutrients, and more phagocytic cells and chemical mediators
- also called neovascularization
Fibrosis (Fibroplasia)
- fibroblasts enter the area and proliferate
- they deposit fibrous structural proteins
- fibroblasts produce collagen which gradually develops more strength (scar tissue made of collagen and there are several types of collagen)
- collagen not inside of cells
- original collagen that is laid down is later replaced by better collagen that is more parallel to tension lines
wound contraction
- myofibroblasts have features of both fibroblasts and smooth muscle cells
- the myofibroblasts establish connections with neighboring cells
- they anchor themselves to the wound bed and exert pull on neighboring cells
- contraction alone may move the wound edge by 0.5mm per day (just like a muscle)
Maturation phase of healing (scar remodeling)
- continuation of collagen deposition, tissue repair, and wound contraction
- scar tissue is remodeled and gains its maximum strength
- collagen fibers are initially almost random, but now become highly organized
- “immature” type III collagen is replaced by stronger type I collagen
- this process often continues for months
Wound healing order
- Induction of acute inflammatory response by the initial injury
- Debridement
- Formation of a healthy granulation bed
- Angiogenesis and fibroplasia
- Epithelialization
- Wound contraction
- remodeling of tissue elements to restore function and to increase wound strength
glucocorticoids
- aka steroids
- strong anti-inflammatory drugs
- slows the migration of phagocytic cells to the site of injury
- cause phagocytic cells already in the area to become less active
- mast cells exposed to steroids are less likely to release histamine and other chemicals that promote inflammation
- good: decrease excess inflammation
- bad: suppress immune system & affect normal adrenal gland function
- NSAID’s (these drugs don’t affect the immune system)
hematocrit
% of whole blood that is made up of RBC’s
anemia
-conditions in which there is a decrease in the quality or quantity of hemoglobin and/or RBCs (decreased hematocrit)
causes of anemia
- defective RBC’s or defective hemoglobin (sickle cell, CO)
- blood loss (trauma, neoplasms, ulcers)
- increased RBC destruction (= hemolysis) which is autoimmune or blood parasites
Polycythemia vera
conditions in which there are excessive RBC numbers or volume (dehydration ism most common cause of increased hematocrit)
Clinical manifestations of anemia
- acute vs chronic
- decrease of RBC’s or hemoglobin function -> hypoxia
- signs are:
- energy level: fatigue
- skin/mucus membrane color: pale or jaundice
- respiratory rate: increased rate and depth
- CNS: dizziness, lethargy
compensation for anemia occurs by
- cardiovascular system (increased heart rate, capillary dilation)
- respiratory system (increased rate & depth)
- renal system (decreased blood flow to kidney triggers renin-angiotensin system)
- hematologic system (bone marrow stimulation: erythropoietin)
classification of anemias by bone marrow activity
- regenerative vs non-regenerative
- reticulocyte count = # immature RBC’s in blood
- regenerative: bone marrow working hard to fix problem
- hemolytic blood disorders, or blood loss
- non-regenerative: bone marrow is the problem
- decreased erythropoiesis
Normal reticulocyte count in %
<1%
Classification of anemias by cell size and color
- macrocytic-normochromic anemias (result from abnormal DNA synthesis and die prematurely, larger than normal)
- Microcytic-hypochromic anemias (disorders of iron metabolism, disorders of porphyrin, heme, or globin synthesis, smaller than normal)
- Normocytic-normochromic anemias (relatively normal size and color, but insufficient number)
macrocytic-normochromic anemias
- pernicious anemia
- folate deficiency
pernicious anemia
- can’t take oral supplement
- cause by malabsorption of vitamin B12
- lack of gastric intrinsic factor which is needed for vitamin B12 absorption
folate deficiency anemia
- lack of folic acid which is essential for RNA and DNA synthesis in the RBC
- humans are totally dependent on dietary intake of folate
Microcytic-hypochromic anemias
- iron deficiency anemia
- lack of iron can also result in gastritis, irritability, headache, numbness, etc.
- 26mg iron needed daily for new RBCs (dietary requirement is 1-2 mg/day)
iron deficiency anemia
- women- pregnancy and menorrhagia
- ulcers, ulcerative colitis, cancer, etc
- medications that cause GI bleeding (NSAIDs)
- insufficient dietary intake of iron
- children < 2 yrs of age
Normocytic-normochromic anemias
- aplastic anemia
- posthemorrhagic anemia
- hemolytic anemia
- anemia of chronic inflammation
aplastic anemia
infiltrative bone marrow disorders
posthemorrhagic anemia
sudden blood loss with N iron stores
hemolytic anemia
auto immune, drugs, toxins, blood parasites
anemia of chronic inflammation
AIDS, SLE, malignancies, renal failure
Sickle cell disease
- homozygous
- production of abnormal hemoglobin S due to an inherited autosomal recessive disorder
- RBC become stretched into an elongated “sickle” shape
- the abnormally shaped RBC’s are very prone to hemolysis
- high incidence of sickle cell trait in Afro-americans and east africans which may provide protection against malaria
Quantitative disorders of leukocyte function
- WBCs
- absolute # or relative number (%)
- decreased bone marrow activity
- premature destruction or WBC’s in circulation
Qualitative disorders of leukocyte function
altered function of WBC’s in inflammation or immune processes
Actual Quantitative WBC disorders
- leukocytosis
- leukopenia
leukocytosis
- increased number WBC
- can be a normal protective response
- can also be caused by pathologic conditions
leukopenia
- decreased # of WBC
- never a normal response, never beneficial
Neutrophil disorders
- neutrophilia
- neutropenia
- agranulocytosis
neutrophilia
=increased number
- seen in early phases of infection (esp. bacterial), inflammation or tissue necrosis
- “left shift”= premature release of somewhat immature neutrophils into the circulation (bands - protective mech.)
- physiologic: stress
- with hemorrhage or hemolysis
- some drugs, metabolic disorders, and neoplasms
neutropenia
- decreased number
- severe prolonged infections
- abnormal distribution and sequestration (collect in one spot)
- decreased bone marrow production
- chemo (doesn’t allow bone marrow to produce), aplastic anemia, radiation
- neupogen: recombinant DNA engineered: stim. bone marrow production (G-CSF) (granulocytes = G)
- increased destruction
- splenomegaly, immune reactions
agranulocytosis
-drastically low neutrophils, eosinophils, and basophils (all 3 granulocytes)
Eosinophil disorders
- eosinophilia
- eosinopenia
eosinophilia
- increased number
- allergic disorders
- dermatologic disorders
- parasite infestation
- some malignancies
- some drugs
eosinopenia
- decreased number
- stress responses
- Cushing’s syndrome (glucocorticoids)
