Ch. 3 - Inflammation and Tissue Repair

inflammation

inflammation

reddening, swelling, warm, painful tissue necessary to isolate the injury, remove damaged cells, and remove infection causing microorganisms

regeneration

Tissue repair and restoration of normal function

acute inflammation

Immediate expected body response to injury

chronic inflammation

an altered inflammatory response due to unrelenting injury

lines of defense

• first line = skin and mucous membranes

• second line = inflammatory response

• third line = immune response

first line of defense

Involves surface and chemical barriers; skin and mucous membranes

skin

Protective, physical barrier against harmful substances in the external environment

mucous membranes

Areas not covered by skin are protected with chemically coated membranes to neutralize or destroy invaders

second line of defense

Kicks in one first line fails; nonspecific, inflammatory response where vasodilation causes erythema/ swelling + phagocytes act to engulf the harmful substance

third line of defense

Activated through the immune response; wages a specific defense depending on the type of invader

acute inflammation

Adaptive response triggered by tissue injury and is essential for healing

goals of acute inflammation

1. To increase blood flow to the site of injury (vascular response)

2. to alert the products of healing to attend to the side of injury (cellular response)

3. To remove injured tissue and prepare the site for repair and healing

acute information example

papercut

• the cut bleeds

• WBC eat whatever pathogen enters the break in skin

• the site is prepared for healing and eventually closes up

vascular response

To increase blood flow to the site of injury; clotting

goal of vascular response

To attract sufficient products of clotting, and healing to the side of injury and prevent infection

blood vessel accommodations during vascular response

• Endothelial cells lining the blood vessels help them to dilate to accommodate increased blood flow to the side of injury

• Lining of the vessel becomes more permeable to allow cells to easily move from the vessel to the injured tissue

reasons for increase blood fluid at the site of injury

1. Blood contains cells active in phagocytosis, and other cells essential to promoting healing and developing immune response

2. Increased fluid dilutes harmful substances at the site of injury

exudate

• layer of watery fluid accumulating at the site of injury with high protein and leukocyte concentrations

• is a sure sign of increased vessel permeability and phagocytosis beginning

inflammatory mediators (definition)

• Potent chemicals/vasoactive inflammatory mediators

• facilitate the process of widening the blood vessels at the side of injury

inflammatory mediators

• cells

  • platelets

  • mast cells

  • neutrophils

  • basophils

  • endothelial cells

  • monocytes

  • macrophages

• blood plasma

  • complement system

  • clotting

  • kinin

WBC inflammatory mediators

• mast cells

  • leukocytes that rapidly respond to the site of injury and rapidly produce/release inflammatory mediators

• basophils

  • Release, histamine, leukotrienes and prostaglandins

• cytokines

  • Regulate onset of vasodilation and vascular permeability

• lymphocytes, monocytes, macrophages

  • trigger, enhance, and stop inflammatory responses

platelet inflammatory mediators

• serotonin

  • causes vasodilation and increases vascular permeability to allow healing cells to arrive

plasma inflammatory mediators

• compliment system

  • destroys and removes microorganisms

• kinin system

  • amplifies inflammatory responses through hormone release

• clotting system

  • Promotes clotting through a cascade of clotting factors

cellular response

• after vessel dilation ,cells essential for healing are needed at the site of injury

• includes chemotaxis, cellular, adherence, and cellular migration

chemotaxis

the process of moving certain cells to the site of injury through chemotactic factors attracting specific cell types

cellular adherence

• attraction and binding of cells constantly moving through the vascular system

• regulated by chemotactic factors from endothelial cells and receptors

cellular migration

White blood cells, erythrocytes, and platelets move across endothelial cells to repair injury

diapedesis

When cells move through and between endothelial junctions

cardinal signs of inflammation

Erythema, heat, edema, pain, and loss of function

lymphadenitis

Inflammation of nearby lymph nodes

systemic manifestations of information

• fever

• leukocytosis (elevated WBC count)

• increased plasma proteins

labs used to detect information

• WBC count > 10,000/mm^3

• altered WBC differential (% of each cell type)

• erythrocyte sedimentation rate (ESR) >100mm/h

• c-reactive protein (CRP) 0.10mg/L = significant inflammatory disease

• decreased prothrombin time = faster coagulation time

• elevated fibrinogen

initial treatment principles for inflammation

1. Reduce blood flow to local area

2. Decrease swelling

3. Block the action of inflammatory mediators (ex. glucocorticoids)

4. Decrease pain (ex. NSAIDs; asprin)

stages of healing and tissue repair

1. inflammatory phase

2. proliferative phase

3. remodeling phase

inflammatory phase

• Acute inflammatory response kicks in and wound is sealed

• wound is sealed by a protective clot, followed by a scab

proliferative phase

• Debris is cleared through neutrophil and macrophage activity (engulfs and digests)

• Extracellular matrix of cells are rebuilt to support cell structure, move cells, store growth factors, and support functional tissue

remodeling phase

restoration of functional activity

• Fibroblasts produce and replace connective tissue

• fibroblasts move to support the constructive phase and manufactures collagen

keloids

Hypertrophic scars resulting from excess collagen at the site of injury; tend to grow back and worse

diet promoting wound healing

• adequate water intake

• adequate proteins, carbs, fats, vitamins, and minerals

  • vitamin A

  • vitamin C

primary intention

• Occurs with wound edges that line up (ex. papercut)

• The wound is closed with all areas of the wound connecting and healing simultaneously

  • Decreased risk of infection and scarring

secondary intention

• Happens with large, open, crater-like wounds

• wounds heal bottom up in a slower process

  • Increased risk of infection and scarring

chronic inflammation

• Persistent, or reoccurring state of inflammation, lasting weeks or longer

• can relate to unrelenting injury, persistent infectious process, or autoimmune conditions

cells of chronic inflammation

• Monocytes

• macrophages

• lymphocytes

• proteinases

• fibroblasts

granulomas

• Nodular inflammatory lesions that encase harmful substances

• form when injury is too difficult to control

• ex. foreign body or certain microorganisms

pancreatitis

• Inflammation of the pancreas, resulting in destruction of the pancreas by pancreatic enzymes

• Digestive enzymes, which usually only activate in the intestines, attack the pancreas when inflamed causing self-destruction to auto-ingestion

• More chronic cases; mostly men

functions of the pancreas

• production of insulin and glucagon

• production and secretion of digestive enzymes for metabolism

• production and secretion of digestive enzymes to the intestines

• pancreatic enzymes mix with bile to digest food

acute pancreatitis

• sudden inflammation of the pancreas that resolves within a few days of treatment

• Occurs with injury to cells producing digestive enzymes, the pancreatic duct, or the digestive enzyme feedback mechanism

causes of acute pancreatitis

• duct blockage by gallstones (hardened bile)

• alcoholism

  • triggers premature enzyme activation and secretion

• inflammatory response

clinical manifestations of acute pancreatitis

• Fever

• pain in the upper abdominal, epigastric, and back areas

• tachycardia

• hypotension

• GI:

  • nausea

  • vomitting

  • anorexia

  • diarrhea

  • bruised umbilicus (cullen)

  • abdominal tenderness

  • guarding

  • ecchymotic sides (greys turner)

treatment of acute pancreatitis

• aggressive IV hydration

• nutritional support

• analgesics

• surgical removal of gall stones

• monitoring of mental status, blood glucose, electrolytes, s/s if infection, respiratory status, and pain

• prevention of shock, renal failure, or systemic multi-organ failure

chronic pancreatitis

• An ongoing inflammatory process of the pancreas with irreversible, cellular and tissue changes

• Lasts more than six months after acute episode

causes of chronic pancreatitis

• chronic alcohol abuse

• autoimmune/hereditary disease

• gallstones

• cystic fibrosis

• high triglycerides

• certain medications

pathophysiology of alcohol abuse on chronic pancreatitis

• causes duct obstructions due to enzyme and protein accumulation

• obstruction = ischemia and loss of cell function

• oxidative stress promotes greater cell injury and organ damage

pathophysiology of autoimmunity on chronic pancreatitis

high levels of circulating antibodies cause pancreatic enlargement and narrowing of ducts

clinical manifestations of chronic pancreatitis

• constant pain radiating from upper abdomen to back

  • debilitating pain

• malabsorption of food

  • diarrhea

  • fatty stool

  • weight loss

• diabetes

treatment of chronic pancreatitis

• pain management

• nutritional support

• pancreatic enzyme pills

• insulin

• low fat diet

• surgery (to restore drainage and remove blockage)

• alcohol abuse cessation

• smoking cessation

• treatment adherence

diagnostic criteria for pancreatitis

• history and physical

• CBC

• ESR

• CRP >10 mg/dL

• elevated serum amylase within 12 hours of onset; normal to low due to loss of function (in chronic)

• elevated lipase within first 24 hours

diagnostic tests for pancreatitis

• pancreatic function test (tests digestive enzyme levels)

• glucose tolerance test (measures damage to insulin making cells)

• ultrasound

• CT scan

• ERCP (gold standard; looks at obstructions in pathways)

• endoscopic ultrasound

• biopsy

rheumatoid arthritis

• a systemic auto-immune disease characterized by chronic inflammation and hyperplasia of synovial membranes

• leads to swelling and thickening of synovial membranes, join erosion, and pain

causes of rheumatoid arthritis

• genetic susceptibility

• an autoimmune triggering event

• development of autoimmunity against synovial cells

• triggered exaggerated inflammatory response

• progressive damage

  • pannus formation

  • cartilage erosion

  • fibrosis

  • joint fixation and deformity

pannus

• granulation tissue, that forms over the inflamed synovium and cartilage as a result of accelerated angiogenesis

• produces enzymes that break down cartilage and erodes bone

• deprives cartilage of nutrients

clinical manifestations of rheumatoid arthritis

• symmetric s/s

• erythema

• pain

• swelling

• lowgrade fever

• anorexia

• warmth

• decreased mobility

• pinky deviation

• malalignment

• weight loss

• weakness

diagnostic criteria for rheumatoid arthritis

• no definitive test

• hx and physical

• elevated serum ESR

• RF significant for antibodies against IgG

• antinuclear antibody

treatment of rheumatoid arthritis

pharmacologic

• anti-inflammatories

• immunosuppressants

• medications to induce remission

• steroids

nonpharmacologic

• rest/activity

• physical therapy

• splints

• hot/cold therapy

• remove stress

• surgery