ACUTE INFLAMMATION: VASCULAR RESPONSE
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What are the three major goals of the inflammatory response?
1) Increase blood flow to the site of an injury, which is referred to as the vascular response.
2) To alert the products of healing to attend to the site of injury, which is referred to as the cellular response
3) To remove the injured tissue and prepare
What are the initial steps in the inflammatory response?
1) Tissue injury
2) Blood vessel dilation
3) Increased capillary permeability
4) Activation of clotting cascade
5) Continued release and circulation of vasoactive inflammatory mediators
What is the objective of the vascular response?
Attract sufficient products of clotting and healing to the site of injury and to prevent infection.
How do the blood vessels change with the vascular response?
-Blood vessels dilate to accomodate increased blood flow to the site of injury
-The lining of the blood vessels (endothelial cells) becomes more permeable, or loosens to allow cells to easily move from the vessel into the injured tissue.
Why are increased blood flow and fluid needed at the site of injury?
1) Phagocytosis of harmful agents
2) Increased fluid dilutes harmful substances
What is exudate and what purpose does it serve?
Exudate (watery fluid) that accumulates at the site of injury has a high protein and leukocyte concentration. This is a sure sign that the vessels have become more permeable and that cells active in phagocytosis are present and are ready to fend off micro
What is the purpose of the inflammatory mediators?
They facilitate the process of widening and loosening of the blood vessels at the site of injury. They are located in many cells, including platelets, mast cells, basophils, neutrophils, endothelial cells, monocytes, and macrophages. They are most commonl
IM'S WITHIN WBCs: What is a mast cell, what is it's purpose, and where are they primarily located?
-An important inflammatory mediator; mast cells are leukocytes that are housed throughout the connective tissues of the body and near all blood vessels.
-This placement allows for rapid response directly at the site of injury.
-Responsible for the product
IM'S WITHIN PLASMA: What is responsible for the activation and deactivation of inflammatory mediators that circulate in the plasma?
Three major interrelated pathways: complement, clotting, and kinin.
-Compliment: chemotaxis (moving cells to the site of injury), opsonization (making bacteria vulnerable to phagocytosis), cell lysis (destruction)
-Clotting: promotes and suppresses coagul
ACUTE INFLAMMATION: CELLULAR RESPONSE
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What are the three steps that regulate the cellular response?
-Also regulated by inflammatory mediators.
1) Chemotaxis: process of moving certain cells to site of injury
2) Cellular Adherence: attraction and binding
3) Cellular Migration: through diapedesis, cells can move between and through endothelial junctions.
What does the cellular response depend on?
The ability of cells, primarily leukocytes, erythrocytes, and platelets, to migrate across endothelial cells and get to the exact site of the injury.
What is the function of the different white blood cells?
-Leukocyte: phagocytosis and removal of dead tissue
-Neutrophil: earliest phagocytic responder
-Macrophage: long-lived phagocytes associated with chronic inflammation
What are the cardinal signs (local manifestations) of inflammation?
Erythema, heat, swelling, pain, and loss of function.
What are some systemic manifestations related to the inflammatory response?
Fever, leukocytosis, higher percentage of plasma proteins.
What are the initial treatment principles for acute inflammation?
1. Decrease blood flow to the local area
2. Decrease swelling
3. Block the action of various inflammatory mediators
4. Decrease pain
Goal of treatment: minimize the damage to healthy, unaffected tissue and promote rapid healing.
Nonpharmacologic treatment
HEALING AND TISSUE REPAIR
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What is the goal of healing and tissue repair?
To cover the wound, clear debris, and restore the structural integrity of the injured area. Divided into three phases: inflammatory phase, proliferative phase, and the remodeling phase.
Covering the Wound
Inflammatory mediators released from platelets and other cells constrict blood vessels and form a clot at the site. A protective scab is formed from dried blood and exudate. Called a 'thrombus.' Role of the thrombus is to prevent additional harmful substa
Clearing the Debris
The inflammatory response activates neutrophils and later macrophages to engulf, digest, and remove harmful substances and debris.
Restoring Structural Integrity
Growth factors and matrix proteins are responsible for rebuilding the extracellular matrix (includes basement membrane and connective tissue layers). Excess collagen production leads to tissue fibrosis and can result in scarring. Granulation tissue forms
Restoring Functional Integrity
Accomplished by one of three processes: resolution (minimal disruption of cells), regeneration (proliferation, differentiation and diapedesis of new cells), or replacement (scar tissue forms when regeneration isn't possible).
What are some conditions that promote wound healing?
-Wound healing depends on adequacy of vascular and cellular inflammatory responses, reformation of ECM, and regeneration of those cells.
-Adequate dietary intake of proteins, carbs, fats, vitamins and minerals.
-Adequate blood flow.
Describe and give an example of primary intention.
Wounds edges are approximated (lined up) or close together, such as that which occurs with a paper cut or surgical incision. The wound is basically closed with all areas of the wound connecting and healing simultaneously.
Describe and give an example of secondary intention.
Larger, open, crater-like wounds that heal from the bottom up. Examples are burns, gun shot wounds, etc.
What are some complication of healing and tissue repair?
Infection, ulceration, dehiscence, keloid development, adhesions.
CHRONIC INFLAMMATION
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Define Chronic Inflammation
A persistant or recurrent state of inflammation lasting several weeks or longer. This state occurs when the acute inflammatory and immune responses are unsuccessful.
What cells are more prominent in chronic inflammatory states?
Monocytes (immature macrophages), macrophages, and lymphocytes that have a long-lasting activity. Proteinases are released by macrophages and non discriminatorily break down dead tissue. Fibroblasts are responsible for collagen development, which contribu
What can chronic inflammation sometimes result in?
Granulomas (nodular inflammatory lesions that encase harmful substances). They form when the injury is too difficult to control by the usual inflammatory/immune mechanisms. Serves to protect surrounding tissue from further damage.
What are the general manifestations of chronic inflammation?
Similar to acute inflammation: redness, heat, pain, swelling, and loss of function. Systemic manifestations include fever, malaise, anemia, fatigue, anorexia, weight loss, or weakness.
How would you treat symptoms of chronic inflammation?
Treatment is aimed at removing the source of injury if possible and managing symptoms. Anti-inflammatory, analgesic, or immune-modifying drugs are often needed.
CLINICAL MODELS
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BURN INJURIES: What is a superficial partial-thickness burn?
AKA First degree burns; damage to the epidermis. Vasodilation of the dermal blood vessels and increased capillary permeability cause erythema, pain, and swelling. They do not result in cell necrosis or scarring. Healing occurs within a week.
Example: Mild
BURN INJURIES: What is a deep partial-thickness burn?
AKA Second degree burns; damage to the epidermal skin layers and penetrates some dermal skin layers. Epidermal and dermal layers separate, fluid accumulates between these layers, and blisters form. Can lead to scarring. Healing occurs within 2-4 weeks.
Ex
BURN INJURIES: What is full-thickness burn?
AKA Third degree burn; damage to the epidermis and dermis and can penetrate subcutaneous layers as well. Destruction of blood vessels is also common as heat cauterizes the vessels. Scarring is often extensive. Loss of elasticity is evidenced by contractur
BURN INJURIES: What are the potential complications that arise from full-thickness burns?
1) Body fluid shifts that cause impaired blood circulation, edema, and dehydration
2) Microorganism invasion that leads to infection
3) Overwhelming metabolic demands that increase the risk for malnutrition
4) Problems with temperature regulation
BURN INJURIES: What are the clinical manifestations with burn injuries?
-Superficial partial thickness: erythema, warmth, pain, swelling, loss of function
-Deep partial thickness: blistering, erythema, warmth, pain, edema, and serous exudate
-Full thickness: erythema, eschar formation, edema, exudate, no pain
BURN INJURIES: What are the diagnostic criteria?
Wound depths are classified according to affected tissue layers. Surface area is determined by using the rule of nines.
BURN INJURIES: What is the treatment for burn injuries?
Initial treatment for minor and moderate burns requires removing the source of injury and stopping the burning process. Minor burns are cleansed with tepid water and sometimes covered with antimicrobial ointment and gauze (when changed, aids in debridemen
RA: What is arthritis?
Generic term for degeneration or inflammation of the joints and refers to a group of diseases of varying pathogenesis.
RA: What is rheumatoid arthritis?
Systemic autoimmune disease characterized by chronic inflammation and hyperplasia of the synovial membranes with increased synovial exudate, leading to swelling and thickening of the synovial membranes, joint erosion, and pain.
RA: What is the pathophysiology of RA?
Exact cause unknown. The triggering injury in RA that leads to inflammation is difficult to pinpoint and is often never determined. In response to this inflammation, lymphocytes and plasma cells form antibodies in the synovial membrane and cartilage. The
RA: What are the clinical manifestations of RA?
Erythema, pain, swelling, warmth, and decreased mobility, pain, stiffness. Malalignment or deviation of symmetrical joints is common. Systemic manifestations include low-grade fever, fatigue, anorexia, weight loss, and weakness.
RA: What are the diagnostic criteria for RA?
There are no definitive tests that exist to diagnose RA. Diagnosis is based on history and physical examination. The presence of RF appears to have the greatest advantage in diagnosing early RA compared with multiple other autoantibody tests.
RA: What is the proposed treatment for RA?
Combination of pharmacologic and nonpharmacologic measures. Medications employed include anti-inflammatory drugs, immunosuppressive drugs, and medications that otherwise induce remission. Active rest, physical therapy, and the use of splints and other dev
ACUTE GASTRITIS: What is gastritis?
Inflammation of the lining of the stomach, or gastric mucosa, thereby impairing gastric function.
ACUTE GASTRITIS: What is the pathophysiology of gastritis?
Exposure to gastric irritants inhibits the production of gastric mucosa and makes the mucosa more vulnerable to acidic stomach contents. Epithelial cells become be necrotic. The underlying gastric tissue is eroded. Hemorrhaging often occurs.
ACUTE GASTRITIS: What are the clinical manifestations of gastritis?
Mild to severe abdominal pain, which can be accompanied by indigestion, loss of appetite, nausea, vomiting, and hiccups. Hematemesis, or vomiting blood, can occur.
ACUTE GASTRITIS: What are the diagnostic criteria?
Take a careful history which might reveal use of aspirin or NSAIDs. Physical examination may reveal abdominal tenderness. Direct visualization of the stomach with an endoscope is needed to visualize ulcers. Stool analysis for occult blood.
ACUTE GASTRITIS: What is the proposed treatment?
Begins with the removal of the gastric irritant. Medications are then needed temporarily to buffer gastric acid and/or decrease gastric acid production. Most acute gastritis improves rapidly when the irritant is removed and treatment is initiated.
CHRONIC GASTRITIS H. PYLORI: What is the pathophysiology?
H. pylori is ingested and multiplies on the epithelial surface cells and mucus barrier. Ir produces enzymes that neutralize gastric acid and the microorganism is able to survive. They then produce toxins that can destroy the mucosal barrier. In response t
CHRONIC GASTRITIS H. PYLORI: What are the clinical manifestations?
Dyspepsia (nausea and heartburn), loss of appetite, vomiting. Most infected people are asymptomatic carriers.
CHRONIC GASTRITIS H. PYLORI: What are the diagnostic criteria?
Direct endoscopic visualization and biopsy of gastric tissue. Breath test can be given to detect the presence of an enzyme given off when the bacterium converts urea to carbon dioxide in the lungs. Protein antibodies against H. pylori can also be detected
CHRONIC GASTRITIS H. PYLORI: What is the proposed treatment?
Multiple antibiotics are needed along with proton pump inhibitors or bismuth, which have antimicrobial properties and raise gastric pH.
CHRONIC GASTRITIS AUTOIMMUNE: What is chronic gastritis as an autoimmune disorder?
Antibodies are produced against gastric parietal cells or intrinsic factor.
CHRONIC GASTRITIS AUTOIMMUNE: What is the pathophysiology?
When antibodies are formed against parietal cells, gastric acid secretion is impaired. IF is needed for absorption of B12 which is critical in the promotion of DNA synthesis in RBCs. Impairment of this process leads to low RBCs and low Hb = pernicious ane
CHRONIC GASTRITIS AUTOIMMUNE: What are the clinical manifestations?
Can be asymptomatic. The presence of pernicious anemia may be the first clue. Manifestations of anemia include weakness, light-headedness, pale mucous membranes, and fatigue. Can also include dyspepsia, vague abdominal pain, nausea, vomiting, and anorexia
CHRONIC GASTRITIS AUTOIMMUNE: What are the diagnostic criteria?
Can be determined only with histologic examination of the gastric mucosa. Biopsy samples are obtained and analyzed for changes in the cells. Antiparietal or anti-IF antibodies may be present in the blood. Also, a low B12 level will be noted in the blood.
CHRONIC GASTRITIS AUTOIMMUNE: What is the proposed treatment?
Aimed at blocking the autoimmune attack against the parietal cells. The administration of B12 IM injection monthly is needed to facilitate absorption.
IBD: What is inflammatory bowel disease?
Chronic inflammatory processes most commonly in the small and large intestine, but it can occur anywhere along the GI tract from the mouth to the anus. The most common forms of IBD are Crohn's Disease and Ulcerative Colitis.
CROHN'S: What is Crohn's Disease?
It is recurrent and characterized by a granulomatous inflammatory process. Can be found anywhere along the GI tract. The small intestine and ascending colon, particularly the mucosal layers, are most often affected.
CROHN'S: What is the pathophysiology?
Exact cause unknown. Chronic inflammation occurs in patchy segments (called 'skip lesions') of the intestine and penetrates all layers of those segments. As the infected segments become further inflamed, interior surfaces thicken due to excessive edema, f
CROHN'S: What are the clinical manifestations?
Related to rapid stool transit time, intestinal edema and fibrosis, and loss of absorptive function: Abdominal pain, intermittent non-bloody diarrhea, malnutrition, occult blood in stool. If colon mucosal layer is involved, diarrhea may contain mucus, blo
CROHN'S: What are the diagnostic criteria?
Patient history, physical examination, and diagnostic tests. Direct visualization with an endoscope (sigmoidoscopy) or with radiographs show a cobblestone pattern to the mucosa with alternating affected and unaffected areas of inflammation.
CROHN'S: What is the proposed treatment?
Treatment is symptomatic. Medications that suppress inflammatory and immune response are often used. Dietary changes are required and foods that irritate the bowel should be avoided. Diet high in calories and protein and low in fat and fiber (during exace
ULCERATIVE COLITIS: What is ulcerative colitis?
Another chronic inflammatory condition of the colon. Found exclusively in the large intestine and does not affect other areas of the GI tract.
ULCERATIVE COLITIS: What is the pathophysiology?
Exact cause unknown. Autoimmunity has been implicated. Does not skip areas of the colon. Inflammation invades the superficial mucosa and causes friability (state where tissue readily bleeds). Hemorrhagic legions in the crypts of Lieberkuhn can form into a
ULCERATIVE COLITIS: What are the clinical manifestations?
Diarrhea, often with rectal bleeding, is the most common. Abdominal pain, fever, weakness, fatigue, and anemia can also occur. Functional losses are related to inflammation, impaired water and electrolyte absorption and notable with extensive disease.
ULCERATIVE COLITS: What is the diagnostic criteria?
Diagnosed through endoscopy. Severity is based on the number of bowel movements with rectal bleeding and the presence of systemic manifestations:
-Mild: <4 BMs/day; no systemics
-Moderate: >4 BMs/day; no systemics
-Severe: >4 BMs/day; systemics and low bl
ULCERATIVE COLITIS: What is the proposed treatment?
Symptomatic. Anti-inflammatory, anti-diarrheal, and immunosuppressive mediations sometimes used. Healthy diet and adequate fluid intake recommended. Avoidance of irritating foods. Surgery may be needed if ineffective or if perforation/obstruction occurs.
Summary of Crohn's Disease
-Location: small intestine and ascending colon
-Pattern: skip lesions
-Depth: primarily submucosal
-Diarrhea: watery
-Abdominal pain: yes
-Bowel obstruction: common
-Cancer risk: increased
Summary of Ulcerative Colitis
-Location: descending colon
-Pattern: continuous
-Depth: Primarily mucosal
-Diarrhea: bloody
-Abdominal pain: yes
-Bowel obstruction: uncommon
-Cancer risk: higher risk than with Crohn's
QUIZ QUESTIONS
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1. You get a paper cut and experience pain at the site. This response is related to-
Increased perfusion at the site.
2. Inflammation is ultimately needed to-
Prepare the site for healing
3. A wound is 6cm x 6cm x 4cm. A wound with these dimensions needs to heal through-
Secondary intention
4. A major difference between the acute and chronic inflammatory response is that in chronic inflammation-
Granulomas form around certain invaders
5. Which is not a local manifestation of acute inflammation?
Leukocytosis
6. Depth of injury is important to determine with burns. You are in the sun too long without sunscreen and develop redness and blistering on your face, chest, and back. What depth of burn did you experience?
Deep partial-thickness burn
7. The hospitalized burn patient wants to know why you need to remove his dressings every day. It is painful and he wants to avoid uncovering his burn injury. You explain that removing the dressings promotes-
Debridement
8. What is the one definitive test to diagnoses rheumatoid arthritis?
One test is not definitive
9. Which of the following is the most common cause of acute gastritis?
Ingestion of aspirin, alcohol, or other chemicals
10. Why is Crohn's disease more likely to cause intestinal obstruction than ulcerative colitis?
Crohn's disease causes granulomas to form in the submucosal layer.