PATHO CH 11

Inflammation

the immune response of tissues to bodily injury (e.g., trauma, heat, radiation, chemicals) or foreign substances such as infectious agents or allergic antigens. inflammation may be acute or chronic

what are the goals of inflammation?

to ensure survival of the body, destroy or kills the invading organism, and rebuild or repair damaged tissue

list four concepts related to inflammation

comfort, infection, elimination, mobility, metabolism, oxygenation

compare and contrast inflammation and infection

infection is an invasion of the body by an organism that causes disease, such as a virus. inflammation if the body’s response to an infection. infections are not always the cause of inflammation

innate immunity

occurs naturally and is the body’s first line of defense against an injury or foreign substance

components of the innate immune system

• physical barriers (skin, mucous membranes, mucus)

• enzymes in epithelial and phagocytic cells

• inflammation relates proteins in the blood such as C-reactive protein

• toll-like receptors that help to sense pathogens and signal a response

• cells that release inflammatory mediators (cytokines)

• antimicrobial peptides

• phagocytes

C-reactive protein (CRP)

a protein found in plasma that increases in response to inflammation. measuring changes in CRP over time can be helpful in monitoring disease progression or response to treatment

signs of inflammation under innate immunity

redness, swelling, heat, pain

acquired or adaptive immunity

form of immunity that is continually refined throughout the life of an individual and is highly specific to a pathogen. it allows an individual, once exposed to a pathogen, to have long-lasting protection against that particular pathogen

characteristics of acute inflammation

• fast onset and relatively short duration

• neutrophils increase

• mild and self-limiting

• local and systemic signs prominent

characteristics of chronic inflammation

• slow onset: over days to weeks, persists for 2 weeks

• increase in monocytes, macrophages, lymphocytes

• persistent and progressive

• local and systemic signs: less severe

examples of acute inflammatory disorders

infections, tissue injury (trauma, physical, or chemical), response to foreign bodies, and immune reactions (hypersensitivity), appendicitis, strep throat, ear infections, lacerations

examples of chronic inflammatory disorders

diabetes mellitus, atherosclerosis, copd

cardinal signs of inflammation

redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function

causes of acute inflammation

• infections (bacterial, viral, fungal, parasitic)

• tissue necrosis associated with ischemia (e.g, myocardial infarction, ischemic stroke), trauma, physical or chemical injury

• reaction to foreign bodies (splinter, prosthesis)

• immune reaction (allergic reaction)

vasodilation

enlargement of vessel wall lumen, often occurring as part of the inflammatory cascade, permitting increased blood flow to the injured area

Phagocytosis

• recognition of the pathogen to be destroyed by the leukocyte

• engulfment of the pathogen by the leukocyte

• killing of the pathogen

main types of mediators related to acute inflammation

• vasoactive amines (histamine)

• lipid mediators (prostaglandins and luekotrienes)

• cytokines and chemokines

• lysosomal components (oxygen free radicals, nitric oxide)

macrophages, mast cells, T lymphocytes

regulates immune cells, induces fever, cachexia

macrophages, endothelial cells, epithelial cells

group of 11 cytokines with both pro-inflammatory and anti-inflammatory properties

macrophages

has both pro-inflammatory and anti-inflammatory effects; plays a role in mediating fever

t lymphocytes

mediates pro-inflammatory response; associated with allergic reactions

three primary plasma protein systems

1) complement system

2) coagulation system

3) kenin system

complement system

• 20 complement proteins that normally circulate in the blood in an inactive form are activated in response to inflammation

• can be activated by either innate or acquired immune response

• can be triggered through three different pathways: classical, lectin, and alternative

• all three pathways amplify the inflammatory process to increase vascular permeability, enhance phagocytosis, and promote vasodilation

coagulation system

• bidirectional relationship between inflammation and coagulation

• Inflammatory mediators like cytokines can activate coagulation

kallikrein-kenin system

• a cascade of metabolic events that interacts with the clotting system

• kinins: potent vasodilators, regulators of the inflammatory process, and are also involved in pain sensation and cell growth

what are examples of lymphocytes?

T cells, B cells and natural killer cells

what are some examples of myeloid leukocytes?

neutrophils, eosinophils, basophils/mast cells, monocytes, macrophages, and dendritic cells

pattern recognition receptors

receptors present on host defense cells, such as phagocytic and dendritic cells, that recognize pathogen-associated molecular patterns and mediate an instant response against the invading microorganism

primary method by which inflammation is regulated

via anti-inflammatory pathways

ex. the hypothalamic-pituitary-adrenal (HPA) axis, which controls the release of glucocorticoids and anti-inflammory cytokines

another ex. the sympathetic nervous system (adrenergic system ) and the parasympathetic nervous system (cholinergic system), play critical roles in regulating the inflammatory response and the inflammatory reflex

inflammatory process is induced by factors that are

• exogenous = pathogens

• and that are

• endogenous = chemicals released from the injured cells

explain how acute inflammation resolves

by the regulation and termination of inflammation, which involve several well integrated processed that help return the system to homeostasis. anti-inflammatory pathways are a primary method to regulate the acute inflammation process.

the spleen, thymus, bone marrow, and lymph nodes are innervated by which regulatory pathway?

SNS

morphology of inflammation

1) serous inflammation

2) fibrinous inflammation

3) purulent (supportive) inflammation or abscess

4) ulcers

serous inflammation

• fluid accumulation as a result of tissue injury that does not contain many cells

• not severe and is reabsorbed by the lymphatic system

• ex. blister from burn

fibrinous inflammation

• result of increased vascular permeability that allows fluid with large proteins (fibrinogen) to leak out of the vessels into the surrounding tissue

• ex. fibrinous pericarditis

purulent (suppurative) inflammation

• formation of pus, which contains many neutrophils, cellular debris, and edema fluid

• ex. pyogenic bacteria such as staphylococcus commonly causes pus formation

• ex. appendicitis and suppurative tonsillitis are ex of acute supportive inflammation

ulceration inflammation

• results from very severe inflammation and is a local defect caused by necrosis of cells and sloughing of necrotic tissue

• ex. gastric ulceration

• not all ulcers are caused by inflammation

resolution

no permanent destruction of normal tissue

ex. complete wound healing and recovery from the common cold

fibrosis inflammation

• may develop is there is significant tissue damage

• scarring occurs when epithelial cells are replaced by fibroblasts

abscess formation

abscess, usually caused by bacteria, is a cavity that contains pus. redness and edema often extend around the abscess in the surrounding tissues

causes of chronic inflammation

• unresolved or repeated acute infections

• autoimmune diseases

• prolonged exposure to irritants (silicosis)

granulomatous formation

• distinct type of chronic inflammation that is characterized by the formation of granulation tissue

• ex. TB, histoplasmosis, syphilis, sarcoidosis, and schistosomiasis

• three cell types involved: epithelioid cells, multinucleated (langhans) giant cells, lymphocytes

what is the primary or most common cell involved in the leukocyte infiltration, tissue damage, and fibrosis associated with chronic inflammation?

macrophages

what factors put a person at risk for developing chronic inflammation?

• poor blood supply

• malnutrition

• abnormal neutrophil function

• prolonged use of anti-inflammatory medications such as corticosteroids

acute-phase response

the physiologic changes that occur shortly after an injury or beginning of an infectious process that results from cytokine-induced systemic reactions

what are the primary signs of systemic inflammation?

• fever (pyrexia): result of specific cytokines being released from neutrophils and macrophages (NSAID drugs reduce fever by inhibiting prostaglandin synthesis)

• an increase in serum proteins: most common serum proteins are CRP, fibrinogen, and serum amyloid.(CRP can be used to clinically determine the degree to which an individual may be experiencing shoulder pain)

• leukocytosis: increased neutrophils suggest acute inflammation while increased monocytes indicate chronic inflammation (a greater proportion of immature neutrophils compared to mature neutrophils is known as a shift to the left)

systemic inflammatory response syndrome (SIRS)

an inflammatory state, related to sepsis, that affects the entire body in which there is abnormal regulation of cytokines. criteria for diagnosis of SIRS in adults include demonstrating at least two of the following: 1) body temperature less than 36°C or more than 38.5°C, (2) heart rate greater than 90 beats per minute, (3) tachypnea greater than 20 breaths per minute or arterial partial pressure of carbon dioxide less than 32 mmHg, (4) white blood cell count less than 4000 cells/mm3 or greater than 12,000 cells/mm3 or the presence of more than 10% immature neutrophils.

list three potential signs of systemic inflammation

infection, pulmonary embolism, anaphylaxis, and adrenal insufficiency

what do organ-specific and tissue-specific autoimmune disorders have in common?

both involve the body’s perception that part of itself is foreign, leading the body to mount an immune response to the normal tissue

organ-specific autoimmune disorders

Hashimoto’s thyroiditis (thyroid gland), pernicious anemia (stomach), addison’s disease (adrenal glands), and type 1 diabetes (pancreas)

what can happen if dead cells are not sufficiently cleared?

an accumulation of dead cells may leak intracellular antigens and DNA, which can provoke an autoimmune response, as occurs in systemic lupus erythematosus

chronic inflammation is an important contributing factor in several disorders such as

alzheimer disease, asthma, atherosclerosis, depression, diabetes mellitus, and obesity

alzheimer disease

a type of dementia, progressive neurodegenerative disorder, hallmarked by the accumulation of beta-amyloid peptide plaques and neurofibrillary tangles in the brain

atherosclerosis

a chronic inflammatory response (involving both innate and acquired immunity systems) of leukocytes (mostly monocytes and macrophages) to low-density lipoproteins particles in the walls of the arteries that begins in childhood

identify commonalities between the disorders that are associated with chronic inflammation

one similarity is that the disorders are thought to be initiated by a stimulus, such as a virus, bacteria, or psychosocial stressor, that activates the immune response. another similarity that some of the disorders have in common is the presence of obesity. many of the disorders result from presence of cytokines

explain treatments to reduce inflammation

include Rest, Ice, Compression and Elevation (RICE) for injuries; phytochemicals found in plant-based foods; antioxidants from fruits, vegetables, whole grains and omega-3 fatty acids; and decreased intake of refined sugar

describe common pharmacologic treatments for inflammation

aspirin, acetaminophen, NSAID, cyclooxygenase inhibitors, and prednisone

name five foods that are identified as phytochemicals which confer anti-inflammatory actions in the human body

carrots, apples, onion, broccoli, and legumes

indicator of acute viral infection

lymphocytes

indicator of acute bacterial infection

neutrophils

associated with allergic reactions

basophils