inflammation and tissue repair

many parts of the chapter that we covered in immunology is cut out!!

when does acute inflammation occur and for how long?

develops within minutes or hours
lasting for several hours or a few days.

the majority of cellular infiltrate during acute inflammation is...

neutrophils

local and systemic signs are more prominent in acute or chronic inflammation?

acute

the majority of cellular infiltrate during chronic inflammation is...

monocytes and lymphocytes

what cells are involved in acute respiratory distress syndrome

neutrophils

what cells and antibodies are involved the most in Asthma?

eosinophils and IgE antibodies

what cells and molecules are involved the most in Glomerulonephritis?

complement system, neutrophils, and monocytes

what is most involved during Septic shock?

cytokines

examples of diseases caused by acute inflammation

acute respiratory distress syndrome, asthma, glomerulonephritis, and septic shock

examples of diseases caused by chronic inflammation

arthritis, asthma, atherosclerosis, and pulmonary fibrosis

causes of inflammation

infections, tissue necrosis, foreign bodies such as splinters, immune reactions such as allergies

5 steps of the inflammatory response

(1) recognition of the injurious agent
(2) recruitment of leukocytes
(3) removal of the agent
(4) regulation (control) of the response
(5) resolution (repair).

what is the exudate state of blood vessels?

increased interendothelial space and vasodilation due to inflammation, leading to protein and leukocyte leakage

what is the transudate state of blood vessels?

increased colloid osmotic pressure, decreased protein synthesis, increased protein loss, protein malnutrition, increased fluid leakage

what is erythema?

redness at the site of inflammation

when the permeability of the microvasculature increases, the outpouring fluid is rich in...

protein

the loss of fluid and increase in vessel diameter leads to...

slower blood flow, increased viscosity of blood, increased concentration of red blood cells in smaller vessels. (vascular congestion)

3 mechanisms responsible for increased vascular permeability

Retraction of endothelial cells (gaps in the vessels) elicited by histamine, bradykinin, leukotrienes, and other chemical mediators.
endothelial injury
Increased transport of fluids and proteins (transcytosis)

differentiate between lymphangitis and lymphadenitis

lymphangitis: inflammation of lymphatic duct
lymphadenitis: inflammation and enlargement of lymph node.
both can be a result of secondary inflammation

Neutrophils and macrophages both originate as...

HSCs in the bone marrow

life span of neutrophils in tissues

1-2 days

life span of inflammatory macrophages

days-weeks

life span of tissue-resident macrophages

years

which cell responds more rapidly to stimuli, neutrophils or macrophages?

neutrophils

which cell can have high levels of nitrous oxide, neutrophils or macrophages?

macrophage

what induces the degranulation of neutrophils?

cytoskeletal rearrangement

which cell produces more cytokines, neutrophils or macrophages?

macrophage

examples of chemoattractants

Bacterial products, Cytokines, complement proteins (particularly C5a), Products of arachidonic acid metabolism

leukocytes rolling on the endothelium is mediated by...

selectins

the firm attachment of leukocytes to the endothelium is mediated by...

integrins

3 steps to phagocytosis

(1) recognition and attachment of the particle to be ingested by the leukocyte
engulfment, with subsequent formation of a phagocytic vacuole
killing or degradation of the ingested material

NETs are often detected in the blood when a patient has...

sepsis

what is responsible for terminating the inflammatory response?

anti-inflammatory mediators (TGF-beta and IL10)

kinins are produced in...

liver

complement proteins are produced in...

liver

what are the arachidonic acid metabolites?

prostaglandins and leukotrienes

example of vasoactive amine and its function

histamine; vasodilation and increased vascular permeability

examples of arachinodic acid metabolites and its function

prostaglandins and leukotrienes; vascular reactions, leukocyte chemotaxis, and other reactions of inflammation

arachidonic acid metabolites are antagonized by...

lipoxins

function of cytokines

leukocyte recruitment and migration

function of complement proteins

generation of multiple breakdown products responsible for leukocyte chemotaxis, opsonization, phagocytosis, cell killing

function of kinins

mediate vascular reaction and activate nociceptors

causes of chronic inflammation

persistent infections, hypersensitivity diseases, prolonged exposure to potentially toxic agents

resident tissue macrophages are made in....

the the fetal liver (yolk sak)

M1 macrophages are activated by...

microbial products such as endotoxin and TNF-gamma

function of M1 macrophages

produce NO and ROS and upregulate lysosomal enzymes which enhance their ability to kill ingested organisms
secrete cytokines that stimulate inflammation.
in host defense against microbes and in many inflammatory reactions.

M2 macrophages are activated by...

IL-4 and IL-13

function of M2 macrophages

tissue repair (They secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis.)

besides M1 macrophages and neutrophils, what cell enhances and amplifies inflammation?

CD4+ t cells

what do the granules in the eosinophil contain that is toxic to parasites?

major basic protein

mast cells are very similar to what cell?

basophil

granulomatous inflammation is what type of hypersensitivity?

type 4

tissue reaction of tuberculosis

caused by Mycobacterium tuberculosis
Caseating granuloma
central necrosis with amorphous granular debris; acid-fast bacilli

tissue reaction of leprosy

Acid-fast bacilli in macrophages; noncaseating granulomas

tissue reaction of syphillis

Gumma: microscopic to grossly visible lesion, enclosing wall of macrophages; plasma cell infiltrate; central cells are necrotic without loss of cellular outline; organisms difficult to identify in tissue

tissue reaction of cat-scratch disease

Rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon

tissue reaction of sarcoidosis

cause is unknown. Noncaseating granulomas with abundant activated macrophages

tissue reaction of crohn's disease

Occasional noncaseating granulomas in the wall of the intestine, with dense chronic inflammatory infiltrate

severe bacterial infections are called

sepsis

clinical/pathological changes in the body as a result of acute-phase response

fever, elevated levels of c-reactive protein, leukocytosis (increased heart rate and blood pressure)

the clinical triad of septic shock

intravascular coagulation, hypotensive shock, and metabolic disturbances including insulin resistance and hyperglycemia.

differentiate between regeneration and scar formation

regeneration: when tissues are able to return to its normal state, and when cell types that can proliferate quickly survive the injury (i.e. epithelial cells)

scar formation: connective tissue deposition when injured tissues are not capable of returning to its original state.

what is fibrosis?

extensive deposition of collagen that occurs in the lungs, liver, kidney, and other organs as a consequence of chronic inflammation, or in the myocardium after extensive ischemic necrosis (infarction).

If fibrosis develops in a tissue space occupied by an inflammatory exudate, it is called....

organization

examples of continuously dividing cells

epithelial cells and hematopoietic cells

examples of nondividing cells

neurons, skeletal and cardiac muscle

liver regeneration is triggered by...

cytokines and growth factors

3 steps of scar formation

inflammation, cell proliferation, remodeling.

what cells are the central cellular players in the repair process?

macrophages (M1 clears necrotic tissue, M2 produces growth factors)

what is angiogenesis?

the process when endothelial and other vascular cells proliferate to form new blood vessels

outline the process of angiogenesis

Vasodilation in response to NO and increased permeability induced by VEGF
breakdown of the basement membrane
Migration of endothelial cells toward the area of tissue injury
Proliferation of endothelial cells behind the tip of migrating cells
Remodeling into capillary tubes
formation of the mature vessel
Suppression of proliferation
deposition of the basement membrane

what growth factor stimulates migration and proliferation of endothelial cells?

VEGF-A, FGF-2, PDGF, TGF-beta

what is notch signaling?

regulates the sprouting and branching of new vessels and thus ensures that the new vessels that are formed have the proper spacing to effectively supply the healing tissue with blood.

factors that impair tissue repair

infection, diabetes, nutritional status, steroids, location of injury (when the exudate is too large to be fully resorbed it undergoes organization, a process during which granulation tissue grows into the exudate, and a fibrous scar ultimately forms)

what are venous leg ulcers?

develop in elderly people as a result of chronic venous hypertension, which may be caused by severe varicose veins or congestive heart failure.
Deposits of hemosiderin resulting from red cell breakdown, chronic inflammation.
These ulcers fail to heal because of poor delivery of oxygen to the site of the ulcer

what are Arterial ulcers?

develop in individuals with atherosclerosis of peripheral arteries
associated with diabetes.
The ischemia results in atrophy and necrosis of the skin and underlying tissues.

what are Pressure sores?

areas of skin ulceration and necrosis of underlying tissues caused by prolonged compression of tissues against a bone, for example, in bedridden, immobile elderly individuals with numerous morbidities.
The lesions are caused by mechanical pressure and local ischemia.

what are diabetic ulcers?

affect lower extremities, particularly feet.
Tissue necrosis and failure to heal are the result of small vessel disease causing ischemia, neuropathy, systemic metabolic abnormalities, and secondary infections.
characterized by epithelial ulceration and extensive granulation tissue in the underlying dermis

In some cases such as post-operation, failure of healing and changes in abdominal pressure may lead to wound rupture. this is called...

dehiscence

what is a hypertrophic scar?

accumulation of excessive amounts of collagen resulting in a raised scar

what is a keloid?

scar tissue growing beyond the boundaries of the original wound and not regressing