Chapter 3 Flashcards
What is the effect of lipoxins
Suppress inflammation and recruitment of leukocytes
What is the composition of transudate
Low protein concentration, no cellular material, and low specific gravity (close to a super filtrate of plasma)
What are the characteristic of chronic inflammation morphology
1) Infiltration of mononuclear cells (monocytes,lymphocytes)
2) Tissue destruction
3) Attempts at healing (angiogenesis and fibrosis)
What is the mechanism of action of asparin
Acetylates and inactivations cyclooxygenases (COX 1&2)
What is the effect of TxA2
Vasoconstriction, promotes platelet coagulation and aggregation
What is the function of PGF2alpha
Contraction of uterus, Bronchial, and small arterioles
What occurs in the first or priming phase of the liver regeneration
IL-6 production by Kupffer cells (allows ability to respond to GFs)
What is the expression level of COX1
Constitutively expressed in all tissues and maintain homeostatic function
What are the common locations for fibrinous inflammation
Pleura, meninges, Cardia
What are the characteristics of purulent/suppurative inflammation or abcess
Production of pus, exuadate containing neutrophils.
What is the function and example of CX3X
Only member is fractalkine
-Promotes strong adhesion of monocytes and T cells (membrane bound form), or chemoattractant (soluble form)
What are the functions of the neutral proteases
Degradation of extracellular companents such as collagen, elastin, and cartilage
What is the most important C-X-C cytokine
IL-8
During first intention wound healing, what occurs by day 5
Neovascularization appears and reaches its peak. Migration of fibroblasts and proliferation triggered by macrophages cytokines. Epidermis reaches its normal thickness
C-C chemokines have what structural characteristic
First two conserved cysteines are adjacent
What are the molecules leading to fever
TNF, IL-6, IL-1 (main one)
What is the maximum amount of liver that can be removed and still result in correction
90%
What are the characteristics of the immune granulomas
Agents that are able to sustain a persistent T cell mediated response. Usually associated with a central area of necrosis
Deficiency of C1 inhibitor can lead to which condition
Hereditary angioedema
What are the two types of granules that are contained in neutrophils
1) Smaller, specific, secondary granules
2) Larger, azurophil, primary granules
What is dehiscence and what is the common cause
Rupture of a wound, common after an abdominal surgery where the intrabdominal pressure increases (from coughing, vomiting, or ileus)
Purulent/suppurative inflammation is generally caused by which pathogen
Pyogenic (pus causing) bacteria, such as staphylcocci
What is a tertiary lymphoid organ, and which cells are present
Lymphocytes, APCs and plasma cells cluster to form lymphoid tissue resembling LN, aka lymphoid organogensis
What type of receptors do eicosanoids bind to
GCPR
How can COX 2 inhibitors lead to thrombosis
COX2 produces prostaglandins that cause vasodilation, while COX 1 produces platelet aggregation and vasoconstriction. Unopposed COX 1 leads to smaller vessels and clot formation
What are the contents of the smaller specific granules
Lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, alkaline phosphatase
What is the role of PDGF in angiogenesis
Recruits smooth muscle cells
What does fibrosis generally mean
Abnormal deposition of collagen that occurs in internal organs in chronic diseases
What is the condition of stasis
Small vessels dilate, causing the blood to move slower and an increase of locate RBCs
What cells are recruited during angiogenesis
Periendothelial cells (pericytes for small capillaries and smooth muscle for larger vessels)
During first intention wound healing, what occurs within the first 24 hours
Neutrophils appear and clear debris. Cut edge of epidermis shows mitotic activity
When is tissue said to be undergoing organization
When fibrosis occurs in a tissue space that is occupied by an inflammatory exudate
How is PGI2 broken down
Into PGF1 alpha, which is a stable end product
C-X-C Cytokines have what characteristics on structures
1 amino acid between the first two of four conserved cysteine residues
What are the three major components of acute inflammation
1) Dilation of blood vessels
2) Increased permeability of the blood vessels
3) Emigration of leukocytes
What group of enzymes make leukotrienes and lipoxins
Lipoxygenases
What is occurring during primary union or healing by first intention
Wound involving on the epithelial layer, typical of a surgical wound
What is the process of granulation of tissue in tissue repair
Migration and proliferation of fibroblasts and deposition of loose connective tissue, forming the granulation tissue (amount varies based on size of wound and amount in inflammation)
C5a has the ability to activate which pathway
Lipoxygenase pathway (increased leukotrienes)
What is the effect of platelet activating factor (PAF)
Vasoconstriction, bronchoconstriction and high levels, but dilation at low levels
Within 6 weeks, what is the size of the large skin defects, and what is the mechanism
large skin defects are 5-10% their original size, mainly by wound contraction
How is Bradykinin broken down
Very quickly via kininase
During first intention wound healing, what occurs during the second week
Collagen accumulation and fibroblast proliferation. Blanching begins as the increased collagen and decreased vasculature causes turning white
Chemoattractants bind to what type of receptors on leukocytes
GCPR, activating GTPs and RAC/Rho/cdc42
What are the contents of the larger azurophil
Myeloperoxidase, lysozymes, defensins, acid hydrolases and proteases
What is the enzyme that creates PGI2
Prostacyclin synthase
What is a condition that glucocorticoids can be given to reduce fibrosis
During corneal infections, so that there is a decrease in collagen deposition
What is the most important source of growth factors to illicit tissue repair
Macrophages
How does angiogenesis occur in scar formation
New blood vessels form to help deliver the blood and oxygen needed. They are very leaky due to underdeveloped inter-endothelial junctions and high levels of VEGF.
What is the common cause of wound ulcerating
Inadequate vascularization during healing
What is the affect of NSAIDs affect lipoxygenases
Does not affect them
What is the pathogenic effect of IL-1 and TNF on skeletal muscle
Insulin resistance
How is TXA2 broken down
Spontaneously (unstable) into the inactive form of TXB2
What are the characteristics of labile tissues
Continual dividing cells that are constantly being lost and replaced by maturation of tissue stem cells. Regeneration occurs as long as the tissue stem cell pool is intact
What are the two mechanisms of liver repair
1) Proliferation of remaining hepatocyte
2) Repopulation from progenitor cells
What are epithelioid cells
Macrophages with large cytoplasms at a site of injury and resemble epithelial cells
What is the enzyme responsible for ROS creation
NADPH oxidase aka phagocyte oxidase
In pseudomonas bacteria, how is the inflitrate different
Dominated by continuous neutrophil recruitment
What is the characteristic of tissue in syphilis
Gamma: microscopic lesion, enclosed wall of histiocytes, plasma cell infiltrate, central cells are necrotic without loss of cellular line
What is the location of thromboxane synthase
In platelet cells
Inhibiting leukotriene production with drugs most helps what condition
Asthma with Zileuton or montelukast (antileukotriene drug)
What is the cause of Cat scratch disease
Gram neg bacillus
How is most superoxide anion converted to hydrogen peroxide
Spontaneous dismutation
What is the overall effect of PGD2 and PGE2
Vasodilation, Increased permeability
What type of injury is there wound contraction
Only secondary intention
What is the pathogenic effect of TNF on blood cells
Thrombus due to increased permeability
What is the effect of leukotriene B4
1) Adhesion of leukocytes to epithelium
2) Chemoattractant and activator of neutrophils
3) ROS generation
4) Lysosomal enzyme release
What is the cause of leprosy
Mycobacterium leprae
What are the most important mediators of acute inflammation
1) Vasoactive amines
2) lipid products
3) cytokines
4) products of complement
What are two examples of serous inflammation
Effusion and skin blisters
What is the role of alpha 1-antitrypsin and alpha 2-macroglobulin
Major inhibitor of neutrophil elastase and works to prevent breakdown of healthy tissue
What molecule do mammals contain on their glycoproteins and glycolipids
Sialic acid and N-acetylgalactosamine
Are activated B cells and plasma cells present at the site of chronic inflammation
Yessirie Bob
What is the characteristic of tissue in cat scratch disease
Rounded or stellate granuloma, giant cells uncommon, debris and recognizable debris
What is a Desmond or aggressive fibromatoses
Incision scars or traumatic injuries followed by exuberant proliferation will recur after excision
What is the strength of a wound following the removal of sutures
10% but increases over next 4 weeks
What is the role of APP and anemia in chronic inflammation
Hepcidin is produced as part of APP. This decreases the availability of iron for RBCs, leading to anemia
What is the characteristic of tissue in crohn’s disease
Occasional noncaseating granuloma in intestine wall, dense chronic inflammation
Which pathogens are associated with leukopenia
Aka decrease in WBCs.
-Typhoid fever, some viruses, rickettsiae, protozoa
What conditions are associated with lymphoid organogenesis
Hashimoto’s thyroiditis and RA
What are the factors involved in the laying down of connective tissue and what is the source
PDGF, FGF-2, and TGF-beta from M2 macros
What is the composition of exudate
High protein concentration and contains cellular debris (due to increased permeability of vessel)
What is the location of prostacyclin synthase
In vascular endothelium
How are the granules of neutrophils able to make hydrogen peroxide into a killing substance
Myeloperoxidase (MPO) which turns Cl- (a halides) into hypochlorite (bleach).
What are Weibel-palade bodies
Storage location of P selectin in the intracellular stores in endothelial cell granules
What is the function of DAF
Blocks formation of the C3 convertase
What molecule does 5-lipooxygenase create
5-HPETE
What does the mannose receptors bind to
Mannose and fuctose on glycoproteins and glycolipids
How do APP cause erythrocyte sedimentation
Fibrinogen binds to RBCs, causing a stack known as rouleaux. This will increase the sedimentation rate
What is the left shift during leukemoid reactions
Leukemoid reactions are which WBCs reach leukemia levels. During this time, there are the increase presence of more immature neutrophils, knows as band cells
What is the role of MMP (matrix metalloproteinases) in tissue remodeling
Degrades the ECM to permit remodeling and extension of vascular tube
What is the characteristic of tissue in tuberculosis
Caceating granuloma aka tubercle, central necrotic area, occasional giant cells, acid fast bacilli
What is the cause of autoinflammatory syndromes
Gain of function mutations in the receptor sensors from inflammasomes, leading to spontaneous inflammation
What is the cause of syphilis
Treponema pallidum
Granulomatous inflammation is associated with collections of which type of cells
Macrophages, often T cells
What is a keloid
Formation of a scar that grows beyond the boundary of the original wound
How do histamines and leukotrienes compare in eliciting vasculature permeability and bronchospasms
Leukotrienes are more potent than histamines
What cells are driving regeneration from progenitor cells and where are they located
Oval cells located in the canals of Hering
What is the immediate transient response and what is it mediated by
The increased permeability of the vessels due to histamines, leukotrienes, and bradykinin
What are the two vasoactive amines
Histamine and serotonin
What are examples that will lead to a foreign body granuloma
Talc (IV drug users), sutures, and fibers that can not be engulfed by phagocytosis
What is the characteristic of tissue in leprosy
Acid fast bacilli in macrophages, noncaseating granuloma
What is characteristic of fibrinous inflammation
Leakage of fibrinogen into the space, forming fibrin. Usually occurs when vascular leakages are large and there is a procoagulant stimulus
Administration of TNF antagonist will help which conditions, but more susceptible to which conditions
Treats: chronic inflammation diseases (RA, psoriasis, IBD)
Susceptible to: mycobacteria (macros cant kill IC bacteria)
What are the molecules leading to leukocyte production
TNF,IL-1,IL-6
What is the most common mechanism of vascular leakage
Contraction of the endothelial cells resulting in the increased interendothelial spaces
What is the role of TGF beta in connective tissue being laid down
1) Fibroblast activation and migration
2) synthesis of collagen and fibronectin
3) Decreased MMP (decreased ECM degredation)
What are the characteristics of the second intention that are different than the primary intention
1) More abundant granulation tissue
2) More pronounce inflammation
3) Accumulation of ECM and large scar
4) Would contraction via myofibroblasts
What are the general ligands fro selectins
Sialyted oligosaccharides bound to mucin like glycoprotein backbones
What is the family of ADAM MMPs
Anchored to the plasma membrane and cleave/release EC domains of cell associated cytokines and growth factors
What is the most important cytokine for the synthesis and deposition of connective tissue protein
TGF-Beta
What is a exuberant granulation or pound flesh
Consists of the formation of excessive amounts of granulation tissues that procured above the layer of surrounding skin and block reepithelization
What is serous inflammation marked by
Exudation of cell poor fluid that does not contain high levels of leukocytes
What is a hypertrophic scar
Scar that is raised and generally involves injury to the deep dermis following thermal or traumatic injury
What is the role of FGF in angiogenesis
Stimulates proliferation of endothelial cells
What is the pathogenic effect of TNF on the heart
Low output
What is the characteristic of tissue in sarcoidosis
noncaseating granulomas with abundant activated macrophages
How is DAF and CD59 attached to a cell and how does this influence conditions it can cause
It is anchored to the membrane via and GPI anchor. Any deficiency in the ability to make this anchor will lead to paroxysmal nocturnal hemoglobinuria (PNH)
What are the causes for transudate
Increased hydrostatic pressure or decreased osmotic pressure
IL1/TNF lead to the formation of which APP
SAP
What is a secondary function of PGD2
Neutrophil attractant
Where is PGD2 and PGE2 created and stored
Mast cells
What is the effect of Leukotrienes C4,D4,E4
1) Bronchospasm
2) increased vascular permeability
3) Vasoconstriction
During first intention wound healing, what occurs by day three
Neutrophils have been replaced by macrophages and granulation tissue invades the incision space. Collagen fibers begin to appear
What occurs in the second or growth phase of liver regeneration
Growth factors, HGF and TGF-alpha, stimulate entry in the cell cycle
What are the characteristics of stable tissues
Normally quiescent (in G0 state) and only minimally proliferate. Under injury, it can proliferate, such as the kidney, pancreas, smooth muscle cells, but have a limited capacity to regenerate
What is the collective group of macrophages referred to
Mononuclear phagocyte system or reticuloendothelial system
What is the role of angiopoietins 1 &2 (Ang 1&2)
Interactions with Tie2 (tyrosine kinase) to help stabilize vessels
What is the site of action for major basic protein
Targets and harmful to parasites
What group of enzymes create prostaglandins
Cyclooxygenases
What are the two type of complications that arise from inadequate formation of granulation tissues
Wound dehiscence and ulceration
Administration of steroid affects which pathway in eiconisoids
Blocks phospholipase A2, and COX2
In wound healing, what is the increases in strength due to
1) Excess of collagen synthesis vs degradation during first 2 months
2) The collagen modification (cross-linking and increased fiber size) when the synthesis ceases
When do foreign body granulomas from
Inert foreign bodies in the absence of T cell
Kinins are derived from which proteins and are activated by which enzymes
Derived from kininogens, and are activated by the activity of kallikriens
What does the enzyme NADPH oxidase do
Reduces oxygen to superoxide anion (.O2)
Where does most leukocyte transmigration occur
Postcapillary venules
How can glucocorticoids result in wearing of scars
Inhibition of TGF beta, leading to diminished fibroblast recruitment and fibrosis
What are the functions of the acid proteases
Degradebacteria and debris within the phagolysosomes, which are supplied by the proton pumps
Where are resident macrophages created
Fetal liver or yolk sac
C chemokines have what function
Specific from lymphocytes (lymphotactin)
IL-6 leads to the formation of which APP
CRP and fibrinogen
What is the cause of tuberculosis
Mycobacterium tuberculosis
What are the three acute phase proteins
CRP, fibrinogen, serum amyloid protein (SRP)
C chemokines have what general structure
Lack first and third conserved cysteins
What population of people is a keloid formation more likely
African American population
What are the two step involved in the laying down of connective tissue
1) Migration and proliferation of fibroblasts into site of injury
2) deposition of ECM proteins
C-C chemokines include which molecules and generally have which function
- Attracting monocytes, eiosinophils, and lymphocytes
- MCP-1, eotaxin, MIP-1alpha, RANTES
During first intention wound healing, what occurs 24 to 48 hours
Epithelial cell edges have begun to migrate and proliferate
What are the arachidonic acid mediators (aka eicosanoids)
Prostaglandins and leukotrienes
How do Liver abscesses affect the liver’s ability to regenerate
There is extensive destruction to the reticulum framework, which leads to scar formation (Even through there are liver cells that can regenerate)rather than regeneration
What is the function of CD59
Blocks the formation of CD59
In secondary healing, what is the process of change in the matrix
1) First the matrix contains fibrin, plasma fibronectin, and type 3 collagen
2) After 3 weeks, this is replaced with a matrix containing type 1 collagen
What is the most prominent lipooxygenase in neutrophils
5-lipooxygenase
What is the effect of PGI2
Vasodilation, inhibits coagulation and platelet aggregation
What is the function of 5-HETE
Chemoattractant for neutrophils
In most organs, kidneys and lungs, what is the main source of collagen
Myofibroblasts
What is the enzyme that creates TxA2
Thomboxane synthase
What are the molecules leading to acute phase proteins
IL-1, IL-6 (main one)
What is the site of action for lysozymes
Hydrolyzes muramic acid N-acetylglucoasamine bond in bacterial coats
Receptors leading to inflammasomes bind to which molecules
1) Uric acid (from DNA break down)
2) ATP
3) Decreased intracellular potassium levels
4) DNA
What is the expression level of COX 2
Induced by inflammatory stimulus and generate prostaglandins involved in the inflammatory response, so it usually expressed at low or non existing levels
What are the characteristics of the permanent tissues
Cells of tissues that are terminally differentiated and no proliferative in postnatal life. Damage results in scar formation
In liver cirrhosis, what is the main collagen producer
Stellate cells
What is the dominant cell in chronic inflammation
Macrophages
What is the condition of paroxysmal nocturnal hemoglobinuria
Excessive complement activation and RBC lysis
