Inflammation 1 (acute) Flashcards
Define Inflammation
a nonspecific bodily response to a variety of injurious agents
name the Four cardinal manifestations of acute inflammation:
redness, swelling, heat and pain
Define Exudate: i
inflammatory extracellular fluid with high protein content, cells and cellular debris
Define Transudate:
thin acellular serous edema fluid
Define Pus:
purulent exudate important to recognize and important to culture because it usually represents infection
Define Leukocytosis:
increased number of white blood cells counted in the blood
Define Acute phase reactants:
proteins produced in abundance with inflammation, including fibrinogen and complement
Define Sepsis:
the systemic inflammatory response syndrome (SIRS) due to an infection (proven or suspected)
Describe inflammation in a general sense
- Inflammation is a reaction to injurious agents.
- **It is not a disease. **
- **It is not specific. **
- It is a nonspecific host response to something injurious. The something may be a bacterial infection, a fungal infection, a viral infection, a toxic substance or material from dead necrotic cells.
- The response, inflammation itself, can become injurious in, for instance, the acute respiratory distress syndrome.
What are the 6 common causes of inflammation?
- (1) infection,
- (2) tissue necrosis,
- (3) immune reaction,
- (4) trauma,
- (5) foreign bodies
- (6) physical and chemical agents.
What is the difference bw sign and symptom?
A symptom is a subjective experience of an aspect of a disease,
sign is an objective physical manifestation of a disease.
What type of inflammation has a rapid onset (seconds to minutes) and short duration (minutes to a few days)?
acute inflammation
Other than redness, heat, swelling and pain, what is another cardinal symptom/sign of acute inflammation?
loss of function, is sometimes added.
There are five distinctive forms of inflammation: name them. Do they have to happen together?
(1) purulent (suppurative), (2) abscessing (necrotizing), (3) fibrinous, (4) serous and (5) granulomatous.
They are not mutually exclusive.
Inflammation is a complex response. There are 3 components of inflammation: name them
- a vascular response,
- a leukocyte (white blood cell) response
- a systemic (total body) response.
The vascular component consists of what?
What does the vascular component allow?
dilatation and increased permeability.
This vascular response permits an outpouring of fluid, plasma proteins and leukocytes (primarily neutrophils) from the blood into the extracellular space.
The fluid which pours out in acute inflammation can evident of what it contains. Name 3 common manifestations
thin (“serous”),
thick with abundant protein (“fibrinous”)
thick like pea soup with protein and inflammatory cells (“purulent”).
What is the liquid portion of blood that has clotted and been centrifuged to separate the clotted cells and proteins?
serum
Why is serum thin?
Serum is thin because it has a low protein content (and no cells).
Define Plasma. How is fibrin related?
is the liquid portion of blood that has been anticoagulated and centrifuged, leaving a protein-rich liquid portion including the blood clotting factors.
Fibrin is one of those clotting factors.
Describe Serous inflammation. give example
a form of usually acute inflammation marked by an outpouring of a thin fluid from blood vessels or mesothelium
[the lining of the chest or abdominal cavities] (effusion) or a skin blister (effusion into space created between the epidermis and dermis by burn or virus).
describe Fibrinous inflammation
a form of usually acute inflammation featuring deposition of fibrin-rich exudate, on pleura, pericardium, peritoneum or meninges, or in the interstitium of any tissue.
Define edema
Edema is tissue swelling due to accumulation of water.
Purulent inflammation is also called suppurative, although some call it suppurative only when it is also necrotizing. What type of inflammation? produces what? caused by what?
It is usually acute and features production of abundant pus (neutrophils, necrotic cellular debris and edema fluid). It is commonly caused by infection with pyogenic (pus-producing) bacteria.
Describe pus in general
It is thick, opaque and variably colored (light green, yellow, tan, crème, off-white).
Pus usually represents infection, so the usual thing to do with it is send a sample to the microbiology laboratory for them to isolate and identify the infecting organism (“culture” it).
Describe pus wrt mucous and blood
Pus can be mixed with mucus. Mucus is grey, slimy, and stringy. Mucopurulent exudate has a spectrum from mostly pus to mostly mucus.
Pus can also be mixed with blood. Blood has a spectrum from red to blue and can solidify (clot). The mixture of blood and pus is commonly pink.
Defects in leukocyte function predispose patients to what?
patients to infections.
leukocyte adhesion deficiency-1 and -2, chronic granulomatous disease, myeloperoxidase deficiency, Chediak-Higashi syndrome, and cryopyrin-associated periodic fever syndromes, which are all rare conditions, cause what?
Congenital leukocyte defects
diabetes mellitus, hemodialysis, malnutrition, and leukemia, which are common, especially diabetes mellitus cause type of defects?
Acquired leukocyte defects are caused by
T/F Inflammation, acute or chronic, has systemic effects on the patient as a whole person
true
The four most important of the systemic effects of acute inflammation (the acute phase response) are:
(1) fever (or hypothermia),
(2) tachycardia (rapid heart rate),
(3) hyperventilation (tachypnea [rapid respiratory rate])
(4) leukocytosis (more white blood cells in circulation in the blood)
The acute phase response is largely mediated what? give specifics
by cytokines
especially IL-1, TNF-a and IL-6
The acute phase response includes changes in what?
plasma protein levels, with increased C-reactive protein, amyloid A, fibrinogen and other proteins.
What is the effect on albumin wrt acute inflammation?
- acute phase response includes changes in plasma protein levels.
- To make more acute phase reactants, the liver has to make less of other proteins, whose level falls as a result.
- Chief among these negative acute phase reactants is albumin.
Other than a decrease in albumin production, what else is altered as a result of acute phase response?
- causes changes in lipid metabolism,
- a negative nitrogen balance,
- changes in hormone synthesis,
- decreased serum iron and zinc,
- elevated white blood cell and platelet counts
- decreased red blood cell production.
What effect does inflammation have on metabolism?
Inflammation switches the body from anabolism to catabolism, and, **initially, a hypermetabolic state. **
Because the acute phase response switches to hypermetabolic and from anabolism to catabolism, what is the effect toward the catabolic molecules? What does this ultimately cause?
The levels of epinephrine, norepinephrine, cortisol and glucagon go up, and skeletal muscle is broken down.
Hepatic synthesis of protein goes up, but skeletal muscle is broken down faster than the amino acids are utilized for protein synthesis, so nitrogen is lost in the urine and the patient goes into a negative nitrogen balance.
***The most important systemic effects of inflammation are alterations what?***
***alterations of body temperature, heart rate, respiratory rate and white blood cell count, usually increases of them. ***
Define the most common form of leukocytosis
Leukocytosis consisting of neutrophils is called neutrophilia and is associated with **bacterial infections as the cause. **
Leukocytosis consisting of lymphocytes is associated with what type of infections?
Viral infections
leukocytosis consisting of eosinophils is associated with what type of infection?
allergies and parasitic infestations
What are Dohle bodies?
patches of dilated endoplasmic reticulum, which appear as “sky-blue peripheral cytoplasmic puddles”
Define and Describe toxic granulations. What do they look like and commonly found?
immature primary cytoplasmic granules characteristic of less mature granulocytes
Toxic granulations are dark blue or purple granules, bigger and coarser than the small, faintly stained neutral granules characteristic of segmented neutrophils.
Predictably, toxic granulations are more common in immature neutrophils.
Severe acute inflammation can cause neutrophils to have what?
(1) Dohle bodies
(2) toxic granulations
What are Acute phase reactants?
proteins produced in abundance with inflammation
What are common acute phase reactants?
- fibrinogen and other clotting factors,
- the complement proteins,
- amyloid A,
- C-reactive protein,
- alpha-1-antitrypsin and other antiproteases,
- hepcidin and ferritin.
T/F Acute phase reactants generally have harmful effects in inflammation
Acute phase reactants generally have beneficial roles in inflammation
What is Serum amyloid A role in inflammation?
seems to play a role in recycling and reusing cholesterol from destroyed and damaged cells
does this by replacing apolipoprotein A in high density lipoprotein and targeting delivery of HDL to macrophages,
suppressing ACAT and enhancing neutral cholesterol esterase and ABC transporters in macrophages.
What is the role of fibrinogen in acute inflammation?
Fibrinogen causes sticky erythrocytes and an increased erythrocyte sedimentation rate (ESR, “sed rate”);
the cells sediment faster when they are stuck together.
Describe the correllations of the ESR to inflammation, age, gender and what it is influenced by
ESR increases with inflammation,
Increases with age;
it is higher in women, and it is influenced by the size, shape and concentration of the erythrocytes.
Why is ESR not a good diagnosis of inflammation? What is it used to screen for?
ESR has low sensitivity and specificity for the diagnosis of inflammation, but it is simple, fast and cheap; it is still used to screen for temporal arteritis and osteomyelitis.
What is CRP?
- C-reactive protein (CRP) is an acute phase reactant composed of 5 identical 206-amino-acid subunits arranged in cyclic symmetry.
What complement cascade is associated with CRP? How is this done?
CRP binds to phosphocholine residues uniquely found on bacteria and, once bound, becomes a ligand for complement C1 binding, initiating the classical complement cascade.
Synthesis of CRP is induced by what?
Synthesis of CRP is induced by cytokines, chiefly IL-6.
Describe the levels of CRP wrt age, ranges, types of infection
The levels of CRP change rapidly (up and down), do not increase with age and have a broad range.
The average normal level of CRP is 1 mg/L, but it increases up to 300 mg/L with acute inflammation.
The level of CRP goes up with bacterial, but not viral infection;
80-85% of patient with CRP >100 mg/L have bacterial infection.
What are Other systemic effects of inflammation?
- anorexia (loss of appetite),
- lethargy,
- somnolence,
- malaise (feeling sick),
- chills,
- rigors (shivering),
- decreased sweating,
- increased blood pressure.
Severely injurious agents cause a syndrome of signs and symptoms attributable to the systemic inflammatory reaction. There are official consensus criteria for this systemic inflammatory response syndrome (SIRS): name them (4)
- Temperature >38 (100.4) degrees or <36 (96.8) degrees
- Heart rate >90/minute
- Respiratory rate > 20/minute or pCO2 <32 mmHg
- White blood cell count >12,000/cu mm or <4,000/cu mm or >10% bands
T/F Sepsis is not a positive blood culture.
true
The majority of patients with sepsis have what type of blood culture?
NEGATIVE blood cultures.
What is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult?
inflammation
What are Acute phase reaction characteristics?
- Fever: IL-1 and TNF
- Somnolence, malaise, anorexia
- Hypotension
- Increased hepatic synthesis of proteins: complement and clotting factors: IL-6
- Leukocytosis, “left shift”
- Elevated ESR (erythrocyte sedimentation rate)
What are the participants in inflammation?
- Circulating cells
- Plasma proteins
- Vascular wall cells
- Connective tissue cells and extracellular matrix
What is this cell?
neutrophil
Name these. Cell on Left is
Cell on right is
eosinophil on left
basophil on right
Name cells
lymphocyte
monocyte
Name these
plasma cells
Name the 3 cells in slide
Macrophage left
mast cell top right
basophil bottom left of right picture
Differentiate between the chronic and acute responses of inflammation
Describe the timing, components, and cellular events of acute inflammation
- Immediate and early response to injury
Components => Vascular changes (Vasodilation and Increased vascular permeability)
Cellular events=> cellular recruitment and activation
(Emigration of leukocytes from the microcirculation to the site of injury)
What are the 3 main vascular changes in acute inflammation? What do they result in?
1) Vascular dilation causes erythema and warmth: rubor and calor
- *2) Extravasation of plasma fluid and proteins causes edema:** tumor
3) Emigration of leukocytes to site of injury: tumor
Describe the Sequence of Vascular Changes in Acute Inflammation
Transient vasoconstriction (seconds)
Increased vascular permeability
- Protein rich fluid leaks into extravascular tissues: transudate first, then exudate; edema
- Concentration of red blood cells: increased blood viscosity and stasis
Differentiate between exudate and transundate
Increased vascular permeability causes what?
- immediate transient response
- endothelial cell retraction
- direct endothelial injury/ immediate sustained response
- leukocyte dependent endothelial injury
- increased transcytosis
- leakage induced by chemical mediators
Describe the immediate transient response
Describe endothelial cell retraction
Describe direct endothelial injury/ immediate sustained response
Describe leukocyte dependent endothelial injury
Describe increased transcytosis
What does leakage induced by chemical mediators look like?
Describe this cell
Neutrophil
- first cell to arrive at the site of acute inflammation/abscesses
- Very short life span: about a day
- Phagocytic—especially for pyogenic cocci
- Contain lots of lysosomes (look like cytoplasmic granules); suppuration and liquefaction of tissue
What are the 3 functions of the neutrophil?
- phagocytosis
- H2O2, activated O2 species
- exocytosis
What does this cell represent?
acute inflammation
What is the sequence of events in leukocyte emigration?
List the steps for the leukocyte emigration to fight the stimulus
margination => rolling => adhesion => transmigration toward the site of the injury
- endothelial activation
- leukocyte activation
- diapedesis
- chemotaxis
What is margination wrt Sequence of events in leukocyte emigration?
leukocyte accumulation at the periphery of blood vessels
What is rolling wrt Sequence of events in leukocyte emigration?
leukocytes are pushed out of the central axial column by flowing blood;
mediated by selectins
What is pavementing wrt Sequence of events in leukocyte emigration?
leukocytes line up along the blood vessel wall
What is a family of surface receptors that bind to selected sugar domains (lectins)? What is their role?
Selectins
Account for the relatively loose and transient adhesions involved in rolling
E-selectin is associated with what?
P-selectin is associated with what?
L-selectin is associated with what?
E-selectin: endothelium
P-selectin: endothelium and platelets
L-selectin: most leukocytes
leukocytes firmly stick to endothelial surfaces via what mechanisms?
adhesion
leukocytes move between endothelial cells and through the basement membrane into the extravascular spaces via what mechanism?
diapedesis
What is mediated by molecules of the immunoglobulin superfamily on endothelial cells that interact with integrins expressed on leukocyte cell surfaces?
adhesion and transmigration
Ig superfamily: Endothelial adhesion molecules are what? What induces them? What integrins are associated and what do they bind to?
ICAM-1 (intercellular adhesion molecule 1)
VCAM-1 (vascular adhesion molecule 1)
Induced by cytokines such as TNF and IL-1
integrins are LFA-1, Mac-1, and VLA-1
LFA-1 and Mac-1: bind to ICAM-1
VLA-1: binds to VCAM-1
Define Chemotaxis
movement of cells or organisms in response to chemicals
Describe the migration of leukocytes toward sites of injury along a chemical gradient
Soluble bacterial products
Complement: C5a
Leukotriene B4 (LTB4)
Cytokines: chemokine family, IL-8
Describe how chemotaxis results in the assembly of pseudopods
- Chemotactic molecules bind to cell surface receptors
- G protein-mediated activation of phospholipase C
- Membrane PIP2 is hydrolyzed into DAG and IP3
- IP3 increases intracellular calcium resulting in the assembly of pseudopods
What is the result of Activation of protein kinase C?
- degranulation and secretion of lysosomal enzymes
- generation of the oxidative burst
What is the result of Activation of phospholipase A2?
arachidonic acid metabolites
What is the process of phagocytosis consist of?
- Recognition and attachment
- Engulfment
- Killing and degradation
Describe the Recognition and attachment mechanisms involved in Phagocytosis
Opsonins: Ig Fc, C3b and collectins
Bind to FcR; CR 1,2 and 3; and C1q respectively
Describe the process of engulfment wrt phagocytosis
- Triggered by binding of opsonized particles
- Pseudopods extend to form phagocytic vacuole
- Membrane of vacuole fuses with the membrane of a lysosomal granule to form phagolysosome
Describe how killing and degradation is done in phagocytosis
- Oxidative burst forms reactive oxygen metabolites: H202
- Azurophilic granules contain MPO: HOCl
- Dead microorganisms are degraded by lysosomal acid hydrolases
What is this an example of?
Skin blister from chickenpox with
effusion of thin serous fluid
What are the arrows indicating?
Shaggy fibrinous pericarditis
What is the arrow pointing to?
Yellow purulent exudate on peritoneum
Describe this slide
Microscopic purulent exudate in pulmonary alveoli
What is this an example of?
Purulent green exudate on bowel serosa
What is this an example of?
Bronchial mucus plug in a patient who
died of asthma (actually mucopurulent)
What is this an example of?
Mucopurulent, mostly purulent exudate
mixed with a little blood (arrow) in a
bronchus with inflamed mucosa
Define a left shift
release of immature neutrophils from bone marrow, especially adolescents (bands)
Describe the slide on the left and the right wrt granules. name them
Left is Dohle bodies
Right is toxic granulations
Define Somnolence
maybe just about to sneeze
Describe when the Acute phase reactants are produced with inflammation
