Chapter 3: Inflammation & Repair Flashcards
What are the cardinal signs of inflammation? What are they caused by?
rubor (redness) and calor (heat) - d/t histamine-mediated vasodilation of arterioles
tumor (swelling) - d/t histamine-mediated increase in ventral permeability
dolor (pain) - PGE2 sensitizes specialized nerve endings to the effects of bradykinin
functio laesa (loss of function)
What degrades bradykinin?
ACE
What is a complication of an ACE inhibitor?
ACE inhibitor inhibits the metabolism of bradykinin –> increases vessel permeability –> angioedema
What are the sequential cellular steps involved in acute inflammation?
- emigration (includes margination, rolling of neutrophils, firm adhesion in venules d/t expression of intern adhesion molecules such as beta2-integrins)
- transmigration (diapedesis) of neutrophils
- chemotaxis
- phagocytosis via opsonization
- intracellular microbial killing
What inactivates beta2-integrins and produces neutrophilic leukocytosis?
catecholamines and corticosteroids
Name some chemotaxis mediators
C5a
leukotriene B4 (LTB4)
bacterial products
IL-8
What is the purpose of exudates?
- dilates bacterial toxins
2. provides opsonins
Macrophages and dendritic cells that have encountered microbes produce which cytokines to activate the endothelial cells of nearby venules to produce selectins?
TNF and IL-1
What are the two main opsonins?
IgG and C3b
In acute inflammation, what is the main cell present?
neutrophil
In chronic inflammation, what is the main cell present?
macrophage/monocyte
How does a neutrophil or monocyte kill bacteria or fungi?
O2-dependent myeloperoxidase (MPO) system
What is the process of the MPO system?
NADPH oxidase enzyme complex converts molecular O2 to superoxide FRs –> releases energy (respiratory burst)
How can you diagnose chronic granulomatous disease?
no color change from clear to blue when conducting an NBT dye test
What are macrophages in the CNS called?
microglial cells
What are macrophages outside the CNS called?
dendritic cells
What is the MC precipitation of hemolysis in G6PD deficiency?
infection
What causes Chronic Granulomatous Disease?
Deficiency in NADPH oxidase
What else should you know about CGD?
X-linked R
NBT dye test is negative (doesn’t change color b/c no respiratory burst)
missing peroxide b/c no NADPH oxidase
What kind of bacteria CAN pts with CGD kill?
catalase negative (e.g. Strep. pyogenes)
What kind of bacteria CAN’T pts with CGD kill?
catalase positive (e.g. Staph)
G6PD deficiency results in a lack of what molecule?
NADPH –> therefore this interferes with normal function of the O2 dependent MPO system
What is the most important chemical mediator in acute inflammation?
histamine
What does histamine do to arterioles?
vasodilates
What does histamine do to venules?
increases vessel permeability
What amino acid makes serotonin?
tryptophan
What effect does serotonin have on vasculature?
vasodilator and increases vascular permeability
What are the 2 anaphylatoxins? What do they do?
C3a and C5a
Stimulate mast cells to release histamine –> vasodilation and increased vessel permeability
What is made by endothelial cells and is a potent vasodilator?
NO
What is the function of IL-1?
associated with fever b/c stimulates the hypothalamus to make PG’s –> stimulates thermoregulatory system to produce fever
What enzymes is blocked by corticosteroids?
phospholipase A2
What enzymes are blocked by aspirin?
COX 1 and 2 irreversibly
What medication blocks the enzyme 5-LOX?
Zileuton
What medication blocks receptors for LTB4, LTC4, LTD4, and LTE4?
Montelukast
If taking a corticosteroid, would you see an increase or decrease in neutrophils?
You would see an INCREASE in neutrophils on CBC b/c corticosteroids block the adhesion molecule LTB4 from being formed.
What affect does epinephrin have on adhesion molecule synthesis and neutrophil count?
DECREASES adhesion molecule synthesis
neutrophil count INCREASES
MCC of skin abscess
S. aureus
What is fibrinous inflammation?
exudate that covers serial surfaces (heart, lungs, peritoneum)
What is serous inflammation?
thin watery exudate (e.g. blister, viral pleuritis)
What percent of peripheral blood lymphocytes are T cells?
60%
What is the ratio of helper to suppressor T cells (CD4:CD8)?
CD4:CD8 = 2:1
What is a unique characteristic of eosinophils?
They have Charcot-Leiden crystals (seen in sputum of asthmatic pts)
What is the effector cell in a Type II hypersensitivity reaction?
Eosinophils
What is the effector cell in a Type I hypersensitivity reaction?
mast cells
What is the benefit of a fever?
O2 binding curve shifts to the right
decreased bacterial/viral reproduction
What disease is associated with pseudomembranous inflammation?
C. difficile
Name the markers on the following cell types:
Helper T cell
Cytotoxic T cell
Marker for Ag recognition site for all T cells
Marker for histiocytes
Marker only on B cells (name virus that utilizes this marker)
Marker found on all leukocytes
Helper T cell - CD4
Cytotoxic T cell - CD8
Marker for Ag recognition site for all T cells - CD3
Marker for histiocytes - CD1
Marker only on B cells (name virus that utilizes this marker) - CD21 (EBV)
Marker found on all leukocytes- CD45
What mediators cause fever?
IL-1 and PGE2
What is the cause of osteomyelitis?
S. aureus
What is the common cause of cellulitis?
Group A Strep. pyogenes
What are causes of fibrous pericarditis?
- SLE
- first week of MI then again in 6 wks later (Dresser’s Syndrome)
- Coxsackie virus
MC organism producing infxn in 3rd degree burns
Pseudomonas auruginosa (pus is green d/t pyocyanin)
Those who suffer from poor wound healing should be checked for what deficiency?
Zn deficiency
What is the pathogenesis of Marfans?
Defect in fibrillin –> poor wound healing
What is the pathogenesis of Ehlers-Danlos?
defect in collagen d/t breaking down –> poor wound healing
What is pathogenesis of Scurvy?
Vitamin C deficiency –> defect in hydroxylation of lysine and proline –> no crossbridging –> abnormal collagen –> poor wound healing, hemorrhaging, hemarthroses
What type of collagen is the initial collagen in wound repair?
Type III collagen
What day does granulation tissue begin to form?
Day 3
What enzyme breaks down type III collagen and replaces it with type I collagen?
collagenase (tensile strength returns to 80% normal w/in 3 months)
What causes keloid formation?
excess Type III collagen deposition
In white individuals, what is keloid formation often due to?
3rd degree burns
What do surgeons inject into sounds in order to prevent excessive scar tissue formation?
glucocorticoids
MCC of impaired wound healing
infections
MC pathogen causing sound infection
S. aureus
How does diabetes increase susceptibility to infection?
decrease blood flow
increase tissue glucose levels
What is the difference between a keloid and hypertrophic scar?
Keloid- raised scars extending beyond borders of original wound
Hypertrophic scar- raised scar remaining in confines of original wound
Scenario: Chronically draining sinus tract of the skin, the physicians tried to put abs on it (didn’t work). There was an ulceration lesion at the orifice of this chronically draining tract. What is it?
squamous cell carcinoma
What cell is involved in lung injury repair?
Type II pneumocyte
What cell in the brain proliferations in response to injury and which one removes the debris?
Astrocytes proliferate
Microglial cells remove debris
In peripheral nerve transection, which cell is key to reinnervation?
Schwann cells
Cardiac muscle damage is permanent or temporary? What kind of repair occurs?
permanent damage
repair by fibrosis
What immunoglobulin is predominantly seen in acute inflammation?
IgM
What cells and immunoglobulins are seen in chronic inflammation?
absolute monocytosis
increased serum IgG
What findings on blood smear are seen in severe inflammatory conditions?
toxic granulation
Dohle bodies
What findings would you see with corticosteroid therapy?
increased plasma neutrophils
decreased B and T cells
What cell types are seen in each scenario?
Acute inflammation
Acute allergic reactions
Viral infections
Chronic inflammation
Acute inflammation - neutrophil
Acute allergic reactions- eosinophil
Viral infections - lymphocytes
Chronic inflammation - monocytes/macrophages but also see a lot of plasma cells and lymphocytes
A granuloma results from an acute or chronic infection?
chronic
What cytokine (released by a T helper cell) activates a macrophage?
gamma INF
What two cells are key players in granuloma formation?
T helper cell and macrophage (Type IV hypersensitivity)
What cell is responsible for a positive PPD test?
T helper cell
What two areas of the kidney are most susceptible to tissue hypoxia?
- straight portion of proximal tubule b/c most of oxidative metabolism located there
- medullary segment of thick ascending limb
What happens to the ESR when you have increased immonoglobulins? Why?
immunoglobulins decrease the negative charge that normally keeps RBCs from sticking to each other –> clumping of RBCs –> increased ESR
*seen in cold agglutination with IgM and multiple myeloma (cryoglobulins)
