DD Boyer Flashcards
Inflammatory cells can come from 2 places. Name them
- tissue based/Sentinels within tissue, 2. vascular from bone marrow and lymphnodes
What do Fibroblasts do in response to injury?
proliferate and produces collagen and other ECM to provide infrastructure
What do endothelial cells (blood vessel lining) in response to injury?
proliferate and form new blood vessels
Regenerative capacity of gastrointestinal system
epithelial cells have normal turnover and regenerate
Regenerative capacity of respiratory system
epithelial cells have normal turnover and regenerate, but septa of alveoli cannot regenerate once damaged
Regenerative capacity of liver
Great
Tissue-based Macrophages in liver
Kupffer cells
Regenerative capacity of Heart
absent
Regenerative capacity of Kidney
epithelial cells have normal turnover and regenerate, but glomeruli do not regenerate
local signs and symptoms of injury
Rubor, Calor, Tumor, Dolor
systemic signs and symptoms of injury
Sleepiness, Anorexia, Fever, Elevated WBC, hypotension
7 basic steps to injury response
Recruit help, increase blood flow, increase vascular permeability, recognition of problems, clear/remove/wall off offending material, collateral damage, stimulate repair and remodeling
how fast does the acute inflammatory phase start and last
rapid initiation: minutes to hours. Short duration
what cells are involved in acute inflammation
Neutrophils
what do Neutrophils do during acute response
phagocytose bacteria, tissue debris, and damaged issue
how fast does the chronic inflammatory phase start and last
initiation is slower (days or longer), but can lask anywhere from days to years.
what cells are involved with chronic inflammation
Macrophages and lymphocytes and Eosinophil
Functions of macrophages
phagocytosis and regulate inflammatory response
Functions of eosinophils
type-1 immune response, parasite difense, phagocytosis
When is repair initiated
during chronic phase
Critical features of acute inflammation - (hint: 3 things)
vasodilation, vascular permeability, and inflammatory cell infiltrate (neutrophils that make puss)
transient chronic phase of inflammatory response begins when?
it is initiated with Acute phase response
features prolonged/persistent chronic inammatory response (4 things)
- may or may not see acute phase 2. persistent infection 3. persistent damage/irritation (ie atheroschlerosis) 4. Antigen-Driven Immune-mediated process
source of cells in acute response
peripheral blood
source of cells in chronic response
Sentinel/local cells in tissue and peripheral blood
vascular response in acute phase
dilation/increased flow, increased permeability that can be transudate or exudate
vascular response in chronic phase
variable persistense of dialation and leakiness, endothelial cells activated and ready to proliferate
repair in chronic phase
macrohphages release growth factors, fibroblasts cause fibrosis and scar, endothelial cells neovascularize
Fibrinopurulent Exudate
Anywhere, but usually a nonconfined space. Usually infectious. Mostly neutrophils
Abscess
within a parenchyma/confined space, cavity is newly formed by accumulation of inflammatory cells. Usually infectious. Mostly neutrophils
Empyema
location within an anatomic space of cavity. Usually infectious. Neutrophils early, MACs and lymphocytes late
Cellulitis
skin, fascia/deep connective tissue. Infectious or inflammatory
Granuloma
within parenchyma, rounded nodular appearance. MACs and lymphocytes. Infectious or foreign body. Mineralized on x-ray or CT scan
Common laboratory tests for inflammation
WBC, Erythrocyte sedimentation rate and C-reactive proteins (acute phase), firbin split/degradation products and platelet count (DIC-related markers), repid ID testing, cultures and serology, Ig quantification
not typically evaluated lab tests for inflammation
chemical mediators (eg Prostaglandins, leukotrienes, thromboxanes, interleukins)
What cells make histamine?
Mast cells and Basophils, platelets
what does histamine do?
Vasodilate, Vascular Perm., constriction of smooth muscles
What cells make serotonin?
Plts
what does serotonin do?
Vascular perm
What cells make Prostaglandins (PG)?
Mast cells, plts, Macs, Lymphs, PMNs, Endo cells
what do Prostaglandins (PG) do?
Vasodialate (PGI2), Plt ag. (+/-), constrict smooth muscle, fever, pain (PGE2, PGI2)
What cells make Leukotrienes LT C4, D4, E4?
Mast cells and Basos, Macs, Lymphs, PMNs
what do Leukotrienes LT C4, D4, E4 do?
Vascular Perm, constrict smooth muscle
What cells make Leukotrienes LT B4?
Mast cells and Basos, Macs, Lymphs, PMNs
what does Leukotrienes LT B4 do?
WBC chemotaxis
What cells make Thromboxanes TXA2?
Plts
what does Thromboxanes TXA2 do?
Vasoconstriction, Plt ag.
What cells make PAF (platelet-activating factor)?
Mast cells and Basos, plts, Macs, PMNs, Endo Cells
what does PAF (platelet-activating factor) do?
Vasodialation (low []s), vasoconstriction, vascular perm, WBC Chemotaxis, plt ag., constrict smooth muscle
What cells make Reactive Oxygen Species?
Macs, Lymphs, PMNs
what does Reactive Oxygen Species do?
Tissue/Microbe Damage
What cells make Nitric Oxide (NO)?
Macs (iNOs), endo cells (eNOs)
what does Nitric Oxide (NO) do?
vasodialation, WBC Chemotaxis (iNOs), relax smooth muscles, tissue/microbe damage (iNOs)
What cells make TNF (tumor necrosis factor)?
Mast Cells and Basos, Macs, Lymphs
what does TNF (tumor necrosis factor) do?
WBC chemotaxis, Fever
What cells make Interleukins (1, 6, ?)?
Macs, Endo Cells
what does Interleukins (1, 6, ?) do?
WBC chemotaxis, Fever
What cells make Chemokines?
Mast cells, Macs, Lymphs, Endo Cells
what does Chemokines do?
WBC chemotaxis
What cells make Cytoplasmic Granule Content?
Macs, PMNs
what does Cytoplasmic Granule Content do?
WBC chemotaxis, tissue/microbe damage
What cells make Substance P?
Nerve Fibers
what does Substance P do?
vascular perm, Pain
What cells make C3a, C5a?
liver
what does C3a, C5a do?
Vasodialation and Vascular perm (through Mast cell stim.), WBC chemotaxis, Tissue/microbe damage (Mac effect on microbes)
What cells make Bradykinin?
liver
what does Bradykinin do?
Vasodialate, Vascular Perm, constrict smooth muscle, Pain
What cells make Thrombin?
liver
what does Thrombin do?
WBC Chemotaxis
What cells make Plasmin?
liver
what does Plasmin do?
Vasodialation
What cellular chem. Mediators are in secretory granules?
Histamine, serotonin, lysosomal enzymes
What cellular chem. Mediators are newly synthesized?
prostaglandins, Leukotrienes, Platelet-activating factors, ROS, NO, cytokines
Why are Macrophages so critical?
They make most chemical mediators! Except histamine, serotonin and substance P
Which mediators tend to have a systemic effect?
Substances P, Prostaglandins, IL-1, TNF, Bradykinin
Arachidonic Acid + lipoxygenase
leukotrienes, lipoxin, and HETE
Arachidonic Acid + cyclooxygenase
Prostaglandins and Thromboxane A
Basic Kinin system pathway
Factor XII => Factor XIIa => kallikrein => bradykinin
Factor XII function
“Hageman Factor”. Important for pain, coagulation, antimicrobial activity, and inflammation
What does Factor XII help produce?
Bradykinin, Plasmin, C3a, C5a, Thrombin, and Fibrin. All use Kallikrein in pathway except Thrombin
Describe the Proliferative Phase
Fibroblasts proliferate and produce collagen and ECM, Endothelial cells proliferate and form new blood vessels.
Describe the Remodeling Phase
Regenerative processes fade, followed by reorganization of connective tissue and contractile response
How does Infrastructure repair occur?
Granulation of tissue occurs via ECM and collagen depositing by fibroblasts, neovascularization, and the presense of macrophages and lymphocytes providing growth factors and cytokines
Where do new cells for Angiogenesis come from?
Pre-existing blood vessels, bone-marrow derived endothelial precursor cells, smooth muscle cells, and pericytes.
What does Suprastructure repair include?
Re-epithelialization via epidermal stem cells in skin/Bulge stem cells in hair follicles/crypt cells in intestine, and regeneration of liver cells.
What do you do when you can’t repair Suprastructure?
Scar tissue that can rupture. (ie after necrosis of myocardium in MI)
What are the big chemical mediators of repair and what releases them?
Macrophages are the big players here. TNF and IL-1 promote fibroblast recruitment and other inflammation. Macs also release Growth Factors (look for the letters GF)
What causes abnormal scar formation?
Inadequate granulation tissue formation or excess/exuberant scar formation/repair
Define cirrhosis
persistent injury overcomes regeneration potential.
What is a Hypertrophic scar?
remains relatively limited to affected area and regression. Indented scar
What is a Keloid?
raised beyond boundary of wound without regression. Protruding scar
What is a Desmoid tumor?
aggressive fibromatoses and benign neoplasm
What is a contracture?
joint deformity when scar crosses a joint.
What is in the Portal triad? How important is repair?
Hepatic artery, portal vein, and bile duct. Restoration during during repair is critical
What are 3 histologic findings of Cirrhosis?
Bridging fibrous bands, regenerative nodules, and altered architecture
What are systemic factors (3) affecting repair?
Nutritional, Metabolic, and Vascular issues
What are local factors (5) affecting repair?
Infection, Persistence of Insult (eg Hep C), Trama with early movement before repair, trama with foreign material, Size/Location of injury
What is Virchow’s Triad?
Endothelial Injury, abnormal blood flow, and hypercoagulability are the three big contributing factors to Thrombosis
What is Edema?
Fluid accumulation in interstitial tissue
What is Effusion?
Fluid accumulation in a body cavity, includes Pleural Effusion and Ascites. Can be transudate and Exudate
What is Anasarca?
Systemic edema and effusions due to one or mixed causes. Usually a transudate
What is Transudate?
accumulated fluid leakage from vessels. Associated with Increased hydrostatic pressure/reduced oncotic pressure
What is exudate?
accumulated fluid and protein leakage from vessels, also usually has WBC. Associated with inflammation
Describe Active Congestion
Dialation of arteries results in increased blood flow. Creates redness of acute inflammation
Describe Passive Congestion
Impaired venous drainage results in stasis and accumulation of deoxygenated blood. Has bluish/dusky tinge. Can be caused by right sided heart failure
What is a hemorrhage?
Burst blood vessel. On skin from smallest to largest they are Petechiae, Purpura, Echymoses. Also can be hematoma and hemothorax/hemopericardium/hemoperitoneum
What causes Infarct?
Ischemia and hypoxia
What is Thrombosis?
Intravascular, mass coagulation of blood (platelets, fibrin, and entrapped cells), adherent to luminal surface of vessel
Predisposing factors for Thrombosis (5 things)
Stasis, non-laminar blood flow, increased blood viscosity (dehydration), damage to endothelium (atherosclerosis), hypercoagulable state
Complications of Thrombosis? (2 things)
reduced blood flow to tissue, fragments causing embolism
Define Embolism
Some material carried in blood, it can be lodged at a point and obstructs a vessel
Embolism variations (6 things)
Thromboembolus, Atheroemboli, fat/bone marrow emboli, tumor emboli, amniotic fluid emboli, air/gas emboli
Define Shock
systemic hypoperfusion of cells and tissue. Seen with lactic acidosis, hypotension, and tachycardia
What is Disseminated intravascular coagulation (DIC)
complication in many disease states where clotting factors become activated in blood vessels.
Tests for DIC
fibrin split products, D-Dimer, Platelet count
