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Healing, Sepsis
Ulcer
loss of epithelial surface
acute inflammation in epithelial surfaces
Fistula
abnormal communication between organs or an organ and a surface
Scar
Causes distortion of structure and sometimes altered function
Chronic inflammation
Marked by replacement of neutrophils and monocytes with lymphocytes,
plasma cells and macrophages
Accompanied by proliferation of fibroblasts and new vessels with
scarring
Autoimmunity
Auto-antigens provoke self-perpetuating immune responses that
cause chronic inflammatory diseases like RA, MS
Responses against common environmental substances cause
chronic allergic diseases, such as bronchial asthma
Granulomatous inflammation
Focus of chronic inflammation encountered in a limited
number of conditions
Cellular attempt to contain a foreign body or an offending
agent that is difficult to eradicate (i.e. Tb)
Microscopic aggregation of macrophages that are
transformed into epithelioid cells, surrounded by a collar
of lymphocytes and occasionally plasma cells
Epithelioid cells have a pale pink granular cytoplasm with
indistinct cell boundaries, often merging as giant cells
Foreign body epitheloids have dispersed nuclei
Infectious body epitheloids have marginal or horse-shoe nuclei
Patterns of Inflammation
Serous Inflammation
Marked by outpouring of thin fluid
From blood serum, e.g. burn blisters
Effusion from mesothelial cells lining the pleural, peritoneal and pericardial cavity
Fibrinous Inflammation
A feature of pericardial and peritoneal inflammation
Vascular permeability allows larger molecules like fibrin to pass or procoagulant
stimulus exists in the interstitium (e.g. cancer cells)
Suppurative Inflammation
Characterized by production of large amount of pus composed of neutrophils,
necrotic cells and edema fluid
Involves pyogenic bacteria e.g. Streptococci and Staphylococcus aureus
Abscesses are focal localized collections of purulent inflammatory tissue caused
by suppuration.
Ulcers
Local defect or excavation of the surface of an organ or tissue by sloughing of
inflammatory necrotic tissue
Acute stage - intense polymorphonuclear infiltration and vascular dilation in
margin
Chronic stage - margin and base develop fibroblastic proliferation, scarring and
accumulation of lymphocytes, plasma cells and macrophages
Fever
Acute-phase protein secretion from liver
Leukocytosis
Tachycardia, increased blood pressure
Shivering, chills
Anorexia, somnolence, malaise
Septic shock
Behavioral
Rigors (Shivering)
Chills
Anorexia
Somnolence
Malaise
Sepsis
Systemic Inflammatory Response Syndrome involves
two or more of the following
temperature >38.3C or <36C
heart rate >90 beats/min; <32 mm Hg
respiratory rate >20 breaths/min, PaCO2 or need for mechanical
ventilation
WBC count >12,000/uL or <4,000/uL or >10% immature forms
(bands)
Septic stimuli
Gram-negative bacteria
LPS, endotoxin
Binds to LPS binding protein (LBP)
Binds to CD14 opsonin receptor
TLR-4 binds LPS and LPS-LBP
Stimulates release of TNF, IL-1, IL-6
Gram-positive bacteria
Exotoxins, superantigens
Bind Vb regions of TCRs and/or to MHC-II
TLR-2 binds cell wall components
Stimulates release of IFN-g, TNF, IL-1, IL-6
Progression of sepsis
Cytokine release and amplification
Vasular response and neutrophil migration
Coagulation cascade
Short arm, extrinsic pathway, activated by expression of Tissue
Factor VIIa Xa thrombin fibrin
high plasma levels of plasminogen-activator inhibitor type-1
(PAI-1) suppress plasmin and fibrinolysis
disseminated intravascular coagulation in 30-50% cases
Counter-inflammatory response
Apoptosis of Th and B-cells
Organ failure
Widespread vasodilation
Decreased production of vasopressin
(ADH) and glucocorticoids
Circulatory collapse and tissue hypoxia
Stable Cells
Undergo few divisions normally, but can be activated from G0
cells when needed
hepatocytes
renal tubular cells
parenchymal cells of glands
mesenchymal cells (smooth muscle, cartilage, connective tissue,
endothelium, osteoblasts)
Regeneration
Proliferation of cells and tissues to replace
lost structures
Whole organs and complex tissues rarely
regenerate after injury
Compensatory growth rather than true
regeneration
Liver hypoplasia and kidney hypertrophy
Stem Cells
Characterized by self-renewal properties and
capacity to generate differentiated cell lineages
obligatory asymmetric replication
one daughter cell retains its self-renewing capacity
the other enters a differentiation pathway
stochastic differentiation
stem cell divisions generate either two self-renewing stem cells
or two cells that differentiate
Stimulation for either outcome is conjectureseemingly random
Therapeutic
Transfer of adult nucleus into enucleated
oocyte restores pluripotency
Induced to differentiate into various cell types
in vitro
Injected into damaged organ
Liver
Oval cells are bipotential progenitors of hepatocytes and biliary cells
Brain
Neural precursor cells generate neurons, astrocytes, and
oligodendrocytes in the subventricular zone and the dentate gyrus of the
hippocampus
Skin
Hair follicle bulge, interfollicular areas of the surface epidermis, and
sebaceous glands
Intestinal epithelium
crypts are monoclonal structures derived from single stem cells
villus contains cells from multiple crypts
Cornea
limbal stem cells maintain corneal transparency
Stable tissues
Parenchymal cells of solid organs in G0
Endothelial cells, fibroblasts, smooth muscle
Limited regeneration after wounding
Permanent tissues
Absolutely nonproliferative
Cardiac muscle, neurons
Growth factors
Polypeptides that promote survival and
proliferation by signal transduction
Increase in cell size
true growth factors
Signaling mechanisms
Receptors with intrinsic tyrosine kinase activity
Dimeric transmembrane molecules
Ligand binding induces stable dimerization and
phosphorylation
7tm GPCRs
Seven transmembrane proteins
Ligand binding induces association with GTP-binding
protein, which swaps GDP for GTP
Gi or Gs protein inactivates or stimulates another
effector
Gs activates membrane adenylyl cyclase; GTPGDP
cAMP activates PKA, etc.
Repair Process
Removal of Debris
begins early and initiated by liquefaction and
removal of dead cells and other debris
Scarring
fibroblasts produce collagen until granulation
tissue becomes less vascular and less cellular
progessive contraction of the wound occurs,
resulting in deformity of original structure
diabetes
Dietary deficiency
ascorbic acid
protein
Granulation at tracheotomy