Extra- basics Flashcards
Acute inflammation signs & causes?
Major cell type?
- Rubor (redness): vasodilation via SM relax from histamin, bradykinin, PG
- Calor (heat) ^ same
- Tumor (swell): post capillary venule leak via histamine and tissue damage (disrupt endo)
- Dolar (pain): PGE2 and bradykinin
- Fever: pyrogens (MO-> IL-1, TNF -> ↑ COX to ↑ PGE2 set point)
- Loss of function
Neutrophils
Activators of neutrophils?
- IL-8
- LTE-B4 (chemotaxis and adhesion as well)
- C5A
- Bacteria (exogenous)- specifically N-formylmethionine terminal AA in some lipids (GPCR)
*then activate Rac/Rho/cdc42 pathway
Cells involved in each:
Acute Asthma
Chronic Asthma
Chronic atherosclerosis
Acute and Chronic Asthma: Eosinophil, IgE
Chronic atherosclerosis: macrophage, lymphocytes
Exudate vs Transudate
Exudate: inflammatory, increase in vascular permeability
- Component: high protein, blood, fluid
- Causes: infection, malignancy
Transudate: no change in permeability
- Components: low protein (main albumin), no cell debris, low specific gravity (ultrafil plasma)
- Causes: ↓osmotic (low albumin) or ↑hydrostatic pressure (HF)
What factors increase vascular permeability?
histamine
bradykinin
leukotrienes
Lymphangitis vs Lymphadenitis
Lymphangitis: vessels inflam, red streak around wound
Lymphadenitis: nodes (hyperplasia, ↑ immune cells)
What initiates leukocyte rolling?
TNF and IL-1 from MO act on endothelial cells of post-cap venules to express E-selectin and ligands for L-selectin within 1-2 hrs
What factors accomplish leukocyte rolling?
Selectins:
L: on leukocytes
E: on endothelium
P: on endothelium and plts
What stimulates P-selectin? Where is it released from?
Thrombin and histamine stimulate Weibel palade bodies to redistribute P-selectin
What protein accomplishes leukocyte transmigration (diapedesis)?
CD31 (PECAM-1)
3 types of Reactive Nitrogen Species? Which is most important in infections?
- eNOS (endothelial)
- nNOS (neuronal)
- iNOS (inducible) <– microbes, IFN-y = kill microbes
What stimulates and inhibits phospholipase A2?
Stimulate: increase cytoplasmic Ca, external kinases
Inhibit: steroids
What degrades bradykinin? Clinical application?
ACE: ACE inhibitors can ↑ level = angioedema
C1 inhibitors: deficiency –> hereditary angioedema
Bradykinin: vasodilates, ↑ permeability, pain
What is an inflammasome?
multiprotein complex develops in cyto in response to damage of infection.
Contains NLR which bind to components of dying/necrotic cells
activators: uric acid, EC ATP, free DNA
Produces IL-1
Physiologic examples of hypertrophy
- body builders (increase muscle <- increase workload)
- uterus in pregnancy (increase hormones)
Physiologic example of hypertrophy
LVH/Cardiomegaly: increase in hemodynamic load (htn)
Hypertrophy:
Characteristics?
Pathyways involved?
Causes?
Characteristics: ↑ protein synthesis
Pathyways involved: PI3k/AKT -> GATA4, NFAT, MEF2
Causes: ↑ functional demand, change in hormone
Hyperplasia
Characteristics?
Causes?
Characteristics: ↑ cell #, DNA, protein, mito
Causes: excess hormone stimulation or GF to increase function capacity or in damaged/resected tissues
Examples of Physiologic Hyperplasia?
- Breast growth @ puberty and pregnancy (glandular epi)
- Liver regeneration (hepatocytes or intrahepatic stem cells)
- Bone marrow (EPO <- Anemia)
Pathologic Hyperplasia?
Stimulation?
Stimulation: virus, excess/inappropriate hormone action or GF
- Endometrial hyperplasia: ↑ estrogen from adipocytes
- Prostatic hyperplasia (↑androgen, DHT)
- HPV
Maligancy can develop from uncontrolled growth
Hypertrophy vs Hyperplasia
Hypertrophy: premanant/non-dividing cells, G0 state
- heart, skeletal m, nerves
Hyperplasia: cells capable of division
- epithelial (GI, breast, skin)
Physiologic Atrophy
- Embryonic structures (notochord)
- Uterus following birth (loss of hormone stimulation)
- breast/uterus/vagina at menopause (↓endocrine stimulation)
Characteristics of Atrophy
Causes?
Character: autophagy, ↓ protein synthesis
Causes: ↓ intracellular organelles, ↓ hormone stimulus
Pathologic Atrophy
- Unused skeletal m: ↓ workload (bed rest, travel, immobile), ubiquination
- Cachexia: poor nutrition (marasmus)
- ↓ Blood Supply: senile atrophy of brain (atherosclerosis)
- Loss of innervation (neuromuscular disorder), disrupt fxn and metabolism of skeletal m
Atrophy in cancer caused by?
muscle wasting
TNF suppresses appetite and depletes lipid stores
atrophy mechanisms
- ubiquinatin-proteasome path
- autophagy
Metaplasia mechanism
Change in cell PRODUCTION to adapt by changing cell type of epithelial cells, NO CHANGE in phenotype.
Clinical Examples of Metaplasia
- Resp tract (colum->squam) <- smolking
- Barretts esophagus (squam->colum) <- acid
- Myositis Ossificans (muscle to bone) <-trauma
- Vit A Def: upper resp (to keratinizing squam), Xeropthalmia (eye to keratinizing squam)
- Apocrine: fibrocystic in breast to lobular
