Flashcards in 11.2 Biochem (cell bio) Deck (148):
Phases of the cell cycle
Interphase: G1, S, G2
G0 is another phase, out of G1
G0 and G1 are of variable duration
Regulatory proteins that control cell cycle events.
They are phase specific (e.g only work in G1 phase)
Cyclins activate CDKs and make cyclin-CDK complexes
They are constitutive (expressed constantly) and inactive.
Must be activated by Cyclins.
Must be both activated and inactivated for cell cycle to progress.
The complexes phosphorylate target proteins in order to drive the cell cycle.
What happens to cyclins once their phase-specific job is complete?
They are degraded by ubiquitin protein ligase
What proteins bind to and inactivate the cyclin-CDK complexes?
p21, p27, and p57
(note: p53 controls the activation of p21)
What cyclins are active at the G1 --> S transition? What TSGs are active there?
Cyclin D and Cyclin E
Rb and p53 (inhibit(!) progression thru the cycle at this point)
Where in the cell cycle is TSG p53 active?
G1 --> S and G2 --> mitosis
How does Cyclin D work?
Cyclin D binds and activates CDK-4.
The complex causes phosphorylation of Rb protein (kinases phosphorylate!)
Rb protein was bound to EF-2, but when it is phophorylated, it is released.
Since EF-2 isn't bound, it can transcribe and synthesize all of the components needed for progression through the S phase
How does Cyclin E work?
Cyclin E binds/activates CDK-2
This allows cell to progress from G1 --> S
What cyclins affect the G2 --> M transition of the cell cycle?
Cycin A and Cyclin B
What does Cyclin A do?
Cyclin A binds to CDK-2
This allows the cell to enter mitosis (prophase)
What does Cyclin B do?
Cyclin B binds to CDK-1
The Cyc B/CDK-1 complex is activated by CDC-25.
Once activated, the complex initiates breakdown of the nuclear lamins (nuclear envelope) so that mitosis can start.
What tumor suppressors are active in the cell cycle?
Rb and p53 normally inhibit G1 --> S
If mutated, there will be unrestrained growth.
Since they are TSGs, they need TWO hits to lose fn- having only once copy is good enough protection.
If Rb is mutated, what tumors result?
Permanent cells and the cell cycle
These cells stay in G0, and regenerate from stem cells.
Neurons, skeletal musc, cardiac musc, RBCs
If you give a pt a cancer drug, these cells will not be affected since they are not rapidly dividing.
Stable (quiescent) cells and the cell cycle
Are in G0, but enter into G1 and go thru the cell cycle when stimulated to do so.
Labile cells and the cell cycle
Labile cells never go to G0, they are rapidly dividing and have a short G1 bc they go thru the cell cycle quickly.
Bone marrow cells, gut epithelium, skin, hair follicles.
Anti-cancer drugs affect these a lot.
What things regulate the cell cycle?
What happens in the RER?
Synthesis of secretory (exported) proteins
Addition of N-linked oligosaccharide to many proteins
Aka the RER of neurons
These synth enz (eg ChAT) and peptide neurotransmitters
What cells are rich in RER?
Mucus-secreting goblet cells of the small intestine
Ab-secreting plasma cells
Things that secrete a lot!
Not attached to a membrane.
Free ribosomes synth cytosolic and organellar proteins (for the mito, the nucleus)
Make things that stay inside the cell (RER makes things that will be secreted)
What happens in the SER?
Site of steroid synthesis
Detoxification of drugs and poisons
What kind of cells are rich in SER?
Steroid-producing cells of the adrenal cortex
Things that detox or make steroids!
Lots of SER in hepatocytes of pts on lots of meds, bc need to detox a lot.
What are the two sides of the golgi called, and which way do they face?
cis-golgi is close to the ER (it receives stuff from the ER)
trans-golgi is closest to the plasma mbr, to sends stuff to the mbr or also to lysosomes
(the medial golgi is in between the cis and trans)
What AAs are modified by the golgi, and how?
Serine, Threonine, Asparagine
The golgi adds O-oligosaccharides to serine and threonine residues, and N-oligosaccharides to asparagine.
How does the golgi handle lysosomal proteins?
It adds mannose-6-P to them, which targets the proteins to the lysosome.
What happens if mannose-6-P is not added to lysosome proteins?
I-cell disease (inclusion cell dz)
Instead of being targeted to the lysosome, the lysosomal proteins just go through the default pathway, which is secretion outside of the cell. So, lysosomes can't work since they don't have the right proteins.
This is an inherited lysosomal storage disorder, often fatal in childhood.
coarse facial features
restricted joint mvmt
high plasma lvls of lysosomal enz
What are the three fates of things that the golgi has packaged and released?
1. Vesicle is targeted to they lysosome (bc it contains lysosomal proteins and is tagged w Mannose-6-P to go there)
2. Goes into a constitutive transport vesicle and is excreted
3. Goes into a secretory storage vesicle- is secreted when needed.
What things are sulfated by the golgi?
Sugars in proteoglycans
Selected tyrosine on proteins
The golgi used core proteins to assemble...
proteoglycans (and then it sulfates their sugars)
What are the 3 vesicular trafficking proteins?
COP-1 retrograde, golgi back to RER
COP-2 anterograde, RER --> cis-golgi
Clathrin- trans-golgi --> lysosomes
also endocytosis: plsm mbr --> endosomes
Cargo molecule binds to a cargo receptor on the pls mbr surface.
Adaptin helps Clathrin bind to the receptor, once enough bind, they are depressed inward (clathrin-coated pit), dynamin pinches them off
So a coated vesicle (clathrin-coated) is no in the cytoplasm.
Uncoating occurs (clathrin and adaptin can be reused), and the transport vesicle is naked.
Naked vesicle fuses w endosome/lysosome.
(really, fuses w endosome, hydrolytic enz enter, and this makes it a lysosome)
Lysosomes use hydrolytic enz to degrade things- this processes the endocytosed molecules so that they can be used by the cell.
T/F a clathrin-coated endocytosed vesicle fuses w the lysosome/endosome
The vesicle must undergo uncoating before it can fuse.
Catabolizes long-chain FA and AAs
Changes long --> medium chain thru B-oxidation, and then they can go to the mito to be degraded.
Means that v long-chain FA will accumulate in blood- this causes neuro defects.
Barrel-shaped protein complex; it degrades damaged or unnecessary proteins that are tagged w ubiquitin
Nuclear localization sequence
Short 4-8 AA sequence rich in Arginine, Lysine, and Proline that targets the proteins to the nucleus (eg found on histones).
Nuclear pores recognize this sequence, and ATPase allows the protein to come in.
Very few things enter or exit the nucleus.
e.g. histones come in
mRNA and ribosomal subunits go out.
Assist in proper folding and txport of polypeptides across the ER, Golgi, beyond.
Some chaperones are synth'd constantly and are involved in normal intracellular protein trafficking.
Others are only made in times of stress (e.g. heat-shock proteins)
If the protein folding is not successful, chaperones facilitate degradation of the dmgd protein (often w ubiquitin)
Heat shock proteins
A type of chaperone protein that is induced by stress (in this case, heat).
They rescue shock-stressed proteins from misfolding.
Ubiquitin is also a hsp- it is added to proteins that misfold and need to be targeted for degredation by the ubiquitin-proteosome complex.
Cell transport structure
Cylinder md of helical array of polymerized a- and B-tubulin.
Each dimer has 2 GTP bound.
MTs are incorporated into flagella, cilia, and mitotic spindles; also involved in slow axoplasmic txport in neurons.
They grow slowly, but collapse quickly.
Molecular motor proteins
These drive up and down the MTs to transport cellular cargo on one end or the other.
Dynein does retrograde transport (+ to -)
Kinesin does anterograde txport (- to +)
Dynein = die! (move closer to the negative)
In neurons, which molecular motor protein carries NTs toward the synapse?
The MTs have their negative end at the cell body, and their positive end at the distal end of the axon.
So, NTs need to go from negative to positive, and kinesin does this.
Microtubule polymerization defect
Decreased fusion of phagosomes and lysosomes,
Decreased phagocytosis, bc phagocytes can't mv
Px recurrent pyogenic infections, partial albinism, peripheral neuropathy.
List the drugs that act on MTs
Paclitaxel (anti-breast cancer)
9+2 arrangement of MTs (9 MT doublets around outside, plus 2 single MTs in middle)
Each doublet has dynein ATPase that links all of the doublets and causes bending of the cilium by differential sliding of doublets
How do ciliated cells communicate so that the cilia on different cells beats in the same direction?
aka Primary ciliary dyskinesia
Dynein is defective, so cilia are immotile.
Causes male and female infertility (sperm, fallopian tube), bronchiectasis, and recurrent sinusitis bc bacteria and particles are not swept out.
A/w situs inversus
List the main cytoskeletal elements
Actin and myosin
Where are actin and myosin found?
Where are Microtubules found?
Neurons (for axonal trafficking)
List the intermediate filaments
IFs are a family of proteins w similar seq/structure. Most are cytoplasmic (except nuclear lamins are nuclear)
GFAP (glial fibrillary acid proteins)
Neurofilaments L, M, H
Nuclear lamins A, B, C
Intermediate filament found in CT: in fibroblasts, leukocytes, endothelium
It supports cellular membranes and keeps certain organelles fixed within the cytoplasm
Intermed Filament found in muscle cells- smooth, skel, and cardiac.
Intermed Filament found in epithelial cells
Keratin is in desmosomes and hemidesmosomes.
Glial fibrillary acid proteins
Intermediate filaments found in astrocytes, schwann cells, and other neuroglia
Intermed filament found in neurons
Neurofilaments L, M, H
Intermediate filaments found in axons of neurons
Nuclear Lamins A, B, C
Intermediate filaments in the nuclear envelope and also with the DNA inside the nucleus
Plasma membrane makeup
Asymmetric lipid bilayer
Contains phospholipids (50%) and cholesterol (50%), and also some sphingolipids, glycolipids, and proteins.
What things increase the melting temp of the plasma mbr?
Long saturated FA content (fewer double bonds, so can pack together really tightly)
These also cause decreased fluidity
What are the phospholipids that make up the plasma mbr?
*really really imp- this is how you make arachnidonic acid products
How do you make arachnidonic acid?
Membrane lipid (phosphatidyl inositol) is converted to arachnidonic acid by Phospholipase A2
What can block Phospholipase A2?
Blocking phospholipase A2 means no arachnidonic acid will be made (and therefore no leukotrienes, prostacyclins, prostaglandins, or thromboxane)
What are the 2 enz that can act on arachnidonic acid?
Lipooxygenase (converts it to hydroperoxides --> leukotrienes)
Cyclooxygenase COX-1 or COX-2 (converts it to endoperoxidases --> PGI2, PGE2, TXA2)
What drug blocks Lipooxygenase?
Blocking lipooxygenase means that arachnidonic acid won't be converted to hydroperoxidases (so no leukotrienes)
What drugs block COX-1 and/or COX-2
Also, corticosteroids block proteins from being synthesized to make COX-2 in the first place.
If COX-1 and COX-2 are inhibited, what effect will this have?
There will be no prostacyclins, prostaglandins, or thromboxane
After arachnidonic acid has been converted to endoperoxides, what are the endoperoxides converted to?
What effects does prostacyclin have?
Decreased platelet aggregation and vasodilation
Decreased uterine tone
What effects does prostaglandin have?
Decreased vascular tone
Increased uterine tone (increased contractions)
Decreased bronchial tone
Increased gastric mucin production
Maintains renal blood flow
Keeps PDA open
What effect does thromboxane have?
TxA2 is pro-thrombotic. It causes
Increased platelet aggregation and vasoconstriction.
After arachidonic acid has been converted to hydroperoxides, what do the hydroperoxides become?
Leukotrienes (LTB4, LTC4, LTD4, LTE4)
What does leukotriene LTB4 do?
Promotes neutrophil chemotaxis
What do leukotrienes LTC4, LTD4, LTE4 cause? What drugs can inhibit them?
They cause bronchoconstriction
Inhibit w Zafirlukast, Montelukast (used for asthma, allergies)
What 3 things do corticosteroids inhibit?
Phospholipase A2 (and by doing so decrease inflammation)
Sodium pump in the plasma membrane
Na+ K+ ATPase
The ATP site is on the cytoplasmic side.
For each ATP consumed, 3 Na+ go out and 2 K+ come in.
During the cycle, the pump is phosphorylated.
Drug that inhibits the Na+ K+ ATPase by binding to the K+ site
How do cardiac glycosides work?
Digoxin and digitoxin directly inhibit the Na+ K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange. (So Ca2+ doesn't go out).
This means there is increased intracellular Ca2+ which leads to increased cardiac contractility.
What are the 5 may signalling pathways of endocrine hormones?
Steroid receptors (inside the cell)
What hormones use cAMP for signaling?
FLAT CHAMP GGC
ADH (V2 receptor)
Most ant pit hormones use cAMP
What hormones use cGMP for signaling?
NO (EDRF - relaxing factor)
What hormones use IP3 for signaling?
ADH (V1 receptor)
GHRH also, but it mostly uses cAMP.
All of the releasing hormones use IP3 with the exception of CRH (which uses cAMP).
What hormones use a steroid receptor?
These can go through the plasma mbr- their receptors are inside the cell:
PET T VAG
What hormones use tyrosine kinase to signal?
Tyrosine kinase uses phosphorylation and has an a and B subunit.
Note: GH causes IGF-1 release; IGF-1 is the hormone that has the action.
How does the tyrosine kinase receptor initiate a signalling cascade?
Transmembrane receptors bind an extracellular ligand (eg.g insulin, PDGF), the the binding cause the transfer of an intracellular phosphate group from ATP to tyrosine side chains on certain cellular proteins- including the tyrosine side chain on the receptor itself (autophosphorylation)
After autophosphorylation, the signalling cascade starts
What are the kinds of tyrosine kinase receptors?
1. PDGF receptors and other growth factor receptors- these are single-pass transmembrane proteins (vs G-coupled, which are 7-pass)
2. Insulin and IGF-1 receptors- these have important subunits:
2 alpha subunits which are bound together by disulfide bonds. The alpha units are extracellular and bind the ligand (eg insulin)
2 beta subunits- these are intracellular and undergo the tyrosine kinase activity needed for auto-phos and the signaling cascade.
What are the tyrosine kinase signalling pathways?
There are 2 separate pathways that can occur:
1. PKC pathway
2. Ras pathway
What is the tyrosine kinase pathway that activates PKC, starting from when a ligand binds the tyr kinase receptor?
Ligand binds receptor
Activated phospholipase C
Splits into IP3 and DAG
IP3 causes intracellular calcium incrs, Ca2+ binds to calmodulin, and CaM kinase is activated
DAG activates PKC (protein kinase C)
Both CaM kinase and PKC affect gene regulation and transcription
Note that the phospholipase C can also be activated by Gq. Pathway is the same.
What is the tyrosine kinase Ras pathway, starting from when a ligand binds the tyr kinase receptor?
Ligand binds tyr kinase receptor
Active Ras protein
Ras activates PK-I
PK-I activates PK-II
PK-II activates PK-III
PK-III affects target gene transcription/translation
What is the role of collagen?
Organizes and strengthens extracel matrix
Most abundant protein in body; extensively modified
Type I collagen
90% of all collagen is Type I
Found in bone, skin tendon
also in dentin, fascia, cornea, late wound repair
Type I - bONE
Type II collagen
Found in cartilage (incl hyaline)
also in vitrious body, nucleus pulposus
Type II - carTWOlage
Type III collagen
found in skin, blood vessels, uterus, fetal tsu, granulation tsu
Type III is the kind that is defective in Ehlers-Danlos
Type IV collagen
Found in basement mbr or basal lamina
(BM of glomeruli in kidney, of capsule of lens)
Type four = under the floor (under the BM)
Type IV is defective in Alport Syndrome
Mne for collagen types
Strong - bone, skin, tendon
Bloody - highly vascularized things
BM - basement mbr
Be (So Totally) Cool, Read Books
I Bone (Skin, Tendon)
What steps of collagen synthesis occur inside vs outside of fibroblasts?
Exocytosis into extracellular space
Step one of making collagen: Synthesis
Synthesis (in RER) involves the translation of collagen alpha chains (pre-pro-collagen), which usually has the structure Gly-X-Y.
X and Y can be proline, hydroxyproline, or hydroxylysine.
Hydroxylation of pre-pro-collagen
Hydroxylation occurs on specific proline and lysine residues, and requires Vitamin C.
If no Vitamin C is present, collagen cannot form and pt will get scurvy.
Glycosylation of collagen
Glycosylation occurs on pro-alpha chain lysine residues.
Procollagen is formed- it's a triple helix of 3 collagen alpha chains.
Once procollagen is formed, it is exocytosed into the extracelluar space.
Once procollogen has been exocytosed outside of the fibroblast, what happens to it first?
First, proteolytic processing- cleavage of the terminal regions of the procollagen changes it to tropocollagen, which is insoluble.
What final processing occurs to tropocollagen?
Cross linking. Lysine and Hydrolysine are covalently linked by lysyl oxidase, reinforcing the staggered tropocollagen molecules. The cross-linking makes collagen fibrils.
What process of collagen formation is inhibited by scurvy?
Scurvy = not enough Vit C.
Hydroxylation of proline and lysine residues req's Vit C, so this would be inhibited in scurvy.
If there is no hydroxylation, nothing else (glycosylyation, exocytosis, etc) can occur.
What process of collagen formation is inhibited in osteogenesis perfecta?
Formation of the triple helix (procollagen).
(Which occurs right after glycosylation of the pro-alpha-chain lysines- so they can be glycosylated, but can't form the procollagen)
What process of collagen formation is disrupted in Ehlers-Danlos syndrome?
Cross-linking to make fibrils.
The collagen is exocytosed and cleaved into tropocollagen, but the covalent lysine-hydroxlysine cross linkage can't occur.
What does Ehlers Danlos cause?
Faulty collagen synthesis causing:
1. Hyperextensible skin
2. Tendancy to bleed/easy bruising
3. Hypermobile joints
Also a/w joint dislocation, berry aneurysms, and organ rupture.
Inheritance pattern of Ehlers-Danlos and which collagen type it affects
There are 6 different types of E-D, and inheritance and severity vary.
Can be auto-dom or auto-rec.
Type III collagen is most likely affected.
What are the Sx of osteogenesis imperfecta?
Multiple fractures (w minimal trauma; may occur during birth process)
Blue sclera- d/t the translucency of the connective tsu over the choroid
Hearing loss d/t abn middle ear bones
Dental imperfections d/t lack of dentin
Note: the fractures can be confused for child abuse
Inheritance, epi, collagen type for Osteogenesis Imperfecta
Genetic bone disorder caused by a variety of genes- most common form is auto-dom with abn Type I collagen. (Type I = bones!)
Incidence is 1:10k
Type II is fatal in utero or in the neonatal period.
Alport's syndrome sx
Progressive hereditary nephritis
Also a/w ocular disturbances
"Can't see, pee, hear"
Type IV collagen is an imp structural component of the BM in kidneys (hematuria), ears, eyes.
Alport's syndrome genetics
D/t a variety of genes resulting in abn Type IV collagen (which is imp for BMs).
Most common form is X-linked recessive.
Wrinkles and skin aging are d/t what?
Reduced production of collagen and elastin
What is elastin?
Stretchy protein in lungs, lg arteries, elastic ligaments, vocal cords, ligamenta flava (connects vertebrae and has relaxed and stretchy conformations)
It is rich in non-glycosylated forms of proline and glycine.
Elastic fibers are made of elastin w fibrillin scaffolding.
Elastin is aka Tropoelastin.
What enz breaks down elastin? What inhibits this enz?
Elastase breaks down elastin
Elastase is normally inhibited by alpha-1-antitrypsin
What defect causes Marfan's syndrome?
A defect in fibrillin
(Elastin + fibrillin scaffolding = elastic fibers)
What causes emphysema?
a-1-antitrypsin usually inhibits elastase, the enz that breaks down elastin. If a-1-antitrypsin is not present, elastase will have excess activity and break down the elastin.
Other than emphysema, what else can be caused by a-1-antitrypsin activity?
Rx: IV infusion of a-1-antitrypsin
What are the characteristics of cells undergoing apoptosis?
Nuclear shrinkage (pyknosis) and basophilia
Pyknotic nuclear fragmentation (karryorhexis)
Nuclear fading (karyolysis)
formation of apoptotic bodies (which are phagocytosed)
Note: there is no inflammation, this is a controlled process!
In what situations is apoptosis initiated?
When cells are deprived of growth factors
When there is cell stress
When there is DNA dmg and the DNA repair process fails to fix it (then p53 triggers apop)
When cytokines like TNF trigger it
When Cytotoxic T cells insert granzyme B into cells, causing the activation of caspases
How does p53 mutation or absence affect apoptosis?
Normally, when there is severe DNA damage that is not repairable, p53 will signal apop.
If p53 is not there or not functional, there can be extensive DNA damage without apoptosis being induced.
What enz execute apoptosis?
Caspase = Cysteine protease that cleaves after ASParatic acid residues
What are the two apoptotic pathways, and how are they activated?
Extrinsic pathway: death receptor mediated. Activated by cell surface death receptor activation.
Intrinsic pathway: mitochondrial. Activated by increased mito permeability, which releases pro-apoptotic molecules into the cytoplasm.
When (by why processes) does the extrinsic pathway of apoptosis occur?
Ligand-receptor interactions (e.g. Fas-Ligand binding to Fas (CD95).
Immune cell (Tkiller) release of perforin and granzyme B
When (and by why processes) does the intrinsic pathway of apoptosis occur?
Hormone induction (menstruation)
Atrophy (endometrium during menopause)
Also occurs as a result of injurious stimuli- radiation, toxins, hypoxia.
Changes in the levels of anti- and pro-apoptotic factors lead to increased mitochondrial permeability and rls of cytochrome c
What specific proteins are involved in the intrinsic pathway of apoptosis?
Increased mito permeability causes rls of pro-apop molecules into cytoplasm:
Bak, Bax, and Bim are pro-apoptotic
Bcl-2 and Bcl-x prevent apoptosis.
Bcl-2 and Bcl-x are lost from mito mbrs when the cell undergoes stress/loses signals. Furthermore, they are replaced with Bak, Bax, and Bim! These cause mito mbr permeability to increase, and makes caspase activating proteins (cytochrome c) and AIF (apop inducing factor) to leak out.
Cytochrome C binds to cytosolic Apaf-1, and the complex activates Caspase-9.
What cell marker is expressed by healthy cells to prevent phagocytosis?
What specific proteins are involved in the extrinsic pathway of apoptosis?
TNFR1 (type 1 TNf-receptor 1
Fas (aka CD 95): Fas ligand bings Fas receptor, leading to the grouping of 3+ Fas molcules to for a binding site for FADD (Fas-assoc'd death domain)
FADD binds inactive caspase-8 (or caspase-10 in humans) --> this causes cleavage and activation of caspase-8, which leads to cleavage/activation of other pro-caspases, and ultimately leads to apoptotic proteolytic cascade (the same pathway used in Tcell seleciton)
FLIP protein can bind to and inhibit cleavage of procaspase-8, inhibiting apop.
What is necrosis, generally?
Enz degredation of a cell resulting from exogenous injury.
Characterized by enz digestion and protein denaturation, w rls of intracellular components.
What are the types of necrosis, and where do they occur?
Coagulative- heart, liver, kidney
Caseous - TB (multinucleated giant cells) of lungs
Fat - pancreas (triglycerides + Ca2+ = soap. see soaponification of fat necrosis)
Fibrinoid - blood vessels
Gangrenous necrosis can be dry (ischemic coagulative) or wet (w bactera, liquefactive) and is common in limbs and GI tract.
What are the characteristics of reversible cell injury?
Cellular swelling (bc of impaired Na+/K+ pump
Nuclear chromatin clumping
Decreased ATP synth
Fatty chg in hepatocytes
Ribosomal detachment (which leads to decreased protein synthesis)
What are the characteristics of irreversible cellular injury?
Nuclear pyknosis, karyolysis, karyorrhexis
Ca2+ influx, leading to caspase activation
Pls mbr dmg
Increased mito permeability, which triggers apop
What are the two categories of infarcts?
Red (hemorrhagic) and Pale
Where do Red (hemorrhagic) infarcts occur?
In loose tsus w collaterals- lungs, liver, intestine
Or, following reperfusion (REd = REperfusion)
Reperfusion injury is d/t dmg by free radicals.
Where do Pale infarcts occur?
In solid tsus w single blood supply, such as heart, kidney, spleen.
What are the characteristics of inflammation?
functio laesa (loss of fn)
Acute phs cytokines: IL-1, IL-6, TNF-a
What is the first step of inflammation?
Histamine, serotonin, and bradykinin cause fluid exudation, which means increased vascular permeability, vasodilation, endothelial injury.
What are the steps of leukocyte activation
Emigration (rolling, tight binding, diapedesis)
Chemotaxis (bacterial products, complement, chemokines)
Phagocytosis and killing
What factors recruit neutrophils to sites of injury/inflam?
LTB4 (leukotriene B4)
In the process of inflam, what is fibrosis?
Fibroblast emigration and proliferation
Deposition of ECM
ECM is collagen- so Vit C is req'd.
ECM is put down quickly, but metalloproteinases remodel the ECM- they require zinc.
So, give pts Vit C and zinc!
Acute inflam is mediated by what? What is the timeframe?
Mediated by neutrophils, eosinophils, and Ab.
Rapid onset: sec- min.
Lasts min- days
Chronic inflam is mediated by what? What are the characteristics?
Mediated by mononuclear cells- characterized by persistent destruction and repair. A/w blood vessel proliferation, fibrosis, and granulomas
What is a granuloma?
Nodular collection of epitheloid macrophages and giant cells. Formation of granulomas is mediated by IL-2 and IFN-gamma. Seen in chronic inflam.
What are the granulomatous diseases?
Some fungal pneumonias
Granulomas occur in chronic inflam- these are all dz's of chronic inflam.
What are the ways of resolving inflam?
Granulation tsu - highly vascularized and fibrotic (it's Type III collagen)
Abscess- fibrosis surrounding pus. body has walled off infection.
Fistula- abn communication
Scarring- collagen deposition resulting in altered structure and fn.
Characteristics of Transudate
Hypocelluar and protein poor
Specific gravity <1.012
Transudate occurs d/t increased hydrostatic prs, decreased oncotic prs, and/or Na+ retention.
Characteristics of Exudate
Cellular (usu inflam cells) and protein rich
Specific gravity > 1.020
D/t lymphocytic obstruction and/or inflam