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123 Cards in this Set
- Front
- Back
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What are the 4 main tissue types?
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epithelia, CT, muscle, nervous
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What do epithelial tissues arise from?
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3 primary germ layers of the embryo: mesoderm, ectoderm, endoderm
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Skin epithelium derived from what germ layer?
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ectoderm
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Digestive tract epithelium derived from what germ layer?
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endoderm
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Epithelium? Mesothelium? Endothelium?
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epi: skin, digestive tract
mesothelium: peritoneal cavity endothelium: blood vessels, lymph vessels, heart |
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What are the morphological characteristics of epithelium?
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cells in close apposition (sheets of cells)
cells rest on BM cells are adhesive (intercellular jxns) tissue is avascular |
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If tissue is avascular, how does it receive nutrition?
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there are capillaries underneath the cells
-overlie vascular CT |
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What is on the apical surface of epithelial cells?
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microvilli, cilia, sterocilia
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What is on the basal surface of epithial cells?
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BM, hemi-desmosomes, plasma membrane interdigitations
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What is on the lateral surface of epithelial cells?
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intercellular jxns (tight, adherent, desmo, gap)
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What are the 5 functions of epithelia?
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1. protection (keratin and mucus prevent drying)
2.absorption (microvilli in kidney and intestine) 3.surface transport (cilia) 4.secretion (secretory glands) 5.sensory reception |
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What are the clinical correlations of CF?
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sputum culture grows Pseudomonas aeruginosa
sweat test reveals high Na and Cl bronchiectasis (toothpaste lines) |
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Prevalence of CF?
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1:2000-2500
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How does CF affect functioning of several organs?
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ducts or other tubes become clogged, usually by thick, sticky mucus or other secretions
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Malfxn of CFTR in sweat gland prevents what?
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Na and Cl reabsorption therefore preventing water influx as well
sweat contains lots of NaCl |
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What is CFTR?
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voltage gated Cl channel on apical membranes of epithelial cells (lung, pancreas, sweat glands)
-glycosylated extracellular domain -12 membrane spanning domain -2 ATP nucleotide binding domains -R domain dependent on PKA |
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What regulates CFTR?
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PKA dependent phosphorylation
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What needs to be bound to CFTR for fxn?
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ATP binding, but ATP hydrolysis indpendent
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Describe structure of CFTR?
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2 sets of 2 transmembrane domains
2 ATP binding cassettes: ABC transporters R domain |
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How is CFTR involved w/ binding actin?
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through ESP50/Ezrin Adapter protein that links actin cytoskeleton
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What is relationship w/ PKA and cholera toxin?
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constant p-lation by PKA
Na out, water out therefore diarrhea |
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In lung epithelia, what is associated w/ CFTR?
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beta adrenergic R b/c when bound leads to increase cAMP activating PKA which then regulates CFTR
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In CFTR, what counterion does Na flux require?
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Cl is counter ion that flows when Na channels open
-water then flows around cells maintaining osmotic pressure -result: isotonic NaCl soln flows from blood to lumen |
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Most common mutation of CF (channelopathy)?
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deltaF508 causes 2/3 of cases
no frameshift b/c deletes 3 nucleotides 2 from Phe 1 from isoleucine |
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What does deltaF508 mutation result in?
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prevents proper folding of protein fails to become fully glycosylated and is quickly degraded by proteosome
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What effect does temp have on misfolding of CFTR?
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at normal temps (37c) degraded
at 23-30 R's will get to cell surface and work even though missing Phe |
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Describe intracellular trafficking of CFTR.
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Normally leaves rER for golgi where it is not glycosylated to mature protein then leaves golgi for apical membrane or recycling endosome
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Where does CFTR eventually end up?
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late endosome to lysosome pathway for degradation
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What are the 5 CF class mutations?
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1. defect in protein production
2. defect in processing (ER-deltaF508) 3.defect in regulation (PKA can't p-late properly) 4.defect in Cl condxn 5. mutations causing decreasing synthesis (mutator in promoter) |
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Action of CFTR in lung epithelia?
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transports Cl out, Na and H20 follow therefore when no CFTR = thick mucus build up
S. aureus P. aeruginosa adheres to mucus |
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What 3 symptoms do CF patients exhibit?
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-male infertility due to vas deferens blockage
-obliteration of pancreatic excrine fxn -progressive tissue deterioration in lung -viscous mucus -recurrent infxns -establishment of Ab resistant strains |
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What is almost always the cause of death in CF?
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loss of lung fxn
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Where is CF incidence high?
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most common inherited disease of Caucasian pop (1 in ever 29) demonstrating heterozygote by providing protection against loss of intestinal fluid during cholera, typhoid fever and tuberculosis b/c bad CFTRs decrease levels of water and Cl secretion in small intestines (2% selective advantage)
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Describe gene therapy for CF?
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deliver normal copy of CFTR gene to site of action by modified & synthetic vectors
-gene transfer to CF airway via nose drops or aerosol is possible but limited efficiency of transfer -risk of serum immunological rxns is primary factor b/c vectors associated w/ acute inflam rxns |
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Continual pressure in bone leads to what?
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resorption
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tension/stress in bone leads to what?
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strengthening and new bone formation
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Describe the inorganic structure of bone matrix
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primarily hydroxyapatite (calcium phosphate) also contains bicarb, citrate, magnesium, potassium, and Na
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What is the inorganic bone matrix good at?
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compression, a crystal!
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Describe the organic structure of bone matrix.
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mostly Type I collagen
ground substance, proteoglycans keratin and chondroitin sulphates glycoproteins: osteocalcin & sialoprotein |
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What is the organic bone matrix good at?
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tension
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What is the fxn of osteocalcin and sialoprotein as components of organic matrix of bone?
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improve adherence of the varous constituents
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What do mesenchymal stem cells differentiate into
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osteoprogenitor cells
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What do osteoprogenitor cells diff. into?
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osteoblasts
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What is the seq of bone cell diff?
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osteoprogenitor-osteoblasts-osteocytes
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What do osteoclasts arise from?
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blood borne monocytes
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Which of the bone cells doesn't originate from mesenchymal stem cells?
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osteoclasts
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What is the name of bone-lining cells on external bone surfaces?
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periosteal cells
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What is the name of bone-lining cells on internal bone surfaces?
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endosteal cells
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Describe the coverings of bone.
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outer covering-periosteum
inner marrow cavities-endosteum |
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What attaches periosteum to bone?
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sharpey's fibers of Type I collagen
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Where do Sharpey's fibers extend from?
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periosteum to bone matrix
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Fxn of periosteum?
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supplies blood vssls to bone
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Fxn of osteoblasts?
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secrete the organic matrix (collagen I) of bone (osteoid) and control mineralization
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What is osteoid?
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Type I collagen and varous proteoglycans (organic matrix of bone)
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Fxn of alkaline phosphatase?
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cell surface enzyme that hydrolyzes phosphate esters at high pH thus increases phosphate concentrations--crystallization
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Fxn of osteocalcin?
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provides nucleation sites for crystal formation
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When do osteoblasts(young) diff into osteocytes (mature)?
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when they become trapped in lacuna thus triggering diff.
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Compare osteoblast and osteocytes
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osteocytes have more heterochromatin, less rER, less golgi relative to blast
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How do osteocytes talk and transfer nutrients?
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via cell processes in canaliculi across gap jns
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Fxn of osteocyts?
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bone turnover and maintenance
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Where are the cell processes of osteocytes located?
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embedded w/n canaliculi, spaces surrounded by mineralized bone
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Nucleation of osteoclasts?
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mutlinucleated via fusion of monocytes
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Fxn of osteoclasts?
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resorbs (eats) bone
secretes acid to dissolve crystal (pH 4.5) secretes enzymes to hydrolyze collagen |
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What hormone inhibits osteoclast?
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calcitonin (tones down ECF Ca)
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Describe components of osteoclast.
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Howships's lacuna or subosteoclastic compartment
-big adherens jxn of actin -bicarb/Cl exchanger to ensure cytoplasmic pH neutrality -Cl channel to prevent excessive rise in intracellular pH -carbonic anhydrase II generates H to create acidic environment -ATP dependent pump |
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in osteoclasts, what follows Cl that is removed by Cl channel?
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H by V-type ATPase to Howships lacuna
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Explain action of carbonic anhydrase in osteoclasts?
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Co2 + water -H2CO3-H + HCO3-
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How do osteoblasts and osteoclasts interact?
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via paracrine agents to control Ca
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Action of MMPs in bone.
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proteases break down collagen in acidic environment created by H pump
-they are released by lysosomes |
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What gland is calcitonin secreted from?
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thyroid gland "C cells"
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What do calcitonin and PTH act on?
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bone, kidney, intestines
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Compare calcitonin w/ PTH
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calcitonin decreasing Ca in ECF
PTH increasing Ca in ECF |
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Where in bone is compact bone? spongy?
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compact: surface
spongy: ends of bone |
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Where is yellow marrow? red?
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yellow: compact bone
red: spongy |
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What is the organization center of compact bone?
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osteon or Haversion system w/ central core canal that carries nutrients
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What 2 canals are found in compact bone?
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Volkmann's canal
Haversian canal |
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What is another name for spongy bone?
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trabecullar bone
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Is spongy bone haversion?
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no, lamellar
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Flat bones are mostly what type of bone?
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spongy
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Where are osteocytes found?
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concentrically arrayed b/n lamellae
osteocytes in adjacent lamella are interconnected by cell processes lodged in canaliculi that are linked by gap jxns |
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What type of ossification for long bones? flat bones?
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long bones and vertebral column: endochondral ossif.
flat: mesenchymal ossif. |
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What is the term for a newly synthesized bone ECM?
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osteoid, deposited in forms of bands or lamella
osteoclasts are trapped w/n osteoid and become osteocytes when the matrix is calcified |
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What is the process of making spongy bone?
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intramembranous ossification
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What 3 things do intramembranous ossification require?
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1. well-vascularized primitive CT
2. bone formation is not preceded by the formation of a cartilage 3. an aggregate of mesenchymal cells differentiates directly into osteoi-producing osteoblasts |
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What is endochondral ossfication?
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replacement of hyaline cartilage by bone
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Explain the process of endochondral ossification.
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periosteal collar forms
chondrocyte hypertrophy secretion of angiogenic factors blood brings calcium calcified cartilage apoptosis of chondrocytes blood vssls bring in osteoclasts, osteoblasts |
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What initiates the formation of the primary ossification center?
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prolif of chondrocytes followed by their hypertrophy at the midpoint of the shaft
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What do hypertrophic chondrocytes secrete?
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vascular endothelial cell growth factor to induce sprouting of blood vessels from the perichondrium (periosteal bud)
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What is happening in the secondary ossification center?
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cartilage at ends replaced w/ spongy bone but some articular cartilage left
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Why doesn't cartilage regrow?
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b/c it doesn't have blood supply
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What do osteoprogenitor cells do in the primary ossfication center?
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they are derived from the perivascular mesenchyme and when they reach the primary ossification center they generate osteoblasts
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What are the 3 zones of bone replacement?
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proliferation zone
hypertrophic zone vascular invasion zone |
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explain what you see in proliferation zone of bone.
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flattenend chondrocytes in columns or clusters parallel to the growth axis
cluster of cells in this zone: chondrion |
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What is the functional unit of growth in the proliferative zone of bone?
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chondron: a cluster of cells
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What is happening in the hypertrophic zone?
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apoptosis of chondrocytes and calcification of the territorial matrix
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What happpens in the vascular invasion zone?
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blood vessels penetrate the transverse calcified septa, and carry osteoprogenitor cells with them
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Where is the epiphyseal plate?
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b/n the metaphysis and the epiphysis
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Explain the epiphyseal plate.
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cartilaginous growth plate where bone is dense and is recognized as an epiphyseal line
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Where is the periosteal collar?
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it extends along the diaphysis
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when is a secondary ossification center established?
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when blood vessels infiltrate the epiphysis
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when is the epiphyseal plate replaced with epiphyseal line?
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occurs gradually from puberty to maturity
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all the epiphyseal cartilage is replaced by bone except where?
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the articular surface
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What is Indian Hedgehog?
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stimulates chondrocyte proliferation in the growth plate and prevents chondrocyte hypertrophy
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What characterizes osteoporosis?
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low bone mass and deterioration of bone tissue that leads to increased bone fragility and risk of fracture particulary of the hip, spine and wrist
*silent killer b/c occurs w/o symptoms |
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explain steps of bone repair
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1. thrombus/hematoma forms
2. WBC's remove debris 3. death of osteocytes 4. osteoprogenitor cells of the periosteum proliferate 5. fibrous and cartilagionus callus forms on inside and outside surface of bone 6. endochondral and intramembraneous ossificatoin occurs, forming a bony callus 7.remodeling occurs as the fracture continues to heal and new bone responds to stresses |
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what happens with too little GH? too much?
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too little: pituitary dwarfism
too much: acromegaly |
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What disease is the most common of a group of growth defects characterized by abnormal body proportions?
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achondroplasia: arms and legs too short but torso is more nearly normal size. they do have cartilage but the rate at which cartilage cells in the growth plates of the long bones turn into bone is slow leading to short bones and reduced ht
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explain symptoms in muscular dystrophies
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muscle weakness and deterioration usually occuring in proximal to distal direction due to muscle protein abnormality
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facts on DMD
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X linked
severe degenerative disorder of skeletal and cardiac mm 1 in 3500 male births onset: early childhood leg weakness, increasing convex curvature of spine and waddle like gait wheelchair bound by 11 or 12 |
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What do DMD patients die of?
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respiratory or cardiac failure
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common signs and symptoms of DMD
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difficulty taking first steps
gower sign: diffiiculty getting up from sitting or supine position walk on toes or balls of feet belly pushed out and shoulders back scoliosis |
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what techinique is used to determine DMD?
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western blot of dystrphen
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explain dystrophin gene
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giant gene spanning 2.4Mbp
99% introns (accounts for high mutation rate) 14kb dystrophin mRNA that enocodes 3,685 aa 7 different dystrophin transcripts with cell type specificities: determined by promotors |
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common mutation in DMD?
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96% with framshift mutation, 30% with new mutation
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what determines the cell type specificity of dystrophin?
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promotors
expressed primarily in skeletal, cardiac and smooth muscle and retina |
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action of dystrophin in muscle?
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links actin-cytoskeleton to membrane glycoprotein complex that interacts with ECM
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where is dystrophin localized?
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to inner surface of plasma membrane where Z lines contact membrane linking muscle cell to ECM and providing structural support for PM of muscle fiber during repeated contraction cycles
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what is dystrophin a member of ?
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spectrin superfamily based on structure..related to alpha actinin
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close cousins of dystrophin?
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utropin, DRP2 (dystrophin related protein-2), dystrobrevin
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Mucle fibers that are lacking dystrophin increase expression of what?
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utrophin
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explain dystrophin associated glycoprotein complex
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3 subcomplexes: alpha, beta dystroglycan complex; sarcoglycan complex; cytosolic adaptor subcomplex
all work as organizer and adaptor for signalling |
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components of cytosolic adaptor subcomplex?
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alpha actinin syntrophins, Grb-2, nitric oxide synthase, caveolin-3 and NOS
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explain dystroglycan complex.
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dystroglycan is proteolytically cleaved into 2 subunits
alpha: bind to laminin, percalan, and agrin beta: binds dystrophin *complex confers structural stability during contraction |
