-
Gibbs Free Energy
ChgG = GhgH - TChgS
-
Syncytiotrophoblast
secretes hCG
-
Decidua Basalis
maternal component of placenta
-
Embryo stages
Zygote -> Morula -> Blastocyst
- §
- Blastocyst -> Trophoblast ->
- placenta
- §
- Blastocyst -> Inner Cell Mass ->
- Epiblast -> 3 derm layers
-
Teratogens:
o ACE Inhibitors – renal damage
o Anti-Cancer
o Aminoglycosides – Ototoxicity (A Mean Guy hit baby in ear)
o Carbamazepine – neural tube defects
o Diethylstilbestrol (DES) – vaginal clear cell carcinoma
o Folate antagonists – neural tube defects
o Lithium – Ebsteins anomaly (heart)
o Phenytoin – retardation, heart defects, Microcephaly
o Tetracyclines – discolored teeth
o Thalidomide – phocomelia (limb issues)
o Valproate – neural tube defects
o Warfarin – abortion, hemorrhage
- o Vitamin A – cleft palate, abortion, heart defects (do not supplement) –
- HOX gene mutation (responsible for Skeletal Development - synpolydactyly
-
Ectoderm - Describe 3 layers
- Surface Ectoderm
- Anterior pituitary, Lens of eye,
- olfactory epithelium, salivary and sweat glands, mammary glands
Neuroectoderm (Neural Tube) – The BOSS
Brain, Retina, CNS cells and neurons
- Neural Crest Cells – Neuroectoderm
- Missionaries
- PNS: ANS, CN’s (Vagus), Sympathetic
- Ganglia, Dorsal Root Ganglia, Schwann Cells
Ear: Inner ear bones
- Eye: anterior chamber, cornea, sclera,
- Ciliary muscle, iris pigment
Adrenal Gland: Chromaffin cells
Mouth: Odontoblasts
Heart: Aorticopulmonary Septum
- GI: ENS, Celiac Ganglion,
- Enterochromaffin cells
Thyroid: Parafollicular cells
Skin: Melanocytes
-
Organogenesis time frame?
3-8 weeks
-
Nuclear Localization Signals
- "Hey PAL, let me in"
- Allows entry into nuclear envelope
- Proline
- Arginine
- Lysine
-
Controls G1 to S Phase
- §
- Cyclin D – CDK4 – Rb -> synthesis
- of DNA
- §
- Cyclin E – CDK2 -> initiate S phase
-
Controls G2 to M phase
- §
- Cyclin A – CDK2 – prophase
- §
- Cyclin B – CDK1 – initiate mitosis
-
Targets proteins for lysosomes in the endoplasmic reticulum
Mannose-6-phosphate
-
I Cell Disease - Pathogenesis and Symptoms
- deficient mannose phopsphorylation
- lysosomal storage disease
- coarse facial features
- clouded corneas
- joint restriction
-
Cell Trafficking - Golgi modifies what 3? COPI and COPII?
- Golgi modifies Serine, Asparagine and Threonine
- COP I - retrograde, COP II anterograde
one cop runs away, but two cops run toward danger
-
most common cause of mental retardation in infants
fetal alcohol syndrome
-
Microtubule drugs
- Mebendazole
- Griseofulvin
- Vincristine/Vinblastine
- Paclitaxel
- Cochicine
-
Mictrotubule motion - Dynein vs Kinesin
- Dynein - retrograde
- Kinesin - anterograde
-
Chediak Higashi - Pathogenesis and Symptoms
o Microtubule Polymerization defect
o Decreased Fusion of Lysosome to Phagosome
o Albinism, recurrent infections, peripheral neuropathy
-
Intermediate Filaments
o Vimentin – connective tissue
o Desmin – muscle cells
o Cytokeratin – epithelial cells
- o Glial Fibrillary Acid Proteins (GFAP)
- - Neuroglia, Schwann cells, astrocytes
o Peripherin – Neurons
o Neurofilaments – Axons
o Nuclear Lamins – nuclear envelope and DNA
-
Kartagener Syndrome - Pathogenesis and Symptoms
- Dynein defect
- Immobile cilia
- bronchiectasis, infertility, situs inversus
-
tyrosine kinase receptor - binds what? describe subunits
o PDGF and other growth factors
o Insulin and IGF-I
- §
- 2b subunits – tyrosine kinase activity
-
involved in transport of endocytosed vesicle from plasma membrane to endosome
Clathrin
-
Arachidonic Acid Pathway - Leukotrienes
Arachidonic Acid -> Lipoxygenase ->Hydroperoxides
- -> LTB4 (NEUTROPHIL CHEMOTAXIS)
- ->LTC4, LTD4 (increased bronchial tone)
-
Arachidonic Acid Pathway - Thromboxane
Arachidonic Acid -> COX1 and 2 -> Endoperoxidases -> TXA (increased PLATELET AGGREGATION, VASCULAR AND BRONCHIAL TONE)
-
Arachidonic Acid Pathway - Prostaglandins
Arachidonic Acid -> COX -> Endoperoxidases -> PGE, PGF (increased UTERINE TONE, decreased VASCULAR TONE, BRONCHIAL TONE)
-
Arachidonic Acid Pathway - Prostacyclin
Arachidonic Acid -> COX -> Endoperoxidases -> PGI (decreased PLATELET AGGREGATION, VASCULAR, BRONCHIAL AND UTERINE TONE)
-
drug inhibits Na+K+ATPase
Digoxin
-
Labile cells - No G0 phase, short G1
skin, hair follicles and bone marrow
-
CD8 and NK cells use this for inducing apoptosis
Perforin and Granzyme B
-
Signs of irreversible cell damage
- Ca2+ influx
- Membrane damage
- Lysosome rupture
- Pyknosis (nuclear clumping)
- Karyorrhexis (fragmentation)
- Karyolysis (nuclear fading)
-
Cellular byproducts: creatine kinase, lactate dehydrogenase, troponin
Cardiac cell death
-
Cellular byproducts: CK, LDH, aldolase
muscle cell death
-
Cellular byproducts: AST, ALT, GGT, AlkPhos
Hepatocyte death
-
Cellular byproducts: amylase only
salivary gland death
-
Cellular byproducts: amylase and lipase
Pancreatic cell death
-
Cellular byproducts: LDH, Haptoglobin, bilirubin
RBC death
-
Intrinsic vs. Extrinsic Pathway for apoptosis
- Intrinsic - Mitochondria - Cytochrome C, Bcl-2, Bax
- Extrinsic - TNF Receptor I
-
expressed on healthy cells to prevent phagocytosis
CD31
-
4 steps in leukocyte extravasation
- 1. rolling - E and P selectin
- 2. tight binding - ICAM-1, LFA-1 (integrin)
- 3. diapedesis - PECAM-1 (squeezing)
- 4. migration - chemotactic agents (C5a, IL-8, LTB4, Kallikrein) remember CILK
-
Important in formation of Granulomas
TNFa
-
protein made by hepatocytes, increases adhesiveness of leukocytes, elevated in MI, stroke and PAD
C reactive protein
-
elevated in osteomyelitis, polymyalgia rheumatica, temporal arteritis, RA, SLE and malignancy
Elevated ESR
-
4 Collagen Types
o Type I – Strong
o Type II – Slippery
- §
- Cartilage, vitreous body
o Type III – Bloody
- §
- Reticulin, blood vessels, uterus
o Type IV – BM
-
6 steps of collagen synthesis
o Synthesis – Preprocollagen
o Hydroxylation – Proline + Lysine + Vitamin C
o Glycosylation – Procollagen
o Exocytosis
o Proteolytic Process – Tropocollagen
o Cross-linking – Collagen Fibrils
-
Type IV collagen defect
Kidney disease, deafness, X-linked recessive
Alport Syndrome
-
Type III collagen defect
Extensible skin, hypermobile digits, easy bruising, berry aneurysm
- Ehlers-Danlos
- Extend-a-Digit!!
-
Type I collagen defect
Blue sclera, hearing loss, dental imperfections, brittle bones
Osteogenesis Imperfecta
-
Fibrillin defect - long fingers, aortic dissection
Marfan's Syndrome
-
Elastase breaks down elastin which is normally inhibited by this enzyme, resulting in emphysema and cirrhosis
a1-antitrypsin deficiency
-
Where are stem cells found
bone, liver, brain, skin, intestinal crypts, skeletal muscle and cornea
-
Oct3 and Oct4 are what?
transcription factors for pluripotent stem cells
-
residual granule from free radical induced lipid oxidation
lipofuscin
-
enzyme mitigating aging effects by maintaining cellular chromosomal length
telomerase
-
family of proteins induced by calorie restriction
Sirtuins
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