Things I don't know: Phys Flashcards
superior hypophysial arteries
supply pars tuberalis, median eminence, infundibulum
arise from internal carotid and posterior communicating artery of circle of Willis
inferior hypophysial artieries
supply pars nervosa
arise from internal carotid
primary capillary plexus
drain into hypophysial portal veins
arise from superior hypophysial arteries
give rise to secondary capillary plexus
11B-hydroxysteroid dehydrogenase 2
- converts cortisol to cortisone in cells where aldosterone is active
kidney, colon, salivary gland
cortisone does NOT bind aldosterone receptor - local neg. feedback on cortisol, CRH and ACTH
permissive effects
TH/GC increase response of fat cells to Epi/NE ability to do lipolysis
second messengers
amplify and disperse signal of hormone once hormone binds the receptor
Factors that alter TBG levels
- increase
- decrease
- hepatitis, heroin, pregnancy
2. steroids (depends on type)
5’/3’ vs 5/3 monodeoiodinase
5’/3’: active T3 (outer iodine chopped off)
5/3: rT3 (inner iodine chopped off)
What can decrease uptake of I- into the follicular cell?
ClO-, TcO-, SCN
hypocholorite, technetium (oxidized), thiocynate
How does TSH (thyrotropin) increase TH secretion?
- increase Na/I symporter activity
- stimulates iodination of thyroglobulin
- stimuates conjugation of iodinated tyrosine to generate T4, T3
- increases endocytosis of iodinated thyroglobulin into follicular cells
- stimulates proteolysis of iodinated thyroglobulin in lysoendosomes
- increase T4, T3 into circulation
- exerts growth factor effects on thyroid cells (hypertrophy, hyperplasia)
glycogen synthase
glycogenesis
add activated UDP glucose (made from glucose to G1P) to glycogen
increased by: G6P
phosphorylation: inactive
glycogen phosphorylase
glycogenolysis releases G1P that can be dephosphorylated to glucose activated by: stress (increase in AMP) inhibited by: G6P phosphorylation: active
gluconeogenesis
liver
glucose made from amino acids, lactate, FA oxidation products
rate limiting enzymes in gluconeogenesis
- phophoenolpyruvate carboxykinase (PEPCK)
- fructose-1,6-bisphosphatase (FBPase)
- glucose-6-phosphatase (G6Pase)
Order that we use energy stores (fed)
- circulating glucose
- glycogen breakdown
- gluconeogenesis
insulin receptor cascade
- receptor TK
- transautophaosphorlate itself
- PI3K binds
- PIP3 (second messenger) is generated
- recruit PDK1 (kinase)
- PDK1 and mTORC2 phosphorylate and activate Akt
Akt
INSULIN
- MOST important protein kinase in mediating insulin function
- phosphorylates and inactivates FOXO (decreases gluconeogenesis)
- activate mTORC1: protein synthesis
AS160 and RGC 1/2
Akt activates (via insulin) proteins that regulate activity of small GTPases involved in GLUT4 translocation
AMPK and GSK-3
phosphorylate glycogen synthase and inactivate it
inactivated by: INSULIN
phosphorylation of glycogen synthase and glycogen phosphorylase
glycogenolysis
dephosphorylation of glycogen synthase and glycogen phosphorylase
glycogenesis
protein phosphatase
removes phosphate from glycogen synthase
activated by: INSULIN
fructose-2,6-bisphosphate
increases in glycolysis
inhibits FBPase
FOXO
transcription factor forG6Pase and PEPCK
glucagon receptor cascade
- Gs
- AC
- cAMP
- PKA
INCREASE blood glucose
PKA
GLUCAGON and ADRENALINE
- activates glycogen phosphorylase kinase to phosphorylate glycogen phosphorylase
- directly phosphorylates glycogen synthase
- inactivates PFK-2
- phosphorylates CREB
phosphofructokinase-2 (PFK-2)
generates fructose-2,6-bisphosphate (increases glycolysis, inhibits gluconeogenesis)
inactivated by PKA
CREB
transcription factor
activates transcription of PEPCK, FPBase, G6Pase (gluconeogenesis)
activated by PKA
glucagon works where
liver: gluconeogenesis, glycogenolysis
does NOT do glycolysis, muscle glucose oxidation
adrenaline works where/how
short term, rapid: glucose to blood for muscle
liver: gluconeogenesis, glycogenolysis
fat: lipolysis
muscle: glucose oxidation
activated by: direct sympathetic innervation, high levels of phenylethanolamine-N-methyltransferase
hormone sensitive lipase (HSL)
adipocyte triglyceride lipase (ATGL)
perilipin
lipolysis activated by (phosphorylated): adrenaline
long term glucose control during fasting
GH and cortisol
increase blood glucose during prolonged fast to get blood to brain
incretins (GLP-1 and GIP1)
gut
enhance insulin release
DDP-4
degrade incretins
order that we use energy stores (fasting)
- creatine phosphate
- glycolysis
- glycogenolysis
- gluconeogenesis
- fat oxidation
autonomic effects on insulin and glucagon
sympathetic: increase glucagon, less insulin
parasympathetic: increase insulin, less glucagon
How is the synthesis of steroid hormones regulated?
GPCR signaling
Gs (cAMP/PKA) or Gq (IP3)
What happens when aldosterone binds the mineralocorticoid receptor?
transcription
- Na/K pump: Na in, K out of body
- ENac: Na in
- SGK1: protein kinase that activates several transporters by post translation modification
renin
converts angiotensinogen to angiotensin I
increase: JG decrease stretch, increase sympathetic tone, decrease BP/BV
JG cells
secrete renin
when: decreased stretch, decreased glomerular flow, increased sympathetic activity
angiotensin converting enzyme
angiotensin I to II
angiotensin II
- increased sm. muscle constriction
- increased salt reputake directly
- increase aldosterone
cortisol
maintain blood glucose in times of fasting/stress for brain, resp. system, CV system
transcription of: PEPCK, pyruvate carboxylase, G6Pase
gluconeogenesis, glycogenolysis, lipolysis, muscle proteolysis
insulin resistance
increase B receptors: sensitizes tissue to EPINEPHRINE
TRANSCRIPTIONAL control ONLY
decrease: growth, immune, reproductive
NE
low circulating levels (lower than needed for adrenergic response): utilized synaptically where local concentrations are high
only two times it can circulate in high enough concentrations to activate adrenergic receptors: HEAVY EXERCISE, PHEOCHROMOCYTOMA
epi receptors
alpha1: Gq (IP3/Ca): vasoconstriction
alpha2: Gi (inhibits cAMP)
beta: Gs (cAMP/PKA): cardiac output, blood to muscle, glycogenolysis, gluconeogenesis, glycolysis, lipolysis
night shift
increased cortisol, altered circadian
higher risk: DM, CV, sleep probs
MC2R
Gs
receptor for ACTH
AGTR1
Gq
angiotensin II receptor
CRHR1/2 and ACTHR
CRH receptor and ACTH receptor
Gs
released by: stress
decreased by: cortisol, receptor desensitization, 11BHSD2
How does chronic stress prepare the body for acute stress
increases B adrenergic receptors so that they are more sensitive to epinephrine
Hormones needed at
- prenatal
- infantile
- juvenile (1-12 yrs)
- adolescent (F 10-14, M 12-16)
- adult
1 and 2: insulin
- GH, Insulin, T3, Vit. D
- add sex steroids to number 3
- limited growth
GHRH receptor
Gs (PKA)
somatostatin receptor
Gi
Why does GH decrease with age?
decrease in GHRH secretion
IGF-1 receptor
receptor TK
mTORC1: mediates muscle growth
GH receptor
JAK/STAT
produce mRNA by binding DNA promoters
GH
gluconeogenesis, lipolysis
protein synthesis
IGF-1 release
IGF-1
muscle and bone growth
glucose uptake in muscle: promote glycogen and lipid storage
hormones that enhance/decrease GH signaling
- insulin: fetal growth, IGF-1 secretion, protein synthesis
- TH: GH production, CNS development
- Testosterone/Estrogen: GH secretion at puberty, close epiphyseal plate, protein synthesis (T only)
- cortisol: inhibits GH release, protein catabolism
TH and GH
REGQUIRED for GH synthesis
Distribution of Ca
in body?
in plasma?
excretion?
body: 99% in bone
blood: 50% free, 40% protein bound, 10% anion bound
excretion: most in feces, little in kidney
normal total serum Ca range
8.5-10.5 mg/dL
Ca uses
bone, tooth muscle contraction AP second messenger cofactor excitation-secretion (exocytosis)
Pi uses
energy (ATP, etc.) second messenger DNA/RNA, membranes bone, tooth phosphorylation of enzymes intracellular anion
Pi distribution
body?
plasma?
excretion?
body: 85% bone, 14% intracellular, 1% extracellular
plasma: 55% free, 10% protein bound, 35% cation bound
excretion: most urinary, feces also significant
normal total serum phosphorus range
3-4.5 mg/dL
children: 4.5-6.5 mg/dL (active bone growth)
How do you know whether Pi and Ca will be mineralized into bone or bone resorption?
bone deposition: Ca x PO4 greater than solubility product
bone resorption: Ca x PO4 less than solubility product
high plasma Ca and P: calcification in bone and soft tissue
low plasma Ca and P: bone resorption
Why is it important to know concentration of intact PTH?
PTH is rapidly cleared from circulation
What activates Vit D from 25 to 1,25
PTH
osteoprotegerin
osteoblast
prevents RANKL from binding RANK
stimulated by: estrogen
inhibited by: PTH
intermittent low dose PTH
increase bone formation
enhance proliferation and differentiation of osteoblasts
What is the best indicator of Vit. D status?
serum 25 (OH)D calcifediol, calcidiol
calciferol
vit. D
cholecalciferol
vit. D3
ergocalciferol
vit. D2
calcitriol
active Vit. D
1, 25
increases: calbindin, epithelial Ca channels, Na/PO4 transporter
activates 24 alpha hydroxylase
24, 25 dihydroxyvitamin D
inactive Vit. D
calcifediol
25 Vit. D
calcidiol
25 Vit D
25 alpha hydroxylase
liver
vit. D3 or D2 to 25 (OH) Vit. D3
1 alpha hydroxylase
kidney
25 to 1,25 Vit D.
inhibited by: Ca, FGF23
stimulated by: PTH
24 alpha hydroxylase
kidney
25 to 24,25 Vit. D
stimulated by: Ca, FGF23, calcitriol
FGF23
decrease: 1 alpha hydroxylase (decrease active Vit. D), Na/PO4 cotransporters in kidney (Npt2a/c), PTH
stimulates: 24 hydroxylase,
inactivates Vit. D
increased by: phosphate, calcitriol, PTH
causes: HYPOPHOSPHOTEMIA
UV light role in vit. D
provitamin D (7-dehyrdocholesterol) to cholecalciferol
how does Vit. D promote intestinal Ca and PO4 absorption?
- Ca enters cell through epithelial channels
- Ca binds calbindin: diffusion to basolateral membrane
- Ca-ATPasw and Na/Ca exchanger to move across basolateral membrane
increase Na/PO4 transporter
How does HIGH vit. D effect bone resorption?
increase bone resorption
inhibits PTH
Which bone cell has gap junctions for communication?
osteoblast
Cbfa1
causes precursor to become osteoblast
PHEX
secreted by osteoblasts
regulates amount of PO4 excreted by kidney
osteocyte
comes from osteoblast
long cellular processes in canaliculi for communication: sense strain, repair
secrete GF to activate osteoblasts
lining cells
former osteoblast
surface of bones
responsible for immediate release of Ca if blood Ca low
protect bone from chemicals
receptors for hormones, factors that induce bone remodeling
which cells come from bone marrow derived
- mesenchymal progenitors
- hematopoietic progenitors
- osteoblast, osteocyte, lining cells
2. osteoclast (monocyte/macrophage)
reserve cells
long bones
source of chondrocytes
slow proliferation
flat chondrocytes
long bones
proliferate rapidly
secrete chondrocyte collagen and matrix to form cartilage
hypertrophied chondrocytes
long bones
undergo apoptosis
indian hedgehog
long bones
secreted by hypertrophied chondrocytes
cause secretion of PTHrp from round chondrocytes
PTHrp
long bones
keeps flat chondrocytes in proliferating phase and delays hypertrophied stage
sclerostin
bone remodeling
secreted by osteocytes
inhibits Wnt signaling in cells near surface
What happens when a bone crack forms?
- osteocytes near crack undergo apoptosis
- osteocytes detect strain: secrete GFs, PGs, NO
- canopy forms: release stromal cells from sclerotin (inhibition factor)
- stromal cells generate pre-osteoblasts and M-CSF to help generate osteoclasts
- pre-osteoblasts: proliferate, Wnt signaling, ILs, bone morphogenic proteins, express RANKL
- formation of osteoclast: acid, cathepsin K
- IGF, TGF-B released
- osteoclast apoptosis
- pre-osteoblast into osteoblast that stop making RANKL and secrete OPG to block pre-osteoclast
- osteoblasts secrete osteoid and then mineralize it (months) then become lining cells, osteocytes, or apoptose
- accumulate minerals for years
BMU (basic multicellular unit)
many spreading over bone in many places
forming and resorbing bone
pancreatic enzyme secretion
- synthesis on rough ER
- hydrophobic leader seq. so that it can pass through the cisterna (membrane) of RER
- budded off into transitional elements
- in golgi: incorporated into vacuoles that concentrate enzymes until mature zymogen granule
- zymogen granule moves to the apical membrane and waits for a stimulus
- Ca is 2nd messenger that causes release
all steps are ongoing except 6
steps 3-5 require ATP
pancreatic secretion
- cephalic phase (sham feeding)
- intestinal
- increase in enzymes but not much aqueous secretion
- major phase
decrease in pH: secretin: release bicarb
digestion products (FA and AA): I cells: CCK: vagovagal: enzyme secretion and bicarb secretion
