B7W4 Med Quiz

what type of cells is parathyroid hormone(PTH) stored in

chief cells of the parathyroid gland

stimulators of parathyroid hormone (PTH)

• low extracellular Ca2+

• low extracellular Mg2+

inhibitors of parathyroid hormone (PTH)

• high plasma Ca2+ (activates CaSR + inhibits exocytosis)

• high extracellular Mg2+

• high vitamin D (inhibits PTH gene transcription)

• FG23 (decreases phosphate reabsorption in gut/kidney)

• prolonged low Mg2+

CaSR

• what type of receptor is it

• where is it located

• what activates it

• what effect does it have on PTH secretion/release

• what type of receptor is it- GPCR

• where is it located- surface of chief cells in parathyroid gland

• what activates it- high extracellular Ca2+

• what effect does it have on PTH secretion- inhibits it via Gq

calcimimetic vs calcilytic agents

• calcimimetic activate CaSR + inhibits PTH secretion

• calcilytic inhibits CaSR + stimulates PTH secretion

effect of PTH on the kidneys

• increase Ca2+ reabsorption (in thick ascending limb + DCT)

• inhibits phosphate reabsorption (in proximal tubule via NaPi transporter)

• makes active vitamin D (1-alpha-hydroxylase activity)

effect of PTH on GI tract

• increased Ca2+ absorption (via calbindin)

• increases phosphate absorption (via NaPi transporters)

where is the PTH1R receptor located

both apical+ basolateral membrane on proximal tubule (PT)

steps of vitamin D synthesis

1. in the skin UV light converts 7-dehydhrocholesterol to vitamin D3 (cholecalciferol)

2. vitamin D3 goes to liver where its hydroxylated to make 25-OHD3(not a regulated step)

3. 25-OHD3 goes to kidney where 1-alpha-hydroxylase converts it to 1,25-(OH)2D3 the active form

Effects of vitamin D

• stimulates Ca2+ reabsorption in kidney (DCT) + small intestine (by promoting synthesis of Ca channels, pumps & binding proteins)

• stimulates phosphate reabsorption in kidney (PT) + small intestine (by increased NaPi)

• inhibits PTH gene expression

• inhibits itself (1-25(OH)2D3 creates enzyme that breaks it down)

Calcitonin

• what cells synthesize it

• where is it stored

• what cells synthesize it- C cells in thyroid gland

• where is it stored- secretory vesicles

what stimulates +inhibits calcitonin release

• stimulated by high extracellular Ca2+

• inhibited by low extracellular Ca2+

effects of calcitonin (on bone formation)

• inhibits osteoclasts (via Gs)

how do sex hormones + glucocorticoids affect bone

• sex hormones- promote bone formation

• glucocorticoids- promotes bone reabsorption

osteoblasts vs osteoclasts

• osteoblasts- build bone + acted on by PTH/Vitamin D

• osteoclasts- breaks down/reabsorbs bone + acted on by calcitonin/Vitamin D

Effect of PTH on bone

• pulsatile/intermittent PTH release

• continuous PTH release

• pulsatile/intermittent PTH release- stimulates osteoblasts (by releasing osteoprotegerin)

• continuous PTH release- stimulates osteoclasts (via M-CSF, IL6, RANK lignad)

effect of Vitamin D on bone

• direct effect

• indirect effect

• direct effect- bone reabsorption via M-CSF

• indirect effect- bone formation (via increased Ca + Pi uptake from kidney/GI tract)

do osteoblasts + osteoclasts have PTH receptors

no ONLY osteoblasts do

what Ca levels do we see pulsatile vs continuous PTH release

• pulsatile- increased serum Ca2+

• continous- low serum Ca2+

between direct and indirect effect of vitamin D which is greater

indirect effects are greater than direct

what is osteocytic osteolysis

the transfer of Ca2+ from interior to bone structure

role of RANK ligand + osteoprotegerin in bone reabsorption

• RANK ligand- binds RANK to increased activity of osteoclasts

• Osteoprotegerin- binds RANK ligand to prevent it from bind RANK (inhibits osteoclasts activation)

role in bone reabsorption

• integrins + vitronectin

• V-type proton pump

• carbonic anhydrase

• lysosomal enzyme

• calcitonin

• integrins + vitronectin- seals lacuna (reabsorption space)

• V-type proton pump- acidifies lacuna, dissolved minerals, stimulates lysosomal enzymes

• carbonic anhydrase- provides H+ for pump

• lysosomal enzyme- hydrolyze matrix proteins

• calcitonin- inhibits osteoclasts (via Gs)

what is Osteoporosis

decreased bone mass caused by a decrease in bone matrix

pathophysiology of osteoporosis

• decreased OPG (osteoprotegerin) allows more RANK to bind RANK ligand this promotes osteoclast maturation (more bone reabsorption)

how do estrogen + glucocorticoids cause osteoporosis

estrogen deficiency + excess corticoids decrease OPG causing osteoporosis

environmental factors for globesity (6 things)

• diet (low fat vs high fat)

• basal metabolism (UCP + neuropeptides)

• hormone levels (cytokines + adipokines)

• amount of sleep

• microbiota

• infectobesity

role of adiponectin in obesity

key insulin sensitive enzyme (as insulin sensitivity increased so adiponectin)

role of leptin in obesity

• neuropeptide that regulates fullness signal to brain

• elevated leptin leads to leptin resistance

resistin in obesity

• adipokine hormone that increases insulin resistance in high levels

role of Uncoupling protein 1 (UCP1)

disrupts proton gradient in electron transport chain so you lose energy as heat and make less ATP

UCP1

• what stimulates it

• what increases expression

• why is there an increased energy expenditure

• what stimulates it - fatty acids in brown adipose tissue

• what increases expression- genetics

• why is there an increased energy expenditure- bc there are increased amounts of CO2 + O2 used

how does sleep affect hunger hormone levels

less sleep= more ghrelin+ less leptin(weight gain)

lipolysis is regulated by what

HSL (hormone sensitive lipase) which is activated by cAMP

what regulates the carnitine shuttle

malonyl CoA (it inhibits it by stopping CATI)

effect of NADH on beta oxidation

• inhibits oxidation

CCK

• site of production

• target

• effect

• site of production- duodenum

• target-stomach

• effect- decrease food intake

Ghrelin

• site of production

• target

• effect

• site of production- stomach

• target- hypothalamus

• effect- promotes food intake

Adiponectin

• site of production

• target

• effect

• site of production- adipocytes

• target- systemic

• effect- lowers blood glucose levels

Leptin

• site of production

• target

• effect

• site of production- adipocytes

• target- hypothalamus + skeletal muscle

• effect- fullness feeling (decrease food intake)

PYY

• site of production

• target

• effect

• site of production- intestine

• target- hypothalamus

• effect- decrease food intake

NPY neurons

• site of production

• target

• effect

• site of production-hypothalamus

• target- hypothalamus

• effect- promotes food intake(decrease energy expenditure)

POMC

• site of production

• target

• effect

• site of production- hypothalamus

• target- hypothalamus+ brainstem

• effect- decrease food intake (increase energy expenditure)

Leptin + resistin relationship

• both adipocytes induced by feeding + decreased by fasting

• leptin deficient mice have elevated resistin levels

effects of resistin deficiency

• corrects insulin resistance

• decreases body weight + body fat

• reduced energy expenditure

• reduced UCP-1

adiponectin levels in people obesity + type 2 DM

reduced (administering it can lover circulating glucose levels)

in obesity what are the levels like

• adiponectin

• leptin

• resistin

• R8P4

• adiponectin- decrease

• leptin- increase

• resistin- increase

• R8P4- increase

GHRH-GR-IGF1 axis

• GHRH binds receptor on somatotrophs into anterior pituitary (Gs) to release GH (PKA activates Ca2+ channels)

• GH binds to receptor on target tissue (JAK/STAT) to release IGF1

what are the long term effects of GH mediated by

IGF-1

Negative Feedback

• GH

• Somatostatin

• GH- acts on somatotrophs to inhibits its own release (autocrine)

• Somatostatin- acts on somatotrophs to inhibit GH release

Negative feedback of IGF-1 to inhibit GH

• directly- acts on somatotrophs to inhibit GH release

• indirectly- acts on hypothalamus to inhibit GHRH release

• indirectly- acts on hypothalamus to stimulate somatostatin release

what time is GH release highest

during sleep (midnight-4am)

stimulators of growth hormone release

• exercise

• stress

• slow wave sleep

• high protein meals

• fasting

• ghrelin

inhibitors of growth hormone release

• somatostatin (binds SSTR)

• obesity

• pregnancy

• hyperglycemia

characteristics of IGF-1

• mediates long term effects of GH

• its receptor is RTK

• GH dependentIGF1

• insulin can bind the IGF1 receptor and vice versa (induces hypoglycemia)

characteristics of IGF-2

• higher during fetal life

• receptor is mannose-6-phosphate not RTK

• IGF2 can bind to IGF1 receptor, just w lower affinity

when is plasma IGF-1 highest

during puberty

Acute effects of GH

• increase lipolysis in adipose tissue

• decreased glucose uptake in skeletal muscle

• increase gluconeogenesis (liver)

• high doses lead to insulin resistance

long- term effects of GH

• directly stimulates amino acid uptake in muscle + bone

• promotes longitudinal bone growth

• simulates extracellular matrix formation

• promotes growth in almost every cell of the body

hormones that regulate body mass

• insulin

• glucocorticoids (cortisol)

• adiponectin

• leptin

hormone that regulate linear growth

• GH

• IGF-1/IGF-2

• insulin

• thyroid hormone

• glucocorticoids

• androgens + estrogens

what 3 things cause a decrease in linear growth

• glucocorticoids

• lack of T3

• defects w insulin receptor

what 2 things increase linear growth

thyroid hormone + sex steroids

Excess GH conditions

• gigantisim- excess GH before puberty

• acromegaly- excess GH after puberty (growth of bone width + vital organs)

GH deficiency conditions

• pituitary dwarfism

• laron’s syndrome- normal GH levels, but non functional receptors + resistant to diabetes, cancer, aging