ENDO 2

what are the three hormones that regulate Ca2+ and PO4 3-

1. calcitonin (made by thyroid)

2. parathyroid hormone (made by parathyroid)

3. 1,25-dihydroxy vit D3 (dihydrocycholecalciferol) (made by kidney)

calcium functions

bones, blood clots, muscle contraction, heart function, nerve signaling

calcium is readily absorbed in GI tract (T/F)

F- calcium is poorly absorbed in GI tract

PO4 3- is easily absorbed in GI tract (T/F)

T- especially when there is excess calcium

what helps bone and GI absorb calcium?

1,25-dihydroxychloecalciferol

for kidney to convert vit D3 to 1, 25-dihydroxchloecalciferol what hormone is required?

PTH

if plasma Ca2+ is too high what happens to 1, 25-dihydroxchloecalciferol levels?

decrease 1, 25-dihydroxchloecalciferol

how does 1, 25-dihydroxchloecalciferol increase Ca2+ absorption?

by increasing calcium binding protein (Ca2+/ATPase pump in epithelial cells)

increased Ca2+/ATPase pumps more Ca2+ from _____ to _________ and then enters bloodstream by diffusion

intestine to eipthelial cell cytoplasm

what is normal level of plasma calcium in body (mMol/L)

2.4 mMol/L

describe the breakdown of calcium “types” in that 2.4 mMol/L

1.0 mMol/L - combines with plasma protein and cannot diffuse across capillary membrane

0.2 mMol/L is diffusable and non ionized

1.2 mMol/L is diffusable and ionized

how does PTH encourage blood calcium to increase?

increases kidney reabsorption of calcium

increases kidney production of dihydroxychloecalciferol (helps increase intestinal calcium absorption)

increases bone dissolution of CaPO4 crystals

what effect on body if significantly increase PO4 3-

no/ very little effect

hypocalcemia causes spontaneous action potentials in periphreal nerves due to increased permeablility of ______ in the neuronal membrane

Na+

as Ca2+ decreases, _____ increases and muscle cells depolarize causing muscle twitch and tetany

Na+

when is twitching and hypocalcemia expected?

in postpartum small dog breeds

at what percent of normal calcium level does tetany occur?

50%

in cows hypocalcemia (milk feaver) manifests as

short twitch phase only in shoulders, mostly get paralysis and fall down

why might cows get paralysis from postpartum hypocalemia

not enough calcium at neuromuscular junction - basal tone lost (basal tone needed for muscle spindle activity and unconcious ativity of pryimidal tract of motor cortex)

why do cows get paralysis but humans and dogs get tetany in hypocalcemia

unknown

hypercalcemia symptoms

depressed nervous system, slow HR and reflexes, heart stops, brain slowed

what causes brain to slow and heart to stop

heart has prolonged plateau in contraction due to action potential repolarization not occuring (similar in brain)

how does each effect instestine

PTH, vitD, calcitonin

PTH no effect

vitD increase Ca2+ and PO4 3- absorption

calcitonin no effect

how does each effect kidney

PTH, vitD, calcitonin

PTH- increases Ca2+ reabsorption and inhibits PO4 3- reabsorption

Vit D- Ca2+ and PO4 3- reabsorption

calcitonin- inhibits Ca2+ and PO4 3- reabsorption and encourages bone desposition

how does each effect bone

PTH, vitD, calcitonin

PTH- bone degrades (resorp)

Vit D- bone degrades (resorp)

calcitonin- bone desposition

what is the purpose of bone degredation?

to increase blood calcium levels

how many parathyroid glands do we have?

generally 4

hypercalcemia caused by (high/low) PTH, hypocalcemia caused by (high/low) PTH

hypercalcemia- high PTH

hypocalcemia- low PTH

PTH causes bone CaPO4 crystals to resorp into bloodstream to increase Ca2+ levles. why does PO4 3- actually decrease in this case?

PTH causes kindey to excrete more PO4 3-

PTH acts (slow/fast)

slow

PTH makes (osteoclatsts/ osteoblasts) dominate

osteoclasts (break down bone)

PTH increases reabsorption in kidney of _______

and decreases reabsorption of ______ by inhibiting transport mechanisms

increases reabsorption: Mg2+, H+, Ca2+

decreases reabsorption: Na+, K+, AAs, PO4 3-

how does PTH increase absorption of Ca2+ and PO4 3- in intestine

by increasing kidney 1,25-dihydroxychloecalciferol production

what would excess witimin D cause in body?

excess resorp of bone (same way excess PTH does)

small quantities of vitimin D actually promote calcification how?

increasing Ca2+ and PO4 3- absorption in intestine, and remineralization from increased cell transport

a decrease in cellular calcium causes parathyroid gland to (increase/decrease) PTH

increase

if calcium defiecency persists, what happens to PTH glands?

hypertrophy

when does natural hypertrophy of PTH gland occur?

during pregnancy and lactation

what causes PTH to decrease and gland hypotrophy?

high calcium

what hormone acts oppisite to PTH

calcitonin

calcitonin decreases plasma Ca2+ how?

decreasing osteoclats absorpative activity, or more long term decreasing osteoclat formation

what age group has most calcitonin?

young

if thyroid gland was removed, lack of calcitonin secretion would have large impact on body (T/F)

F- calcitonin is a secondary mechanism for Ca2+ control, but PTH is the major factor

calcitonin works short term but isnt activated by high Ca2+ after a milk meal (T/F)

T, (gut-thyroid axis acts faster)

hypoparathyroidism causes (high/low) blood calcium

low

in lack of parathyroid glads, why can you not simply supplement with PTH to prevent Ca2+ deficency?

what treatment is used?

PTH cost& antibodies make it impractical

large Vit D doses (100 000 unit/day) and 1-2g Ca2+/day keeps levels in range and prevents tetany

hyperparathyroidism is more common in what gender?

women (tumor)

if hyperparathyroidism is mild what compensates for increased osteoclats?

osteoblasts

if hyperparathyroism is severe what happens in body?

kidney stones (due to high Ca2+ and PO4 3-), bone weakening, hypercalcemis-lack of repolarization in heart and brain

what age group is effected by rickets most?

children (lack of dietary vit D)

in rickets is Ca2+ or PO4 3- deficency more prevalent?

PO4 3- greatly depressed due to kidney excreting lots of PO4 3- (no reg system)

Ca2+ mildly depressed - PTH prevents severe drops

rickets in adults (osteomalacia) is mostly caused by a Ca2+ and Vit D deficency due to

failure to absorb fats (fat lost in feces takes vit D with it) - induced by excess castor oil, laxitives or enal rickets from kidney dammage and no dihydroxychloecalciferol production

osteoporosis is related to abnormal calcification (T/F)

F- osteoporosis has to do with diminshed bone matrix due to low osteoblast activity

6 “causes” of osteoporosis

1. lack of physical activity

2. malnutrition (preventing matrix formation)

3. lack of vit C (needed for all cells to secrete)

4. post menopause lack of estrogen (osteoblast stimulating)

5. old age (low GH, poor met function)

6. cushings disease (too much glucocorticoid- decreased bone deposition, increased protein catabolism and decrease osteoblast activity)

hormones of the adrenal cortex are synthesyzed from what?

cortisol

mineralcorticoids include:

glucocorticoids include:

androgens include:

mineralcorticoids include: aldosterone (regulate Na+/K+ balance)

glucocorticoids include: cortisol (regulate glucose metabolism)

androgens include: weak DHEA (supplement sex steroids in the gonads)

mineralcorticoids are produced in arenal cortex zona _______

glomerulosa

glucocorticoids are procuced in the adrenal cortex zona ______

fasiculata

weak androgens are produced in arenal cortex zona _____

reticularis

from most superficial to most deep rank the zones of the adrenal cortex:

zona glomerulosa

zona fasiculata

zona reticularis

aldosterone function

promotes Na+ absorption and K+ secretion in the nephron

what is the narrow maintained level of K+ in extracellular fluid

4.5mM/L

(doubling would be lethal)

K+ is freely filtered in the glomerulus of nephron and almost all of it is reabsorbed, what regulates how much is excreted?

aldosterone

aldosteorne only regulates 2% of Na+ reabsorption why?

by time glomerular filtrate eneters distal tubule most of the sodium has already been reabsorbed

a decrease in Na+ does what to blood pressure

decreases

reabsorption of Na+ has little effect on extracellular Na+ concentration (T/F)

T- due to osmotic absorption of water

where is aldosetrone receptor (place on DCT kidney cell)

cytoplasm ( then moves to nucleus) to increase enzymes, receptors and transport proteins for Na+, K+ and H+ in kidney

how long does aldosterone take to work in body?

45 mins, peak after hours

what are two enzymes that aldosterone increases the transcription of?

Na+/K+ ATPase (at basolateral membranes)

channel proteins at lumenal facing (urine facing) membrane of tubular cell

what does an increase in channel proteins at lumenal facing (urine facing) membrane of tubular cell allow for

rapid Na+ absorption into blood and K+ excretion into urine (and H+)

what are 4 factors of aldosterone regulaton? in order of importance

1. increased K+ in extracellualr fluid

2. renin angio-testin system

3. decreased Na+ i extracellular fluid

4. ATCH

what is the renin-angiotestin system?

a system that activates when you have low blood volume and low blood flow to kindey, angiotestinII stimulates aldosterone release from adrenal cortex

ATCH has small effect in Na+/K+ regulation (T/F)

T- but lack of ACTH can have significant effects

what hormones produced by adrenal medulla?

epinephrine, norepinephrine

epinephrine, norepinephrine have similar effects to ____ nervous system but effects last 10x longer

sympathetic

what is the adrenal medulla innervated by?

preganglionic sympathetic axons that secrete fight or flight hormones

hypothalamus activating the sympathetic nervous system causes HR to increase and adrenal medula to secrete which causes:

increased blood flow to muscles, increased alertness, metabolic rate, blood glucose

the pancreas is primarily by mass (endocrine/exocrine) cells with small Islets of Lengerhans as (endocrine/exocrine) cells

exocrine

endocrine

what cell types in islets of langerhans

a, B, delta

what do a, B, delta cells do

a- glucagon (increase blood glucose)

B- insulin (decrease blood glucose)

delta- somatostatin (depress insulin&glucagon)

insullin binds _____ receptors

RTK

what does insulin RTK cascade signal for?

protein synthesis and movement of GLUT4 carrier to membrane to allow for more glucose facillitated diffusion into cell

resting muscle when insulin is not present relies on ____ for metabolism

FAs (gluconeo)

insulin blocks Fa release from adipose (T/F)

T

the brain doesnt need insulin for glucose transport (T/F)

T - the brain is already insulin permeable

insulin effect on fat storage

increase fat storage, increase glucose use in tissue, promote FA syntheiss in liver cells and creation of more adipose

why would insulin block HSL

to prevent triglyceride hydrolysis (FA release)

insulin increases glucose into fat cells where some is made into FAs, but most is made into _____

a-glycerophosphate

what does a-glycerophosphate do?

supply glycerol to combine with FAs and make triglycerides

why can diabetic blood be “milky”

in insulin deficiency adipose can not take up FAs from liver in lipoproteins

low insulin triggers HSL which:

TAG→ FA + glycerol

why do diebetics get atherosclerosis?

excess FA in plasma promotes liver to convert FA into phospholipid, cholesterol and excess TAGs that are released in blood as lipoproteins

what causes ketoacidosis in diabetics?

excessive acetoacetic acid in liver cells depresses acetoacetic acid use in periphreal tissue- ketone bodies are produced→ketosis→ketoacidosis

what is common ketones produced

B-hydroxybutyric acid

acetone

when is glycogen converted to lactic acid?

anerobic exersize

in the liver how is most glucose stored?

as glycogen

what enzyme is unique that the liver has for glycogen→ free glucose to other tissues?

glucose 6 phosphatase

what enzyme breaks glycogen into glucose, what is it inhibited by?

glygogen phosphorylase, insulin

when liver glycogen storage is maxed, where does glucose go now?

to adipose tissue (by FA packaged in LDL)

an insulin defiecency causes a decrease in glucose usage while liver makes more glucose, what does this do to blood glucose?

hyperglycemia, hypotensin, osmotic diuress, dehydration