A&P Final Exam

homeostasis

A tendency to maintain a balanced or constant internal state

negative feedback

a stimulus initiates reactions that reverse the stimulus to return back to homeostasis

positive feedback

original stimulus is enhanced

what % of bone is organic

25%

What % of bone is inorganic?

75%

organic component of bones is made of

-bone cells
-osteoid (collagen 1) - cement

osteoid

cement like protein in the inorganic bone

3 types of bone cells

-osteoblasts
-osteocytes
-osteoclasts

osteoblasts

immature / bone forming cells

osteocytes

mature bone cells

osteoclasts

-(phagocytic) bone destroying cell
-release Ca++ when hypocalcemia happens

what causes the release of 5 Ca++ ions in the blood

-Calcium hydroxyapitite (Ca)5(PO4)3OH
-with acid
-by product is also 3 PO4 and OH

two types of osteoclasts

-immature osteoclast / precursor osteoclast-mature osteoclast

how much calcium is in an adult human

1 kg or 1000 g

Where is 99% of the body's calcium stored?

bones

where is the 1% of calcium stored

in the blood plasma (.5% free ionic form, .5% plasma protein bound)

normal blood Ca++ range

8.6-10.3 mg/dL

average blood Ca++ range

9 mg/dL

hypocalcemia

deficient calcium in the blood (under normal blood calcium)

main source of Ca++

food from intestines

what is Ca++ used for

muscle contraction, nerve impulse, protein/hormone function

what vitamin is important for Ca++ absorption

Vitamin D

Vitamin D synthesis

1. UV light reacts with 7-dehydrocholestrol to produce cholecalciferol (comes into blood)

2. 25'-hydroxylase converts it into 25'-hydroxycholecalciferol / calcidiol

3. calcidiol is converted by 1-α-hydroxylase to 1'-25'-dihydroxycholecaliferol / calcitriol

7-dehydrocholesterol

Vitamin D found in the skin

7-dehydrocholesterol + sunlight makes

cholecalciferol

where is 25'-hydroxylase produced

in the liver

what does 25'-hydroxylase use as a substrate

cholecalciferol to make 25'-hydroxycholecalciferol / calcidiol

25'-hydroxycholecalciferol / calcidiol

inactive form of vitamin D

where is 1-α-hydroxylase enzyme produced

kidneys

what does 1-α-hydroxylase use as a substrate

calcidiol to make 1'-25'-dihydroxycholecaliferol / calcitriol

1'-25'-dihydroxycholecaliferol / calcitriol

-active vitamin D
-penetrates intestinal cells and binds to cell's nuclear receptor activating it

when nuclear receptor is activated (process)

1. TRPV6 is mobilized from the center of the cell to the apical side
2. this causes an influx of ca++ inside the epithelial cell
3. Ca++ will bind to Cal bindin protein in the cytoplasm and made mobil
4. Ca++ will now move from the apical side to basolateral side
5. Ca++ will be transported to blood by PMCA and NCX

TRPV6

-transient receptor potential villinoid 6
-Ca++ channel (transporter) on the apical side causing Ca++ influx into epithelial cell

apical side

faces away from other tissues (blood) and toward environment (lumen)

where does Ca++ bind to once influxed into the cell by TRPV6

cal bindin protein in the cytoplasm, making Ca++ mobile

how is Ca++ transported to the blood

by PMCA and NCX channels on the basolateral side

PMCA

Plasma membrane calcium ATPase

NCX

sodium calcium exchanger

basolateral side

faces toward other tissues (blood) and away from environment (lumen)

what does vitamin D increase

-TRPV6 mobilization
-cal binding protein
-PMCA and NCX production

what are the 3 calcium channels

-TRPV6
-PMCA
-NCX

mineralization of the bone

bone formation (adds Ca++)

demineralization of the bone

bone resorption (removes Ca++)

what hormones are needed for bone formation

-IGF-1 (insulin like growth factor 1)
-growth hormone
-estrogen (female) and androgen (male)

what hormones are needed for bone resorption

-PTH (parathyroid hormones)
-glucorticoid excess / cortisol ecess (cell death of osteoblasts)
-RANKL (increased level caused by thyroid hormone deficiency )

transcellular absorption/transport

-Ca++ transported though the cell from urine
-transport happens in DCT
-hormone dependent, uses TRPV5 (kidney specific transporter)

TRPV6 and TRPV5

TRPV6 is intestines
TRPV5 is kidney

DCT

-distal convoluted tubule
-located in the kidney tubule (upper)

excess glucocorticoid/cortisol causes

apoptosis of osteoblasts

paracellular absorption

-absoprtion between 2 cells
-occurs in the TAL of henle
-hormone independent
-K+ comes into lumen of the tube and Ca++ pushed out and absorbed by blood

TAL of Henle

Thick ascending loop of henle location in the kidney tubule (lower/side)

PTH

-parathyroid hormone produced from parathyroid gland
-regulates transcellular transport at DCT

RANKL

-Receptor activator of nuclear factor kappa-B ligand
-causes bone resorption-is a ligand

where does the hypocalcemia signal go to

the parathyroid gland to the chief cells that have CaSR

chief cells

-contains calcium sensing receptors to detect low blood Ca++ (hypocalcemia signal binds here)
-located in parathyroid gland
-produces PTH if there is low blood Ca++

Hypocalcemia negative feedback process (not kidney involved)

1. stimulus binds to chief cell's CaSR
2. will produce PTH
3. PTH binds to PTH receptor in the osteoblast cell
4. RANKL is produced
5. RANKL will bind to RANK (receptor) present on immature osteoclast (destroying bone cells)
6. mature osteoclast will be formed
7. the mature osteoclast will produce H+/acid
8. it will be pushed through the H+/ATPase pump and dissolve hydroxyapatite, releasing Ca++ to the blood (back to homeostasis)

PTH binds to the PTH receptors in the osteoblast cell and produces what

produces RANKL

RANKL will bind to the RANK where and will produce

-binds located on immature osteoclast
-makes mature osteoclast

what will mature osteoclast produce

H+/acid through the H+/ATPase pump, which will dissolve hydroxyapatite, releasing Ca++ to the blood

PTH binds to PTH receptor in the kidney tubules and what occurs

increases 1-α-hydroxylase production (increasing Vitamin D) & transcellular Ca++ absorption (important for hypocalcemia)

what increases OPG protein

estrogen

OPG

-osteoprotegerin
-decoy receptor for RANKL
-stops RANKL from promoting bone destruction (aka formation of mature osteoclast)

menopausal mom don't get the beneficial effect of OPG why and what are the results therefore?

-they have low estrogen levels
-estrogen increases OPG
-therefore, they can get osteoporosis (brittle/fragile bone)

GLUT (glucose transporter)

type of uniporter

glucose transporters

uniporter (one way, one molecule) and symporter (one way, two molecules)

SGLUT / SGLT (sodium glucose transporter)

-type of symporter
-both sodium and glucose transporter in the same direction

GLUT 1 and GLUT 3

present in brain

GLUT 2

present in liver and pancreatic β cell

GLUT 2 and GLUT 5

present in small intestines

SGLT 1 and SGLT 2

present in kidney and small intestines

GLUT 4

present in skeletal muscle and adipose tissue

Where is the L-type Ca++ channel located?

along the wall of T-tubule

what drugs block L-type Ca++ channel

Amlodipine and Nifedipine

RyR

ryanodine receptor (antagonist)

DHP transporter

-pharmacological name of L type Ca++ channel
-antagonist

what is the relationship for km, affinity, and dosage

-the higher the km, the lower the affinity, therefore you need a larger dose which will increase the side effects
-the lower the km, the higher affinity, therefore you need a low dose which will lead to decreased side effects

physiological dose

- lowest concentration / no side effects

pharmacological dose

high concentrations that leads to side effects

hexokinase

phosphorylates only 6C sugars

glucokinase

Phosphorylates glucose

Km of hexokinase

.5 mg

Km of glucokinase

.75 mg

all plasma proteins are produced from the liver except

immunoglobulin

how is immunoglobulin produced

B lymphocyte is modified to a plasma cell which will then produce immunoglobulin

liver damage/cirrhosis

decrease in plasma proteins which decrease oncotic pressure

hydrostatic pressure

blood/water pressure

normal blood pressure

120/80 mmHg

μc

oncotic pressure in capillaries

Pc

hydrostatic pressure in capillary

Pi

hydrostatic pressure in the interstitial fluid (ISF)

μi

oncotic pressure of interstitial fluid (ISF)

Pc of arterial side =

35 mmHg

Pc of venous side =

18 mmHg (pressure dropped so water loss)

μc of arteriole side and venous side =

28 mmHg (therefore, no protein loss)

pi of arterial and venous side

-3 mmHg

μi of arterial and venous side

3 mmHg

net driving force =

(Pc - Pi) - (μc - μi)

arterial side NDF =

13 mmHg (pushes pressure so filtration occurs on arterial side)

+NDF vs -NDF

+ is pushing pressure (more hydrostatic pressure than oncotic pressure)- is pulling pressure

why are lympathic capillaries present on the venous side of capillaries

-since capillaries of venous side aren't 100% efficient at fluid absorption it will absorb any leftover fluid from arteriole side
-only toward hearts