14 – Ca, P, Vit D and Vit K

Question 1

What are the minerals and vitamins involved with Ca & P metabolism?

Answer 1

• Calcium
• Phosphate
• Vitamin D
• Vitamin K

Question 2

What are the functions of calcium?

Answer 2

• Bone strength and maintenance
• Can contribute to membrane potential
• Blood clotting (cofactor at multiple points)
• Serves as 2nd messenger to rely info form outside to inside the cell
• *major component of milk

Question 3

Absorption of calcium: 2 distinct mechanisms

Answer 3

1. Active, transcellular absorption
   a. Upregulated to increase Ca absorption when body Ca stores are low
2. Passive, paracellular absorption
   a. Occurs all the time
   b. Passive diffusion, so rate is dependent on dietary Ca concentration

Question 4

Where does passive paracellular absorption of Ca occur?

Answer 4

• Jejunum and ileum
• *When dietary calcium levels are moderate or high

Question 5

Passive paracellular absorption of Ca

Answer 5

• Diffuses through tight junctions into basolateral spaces around enterocytes and into blood
• Up to 50% absorption in monogastrics
• Less important in ruminants because rumen dilutes Ca in digesta

Question 6

Where does active transcellular absorption of Ca occur?

Answer 6

• Duodenum
• Up regulated when body Ca stores are low

Question 7

What are the 3 steps of active transcellular absorption of Ca?

Answer 7

1. Facilitated diffusion of calcium into enterocyte
2. Transport across the enterocyte
   a. *regulated at this step
   b. Controlled by amount of carrier protein calbindin present in cell
   c. *Vit D activation of Vitamin D receptor (VDR) increases synthesis of calbindin
3. Active transport into ECF (ATP>ADP)

Question 8

What inhibits Ca absorption?

Answer 8

• Compounds that form insoluble Ca salts
  o Oxalates, phytates, phosphates all form insoluble salts
  o Undigested fats for Ca soaps
• *large part of ingested Ca is NOT absorbed and is excreted in feces (low digestibility)

Question 9

What is the major Ca binding factor in the blood?

Answer 9

• Gamma-carboxyglutamate (Gla) residues in serum proteins (albumin)
• *vit K is a cofactor in the enzymatic production of Gla

Question 10

What can be seen with Vit K deficiency?

Answer 10

• Reduce bone density and cause osteoporosis
  o Vit K need for gamma-carboxylation and activation of osteocalcin
• Clotting deficiency

Question 11

Poisoning with Vit K antagonists (ex. warfarin and dicoumarol)

Answer 11

• Interfere with regeneration of Vit K by inhibiting its reductase
  o Leads to deficiency of ACTIVE Vit K
• *a single feeding of poisoned bait can kill the rodent, and also cause bleeding disease in wildlife, dogs, or cats that INGEST them

Question 12

Vitamin K deficiency: in different species

Answer 12

• Human newborns: have NO stores of Vit K
  o If they don’t get a supplement=hemorrhagic disease of newborns can result
  o Usually given a 1mg injection of Vit K at birth
• Deficiencies are rare in ruminants and non-human monogastrics
• Deficiency in chickens and pigs leads to spontaneous hemorrhages

Question 13

What are some sources of Vit K?

Answer 13

• Plants and bacteria
  o Intestinal synthesis is important (ruminants do NOT require additional Vit K)
• High levels of feed antibiotics may reduce Vit K synthesis
• Synthetic source: menadione
  o Susceptible to oxidation if exposed to sunlight, moisture, choline or trace elements

Question 14

How is calcium excreted? (3)

Answer 14

1. Kidney
   a. Excreted this way when calcium concentration in serum is high
   b. Tightly regulated
2. Secretion into intestinal lumen when calbindin is downregulated (epithelial cells are sloughed and unabsorbed Ca goes with them)
   a. FECAL excretion
3. Sweat (small amount)

Question 15

Calcium levels in body/storage

Answer 15

• 99% in bones and teeth (hydroxyapatite)
• Bone resorption changes with Ca
  o Osteoclasts remove Ca-P from bone
  o Osteoblasts deposit Ca-P in bone

Question 16

What are the 3 ways calcium levels are regulated?

Answer 16

1. PTH: secreted when Ca low
   a. Rapid and slower effects
2. Vit D
3. Other hormones: calcitonin, estrogen

Question 17

PTH: rapid effects

Answer 17

• Increases Ca reabsorption across the renal glomerulus
• Decrease urinary Ca loss

Question 18

PTH: slower effects

Answer 18

• Stimulates production of Vit D in kidney
• Vitamin D3 increases rate of intestinal Ca absorption
• Increase release of bone Ca stores (recruits osteoclasts)

Question 19

Where are Vit D precursors found?

Answer 19

• Plant and animal tissues
  o Plant: ergosterol
  o Animals: 7-dehydrocholesterol
• *converted to Vit D by sunlight UVB on the skin
  o Activation may be impaired by fur coat or when animals are indoors

Question 20

What are the steps of how Vit D works with PTH to regulate Ca and P metabolism?

Answer 20

1. Increases Ca absorption
2. Induces gut epithelial calbindin expression
3. Increases P absorption
4. Stimulates synthesis of collagen and other bone matrix proteins by osteoblasts
5. Stimulates bone resorption by osteoclasts and stimulates osteoclast recruitment
6. **Net effect is higher blood Ca concentrations

Question 21

Calcitonin

Answer 21

• Important in fish
• Relatively unimportant in terrestrial animals
• Has opposite effect of PTH

Question 22

Estrogen

Answer 22

• Regulates osteoclast and osteoblast populations
• When levels are low=more bone reabsorbed (can lead to osteoporosis)
  o Supplemental estrogen prevents osteoporosis in postmenopausal women

Question 23

What are the functions of phosphorus?

Answer 23

• Most abundant intracellular anion (phosphate)
• Structural: essential part of bone mineral (75-85%)
• Remaining 15-25% is in soft tissues

Question 24

Phosphorus functions in soft tissues

Answer 24

• Component of cell membranes (phospholipids)
• Metabolic: ATP, RNA, DNA, NADP, etc

Question 25

Phosphate intestinal absorption (similar to Ca)

Answer 25

• Passive paracellular diffusion
• Active transcellular transport
  o Actively stimulated by Vit D
• **excretion and absorption regulated by PTH and Vit D

Question 26

PTH, Vit D and P regulation: when [P] in blood is low

Answer 26

• Stimulates Vit D3 production
• *decreases PTH secretion
• Increases intestinal absorption of P
• Increases serum [P]

Question 27

PTH, Vit D and P regulation: when [P] in blood is high

Answer 27

• Increases PTH secretion and decreases Vit D3 production
  o Have a ‘fighting effect of Vit D”
• ***PTH decreases renal absorption of P (PEE out your P)
• Decreases serum [P]

Question 28

When does the regulation of Ca and P work well in terms of Ca:P ratio in diet?

Answer 28

• 1.2:1 to 2:1
  o *maximize Ca absorption in monogastrics

Question 29

Excessive dietary P can interfere with Ca absorption in small intestine

Answer 29

• Most phosphate salts are highly insoluble in water (ex. calcium phosphate)
• Animals and plant ingredients both have phosphates
  o Animal P is lower and more digestible=more readily absorbed
• High dietary phytate is problematic
• *high dietary P levels lead to large fecal losses and bone resorption

Question 30

Phytate

Answer 30

• High dietary phytate is problematic
• *phytate is mostly insoluble, phosphate rich plant compound
  o Binds dietary cations=prevents absorption
• Found in bran or husk of many grains, legumes and seeds
• *can treat plant-based feed ingredients with PHYTASE to reduce phytate levels and free phosphate

Question 31

Answer 31

Question 32

What are your sources of Ca?

Answer 32

• Insufficient in plant sources
• *to get a balanced Ca-P ratio, normally add
  o Meat meal for protein/P
  o Dicalcium phosphate for P
  o Limestone or calcium carbonate (oyster shells) to balance Ca:P ratio (No P in there)
• Can use bone meal for P and has some Ca=but more useful as a P source
• *Ca is cheap and P is expensive

Question 33

Ca, Vit D, Phosphorus deficiency

Answer 33

• Similar symptoms for all 3 nutrients
• Difficult to distinguish one from another w/o doing blood chemistry
• Osteoporosis: brittle bones
• *rickets in young and osteomalacia and poor pigmentation in older animals
  o Abnormalities of erythrocytes, leukocytes and platelets
  o Pica (behaviour_ where animals consume dirt or chew on pen materials

Question 34

When does cage layer fatigue occur? Why does it occur? What does it cause?

Answer 34

• Occurs in laying hens at peak production
• Due to high requirement for Ca for egg shell formation
• *Causes bone deformities, fractures and paralysis
• Pullets should be fed high Ca to build up reserves and proper Ca, P and Vit D levels should be maintained in diet
  o “bone bank”

Question 35

Ca toxicity

Answer 35

• Does not occur normally
• *excess Ca is simply NOT absorbed

Question 36

P toxicity

Answer 36

• Rare
• Usually due to kidney failure

Question 37

Vit D toxicity

Answer 37

• Calcification of soft tissue
  o Hypertension
  o Renal failure
• Avoid megadose of vit D
• Toxicity often due to errors in calculation/unit interpretation during feed formulation