physiology of lipid digestion and the absorption of calcium, iron and vitamins

Question 1

what are ingested lipids comprised of

Answer 1

>fat/oils triacylglycerols TAG 
>fatty acids may be saturated or unsaturated 
>phospholipids (glycerophospholipids)
>cholesterol and cholesterol esters 
>fatty acids

Question 2

what must ingested lipids be converted into

Answer 2

an Emulsion

Question 3

emulsification

Answer 3

occurs by:

• mouth > chewing
• stomach > gastric churning and squirting through the narrow pylorus, content mixed with digestive enzymes from mouth and stomach
• small intestine > segmentation and peristalsis mix the luminal content with pancreatic and biliary secretions

Question 4

how are emulsion droplets stabilised

Answer 4

> by the additions of a coat of amphiphilic molecules that form a surface layer on the droplets that include :

• certain products of lipid digestion
• biliary phospholipids
• cholesterol
• bile salts (when the droplets have progressively been reduced to unilamellar and mixed micelles)

Question 5

benefit of emulsion droplets

Answer 5

increased surface area to volume ratio

>so lipases and esterases are more likely to interact with it to accomplish digestion

Question 6

how does lipid digestion of TAG by lipases occur

Answer 6

> mouth = unimportant
stomach - gastric phase - by gastric lipase (lingual lipase in saliva) modest importance in adults, more so in infants
gastric lipase secreted in response to gastrin from chief cells

Question 7

lipid digestion at the pancreatic lipases produces …

Answer 7

2 monoacylglycerol and free fatty acids

Question 8

how does lipid digestion by pancreatic lipases occur

Answer 8

> duodenum - intestinal phase - by pancreatic TAG lipase
pancreatic lipases are secreted from acinar cells of pancreas in response to CCK which also stimulates bile flow
pancreatic lipase mainly hydrolyses TAGs at the 1 and 3 positions

**full activity requires
colipase co-factor
alkaline pH
calcium ions 
bile salts 
fatty acids

Question 9

what is the role of bile salts

Answer 9

> they are released into the duodenum in bile from the gall bladder in response to CCK, they act as detergents to help emulsify large lipid droplets to small droplets ie separates them for increased surface area for lipase action
they block the access of the enzyme to TAGs
they are amphipathic

Question 10

what does failure to secrete bile salts lead to

Answer 10

> lipid malabsorption

>secondary vitamin deficiency

Question 11

function of colipase

Answer 11

> stops bile salts from inhibiting the enzyme from interacting with TAGs
is an amphipathic polypeptide secreted with lipase by the pancreas
binds to bile salts and lipase allowing access by the latter to tri and di- acylglycerols
secreted as inactive procolipase which is activated by trypsin

Question 12

where are the final products of lipid digestion stored

Answer 12

mixed micelles
>
(as TAGs towards the surface of the emulsion droplets are hydrolysed, they are replaced by TAGs within the core , decreasing droplet size until a mixed micelle results)

Question 13

how are lipids absorbed

free fatty acids and monoacylglycerols

Answer 13

transfer between mixed micelles and the apical membrane of enterocytes entering by the cell by passive diffusion and/or membrane fatty acid translocases/fatty acid binding protein/fatty acid transport protein

• short chain diffuse through enterocytes and exit through basolateral membrane and enter villus capillaries
• *long chain (monoglycerides) are resynthesised to triglycerides in the endoplasmic reticulum and are subsequently incorporated into chylomicrons

Question 14

chylomicron formation

Answer 14

monoglyercide resynthesised into triglycerides in the endoplasmic reticulum
>cholesterol esters and phospholipid synthesis results in a nascent chylomicron
>Alipoprotein does something and makes this into a chylomicron which then undergoes exocytosis and is carried in lymph vessels to systemic circulation

Question 15

cholesterol absorption

Answer 15

> due to transport by endocytosis in clatherin coated pits by Niemann-Pick C1 like 1 protein
ezetimibe binds to NPC1L1 prevents internalisation and thus cholesterol absorption used in conjunction with statins in hypercholesterolaemia

Question 16

calcium ion absorption

Answer 16

> occurs by passive (small intestine) and active (duodenum and jejunum) transport mechanisms
with calcium in the chyme it is mainly active
active calcium absorption is regulated by 1,25 -dihydroxyvitamin D and parathyroid hormone

Question 17

what is iron

Answer 17

> important constituent in haemoglobin and myoglobin and acts as co-factor for numerous enzyme mediated processes
crucially important in carriage of oxygen by haemoglobin

Question 18

what kind of process is the loss of iron from the body

Answer 18

> unregulated

>iron balance in the body depends on tight regulated absorption of iron cross the duodenum which matches losses

Question 19

what is dietary iron

Answer 19

mainly in the oxidise form F3+
>presents as inorganic iron, haem and ferratin
>can get from meat and vegetables

Question 20

absorption of iron

Answer 20

> Fe2+ absorbed across the apical membrane by transport process
Fe2+ conveyed to basolateral membrane via a ‘molecular chaperone’
Fe2+ transported across the basolateral membrane by transport process
Fe2+ oxidized to Fe3+ and then transported to tissues
Import of haem across apical membrane followed by cytoplasmic metabolism to release Fe2+

Question 21

what does an iron deficiency cause

Answer 21

microcytic anaemia

Question 22

what does iron in excess cause

Answer 22

toxic die to accumulation in the liver, pancreas and heart

Question 23

reduced Fe2+ state

Answer 23

> dietary iron is largely in the oxidised ferric state but only the reduced ferrous state (2+) can be absorbed across the apical membrane of the duodenal enterocytes
reduction to Fe2+ occurs by Fe3+ accepting an electron

*this is promoted buy things like HCL in the stomach, vitamin C..

Question 24

absorption of iron - influx and efflux

Answer 24

> Fe2+ influx via DMT1 is succeeded by transport by mobilferrin to ferroportin 1 that mediates efflux

> Some Fe2+ combines with cytoplasmic apoferratin and is stored (oxidised to Fe3+) as ferratin

> Haem, entering by an uncertain mechanism, is degraded by haem oxidase to release

> Fe2+ that may be stored, or exported. Biliverdin is also produced

Question 25

transport of iron

Answer 25

to the blood

>Fe3+ + transferrin … delivers to tissues expressing a transferrin receptor ie erythroblasts

Question 26

absorption of vitamin B12 (cobalamin)

Answer 26

> B12 ingested in food bound to proteins
stomach acid releases vitamin B12 from protein
hatocorin secreted n saliva binds vitamin B 12 released in the stomach
stomach parietal cells release intrinsic factor
pancreatic proteases digest haptocorin in small intestine, so vitamin B12 is released
b12 binds to the intrinsic factor in the small intestine
vitamin B12-intrinsic factor complex absorbed in terminal ileum by endocytosis

Question 27

absorption of fat soluble vitamins

Answer 27

ie A D E K
>absorption requires adequate bile secretion and an intact intestinal mucosa
>incorporated into mixed micelles
>usually passively transported into enterocytes
>incorporated into chylomicrons or VLDLs
>distributed by intestinal lymphatics

Question 28

absorption of water soluble vitamins

Answer 28

ie B complex C and H
>transport processes on the apical membrane are similar to those described for monosaccharides, amino acids di and tri peptides
may be either sodium dependent or sodium independent