Absorption of ions and water Flashcards
Absorption in the small intestine
Processes
Enhanced after a meal
Postprandial state
Movement
Transcellular
Solute crosses two cell membrane
Active transport / ATP
Paracellular
Solute moves passively
Between cells / via tight junctions
Volume of liquid
Saliva
0.5-1.5L / day
Too much / too little
Constipation
Diarrhoea
Absorption
Water
Absorption of water depends on the absorption of ions, principally Na+ and Cl-
Transport of Na+ and Cl-
Into the lateral intercellular spaces
Resulting high NaCl near the apical end of the intercellular space
Causes it to be hypertonic which causes an osmotic flow of water from the lumen
Via the tight junctions into the intercellular spaces
Sodium - absorption
Sodium
Na+ is absorbed along the entire length of the intestine
3 different transport routes of entry!
Na+/K+ ATPase
Creates the gradient (basal side)
Keeps intracellular Na+ low
Na/Glucose transport or Na/Amino acid transport
SGLT1 (luminal side)
Highest in jejenum
Allows Na to enter the when glucose, galatose and neutral AA’s present
Electrochemical gradient
- Na/Glucose transport or Na/Amino acid transport
- Na-H exchanger
Exchanged for H+ (protons)
Electrochemical gradient
Small intestine (jejenum)
When pH is neutral or alkaline (Secretion HCO3-)
- Parallel Na-H and Cl-HCO3 Exchange - electroneutral
Same as before exchanged for H+ (protons)
Electrochemical gradient
Coupled to a Cl-HCO3 Exchanger
Electroneutral (Na+ & H+ and Cl- & HCO3-)
Primary method of Na+ absorption between meals (fasted state)
Does not require glucose
Regulated by intracellular cAMP / cGMP & Ca2+
Carbonic Anhydrase
Reversible reaction
H20 + CO2 ↔ HCO3- + H+
Chloride absorption is closely linked to Na+ absorption. Electroneutral NaCl absorption also mediates Cl- absorption in the ileum and proximal part of the colon.
Clinical importance
E coli food poisoning
Enterotoxin binds to enterocytes
Toxin is internalised (endocytosis)
Interacts with Gs > increasing cAMP levels
Enhanced Cl- secretion
Blocks Na+ and Cl- uptake
Calcium Absorption
Calcium
Dietary sources (~500 mg/day of Ca2+)
Intestinal secretion (~325 mg/day of Ca2+)
Net update (~175 mg/day of Ca2+)
Passive Transport
Paracellular route
Active Transport
Transcellular route
Duodenum
VDR (Vitamin D Receptor) – Nuclear receptor
Uptake
TRPV6 Receptor
Transient Receptor Potential Cation Channel Subfamily Vanilloid Member 6
Calbindin-D9K (buffers Ca2+) > Reduces free Ca2+
PMCA (Plasma Membrane Ca2+ ATPase)
NCX (Na-Ca exchanger)
Transfer calcium out of enterocyte
VDR
Binding of vitamin D
Increases receptor transcription (apical / basal)
Promotes uptake from lumen > into body
Vitamin D deficiency
Deficiency of Vitamin D
Poor diet / lack of sun
Bone softening
Demineralisation
Cause
Hypocalcaemia
Bone softening
Not the same as osteoporosis
Osteoporosis
- creation of new bone tissue does not keep up with removal of old tissue
- bone becomes brittle and weak
-Vit D , Ca , adequate pro , moderate to low Na
Osteomalacia
-adult rickets - softening of the bone
- due to vitamin D deficiency - lack of sunlight or dietary intake
-Vit D and Ca supplementation
Dietary Iron
Variety of sources
Haem iron (animal sources)
Non haem iron (inorganic)
Recommended dietary allowance (RDA) 16-18 mg/day
Need to absorb 1-2mg (<10%)
Inorganic
Most > Non absorbed
Oxalates
Haem
More bioavailable
Derived from myoglobin and haemoglobin
10% of ingested Fe is absorbed into the blood each day
Role for Iron in Human Body
Oxygen transport
Haemoglobin (Oxygen carrying cell (Erythrocyte / RBC’s)
Myoglobin
Haematopoiesis
Energy production
ETC
Iron sulphur clusters
Enzymes
Cytochrome P450 (CYP450)
DNA Helicase
Fe is necessary for normal health
Absorption of Iron
Absorption of iron takes place in the small intestine
In food, Fe exists as ferritin, but it cannot be absorbed in this form
Fe3+ -> Fe2+ (enzyme: ferric reductase; transporter: DMT1)
In cells, Fe2+ -> Fe3+ (enzyme: hephaestin; transporter: ferroportin)
Fe3+ is then transported into the blood via a protein carrier -transferrin
Ferritin = ferric
DMT1 = divalent metal transporter 1
Ferric reductase is an oxidoreductase
Fe in the body can lead to ferrous ( Fe2+) and ferritin ( Fe3+)
Iron and transferrin
Transferrin receptor aid transport of Fe + transferrin
Liver can release stored Fe back to circulation through ferroportin
Fe + transferrin –> erythropoiesis ( 75percentage) –> synthesis of erythrocytes
Fe + transferrin –> liver –> storage as ferritin
Erythropoiesis- takes place in the bone marrow
Hepcidin
Hepcidin is the master regulator of Fe
Hepcidin inhibits ferroportin in the liver ↓ plasma Fe concentration
Hepcidin inhibits ferroportin in the spleen too
The spleen recycles damaged/dead RBC release Fe. Ferroportin transports these Fe to circulation. Hepcidin action = ↓ plasma Fe concentration
Hepcidin reduce absorption of Fe from the lumen of the small intestine.
Ferroportin is the transporter for Fe release into circulation
GFP labelled Fpn
Fpn is in the plasma membrane of iron exporting cells
↓Fe levels > ↓Hepcidin > ↓inflammation
Regulation of Fe
Stimulation of hepcidin helps to regulate plasma Fe concentration
IL-6 (an inflammatory cytokine) stimulate hepcidin release
↑ plasma Fe = hepcidin stimulation
Lipopolysaccharide from bacteria
Haemochromatosis (HFE) protein interact with other protein to stimulate hepcidin release. Mutation of the HFE gene haemochromatosis (Fe overload in the tissues)
Impaired HFE protein = impaired hepcidin release = excess Fe in tissues
Overexpression of Hepcidin > Chronic anaemia (ACD) > Death
Heme transport
Heme is from haemoglobin and myoglobin
Fe is removed from heme using Heme oxidase (HO-1)
Heme – Fe = Porphyrin
Porphyrin breakdown product is biliverdin bilirubin (using enzyme: biliverdin reductase)
Disorders related to this process: Hyperbilirubinemia, haemolytic anaemia
Hemolytic anaemiais a disorder in which red blood cells are destroyed faster than they can be made.
Anaemia of chronic disease ( ACD)
ACD can be due to rheumatoid arthritis
↑hepcidin levels
Erythropoiesis is inhibited
↑Phagocytosis of RBC
Hereditary Haematochromatosis
Faulty iron metabolism
Absence of hepcidin
Iron accumulation
Organ damage
Liver failure
Treated by phlebotomy
Discriminating ACD from IDA
IDA
Iron deficiency anaemia (diet)
ELISA test for Ferritin
Ferritin levels will be low
ACD
Chronic disease
Ferritin levels will be high
