Lecture 8 - Plasma Ca2+ And Vitamin D Flashcards
What are ca2+ ions in the intracellular fluid essential for?
Muscle contraction, neurotransmitter release and enzyme activation
What is the extracellular function for ca2+?
Blood coagulation - it is a key cofactor in the clotting cascade
What can ca2+ also exist as?
Calcium salts in bone which provide the structural integrity of the skeleton
What happens when Extracellualr ca2+ falls below normal?
The nervous system becomes progressively more excitable because of increased permeability of neuronal membranes to Na+
What does hyperexcitability cause?
Tetanic contractions - because at the neuronal muscle junction it will cause uncontrolled muscle contractions which lead to a condition called hypocalcaemic tetany
What is hypocalacaemic tetany?
It occurs in the hand and it leads to very painful muscle spasms
What are the different types of extracellular ca2+?
Protein bound (albumin), anion complexed (bicarbonate) and ionised
What are the tissues involved in ca2+ homeostasis?
GI tract, Kidney and bone
How much ca2+ do we absorb every day?
1000mg
How much ca2+ is absorbed?
35% - therefore 35% needs to get rid,
15% through the GI tract
20% through the kidneys
What is the readily exchangeable pool?
It is the ca2+ ions on the surface of the bones but they don’t stay on the surface they move in one direction or the other.
- they might flow into the bone to be incorporated as a ca2+ salt in the bone
- or into the extracellular fluid
What are the main target organs or ca2+ homeostasis?
Intestine, kidney and bone
What organs have vitamin D metabolites?
Intestine and kidney
Where is 60% of the total plasma ca2+ filtered and then reabsorbed?
In the PCT of the kidney by active transport, 30% is in the TAL through passive diffusion, 30% is absorbed through active transport in the DT, 9% collecting duct
Where are the passive mechanisms of the kidney absorption found?
In the loop of henle of the nephron in the kidney, the ca2+ ions move between the cells by paracellular transport
What are the active mechanism for the reabsorption of ca2+ in the kidney?
PCT and DT - have a transcellular transport of ca2+,
Ca2+ ions are moved into the cell from the lumen and then moved out across the opposite membrane into the blood
What is trancellular transport driven by?
The concentration gradient of ca2+ in the lumen
What happens if the conc in the lumen is higher than 2.5mM (in the blood)?
Ca2+ moves down the conc gradient (paracelllar pathway_ there is no limiting step
Higher the conc gradient =
The more ca2+ will be transported
What pump is involved in the active mechanism?
PMCA pump which pumps ca2+ out of the cell
What is an advantage and disadvantage of the active pathway?
It never stops, but disadvantage = there is a rate limiting step
What does the parathyroid hormone do?
Opens the ca2+ channel to get more ca2+ ions to enter the lumen for the paracellular pathway
What are the 3 hormones that regulate the Extracellular ca2+?
Parathyroid hormone, 1,25 DHCC and calcitonin
What form of vitamin D is found in human ?
Vitamin D3
What cells are the principal site for the parathyroid hormone (PTH)?
Chief cells
What is the main effect for PTH?
Increase plasma ca2+ - it is a hypercalcaemic hormone
What is the stimulus for PTH?
A decrease in plasma ca2+
What part of the nephron is stimulated by the PTH?
The distal tubule
What else does the PTH stimulate?
The activity of 1-alpha-hydroxylase which catalyses the formation of 1,25-DHCC
What is the 1,25 DHCC structure similar to?
A steroid hormone
What 2 sources do humans acquire vitamin D from?
The diet and the skin by ultraviolet radiation
What year did lots of people have vitamin D deficiency?
In 1929 - the Great Depression, as people couldn’t afford food. Started fortifying food to add vitamin D like a supplement (Kelloggs still do it)
Is vitamin D3 inactive or active?
Inactive - therefore it must be converted to 1,25DHCC
What does calcitonin do?
Acts to decrease plasma ca2+ levels - it is the only home one that causes a decrease in plasma ca2+
What is hypocalcaemia caused by?
A deficiency in vitamin D activity
What does hypocalcaemia result in?
It results in neuromuscular excitability
What are the symptoms for neuromuscular excitability?
Numbness, tingling, hyperventilations and tetany. Also a prolonged Q-T interval
What can hypocalcaemia result in?
A metabolic bone disease
What are examples of a metabolic bone disease?
Osteomalacia and rickets
What are the two phases of bone?
An organic matrix (osteroid) whic becomes mineralised to form hydroxyapatite
What does too little collagen cause
Too little mineralisation - the organic matrix is lower than normal (bones bend outwards)
How can you get a deficinency of vitamin D
Insufficient exposure to sunlight and in the diet,
Malabsorption of vitamin D in GI tract and inability to convert vitamin D to 1,25DHCC
what happens if there is a mutation in the receptor for 1.25DHCC?
Can cause a disease called rickets type II
What is rickets type II characterised by?
Impaired intestinal absorption
What are the treatments for type II rickets?
Calcitriol, dietary ca2+, injections if malabsorption can not be ovecome by dietary supplements
