Case 25- calcium and old age Flashcards
Bone formation and reabsorption- during life
1) During growth- rate of bone formation > resorption and skeletal mass increases
2) Once adult bone mass achieved. Rate of Formation = Resorption, maintain bone mass
3) From 30+ years- rate of resorption begins to > formation, bone mass slowly decreases
4) Bone formation and resorption occurs mainly in trabecular bone
Bone formation and reabsorption- Ca+2
1) 99% body Ca2+ in bone
most in hydroxyapatite crystals -Ca10(PO4)6(OH)2
2) Very little Ca2+ (<1%) can be released from bone
3) However, bone is the major reservoir of Ca2+ in the body
4) Bone- dynamic tissue
continually being formed and reabsorbed, remodeling, 10-15% of total adult bone mass turns over each year
The four cell types present in bone
1) Osteoprogenitor cells- stem cells, can differentiate into other bone cell types
2) Osteoblasts- synthesise the organic bone matrix (osteoid)
3) Osteocytes- inactive (mature) osteoblasts, become trapped in mineralised bone
4) Osteoclasts- erode mineralised bone and remodel, found on the surface of the sites of bone resorption
The interaction between bone cell types
Osteoprogenitors- differentiate into osteoblasts
Osteoblasts- synthesise and mineralise collagen to form osteoid. Inactivated to form osteocytes
Osteocytes- inactive osteoblasts- trapped within bone. Regulate activity of osteolasts
Osteoclasts- enzymatic resorption of bone in remodelling, are the differentiated blood monocytes
Osteobasts and osteocytes- growth:
Hormones act on osteoblasts, which in turn regulate osteoclastic activity
Osteoblasts produce osteoid component of mineralised bone matrix
As matrix is laid down osteoblasts become trapped within bone – osteocytes in lacunae
Osteoclasts- remodelling
1) During bone development, woven bone is eroded by osteoclasts activity and remodelled
2) Osteoclasts secrete= H+ and Cl- ions to create an acidic environment for solubilising the bone matrix. Cathepsin K protease into the subosteoclastic compartment to degrade collagen and proteins
3) The process is stimulated by the parathyroid hormone (PTH) and inhibited by calcitonin
Physiological actions of calcium
Calcium salts in bone- structural integrity of the skeleton
Calcium ions in extracellular and intracellular fluids
1) neurotransmitter release at synapse
2) blood coagulation
3) hormonal secretion
4) enzymatic regulation
5) muscle contraction
Physiological actions of calcium
Calcium salts in bone- structural integrity of the skeleton
Calcium ions in extracellular and intracellular fluids
1) neurotransmitter release at synapse
2) blood coagulation
3) hormonal secretion
4) enzymatic regulation
5) muscle contraction
Distribution of calcium in the body
Total body calcium (1-1.3 kg)
Bone- 99%
Body fluids- 1%, the majority is in intracellular fluid but some is in the plasma and interstitial fluid
Calcium levels are tightly regulated
For example:
1) If extracellular Ca2+ falls below normal
increased permeability of neuronal membranes to Na+, nervous system becomes progressively more excitable
2) Hyper excitability causes tetanic contractions
Hypocalcaemic tetany
3) Trousseau sign with hypocalcaemia- obstetric hand/carpopedal spasam
Calcium levels- A characteristic posture when the sphygmomanometer cuff is inflated above the systolic blood pressure
1) Wait 3 minutes
2) Flexion of wrist
3) Hyperextension of fingers and thumb
Organs involved with calcium homeostasis
1) Intestine- absorption/secretion
2) Kidney- filtration/reabsorption
3) Bone- formation/resorption
Calcium homeostasis (daily balance)
Diet- 1000mg Faecal excretion- 800mg Urinary excretion- 200mg (2% of filtered load) Bone cellular fluid- 1000mg Rapidly exchangeable pool- 4000mg Bone formation- 500mg Bone resorption- 500mg
Intestinal calcium absorption
If concentration of calcium higher in lumen than in blood, can move into blood passively
But calcium often lower in blood so needs to be actively transported across basolateral wall of epithelium into blood
Function of calcium in the bone
Strengthens bone- structural
Integrity of skeleton
Enzyme which stimulates and inhibits bone resorption
Stimulates- PTH
Inhibits- Calcitonin
Cathepsin K protease
Enzyme secreted by osteoclasts which decrease collagen and protein
How is calcium transported in the blood
Most calcium is actively transported into the duodenum and jejunum epithelial cells from the lumen and then goes to the blood across the basolateral membrane
How is calcium moved from epithelial cells into the blood
Calbindin mops up calcium in the cell which helps to maintain concentration gradient
Calcium moves from epithelial cells into blood across basolateral membrane - calcium ATPase and Na/Ca exchanger
Calbindin
A vitamin K-dependent transport protein
Binds to calcium in cytosol of cells which means lower concentration so more can move into the cell by active transport
Kidneys in calcium homeostasis
Reabsorption of calcium- only 1% is lost in the urine
60% active transport in proximal tubule
30% passive diffusion in the loop of Henle
9% active transport in distal tubule
Regulating Ca+2 concentration
Non-hormonal= rapidly exchangeable pool (surface of skeleton) fast, but limited capacity
Hormonal=
1) Parathyroid hormone (PTH)
2) 1,25 dihydroxycholecalciferol (1,25 DHCC/ Calcitriol)
(cholecalciferol = vitamin D3)
3) Calcitonin
Parathyroid hormone (PTH)
1) Synthesised and secreted by the parathyroid glands; lie posterior to the thyroid glands
2) Chief cells= PTH synthesis
3) PTH is translated as a pre-prohormone (115 aa)
4) Following cleavage you have a biologically active peptide of 84 aa
PTH function
1) To increase plasma (Ca+2)- Hypercalcaemic
2) The stimulus of PTH secretion is a decrease in plasma [Ca+2]
3) Secretion of PTH is inversely related to [Ca+2]
PTH action on bone
1) Directly on bone to stimulate Ca2+ resorption- increase in osteoclast number, increase in osteoclast activity
2) Directly on bone to decrease collagen synthesis by osteoblasts (i.e. decrease bone formation)
PTH action on the kidneys
1) Directly to stimulate Ca2+ reabsorption in the distal tubule
2) Directly to stimulate the activity of 1alpha-hydroxylase, which catalyzes the formation of 1,25 DHCC from Vitamin D
PTH action on the intestine
1) Has no direct effect
2) Acts indirectly by stimulating 1,25 DHCC synthesis- stimulates calcium absorption
1,25- dihydroxycholecalciferol
The active form of vitamin D
Needs help from 1-α hydroxylase to convert vitamin D3 to 1,25 DHCC
Role of 1,25 DHCC
Stimulates calcium absorption and increases plasma calcium concentration
How it works- Greater expression of calbindin so helps to sequester larger amounts of Ca - increases capacity of epithelial cell to pull Ca out of lumen so increased concentration in epithelial cells to be actively transported into the blood
Role of 1,25 DHCC
Stimulates calcium absorption and increases plasma calcium concentration
How it works- Greater expression of calbindin so helps to sequester larger amounts of Ca - increases capacity of epithelial cell to pull Ca out of lumen so increased concentration in epithelial cells to be actively transported into the blood
MOA of 1,25 DHCC
Kidney- Increases tubular reabsorption of calcium, relatively minor effect
Bone- promotes action of PTH, relatively minor. Net effect=resorption
Intestine- main action is on the intestine, increases calcium reabsorption
Calcitonin
Synthesised and secreted by parafollicular C cells of the thyroid
Major stimulus of calcitonin secretion increases plasma calcium levels
Calcitonin is a physiological antagonist to PTH with regard to calcium homeostasis
Main target of calcitonin
Bone
- mainly osteoclast
- inhibits osteoclast motility and cell shape
- inactivates cell
- major effect is a rapid decrease in calcium inhibition of bone resorption
- inhibits bone removal, promotes bone formation
Effect of calcitonin
Kidney- decrease tubular reabsorption of calcium (weak effect)
Intestine- no effect
Role of calcitonin in human calcium homeostasis
Very minor role
Chronic excess does not produce hypocalcaemia
Removal of parafollicular cells does not cause hypercalcaemia
May be more important in bone remodelling than in calcium homeostasis
PACism: life expectancy and multimorbidity
• In 2015 life expectancy at 65 was +18.6 (men), +21.1 (women) – most
of these years are spent with 1 or 2 diseases
• By 2035 life expectancy at 65 will be higher, but with more time spent
with MLTCs (2+ diseases)
PACSim support needs
Between 2015 and 2035 absolute numbers of people 65+ will
increase by 48.6%
• Numbers of people 65+ living independently will increase 61%
Older people and health globally
• Overall life expectancy increasing faster than healthy life expectancy • Increase in chronic non-communicable diseases (NCDs) • Scope for prevention eg treatment of hypertension • Social and economic benefit • Traditional care systems may not meet needs for NCDs eg dementia
Attitudes and culture- Ageing
1) Attitudes improving but ongoing evidence of ageism and negative stereotyping, including in healthcare
2) This is seen in Workplace discrimination, Gender-based abuse and a Lack of prioritisation in policy
Changing healthcare needs of the elderly
• Changing “frontline” presentations (GP, A and E) • Lack of guidelines and infrastructure appropriate for multimorbidity
Elderly- Changing frontline presentations
• Numbers of older people presenting to A and E are rising disproportionately to increases in the population • Older people are likely to spend longer in A and E and are more likely to be admitted
Elderly- system challenges
• NHS historically set up to deal with single system conditions (eg cardio or GI or respiratory) rather than multimorbidity • Research and guidelines based on single conditions in younger populations (OP excluded) • Lack of guidance and evidence base in relation to OP with complex pathologies • Lack of service integration
Policies aiming to improve healthcare OP
1) Kings fund (2014)
2) NHS long term plan (2018)
Kings fund
King’s Fund (2014) – evidence synthesis: • Shift from high cost reactive care to preventative and supportive care • Continuity of care (eg GP) • Prevention through lifestyle change • Comprehensive Geriatric Assessment (CGA) • Successful interventions
Comprehensive Geriatric assessment (CGA)
• Moves forward from the biopsychosocial
model
• Person-centred
• An approach to managing MLTCs
• Requires the complementary skills of the
MDT to make a truly holistic assessment
• Different settings e.g. emergency care,
community, day hospital
Established evidence bases, results in a reduced- Length of stay, Costs, Admission to longterm care, Post-operative complications
NHS long term plan (2018)
1) New service model- community based MDT teams
2) Social prescribing
3) ‘Same day’ emergency care/CGA
4) Integration of health and social care
5) Prioritise prevention- smoking, alcohol, air pollution, inequalities, screening
Ageing and ethics
1) Consent and capacity
2) End of life care and resuscitation
3) When to investigate and when to pallitate (risk/benefit balance)
Ageing and clinical research
1) Research is most often condition or systems based
2) Older people are often excluded from trials
3) Lack of evidence in relation to multi-morbidity (at any age)
4) Disproportionate concern about risk
Frailty
A medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death
Frailty
A medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death
Examples of frailty
Neurology- slower reaction time
Cardiovascular- heart valve calcification
Psychiatry- loss of neurons and brain mass
Why measure frailty
1) Identification of older people ‘at risk;
2) Planning services, support and recources- Immediate, long term
3) Intervention to prevent morbidity/mortality- Physical activity, dietary supplementation, reduction of polypharmacy
4) Improves quality of life
How can we measure frailty
2 main academic models:
1) Frailty phenotype (Fried)- rule based ‘objective’
2) Frailty index (Rockwood)- deficit model ‘subjective’
How can we measure frailty
Choice depends on context (eg): • Rockwood Clinical Frailty Score (CFS) • Gait speed/TUG • Self-report eg PRISMA-7
How should we care for older people with frailty and MLTCs?
Holistic, integrated approach (person, pathology, environment) Person-centred care: • Dignity respect and compassion • Care co-ordination and transition • Personalised (not standardised by disease) • Enabling (not disabling) Multidisciplinary>CGA
