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Lect 7: Nutritional & metabolic disorder in ageing & neurological…
Lect 7: Nutritional & metabolic disorder in ageing & neurological disorder
Osteoporosis
Decreased Ca salt deposition in bone
Fragility fractures of vertebrae, proximal femur
Hip fractures -> embolism of marrow ->ends up in lungs -> pneumonia & death
Dowager’s hump -> osteomalacia -> severe loss of Ca salts in bone
Risk factors
Smoking
Ca intake
Vitamin d deficiency
Family history
Parathyroid hormone
Decreased in obesity/ increased in low BMI
Ca regn
Parathyroid gland detects plasma Ca via Ca sensing receptor to release PTH when Ca is low
PTH stimulates osteoclasts to reabsorb bone & release Ca
PTH stimulates kidney to reduce Ca excretion & increase phosphate excretion
PTH increases VitD 1alpha-hydroxlase to increase 1,25(OH) VitD pdn in kidney
Balance
Increased phosphatase & 1,25(OH) VitD stimulates FGF23 pdn
FGF23 stimulates kidney to reduce phosphate reabsorption -> by reducing VitD 1alpha hydroxylase & decreases PTH
Vitamin D
DEXA- dual x-ray absorptiometry
Osteoporosis diagnosis
2 x rays of diff energies to detect
Fat/soft tissue
Bone
Clinical biochemistry -> markers for showing increased risk/has osteoporosis
Bone reabsorption
C & N terminal collagen -> useful marker of increased bone deposition
Urinary calcium
Bone formation
Bone alkaline phosphatase
Osteocalcin
Markers of therapy
Metabolism
From diet -> dairy pdts
Goes to liver -> pro vitamin D in blood converted in kideny to 1,25(OH) VitD
Into blood stream where it is bound to vitamin D binding protein -> activates vitamin D receptor -> increase gene transcription -> increase of ca trpter in gut & kidney
Treatment
Ca supplementation + vitamin D
Biphosphonates -> inhibit bone resorption (etidronate,zoledronate)
Oestrogen Receptor Modulation ->inhibit bone resorption (HRT)
Hormone treatment ->PTH (teriparatide)
Neurological problems from osteoporosis ->involve nerve entrapment & severe spinal problems
Severe curving of spine -> Osteroporosis kyphosis
2 danger points in cervical cord & lumbar cord
Cervical listhesis
Severe case of osteoporosis
MRI -> damage to spine & column shifted to one side -> major disability in arms & severe pain
Paget’s disease
Osteoporosis of skull
Primary progressive deafness/tinnitus
Vertigo -> cochlear lose Ca
Primary tooth loss
Secondary osteonecrosis of jaw from bisphosphonates
Iron
Disordered iron metabolism
Iron deficiency anaemia
Decreased muscle func & cognitive func
Transfusional overload (thalassaemia, sickle cell anaemia) - Diabetes, endocrine dysfunc
Iron uptake
Uptake regulated in gut
Fe3+ converted to 2+ -> comes in with metal trpter into entrhocyte -> some used internally, some stored
Goes into blood stream where it is converted to 3+ -> bind to binding protein Transferrin & circulates in body
Iron loss->unregulated
Absorption in upper GI
Reg by body iron store by hepcidin
Fe exported to plasma by Ferroportin & Haephestin
Bound to plasma Transferrin
Hemochromatosis
Common genetic disorder
Elevated transferrin iron saturation
Commonly recessive HFE mutations
Diabetes, cardiomyopathy
Iron & neurological disorders
Freidreich’s ataxia
All extremely rare
Brain iron uptake
Periphery gets its own iron from Transferrin
BBB in brain -> reg everything
System on blood vessels of brain->Transferrin binds -> drops off iron onto endothelial cells and into brain itself
Another transferrin system -> circulates all the Fe in brain
Closed system
Transferrin dep
Highly expressed on neurons
Mitochondrial oxidative metabolism (IDA)
Brain takes 20% of body’s O2 ->high metabolic demand from mitoc oxidation of glucose; since mitoch FE rich -> hv high req for FE
Accum of Fe with age in glia
Fe deficiency anaemia (IDA)
Increases with age
Primary: diet; Secondary: GI disease (inflammatory disorders like Coeliac disease -> reduces Fe absorption)
Also due to chronic inflammatory disease
Improved EEG measures with Fe supplementation
Improved quality of life
X RCT (randomised clinical trial) of anaemia treatment in elderly
Clinical Fe biochemistry
Ferritin -> better marker for Fe stores
Folate & B12 deficiency
Similar clinically
Dietary & age related GI problems -> Coeliac
Neurological problems
Hyperhomocystinaemia -> relates to dementia
Macrocytic Hypochromic Anaemia
RBCs larger in size but reduced Hb content
Fatigue, muscle weakness
Cognitive impairment, depression
Paraesthesia, ataxia
Visual impairment
Folate
Folate deficiency
1 in 10 over 75 -> 2% anaemic
Folate comes from green leafy vegetables
Folate uptake
Proton coupled folate trpter in proximal jejunum at low pH
Reduced folate carrier at near neutral pH
Folate receptor helps with cellular uptake
Risk factors
Poor diet
Coeliac disease
Water soluble vitamin
Congestive heart failure
Diuretics so increase water output -> lose folate
Alcohol abuse
Vitamin B12
Vitamin B12 deficiency
Plasma B12
1 in 10 over 75 -> deficient
Only 10% show clinical signs of deficiency
Found in high meat diets
Vitamin B12 uptake
Vitamin B12 from food broken down -> binds to Haptocorrin in stomach
Haptocorrin deg in upper GI & B12 binds Gastric Intrinsic Factor (GIF)
Forms complex with Cubilin on surface of gut cells & enters cell via endocytosis
Proteins deg in lysosomes
B12 exported to blood via MBD1
Binds to transcobalamin for distribution
Treatment
B12 injection
Folate supplementation
Diagnosis
Sural nerve biopsy in folate deficiency neuropathy
Severe reduction of large myelinated fibres
Smith AD (2016)
Loss of folate seem to correlate with homocysteine
B vitamin supplementation -> cognitive decline in early dementia patients