Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 77 Mineral Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Minerals
v Minerals are Inorganic elements
v Not synthesized in human body
v Widely distributed in nature
v Present in foods of Plant and
Animal origin
1
?Minerals in human body
have various structural and
functional roles
?Hence it is essential to
ingest Minerals through
diet.
2
Human Body Ingests
Seven Food Nutrients
Dietary Fiber
Minerals
Water
Food Substances
Vitamins
Proteins
Lipids
Carbohydrates
3
?Minerals are classified
based on:
vFunctional need to body
vIts daily requirement
4
Two Broad Classes Of Minerals
? Macro elements
? Micro/trace elements-
? Ultra trace element (required
in amounts <1 mg/d)
5
?Macro/Principle/Chief
elements
? Body needs Macro elements
relatively in large quantities
? present in body tissues at
concentrations >50 mg/kg
? Requirement of these Minerals is
>100 mg/day
6
Macro elements
1. Calcium (Ca)
2. Phosphorus (P)
3. Sulfur (S)
4. Magnesium (Mg)
5. Sodium (Na)
6. Potassium (K)
7. Chloride (Cl)
7
? Micro Minerals /Trace Elements
? Body needs Micro Minerals
relatively in less amount
? Present in body tissues at
concentrations <50 mg/kg
? Requirement of these
Minerals is 100 mg/day
8
Name Of 10 Essential
Micro/Trace Elements
1. Iron (Fe)
2. Copper (Cu)
3. Cobalt (Co)
4. Chromium (Cr) (120 ?g/d)
5. Fluoride (F)
6. Iodine (I) (150 ?g/d)
7. Manganese (Mn)
8. Molybdenum (Mo) (75 ?g/d)
9. Selenium (Se) (35 ?g/d)
10.Zinc (Zn)
9
Possibly Essential Elements
for Humans (functions not
known)
Nickel(Ni), Silicon(Si), tin(Sn),
Vanadium(V)
10
Toxic elements
Arsenic, Lead, Mercury
11
Nutritional y Important Minerals (60Kg)
Macro Minerals
Trace Elements
Element
g/kg
Element
mg/kg
Ca
15
Fe
20-50
P
10
Zn
10-50
K
2
Cu
1-5
Na
1.6
Mo
1-4
Cl
1.1
Se
1-2
S
1.5
I
0.3-0.6
Mg
0.4
Mn
0.2-0.5
Co
0.02-0.1
12
Distribution of Calcium,
Phosphate and Magnesium in
the Body
Tissue
Calcium
Phosphate
Magnesium
Skeleton
99%
85%
55%
So t tissue
1%
15%
45%
Extracel ular fluid
<0.2%
<0.1%
1%
Total
1000 g (25 mol)
600 g (19.4 mol)
25 g (1.0 mol)
13
Equilibria and determinations of calcium in serum.
14
Physiochemical States of Calcium, Phosphate,
and Magnesium in Normal Plasma
State
Calcium
Phosphate
Magnesium
Free (ionized)
50
55
55
Protein-bound 40
10
30
Complexed
10
35
15
Total (mg/dL)
8.6-10.3
2.5-4.5
1.7-2.4
(mmol/L)
2.15-2.57
0.81-1.45
0.70-0.99
Free calcium
4.6-5.3
(mg/dL)
15
Functions of calcium
Intracellular calcium
1.Muscle contraction
2.Hormone secretion
3.Second Messenger
4.Glycogen metabolism
5.Cell division
6.Enzyme activation
16
Enzymes regulated by Ca++
Adenyl cyclase
Ca++ dependent protein kinases (PKC)
Ca++ -Mg++ -ATPase
Glycerol-3-phosphate dehydrogenase
Glycogen synthase
Myosin kinase
Phospholipase C
Phosphorylase kinase
Pyruvate carboxylase
Pyruvate dehydrogenase
Pyruvate kinase
17
Functions of calcium
Extracellular calcium
1.Bone mineralization
2.Blood coagulation
18
Calcium Dietary Requirements
?Adult : 800 mg/day
?Pregnancy, lactation and post-menopause:
1500mg/day
?Growing Children: (1-18 yrs): 1200 mg/day
?Infants: (< 1 year): 300-500 mg /day
19
Dietary Calcium sources
? Rich Calcium Sources
- Milk and Milk Products
- Mil et (Ragi)
- Wheat-Soy flour
- Black strap molasses
20
? Calcium Good sources
- Yoghurt, sour cream, ice cream
- Tofu
- Guava ,Figs
- Cereals
- Egg yolk
- Legumes
21
- Green leafy vegetables as collard,
kale , Broccolli, Cabbage and raw
turnip
- Small Fish as trout, salmon and
sardines with bones
- Meat
- Almonds, brazil nuts, dried figs,
hazel nuts
- Also soybean flour and cottonseed
flour
22
?Absorption of Calcium
occurs in the Duodenum
and proximal Jejunum
?Mediated by Calbindin
(synthesized by mucosal cel s)
23
Factors Promoting Calcium Absorption
v Parathyroid Hormone (PTH) indirectly enhances
Ca absorption through the increased activation of Calcitriol
vCalcitriol /activated Vitamin D induces the synthesis
of Ca binding protein Calbindin
vAcidity Increases the solubility of calcium salts
vAmino acids Lysine and Arginine form soluble complexes
with Calcium
24
Factors Inhibiting Calcium Absorption
Phytates and Oxalates present in plant origin diet form insoluble salts
The high content of dietary Phosphates forms insoluble Ca phosphate
Dietary ratio of Ca : P ---1:1 / 2:1 is ideal for Ca absorption
The Free Fatty acids forms insoluble Ca soaps
Alkaline condition
Low Estrogen levels Estrogen increases Calcitriol levels
High content of Dietary fiber, Caffeine, Sodium
Excess Magnesium in diet inhibits Calcium absorption
(Magnesium competes with Calcium for absorption)
25
Factors Regulating Blood Calcium
Levels
?Parathyroid Hormone (PTH)
?Vitamin D- Calcitriol
?Calcitonin
26
Organs involved for action of PTH
Intestine
Bone
Kidney
27
PTH Action on the Bone
Stimulating osteoclastic bone resorption-
Indirect effect through local mediators
(RANK ligand, tissue growth factor )
blood Ca level
This Inhibits osteoblast function- Directly by
interacting with their PTH receptors
28
Action Of PTH on the Kidney and Intestine
Parathyroid hormone acts on distal tubule through a cAMP dependent
mechanism and Increases renal re absorption of Calcium
PTH increases phosphate excretion at the proximal tubule
by lowering the renal phosphate threshold.
Action on the Intestine: indirect
PTH is a trophic factor for renal 25(OH)D1 hydoxilase.
Increases conversion of 25(OH)D to the active metabolite 1,25(OH)2D
increases the intestinal absorption of Ca by promoting the
synthesis of Calcitriol.
29
Effect of vitamin D
vIncrease calcium binding protein synthesis
vIncrease calcium absorption
vIncrease phosphate absorption
30
31
Causes of Hypocalcemia
Hypoalbuminemia
Chronic renal failure
Magnesium deficiency
Hypoparathyroidism
Pseudohypoparathyroidism
Osteomalacia and rickets due to vitamin D def. or resis.
Acute hemorrhagic and edematous pancreatitis
Healing phase of bone disease of treated hyperpara
and hematological malignancies (hungry bone synd.)
32
Causes of Hypercalcemia
Primary hyperparathyroidism
Parathyroid adenoma, hyperplasia,
carcinoma
Malignancy
Skeletal metastases
Humoral hypercalcemia
PTH-rP
Hematological malignancy
Cytokines (interleukin-1, tumor
necrosis factor, etc.)
1,25-Dihydroxyvitamin D (lymphoma)
Familial hypocalciuric hypercalcemia
33
Causes of Hypercalcemia contd
Idiopathic hypercalcemia of infancy
Vitamin overdose, vitamin D
Granulomatous diseases (e.g., sarcoidosis, tuberculosis)
Renal failure
Chronic, acute (diuretic phase) or after transplant
Chlorothiazide diuretics
Lithium therapy
Milk-alkali syndrome
Immobilization
Increased serum proteins
Hemoconcentration,
Paraprotein
34
Factors altering the distribution of calcium
Factors altering protein binding of calcium
Altered concentration of albumin or globulin
Heparin
pH
Free fatty acids
Bilirubin
Drugs
Temperature
Factors altering complex formation
Citrate
Bicarbonate
Lactate
Phosphate , Sulphate
Anion gap
35
Preanalytical Factors in Measurement of
Serum Total or Free Calcium
In Vivo
Tourniquet use and venous occlusion (protein bound ca
Incrd)
Changes in posture: increase of total calcium on standing
Decrease of total ca on recumbency
Exercise (free ca)
Hyperventilation (free ca)
Fist clenching
Alimentary status
Alterations in protein binding
Alterations in complex formation
Prolonged bed rest (both total and free ca increased)
36
Preanalytical Factors in Measurement of
Serum Total or Free Calcium contd
In Vitro
Inappropriate anticoagulants
Dilution with liquid heparin
Interfering concentrations of
heparin
Contamination with calcium
Corks, glassware, tubes
Specimen handling
Alterations in pH ( free calcium)
Adsorption or precipitation of calcium
Spectrophotometric interference
Hemolysis, icterus, lipemia
37
Causes of Hypophosphatemia
v
Shift of phosphate from extracel ular to intracel ular space
Glucose
Insulin
Respiratory alkalosis-accelerates glycolisis
v
Renal phosphate wasting
Lowered renal phosphate threshold
Primary or secondary hyperparathyroidism
Renal tubular defects
Familial hypophosphatemia
Fanconi syndrome
v Decreased net intestinal absorption
Increased Loss---Vomiting, Diarrhoea, antacids
Decreased absorption
Malabsorption
Vitamin D deficiency
v Intracel ular phosphate loss
Acidosis Ketoacidosis, Lactic acidosis
38
Clinical manifestation of serum phosphate depletion
depend on length and degree of deficiency
Plasma conc <1.5 mg/dL----produce clinical manifestation
Glycolysis impaired
Muscle weakness
Acute respiratory failure
Decreased cardiac output
Very low serum phosphate (<1 mg/dL)
Rhabdomyolysis
Tissue hypoxia
Mental confusion, Coma
Serum phosphate concentration <0.5 mg/dL
Hemolysis of red blood cells
39
Causes of Hyperphosphatemia
Decreased renal phosphate excretion
Decreased glomerular filtration rate
Renal failure
Increased tubular reabsorption (increased threshold)
Hypoparathyroidism
Pseudo hypoparathoidism
Acromegaly
Increased phosphate intake
Oral or intravenous administration
Phosphate containing enema
Increased extracellular phosphate load
Transcellular shift
Lactic acidosis, Resp acidosis, DKA
Cell lysisRhabdomyolysis
Intravascular hemolysis
40
Magnesium
Fourth most abundant cation in the body
RBC content of Mg= 3 times of serum
Absorbed from distal small bowel
Excreted mainly through kidney
Daily requirement: 300-350 mg/d (male)
Reference interval 1.7-2.4 mg/dL
Mg is important in neuromuscular excitability
Activator of large number of enzymes:
Alkaline phosphatase, hexokinase, Adenylyl cyclase,
cAMP dependent kinase, Squalene synthase,
Glutamine synthase
Required for many cellular transport processes:
insulin dependent glucose uptake.
41
Causes of Magnesium deficiency
GI disorder
Prolonged nasogastric suction
Malabsorption syndrome
Acute and chronic diarrhoea
Protein calori malnutrition
Renal loss
Chronic parenteral fluid therapy
Osmotic diuresis
Glucose (DM)
Mannitol
Metabolic acidosis
Urea
Starvation,
Hypercalcemia
ketoacidosis
Alcohol
Alcoholism
Drugs Diuretics
Aminoglycoside
42
Causes of hypermagnesemia
Excessive intake
Orally (usually in the presence of CRF)
Antacid
Cathartic
Rectally Purgation
ParentallyTreatment of pregnancy induced HT
Treatment of magnesium deficiency
Renal failure
Chronic usually with administration of magnesium
Antacid
Cathartic
Enema
Infusion
Acute Rhabdomyolysis
Lithium ingestion
43
Distribution of Iron in a 70-kg Adult Male
Transferrin
3-4 mg
Hemoglobin in red blood cel s 2500 mg
In myoglobin and various
300 mg
enzymes
In stores (ferritin)
1000 mg
Absorption
1 mg/d
Losses
1 mg/d
In an adult female of similar weight, the amount in stores would general y be less
(100-400 mg) and the losses would be greater (1.5-2 mg/d).
44
Nonheme iron transport in enterocytes
45
Absorption of iron
46
The transferrin cycle
47
Recycling of iron in macrophages
48
Schematic representation of the reciprocal relationship between
synthesis of ferritin and the transferrin receptor (TfR1).
49
Role of hepcidin in systemic iron regulation
50
Regulation of hepcidin gene expression
51
Changes in Various Laboratory Tests Used to Assess Iron-Deficiency Anemia
Parameter
Normal
Negative Iron
Iron-Deficient
Iron-Deficiency
Balance
Erythropoiesis
Anemia
Serum ferritin 50-200
Decreased <20
Decreased <15
Decreased <15
(g/dL)
(TIBC) (g/dL)
300-360
Slightly increased Increased >380
Increased >400
>360
Serum iron
50-150
Normal
Decreased <50
Decreased <30
(g/dL)
Transferrin
30-50
Normal
Decreased <20
Decreased <10
saturation (%)
RBC
30-50
Normal
Increase
Increase
protoporphyrin
(g/dL)
Soluble
4-9
Increase
Increase
Increase
transferrin
receptor (g/L)
RBC
Normal
Normal
Normal
Microcytic
morphology
Hypochromic 52
Diagnosis of Microcytic Anemia
Tests
Iron
Inflammation Thalassemia
Sideroblastic
Deficiency
Anemia
Smear
Micro/hypo
Normal
Micro/hypo
Variable
micro/hypo
with targeting
SI (g/dL)
<30
<50
Normal to
Normal to
high
high
TIBC (g/dL)
>360
<300
Normal
Normal
Percent
<10
10?20
30?80
30?80
saturation
Ferritin (?g/L) <15
30?200
50?300
50?300
Hemoglobin
Normal
Normal
Abnormal
Normal
pattern
53
Zinc
Second most abundant trace element in the body
The most available dietary sources of zinc : red meat and fish,
Germ and whole bran
Dietary reference intake
Male: 11 mg/d Female: 8 mg/d
Infants and young children= need small amount
Strict vegetarians= 50% more zinc /d
Zinc in human breast milk is efficiently absorbed because of
presence of picolinate and citrate.
54
Zinc metabolism
55
Examples of Zinc containing enzymes
Cabonic anhydrase
Alkaline phosphatase
RNA and DNA polymerase
Thymidine kinase and carboxy peptidase
Alcohol dehydranase
56
Reference interval of zinc
A guidance reference interval: 80-120 ?g/dL
Plasma samples are preferred to serum
Serum concentration is 5% higher than that of plasma
Concentration decreased after food
Concentration is higher in the morning
57
Clinical deficiency of zinc
Signs and symptoms :
Depressed growth with stunting---cereal based diet
Increased incidence of infection
Diarrhoea
Skin lesions
Alopecia
58
Acrodermatitits enteropathica
Autosomal recessive inborn error
Mutation on SLC (solute linked carrier)39a4 gene
on chromosome 8 q24.3
Affects zinc absorption from intestinal mucosa
1.Periorificial dermatitis
2.Alopecia
3.diarrhoea
59
Role of zinc on immune function
Increase in the activity of serum thymulin--
the thymus specific hormone involved in T cell function
Maintain balance develops between Th1 and Th2 helper cells
Increase the lytic activity of natural killer cells
Improve cell mediated immunity
60
Dietary sources of copper
Organ meats , liver, kidney
Shell fish
Whole grain cereals
Cocoa containing products
Absorption
The extent of absorption: 20-50%
Absorption reduced by: Zinc, molybdate, iron
61
Absorption increased by aminoacids
Metabolism of copper
62
Functions of Copper
In cellular respiration: cytochrome c oxidase-located on
mitochondrial membrane
Formation and maintenance of myelin : cytochrome c oxidase
Iron homeostasis: ceruloplasmin
Melanin formation: tyrosinase
Neuro transmitter production : Dopamine -hydroxylase catalyzes
the conversion of dopamine to the neurotransmitter norepinephrine
MAO- catalyzes the metabolism of seroronin
Synthesis of connective tissue: lysyl oxidase- stabilization of
extracellular matrix- enzymatic cross linking of collagen and elastin
Protection against oxidants: Superoxide dismutase- protects against
free radical damage
63
Menkes disease
Kinky or steely hair disease
X linked , affects only male infants
Mutations in the gene ATP7A gene for a
copper binding P type ATP ase: Responsible for directing the
efflux of copper from cells
Copper is not mobilized from the intestine--accumulates
Activities of enzymes are decreased--because of defect of its
incorporation into the apoenzyme
Absence of hepatic involvement
64
Wilson disease
Mutation in a gene encoding a copper binding P type ATPase
Copper fails to be excreted in the bile and accumulates
in liver, brain, kidney and RBC
Inhibit the coupling of copper to apoceruloplasmin and
leads to low level of ceruloplasmin in plasma
Hemolytic anemia, chronic liver disease, neurologic syndrome
Kayser-Fleisher ring
Liver biopsy should be performed
Treatment:
65
Major Laboratory tests used in the
investigation of diseases of copper metabolism
Test
Normal adult range
Serum copper
10-22?mol/L (70-
140?g/dL)
Ceruloplasmin
200-600 mg/L
Urinary copper
<1 ?mol (60?g)/24h
Liver copper
20-50 ?g/g dry weight
66
Major Laboratory tests used in the
investigation of diseases of copper metabolism
Test
Wilson disease
Serum copper
<8 ?mol/L
Ceruloplasmin
<200 mg/L
Urinary copper
>3 ?mol/24h
Liver copper
>250 ?g/g dry weight
67
Copper and Anaemia
Interfering iron transport
Part of ALA synthase
Microcytic hypochromic
Iron resistant
68
Selenium
Selenium is an essential element for humans
Constituent of the enzyme glutathione peroxidse
The most biologically active compounds contain
Selenocysteine: Selenium is substituted for sulphur
in cysteine;
incorporated into protein by specific codon.....
Ingested selenium compounds include
selenate, selenite , selenocysteine,
Selenomethionine
RDA= 55?g/d
69
Dietary sources and metabolism of Selenium
Mainly as selenomethionine from plants
Selenium from Inorganic salts are more
rapidly incorporated than organic sources
50-60% of total plasma selenium- selenoprotein P
30%-- GSHPX-3
Rest- into albumin as selenomethionine
Major route of excretion: Urine ( 20-1000?g/L) 70
Metabolic pathways of selenium
71
Functions of Selenium
Glutathione Peroxidase
Remove an oxygen atom from H2O2 and lipid hydroperoxide
1. GSHPx-1 in red cell s, 2. GSHPx-2 in gastrointestina mucosa,
3. blood plasma GSHPx-3,
4. the cell membrane? located GSHPx-4.
Iodothyronine Deiodinase
T4 T3
Thioredoxin Reductases
Selenoprotein P-transport protein and has antioxidant function
72
Severe Deficiency
Keshan Disease.
Kashin-Beck Disease
Marginal Deficiencies
Thyroid Function
Immune Function? both cell mediated and B cell function are impaired
Reproductive Disorders--necessary for testostereone synthesis
and maintenance of sperm viability
Mood Disorders-anxiety, confusion, hostility
Inflammatory Conditions- arthritis, pancreatitis
Viral Virulence--Coxackie virus
73
Cancer Chemoprevention
Toxicity of Selenium
Garlic odor
Hair loss
Nail damage
Reference interval: 63-160 ?g/L
Selenium depletion: <40?g/L
Tolerable upper limit 400 ?g/d
Laboratory assessment: CFAAS (Carbon furnace AAS)
ICP(inductively coupled plasma)-MS
74
Vitamin E sparing effect of Selenium
75
Fluoride
Most widely used pharmacologically beneficial trace
elements
Supplementation:
Water
Salt
Sugar
Milk
76
Function of fluoride
The fluoride is exchanged for hydroxil in the
crystal structure of apatite, a main component of
skeletal bone and teeth.
Stabilizes the regenerating tooth surface.
To reduce decay of the erupting teeth as well as
Topical effect on adult teeth.
Pharmacological doses of fluoride may reduce the
incidence of bone fracture in patients with
osteoporosis.
77
Absorption, transport, metabolism
and excretion of Fluoride
Absorbed from the stomach and the small intestine
Peak increase in blood plasma occurs within 1 hour
Ions are rapidly cleared from plasma into tissues
In exchange with anion e,g. hydoxil, citrate, carbonate
96% of the 2.6 g of total body fluoride is located
in bones and teeth
90% of excess fluoride is excreted in urine
78
Toxicity of Fluoride
Dental fluorosis: The mottling of enamel in the
erupting teeth of children
A disfiguring condiition
Caused by ingestion of fluoride containing toothpaste
Skeletal fluorosis: Occupational exposure to
inhaled fluoride dust among Cryolite workers
during aluminium refining: Bone abnormalities
79
Laboratory assessment of status of Fluoride
Analysis of drinking water
Determination of fluoride in urine
Direct determination using fluoride specific electrode
Reference interval of Fluoride
Concentration in body fluids and tissue vary widely
For urine: a guideline interval is: 0.2 ? 3.2 mg/L
80
Dental fluorosis
81
Common sources of dietary iodine
naturally in soil and seawater
Iodized table salt
Cheese
Cows milk
Eggs
Frozen Yogurt
Ice Cream
Iodine-containing multivitamins
Saltwater fish
Seaweed (including kelp, dulse, nori)
Shellfish
Soy milk, Soy sauce
Yogurt
82
Synthesis o thyroid hormones
83
Deficiency of iodine
Hypothyroidism
PREGNANCY-RELATED PROBLEMS:
miscarriages, stillbirth, preterm delivery,
congenital abnormalities in their babies
Children of mothers with severe iodine deficiency
during pregnancy
mental retardation (preventable cause)
problems with growth, hearing, and speech
Cretinism ( permanent brain damage, mental retardation,
deaf mutism, spasticity,)
84
The recommended average daily intake of iodine
Adult: 150 ?g/d
children: 90?120 ?g/d
pregnant women: 200 ?g/d
Urinary iodine is >10 ?g/dL in iodine-sufficient
populations
85
MEDIAN POPULATION URINARY IODINE VALUES
AND IODINE NUTRITION
MEDIAN URINARY IODINE
CORRESPONDING IODINE
IODINE NUTRITION
CONCENTRATION (g/L)
INTAKE (g/day)
<20
<30
SEVERE DEFICIENCY
20-49
30-74
MODERATE DEFICIENCY
50-99
75-149
MILD DEFICIENCY
100-199
150-299
OPTIMAL
200-299
300-449
MORE THAN ADEQUATE
>299
>449
POSSIBLE EXCESS
86
This post was last modified on 05 April 2022