Download MBBS Biochemistry PPT 77 Mineral Lecture Notes

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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