Mineral metabolism

A complete text on mineral metabolism with clinical references, meant fof both UG and PG teaching.

1. Mineral Metabolism
DrAbhra Ghosh

2. •Ourbodyconsistsofatleast29elements
Categorizedinfivegroups
•GrI:C,H,O,N–Thoseformingcomponents
ofmacromoleculessuchascarbohydrates,
proteins,lipidsetc
•GrII:Na,K,Cl,Ca,P,Mg,S-Mineralswhose
dailyrequirementis>100mg/day.
-Knownasmacroelements

3. •GrIII:Cr,Co,Cu,I,Fe,Mn,Mo,Se,Zn
-Mineralswhoserequirementis<100mg/day.
•GroupIV:Cd,Ni,Si-Possibletraceelement.
•GroupV:As,CN-,Hgetc-Notessentialbut
toxic.

4. SODIUM(Na,Atno.–11,Atomicmass–23)
•Chiefelectrolyteinthebody
•PresentasNaClandNaHCO3
•Largeconc.inextracellularfluidcompartment
•Source:Widelydistributedinfoodmaterial.
Majorsourceistablesalt.
•Dailyrequirement:
-0.1-0.5gforinfants
-0.3-2.5gforchildren
-1-3.5gforadults

5. Absorption:
•Activelybysodiumpump.
•Thesepumparepresentinbasalandlateral
plasmamembraneofintestinalandrenalcells.
SODIUM PUMP
•AlsoknownasNa+-K+ATPase
•RequiresATPandMg+2ascofactor
•It’saglycoproteinhaving2!and2"chains.
•Inhibitors:
-Ouabain:Glycosideofasteroid,usedas
cardiotonicdrug

6. Action of Na+-K+ pump

7. Functions:
1.Fluid balance: Na maintains crystalloid osmotic
pressure of ECF.
2.Neuromuscular excitability: Na is associated with
neuromuscular irritability.
3.Acid base balance: Na+-H+ exchange in renal
tubule to acidify urine.
4.Maintenance of viscosity of blood
5.Role in resting membrane potential: Plasma
membrane has poor Na+ permeability. Na pump
keeps Na+conc. on the higher side. This is known
as polarization –creates resting membrane
potential.

9. 6.Roleinactionpotential:Stimulationcauses
depolarizationofnerveormusclebyincreasing
permeabilitytoNa+.

10. Normalvalue:
-Inplasma–136–145mEq/L
-Withincells–12mEq/L
CLINICAL APECTS
Two conditions associated with sodium levels are:
1.Hypernatremia:
•Increasedsodiuminbloodisknownas
hypernatremia(>150mEq/L)
•Itreferstoexcessiveextracellularsodium
relativetothewater.

11. Causesofhypernatremia:
a.Simpledehydration–Duetoexcessivesweating
withinadequatewaterreplacement.
b.Diabetesinsipidus–Waterlossduetolackof
ADHorabsenceofreceptorsontargetcells
c.Osmoticloading–Osmoticeffectsofglucose,
urea,aminoacidscausesosmoticdiuresis.
d.Excesssodiumintake–Excessadministrationof
isotonicsalineorNaHCO3

12. e.Steroidtherapy–Mineralocorticoidscontrol
metabolismofsodiumbyincreasingreabsorption
fromkidneytubules.
InConn’ssyndrome,aldosteronefrom
tumorsofadrenalglandisproducedcausing
hypernatremia.
Symptoms:
Thirst,drymucusmembrane,fever,restlessness,
confusion,spasms.

13. 2.Hyponatremia:
Decreasedsodiumlevelinbloodiscalled
hyponatremia.
Causesofhyponatremia:
a.Diureticmedication–Thesegroupofdrugacts
bypromotingexcretionofNabykidney.
b.Kidneydiseases–Duetokidneydysfunction,
Na+isnotreabsorbed.
c.Gastrointestinalloss–Diarrhearesultsinlossof
fluidwithsodium/chloride.

14. SIADH(Syndromeofinappropriatesecretionof
anti-diuretichormone)isaconditionwith
-hyponatremia;
-normalglomerularfiltrationrate
-normalserumureaandcreatinineconcentration.
DIAGNOSTICCRITERIAOFSIADH
a.Hyponatremia(<135mmol/L)
b.Decreasedosmolality(<270mOsm/kg)
c.Urinesodium>20mmol/L
d.Urineosmolality>100mOsm/kg.

15. CausesofSIADH:
a.Infections(Pneumonia,sub-phrenicabscess,TB,
aspergillosis)
b.Malignancy(Cancerofthecolon,pancreas,
prostate,smallcellcancerofthelungs)
c.Trauma(Abdominalsurgery,headtrauma)
d.CNSdisorders(Meningitis,encephalitis,brain
abscess,cerebralhemorrhage)
e.Druginduced(Thiazidediuretics,carbamazepine,
chlorpropamide,opiates).

16. PSEUDOHYPONATREMIA
-Duetoseverehyperglycemia
-Movementofwaterfromtheintracellularfluid
(ICF)totheextracellularfluid(ECF),dilutingall
ofthesolutesinECFtorestoreosmoticbalance.
-Resultsindecreaseinplasmasodium
concentration
-Alsoknownashypertonichyponatremia.
-Thisisconsidered“pseudo”(or“false”)
hyponatremiaasitdoesnotreflectadeficiencyin
totalbodysodiumstores,suchasoccursinrenal
sodiumloss.

17. POTASSIUM (K, Atomic no. –19, At. mass –39)
•Potassium is the majorintracellular cation
•Source: Widely distributed in the vegetable foods
•Daily requirement: 3–4 g per day
•Normal value:
-In plasma -3.5–5.2 mmol/L.
-In cells -160 mEq/L.

18. Functions:
1.Influences muscular activity
2.Maintains acid base balance
3.Acts as cofactor for certain enzymes, eg.
Pyruvate kinase
4.Involved in nerve conduction process
Clinical aspect:
Why plasma potassium must be measured on fresh
sample?

19. Hyperkalaemia:
•Excretionofpotassiumishighlyeffective.
•Plasmapotassiumlevelabove5.5mmol/L
•Conditionswhichcangiveriseto
hyperkalaemiaare
1.Anuria:Completeshutdownofkidneyfunction
resultsinincreasingconcentrationofK+
2.Tissuedamage:Damagetothecellcauses
releaseofK+intoECF

20. 3.Violentmusclecontraction:Exercisecauses
releaseofpotassiumfrommusclecellintoECF
4.Addison’sdisease:Inabsenceofaldosterone,
exchangeofNa+forK+isreducedcausing
retentionofK+
5.DiabetesMellitus:Inketoacidosis,thereis
substantiallossofintracellularK+totheECF
causinghyperkalaemia.

21. Symptoms:
•Increased membrane excitability causing
ventricular arrythmiaand ventricular
fibrillation.
•Flaccidparalysis,
•Bradycardia
•Cardiacarrest
-ECGshows
•ElevatedTwave,
•WideningofQRScomplex
•LengtheningofPRinterval

22. Treatment:
•Intravenous glucose and insulin to promote
glycogenesis
•Intravenous calcium gluconate (10%, 10 mL over
5 min) to stabilize myocardium
•1.4% sodium bicarbonate to correct acidosis
•Dialysis

23. Hypokalaemia:
•Plasmapotassiumlevelisbelow3mmol/L
•Conditionswhichcangiverisetohypokalaemia
are
1.LossofK+inGIsecretions
-Prolongvomitinganddiarrhea
-Mucoussecretingtumornamedcillousadenoma
-Habitualuseoflaxatives
2.Familialperiodicparalysis
3.Treatmentofdiabeticketoacidosis

24. 4.LossofK+inurine
-Useofdrugslikethiazides,acetazolamide
-Conn’stumorcausingsymptomofprimary
hyperaldosteronism
-Cushingsyndrome
5.Renaltubularacidosis

25. Symptoms:
Muscularweakness,fatigue,musclecramps,
hypotension,decreasedreflexes,palpitation,cardiac
arrythmiasandcardiacarrest.
-ECGshows
•Flattenedwaves
•Twaveisinverted
•STsegmentisloweredwithAVblock.

26. Treatment:
•Adequate potassium supplementation (200 to
400 mmol for every 1 mmol fall in serum
potassium)
•100 mmol KClper day in 3–4 divided doses.
•In acute cases, intravenous supplementation
may be given; but only in small doses

27. Chloride (Cl, Atomic no. -17 , atomic mass –35)
•Taken in diet as sodium chloride
•Vegetables and meats have small proportions of
chloride.
Daily Requirement: About 100-200 mmol as
sodium chloride (table salt).
Absorption:
•Occurs in small intestines
•Exchange process with the HCO3
Excretion:
•Sweat, faeces, renal

28. Normal levels:
•Plasma -96–106 mEq/L
•CSF -125 mEq/L.
•Chloride in CSF is higher than any other body
fluids.
•Since CSF protein content is low, Cl—is
increased to maintain Donnanmembrane
equilibrium.

29. Hyperchloremia:
1. Dehydration
2. Cushing’s syndrome. Mineralocorticoids cause
increased reabsorption from kidney tubules
3. Severe diarrhea leads to loss of bicarbonate and
compensatory retention of chloride
4. Renal tubular acidosis.

30. Hypochloremia:
1.Excessivevomiting-HClislost,soplasmaCl—
islowered.Therewillbecompensatoryincreasein
plasmabicarbonate.Thisiscalledhypochloremic
alkalosis.
2.Excessivesweating.
3.InAddison’sdisease,aldosterone↓,renal
tubularreabsorptionofCl-↓,andmoreCl-is
excreted.

31. Cystic fibrosis:
•Geneticdisorder
•AssociatedwithCFTR,cyclicAMPdependent
regulatoryproteinforchloridechannel
•PointmutationinCFTRcausesabnormalityofCl-
permeability.
•Increasedviscosityofbodilysecretions.

32. ClinicalFeatures:
•Chronicbacterialinfectionsoftherespiratory
tractandsinuses
•Fatmaldigestionduetopancreaticexocrine
insufficiency
•Infertilityinmalesduetoabnormaldevelopment
ofthevasdeferens,and
•Elevatedlevelsofchlorideinsweat,greaterthan
>60mmol/L.

33. Source:
•Amino acids cysteine and methionine.
•Proteins contain about 1% sulfur by
weight.
•Inorganic sulfates of Na+, K+ and Mg++
remain unavailable
Excretion:
•Inorganic sulfate
•Organic sulfate or ethereal sulfate
•Neutral sulfur or unoxidized sulfur
SULFUR (S, Atomic no. –16, Atomic mass –32)

36. CALCIUM (Ca, Atomic no. –20, Atomic mass –40)
•Chiefmineralpresentinboneandteeth
•Source:
Milk,Cheese,egg–yolk,beans,cabbageetc.
•Distribution:
1.Ionised
2.Proteinbound
3.Complexedcalciumboundwithorganicacids

37. Absorption:
1.Simplediffusion
2.Activetransport:requiresCa+2ATPaseand
calciumbindingprotein
Factorsaffectingabsorption:
1.pHoftheintestinalfluid:acidicpHfavours
absorption
2.Compositionofthediet:
-Highproteindietfavoursabsorption
-Fattydiethindersabsorption
-Sugarsandorganicacidspromotesabsorption

38. -Phytic acid ↓ Ca absorption
-Oxalates ↓ calcium absorption
-Excess fibres↓ calcium absorption
-Phosphates, Magnesium, Iron ↓ calcium
absorption
-VitD promotes Ca absorbtion
3. Homonal
-Parathormone increases vitD activation, leading to
increase in calcium absorption
-Calcitonin ↓ calcium absorption
-Glucocorticoids ↓ calcium transport

39. Functions:
1.Calcificationofbonesandteeth
2.Roleinbloodcoagulation
3.Neuromusculartransmission
4.Excitabilityofnerves
5.Musclecontraction
6.Actsassecondarymessenger
7.Secretionofhomones

41. CalciuminBlood
i.Normalbloodlevel:9–11mg/dL
ii.Ionizedcalcium:About5mg/dLofcalciumisin
ionizedformandismetabolicallyactive.
Another1mg/dLiscomplexedwithphosphate,
bicarbonateandcitrate.Thesetwoformsare
diffusiblefrombloodtotissues.
iii.Proteinboundcalcium:Approx.4mg/dL,
nondiffusible

44. Hypercalcaemia:
Calcium level > 11.0 mg/dL
Causes:
1.Primary hyperparathyroidism
-Tumors
-Ectopic source (MEN I, MEN II)
2.Malignancy
-Humoral hypercalcemia of malignancy
-Direct involvement of bone
-Hematological malignancies
3.Granulomatous disease
-Tuberculosis, sarcoidosis

45. 4.Overdose of vitamins
-IntoxicatonofvitA,hypervitaminosisD
5.Drug-inducedHypercalcemia
-Thiazide,spironolactone
6.Misc
-Idiopathichypercalcemiaofinfancy
-Increasedserumproteins

46. Symptoms
1. Anorexia, nausea, vomiting
2. Polyuria and polydypsia(ADH antagonism)
3. Confusion, depression, psychosis
4. Renal stones
5. Ectopic calcification and pancreatitis
6. Blood alkaline phosphatase is increased.

47. Management:
•Adequate hydration, IV normal saline
•Furosemide IV to promote calcium excretion
•Steroids, if there is calcitriol excess
•Beta blockers in thyrotoxicosis
•Definitive treatment for the underlying disorder.

48. Hypocalcaemia:
Calcium level < 8.5 mg/dL
Causes
1.Hypoalbuminaemia
2.Hypoparathyroidism
-Surgical-induced
-Autoimmune
-Hypoparathyroidism of infancy
3.Renal failure
4.Pseudohypoparathyroidism
5.Addison’s disease, Pernicious anaemia, acute
pancreatitis, Hungry bone disease
6.Magnesium deficiency

49. Symptoms
1. Muscle cramps
2. Paresthesia, especially in fingers
3. Neuromuscular irritability, muscle twitchings
4. Tetany (Chvostek’s sign, Trousseau’s sign)
5. Seizures
6. Bradycardia
7. Prolonged QT interval

50. Treatment:
1. Oral calcium, with vitamin D supplementation
2. Underlying cause should be treated
3. Tetany needs IV calcium (usually 10 mL 10%
calcium gluconate over 10 minutes, followed by
slow IV infusion. IV calcium should be given only
very slowly.

51. Tetany:
-Accidental surgical removal of parathyroid glands
-Autoimmune diseases.
-Neuromuscular irritability is increased.
Symptoms:
-Carpopedal spasm
-Laryngismus and stridor
-Chvostek’s sign
(tapping over facial nerve causes facial contraction)
-Trousseau’s sign (inflation of BP cuff for 3
minutes causes carpopedal spasm)

52. -IncreasedQ-TintervalinECGisseen.
-Serumcalciumis↓,phosphatelevel↑.
-Urinaryexcretionofbothcalciumandphosphate
↓.
Treatment:
-Intravenousinjectionofcalciumsalts.

53. Osteoporosis:
↓Calciumabsorptionduetoincreasedage
↓conc.ofandrogens/estrogens
↓conc.ofvitaminD

55. Osteopetrosis
•Marblebonedisease.↑bonedensity.
•MutationingeneofcarbonicanhydrasetypeII.
•Inabilityofboneresorptionbyosteoclasts.
Paget’sDisease
•Localizeddisease,characterizedbyosteoclastic
boneresorption
•Disorderedreplacementofbone.
•Commoninpeopleabove40andmayaffectoneor
severalbones.
•Familialincidence
•Treatment-Bisphosphonates.

56. Hypocalcaemiainrenalfailuremaynotbe
associatedwithtetany
•Renalfailureisassociatedwithacidosis
•Acidosispromotesionization
•Ioniccalciummaynotbelowered

57. Solubilityproductofcalciumandphosphorous:
•Thereisareciprocalrelationshipofcalcium
withphosphorus.
•Theionicproductofcalciumandphosphorusin
serumiskeptasaconstant.
•Innormaladults,calcium=10mg/dL×
phosphorus4mg/dL;soionicproductis40.

58. IRON (Fe, Atomic no. –26, Atomic mass –56)
Most essential trace elements in the body
Total iron content in a human -2.3 gm to 3.8 gm
Storage form:
•Essential (or functional) iron
•Storage iron

59. Essential Iron : Involved in normal metabolism of cell
HaemProteins
Cytochromes
Iron Requiring Enzymes
Haemoglobin
Myoglobin
Catalases
Peroxidases
Xanthine oxidase
Cytochrome C reductase
Acyl-CoA dehydrogenase
NADH reductase
Group of
organo-iron
compounds,
mainly found in
mitochondria

60. Haber’sreaction:
Alsoknownas-Haber-Weiss-Fenten’sreaction
H2O2reactswith“Superoxide”anion,inpresence
ofFe++(ferrous)toformHydroxylradicaland
singletoxygen.
O2-+ H2O2 OH*+-O2 + OH-Fe++

61. Storage form
FerritinHaemosiderin
•Major storage protein of
iron
•24 monomeric unit
•Spherical shell with six
pores
•Pores have catalytic
activity
•Iron present as ferric
oxyhydroxyphosphate
•Partialllystripped ferritin
•Present in iron overload
•Microscopically visible Fe
staining particle
•Slow mobilization of iron

62. Transferrin:
•Non heamiron binding glycoproteins
•Binds with two atoms of iron (ferric state)
•Soluble in plasma
•Fe+2has to be converted into Fe+3 form
•Ceruloplasmin and ferroxidase II required
•Only 30-33% is saturated
Functions:
•Transport of iron to RE cells, bone marrow

63. Source:
Exogenous:
•Leafy vegetables, pulses, cereals
•Liver, meat
•Jaggery
•Milk is poor source
Endogenous:
•Fe stored in RE cells and intestinal mucosal
cells
•Effete red cells

64. Absorption:
Factors:
•ReducedformofIronbyferrireductase
•AscorbicAcid
•InterferingSubstanceslikephytates,oxalic
acidetc.
•OtherMinerals
•MucosalBlockTheory(Garnick’shypothesis)

70. RegulationofAbsorptionbyFourMechanism
i.Mucosalregulation
ii.Storesregulation
-↓ironstore,↑absorption
iii.Erythropoieticregulation
-Anaemiaprovidesasignalforincreasemucosal
absorption
iv.Regulationattheleveloftranscription

72. ConservationofIron:
•LysisofRBCcausesreleaseofHb
•FreeHbremainsinthecirculationbybinding
withHaptoglobin
•Hbwhendissociatesintohemeandglobin,
hemepartbindswithhemopexin.
•Theseproteinsareexampleofacutephase
proteins

73. ExcretionofIron:
i.Ironisaone-wayelement.
ii.Homeostasisisdoneattheabsorptionlevel.
iii.Anytypeofbleedingwillcauselossofiron
fromthebody
iv.Fecescontainunabsorbedironalongwith
desquamatedcell.
v.Lossofuppercellularlayerofskin

74. IRON OVERLOAD
Excessive absorption
Repeated transfusion
Parenteral iron therapy
TYPES
HemochromatosisHemosiderosis
Primary hereditary
(Idiopathic)
Secondary

75. Hemochromatosis:
Overloading of cells with iron associated with cell
injury
a.Primary (Idiopathic) Haemochromatosis:
-Inherited disorder
-Autosomal recessive
-Involves liver, spleen, skin
Classic triad for diagnosis:
1.Micronodular cirrhosis
2.Diabetes mellitus
3.Bronze pigmentation of skin

76. Pathophysiology:

77. •HFE,locatedonchromosome6
•AssociatedwithMHCIgenes.
•MissensemutationsofHFEinindividualsare
associatedwithprimaryhaemochromatosis:
1.Cysteinyltoatyrosylresidue(CY282Y)
2.Histidinetoanaspartylresidue(H63D)
-disruptsthestructureofHFEprotein.
Screeningtest:
Serumtransferrinsaturation>62percent

78. Secondaryhemochromatosis:
•Ineffectiveerythropoiesisasinthalassaemia,
erythrogenesisimperfecta
•Evendistributionofironbetweenmacrophages
andhepatocytes
•Hepatocellularnecrosisandsecondaryscarring

79. IRONDEFICIENCY:
Threestagesofirondeficiencyare:
1.Ironstoragedepletion
2.Irondeficiency
3.Irondeficiencyanaemia.
1.IronStorageDepletion:
•Notusuallyrecognizable
•Doesnotelicitamedicalexamination.
•Serumferritin↓

80. 2.IronDeficiency:
•Ironstoresarealmostexhausted
•Serumferritinislow
•Transferrinsaturationislow
•Erythrocyteprotoporphyrinincreases
•Haemoglobinconcentrationfalls
3.IronDeficiencyAnaemia:
•Irondeficiencyanaemiaismanifestedas
hypochromicmicrocyticanaemia.

81. Iron deficiency anaemia:
•Mostcommonnutritionaldeficiency
•Commonestsufferer–Pregnantwoman
Causesofirondeficiency:
•Nutritionaldeficiency
•Hookworminfestation
•Repeatedpregnancies
•Chronicbloodloss
•Nephrosis
•Lackofabsorption
•Leadpoisoning

82. Microscopic Appearance:
•Microcytichypochromicanaemia
•Hemoglobinlevelis<12g/dL
Clinicalmenifestations:
•Apathy
•Achlorhydria
•PlummerWilsonsyndrome
•Impairedattention,irritability,loweredmemory

83. Laboratoryfindings:
i.Serumironlevels↓
ii.Totalironbindingcapacity(TIBC)↑in
hypochromicanemia
iii.Solubletransferrinreceptorlevel(TfR)↑in
irondeficiencyanaemia,hemolyticanaemia,
polycythemia.

88. SULFUR (S, Atomic no. –16, Atomic mass –32)
Anessentialelement
Source:
Sulphuristhusavailableinmeat,fish,legumes,egg,
liver,cereals.Adequateproteinindietfulfills
Sulphurrequirement
Absorption:
•Ingestedasorganicsulphatesasinproteinsoras
inorganicsulphate.
•Inorganicsulphateisabsorbedviapassive
transport
•SulphurcontainingAAsareabsorbedviaactive
transport.

89. Excretion
•Oxidizedinlivertosulfate(SO4)
•Thiscontains3categories
i.Inorganicsulfates
ii.Organicsulfateoretherealsulfate
iii.Neutralsulfurorunoxidizedsulfur:This
fractionconstitutes

90. Functions:
•Formationsof‘activesulphate’(PAPS):
Transulfurationreaction
•Sulphurisinvolvedintheformationofproteins
suchaskeratin,chondroproteins,sulpholipids.
•ActivecentresofenzymessuchasAcylcarrier
protein(ACP)andmultienzymecomplexof
fattyacidsynthesis.
•Secondaryandtertiarystructureofproteinsby-
S-S-linkage

91. •Iron-sulphurproteinsofelectrontransport
chain.
•S-adenosylmethionineisaco-substratefor
methylferases(transmethylation).
•Coenzymes-biotin,pantothenicacid,thiamine,
lipoicacid
•Importantconstituentsofmucopolysaccharides,
sulfolipids
•Detoxificationofphenol,skatole,indoleand
steroidswithsulphateions.

92. S-adenosyl methionine:

93. Copper (Cu, Atomic no. -29, Atomic mass –63.5 )
•Totalcontentofcopper–100to150mg
•Distributedinmuscle,bones,liver
•Presentinthreeforms:
1.Erythrocuprein(inredbloodcells)
2.Hepatocuprein(inliver)
3.Cerebrocuprein(inbrain)
Source:
•Meat,shellfish,legumes,nutsandcereals
•Milkandmilk-productsarepoorsources

94. Absorption:
•Mainlyfromduodenum
•Metallothionein–lowmolecularweightprotein
•Inplasma–bindswithhistidine
•Removedbyliver
Roleofliver:
Twopossibleroutes-
1.CuisexcretedinthebileintotheGItractfrom
whichitisnotreabsorbed
2.IncorporationintoCaeruloplasmin

95. Serumcopper:
Presentintwoform-
1.DirectreactingCu–looselyboundtoalbumin
2.Boundform–Boundtoα-globulinfractionof
theserum

96. Functions of copper:
1.Role in enzyme action
2.Role of Cu++in Fe Metabolism
3.Role in Maturation of Elastin
4.Role in Bone and Myelin Sheath of Nerves
5.Role in Haemocyanin

97. Copper deficiency:
1.Loss of weight
2.Bone disorder
3.Microcytic hypochromic anaemia
4.Greying of hair
5.Atrophy of myocardium

98. Caeruloplasmin
•Coppercontainingα2-globulin,aglycoprotein
•Molecularweightis≈151,000.
•Eightsitesforbindingcopper-½asCu+,½as
Cu++
•Plasmacontainsapprox.30mg/100mlandabout
75to100µgofCu
•Ithasenzymeactivitiese.g.copperoxidase,
histaminaseandferrousoxidase
SiteofSynthesis:liver,Cuionsbindwith
apocaeruloplasmin.

99. Level of caeruloplasmin with age and sex:
•Low concentrations at birth, gradually increases
to adult levels
•Females have higher concentrations than males.
Functions of Caeruloplasmin:
•90 per cent or more of total serum copper is
contained in caeruloplasmin.
•Functions as a ferroxidase and helps in
oxidation Fe++ to Fe+++

100. Clinical Importance
•Increase: pregnancy, inflammatory processes,
malignancies, oral oestrogentherapy and
contraceptive pills.
•Decrease: Wilson’s disease, Menke’s disease

101. Wilson’s disease
•Also known as hepatolenticular degeneration
•Autosomal recessive
Metabolic defect:
•Abnormal incorporation of Cu into
apoceruloplasmin
•Impaired ability of excrete Cu by liver

102. Molecular defect:
•Mutations in copper binding P type ATPase
•Contains 1411 amino acids
Mechanism:
1.Defective excretion of copper into the bile
2.A reduction of incorporation of copper into
apocaeruloplasmin
3.Accumulation of copper in liver, brain, kidney
and RB cells.
4.Near-zero copper balance, resulting in copper
toxicity.

103. Clinicalfeatures:
•TotalbodyretentionofCu↑
•Liver:Progressivehepaticcirrhosisofacoarse
nodulartype→hepaticfailure.
•Brain:Dysfunctionoflenticularregionofthe
brain,necrosisandsclerosis
•Kidneys:Defectsinrenalreabsorption→
aminoaciduria.

104. •Eyes:Copperdepositionin“Descemet’s
membrane”oftheeyecausesagoldenbrown,
yelloworgreenringroundthecornea-
“Kayser-Fleischerring”.
•Blood:TheserumCuislow
•Urine:UrinaryexcretionofCuismarkedly
increased↑.
•Treatment:AdministrationofCu-chelating
agentlike“penicillamine”.

105. MENKE’SDISEASE
Synonym:KinkyorSteelhairsyndrome
Inheritance:
X-linkeddisorderofintestinalcopperabsorption.
Metabolicdefect:
Transportofcopperthroughbasolateralmembrane
ofenterocytes

107. Defectatmolecularlevel:
•Mutationsinthegenefora“copperbindingP
typeATPase”.
•Itisresponsiblefordirectingtheeffluxof
copperfromcells.
ClinicalFeatures:
•Hairappearsstrikinglypeculiar:kinky,colorless
orsilvery,andbrittle
•Mentalretardation
•Temperatureinstability
•Abnormalboneformation
•Susceptibilitytoinfection

108. ZINC (Zn, Atomic no. –30, Atomic mass –65)
Sources:
Animal sources: Liver, milk, dairy products, eggs.
Vegetable sources: Unmilledcereals, legumes,
pulses, oil seeds, yeast cells, spinach, lettuce
Absorption:
•Small fraction get absorbed
•Helped by LMW zinc binding factor from
pancreas
•Calcium, phosphate, phytic acid interfere with
absorption
Excretion:
•Via feaces, urine and minimally via sweat

109. Functions:
1. Role in Enzyme Action:
Superoxide dismutase, Carbonic anhydrase,
Leucine amino peptidase (LAP), Carboxy
peptidase, Alcohol dehydrogenase etc
2. Role in Vitamin A Metabolism:
•Release of vitamin A form liver
•Activation of retinene reductase
3. Role in Insulin Secretion:
Helps in storage and release of insulin

110. 4. Role in Growth and Reproduction
5. Role in Wound Healing
•Helps in formation of granulation tissue
6. Role in Biosynthesis of Mononucleotides
•Synthesis and incorporation of mononucleotides
in nucleic acid requires zinc
•Deficiency causes increased activity of
ribonuclease

111. Deficiencymanifestations:
1.PredispositiontoDM
2.Leukaemias
3.Malignancies
-Decreasedzinccontentoftheprecancerous
leisonsintheliver
4.Hepaticdiseases
5.AcuteMI
-Releaseofhumoralfactorfrom
polymorphonuclearleucocytescalled“Leucocytes
endogenousmediator(LEM).”
6.Dermatitis

112. ZINCDEFICIENCYDISEASE
AcrodermatitisEnteropathica:
•Arareinheriteddisorderinwhichprimarydefectis
inzincabsorption.
•Inheritance:Autosomalrecessive.
•Clinically:
-Dermatologic-acrodermatitis(inflammation
aroundmouth,nose,fingers,etc.)
-Diarrhea,alopecia,ophthalmologicmanifestations,
neuropsychiatricfeatures,growthretardationand
hypogonadism.

113. Deficiency of zinc can cause rickets like features
•Regulatory proteins of transcription bind with
high affinity to the motifs of DNA
•There are 3 types of motifs:
-Helix-turn helix
-Zinc finger motif
-Leucine-Zipper
•Calcitriol receptor gene has two zinc finger
motifs
•Mutation in either of the two zinc-finger motifs
results in resistance to the action of VitD

114. Selenium (Se, Atomic no. –34, Atomic mass –79)
Source:
•Plant material
•Selenium uptake in plant tissue is passive and is
influenced by its concentration in soil
Absorption:
•Mainly from the duodenum
•Active process
In plasma:
Bound to plasma proteins particularly β-lipoproteins

115. Metabolic roles:
1.Acts as prosthetic group
•Prosthetic group of Glutathione peroxidase
•Both in cytosol and mitochondria
•Acts as supplementary to Vitamin E
2.Relation with Vitamin E
•Sparing action on Vitamin E
-Require for normal pancreatic function and
absorption of vitE
-Acts with Gluperox.
-Helps in retention of VitE

116. 3.Relationwithheavymetals
Hasaffinitytowardsheavymetals(Cd,Hg)and
reducestoxicity
4.AssociateofNHIproteins
Remainasselenideinvariousnonhaemiron
proteins
5.Activationofthyroxin
5’de-iodinaseisaseleniumcontainingenzyme.In
Sedeficiency,thisenzymebecomesinactive,
leadingtohypothyroidism

117. Selenium toxicity:
Acute:
Diarrhoea, elevated pulse rate and temperature,
tetanic spasms, labored breathing, respiratory failure.
Chronic:
Impaired vision and movement disorders (Blind
staggers) resulting in paralysis and death.
In humans:
•Chronic dermatitis, loss of hair and brittle nails
•Garlicky breath, caused by exhalation of dimethyl
selenide

118. Deficiency disorders:
Keshandisease:
•Manifesting as cardiomyopathy
•Keshancounty of north-eastern China
•Acute or chronic cardiac enlargement, arrhythmia
and ECG changes
•Prophylaxis with sodium selenite is highly
effective.

119. Kaschinbeckdisease:
•Endemichumanosteopathy(asosteoarthritis).
•SeeninseveralpartsoftheeasternAsia
•Degenerativeosteoarthrosisaffectingchildren
between5and13yearsofage.
•Shorteningoffingersandlongbones
•Severeenlargementanddysfunctionofthe
joints
•Prophylacticseleniumadministration

120. Roleofseleniumincancer:
MechanismofAnti-cancerActivity:
•Probablyseleniumbringsaboutchangesin
carcinogenmetabolism
•Protectsfromcarcinogeninducedoxidant
damageand
•Toxicityofseleniummetabolitestotumorcells.

121. Role of Selenium in HIV infection:
•Selenium as a dietary supplement to HIV
patients reduces viral load.
•Intake of 200 µg of high selenium yeast daily,
produces 12% drop in blood virus
•Se makes the virus more docile, less virulent and
less likely to replicate.

122. Manganese(Mn,Atomicno.-25,Atomicmass-55)
Source:
Cereals, vegetables, fruits, nuts and tea.
Liver and kidneys are rich source
Functions:
1.Role in Enzyme Action:
-Arginase, isocitrate dehydrogenase(ICD),
cholinesterase, lipoprotein lipase, enolase
-Mitochondrial form of Superoxide dismutase
-Carboxylases in CO2 fixation reaction
2.Role in Animal Reproduction

123. 2.Role in Bone Formation:
-Deposition of Mucopolysaccharides (MPS) in the
cartilaginous matrices specially chondroitin
sulfate
4.Role in Porphyrin Synthesis:
-Promotes δ-ALA synthetase activity
5.Role in carbohydrate metabolism
6.Role in Fat Metabolism
Deficiency:
•Impaired growth and skeletal deformities.
•Abnormal organic matrix of bone and cartilage

124. Fluorine (F, Atomic no. -9, Atomic mass -19)
Source:
•Drinking water
•Tea, salmon, sardine
Absorption:
•Form HF by reacting with HCL
•Facilitate diffusion –F-H+ cotransporter or F-
OH−exchangers
In plasma:
Ionic form and Bound from
Excretion:
Excreted by kidney or deposition in bone

126. Fluoridetoxicity:
Fluorosis:
Excessoffluorideinwaterordietoritsinhalation
isharmfulandisconsideredtobethemaincauseof
thecripplingdiseaseknownas‘fluorosis’
Mechanism:
1.Impairmentofcellularrespiration
2.GenerationofROS
3.Releaseofhormoneandneurotransmitter
4.Inflammation
5.Effectoncollagensynthesis

127. Dentalfluorosis:
Characterizedbyhypomineralizationoftooth
enamel
•“Verymild”:small,opaque,"paper”whiteareas
scatteredirregularlyoverthetooth,covering<25%
ofthetoothsurface.
•“Mild":mottledpatchescaninvolveuptohalfof
thesurfaceareaoftheteeth.
•“Moderate”:mottlingofallofthesurfacesofthe
teeth.
•“Severe”:fluorosisischaracterizedbybrown
discolorationanddiscreteorconfluentpitting

129. Skeletalfluorosis:
Constantexposuretofluorideoveralongperiodof
time.
Clinical:
Mild:Generalizedboneandjointpains
Moderate:Stiffness,rigidityandrestricted
movementofspineandjoints.
Severe:Flexiondeformitiesofspine,hipsand
knees,genuvalgum,genuvarum,bowingand
rotationaldeformitiesoflegs,neurological
complications,cripplingandbedriddenstage.

130. Radiologic:
Mild:Osteosclerosisonly
Moderate:Periostealboneformation,calcifications
ofinterosseousmembrane,ligaments,muscular
attachments,capsulesandtendons
Severe:Associatedmetabolicbonedisease(rickets
neo-osseousmalacia,osteoporosis,neoosseousporosis,
andsecondaryhyperparathyroidism),exostoses,
osteophytosis.

132. Permissible amount:
•Drinking water -1.5 mg/L
•Daily intake must not cross 3mg/day
•Serum -4 µg/100 mL

133. Cobalt (Co, Atomic no. –27, Atomic mass –59)
Source:
•Animal source
•Present as integral part of VitB12Functions:
•Role in formation of cobamideenzyme
-To form adenosyl cobalamineby B12 reductase
enzyme
•Bone marrow function
•Acts as cofactor
-Eg.glycyl-glycine dipeptidase

134. Nickel (Ni, Atomic no. –28, Atomic mass –58.6)
Source:
Mainly animal source, Accumulate in lungs
Normal levels:
Plasma -0.5 µg/dL
Functions:
•Role in enzyme action
-Urease and methylcoenzymereductase
•Role in growth and reproduction
•Pigments production in fish, birds etc.

135. Toxicity and clinical significance
Prolonged exposure results in respiratory tract
neoplasia and dermatitis
(a) Decreased : cirrhosis liver and in cases of
chronic uraemia.
(b) Increased :
-Increased in blood to about twice the normal
values within 12 to 36 hours in acute myocardial
infarction.
-An abnormally high nickel concentration also
occurs in cases of acute ‘stroke’ and in severe burns

136. Chromium (Cr, Atomic no. –24, Atomic mass –52)
Source: Yeast, grains, cereals
Functions:
1.Role in Carbohydrate Metabolism
-True potentiator of insulin and is known as Glucose
tolerance factor (GTF).
-Chromium containing protein chromodulin
facilitates binding of insulin to its receptor and
receptor kinase signaling.
2.Role in Lipid Metabolism
-Helps in mobilization of cholesterol
3.Role in Protein Metabolism

138. PHOSPHORUS (P, Atomic no. –15 , Atomic mass –31)
Source:Cheese,milk,nuts,organmeats,egg
Milkisthebestsource(containsabout
100mg/dLphosphate)
Requirement:500mg/day
Bodydistribution:
Totalbodyphosphate-25mol(700g)
85%(600g)inbones
15%insofttissues
1%inECF

139. Absorption:
•90 per gets absorbed
•Stimulated by both PTH and Vit. D
•The Ca:Pratio in diet affects the absorption and
excretion of phosphorus.
Regulation:
•Kidneys
•GI tract

141. Functions:
•Bonemineralization
•Energytransfer
•Acidbasebalance
•Activationofenzymes
•Phospholipids,lipoproteinssynthesis

143. Normallevels:
Inserum:
•Adults -3 -4 mg/dL
•Children -5 -6 mg/dL
•There’s a postprandial decrease of phosphorus
In whole blood:
•Total phosphate –40 mg/dL
•RBC and WBC stored the maximum amount

145. FibroblastGrowthFactor23(FGF-23)
-ProteinencodedbytheFGF23gene
-Locatedonchromosome12
-Itdownregulatesthegenefor1alphahydroxylase

146. Causesofhyperphosphatemia
1.Increasedabsorptionofphosphate
ExcessvitaminD,phosphateinfusion
2.Increasedcelllysis
Chemotherapyforcancer,bonesecondaries
Rhabdomyolysis
3.Decreasedexcretionofphosphorus
Renalimpairment,hypoparathyroidism
4.Hypocalcemia
5.Massivebloodtransfusions
6.Thyrotoxicosis
7.Drugs-Chlorothiazide,Nifedipine,Furosemide.

147. Causes of hypophosphatemia
1. Decreased absorption of phosphate
Malnutrition, malabsorption, chronic diarrhea,
vitamin D deficiency
2. Intracellular shift
Insulin therapy, glucose phosphorylation
3. Increased urinary excretion of phosphate
Hyperparathyroidism, fanconi’ssyndrome,
hypophosphatemicrickets
4. Hereditary hypophosphatemia
5. Hypercalcemia
6. Chronic alcoholism
7. Drugs -Antacids, Diuretics, Salicylate intoxication

148. Autosomaldominanthypophosphatemicrickets
•Rarehereditarydisease
•Causedbyamutationinthefibroblastgrowth
factor23(FGF23)
•Excessivelossofphosphateintheurine
Biochemically
•Lowserumphosphate
•InappropriatelynormallevelsofVitD

149. X-linkedhypophosphatemia
•AssociatedwithPHEXgene
•ThePHEXproteinregulatesexpressionof
fibroblastgrowthfactor23
•GenemutationsinPHEXexcessiveexpression
ofFGF23
Biochemically:
•Hypophosphatemia
•Lowlevelofcalcitriol

150. ↑ Ca+2 ↓ PO4-3-Primary hyperparathyroidism
↑ Ca+2↑ PO4-3-Malignancy tumourdeposits
in bone, post-dialysis in renal failure
↓ Ca+2↑ PO4-3-Hypoparathyroidism
↓ Ca+2↓ PO4-3 -Vit. D deficiency

151. MAGNESIUM (Mg, Atomic no. –12, Atomic mass –24)
Source:
Cereals, beans, green vegetables, potatoes, almonds
and dairy products
Distribution:
•Total body magnesium is 2400 mEq
•2/3rdoccurs in bones
•1/3rdEC fluid and remainder in soft tissues
Normal levels:
•Plasma –1.8 –2.6 mEq/L
•1/3rdis protein bound, 2/3rdis ionic
•CSF –½ of plasma

152. FACTORS AFFECTING ABSORPTION:
1. Size of Mg load
2. Dietary calcium -Ca and Mg shares an antiport
transporter
3. Motility and mucosal state
4. VitD -↑ absorption.
5. Parathormone -↑ absorption.
6. Growth hormone -↑ absorption.
7. Other factors
–High protein diet, neomycin therapy ↑ absorption.
–Fatty acids, phytates, phosphates ↓ absorption.

153. Factors Affecting Renal Excretion
• Calcium intake -Increased dietary calcium cause
↑ excretion of Mg
• Parathormone (PTH) -↓ excretion
• Antidiuretic hormone (ADH) -↑ excretion
• Growth hormone (GH) -↑ excretion
• Aldosterone -↑ excretion
• Thyroid hormones -80 per cent greater excretion
in hyperthyroidism

154. FUNCTIONS:
1.Mg++is the activator of many enzymes
requiring ATP.
2.Neuromuscular irritability is lowered by
magnesium.
3.Insulin-dependent uptake of glucose is reduced
in magnesium deficiency. Magnesium
supplementation improves glucose tolerance

155. Whyalcoholismcausesdeliriumtremens?
•Deliriumtremens–rapidonsetofconfusion
duetowithdrawalfromalcohol
•Oralingestionof1.0mlof95%alcohol/kg↑
urinaryexcretion2-3fold
•Theincreasedexcretionpartiallyaccountsfor
Mg-deficiencyinchronicalcoholicswith
deliriumtremens

156. HYPOMAGNESEMIA:
Magnesium levels <1.7 mg/dL
Cause:
1. Increased urinary loss (Tubular necrosis)
2. Hyperaldosteronism, volume expansion
3. Familial hypomagnesemia
4. Increased intestinal loss
5. Liver cirrhosis
6. Malabsorption
7. Protein calorie malnutrition
8. Hypoparathyroidism
9. Toxemia of pregnancy

157. Causesofhypermagnesemia:
1.Excessintakeorallyorparenterally
2.Renalfailure
3.Hyperparathyroidism
4.Oxalatepoisoning
5.Rickets
6.Multiplemyeloma
7.Dehydration
8.Drugs:Aminoglycosides,calcitriol,tacrolimus

158. Whentotestformagnesium?
1.Cardiacarrythmia
2.Resistanthypokalemia
3.Pregnancywithpre-eclampsia
4.Tetanynotrespondingtocalciumtherapy