Mineral-Associated Disorders😍

Metal cofactor Enzymes

Metal cofactor
Reaction
Potassium
• Na⁺-K⁺ ATPase,
Pyruvate kinase
Magnesium
• All kinase/ phosphorylase/ carboxylase/ Phosphatase/ Mutase/ Enolase
Except pyruvate kinase
Glycogen phosphorylase - calcium
Manganese
Kinase
Phosphatase
Mitochondrial SOD
man with SODa
Copper
Tyrosinase (Melanin production),
Complex 4 (Cytochrome C oxidase),
Lysyl oxidase (Covalent cross linking of Collagen)
Ceruloplasmin
Cytosolic SOD
Zinc
Anhydrase/Dehydratase/Dehydrogenase
Carbonic anhydrase
Carboxypeptidase A & B
LDH → Lactate dehydrogenase
Glutamate dehydrogenase
Alcohol dehydrogenase
ALA dehydratase
Cytosolic SOD
Selinium
Glutathione Peroxidase
Deiodinase
Thiioredoxin reducatase
Iron
Heme iron:
Complex III & IV (Cytochrome)
Near Oxygen half → heme iron

Non-heme:
Complex I & II (Fe-S cluster)
Molybdenum
Xanthine oxidase
Sulfite oxidase
Moly and Shantha with Sulfikar

Calcium

  • Richest grain:
    • Ragi
  • Sources: Milk, eggs, fish, meat
  • Used as an important weaning food
  • Metabolism requires: Vitamin D

Disorders

Disorder
Causes
Features
Management
Hypocalcemia
↓PTH, ↓Vit D, CRF, malabsorption, pancreatitis
Tetany, cramps, seizures
IV calcium gluconate, Vit D
Hypercalcemia
↑PTH, Vit D toxicity, thiazides, bone mets
Fatigue, confusion, kidney stones, arrhythmia
Treat cause, IV fluids, bisphosphonates

Absorption Modulators

  • ↑: Vitamin D, PTH, lysine, acidic pH
  • ↓: Phytates, oxalates, phosphates

Iodine

Cretinism

  • Condition with irreversible intellectual abnormalities.

Endemic Cretinism

  • Cause: Nutritional deficiency of iodine
  • Types:
    • Neurological cretinism
      • Features: Strabismus, spastic diplegias
    • Myxedematous cretinism
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National Iodine Deficiency Disorder Control Programme (NIDDCP)

  • 1962: National goitre control programme
  • 1992: NIDDCP
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  • Organization: At district level.
  • Target: Goitre rate <5% in children.

Strategy

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  • Iodization of salt: Potassium iodate used
    • Not potassium Iodide
    • Ensured by salt commissioner under:
      • Ministry of Commerce & Industry.
      • Headquarters in Jaipur, Rajasthan.
    • Levels
      • At production: >30 ppm.
      • At Consumer: >15 ppm.

Programme Indicators

Category
Indicator
Process indicators
Iodine in household salt
Process in house
Principal impact indicators
Epidemiological indicator
Urinary iodine excretion > 100 U/dl
Impact principal by urination
Environmental iodine deficiency indicator
↓↓ Iodine in diet
Neonatal hypothyroidism rate
Environment = Neonates
Long term impact indicators
Goitre rate
Long goitre

Iron

Iron Metabolism (for IDA):

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  • Absorption: Duodenum.
  • Dietary Fe3+ → Fe2+ (by Cytochrome B Reductase) for absorption.
  • Fe2+ into duodenal cells via DMT1 (Divalent Metal Transporter).
  • Fe2+ → Fe3+ (by Hephaestin and Ceruloplasmin) inside cell.
  • Fe3+ out of duodenal cells via Ferroportin.
  • Transport: Transferrin bound Fe3+ (Normal Saturation: 33%).
  • Storage: Ferritin.
  • Regulated by Hepcidin.

Absorption

  • Ferric iron (Ingested) → Ferrous iron (Absorbed).
    • FerrUs → comes to us
  • Activated by: Vitamin C
  • Inhibited by: Phytates, tannin, oxalates, fiber, calcium.
Mnemonic:
  • "I'm Iron. My religion was 3."
    • This refers to Fe³⁺ 
  • "I need to go to a country, but I can only do so by crossing another country which told me 'Do CHange' your religion."
    • Do CHange → Duodenal Cytochrome B (Duodenal Cyto B)
    • Duodenal Cytochrome B reduces Fe³⁺ to Fe²⁺.
  • I gave into 'demand’
    • demand → DMT1 (Divalent Metal Transporter 1)
    • DMT1 transports the non-heme Fe²⁺ (ferrous iron) into the enterocyte.
  • "I changed to religion 2 and entered."
    • This represents Fe²⁺ (ferrous iron), the form that enters the cell via DMT1.
  • "And then escaped by a ferri."
    • ferri → Ferroportin 1
    • Ferroportin 1 transports iron out of the enterocyte, across the basolateral membrane.
  • “Sid tried to kill me when I was on Ferri
    • Hepcidin inhibits Ferroportin
  • "Hamza/Hafsa helped me change my religion back to 3."
    • Hamza/Hafsa → Hephaestin
    • Hephaestin oxidizes Fe²⁺ back to Fe³⁺ at the basolateral membrane, before it enters circulation.

Disorders

Disorder
Features
Diagnosis
Treatment
IDA
Microcytic hypochromic anemia
↓ Ferritin (1st), ↑TIBC
Oral iron + Vit C;
Vit E for radicals
Hemochromatosis
Liver damage, DM,
Skin pigmentation
HFE mutation
Phlebotomy, Deferoxamine

Mineral Iron

Sources

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  • Heme:
    • Animal source (20 - 40% bioavailability).
  • Non-Heme:
    • Plant source (6 - 9% bioavailability):
      • Pumpkin seeds (Rich).
      • Pista.
      • Dates.
      • Green leafy vegetables.
    • Poor man’s source: Jaggery
      • Note: Iron in jaggery due to iron vessel used for production.
  • Pregnancy:
    • Iron cannot be fully supplemented by diet alone
    • Supplementation required regardless of Hb or socioeconomic status
  • Mass prophylaxis:
    • Use Tablet ferrous sulphate
      • (Us Ate)
    • Withhold in:
      • Acute illness (fever, pneumonia, diarrhea)
      • Known thalassemia major
      • History of repeated blood transfusion
  • Always continue iron for 3 months after Hb normalizes
    • To replenish iron stores

WHO Anemia Definition (Hemoglobin Levels):

  • Best for epidemiological surveys
  • Insensitive for early nutrient depletion
  • Levels:
    • Healthy Adult Male: <13 g/dL
    • Healthy Adult Female: <12 g/dL
    • Pregnant Woman: <11 g/dL
    • CKD Patient: <10 g/dL
    • Children 6 months—5 years: Hb <11 g/dl
    • Children 6-14 years: Hb <12 g/dl

Causes

  • Dietary, blood loss (trauma, PUD, colon cancer, menorrhagia)
  • Hookworm infection

Approach to anemia in children:

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Iron Deficiency Anemia

  • Most common cause of nutritional disorders in the world
  • Most common cause of anemia in the world
  • Vitamin C helps in the absorption of iron
  • Associated with celiac disease

Copper

Disorder
Cause
Menkes
ATP7A mutation (↓absorption)
↓ lysyl oxidase activity (copper-dependent)
defective collagen cross-linking
Symptoms
Brittle, “kinky” hair, woolly hair
Trichorrhexis nodosa
Pili torti
• Developmental delay
hypotonia
• Risk of
cerebral aneurysms

Treatment
• Poor Prognosis (
death by 3 years)
• Poor response to Cu supplements
Wilson’s
• AR
• ATP7B defect
on chromosome 13.
(↓excretion)

Liver cirrhosis.
Kayser-Fleischer rings in Descemet membrane of cornea
Sunflower cataract
Copper deposits in putamen (basal ganglia) Lenticular nucleus
hepatolenticular degeneration.
Psychosis or Parkinson-like symptoms

Inverstigations
Screening/Most specific: 24h urinary copper
• ↓↓
serum ceruloplasmin
Liver Biopsy:
Confirmatory
Mallory hyaline bodies

T2 MRI
Giant face of Panda

Treatment
Copper chelators
Trientine, D- Penicillamine.
DOC (in maintenance phase):
Zinc acetate
DOC For neurological features:
Tetrathiomolybdate

Nazer prognostic index
• For liver transplantation
Serum bilirubin
AST levels
Prothrombin time

His PT (Prothrombin time) sir Nazeer (Nazer) wanted liver transplantation
He Got all ST (AST) money together → to pay sirs bill (Serum bilirubin)
MEDNIK
AP1S1 gene
Menkes + Wilson features
• Rx: Supportive
Toxicity
Brass utensils
• Hemolysis, renal damage
• Rx: Remove source, supportive
Scurvy like symptoms
Decreased collagen synthesis due to copper deficiency

  • Note
    • Rings
      Disease
      Layer of Cornea
      Kayser Fleischer ring
      Wilson’s disease
      • Copper in Descemet’s membrane
      Fleischer's ring
      Keratoconus
      Fe Deposition Basal epithelial layer
      Pseudofleischers ring
      Hypermetropia
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Term
FB
Chalcosis
Copper FB
Siderosis
Iron FB
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  • Hudson nte stallil () Iron bulb ()
  • Stock () of teri ()

Selenium

  • Daily requirement: 50–60 mcg/day
  • Functions as an important antioxidant
  • Selenocysteine:
    • 21st amino acid
    • Coded by UGA (Stop codon)
    • Formed by co-translational modification
    • Serine → Selenocysteine
    • Found in:
      • Glutathione peroxidase
        • Protects against oxidative stress
      • Thioredoxin reductase
        • Redox balance in cells
      • Glycine Reductase
      • Deiodinase
        • Thyroid hormone conversion: T4 → T3
      • Selenoprotein P
        • Transports selenium in plasma
      • NOT GLUTATHIONE REDUCTASE (Dep on Vit B2)
    • ”Mneumonic: Selena’s sister serena from UGAnda“
    • "Selena glue thinnu diarrhea aayi"
  • Pyrrolysine:
    • 22nd Amino acid
    • Coded by UAG
    • From Lysine
  • Both 21 22 due to cotranslational modification

  • Stop Codons:
    • UAA
    • UGA (Selenocysteine)
    • UAG (Pyrrolysine)

Disorders

Disorder
Features
Management
Selenium deficiency
Keshan Disease
Dilated Cardiomyopathy,
weakness, hypothyroidism
Selenium supplement
Selenium Toxicity
Selenosis
- Alkali disease in cattle
- Blind staggers
Hair/nail loss, garlic breath, diarrhea
Remove exposure

Fluorine

Mottled teeth
Mottled teeth
Fluorosis
Fluorosis

National Program for Prevention and Control of Fluorosis

  • Normal fluoride level in drinking water: 0.5–0.8 mg/L
  • Fluorine is called a "Double-edged sword"

Disorders

ppm (mg/L)
Meaning
< 0.5 ppm
Dental caries
1 ppm =
1 mg fluoride per 1 L water
1.5 ppm
WHO upper safe limit
> 1.5 ppm
Dental fluorosis.
3–5 ppm
Risk of skeletal fluorosis
(chronic)
10 ppm
Crippling skeletal fluorosis
(long term)
Acute toxic dose (ATD)
5–10 mg/kg BW
Certainly lethal dose (CLD)
32–64 mg/kg BW

Dental Fluorosis

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  • Fluoride in water is >1.5 mg/L
  • Manifestation: Mottling of upper incisors
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Dental Caries

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  • Fluoride in water is <0.5 mg/L
  • Due to fluoride deficiency

Genu Valgum (Knock-knee syndrome)

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  • Cause: Excess fluorine
 
 
 

Crippling Fluorosis

  • Occurs when fluoride in water is >10 mg/L

Nalgonda Technique

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  • Purpose: Defluoridation of water (removes excess fluoride)
  • Method:
    • Addition of: (LAB)
    • Component
      Function
      Lime
      Precipitation of fluoride
      • Form dense floc
      Alum
      Coagulant
      • + H2O ⇒ AlOH
      adsorbs fluoride ions
      Bleaching powder / Sodium hypochlorite
      Disinfects
  • to fix vaishna’s teeth → Put Lime and bleaching powder in Aluminium pathram
  • Developed by: NEERI Institute, Nagpur
    • National Environmental Engineering Research Institute

Zinc

  • Zinc deficiency → ↓ Retinol dehydrogenaseVisual disturbance
  • Sources: Breast milk (picolinic acid aids absorption)
  • Function:
    • Essential for 100+ enzyme activities.
    • 2nd most common trace element in body after Iron
    • Important in forming zinc fingers (transcription factor motif) → part of gene transcription
    • Major antioxidant → part of SOD

Disorders

Disorder
Features
Treatment
Deficiency
↓ Immunity, diarrhea, ↓healing
Zinc sulphate (esp. in diarrhea)
Acrodermatitis Enteropathica
Diarrhea + dermatitis (mouth, anus)
Lifelong zinc
  • WHO dose in diarrhea:
    • <6 months: 10 mg/day × 14 days
    • >6 months: 20 mg/day × 14 days
  • Deficiency causes:
    • Diarrhoea
    • Delayed wound healing
    • Hypogonadism
      • Male hypogonadism and sexual dysfunction
    • Suppressed immunity
    • Dysgeusia (altered taste), anosmia (loss of smell)
    • Predispose to alcoholic cirrhosis.

Acrodermatitis Enteropathica

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  • Autosomal Recessive
  • Daily requirement: 5–10 mg/day

Types of Zinc Deficiency

  1. Congenital:
      • Autosomal recessive (Zip4 transporter protein deficiency).
      • After 6 months / weaning (maternal milk aids zinc absorption)
  1. AcquiredChronic alcoholics

Main Features (DDA Mnemonic)

  • Dermatitis
    • acral, periorificial
    • Presents with extensive inflammatory rashes
      • oral cavity,
      • genital region.
    • Rash distribution:
      • Cheeks
      • Mouth
      • Anal region
  • Diarrhoea
  • Alopecia
  • Mnemonic: Z → vayil kude keri appi pokunnath

Treatment:

  • Zinc supplementation
  • Zinc deficiency → ↓ Retinol dehydrogenaseVisual disturbance