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🎓 COMPLETE LECTURE NOTES — FIRST AID BIOCHEMISTRY SECTION II (Pages 61–69)

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PART 1: AUTOSOMAL TRISOMIES

What is a Trisomy? (Plain English First)

• This means Down syndrome is the most common trisomy we see in live births.

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1. DOWN SYNDROME (Trisomy 21)

What is it?

Findings (Signs you see in the patient):

Risk Factors:

Prenatal Screening:

• Nuchal translucency = A fluid-filled space at the back of the baby's neck seen on ultrasound. When it's increased, it's a warning sign. (Nuchal = relating to the back of the neck)
• Hypoplastic nasal bone = The nose bone is underdeveloped or absent

• AML (<3 years of age / ALL <3 years of age) = blood cancer risk in young children
• Alzheimer disease (early onset)
• Atresia (duodenal)
• Abnormal facies

Prenatal Screening Tests Table (from the book):

• β-hCG: ↑ (increased)
• PAPP-A: ↓ (decreased) - PAPP-A = Pregnancy-Associated Plasma Protein A

• β-hCG: ↑
• Inhibin A: ↑
• Estriol: ↓
• AFP: ↓ (Alpha-Fetoprotein is low - this is the opposite of neural tube defects where AFP is high)

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2. EDWARDS SYNDROME (Trisomy 18)

What is it?

Findings:

• Intellectual disability
• Rocker-bottom feet = The soles of the feet have an unusual curved shape like the bottom of a rocking chair
• Overlapping fingers = The second finger overlaps the third, and the fifth overlaps the fourth - a classic finding
• Micrognathia = Very small jaw (micro = small, gnathia = jaw)
• Low-set ears
• Small (low) ears, congenital heart disease (especially VSD)
• Omphalocele = Internal organs (intestines, liver) herniate out through the belly button because the abdominal wall didn't close properly. (Omphalos = navel/belly button in Greek)

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3. PATAU SYNDROME (Trisomy 13)

What is it?

Findings:

• Microcephaly = Small head (micro = small, cephaly = head). The brain is underdeveloped.

• VSD = hole between the ventricles of the heart
• Omphalocele = belly organ herniation (same as Edwards)
• Meningomyelocele = the spinal cord and its coverings protrude through a gap in the backbone

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NONDISJUNCTION (The diagram in your book):

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PART 2: GENETIC DISORDERS BY CHROMOSOME (Page 62)

• ADPKD (PKD2) = Adult Polycystic Kidney Disease type 2 - kidneys develop multiple fluid-filled cysts
• Achondroplasia = A form of dwarfism - the bones don't grow to normal length
• Huntington disease = A fatal brain disease causing uncontrolled movements (chorea), personality changes, and dementia. Symptoms start in middle age (30s-40s). The patient cannot control their movements - their limbs and body move involuntarily.

• Cri-du-chat syndrome = (French for "cry of the cat") - we'll explain in detail below
• FAP (Familial Adenomatous Polyposis) = hundreds to thousands of polyps (small growths) in the colon, which become cancerous if not treated

• Wilms tumor = Kidney cancer in young children
• β-globin gene defects = sickle cell disease (where blood cells become sickle-shaped and block vessels), β-thalassemia (inadequate hemoglobin production)
• MEN1 = Multiple Endocrine Neoplasia type 1 - tumors of parathyroid, pituitary, pancreas

• Patau syndrome (as we just learned)
• Wilson disease = Copper accumulates in the body (liver, brain, eyes - Kayser-Fleischer rings)
• Retinoblastoma (RB1) = A tumor of the retina (back of the eye) in young children - the "RB1" gene is a tumor suppressor gene
• BRCA2 = Breast/ovarian cancer gene

• Prader-Willi syndrome = extreme hunger, obesity, short stature, small hands/feet, intellectual disability
• Angelman syndrome = severe intellectual disability, seizures, happy puppet-like behavior
• Marfan syndrome = Very tall, long limbs, lens dislocation, aortic aneurysm

• ADPKD (PKD1) = Most common form of adult polycystic kidney disease
• α-globin gene defects = α-thalassemia (not enough alpha globin chains for hemoglobin)
• TSC2 = Tuberous sclerosis type 2

• NF1 = Neurofibromatosis type 1 - multiple nerve tumors (neurofibromas), café-au-lait spots
• BRCA1 = Breast/ovarian cancer gene
• TP53 (Li-Fraumeni syndrome) = TP53 is the most important tumor suppressor gene in the body. Li-Fraumeni syndrome = multiple cancers in a family due to inherited TP53 mutation

• NF2 = Neurofibromatosis type 2 - bilateral acoustic neuromas (tumors on the hearing nerves)
• DiGeorge syndrome (22q11) = deletion of chromosome 22q11 causes heart defects, absent thymus (so T-cells can't develop → immune deficiency), hypocalcemia (low calcium because parathyroids are absent), cleft palate

• Fragile X syndrome = Most common inherited cause of intellectual disability
• Turner syndrome (XO) = Female with only one X chromosome
• XLA = X-linked agammaglobulinemia (no B cells, no antibodies)
• Klinefelter syndrome (XXY) = Male with extra X chromosome

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ROBERTSONIAN TRANSLOCATION

What is it? (Plain English)

Which chromosomes does it involve?

How it works (look at the diagram in your book):

1. Normal parent cells: separate chromosome 14 and chromosome 21
2. Robertsonian translocation occurs: chromosomes 14 and 21 fuse together - now one of the parent's 46 chromosomes is actually a fusion chromosome (14;21)
3. The parent is a "balanced carrier": They have all the genetic material - the 14;21 fusion plus a normal 14 and normal 21 - so they are physically normal. But...
4. When they have children: the eggs/sperm they produce may have unbalanced combinations
   • Normal gamete: normal 14, normal 21 → normal child
   • Unbalanced gamete: the 14;21 fusion chromosome + an extra 21 → Down syndrome in the child!

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CRI-DU-CHAT SYNDROME

• Microcephaly = Small head
• Moderate to severe intellectual disability
• High-pitched crying (the defining feature - like a cat's meow)
• Epicanthal folds (same eye finding as Down syndrome)
• Cardiac abnormalities (VSD) = heart defects
• 1cr when 1am Very SaD - a mnemonic: 1 cry when I am Very Sad → chromosome 5 deletion

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WILLIAMS SYNDROME (Page 63)

Findings:

• Supravalvular aortic stenosis = narrowing of the aorta ABOVE the aortic valve (the main artery leaving the heart is too narrow) - this is the most characteristic finding
• Pulmonary artery stenosis = narrowing of the lung artery
• Renal artery stenosis = narrowing of the kidney artery → can cause high blood pressure

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PART 3: BIOCHEMISTRY - NUTRITION

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ESSENTIAL FATTY ACIDS

What are "essential" nutrients? (Plain English)

The Two Main Types:

• Found in: nuts, seeds, plant oils
• Your body converts it to arachidonic acid
• Arachidonic acid is the precursor (starting material) for making leukotrienes and prostaglandins - these are chemical messengers involved in inflammation and immune responses. (Think: aspirin and ibuprofen work by blocking the production of prostaglandins, which is why they reduce pain and inflammation)

• Found in: seafood, fish oil, flaxseeds
• Its metabolites (the things your body makes from it) have cardioprotective (heart-protecting) and antihyperlipidemic (fat-lowering in blood) effects. This is why doctors recommend fish oil supplements!

Trans Fats - The Bad Ones:

• LDL = "Bad" cholesterol - takes fat to arteries and deposits it (causes heart disease)
• HDL = "Good" cholesterol - picks up fat from arteries and brings it to the liver to dispose of
• Trans fats make your bad cholesterol go UP and your good cholesterol go DOWN = double damage to the heart!

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FAT-SOLUBLE VITAMINS: A, D, E, K

How to remember them: "A, D, E, K" - "All Dogs Eat Kibble" or simply ADEK

Why does fat-soluble absorption matter?

1. Bile must emulsify (break up) the fat - bile comes from the liver/gallbladder
2. Pancreatic enzymes must help digest fats
3. Intact ileum (last part of small intestine) must absorb them

• Good news: You don't run out quickly
• Bad news: Too much = TOXICITY - and fat-soluble vitamins are MORE toxic than water-soluble ones because excess can't be excreted in urine easily

When do people get fat-soluble deficiencies?

• Cystic fibrosis = thick mucus blocks the pancreatic duct → no pancreatic enzymes → can't digest fat → fat-soluble vitamins pass out in stool
• Celiac disease = gluten destroys the intestinal lining → can't absorb fat properly
• Mineral oil intake = mineral oil coats the gut and prevents fat absorption

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WATER-SOLUBLE VITAMINS: B-complex + Vitamin C

• Less risk of toxicity (excess is excreted)
• BUT you need to eat them regularly because you don't store them well

• Dermatitis = skin inflammation/rash
• Glossitis = inflamed, red, shiny tongue (glosso = tongue)
• Diarrhea

• B₂ → becomes FAD (cofactor for many enzymes)
• B₃ → becomes NAD+ (used in energy reactions)
• B₅ → becomes CoA (Coenzyme A - central to metabolism)

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DIETARY SUPPLEMENTATION TABLE

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PART 4: VITAMINS IN DETAIL (Pages 64-67)

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VITAMIN A (Retinol, Retinal, Retinoic Acid) — Page 64

Function:

• Antioxidant = It neutralizes free radicals (dangerous molecules that damage cells). Think of it like a rust-preventer for your cells.
• Retinal = A form of Vitamin A that is literally part of the molecule rhodopsin - the light-sensing pigment in the rod cells of your retina (back of eye). Without Vitamin A → no rhodopsin → can't see in dim light.
• Epithelial differentiation = Epithelial cells are the lining cells of organs (skin, intestines, lungs, eyes). Vitamin A ensures these cells mature normally into specialized cells. Without it, they become the wrong type of cell (squamous metaplasia - they turn into a simpler, flat cell type).
• Prevents squamous metaplasia = Squamous metaplasia means a specialized epithelial cell type being replaced by flat squamous cells. Vitamin A prevents this wrong transformation.
• "Pancreatic cells, mucous membranes" = Vitamin A keeps glandular cells and mucus-producing cells healthy.

Deficiency:

Excess (Too much Vitamin A):

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VITAMIN B₁ — THIAMINE (TPP) — Page 64

Also called:

Function:

1. Branched-chain ketoacid dehydrogenase = breaks down certain amino acids (leucine, isoleucine, valine)
2. α-Ketoglutarate dehydrogenase (TCA cycle) = a step in the Krebs cycle (energy-producing cycle in every cell's mitochondria)
3. Pyruvate dehydrogenase (HMP shunt) = converts pyruvate → acetyl-CoA. This is the gate between glycolysis (breaking down glucose) and the Krebs cycle
4. Transketolase = enzyme in the pentose phosphate pathway

Deficiency:

• This is KEY: Giving IV glucose (dextrose) to a thiamine-deficient patient makes things WORSE because glucose metabolism requires thiamine!
• Always give thiamine BEFORE dextrose in emergency situations!
• "Diagnosis by ↑ in RBC transketolase activity following vitamin B₁ administration" = To diagnose B₁ deficiency, you measure the transketolase enzyme in red blood cells - it will be low, and if you add thiamine it activates.

Disorders caused by B₁ deficiency:

1. Wernicke Encephalopathy

• Confusion = Sudden mental confusion - person doesn't know where they are
• Ophthalmoplegia = Paralysis of eye muscles → eyes can't move properly, diplopia (double vision)
• Ataxia = Loss of coordination - person staggers when walking, can't balance

2. Wernicke-Korsakoff Syndrome

• Confabulation = The patient makes up stories to fill gaps in memory without realizing they're doing it. It's not lying - they genuinely believe their fabricated memories. ("I was just at the casino last night!" when they've been in the hospital for a week.)

3. Dry Beriberi

• Beri = weakness in Sinhalese (the language of Sri Lanka, where beriberi was first described)
• Dry beriberi = affects the nervous system → peripheral neuropathy (weakness and numbness of limbs, especially legs)
• Mnemonic: Ber1Ber1 → vitamin B1 (one = 1)

4. Wet Beriberi

• Wet = affects the heart (fluid accumulates because heart fails → "wet" = edema/fluid)
• The heart needs thiamine for energy. Without it, it dilates and fails → HIGH output failure (the heart beats faster and harder to compensate, but eventually fails)
• Edema (swelling) develops

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VITAMIN B₂ — RIBOFLAVIN (FAD, FMN) — Page 65

Also called: Riboflavin

Function:

• FAD = Flavin Adenine Dinucleotide - an electron carrier in the Krebs cycle
• FMN = Flavin Mononucleotide - electron carrier in the electron transport chain (the final step of energy production)
• "FAD and FMN are derived from riboflavin (B₂ = 2 ATP)" - mnemonic: B₂ makes 2 ATP equivalents
• Redox reactions = oxidation-reduction reactions - the fundamental chemistry of energy metabolism (electrons being transferred)

Deficiency:

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VITAMIN B₃ — NIACIN (NAD⁺) — Page 65

Also called: Niacin, Nicotinic acid

Function:

• NAD⁺ = Nicotinamide Adenine Dinucleotide - the most important electron carrier in metabolism. Almost every major energy-producing reaction in the body needs NAD⁺. (B₃ = 3 ATP equivalents - mnemonic)
• NADP⁺ = Used in anabolic (building) reactions
• Derived from tryptophan = Your body CAN make a small amount of niacin from the amino acid tryptophan. But it's not enough if you're eating a niacin-poor diet.
• Used medically: High-dose niacin is used as a drug to lower VLDL (bad lipoprotein that carries triglycerides) and raise HDL (good cholesterol). It's basically a cholesterol drug!

Deficiency — PELLAGRA:

1. Diarrhea (gut cells can't function)
2. Dermatitis (skin rash - specifically the "Casal necklace" - a rash around the neck, and rash on sun-exposed areas that looks like a sunburn that doesn't heal)
3. Dementia (brain affected - cognitive changes, hallucinations)

1. Poor diet (eating mainly untreated corn with little protein)
2. Hartnup disease (explained below)
3. Malignant carcinoid syndrome = a tumor that uses up tryptophan to make serotonin, leaving none to make niacin
4. Isoniazid (INH) = TB drug that depletes B₆, which is needed to convert tryptophan to niacin

Excess (Too much Niacin - as a drug):

• Why? Niacin causes prostaglandin release → vasodilation (blood vessel widening) in the skin
• How to prevent: Take aspirin 30 min before niacin - aspirin blocks prostaglandins!
• "Can avoid by taking aspirin before niacin" - aspirin doesn't block the lipid-lowering effects, only the flushing
• Also: pruritus (itching), hyperglycemia (raises blood sugar), hyperuricemia (raises uric acid → can cause gout)

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HARTNUP DISEASE

• Tryptophan can't be absorbed from food properly
• Tryptophan is wasted in urine (aminoaciduria)
• Less tryptophan → less niacin → pellagra-like symptoms

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VITAMIN B₅ — PANTOTHENIC ACID (CoA) — Page 65

Also called: Pantothenic acid ("pento" = five → B₅; "thenic" = acid)

Function:

• Coenzyme A (CoA) = One of the most important molecules in metabolism! CoA is the "handle" that carries acetyl groups and acyl groups to different enzymes. Acetyl-CoA is the starting point for:
  • Entering the Krebs cycle
  • Fatty acid synthesis
  • Cholesterol synthesis
• Acyl transfers = moving fatty acid pieces from one molecule to another - this is fundamental in fat metabolism

Deficiency:

• Enteritis = intestinal inflammation
• Alopecia = hair loss
• Paresthesias = tingling/burning sensations - especially in the feet ("burning feet syndrome")
• B₅ deficiency is RARE in practice

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VITAMIN B₆ — PYRIDOXINE (PLP) — Page 66

Also called: Pyridoxine

Function:

1. Transamination = Moving an amino group (NH₂) from one molecule to another. This is how amino acids are made and broken down. ALT and AST are transaminase enzymes (doctors measure these in liver blood tests!)
2. Decarboxylation reactions = removing CO₂ from molecules
3. Glycogen phosphorylase = breaks down glycogen (stored glucose)
4. Synthesis of glutathione, cystathionine, heme = important molecules in the body
5. Synthesis of neurotransmitters including: serotonin, epinephrine, norepinephrine, histamine, dopamine, and GABA = This is a KEY point! B₆ is needed to make brain chemicals! Without B₆:
   • Less serotonin → mood problems
   • Less dopamine → movement problems
   • Less GABA → seizures (GABA is the brain's main inhibitory signal)
   • Less norepinephrine/epinephrine → autonomic problems

Deficiency:

• Seizures = Because you can't make GABA (the brain's brake pedal), the brain becomes over-excited
• Peripheral neuropathy = nerve damage causing weakness/numbness
• Isoniazid (INH) = TB drug that inactivates B₆. This is why isoniazid is given with B₆ supplementation!
• Oral contraceptives = can deplete B₆
• Sideroblastic anemia = B₆ is needed to make heme (the iron-containing part of hemoglobin). Without it, iron accumulates in red blood cell precursors forming "ringed sideroblasts" - iron-loaded cells that look like a ring under the microscope

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VITAMIN B₇ — BIOTIN — Page 66

Also called: Biotin

Function:

1. Pyruvate carboxylase (gluconeogenesis): pyruvate (3C) → oxaloacetate (4C) - making glucose from non-glucose sources
2. Acetyl-CoA carboxylase (fatty acid synthesis): acetyl-CoA (2C) → malonyl-CoA (3C) - the first step in making fat
3. Propionyl-CoA carboxylase (fatty acid oxidation): propionyl-CoA (3C) → methylmalonyl-CoA (4C)

Deficiency:

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VITAMIN B₉ — FOLATE — Page 66

Also called: Folate (found in foliage → leafy green vegetables, and absorbed in the jejunum - remember: "foliage in the jejun-gle")

Function:

• THF = Tetrahydrofolate = the active form of folate in the body
• 1-carbon transfers = Moving single carbon units (like methyl groups, CH₃) from one molecule to another
• Why does this matter? You NEED these 1-carbon transfers to build the purine and pyrimidine bases that make up DNA and RNA. Without folate → can't make DNA → cells that divide rapidly (like blood cells, gut lining) fail first

Deficiency:

• Macrocytic anemia = Red blood cells are LARGE (macro = big). Why? Because without DNA synthesis, cells can't divide properly → they keep growing without dividing → giant cells (megaloblasts)
• Megaloblastic = The red blood cell precursors in the bone marrow are huge (megalo = large)
• Hypersegmented PMNs = Polymorphonuclear neutrophils (white blood cells) normally have 3-5 lobes in their nucleus. In folate/B₁₂ deficiency, they have 6+ lobes ("hypersegmented"). This is a classic blood smear finding.
• Glossitis = inflamed tongue (red and smooth)
• NO neurologic symptoms = This is KEY! Folate deficiency does NOT cause nerve damage. B₁₂ deficiency DOES. This is how you distinguish them!

• ↑ homocysteine (amino acid that builds up when folate is missing)
• Normal methylmalonic acid (this is the key distinguishing test - methylmalonic acid is elevated in B₁₂ deficiency but NORMAL in folate deficiency)

• Chronic alcohol overuse
• Drugs: phenytoin (seizure drug), trimethoprim (antibiotic), methotrexate (cancer/autoimmune drug) - these all interfere with folate metabolism
• Pregnancy

Critical Clinical Point — Neural Tube Defects:

• Spina bifida = spinal cord doesn't close → spinal cord exposed
• Anencephaly = brain doesn't develop properly

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VITAMIN B₁₂ — COBALAMIN — Page 67

Also called: Cobalamin (contains cobalt - hence the blue color of B₁₂ pills)

Function:

• Converts homocysteine → methionine (an amino acid)
• At the same time, converts methyl-THF → THF (recycling folate back to its active form!)
• This is why B₁₂ deficiency can cause SECONDARY folate deficiency - folate gets "trapped" as methyl-THF and can't be used

• Converts methylmalonyl-CoA → succinyl-CoA (for the Krebs cycle)
• Fatty acids with odd carbon numbers and branched-chain amino acids need this pathway
• Without B₁₂ → methylmalonic acid accumulates → elevated serum methylmalonic acid (this is the diagnostic test!)

• THF + methionine cycle ↔ B₁₂ connects these cycles
• B₁₂ on one side handles the methylmalonyl-CoA path (right side)
• B₆ converts homocysteine down to cysteine

Where does B₁₂ come from?

• Bacteria make B₁₂, then animals eat the bacteria, then we eat the animals
• Vegans have NO dietary B₁₂ source → must supplement!

Absorption of B₁₂ — Very Important!

1. B₁₂ in food is released by stomach acid and pepsin
2. It binds to R-binder proteins in saliva
3. Pancreatic enzymes release B₁₂ from R-binders
4. B₁₂ then binds Intrinsic Factor (IF) - a protein made by parietal cells of the stomach
5. The B₁₂-IF complex travels to the terminal ileum (last part of small intestine) and is absorbed there

Deficiency — why it develops:

• Malabsorption syndromes (sprue, enteritis)
• Diphyllobothrium latum = a fish tapeworm that competes with you for B₁₂ in the gut!
• Achlorhydria = no stomach acid → B₁₂ can't be released from food
• Bacterial overgrowth = gut bacteria consume B₁₂ before you can absorb it
• Pernicious anemia = autoimmune attack on parietal cells → no intrinsic factor → no B₁₂ absorption
• Gastric bypass surgery = removes parietal cells → no intrinsic factor
• Crohn's disease / surgical resection of terminal ileum = the absorption site is gone
• Metformin (diabetes drug) - interferes with B₁₂ absorption
• Veganism = no dietary source

Deficiency symptoms:

• Macrocytic megaloblastic anemia = Same as folate (big red blood cells that can't divide)
• Hypersegmented PMNs = Same as folate
• Subacute Combined Degeneration = This is what makes B₁₂ UNIQUE from folate! The spinal cord undergoes degeneration:
  • Dorsal columns = carry vibration and proprioception (sense of body position) → loss of vibration sense and position sense
  • Lateral corticospinal tracts = carry motor signals → weakness/spasticity
  • Spinocerebellar tracts = carry balance information → ataxia (poor coordination)
  • Why "combined"? Because multiple tracts are affected together
  • Why does this happen? B₁₂ is needed for myelin synthesis (the fatty sheath around nerves). Without it, myelin degenerates → nerves can't conduct signals

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VITAMIN C (Ascorbic Acid) — Page 67

Also called: Ascorbic acid ("Scurvy" = disease → anti-Scurvy → aScorbic acid)

Function:

1. "Antioxidant; also facilitates iron absorption by reducing it to Fe²⁺ state" = Vitamin C converts iron from Fe³⁺ (ferric, hard to absorb) to Fe²⁺ (ferrous, easy to absorb). This is why nutritionists say "take your iron pill with orange juice!"
2. "Necessary for hydroxylation of proline and lysine in collagen synthesis" = Collagen is the most abundant protein in your body - it makes up tendons, ligaments, skin, bone, blood vessel walls, cornea. To make collagen, you must hydroxylate proline and lysine (add OH groups to these amino acids). This step requires Vitamin C as a cofactor! Without Vitamin C → weak, defective collagen.
3. "Necessary for dopamine β-hydroxylase (converts dopamine to NE)" = Helps make norepinephrine from dopamine.

Deficiency — SCURVY:

• Swollen, bleeding gums = Gums bleed easily because the blood vessel walls and gum tissue are weak (no good collagen to hold them together)
• Easy bruising = Tiny blood vessels break easily without good collagen support
• Petechiae = Tiny pinpoint red/purple spots on skin from bleeding into the skin
• Hemarthrosis = Bleeding into joints - painful swollen joints (hema = blood, arthrosis = joint)
• Perifollicular hemorrhages = Bleeding around hair follicles - you see little red spots around each hair
• Subperiosteal hemorrhages = Bleeding under the periosteum (the covering around bones) - very painful
• "Corkscrew" hair = The hair grows in a coiled, corkscrew pattern because the collagen structure in hair is abnormal
• Poor wound healing = Wounds don't heal because new collagen can't form
• Anemia = Bleeding + reduced iron absorption

Excess Vitamin C:

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VITAMIN D — Page 68

Sources:

• D₃ (Cholecalciferol) = Made when skin (stratum basale) is exposed to sunlight (UV-B rays). Also found in fish, milk, plants.
• D₂ (Ergocalciferol) = From ingestion of plants, fungi, yeasts.

1. Liver converts D₂/D₃ → 25-OH D₃ (storage form, 25-hydroxyvitamin D) - via 25-hydroxylase enzyme
2. Kidney converts 25-OH D₃ → 1,25-(OH)₂ D₃ = Calcitriol (the ACTIVE form) - via 1α-hydroxylase enzyme

Regulation:

• PTH = Parathyroid Hormone = released when calcium is low → tells kidneys to activate more Vitamin D → absorb more calcium
• Low calcium or low phosphate → make more active Vitamin D → absorb more calcium and phosphate

Function:

• "↑ intestinal absorption of Ca²⁺ and PO₄³⁻" = The main job! Vitamin D helps your gut absorb calcium and phosphate from food
• "↑ bone mineralization at low levels" = At normal/low doses, it helps deposit calcium into bone
• "↑ bone resorption at higher levels" = At higher levels, it actually helps break down bone to release calcium when needed

Deficiency:

• Rickets = The growing bones of children become soft and deformed because there's not enough calcium being deposited. The classic deformity is genu varum ("bowlegs") = the legs bow outward. You can see this in the X-ray image in your textbook - note the bowleg deformity marked with a red arrow.
• Osteomalacia = Same concept in adults - bones become soft (malacia = softening). Causes bone pain and muscle weakness.
• Hypocalcemic tetany = Low calcium → muscles become hypersensitive → painful muscle spasms (tetany). The classic sign is Chvostek's sign (tap the facial nerve → facial muscles twitch) and Trousseau's sign (inflate blood pressure cuff → hand goes into flexion spasm).

• Malabsorption
• ↓ sun exposure
• Poor diet
• Chronic kidney disease (CKD) = kidneys can't activate Vitamin D
• Advanced liver disease = liver can't do the first hydroxylation step
• Darker skin = more melanin blocks UV light → less Vitamin D synthesis → predisposes to deficiency
• Prematurity

Excess:

• Granulomatous diseases (like sarcoidosis, tuberculosis) = the macrophages (immune cells) in the granulomas express the 1α-hydroxylase enzyme and activate Vitamin D themselves, causing hypercalcemia even in the absence of sun exposure!
• Hypercalcemia = High calcium → nausea, kidney stones, confusion ("bones, groans, stones, and psychic moans" - the symptoms of high calcium)

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VITAMIN E (Tocopherol, Tocotrienol) — Page 68

Function:

• Vitamin E is a fat-soluble antioxidant that is especially important in protecting cell membranes (which are made of fat) from oxidative damage by free radicals

Deficiency:

• Hemolytic anemia = Red blood cells break (hemolysis) because their membranes aren't protected from oxidative damage. (Hemo = blood, lysis = breaking)
• Acanthocytosis = Red blood cells get spiky projections (acantho = spine/thorn). These abnormal RBCs are fragile.
• Spinocerebellar degeneration = The nerve tracts in the spinal cord degenerate - this looks very similar to B₁₂ deficiency neurologically. Causes:
  • Loss of proprioception (knowing where your body is in space)
  • Loss of vibration sense
  • Ataxia (poor coordination)
• "Closely mimics Friedreich ataxia" = Friedreich ataxia is a genetic disease of the spinocerebellar tracts. Vitamin E deficiency looks exactly the same clinically!

Excess:

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VITAMIN K (Phytonadione, Phylloquinone, etc.) — Page 69

Forms:

• Phytonadione, Phylloquinone, Phytonadione, Menaquinone

Function:

• Vitamin K is needed to γ-carboxylate (add carboxyl groups to) certain clotting factors
• Clotting factors that need Vitamin K: II, VII, IX, X, Protein C and Protein S
• Think: "1972" = factors 2, 7, 9, 10 (the digits of the years backwards - a memory trick!)
• "Warfarin inhibits vitamin K-dependent synthesis" = Warfarin (the blood thinner) works by blocking the epoxide reductase enzyme that regenerates active Vitamin K → clotting factors can't be made → blood clots less easily

Deficiency:

• Neonates (newborns) have very little Vitamin K because:
  1. Breast milk has little Vitamin K
  2. The gut is sterile at birth (no bacteria to make Vitamin K)
• PT = Prothrombin Time (tests the extrinsic coagulation pathway - factors I, II, V, VII, X)
• aPTT = Activated Partial Thromboplastin Time (tests the intrinsic pathway - factors I, II, V, VIII, IX, X, XI, XII)
• Both are prolonged because the Vitamin K-dependent factors are missing
• Normal bleeding time = Bleeding time tests platelet function (platelets are fine - they don't need Vitamin K)
• "Breast-fed infants Don't Know about vitamins D and K" = mnemonic! Breastfed babies need supplemental D and K
• "Neonates are given vitamin K injection at birth to prevent hemorrhagic disease of the newborn" = Standard practice worldwide

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ZINC — Page 69

Function:

• Zinc fingers = A structural shape that DNA-binding proteins (transcription factors) use to grab onto DNA. Many important genes require zinc finger proteins to be "switched on." Literally, zinc forms a "finger-like" structural domain.
• Zinc also important for: immune function, wound healing, smell, taste, sperm production

Deficiency:

• Hypogonadism = Testes don't work well → low testosterone → reduced body hair and sexual dysfunction
• Dysgeusia = Taste is distorted (dys = abnormal, geusia = taste)
• Anosmia = Loss of smell (an = without, osmia = smell)

• Acrodermatitis enteropathica = A genetic condition where the zinc transporter in the intestine is defective → severe zinc deficiency despite eating normal amounts
• Acral = relating to the tips (fingers, toes) → rash at fingertips/toes
• Periorificial = around body openings (mouth, eyes, nose, genitals) → characteristic rash placement
• Look at the image in your textbook - you can see the severe rash

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PART 5: PROTEIN-ENERGY MALNUTRITION — Page 69

KWASHIORKOR

• Protein (specifically albumin) keeps water inside blood vessels through osmotic pressure (oncotic pressure)
• No protein → no albumin → water leaks out of blood vessels into body tissues → EDEMA (swelling)
• The belly fills with fluid (ascites) → the classic "swollen belly" or "pot belly" appearance seen in malnourished children in images

• The liver needs protein to make apolipoproteins (the proteins that carry fat out of the liver)
• No protein → no apolipoproteins → fat accumulates in the liver (fatty liver / hepatic steatosis)

• Malnutrition
• Edema
• Anemia
• Liver (fatty)
• Skin lesions (e.g., hyperkeratosis = thick scaly skin, dyspigmentation = patchy coloring)

MARASMUS

• No edema = Because there IS some protein being made (just very little of everything)
• Muscle wasting = The body breaks down its own muscles for energy
• "Linear growth maintained in acute protein-energy malnutrition (vs chronic malnutrition)" = In acute starvation, height is preserved initially but weight drops. In chronic malnutrition, even height suffers (stunted growth).