Fat soluble Vitamins Flashcards
What are the fat soluble vitamins absorbed via?
Form micelles
- Absorbed by enterocytes
- Packaged into chylomicrons
What are micelles?
- Clusters of lipids
- Hydrophobic groups inside
- Hydrophilic groups outside
Diseases of what can cause fat malabsorption (and therefore vitamin)? (3)
- Bile
- Pancreatic
- Intestinal
What diseases may cause fat malabsorption?
- Cystic fibrosis (lack of pancreatic enzymes)
- Celiac sprue
- Croh’s disease
- PBC
- PSC
What is vit A also known as?
Retinol
What are the retinoids (retinal, retinoic acid) derived from?
Vit A (retinol)
What are retinoids important for?
- Vision
- Growth
- Epithelial tissues
What is Beta-Carotene?
Pro-vitamin A (a carotenoid)
- Provides the major source of vit A in the diet
What vitamins are thought to have antioxidant properties?
- Vit C, E and A
Where is Retinal found?
Visual pigments
- Rods, cons in retina
Whar is the ligh-sensitive protein receptor called?
Rhodopsin
What does rhodopsin require?
Vit A
What substances does retinoic acid control/regulate the level of protein synthesis of?
- Keratin
- Mucous
What autoimmune disease may retinoic acid be used to treat?
Psoriasis
- Regulates keratin production
In what foods can Vit A be found?
- Liver
- Dark green and yellow vegetables
Where is Vit A stored?
Liver
- Years to develop deficiency
What are the symptoms of Vit A deficiency?
Visual symptoms
- Night blindness
- Xeropthalmia
Keratinization (thickend, dry skin)
Growth failure in children
What is Xeropthalmia?
Keratinisation of cornea -> blindness
- May be caused by Vit A deficiency
What diseases may Vit A be used to treat?
- Measles
- Psoriasis
- Acne
- AML - M3 subtype (acute promyelocytic leukemia)
How can All-trans-retinoic acid be used to treat Acute promyleocytic leukemia? (AML- M3 subtype)
- Induces malignant cells to complete differentiation
- Becomes non-diving mature granulocytes/ macrophages
What is the classical finding on histology of AML?
Auer rods
Excess vit A (Hypervitaminosis A) has what symptoms?
- Dry itchy skin
- Enlarged liver
What is another name (scientific name) for isotretinoin?
13-cis-retinoic acid
What teratogenic substance can be used to treat acne?
Isotretinoin
What are the 3 key roles of Vit C?
- Iron absorption
- Collagen synthesis
- Dopamine synthesis
What are the 2 ways we absorb iron?
- Heme (found in meats)
- Non-heme iron (Fe2+ state, important for vegans, aided by vit C)
How does Vit C aid in the absorption of iron?
Converts Fe3+ to Fe2+
What is methemoglobinemia?
Iron converted to Fe3+ state can be life-threatening
How is methemoglobinemia treated?
Vit C
- Converts Fe3+ back into Fe2+
How is Vit C useful in Collagen synthesis?
Hydroxylates proline and lysine
Where does hydroxylation of proline and lysine occur?
Endoplasmic reticulum
Dopamine Beta Hydroxylase requires what as a cofactor\/
Vit C
What are the symptoms of scurvy?
- Sore gums
- Loose teeth
- Fragile blood vessels -> easy bruising
Vitamin C excess can cause what conditions?
- Iron overload (predisposition usually)
- Kidney stones
What kind of kidney stones are those with Vit C excess likely to get?
Calcium oxalate stones
- Vit C metabolized into oxalate
Why are smokers needed to get more Vit C?
Antioxidant properties
What are the 2 types of Vit D?
D2 (ergocalciferol)
- Plants
D3 (cholecalciferol)
- Fortified milk
What is the other source of Vit D3 (cholecalciferol) outside of diet?
Sunlight
Vit D3 must be hydroxylated twice
Where is it hydroxylated?
25 hydroxylation
- Liver, constant activity
1 Hydroxylation
- Kidney, regulated by PTH
25-OH Vit D is known as what?
Calcidiol
- Synthesised in liver
What is 1,2-OH Vit D known as?
Calcitriol
- Synthesised in kidney
What is the active form of Vit D known as?
1,25-OH2 Vit D
Calcitriol
What is the storage form of Vit D called?
25-Oh Vit D
- Constantly produced in liver
What is the best serum indicator of Vit D level?
25-OH Vit D
- Long half-life
What cells convert Vit D to its active form (1,25-OH Vit D)?
PCT
Why do those with sarcoidosis have hypercalcemia?
Vit D converted to active form outwith kidney by macrophages which express 1a-hydroxylase
25-OH vitamin D is converted to 1,25-OH2 Vit D (active form) by what enzyme?
1alpha- hydroxylase
What hormone activates 1alpha hydroxylase? (activates Vit D)
PTH
How does Vit D increase Ca2+ and P043- levels?
- Increases absorption
- Demineralises bones, increased Ca2+ and P043- resorption
Vit D deficiency has what symptoms?
- Hypocalcemia (seizures, tetany) and hypophosphatemia
Poor bone mineralization
- Osteomalacia
- Rickets
What are the features of osteomalacia?
- Decreased Vit D
- Bone pain / tenderness
- Fractures
- High PTH
- Reduced bone density on CXR
How does rickets affect the growth plates?
- Deficient mineralization of growth plates
- Growth plate thickens without mineralization
What are the clinical features of Rickets?
- Bone pain
- Distal forearm/knee most affected (rapid growth)
- Delayed closure of fontanelles
- Bowling of femur/tibia (classic X-ray finding)
What are the 2 main mechanisms by which hypocalcemia can occur in renal failure?
Phosphate not excreted
- Increased Phosphate -> decreased calcium
Decreased 1,25 OH2 Vit D as it cannot be activated
What are the levels of PGH in renal failure?
Increased
What infants are at risk of vit D deficiency?
Exclusively breast fed
- Especially if mother has dark skin
What is Vitamin E also known as?
Tocopherol
What is the function of Vit E?
- Antioxidant
- Key role in protecting RBCs from oxidative damage
What are the features of Vit E deficiency? (v rare)
- Hemolytic anemia
- Muscle weakness
- Ataxia
- Loss of proprioception/vibration
What can differentiate Vit E deficiency from Vit D?
Both have ataxia and loss of proprioception/vibration
- Hemolytic in Vit E
- Megalobalstic in B12
- Muscle weakness only in vit E
What is the least toxic of all the fat-soluble vitamins?
Vit E
Excessive Vit E may interfere with what drug?
May cause increased INR in warfarin use
What are the Vit K dependent clotting factors?
II, VII, IX, X, C, S
- Post-translational modification of these factors into active forms
The precursor Glutamate residue becomes y-carboxylation (Gla) Residue through the addition of what?
Carboxyl group
y carboxylation (CO2 added)
What vitamin acts as a cofactor for the y carboxylation of Glutamate residue to y-carboxylation (Gla) Residue?
Vitamin K
What is the y-carboxyglutamte (Gla) rsidue?
An activated clotting factor
What are the 2 places Vit K is found/created?
K1 form
- Cabbage, kale, spinach
K2 form
- GI bacteria
When a precursor molecule is converted to an activated clotting factor thru a carboxylation reaction what happens to Vit K?
Goes from reduced form to oxidised Vit K
What enzyme rejuvenates Reduced Vit K from Oxidised?
Epoxide reductase
What does Warfarin inhibit?
Epoxide reductase
What are the key lab findings in vit K deficiency?
- Elevated PT/INR
- Can see elevated PTT (less sensitive)
- Normal bleeding time
Why is Vit K deficiency very rare?
GI bacteria produce sufficient quantities
What can cause Vit K deficiency?
- Warfarin
- Antibiotics thru decreased GI bacteria
Why are babies given Vit K at birth?
Sterile GI tract at birth
- Insufficient vit K in breast milk
What are the symptoms of Zinc deficiency in children?
- Poor growth
- Poor sexual development
What are the symptoms of Zinc deficiency in adults?
- Poor wound healing
- Loss of taste (required by taste buds)
- Immune dysfunction (required for cytokine production)
- Dermatitis, red skin, pustules (patients on TPN)
What is zinc found in?
Meat - chicken
Where is zinc absorbed?
Duodenum
What are risk factors for zinc deficiency?
- Alcoholism (low zinc associated with cirrhosis)
- Chronic renal disease
- Malabsorption
What is acrodermatitis enteropathica?
- Zinc absorption impaired
- Mutations in gene for zinc transportation
How is acrodermatitis enteropathica inherited?
AR
What are the symptoms of acrodermatitis enteropathica?
Dermatitis
- Hyperpigmentation (often red) skin
- Classically perioral and perianal
- Also arms and legs
- Loss of hair
- Diarrhea
- Poor growth
- Immune dysfunction (infections)
What are zinc fingers?
Protein segments that contain zinc
- Called domain or motif sometimes
What kind of proteins contain zinc fingers?
Proteins that bind proteins, RNA, DNA
- Often bind specific DNA sequences
How can proteins with zinc fingers effect DNA?
Often bind specific DNA segments
- Influence/modify genes and gene activity
