Vitamin A: Retinol, Function & Reserves

Vitamin A

• Vitamin A is a group of related natural and synthetic chemicals
• These chemicals exert a hormone-like activity or function.
• Professor Elmer McCollum discovered vitamin A
• In 1913 he isolated a substance called "factor A" that was later renamed vitamin A
• Retinol is the most important form of vitamin A
• Retinol is the transport and storage form as a retinol ester
• Retinol is transported in chylomicrons to the liver for esterification and storage
• More than 90% of vitamin A reserves are stored in the liver
• Retinol is oxidized in vivo to retinal(visual pigment form) and retinoic acid
• Vegetables supply carotenoids, many of which are provitamins
• Beta-carotene is the most important provitamin that can be metabolized to active vitamin A in vivo
• Retinoids refers to both natural and synthetic chemicals that are structurally related to vitamin A
• Retinoids do not necessarily have vitamin A activity

Function of vitamin A

• Maintains normal vision in reduced light, retinal is responsible for this function
• The visual process involves four forms of vitamin-A containing pigments: rhodopsin and iodopsins
• Rhodopsin is found in rods in reduced light and iodopsins in cone cells for bright light
• One of the earliest manifestations of vitamin A deficiency is impaired vision in reduced light (night blindness)
• Potentiates the differentiation of specialized epithelial cells, mainly mucus-secreting cells, retinoic acid is responsible for this function
• Epithelium undergoes squamous metaplasia and differentiation to a keratinizing epithelium when deficient
• In vitamin A deficiency, the most devastating changes happen in the eyes, also called xerophthalmia (dry eye)

Vitamin A deficiency - ocular changes

• Dryness of the conjunctivae(xerosis) occurs as the normal lachrymal and mucus-secreting epithelium is replaced by keratinized epithelium
• Keratin debris can build leading to small opaque plaques(Bitot's spots)
• Plaques creep to the cornea, leading to erosions of the roughened corneal surfac
• The cornea softens(keratomalacia) and is destroyed, which can lead to total blindness and formation of corneal ulcers

In addition to ocular epithelium

• Causes the epithelium lining the upper respiratory passages and urinary tract to be replaced by keratinizing squamous cells (squamous metaplasia)
• Loss of the mucociliary epithelium of the airways predisposes to secondary pulmonary infections
• Desquamation of keratin debris in the urinary tract can cause formation of nidus
• Nidus is an organic core for renal and urinary bladder stones
• Both vitamin B6 and vitamin A participate in the normal metabolism of epithelial cells
• Deficiencies of vitamins causes reduction of their lifespan and increased rate of epithelia sloughing
• Epithelia sloughing leads to -> coalescence of sloughed cells -> organic core forms for urinary tract stones
• Hyperplasia and keratinization of the epidermis causes plugging of the ducts of the adnexal glands
• This can produce follicular or papular dermatosis
• One benefit is that it enhances immunity to infections, particularly in children through the immune system

Other Important Points

• During infection, bioavailability of vitamin A is reduced
• Impairment of the immunity leads to higher mortality rates in children from common infections like measles, pneumonia, and infectious diarrhea
• Supplements of vitamin during the course of infections dramatically improve the clinical outcome
• In areas where vitamin A deficiency is endemic, dietary supplements reduce mortality rate by 20% to 30%
• Acute hypervitaminosis A symptoms are headache, vomiting, stupor, papilledema, symptoms that are suggestive of brain tumor
• Chronic hypervitaminosis A symptoms are weight loss, nausea, vomiting, dryness of the mucosa of the lips, bone and joint pain, hepatomegaly, and hyperostosis

Vitamin K

• It is necessary for producing clotting factors in the liver
• Should be called Vitamin "C" because of the connection with clotting factor production
• Letter "K" was taken from German word "Koagulation"
• Vitamin K is required for the production of clotting factors VII, IX, X, and prothrombin
• A diverse group of proteins that have no connection to coagulation have also been found to be vitamin K dependent
• Of particular interest is osteocalcin, a noncollagenous protein secreted by osteoblasts γ-carboxylation of osteocalcin helps binding to calcium, meaning Vitamin K may favor calcification of bone proteins
• The major consequence of vitamin K deficiency is the development of bleeding diathesis
• In neonates, causes hemorrhagic disease of the newborn, bleeding can occur in skin, umbilicus, and viscera
• Bleeding diathesis warrants routine prophylactic vitamin K therapy for all newborns due to the estimated 3% prevalence
• Normal full-term infants, by the end of the 1st week of age, endogenous flora provide sufficient vitamin K to correct any lingering deficit
• Adults suffering from vitamin A deficiency or decreased synthesis of vitamin K dependent factors may have bleeding diathesis, characterized by hematomas, melena, ecchymoses, and bleeding from the gums

Protein-Energy Malnutrition (PEM)

• Refers to a range of clinical syndromes
• It is characterized by an inadequate dietary intake of proteins and calories to meet the body's needs
• From a functional standpoint, the body has two protein compartments: somatic and visceral
• Somatic protein compartment represented by skeletal muscles
• Visceral protein compartment represented by protein stores in the visceral organs, primarily the liver
• The two compartments are regulated differently
• The somatic compartment is affected more severely in marasmus
• the visceral compartment is depleted more severely in kwashiorkor
• Mild and moderate forms are spotted by comparing body weight with standard tables
• Measurement of serum protein provides a measure of the adequacy of the visceral protein compartment
• A malnourished child's weight falls to less than 80% of normal
• Marasmus is diagnosed when the level falls to 60% of normal weight for gender and age
• A marasmic child suffers from retardation and loss of muscles

Important Points about PEM

• Muscle mass loss results from catabolism and depletion of the somatic protein compartment
• Adaptational response that serves to provide the body with amino acids as a source of energy
• Visceral protein compartment is depleted marginally, serum albumin levels are either normal or only slightly reduced
• Subcutaneous fat is mobilized and used as fuel
• Extremities are emaciated, the head appears too large for the body
• Anemia, multivitamin deficiencies, and evidence of immune deficiency(antibodies are made of protein) are present
• Concurrent infections impose stress on an already weakened body
• Kwashiorkor occurs when protein deprivation is relatively greater than the reduction in total calories
• It is the most common form seen in African children
• Common in African children who were weaned and fed exclusively a carbohydrate diet
• Kwashiorkor is more severe than marasmus
• Protein deprivation is associated with severe loss of the visceral protein compartment
• Severe loss then causes hypoalbuminemia, which creates generalized edema
• Those with severe kwashiorkor have a weight 60%-80% of normal, the loss of weight is masked by fluid retention, edema
• Exhibits relative sparing of subcutaneous fat and muscle mass
• Modest loss is masked by edema, where two children are shown, one with marasmus on the left, and kwashiorkor on the right

Kwashiorkor in children

• Characteristic skin lesions, with alternating zones of hyperpigmentation areas of desquamation and hypopigmentation, can give a "flaky paint" appearance
• This include overall loss of color or alternating bands of pale and darker hair
• Straightening, fine texture
• Loss of firm attachment to the scalp
• Other possible symptoms are fatty liver, apathy, listlessness, loss of appetite, vitamin deficiency, defects in the immunity, and secondary infections
• Small intestines: mucosal atrophy, loss of villi and microvilli

Anorexia Nervosa

• Self-induced starvation, results in marked weight loss
• Eating disorder occurs primarily in previously healthy young women that wish to attain thinness
• Clinical findings are generally similar to those in severe PEM
• Effects on the endocrine system include amenorrhea, resulting from decreased secretion of gonadotropin-releasing hormone. Follicle-stimulating hormones can serve as a diagnostic feature
• Decreased thyroid hormones release lead to cold intolerance, bradycardia, constipation, and changes in the skin and hair

Anorexia Nervosa and Bulimia

• Skin becomes dry and scaly, may be yellow due to excess of carotene in the blood
• Body hair may be increased but is usually fine and pale (lanugo)
• Loss of bone density due to low estrogen mimicking postmenopausal acceleration of osteoporosis
• Also experience anemia, lymphopenia, and hypoalbuminemia
• Increased susceptibility to cardiac arrhythmia and sudden death, resulting in all likelihood from hypokalemia
• Bulimia is a condition in which a patient binges on food and then induces vomiting
• Menstrual irregularities are common, amenorrhea occurs in less than 50% of bulimic patients because weight and gonadotropin levels are maintained near normal
• Hypokalemiacan lead to arrhythmias
• Aspirations of gastric content can lead to aspiration pneumonia
• Other medical complication are esophageal and stomach, or cardiac rupture, leading to death

Trace Elements

• Metals that occur at concentrations smaller than 1 μg per gram of wet tissue
• Five trace elements: iron, zinc, copper, selenium, and iodine all are well-characterized for their deficiences that lead to various disorders
• Iron: hypochromic, microcytic anemia
• Iodine: hypothyroidism, goiter
• Selenium: Keshan disease, myopathy, congestive cardiomyopathy in children and young women
• Copper: muscle weakness, hypopigmentation
• Zinc: a distinctive rash, acrodermatitis enteropathica, anorexia, diarrhea, growth retardation, hypogonadism, infertility, impaired wound healing, impaired night vision, impaired immune function, and depressed mental function