Disorders Of Vitamins
Vitamins are organic substances which cannot be synthesised within the body and are essential for the maintenance of the normal structure and function of cells.
Table of Contents
Read And Learn More: General Pathology Notes
Thus, these substances must be= provided in the human diet. Most of the vitamins are of plant or animal origin so they normally enter the body as constituents of ingested plant food or animal food.
They are required in minute amounts in contrast to the relatively large amounts of essential amino acids and fatty acids. Vitamins do not play any part in production of energy.
Etiology Of Vitamin Deficiencies:
- In developing countries, multiple deficiencies of vitamins and other nutrients are common due to generalised malnutrition of dietary origin.
- In developed countries, individual vitamin deficiencies are noted more often, particularly in children, adolescent, pregnant and lactating women, and in some due to poverty.
- General secondary causes of conditioned nutritional deficiencies listed already (i.e. interference in ingestion, absorption, utilization, excretion) can result in vitamin deficiency in either case.
- Chronic alcoholism is a common denominator in many of vitamin deficiencies.
A few other noteworthy features about vitamins are as under:
- While vitamin deficiency as well as its excess may occur from another disease, the states of excess and deficiency themselves also cause disease.
- Vitamins in high dose can be used as drugs.
Classification Of Vitamins
Vitamins are conventionally divided into 2 groups: fatsoluble and water-soluble.
1. Fat-soluble vitamins:
- There are 4 fat-soluble vitamins: A, D, E and K. They are absorbed from the intestine in the presence of bile salts and intact pancreatic function.
- Their deficiencies occur more readily due to conditioning factors (secondary deficiency).
- Beside the deficiency syndromes of these vitamins, a state of hypervitaminosis due to an excess of vitamins A and D also occurs.
2. Water-soluble vitamins:
- This group conventionally consists of vitamin C and members of the B complex group. Besides, choline, biotin and flavonoids are new additions to this group.
- Water-soluble vitamins are more readily absorbed from the small intestine. Deficiency of these vitamins is mainly due to primary (dietary) factors.
- Being water soluble, these vitamins are more easily lost due to the cooking or processing of food.
Sums up the various clinical disorders produced by vitamin deficiencies
Vitamin deficiencies:
Fat-Soluble Vitamins
1. Vitamin A (Retinol): Physiology:
Vitamin A or retinol is a fat-soluble alcohol. It is available in diet in 2 forms:
- As preformed retinol, the dietary sources of which are animal-derived foods such as yolk of eggs, butter, whole milk, fish, liver, kidney.
- As provitamin precursor carotenoid, which is derived from β-carotene-containing foods such as yellow plants and vegetables for example,Carrots, potatoes, Pumpkins, Mangoes, Spinach.
β-carotene can be absorbed intact or converted in the intestinal mucosa to form retinaldehyde which is subsequently reduced to retinol. Retinol is stored in the liver cells and released for transport to peripheral tissues after binding to retinol-binding protein found in blood.
The physiologic functions of retinol are as follows:
- Maintenance of normal vision in reduced light.
- This involves formation of 2 pigments by oxidation of retinol:
- Rhodopsin, a light-sensitive pigment in reduced light synthesised in the rod cells, and iodopsins are sensitive in bright light and formed in cone cells of retina.T
- hese pigments then transform the radiant energy into nerve impulses.
- This involves formation of 2 pigments by oxidation of retinol:
- Maintenance of structure and function of specialised epithelium.
- Retinol plays an important role in the synthesis of glycoproteins of the cell membrane of specialised epithelium such as mucus-secreting columnar epithelium in glands and mucosal surfaces, respiratory epithelium and urothelium.
- Maintenance of normal cartilaginous and bone growth.
- Increased immunity against infections in children.
- Anti-proliferative effect.β-carotene has anti-oxidant properties and may cause regression of certain non-tumorous skin diseases, premalignant conditions and certain cancers.
Lesions In Vitamin A Deficiency:
- Nutritional deficiency of vitamin A is common in countries of South-East Asia, Africa, Central and South America.
- Whereas malabsorption syndrome may account for conditioned vitamin A deficiency in developed countries.
Morphologic Features:
Consequent to vitamin A deficiency, the following pathologic changes are seen:
- Ocular lesions: Lesions in the eyes are most obvious. Night blindness is usually the first sign of vitamin A deficiency.
- As a result of replacement metaplasia of mucus-secreting cells by squamous cells, there is dry and scaly scleral conjunctiva (xerophthalmia).
- The lacrimal duct also shows hyperkeratosis.
- Corneal ulcers may occur which may get infected and cause keratomalacia.
- Bitot’s spots may appear which are focal triangular areas of opacities due to the accumulation of keratinised epithelium.
- If these occur on cornea, they impede the transmission of light. Ultimately, infection, scarring and opacities lead to blindness.
- Cutaneous lesions: The skin develops papular lesions giving a toad-like appearance (xeroderma). This is due to follicular hyperkeratosis and keratin plugging in the sebaceous glands.
- Other lesions These are as under:
- Squamous metaplasia of the respiratory epithelium of the bronchus and trachea may predispose to respiratory infections.
- Squamous metaplasia of pancreatic ductal epithelium may lead to obstruction and cystic dilatation.
- Squamous metaplasia of the urothelium of the pelvis of kidney may predispose to pyelonephritis and perhaps to renal calc
- Long-standing metaplasia may cause progression to anaplasia under certain circumstances.
- Bone growth in vitamin A-deficient animals is retarded.
- Immune dysfunction may occur due to damaged barrier epithelium and compromised immune defences.
- Pregnant women may have an increased risk of maternal infection, mortality and impaired embryonic development.
Hypervitaminosis:
Very large doses of vitamin A can produce toxic manifestations in children as well as in adults. These may be acute or chronic.
- Acute toxicity:
- This results from a single large dose of vitamin A.
- The effects include neurological manifestations resembling brain tumour, for example, Headache, Vomiting, Stupor, and Papilloedema.
- Chronic toxicity: The clinical manifestations of chronic vitamin A excess are as under:
- Neurological such as severe headache and disordered vision due to increased intracranial pressure.
- Skeletal pains due to loss of cortical bone by increased osteoclastic activity as well as due to exostosis.
- Cutaneous involvement may be in the form of pruritus, fissuring, sores at the corners of the mouth and coarseness of the hair.
- Hepatomegaly with parenchymal damage and fibrosis.
- Hypercarotenaemia is the yellowness of palms and skin due to excessive intake of β-carotene containing foods like carrots or due to inborn error of metabolism.
The effects of toxicity usually disappear on stopping excess of vitamin A intake.
2. Vitamin D (Calcitriol): Physiology:
This fat-soluble vitamin exists in 2 activated sterol forms:
- Vitamin D2 or calciferol
- Vitamin D3 or cholecaliferol
The material originally described as vitamin D1 was subsequently found to be impure mixture of sterols. Since vitamin D2 and D3 have similar metabolism and functions, they are therefore referred to as vitamin D. Normal serum level of total vitamin D is 15-75 pg/ml (36-180 pmol/L).
There are 2 main sources of vitamin D:
- Endogenous synthesis:
- 80% of the body’s need of vitamin D is met by endogenous synthesis from the action of ultraviolet light on 7-dehydrocholesterol widely distributed in oily secretions of the skin.
- The vitamin so formed by irradiation enters the body directly through the skin.
- Pigmentation of the skin reduces the beneficial effects of ultraviolet light.
- Exogenous sources:
- The other source of vitamin D is diet such as deep sea fish, fish oil, eggs, butter, milk, some plants and grains.
- Irrespective of the source of vitamin D, it must be converted to its active metabolites (25- hydroxy vitamin D and 1,25-dihydroxy vitamin D or calcitriol) after its metabolism in the liver and kidney for being functionally active.
- 1, 25-dihydroxy vitamin D (calcitriol) is 5-10 times more potent biologically than 25- hydroxy vitamin D.
The production of calcitriol by the kidney is regulated by:
- Plasma levels of calcitriol (hormonal feedback)
- Plasma calcium levels (hypocalcaemia stimulates synthesis); and
- Plasma phosphorus levels (hypophosphataemia stimulates synthesis).
The main storage site of vitamin D is the adipose tissue rather than the liver which is the case with vitamin A.
The main physiologic functions of the most active metabolite of vitamin D, calcitriol, are mediated by its binding to nuclear receptor superfamily, vitamin D receptor, expressed on a wide variety of cells.
These actions are as under:
- Maintenance of normal plasma levels of calcium and phosphorus:
- The major essential function of vitamin D is to promote the mineralisation of bone. This is achieved by the following actions of vitamin D:
- Intestinal absorption of calcium and phosphorus is stimulated by vitamin D.
- On bones Vitamin D is normally required for mineralisation of epiphyseal cartilage and osteoid matrix.
- However, in hypocalcaemia, vitamin D collaborates with the parathyroid hormone and causes osteoclastic resorption of calcium and phosphorus from bone so as to maintain normal blood levels of calcium and phosphorus.
- On kidneys, Vitamin D stimulates the reabsorption of calcium at the distal renal tubular level, though this function is also parathyroid hormone-dependent.
- Anti-proliferative effects: Vitamin D receptor is expressed on the parathyroid gland cells by which active form of vitamin D causes anti-proliferative action on parathyroid cells and suppresses the parathormone gene.
Besides, vitamin D receptor is also expressed in cells of organs which do not have any role in mineral ion homeostasis and has anti-proliferative effects on them for example Skin, breast cancer cells, and prostate cancer cells.
Lesions In Vitamin D Deficiency:
- Deficiency of vitamin D may result from:
- Reduced endogenous synthesis due to inadequate exposure to sunlight
- Dietary deficiency of vitamin D
- Malabsorption of lipids due to lack of bile salts such as in intrahepatic biliary obstruction pancreatic insufficiency and malabsorption syndrome,
- Derangements of vitamin D metabolism as occur in kidney disorders (chronic renal failure, nephrotic syndrome, uraemia), liver disorders (diffuse liver disease) and genetic disorders, and
- Resistance of end-organ to respond to vitamin D.
A deficiency of vitamin D from any of the above mechanisms results in 3 types of lesions:
- Rickets in growing children
- Osteomalacia in adults, and
- Hypocalcaemic tetany due to neuromuscular dysfunction.
1. Rickets:
The primary defects in rickets are
- Interference with the mineralisation of bone, and
- Deranged endochondral and intramembranous bone growth.
- The pathogenesis of lesions in rickets is better understood by contrasting them with sequence of changes in normal bone growth as outlined in.
Morphologic Features:
Rickets occurs in growing children from 6 months to 2 years of age. The disease has the following lesions and clinical characteristics :
- Skeletal changes These are as under:
- Craniotabes is the earliest bony lesion occurring due to small round unossified areas in the membranous bones of the skull, disappearing within 12 months of birth.
- The skull looks square and box-like.
- Harrison’s sulcus appears due to indrawing of soft ribs on inspiration.
- Rachitic rosary is a deformity of chest due to cartilaginous overgrowth at costochondral junction.
- Pigeon-chest deformity is the anterior protrusion of sternum due to action of respiratory muscles.
- Bow legs occur in ambulatory children due to weak bones of lower legs.
- Knocked knees may occur due to enlarged ends of the femur, tibia and fibula.
- Lower epiphyses of radius may be enlarged.
- Lumbar lordosis is due to involvement of the spine and pelvis
Contrasting features of rickets with normal bone growth:
Biochemical changes:
These are as follows:
- Lowered levels of active metabolites of vitamin D (25-hydroxy vitamin D and 1, 25- dihydroxy vitamin D).
- Plasma calcium levels are normal or slightly low.
- Plasma phosphate levels are lowered.
- Plasma alkaline phosphatase is usually raised due to osteoblastic activity. Vitamin D-dependent rickets is an autosomal dominant disorder of vitamin D.
- The disease responds rapidly to the administration of 1,25-dihydroxy vitamin D.
2. Osteomalacia:
Osteomalacia is the adult counterpart of rickets in which there is failure of mineralisation of the osteoid matrix. It may occur following dietary deficiency, poor endogenous synthesis of vitamin D, or as a result of conditioned deficiency.
Morphologic Features:
- Due to a deficiency of vitamin D, the osteoid matrix laid down fails to get mineralised .
- In H & E stained microscopic sections, this is identified by widened and thickened osteoid seams (stained pink) and decreased mineralisation at the borders between osteoid and bone (stained basophilic).
- von Kossa’s stain for calcium may be employed to mark out the wide seams of unstained osteoid while the calcified bone is stained black.
- In addition, there may be increased osteoclastic activity and fibrosis of marrow.
Clinical features Osteomalacia is characterised by:
- Muscular weakness
- Vague bony pains
- Fractures following trivial trauma’
- Incomplete or greenstick fractures, and
- Looser zones or pseudofractures at weak places in bones.
Biochemical changes These are:
- Normal or low serum calcium levels
- Plasma phosphate levels lowered, and
- Raised serum alkaline phosphatase due to increased osteoblastic activity.
- It may be worthwhile to note here that another chronic disorder of the skeleton seen in the elderly, osteoporosis, is clinically similar but biochemically different disease.
3. Hypervitaminosis:
D Very large excess of vitamin D may cause increased intestinal absorption of calcium and phosphorus, leading to hypercalcaemia, hyperphosphataemia and increased bone resorption. These changes may result in the following effects:
- Increased urinary excretion of calcium and phosphate
- Predisposition to renal calculi
- Osteoporosis, and
- Widespread metastatic calcification is more marked in the renal tubules, arteries, myocardium, lungs and stomach.
3. Vitamin E (α-Tocopherol): Physiology:
Out of many naturally-occurring tocopherols and tocotrienols, α-tocopherol is biologically the most active fat-soluble compound for humans. Vitamin E is found in most of the ordinary foods such as vegetables, grains, nuts and oils.
It is absorbed from the intestine and transported in blood in the form of chylomicrons. It is stored in fat depots, liver and muscle.
The main physiologic functions of vitamin E are as under:
- Anti-oxidant activity Active form of vitamin E acts as an antioxidant and prevents the oxidative degradation of cell membranes containing phospholipids.
- Scavenger of free radicals Vitamin E scavenges free radicals formed by a redox reaction in the body and thus maintains the integrity of the cell.
- Inhibits prostaglandin synthesis.
- Activates protein kinase C and phospholipase A2.
Lesions In Vitamin E Deficiency:
- The deficiency of vitamin E is mainly by conditioning disorders affecting its absorption and transport such as abetalipoproteinaemia, Intra and extrahepatic biliary cholestasis, cystic fibrosis of the pancreas and malabsorption syndrome.
- Low birth weight neonates, due to physiologic immaturity of the liver and bowel, may also develop vitamin E deficiency.
Lesions of vitamin E deficiency are as follows:
- Neurons with long axons develop degeneration in the posterior columns of spinal cord.
- Peripheral nerves may also develop myelin degeneration in the axons.
- Skeletal muscles may develop denervation.
- Retinal pigmentary degeneration may occur.
- Red blood cells deficient in vitamin E such as in premature infants have reduced lifespan.
- In experimental animals, vitamin E deficiency can produce sterility in both male and female animals.
4. Vitamin K Physiology:
Vitamin K1 (K for Koagulations in Danish) exists in nature in 2 forms:
- Vitamin K1 or phylloquinone, obtained from exogenous dietary sources such as most green leafy vegetables; and
- Vitamin K2 or men a quinone, produced endogenously by normal intestinal flora.
Phylloquinone can be converted into menaquinone in some organs. Like other fat-soluble vitamins, vitamin K is absorbed from the small intestine and requires adequate bile flow and intact pancreatic function.
The main physiologic function of vitamin K is in hepatic microsomal carboxylation reaction for vitamin K-dependent coagulation factors (most importantly factor II or prothrombin; others are factors VII, IX and X).
Lesions In Vitamin K Deficiency:
- Since vitamin K is necessary for the manufacture of prothrombin, its deficiency leads of hypoprothrombinaemia .
- Estimation of plasma prothrombin, thus, affords a simple in vitro test for determining whether there is deficiency of vitamin K. Subjects with levels below 70% of normal should receive therapy with vitamin K.
- Because most of green vegetables contain vitamin K and it can be synthesised endogenously, vitamin K deficiency is frequently a conditioned deficiency.
The conditions which may bring about vitamin K deficiency are as follows:
- Haemorrhagic disease of the newborn: The newborn infants are deficient in vitamin K because of minimal stores of vitamin K at birth, lack of established intestinal flora for endogenous synthesis and limited dietary intake since breast milk is a poor source of vitamin K. Hence the clinical practice is to routinely administer vitamin K at birth.
- Biliary obstruction: Bile is prevented from entering the bowel due to biliary obstruction which prevents the absorption of this fat-soluble vitamin. Surgery in patients of obstructive jaundice, therefore, leads to a marked tendency to bleeding.
- Due to malabsorption syndrome: Patients suffering from malabsorption of fat develop vitamin K deficiency, for example, Coeliac Disease, Sprue, Pancreatic disease, Hypermotility of the bowel etc.
- Due to anticoagulant therapy: Patients on the warfarin group of anticoagulants have impaired biosynthesis of vitamin K-dependent coagulation factors.
- Due to antibiotic therapy: The use of broad-spectrum antibiotics and sulfa drugs reduces the normal intestinal flora.
- Diffuse liver disease: Patients with diffuse liver disease (e.g. cirrhosis, amyloidosis of the liver, hepatocellular carcinoma, hepatoblastoma) have hypoprothrombinaemia due to impaired synthesis of prothrombin. Administration of vitamin K to such patients is of no avail since the liver, where prothrombin synthesis utilising vitamin K takes place, is diseased.
Water-Soluble Vitamins
1. Vitamin C (Ascorbic Acid): Physiology:
Vitamin C exists in natural sources as L-ascorbic acid closely related to glucose. The major sources of vitamin C are citrus fruits such as orange, lemon, grape fruit and some fresh vegetables like tomatoes and potatoes. It is present in small amounts in meat and milk.
The vitamin is easily destroyed by heating so that boiled or pasteurised milk may lack vitamin C. It is readily absorbed from the small intestine and is stored in many tissues, most abundantly in adrenal cortex.
The physiologic functions of vitamin C are due to its ability to carry out oxidation-reduction reactions:
L-Ascorbic Acid ⇌ dehydro L-Ascorbic acid + 2H++ 2e
- Vitamin C has been found to have antioxidant properties and can scavenge free radicals.
- Ascorbic acid is required for hydroxylation of proline to form hydroxyproline which is an essential component of collagen.
- Besides collagen, it is necessary for the ground substance of other mesenchymal structures such as osteoid, chondroitin sulfate, dentin and cement substance of vascular endothelium.
- Vitamin C being a reducing substance has other functions such as:
-
- Hydroxylation of dopamine to norepinephrine,
- Maintenance of folic acid levels by preventing oxidation of tetrahydrofolate, and
- Role in iron metabolism in its absorption, storage and keeping it in a reduced state.
Lesions In Vitamin C Deficiency:
- Vitamin C deficiency in the food or as a conditioned deficiency results in scurvy.
- The lesions and clinical manifestations of scurvy are seen more commonly at two peak ages: in early childhood and in the very aged.
These are as under:
- Haemorrhagic diathesis: A marked tendency to bleeding is characteristic of scurvy. This may be due to deficiency of intercellular cement which holds together the cells of capillary endothelium. There may be haemorrhages in the skin, mucous membranes, gums, muscles, joints and underneath the periosteum.
- Skeletal lesions: These changes are more pronounced in growing children. The most prominent change is the deranged formation of osteoid matrix and not deranged mineralisation (c.f. the pathological changes underlying rickets already described). Growing tubular bones as well as flat bones are affected.
- The epiphyseal ends of growing long bones have cartilage cells in rows which normally undergo provisional mineralisation.
However, due to vitamin C deficiency, the next step of laying down of osteoid matrix by osteoblasts is poor and results in failure of resorption of cartilage. Consequently, mineralised cartilage under the widened and irregular epiphyseal plates project as scorbutic rosary.
The skeletal changes are further worsened due to haemorrhages and haematomas under the periosteum and bleeding into the joint spaces.
- Delayed wound healing: There is delayed healing of wounds in scurvy due to following: deranged collagen synthesis; poor preservation and maturation of fibroblasts; and localisation of infections in the wounds.
- Anaemia: Anaemia is common in scurvy. It may be the result of haemorrhage, interference with formation of folic acid or deranged iron metabolism. Accordingly, anaemia is most often normocytic normochromic type; occasionally it may be megaloblastic or even iron deficiency type.
- Lesions in teeth and gums: Scurvy may interfere with development of dentin. The gums are soft and swollen, may bleed readily and get infected commonly.
- Skin rash: Hyperkeratotic and follicular rash may occur in scurvy.
2. Vitamin B Complex:
The term vitamin B was originally coined for a substance capable of curing beriberi (B from beriberi).
Now, vitamin B complex is commonly used for a group of essential compounds which are biochemically unrelated but occur together in certain foods such as green leafy vegetables, cereals, yeast, liver and milk. Most of the vitamins in this group are involved in metabolism of proteins, carbohydrates and fats.
The principal members of vitamin B complex are:
- Thiamine (vitamin B1)
- Riboflavin (vitamin B2)
- Niacin or nicotinic acid (vitamin B3)
- Pantothenic acid (vitamin B5)
- Pyridoxine (vitamin B6)
- Folate (folic acid)
- Cyanocobalamin (vitamin B12) and biotin.
There is no definite evidence that any clinical disorder results from deficiency of pantothenic acid (vitamin B5).
1. Thiamine (Vitamin B1): Physiology:
Thiamine was the first in the family of vitamin B complex group and hence named B.
- Thiamine hydrochloride is available in a variety of items of diet such as peas, beans, pulses, yeast, green vegetable roots, fruits, meat, pork, rice and wheat bran. The vitamin is lost in refined foods such as polished rice, white flour and white sugar.
- A few substances in the diet (strong tea, coffee) act as anti-thiamines. Since the vitamin is soluble in water, a considerable amount of the vitamin is lost during cooking of vegetables. The vitamin is absorbed from the intestine either by passive diffusion or by energy-dependent transport.
- Reserves of vitamin B1 are stored in the skeletal muscles, heart, liver, kidneys and bones. The main physiologic function of thiamine is in carbohydrate metabolism.
- Thiamine after absorption is phosphorylated to form thiamine pyrophosphate which is functionally active compound.
- This compound acts as coenzyme for carboxylase so as to decarboxylate pyruvic acid, synthesises ATP and also participates in the synthesis of fat from carbohydrate. In addition, thiamin plays a role in peripheral nerve conduction by an unknown mechanism.
Lesions In Thiamine Deficiency:
- Thiamine deficiency can occur from primary or conditioned causes, chronic alcoholism being an important cause.
- The deficiency state leads to failure of complete combustion of carbohydrate and accumulation of pyruvic acid.
- This results in beriberi which produces lesions at 3 target tissues (peripheral nerves, heart and brain).
Accordingly, beriberi is of 3 types:
- Dry beriberi (peripheral neuritis)
- Wet beriberi (cardiac manifestations)
- Cerebral beriberi (Wernicke-Korsakoff’s syndrome)
It is worth noting that lesions in beriberi are mainly located in the nervous system and heart. This is because the energy requirement of the brain and nerves is solely derived from the oxidation of carbohydrates which is deranged in beriberi, while lesions in the heart appear to arise due to reduced ATP synthesis in beriberi which is required for cardiac functions.
The features of 3 forms of beriberi are as under:
- Dry beriberi (peripheral neuritis): This is marked by neuromuscular symptoms such as weakness, paraesthesia and sensory loss. The nerves show polyneuritis, myelin degeneration and fragmentation of axons.
- Wet beriberi (cardiac manifestations): This is characterised by cardiovascular involvement, generalised oedema, serous effusions and chronic passive congestion of viscera.
- The heart in Beriberi is flabby (due to thin and weak myocardium), enlarged and globular in appearance due to 4-chamber dilatation.
- Microscopic examination of the heart shows hydropic degeneration of myocardial fibres, loss of striations, interstitial oedema and lymphocytic infiltration.
- Cerebral beriberi (Wernicke-Korsakoff’s syndrome): It consists of the following features:
-
- Wernicke’s encephalopathy occurs more often due to conditioned deficiencies such as in chronic alcoholism. It is characterised by degeneration of ganglia cells, focal demyelination and haemorrhage in the nuclei surrounding the region of ventricles and aqueduct.
- Microscopic examination shows degeneration and necrosis of neurons, hypertrophy hyperplasia of small blood vessels and haemorrhages.
- Korsakoff’s psychosis results from persistence of psychotic features following brain
haemorrhage in Wernicke’s encephalopathy.
- Wernicke’s encephalopathy occurs more often due to conditioned deficiencies such as in chronic alcoholism. It is characterised by degeneration of ganglia cells, focal demyelination and haemorrhage in the nuclei surrounding the region of ventricles and aqueduct.
2. Riboflavin (Vitamin B2): Physiology:
Riboflavin used to be called ‘yellow respiratory enzyme’ (flavus = yellow), now known as ‘cytochrome oxidase enzyme’ which is important in view of its role as cellular respiratory coenzyme. The vitamin is usually distributed in plant and animal foods such as liver, beef, mutton, pork, eggs, milk and green vegetables.
Like other water-soluble vitamins, it is rapidly absorbed from the bowel and stored in tissues like the liver.
Lesions In Riboflavin Deficiency:
- Lesions due to primary or conditioned deficiency of riboflavin (ariboflavinosis) are as follows:
- Ocular lesions consist of vascularisation of the normally avascular cornea due to the proliferation of capillaries from the limbus.
- Subsequently, conjunctivitis, interstitial keratitis and corneal ulcers may develop.
- Cheilosis and angular stomatitis are characterised by the occurrence of fissures and cracks at the angles of the mouth.
- Glossitis is development of red, cyanosed and shiny tongue due to atrophy of the mucosa of the tongue (‘bald tongue’).
- Skin changes appear in the form of scaly dermatitis resembling seborrheic dermatitis on nasolabial folds on the face, scrotum and vulva.
- Anaemia may develop in some cases.
3. Niacin or Nicotinic Acid (Vitamin B3): Physiology:
As with thiamine and riboflavin, niacin or nicotinic acid or vitamin B3 is also widely distributed in plant and animal foods such as the liver, kidney, meat, green vegetables and whole grain cereals. Niacin includes the biologically active derivative nicotinamide which is essential for the formation of 2 oxidative coenzymes (dehydrogenases):
- NAD (nicotinamide adenine dinucleotide) which is required for dehydrogenation in the metabolism of fat, carbohydrates and proteins.
- NADP (nicotinamide adenine dinucleotide phosphate) is essential for dehydrogenation in the hexose monophosphate shunt of glucose metabolism.
Lesions In Niacin Deficiency:
- A deficiency of niacin causes pellagra, so named because of the rough skin of such patients (Italian pelle agra = rough skin).
- Pellagra may result from a dietary deficiency in those who largely subsist on maize since niacin in maize is present in bound form and is hence not absorbable.
- Since niacin can be endogenously synthesised from tryptophan, a diet deficient in this amino acid or disorders of tryptophan metabolism such as in carcinoid syndrome or Hartnup syndrome results in niacin deficiency.
Lesions in pellagra are characterised by 3Ds:
- Dermatitis: The sun-exposed areas of the skin develop erythema resembling sunburn. This may progress to a chronic type of dermatitis with blister formation.
- Diarrhoea: Lesions similar to those seen in the skin may develop in the mucous membrane of the alimentary tract resulting in glossitis, lesions in the mouth, oesophagus, stomach and colon and cause diarrhoea, nausea, vomiting and burning sensation.
- Dementia: Degeneration of neurons of the brain and of the spinal tract results in neurological symptoms such as dementia, peripheral neuritis, ataxia and visual and auditory disturbances.
Toxicity Of Niacin:
Toxicity due to the administration of high doses of niacin as therapy for dyslipidaemia has been observed but not due to dietary excess. It is characterised by flushing of skin and liver derangement.
4. Pyridoxine (Vitamin B6): Physiology:
Pyridoxine or vitamin B6 is widely distributed in all animal and plant foods such as meat, liver, eggs, green vegetables and whole grain cereals. Pyridoxine exists in 3 closely related naturally-occurring substances—pyridoxine, pyridoxal and pyridoxamine. All of these can be converted into biologically active coenzyme, pyridoxal 5-phosphate.
The major physiologic functions of pyridoxine are related to:
- Fat metabolism
- Protein metabolism
- Amino acid metabolism such as decarboxylation of amino acids, transmethylation of methionine, conversion of tryptophan to niacin
- Steroid metabolism
- Neurotransmitter synthesis, and
- Haem synthesis.
Lesions In Pyridoxine Deficiency Vitamin B:
- 6 deficiency may result from inadequate dietary intake or may result from secondary deficiency such as increased demand in pregnancy.
- Lactation, chronic alcoholism and intake of certain drugs (for example, Isoniazid in the treatment of tuberculosis, penicillamine, oestrogen in oral contraceptives etc).
The lesions of pyridoxine deficiency include the following:
- Convulsions in infants born to mothers who had been administered large doses of vitamin B6 for hyperemesis gravidarum (pyridoxine dependence)
- Dermatitis and seborrhoea
- Cheilosis and angular stomatitis
- Glossitis (bald tongue)
- Neuropathy
- Depression, confusion
- Sideroblastic anaemia.
5. Folate (Folic Acid) and Cyanocobalamin (Vitamin B12):
Both these vitamins included in the B complex group are required for red cell formation. Their deficiency leads to megaloblastic anaemia.
6. Biotin Or Physiology:
Biotin is a water-soluble vitamin and a member of the vitamin B complex group. It is available in food sources such as organ meat, soya beans, and egg yolk; however egg white has a protein avidin which binds to biotin and blocks its bioavailability.
The major physiologic functions of biotin are as under:
- In gene expression
- In gluconeogenesis
- In fatty acid synthesis
- In the catabolism of certain amino acids such as leucine
- As a carrier of CO2 in carboxylase enzymes.
Lesions In Biotin Deficiency:
- Biotin deficiency is rare and develops due to inborn errors of metabolism and in patients on parenteral nutrients devoid of biotin.
The lesions of biotin deficiency are as under:
- Mental and neurologic symptoms such as hallucination, depression, paraesthesia
- Anorexia
- Nausea
- Scaly, seborrhoeic dermatitis
- In infants, hypotonia, alopecia and rash near ears.
- In concluding the discussion of vitamin B complex, it must be mentioned that many of animal and plant foods contain vitamin B complex groups of vitamins.
- Their deficiency, whether primary from poverty, ignorance etc or secondary from conditioning factors like chronic alcoholism, is more frequently multiple vitamin deficiencies.
- Hence, the clinical practice is to administer a combination of these members of the vitamin B complex.
Biotin These are two types:
1. Choline: Physiology:
Choline is a precursor form of acetylcholine and betaine. Choline is widely distributed as lecithin in foods such as egg yolk, milk, wheat and organ meat. Choline is also synthesised in the liver.
The major physiologic functions of choline are as under:
- In the maintenance structural integrity of cell membranes
- In transmembrane signalling pathways
- In cholinergic neurotransmission
- In the metabolism of lipids and cholesterol.
Lesions In Choline Deficiency:
- Choline deficiency develops in patients on choline-free parenteral nutrients.
- The lesions of choline deficiency are as under:
- Fatty liver with deranged liver enzymes
- Skeletal muscle damage with elevated CPK levels.
- The lesions of choline deficiency are as under:
2. Flavonoids: Physiology:
Flavonoids are a form of polyphenols present in several fruits and vegetables and are the constituents which impart colour, flavour and taste to these edible products. Particular food and vegetables rich in flavonoids are berries, grapes, apples, broccoli, onions, legumes etc.
The major physiologic functions of flavonoids are as under:
- As antioxidants
- In cell signalling pathways
Lesions In Flavonoid Deficiency:
- Flavonoids have been a recent addition to the family of vitamins.
- Present data on animal experiments and human clinical studies indicate that they play a role in the prevention of neurodegenerative diseases, osteoporosis and diabetes.
Disorders of Vitamins:
- There are 4 fat-soluble vitamins: A, D, E and K. Water-soluble vitamins consist of vitamin C and members of B complex group; in addition, choline, biotin and flavonoids are newer members of this group.
- Vitamin A deficiency causes ocular lesions (night blindness, xerophthalmia, Bitot’s spots), xeroderma, and squamous metaplasia of various specialised epithelia (respiratory, pancreatic ductal, urothelium). A state of hypervitaminosis A may produce acute and chronic toxicity.
- Vitamin D is derived from endogenous (synthesis from UV light) and exogenous (sea fish, eggs, butter) sources. Its deficiency may produce rickets in growing children and osteomalacia in adults.
- Hypervitaminosis D may lead to hypercalcaemia, hyperphosphataemia and increased bone resorption.
- Vitamin E deficiency may cause degeneration of neurons, peripheral nerves and retinal
pigment. - Vitamin K deficiency causes hypoprothrombinaemia and may produce haemorrhagic disease of newborns.
- Vitamin C deficiency results in scurvy having lesions and clinical manifestations in early childhood and in the very aged. These are haemorrhagic diathesis, skeletal derangements and delayed healing.
- The principal members of the vitamin B complex and their deficiency diseases are:
-
- Thiamine (vitamin B1) causing beriberi
- Riboflavin (vitamin B2) causes lesions on the cornea and angle of the mouth
- Niacin or nicotinic acid (vitamin B3) causes pellagra having 3 Ds (dermatitis, diarrhoea, dementia)
- Pantothenic acid (vitamin B5 ) is not known to cause any deficiency state
- Pyridoxine (vitamin B6) causes dermatitis and seborrhea
- Cyanocobalamin (vitamin B12) and
- Folate (folic acid) is responsible for megaloblastic anaemia, and A rare deficiency of biotin may cause mental and neurological symptoms.
- Besides, deficiency of choline may cause fatty liver and flavonoids to act as antioxidants.
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