Q. Write a short essay/note on clinical features, diagnosis, and treatment of vitamin A deficiency.
Vitamin A is a fat-soluble vitamin. Vitamin A is the name given to a group of related compounds and mainly includes retinoids and carotenoids.
- Retinoids/Retinol (vitamin A alcohol): Retinoid is the generic term that encompasses vitamin A in its various forms and both natural and synthetic chemicals that are structurally related to vitamin A, but may not necessarily have vitamin A-like biologic activity. Its oxidized metabolites, retinaldehyde and retinoic acid (vitamin A acid) are biologically active compounds. It is the chemical name given to vitamin A. It is the transport form and, as retinol ester, also the storage form.
- Carotenoids: There are more than 600 carotenoids in nature, and approximately 50 of these can be metabolized to vitamin A. The most common carotenoid in the food having provitamin A activity is β-Carotene. Major portions of carotenoids are absorbed as such and are stored in liver and fat.
Sources of Vitamin A
- Animal-derived foods: Preformed retinol is found only in foods of animal origin. Food source include liver, fish, milk, eggs, butter, and cheese.
- Yellow and green leafy vegetables: Vegetable sources of provitamins A carotenoids include dark green and deeply colored fruits and vegetables. Moderate cooking of vegetables enhances carotenoid release for uptake in the gut.
- Absorption of carotenoid is facilitated by fat in a meal.
Functions of Vitamin A
Vitamin A has several metabolic roles. The main functions of vitamin A in human are as follows:
- Maintenance of normal vision: Vitamin A is essential for vision (especially dark adaptation).
- Host resistance to infections: Keratinization of mucous membranes in vitamin A deficiency adds up to the risk to infections. Retinol binding protein (RBP) is a negative ‘acute phase protein’.
- Immune function: Vitamin A has ability to stimulate the immune system. Retinoids are needed for normal growth, fetal development, fertility, hematopoiesis and immune function.
- Control of cell growth and differentiation: Maintenance of the surface linings of the eyes, epithelial cell growth and repair, and the epithelial integrity of the respiratory, urinary, and intestinal tracts. In vitamin A deficiency, mucus-secreting cells are replaced by keratin-producing cells and this process is known as squamous metaplasia.
- Regulation of lipid metabolism: It is a key regulator of fatty acid metabolism, including fatty acid oxidation in fat tissue and muscle, adipogenesis, and lipoprotein metabolism.
- Antioxidant: Retinoids, β-carotene, and some related carotenoids act as photoprotective and antioxidant agents.
- Other functions: Bone growth, reproduction and it also important for embryonic development and the regulation of adult genes.
- Tretinoin i.e. all-trans retinoic acid (ATRA) is also used to treat acute promyelocytic leukemia (APL), isotretinoin, is used to treat acne.
Vitamin A Deficiency (Table 1.1)
Effects in the eye:
- Bitot's spots: These areas of abnormal squamous cell proliferation and keratinization of the conjunctiva can be seen in young children with vitamin A deficiency (VAD).
- Poor adaptation to darkness (nyctalopia): Can lead to night blindness, which is an early symptom.
- Xerophthalmia (dry eye): Results from keratinization of the conjunctiva.
- Keratomalacia: In advanced deficiency; the cornea becomes hazy and can develop erosions, which can lead to its destruction (keratomalacia).
Increased susceptibility to infections:
Keratinization of the mucous membranes of respiratory tracts and urinary tract takes place, increasing the susceptibility to infections (e.g. respiratory infections).
Other features: Fatigue, anemia, diarrhea, decreased growth rate, decreased bone development and infertility.
- Serum retinol level: Normal range is 28 to 86 μg/dL (1 to 3 µmol/L). The level decreases in vitamin A deficiency.
- Albumin levels are indirect measures of vitamin A levels.
- Complete blood count (CBC) with differential count to be done if there is a possibility of anemia, infection, or sepsis.
- It is mainly on the basis of the clinical features.
- Blood levels of vitamin A will usually be low.
- Response to replacement therapy is the best way for the diagnosis.
Prophylactic vitamin A dose of 60 mg every 6 months is recommended in high-risk individuals and patients with malabsorption syndrome require vitamin A supplements.
Prophylactic supplements of vitamin A palmitate in oil
- Children between 1 and 5 years of age: 60,000 RAE (retinol activity equivalents) (200,000 IU) per oral every 6 month
- Infants < 6 months: can be given a one-time dose of 15,000 RAE (50,000 IU)
- 6 to 12 months: can be given a one-time dose of 30,000 RAE (100,000 IU).
Vitamin A Toxicity
Q. Write short essay/note on hypervitaminosis A and its signs.
- Types of toxicity: Vitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both types cause headache and increased intracranial pressure (pseudotumor cerebri).
- Acute toxicity also causes nausea and vomiting. Single doses of 300 mg in adults or 100 mg in children can be harmful.
- Chronic toxicity also causes changes in skin, hair (loss), and nails; liver and bone damage; double vision, ataxia, hyperlipidemia and vomiting.
- Retinol is teratogenic and incidence of birth defects in infants is high with vitamin A intakes of >3 mg a day during pregnancy.
- Diagnosis is usually clinical. Unless birth defects are present, adjusting the dose almost always leads to complete recovery.
Recommended dietary allowances (RDAs)/adequate intake of fat soluble vitamins for individuals (Table 1.2).
Carotenemia is common among infants and toddlers who eat large amounts of carrots and green leafy vegetables. It can be confused with jaundice, but discoloration of skin spontaneously resolves once the intake of food is reduced.
VITAMIN B COMPLEX
Thiamine is an important water-soluble vitamin.
- Involved in carbohydrate, fat, amino acid, glucose, and alcohol metabolism.
- Vitamin B1 is essential for the coenzyme, thiamine pyrophosphate (TPP). It is required for the following reactions:
- Decarboxylation of pyruvate (glycolytic pathway) to acetyl CoA (Krebs cycle)
- Transketolase in the hexose monophosphate (HMP/pentose) shunt pathway
- Decarboxylation of α-ketoglutarate to succinate (Krebs cycle).
- Has an additional role in neuronal conduction.
- These vitamins can be produced by plants and some microorganisms. However, animals cannot synthesize them.
- Human beings require thiamine from diet, though small amounts may be obtained from synthesis by intestinal bacteria.
- Whole wheat flour, unpolished rice, cereals, grains, beans, nuts and yeast are the good sources of thiamine. Milled rice and grains contain little or no thiamine. Thus, thiamine deficiency is more common in individuals who rely heavily on a rice-based diet.
- It is also present in liver, meat and eggs.
- Up to 30 mg of thiamine can be stored in body tissues. Required daily allowance (RDA) is 1–1.5 mg/day
- Requirement increases with increased carbohydrate intake, pregnancy and lactation, smoking, alcoholism, prolonged antibiotic intake, serious or prolonged illness.
Causes of Thiamine Deficiency (Table 1.3) Consequences of Thiamine Deficiency
Impaired glucose oxidation
- Cells cannot metabolize glucose aerobically to generate energy as ATP. Neuronal cells are most susceptible, since they depend almost exclusively on glucose for energy requirements.
- Causes an accumulation of pyruvic and lactic acids, which produce vasodilatation and increased cardiac output.
Clinical Syndromes of Thiamine Deficiency (Table 1.4)
Q. Write short essay/note on clinical features of beriberi/vitamin B1 (thiamine) deficiency.
- Wet (cardiovascular) beriberi: Wet beriberi is the term used for the cardiovascular involvement of thiamine deficiency.
- First effects are vasodilatation, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis.
- Edema: Initially, there is edema of the legs, but later it can involve the whole body, with ascites and pleural effusions. Edema is caused by the metabolites such as pyruvate and lactate, which cause extreme peripheral vasodilatation and leakage of fluid through capillaries. Vasodilatation can continue, sometimes resulting in shock.Infantile beriberi occurs in infants (usually by age 3 to 4 weeks) who are breastfed by thiamine-deficient mothers. Heart failure can suddenly develop and present with edema, aphonia, tachycardia, tachypnea and absent deep tendon reflexes. If prompt treatment is not given, death occurs quickly. Treatment is to give thiamine to the nursing mother, which passes to the infant through the breast milk.Shoshin beriberi: A more rapid form of wet beriberi is termed acute fulminant cardiovascular beriberi, or Shoshin beriberi. The predominant injury is to the heart, and rapid deterioration follows the inability of the heart muscle to satisfy the body's demands because of its own injury. The patient does not develop edema but may develop cyanosis of the hands and feet, distension of neck veins, tachycardia, veins, restlessness, and anxiety.
- Dry beriberi: Dry beriberi usually presents insidiously with symmetrical peripheral neuropathy.
- Initial symptoms: They are bilateral and roughly symmetric and include heaviness and stiffness of the legs.
- Later: Weakness, numbness, and pins and needles (occurring in a stocking-glove distribution).
- Distribution of neuropathy: They affect predominantly the lower extremities, beginning with paresthesias in the toes, burning in the feet (severe at night), muscle cramps in the calves, pains in the legs, and plantar dysesthesias.
- Physical signs: Calf muscle tenderness, difficulty rising from a squatting position, and decreased vibratory sensation in the toes. The ankle jerk reflexes are lost.
- Histological examination of involved nerve shows noninflammatory degeneration of myelin sheaths (demyelination).
- Continued deficiency worsens polyneuropathy and can eventually involve the nerves of the arms (wrist and/or foot drop). Deficiency may also cause degeneration of thalamus, mammillary bodies, and cerebellum.Biochemical tests:
- Measurement of thiamine, pyruvate and lactate levels in blood.
- Transketolase activity of whole blood or erythrocyte.
Q. Write short essay/note on management/treatment of beriberi/vitamin B1 (thiamine) deficiency.
Q. Write short essay/note on Wernicke's encephalopathy.
- Wernicke's encephalopathy: It is an acute neuropsychiatric condition due to an initially reversible biochemical brain lesion caused by depletion of vitamin B1 (thiamine).Causes (refer Table 1.3)Clinical features:
- Wernicke's encephalopathy (WE) is a triad of nystagmus, ophthalmoplegia, and ataxia, along with confusion. Impairment in the synthesis of one of the important enzymes of the pentose phosphate pathway (erythrocyte transketolase) may explain such a predisposition.
- Encephalopathy characterized by profound disorientation, indifference, and inattentiveness, impaired memory and learning are also evident. In untreated patients will progress through stupor and coma to death.
- Oculomotor dysfunction: Nystagmus, lateral rectus palsy, and conjugate gaze palsies reflect lesions of the oculomotor, abducens, and vestibular nuclei.
- Gait ataxia: Ataxia primarily involves stance and gait and is likely due to a combination of polyneuropathy, cerebellar involvement, and vestibular dysfunction.
Diagnosis: Diagnosis is confirmed by measurement of the circulating thiamine concentration or transketolase activity in red cells using fresh heparinized blood.
- Korsakoff's psychosis/syndromeQ. Write short note on Korsakoff's psychosis/syndrome.
- Korsakoff's psychosis (KS) is caused by deficiency of thiamine with involvement of central nervous system.
- Memory disturbances: It is predominantly associated with defect in retentive memory (severe defect in storing new information and learning). Thus, there are disturbances of short-term memory. There is marked deficits in anterograde and retrograde memory, apathy, an intact sensorium, and relative preservation of long-term memory and other cognitive skills.
- Confabulation: It presents clinically by hallucinations and confabulation (in some but not all cases). Confabulation is a memory disturbance, characterized by the production of fabricated, distorted or misinterpreted memories about oneself or the world, without the conscious intention to deceive. Attention and social behavior are relatively preserved. Affected individuals can carry on a socially appropriate conversation that may seem normal to an unsuspecting spectator.
- The syndrome is common in chronic alcoholics but may also be seen with thiamine deficiency resulting from gastric disorders, including carcinoma, chronic gastritis, or persistent vomiting.
- Outcome: Varies. Complete or almost complete recovery occurs in less than 20% of patients. In the remainder of patients, the recovery is gradual and incomplete.
- Leigh syndrome: Thiamine deficiency may be associated with a progressive subacute necrotizing encephalomyopathy. It is a sporadic mitochondrial disorder with a subacute neurologic course. Symptoms include ataxia, dysarthria, areflexia, disorders of movement, atrophy of muscle and weakness.
Q. Write short essay/note on clinical features and management of niacin deficiency (pellagra).
Vitamin B3 niacin (nicotinamide) deficiency causes metabolic encephalopathy called pellagra. It is found mostly in populations in which corn is the major source of energy in parts of China, Africa, and India. Pellagra means raw skin.
Pellagra has been easily remembered a disease of four Ds namely 1) dermatitis, 2) diarrhea, 3) dementia (depression) and 4) death. However, these features are not always observed and the mental changes are not a true dementia.
- Skin manifestations:
- Casal's necklace or collar rash: Characteristic skin rash develops that is hyperpigmented and scaling that develops in skin areas exposed to sunlight (similar in color to sunburn). This rash forms a ring around the neck and is termed as Casal's necklace.
- Dermatitis: Lesions of the skin may progress to vesiculation, cracking (ulceration), exudation and secondary infection.
- Symmetrical chronic thickening, dryness and pigmentation may be seen on the dorsal surfaces of the hands.
- GI tract:
- Diarrhea: It may be in part due to proctitis and in part due to malabsorption. It is often a feature accompanied by anorexia, nausea, glossitis and dysphagia indicating noninfective inflammation of the entire gastrointestinal tract.
- Other features include raw, painful, bright red tongue (glossitis), angular stomatitis, vaginitis, esophagitis, vertigo, and burning dysesthesias.
- Dementia: This occurs in chronic severe deficiency and may also develop hallucinations and acute psychosis. Milder deficiency may present with depression, apathy and sometimes thought disorders. Other neurologic symptoms include insomnia, anxiety, disorientation, tremor delusions, dementia, and encephalopathy.
- Diagnosis in endemic region depends on the clinical features. Other vitamin deficiencies can also produce similar changes (e.g. angular stomatitis).
- Dramatic improvement: The response is usually rapid in the skin (within 24 hours), diarrhea and a striking improvement occurs in the patient's mental state occurs with nicotinamide treatment.
Vitamin B12 and Folic acid discussed under Chapter 8.
Q. Write short essay/note on vitamin C and clinical features of scurvy.
Vitamin C (ascorbic acid) is a water-soluble vitamin
- Formation of collagen from procollagen. It is essential for wound healing and facilitates recovery from burns. It is needed for hydroxylation of proline to hydroxyproline (in protocollagen) and lysine to hydroxylysine (in mature collagen).
- Antioxidant properties: Ascorbic acid is the most active powerful reducing agent controlling the redox potential within cells.
- It is involved in intracellular electron transfer and supports immune function.
- Promotes absorption of nonheme iron.
- It is needed for the formation of carnitine, hormones, and amino acids.
- Formation of intercellular cement substances in connective tissues, bones, and dentin, when defective, resulting in weakened capillaries with subsequent hemorrhage and defects in bone and related structures.
Causes of Vitamin C Deficiency
- Infants fed only on boiled cow's milk during the first year of life are at risk.
- Individuals, who do not eat vegetables such as elderly, people who live alone (singly) and chronic alcoholics.
- Pregnant and lactating women and those with thyrotoxicosis require more vitamin C because of increased utilization.
- Individuals at risk of deficiency:
- Anorexia nervosa or anorexia from other diseases such as AIDS or cancer
- Type 1 diabetes require increased vitamin C
- Patients undergoing peritoneal dialysis and hemodialysis
- Diseases of small intestine such as Crohn's, Whipple, and celiac disease.
Deficiency of Vitamin C-Scurvy
Scurvy is caused by deficiency of vitamin C.
Types of scurvy: Adult scurvy and infantile scurvy.
Clinical features of adult scurvy
- Early symptoms may be nonspecific, with malaise, weakness, lethargy and muscle pain (myalgias may be due to reduced production of carnitine).
- Bone disease: More common in growing children and manifests after 1–3 months. It is characterized by deranged formation of osteoid matrix and bone pain. Fractures, dislocations, and tenderness of bones are common in children.
- Hemorrhages: Hemorrhaging is a hallmark feature of scurvy and can occur in any organ. Hair follicles are one of the common sites of cutaneous bleeding. Marked tendency to bleed into the skin (easy bruising, petechiae, ecchymosed, perifollicular hemorrhages), bleeding into muscles, joints and underneath peritoneum. Bruising and hemorrhage may be spontaneous. Most commonly on the legs and buttocks where hydrostatic pressure is the greatest.
- Delayed/poor wound healing and breakdown of old scars.
- Anemia: It may cause high-output heart failure.
- Gums: Inflamed spongy gums (gum swelling) friability, bleeding and infection with loosening of teeth; mucosal petichiae are common.
- Skin changes: Roughness, keratosis of hair follicles with ‘corkscrew’ hair, perifollicular hemorrhages.
- Other features: Emotional changes, shortness of breath.
Clinical features of infantile scurvy (Barlow's disease)
- Subperiosteal hemorrhage into shafts of long bones.
- Scorbutic rosary denotes enlargement of costochondral junctions, which are tender. May be associated with pectus excavatum.
- Retrobulbar, subarachnoid and intracerebral hemorrhages.
- Painful limbs giving rise to ‘pseudoparalysis’.
Laboratory investigations and diagnosis
- Diagnosis is usually made clinically in a patient who has skin or gingival signs and is at risk of vitamin C deficiency.
- Plasma ascorbic acid is very low.
- Vitamin C level of <11 μmol/L (0.2 mg/100 mL).
- Anemia: It may be normochromic, normocytic (due to bleeding), megaloblastic (due to reduced erythropoiesis) and microcytic hypochromic anemia (due to impaired iron absorption and impaired heme synthesis).
- Capillary fragility test can be checked by inflating a blood pressure cuff and looking for petechiae on the forearm.
- Bleeding time, clotting time and Prothrombin time: To rule out other bleeding disorders.
- Imaging Studies: The findings include 1) loss of trabeculae results in a ground-glass appearance, 2) thinning of cortex, 3) a line of calcified, irregular cartilage (white line of Frankel) may be visible at the metaphysis, and 4) the epiphysis may be compressed.
Vitamin D is a fat-soluble vitamin. It is required for the maintenance of adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralization, and neuromuscular transmission.
Physiology (refer page 53 of Chapter 2)
Vitamin D exists in 2 activated sterol forms (Box 1.1).
Main steps of vitamin D metabolism
- Less effective as precursor to 1,25 (OH)2-Vit D
- In liver: Vitamin D (D3) is converted into 25-hydroxyvitamin D (25 (OH) D3) (calcidiol) by the action of 25-hydroxylases.
- The enzyme 1α-hydroxylase (mitochondrial cytochrome P450) converts 25-hydroxyvitamin D (25 (OH) D3) into 1,25-dihydroxyvitamin D, (1,25(OH)2D3) (calcitriol). Previously thought exclusively renal.
- Requires two factors
- 25OH-Vit D3-1-alpha-OHase
- Vitamin D receptor (VDR)
- Regulation of plasma levels of calcium and phosphorus: The main functions of 1, 25-dihydroxyvitamin D on calcium and phosphorus homeostasis are:
- Stimulates intestinal absorption of calcium: 1, 25-dihydroxyvitamin D stimulates intestinal absorption of calcium in the duodenum through the interaction of 1, 25-dihydroxyvitamin D with nuclear vitamin D receptor.
- Stimulates calcium reabsorption in the kidney: 1, 25-dihydroxyvitamin D increases calcium influx in distal tubules of the kidney.
- Interaction with PTH in the regulation of blood calcium.
- Mineralization of bone: Vitamin D plays a role in the mineralization of osteoid matrix and epiphyseal cartilage in both flat and long bones. Vitamin D stimulates osteoblasts to produce the calcium-binding protein osteocalcin, which is involved in the deposition of calcium during development of bone.
- Immunomodulatory: Vitamin D is involved in the innate and adaptive immune system.
Vitamin D Deficiency
Q. Write briefly on clinical features, investigations, treatment and prevention of rickets.
Causes of Vitamin D Deficiency (Box 1.2)
- In children: Deficiency of vitamin D in a growing child before the epiphyses has fused results in failure of growing bone to mineralize.
- Rickets: Bone softening disease, deformity of long bones occurs.
- In adults:
- Osteomalacia: Bone thinning disorder, proximal muscle weakness and bone fragility.
- Osteoporosis: Decrease of bone mineralization and increased bone fragility.
Rickets in Children (Fig. 1.1)
In children, before the closure of epiphyses, vitamin D deficiency causes retardation of growth associated with an expansion of the growth plate known as rickets.
Gross skeletal changes in rickets
It depends on the severity and duration of the vitamin D deficiency and also the stresses to which individual bones are subjected.
During the nonambulatory stage of infancy
- Craniotabes: The skull appears square and box-like. Delayed closure of anterior fontanelle, frontal and parietal bossing.
- Frontal bossing: Excess of osteoid produces frontal bossing and a squared appearance to the head.
- Delayed eruption of primary teeth, enamel defects and caries teeth.
- Rachitic rosary: Overgrowth of cartilage or osteoid tissue at the costochondral junction causes deformation of the chest producing the ‘rachitic rosary’.
- Pigeon breast/chest deformity: The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward. This creates anterior protrusion of the sternum producing pigeon breast deformity (pectus carinatum).
- Harrison's sulcus/groove: It is due to the muscular pull of the diaphragmatic attachments to the lower ribs.
- Respiratory infections and atelectasis.
During the nonambulatory stage
- Lumbar lordosis: This occurs when an ambulating child develops rickets. It is characterized by deformities affecting the spine, pelvis, and tibia. Scoliosis, kyphosis and lordosis.
- Bowing of the legs: Due to affection of tibia, knock knees, anterior curving of legs.
- Seizures and tetany: Secondary to hypocalcemia in Vitamin D deficiency rickets and VDDR type 1.
- Hypotonia and delayed motor development: In rickets developing during infancy.
- Protuberant abdomen, bone pain, waddling gait and fatigue.
- Asymptomatic: Detected on radiological evaluation.
- Wrist radiograph: Findings include 1) lower ends of the shaft of radius and ulna become splayed, 2) epiphyseal surfaces—fuzzy and ill-defined, and 3) unossified zone between shaft and radial epiphysis—widened (‘saucer’ deformity).
- Serum calcium: Low
- Serum phosphate: Low (due to associated secondary hyperparathyroidism).
- Serum alkaline phosphatase: Increased due to increased osteoblast activity.
- Plasma 25-hydroxyvitamin D3 level: Low in most of the cases.
- Adequate consumption of vitamin D (1000-5000 IU/day).
- Adequate exposure to sunlight (from 30 minutes to 2 hours/week for infants).
Q. Discuss the causes, clinical features, investigations and treatment in case of osteomalacia.
- Vitamin D deficiency in adults is accompanied by hypocalcemia and hypophosphatemia which result in impaired (hypo/under/inadequately) mineralization of bone matrix proteins, a condition known as osteomalacia. Thus, osteomalacia is a disorder of mineralization of the organic matrix of the skeleton in adults when the epiphyseal growth plates have closed. In contrast, in rickets, the growing skeleton is involved.
- Hypomineralized bone matrix is biomechanically inferior (weak) to normal bone. This bone is prone to bowing and gross skeletal fractures or microfractures which are most likely to affect vertebral bodies and femoral neck.
Many disorders (Table 1.5) can result in osteomalacia, mainly through alteration in vitamin D metabolism or because of phosphate wasting.
- Bone pains, muscle weakness, fractures of bones with minor trauma.
- Pain in the hip may cause antalgic gait.
- Weakness of proximal muscle results in wadding gait and may resemble primary muscle disease.
- Collapse of vertebrae causes local pain and deformity.
- Softening of skeleton may produce deformities such as kyphosis, coxa vara, pigeon chest and triradiate pelvis with a narrow public arch.
- Serum calcium: Low or normal. Secondary hyperparathyroidism releases calcium from bone and increased resorption of calcium by the kidney. This results in maintenance of normal serum calcium in most patients.
- Serum phosphorus: Low.
- Serum alkaline phosphatase: Raised.
- Serum 25-hydroxyvitamin D3 levels: Low (<30 ng/mL).
- PTH levels: Raised.
Urinary excretion of calcium: Reduced
- Bone density: Reduced (osteopenia).
- Epiphyseal growth plate: Increased in thickness, cupped and hazy at the metaphyseal border.
- Cortical thinning: Due to secondary hyperparathyroidism.
- Other features: Presence of nontraumatic fractures, radiolucent bands called pseudofractures (Looser's zones).
- Bone mineral density as assessed by dual-energy X-ray absorptiometry (DEXA) is reduced at spine, hip and forearm, with the maximum deficits at the cortical-rich bone in the forearms.
Q. Write short answer on hypervitaminosis D.
Hypervitaminosis D causes hypercalcemia, which manifest as 1) nausea and vomiting, 2) excessive thirst and polyuria, 3) severe itching, 4) joint and muscle pains, 5) disorientation and coma, and 6) metastatic calcifications.
- Trace elements are elements which occur or function in living tissues in concentrations most conveniently expressed in µg/l
- The term ‘trace’ is used to concentrations of element not exceeding 250 µg/gram of extracellular matrix. Trace elements are naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100 mg/day
- Bioavailability of minerals is low in vegetarian diet and excess amounts are injurious to health.
Classification of Trace Elements (Box 1.3)
- There are about 15 trace elements of which only 10 are essential nutrients in humans. These include: Iron, zinc, copper, chromium, selenium, iodine, fluorine, manganese, molybdenum and cobalt.
- Biochemical functions of trace elements: Acts as components of prosthetic groups or as cofactors for enzymes.
Q. Write short note on daily requirement of iron and important dietary sources of iron.
- Most essential trace element.
- Iron distribution in healthy young adults is given in Table 1.6.
- Daily body requirement: 0.5–2 mg/day, 3–5 mg/day (pregnancy).
- Daily excretion: 0.9 mg/day, 1.3 mg/day (during menses).
- Site of absorption: From the duodenum and proximal jejunum.
- Deficiency state:
- Anemia, (discussed under chapter 8) weakness, headache, irritability, and varying degrees of fatigue and exercise intolerance.
Acute Iron Poisoning
- Develops when iron level is exceeds 60 mg/kg elemental iron
- Clinical features: Vomiting, abdominal pain, bloody diarrhea, shock, dehydration, cyanosis, acidosis, and coma. Can cause hepatotoxicity and bowel obstruction.
Q. Write short note on fluorosis and its radiological signs.
- Fluorine: Fluorine's ionic form is known as fluoride. It is component of bone mineral and alters its physical characteristics. Fluoride helps to prevent dental caries, because it increases the resistance of the enamel to acid attack. Requirement in adults is between 1.5 and 4 mg/day and 96% of fluorides in the body found in bone and teeth.
- Deficiency: Intake of <0.1 mg/day in infants and <0.5 mg/day in children predisposes to an increased incidence of dental caries.
- Toxicity: Results in fluorosis. This develops when fluoride content in the water is high (>3 to 5 ppm).
- Acute ingestion of >30 mg/kg body weight usually manifests with gastrointestinal symptoms like diarrhea, vomiting leading to renal failure and may cause death.
- Dental fluorosis: It is characterized by mottling of teeth where the enamel loses its luster, appears teeth chalky white with transverse yellow bands. It becomes rough, pigmented, pitted and brittle (fluorite teeth).
- Skeletal fluorosis: Its features are:
- Sclerosis of bones (especially of spine, pelvis and limbs).
- Calcification of ligaments, interosseous membrane and tendinous insertions.
- Osteoporosis with brittle bones.
- Severe pain and stiffness in joints, stiffness in neck and backbone, bow legs. Other features are weakness, anemia and weight loss.
Q. Write short note on angular stomatitis.
- Angular stomatitis refers to cracking of the epithelium at the edge of the lips. It presents with erythema, maceration, scaling, and fissuring at the corners of the mouth. Most commonly bilateral and very painful.
- Causes of angular stomatitis (Table 1.7)
ENTERAL AND PARENTERAL NUTRITION SUPPORT
Some form of nutritional support is needed for patients who cannot eat, should not eat, will not eat or cannot eat enough.
Indications for Nutritional Support
- Severely malnourished patients on admission to hospital
- Moderately malnourished patients who are not expected to eat for more than 3–5 days (because of their physical illness).
- Normally nourished patients not expected to eat for more than 5 days or to eat less than half their intake for more than 8–10 days.
Types of Nutritional Support
- Enteral nutrition should be used if the gastrointestinal tract is functioning normally.
- Parenteral nutrition.
Enteral Nutrition (EN)
- Patients who are not able to swallow may need artificial nutritional support (e.g. after acute stroke or throat surgery, or long-term neurological disorders such as motor neuron disease and multiple sclerosis).
- Whenever possible, the enteral route should be used.
Nutritional support via placement of tubes through the nose, esophagus, stomach, or intestines (duodenum or jejunum).
Prerequisite: Must have functioning GI tract.
Advantages and disadvantages of enteral nutrition (Table 1.8)
Methods of enteral nutrition (Table 1.9)
Complications of enteral feeding: 1) Access problems (e.g. tube obstruction), 2) Administration problems (e.g. aspiration pneumonia), 3) Gastrointestinal complications (e.g. diarrhea), 4) Metabolic complications (e.g. overhydration).
Rate and method of delivery*
- Bolus: 300 to 400 mL rapid delivery via syringe several times daily
- Intermittent: 300 to 400 mL, over 20 to 30 minutes, several times/day via gravity drip or syringe
- Cyclic: via pump usually at night
- Continuous: via gravity drip or infusion pump.
*Determined by medical status, feeding route and volume, and nutritional goals.
Q. Write short essay/note on total parenteral nutrition.
- Central access: Total pareneteral nutrition (TPN) both long- and short-term placement.
- Peripheral parenteral nutrition (PPN).
Venous sites from which the superior vena cava may be accessed are subclavian vein, internal or external jugular vein, axillary vein, brachial vein, basilic vein and cephalic vein.
Advantages and disadvantages of parenteral nutrition (Table 1.10)
Indications for total parenteral nutrition (Table 1.11)
Complications of parenteral nutrition (Table 1.12)
Definition: Refeeding syndrome is a syndrome consisting of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished.
Time of occurrence: Usually occurs within 4 days of restarting nutritional support.
- When nutritional support is given to a starved or severely malnourished patient, there is a rapid change from a catabolic to an anabolic state.
- Administration of carbohydrates stimulates release of insulin. This causes cellular uptake of phosphate, potassium and magnesium and may lead to significant falls in their levels in the serum. This results in electrolyte imbalance and can produce serious consequences (e.g. cardiac arrhythmias).
- Initial features may be nonspecific.
- Later: Rhabdomyolysis, leucocyte dysfunction, respiratory and cardiac failure, hypotension, arrhythmias, seizures, coma and sudden death.
- Underdiagnosed and undertreated, but treatable.
Protein-energy malnutrition (PEM) or protein-calorie malnutrition refers to a group of malnutrition where there is inadequate calorie or protein intake. Severe PEM is a serious, often lethal disease and usually affects children of low-income countries. PEM include marasmus, kwashiorkor and intermediate states of marasmus-kwashiorkor.
Q. Write short note on marasmus
- Marasmus is the childhood form of starvation. It develops due to inadequate intake of protein and calories.
- It is characterized by emaciation with obvious muscle wasting and loss of body fat. There is no edema. The hair is thin and dry. The marasmic child does not appear as apathetic or anorexic as with kwashiorkor. Diarrhea is frequent and there may be signs of infection.
- Inadequate protein intake: Kwashiorkor develops due to an inadequate protein intake with reasonable caloric (energy) intake.
- Kwashiorkor occurs in a young child displaced from breastfeeding by a new baby. It is may be precipitated by infections (e.g. measles, malaria and diarrheal illnesses). Child appears apathetic and lethargic with severe anorexia.
- Edema: In kwashiorkor, marked protein deprivation causes hypoalbuminemia leading to generalized or dependent edema.
- Skin lesions: Children with kwashiorkor have characteristic skin lesions. This consists of alternating zones of hyperpigmentation, and hypopigmentation, producing ‘flaky paint’ appearance.
- Hair changes: The hair is dry and sparse. There may be loss of color or alternating bands of pale and darker hair (Flag sign).
- Other features: The other features that differentiate kwashiorkor from marasmus are:
- Abdomen is distended due to hepatomegaly (presence of enlarged, fatty liver) and/or ascites.
- Development of apathy, listlessness, and loss of appetite.
- Likely presence of vitamin deficiencies.
- Defects in immunity and secondary infections.
Differences between Kwashiorkor and Marasmus are listed in Table 1.13.
Q. Describe the risk factors, clinical features, complications and management of obesity.
Definition: Obesity is defined as an accumulation of excess body fat (adipose tissue) that is of sufficient magnitude to impair health. Latin word ‘obesus’ meaning stout, fat, plump.
Prevalence of obesity: Obesity is a major health problem in developed countries and an emerging health problem in developing countries, such as India.
Classification of Overweight and Obesity by Body Mass Index (Table 1.14)
Types of Obesity According to Body Fat Distribution
The distribution of the stored fat is importance in obesity and accordingly obesity is divided into:
- Central (‘abdominal’, ‘visceral’, ‘android’ or ‘apple-shaped’) obesity: This type of obesity shows increased accumulation of fat in the trunk and in the abdominal cavity/intra-abdominal (in the mesentery and around viscera). It is associated with a greater risk for several diseases (e.g. type 2 diabetes, the metabolic syndrome and cardiovascular disease) than generalized obesity.
- Generalized (‘gynoid’ or ‘pear-shaped’) obesity: This type is characterized by excess accumulation of fat diffusely in the subcutaneous tissue.
Q. Write short essay/note on causes of obesity.
Accumulation of fat in obesity can be considered by the result of caloric imbalance between the energy consumption (intake of calories) in the diet and energy expenditure through exercise and bodily functions. However, the pathogenesis of obesity is complex and incompletely known.
- Genetic aspects of human obesity:
- Obesity is a polygenic disorder, with small contributions from a number of different genes.
- Single-gene (monogenic forms) disorders are rare and produce severe childhood obesity. These include mutations in the leptin gene and leptin receptor gene, mutations of POMC (Proopiomelanocortin), Mc4R (melanocortin-4 receptor) genes.
- A few genetic conditions in which obesity is a feature include the Prader–Willi and Laurence–Moon–Biedl syndromes.
- Environmental contributors to human obesity:
- Food: Many environmental factors can influence food intake. Increased consumption of energy-dense foods, larger food portion size, and increased variety of food, increased availability, reduced cost and increased caloric beverages (soft drinks, juices) promote obesity.
- Physical activity: It can be divided into three categories: (1) exercise (fitness and sports-related activities); (2) work-related physical activity; and (3) non-exercise, non-employment (spontaneous) activity. Increased sedentary behavior, reduced activities of daily living and decreased employment physical activity promote obesity.
- Reversible causes of obesity and weight gain:
- Minority of patients presenting with obesity have specific cause which can be identified and treated (Table 1.15). Compared to idiopathic obesity, these patients have short history of marked weight gain.
Pathogenesis (Fig. 1.2)
Body weight regulation (regulation of energy balance) or dysregulation depends on a complex interplay of both hormonal/endocrine and neural mechanism that control appetite and satiety. Neurohumoral mechanisms can be subdivided into three components.
1. Peripheral Afferent System
Peripheral afferent system can be further subdivided into peripheral appetite suppressing signals and peripheral appetite stimulant signals.
Peripheral appetite suppressing signals
- Leptin (Greek term leptos, meaning ‘thin’.) Leptin is a hormone secreted by fat cells and it stimulates POMC/CART pathway (Fig. 1.3) and inhibits NPY/AgRP pathway and appetite is suppressed (anorexigenic). Increased leptin stimulates physical activity, heat production (thermogenesis), and energy expenditure.
- Adiponectin: It is a hormone (fat-burning molecule) and the ‘guardian angel against obesity,’ and is produced mainly by fat cells (adipocytes). Its levels are lower in obese.
- Resistin: Primarily produced by macrophages and not fat cells. It causes insulin resistance.
- Gut hormones: These include PYY, pancreatic polypeptide, insulin, and amylin.
- Insulin: It is secreted by cells of the pancreas and act centrally to activate the appetite suppressing pathway.
- Peptide YY (PYY): It is secreted by the endocrine cells (L cells) in the ileum and colon. It reduces appetite. Other peripheral appetite suppressing signals include glucagon-like peptide 1 (GLP1) and oxyntomodulin.
- Amylin: It is a peptide secreted with insulin from pancreatic β-cells.
Peripheral appetite stimulating signals
- Gut hormones:
- Ghrelin: It is produced by the oxyntic cells of the fundus of the stomach and in the arcuate nucleus of the hypothalamus. Ghrelin increases food intake (orexigenic effect) and stimulates appetite by activating the central appetite stimulating NPY/AgRP pathway.Fig. 1.2: Regulation of energy balance. Peripheral afferent system (appetite suppressing and stimulating signals) influences the activity of the hypothalamus, which is the central regulator of appetite and satiety. Signals from hypothalamus in turn act on peripheral efferent system (food intake and energy expenditure). See text for details.
- Retinol binding protein 4 (RBP4): Secreted by fat cells. Its actions counteract with those of insulin. Raised levels of RBP4 found in Type 2 diabetes mellitus.
2. Central Processing (Table 1.16)
The arcuate nucleus of the hypothalamus processes and integrates neurohumoral peripheral afferent signals and generates efferent signals. It consists of:
a) Central appetite suppressing (anorexigenic pathway or leptin melanocortin pathway)
- In this pathway, POMC (pro-opiomelanocortin)/CART (cocaine and amphetamine-regulated transcripts) neurons enhance energy expenditure and weight loss through the production of the anorexigenic (suppresses appetite) neuropeptides mainly αMSH (α-melanocyte stimulating hormone) by cleavage of POMC by PC1 (prohormone convertase).
- It exerts its appetite suppressing action via the activation of the melanocortin receptors 3 and 4 (MC3/4R) in second-order neurons.
- Second order neurons in turn produce factors such as thyroid releasing hormone (TSH) and corticotropin releasing hormone (CRH) that increase the basal metabolic rate and anabolic metabolism, thus regulate food intake favoring weight loss.
b) Central appetite stimulating (orexigenic) pathway: It consists of:
- NPY (neuropeptide Y)/AgRP (agouti-related peptide) containg neurons promote food intake (orexigenic effect) and weight gain, through the activation of Y1/5 receptors in secondary neurons.
- Secondary neurons in turn release factors such as melanin-concentrating hormone (MCH) and orexin, which stimulate appetite. This pathway also decreases energy expenditure.
These pathways interact with each other and communicate with other parts of the brain, and influence the autonomic nervous system and ingestive behavior. These central pathways are in turn influenced by a variety of peripheral signals discussed above.
3. Peripheral Efferent System
It is organized into two pathways namely anabolic and catabolic that control food intake and energy expenditure, respectively.
Energy intake (Food intake)
- Food: The increase in obesity can be related to the type of food consumed (i.e. food containing sugar and fat) and also psychological factors.
- Control of appetite: Signals may affect different aspects of eating behavior. For example
- Ghrelin (peptide produced by the stomach) increases hunger but does not affect satiation or satiety.
- Cholecystokinin causes satiation, but has no effect on satiety.
- Leptin act on multiple pathways, its deficiency causes increased hunger and reduced satiation and satiety.
- Following a meal, substances such as cholecystokinin (CCK), bombesin, and glucagonlike peptide 1 (GLP1) are released from the small intestine, and glucagon and insulin from the pancreas. These hormones are involved in the control of satiety. The control of appetite is extremely complex. Many transmitters in the central nervous system affect appetite:
- Appetite inhibitors: dopamine, serotonin, γ-aminobutyric acid
- Appetite stimulators: e.g. opioids
- Regulation of food intake by central nervous system (Table 1.16).
It can be divided into resting (or basal) metabolic rate, the thermic effect of food, and physical activity energy expenditure.
- Resting basal metabolic rate (BMR): BMR is the energy expenditure and accounts for about 70% of daily energy expenditure, whereas active physical activity contributes to 5–10% of energy expenditure.
- Physical activity: Obese individuals tend to spend more energy during physical activity as they have a larger mass to move.
Pathologic Consequences of Obesity (Complications of Obesity)
Q. Write short essay/note on complications of obesity.
Morbidity and mortality: Obesity is associated with an increase in mortality and morbidity. Obese individuals are at risk of early death, mainly from diabetes, coronary heart disease and cerebrovascular disease.
Metabolic Complications of Obesity
Central obesity or upper body fat distribution is associated with increased concentration of FFA (free fatty acid) which can produce several metabolic complications of obesity.
Insulin resistance and type 2 diabetes mellitus
- Insulin resistance is the decrease/failure of target (peripheral) tissues to insulin action. Insulin resistance can develop in obesity and may produce type 2 diabetes mellitus. Central/upper body/visceral obesity are found in more than 80% of patients with type 2 diabetes.
- Causes of insulin resistance in obesity:
- Obese individuals have excess circulating free fatty acids (FFAs) and there is an inverse correlation between fasting plasma FFAs and insulin sensitivity. Central obesity is associated with insulin resistance. Excess intracellular FFAs increases gluconeogenesis.
- Adipokines: Adipose tissue acts as a functional endocrine organ and secrets variety of proteins into the systemic circulation, which are termed adipokines (or adipose cytokines). In obesity, adiponectin (one of the adipokines) levels are reduced, which contributes to insulin resistance.
- Consequences of insulin resistance (Box 1.4)
- Upper body obesity and type 2 diabetes mellitus are associated with an atherogenic lipid profile. Dyslipidemia includes increased triglycerides, increased low-density lipoprotein (LDL) cholesterol with very low density lipoprotein (VLDL) cholesterol, decreased high-density lipoprotein (HDL) cholesterol, and decreased levels of the vascular protective adipokine adiponectin.
- Dyslipidemia increases the risk of cardiovascular diseases (atherosclerosis, cardiomyopathy) in the metabolic syndrome (Fig. 1.4).
Endocrine Manifestations of Obesity
Reproductive disorders associated with obesity are listed in Table 1.17.
Mechanical Complications of Obesity
Q. Write short essay/note on mechanical complications of obesity.
- Osteoarthritis: Excessive body weight in obesity predisposes to increased prevalence of lower extremity degenerative joint disease (osteoarthritis) and also gout.
- Venous stasis/varicose veins
- Acanthosis nigricans: It manifests as darkening and thickening of the skinfolds on the neck, elbows, axilla and dorsal interphalangeal spaces. It reflects the severity of underlying insulin resistance.
- Urinary incontinence
- These include reduced chest wall compliance, increased work of breathing, increased minute ventilation (due to increased metabolic rate), and decreased functional residual capacity and expiratory reserve volume.
- Obstructive sleep apnea: Sleep apnea is common in patients with severe obesity. Sleep apnea can be obstructive (most common), central, or mixed and is often associated with an increased risk of hypertension, right heart failure and sudden death.
- Obesity and asthma: Reduced TLC (total lung capacity), reduced RV (residual volume) and FRC (functional residual capacity).
Obesity and Cancer (Table 1.18)
- Obesity is the biggest preventable cause of cancer after smoking. Accounts for 14% of cancer deaths in men and 20% in women.
Following are more prevalent in obese patients:
- Gastroesophageal reflux disease
- Gallstones: Obesity is associated with increased secretion of cholesterol in the bile, super saturation of bile, and a higher incidence of gallstones, especially cholesterol gallstones.
- Fatty liver (steatosis) and nonalcoholic steatohepatitis (NAFLD): NAFLD can progress to hepatic cirrhosis and rarely to hepatocellular carcinoma.
Obesity and Retinal Disease
- Overweight diabetics are twice more likely to develop retinopathy than non obese.
- Waist to hip ratio was only second to glycemic control in its importance in preventing retinopathy in studies.
Conditions and complications associated with obesity are summarized in Table 1.19.
Clinical Assessment, Investigations and Diagnosis
Aims of assessing of obesity is to:
- Evaluate and severity of obesity: Severity of obesity can be quantified using the BMI (Table 1.14).
- Exclude an underlying cause
- Identify complications
- Prepare a management plan
Q. Write short essay/note on diseases for which obesity is a risk factor.
Q. Write short essay/note on management of obesity.
Types of Radiation
They are divided into two types:
- Ionizing radiation: Used in X-rays, computed tomography (CT), radionucleotide scans and radiotherapy. Radiations interact with atoms, and release energy and results in ionization which can cause molecular damage.
- Penetrating radiation: It includes uncharged neutrons or high-energy electromagnetic radiations such as X-rays and gamma (γ) rays. It affects the skin and deeper tissues.
- Nonpenetrating radiation: It includes charged subatomic alpha (α) and beta (β) particles.
- Non-ionizing radiations: Ultraviolet (UV) rays of sunlight visible light, laser, infrared and microwave. It affects only skin. Non-ionizing UV is used for therapy in skin diseases and laser therapy for diabetic retinopathy.
Dosage and Exposure
- Dosage: The dose of radiation depends on the energy absorbed by a unit mass of tissue. It is measured in joules per kilogram (J/kg); 1 J/kg = 1 gray (1 Gy) = 100 rads.
- It is measured in becquerels (Bq). 1 Bq is defined as the activity of a quantity of radioactive material in which one nucleus decays per second; 3.7 × 10 Bq = one curie (Ci) (older terminology was non SI unit).
- To take account of different types of radiation and variations in the sensitivity of various tissues, weighting factors are used to produce a unit of effective dose. Therefore, for measurement a dose equivalent called a sievert (Sv) is used. Sv value reflects the absorbed dose weighted for the damaging effects of a particular type of radiation and is most useful in evaluating the long-term effects of radiation exposure.
- Background radiation: It is exposure of humans to naturally occurring radioactivity (e.g. radon gas and cosmic radiation). Average annual background radiation is about 2.5 mSv per year (varies according to local geology). A chest X-ray delivers 0.02 move, and CT of the abdomen/pelvis about 10 mSv.
Effects of Radiation Exposure
Q. Write short essay/note on effects of radiation exposure.
Excessive exposure to ionizing radiation: It may occur accidently in industry, nuclear power plants and hospitals. It may be also due to deliberate nuclear explosions designed to eliminate populations and rarely by poisoning, e.g. with polonium.
- Radiation sickness:
Q. Write short note on radiation sickness.
- Mild acute radiation sickness: It is characterized by nausea, vomiting and malaise follow doses of about 1 Gy lymphopenia develops within several days, followed 2–3 weeks later by a fall in all WBCs and platelets.
- Acute radiation sickness: It involves several systems and the extent of damage depends on the dose of radiation. Commonly involved systems are hematopoietic, gastrointestinal, central nervous system and skin.
- Effects on the individual are classified as either deterministic or stochastic.
Deterministic (threshold) effects
- Intensity of exposure: Radiation effects depend on the type of radiation, the distribution of dose and the dose rate. The severity of deterministic effects is proportional to the dose of radiation above a threshold level.
- Tissue vulnerability:
- Tissue with labile cells: Tissues with actively dividing cells (labile cells), such as bone marrow and gastrointestinal mucosa, are more sensitive to ionising radiation.
- Hemopoietic system: Lymphocyte depletion is the most sensitive indicator of bone marrow injury and after exposure to a fatal dose, marrow aphasia is a commonest cause of death.
- Gastrointestinal mucosal toxicity: May cause death due to severe diarrhea, vomiting, dehydration and sepsis.
- Gonads: Highly radiosensitive and may cause temporary or permanent sterility.
- Eye: Cataracts.
- Skin: Radiation dermatitis (radiation burns) characterized by skin erythema, purpura, blistering and secondary infection may occur. Complete loss of body hair develops after an exposure > 5 Gy.
- Lung: Acute inflammatory reactions, pulmonary fibrosis.
- Central nervous system syndrome: Exposures of >30 Gy are followed rapidly by nausea, vomiting, disorientation and coma. Death due to cerebral edema can follow within 36 hours. It may also cause permanent neurological deficit.
- Thyroid gland due to its capacity to concentrate iodine is responsible for its susceptibility to damage even after exposure to relatively low doses of radioactive.
Stochastic (chance) effect is directly proportional to the dose of radiation.
- Carcinogenesis: It represents a stochastic effect. With acute exposures, leukemias (e.g. acute myeloid leukemia) may develop after a latent period of 2–5 years and solid tumors (e.g. skin, thyroid and salivary glands) after a latent period of about 10–20 years. Thereafter the incidence of cancer increases with time. Cancer risk depends on the amount of radiation received, the time to accumulate the total dose and the interval following exposure.
- Teratogenic effects.
Physiological Effects of High Altitude
- In high altitude, the proportions of oxygen, nitrogen and carbon dioxide in air do not change but their partial pressure falls in proportion to barometric pressure.
- At high altitude, oxygen tension is reduced within the lung alveoli. This result in a fall in arterial oxygen saturation.
Illnesses at High Altitude
Q. Write short essay/notes on mountain sickness.
Ascent to altitudes up to 2500 m or travel in a pressurized aircraft cabin is harmless to normal individuals. Above 2500 m high-altitude illnesses may develop in healthy individuals, and above 3500 m these commonly develop. Sudden ascent to altitudes above 6000 m (e.g. by aviators, balloonists and astronauts), may cause decompression sickness with the clinical features similar to in divers, or even loss of consciousness. However, most high altitude illness develops in travellers and mountaineers.
Acute mountain sickness (AMS)
Acute mountain sickness is a syndrome characterized by headache, fatigue, anorexia, nausea and vomiting, difficulty sleeping or dizziness. Ataxia and peripheral edema may be present.
- Etiology: Not fully understood. Probably hypoxemia increases cerebral blood flow and intracranial pressure.
- Symptoms: Develop within 6–12 hours of an ascent and vary in severity from trivial to completely incapacitating.
Chronic mountain sickness (Monge's disease)
- It occurs on long exposure to high altitude.
- Symptoms: Headache, poor concentration and signs of polycythemia.
- Physical examination: Cyanosis and clubbing of fingers.
High-altitude cerebral edema (HACE)
- High-altitude cerebral edema is a rare, life-threatening condition and usually proceeded by AMS.
- Symptoms: Ataxia and altered consciousness. In addition to features of AMS, the patient also develops confusion, disorientation, visual disturbance, lethargy and can lead to loss of consciousness.
High-altitude pulmonary edema (HAPE)
Q. Write short essay/notes on high altitude pulmonary edema.
- High-altitude pulmonary edema is a life-threatening condition.
- Time of occurrence: It usually occurs in the first 4 days after ascent above 2500 m. Unlike HACE, HAPE may develop de novo without the preceding signs of AMS.
- Initially, dry cough, exertional dyspnea and extreme fatigue. Later, the cough becomes wet and may be with blood-stained sputum.
- Tachycardia and tachypnea develop at rest. Crepitations may be heard in both lung fields. It may lead to severe hypoxemia, pulmonary hypertension.
- Radiologically show diffuse alveolar edema.
- Decreased arterial oxygen saturation.
High-altitude retinal hemorrhage
It may be found in about 30% of trekkers at 5000 m and is usually asymptomatic and resolve spontaneously. Visual defects can develop when the hemorrhage involves the macula. There is no specific treatment.
Can develop at altitudes over 6000 m. Risk factors are dehydration, inactivity, cold and use of oral contraceptive pill at high altitude.
Cough is common at high altitude and usually benign. Causes include breathing of dry, cold air and increased mouth breathing. It may be similar to cough that occurs in early HAPE.
Q. Write short note on lathyrism.
Lathyrism is a paralyzing disease caused by eating seeds of Lathyrus sativus (khesari dal).
Epidemiology: It is prevalent mostly people in India (e.g. Madhya Pradesh, Uttar Pradesh, Bihar and Orissa), Bangladesh, Pakistan, Nepal and Algeria.
Etiology: Lathyrus sativus (khesari dal) is a good source of protein. It is relatively cheap pulse and is consumed mostly by the poor agricultural laborer. But it contains L-ODAP (β-N-oxalyl-l-α-diamino propionic acid) also called β-N-oxalyl-amino-L-alanine, or BOAA, which is an excitatory neurotoxin and glutamate agonist. If the diets containing more than 30% of this dhal is consumed over a period of 2 to 6 months will produce lathyrism.
Clinical features: Affects mainly young males between 15 to 45 years of age. In humans it mainly affects nervous system and is called neurolathyrism which produces pure motor spastic paraplegia. Sensations and sphincters are preserved.
- Latent stage: Patient appears healthy but when subjected to physical stress exhibits ungainly gait. If the disease is recognized at this stage, age, withdrawal of pulse from the diet will result in complete remission of disease.
- No-stick stage: During this stage, the patient walks with difficulty having short jerky steps but does not need the aid of a stick.
- Two-stick stage: Symptoms are more severe at this stage. Due to excessive bending of the knees and crossed legs, the patient requires support by two crutches for support. The gait is slow and clumsy and complains of easy tiredness after walking a short distance.
- Crawler stage: Finally spastic paralysis develops which becomes irreversible. It becomes impossible to maintain erect posture as the knee joints cannot support the weight of the body. The thigh and leg muscles become atrophied and patient crawls by throwing his weight on his hands.
- Vitamin C prophylaxis 500–1000 mg for a week
- Banning the crop if possible
- Removal of toxin:
- Steeping method: Soaking the pulse in hot water for 2 hours and the soaked water is drained off completely. The pulse is washed again with clean water and then drained off and dried in the sun. There will be loss of vitamins and minerals by this method.
- Parboiling: Suitable for large scale operation and is similar to parboiled rice. It destroys trypsin inhibitors.