Nutrition and Environmental Medicine Question and Answers

Nutrition and Environmental Medicine Nutritional Assessment

Question 1. Discuss the methods of nutritional assessment in an adult.
Answer:

Nutritional screening should include dynamic parameters rather than static ones, For Example, recent weight loss, current body mass index (BMI), recent food intake, and disease severity.

Nutritional Anthropometry:

• Body weight and BMI
• Skinfold measurements: Subcutaneous fat tissues (SFTs) normally account for half of the entire body fat mass, and the measurement of SFT gives information on the energy stores of the body, mainly fat stores (i.e., triglycerides). Biceps, triceps, subscapular, and suprailiac skin-fold thickness are measured.
• Mid-upper arm muscle circumference (MAMC) reflects the muscle mass, while the mid-arm muscle area (MAMA) gives information about the muscle protein stores, as half of the body’s proteins are stored in the skeletal muscles.

Read And Learn More: General Medicine Question And Answers

• The MAMA is calculated from the MAMC and the triceps SFT [MAMA = MAMC − (0.314 × SFT)].
• Assessment of body composition: Body composition describes the body compartments, such as fat mass, fat-free mass, muscle mass, and bone mineral mass. The methods used are bioelectrical independence analysis, creatinine height index, dual energy X-ray absorptiometry,
  magnetic resonance imaging (MRI), computed tomography (CT), dilution method, and neutron activation.
• Laboratory investigations: Complete blood count, lipid profile, electrolytes, albumin, transferrin, prealbumin/transthyretin (TTR), retinol-binding protein (RBP), insulin-like growth factor-1 (IGF-1).

Signs and Symptoms of Micronutrient Defiiencies:

Signs and symptoms of micronutrient defiiencies have been shown in Table:

Vitamin A

Question 2. Write a short essay/note on clinical features, diagnosis, and treatment of vitamin A deficiency.
Answer:

• Vitamin A is the name given to a group of fat-soluble vitamins and includes provitamin A carotenoids and preformed vitamin A.
  • Provitamin A carotenoids—found in plants. For example, beta-carotene, alpha-carotene, and beta-cryptoxanthin. Sources—dark green and deeply colored fruits and vegetables.
  • Vitamin A (retinol, retinal, retinoic acid, and retinyl esters) is the most active form of vitamin A; it is mostly found in animal sources of food and is also the form supplied by most supplements. Sources—liver, fish, milk, eggs, butter, cheese.

Vitamin A metabolism:

• Provitamin A (from plant sources) is cleaved to retinal before absorption. This step is subject to feedback regulation. Therefore, excessive intake of vitamin A from plant sources rarely causes toxicity.
• Preformed vitamin A (from animal sources/supplements): This step is highly efficient and is not subject to feedback regulation. Therefore, excessive intake of vitamin A from animal sources can cause toxicity.
• 50–85% of total body retinol is stored in the liver.

Functions of vitamin A:

• Vitamin A has several metabolic roles. The main functions of vitamin A in humans are as follows:

Maintenance of normal vision:

• Vitamin A is essential for dark adaptation and its deficiency causes nyctalopia. Mainly controlled by retinaldehyde.

Host resistance to infections:

• Vitamin A deficiency causes keratinization of mucous membranes and thereby increases the risk of infections. RBP is a negative “acute phase protein”.

Immune function:

• Vitamin A has the ability to stimulate the immune system. Retinoids are required for normal growth, fetal development, fertility, hematopoiesis, and immune function.

Control of cell growth and differentiation:

Vitamin A is needed for the maintenance of the surface linings of the eyes, growth and repair of epithelial cells, and integrity of the epithelial cells 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:

Fatty acid metabolism, including fatty acid oxidation in fat tissue and muscle, adipogenesis, and lipoprotein metabolism require vitamin A.

Antioxidant:

Retinoids, beta-carotene, and some related carotenoids act as photoprotective and act as antioxidants.

Other functions:

Vitamin A is involved in growth of bone, reproduction, 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 psoriasis and 13-cis-retinoic acid is used in the treatment of acne.

Vitamin A Defiiency:

Clinical Features/Manifestations:

Vision:

• Xerophthalmia describes a spectrum of eye disease caused by vitamin A deficiency, which includes Bitot’s spots, corneal xerosis and keratomalacia.

Bitot’s spots:

• In young children with vitamin A deficiency, areas of abnormal squamous cell proliferation and keratinization of the conjunctiva known as Bitot’s spots can be seen.

• Corneal xerosis refers to dryness of cornea.

Keratomalacia:

• In advanced disease, the cornea becomes hazy and erosions can develop, finally leading to its destruction (keratomalacia).
• Night blindness (nyctalopia) and retinopathy.

Nonspecific skin changes:

• Xerosis of skin in vitamin A deficiency has been shown.
• Hyperkeratosis
• Phrynoderma (follicular hyperkeratosis)
• Impairment of humoral and cell-mediated immunity causing increased susceptibility to infections.

Other features:

• Fatigue
• Anemia
• Diarrhea
• Decreased growth rate
• Decreased bone development
• Infertility.

Laboratory Investigations:

• Serum retinol level: Normal range is 28–86 μg/dL (1–3 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.

Diagnosis:

• It is mainly on the basis of the clinical features. Response to replacement therapy is the best way for the diagnosis.
• Serum retinol levels <20 mg/dL suggest deficiency, or the ratio of retinol RBP <0.8 suggests deficiency.

Prophylactic vitamin A at a dose of 2,00,000 IU every 6 months is to be given to all high-risk individuals. Patients with
malabsorption syndrome need vitamin A supplements.

Treatment:

• Xerophthalmia (irrespective of stage) should be treated with 2,00,000 IU of vitamin A in oily solution, usually contained in a soft-gel capsule. Three doses: day 0, day 1, and day 14.
• If child is suffering from measles give two capsules of 2,00,000 IU for 2 consecutive days.

Prevention:

• Children between 1 and 5 years of age: 60,000 retinol activity equivalent (RAE) (2,00,000 IU) per oral every 6 months
• Infants <6 months: It can be given a one-time dose of 15,000 RAE (50,000 IU).
• 6–12 months of age: It can be given a one-time dose of 30,000 RAE (1,00,000 IU).
• 1 retinol activity equivalent = 1 mg of retinol = 12 mg of beta-carotene = 24 mg of other provitamin A = 3.33 IU of retinol.

Vitamin A Toxicity:

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 of toxicity cause headache and increased intracranial pressure (pseudotumor cerebri).
  • Acute toxicity also produces nausea and vomiting, vertigo, diplopia, bulging fontanels, seizures, exfoliative dermatitis. Single dose of 300 mg in adults and 100 mg in children can be harmful.
  • Chronic toxicity occurs with amounts higher than 10 times the RDA—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 (spontaneous abortions and fetal malformations, including microcephaly and cardiac anomalies).
• 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.
  • 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 carotenoid rich food is reduced.

Dietary reference intake for water-soluble vitamins has been shown in Table:

Dietary reference intakes (DRIs) include the following measures describing optimal nutrient intake:

Recommended dietary allowance (RDA):

• The level of dietary intake that is suffient to meet the daily nutrient requirements of 97% of the individuals in a specifi life stage group.

Adequate intake (Al):

• An approximation of the average nutrient intake that sustains a defied nutritional state, based on observed or experimentally determined values in a defied population.

Upper tolerable level (UL):

• The maximum level of daily nutrient intake that is likely to pose no risk of adverse health effcts in almost all individuals in the specifid life stage or gender group.

RDAs and Als may both be used as goals for individual intake. The Al is used when there are insuffient data to determine the RDA for a given nutrient.

Vitamin B Complex

Thiamine (B₁):

Functions: 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 alpha-ketoglutarate to succinate (Krebs cycle).
• Has an additional role in neuronal conduction.

Sources:

• These vitamins can be produced by plants and some microorganisms. However, animals cannot synthesize them. In humans, the source is diet, though small amounts may be synthesized by intestinal bacteria.

Dietary sources:

• Good dietary sources of thiamine are whole wheat flour, unpolished rice, cereals, grains, beans, nuts and yeast. There is little or no thiamine in milled rice and grains. Thus, thiamine deficiency is more common in individuals who consume mainly a rice-based diet.

It is also present in liver, meat, and eggs.

Requirement:

• Up to 30 mg of thiamine can be stored in body tissues. Required daily allowance (RDA) is 0.5–0.9 mg daily for children, 1.2 mg daily for adult men, and 1.1 mg daily for nonpregnant adult women.

Requirement increases with increased carbohydrate intake, pregnancy and lactation, smoking, alcoholism, prolonged antibiotic intake, serious or prolonged illness.

It causes of thiamine deficiency are listed in Box 1.1 and clinical
syndromes of thiamine deficiency are mentioned.

Consequences of Thiamine Defiiency:

• Consequence of thiamine deficiency is impaired glucose n oxidation.
• Cells cannot metabolize glucose aerobically to generate energy as ATP.
• Neuronal cells are most susceptible, because they depend almost exclusively on glucose for energy requirements.
• Causes an accumulation of pyruvic and lactic acids. This in turn produces vasodilatation and increased cardiac output.

Causes of thiamine deficiency:

Lack of thiamine intake:

• Starvation state
• Food items like milled rice, raw freshwater fish, raw shellfish, and ferns that have a high level of thiaminase
• Food high in anti-thiamine factor, such as tea, coffee, and betel nuts
• Alcoholic state

Increased consumption states:

• Diets high in carbohydrate or saturated fat intake
• Pregnancy and lactation
• Hyperthyroidism
• Fever—severe infection
• Increased physical exercise

Decreased absorption:

• Chronic intestinal disease
• Alcoholism
• Malnutrition
• Gastric bypass surgery
• Malabsorption syndrome—celiac and tropical sprue

Increased depletion:

• Diarrhea
• Peritoneal dialysis, hemodialysis, diuretic therapies
• Hyperemesis gravidarum

Clinical syndromes of thiamine deficiency:

• Wet beriberi—high cardiac output failure
• Dry beriberi—peripheral neuropathy
• Wernicke’s encephalopathy
  Korsakoff’s psychosis
• Leigh syndrome (progressive subacute necrotizing encephalomyopathy)

Beriberi:

Write short essay/note on clinical features of beriberi/vitamin B₁ (thiamine) deficiency.

1. 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.
• Later, congestive heart failure develops, causing orthopnea, and pulmonary and peripheral edema. Marked cardiomegaly is present.
• Infantile beriberi occurs in infants (usually by age 3–4 weeks) who are breastfed by thiamine-deficient mothers. Heart failure can develop suddenly and presents with edema, aphonia, tachycardia, tachypnea, and absent deep tendon reflexes. If prompt treatment is not given, death occurs quickly.
  • Shoshin beriberi: A more rapid form of wet beriberi is termed acute fulminant cardiovascular beriberi.

2. Dry beriberi: Dry beriberi usually manifests insidiously with symmetrical peripheral neuropathy.

• Early symptoms: There is bilateral and roughly symmetrical heaviness and stiffness of the legs.
• Later symptoms: These include weakness, numbness, and pins and needles (occurring in a stocking-glove distribution).
• Distribution of neuropathy: They affect predominantly the lower limbs. They begin 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.
• Deficiency may also cause degeneration of thalamus, mammillary bodies, and cerebellum.

Biochemical tests:

• Measurement of thiamine, pyruvate, and lactate levels in blood or urine.
• Erythrocyte thiamine transketolase activity.

Write short essay/note on management/treatment of beriberi/vitamin B₁ (thiamine) deficiency.

Management:

• Complete bed rest.
• 200 mg thiamine 3 times a day given till acute symptoms disappear, after that 10 mg/day till recovery.
• Parenteral thiamine produces marked diuresis (in wet beriberi), resulting in dramatic improvement in the symptoms.

Write short essay/note on Wernicke’s encephalopathy.

3. Wernicke’s encephalopathy: It is an acute neuropsychiatric condition. Initially, it is reversible biochemical brain lesion caused by depletion of vitamin B1 (thiamine). Its causes are listed.

Clinical features:

• Wernicke’s encephalopathy (WE) is a triad of global confusion, 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: It is characterized by confusion, severe disorientation, indifference, and inattentiveness. There is also impaired memory and learning. If untreated patients will progress through stupor and coma to death.
• Oculomotor dysfunction: Nystagmus, lateral rectus palsy, and lesions of the oculomotor, abducens, and vestibular nuclei resulting in conjugate gaze palsy.
• Gait ataxia: Ataxia mainly involves stance and gait. It is probably due to a combination of polyneuropathy, cerebellar involvement, and vestibular dysfunction.

Diagnbosis:

For confirmation of the diagnosis, measure the circulating thiamine concentration or transketolase activity in red cells using fresh heparinized blood.

MRI may show periventricular lesions surrounding third ventricle, aqueduct and fourth ventricle with petechial hemorrhages in acute cases and atrophy of mammillary bodies in chronic cases.

Management:

• Wernicke’s disease is a medical emergency and requires immediate administration of thiamine.
• Dosage: 500 mg of thiamine intravenously, infused over 30 minutes, 3 times daily for 2 consecutive days and 250 mg intravenously or intramuscularly once daily for an additional 5 days, in combination with other B vitamins.
• Magnesium is often needed because it is a cofactor required for normal functioning of thiamine-dependent enzymes.
• Wernicke’s encephalopathy may be precipitated by administration of intravenous glucose solutions to individuals with thiamine deficiency. In susceptible individuals, glucose administration should be preceded or accompanied by thiamine 100 mg IV.

4. Korsakoff’s psychosis/syndrome:

Write a short note on Korsakoff’s psychosis/syndrome.

• Korsakoff’s psychosis 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 are also marked deficits in anterograde and retrograde memory.
• Other features include apathy, an intact sensorium and relative preservation of long-term memory and other cognitive skills.
• Confabulation: It 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 maintained. Affected individuals can perform conversation that may seem normal to an unsuspecting spectator.
• The syndrome is common in chronic alcoholics. It may also be seen with thiamine deficiency due to gastric disorders (e.g., carcinoma, chronic gastritis, or persistent vomiting).

Treatment: Parenteral thiamine (100 mg IM daily for 7 days).

Thiamine metabolism dysfunction syndromes:

Thiamine-responsive megaloblastic anemia:

• Mutations in the SLC19A2 gene (encodes thiamine transporter)
• Syndrome of megaloblastic anemia, diabetes mellitus, and sensorineural deafness
• Affects infants and adolescents.

Thiamine metabolism dysfunction syndrome type 2:

• Mutations in the SLC19A3 gene (encodes thiamine transporter)
• Causes episodic encephalopathy
• May be precipitated by a febrile episode.

Vitamin B₂ (Riboflvin)

Source: Milk and eggs, meats, fish, green vegetables, yeast, and enriched foods (fortified cereals and breads).

Actions:

• Essential component of coenzymes involved in multiple cellular metabolic pathways like tricarboxylic acid (TCA) cycle and beta-oxidation of fatty acids.
• Flavoproteins are involved in multiple redox reactions and function as electron transporters.

Defiiency:

Diagnosis:

• Erythrocyte glutathione reductase assay—coefficient >1.4 indicates riboflavin deficiency.
• Plasma, RBC or urine riboflavin concentrations.

Causes:

• Anorexia nervosa
• Malabsorptive syndromes
• Glutaric acidemia type 1
• Multiple acyl-coenzyme A (CoA) dehydrogenase deficiency (MADD)
• Brown-Vialetto-Van Laere syndrome (defect in riboflavin transporter)
• Long-term use of barbiturates—can cause oxidation of riboflavin.
• Lactose intolerance—because dairy products are a good source of riboflavin.

Features of riboflavin deficiency include:

• Cheilitis
• Stomatitis
• Glossitis
• Normochromic anemia
• Seborrheic dermatitis

Pure deficiency of riboflavin is rare:

Therapeutic uses:

• Multiple CoA dehydrogenase deficiency
• Lactic acidosis due to zidovudine/stavudine—responds to riboflavin

RDA:

• 0.5–0.9 mg daily in children
• 1.3 mg daily for adult men
• 1.1 mg daily for nonpregnant adult women

Vitamin B₃ (Niacin)

Sources:

• Yeast, meats (especially liver), grains, legumes, corn used
  in tortilla, and seeds.
• Tryptophan can be converted to a niacin derivative in the liver. However, it requires approximately 60 mg of tryptophan to produce 1 mg of niacin, and this process requires vitamin B6 (pyridoxine).

Actions: NAD/NADP are co-factors for many enzymatic redox reactions.

RDA: Dosed as a “niacin equivalent” (NE), in which 1 NE is equal to 1 mg of niacin, or 60 mg of dietary tryptophan. RDA is 6–12 mg daily in children, 16 mg for adult males, and 14 mg daily for nonpregnant adult females.

Pellagra:

Causes of pellagra:

• Inadequate intake: Maize or jowar (sorghum) diet, malnutrition, chronic alcoholism (who eat little), anorexia nervosa
• Generalized malabsorption (rare).
• Drug-induced:
  • Prolonged isoniazid therapy
  • Pyrazinamide
  • 6-mercaptopurine
  • 5-fluouracil
  • Azathioprine
  • Ethionamide
  • Carbamazepine
  • Phenytoin
  • Phenobarbitone.
• Other disorders:
  • Hartnup’s disease: It is a rare genetic disorder, in which
    there is reduced absorption of basic amino acids including tryptophan by the gut.
  • Carcinoid syndrome and pheochromocytoma: In these conditions, tryptophan metabolism is diverted away from the formation of nicotinamide to form amine-producing pellagra-like symptoms.

Write short essay/note on clinical features and
management of niacin deficiency (pellagra).

• Vitamin B₃ niacin (nicotinamide) deficiency causes a metabolic encephalopathy called pellagra. Causes of pellagra are listed.
• 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.

Clinical Features:

Pellagra has been easily remembered a disease of four Ds namely:

1. Dermatitis
2. Diarrhea
3. Dementia (depression)
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. This rash forms a ring around the neck and is termed 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.

Gastrointestinal (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 GI 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:

• 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 with nicotinamide treatment.
• Niacin status can be assessed by measuring urinary N-methylnicotinamide, 2-pyridonenicotinamide or by measuring the erythrocyte NAD:NADP (ratio).

Vitamin B₅ (Pantothenic Acid):

Sources:

• Egg yolk, liver, kidney, broccoli, and milk
• Pantothenic acid is also produced by bacteria in the colon
• Main dietary source of pantothenic acid is in the form of coenzyme A.

Actions:

CoA is involved in metabolism of vitamins A, D, cholesterol, steroids, heme A, fatty acids, carbohydrates, amino acids, and proteins.

RDA:

• The recommended intake for pantothenic acid is expressed as adequate intake (AI) rather than recommended dietary allowance (RDA).
• The AI is 2–4 mg daily for children and 5 mg daily for adult men and women.

Deficiency: Pantothenic acid deficiency is very rare in humans.

Clinical manifestations:

• Paresthesias and dysesthesias, referred to as “burning feet syndrome”
• Gastrointestinal disturbance, depression, muscle cramps, hypoglycemia, ataxia, etc.

Management/Treatment:

Oral pantothenic acid (vitamin B₅) – 5 mg/day.

Diagnosis:

• Blood, plasma, serum or urine pantothenic acid levels
• Urine levels are most reliable indicator of dietary intake.

Vitamin B₅ (Pyridoxine):

Vitamin B6 consists ofpyridoxine, pyridoxamine, pyridoxal, and the phosphorylated derivatives of each of these compounds.

Sources:

• Pyridoxine and pyridoxamine are predominantly found in plant foods.
• Pyridoxal is most commonly derived from animal foods.
• Meats, whole grains, vegetables, and nuts are the best sources.

Actions:

• Gluconeogenesis
• Decarboxylation of amino acids
• Conversion of tryptophan to niacin
• Heme synthesis
• Sphingolipid biosynthesis
• Neurotransmitter synthesis
• Steroid hormone modulation
• Trans-sulfuration pathway by which homocysteine is converted into cystathionine and its subsequent conversion to cysteine.

RDA:

• 0.5–1 mg in children
• 1.3 mg daily for young men and women
• 1.7 mg daily for men older than 50 years
• 1.5 mg daily for women older than 50 years

Defiiency:

Overt deficiency is rare.

Causes:

• Drugs—isoniazid, penicillamine, hydralazine, and levodopa/carbidopa
• Associated with—asthma, diabetes, alcoholism, heart disease, pregnancy, breast cancer, Hodgkin’s lymphoma, and sickle-cell anemia

Clinical manifestations:

• Nonspecific stomatitis, glossitis, cheilosis, irritability, confusion, and depression, and possibly peripheral neuropathy.
• Severe deficiency is associated with seborrheic dermatitis, microcytic anemia, and seizures
• A number of genetic syndromes affecting PLP-dependent enzymes such as homocystinuria, cystathioninuria, and xanthurenic aciduria mimic vitamin B6 deficiency.
• An inborn error of pyridoxine metabolism is responsible for pyridoxine-dependent epilepsy.
• Cystathionine synthase is a PLP-dependent enzyme, which produces cystathionine from serine and homocysteine. As a result, vitamin B6 insufficiency can lead to elevations in plasma homocysteine concentrations, a risk factor for the development of atherosclerosis and venous thromboembolism.

Diagnosis:

• PLP concentrations >30 nmol/L (>7.4 ng/mL) are normal.
• Erythrocyte transaminase activity, with and without PLP added.
• Urinary 4-pyridoxic acid excretion >3.0 mmol/day
• Urinary excretion of xanthurenic acid is normally <65 mmol/day following a 2 g tryptophan load. Increased xanthurenic acid excretion suggests vitamin B6 deficiency due to abnormal tryptophan metabolism.

Toxicity: Peripheral neuropathy, dermatoses, photosensitivity, dizziness, and nausea have been reported with pyridoxine of over 250 mg/day.

Treatment:

• 50 mg/day in regular deficiency
• In case of deficiency secondary to certain drugs—higher doses of 100–200 mg/day are given.

Biotin:

• Sources: Liver, egg yolk, soybean products, and yeast
• Actions: Essential cofactor for several carboxylase enzyme complexes involved in carbohydrate, amino acid, and lipid metabolism.
• RDA: The AI is 8–12 mg daily for children and 30 mg daily for adults.

Defiiency:

Deficiency is rare.

Causes:

• Long-term parenteral nutrition
• Consumption oflarge amounts of raw egg whites (which contain avidin, a substance that binds to biotin and prevent its absorption), can also lead to biotin deficiency.
• Secondary biotin deficiency can occur due to lack of a specific enzyme (biotinidase), which is required for release of protein-bound biotin to make it bioavailable.

Clinical manifestations:

• Dermatitis around the eyes, nose and mouth, conjunctivitis, alopecia
• Neurologic symptoms, including changes in mental status, lethargy, hallucinations, and paresthesias
• Myalgia, anorexia, and nausea
• Multiple carboxylase deficiency—inherited defects of biotin metabolism
• The infantile form is caused by a deficiency of holocarboxylase synthetase and presents in the first week of life with lethargy, poor muscle tone, and vomiting.
• A later-onset form is caused by biotinidase deficiency and is associated with a slow but progressive loss of biotin in the urine, leading to organic aciduria; it is characterized by ataxia, ketoacidosis, dermatitis, seizures, myoclonus, and nystagmus.

Diagnosis:

• Decreased urine biotin concentrations
• Increased urinary excretion of 3-hydroxyisovaleric acid after leucine
  challenge
• Decreased activity of biotin-dependent enzymes in lymphocytes.

Vitamin C

Write short essay/note on vitamin C and clinical features of scurvy.

Vitamin C (ascorbic acid) is a water-soluble vitamin.

Sources:

• Citrus fruits, tomatoes, potatoes, brussel sprouts, cauliflower, broccoli, strawberries, cabbage, and spinach
• Breast milk provides an adequate source of ascorbic acid for newborns and infants.

Metabolism:

• Ascorbic acid is absorbed in the distal small intestine.
• Usual dietary doses of up to 100 mg/day are almost completely absorbed. As dietary concentrations increase, a smaller fraction is absorbed.
• Pharmacologic dosing (>1,000 mg/day) can result in absorption rates of <50%
• Blood concentrations of ascorbic acid are regulated by renal excretion. Excess amounts are filtered by renal glomeruli and reabsorbed via the tubules to a predetermined threshold.
• Dehydroascorbic acid is the preferred form for erythrocytes and leukocytes.
• The greatest concentrations of ascorbic acid are found in the pituitary, adrenal, brain, leukocytes, and the eye.

Functions:

These include:

• 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, neurotransmitters, 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.

RDA:

• 15–45 mg daily in children
• 75 mg/day for adult women
• 90 mg/day for men
• Pregnant or lactating women and the elderly have requirements up to 120 mg/day.

Defiiency of Vitamin C—Scurvy:

Scurvy is caused by deficiency of vitamin C.

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 requires increased vitamin C
• Patients undergoing peritoneal dialysis and hemodialysis
• Diseases of small intestine such as Crohn’s, Whipple’s, and celiac disease.

Types of scurvy: Adult scurvy and infantile scurvy.

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, ecchymosis, 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.
• Gums: Inflamed spongy gums (gum swelling) friability, bleeding and infection with loosening of teeth; mucosal petechiae are common.
• Skin changes: Roughness, keratosis of hair follicles with ‘corkscrew’ hair, perifollicular hemorrhages.
• Nails: Splinter hemorrhages.
• Other features: Emotional changes, shortness of breath.

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 and leukocyte vitamin C levels can be measured.
  • Leukocyte vitamin C levels are more reliable as recent treatment will improve plasma levels but tissues will still be deficient in vitamin C.
  • Plasma vitamin C level of <11 μmol/L (0.2 mg/100 mL).
  • Anemia: It can be normochromic, normocytic (due to bleeding), megaloblastic (due to reduced erythropoiesis) or microcytic hypochromic anemia (due to impaired iron absorption and impaired heme synthesis).
  • Hess’ 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:

• Loss of trabeculae results in a ground-glass appearance
• Thinning of cortex
• A line of calcified, irregular cartilage (white line of Frankel) may be visible at the metaphysis.
• The epiphysis may be compressed and circular calcification surrounding epiphyseal center of ossification (Wimberger’s ring sign) X-ray of scurvy showing Frankel line and Wimberger’s ring sign.

Toxicity:

• Acute: High doses >2 g of vitamin C— abdominal pain, diarrhea, nausea.

Chronic:

• Increased prevalence of kidney stones.
• Iron overload—can cause fatal arrhythmias.
• Hemolysis in G6PD deficiency.
• False-negative guaiac reactions and interference with tests for urinary glucose.
• Interference with activity of certain drugs—like bortezomib
  in myeloma.

Management/Treatment:

• Ascorbic acid at 100 mg 3–5 times a day until total of 4 g is reached, and then reduce the dose to 100 mg daily.
• Encourage consumption of foods with high vitamin C.
  • Citrus fruits, especially grapefruits and lemons.
  • Vegetables, including broccoli, green peppers, tomatoes, potatoes, and cabbage.
  • The recommended dose for adults is 120 mg daily, although a dose of 60 mg daily is all that is required to prevent scurvy.
  • Diets high in vitamin C may lower the incidence of certain cancers, particularly esophageal and gastric cancers.
  • Vitamin C supplementation can be useful in upper respiratory tract infections, Chediak-Higashi syndrome, and osteogenesis imperfecta.
  • There is inconclusive evidence of the protective role of vitamin C in the management of COVID-19 pneumonia

Vitamin D

Write a short note on vitamin D.

Vitamin D is a fat-soluble secosteroid responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc.

Physiology:

Vitamin D₃ (Cholecalciferol)

• Produced in skin with direct sunlight. Cod liver oil is a rich source.
• Preferred form of supplementation

Vitamin D₂ (Ergocalciferol):

• Less effective as precursor to 1,25(OH)2-vitamin D
• Hepatic conversion of vitamin D3 to 25-OH-vitamin D (calcitriol)
• Conversion of 25-OH-vitamin D to 1,25(OH)2-vitamin D (calcitriol)

Functions:

Vitamin D exists in two activated sterol forms.

Its functions include:

• 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.
• Antiproliferative effects: The vitamin D receptor (VDR) is expressed in the parathyroid gland, and 1,25(OH)2 D has an antiproliferative effect on parathyroid cells and it suppresses the transcription of the parathyroid hormone gene.
• Immunomodulatory: Vitamin D is involved in the innate and adaptive immune system.

Vitamin D Defiiency:

Write briefly on clinical features, investigations, treatment, and prevention of rickets.

Causes of vitamin D deficiency are listed. Diseases caused due to vitamin D deficiency are:

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.

Causes of vitamin D deficiency:

• Impaired cutaneous production due to limited exposure to sunlight
• Dietary absence: Diets deficient in calcium and vitamin D
• Malabsorption
• Impaired hydroxylation by the liver to produce 25 hydroxyvitamin D
• Impaired hydroxylation by the kidneys to produce 1,25 dihydroxy vitamin D (vitamin D-dependent rickets type 1, chronic renal insufficiency)
• End-organ insensitivity to vitamin D metabolites [hereditary vitamin D-resistant rickets (HVDRR), vitamin D-dependent rickets type 2]

Rickets in Children:

• 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 depend 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:

Head:

• Craniotabes: The skull appears square and box-like, there is 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.

Chest:

• 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 ambulatory stage:

• This occurs when an ambulating child develops rickets. It is characterized by deformities affecting the spine, pelvis, and tibia. Scoliosis, kyphosis, and lumbar lordosis are characteristic.
• Bowing of the legs: Due to affection of tibia, knock knees, anterior curving of legs.

Extra skeletal manifestations:

• Seizures and tetany: Secondary to hypocalcemia in vitamin D deficiency rickets.
• Hypotonia and delayed motor development: In rickets developing during infancy.
• Protuberant abdomen, bone pain, waddling gait, and fatigue.
• Asymptomatic: Detected on radiological evaluation.

Investigations:

Wrist radiograph:

Findings include:

• Lower ends of the shaft of radius and ulna become splayed.
• Epiphyseal surfaces—fuzzy and ill-defined.
• Unossified zone between shaft and radial epiphysis gets widened (‘saucer’ deformity).

Blood:

• 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.

Comparison of conditions involving bone metabolism is presented in table

Prevention:

• Adequate consumption of vitamin D (1,000–5,000 IU/day)
• Adequate exposure to sunlight (from 30 minutes to 2
  hours/week for infants).

Osteomalacia:

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 mineralization of bone matrix proteins, a condition known as osteomalacia.
• Thus, it 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.

Causes of osteomalacia are listed

Treatment of rickets:

• Treat the underlying cause.
• Supplementation diet with calcium and vitamin D.
• For nutritional deficiency of vitamin D: Ergocalciferol, 1,50,000–6,00,000 IU orally or intramuscularly as a single dose. Or give Ergocalciferol in a dose of 2,000 IU every day.

Causes of osteomalacia:

• Nutritional abnormalities: Dietary deficiency of vitamin D, parenteral nutrition
• Malabsorption: Tropical sprue, celiac disease, hepatobiliary diseases, pancreatic insufficiency
• Disorders of vitamin D metabolism: Vitamin D dependency type I and type II, anticonvulsants, chronic renal failure
• Acidosis: Distal renal tubular acidosis (type I)
• Phosphate depletion: Use of nonabsorbable antacids, tumor associated osteomalacia
• Others: Multiple myeloma, nephrotic syndrome, lead poisoning, inadequate sun exposure

Clinical Features:

• Bone pains, muscle weakness, fractures of bones with minor trauma.
• Pain in the hip may cause antalgic gait.
• Weakness of proximal muscle results in waddling 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 pubic arch.

Laboratory Investigations:

Blood (same as for rickets).

Urinary excretion of calcium: Reduced.

Radiological Findings:

• Bone density: Reduced (osteopenia), diffuse demineralization.
• 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 pseudo-fractures (Looser’s zones).
• Bone scan may be normal or show discrete foci of increased radionuclide uptake.
• 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.

Treatment of osteomalacia:

• Treat the underlying cause wherever possible.
• Dietary deficiency: It is corrected by 1,000–4,000 IU of vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) for 3 months. This is followed by lower doses as maintenance. Vitamin D should be taken with fatty diet for maximum absorption.
• Osteomalacia due to malabsorption: Give 50,000–1,00,000 IU of vitamin D + calcium supplementation. Small doses of calcitriol (0.5–1.0µg daily) also effective.
• Chronic renal failure: Calcitriol with weekly monitoring of calcium level.

Role of Vitamin D in Health and Disease:

It has been shown in Table:

Hypervitaminosis D:

Write a short answer on hypervitaminosis D:

Hypervitaminosis D causes hypercalcemia, which manifests as:

• Nausea and vomiting
• Excessive thirst and polyuria
• Severe itching
• Joint and muscle pains
• Disorientation and coma
• Metastatic calcifications

Treatment of hypervitaminosis: Hydration and treatment of hypercalcemia.

Vitamin E Alpha Tocopherol

Sources: Almonds, vegetable oils, and cereals

Actions:

• Acts as free radical scavenger and antioxidant
• Protects LDL and PUFA in membranes from oxidation
• Inhibits prostaglandin synthesis, activities of phospholipase A₁, and protein kinase C.

Defiiency:

Causes:

• Pancreatic exocrine insufficiency
• Cholestatic liver disease
• Extensive resection or disease affecting small intestine
• Ataxia with vitamin E deficiency, due to a mutation in the gene encoding hepatic alpha-tocopherol transfer protein
  (TTPA)
• Abetalipoproteinemia, due to mutations in the microsomal triglyceride transfer protein.

Diagnosis:

• Alpha-tocopherol levels of <0.5 mg/dL (5 mg/mL or 11.5 mmol/L)—deficiency.
• For patients with marked hyperlipidemia, effective serum vitamin E level = alpha-tocopherol (mg)/total lipids (g); where total lipids = cholesterol + triglycerides.
• A normal result is >0.8 mg.

Clinical manifestations:

• Spinocerebellar syndrome—ataxia, hyporeflexia, and loss of proprioceptive and vibratory sensation.
• Ophthalmoplegia, skeletal myopathy, pigmented retinopathy.
• Brown bowel syndrome (intestinal lipofuscinosis) is a brown pigmentation of the bowel that occasionally presents with
  bowel dilatation and pseudo-obstruction (due to lipofuscin accumulation within the smooth muscle mitochondria).
• Life span of red blood cells is shortened.
• In premature infants, vitamin E deficiency may cause a hemolytic anemia.

Treatment:

• For infants and children: 17–35 mg/kg/day of RRR-alpha-tocopherol.
• For adults: 800–1200 mg/day.

Vitamin K

Sources:

• Dietary vitamin K₁ (phylloquinone) is found in green vegetables like spinach and broccoli, and in some oils.
• Vitamin K₂ (menaquinone) is found in bacterial flora, meat (especially liver), cheeses, fermented soybeans, and eggs.

Actions:

• Coagulation: Vitamin K is essential for activity of several carboxylase enzymes within hepatic cells, and therefore is necessary for the activation of coagulation factors VII, IX, X, and prothrombin.
• Activation of proteins C and S
• Reversal of coumarin-like anticoagulants
• Bone formation
• Coronary vascular calcification

Defiiency:

Causes:

• Cystic fibrosis
• Primary biliary cholangitis
• Primary sclerosing cholangitis
• Biliary atresia
• Familial intrahepatic cholestasis and other inherited disorders associated with cholestasis
• Malabsorption syndromes
• Liver failure
• Medications: 2nd, 3rd generation cephalosporins, orlistat
• Very high doses of vitamin E can cause vitamin K deficiency

Clinical manifestations:

• Easy bruising
• Mucosal bleeding
• Splinter hemorrhages
• Melena
• Hematuria
• Other manifestations of impaired coagulation.

Diagnosis:

• Symptomatic patients with mild deficiency—only PT is elevated; in severe deficiency—both PT and aPTT are elevated.
• Levels of PIVKA-II (protein induced in vitamin K absence or antagonist-II, also known as des-gamma-carboxy prothrombin) are more sensitive than PT in detecting vitamin K deficiency. PIVKA-II is also elevated in the presence of vitamin K antagonist (VKA) drugs or certain tumors such as hepatocellular carcinoma.
• Measuring vitamin K-dependent factors (i.e., prothrombin,
  factors VII, IX, X, or protein C). In patients who are vitamin
  K deficient, levels of these factors often are <50% of normal.
• Phylloquinone levels can also be measured directly but are
  impractical for clinical use.

Treatment:

• Vitamin K can be administered in doses of 1–25 mg (usually 10 mg) via oral, intramuscular, subcutaneous, or intravenous routes.
• When vitamin K deficiency occurs in patients who are also receiving coumarin-like anticoagulants, doses of vitamin K should be minimized in order to prevent refractoriness to further anticoagulation.

Trace Elements

• The term ‘trace’ is used for concentrations of elements not
  exceeding 250 µg/g of extracellular matrix.
• Trace elements are naturally occurring, homogeneous,
  inorganic substances required in humans in amounts
  <100 mg/day.
• Classification of trace elements is presented in Box 1.6.
• 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.

Iron:

Write a short note on daily requirement of iron and important
dietary sources of iron.

Most essential trace element.

Deficiency state:

• Asymptomatic
• Anemia (refer Chapter 8), weakness, headache, irritability,
  and varying degrees of fatigue and exercise intolerance.

The causes of iron overload have been shown in Table

Acute Iron Poisoning:

• Develops when iron level 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
• Cardiomyopathy, heart failure, and/or arrhythmias
• Diabetes mellitus
• Hypogonadism, decreased libido, and impotence
• Skin involvement with hyperpigmentation (the bronze color in “bronze diabetes”)
• Arthropathy, especially involving the second and third metacarpophalangeal joints, and often with chondrocalcinosis.

Treatment:

• Gastric lavage with sodium bicarbonate solution.
• Desferrioxamine 15 mg/kg/h IV, increased to maximum dose of 35 mg/kg/h.
• Correction of acidosis and shock.
• Extracorporeal removal with exchange transfusion or continuous venovenous hemofiltration.
• Phlebotomy can be done if no significant anemia present

Fluorosis

Write short note on fluorosis and its radiological signs.

• Fluorine’s ionic form is known as fluoride.
• It is a 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 (>3–5 ppm).
• Acute ingestion of >30 mg/kg body weight usually manifests with GI symptoms such as 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, teeth appear chalky white with transverse yellow bands. It becomes rough, pigmented, pitted and brittle (fluoride 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.

Angular Stomatitis:

Write a 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 have been shown

Angular Stomatitis:

Write a 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 have been shown

Causes of angular stomatitis:

• Iron deficiency anemia
• Secondary infection of Candida albicans, Staphylococcus
• Vitamin deficiency:
  • Riboflavin (B₁) deficiency
  • Pyridoxine (B₆) deficiency
  • Niacin deficiency (pellagra)
• Herpes labialis at the angle of mouth
• Angular stomatitis is associated with cheilosis in niacin deficiency and pellagra

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 >3–5 days (because of their physical illness).
• Normally nourished patients not expected to eat for >5 days or to eat less than half their intake for >8–10 days.

Types of Nutritional Support:

• Enteral nutrition should be used, if the GI tract is functioning normally.
• Parenteral nutrition.

Discuss the advantages and problems associated with enteral nutrition:

Enteral Nutrition:

• Prerequisite: Must have functioning GI tract. Patients who are not able to swallow may need artificial nutritional support For Example, after acute stroke or throat surgery, or longterm neurological disorders such as motor neuron disease and multiple sclerosis).
• Whenever possible, the enteral route is preferred and to be used.
• Advantages and disadvantages of enteral nutrition have been.
• Methods of enteral nutrition have been.

Complications of enteral feeding:

• Access problems (For Example, tube obstruction)
• Administration problems (For Example, aspiration pneumonia)
• Gastrointestinal complications (For Example, diarrhea)
• Metabolic complications (For Example, overhydration).

Rate and method of delivery:

• Bolus: 300–400 mL rapid delivery via syringe several times daily
• Intermittent: 300–400 mL, over 20–30 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.

Types of enteral formulations:

• Standard polymeric formulas:
  • Isotonic to serum
  • Caloric density of approximately 1 kcal/mL
  • Lactose-free
  • Protein content of about 40 g/1,000 mL (40 g/1,000 kcal)
  • Nonprotein calorie to nitrogen ratio of approximately 130
  • Mixture of simple and complex carbohydrates
  • Long-chain fatty acids (although some are now including medium-chain and omega-3 fatty acids)
  • Essential vitamins, minerals, and micronutrients
• Polymeric formulas with fiber
• Immune-enhancing formulas
• Protein-enriched formulas
• Concentrated formulas: Useful for patients requiring volume restriction
• Predigested (elemental and semi elemental—previously called): Useful in thoracic duct leak, chylothorax, chylous
  ascites, malabsorption syndromes, nontolerance to standard enteral feeds (e.g., persistent diarrhea)
• Critical illness: Special formulations for certain critical illnesses, have not proved beneficial over the others.

Contraindications to enteral feeding: The intestinal tract cannot be used effectively in some patients because of the following:

• Persistent nausea or vomiting
• Postprandial abdominal pain or diarrhea
• Mechanical obstruction or severe hypomotility
• Malabsorption
• Presence of high-output fistula

Parenteral Nutrition:

Parenteral nutrition should be considered if energy intake cannot, or it is anticipated that it cannot be met by enteral
nutrition (<50% of daily requirements) for >7–10 days.

Discuss the indications, types and complications associated with total parenteral nutrition.

Central access: Total parenteral nutrition (TPN) both long, and short-term placement.

• The infusion of hyperosmolar (usually >1,500 mOsm/L) nutrient solutions requires a large-bore, high-flow vessel to minimize vessel irritation and damage.
• Percutaneous subclavian vein catheterization and peripherally inserted central venous catheterization (PICC) are the
  most commonly used techniques for central parenteral nutrition (CPN) access.
• The internal jugular, saphenous, and femoral veins are also used, although they are less desirable because of decreased patient comfort and difficulty in maintaining sterility.
• Tunneled catheters are preferred in patients who are likely to receive >8 weeks of TPN to reduce the risk of mechanical failure.

CPN macronutrient solutions:

• Crystalline amino acid solutions
• Branched-chain amino acids for patients of hepatic encephalopathy,
  renal insufficiency
• Glucose (dextrose) solutions
• Lipid emulsions

Peripheral parenteral nutrition (PPN): Peripheral parenteral nutrition is often considered to have limited usefulness because of the high risk of thrombophlebitis.

Advantages and disadvantages of parenteral nutrition have been shown.

Indications for total parenteral nutrition have been shown.

Complications of parenteral nutrition have been shown in Table

Indications of parenteral nutrition:

• Nonfunctioning GIT
• Nil per oral (NPO) >5 days
• GI fistula
• Acute pancreatitis
• Short bowel syndrome
• Malnutrition with >10–15% weight loss
• Nutritional needs not met; patient refuses food

Refeeding syndrome:

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.

Mechanism:

• 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).

Clinical features:

• Initial features may be nonspecific.
• Later: Rhabdomyolysis, leukocyte dysfunction, respiratory and cardiac failure, hypotension, arrhythmias, seizures, coma, and sudden death.

Treatment of refeeding syndrome:

• Start nutrition at 5–10 kcal/kg/day, and increase levels gradually.
• Provide thiamine, multivitamins and trace elements.
• In thiamine-deficient patients, Wernicke’s encephalopathy can be precipitated by refeeding with carbohydrates. This is prevented by providing thiamine before starting nutritional support.
• Restore the circulatory volume. Monitor fluid balance and clinical status.
• Replace PO, K, and Mg.

Protein Energy Malnutrition

Protein–energy malnutrition (PEM) or protein–calorie malnutrition includes marasmus, kwashiorkor and intermediate states of marasmus-kwashiorkor.

Marasmus:

Write a 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 apparent 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.

Kwashiorkor:

• 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 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.

Treatment of PEM:

• Provision of protein and energy supplements.
• Control of infection.

Obesity

Describe the risk factors, clinical features, complications, and management of obesity.

Describe and discuss the etiology of obesity including modifiable and nonmodifiable risk factors and secondary
causes.

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.

Measurement of obesity:

• Body mass index—weight/height2 in kg/m2
• Anthropometry—skinfold thickness
• Densitometry—underwater weighing
• CT/MRI imaging
• Electrical impedance

Classification of overweight and obesity by BMI:

Types of obesity according to body fat distribution:

The distribution of the stored fat is important 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 (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.
• Increased Waist: Hip ratio— >0.9 in females, >1 in males is abnormal.

• Hypothesis—intra-abdominal adipocytes are more lipolytically active than others—release free fatty acids into portal circulation—cause adverse metabolic reactions, especially on the liver.
• Generalized (‘gynoid’ or ‘pear-shaped’) obesity: This type is characterized by excess accumulation of fat diffusely in the subcutaneous tissue.

Etiology:

• 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.

Describe and discuss the monogenic and polygenic forms of obesity.

Monogenic and Polygenic Obesity:

Adipocyte and Adipose Tissue:

• Adipose tissue consists of adipocytes and stromal/vascular component (preadipocytes, macrophages, fibroblasts, collagen tissue).

Adipose mass increases by:

• Enlargement of adipose cells through lipid deposition
• Increase in number of adipocytes
• Increase in number of infiltrating macrophages.

Pathogenesis:

Peripheral Affrent 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 (pro-opiomelanocortin)/CART (cocaine and amphetamineregulated transcript) pathway and inhibits NPY/AgRP pathway causing appetite to be 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 peptide YY (PYY), pancreatic polypeptide, insulin, and amylin.
  • Insulin: It is secreted by cells of the pancreas andacts centrally to activate the appetite suppressing pathway.
  • Peptide YY: 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 b-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.

Obestatin: It is a peptide produced by the same gene that encodes ghrelin. It counteracts the increase in food intake induced by ghrelin.

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.

Central Processing:

The arcuate nucleus of the hypothalamus processes and neurohumoral peripheral afferent signals and generates efferent signals.

Central Processing It consists of:

Central appetite-suppressing (anorexigenic pathway or leptin
melanocortin pathway): In this pathway, POMC/CART neurons enhance energy expenditure and weight loss through the production of the anorexigenic (suppresses appetite) neuro-peptides mainlya-MSH (a-melanocyte-stimulating hormone) by cleavage of POMC by PC1 (prohormone convertase).

Central appetite-stimulating (orexigenic) pathway It consists of:

• NPY (neuropeptide Y)/AgRP (agouti-related peptide) containing 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.

Peripheral Effrent 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 acts on multiple pathways, its deficiency causes increased hunger and reduced satiation and satiety.

Following a meal, substances such as cholecystokinin (CCK), bombesin, and glucagon–like peptide-1 (GLP-1) 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, g-aminobutyric acid
• Appetite stimulators: Opioids

Energy expenditure:

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.

Thermic effect of food (thermogenesis): About 10% of ingested energy is spent in the process of digestion, absorption, and metabolism of nutrients irrespective of physical activity. This is called as dietary-induced thermogenesis which is lower in obese individuals.

Physical activity: Obese individuals tend to spend more energy during physical activity as they have a larger mass to move.

Theory of Body Weight ‘Set Point’ in Hypothalamus:

Pathologic Consequences of Obesity (Complications of Obesity):

Describe the pathogenesis of obesity and its consequences.

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 response 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 is found in >80% of patients with type 2 diabetes.

Causes of insulin resistance in obesity:

• Obese individuals have excess circulating FFAs and there is an inverse correlation between fasting plasma FFAs and insulin sensitivity. Central obesity is associated with insulin resistance. Excess intracellular FFAs increase gluconeogenesis.
• Adipokines: Adipose tissue acts as a functional endocrine organ and secretes 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:

Dyslipidemia:

• 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.

Endocrine manifestations of obesity:

• Reproductive disorders associated with obesity are listed in Table.

Consequences of insulin resistance:

• Muscle: Hyperglycemia and diabetes mellitus
• Kidneys: Salt retention and hypertension
• Ovaries: Increase testosterone and polycystic ovary syndrome (PCOS)
• Heart: Increase plasminogen activator inhibitor-1 (PAI-1)
  and acute coronary syndrome
• Cancers: Colon, prostate, breast
• Sympathetic system: Increased cytokines and blood pressure

Mechanical complications of obesity:

Osteoarthritis : Extremity degenerative joint disease (osteoarthritis) and also gout.

Venous stasis/varicose veins:

• Acanthosis nigricans: Reflects the severity of underlying insulin resistance.
• Increased friability of skin: It may be seen especially in skinfolds, thereby increasing the risk of fungal and yeast infections.

Urinary incontinence:

Pulmonary disease:

• 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 hypoventilation syndrome is also known as Pickwickian syndrome.

Obesity and asthma: Reduced TLC (total lung capacity), reduced RV (residual volume) and FRC (functional residual capacity).

Obesity and cancer:

• Obesity is the biggest preventable cause of cancer after smoking.
• Accounts for 14% of cancer deaths in men and 20% in women.

Gastrointestinal disorders:

Following are more prevalent in obese patients:

Gastroesophageal reflux disease:

• Gallstones: Obesity is associated with increased secretion of cholesterol in the bile, supersaturation of bile, and a higher incidence of gallstones, especially cholesterol gallstones.
• Fatty liver (steatosis) and nonalcoholic steatohepatitis: Nonalcoholic fatty liver disease (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 nonobese.
• 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.

Clinical Assessment, Investigations, and Diagnosis:

Aims of assessing of obesity are to:

• Evaluate and quantify severity of obesity: Severity of obesity can be quantified using the BMI.
• Exclude an underlying cause
• Identify complications
• Prepare a management plan

Appearance of a patient with morbid obesity is shown.

Describe and enumerate the indications, pharmacology, and side effects of pharmacotherapy for obesity.

Management:

Goal:

• Initially to reduce weight by about 10% from baseline
• Reduce weight of about 0.5–1 kg/week for 6 months.

Life style modification diet:

• Low calorie diet, low in saturated fats, low density foods, normal protein intake and increased fibers in diet.
• 1,000 kcal deficit produces 1 kg weight loss per week. No matter what the calorie intake is the constituents remain in same proportion (i.e., carbohydrates 55%, fat 30%, and protein 15%).
• Total fasting: Not recommended. There is diuresis, natriuresis, and all deficiencies.
• Refeeding syndrome: Severe and potentially fatal electrolyte, fluid and metabolic abnormalities when feeding is resumed.
• Physical activity: Regular physical activity enables to maintain loss of weight. Has to be done under supervision. Moderate exercise
  to be done for 30–45 minutes and 3–5 days/week.
• Behavioral modification: Useful as adjunct to diet and physical exercise; Patient often needs motivation to lose weight.

Drug therapy (pharmacotherapy): Lifestyle modification should be considered before starting drug therapy.

• Centrally acting drugs

Sibutramine:

• Mechanism of action: Centrally acting, mono-amine reuptake inhibitor (primarily serotonin and norepinephrine). By sympathetic stimulation, it prevents decrease in BMR. It reduces appetite.
• Dose: 10–15 mg once daily.
• Side effcts: Hypertension, tachycardia, sweating, dizziness, and headache.
• Contraindications: Coronary artery disease, cardiac arrhythmias, uncontrolled hypertension.

Rimonabant:

Mechanism of action: Endocannabinoid 1 (CB1) receptor blocker. It has both central and peripheral actions and reduces weight and weight-related metabolic factors.

FDA approval: BANNED

Side effcts: Depression, anxiety, suicidal tendencies.

• Peripherally acting drugs

Orlistat:

Mechanism of action: Nonsystemic reversible inhibitor of gastric and pancreatic lipases by forming a covalent bond with
serine residue. It acts on stomach and intestine.

Dose: 120 mg BD or TID with meals.

FDA approval: For adults and adolescents as well as children.

Side effcts: Flatulence, defecation increases, oily evacuation, rectal leakage, steatorrhea.

Olestra: Olestra is synthesized using a sucrose molecule, which can support from 6 to 8 fatty acid chains arranged radially like an octopus. Too large to move through the intestinal wall and be absorbed. Same taste and mouth feel as fat. Approval as a food additive up to 35% replacement of fats in home cooking and 75% in commercial uses.

Others:

• Phentermine: Amphetamine like drug, acts centrally to reduce appetite. It has low addictive potential, modest efficacy and CVS side effects.
• Metformin: Decreases appetite and thereby reduces weight. Since most DM 2 patients are obese, this is a good choice in DM 2.
• Tesofensine (TE) is a norepinephrine, dopamine, and serotonin reuptake inhibitor. Primarily used as an appetite suppressant.
• Betahistine: Stimulates the histamine-1 receptor and reduces the craving not only for food in general but for fatty foods in particular. Not approved by FDA.
• Amylin (pramlintide): Part of the endocrine pancreas and contributes to glycemic control. Functions as a synergistic partner to insulin.
• Liraglutide, a GLP-1 agonist (1.8 or 3 mg daily), is an option for overweight or obese patients.
• Lorcaserin, serotonin agonist approved by FDA

Combination therapy:

• Phentermine-topiramate
• Bupropion-naltrexone

Bariatric surgical techniques: Divided into three groups:

1. Malabsorptive procedures: Induce decreased absorption of nutrients by shortening the functional length of the small intestine (e.g., biliopancreatic diversion and Roux-en-Y gastric bypass). These procedures cause deficiency of nutrients, malnutrition and in some cases, anastomotic leaks and the dumping syndrome (e.g., with the duodenal switch).

2. Restrictive procedures: Reduce the storage capacity of the stomach and as a result early satiety arises, leading to a decreased caloric intake (e.g., adjustable gastric banding, vertical banded gastroplasty and sleeve gastroplasty).

3. Restrictive plus malabsorptive procedures (e.g., duodenal switch, Roux-en-Y gastric bypass, intragastric balloon).

Liposuction: It is the removal of large amounts of fat by suction (liposuction). It does not deal with the underlying cause and weight
regain frequently occurs. There is no reduction in cardiovascular risk factors with the procedure.

Others:

• Electrical stimulation (vagal blockade) systems

Hydrogels: Hydrogels are orally administered products, taken twice daily before meals, which expand in the stomach and
intestines to create a sensation of satiety. They are not systemically absorbed, and are eliminated through the feces.

Dietary supplements: Although over-the-counter dietary supplements are widely used by individuals attempting to lose weight—like ephedra, green tea, chromium, chitosan, and guar gum. These are not recommended and are inadequate and unsafe methods to lose weight. Various surgical options for the treatment of obesity are shown.

Describe and enumerate the indications and side effects of bariatric surgery.

Bariatric Surgery:

Indications:

BMI ≥40 kg/m2 without comorbid illness

BMI 35.0–39.9 kg/m2 with at least one serious comorbidity like:

• Type 2 diabetes
• Obstructive sleep apnea (OSA)
• Hypertension
• Hyperlipidemia
• Obesity hypoventilation syndrome (OHS)
• Pickwickian syndrome (combination of OSA and OHS)
• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis (NASH)
• Pseudotumor cerebri
• Gastroesophageal reflux disease
• Asthma
• Venous stasis disease
• Severe urinary incontinence
• Debilitating arthritis
• Impaired quality of life
• Disqualification from other surgeries as a result of obesity (i.e., surgeries for osteoarthritic disease, ventral hernias,
  or stress incontinence)

BMI between 30.0–34.9 kg/m² and one of the following comorbid conditions like:

• Uncontrollable type 2 diabetes
• Metabolic syndrome

Contraindications:

• Untreated major depression or psychosis
• Uncontrolled and untreated eating disorders (e.g., bulimia)

• Drug and alcohol abuse
• Severe cardiac disease, in which anesthesia may be dangerous and contraindicated
• Severe coagulopathy
• Compliance issues with long-term nutritional replacement (e.g., vitamins)

Adverse effects:

During the procedure:

• Hemorrhage
• Infections
• Gastrointestinal leaks
• Anesthesia-related complications

Postoperative:

• Bowel obstruction
• Dumping syndrome
• Gallstones
• Hernias
• Malnutrition, hypoglycemia
• Gastroesophageal reflux disease
• Repeat surgery may be required.

Environmental Diseases

Radiation Exposure:

Types of Radiation:

Ionizing radiation: Used in X-rays, computed tomography (CT), radionuclide 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 (g) rays. It affects the skin and deeper tissues.
• Nonpenetrating radiation: It includes charged subatomic alpha and beta particles.

Nonionizing radiations: Ultraviolet (UV) rays of sunlight visible light, laser, infrared and microwave. It affects only skin.
Nonionizing UV is used for therapy in skin diseases and laser therapy for diabetic retinopathy.

Sources: Background radiation, medical exposure, industrial exposure, and accidental or deliberate nuclear events.

Effcts of Radiation Exposure:

Write short essay/note on effects of radiation exposure.

Radiation Sickness:

Write short note on radiation sickness.

• Mild acute radiation sickness: It is characterized by nausea, vomiting, and malaise following doses of about 1 Gy. Lymphopenia develops within several days, followed 2–3 weeks later by a reduction 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, GI, central nervous system, and skin.
• Effects on the individual are classified as either deterministic or stochastic.
• Deterministic (threshold) effects
  • Nature of tissue: Tissues with actively dividing cells (labile cells), such as bone marrow and GI mucosa, are more sensitive to ionizing radiation.
  • Hemopoietic system: Lymphocyte depletion is the most sensitive indicator of bone marrow injury. After exposure to a fatal dose, aplasia of the bone marrow is a most common 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 and pulmonary fibrosis.
  • Central nervous system syndrome: Exposure of >30 Gy causes nausea, vomiting, disorientation, and coma. Death
    due to cerebral edema can follow within 36 hours. It may also cause permanent neurological deficit.
  • Bone necrosis and lymphatic fibrosis occur following regional irradiation, particularly for breast cancer.
  • Thyroid gland due to its capacity to concentrate iodine is responsible for its susceptibility to damage even after
    exposure to relatively low doses of radioactivity.
  • Stochastic effects: 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.

High Altitude:

Illnesses at High Altitude:

Write short essay/note on mountain sickness.

• For normal individuals, ascent to altitudes up to 2,500
  m or travel in a pressurized aircraft cabin is harmless.
• Above 2,500 m high-altitude illnesses may develop in healthy individuals, and above 3,500 m symptoms commonly develop.
• Sudden ascent to altitudes above 6,000 m (e.g., by aviators, balloonists and astronauts) may cause decompression sickness.
• The clinical features of decompression sickness are similar to in divers and even cause loss of consciousness.
• However, most high-altitude illness develops in travelers and mountaineers.

High-altitude physiology:

• Hypobaric hypoxia—pressure gradient as well as oxygenation decreases with increase in altitude.
• Acclimatization—complex physiological processes occurring in the body in response to acute hypobaric hypoxia; adaptation—different from acclimatization as it occurs in individuals living chronically in high-altitude areas.
• Ventilation—hypoxia stimulates peripheral chemoreceptors causing increase in minute ventilation called hypoxia
  ventilation response (HVR).
• Arterial blood gases—hyperventilation leads to decreased pCO2 and increased pH—respiratory alkalosis. This is sensed
  by the central chemoreceptors and ventilation is inhibited.
• Renal compensation—within 24–48 hours, kidney starts excreting bicarbonate; therefore, decreasing pH so as to allow
  ventilation that leads to alkalosis.
• Circulatory changes—increased cardiac, pulmonary, and cerebral blood flow.
• Hematological changes—rise in Hb to increase oxygen
  carrying capacity of blood.

Acute Mountain Sickness:

• Acute mountain sickness (AMS) 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:

• High-altitude cerebral edema (HACE) is a rare, life-threatening condition and usually preceded 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.
• Signs: Papilledema and retinal hemorrhages are common. Focal neurological signs may be detected.

Treatment of acute mountain sickness:

• Mild cases require rest and simple analgesics.
• Symptoms usually resolve after 1–3 days at a stable altitude, but may recur with further ascent. Occasionally, it may then progress to cerebral edema.
• Supplemental oxygen may help.
• If the symptoms persist, it indicates the need to descend but
  may respond to acetazolamide (carbonic anhydrase inhibitor) that produces a metabolic acidosis and stimulates ventilation.
• Acetazolamide is used as a prophylaxis, if a rapid ascent is planned.
• Hyperbaric therapy

Treatment of high-altitude cerebral edema:

• Improve oxygenation
• Descent is needed, and if descent is not possible, oxygen therapy in a portable pressurized bag is useful
• Dexamethasone: 8 mg immediately and 4 mg four times daily
• Supplemental oxygen
• Hyperbaric therapy

High-altitude Pulmonary Edema:

Write short essay/note on high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a life-threatening
condition.

Time of occurrence: It usually occurs in the first 4 days after ascent above 2,500 m. Unlike HACE, HAPE may develop de novo without the preceding signs of AMS.

Types: classic HAPE—acute ascent in those residing at low altitude, re-entrant HAPE—acute ascent in those residing at high altitude after residing at low altitude.

Symptoms:

• 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.

Investigations:

• Radiologically, show diffuse alveolar edema.
• Decreased arterial oxygen saturation.

High-altitude retinal hemorrhage:

• It may be found in about 30% of trekkers at 5,000 m and is usually asymptomatic and resolve spontaneously.
• Visual defects can develop when the hemorrhage involves the macula.
• There is no specific treatment.

Venous thrombosis:

• Can develop at altitudes over 6,000 m.
• Risk factors are dehydration, inactivity, cold and use of oral contraceptive pill at high altitude.

Refractory cough:

• 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.

Heat-Related Illness

Write short essay/note on causes and clinical features of hyperthermia.

Hyperthermia:

• Definition: Hyperthermia is defined as an elevation of the core body temperature above the normal diurnal range of 36–37.5°C due to failure of thermoregulation.
• A temperature above 40°C (or 104°F) is generally considered as severe hyperthermia.
• Heat-related illnesses are listed.

Pathophysiology:

• Temperature elevation is accompanied by an increase in oxygen consumption and metabolic rate, resulting in hyperpnea and tachycardia.
• Above 42°C (108°F), oxidative phosphorylation becomes uncoupled, and a variety of enzymes cease to function.
• A cytokine-mediated systemic inflammatory response develops, and production of heat shock proteins is increased.
• Blood is shunted from the splanchnic circulation to the skin and muscles, resulting in GI ischemia and increased permeability of the intestinal mucosa.
• Hepatocytes, vascular endothelium, and neural tissue are most sensitive to increased core temperatures, but all organs may ultimately be involved.
• In severe cases, patients develop multiorgan system failure and disseminated intravascular coagulation (DIC).
• Treatment of high-altitude pulmonary edema
• Reversal of hypoxia with immediate descent and oxygen administration.
• Nifedipine (20 mg four times daily) is given to reduce pulmonary arterial pressure. If there is delay in descent, oxygen therapy in a portable pressurized bag should be given.
• Other treatment options: Hyperbaric therapy, positive airway pressure, tadanafil/sildenafil, dexamethasone, salmeterol.

Heat-related illnesses:

• Heat cramps
• Heat edema
• Heat exhaustion
• Exertional heat injury
• Heatstroke

Heatstroke:

Write short essay/note on heatstroke.

Types of Heatstroke:

Classic/Nonexertional:

• “Summer Heat Waves”
• No sweat in 84–100% of patients
• More insidious onset
• Usually affects elderly and debilitated patients with chronic underlying disease
• Rhabdomyolysis and acute renal failure (ARF) rare.

Exertional:

• Young, healthy, laborers, athletes, military recruits who over exert themselves in high ambient (temperatures or in a hot environment) to which they are not acclimatized.
• Rhabdomyolysis and ARF common.
• Usually have predisposing factor.

Predisposing Factors:

• Increased heat production: Hyperthyroidism, exercise, sepsis.
• Impaired heat loss (impaired sweating)
  • Drugs: Anticholinergics, anti-Parkinsonian drugs, antihistamines, butyrophenones, phenothiazines, tricyclics.
  • Abnormal sweat glands: Examples: sweat gland injury following acute heatstroke, barbiturate poisoning; cystic fibrosis; and healed thermal burn.
  • Salt and water depletion: diuretic induced.
  • Hypokalemia
• Impaired voluntary mechanisms: Coma, physical disability, mental illness
• Impaired delivery of blood to peripheral circulation: Cardiovascular disease, hypokalemia (decreased muscle blood flow), dehydration.
• Others: Elderly, high ambient temperature and humidity, poor ventilation, lack of acclimatization, obesity, fatigue, diabetes mellitus, malnutrition, and alcoholism.

Clinical Features:

• It may develop without any warning prodrome prior to development of nonexertional heatstroke (classic heatstroke).
• As thermoregulatory mechanisms fail body temperature rises rapidly and patient can deteriorate rapidly from apparent baseline health to coma or mentally dull state.

Three cardinal signs are:

• CNS dysfunction
• Hyperpyrexia (core temperature >40°C)
• Hot dry skin. Pink or ashen depending on circulatory
  state. However, it may be clammy and sweat.
• Clinical features of heat exhaustion and heatstroke are depicted.

Central nervous system:

• Direct thermal toxicity causes cell death, cerebral
  edema, and local hemorrhage. Irritability or irrational
  behavior may precede the development of either form of
  heatstroke.
• Confusion, aggressive behavior, delirium, convulsions,
  and pupillary abnormalities may progress rapidly to coma.
• ± decorticate posturing, fecal incontinence, flaccidity or hemiplegia (however, focal signs are unusual).
• Cerebellar signs, including ataxia and dysarthria
• Hypothalamic damage may exacerbate heatstroke by further impairing sweating and heat loss.
• Lumbar puncture may show increased protein, xanthochromia, and slight increase in lymphocytes

Cardiovascular system:

• Tachycardia, dysrhythmias
• Hypotension or normotensive with wide pulse pressure.
• Hyperdynamic-hemodynamic profile.

Myocardial pump failure: Myocardial damage and frank infarction frequent even in patients with normal coronaries due to the effect of heat on myocytes and coronary hypoperfusion secondary to hypovolemia.

Respiratory system:

• Extreme tachypnea with respiratory rate up to 60/minute.
• Crackles and cyanosis—signs of pulmonary edema
• Direct thermal injury to pulmonary vascular endothelium may lead to cor pulmonale or acute respiratory distress syndrome (ARDS).

Metabolic:

• Dehydration leading to raised urea and creatinine, and hemoconcentration.
• Sweating results in low levels of Na, Mg, K, during early phase of the illness. Hypokalemia decreases sweat secretion and therefore exacerbates the condition.
• Rhabdomyolysis resulting in hyperkalemia, hypocalcemia, and renal failure.
• Metabolic acidosis and respiratory alkalosis common.

Splanchnic:

• Ischemic intestinal ulceration common. May lead to hemorrhage.
• Hepatic damage common. In 5–10%, hepatic necrosis may be severe enough to cause death.

Renal:

• As a direct result of heat potentiated by dehydration and rhabdomyolysis.
• Acute renal failure 5–6 times more common in patients with exertional heatstroke in whom it occurs in 30–35%.

Hematological:

• Anemia and bleeding: Result from direct inactivation of platelets and clotting factors by heat, liver failure, and platelet aggregation due to heat.
• Disseminated intravascular coagulation: Due to activation of clotting cascade by damaged vascular endothelium. Latter may be damaged as a direct result of heat.

Investigations in heatstroke:

• Temperature recording
• Electrolytes, urea, creatinine, calcium
• Liver function tests
• Creatine phosphokinase (CPK)
• Arterial blood gas (ABG)
• ECG monitoring
• Urine output

Full blood count (FBC), clotting, fibrinogen, FDP, D-dimer:

• Anemia frequent, platelets low/normal, lymphocytosis
• Test urine for myoglobin

Investigations:

Management:

• The most important causes of severe hyperthermia [>40°C (104°F)] due to a failure of thermoregulation are heatstroke, neuroleptic malignant syndrome (NMS), and malignant hyperthermia [Other differentials refer.
• The context in which symptoms develop usually suggests the etiology (e.g., exertional heatstroke following exercise in high ambient temperature and humidity; malignant
• hyperthermia after anesthetic agents; NMS among patients treated with antipsychotic medications).

First aid for heatstroke or sunstroke:

• Remove victim to cooler location, out of the sun.
• Loosen or remove clothing, and if possible, immerse the victim in very cool water.
• If immersion cannot be done, cool victim with water, or wrap in wet sheets and fan to facilitate quick evaporation.
• Use cold compresses mainly in the region of the head and neck, armpits and groin.
• Seek medical attention immediately—continue first aid to lower temperature. Until medical help takes over.
• Not to administer any medication to lower fever because it is not useful and may be in fact cause more harm.
• Do not use an alcohol rub.
• Do not give anything by mouth including water until the condition has been stabilized.

In hospital care: Usually treat the heatstroke in a critical care unit. Various cooling methods are listed.

Supportive:

• IV volume replacement.
• If inotrope required dobutamine probably drug of choice.
• Urgent treatment of hyperkalemia
• Do not treat hypocalcemia per se; only give calcium, if ECG changes of severe hyperkalemia occur as calcium may exacerbate rhabdomyolysis.
• Small dose of mannitol may benefit patients with rhabdomyolysis, intravenous lorazepam for shivering.
• Avoid following medications
  • Acetylsalicylic acid (ASA): Uncouples oxidative phosphorylation and increases temperature.
  • Paracetamol: Increases hepatic dysfunction and may create toxicity.
  • Dantrolene is not effective, but good for malignant hyperthermia.

Various cooling methods that can be carried out in heatstroke:

• Evaporative
• Immersion
• Strategic ice packs
• Ice cold IV fluids
• Ice packing
• Cooling blankets
• Gastric lavage
• Peritoneal lavage
• Cardiac bypass
• Endovascular cooling
• Catheters

Hypothermia:

Definition: Hypothermia is defined as a core temperature
below 35°C (95°F).

• Mild hypothermia: Core temperature 32–35°C (90–
  95°F).
• Moderate hypothermia: Core temperature 28–32°C
  (82–90°F).
• Severe hypothermia: Core temperature below 28°C
  (82°F).

Primary hypothermia happens because of overwhelming cold exposure. Heat production in itself is normal.

Secondary hypothermia: Hypothyroidism, Addison’s
disease, malnutrition, burns, hypothalamic abnormalities,
sepsis, thiamine deficiency, alcohol intoxication, hypoglycemia, etc.

Clinical Symptoms:

Investigations:

These include: Blood glucose, renal function tests, electrolytes including calcium, CPK, TSH, ABG, complete hemogram, X-ray chest, and ECG.

Electrocardiographic changes:

• Hypothermia causes characteristic ECG changes because of slowed impulse conduction through potassium channels. This results in prolongation of all the ECG intervals, including RR, PR, QRS, and QT.
• Elevation of the J point (only if the ST segment is unaltered), producing a characteristic J or Osborn wave. The height of the Osborn wave is roughly proportional to the degree of hypothermia.

Management:

• Evaluation and support of the airway, breathing, and circulation.
• Prevention of further heat loss.
• Initiation of rewarming appropriate to the degree of hypothermia. Various rewarming methods are:

Passive rewarming:

• Endogenous heat production: Shivering, metabolic rate, TSH, sympathetic activity.
• I nvolves decreasing heat loss—remove from cold environment, remove wet clothes, provide blanket.
• Active external rewarming and active internal (core) rewarming

Treatment of complications: Careful attention to potential complications, including hypotension during active rewarming, arrhythmia, hyperkalemia, hypoglycemia, rhabdomyolysis, bladder atony, and bleeding diathesis

Drowning Submersion Injuries

Write a short essay on near drowning in fresh water.

• Drowning: Asphyxiation caused by submersion in a liquid that causes interruption of the body’s oxygen absorption.
• Near drowning: Term formerly used to describe victim’s survival at least 24 hours after submersion.
• Salt versus fresh water is no longer emphasized as degree of pulmonary insult is determined by quantity aspirated.
• Wet drowning: Aspiration of water into airways and lungs (85%). 1–3 cc of aspirated water will lead to destruction of surfactant, alveolar instability, noncardiogenic pulmonary edema, and impaired gas exchange.
• Dry drowning: Severe parasympathetically mediated laryngospasm (15%).
• Aspiration of >11 mL/kg of body weight must occur before blood volume changes occur, and >22 mL/kg before electrolyte changes take place.
• It is unusual for nonfatal drowning victims to aspirate >3–4 mL/kg.
• Both types result in common pathway of hypoxia which leads to acidosis, cardiac arrest, and brain death.

Pathophysiology of Drowning:

Risk Factors for Drowning:

Three peaks in incidence:

• Toddlers
• Adolescents
• Elderly

Various stages of drowning are shown in Flowchart.

Signs and Symptoms:

• About 70% of patients develops signs within 7 hours.
• Alertness, agitation, coma.
• Cyanosis, coughing, and pink frothy sputum (pulmonary edema).
• Tachypnea, tachycardia.
• Low-grade fever.
• Rales, rhonchi, and less often wheezes.
• Signs of associated trauma to the head and neck should be sought.
• Persons with hypothermia can have significant hypovolemia and hypotension due to a “cold diuresis”. This occurs because during the early phase of vasoconstriction, blood moves to the core, causing central volume receptors to sense fluid overload, and resulting in decreased antidiuretic hormone production.

End organ effects:

Pulmonary: Fluid aspiration results in varying degrees of hypoxemia, noncardiogenic pulmonary edema—ARDS.

Neurologic: Hypoxemia and ischemia cause neuronal damage, which can produce cerebral edema and elevations in intracranial pressure which can progress into hypoxic ischemic encephalopathy.

Cardiovascular: Arrhythmias secondary to hypothermia and hypoxemia like sinus tachycardia, sinus bradycardia,
and atrial fibrillation.

Acid-base and electrolytes: A metabolic and/or respiratory acidosis is often observed. Rarely drowning in concentrated seawater can produce life-threatening hypernatremia, hypermagnesemia, and hypercalcemia due to absorption of swallowed seawater.

Risk factors for drowning:

• Drug and alcohol intoxication
• Cardiac arrest
• Hypoglycemia
• Seizure
• Suicidal or homicidal behavior
• Child abuse
• Inadequate adult supervision
• Inability to swim or overestimation of swimming capabilities
• Risk-taking behavior
• Hypothermia, which can lead to rapid exhaustion or cardiac arrhythmias
• Undetected primary cardiac arrhythmia: Cold water immersion and exercise can cause fatal arrhythmias in patients with the congenital long QT syndrome type 1. Similarly, mutations in the cardiac ryanodine receptor (RyR)-2 gene, which is associated with familial polymorphic VT in the absence of structural heart disease or QT prolongation, have been identified in some individuals with unexplained drowning.
• Hyperventilation prior to a shallow dive: Swimmers commonly hyperventilate in order to prolong the duration of underwater swimming, and by so doing they reduce the arterial partial pressure of carbon dioxide (PaCO2) while the content of oxygen (CaO2) does not increase appreciably. As the individual swims, oxygen is consumed and the partial pressure of oxygen (PaO2) falls to 30–40 mm Hg before the PaCO2 rises sufficiently to trigger the urge to breathe. This can lead to cerebral hypoxia, seizures, and loss of consciousness, which can result in drowning.

Renal: Renal failure due to acute tubular necrosis resulting from hypoxemia, shock, hemoglobinuria, or myoglobinuria is rare.

Poor prognostic signs of drowning are listed

Poor prognostic signs of drowning:

• Duration of submersion >5 minutes (most critical factor)
• Time to effective basic life support >10 minutes
• Resuscitation duration >25 minutes
• Glasgow coma scale <5 (i.e., comatose)
• Persistent apnea and requirement of cardiopulmonary resuscitation in the emergency department
• Arterial blood pH <7.1 upon presentation

Management:

• It includes prehospital care, emergency department (ED) care, and inpatient care.
• Ventilation is the most important initial treatment of submersion injury.
• The Heimlich maneuver or other postural drainage techniques to remove water from the lungs are of no proven value, and rescue breathing should not be delayed in order to perform these maneuver.
• Standard CPR protocol needs to be followed.
• Identify spine injuries and other major organ injuries and manage accordingly.
• Supportive care: Renal failure, shock, infections, etc.