Nutritional Disorders.pptx

NUTRITION AL DISORDER S MBCHB III/BDS III Prof. Lucy Muchiri 2024 NUTRITIONAL DISEASES An adequate diet should provide:  Sufficient energy in the form of carbohydrates, fats and proteins  Vitamins & minerals - function as co-enzymes or hormones in vital metabolic pathways or, as fo...

NUTRITION AL DISORDER S MBCHB III/BDS III Prof. Lucy Muchiri 2024 NUTRITIONAL DISEASES An adequate diet should provide:  Sufficient energy in the form of carbohydrates, fats and proteins  Vitamins & minerals - function as co-enzymes or hormones in vital metabolic pathways or, as for Ca & Phosphates are important structural components MAIN NUTRITIONAL DISORDERS  Obesity  Kwashiorkor  Marasmus  Anorexia nervosa  Bulimia nervosa  Vitamin deficiency  Trace element deficiency 3 MALNUTRITION  The World Health Organization defines malnutrition as "the cellular imbalance between supply of nutrients & energy, and the body's demand for them to ensure growth, maintenance, and specific functions“  Primary: related to diet  Secondary: related to  Nutrient malabsorption  Impaired nutrient utilization or storage  Excess nutrient losses  Increased need for nutrients PROTEIN-ENERGY MALNUTRITION  Inadequate intake of protein & calories  Two main clinical syndromes:  Marasmus * starvation in infant with overall lack of calories * somatic protein compartment (skeletal muscles) affected  Kwashiorkor * protein deprivation more severe than deficit in calories * visceral compartment (protein stores in liver ) affected  MARASMUS  Is a consequence of protein energy deficiency characterized by:  Wasting of muscles and fat tissue (“skin & bone”)  growth retardation  Serum protein is normal, NO edema  Can occur at any age & can be easily compensated by normalizing nutritional supply of proteins & other nutrients  Clinical Features:  Weight is less than 60% of normal  Loss of muscle mass & subcutaneous fat  emaciation of extremities, head appears too large for body  Usually associated anemia, multivitamin deficiencies & immune deficiency (T-cell mediated immunity)  concurrent infections KWASHIORKOR  Is a childhood protein energy deficiency  Occurs when protein deprivation is greater than reduction in total calories  Typically in children who have been weaned off the mother’s breast when the second child is born  S/S: hypoalbuminemia & generalized or dependent edema  Loss of weight masked by edema  Usually sparing of muscle & subcutaneous fat  Weight is between 60% -80% of normal  Other clinical features include:  FLAKY PAINT appearance of skin (alternating zones of hyperpigmentation, areas of desquamation & hypopigmentation)  Alternating bands of pale and dark hair – FLAG sign  Enlarged FATTY LIVER  Atrophy and loss of small intestinal villi, leading to concurrent loss of small intestinal enzymes disaccharidase deficiency  Apathy and listlessness  Loss of appetite  Other vitamin deficiencies, & defects in immunity Marasmus Kwashiorkor KWASHIORKOR MARASMUS Clinical features Clinical features  Occurs in children  Common in infants under 1 between 6 months 3 year of age years of age  Growth failure  Growth failure  Muscle wasting but  Wasting of all tissues preserved adipose tissue including muscles &  Edema, localized or adipose tissue  Edema absent generalized  Enlarged fatty liver  Serum proteins low  No hepatic enlargement  Serum proteins normal  Anemia present  Anemia present  Alternate bands of light  Monkey-like face, and dark hair – FLAG protuberant abdomen, thin sign limbs 11 KWASHIORKOR MARASMUS  Morphology  Morphology  Enlarged fatty liver  No fatty liver 10/07/2024  Atrophy of different  Atrophy of different tissues and organs but tissues and organs NUTRITIONAL DISORDERS subcutaneous fat including subcutaneous preserved fat  Small bowel – mucosal  Rarely seen atrophy & loss of villi and micro villi  Bone marrow hypoplastic  Hypoplastic  Cerebral atrophy  Present  Thymic & lymphoid  Less marked atrophy 12  10/07/2024 NUTRITIONAL DISORDERS 13 KWASHIORKOR AND MARASMUS  10/07/2024 NUTRITIONAL DISORDERS 14 MARASMUS PEM IN DEVELOPED WORLD  Secondary PEM  Develops in chronically ill, older and bed-ridden patients  Obvious Signs of secondary PEM include:  Depletionof subcutaneous fat in arms, chest wall, shoulders or metacarpal regions  Wasting of quadriceps & deltoid muscles  Ankle or sacral edema CACHEXIA  PEM in patients with AIDS or advanced CANCER is known as cachexia  Characterized by extreme weight loss, fatigue, muscle atrophy, anemia, anorexia, & edema  Exact cause not known, some theories  Mediators secreted by tumors contribute to cachexia:  Proteolysis inducing factor  lipid- mobilizing factor ANOREXIA NERVOSA  Self induced starvation resulting in marked wt loss  Clinical features similar to severe PEM  Addition endocrine system dysfunction:  AMENORRHEA (GnRH secretion decreases)  Symptoms of HYPOTHYROIDISM  BONE DENSITY decreased  Dehydration & electrolyte abnormalities  Major complication: CARDIAC ARRHYTHMIA & SUDDEN DEATH due to hypokalemia BULIMIA NERVOSA  Patient binges on food & then induces vomiting  More common than anorexia nervosa  No specific signs or symptoms  Diagnosis depend on psychological assessment  Major complications occur due to frequent vomiting & chronic use of laxatives & diuretics:  Electrolyte imbalance (hypokalemia)  cardiac arrhythmias  Pulmonary aspiration of gastric contents  Esophageal and gastric rupture  OBESITY  Obesity is defined as an accumulation of excess of adipose tissue that imparts health risk.  A body weight of 20% excess over ideal wt for age, sex and height is considered as health risk Etiology  Obesity results when calorie intake exceeds utilization as in:  Over-eating  Inactivity and sedentary life-style 19 OBESITY CONT’D  Genetic predisposition to develop obesity  Loss of function mutation in leptin  Mutation of melanocortin receptor 4(MC4R)  Haploinsufficiency of BDNF (brain derived neurotrophic factor) associated with obesity in WAGR syndrome (Wilms tumor, aniridia, genitourinary defects, mental retardation)  Diets largely derived from carbohydrates and fats than protein rich food  Secondary obesiy due to hypothyroidism, Cushings d/s, insulinoma, and hypothalamic disorders OBESITY CONT’D  How to measure fat accumulation:  Body mass index (BMI: kg/m2):  Normal BMI  18.5 to 25  25-30  overweight  >30  obese  Skin fold measurements  Various body circumferences particularly the ratio of waist-to-hip circumference  Distribution of fat also has an effect: central or visceral obesity associated with more risk than excess accumulation of fat in subcutaneous tissue OBESITY CONT’D Two basic types of obesity: A. Life-long obesity: Also called hyperplastic obesity  Begins in childhood, is characterized by increased number of adipocytes in peripheral parts of the body B. Adult onset obesity:  Also called hypertrophic obesity  Characterized by increased size of fat cells & central obesity  Fat accumulates in the trunk  HOW DOES THE BODY PREVENT THE DEVELOPMENT OF OBESITY? o Balance between calorie intake & expenditure. o Critical role in this regulation is played by Leptin o Neuro-humoral mechanism regulating energy balance – 3 components: 1. Peripheral or afferent system  generates signals from various sites. Components are: Leptin & adiponectin produced by fat cells  Ghrelin from the stomach  Peptide YY (PYY) from the ileum and colon  Insulin from the pancreas 2. Arcuate nucleus in hypothalamus processes signals & generate efferent signals. Consists of two subsets of firstorder neurons:  (1) POMC (pro-opiomelanocortin) and CART (cocaine and amphetamine-regulated transcripts) neurons  POMC/CART neurons enhance energy expenditure & weight loss through the production of the anorexigenic α-melanocyte- stimulating hormone (MSH), and  The activation of melanocortin receptors 3 and 4 (MC3/4R) in second-order neurons  These second order neurons are in turn responsible for producing factors such as thyroid releasing hormone (TSH) & corticotropin releasing hormone (CRH) that increase basal metabolic rate & anabolic metabolism, thus favoring weight loss   (2) neurons containing NPY (neuropeptideY) and AgRP (agouti-related peptide)  the NPY/AgRP neurons promote food intake (orexigenic effect) and weight gain, through the activation of Y1/5 receptors in secondary neurons  These secondary neurons then release factors such as melanin-concentrating hormone (MCH) and orexin, which stimulate appetite  These first-order neurons communicate with second- order neurons in the hypothalamus 3. Efferent system  2 pathways anabolic & catabolic pathway - controls food intake & energy expenditure respectively LEPTIN  Leptin binds to leptin receptors in the hypothalamus, increases energy consumption by:  stimulating POMC/CART neurons  produce anorexigenic neuropeptide( MSH) and  inhibiting NPY/AgRP neurons  produce or exigenic neuropeptides   suppressing food intake & increasing expenditure of calories  Thermogenesis, an important catabolic effect mediated by leptin, controlled in part by hypothalamic signals that increase release of norepinephrine from sympathetic nerve endings in adipose tissue  Leptin also functions as a proinflammatory cytokine & participates in regulation of hematopoiesis and lymphopoiesis ADIPONECTIN  Called the “fat-burning molecule” & the “guardian angel against obesity,” directs fatty acids to muscle for their oxidation  Decreases influx of fatty acids to liver & total hepatic triglyceride content  Decreases glucose production in the liver, causing an increase in insulin sensitivity &  Protecting against the metabolic syndrome GUT HORMONES  Gut peptides act as short-term meal initiators & terminators  They include ghrelin, PYY, pancreatic polypeptide, insulin, & amylin among others  Ghrelin produced in the stomach & in the arcuate nucleus of hypothalamus.  The only known gut hormone that increases food intake (orexigenic effect)  Stimulates NPY/AgRP neurons to increase food intake  Ghrelin levels rise before meals & fall between 1 & 2 hours after eating  In obese individuals the postprandial suppression of ghrelin is attenuated & may contribute to overeating  PYY (Pancreatic peptide YY) is secreted from endocrine L-cells in the ileum and colon  Plasma levels of PYY are low during fasting & increase shortly after food intake  Levels of PYY generally decrease in individuals with Prader-Willi syndrome (caused by loss of imprinted genes on chromosome 15q11- q13), a disorder marked by hyperphagia and obesity  These observations have led to ongoing work to produce PYYs for the treatment of obesity Amylin  Peptide secreted with insulin from pancreatic β- cells that:  Reduces food intake & weight gain,  also being evaluated for treatment of obesity & diabetes  Both PYY & amylin act centrally by stimulating POMC/CART neurons in the hypothalamus, causing a decrease in food intake ADVERSE CONSEQUENCES OF OBESITY 1. Hyper insulinaemia & insulin resistance Non- Insulin dependant diabetes (type 2 DM) 2. Hypertension 3. Hyper-triglyceridemia & low HDL Atherosclerosis Coronary artery disease 4. Cholelithiasis 5. Non-alcoholic fatty liver disease 6. Hypoventilation syndrome / Pickwickian syndrome:  c/c by Hypersomnolence, both at night and during the day  often associated with apneic pauses during sleep (sleep apnea)  polycythemia  right-sided heart failure (cor pulmonale). 7. Cancer 8. Osteoarthritis OBESITY 34 DISORDERS OF VITAMINS VITAMINS  Fat soluble vitamins a) Vit A b) Vit D c) Vit E d) Vit K  Water soluble vitamins a) Vit B complex b) Vit C  VITAMIN DEFICIENCY STATES Water soluble Dietary sources Consequence of deficiency Vitamin B1 (Thiamine) Cereals , milk, eggs, fruits, yeast Beriberi, Neuropathy, Cardiac failure, extract Kosakoff’s psychosis, Wernicke’s encepahlopathy B2 (Riboflavine) Cereals , milk, eggs, fruits, liver Ariboflavinosis (Mucosal fissuring, Cheilosis and Glossitis, Angular stomatitis) B6 (Pyriodoxine) Cereals , milk, meat, fish Cheilosis, glossitits, Neuropathy, Sideroblastic anemia B12 (Cobalamin) Meat, fish, egg, cheese Megaloblastic anemia, Subacute combined degeration of spinal cord Folate (B9) Green vegetables, fruit Megaloblastic anaemia , Neural tube defects, Mouth ulcers, Villus atrophy of small gut Niacin (nicotinic acid) Meat, milk, egg, peas, beans, Pallegra: 3 Ds (B3) yeast extract Dermatitis, Diarrhoea, Dementia C (ascorbic acid) Citrus fruits, green vegetables Scurvy, Swollen bleeding gums, Bruising and bleeding PELLAGRA 10/07/2024 NUTRITIONAL DISORDERS 38 PELLAGRA 10/07/2024 NUTRITIONAL DISORDERS 39  VITAMIN DEFICIENCY STATES Fat soluble Dietary sources Consequence of Vitamin deficiency A β-carotenes in carrots etc Vit. Night blindness, (retinol) A in fish, eggs, liver, xerophthalmia, ,squam margarine ous metaplasia, infctns mainly measles D Rickets ( children) (calcitriol) Milk, fish, eggs, liver Osteomalacia ( adults) Hypocalcemic tetany E Cereals, eggs, vegetable oils Neuropathy, (α- tocopherol) Anemia(reduced red cell life span) K Blood coagulation Vegetables, liver Defects VITAMIN A  Major functions of vitamin A: maintenance of normal vision, regulation of cell growth & differentiation, regulation of lipid metabolism  Vitamin A - name given to a group of compounds that include retinol, retinal, & retinoic acid, which have similar biologic activities  Retinol is the chemical name given to vitamin A - the transport form, & as retinol ester the storage  Vitamin A is a fat-soluble vitamin, its absorption requires bile, pancreatic enzymes, & some level of antioxidant activity in the food  Retinol (generally ingested as retinol ester) & β-carotene are absorbed in the intestine, where β-carotene is also converted to retinol  Retinol is then transported in chylomicrons to the liver for esterification and storage  Uptake in liver cells takes place through the apo- lipoprotein E receptor  More than 90% of the body’s vitamin A reserves are stored in the liver, predominantly in the perisinusoidal stellate (Ito) cells  Retinol esters stored in the liver can be mobilized; before release, retinol binds to a specific retinol binding protein (RBP), synthesized in the liver  Uptake of retinol/RBP in peripheral tissues is dependent on cell surface receptors specific for RBP  After uptake, retinol binds to a cellular RBP, & the RBP is released back into the blood  Retinol may also be stored in peripheral tissues as retinol ester or may be oxidized to form retinoic acid FUNCTIONS OF VITAMIN A  Maintenance of normal vision  Cell growth and differentiation - Vitamin A maintains differentiation of mucus-secreting epithelium:  when a deficiency state exists, the epithelium undergoes squamous metaplasia, differentiating into a keratinizing epithelium  Metabolic effects of retinoids  key regulators of fatty acid metabolism, including fatty acid oxidation , adipogenesis, & lipoprotein metabolism  Host resistance to infections  Vitamin A supplementation can reduce morbidity & mortality from some forms of diarrhea, in preschool children with measles, & improve clinical outcome  Beneficial effect of vitamin A in diarrheal diseases may be related to the maintenance & restoration of the integrity of the gut epithelium  Ability to stimulate the immune system  Photoprotective and antioxidant property  VITAMIN A DEFICIENCY  Eye changes:  Earliest manifestations is impaired vision, particularly in reduced light (night blindness)  Persistent deficiency gives rise to epithelial metaplasia and keratinization  The most devastating changes occur in the eyes and are referred to as xerophthalmia (dry eye)  First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lacrimal and mucus-secreting epithelium is replaced by keratinized epithelium  Followed by a buildup of keratin debris in small opaque plaques (Bitot spots)  Progresses to erosion of the roughened corneal surface, softening & destruction of the cornea (keratomalacia)  Blindness ultimately ensues VITAMIN A DEFICIENCY CONT’D  Squamous metaplasia in respiratory & urinary tract predisposing to infections & renal stones respectively  Hyperplasia & hyperkeratinization of the epidermis with plugging of ducts of adnexal glands produce follicular or papular dermatosis  Another very serious consequence is immune deficiency, responsible for higher mortality rates from common infections such as measles, pneumonia, & infectious diarrhea VITAMIN A TOXICITY  The symptoms of acute vitamin A toxicity include  Headache  Dizziness  Vomiting  stupor and  blurred vision,  Symptoms may be confused with those of a brain tumor (pseudotumor cerebri)  Chronic toxicity is associated with weight loss, anorexia, nausea, vomiting, bone and joint pain  Retinoic acid stimulates osteoclast production & activity, leading to increased bone resorption & high risk of fractures VITAMIN D  The major function of this fat-soluble vitamin D is:  Maintenance of adequate plasma levels of calcium & phosphorus to support metabolic functions, bone mineralization, & neuromuscular transmission  Vitamin D is a key regulator of calcium & phosphate homeostasis  The major source of vitamin D for humans is its endogenous synthesis from a precursor,7-dehydrocholesterol, in a photochemical reaction that requires solar or artificial UV light in the range of 290 to 315 nm (UVB radiation)  This reaction results in the synthesis of cholecalciferol, known as vitamin D3  Vitamin D is produced from 7-dehydrocholesterol in the skin or is ingested in the diet VITAMIN D CONT’D  It is converted in the liver into 25(OH)D, & in the kidney to 1,25(OH)2D (1,25-dihydroxyvitamin D), the active form of the vitamin  1,25(OH)2D stimulates expression of RANKL, an important regulator of osteoclast maturation & function, on osteoblasts, &  Enhances intestinal absorption of calcium & phosphorus in the intestine  VITAMIN D DEFICIENCY  Causes:  lack of dietary vit D  inadequate exposure to sunlight  intestinal malabsorption of fat  impaired hydroxylation due to hepatic and renal diseases  Mechanism:  lack of vit D impairs mineralization of the growing skeleton  Signs of deficiency Rickets (children) Osteomalacia (adults) Hypocalcemic etany SIGNS OF RICKETS Skeletal deformities – bow legs & lumbar lordosis THORACIC CHANGES IN RICKETS  Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the “rachitic rosary”  The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles & thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity)  Harrisons sulcus (horizontal groove along lower border of thorax) SKULL CHANGES  During the non-ambulatory stage of infancy, the head & chest sustain the greatest stresses  The softened occipital bones may become flattened, & parietal bones can be buckled inward by pressure; with the release of the pressure, elastic recoil snaps the bones back into their original positions (craniotabes)  An excess of osteoid produces frontal bossing & a squared appearance to the head.  MORPHOLOGY OF RICKETS Vitamin D deficiency in both rickets & osteomalacia results in an excess of unmineralized matrix. The following sequence occurs in rickets:  Overgrowth of epiphyseal cartilage due to inadequate provisional calcification & failure of the cartilage cells to mature & disintegrate  Persistence of distorted, irregular masses of cartilage which project into the marrow cavity  Deposition of osteoid matrix on inadequately mineralized cartilaginous remnants MORPHOLOGY OF RICKETS CONT’D  Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral Junction  Abnormal overgrowth of capillaries and fibroblasts in the disorganized zone resulting from microfractures and stresses on the inadequately mineralized, weak, poorly formed bone  Deformation of the skeleton due to the loss of structural rigidity of the developing bones  A B A. Normal costochondral junction of a young child illustrating formation of cartilage palisades and orderly transition from cartilage to new bone B. Detail of a rachitic costochondral junction in which the palisades of cartilage is lost, darker trabeculae are well-formed bone; paler trabeculae consist of uncalcified osteoid.  VITAMIN C DEFICIENCY  Causes: Dietary lack of fresh fruits and vegetables  Mechanism: impaired collagen synthesis ( Vitamin C is needed for collagen synthesis and collagen cross-linking and tensile strength)  Vit C deficiency leads to SCURVY c/c by bone disease in growing children and by hemorrhages and healing defects in both children and adults  Vascular pattern –gingival bleeding, petechiae and ecchymoses  Skeletal changes – soft bones, growth retardation  Delayed wound healing LIST OF DEFICIENCES OF ESSENTIAL MINERALS – FURTHER READING  Iron - microcytic hypochromic anemia  Iodine- hypothyroidism, goiter, growth retardation  Copper- neuromuscular disorders  Zinc- acrodermatitis enteropathica (rash around eye mouth nose and anus), infertility, growth retardation, anorexia and diarrhoea  Fluoride- dental caries  Selenium – keshan disease congestive cardiomyopathy due to combination of dietary deficiency of Se & presence of mutated strain of Coxsackie virus  End Thank you