Pathological Manifestations of Nutritional Deficiencies PDF

Objectives Define dietary insufficiency and describe the conditions leading to it Define Severe acute malnutrition and its manifestations Eating disorders Highlight the necessary vitamins, their functions in health & discuss vitamin deficiencies Trace elements and deficiency syndromes...

Objectives Define dietary insufficiency and describe the conditions leading to it Define Severe acute malnutrition and its manifestations Eating disorders Highlight the necessary vitamins, their functions in health & discuss vitamin deficiencies Trace elements and deficiency syndromes Appropriate diet provides : 1. Sufficient energy – for body’s daily metabolic needs 2. Amino acids and fatty acids - used as building blocks for synthesis of proteins and lipids 3. Vitamins and minerals - function as coenzymes or hormones in vital metabolic pathways or, as in the case of calcium and phosphate, as important structural components. Ca Dietary Insufficiency Malnutrition : consequence of inadequate intake/digestion/absorption of proteins and calories resulting in the loss of fat and muscle mass, weight loss, and generalized weakness. ---- Classified 1. Primary malnutrition - dietary component(s) missing from the diet. 2. Secondary malnutrition - e.g. malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients. Dietary Insufficiency There are several conditions that may lead to primary or secondary malnutrition : 1. Poverty 2. Acute and chronic illnesses 3. Chronic alcoholism 4. Ignorance and failure of diet supplementation 5. Self-imposed dietary restriction 6. Other causes Severe Acute Malnutrition (SAM) The WHO defines SAM as “a state characterized by a weight for height ratio that is 3 standard deviations below the normal range”. It manifests as a spectrum of clinical syndromes, all resulting from a dietary intake of protein and calories that is inadequate to meet the body’s needs. know them ! At two ends of SAM are - Marasmus and- Kwashiorkor (considerable overlap exists)  Marasmus Develops when the diet is severely lacking in calories. Growth retardation, loss of muscle mass as a result of catabolism and depletion of muscle proteins. The visceral proteins more critical for survival is depleted only marginally. Subcutaneous fat is also used as fuel. Leptin secretion is low. It stimulates the hypothalamic- pituitary-adrenal axis to produce cortisol that contribute to lipolysis. Anemia and multivitamin deficiencies are present. Immune deficiency, particularly of T-cell–mediated immunity.  Kwashiorkor Not balbumin , as edema this as previous bat bosmotic pressin Protein deprivation is relatively greater than the reduction in total calories. Protein deprivation is associated with loss of the visceral proteins resulting in hypoalbuminemia and generalized or dependent edema. Enlarged, fatty liver (resulting from reduced synthesis of the carrier protein component of lipoproteins). Vitamin deficiencies and Immune deficiency Kwashiorkor Loss of hair color, fine texture, and loss of firm Flaky paint skin; alternating zones of hyperpigmentation, attachment to the scalp. desquamation, and hypopigmentation.  Childhood malnutrition Marasmus - Note the Kwashiorkor - The loss of muscle mass and infant shows subcutaneous fat; the generalized edema, head appears to be too seen as ascites and large for the emaciated puffiness of the face, body hands, and legs. muscle mass losh Viscera loss Morphology of SAM The main anatomic changes – (1) growth failure (2) peripheral edema in kwashiorkor, and (3) loss of body fat and atrophy of muscle, more marked in marasmus. The liver in kwashiorkor – enlarged and fatty The small bowel in kwashiorkor - decrease in mitotic cells in the crypts of the glands, associated with mucosal atrophy and loss of villi and microvilli. The bone marrow in both - may be hypoplastic, mainly as a result of decreased numbers of red cell precursors, mild to moderate anemia The brain in infants - show cerebral atrophy, a reduced number of neurons, and impaired myelinization of white matter. Cachexia Secondary malnutrition - common complication in acquired immunodeficiency syndrome (AIDS) or advanced cancers Sustained production of TNF contributes to cachexia, a pathologic state characterized by weight loss and anorexia that is seen in some chronic infections and neoplastic diseases. TNF regulates energy balance by promoting lipid and protein mobilization and by suppressing appetite.  Anorexia Nervosa Psychiatric condition characterized by self-induced starvation, resulting in marked weight loss. Has the highest death rate of any psychiatric disorder. Anorexia Nervosa Clinical findings - similar to SAM + effects on the endocrine system Amenorrhea - diagnostic feature Decreased thyroid hormone release - cold intolerance, bradycardia, constipation, dry and scaly skin, dehydration and electrolyte abnormalities Pathognomonic - Increased fat in the marrow - peculiar deposition of mucinous matrix material gelatinous transformation Anemia, lymphopenia, and hypoalbuminemia. Major complication - Increased susceptibility to cardiac arrhythmia and sudden death, resulting from hypokalemia. Bone marrow in Anorexia nervosa - Increased fat in the marrow associated with deposition of mucinous matrix material (gelatinous transformation) Normal Bone marrow  Bulimia Psychiatric condition in which the patient binges on food (carbohydrates) and then induces vomiting. More common than anorexia nervosa and has a better prognosis Weight and gonadotropin levels remain near normal - amenorrhea occurs in less than 50% of pts The major medical complications (vomiting and use of laxatives and diuretics): (1) electrolyte imbalances (hypokalemia)-which predispose the patient to cardiac arrhythmias; (2) pulmonary aspiration of gastric contents; and (3) esophageal and gastric rupture Vitamin Deficiencies Thirteen vitamins are necessary for health; Vitamins A, D, E, and K - fat-soluble, and all others - water-soluble Fat-soluble vitamins - readily stored in the body, but they may be poorly absorbed in fat malabsorption disorders, caused by disturbances of digestive functions Certain vitamins can be synthesized endogenously—vitamin D from precursor steroids; vitamin K and biotin by the intestinal microflora; and niacin from tryptophan, an essential amino acid. Notwithstanding this endogenous synthesis, a dietary supply of all vitamins is essential for health. Deficiency - primary (dietary in origin) or secondary to disturbances in intestinal absorption, transport in the blood, tissue storage, or metabolic conversion Deficiency of a single vitamin is uncommon Single or multiple vitamin deficiencies may be associated with SAM. Vitamin A Exn deficiency- > Pathology Maintenance of normal vision, regulation of cell growth and differentiation, regulation of lipid metabolism, enhances ① immunity to infections. The generic term retinoids encompasses & vitamin A in its various forms (retinol, retinal, and retinoic acid) ③ ⑭ ⑤ Vitamin A Deficiency Earliest manifestation - Impaired vision in reduced light - night ~ blindness Normal lacrimal and mucus-secreting epithelium Persistent deficiency is replaced by keratinized epithelium Epithelial metaplasia build-up of keratin debris in small opaque and keratinization plaques (Bitot spots) Lead to progresses to erosion of roughened corneal surface “xerophthalmia” or dry eye softening and destruction of the cornea (keratomalacia), and blindness Vitamin A Deficiency low socrectomic dryness Marked conjunctival and corneal xerosis - Bitot's spots are foamy, cheesy accretions of desquamated keratin  Vitamin A Deficiency Xerophthlmia is the clinical spectrum of ocular manifestations of vit A deficiency ① Vitamin A Deficiency & &  Vitamin A Deficiency Hyperplasia and hyperkeratinization of the epidermis and plugging of the ducts of the adnexal glands - follicular or papular dermatosis. Serious consequence - immune deficiency, which is responsible for higher mortality rates from common infections such as measles, pneumonia, and infectious diarrhea. Vitamin D Major function - maintenance of adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralization, and neuromuscular transmission. Major source -- endogenous synthesis from a precursor, 7- dehydrocholesterol, in a photochemical reaction that requires & solar or artificial UV light. This reaction results in the synthesis of cholecalciferol, known as vitamin D3. Other source - fish, plants, and grains – depend on adequate - - intestinal fat absorption Vitamin D metabolism The production of 1,25-dihydroxyvitamin D in the kidney is regulated by three main mechanisms: 1. Hypocalcemia - stimulates secretion of parathyroid hormone (PTH), upregulates the expression of 1α- hydroxylase. 2. Hypophosphatemia - upregulates 1α-hydroxylase increase expression, increasing the production of 1,25- * C dihydroxyvitamin D 3. Increased levels of 1,25-dihydroxyvitamin D - through a feedback mechanism, downregulate its own synthesis through inhibition of 1α-hydroxylase activity.  Vitamin D deficiency * 29 loose phosphorous Vitamin D Deficiency Rickets - growing children Osteomalacia - adults Hypocalcemic tetany Disrupts calcium and phosphorus homeostasis Vitamin D Deficiency The normal reference range for circulating 25-(OH)-D is 20 to 100 ng/mL; < 20 ng/mL constitute vitamin D deficiency diets deficient in calcium and vitamin D, limited exposure to sunlight. less common causes of rickets and osteomalacia - renal disorders causing decreased synthesis of 1,25-dihydroxyvitamin D, phosphate depletion, malabsorption disorders, and some rare inherited disorders. milder forms of vitamin D deficiency leading to an increased risk of bone loss and hip fractures are quite common in older adults Vitamin D Deficiency Vitamin D deficiency in both rickets (children) and osteomalacia (adults) results in an excess of unmineralized matrix. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized disturbs In adults with osteomalacia - the lack of vitamin D deranges the normal bone remodeling (occurs throughout life) Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks h Vitamin D Deficiency - Rickets The gross skeletal changes in rickets – non- ambulatory (infant) Craniotabes, excess of osteoid produces frontal bossing and a squared appearance to the head. Rachitic rosary - deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction Pigeon breast deformity - the weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum  Vitamin D Deficiency - Rickets Rachitic rosary - deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction  Normal Detail of a rachitic costochondral junction in which Normal costochondral junction of a young child the palisades of cartilage is lost. Darker trabeculae are illustrating formation of cartilage palisades and orderly well-formed bone; paler trabeculae consist of transition from cartilage to new bone. uncalcified osteoid. Vitamin D Deficiency - Rickets Ambulating child - deformities are likely to affect the spine, pelvis, and tibia, causing lumbar lordosis and bowing of the legs Soft  Vitamin C (Ascorbic Acid) how present Clinically ? Not synthesized endogenously in humans; therefore we are entirely dependent on the diet Functions: collagen synthesis, neurotransmitter synthesis, antioxidant functions, modulating the immune response. Sources - milk, animal products (liver, fish), a variety of fruits and - vegetables. Important feature! Vitamin C Deficiency Deficiency - older individuals, persons who live alone, chronic alcoholics, in patients undergoing peritoneal dialysis and hemodialysis, in food faddists, in infants who are maintained on formulas A deficiency of water-soluble vitamin C leads to scurvy. Scurvy is characterized by bone disease in children and by haemorrhages and healing defects in both children and adults.  2 - 7 10 -  name & Syndrome case Imp know S the names --- fxn) - alcobiliz Psycharic ? Thiamine - & & - Niscih Vitamin B6(pyridoxine) deficiency Dermatitis Cheilosis Glossitis  O & ④ ⑤ ⑥ ⑰ 0 - -  Zinc Acrodermatitis enteropathica Goitre References Pathologic basis of disease, Robbins & Cotran, 10th edition, Chapter 9, Section on Nutritional diseases (pages 433 to 444)