1. Environmental & Nutritional Diseases Ashley Inman 11-10-2014

2. Outline Environmental Diseases Malnutrition Obesity Vitamin Deficiencies

3. Carbon Monoxide Important cause of accidental and suicidal death Nonirritating, colorless, tasteless, odorless gas Automotive engines, furnaces, cigarettes Hemoglobin has much stronger affinity for CO than oxygen  carboxyhemoglobin

5. Lead Poisoning Binds to sulfhydryl groups in proteins and interferes with calcium metabolism Exposure may occur through contaminated air, food, and water Lead paint in older homes Children more susceptible due to higher intestinal absorption and a more permeable blood-brain barrier

8. Basophilic stippling On PBS

9. Smoking  Most prevalent preventable cause of human death

11. Alcohol Acute: –Mainly CNS effects –Depressant that can lead to respiratory arrest Chronic: –Liver: fatty change; cirrhosis –Thiamine deficiency –Alcoholic cardiomyopathy –Pancreatitis (acute & chronic) –Bleeding from gastritis and gastric ulcers –Increased incidence of oral, esophageal, liver, and breast cancer

12. Malnutrition Also called “protein energy malnutrition” Results from inadequate intake of proteins and calories or problems with digestion/malabsorption of proteins BMI <16 kg/m 2 (normal 18.5-25 kg/m 2 ) 2 main forms: –Marasmus –Kwashiorkor

13. Two protein compartments Somatic compartment: –Proteins in skeletal muscle –Reduced circumference of mid-arm –Affected more by marasmus Visceral compartment: –Protein stores in visceral organs (mostly liver) –Decrease in serum proteins (albumin) –Affected more by kwashiorkor

14. MARASMUS < 60% body weight< 60% body weight Diet lacks protein & carbohydrateDiet lacks protein & carbohydrate Loss of muscle mass (somatic protein)- amino acids for energyLoss of muscle mass (somatic protein)- amino acids for energy Loss of subcutaneous fat (broomstick)Loss of subcutaneous fat (broomstick) Serum proteins (visceral compartment) NORMALSerum proteins (visceral compartment) NORMAL EMACIATION- loss of muscle and fatEMACIATION- loss of muscle and fat

15. MARASMUS Head appears too large; “stick figure”Head appears too large; “stick figure” Multiple vitamin deficiencies coexistMultiple vitamin deficiencies coexist Immune deficiency- especially T cell immunityImmune deficiency- especially T cell immunity

19. KWASHIORKOR Protein deprivation > caloric deprivationProtein deprivation > caloric deprivation **2 nd birth First child is weaned too soon and put on a high carbohydrate diet**2 nd birth First child is weaned too soon and put on a high carbohydrate diet MORE dangerous than MarasmusMORE dangerous than Marasmus Severe loss of visceral proteinSevere loss of visceral protein Hypoalbuminemia causes generalized EDEMA which can mask the loss of weightHypoalbuminemia causes generalized EDEMA which can mask the loss of weight Subcutaneous fat and muscle are SPAREDSubcutaneous fat and muscle are SPARED

20. SIGNS OF KWASHIORKOR Flaky Paint Skin- alternating zones of hypo- and hyper-pigmentation and desquamationFlaky Paint Skin- alternating zones of hypo- and hyper-pigmentation and desquamation Hair loss or color changeHair loss or color change FATTY LIVER- due to loss of apolipoproteins; also small intestine atrophy with loss of villi and disaccharidase deficiencyFATTY LIVER- due to loss of apolipoproteins; also small intestine atrophy with loss of villi and disaccharidase deficiency PITTING EDEMA and ascites due to hypoalbuminemiaPITTING EDEMA and ascites due to hypoalbuminemia

21. Signs Continued… (Seen in both marasmus & kwashiorkor) Growth failureGrowth failure Multivitamin deficienciesMultivitamin deficiencies Immune defects and infectionsImmune defects and infections Anemia- usually hypochromic/microcyticAnemia- usually hypochromic/microcytic Cerebral atrophy in infants due to loss of neurons and impaired myelinization of white matterCerebral atrophy in infants due to loss of neurons and impaired myelinization of white matter May have hypoplastic bone marrow (mainly due to loss of RBC precursors)May have hypoplastic bone marrow (mainly due to loss of RBC precursors)

23. Table 10-20 COMPARISON OF SEVERE MARASMUS-LIKE AND KWASHIORKOR-LIKE SECONDARY PROTEIN-ENERGY MALNUTRION Syndrome SyndromeClinical Time Course Clinical Features LaboratoryFindingsPrognosis Marasmus- like Protein energy malnutrition Chronic illness (e.g.,chronic lung disease, cancer Months History of weight loss Muscle wasting Absent subcutaneou s fat Normal or mildly reduced serum proteins Variable; depends on underlying disease Kwashiorkor -like protein energy malnutrition Acute, catabolic illness (e.g., severe trauma, burns, sepsis Weeks Normal fat and muscle EdemaEasily Serum albumin <2.8 gm/dl Poor

24. CACHEXIA CANCER and AIDSCANCER and AIDS Loss of muscle and fatLoss of muscle and fat FatigueFatigue Good appetiteGood appetite Higher metabolic rateHigher metabolic rate Cytokines- TNF, IL-6Cytokines- TNF, IL-6 Proteolysis-inducing factor (PIF)Proteolysis-inducing factor (PIF)

27. ANOREXIA NERVOSA Self-induced starvationSelf-induced starvation Like PEM plus:Like PEM plus: –Amenorrhea (decreased secretion of gonadotropin- releasing hormone w/ subsequent endocrine effects) –Hypothyroidism –Scaly, yellow skin and lanugo –Decreased bone density (mimicks postmenopausal osteoporosis) Anemia, lymphopenia, hypoalbuminemiaAnemia, lymphopenia, hypoalbuminemia HYPOKALEMIA AND CARDIAC ARRHYTHMIA  SUDDEN DEATHHYPOKALEMIA AND CARDIAC ARRHYTHMIA  SUDDEN DEATH

29. BULIMIA Binge eating followed by induced vomitingBinge eating followed by induced vomiting < ½ have amenorrhea, but menstrual irregularities common< ½ have amenorrhea, but menstrual irregularities common Weight and gonadotropin levels near normalWeight and gonadotropin levels near normal

30. BULIMIA Major complications due to frequent vomiting and chronic use of laxatives: –Hypokalemia and CARDIAC ARYTHMIA –Aspiration of gastric contents –Mallory-Weiss Syndrome- longitudinal laceration of the esophagus or stomach –Boerhaave’s Syndrome- rupture of esophagus or stomach

32. Obesity Hypertension Insulin resistance DM type II High serum lipids Atherosclerosis Gallstones Osteoarthritis Malignancy Nonalcoholic fatty liver disease Sleep apnea

34. Metabolic Syndrome Visceral/intra-abdominal adiposity Insulin resistance Hyperinsulinemia Glucose intolerance Hypertension Hypertriglyceridemia Low HDL cholesterol

35. VITAMINS Fat Soluble- A, D, E, KFat Soluble- A, D, E, K –Absorbed in the ileum –Toxic- accumulate in fatty tissues Water soluble- B’s, C, FolateWater soluble- B’s, C, Folate –Toxicity rare b/c excreted in urine Fat soluble vitamins are more readily stored, BUT they are poorly absorbed in fat malabsorption disorders (cystic fibrosis, celiac disease, ileal resection)Fat soluble vitamins are more readily stored, BUT they are poorly absorbed in fat malabsorption disorders (cystic fibrosis, celiac disease, ileal resection)

36. VITAMINS ENDOGENOUS Synthesis- D, K and NiacinENDOGENOUS Synthesis- D, K and Niacin DIET- all the othersDIET- all the others Vitamin Deficiency can be PRIMARY (diet) or Secondary (malabsorption)Vitamin Deficiency can be PRIMARY (diet) or Secondary (malabsorption)

37. VITAMIN A (RETINOL) Functions:Functions: –Night vision –Growth and differentiation of mucus-secreting epithelium –Immunity (children) Vitamin A stored in ITO CELLS in the liver;Vitamin A stored in ITO CELLS in the liver; 6-month supply 6-month supply

39. VITAMIN A DEFICIENCY Night blindness (insufficient retinal rhodopsin)Night blindness (insufficient retinal rhodopsin) Xerophthalmia (dry eye)- keratinized squamous epithelium replaces mucus-secreting epitheliumXerophthalmia (dry eye)- keratinized squamous epithelium replaces mucus-secreting epithelium Bitot spots (keratin debris) and keratomalacia (destruction of the cornea)Bitot spots (keratin debris) and keratomalacia (destruction of the cornea) Squamous metaplasia in LUNG (infections) and BLADDER (stones)Squamous metaplasia in LUNG (infections) and BLADDER (stones) Increased mortality in measles and diarrheaIncreased mortality in measles and diarrhea

41. Corneal Destruction

42. VITAMIN A TOXICITY Increased intracranial pressureIncreased intracranial pressure Papilledema, headache, vomitingPapilledema, headache, vomiting Bone pain and hypercalcemia (increased osteoclast activity)Bone pain and hypercalcemia (increased osteoclast activity)

43. VITAMIN D Major function is to maintain adequate plasma levels of CALCIUM and PHOSPHORUSMajor function is to maintain adequate plasma levels of CALCIUM and PHOSPHORUS

44. VITAMIN D FUNCTIONS Stimulates intestinal absorption of calcium and phosphorusStimulates intestinal absorption of calcium and phosphorus Interacts with PTH to regulate blood calcium levelsInteracts with PTH to regulate blood calcium levels Stimulates PTH-dependent re-absorption of calcium in the distal renal tubuleStimulates PTH-dependent re-absorption of calcium in the distal renal tubule

46. VITAMIN D DEFICIENCY HYPOCALCEMIA and loss of bone: RICKETS or OSTEOMALACIA HYPOCALCEMIA and loss of bone: RICKETS or OSTEOMALACIA –Malnutrition –Intestinal malabsorption (pancreatic insufficiency) –Inadequate sunlight exposure –Liver disease –Renal disease

48. Normal Vitamin D Deficient

51. RICKETS Osteoid with inadequate mineralizationOsteoid with inadequate mineralization Disorganized fibroblasts and capillariesDisorganized fibroblasts and capillaries MicrofracturesMicrofractures Deformed bonesDeformed bones Square head, “rachitic” rosary, pigeon breast deformity, lumbar lordosis, and bowed legsSquare head, “rachitic” rosary, pigeon breast deformity, lumbar lordosis, and bowed legs

54. OSTEOMALACIA Abnormal bone remodelingAbnormal bone remodeling Inadequate mineralization of new boneInadequate mineralization of new bone Normal contoursNormal contours Fractures and microfracturesFractures and microfractures –Mostly involving the vertebrae and femoral neck

57. VITAMIN D TOXICITY Not caused by prolonged exposure to sunlight; results from oral overdoseNot caused by prolonged exposure to sunlight; results from oral overdose Metastatic calcification of soft tissuesMetastatic calcification of soft tissues In children: growth retardationIn children: growth retardation In adults: renal calculi; bone painIn adults: renal calculi; bone pain

58. VITAMIN E “Antioxidant”“Antioxidant” Deficiency- nervous system- degeneration of posterior column axonsDeficiency- nervous system- degeneration of posterior column axons –Loss of position and vibration sense; ataxia, muscle weakness –Hemolytic anemia of premature infants Toxicity: decreasd synthesis of vitamin K- dependent coagulation factorsToxicity: decreasd synthesis of vitamin K- dependent coagulation factors

59. VITAMIN K Clotting factors II (prothrombin), VII, IX and X are carboxylated in the liver and Vitamin K is a cofactorClotting factors II (prothrombin), VII, IX and X are carboxylated in the liver and Vitamin K is a cofactor Also, carboxylation of protein C and S (anticoagulants)Also, carboxylation of protein C and S (anticoagulants) Vitamin K is “recycled” in the liver and gut bacteria make the vitamin, but some dietary source is requiredVitamin K is “recycled” in the liver and gut bacteria make the vitamin, but some dietary source is required

60. Vitamin K Deficiency Causes –fat malabsorption –reduced gut bacterial flora administration of wide specturm antibiotics neonatal period before gut is colonized –liver disease Effects of vitamin K deficiency –bleeding diathesis – 3% prevalence of vitamin K-deficiency among neonates warrants prophylactic vitamin K therapy for all newborns

61. Vitamin K Deficiency

62. THIAMINE (B1) Not in polished rice, white flour or refined sugarNot in polished rice, white flour or refined sugar ¼ of all alcoholics are thiamine deficient¼ of all alcoholics are thiamine deficient Cofactor in oxidative decarboxylation  deficiency of thiamine results in DECREASED ATPCofactor in oxidative decarboxylation  deficiency of thiamine results in DECREASED ATP Cardiovascular and nervous system problemsCardiovascular and nervous system problems

63. THIAMINE DEFICIENCY Dry beriberi (polyneuropathy): myelin degeneration Wet beriberi (cardiovascular): vasodilitation produces heart failure and edema Wernicke-Korsakoff Syndrome: Wernicke- ataxia/confusion Korsakoff- amnesia, confabulation

65. NIACIN (B3) NAD and NADP are cofactors in oxidation- reduction reactionsNAD and NADP are cofactors in oxidation- reduction reactions Grains, legumes and seed oils (corn-based diets)Grains, legumes and seed oils (corn-based diets) Deficiency of tryptophan (used to synthesize niacin)Deficiency of tryptophan (used to synthesize niacin) Deficiency- PELLAGRA (3 D’s)Deficiency- PELLAGRA (3 D’s) dermatitis, diarrhea (epithelial atrophy) and dementia (posterior column changes as in B-12 deficiency) dermatitis, diarrhea (epithelial atrophy) and dementia (posterior column changes as in B-12 deficiency)

66. Niacin, Pellagra 3 D’s of Pellagra –Dermatitis –Diarrhea –Dementia

67. VITAMIN C (ASCORBIC ACID) (Citrus) fruits and vegetables(Citrus) fruits and vegetables Bone disease in growing childrenBone disease in growing children Hemorrhage and poor wound healing in children and adultsHemorrhage and poor wound healing in children and adults Vitamin C is a cofactor in formation and maturation of procollagenVitamin C is a cofactor in formation and maturation of procollagen Hydroxylation is impaired and crosslinks are not formedHydroxylation is impaired and crosslinks are not formed

68. VITAMIN C DEFICIENCY SCURVYSCURVY Capillary and venule walls are weak with hemorrages (purpura and ecchymoses)Capillary and venule walls are weak with hemorrages (purpura and ecchymoses) Trauma- hematoma and hemarthrosis (joints)Trauma- hematoma and hemarthrosis (joints) Child- too much cartilage and not enough osteoid protein); bowed legs and deformed chestChild- too much cartilage and not enough osteoid protein); bowed legs and deformed chest Bacterial infection associated with gingival hemorrhageBacterial infection associated with gingival hemorrhage

70. Vitamin C deficiency

71. Vitamin C Deficiency

72. Normal “Rickets”

75. Cobalamin (B12) Stores last 3-5 years Only in animal products (eggs, meat, dairy) Requires intrinsic factor for reabsorption in terminal ileum Functions in DNA synthesis Deficiency: –Pernicious anemia (most common) –D. latum –Terminal ileum disease (Crohn’s) –Strict vegan diet

76. Cobalamin (B12) Deficiency Megaloblastic anemia CNS: posterior column and lateral corticospinal tract demyelination Glossitis

77. FOLATE Marginal body storesMarginal body stores Most common vitamin deficiency in U.S.Most common vitamin deficiency in U.S. Functions in DNA synthesisFunctions in DNA synthesis Neural tube defects in the fetusNeural tube defects in the fetus Megaloblastic anemia (no neurologic dx)Megaloblastic anemia (no neurologic dx) GlossitisGlossitis Certain drugs can lead to deficiency:Certain drugs can lead to deficiency: –Alcohol, methotrexate, phenytoin, oral contraceptives, trimethoprim, 5-fluorouracil

78. Zinc Trace elementTrace element Component of enzymes (oxidases)Component of enzymes (oxidases) Causes of deficiency:Causes of deficiency: –Alcoholism –Diabetes mellitus –Chronic diarrhea

79. Zinc Deficiency Acrodermatitis (rash around eyes, mouth, nose, and anus)Acrodermatitis (rash around eyes, mouth, nose, and anus) AnorexiaAnorexia DiarrheaDiarrhea Growth retardationGrowth retardation Impaired wound healingImpaired wound healing Hypogonadism/ InfertilityHypogonadism/ Infertility

81. Other Trace Elements Copper: –Deficiency: microcytic anemia; poor wound healing –Toxicity: Wilson’s disease Selenium: –Function: component of glutathione peroxidase –Deficiency: dilated cardiomyopathy Chromium deficiency: –Function: component of glucose tolerance factor and cofactor for insulin –Deficiency: impaired glucose tolerance

82. Other Trace Elements Iodine: –Function: synthesis of thyroid hormone –Deficiency: goiter; hypothyroidism Fluoride: –Function: component of calcium hydroxyapatite in bone and teeth –Deficiency: dental caries –Excess: chalky deposits on teeth; calcification of ligaments