Environmental & Environmental & Nutritional Nutritional Diseases Diseases Ashley Inman Ashley Inman 11-10-2014 11-10-2014
Jan 11, 2016
Environmental & Environmental & Nutritional DiseasesNutritional Diseases
Ashley InmanAshley Inman
11-10-201411-10-2014
Outline
• Environmental Diseases
• Malnutrition
• Obesity
• Vitamin Deficiencies
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
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
Basophilic stipplingOn PBS
Smoking
Most prevalent preventable cause of human death
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
Malnutrition
• Also called “protein energy malnutrition”
• Results from inadequate intake of proteins and calories or problems with digestion/malabsorption of proteins
• BMI <16 kg/m2 (normal 18.5-25 kg/m2)
• 2 main forms:– Marasmus– Kwashiorkor
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
MARASMUSMARASMUS
• < 60% body weight< 60% body weight
• Diet lacks protein & carbohydrateDiet lacks protein & carbohydrate
• LossLoss of of musclemuscle mass ( mass (somaticsomatic proteinprotein)- )- amino acids for energy amino acids for energy
• Loss of subcutaneous fat (broomstick)Loss of subcutaneous fat (broomstick)
• Serum proteinsSerum proteins (visceral compartment) (visceral compartment) NORMALNORMAL
• EMACIATION- loss of muscle and fatEMACIATION- loss of muscle and fat
MARASMUS MARASMUS
• Head appears too large; Head appears too large; ““stick figurestick figure””
• Multiple vitamin deficiencies coexistMultiple vitamin deficiencies coexist
• Immune deficiency- especially T cell Immune deficiency- especially T cell immunityimmunity
KWASHIORKORKWASHIORKOR
• Protein deprivationProtein deprivation > caloric deprivation > caloric deprivation• **2**2nd birth nd birth First child is weaned too soon First child is weaned too soon and and
put on a high carbohydrate dietput on a high carbohydrate diet• MORE dangerousMORE dangerous than Marasmus than Marasmus• Severe loss of visceral proteinSevere loss of visceral protein• HypoalbuminemiaHypoalbuminemia causes generalized EDEMA causes generalized EDEMA
which can mask the loss of weightwhich can mask the loss of weight• Subcutaneous fat and muscle are SPAREDSubcutaneous fat and muscle are SPARED
SIGNS OF KWASHIORKORSIGNS OF KWASHIORKOR
•Flaky Paint Skin- alternating zones of hypo- Flaky Paint Skin- alternating zones of hypo- and hyper-pigmentation and desquamationand hyper-pigmentation and desquamation•Hair loss or color changeHair loss or color change•FATTY LIVER-FATTY LIVER- due to loss of due to loss of apolipoproteins; also apolipoproteins; also smallsmall intestine atrophyintestine atrophy with loss of villi and disaccharidase deficiency with loss of villi and disaccharidase deficiency •PITTING EDEMA PITTING EDEMA and ascites due to and ascites due to hypoalbuminemiahypoalbuminemia
Signs Continued…Signs Continued…(Seen in both marasmus & kwashiorkor)(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 Cerebral atrophy in infants due to loss of
neurons and impaired myelinization of neurons and impaired myelinization of white matterwhite matter
• May have hypoplastic bone marrow May have hypoplastic bone marrow (mainly due to loss of RBC precursors)(mainly due to loss of RBC precursors)
Table 10-20 Table 10-20
COMPARISON OF SEVERE MARASMUS-LIKE AND COMPARISON OF SEVERE MARASMUS-LIKE AND KWASHIORKOR-LIKE SECONDARY PROTEIN- KWASHIORKOR-LIKE SECONDARY PROTEIN-ENERGY ENERGY MALNUTRION MALNUTRION
SyndromeSyndrome ClinicalClinical Time Time CourseCourse
Clinical Clinical FeaturesFeatures
LaboratoryLaboratory
FindingsFindings
PrognosisPrognosis
MarasmusMarasmus--likelike
Protein Protein energy energy malnutritionmalnutrition
Chronic Chronic illness illness (e.g.,chronic (e.g.,chronic lung lung disease, disease, cancercancer
MonthsMonths History of History of weight loss weight loss Muscle Muscle wasting wasting Absent Absent subcutaneousubcutaneous fats fat
Normal or Normal or mildly mildly reduced reduced serum serum proteinsproteins
Variable; Variable; depends on depends on underlying underlying diseasedisease
KwashiorkorKwashiorkor--like protein like protein energy energy malnutritionmalnutrition
Acute, Acute, catabolic catabolic illness (e.g., illness (e.g., severe severe trauma, trauma, burnsburns, , sepsissepsis
WeeksWeeks Normal fat Normal fat and muscle and muscle
EdemaEdema
EasilyEasily
Serum Serum albumin albumin <2.8 gm/dl<2.8 gm/dl
PoorPoor
CACHEXIACACHEXIA
• 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)
ANOREXIA NERVOSAANOREXIA NERVOSA• Self-induced starvationSelf-induced starvation• Like PEM plus:Like PEM plus:
– Amenorrhea Amenorrhea (decreased secretion of gonadotropin-(decreased secretion of gonadotropin-releasing hormone w/ subsequent endocrine effects)releasing hormone w/ subsequent endocrine effects)
– HypothyroidismHypothyroidism– Scaly, yellow skin and lanugoScaly, yellow skin and lanugo– Decreased bone density (mimicks postmenopausal Decreased bone density (mimicks postmenopausal
osteoporosis)osteoporosis)
• Anemia, lymphopenia, hypoalbuminemiaAnemia, lymphopenia, hypoalbuminemia• HYPOKALEMIA AND CARDIAC ARRHYTHMIA HYPOKALEMIA AND CARDIAC ARRHYTHMIA
SUDDEN DEATHSUDDEN DEATH
BULIMIA BULIMIA
• Binge eating followed by induced Binge eating followed by induced vomitingvomiting
• < ½< ½ have amenorrhea, but menstrual have amenorrhea, but menstrual irregularities commonirregularities common
• Weight and gonadotropin levels near Weight and gonadotropin levels near normalnormal
BULIMIA
• Major complications due to frequent vomiting and chronic use of laxatives:– HypokalemiaHypokalemia and CARDIAC ARYTHMIAand CARDIAC ARYTHMIA– Aspiration of gastric contentsAspiration of gastric contents– Mallory-WeissMallory-Weiss Syndrome- longitudinal Syndrome- longitudinal
laceration of the esophagus or stomachlaceration of the esophagus or stomach– BoerhaaveBoerhaave’’ss Syndrome- rupture of Syndrome- rupture of
esophagus or stomachesophagus or stomach
Obesity
• Hypertension• Insulin resistance• DM type II• High serum lipids• Atherosclerosis• Gallstones• Osteoarthritis• Malignancy• Nonalcoholic fatty liver disease• Sleep apnea
Metabolic Syndrome
• Visceral/intra-abdominal adiposity
• Insulin resistance
• Hyperinsulinemia
• Glucose intolerance
• Hypertension
• Hypertriglyceridemia
• Low HDL cholesterol
VITAMINSVITAMINS
• Fat SolubleFat Soluble- A, D, E, K- A, D, E, K– Absorbed in the ileumAbsorbed in the ileum– Toxic- accumulate in fatty tissuesToxic- accumulate in fatty tissues
• Water solubleWater soluble- B- B’’s, C, Folates, C, Folate– Toxicity rare b/c excreted in urineToxicity rare b/c excreted in urine
• Fat soluble vitamins are more readily stored, BUT Fat soluble vitamins are more readily stored, BUT they are poorly absorbed in fat malabsorption they are poorly absorbed in fat malabsorption disorders (cystic fibrosis, celiac disease, ileal disorders (cystic fibrosis, celiac disease, ileal resection)resection)
VITAMINS VITAMINS
• ENDOGENOUS Synthesis- D, K and ENDOGENOUS Synthesis- D, K and NiacinNiacin
• DIET- all the othersDIET- all the others
• Vitamin Deficiency can be PRIMARY (diet) Vitamin Deficiency can be PRIMARY (diet) or Secondary (malabsorption)or Secondary (malabsorption)
VITAMIN A (RETINOL)VITAMIN A (RETINOL)
•Functions:Functions:– Night visionNight vision– Growth and differentiation of mucus-secreting Growth and differentiation of mucus-secreting
epitheliumepithelium– Immunity (children)Immunity (children)
•Vitamin A stored in Vitamin A stored in ITOITO CELLSCELLS in the liver; in the liver; 6-month supply6-month supply
VITAMIN A DEFICIENCYVITAMIN A DEFICIENCY
• Night blindness (insufficient retinal rhodopsin)Night blindness (insufficient retinal rhodopsin)• Xerophthalmia (dry eye)- keratinized squamous Xerophthalmia (dry eye)- keratinized squamous
epithelium replaces mucus-secreting epitheliumepithelium replaces mucus-secreting epithelium• Bitot spots (keratin debris) and keratomalacia Bitot spots (keratin debris) and keratomalacia
(destruction of the cornea)(destruction of the cornea)• Squamous metaplasia in LUNG (infections) and Squamous metaplasia in LUNG (infections) and
BLADDER (stones)BLADDER (stones)• Increased mortality in measles and diarrheaIncreased mortality in measles and diarrhea
Corneal Destruction
VITAMIN A TOXICITYVITAMIN A TOXICITY
• Increased intracranial pressureIncreased intracranial pressure
• Papilledema, headache, vomitingPapilledema, headache, vomiting
• Bone pain and hypercalcemia (increased Bone pain and hypercalcemia (increased osteoclast activity)osteoclast activity)
VITAMIN DVITAMIN D
• Major function is to maintain adequate Major function is to maintain adequate plasma levels of CALCIUM and plasma levels of CALCIUM and PHOSPHORUS PHOSPHORUS
VITAMIN D FUNCTIONSVITAMIN D FUNCTIONS
• Stimulates intestinal absorption of Stimulates intestinal absorption of calcium calcium and and phosphorusphosphorus
• Interacts with PTH to regulate blood Interacts with PTH to regulate blood calciumcalcium levels levels
• Stimulates PTH-dependent Stimulates PTH-dependent re-absorption re-absorption of calcium in the distal renal tubuleof calcium in the distal renal tubule
VITAMIN D DEFICIENCYVITAMIN D DEFICIENCY
• HYPOCALCEMIA and loss of bone: HYPOCALCEMIA and loss of bone: RICKETS or OSTEOMALACIARICKETS or OSTEOMALACIA– MalnutritionMalnutrition– Intestinal malabsorption (pancreatic Intestinal malabsorption (pancreatic
insufficiency)insufficiency)– Inadequate sunlight exposureInadequate sunlight exposure– Liver diseaseLiver disease– Renal disease Renal disease
NormalVitamin D Deficient
RICKETSRICKETS
• Osteoid with inadequate mineralizationOsteoid with inadequate mineralization
• Disorganized fibroblasts and capillariesDisorganized fibroblasts and capillaries
• MicrofracturesMicrofractures
• Deformed bonesDeformed bones
• Square head, Square head, ““rachiticrachitic”” rosary, pigeon rosary, pigeon breast deformity, lumbar lordosis, and breast deformity, lumbar lordosis, and bowed legs bowed legs
OSTEOMALACIAOSTEOMALACIA
• 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 Mostly involving the vertebrae and
femoral neckfemoral neck
VITAMIN D TOXICITYVITAMIN D TOXICITY
• Not caused by prolonged exposure to Not caused by prolonged exposure to sunlight; results from oral overdosesunlight; 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
VITAMIN EVITAMIN E
• ““AntioxidantAntioxidant””
• Deficiency- nervous system- degeneration Deficiency- nervous system- degeneration of posterior column axonsof posterior column axons– Loss of position and vibration sense; ataxia, Loss of position and vibration sense; ataxia,
muscle weaknessmuscle weakness– Hemolytic anemia of premature infantsHemolytic anemia of premature infants
• Toxicity: decreasd synthesis of vitamin K-Toxicity: decreasd synthesis of vitamin K-dependent coagulation factorsdependent coagulation factors
VITAMIN KVITAMIN K
• Clotting factors Clotting factors II II (prothrombin), (prothrombin), VIIVII, , IXIX and and XX are carboxylated in the liver and are carboxylated in the liver and Vitamin K is a cofactorVitamin K is a cofactor
• Also, carboxylation of Also, carboxylation of protein C and Sprotein C and S (anticoagulants)(anticoagulants)
• Vitamin K is Vitamin K is ““recycledrecycled”” in the liver and gut in the liver and gut bacteria make the vitamin, but some bacteria make the vitamin, but some dietary source is requireddietary source is required
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
Vitamin K Deficiency
THIAMINE (B1)THIAMINE (B1)
• Not in polished rice, white flour or refined Not in polished rice, white flour or refined sugarsugar
• ¼ of all alcoholics are thiamine deficient¼ of all alcoholics are thiamine deficient
• Cofactor in oxidative decarboxylation Cofactor in oxidative decarboxylation deficiency of thiamine results in deficiency of thiamine results in DECREASED ATPDECREASED ATP
• Cardiovascular and nervous system Cardiovascular and nervous system problemsproblems
THIAMINE DEFICIENCYTHIAMINE DEFICIENCY
Dry beriberiDry beriberi (polyneuropathy): myelin (polyneuropathy): myelin degenerationdegeneration
Wet beriberiWet beriberi (cardiovascular): vasodilitation (cardiovascular): vasodilitation produces heart failure and edemaproduces heart failure and edema
Wernicke-Korsakoff Syndrome:Wernicke-Korsakoff Syndrome:
WernickeWernicke- ataxia/confusion - ataxia/confusion KorsakoffKorsakoff- - amnesia, confabulationamnesia, confabulation
NIACIN (B3)NIACIN (B3)
• NAD and NADP are cofactors in oxidation-NAD and NADP are cofactors in oxidation-reduction reactionsreduction reactions
• Grains, legumes and seed oils (corn-based diets)Grains, legumes and seed oils (corn-based diets)• Deficiency of tryptophan (used to synthesize Deficiency of tryptophan (used to synthesize
niacin)niacin)• Deficiency- Deficiency- PELLAGRAPELLAGRA (3 D (3 D’’s)s) dermatitisdermatitis, , diarrhea diarrhea (epithelial atrophy) and (epithelial atrophy) and
dementiadementia (posterior column changes as in B-12 (posterior column changes as in B-12 deficiency)deficiency)
Niacin, Pellagra
• 3 D’s of Pellagra– Dermatitis– Diarrhea– Dementia
VITAMIN C (ASCORBIC ACID)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 Hemorrhage and poor wound healing in children
and adultsand adults• Vitamin C is a cofactor in formation and Vitamin C is a cofactor in formation and
maturation of procollagenmaturation of procollagen• Hydroxylation is impaired and crosslinks are not Hydroxylation is impaired and crosslinks are not
formedformed
VITAMIN C DEFICIENCYVITAMIN C DEFICIENCY
• SCURVYSCURVY • Capillary and venule walls are weak with Capillary and venule walls are weak with
hemorrages (purpura and ecchymoses)hemorrages (purpura and ecchymoses)• Trauma- hematoma and hemarthrosis (joints)Trauma- hematoma and hemarthrosis (joints)• Child- too much cartilage and Child- too much cartilage and not enoughnot enough
osteoidosteoid protein); bowed legs and deformed protein); bowed legs and deformed chestchest
• Bacterial infection associated with gingival Bacterial infection associated with gingival hemorrhagehemorrhage
Vitamin C deficiency
Vitamin C Deficiency
Normal“Rickets”
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
Cobalamin (B12) Deficiency
• Megaloblastic anemia
• CNS: posterior column and lateral corticospinal tract demyelination
• Glossitis
FOLATEFOLATE• 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 (Megaloblastic anemia (nono neurologic dx) neurologic dx)• GlossitisGlossitis• Certain drugs can lead to deficiency:Certain drugs can lead to deficiency:
– Alcohol, methotrexate, phenytoin, oral contraceptives, Alcohol, methotrexate, phenytoin, oral contraceptives, trimethoprim, 5-fluorouraciltrimethoprim, 5-fluorouracil
ZincZinc
• Trace element Trace element
• Component of enzymes (oxidases)Component of enzymes (oxidases)
• Causes of deficiency:Causes of deficiency:– AlcoholismAlcoholism– Diabetes mellitusDiabetes mellitus– Chronic diarrheaChronic diarrhea
Zinc Deficiency
• Acrodermatitis (rash around eyes, mouth, Acrodermatitis (rash around eyes, mouth, nose, and anus)nose, and anus)
• Anorexia Anorexia
• DiarrheaDiarrhea
• Growth retardationGrowth retardation
• Impaired wound healingImpaired wound healing
• Hypogonadism/ InfertilityHypogonadism/ Infertility
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
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