Nutritional, Environmental Disorders Flashcards
How do you get lead poisoning
Lead is absorbed via lungs or GI and follows calcium into bones
Threshold
Symptoms lead poisoning
GI (“lead colic”), CNS (irritability, ataxic, drowsy), microcytic hypochromic anemia w/ basophilic stippling, increased bone density at growth plates, peripheral neuropathy (foot drop, GI colic), nephropathy (Falconi syndrome)
Falconi syndrome
Impaired proximal renal tubular reabsorption of AA, phosphate, glucose
Mercury poisoning sources, symptoms
Dental amalgams, contaminated fish
Tremor, gingivitis, bizarre behavior, kidney damage
Cancer a/w:
Aromatic amines, benzene, nickel, vinyl chloride
AA: bladder
Ben: multiple myeloma, leukemia
Nickel: sinus, lung
VC: angiosarcoma of liver
Arsenic poisoning symptoms, diseases caused
GI pain, heart, CNS (2-8 wk post)
Chronic: skin cancer on palms, soles
Cadmium poisoning: sources, symptoms/diseases
Mining, electroplating nickel-cadmium batteries -> contaminated soil/water
Subtle renal disease, calcium loss -> osteomalacia/ porosis
Problems for chimney sweeps in old times
Soot -> scrotal cancer
Cancers caused by smoking
Oral (lip, in mouth), larynx, lung, pancreas, esophagus, bladder, kidney, uterine cervix
Component of cigarette smoke causing cancer
Polycyclic aromatic hydrocarbons
Most and least common lung cancers from smoking & an in between
Most: small cell (oat cell)
Least: bronchioalveolar adenocarcinoma
Mid: non-small cell bronchioalveolar
Heart disease, lung cancer, emphysema risk with cessation of smoking
HD: greatly reduced w/in 5 years
Lung: decreases 21% in 5 yr, risk lasts for 30 y
Emp: never goes away but won’t get worse
Acute alcoholic injuries
Drunkenness, fatty change of liver, acute alcoholic hepatitis
Chronic alcoholic injuries
Cirrhosis, alcoholic cardiomyopathy, acute/ chronic pancreatitis, alcohol dependence/ withdrawal
Reversible injury associated with drinking & cause
Acute fatty change of the liver d/t TG synth (can’t put all EtOH 2-C frags into Krebs) -> dec lipid secretion by liver
GGT goes up, not AST/ALT, alkaline phosphatase
*Lasts for days, may cause sudden death d/t metabolic derangement
Other causes of fatty liver
Glucose/sugar shunted from Krebs to fat production bc ADH makes too much NADPH (while DH EtOH) & H2 has to go somewhere
*Also oxidizing EtOH = free radicals, acetaldehyde
Acute alcoholic hepatitis
Rare rxn; throw up a lot -> death
*Must be genetically susceptible
Lab dx alcoholic hepatitis
Mallory bodies (pink clumped precytokeratin filaments) with neutros around Mallory body hepatocytes & neutros, eos, lymphs in portal triad
Fibrosis b/t portal triads (bridging) -> cirrhosis
AST, ALT, GGT, alk phos elevated
Portal HTN & esophageal varices
Cirrhosis prevents connection of nodules to central veins = congestion
Blood backs up into coronary vein -> esophageal veins
Also spleen enlargement
Alcoholic cardiomyopathy
Form of dilated cardiomyopathy, can cause splinter hemorrhages
D/t myocyte toxicity by loosening BM dystrophin
EtOH shortest SCFA, which heart lives on, but this messes it up
Acute and chronic pancreatitis findings
Acute: Ranson’s criteria
Chronic: toothpaste-y stuff in ducts, stones, chain of lakes, grittiness on sectioning, possible fat saponification
Ranson’s criteria
At admission: >55 y, WBC >16, glucose >200, serum LDH >350, AST >250
After 48 hr: hematocrit falls >10%, urea rises >5mg/L, arterial PO2 -4, estimated fluid sequestration >6L
Fetal alcohol syndrome features
Short palpebral fissures, flat midface, short nose, flat philtrum, thin upper lip, micrognathia, minor ear abnormalities, low nasal bridge, epicanthal folds
MR, social problems
Infections from IVDA
Infections: Hep B, C, AIDS, endocarditis
Talc granulomatosis
Characteristics of cocaine
Acute HTN surge, vasoconstriction (paradoxical inotrope), possible stroke
Acute OD: seizure, cardiac arrhythmia, death
Chronic overuse: temp 105
Features of ASA OD
Metabolic acidosis, resp alkalosis, tinnitus, high anion gap, vomiting
Features of acetaminophen OD & tx
Throw up once, okay for one day (liver depleting GSH), come back dying of hepatic failure with drug level
Solar elastosis
Elastic replaced by scar tissue
Non-ionizing EM radiation at 1-10^18 Hz
Long wavelength, low freq
Electric power, radio waves, microwaves, infrared, UV light
Vibration and rotation of atoms in biologic molecules
Non-ionizing EM radiation at 10^18-10^27 Hz
Short wavelength, high freq
X-ray, gamma ray, cosmic rays
Ionize target molecules and eject electrons
Hematopoietic syndrome d/t radiation
200 rad (2Gy) to 700 rad of photons -> radiation-sensitive BM stem cells depleted = pancytopenia with anemia, infections, bleeding Attrition of gonadal stem cells
Gastrointestinal syndrome d/t radiation
1000 rads, depletes GI mucosa = malnutrition, malabsorption, electrolyte imbalance, septicemia
CNS syndrome d/t radiation
Several thousand rads, generalized endoth damage w/ vascular leakage = neuro symptoms, cardiovascular sx
*Rapidly fatal (hr to days)
Local vascular damage d/t radiation mechanism
Radiation fibroblasts: scarring with 2’ tissue disorganization, atrophy
Telangiectasia, ulceration, erosion, ischemic
Vascular stenosis d/t sclerosis, mural fibrinoid material, intimal foam cell accumulation, thrombosis
Marasmus vs. kwarshiorkor
M: wasting d/t insufficient calories; fretful, desperate for food; no SQ fat, die of infxns
K: protein malnutrition; rash, scaly skin, distended abd, anemic, apathetic; fatty liver, edema
Central vs. peripheral fat (apple vs. pear)
Apple: internal fat, assc. with DM2, dyslipidemias, cancer, HTN, heart/kidney disease
Unexpected effects of BMI >35
Non-alc fatty liver, gallstones, sleep apnea (Pickwickian syndrome), arthritis, cancer (esoph, GB, colon, thyroid, kidney, endometrium)
Enzymes required for absorption of fat-soluble vitamins
Bile & panc enzymes (triggered by fat)
ApoE-R (vit A)
Stored in fat, liver
Vitamin A functions
Fight infections, normal columnar and transitional epithelium (skin follicles, resp tree, kidney/ureters), normal growth
Vit A and cancer; why?
Inverse relationship because retinoids modify cellular diff/prolif
Vit A teratogen
Retin-A, a beta-carotenoid (alpha non-teratogenic)
Vit A deficiency
Night blindess -> perm blindness via keratostomia, corneal ulcer, corneal/scleral thickening (Bitot spot)
Mucosa/skin -> keratin = stones, tumors
Follicular hyperkeratosis
Vitamin A deficiency causes (aside from poverty)
GI disorders/ malabsorption: sprue, celiac, CF, steatorrhea, cirrhosis, chronic hepatitis, other liver problems
*Nursing women may deplete stores
Vit A sources
Eggs, milk, butter, fish, polar bear liver (too much)
Carotenoids from yellow veg, leafy greens (carrots, yellow squash, red, yellow peps, spinach, salad)
Vitamin A toxicity
HA, n/v, blurred vision, papilledema, stupor, alopecia, weight loss
Overstimulated osteoclast -> bone/jj pain, bone resorption, fx, symmetrical hyperostosis
Vit D deficiency
Weak bones, lose mm strength, lose immune fxn, cancer (colon, breast, pancreas, prostate)
High inflammation levels
Vit D effect on small intestine?
D-OH-2 triggers Ca2+ absorption
Structure of vit D
Prohormone, modified by liver and kidney to become D-OH-2 and active
Skeletal vit D functions
Maintain Ca/phosphorus homeostasis (absorb Ca in small int and reabsorb in kidney) to maintain blood Ca, too much -> bone to make stronger (PO4 follows, so low vit = low Ca and PO4)
Nonskeletal vit D functions
Steroid hormone made from chol produced by breast, prostate, colon, MFs, squamous cells
Regulates expression of genes, many imp in cancer
Low it D blood levels
D-OH-2 below 20 ng/ml assc with 30-50% increase in breast, prostate, colon cancers
Synthesis of vit D
Skin 7-dehydro-chol + UVB = vit D3 (chole)
Food vit D in liver -> D-OH-1 (ergo)
Vit D-OH-1 in kidney -> vit D-OH-2 *active
How to become vit D deficient & prevention
Not enough sunlight (more melanin, clouds, sunscreen)
Low D in diet
Bad kidneys (no conversion)
*Cod liver oil (except renal)
Diseases caused by vit D deficiency
Rickets in kids under 2 with unfused growth plates (also renal rickets)
Osteomalacia in adults (mostly renal)
Signs of rickets
Frontal bossing - squared off head
“Rachitic rosary” of anteriorly-protruding ribs
Lumbar lordosis, bowed legs
“Soft bones” and pseudo-fractures, growth retardation, hypercalciuria (nephrocalcinosis, renal calculi)
Signs of osteomalacia
Progressive weakness, pain in bones of arms, legs, spine, pelvis (bone tenderness)
Pathologic fx, too soft -> death
Lab findings to differentiate osteomalacia from osteoporosis
Mal: too much osteoid (collaged supporting calcium in bone), not enough Ca2+
Por: normal ratio osteoid to calcium, not enough bone
Ideal concentration for vit D
> =30, not consistently over 200 -> hypercalcemia, hyperphosphatemia
Sources of vit D
Cod liver oil, salmon, mackerel, tube, sardines/ anchovies, milk, margarine, fortified cereal, egg, liver/beef, swiss cheese
Vit D toxicity
Constipation, anorexia, dehydration, fatigue, irritability, vom, hypercalcinuria/ emia, HTN, polydipsia, polyuria, damage to kidney & bone, calcifications in soft tissues; tight PQRS d/t hyper-excitable heart
Vit E functions
Antioxidant, immune (cell signal, gene exp reg, *a-tocopheral inh PKC), prevents clotting, suppresses ArachAcid metabolism and increases prostacyclin)
Vit E deficiency symptoms
Premies: failure to thrive, decreased reflexes, weak mm, abnrl eye movements, hemolytic anemia
Fat malabsorption: peripheral neuropathy, ataxia, sk myopathy, retinopathy, impaired immune response
Who gets vit E def?
Crohn disease, CF, inability to secrete bile, steatorrhea, chronic diarrhea (need water soluble vit E)
Abetalipoproteinemia
*Risk of A, D def too
Abetalipoproteinemia
Poor absorption fat -> poor nerve impulses, mm weakness, retinal degen -> blindness
*Acanthocytes (spur cells)
Ataxia & vit E deficiency (AVED)
Rare, inherited disorder
Liver’s alpha-tocopherol transferase defective or absent
Lose ability to walk without huge doses vit E
Sources of vit E
Wheat germ oil, almonds, sunflower seeds, nuts/seeds… corn oil, spinach, broccoli, kiwi, mango
Vit K functions
Cofactor for clotting factors made by gut bacteria
Vit K deficiency: who? symptoms?
Liver disease, malabsorption, broad spectrum antibiotics, newborns, rare disorders
Bleeding: hematomas, hematuria, melena, gums, nose
Sources of vit K
Cabbage, cauliflower, spinach, other greens, fortified cereals
Therapeutic use of vit K
Reverses Coumadin in high doses
Too much vit K
Interferes with anticlotting meds, jaundice, RBC hemolysis, brain damage
B vitamins: 1, 2, 3, 6, 9, 12
1: thiamine
2: riboflavin
3: niacin
6: pyridoxine
9: folate
12: cobalamin
Thiamine function, deficiency
Carb/AA metabolism; peripheral nerve conduction
Beriberi
Riboflavin function, deficiency
Redox reactions
None (technically ariboflavinosis)
Niacin function, deficiency
Essential to Krebs/ glycolysis
Pellagra
Pyridoxine function, deficiency
Cofactor in many reactions
Cheilitis, glossitis, dermatitis, peripheral neuropathy
Folate function, deficiency
With cyanocobalamin, turns precursor RBC into mature RBC
Megaloblastic anemia
Cobalamin function, deficiency
Cyanocobalamin with folate, turns precursor RBC into mature RBC
Megaloblastic anemia/ pernicious anemia
Beriberi symptoms
Dry: peripheral neuropathy and atrophy
Wet: high output heart failure from peripheral vasodilation, edema, enlarged heart, arrhythmias
Wernicke-Korsakoff syndrome
Confusion, ataxia, ophthalmoplegia, confabulation, atrophy of cerebellar vermis, deign of mam bodies
*Alcoholics, really weird diets
Sources of thiamine
Grains, yeast, pork liver, oatmeal
Riboflavin deficiency
Cheilosis, glossitis, eye changes (invading capillaries), anemia, seborrheic dermatitis
Seen in alcoholics, 3rd world poor diet
Sources of riboflavin
Milk, eggs, nuts, beef, meat, liver, fish, whole grain cereals, green veg
Pellagra
B3 def in alcoholics, debilitating illnesses, diet with corn as staple
Dermatitis (worse in sun), dementia, diarrhea, death
Sources of niacin
Endogenous from tryptophan (meat, liver, eggs), liver, chicken, beef, fish, cereal, peanuts, legumes, green leafy veg
Sources of pyridoxine
Potatoes, bananas, garbanzos, chicken, beef, fish, oatmeal, sunflower seeds, spinach, tomato juice, avocado, PB, soybean, etc.
Who gets pyridoxine deficiency?
Use of B6 antagonist (INH), alcoholism, pregnancy (increased demand), homocysteinuria (increased demand), poor diet
Pyridoxine def symptoms
Peripheral neuropathy, cheilosis, glossitis, dermatitis, microcytic anemia
Folate functions
Transfer of 1-C units in DNA synthesis
Fights heart disease
Folate deficiency
Megaloblastic anemia (microcytic because can’t form properly)
Folate sources & anti-sources
Dark green leafy stuff, fruits, nuts, veg, beans
Bad: sunshine destroys it, but melanin somewhat protects
Sources of cobalamin & who gets deficient?
Meat, dairy
Strict vegetarians, alcoholics, malabsorption (pernicious anemia, other GI malabsorption syndromes)
B6 and B12 deficient - what’s the problem?
Elevated homocysteine = risk for heart attack
Folate vs. B12 deficiency
B12: neuro symptoms
Folate: no neuro symptoms
Pernicious anemia
AI atrophic gastritis -> withering stomach parietal cells & stop making IF (glycoprotein carrier of B12)
Result: megaloblastic macrocytic anemia
Vit C functions
Heals wounds (collagen)
Keeps caps from bleeding
Immune functions (antioxidant)
Mm and bones strong (crosslinks collagen, carnitine)
Vit C deficiency
Scurvy: teeth falling out from bleeding gums, rash, corkscrew arm hairs, petechiae -> bruises, capillary fragility
Sources of vit C
40-60 mg/day; citrus fruits, rose hips, sauerkraut (cabbage), malt, broccoli, liver, willow bark
Zinc functions
Need it for wound healing & pregnancy (zinc fingers)
Zinc deficiency
Cheilitis, rash at eyes, toes, alopecia, anorexia, diarrhea, smell/taste problems, memory problems, leukonychia (fingernail spots)
Who gets zinc deficient?
⅓ world where soil doesn’t have enough Zn
People on TPN without added Zn
A/D deficienct - can’t use the zinc you have
Components of smog
Sulfur dioxide, CO, ozone, nitrogen dioxide, lead, particulate matter
Ozone formation & effect
Sunlight driven rxns of nitrogen oxides released by auto exhaust
Generates free radicals, damages resp tract/ alveoli, smog
Sulfur dioxide, particles, acid aerosols source & effect
Coal- ad oil-fired power plants, industrial processes
Particles: main cause morbidity and death, phago by MFs, neutros -> release mediators/ cause inflam
CO sources & poisoning
Auto engines, fossil fuel burning, home oil burning, cig smoke
Binds Hb, prevents O2 transport (200x affinity) -> slow CNS depression, systemic hypoxia, death
*May appear red-skinned
Wood smoke, radon, and bioaerosols
Wood smoke -> predisposes to lung infxn, may contain polycyclic hydrocarbons
Radon - not harmful at low levels
Bioaerosols - may contain pathogenic microbes
Organic solvents like chloroform, carbon tetrachloride source and symptoms
Degreasing/ dry cleaning agents, paint removers
Dizziness, confusion, CNS dep, coma, kidney/ liver toxicity
Organic solvents benzene and 1,2-butadiene source and symptoms
Occ exposure of rubber workers, increase risk of leukemia by disrupting progenitor cell diff in BM
*CYP2E1 for benzene
Organochlorides: DDT, PCBs, TCDD
Most are endocrine disrupts, long-term health effects unclear except DDT -> neurologic toxicity
PCBs
PCBs & dioxins -> chloracne (pigment, cyst, hyperkeratosis, acne), folliculitis; induces CYP450
BPA
Potential endocrine disruptor, heart disease; extent of effects unclear
Mineral dust: coal dust, silica, asbestos, beryllium
Pneumoconioses/ non-neoplastic lung diseases
*Asbestos extends to family members/ close contacts
Pros and cons of estrogen therapy
Post-menopause: HRT to prevent or slow osteoporosis, ? reduce risk of MI
Increased risk endometrial/ breast carcinoma
Estrogen vs. estrogen + progestin hormone replacement therapy
Est alone: increased risk endometrial carcinoma
Est + progest: drastically reduced risk endo car but inc risk breast carc
Either: inc risk thromboembolism
Oral contraceptive effect on: breast carcinoma, endometrial/ ovarian cancer, cervical ca, thromboembolism, CVD, hepatic adenoma
BC: no inc risk
E/O: protective
Cerv: ? inc risk (may just be d/t sexual activity)
TE: inc risk, still lower than risk d/t pregnancy
CVD: no inc risk for nonsmoker/ under 30, inc risk in over 35 smoker
HA: clear association
Factors affecting clinical severity of burns
Depth, % body covered, ? internal injuries from inhalation toxic/ hot fumes, prompt and efficacious tx (wound management, fluids, electrolytes)
Full thickness burns
3, 4th degree burns
Total destruction of epidermis and dermis, including dermal appendages with stem cells
Appear white, charred, dry, anesthetic
Partial thickness burns
Deeper portions of dermal appendages spared; pink, mottled, blistered, painful
1st degree: epithelium only
2nd degree: epidermis and superficial dermis
Burns & shock
Is over 20% body, rapid shift of fluid to interstitium at site and systemically -> hypovolemic shock, with pulmonary edema d/t protein loss into interstitium
Burns & inhalation injury
Direct effect of heat on mouth, nose, upper airway or inhalation of heated air or gas
Inhalation of water- vs. lipid-soluble gas
Water-soluble chlorine, sulfur oxide, ammonia -> acid or alkalis in airway = inflam, swelling
Lipid-soluble nitrous oxide, products of burning plastics -> reach deeper airway = pneumonitis
*Both 24-48 hrs later
Leading COD in burn patients
Septic organ system failure d/t microorganisms invading burn wounds (Pseudomonas, S. aureus)
Symptoms of anorexia nervosa
Amenorrhea, cold intolerance, bradycardia, constipation, chains in skin/hair, dehydration, electrolyte abnormalities, scaly dry yellow skin (excess carotene in blood), increased but fine and pale body hair (lanugo), decreased bone density, anemia, lymphopenia, hypoalbuminemia
Anorexia nervosa increases risk for:
Cardiac arrhythmia & sudden death d/t hypokalemia
Complications of bulimia
Due to electrolyte imbalances (d/t vomiting; hypokalemia) & consequent inc risk of arrhythmia, pulmonary aspiration of gastric contents, esophageal/ stomach rupture
Leptin (and adiponectin)
From fat cells, regulated by adequacy of fat stores; with enough fat, reduces food intake by stimulating POMC/CART neurons, inhibiting NPY/AgRP neurons; stimulates thermogenesis
*Loss of fxn = obesity
Insulin
From pancreatic beta cells
Ghrelin
From stomach, stimulates appetite, “meal initiator”, ? stimulates NPY/AgRP neurons in hypothalamus
Peptide YY
From ileum/colon endocrine cells, released post-prandially, a satiety signal; ? stimulates POMC/CART neurons to reduce intake
Genes ? involved in obesity
Leptin loss of function mutation
Melanocortin-4-R (MC4R)
Leptin resistance
Types of neurons that activate efferent neurons to promote energy expenditure, and those that promote food intake
*All regulated by arcuate nuc of hypothalamus
EE: POMC/CART neurons
Food: NPY/AgRP neurons
Cancers associated with obesity
Men: esophagus, thyroid, colon, kidney
Women: esophagus, endometrium. gallbladder, kidney
Other disorders associated with obesity
HTN, nonalcoholic steatohepatitis, gallstones, hypoventilation syndrome (Pickwickian syndrome), osteoarthritis (DJD), chronic inflammation
