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Path - Chapter 9


What is the single leading cause of global health loss (morbidity and premature death)? Undernutrition
What are the leading causes of death in developed countries? Ischemic heart disease; cerebrovascular disease
What constitute 5 of the 10 leading causes of death in DEVELOPING countries? Infectious Disease (HIV, respiratory infections)
T/F 70% of all child deaths are preventable, and only due to 5 conditions? TRUE; pnuemonia, diarrhea, malaria, measles, perinatal/neonatal problems
What are the three categories of EID? newly evolved strains; endemic in another species turned to humans; diseases present but increasing incidence
These are the diseases that are expected to be affected by the inevitable warming of the earth? Cardiovascular, cerebrovascular, respiratory disease (heatwaves); Gastroenteritis/Infectious Disease epidemics (heavy rains, disruption of clean water, floods); Vector-borne infectious diseases (warming, crop failures); Malnutrition (disruption of crops)
These are exogenous chemicals in the environment that may be absorbed into the body through inhalation, ingestion, and skin contact? Xenobiotics
How are most solvents and drugs transported in the blood? Lipophilic (via lipoproteins and can pentrate through plasma membrane of cells)
Hydrolysis, reduction, oxidation are what phase of metabolisis of solvents, drugs or xenobiotics? Phase 1
Glucuronidation, sulfation, Methylation, Conjugation are what phase of metabolisis of solvents, drugs, and xenobiotics? Phase 2
What is the most important catalyst of phase 1 reactions? CYP (cytochrome p450)
T/F Both detoxification and Activation of xenobiotic by CYP can lead to formation of reactive oxygen species? TRUE;
Why is there a great variation of CYP activity amongst individuals? genetic polymorphisms AND chemicals/drugs that induce or diminish CYP activity
Drugs, smoking, alcohol and hormones (Increase or decrease) CYP activity? INCREASE (inducers)
Fasting and Starvation (increase or decrease) CYP activity? DECREASE (diminishers)
How do CYP inducers increase CYP activity? bind nuclear receptors > heterodimerize with retinoic X receptor (RXR) > formation of transcriptional activation complex > associates with promoter of CYP gene
What are the nuclear receptors that participate in CYP induction? PPAR, PXR, CAR, aryl hydrocarbon receptor
What does OZONE cause? decreased lung function; Increased airway reactivity; lung inflammation; decrease exercise capacity; increased hospitalizations
What does Nitrogen Dioxide cause? Increased airway reactivity, decreased lung function, increased respiratory infections
What does Sulfur Dioxide cause? Increased respiratory symptoms, increased mortality, increased hospitalizations, decreased lung function
What does Acid Aerosols cause? Altered mucociliary clearance; increased respiratory infections, decreased lung functions, increased hospitalizations
What do Particulates cause? Increased respiratory infections; Decreased lung function; excess mortality; increased asthmatic attacks
What is the difference between "good" ozone and "bad" ozone? Good is made from O2 and sun and is in stratosphere; Bad is @ ground level and made with nitrogen oxides + volatile organic compounds + sun (from industrial emissions and motor vehicle exhaust
Ozone toxicity is mediated by production of these dangerous molecules? free radicals (damage epithelium and type 1 alveolar cells)
Ozone -induced asthma is associated with what? airway hyper-reactivity and neutrophilia
This air pollutant, created by coal plants can cause a burning sensation in the throat, difficulty breathing, and asthma attacks in susceptible people? Sulfur Dioxide
What size particulates are most dangerous to inhale? Less than 10 micrometers
What happens to inhaled particulates that are less than 10um? go into alveoli, phagocytosed by macrophages, release inflammatory mediators (macrophage inflammatory protein 1a and endothelin)
This pollutant is an important cause of accidental and suicidal death, due to hemoglobins 200x higher affinity for it than oxygen? Carbon Monoxide
A patient working in tunnels all his life is exposed to low levels of carbon monoxide, which areas of the basal ganglia are particularly marked with ischemic changes? Lenticular nuclei, and basal ganglia
What is the characteristic feature of acute carbon monoxide poisoning? generalized cherry-red color of skin and mucosa
How may the brain appear if an attempted suicide with carbon monoxide didn't work and patient lived? Edematous, with punctate hemmorhages and hypoxia-induced neuronal changes
What causes the cherry-red color of skin and mucosa in suicidal carbon monoxide poisoning? high level of carboxyhemoglobin
This indoor pollutant predisposes to lung infection and may contain the carcinogenic polycyclic hydrocarbons? Wood smoke
What are bioaerosols? microbiologic agents capable of causing infectious disease (indoor pollutant) …legionnaires, viral pnuemonia, allergens
formaldehyde is a dangerous indoor pollutant because of what? it is a carcinogen, causes breathing difficulties and a burning sensation
What can subclinical lead poisoning lead to in children? [BRAIN DAMAGE] low intellectual capacity; behavioral problems; hyperactivity; poor organizational skills
What are the major anatomic targets of lead poisonign? bone marrow and blood; nervous system; GI tract; kidneys
Why are children more affected by lead poisoning? higher intestinal absorption of lead; more permeable blood-brain barrier
What effects does lead have on cartilage and bone? inhibits healing of fractures by increasing chondrogenesis and delaying cartilage mineralization
What two enzymes in heme synthesis are affected by lead? D-aminolevulinic acid and ferrochelatase
What kind of anemia results from lead poisoning? mycrocytic hypochromic (due to suppression of hemoglobin synthesis) __ accompanied by mild hemolysis
What can be seen due to inhibition of ferrochelatase within bone marrow? Scattered ringed sideroblasts (red cell precursors with iron laden mitochondria) _ Prussian Blue Stain
What toxin causes appearance of punctate basophilic stippling of red cells? Lead poisoning
What kind of neuronal damage is suffered in adults by lead poisoning? peripheral demyelinating neuropathy
What are the first muscles to be affected in adults with lead poisoning? Extensor muscles of the wrist and fingers (wristdrop) followed by paralysis of peroneal muscles (footdrop)
What are kidney manifestations of lead poisoning? proximal tubular damage with intranuclear lead inclusions; interstitial fibrosis; renal failure
What can result from decrease in uric acid excretion? Gout ("saturnine")
A patient comes in with headache & complains of memory loss. He has been working at a foundry and has been noticing some intermittent weakness when trying to lift a hammer causing his hands to drop. Examination also shows mild anemia. What is the cause? Lead poisoning
An xray is seen with a very dense epiphyses in a small child living in an old home, what could be the cause? lead; impaired remodeling of calcified cartilage
What are the main sources of exposure to mercury today? contaminated fish (methyl mercury) ; mercury vapors in dental amalgam
The development of what organ is extremely sensitive to exposure of methyl mercury? Brain
What is the main protective mechanism against mercury-induced CNS and kidney damage? Intracellular glutathione (mercury is toxic because it binds to thiol groups)
What three systems are affected by arsenic poisoning? GI, cardiovascular, CNS
Why does arsenic interfere with mitochondrial oxidative phosphorylation? It can replace the phosphates in ADP
Prolonged exposure to this toxin causes hyperpigmentation, hyperkeratosis, and may cause basal and squamous cell carcinoma? Arsenic
A recent chinese immigrant comes in with multiple skin tumors around the palms and soles. When asked about his life back in China, he says that his family normally drank well water from the ground. What other organ should be checked for possible malignanc Lung (arsenic can cause skin tumors of basal and squamous cell carcinoma as well as lung cancers)
What is the most important source of cadmium for the general population? Food (cadmium contaminates soil and plants)
This toxin often found in food can cause obstructive lung disease caused by necrosis of alveolar macrophages, and kidney damage (tubular damage > then end-stage renal disease, and skeletal abnormalities (osteomalacia, osteporosis)? Cadmium
What cancer is associated with Cadmium? lung cancer
What do rubber workers get exposed to that leads them to develop leukemia? benzene (CYP2E1)
These agents used in dry cleaning and paint removal can cause dizziness, confusion, coma and death? chloroform and carbon tetrachloride
DDT, polychlorinated byphenyls and dioxin are? (organic solvents, polycyclic hyrdocarbons, organochlorines)? organochlorines
What do most organochlorines dunction as (in the body)? endocrine disruptors (anti-estrogenic and anti-adrogenic)
Acne, cyst formation, hyperpigmentation, hyperkeratosis which is generally found around the face and behind the ear is caused by this organochlorine? Dioxins and PCBs (this is called CHLORANCE arsenic also has skin changes)
Folliculitis and Chlorance are caused by? Dioxins and PCBs
This is a chronic, non-neoplastic lung disease caused by exposure to mineral dusts such as coal dust, silica, asbestos, beryllium? pneumoconiosis
angiosarcoma of the liver can be caused by exposure to this chemical? vinyl chloride
Exposure to this can cause a testicular dysgenesis syndrome (hypospadias, cryptochidism, testicular cell abnormalities)? phthalates (plasticizer)
What is the most preventable cause of human death? smoking
what does nicotine do to the body? increases heart rate, blood pressure, cardiac contractility and cardiac output
What are the most common diseases associated with smoking in the lung? emphysema, chronic bronchitis, COPD, lung cancer
What mechanism is responsble in smokeing induced emphysema? recruitment of leukocytes to the lung and increase elastase production leading to injury of lung tissue
Which components of cigarrette smoke are carcinogens and are directly involved with the development of lung cancer? polycyclic hydrocarbons and nitrosamines
T/F smoking multiplies the risk of other carcinogenic influences? TRUE; (asbestos induced cancer increases with smoking)
Aside from lung cancer, what other cancers are developed through cigarette use? oral cavity, esophagus, pancreas, bladder
What effects of smoking are aimed at the circulatory system? atherosclerosis and myocardial infarction (increased platelet aggregation; decreased myocardial oxygen supply due to hypoxia)
What does smoking during pregnancy cause? decreased fetal birth weight and spontaneous abortions
how can second hand smoked be measured? blood cotinine (metabolite of nicotine)
Why can chronic alcoholics tolerate up to 700 mg/dl of ethanol concentration? induction of CYPs
What is most of the alcohol in the blood transformed to in the liver by ADH, MEOS, and catalase? acetaldehyde
What three enzymes in the liver transform alcohol into acetaldehyde? alcohol dehydrogenase (ADH) (primary in cytosol of hepatocytes), microsomal ethanol-oxidizing system (at high alcohol consumption), and catalase
What is acetaldehyde converted to by ALDH? acetate (a substrate of the mitochondrial respiratory chain)
What function does CYP2E1 have during ethanol metabolism? it is involved in the microsomal oxidation system (in smooth endoplasmic reticulum)
Why does alcohol potentiate the depressant effects of narcotic, sedative and psychoactive drugs? alcohol competes with these drugs for available CYP2E1 and thus slows their metabolism
What cancer is acetaldehyde associated with? oral cancer (esophageal and laryngeal)
What do 50% of asians have very low levels of? ALDH (ALDH*2 is a dominant negative; homozygotes cannot tolerate alcohol)
The deficiency of this metabolic product of alcohol metabolism is the cause of accumulation of fat in the liver of alcoholics as well as lactic acidosis? NAD (NAD is converted to NADH in mitochondria via ALDH, NADH/NAD increases and decreases available NAD for fatty acid oxidation and conversion of lactate into pyruvate)
What are the effects of released endotoxin from gram-negative bacteria in the flora caused by alcohol? production of TNF and cytokines leading to hepatic injury
What are the acute effects of alcohol consumption fatty change/hepatic steatosis ; gastritis and ulceration; CNS depressant (disordered cortical, motor, and intellectual behavior, respiratory depression)
A child born with microcephaly, growth retardation and facial abnormalaties is seen with a mother that did what in her first trimester? Drank alcohol (fetal alcohol syndrome)
What is the main site of chronic alcohol injury? liver (hepatitis and cirrohsis, portal hypertension, hepatocellular carcinoma)
peripheral neuropathies and Wernicke-Korsakoff syndrome are a result of this vitamin deficiency in alcoholics? Vitamin B1 (thiamine)__also causes beri-beri
Chronic alcoholism can cause this cardiovascular problem? dilate congestive cardiomyopathy (alcohol cardiomyopathy)
Heavy alcohol ingestion causes a (increase or decrease) of HDL? decrease
What does wine contain which may promote longevity? resveratrol
What cancer is HRT associated with increased risk for? Breast cancer (after 5-8 years); (highest risk for lobular carcinomas and ductal-lobular cancer)
Under what age does HRT have a protective role against atherosclerosis and coronary disease in women? 60
What does HRT increase the risk for? Breast cancer and Thromboelmbolism (venous)
Use of oral contraceptives increases the risk for these? thromboembolism; Cardiovascular disease (smokers); Cancers (endometrial and ovarian); Hepatic Adenoma
What cancer is oral contraceptives associated with? endometrial and ovarian
Why do oral contraceptives increase the risk of thromboembolism? Increased generation of acute phase proteins (CRP) and coagulation factors (pregnancy is associated with a hyoercoaguable state)
What do anabolic steroids inhibit the release of? LH and FSH (increases the amount of estrogen)
These are some Problems associated with anabolic steroid use? stunted growth, gynecomastia, testicular atrophy, Hepatic Cholestasis
What can oral administration of anabolic steroids lead to? Hepatic cholestasis (inhibition of bile flow)
What does about 5% of the acetaminophen get broken down to by CYP (CYP2E1)? NAPQI (N-acetyl-p-benzoquinoeimine) this is the cause of the hepatocellular injury incurred at high doses of Acetominophen
What 2 ways does NAPQI damage hepatic cells upon accumulation? binds hepatic proteins which damages cell membrane and mitochondrial dysfunction; depletion of Glutathione can cause susceptibility to reactive oxygen species
What normally conjugates and inactivates NAPQI? Glutathione
Adminestering what during the early stages of Aceteminophen overdose will induce recovery by erstoring GSH (glutathione)? N-acetylcysteine
Overdose of this drug results in accumulation of NAPQI and hepatocellular injury leading to centrilobular necrosis and liver failure? Acetominophen
What results from acute overdose of acetylsalicyclic acid? alkalosis (stimulation of the respiratoyr center) > metabolic acidosis > uncoupling of oxidative phosphorylation and inhibition of the krebs cycle> formation of non-ionized forms of salicylates > nausea and coma > death
What results from salicylism (chronic aspirin use)? headache, tinnitus, confusion, nausea, vomiting, diarrhea, convulsions, coma; Acute erosive gastritis; Gastric ulceration and Bleeding; Petechial hemmorhages in the skin
What can result from taking proprietary mixtures of aspirin and phenacatin over years? analgesic nephropathy ( tubulointerstitial nephropathy with renal papillary necrosis
What phase reactions break down 95% of acetaminophen? Phase 1 (followed by excretion in urine as glucuronate or sulfate conjugates)
What can excessive use of oils of wintergreen result in? Salicylate poisoning
This drug produces intense euphoria and stimulation, has no physical dependance, and overdose can result in seizures, cardiac arrhythmias and respiratory arrest? cocaine
How does cocaine act like a sympathomimetic? prevents reuptake of dopamine in the CNS; prevents reuptake of both Epinephrine and NoE at adrenergic nerve endings, thus causing excess stimulation
How does cocaine cause myocardial ischemia? increases the oxygen demand by stimulating the heart (tachycardia, hypertension); Decreases bloodflow byt causing platelet aggregation, and vasoconstriction
How does cocaine produce lethal arrythmias? disruption of normal ion transport in the myocardium
These two CNS effects are most common in cocaine? Hyperpyrexia and seizures
What are cocaine's effects on pregnancy? decreased blood flow to the placenta and fetal hypoxia; spontaneous abortion; impaired neurological development
Why is sudden death a huge risk for heroin users? purity of drug is uknown; incarceration may lead to loss of tolerance
A granuloma with talc crystals enclosed in foreign body giant cells may indicate use of this drug? Heroine (it is often cut with talc and quinine)
What are the four most common sites for infection? skin and subcutaneous tissues, heart valves, liver and lungs
A patient with endocarditis comes in, he has a history if IV drug abuse. Which drug is most likely? Heroine (infection of the tricuspid is a serious complication)
What are the two major renal problems in heroine users? amyloidosis and focal glomerulosclerosis
This drug acts by releasing dopamine in the brain, often produces euphoria followed by a crash, and can result in violent behaviors, confusion and psychotic features? methamphetamine
This drug causes a release of serotonin from the brain, interferes with it's synthesis, is toxic to the serotonin receptor, taken orally, and may produce euphoria and hallucinations? MDMA (ecstasy)
This drug has potential in treating nausea secondary to chemothetrapy as well as some chronic pain diseases? Marijuana
What does the endogenous cannibinoid system participate in ? regulation of the hypothalamic-pituitary-adrenal axis (appetite, food intake, energy balance, fertility and sexual behavior)
What can chronic inhalation of vapors containing toulene cause? cognitive abnormalities, and MRI detectable brain damage from mild to severe dementia
This type of mechanical trauma is produced by scraping or rubbing? abrasion
This type of injury is characterized by damage o fblood vessels and extravasation of blood into tissues and is produced by a blunt object? Contusion
A blunt object which hits the body causes a tear or disruptive stretching which is called what? laceration
What is the difference between a penetrating wound and a perforating wound? perforating simply means it also exitied (on top of the penetrate)
What are the three types of causations involved in injuries suffered during automobile crashes? hitting something interior or being hit by something interior; being thrown; being trapped in a burning vehicle
What should you look for in a driver not wearing his seatbelt involved in an automobile accident? sternal/rib fractures, heart contusions, aortic lacerations, lacerations of the spleen and liver
What factors determine the clinical significance of burn injury? depth, percent of body, inhalation of hot and toxic fumes, efficacy of therapy
What are the three categories of burn injuries and what do they mean? superficial (epidermid); partial (dermis); full-thickness (subcutaneous and possible muscle)
These are the greates threat to life in burn victims (especially > 20%)? shock (hypovolemic due to shifting of fluids); sepsis; respiratory insufficiency
What happens to the metabolism of a person that has suffered extensive burns? Increases (can double @ 40% burn)
What are the most common opportunistic organisms in burn victims? pseudomonas aeruginosa, Staph aureas, Candida
Why are burns ideal sites for bacteria? excellent nutrients (serum and debris), poor circulation (inhibits immune response, no oxygen
What has resulted in a decline in burn sepsis on the past 30 years? burn wound excision and grafting
Upper airway damage is more likely with (water soluble or lipid soluble gases)? Water soluble gases (lipid soluble does deeper airways producing pneumonitis)
What causes hypertrophic scarring after burn injury? excess neuropeptide released from damaged nerve endings (substance P)
Which thickness burns shows white, charred and anesthetic? Full
What can prolonged exposure to elevated ambient temperatures result in? heat cramps, heat exhaustion, heat stroke
In heat stroke, what is the underlying mechanism? marked generalized vasodilation with peripheral pooling of blood and decreased effective circulating blood vloume
Why can necrosis of the muscle (rhabdomyolysis) occur during heat stroke? nitrosylation of ryanodine receptor type 1 (RYR1)
mutations in RYR1 can cause this? malignant hyperthermia (rise in core body temp in response to common anesthetics)
What occurs at a body temperature of 90F? LOC, bradycardia and atrial fibrillation
What is the direct effect of hypothermia? physical disruption of cells caused by high salt concentration due to crystallization of inte-extracellular water
What are the effects of slowly developing chilling of the body? vasoconstriction and increased vascular permeability (edema and hypoxia)
What two types of injuries are caused by electricity? burns and conduction disruption (v-fib, respiratory center failure)
Which type of electricity is more likely to produce paralysis of the medullary center and extensive burns (large current flows or small current flows)? Large current flows
What does AC current induce? tetanic muscle spasms (you will hold the cord for a longer period of time)
What are the three types of radiation units? Curie (amount emitted from the source), Gray (amount absorbed), Sievert (biologic effect)
What are the main determinants of biologic effects of ionizing radiation? rate of delivery (fractionated allows cells to repair); Field Size ; Cell prol. (rapidly dividing cells are more effected); Oxygen effects/hypoxia (poorly vasc. tissues less sensitive to damage); Vascular damage (late onset narrowing and occ. of vessels)
What is the most important mechanism of DNA damage by ionizing radiation? production of reactive oxygen species from the radiolysis of water (center of tumors poorly vascularized are less sensitive to radiation therapy)
What are some histologgical findings of tissue exposed to ionizing radiation? cellular pleomorphism, giant cell formation, conformational changes in the nucleus, abnormal mitotic figures, vascular changes and interstitial fibrosis, Atrophy and fibrosis occur in many tissues late
What can happen within hours of exposure to very high levels of radiation and large exposure fields? lymphopenia, shrinkage of lymph nodes and spleen
What are some effects on the lymphoid and hematopoetic systems due to radiation? lymphopenia, aplastic anemia (at high doses), anemia, granulocytopenia, thrombocytopenia
What is a common consequence of radiation therapy for cancer and occurs weeks or months after irradiation, due to replacement of dead parenchymal cells by connective tissue? fibrosis
What is the most serious type of DNA damage caused by radiation? double stranded DNA breaks
What are the two mechanisms for repair of DSB (double stranded breaks)? homologous recombination and nonhomologous end-joining(NHEJ can induce mutations and is more common pathway of repair)
What type of cancer are uranium miners more likely to get, due to their exposure to pollonium 214 and 218 (radon daughters)? Lung carcinomas
What is the difference between primary and secondary malnutrition? primary
What BMI is considered malnutrition? less than 16 kg/m2
What are the two differentially regulated protein compartments in the body? somatic (in skeletal muscles) and visceral (organs such as the liver)
Which protein compartments are affected more by marasmus and kwashiokor respectively? marasmus
Serum albumin levels in marasumus are (increased, normal, reduced)? normal or slightly reduced (less effect on visceral)
Levels of cortisol in a patient with marasmus is excpeected to be (high, low)? High (low leptin stimulates the HPA axis to secrete cortisol to stimulate lipolysis)
What physical features can be seen in patients with marasmus? apparently large head and emaciated extremities
T/F immune deficiency , particularly T-cell mediated immunity is seen in marasmus? TRUE;
This disease occurs when protein deprivation is greater than the reduction in total calories? Kwashiokor
What are some conditions which may lead to kwashikor? carbohydrate exclusive diets; protein-losing enteropothies, nephrotic syndrome, Burns
Hypoalbunemia and resulting generalized and dependent edema is seen with (marasmus or kwashikor)? Kwashiokor (visceral protein compartment is affected)
These patients often do not look starved, hair color changes, and "flaky paint" appearance to their skin (marasmus or kwashikor)? Kwashiokor
Fatty liver, caused by reduced synthesis of carrier protein components of lipoproteins are seen in (marasmus or kwashikor)? Kwashiokor
An elderly nursing home patient is evaluated, he presents with atrophy to both quadriceps and deltoid muscles, and has edema in both ankles. He is currently fighting an infection. What could be the underlying problem? PEM (protein energy malnutrition)
What occurs in the mucosa of the small bowel in Kwashikor? decreased mitotic index, mucosal atrophy and loss of villi and microvilli, disaccharidase deficiency
Hypoplastic bone marrow and anemia are present in (kwashikor, marasmus, both)? Both
Infants born to mothers of PEM show what changes in the brain? cerebral atrophy, decreased neurons, impaired myelinization
What is PEM known as in patients with cancer and AIDS? cachexia
What is the primary cause of mortality in cachexia? atrophy of the respiratory muscles and diaphragm
What are two cachetic agents produced by tumors? PIF (proteolysis inducing factor) and LMF (lipid mobilizing factor)
How does PIF and proinflammatory cytokines induced by LMF result in skeletal muscle breakdown? NF-kB activation of the ubiquitin proteosome pathway leadign to degradation of the myosin heavy chain
What are the two muscle ubiqutin ligases produced through PIF and pro-inflammatory cytokine activation of NF-kB? MuRF-1 and MAFBx
This is typically a diagnostic feature of anorexia in young women? ammenorrhea
Decreased thyroid release secondary to anorexia produce these symptoms? cold intolerance, bradycardia, constipation
Hypokalemia, secondary to anorexia AND bulemia can increase the susceptibility to what? cardiac arrythmia and sudden death
Decreased levels of GnRH are typically seen in (anorexia nervosa, bulimia, both)? Anorexia nervosa
What are the major medical complications of vomiting due to bulimia? hypokalemia; pulmonary aspiration; esophageal and gastric cardiac rupture
What vitamins can be syntehsized endogenously? D, K, niacin
Fat absorbtion problems will affect which vitamins? ADEK
Retinol and B-carotene are absorbed where? And stored where? intestine, liver (B-carotene is convereted to retinol in the intestine)….VITAMIN A
Which cells store 90% of the bodies vitamin A? Ito cells in the liver
What are the main effects of Vitamin A? vision, cell growth and differentiation, metabolism, immunity
What happens to mucosal epithelium under a state of Vitamin A deprivation? squamous metaplasia into a keratinizing epithelium
How does vitamin A play a role in metabolism? RXR (retinoic X receptor) can forma heterodimer with metabolic nuclear receptors (i.e PPAR, regultor of fatty acid oxidation, adipogenesis)
This nuclear receptor forms a heterodimer with RXR and regulates fatty acid oxidation, adipogenesis, and lipoprotein metabolism? PPAR (peroxisome proliferator-activates receptors)
How can infections reduce the bioavailability of Vitamin A? reduced liver production of retinol binding protein and decreased circulating vitamin A
What are retinoids clinically used to treat? skin disorders and acute promyeloblastic leukemia
How can retinoids treat acute promyeloblastic leukemia? a fusion gene encodes an abnormal RAR (retinoic acid receptor) which blocks differentiation; large doses of ALL-TRANS retinoic acid overcomes this block and causes differentiation of the tumor cells which eventually die by apoptosis
What changes in vision are seen with Vitamin A defieciency? night blindness; xerophthalmia (dry); Bitot spots; keratomalacia; blindness
What are mucosal changes and clinical significance in Vitamin A deficiency? squamous metaplasia, increased pulmonary infections (destruction of mucociliary epithelium); kidney stones
A fisherman comes back from sea and is admitteed to the hospital with headache, dizziness, vomiting, stupor, and blurred vision. He tells of a "giant catch" at sea which everyone ate, even the LIVER. What happened? Vitamin A toxicity
T/F retinoic acid stimulates osteoclast activity? TRUE; high risk of fractures with chronic Vitamin A toxicity
Vitamin D is required to prevent these diseases? rickets, osteomalacia and hypocalcemic tetany
What is the main source of Vitamin D? endogenous conversion of 7-dehydrocholesterol via sunlight
Where does conversion of 25-OH-D into 1,25 hydroxycholecalciferol occur? kidney
Increasing PTH increase the activity of this kidney enzyme important for Vitamin D synthesis? 1a-hydroxylase
hypophosphatemia (increases or decreases 1a-hydroxylase)? Increases (increased 1,25 dihydroxyvitamin D)
What effects do vitamin D have on calcium and phosphurus homeostasis? increase intestinal absorption of calcium; increase reabsorption of calcium in kidney; increased expression of RANKL on osteoblasts (binds RANK on preosteoclasts inducing differentiation of osteoclasts)
How does Vitamin D contribute to the mineralization of osteoid matrix? stimulates osteoblasts to produce osteocalcin (a calcium binding protein) involved in deposition of calcium in bone development
What is the mechanism of decreased mineralization of bone during vitamin D deficiency? hypophosphatemia persistence while calcium levels are normal (calcium is provided by resorption of bone, but phosphate is lost continuosly and due to decreased Vitamin D, cannot be absorbed by the intestines)
What are phosphatonins? these are produced by bone (fibroblast growth factor 23) and block absorption of phosphate in the intestine, block phosphate reabsorption in the kidney.
These are some effects seen in rickets? craniotabes, frontal bossing, squared appearance of the head, rachitic rosary, pigeon breast deformity, lumbar lordosis and bowing of the legs
inadequately mineralized bone with excess of persistent osteoid is seen in this disease of adults; it can cause bones to be weak and vulnerable to fractures? osteomalacia
Production of 1,25 dihydroxyvitamin D in macrophages due to the induction of the vitamin D receptor and CYP27B results in the synthesis of this anti-microbial peptide? cathelicidin (active against mycobacterium tuberculosis)
which cancers are associated with vitamin D defieicney? colon, prostate, breast
Which vitamin is responsible for activation of lysyl and prolyl hydroxylases from inactive precursors, providing hydroxylation of procollagen? Vitamin C
What are the direct and indirect effects of the antioxidant properties of Vitamin C? directly scavenges free radicals and indirectly regenerates the antioxidant form of Vitamin E
Bleeding in gums, skin, as well as jointsl inadequate synthesis of osteoid, impaired wound healing, WHAT vitamin defieciency? Vitamin C
Spinocerebellar degeneration in deficiency, this vitamin is a major antioxidant? Vitamin E
Bleeding diathesis in deficiency of this vitamin; it also is involved in carboxylation of procoagulants 2,7,9,10,C,S? Vitamin K
Dry and wet beri beri, wernicke korsakoff? thiamine B1
Ariboflavinosis, cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization? riboflavin B2
Pellagra (dementia, dermatitis, diarrhea)? niacin
cheilosis, glossitis, dermatitis, peripheral neuropathy? B6
megaloblastic pernicious anemia? B12
scurvy? vitamin C
megaloblastic anemia, neural tube defects? folate
[Trace element deficiency?] Rash, anorexia and diarrhea, growth retardation, depressed mental functioning, depressed wound healing, impaired night vision, infertility Zinc
[Trace element deficiency?] hypochromic, microcytic anemia iron
[Trace element deficiency?] goiter and hypothyroidism iodine
[Trace element deficiency?] muscle weakness, neurological defects, abnormal collagen cross-linking copper
[Trace element deficiency?] dental carries flouride
[Trace element deficiency?] myopathy, cardiomyopathy (keshan disease) selenium
What BMI classifies a person as obese? >30
Accumulation of fat where is associated with a much higher risk of disease? trunk (apples)
The afferent system involved in the regulation of energy recieves signals from where? Leptin (adipose), ghrelin (stomach, Insulin (pancreas), PYY (intestines)
Where in the brain is energy balance regulated? arcuate nucleus
What are the 1st order nuerons located in the brain? POMC and CART; NPY and AgRP
Which 1st order neurons in the arcuate nucleus enhance energy expenditure, which ones enhance food intake? POMC and CART (increase energy expense); NPY/AgRP (enahnce food intake)
How do POMC and CART enhance energy expense? MSH production and icnreased expression of MC3/4R in second order neurons
How do NPY/AgRP enhance food intake? activation of Y1/5 in second order neurons
What is derived from the OB gene and senses energy sufficiency? leptin (produced by fat cells)
Leptin increases which first order neurons in the arcuate nucleus of the hypothalamus? POMC/CART
What can a mutation in MCR4 (melanocortin receptor 4) result in ? early onset obesity
This protein produced by adipocytes directs fatty acids to muscle for their oxidation, increases insulin sensitivity and protects against metabolic syndrome? adiponectin
Increased levels of what liver produced protein can be found in obese patients due to high pro-inflammatory cytokines produced by adipose tissue? C-reactive protein
This is the only known gut hormone that INCREASES food intake? Ghrelin
Ghrelin stimulates which first order neurons in the hypothalamus? NPY/AgRP
Levels of PYY are depressed in persons with this syndrome (caused by imprinting and subsequent deletion), and may lead to the development of hyperphagia and obesity? Prader-Willi
PYY and Amylin stimulate what nuerons in the Hypothalamus? POMC/CART
How is weight gain linked to hypertension? excess insulin leads to retention of sodium and increase in blood volume, production of excess norepinephrine, and smooth muscle proliferation
What is pickwickian syndrome? hypoventilation syndrome, a constellation of respiratory abnormalities seen in the very obese (also see obstructive sleep apnea)
This disorder seen in obese patients is associated with apneic pauses during sleep, polycythemia, and eventual right-sided heart failure? Hypersomnolence
These are disorders associated with obesity? type 2 diabetes; metabolic syndrome; hypertension; hypertriglyceridemia; coronary disease; pickwickian; osteoarthritis
What are the cancers associated with obesity in men, and in women? esophagous, kidney, thyroid and colon [men] ; esophagus, kidney, endometrial, gallbladder [women]
What is the proposed theory for increased cancer risk in obese patients? hyperinsulinemia and insulin resistance (cell growth; IGF-1 which increases growth and VEGF); increase in estrogen and androgen production with sunsequent down-regulation of sex-hormone bindign globulin
A mutation of codon 249 of the p53 gene in hepatocellular carcinoma, what is the cause? aflatoxin
Nitrosamines and nitrosamides are endogenously produced from diet (preservatives and some vegetables) and are primarily associated with what cancers? gastric carcinomas
High animal fat intake and low fiber intake is associated with this cancer? colon cancer
Retinoids are effective agents in the therapy of what cancer? acute promyelocytic leukemia
Created by: lamsonma