Ch 9 Flashcards
(145 cards)
1
Q
From 1990 to 2010, which of the following decreased and which ones increased:
A. mortality due to HIV/AIDS
B. Mortality from infection, maternal, neonatal, and nutritional disorder
C. Noncommunicable diseases like cancer, CV disease, and diabetes
A
A and C increased.
B decreased.
2
Q
What is the single leading global cause of health loss (defined as morbidity and premature death)
A
Undernutrition
3
Q
What are the leading cause of death in developed countries?
A
Ischemic heart disease and cerebrovascular disease
4
Q
In postnatal period, about 50% of all deaths in children younger than 5 are attributed to only what three conditions?
A
- pneumonia
- diarrheal disease
- malaria
5
Q
Change in global climate is expected to have a serious negative impact on human health which includes:
A
- Cardiovascular, cerebrovascular, respiratory disease (made worse by heat waves and air pollution)
- Gastroenteritis, cholera, and other food borne and water borne infectious disease due to contamination and disruption of clean water
- Vector-borne infectious disease - related to increased temperature, crop failure, and more extreme weather variation
- Malnutrition - change in local climate
6
Q
In what two ways is xenobiotics metabolized?
A
- Phase I: reaction, chemicals undergo hydrolysis, oxidation or reduction which produces the Primary metabolite. Products of phase I reactions are often metabolized into water soluble compounds through phase II.
- Phase II: reactions which include glucoronidation, sulfation, methylation, conjugation and glutathione
7
Q
What is the most important catalyst of phase I reaction of metabolism of xenobiotics/drugs?
A
cytochrome p-450 enzyme system (CYP)
8
Q
P-450 system catalyzes reactions that either 1 xenobiotics, or less commonly, convert xenobiotics into 2
A
- detoxify
2. convert into active compounds that cause cellular injury
9
Q
What are some inducers of P450?
A
Environmental chemicals, drugs, smoking, alcohol, hormones
10
Q
What fasting or starvation decrease or increase CYP activity?
A
decrease
11
Q
Inducers of CYP do so by binding to nuclear receptor which then heterodimerize with 1 receptor to form a transcriptional activation complex that associates with promoter located in the _ 2_region of CYP gene.
A
- Retinoic X receptor (RXR)
2. 5’ flanking region
12
Q
Which 6 pollutants does the US Environmental Protection Agency monitors and sets allowable upper limits?
A
- Sulfur dioxide
- Carbon monoxide
- ozone
- nitrogen dioxide
- lead
- particulate matter
Collectively these make up smog in air.
13
Q
How is ozone created? and what role does it play in protecting the earth?
A
Ozone is produced by interaction of UV radiation and oxygen in the stratosphere and naturally accumulates int he zone layer 10 to 30 miles above earth’s surface. This layer protects early by absorbing the most dangerous UV radiation emitted by the sun.
14
Q
In the past 35 years, the stratospheric zone layer decreased in both thickness and extend to due to the widespread use of what gases as found in air conditioners and refrigerators and as aerosol propellents?
A
Chlorofluorocarbon gases
15
Q
In contrast to the “good” ozone in the stratosphere, what produces the ozone that accumulates in the lower atmosphere (ground level ozone)? How does it cause harm to human?
A
Gas formed by the reaction of nitrogen oxides and volatile organic compounds in presence of light, like industrial emissions and motor vehicle exhaust. Ozone toxicity is in large part mediated by production of free radicals, which injure epithelial cells along the respiratory tract and type I alveolar cells, and cause the release of inflammatory mediators.
16
Q
What sized particulate matter (aka soot) is the most harmful for human?
A
Ultrafine particles less than 10um in diameter cuz it can pass through the filters in the nose and get into the lungs uninterrupted and cause inflammation in the alveoli
17
Q
What kind of environment might one encounter carbon monoxide? What are signs and symptoms of carbon monoxide poisoning.
A
Chronic poisoning may occur in people who work in tunnels, underground garage, in highway toll booths with high exposures to automobile fumes.
Acute exposure, small closed garage, gasoline-powered generators
Acute poisoning: induce CNS depression. Hemoglobin saturation decreases drastically causing hypoxia. Can lead to unconsciousness and death when saturation drops to 60-70%.
In light skinned people, cherry-red color of the skin and mucous membrane (due to high levels of carboxyhemolgobin)
18
Q
The slowly developing hypoxia as seen with CO poisoning evoke widespread ischemic changes in the CNS but particularly marked in what part of the brain?
A
Basal ganglia and lenticular nuclei.
19
Q
Checking blood levels of what compound is a way to diagnose carbon monoxide poisoning?
A
carboxyhemoglobin level
20
Q
What are some examples of indoor air pollutants that can cause diseases?
A
- cigarette smokes
- bioaerosols (microbiologic agents that can cause disease like Legionnaires disease viral pneumonia)
- Radon present in soil and in homes that can cause lung cancer
- polycyclic hydrocarbons (from cooking oil)
- formaldehyde
21
Q
What is the mechanism via which lead poisoning cause disease?
A
Lead is readily absorbed metal that binds to sulfhydryl groups in proteins and interferes with calcium metabolism, effects that leads to hematologic, skeletal, neurologic, GI, and renal toxicities.
22
Q
what are some environmental sources of lead exposure risks?
A
- Mining
- foundries,
- batteries
- old lead containing peeling paint
- spray paint
23
Q
beyond what level does the CDC recomment to limit lead exposure?
A
5ug/dL
24
Q
At what level of blood lead content is treatment mandated?
A
45ug/dL
25
What are some signs of low-level lead poisoning in youngsters?
subtle deficits in intellectual capacity, behavioral problems like hyperactivity, poor organizational skills.
26
With lead poisoning what disturbances are seen in kids vs adults?
In kids you'll see CND disturbances.
| In adults: peripheral neuropathies predominate
27
Where are lead lines found? epiphyses in chidlren
Lead interfere with normal remodeling of cartilage and primary bone trabeculae in epiphyses in children. this causes bone density detected as radio dense lead lines.
Also seen in gum due to hypermigmentation
28
what effect does lead exposure have on bones?
inhibits healing of fractures by increasing chondrogenesis and delay cartilage mineralization. It also interferes with normal remodeling of cartilage and primary bone trabculae in epiphyses in kids
29
what effect does lead have on heme biosynthesis?
lead inhibits the activity of two enzymes involved in heme synthesis, delta-aminolevulinic acid dehydratase and ferrochelatase.
30
which type of anemia is associated with lead poisoning?
microcytic hypochromic anemia stemming from suppression of hemoglobin synthesis.
31
how is lead poisoning diagnosed?
- suspected on the basis of neurologic and behavior changes in kids and detection of elevated blood levels of lead and free red cell protoprophyrin
32
what major anatomic targets does lead poisoning involve?
- bone marrow and blood
- nervous system
- GI
- kidneys
33
At around what blood level of lead are you likely to see decreased hemoglobin synthesis?
about 40um/mL
34
At around what blood levels of lead are you likely to see decreased nerve conduction velocity, increased level of erythrocyte protoporphyrin, altered vitamin D metabolism and calcium homeostasis?
Aroudn 10-20 um/mL
35
What the biochemistry of how mercury poisoning causes damage?
Like lead, mercury binds to sulfhydryl groups in certain proteins with affinity, leading to damage in CNS and kidney.
36
What are some sources of mercury?
contaminated fish (methyl mercury) and mercury vapors released from metallic mercury in dental amalgam, a possible occupational hazard for dental worker
37
What are some signs and symptoms of mercury poisoning?
- tremor, gingivitis, bizarre behavior like Mad Hatter in Alice in wonderland.
- Developing brain is extremely sensitive to mercury. it causes disturbing neuromotor cognitive, and behavioral functions.
38
What intracellular antioxidant acts as the main protective mechanism against mercury-induced CNS and kidney damage? How?
Glutathione by acting as sulfhydryl donor
39
What clinical signs are associated with Minamata disease?
cerebral palsy, deafness, blindness, mental retardation, and other major CNS defects in children exposed to methyl mercury in utero.
40
What is the main mode of how arsenic exposure cause disease?
Arsenic salt interfere with several aspect of cellular metabolism, leading to toxicities that are most prominent in the GI tract, nervous system, skin, and heart.
41
Most of the diseases associated with arsenic exposure is due to which form of arsenic?
Trivalent compounds, arsenic trioxide, sodium arsenite, arsenic trichloride
42
If large quantities of arsenic was ingested, what toxicities are you likely to see and what is the underlying cause of those toxicities?
- Acute GI toxicities
-CV toxicities
-CNS toxicities
These toxicities are partly due to interference of mitochondria oxidative phosphorylation since trivalent arsenic can replace the phosphates in ATP.
43
which metal is used as a frontline treatment for acute promylocytic leukemia?
arsenic trioxide
44
What neurological symptoms are associated with arsenic exposure and how soon are these signs apparent?
occurs within 2-8 weeks after exposure, consist of sensorimotor neuropathy that causes paresthesias, numbness and pain.
45
what skin abnormalities are associated with arsenic exposure?
Chronic exposure to arsenic causes skin changes consisting of hyperpigmentation and hyperkeratosis
46
What is one single greatest risk of arsenic exposure?
Increased risk for developing cancer particularly of lungs, bladder and skin. Arsenic induced skin tumors are different from sun exposed in that arsenic induced tumors appear on palms and soles
47
What organs are mainly affected by cadmium toxicity and what is the underlying mechanism?
Kidneys (renal tubular damage) and lungs (obstructive lung disease) through involvement of increased production of reactive oxygen species.
48
What is the most important source of cadmium exposure for the general public?
Food contaminated with cadmium.
49
Which metal uses the same transporter as zinc for uptake into cells.
cadmium. ZIP8 is the transporter
50
what effect does cadmium exposure have on skeletal system?
Calcium loss. --> osteomalacia and osteoprosis associated with renal disease. Itai-Itai (Japanese for ouch ouch)
51
Acute exposure to organic solvents like chloroform, carbon tetrachloride as seen in dry cleaning agents and paint removers, are associated with what acute symptoms?
- dizziness
- confusion
- leads to CNS depression and even coma
- Toxic to liver and kidney
52
Occupational exposure of rubber works to benzene and 1,3 butadiene increases the risk of what cancer?
Leukemia
53
Polycyclic hydrocarbons is among the most potent carcinogens and industrial exposures have been implicated in the development of what cancers?
- Lung and bladder cancers. (think
54
Dioxins and PCB causes skin disorders characterized by _
folliculitis and dermatisos known as chloracne that is characterized by acne, cyst formation, hyperpigmentation, hyperkeratosis, generally around face and behind ears.
55
Inhalation of coat dust, silica, asbestos and beryllium have all been implicated for what chronic condition?
nonneoplastic lung disease known as pneumoconioses
56
Exposure to what substance is known to increase risk of cancer for the person exposed and extends to the family members of those exposed?
asbestos
57
a person who works at factory that makes plastic products like pipes, wires, and cable coatings are at risk of exposure to what chemical and what cancer is it associated with?
Exposure to vinyl chloride used int he synthesis of polyvinyl resins. Leads to development of angiosarcoma of liver.
58
Bisphenol A (BPA) used in the synthesis of polycarbonate food and water containers and of epoxy resins that line almost all food bottles and cans, is known to cause what?
- BPA is a potential endocrine disruptor.
| - studies also shows elevated levels linked to heart disease in adult population
59
What compounds found in cigarettes is known to be the potent carcinogens directly involved in the development of lung cancers?
Polycyclic hydrocarbons and nitrosamines
60
what metabolites of alcohol is responsible for the acute affect of alcohol consumption and what cancer is associated with it?
Acetaldehyde. --> oral cancer
61
Some Asians have very low alcohol dehydrogenase activity due to what substitution?
Substitution of lysine for glutamine at residue 487, due to dominant negative effect of mutated ALDH2*2
62
How does alcohol consumption lead to lactic acidosis?
Alcohol oxidation by alcohol dehydrogenase causes reduction of NAD to NADPH. NAD is needed for conversion of lactate into pyruvate. Its deficiency is a main cause of accumulation of fat in the liver of alcohol. The increased NADPH/NAD ratio is what causes lactic acidosis.
63
What are some clinical signs of chronic alcoholism?
- Liver: fatty acid change, acoholic hepatisis, cirrhosis which is associated with HTN, and increased risk fo hepatocellular carcinoma
- GI: massive bleeding from gastritis, gastric ulcer, esophageal varices
- Thiamine deficiency --> peripheral neuropathies and Wernicke's Korsakoff syndrome; cerebral atorphy, cerebellar dengeration, optic neuropathy
- Alcoholic cardiomyopathy --> increased htx, decreased HDL --> increased coronary heart disease risk
64
What are some signs of fetal alcohol syndrome?
- Microcephaly, growth retardation, facial abnormalities
| - reduction in mental function as the child grows
65
A common adverse affect of antibiominocycline is
discoloration of skin
66
Women who are on menopausal hormone therapy are at increased risk of _
breast cancer, stroke, venous thromboembolism.
67
Oral contraceptive increases the risk of diseases?
- Cervical carcinomas in women who are infected with HPV.
- Thromboembolism
- Hepatic adenoma
68
What are some adverse affects of anabolic steroids intake?
- Stunts growth
- acne
- gynecomastia
- testicular atrophy in males
- growth of facial hair and menstrual changes in woman
- psychiatric disturbances and an increased risk of MI
- hepatic cholestasis in some people
69
50% of acute liver failure is due to acetaminophen. Explain how acetaminophen cause liver damage.
1. covalent binding to hepatic proteins which cause damage to cellular membranes and mitochondrial dysfunction
2. depletion of GSH making hepatocytes more susceptible to ROS injury
70
What are the acute symptoms of acetominophen toxicities?
- nausea, vomitting, diarrhea, sometimes shock.
| - jaundice may develop few days later.
71
Explain how overdose of acetylsalicylic acid cause damage.
Alkalosis as a consequence of stimulation of respiratory center in medulla. Followed by metabolic acidosis and accumulation of pyruvate and lactate caused by uncoupling of oxidative phosphorylation and inhibition of Krebs cycle.
- metabolic acidosis enhances formation of non-ionized forms of salicylates which diffuse to brain and produce nausea and sometimes coma
72
what are some signs and symptoms of chronic excess intake of aspirin.
- 3gm or more daily
- headaches, mental confusion, drowsiness, nausea, vomitting, diarrhea. CNS changes may progress to convulsion and coma
- Erosive gastritis --> overt or covert GI bleeding and lead to gastric ulceration
- Bleeding tendencies, petechial hemorrhages on skin, internal viscera and bleeding from gastric ulceration
- tubulointerstitial nephritis
73
What are the acute and chronic affects of cocaine abuse?
CV: sympathomimetic - facilitates neurotransmission in CNS where it blocks reuptake of dopamine, and at adrenergic nerve endings, where it blocks the reuptake of both E and NE while stimulating the presynaptic release of NE. Leads to: tachycardia, hypertension, peripheral vasoconstriction, induce myocardial ischemia by causing coronary artery vosoconstriction by enhancing platelet aggregation and thrombos formation. LETHAL arrhythmias by enhanced sympathetic activity of disrupting normal ion (K, Ca, Na) transport in Myocardium
CNS: hyperpyrexia and seizure
-Perforation of nasal septum, development of dilated cardiomyopathy
74
What are the CNS effect of heroin abuse?
Europhoria, halluciation, somnolence, sedation
75
Besides the CNS effect that most heroin addict take the drug for, it comes with some physical effects, name some
- Pharmacologic action of the agent-->damage to body tissue
- Reaction to cutting agents or contaminants
- hypersensitivity reaction to drug or its adulterants (quinine)
- disease contracted incident to the use of contaminated needle
76
What are common affects of heroin overdose pts present to with that can be fatal?
- Respiratory depression, arrhythmia and cardiac arrest and severe pulmonary edema
77
Explain the pulmonary injury caused by heroin.
- severe edema
- septic embolism from endocarditis
lung abscess
-opportunistic infection
-foreign-body granulomas from talc and other adulterants
78
What are the common sites that are infected in a chronic user of heroin?
Skin, subcutaneous tissues, heart valaves, liver, and lungs.
In heart: 10% have endocarditis with right-side heart valves involvement, particularly cuspid.
79
What are the telltale signs of heroin addiction?
Skin lesions: abscessses, cellulitis, ulceration due to subcutaneous
-scarring at injection sites, hyperpigmentaiton over commonly used veins and thrombosed veins usually sequlae of repeated intravenous inoculation.
80
How does ampahtamine affect the CNS?
- Acts by releasing dopamine in the brain which inhibits presynpatic neurotransmission at corticostriated space, slowing glutamate release .
- Produces feelings of euphoria followed by crash.
81
What are affects seen in long timer user of meth?
- violent behaviors, confusion, and psychotic features that include paranoia and hallucination.
82
Which street drug is associated with increase in serotonin release in CNS and as the drug wears off the increased release of serotonin is coupled with its ability to interfere with serotonin synthesis causing subsequent postuse drop in serotonin and also reduces the number of serotonergic axon terminals in the striatum and cortex and it may increase the peripheral effects of dopamine and adrenergic agents
MDMA aka ecstasy
83
Part of the reason why pot heads have excessive appetite and eat a lot after smoking is cuz of it's association with what endogenous system?
Cannabinoid system with CB1 and CB2 receptors which regulate hypothalamic-pituitary-adrenal axis and modulates the control of appetite, food intake, and energy balance as well as fertility and sexual behavior.
84
Burns over _% of body shifts body fluids into the interstitial compartments both in the burn site and systemically due to systemic inflammatory response syndrome leading to shock
20%
85
What are the greatest threat to life in severely burned victims?
- shock, sepsis, and respiratory insufficiency
86
Hypermetabolic state is associated with what mechanical trauma?
Thermal burns. It is estimated that when more than 40% of the body surface is burned, resting metabolic rate may double
87
In burn victims, the most common offender of infection is what bacteria?
Pseudomonas aeruginosa, an opportunistic gram positive bacteria
88
What is the difference between Heat cramps, heat exhaustion, and heat stroke? which one is most severe?
Heat cramps = loss of electrolytes via sweating resulting in voluntary muscle cramps. associated with vigorous exercise
Heat exhaustion = most common hyperthermic syndrome. Results from failure of the CV system to compensate for hypovolemia caused by dehydration
Heat stroke = associated with high ambient temperature high humidity, and exertion. elderly with CV disease are at greatest risk. Thermoregulatory mechanisms fail, sweating ceases, and core body temp rises leading to multiorgan dysfunction that can be rapidly fatal.
89
Explain the pathophysiology of heat stroke, particularly the effect seen on skeletal muscles.
Thermoregulatory mechanism fail, sweating ceases, and core body temp rises. There's marked generalized vasodilation with peripheral pooling of blood and decreased effective circulating blood volume. Hyperkalemia, tachycardia, arrhythmia and other systemic effects are common. Sustained contraction of skeletal muscle that can exacerbate the hyperthermia and lead to muscle necrosis resulting from nitrosylation of ryandodine receptor 1. RYR1 regulates Ca release from sarcoplasm. Heat stroke deranges RYR1 function and allows Ca to leak into cytoplasm where it stimulates muscle contraction and heat production.
90
Some patients with malignant hyperthermia have a mutation in what gene?
RYR1 gene which encodes RYR1 protein.
91
What are the two mechanism via which hypothermia cause injury?
1. Direct effect - mediated b physical disruption within cells by high salt concentration caused by crystallization of intra and extracellular water.
2. Indirect effect stems from circulatory changes. Slow chilling may induce vasoconstriction and increase vascular permeability, leading to edema and hypoxia, "trench foot" changes.
92
At body temp below 90, what physiological changes are seen?
loss of consciousness, followed by bradycardia and afib.
93
Electrical shock causes injury in what two ways?
1. burns
2. venticular fibrillation or cardiac and respiratory center failure, resulting from disruption of normal electrical impulses
94
What are the main sources of ionizing radiation?
X-rays, gamma rays, high-energy neutrons, alpha particles, beta particles
95
What is the major way by which ionizing radiation damage DNA
The production of ROS from reactions with free radical generated by radiolysis of water. Poorly vascularized tissues with low oxygenation is pretty resistant to this type of damage.
96
What cytoplasmic changes are associated with radiant energy affecting cells?
- cytoplasmic swelling,
- mitochondrial distortion
- degeneration of ER
- constellation of cellular pleomrophism, giant-cell formation,
- abnormal mitotic figures
97
Explain the affect on vasculature with radiant energy
Damage to endothelial cells may cause narrowing or occlusion of blood vessels leading to impaired healing, fibrosis, and chronic ischemic atrophy.
98
Irradiation With high dose levels and high exposure fields, what damage is expected within hours?
severe lymphopenia. Kills lymphocytes directly in circulation and in tissues (nodes, spleen, thymus, gut)
99
With total body irradiation , what are likely to see within 1 week? Within 2-3 weeks?
Within a week you'll see Thrombocytopneia.
| within 1-2 weeks you'll see neutropenia. WIthin 2-3 weeks you'll see anemia.
100
With radiation of 10-20Sv, how soon are you likely to see GI issues?
5-14 days. diarrhea, fever, electrolye imbalance, vomitting.
101
With radiation of 50 Sv or greater, how soon are you likely to see CSN issues?
Within 1-4 hours. Ataxia, coma, convulsion, vomitting
102
What range is considered normal BMI?
18.5-25
103
Below what % is a child considered malnourished?
80%
104
What defines marasmus and what are some clinical signs?
- when weight falls to 60% of normal for sex, height, and age.
A marasmic child suffers growth retardation, loos of muscle resulting from catabolism and depletion of somatic protein compartment.
- Extremities are emaciated
- low production of leptin
-Anemia, vitamin deficiencies
-immune deficiency (mainly T-cells
105
What distinguishes marasmus from kwashiorkor?
In kwashiorkor, it's protein deprivation is more severe than the deficit of total calories. This is more common in kids who were weaned too early and then fed exclusively carbohydrate diet as seen in African children, and impoverished countries of Southeast Asia.
- Depletion of visceral protein compartment and resultant hypoalbuminemia gives rise to generalized or dependent edema.
- Compared to marasmus, in kwashiorkor, there's releative sparing of subcutaneous fat and muscle mass.
- Kids with Kashiorkor have skin lesion, alternating zones of hyper and hypopigmentations, giving flaky paint apearance.
- Enlarged liver (due to reduced synthesis of carrier protein component of lipoproteins
106
What signs and symptoms is cachexia associated with?
- Extreme weight loss
- fatigue
- muscle atrophy
- anemia,
- anorexia
- edema
107
What are the mediators involved in cachexia?
1. proteolysis-inducing factor which is a glycosylated polypeptide excreted in urine of weight-losing patients with pancreatic, breast, colon, and other cancers
2. Lipid-mobilizing factor which increases fatty acid oxidation, and proinflammatory cytokines such as TNF and IL-6
Downstream pathway involves NF-kB-induced activation of ubiquitin proteasome pathway
108
What are the clinical findings of anorexia nervosa?
- generally similar to severe PEM.
- endocrine system affects are prominent. --> amenorrhea due to decreased GRH and FSH and LH. this is so common that it is regarded as the diagnostic feature.
- decreased thyroid hormone release --> told intolerance, bradycardia, constipation, skin and hair changes
- decreased bone density, mimics postmenopausal acceleration of osteoporosis.
- increased risk of cardiac arrhythmia and sudden death due to hypokalemmia
109
What are some characteristics of Bulimia?
- binge eating and then throwing up
- amenorrhea occurs in less than 50% of pts cuz gondadotropin levels remain near normal.
- major complication is due to chronic vomiting laxative and diuretics use.
- electrolyte imbalance (hypokalemia), pulmonary aspiration, esophageal and gastric rupture
110
what is the normal function of vitamin A?
Maintenance of normal vision, regulation of cell growth and differentiation, and regulation of lipid metabolism.
111
Where are the majority of body's vitamin A stored?
Liver, mainly in the perisinusoidal stellate (Ito) cells.
112
What receptors does Vitamin A use to get into the liver?
apolipoprotein E receptor
113
With vitamin A deficiency what changes are you likely to see on mucus-secreting epithelium?
squamous metaplasia differentiating into a keratinizing epithelium by acting the retinoic acid receptor (RAR) and cause the release of corepresssor and obligatory formation of heterodimers with another retinoid receptor retinoic X receptor RXR and together (RAR/RXR) bind to retinoic acid response element in the regulatory region of genes that encode receptors for growth factors, tumor suppressor genes and secreted protein
114
Which derivative of vitamin A has the highest affinity for RAR and is involved in cell growth and differentiation
All-trans-retinoic-acid
115
which form of retinoic acid defines vitamin A's role in drug metabolism and activates the RXR?
9-cis retinoic acid
116
What function of vitamin A allows it to play a role in host resistance to infections?
Related to the maintenance and restoration of integrity of the epithelium of the gut.
117
What are signs of Vitamin A deficiency?
- Impaired vision (particularly in reduced light (night-blindness)
- epithelial metaplasia and keratinization
- xerophthalmia --> Bitot spot -- keratomalacia --> blindness
- In the lung, squamous metaplasia leads to frequent infections
- In kidney and bladder -- desquamation of keratin debris predispose to stones
118
what are some acute and chronic signs of Vitamin A toxicity?
Acute: headahce, dizziness, vomiting, stupor, blurred vision
Chronic: weight loss, anorexia, nausea, vomiting, bone and joint pain cuz retinoic acid stimulates osteoclast activity. Congenital defects
119
What are the major function of Vitamin D?
- maintenance of adequate plasma levels of Ca and phos
- support metabolic funcitons
- bone mineralization
- neuromuscular transmission
- prevents ricks, osteomalacia, hypocalcemic tetany
120
Explain how 1,25 dihydroxyvitamin D is regulated by the kidney
Three main mechanisms:
1. Hypocalemia stimulates ecretion of PTH which augments conversion of 25-OH-D to 1,25 dihydroxyvitamin D via 1a-hydroxylase
2. hypophosphatemia directly activates 1a-hydroxylase
3. Through a feedback mechanism
121
Which form of vitamin D is the active form and binds to it's nuclear receptor?
1,25 dihydroxyvitamin D
122
What effect does vitamin D have on calcium and phosphorus homeostasis?
1. stimulation of intestinal calcium absorption via activating transcription of TRPV6 which encodes critical calcium transport channel
2. stimulation of Calcium reabsorption in the kidney via expression of TRPV5
3. Interaction with PTH in regulation of blood calcium. vit D and PTH enhance RANKL (receptor activator of NF-kB ligand) on osteoblasts. RANKL binds to its receptor (RANK) on preosteoclasts
4. Mineralization of bone by stimulating osteoblast to synthesize calcium binding protein osteocalcin
123
When hypocalcemia occurs due to vitamin D deficiency explain how blood calcium level is restored.
PTH production is elevated and it works to:
1. activate renal 1a-hydroxylase increasing the amount of active vit D and calcium absorption
2. increase resorption of calcium from bone by osteoclast
3. decrease renal calcium excretion
4. increased renal excretion of phosphate
124
Below what level is one considered vitamin D deficient?
below 20ng/mL
125
Vitamin D deficiency in both rickets and osteomalacia results in an excess of _
unmineralized matrix.
126
With vitamin D deficiency leading to rickets, explain the sequence of events as signs of rickets.
- overgrowth of epiphyseal cartilage due to inadequate provisional calcification and failure of cartilage cells to mature and disintegrate
persistence of distorted, irregular masses of cartilage,
- deposition of osteoid matrix on inadequately mineralized cartilaginous remnants
-disruption of the orderly replacement of cartilage
-abnormal overgrowth of capillaries and fibroblasts leading to inadequately mineralized, weak, poorly formed bone
-deformation of skeleton
127
What structural morphological changes are seen in kids with rickets?
- craniotabes
- frontal bossing
- squared appearance to the head
- rachitic rosary
- pigeon breast deformity
- lumbar lordosis
- bowing of legs
128
In kids, hypervitaminosis D may take the form of _
Metastaic calcifications of soft tissues such as kidney; adults it causes bone pain and hypercalcemia.
129
Scurvy is charactered by_
vitamin C deficiency leading to bone disease in growing children, and by hemorrhages and healing defects in both children and adults.
130
What is the function of vitamin C?
Has a role in many biosynthetic pathway by accelerating hydroxylation and amidation reactions. the best established function of vitamin C is the activation of prolyl and lysyl hydroxylase from inactive precursors providing for hydroyxlation of procollagen.
131
What's the reason for hemorrhages as seen in scurvy?
Inadequately hydroxylated procollagen cannot acquire a stable helical configuration cuz they're inadequately cross-linked, lack tensile strength and are prone to degradation. Collagen has the highest content of hydroxyproline and found particularly in blood vessel accounting for predispoition to hemorrhages in scuvy.
132
Neurohumoral mechanism that regulate energy balance can be subdivided into three components, namely_
1. peripheral or afferent systems which generate signals from various sites. they include: leptin, ghrelin, peptide Y, insulin
2. Arcuate nucleus in the hypothalamus includes POMC, and NPY and AgRUP
3. Effector system: anabolic or catabolic
133
What is the role of POMC/CART pathway?
enhance energy expenditure and weight loss through production of MSH, and activation of melanocortin receptors 3 and 4 (MCR3 and 4). these then produce factors like THS, CRH which increase basal metabolic rate and anabolic metabolism and thus favors weight loss
134
What is the role of NPY/AgRP
promotes food intake and weight gain via Y1/5 receptors and second order neurons release MCH and orexin which stimulate appetite
135
what is leptin and what is it's role?
Leptin, gene product of ob gene in fat cells that binds to OB-R receptor. It is secreted when fat stores are sufficient and in the hypothalamus stimulates POMC/CART which produce anorexigenic neuropeptides (MSH) and inhibits NPY/AgRP that are orexigenic
136
Loss of function of leptin
develops early onset of obesity
137
In WAGR syndrome, what is responsible for obesity that's seen in these patients?
Haploinsufficiency of brain derived neurotrophic factor (BDNF) which is an important component of signaling downstream MC4R in hypothalamus. Obese peps have elevated levels of BDNF
138
OB-R receptor uses what signaling pathway?
JAK/STAT pathway
139
What is the role of adiponectin?
It's considered the fat burning molecule, the guardian angel against obesity. Simulates fatty acid oxidation in muscle causing decrease in fat mass.
140
Would you expect adiponectin levels to be high or low in obese people?
Lower in obese people. in normal people it's blood levels is like 1000 times higher than other neuropeptide hormones
141
Where is ghrelin produced and what is its function?
Produced in stomach. Acts by binding to GF secretagogue receptor and works by stimulating NPY/AgRP to increase food intake. In obese people postprandial suppression of ghrelin is attenuated and contributes to overeating
142
What is the role of PYY?
Both PYY and amylin act centrally by sitmulating POMC/CART neurons in the hypothalamus and cause decrease in food intake
143
How does increased adipocyte create a chronic proinflammatory state?/
Adipocyte produces cytokines like TNF, IL6, IL1, IL18, chemokines and steroid hormones and high levels of circulating CRP
144
Explain a way that obesity can drive development of cancer.
Obesity causes insulin resistance and elevated insulin levels inhibits production of IGF-binding proteins (IFBP1 and2, thereby causing a rise in levels of free insulin like growth factor 1 (IFG1) which is mitogenic and can stimulate Ras and PI3k/ART pathways to promote growth of both normal and neoplastic cells
145
How is aflatoxin involved in cancer development
- involved in hepatocellular carcinoma.
| - cooperates with HepB virus. exposure to aflatoxin cause specific mutation in TP53;
