Ch 9&10 Flashcards
(49 cards)
Xenobiotics are EXOGENOUS chemicals in the environment in air, water, food, and soil, that can be absorbed into the body
^** Can include environmental chemicals, drugs, smoking, alcohol, or hormones
Xenobiotics, along with drugs and solvents can be transported in the blood (lipophilic) and therefore either act at the site of injury or at a distant site
Once distributed to the tissues, the agents can either be stored, directly toxic, or metabolized to ____ water soluble products that can be excreted, or active toxic metabolites
Metabolizing chemical agents like xenobiotics occurs in 2 phases, phase 1 (hydrolysis or reduction or oxidation) leading to a primary metabolite and Phase 2 (gluuronidation, sulfation, methylation, or conjugation) leading to a secondary water solube metabolite that is excreted (detoxified)
^** The most important catalyst of phase 1 reactions is the ____ enzyme system that can convert xenobiotics into toxic or nontoxic metabolites
Inactive
Cytochrome P-450 (CYP)
Chronic CO poisoning can occur in those who work in tunnels, underground garages, or highway toll booths and acute CO poisoning can be from a closed garage or after a mining fire
Since CO has a 200x greater affinity for hemoglobin than oxygen does for hemoglobin, the CO binds to Hg and causes less O2 transport and systemic hypoxia develops
CO kills by inducing ___ depression, so chronic patients have slowly developing ischemic changes in the CNS (mainly in the basal ganglia and lenticular nuclei)
*****Acute patients are characterized by a ____ color of the skin and mucous membranes
CNS
Cherry red
Metals that are toxic include Lead, Mercury, Arsenic, and Cadmium
1) Lead
** Lead binds to sulfhydryl groups in proteins and interferes with ___ metabolism leading to hematologic, skeletal, neurological, GI, and renal toxicities
Blood and marrow changes (such as radiodense deposits in epiphyses of children) occur rapidly and for the blood component,if one were to see ___cytic, ___chromic anemia, accompanied by mild hemolysis THINK LEAD POISONING** and this is due to the fact that it inhibits enzymes involved in heme synthesis (no hemoglobin is made)
Also ____ can be detected (RBC precursors with iron-laden mitochondria) and a punctate ____ stippling of the red cells*****
In children, since they have a higher GI absorption and more permeable BBB, ___ damage often occurs leading to decreased IQ, learning disabilities, blindness, etc
In adults, CNS is also involved but MAINLY it is PNS involvement like a peripheral _____ of neuropathy leading to a wrist drop and foot drop
Finally, the GI and kidneys are also commonly affected
2) Mercury
** The major source of mercury is contaminated fish and the developing ___ is sensitive to methyl mercury and this causes accumulation in the CNS and damage to the kidney
If a fetus is exposed to high levels of mercury in utero, it can lead to ____ disease characterized by cerebral palsy, deafness, and blindness
3) Arsenic
** Found in the soil and water along with some wood preservatives and herbicides
Causes toxic effects in the GI tract, CNS, and CV systems and long term exposure can lead to skin lesions and carcinomas typically found on the palms and soles
4) Cadmium
Normal exposure occurs from nickel-cadmium batteries and chemical fertilizers causing the food to become contaminated
*** The major organ system involved with excess cadmium is obstructive ___ diseases ** causes by necrosis of alveolar epithelial cells or retinal tubular damage (kidney disease) that can lead to end-stage renal failure
1) Calcium
Microcytic, hypochromic
Ring sideroblasts, basophilic
Brain
Demyelination
2) Brain
Minamata disease
4) Lung
Liver angiosarcomas can be caused by ___
Male and female infertility is often due to mercury or lead
Cataracs often due to UV radiation
Fibrosis in the respiratory system often due to silica or asbestos
Lung cancer often due to asbestos
Nasal cancer often due to wood dust
Chronic obstructive lung disease often due to ____
Heart diseases often due to carbon monoxide
Vinyl chloride
Cadmium
Agents in smoke have a direct irritant effect on the _____ mucosa causing inflammation and increased mucous production (bronchitis) along with increased leukocyte recruitment causing elastase to be produced and therefore ____
Remember, phase 1 enzymes, mainly ____ facilitates excretion of toxic chemicals (along with phase 2 enzymes) however, some of the byproducts that are created are electorphilic and can cause DNA adducts leading to gene mutations in oncogenes or tumor suppressor genes if accumulated
^** Nitrosamines (NNK) and Polycyclic hydrocarbons such as ____ DNA adducts are directly involved in lung cancer development (these are carcinogens) and along with lung cancers, mouth and esophagus, pancreas, bladder, cervix, and bone marrow cancers can also arise
Non-malignant problems with smoking include most often those involved with the lungs (emphysema, chronic bronchitis, chronic obstructive pulmonary diseases along with its development of ____ and therefore MIs
Finally, smoking can also affect the developing fetus and lead to spontaneous abortions and preterm births causing intrauterine growth retardation
Also, smokeless tobacco is important for oral cancers
Tacehobronchial, emphysema
Benzo[a]pyrene
Atherosclerosis
Most of the ethanol in the blood is oxidized to ____ via 3 pathways include ADH (Alcohol dehydrogenase), the ___ system and Catalase and then acetaldehyde is transfered into the mitochondria where it is converted via ALDH (aldehyde dehydrogenase) to be utilized in the respiratory chain
Converting alcohol (ethanol) to acetaldehyde via ADH and then acetic acid via ALDH converts ____ to ____ and the increased NADH/NAD ratio leads to ____ (aka accumulation of fat in the liver) and ____ since NAD is needed for fatty acid oxidation in the liver and also needed for conversion of lactate into pyruvate
Also, when Ethanol is in high concentrations, it ___ the metabolism of other drugs (because remember, other drugs are detoxified by the CYP system as well) since the CYP2E1 enzymes are being used to convert ethanol to acetaldehyde in microsomes (in the SER)
Acetaldehyde, CYP (CYP2E1)
Steatosis, lactic acidosis
Inhibits
Acute alcoholism affects mainly the ____, but can also cause hepatic (steatosis) and gastric (acute gastritis or ulcerations) systems
Chronic alcoholism’s major effect is on the liver cause steatosis, alcoholic hepatitis, and cirrhosis (liver damage from scarring) leading to portal hypertension and increased risk for hepatocellular carcinomas
^** Chronic alcoholism also affects the stomach, and ALL other organ systems including GI tract (gastritis and gastric ulcer can cause bleeding), CV system (can cause alcoholic cardiomyopathies), fetal alcohol syndrome, ____ deficiency is often common (causing peripheral neuropathies or Wernicke-Korsakoff syndrome), and cancers (most commonly ____ is the main agent that causes oral cavity, laryngeal and esophageal cancers)
^** Realize that you have an increased risk for these cancers in those who smoke
CNS
Vitamin B1 (Thiamine), acetaldehyde
Oral contraceptives can protect against endometrial and ovarian cancers, but have an INCREASED RISK for _____ (venous thrombosis and pulmonary embolisms) due to the hypercoagulable state induced by elevated hepatic synthesis of coagulation factors, especially those with the factor V leiden mutation
^** Also OCs have an INCREASED RISK of a cancer called ____, especially in older women who have used them for a long time
Thromboembolism
Hepatic adenoma
The most commonly used painkiller in the world is Acetaminophen
Normally (95%), it undergoes detoxification via phase 2 enzymes;
However, sometimes (5%) it is metabolized via ____ enzymes to ___ and if this occurs, the NAPQ is normally conjugated with GSH to cause no toxicity
At HIGH levels of Acetaminophen however, unconjugated NAPQI accumulates causing protein adducts and lipid peroxidation and leads to hepatocellular injury (due to decreased GSH leaving hepatocytes susceptible to ROS and binding of hepatic proteins causing mitochondrial dysfucntion and membrane damage) causing _____ and this can progress to liver failure
^** Remember, chronic alcoholics also are using much of their CYP2E1 enzyme so even low doses of aspirin in chronic alcoholics have effects
Also realize if one were given a drug to increase GSH levels, it could help them
Acute Aspirin overdose causes alkalosis followed by metabolic ____ and the accumulation of pyruvate and lactate
Chronic aspirin toxicity can lead to ___ ulcerations and bleeding and the bleeding is due to the fact that ____ is blocked, which is needed for platelet aggregation
CYP (CYP2E1), NAPQ
Cetrilobular necrosis
Acidosis
Gastric, Thromboxane A2
*****Name the burn classification
1) Confined to the epidermis
2) Involves the dermis
3) Extends to the subcutaneous tissue
In burn patients, if more than 20% of the body is burned, a systemic ____ response syndrome can cause shock, sepsis, infection, or respiratory insufficiency and if 40% or more of the body is burned, a hyp__metabolic state occurs
*****If a burn is white or charred, dry and painless, it is a ____ burn
If the burn is pink or mottled with blisters and painful then it is a ____ burn
The devitalized tissues undergo ___ necrosis, adjacent to vital tissues that quickly accumulate inflammatory cells and marked exudation
1) Superficial burns (used to be called 1st degree)
2) Partial thickness burns (used to be called 2nd degree)
3) Full thickness burns (used to be called 3rd degree)
Inflammatory, Hypermetabolic
Full thickness
Partial thickness
Coagulative necrosis
Tissues with a ___ rate of cell division are the most vulnerable to radiation and include the gonads, bone marrow, lymphoid tissue, and mucosa of the GI tract
Ionizing radiation can have a direct effect, however more importantly, it has its effect via ____ formation
^** The major mechanism of DNA damage is due to ___, which are produced from reactions with free radicals generated by radiolysis of water or molecular oxygen and the most serious damage to DNA is DSBs (double stranded breaks)
Poorly vascularized tissues with less oxygenation (aka hypoxia) are ___ sensitive to radiation since there is not as much oxygen present to be converted to ROS (so for example, the center of a tumor is less oxygenated and therefore less sensitive)
Ionizing radiation that causes DNA damage can cause cell death, fetus or germ cell teratogenesis, or carcinogenesis
Ionizing radiation can also injure epithelial cells of blood vessels leading to impaired healing, sub intimal ___, and chronic ischemic atrophy
High
Free radical
ROS
Less
Fibrosis
**The gonads, blood and bone marrow are the three systems affected early from radiation **
Hours after radiation, lymphopenia often occurs along with shrinkage of the lymph nodes and spleen
Hematopoietic precursors are also affected early such as marrow aplasia
___ appears several days after injury, _____ occurs after the end of the first week, and ___ will occurs 2-3 weeks after injury
Fibrosis occurs ___ in the injury process (weeks or months)
^** The ___ often undergo interstitial fibrosis months to years after radiation, the GI tract walls also undergo fibrosis, and atrophy and fibrosis of the gonads occur for lower body cancer treatments
*** So to recap, ionizing radiation can cause sclerosis (stiffening of a structure) and vascular damage causing ischemic necrosis of the parenchymal cells causing their replacement by fibrous tissue (aka fibrosis)
Last but not least, remember once again treating a tumor with radiation (like a Hodgkin lymphoma) can have an increased risk of developing other neoplasms in any organ after exposure such as acute myeloid leukemia, myelodysplastic syndrome, or solid tumors and this risk of secondary cancer following irradiation is greatest in children
Neutropenia, thrombocytopenia, anemia
Late
Lung
In malnourished children, PEM (protein-energy malnutrition) presents as either Marasmus or Kwashiorkor syndrome
There are two types of compartments in the body, the ___ compartment is represented by proteins in skeletal muscles and the ___ compartment is represented by proteins in visceral organs (mainly the liver)
Marasmus syndrome has a depletion in the ___ protein compartment leading to loss of muscle mass (emaciated extremities aka weak), loss of body fat, and growth retardation (therefore the child’s weight is 60% or less of a normal child)
Kwashiorkor syndrome has severe depletion of the ___ protein compartment and the resultant hypoalbuminemia gives rise to ___ (loss of weight is masked by increased fluid retention)…. Hepatomegaly occurs here
^**Realize this in this syndrome, protein deprivation is much more severe than the deprivation of calories (such as in children only fed a carb diet)
Along with edema, skin lesions, and fatty liver (hepatomegaly) are seen in Kwashiorkors syndrome
Somatic, visceral
Somatic
Visceral, edema
In patients with decreased GnRH, leading to decreased LH and FSH and therefore Amenorrhea this is a diagnostic feature for ____
Anorexia nervosa
ADEK vitamins are ___-soluble and all other are ____-soluble
1) Vitamin A can also be called ____ or ____
Vitamin As major function is the maintenance of normal vision, regulation of cell growth and differentiation (aka maintaining specialized epithelia), regulation of lipid metabolism, and maintenance of resistance to infection
A vitamin A deficiency leads first to impaired vision, specifically ___
Presistent deficiency gives rise to epithelial ____ and ____zation
Xerophthalmia (aka ____) is the most devastating changes and occurs from the mucous secreting epithelium and lacrimal epithelium is replaced by keratinized epithelium
Then, a buildup of keratin causes small opaque plaques called ___ which can progress to the erosion of the roughened corneal surface called ___
^** Corneal ulcers are also present
In addition to the eye changes, the upper respiratory and ___ tract undergo squamous epithelium metaplasia and the pelvic (kidney) keritinization can build up leading to kidney stones
Finally, immune deficiency occurs and measles can often occur leading to death
Fat, water
Retinol or B-carotene
Night blindness
Metaplasia and keratinization
Dry eye
Bitot spots, keratomalacia
Urinary (kidney)
Vitamin D (could also be called ____ aka D3 or the precursor form 7-dehydrocholesterol)
The major function of vitamin D is the maintenance and facilitation of adequate plasma levels of ___ and ____ to support metabolic functions, bone mineralization, and neuromuscular transmission
In children, a vitamin D deficiency leads to ____ and in adults it leads to ____ and hypocalcemic tetany
When Vitamin D deficiency occurs, ___ levels are elevated and this leads to increased excretion of ____ aka (hypophosphatemia) but normal calcium levels since calcium is resorbed from the bone….
^** This is why skeletal deformities occur, since to little phosphorus is in the body and therefore mineralization is impaired
Vitamin D deficiencies can occur from various causes, but an important one is limited exposure to ____
In children with Rickets, soft occipital bones called ____ develop, and an excess of osteoid produces frontal bossing and a squared appearance to the head
****In the chest, overgrowth of cartilage or osteoid tissue at the costochondral junction causes ____* and a ___ deformity of the chest
When an ambulating child develops rickets, they develop lumbar lordosis and ___ of the legs
In osteomalacia, the newly formed osteoid matrix is inadequately mineralized and this produces the excess of persistent osteoid that is characteristic of osteomalacia
^** The bones are weak and vulnerable to gross fractures or microfractures
Cholecalciferol
Calcium and Phosphorus Rickets, Ostemalacia
PTH, Phosphorus
Sunlight
Craniotabes
Rachitic rosary, pigeon breast
Vitamin C is a ___ soluble vitamin
The most important function is for the activation of prolyl and lysyl hydroxylases allowing for hydroxylation of ____
Deficiency leads to the development of ____ and is characterized by ___ disease in growing children (aka inadequate synthesis of osteoids), and in both children and adults ____ due to poor vessel support that leads to bleeding tendency in gums, skin, periosteum, or joints, and impaired ___
^** Realize all of these are due to impaired collagen formation
***Vitamin C can also be called ____
Water
Pro-collagen
Scurvy, Bone, hemorrhage, wound healing
Ascorbic acid
____ deficiency can lead to chronic blood loss and hypochromic microcytic anemia
Iron
**** KNOW ALL THIS*******
A BMI under _____ is considered underweight, normal is 18.5-25, and obesity is a BMI greater than ____
Obesity is associated with insulin resistance and hyperinsulinemia, which are important features in ____ and with an increased insulin concentration, retention of sodium, expansion of blood volume, production of excess NE, and smooth muscle proliferation might all occur which are hallmarks of ____
Obesity also causes hypertriglyceridemia and low HDL, associated with an increased risk for ____ disease
Often in diabetic patients, obesity is assocaited with nonalcoholic ____ disease and this can progress to fibrosis and cirrhosis
An increased total body cholesterol, increased cholesterol turnover, and augmented biliary excretion of cholesterol all lead to an increased risk of ____
Obesity is also associated with a constellation of respiratory abnormalities such as _____ syndrome also called Pickwickian syndrome… or Obesity can be associated with ____ aka sleep apnea or excessive daytime sleepiness/prolonged nighttime sleeping
^** Hypersomnolence is associated with polycythemia (increased hemoglobin in the blood) and eventually right sided heart failure called cor pulmonale
Finally, increased fat (adiposity) can lead to the predisposition of ____
18.5, 30
Type 2 diabetes, hypertension
Coronary artery
Fatty liver
Cholelithiasis (gallastones)
Hypoventilation, hypersomnolence
Osteoarthritis
Along with all the consequences listed in the previous notecard associated with obesity, cancer can also occur from obesity
Like we already said, insulin resistance leads to ____ and this inactivated ____ and with no IGF binding proteins, IGF is free and the free IGF-1 binds to its receptor and activates the RAS and PI3K/AKT pathways leading to cell proliferation and decreased apoptosis
Also, obesity leading to insulin resistance leading to hyperinsulinemia can have effects on ____ that regulate cell growth in the uterine, breast, and some other tissues via
1) Increased peripheral ___ activity
2) The increased aromatase causes increased ___ availability (made from androgen precursors)
3) Increased androgen synthesis in the ___ and adrenals
4) Inhibition of ____ in the liver to cause further increases in estrogen
*** ____ is secreted by adipose tissue and is inversely correlated with obesity so in obese patients this is decreased, and its decreased concentration causes hyperinsulinemia
Finally, the ____ state can also be carcinogenic itself and is tested for via acute phase reactants like fibrinogen
Hyperinsulinemia, IGF binding proteins (IGFBP1 and IGFBP2)
Sex hormones
1) Aromatase
2) Estrogen
3) Ovaries
4) SHBG (Sex-hormone binding protein)
Adiponectin
Proinflamamtory
***Diet
A mutation in codon 249 of the TP53 gene, found in hepatocellular carcinomas is diagnostic for ___
^** Note this is an exogenous substance and often found in Asia and Africa, generally in cooperation with HEP B virus
Gastric cancers are related to ___ and ____, both endogenous substances that can come from sodium nitrite added to foods as a preservative, or commonly found in vegetables degraded by bacterial flora in the gut
A high fat intake and a low fiber intake will cause ___ cancer
Finally, Vitamins ___, ____, and ____ along with ____ have been shown to have antioxidant properties
Aflatoxin
Nitrosamine and nitrosamides
Colon
A,C and E (Aka ACE), selenium
The ___ period is the first 4 weeks of life, ____ is the first year of life after the first 4 weeks, then age 1-4 and 5-14
In children under the age of 1, congenital anomalies (anatomic defects that are present at birth), disorders related to short gestation/low birth weight aka prematurity, and SIDS (sudden infant death syndrome) are the main causes of death
**^^ Even though congenital means “born with” it does not necessarily mean it is due to a genetic defect
However from years 1-4 and 5-9 the main causes of death are accidents (unintentional injuries) and ____
Also at the age of 5-9, ____ are common life influenza or pneumonia and can cause death
Finally, 10-14 is mainly suicide that causes the most deaths
Neonatal, Infancy
Malignant neoplasms
Infections
There are 4 important congenital anomalies to know
Also know the term morphogenesis = organ and tissue development
1) ___ are due to primary errors in morphogenesis in which there is an INTRINSICALLY abnormal developmental process and due often to multifactorial defects although single gene or chromosomal defects can also cause it
2) ___ results from secondary destruction in an organ or body region that was previously normal in development and therefore arise from an EXTRINSIC disturbance in morphogenesis
3) ___s are due also to and EXTRiNSIC disturbance of development due to localized or generalized compression of the growing fetus by abnormal biochemical forces leading to structural abnormalities
4) A ___ is a cascade of anomalies triggered by a single initiating abberation
Name the type of congenital anomaly cause
**A) Uterine constraint (can be either from maternal factors like a first pregnancy, small uterus, leiomyomas OR placental factors like oligohydraminos, multiple fetuses etc)
**B) Congenital heart defect
**C) Amniotic band
D) Oligohydraminos/ Potters
**E) Anencephaly (no brain)
F) Cleft lip/ cleft palate
G) Club feet
H) Polydactyly/syndactyly
I) Trisomy 13
1) Malformations
2) Disruption
3) Deformation
4) Sequence
A) Deformation B) Malformation C) Disruption D) Sequence E) Malformation F) Malformation G) Deformation H) Malformation I) Malformation
Like we just said, a sequence has a single initiating aberration and in the case of the Potter’s sequence, ____ agenesis (aka no kidney formation) or ___ leakage would be considered that initiating aberration (other causes can also be considered)
The initiating aberration leads to decreased amniotic fluid (called ____) and this can cause amnion nodosum (nodules in the amnion) and fetal ___ which leads to other causes like altered facies, positioning defects of the hands and feet, breech presentation, and pulmonary hypoplasia
Renal, Amniotic
Oligohydraminos, compression
