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Robbins Pathology MOD2 (Chptr 7-10) > Chapter 9 > Flashcards

Chapter 9 Flashcards

1
Q

How does 1,25(OH2)D stimulate mineralization of the bone

A

Stimulates osteoblasts to synthesize calcium binding protein osteocalcin, which stimulates calcium deposition

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2
Q

What are the nuclear receptors associated with CYP induction

A
  • acyl hydrocarbon receptor
  • peroxisome proliferator-activated receptor (PPAR)
  • two orphan nuclear receptors
  • constitutive androstane receptor (CAR)
  • pregnant X receptor (PXR)
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3
Q

How does 1,25(OH2)D Increased intestinal absorption

A

Calcium absorption in the duodenum via binding with RXR complex and increased transcription of TRPV6, which is a calcium transporter

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4
Q

What are the non-vitamin D effects of 1,25(OH2)D

A

-Immunomodulator and anti proliferative effects

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5
Q

What do renal disorders cause with regards to vitamin D

A

-Decreased synthesis of 1,25(OH2)D, phosphate depletion (no reabsorbance), malabsorption disorders

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6
Q

Which vitamin deficiency is commonly producing overgrowth of cartilage or osteoid tissues at the costochondral joints, known as rachitic rosary

A

Vitamin D

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7
Q

What is the chemical commonly found in inhaled vapor drugs

A

Toluene

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8
Q

Most of the alcohol in the blood is converted into what and in what location

A

Acetylaldehyde in the liver

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9
Q

What is the affect of RBC levels following high doses of radiation

A

Anemia appears 2-3 weeks later (half life 120 days), and persists for months.

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10
Q

How does 1,25(OH2) stimulate breakdown of bone in hypocalcemic and high PTH levels

A

Activates expression of RANKL on osteoblasts, which bind to osteoclasts, releasing phosphate and calcium from bone (via HCL and cathepsin K)

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11
Q

How do sustained muscle contractions occur in heat stroke victims

A
  • nitrosylation of RYR1 receptors
  • Impairs RYR1 receptors allowing calcium to leak out
  • Causes muscle contractions
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12
Q

What is smoking associated with with regards to CV

A

Atherosclerosis and subsequent MIs

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13
Q

What is the process of metabolization of the small fraction of acetaminophen

A
  • CYP2E metabolizes to NAPQI (N-acetyl-p-benzoquinoneimine)

- NAPQ interests with glutathione, which detoxifies it

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14
Q

What are the three cell types affected by marrow aplasia

A

Granulocyte, platelets, RBCs

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15
Q

What are the most common acute affects on CNS with cocaine use

A

-hyperpyrexia and seizures

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16
Q

With the increases in temperature, what is the result in CV diseases

A

Worse due to heat wave and air pollution

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17
Q

What is the relation of vitamin C to vitamin E

A

Vitamin C may have antioxidant activity to regenerate vitamin E

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18
Q

Where are the general effects of arsenic poisoning seen

A

Heart, GI, nervous system, skin

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19
Q

How is the level of phosphate excretion in the kidney affected

A

Bone fibroblast growth factor 23 (FGF23), which is a phosphatonin, which blocks the uptake of phosphate in the intestine and kidneys

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20
Q

What are the chemical properties of most solvents and drugs

A

Lipophilic

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21
Q

What is malignant hyperthermia

A

Inherited mutations in RYR1 cause post anesthetic administration to cause a heat stroke like rise in core body temperature

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22
Q

What compartment is primarily affected in Kwshiorkor

A

Visceral compartment since protein deprivation is more than total calories

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23
Q

What is microcytic hypochondriac anemia and what causes it

A

Lead causes the decrease in heme production and subsequent hemoglobin

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24
Q

In the NPY pathway, what is released from the primary neurons onto the secondary neurons

A

NPY onto T 1/5 receptors

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25
Q

What is the skin affect of use of the antibiotic minocycline

A

Discoloration of the skin

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26
Q

With the increases in temperature, what is the result in GI, cholera, and water born illnesses

A

Increases as flood and heavy rains contaminate the clean water

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27
Q

What is a diagnostic feature of anorexia

A

Amenorrhea (caused by decreased levels of LH and FSH)

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28
Q

What are the common causes of death in burn victims

A

-Pneumonia, septic shock with renal failure or acute respiratory distress

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29
Q

How does nicotine work

A

Binds to nicotinic acetylcholine receptors in the brain, causes the release of catecholamines from the SNS, resulting in the increase in HR, BP and CO

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30
Q

Radon gas damage is due to which two decay particulates

A

Polonium 214 and 218

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31
Q

What is the amino acid change in defect alcohol dehydrogenase

A

Normal ALDH1 —> inactive ALDH2 (lysine for glutamate at codon 487)

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32
Q

What is the risk of miners to develop lung cancer as composed to those not exposed to mining chemicals

A

10 fold increase

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33
Q

What is the presentation of acute vitamin A toxicity

A

Headache, vomiting, stupor, blurred vision, may be confused with symptoms of pseudotumor cerebral

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34
Q

Alcohol dehydrogenase breaks down alcohol in which compartment

A

Cytosol

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35
Q

What is the main target of damage with radiation in the range of 2-10 Sv and what is the main sign

A

Bone marrow, showing hair loss, vomiting, hemorrhage, leukopenia in 2-6 weeks

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36
Q

What is the condition of chloracne characterized by

A

Acne, cyst formation, hyperpigmentation, hyperkeratosis generally around the ears and face

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37
Q

What is the risk of anabolic steroids and hormones

A

-Inhibits production and release of LH and FSH via feedback, as well as increase the amount of estrogens due to the metabolites of steroids

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38
Q

What is inhibited by PYY

A

NPY pathway

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39
Q

What is the result of CYP metabolism of carbon tetrachloride

A

Toxic trichloromethyl free medical

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40
Q

What is the mechanism of adiponectin action

A

Binds to AdipoR1 and 2
Activated PKA
Inactivates acetyl CoA carboxylase (required for FA synthesis)

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41
Q

What are the clinical presentations of someone using anabolic steroids

A
  • Stunted growth in adolescence
  • Acne, gynocomastia, testicular atrophy in males
  • Facial hear and menstrual changes in females
  • Hepatic cholestasis (in oral administration)
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42
Q

How can vitamin K be synthesized endogenously

A

Intestinal microflora

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43
Q

What hormones related to eating are produced in the ileum and colon

A

Peptide YY (PYY)

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44
Q

With the increases in temperature, what is the result in vector borne infectious diseases

A

Such as coccy, which is increasing as droughts in CA occur

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45
Q

What are first order neurons from the hypothalamus and what is their general result

A

1) CART/POMC (increases energy expenditure)

2) NPY/AgRP (increases food intake)

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46
Q

What are the two products during cachexia and what is their effect

A
  • Proteolysis inducing factor (excreted in urging in weight losing patients)
  • Lipid mobilizing factor (increased FA oxidation and proinflammatory cytokines)

—> both lead to NFkB and degredation of skeletal muscles and their myosin heavy chains

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47
Q

Why is lead poisoning more common in children than adults

A

Children absorb about 50% of ingested lead, while adults only about 15%. In addition, passes through the BBB more readily

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48
Q

When is a child said to have marasmus

A

Weight falls to 60% of normal for sex, age, and height

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49
Q

What are the clinical presentations of Minamata disease

A

Cerebral palsy, deafness, blindness, mental retardation, CNS defects in utero

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50
Q

Vitamin D toxicity will present as what

A

Metastatic calcifications of soft tissue such as kidneys, bone pain and hypercalcemia

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51
Q

Vitamin D deficiency in rickets and osteomalacia result in what underlying condition

A

Excess of unmineralized matrix

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52
Q

What are the blood level of marasmus patients

A
  • normal albumin levels
  • low leptin levels
  • High cortisol (fat burning)
  • vitamin deficiency
  • T cell deficiency
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53
Q

What is the risk of oral contraceptives and cervical cancers

A

Increased risk with those with HPV

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54
Q

What is the mechanism to counter act acetaminophen overdoes

A

N-acetylcysteine to replace the GSH levels

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55
Q

Inhalation of mineral dust can lead to which kind of cancer

A

Lung, aka pneumoconioses

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56
Q

What is the most active form of vitamin D and where is it converted

A

1,25(OH)2D in the kidney

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57
Q

What are the general clinical presentations of aspirin overdose

A

-headaches, dizziness, tinnitus (ringing of ears), hearing impairment, confusion, drowsiness, vomiting, diarrhea, gastric issues

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58
Q

Superficial burns contain which layer

A

Epidermis

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59
Q

What are the common signs seen in patients with secondary PEM

A
  • Depletion of subQ fat in arms, chest, shoulder, or metacarpals
  • Wasting of quads or deltoids
  • Ankle or sacral edema
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60
Q

Acute alcoholism leads to which effects

A
  • hepatic and gastric changes (fatty or hepatic changes)
  • gastritis and ulceration
  • depressant, first in the subcortical regions
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61
Q

How is vitamin D transported in the blood to the liver

A

Plasma alpha1 globulin (aka D binding protein or DBP)

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62
Q

Immediately following hypocalcemia in which calcium levels return to normal, what are the levels of phosphate

A

Remain low due to phosphatonins, which prevent mineralizaion of bone

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63
Q

What is aplastic anemia

A

Very high doses of radiation kill the marrow stem cells and induce permanent drops in levels

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64
Q

How does cancer due to arsenic present

A

Multiple and appear on the palms and soles, and non-malignant respiratory disease

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65
Q

What is the result of lead on hemoglobin synthesis and what levels are increased in the body

A

Suppresses synthesis via the enzymes that place iron into protoporphyrin, therefore there will be elevated levels of protoporphyrin in the blood

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66
Q

What size particles of soot are the most damaging

A

Ultra fine particles less than 10 micrometers in diameter, which are engulfed by macros and induce inflammation. Greater than this size are trapped in mucous of airways

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67
Q

What are the blood levels in kwashiorkor

A

Hypoalbuminia

  • Increased fluid retention (edema)
  • Immune cell deficiencies
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68
Q

How do flat bones form

A

Intramembranous bone formation (mesenchymal cells differentiate into osteoblasts

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69
Q

What is primary malnutrition

A

Missing the major components in the diet

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70
Q

50% of all deaths in children younger than 5 are attributed to which 3 conditions

A
  • pneumonia
  • diarrheal disease
  • malaria
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71
Q

What is a major mechanism that DNA is damaged by ionizing radiation

A

Radiolysis of water generates ROS that damage tissues and cells

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72
Q

How does 1,25(OH2)D stimulate calcium absorption in the kidney

A

Increased calcium influx via increased expression of TRPV5

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73
Q

What are the clinical presentations of heat stroke

A
  • vasodilation with peripheral pooling of blood.
  • Hyperkalemia, tachycardia, arrhythmias
  • Sustained contraction of skeletal muscles
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74
Q

What part of the tumor is less sensitive to radiation damage

A

The center hypoxic portion due to the lack of oxygenation

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75
Q

What are the commonly seen kidney issues with opiate users

A
  • amyloidosis (secondary to infections)

- focal and segmental glomerulosclerosis (induces nephrotic syndrome and proteinuria)

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76
Q

What is the direct product of alcohol oxidation and what is the clinical presentation

A

Acetylaldehyde and results in the acute affects of alcohol, as well as the increased risk of oral cancers

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77
Q

What is the result of haploinsufficency of brain derived neurotrophic factor (BDNF) in MC4R pathway

A

Associated with obesity in WAGR patients (Wilms tumor)

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78
Q

BPA exposure results in what

A

Endocrine disrupter, heart disease

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79
Q

What are the principal lesions as a result of thiamine deficiency in alcoholics

A

-peripheral neuropathies, Wernicke-Korsakoff syndrome, cerebral atrophy, cerebellar degeneration, optic neuropathy

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80
Q

Chronic alcoholism is associated with increases in which cancers due to acetylaldehyde

A

-Esophageal and laryngeal cancer (especially those with ALDH*2)

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81
Q

Full thickness burns contains which layer

A

Subcutaneous tissue, with sometimes including the muscle underneath

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82
Q

How does cadmium get uptaken into the cells

A

Via ZIP8, which is a zinc transporter

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83
Q

Which enzymes are inhibited by lead

A
  • aminolevulinic acid dehydratase

- ferrochelatase

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84
Q

What is the mechanism of action for arsenic poisoning

A

Interferes with mito oxphos, as trivalent arsenic replaces the phosphates in ATP

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85
Q

What do symptoms do dioxins and PCBs cause

A

Folliculitis and dermatosis known as chloracne

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86
Q

What is the effect of combination progesterone-estrogen therapy on cancers in women

A

-Increased risk of breast cancer after 5 to 6 years

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87
Q

What is a major complication of anorexia

A

Cardiac arrhythmias and sudden death as a result of hypokalemia

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88
Q

How can niacin be synthesized endogenously

A

Tryptophan

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89
Q

What does retinol bind to and where is it synthesized

A

Binds to retinol binding protein (RBP), which is synthesized in the liver

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90
Q

What is a common consequence of radiation in the field

A

Fibrosis as a result of dead paranchymal cells be replaced by connective tissue

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91
Q

What are the direct effects of injury as a result of hypothermia

A

Physical disruption within cells by high salt concentrations due to the crystallization of intra and extracellular water

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92
Q

What is the risk of oral contraceptives and thromboembolism

A

3 to 6 times increase due to elevated production of coagulation factors

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93
Q

What are the three main mechanisms that 1,25(OH2)D production is regulated

A

1-hypocalcemia stimulates PTH release, which stimulates conversion in kidney
2-Hypophosphatemia activates alpha1-OHase
3-Increased 1,25(OH2)D stops PTH activation of alpha1-OHase

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94
Q

How is lead able to cause damage

A

Binds to sulfhydryl groups in proteins and interferes with calcium metabolism and subsequent inhibition of NT release

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95
Q

What is the single leading global cause of health loss

A

Undernutrition (1/3 of Disease burden)

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96
Q

How do neuro defects present in arsenic poisoning

A

2 to 8 weeks later consisting of sensorimotor neuropathy causing paresthesis, numbness and pain

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97
Q

What is mortality of cachexia usually due to

A

Atrophy of the diaphragm and respiratory muscles

98
Q

What is the affect of vitamin A on metabolism

A

9-cis-retinoic acid binds to PPAR (peroxisome proliferator-activated receptors) which are key regulators for the oxidation of fat tissues and muscles

99
Q

What is pickwickian syndrome and what is it associated with

A

Obesity leads to Hypoventilation, hypersomnolence (sleep apnea, polycythemia, right sided heart failure)

100
Q

What are the 5 infectious agents leading from top 10 causes of death

A
  • respiratory infections
  • HIV/AIDs
  • diarrheal diseases
  • TB
  • Malaria
101
Q

What condition can readily resemble a pseudotumor cerebri

A

Vitamin A toxicity

102
Q

What is the risk of oral contraceptives and breast carcinomas

A

No increase

103
Q

What occurs within hours of high doses of radiation

A

Severe hymphopenia, shrinkage of LN and spleen. Returns to normal writhing weeks to months

104
Q

What are the clinical presentations of marasmus

A

Growth retardation, loss of uncle, depletion of peripheral compartment, emancipated extremities, head to large for body, immune deficiency

105
Q

Due to tobacco smoke, what organ is affected by the carcinogen N-nitrosonornicicotin (NNN)

A

Esophagus

106
Q

What are the CV effects of alcoholism

A
  • Myocardium dialated congestive cardiomyopathy (aka alcohol cardiomyopathy)
  • hypertension
  • decreased HDL production
  • acute and chronic pancreatitis
107
Q

What is the general mechanisms and location of damage in cadmium poisoning

A

Toxic to the kidneys and lungs through production of ROS

108
Q

What is the relationship between the blood alcohol levels with the breath

A

They are proportional

109
Q

What is the risk of oral contraceptives and hepatic adenoma

A

Increased risk of this rare benign tumor, which is well encapsulated mass

110
Q

What is marrow aplasia and what are the blood levels of neutrophils following high doses of radiation

A

Radiation affects the bone marrow and the cells there. Causes slight increase in neutrophils, followed by neutropenia (have half life of 1 day). Reaches zero around week 2. Recovery take 2-3 months

111
Q

Which psychiatric disorder has the highest death rate

A

Anorexia

112
Q

What is the product formed from carbon monoxide and Hb

A

Carboxyhemoglobin

113
Q

The microsome oxidation system uses what to convert alcohol into acetylaldehyde

A

-CYP2E1 in the SER

114
Q

What is released from POMC first order neurons onto the secondary neurons

A

MSH onto the melanocorticin receptors 3 and 4

115
Q

How can Vitamin D be synthesized endogenously

A

Precursor steroids

116
Q

What is the mechanism that benzene is toxic

A

It is oxidized by hepatic CYP2E1, which forms a toxic metabolism. This results in disruption of differentiation of hematopoietic cells in bone marrow, leading to aplasia and leukemias

117
Q

What are heat cramps and what is the body core temp

A

Loss of electrolytes due to sweating, and maintained at normal

118
Q

What are the greatest threats to a burn patient

A

Shock, sepsis, and respiratory insufficiency

119
Q

What is the mechanism of ozone toxicity

A

Production of free radicals, which injury epithelial cells along the respiratory tract, Type 1 alveoli, and inflammation

120
Q

What are the clinical presentations of acetaminophen overdose

A

Nausea, vomiting, diarrhea, shock, followed by days of jaundice

121
Q

Due to tobacco smoke, what organ is affected by the carcinogen polycyclic aromatic hydrocarbons, NNK, NNN

A

Oral cavity

122
Q

What conditions will decrease the activity of CYP

A

Starving or fasting conditions

123
Q

What is a natural source of acetylsalicylic acid

A

Methyl salicylate contained in ointments that contain wintergreen

124
Q

How can the amount of second hand smoke be measured

A

The amount of cotinine, which is a metabolite of nicotine

125
Q

What is the risk of oral contraceptives and endometrial and ovarian cancers

A

Protective/decreased risk

126
Q

What is the result of lead in the blood in children

A

-deficits in intellectual capacity, hyperactivity (ADHD), poor organizational skills

127
Q

What are the most commonly inhaled substances leading to pneumoconioses

A

Coal dust, silica, asbestos, beryllium

128
Q

What hormones related to eating are produced in the stomach

A

Ghrelin

129
Q

What is the most common form of hyperthermic syndrome

A

Heat exhaustion

130
Q

What form of mercury is most letha to developing brains and what is the mechanism

A

Methyl mercury, due to its lipid solubility and accumulation in the brain

131
Q

Rubber workers and their exposure are at increased risk of what

A

Leukemia, particularly acute myeloid leukemia

132
Q

What is the substrate and product converted in the kidney and what is the enzyme

A

25(OH)D to 1,25(OH)2D Via 1alpha(OHase)

133
Q

What is secondary malnutrition

A

Resulting from the malabsorption, impaired storage or utilization, excess loss or increased need for nutrients

134
Q

What is the hyperbolic state associated with burns

A

Excess heat loss results in an overactive metabolic state to replace the lost heat, where BMR can double

135
Q

What is acetylaldehyde converted into and by which enzyme

A

Converted into acetate by Acetylaldehyde in the mitochondria

136
Q

What is the main target of damage with radiation in the range of 0-1 sv, and what are the main symptoms

A

None

137
Q

What are the examples of organochlorides

A

Synthetic lipophilic products that resist degredation such as
DDT,lindane,aldrin, dieldren, PCBs and dioxin

138
Q

What is the mechanism of action of acetaminophen overdoes

A

Unconjugated NAPQI builds up in the liver due to the limited amount of glutathione available, leading to damage (centilobular necrosis)

1) covalent binding to hepatic proteins causing cellular and mito damage
2) Depletion of GSH leads to inability to neutralize ROS

139
Q

What are common blood level findings in patients with anorexia

A
  • Decreased LH and FSH
  • Decreaed bone density
  • Decreased thyroid hormone
140
Q

What are the clinical presentations of lead poisoning

A
  • lead lines, as hyperpigmentation of gums
  • increased bone epiphysis density in kids
  • inhibition of bone fracture healing
  • suppression of heme synthesis, anaemia
  • Demylanation of of nerves
  • Chronic tubulointerstital disease in kidneys
141
Q

What does hypocalcemia incur during vitamin D deficiency

A

PTH is elevated leading to:

1) Renal alpha-1 OHase activation (increased vit D and calcium
2) resorption of bone by osteoclasts
3) Decreased renal excretion of calcium
4) Increased excretion of phosphate

142
Q

What are the clinical presentations of a patient exposed to high levels of organosolvents such as benzene, butadiene, chloroform, and carbon tetrachloride

A

Dizziness, confusion, CNS depression, coma

143
Q

What is a major diagnostic complication of aspirin poisoning

A

Acute erosive gastritis leading to intestinal bleeding and ulceration

144
Q

What is the main target of damage with radiation in the range of 1-2 Sv and the main sign

A

Lymphocytes producing lymphopenia/granulocytopenia in 1 day to 1 week

145
Q

How do long bones form

A

Endochondral ossification, where cartilage is formed, then replaced by bone

146
Q

Where are CYP450s primarily located

A

ER of the liver

147
Q

What is the relationship between aflatoxin and cancer

A

Causes mutation in codon 249 in TP53, leading to hepatocellular carcinomas

148
Q

How does Vitamin A help regulate genes

A
  • retinoic acid receptors (RARs) activated and bind to RXR.

- Complex binds to regions controlling gene expression and tumor suppressors

149
Q

Obese patients have high levels of circulation what

A

CRP

150
Q

Metabolism of alcohol causes what down stream effects

A
  • CYP2E1 releases ROS leading to lipid peroxidation of hepatocytes
  • Released of LPS from gram neg
  • TNF from LPS release
151
Q

IN what ways does smoking increase the risk of CVs and MI

A

-Increase in platelet aggregation, Decreased myocardial oxygen supply, increased oxygen demand, and increased chance of Vfib

152
Q

Rubber workers are exposed to which agents

A

Organosolvents such as benzene and 1,3-butadiene

153
Q

In patients with osteomalasia, where are the likely locations of microfractures

A

Vertebral bodies and femoral neck

154
Q

What are the forms that cadmium poisoning will take

A
  • Obstructive lung disease due to necrosis of alveolar epithelial cells
  • renal tube damage that can progress to end stage renal disease
155
Q

What group of patient is commonly seen to have kwashiorkor

A

African children who have been weaned too early and are fed a carb diet

156
Q

What can cause vitamin A toxicity

A

-Polar bear liver, whale, sharks or tuna livers

157
Q

Due to tobacco smoke, what organ is affected by the carcinogen 4-aminobiphenyl, 2 naphthlamine

A

Bladder

158
Q

What occurs with blood vessels during radiation

A

Usually will see dilation, then shrinking of the lumen as it is filled with fibrosis due to healing, as well as thickening of the lamina

159
Q

What does catalase breakdown of ethanol occur

A

In peroxisomes

160
Q

What is required for the absorbance of vitamin A

A

-Bile, pancreatic enzymes, antioxidant activity in food

161
Q

What is the most dangerous damage to DNA

A

Double stranded breaks

162
Q

Which compartment is affected by marasmus and why

A

Peripheral and somatic compartment with subQ fats and proteins being used as fuel

163
Q

Bioaerosols are able to cause infectious diseases such as

A

Legionnaires disease, viral pneumonia, common cold

164
Q

What is the mechanism of action for dabigatran and when is it commonly used

A

Direct inhibitor of thrombin, and given to patients with atrial fibrillation to prevent thromboembolism

165
Q

What are the major effects of vitamin A deficiency

A
  • Night blindness
  • epithelial changes to metaplasia
  • xerophthalmia (conjunctiva being replaced with keratin)
  • Bitot spots (build up of keratin debris following dry eyes)
  • keratomalacia (erosion of corneal surface following dry eyes)
  • Immune deficiencies
166
Q

What is the main protective mechanism against mercury poisoning

A

Intracellular glutathione, which acts as a sulfhydryl donor

167
Q

What is the earliest manifestation of vitamin A deficiency

A

Night blindness

168
Q

What are the common complication so bulemia

A

1) electrolyte imbalance (hypokalemia)
2) pulmonary aspiration of gastric juice
3) esophageal and gastric rupture

169
Q

What is released from the secondary neurons in the NPY pathway

A

MCH ad orexin

170
Q

Acetaminophen is metabolized by which enzyme and what is the excreted molecules

A

95% is Metabolized by phase 2 enzymes and excreted in urine as glucoronate or sulfate conjugates

171
Q

What is the most common infection of opiate users, and what are the other commonly seen ones

A

-Viral hepatitis (most common)
-10% had endocarditis, especially right sided heart valves (tricuspid) causes by S. Aereus
-

172
Q

Prader Willi syndrome is marked by which chromosome deletion and subsequent deletion of which eating hormone

A

15q11-q13 with decreased levels of PYY leading to obesity

173
Q

What are the changes seen in adult CNS during lead poisoning

A

Peripheral demyelination neuropathy, which involves the motor end units of the most commonly used muscles. In particular the extensor muscles of wrist and fingers, followed by the perineal muscles

174
Q

What are the presentation fo chronic vitamin A toxicity

A

Weight loss, anorexia, nausea, vomiting, and bone/joint pain

175
Q

Where is most absorbed lead stored and for how long

A

Stored in teeth and bones, usual with a half life of 20-30 years

176
Q

What is the stimulated and inhibited with leptin

A

Stimulates CART pathway

Inhibits NPY pathway

177
Q

What occurs during phase 1 reactions to metabolize metabolites

A

Undergo hydrolysis, oxidation or reduction

178
Q

How does vitamin A deficiency cause follicular or popular dermatosis

A

-Hyperplasia and hyperkeratinization of epidermis cause plugging of the ducts if the adnexal glands

179
Q

PEM preferentially affects who the most

A

Aka protein energetic malnutrition aka malnutrition affect Children

180
Q

What hormones released to eating are produced in the fat cells

A

Leptin and adiponetin

181
Q

What is the effect of platelet levels following high does of radiation

A

Thrombocytopenia appears by the end of the first week (10 day half life)

182
Q

What is a heat stroke

A

Assoacited with high temp, humidity, and exertion. The body temp can reach as high as 40degrees C.

183
Q

Where are organosolvents such as chloroform and carbon tetrachloride found

A

Degreasing and dry cleaning agents, as well as paint removers

184
Q

What are the most toxic forms of arsenic

A

-arsenic trioxide, sodium arsenite, arsenic trichloride

185
Q

What is the process of CYP induction

A
  • Inducers bind to nuclear receptors
  • Dimerize with retinoic X receptor (RXR) to associate with promoter
  • increased CYP
186
Q

What are the physical morphologies seen in rickets

A
  • Softened occipital bones become flattened, and parietal bones may buckle inward, and elastic recoil back into place with release of pressure (craniotabes)
  • Frontal bossing and squared appearance of the head
  • pigeon chest
  • lumbar lordosis and bowing of the legs
187
Q

What are conditions that can cause Kwashiokor

A

Protein losing enteropathies, nephrotic syndrome, extensive burns, fad diets,

188
Q

What are the three enzymes in the lover that are responsible for conversion of alcohol to acetylaldehyde

A
  • alcohol dehydrogenase
  • ethanol oxidizing system
  • catalase
189
Q

What is the most common source of exposure of cadmium

A

Food

190
Q

Which derivative of vitamin A has the highest affinity for RARs

A

Al trans-retinoic acid

191
Q

What are the effects of obesity on hormone levels

A

INcreased estrogen via aromatase
Increased androgens in ovaries and adrenals
Inhibits sex hormone binding globulin (SHBG) in liver

192
Q

Where is the majority of required vitamin D synthesized and what percentage

A

90% in the skin

193
Q

What is the result of adiponectin

A

Fatty acid oxidation and decreased fat mass “fatt burning molecule” and “guardian against obesity”

194
Q

Exposure to vinyl chloride results in which condition

A

Angiosarcoma

195
Q

Through which enzyme do macrophages have the ability to produce 1,25(OH2)D

A

CYP27B

196
Q

What is substrate and product of the liver in vitamin D metabolism and what is the exnzyme

A

Vitamin D to 25(OH)D via 25OHase (aka CYP27A1)

197
Q

Alcoholism leads to which vitamin deficiency

A

Thiamine (B1) deficiency

198
Q

What are the skin changes associated with arsenic poisoning

A

Hyperpigmentation and hyperkeratosis

199
Q

What are the results of increased insulin levels

A

Retention of sodium, expansion of blood volume, excess Norepinephrine, smooth muscle proliferation

200
Q

What are conditions that can lead to vitamin A deficiency in otherwise healthy individuals

A

-Use of laxatives, malabsorption syndromes such as celiac disease and crohns, and colitis

201
Q

What is the mechanism of warfarin, and what is the issue with using it

A

It is a vitamin K antagonist, but can be interfered by vitamin K rise foods

202
Q

How can Vitamin D deficiency diets be supplemented

A

Fish oils

203
Q

How does lead poisoning lead to gout

A

Renal failure with decreased uric acid excretions can lead to “saturnine gout”

204
Q

How many NADH are produced from a molecule of ethanol

A

2 NADH

205
Q

How do the immunomodulary and antiproliferative effects occur mechanistically

A

1,25(OH2)D binds to the membrane bound VitD receptor, mVDR, which citrates PKC and opens calcium channels

206
Q

Alcohol and cirrhosis lead to increases in which cancers

A

Hepatocellular carcinoma

207
Q

What is stimulates by ghrelin

A

NPY pathway

208
Q

In patients with Kwashiorkor, what is the change seen in the bowel

A

-decrease glandular crypts resulting in loss of villi. Results in disaccharidase deficiency. So infants do not respond well to milk based diets

209
Q

What are the major consequences of using anticoagulants

A

Bleeding disorders, but also emboli stroke and other thrombin complications

210
Q

What is heat exhaustion and what causes it

A

Failure of CV to compensate for hypovolemia caused by dehydration. Results in fainting and collapse and can be reversed with rehydration

211
Q

What population is MHT used in and what is the reasoning

A

Only in postmenopausal women because of the increased risk of uterine cancer

212
Q

What occurs during phase 2 of metabolism of xenobiotics

A

Phase 1 products are metabolized into water soluble compounds via glucuronidase, sulfation, methylation, conjugation with glutathione

213
Q

What is the risk of oral contraceptives and CV

A

Doubles the coronary disease risk in women who smoke and are older than 35

214
Q

Alcoholism leads to what conditions in the GI tract

A

Bleeding from ulcer, esophagus, and gastritis

215
Q

What is the only hormone with oregenic effects

A

Aka Increased food uptake by ghrelin

216
Q

What is the effect of MHT on risk of DVT and strokes

A

Thrombosis is more pronounced in individuals with hypercoagulative states such as factor 5 or Prothrombin mutations
-Increased risk in first 2 years

217
Q

What is the effect of acuter salicylate overdose

A
  • alkalosis via stimulation of the respiratory center in medulla
  • followed by metabolic acidosis due to buildup of lactate and pyruvate as a result of uncoupling of oxphos and inhibition of Krebs
  • Nonionized Forms of salicylate go to brain to cause nausea and coma
218
Q

What are the clinical presentation of kwashiorkor

A

-Edema, skin lesions with alternating hyper-pigmentation zones (areas of desquamation), and hypopigmentation (area of flaky paint), loss of hair color or alternating pale and color hair, fatty liver (decreased synthesis of carrier proteins for lipoproteins)

219
Q

Partial thickness burn contains which layer

A

Dermis

220
Q

Where is vitamin C commonly seen in modern world

A
  • Patients undergoing peritoneal dialysis and hemodialysis

- infants on formulas of evaporative milk without Vit C supplementation

221
Q

What is the effect of organochlorines

A

Disruption of hormonal balance because of antiestrogen or antiandrogen activity

222
Q

How does vitamin A toxicity lead to bone fractures

A

Retinoic acid will stimulate osteoclast formation, leading to bone resorption

223
Q

What are xenobiotics

A

Exogenous chemicals in the environmental air, water, food, and soil that are absorbed into the body through ingestion, inhalation, and skin contact.

224
Q

What are the changes seen in the blood and bone marrow as a result of lead poisoning

A
  • Ring sideroblasts, which are red cel precursors with iron laden macrophages in the bone marrow
  • in the blood, punctuate basopilic stippling of the red cells
225
Q

What is analgesic nephropathy

A

Mixture of aspirin, phenoacitin, acetaminophen when taken over many years canes cause tubulointerstital nephritis with papillary necrosis

226
Q

What percentage does cachexia occur in cancer patients and which particular cancers

A

50%, especially GI, pancreatic and lung cancers

227
Q

How does mercury cause damage to the body

A

Binds to sulfhydryl groups in proteins with high affinity, leading to CNS and kidney damage

228
Q

What vitamin deficiencies are seen in women who have frequent pregnancies followed by lactation

A

Vitamin D

229
Q

What is the major source of vitamin D for humans and what does it required

A

7-dehydrocholesterol and requires UVB (290-315)

230
Q

What is the most common DNA repair mechanism andwhat is the effect

A

NHEJ, which can lead to deletions and mutations

231
Q

What is the main target of damage with radiation in the range of 10-20Sv

A

Small bowel, showing diarrhea, fever, vomiting, electrolyte imbalance in 5-14 days

232
Q

Vitamin C can lead to which cause of death

A

Hemorrhages, commonly seen in scurvy

233
Q

How is vitamin A packaged, uptaken and stored

A

Packaged in chylomicrons, uptaken by the liver via Apolipoprotin E, then store in perisinusoidal stellate (Ito) cells

234
Q

What are the pulmonary injuries associated with opiate use

A

Edema, septic embolism from endocarditis, lung abscess, infections, foreign body granulomas, often highlighting talc in the spleen levied, lungs and LNs

235
Q

What are the blood levels of gonadotropin in bulemia patients

A

Normal due to normal weight (results in 50% no having amenorrhea)

236
Q

Due to tobacco smoke, what organ is affected by the carcinogen polycyclic aromatic hydrocarbons, NNK, and polonium 210

A

Lung and larynx

237
Q

When are the effects of hypothermia and hypoxia on limbs finally seen

A

When they return to normal temperature

238
Q

Due to tobacco smoke, what organ is affected by the carcinogen NNK

A

Pancreas

239
Q

In the POMC pathway, what are the products released from the secondary order neurons

A

TSH and CRH

240
Q

With regards to eating, what processes and integrates the information

A

Arcuate nucleus of the hypothalamus

241
Q

What is the most serious consequence of chronic arsenic exposure

A

Development of cancers, especially skin, lungs and bladder

242
Q

What skeletal abnormalities are associated with cadmium poisoning

A

Calcium loss that can be associated with osteoporosis and osteamalacia known as Itai-Itai

Robbins Pathology MOD2 (Chptr 7-10) (4 decks)

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