Environmental Pathology

Chapter 6 Environmental Pathology



I. Chemical Injury

• The two leading causes of illness and death in the United States are tobacco and alcohol use.

A. Tobacco use

Smoking: most important preventable cause of disease and death in United States


1. Tobacco is the leading cause of premature death in the United States.

2. The rate of cigarette smoking is increasing in females and decreasing in males.

3. Chemical components of tobacco

a. Nicotine

(1) Rapidly absorbed

(2) Most addictive chemical in tobacco smoke

(3) Cotinine is the most important metabolite of nicotine.


Cotinine: metabolite of nicotine; used for screening



• Screening test in blood or urine for detecting nicotine

b. Polycyclic hydrocarbons are the primary carcinogens.

4. Smokeless tobacco (e.g., chewing tobacco)

a. Can cause nicotine addiction and cancer

b. Risk for squamous cell cancer of buccal mucosa and gums

5. Passive (secondhand) smoke inhalation

a. Greatest impact on children

(1) Increased risk of respiratory and middle ear infections

(2) Exacerbates asthma

b. Increased risk for lung cancer and coronary artery disease

6. Systemic effects associated with tobacco use (Table 6-1)

7. Beneficial effects of smoking cessation

a. Live longer, regardless of age, than those who continue to smoke

• If cessation before age 50, reduction in risk of dying in next 15 years is cut in half compared with those who continue to smoke.

b. Lower risk for cardiovascular disease

• Approaches nonsmoker after 15 years

c. Lower risk for lung cancer

• Approaches nonsmoker after 15 years

d. Lower risk for stroke

• Approaches nonsmoker after 5 to 15 years


Table 6-1 Systemic Effects Associated with Tobacco USE

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Nicotine patch: effective in treating ulcerative colitis


e. Other benefits

(1) Reduced risk for cancers of the mouth, larynx, esophagus, pancreas, kidney, and urinary bladder

(2) Improved pulmonary function regardless of severity of the disease

(3) Reduced risk for pneumonia, influenza, and bronchitis

B. Alcohol abuse

1. Alcohol metabolism

a. Absorption occurs in the stomach (25%)

b. Metabolism occurs in the stomach and liver

• Alcohol dehydrogenase is the rate-limiting enzyme.


Alcohol metabolism: ↑ NADH is key to lab abnormalities


c. Important products of alcohol metabolism (Fig. 6-1)

(1) Increased reduced nicotinamide adenine dinucleotide (NADH)

(a) Causes conversion of pyruvate to lactate

(b) Causes conversion of acetoacetate to β-hydroxybutyrate

(c) Causes conversion of dihydroxyacetone phosphate to glycerol 3-phosphate

(2) Acetyl coenzyme A (acetyl CoA)

(a) Used to synthesize fatty acids for triglyceride synthesis

(b) Used to synthesize ketoacids

d. Alcohol induction of the cytochrome P-450 enzyme system

• Increases alcohol metabolism, which increases the tolerance for alcohol

e. Legal blood alcohol limit for driving

• Ranges from 80 to 100 mg/dL

2. Risk factors for alcohol-related disease

a. Amount

b. Duration

c. Female sex

image

6-1: Alcohol metabolism. See text for discussion. DHAP, dihydroxyacetone phosphate; NAD+, nicotinamide adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide; βOHB, β-hydroxybutyric acid; TG, triglyceride.


(From Pelley JW, Goljan EF: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby, 2007, p 172, Fig. 9-6.)



Women: less gastric alcohol dehydrogenase than men


(1) Decreased gastric alcohol dehydrogenase levels

• Causes higher alcohol levels in women than in men, even after drinking the same amount of alcohol

(2) Genetic susceptibility

3. Systemic effects associated with alcohol abuse (Table 6-2)


Table 6-2 Systemic Effects Associated with Alcohol Abuse

image


Alcohol abuse: most common cause of thiamine deficiency


4. Laboratory findings in alcohol abuse

a. Fasting hypoglycemia

• Excess NADH causes pyruvate (substrate for gluconeogenesis) to convert to lactate.

b. Increased anion gap metabolic acidosis

(1) Lactic acidosis

(2) β-Hydroxybutyric ketoacidosis

(a) Excess acetyl CoA is converted to β-hydroxybutyrate.

(b) Not detected with urine dipstick or blood test for ketone bodies


↑ Anion gap metabolic acidosis in alcohol abuse: lactic acid, β-hydroxybutyric acid


c. Other findings

(1) Hyperuricemia (potential for developing gout)

• Lactic acid and β-hydroxybutyric acid compete with uric acid for excretion in the proximal tubules.

(2) Hypertriglyceridemia

• Increased production of glycerol 3-phosphate, the key substrate for triglyceride synthesis in the liver

(3) Serum aspartate aminotransferase (AST) greater than serum alanine aminotransferase (ALT) in liver disease (90% sensitivity, 75% specificity)

• Alcohol is a mitochondrial toxin that causes release of AST, which is located in the mitochondria.


Alcohol liver disease: AST > ALT; ↑ GGT


(4) Increased serum γ-glutamyltransferase (GGT; 75% sensitivity, 90% specificity)

• Alcohol induces hyperplasia of the smooth endoplasmic reticulum causing increased synthesis of GGT.

C. Other drugs of abuse

• Sedatives, stimulants, hallucinogens (Table 6-3)

1. CNS effects of long-term drug abuse

a. Damage to neurotransmitter receptor sites

b. Cerebral atrophy (e.g., alcohol)

2. Complications of intravenous drug use (IVDU)

a. Hepatitis B


Table 6-3 Selected Drugs of Abuse and Their Effects

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* Used medically to decrease nausea and vomiting associated with chemotherapy and to decrease intraocular pressure in glaucoma.



Hepatitis B: most common systemic complication of IVDU


b. HIV

c. Infective endocarditis (tricuspid/aortic valves)

• Caused by Staphylococcus aureus

d. Tetanus

• Complication of “skin popping” using a dirty needle

D. Adverse effects of therapeutic drug use (Table 6-4)

1. Acetaminophen

a. Conversion to free radicals in the liver

b. May result in damage to the liver (e.g., fulminant hepatitis)

c. May result in damage to the kidneys (e.g., renal papillary necrosis)

2. Aspirin (acetylsalicylic acid) overdose

a. General symptoms

• Tinnitus, vertigo, change in mental status (confusion, seizures), tachypnea

b. Acid-base disorders

(1) Respiratory alkalosis may occur initially (within 12–24 hours).

(a) Due to direct stimulation of the respiratory center

(b) Respiratory acidosis may occur as a late finding.

(2) Shift to metabolic acidosis with an increased anion gap

• Occurs more often in children

(3) Mixed primary respiratory alkalosis and metabolic acidosis

• Occurs more often in adults

c. Hyperthermia


Table 6-4 Adverse Reactions Associated with Therapeutic Drug USE

image


Salicylate poisoning: danger of hyperthermia


(1) Salicylates damage the inner mitochondrial membrane.

(2) Oxidative energy is released as heat, not as adenosine triphosphate.

d. Hemorrhagic gastritis, fulminant hepatitis

Related posts:

  1. White Blood Cell Disorders
  2. Vascular Disorders
  3. Genetic and Developmental Disorders
  4. Red Blood Cell Disorders

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Jun 25, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Environmental Pathology

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