Week 11 Pathology

Tobacco.

  • Major diseases
    • Lung cancer
      • Upto 90% of all lung cancers are attributable to tobacco.
      • Cigarette smoking with asbestos exposure has a synergistic effect on rates of lung cancer
    • Cardiovascular disease
      • Smoking is a multiplicative RF with HTN, high Chol for dev of atherosclerosis and coronary artery disease.
    • Chronic respiratory diseases
      • Also increases respiratory infections, exacerbated asthma
  • Maternal smoking
    • Fetal hypoxia–> low birth wt, prematurity, increased incidence of spontaneous abortion
  • Impairs healing
  • Smoke has a particulate phase(tar) and gas phase.
    • It has 43 known carcinogens and carcinogenic metals – arsenic, nickel, cadmium
    • Irritants – nitrogen dioxide, formaldehyde
    • Cilia toxins – cyanide, CO
    • Nicotine – readily crosses BBB and stimulated the nicotinic receptors–> increased HR, BP, CO, coronary artery flow, Fatty acid mobilisation. Nicotine is responsible for the tobacco addiction.

 

Alcohol: Organ effects.

Organ Lesion Mechanism
Liver Fatty changeAcute hepatitisAlcoholic cirrhosis Toxicity
Nervous system Wernicke syndromeKorsakoff syndromeCerebellar degenerationPeripheral neuropathy Thiamine defToxicity and thiamine defNutritional defThiamine deficiency
Cardiovasc system CardiomyopathyHTN ToxicityVasopressor
Gastrointestinal GastritisPancreatitis ToxicityToxicity
Skeletal Muscle Rhabdomyolysis Toxicity
Reproductive sys Testicular atrophySpont abortion Unkown
Fetal alcohol syndrome Growth retardationMental retardationBirth defect toxicity

 

 

Adverse drug reactions: Types.

Mecahnism Example Adverse effect
Overdose –> toxicity Acetaminophen Liver necrosis and failur
Predictable due to pharmacological mech NSAIDs Peptic ulcer
Altered drug metabolism due to:

  • cytochrome P450 CYP2C9 variants
  • cytochrome P450 CYP2D6 variants
  • OCP
  • Some antipsychotics
BleedingExcess sedation, parkinsonism
Idiopathic Chloramphenicol Aplastic anaemia

 

OCP – Oral Contraceptive Pills

  • Most combine synthetic ethinyl estradiol or mestranol with a progestin
  • Past or current use of OCP isnt associated with an increased risk of Breast cancer. It lowers rates of ovarian and endometrial cancer.
  • Women infected with HPV and also using OCP have an increased risk of cervical cancer.
  • Side Effects
    • VTE/PE
    • Risk of MI is increased in women >35yo and smoker who take OCP.
    • Ischaemic stroke
    • Benign liver tumours

 

Air pollution (yes it has been asked !)

Pollutant Population at risk Effects
Ozone Health adults and childrenAthletes/ outdoor workers

Asthmatics

Decreased lung functionIncreased airway reactivity

Lung inflammation

Decreased exercise tolerance

Increased hospitalisations

Nitrogen dioxide Health adultsAsthmatics

Children

Increased airway reactivityDecreased lung function

Increased resp infections

Sulfur dioxide Healthy adultsPatients with chronic lung disease

Asthmatics

Increased resp symptomsIncreased mortality

Increased hospitalisations

Decreased lung function

Acid aerosols Healthy adultsChildren

Asthmatics

Altered mucocilliary clearanceIncreased resp infections

Decreased lung function

Increased hospitalisations

Particulates ChildrenPts with chronic lung/heart disease

Asthmatics

Increased resp infectionsDecreased lung function

Excess mortality

Increased attacks.

 

Lead poisoning

  • Sources of exposure
    • Occupational – usually inhalational – spray painting, foundry work, battery burning, mining
    • Non occupational – water supply, paint dust, flakes, house dust, urban soil, newsprint, car exhaust
    • Children can absorb lead more easily than adults
  • Complications
    • Accumulates in bone and developing teeth (t1/2 of 30yrs)
    • hypochromic anaemia
    • Competes with Ca2+
    • Adult – memory loss, headache
    • Child – mental deterioration, encephalopathy
    • Gingiva – lead line
    • Deposits in epiphyses of children’s bones
    • Demyelination peripheral nerves
    • Renal – chronic tubulointerstitial disease
    • Abdo pain

Radiation injuries

  • Radiowaves – thermal effects, cataracts
  • Microwaves – lens opacities
  • Infrared – cataracts
  • Visible light – retinal burns
  • UV – skin burns, cancer

 

Acute and delayed Cx of ionizing radiation

Organ Acute Delayed
Bone Atrophy Hypoplasia, leukaemia
Heart Interstitial fibrosis
Lung Oedema, endothelial and epithelial cell death Interstital and intra alveolar fibrosis, cancer
Skin Erythema Fibrosis of dermis, cancer
GIT Oedema, mucosal ulcers Ulcers, fibrosis, strictures, adhesions, cancer
Brain Oedema, necrosis Tubular atrophy
Testis Necrosis Tubular atrophy
Ovary Atresia of follicles Stromal fibrosis
Thymus Atrophy Lymphoma

 

Mechanical injuries / Wounds

  • Laceration is an irregular tear in the skin produced by overstretching
  • Incision is a cut made – skin edges are not traumatised or haemorrhagic.
  • Contusion – injury caused by blunt force that damages small blood vessels and causes interstitial bleeding, usually without disruption to the continuity of the tissue.

 

Burns

  • Partial is painful, can be wet or dry – skin appendages such as hair follicles and sweat glands survive
  • Full- painless, loss of skin appendages, wound contractures and cannot regenerate normal.
  • Rule of 9s – head 9%, UL 9% each, LL 18% each, trunk 36%, genitals 1% (percentage of total surface area)
  • Fluid resus crucial in initial resus
    • Need fluid resus if > 15% total body area burnt
  • Parklands formula to find 24hr amount required- give half within 8hrs of injury then the remainder for rest of remaining 24hrs.
  • Formula: 4ml/burn %/kg,
  • Needs tetanus and Abx if infected.
  • Most common cause of infection is pseudomonas aeruginosa.

 

Cold injury

  • Bradycardia, AF, increased blood viscosity, peripheral vasoconstriction and resulting tissue hypoxia/infarction–> gangrene or frostbite.
  • Slow chilling can induce vasoconstriction and increased permeability –> eg trench foot
  • Atrophy and fibrosis may follow
  • Sharp drop in temp can lead to vasoconstriction and increased viscosity –> infarction and damage to peripheral nerves. Oedema only develops after there is reperfusion.

 

Electrical injuries.

  • May have no effect
  • Cardiac arrest via disruption to neuro-reg impulses
  • Thermal injury to tissues in the path of the electrical current.
  • Degree of injury depends on the intensity of the current as well as the tissue resistance.
  • More resistance leads to more heat generation. Resistance reduces with increasing water content.
  • Dry skin may cause a skin burn. Wet skin will transmit the electricity so it can interupt regulatory pathways–> ventricular fibrillation etc.

 

Blast injuries.

  • Air blast – violent increase in pressure in atmosphere
    • Compression wave may collapse the thorax or violently compress the abdomen –> rupture of internal organs. The pressure wave may enter airways and damage alveoli.
    • Then there is a wave of decreased pressure which can cause sudden expansion of the abdomen or thorax –> rupture of intestines or lungs.
  • Immersion blast – violent increase in pressure in water. Injuries are similar to air blast.

 

Decompression sickness/Caisson Disease

  • Occurs in people who are spending long periods in high pressure areas eg underwater workers and then have a rapid decompression. Symptoms seen in hours after ascent.
  • Solubility increases with increasing atmospheric pressure so more O2 and Nitrogen dissolve in blood as you spend time in high pressure. Then when you rapidly decompress –> minute bubbles precipitate in blood and tissues leading to
    • Gas emboli in lungs –> breathing difficulties and severe substernal pain
    • Periarticular gas precipitates –> bends
    • CNS –> headache, visual disturbances, behavioural disorientation
    • Inner ear –> vertigo and staggers
    • Caissons disease of bone – foci of aseptic necrosis (embolic occlusion of vascular supply), this can manifest days later.

 

Malnutrition / Vitamins:

  • Malnutrition in Western society is seen in homeless people, low socioeconomic groups, chronic alcoholics, pts with acute or chronic illness may have higher nutritional requirements which are not being met, self imposed dietary restrictions (anorexia, vegans etc)
  • Malabsorption syndromes, genetic diseases, medications.
  • Protein energy malnutrition
    • Marasmus – chronic illness, develops over months, hx of wt loss, muscle wasting and absent subcut fat. Normal or mildly reduced serum proteins
    • Kwashiorkor – more acute catabolic illness, develops over weeks, pt has normal fat and muscle, pt has oedema and easily pluckable hair. Low serum albumin and poor prognosis.

 

Vitamins and Minerals

ADEK – fat soluble

 

Vitamins

Deficiency syndrome
A Night blindness, xeropthalmia, squamous metaplasia, vulnerability to infection
D Rickets, osteomalacia
E Spinocerebellar degeneration
K Bleeding
B1/thiamine Dry and wet Beri Beri, Wernicke’s syndrome.
B2/riboflavin Stomatitis, glossitis, dermatitis
Niacin Pellagra – dermatitis, dementia, diarrhoea
B6/pyridoxine Glossitis, dermatitis, peripheral neuropathy
B6/pyridoxine Glossitis, dermatitis, peripheral neuropathy
B12 Interferes with normal folate metabolism–> megaloblastic anaemia, degeneration of posterior spinal cord tracts
C Scurvy/collagen dysfunction – gum breakdown, teeth fall out
Folate Megaloblastic anaemia, Neural tube defects

Minerals

Iron Microcytic hypochromic anaemia
Zinc Growth retardation, infertility
Iodine Goitre and hypothyroidism
Copper Muscle weakness, neurological defects, hypopigmentations, abnormal collagen linking
Selenium Myopathy, rarely cardiomyopathy

Viva questions:

  • What are the main substances responsible for air pollution ?
  • What are the effects/complications of tobacco smoking
  • What types of adverse drug reactions are you aware of ?
  • What are the organ system effects of alcohol abuse ?
  • What is the difference between a partial-thickness and a full-thickness burn?
  • Tell me about the potential systemic consequences of a major burn
  • Tell me about electrical injuries
  • Tell me about decompression sickness
  • Tell me about radiation injury