Cellular Injury & Defects Flashcards

1
Q

What causes cell hypoxia?

A

Ischemia or inadequate oxygen carrying capacity of blood

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2
Q

Name 7 causes of cellular injury

A
  • hypoxia
  • physical agents
  • chemical agents/drugs
  • infectious agents
  • immunological reactions
  • genetic defects
  • nutritional imbalances
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3
Q

A patient’s liver cells responds to toxic injury, what cellular adaptation is occurring?

A

Focal pathological hyperplasia

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4
Q

A patient with a history of cardiac injury has a cellular reaction occurring with his remaining cardiac myocytes, what cellular adaptation is occurring?

A

Focal pathological hypertrophy

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5
Q

A chronically bedridden patient is most likely experiencing ______________ of his quadriceps muscles

A

Atrophy

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6
Q

A patient who is exercising regularly would expect what normal cellular response?

A

Physiological hypertrophy

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7
Q

Response of bronchial epithelium in a patient who chronically smokes would expect what cellular adaptation?

A

Squamous metaplasia

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8
Q

Name 4 universal biomechanical themes of cellular injury

A
  • Lack of oxygen
  • Increased intracellular calcium
  • Depletion of ATP
  • Defects in membrane permeability
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9
Q

What can lack of oxygen or excess oxygen cause in a cell?

A

Decreased synthesis of ATP leading to cell death

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10
Q

What does an increase in intracellular calcium or loss of calcium homeostasis cause?

A

Activation of calcium dependent enzymes

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11
Q

What does depletion of ATP cause?

A

Loss of membrane function and intracellular processes

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12
Q

What forms of cellular accumulation are reversible?

A

Cellular swelling and steatosis

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13
Q

What cellular events occur before the point of no return from hypoxic/ischemic injury?

A
  • compromised aerobic respiration
  • increased rate of anaerobic glycolysis
  • decreased cellular pH
  • decreased ATP -> x mito-> x Na/K ATPase pump -> H2O in = acute cellular swelling
  • detachment of ribosomes from RER
  • mitochondrial swelling
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14
Q

What cellular events occur due to hypoxia/ischemia after the point of no return, meaning they are irreversible?

A
  • Vacuolization of mitochondria
  • Rupture of lysosomes/activation of Ca dependent enzymes
  • Nuclear changes (pyknosis, karryorrhexis, karyolysis)
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15
Q

What enzymes can be detected in the blood after lysosomes rupture indicating cell death?

A

Lactate dehydrogenase and creatine kinase

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16
Q

What is mitochondrial vacuolization?

A

When a lysosome fuses with mitochondria and causes bursting and swelling resulting in cell death

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17
Q

What is pyknosis?

A

Small, shrunken, dark nucleus indicating irreversible cell injury

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18
Q

What is karryorrhexis?

A

Fragmented nucleus indicating irreversible cell injury

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19
Q

What is karyolysis?

A

Faded nucleus indicating irreversible cell injury

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20
Q

What enzymes are you looking for when taking a blood test for a possible heart attack patient?

A

High levels of troponin I in the blood as well as elevated levels of creatine kinase and lactate dehydrogenase

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21
Q

What is free radical induced injury?

A

A final common pathway in a variety of cell processes

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22
Q

Name 4 examples of cellular processes which lead to free radical induced injury

A
  • chemical & radiation injury
  • cellular aging
  • O2 toxicity
  • microbial killing by phagocytes
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23
Q

What does free radical induced injury consist of?

A

chemical species that are highly reactive and unstable (uneven e-)

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24
Q

What does free radical damage result in?

A

Lipid peroxidation of cell membranes
Oxidative modification of cell proteins
Damage to cell DNA

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25
Q

What are important attributes of hydrogen peroxide (H2O2)?

A

Forms free radicals via iron catalyzed Fenton reaction
Diffuses widely within a cell

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26
Q

What enzymes convert O2 ——> O2 - (Superoxide anion)?

A

Xanthine oxidase, NADPH oxidase

27
Q

What enzyme converts O2- ——> H2O2? What is the coenzyme?

A

Enzyme = Superoxide Dismutase (SOD), Coenzyme = H2O

28
Q

What enzyme converts H2O2 ——> H2O + O2?

A

Catalase

29
Q

What can glutathione do to free radicals?

A

Harmless conversion of H2O2 ——> H20 + O2

30
Q

What vitamins are antioxidants?

A

Vitamin C and E

31
Q

What are some things that may cause free radical production?

A

Radiation, mutagens, ischemic attacks, oxygen therapy, mitochondrial metabolism

32
Q

What are important attributes of superoxide anion (O2-)?

A

Generated by leaks in the electron transport chain and some cytosolic reactions

33
Q

What are important attributes of hydroxyl radicals (•OH)?

A
  • Generated from H2O2 via iron catalyzed Fenton reaction
  • Most responsible for attack on macromolecules
34
Q

Which free radical is most responsible for attacks on macromolecules?

A

Hydroxyl radical

35
Q

What are important attributes of peroxynitrite (ONOO•)?

A

Formed from the reaction of nitric oxide (NO) with superoxide anion (O2-) to damage macromolecules

36
Q

What reaction forms peroxynitrite?

A

Nitric oxide (NO) and superoxide anion (O2-)

37
Q

What are lipid peroxide radicals (RCOO•)?

A

Organic radicals produced during lipid peroxidation

38
Q

How is hypochlorous acid (HOCl) produced?

A

By macrophages and neutrophils during respiratory bursts that accompany phagocytosis

39
Q

What are symptoms of trisomy 21 (Down Syndrome)?

A

Decreased IQ
Simian crease
Protruding tongue and epicanthic folds
Tetralogy of Fallot (Congenital heart anomaly)

40
Q

What are symptoms of Trisomy 18 (Edward’s Syndrome)?

A

Severe cardiac malformations
Rocker-bottom feet, clenched hands, low-set ears
Majority die within one year

41
Q

What are symptoms of Trisomy 13 (Patau Syndrome)?

A

Severe cognitive and growth delay
Cleft lip and palate
Nervous system and cardiac malformations

42
Q

What causes Cri-du-chat syndrome?

A

5p- (5p minus) syndrome characterized by deletion of portion of the p-arm on
chromosome 5

43
Q

What are the symptoms of Cri-Du-Chat syndrome?

A
  • Infants possess high-pitched cry that sounds like a cat
  • intellectual disability and delayed development, microcephaly, low birth weight, and weak muscle tone (hypotonia) in infancy
  • Distinctive facial features: widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face
  • Several organ defects
44
Q

What causes Kleinfelter syndrome?

A

Males possessing an extra X chromosome

45
Q

What are symptoms of Kleinfelter syndrome?

A

Male hypogonadism and infertility due to lack of androgens
Tall, thin legs
High pitched voice and gynecomastia (breast development)

46
Q

What causes Turner’s syndrome?

A

Presence of only one X chromosome in females

47
Q

What are symptoms of Turner’s syndrome?

A
  • Females with amenorrhea and sterility
  • short stature, webbed neck
48
Q

What are two examples of inborn errors of amino acid metabolism?

A

Phenylketonuria (PKU) and Alkaptonuria (Ochronosis)

49
Q

What causes phenylketonuria?

A

Autosomal recessive deficiency of the hepatic enzyme phenylalanine hydroxylase leading to excess phenylalanine

50
Q

What enzyme breaks down phenylalanine ——> tyrosine

A

Phenylalanine hydroxylase

51
Q

What are the symptoms of phenylketonuria?

A

Progressive mental deterioration, seizures, musty odor from phenylacetic acid
Fair skin, blond hair, blue eyes

52
Q

What causes alkaptonuria?

A

Defect in the enzyme homogentisate 1,2-dioxygenase (HGD), which participates in tyrosine degradation.

53
Q

What is alkaptonuria also known as?

A

Ochronosis

54
Q

What does alkaptonuria (Ochronosis) cause?

A

Elevated levels of tyrosine resulting in arthropathy

55
Q

How can you diagnose alkaptonuria?

A

Urine test to demonstrate oxygenation of homogentisic acid (urine appears dark)

56
Q

What is dystrophic calcification?

A

Calcium deposition in dead and necrotic tissues

57
Q

What type of calcification would be expected to occur after an Achilles’ tendon repair?

A

Dystrophic calcification

58
Q

What type of calcification occurs in valves, tendons, and ligaments?

A

Dystrophic calcification

59
Q

What type of calcification causes calcific aortic stenosis?

A

Dystrophic calcification

60
Q

What is metastatic calcification?

A

Calcium deposition in normal tissues (living) due to hypercalcemia

61
Q

What can cause metastatic calcification and hypercalcemia?

A

PTH-secreting tumour, causing hyperparathyroidism and increased osteoclast activity

62
Q

What causes Lesch-Nyhan syndrome?

A

X-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

63
Q

What are the symptoms of Lesch-Nyhan syndrome?

A
  • accumulation of uric acid in body fluids
  • neurological signs: poor muscle control, cognitive disability in 1st year of life
  • 2nd year: self-mutilating behaviours (lip & finger biting)
  • basal ganglia damage leads to writhing movements
  • poor use of vit B12 may lead to megaloblastic anemia
64
Q

What is accumulation of uric acid in body fluids associated with?

A

Gout and kidney dysfunction