Cellular Injury & Defects

Question 1

What causes cell hypoxia?

Answer 1

Ischemia or inadequate oxygen carrying capacity of blood

Question 2

Name 7 causes of cellular injury

Answer 2

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

Question 3

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

Answer 3

Focal pathological hyperplasia

Question 4

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

Answer 4

Focal pathological hypertrophy

Question 5

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

Answer 5

Atrophy

Question 6

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

Answer 6

Physiological hypertrophy

Question 7

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

Answer 7

Squamous metaplasia

Question 8

Name 4 universal biomechanical themes of cellular injury

Answer 8

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

Question 9

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

Answer 9

Decreased synthesis of ATP leading to cell death

Question 10

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

Answer 10

Activation of calcium dependent enzymes

Question 11

What does depletion of ATP cause?

Answer 11

Loss of membrane function and intracellular processes

Question 12

What forms of cellular accumulation are reversible?

Answer 12

Cellular swelling and steatosis

Question 13

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

Answer 13

• 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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

Lactate dehydrogenase and creatine kinase

Question 16

What is mitochondrial vacuolization?

Answer 16

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

Question 17

What is pyknosis?

Answer 17

Small, shrunken, dark nucleus indicating irreversible cell injury

Question 18

What is karryorrhexis?

Answer 18

Fragmented nucleus indicating irreversible cell injury

Question 19

What is karyolysis?

Answer 19

Faded nucleus indicating irreversible cell injury

Question 20

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

Answer 20

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

Question 21

What is free radical induced injury?

Answer 21

A final common pathway in a variety of cell processes

Question 22

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

Answer 22

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

Question 23

What does free radical induced injury consist of?

Answer 23

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

Question 24

What does free radical damage result in?

Answer 24

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

Question 25

What are important attributes of hydrogen peroxide (H2O2)?

Answer 25

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

Question 26

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

Answer 26

Xanthine oxidase, NADPH oxidase

Question 27

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

Answer 27

Enzyme = Superoxide Dismutase (SOD), Coenzyme = H2O

Question 28

What enzyme converts H2O2 ——> H2O + O2?

Answer 28

Catalase

Question 29

What can glutathione do to free radicals?

Answer 29

Harmless conversion of H2O2 ——> H20 + O2

Question 30

What vitamins are antioxidants?

Answer 30

Vitamin C and E

Question 31

What are some things that may cause free radical production?

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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

Answer 33

- Generated from H2O2 via iron catalyzed Fenton reaction - Most responsible for attack on macromolecules

Question 34

Which free radical is most responsible for attacks on macromolecules?

Answer 34

Hydroxyl radical

Question 35

What are important attributes of peroxynitrite (ONOO•)?

Answer 35

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

Question 36

What reaction forms peroxynitrite?

Answer 36

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

Question 37

What are lipid peroxide radicals (RCOO•)?

Answer 37

Organic radicals produced during lipid peroxidation

Question 38

How is hypochlorous acid (HOCl) produced?

Answer 38

By macrophages and neutrophils during respiratory bursts that accompany phagocytosis

Question 39

What are symptoms of trisomy 21 (Down Syndrome)?

Answer 39

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

Question 40

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

Answer 40

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

Question 41

What are symptoms of Trisomy 13 (Patau Syndrome)?

Answer 41

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

Question 42

What causes Cri-du-chat syndrome?

Answer 42

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

Question 43

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

Answer 43

- 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

Question 44

What causes Kleinfelter syndrome?

Answer 44

Males possessing an extra X chromosome

Question 45

What are symptoms of Kleinfelter syndrome?

Answer 45

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

Question 46

What causes Turner's syndrome?

Answer 46

Presence of only one X chromosome in females

Question 47

What are symptoms of Turner's syndrome?

Answer 47

- Females with amenorrhea and sterility - short stature, webbed neck

Question 48

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

Answer 48

Phenylketonuria (PKU) and Alkaptonuria (Ochronosis)

Question 49

What causes phenylketonuria?

Answer 49

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

Question 50

What enzyme breaks down phenylalanine ——> tyrosine

Answer 50

Phenylalanine hydroxylase

Question 51

What are the symptoms of phenylketonuria?

Answer 51

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

Question 52

What causes alkaptonuria?

Answer 52

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

Question 53

What is alkaptonuria also known as?

Answer 53

Ochronosis

Question 54

What does alkaptonuria (Ochronosis) cause?

Answer 54

Elevated levels of tyrosine resulting in arthropathy

Question 55

How can you diagnose alkaptonuria?

Answer 55

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

Question 56

What is dystrophic calcification?

Answer 56

Calcium deposition in dead and necrotic tissues

Question 57

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

Answer 57

Dystrophic calcification

Question 58

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

Answer 58

Dystrophic calcification

Question 59

What type of calcification causes calcific aortic stenosis?

Answer 59

Dystrophic calcification

Question 60

What is metastatic calcification?

Answer 60

Calcium deposition in normal tissues (living) due to hypercalcemia

Question 61

What can cause metastatic calcification and hypercalcemia?

Answer 61

PTH-secreting tumour, causing hyperparathyroidism and increased osteoclast activity

Question 62

What causes Lesch-Nyhan syndrome?

Answer 62

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

Question 63

What are the symptoms of Lesch-Nyhan syndrome?

Answer 63

- 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

Question 64

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

Answer 64

Gout and kidney dysfunction