Cellular Injury & Defects Flashcards
What causes cell hypoxia?
Ischemia or inadequate oxygen carrying capacity of blood
Name 7 causes of cellular injury
- hypoxia
- physical agents
- chemical agents/drugs
- infectious agents
- immunological reactions
- genetic defects
- nutritional imbalances
A patient’s liver cells responds to toxic injury, what cellular adaptation is occurring?
Focal pathological hyperplasia
A patient with a history of cardiac injury has a cellular reaction occurring with his remaining cardiac myocytes, what cellular adaptation is occurring?
Focal pathological hypertrophy
A chronically bedridden patient is most likely experiencing ______________ of his quadriceps muscles
Atrophy
A patient who is exercising regularly would expect what normal cellular response?
Physiological hypertrophy
Response of bronchial epithelium in a patient who chronically smokes would expect what cellular adaptation?
Squamous metaplasia
Name 4 universal biomechanical themes of cellular injury
- Lack of oxygen
- Increased intracellular calcium
- Depletion of ATP
- Defects in membrane permeability
What can lack of oxygen or excess oxygen cause in a cell?
Decreased synthesis of ATP leading to cell death
What does an increase in intracellular calcium or loss of calcium homeostasis cause?
Activation of calcium dependent enzymes
What does depletion of ATP cause?
Loss of membrane function and intracellular processes
What forms of cellular accumulation are reversible?
Cellular swelling and steatosis
What cellular events occur before the point of no return from hypoxic/ischemic injury?
- 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
What cellular events occur due to hypoxia/ischemia after the point of no return, meaning they are irreversible?
- Vacuolization of mitochondria
- Rupture of lysosomes/activation of Ca dependent enzymes
- Nuclear changes (pyknosis, karryorrhexis, karyolysis)
What enzymes can be detected in the blood after lysosomes rupture indicating cell death?
Lactate dehydrogenase and creatine kinase
What is mitochondrial vacuolization?
When a lysosome fuses with mitochondria and causes bursting and swelling resulting in cell death
What is pyknosis?
Small, shrunken, dark nucleus indicating irreversible cell injury
What is karryorrhexis?
Fragmented nucleus indicating irreversible cell injury
What is karyolysis?
Faded nucleus indicating irreversible cell injury
What enzymes are you looking for when taking a blood test for a possible heart attack patient?
High levels of troponin I in the blood as well as elevated levels of creatine kinase and lactate dehydrogenase
What is free radical induced injury?
A final common pathway in a variety of cell processes
Name 4 examples of cellular processes which lead to free radical induced injury
- chemical & radiation injury
- cellular aging
- O2 toxicity
- microbial killing by phagocytes
What does free radical induced injury consist of?
chemical species that are highly reactive and unstable (uneven e-)
What does free radical damage result in?
Lipid peroxidation of cell membranes
Oxidative modification of cell proteins
Damage to cell DNA
What are important attributes of hydrogen peroxide (H2O2)?
Forms free radicals via iron catalyzed Fenton reaction
Diffuses widely within a cell
What enzymes convert O2 ——> O2 - (Superoxide anion)?
Xanthine oxidase, NADPH oxidase
What enzyme converts O2- ——> H2O2? What is the coenzyme?
Enzyme = Superoxide Dismutase (SOD), Coenzyme = H2O
What enzyme converts H2O2 ——> H2O + O2?
Catalase
What can glutathione do to free radicals?
Harmless conversion of H2O2 ——> H20 + O2
What vitamins are antioxidants?
Vitamin C and E
What are some things that may cause free radical production?
Radiation, mutagens, ischemic attacks, oxygen therapy, mitochondrial metabolism
What are important attributes of superoxide anion (O2-)?
Generated by leaks in the electron transport chain and some cytosolic reactions
What are important attributes of hydroxyl radicals (•OH)?
- Generated from H2O2 via iron catalyzed Fenton reaction
- Most responsible for attack on macromolecules
Which free radical is most responsible for attacks on macromolecules?
Hydroxyl radical
What are important attributes of peroxynitrite (ONOO•)?
Formed from the reaction of nitric oxide (NO) with superoxide anion (O2-) to damage macromolecules
What reaction forms peroxynitrite?
Nitric oxide (NO) and superoxide anion (O2-)
What are lipid peroxide radicals (RCOO•)?
Organic radicals produced during lipid peroxidation
How is hypochlorous acid (HOCl) produced?
By macrophages and neutrophils during respiratory bursts that accompany phagocytosis
What are symptoms of trisomy 21 (Down Syndrome)?
Decreased IQ
Simian crease
Protruding tongue and epicanthic folds
Tetralogy of Fallot (Congenital heart anomaly)
What are symptoms of Trisomy 18 (Edward’s Syndrome)?
Severe cardiac malformations
Rocker-bottom feet, clenched hands, low-set ears
Majority die within one year
What are symptoms of Trisomy 13 (Patau Syndrome)?
Severe cognitive and growth delay
Cleft lip and palate
Nervous system and cardiac malformations
What causes Cri-du-chat syndrome?
5p- (5p minus) syndrome characterized by deletion of portion of the p-arm on
chromosome 5
What are the symptoms of Cri-Du-Chat syndrome?
- 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
What causes Kleinfelter syndrome?
Males possessing an extra X chromosome
What are symptoms of Kleinfelter syndrome?
Male hypogonadism and infertility due to lack of androgens
Tall, thin legs
High pitched voice and gynecomastia (breast development)
What causes Turner’s syndrome?
Presence of only one X chromosome in females
What are symptoms of Turner’s syndrome?
- Females with amenorrhea and sterility
- short stature, webbed neck
What are two examples of inborn errors of amino acid metabolism?
Phenylketonuria (PKU) and Alkaptonuria (Ochronosis)
What causes phenylketonuria?
Autosomal recessive deficiency of the hepatic enzyme phenylalanine hydroxylase leading to excess phenylalanine
What enzyme breaks down phenylalanine ——> tyrosine
Phenylalanine hydroxylase
What are the symptoms of phenylketonuria?
Progressive mental deterioration, seizures, musty odor from phenylacetic acid
Fair skin, blond hair, blue eyes
What causes alkaptonuria?
Defect in the enzyme homogentisate 1,2-dioxygenase (HGD), which participates in tyrosine degradation.
What is alkaptonuria also known as?
Ochronosis
What does alkaptonuria (Ochronosis) cause?
Elevated levels of tyrosine resulting in arthropathy
How can you diagnose alkaptonuria?
Urine test to demonstrate oxygenation of homogentisic acid (urine appears dark)
What is dystrophic calcification?
Calcium deposition in dead and necrotic tissues
What type of calcification would be expected to occur after an Achilles’ tendon repair?
Dystrophic calcification
What type of calcification occurs in valves, tendons, and ligaments?
Dystrophic calcification
What type of calcification causes calcific aortic stenosis?
Dystrophic calcification
What is metastatic calcification?
Calcium deposition in normal tissues (living) due to hypercalcemia
What can cause metastatic calcification and hypercalcemia?
PTH-secreting tumour, causing hyperparathyroidism and increased osteoclast activity
What causes Lesch-Nyhan syndrome?
X-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
What are the symptoms of Lesch-Nyhan syndrome?
- 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
What is accumulation of uric acid in body fluids associated with?
Gout and kidney dysfunction
