Cell Injury Flashcards
What can cause cell injury?
Hypoxia. Toxins. Physical agents: trauma, temp, pressure, electricity. Radiation. Microorganisms. Immune. Deficiencies.
What is the difference between hypoxia and ischemia?
Hypoxia = decreased oxygen.
Ischemia = decreased blood supply
Outline the 4 types of hypoxia
Hypoxaemia hypoxia = O2 arterial content low.
Anaemic hypoxia = decreased Hb ability to carry O2.
Ischaemic hypoxia = interrupted blood supply.
Histiocytic hypoxia = inability to utilise O2 due to disabled oxidative phosphorylation enzymes
Explain how the immune system can damage body cells?
Hypersensitivity = secondary injury to vigorous immune reaction.
Autoimmune reaction = fail to distinguish self
Which cell components are most susceptible to injury?
Cell membranes nucleus,
proteins,
mitochondria
What happens at a molecular level during hypoxia
Lower O2 = lower oxidative phosphorylation = lower ATP
1) failure of Na K ATPase pump = ion gradient lost = ions pour in = cell swelling.
2) raised glycolysis = lower pH.
3) lower protein synthesis = lipid deposition
Outline what occurs in prolonged hypoxia
Irreversible = massive influx of Ca2+ = activation of phospholipase, proteases, endonucleases
Explain what free radicals are and how they cause damage
Single unpaired electron in an outer orbit = unstable configuration that will react with other molecules
mutagenic = carcinogenic, lipid peroxidation, autocatalytic chain reaction
Name the 3 free radicals that are of particular biological significance in cells
OH (hydroxyl),
O2- (superoxide),
H2O2 (hydrogen peroxide)
How are radicals produced?
Oxidative phosphorylation, inflam, radiation, contact with unbound metals, drugs/chemicals
How does the body control free radicals
A, C, E vits donate electrons, metal carrier/storage proteins sequester iron/copper, enzymes neutralise
What are heat shock proteins?
Aim to mend mis-folded proteins
Describe the 3 ways injured/dying cells look like under a microscope
Pyknosis = irreversible condensation of nucleus chromatin
karyorrhexis = fragmentation of nucleus with chromatin distributed irregularly throughout cytoplasm.
karyolysis = dissolution of a cell nucleus
Describe what injured/dying cells look like under an electron microscope
Can now visualise organelles: irreversible =
myelin figures (damaged cell membrane collection of fat), lysis of ER, mitochondrial swelling, rupture of lysosomes, nucleus pyknosis, karyolysis or karyorrhexis
How can we diagnose cell death?
Testing cell function with uptake of dye, if alive = no dye due to impermeable cell membrane
Define apoptosis, necrosis and oncosis
Apoptosis = controlled cell death non-random DNA cleavage.
Necrosis = morphologic changes that occur after a cell has been dead for a period of time.
Oncosis = cell death with swelling, DNA cleaved in random lengths
What are the types of necrosis?
Coagulative: solid organs, protein denaturation.
Liquefactive: loose tissue, enzyme release = liquefaction of tissue.
Caseous: infections, structureless debris (cheese look).
fat necrosis: action upon fat by digestive enzymes, appear as white chalky deposits
Define gangrene
Necrosis visible to the naked eye
Define infarction
Necrosis caused by reduction in arterial blood flow
Define infarct
Area of necrotic tissue as a result of low arterial blood supply
What is the difference between wet and dry necrosis?
Dry = necrosis modified by exposure to air (coagulative necrosis).
Wet = necrosis by infection (liquefactive necrosis) (can be wet gas gangrene: presence of anaerobic bacteria that prod gas)
What are the causes of an infraction?
Thrombosis, embolism, blood supply twisting: sigmoid colon or spermatic cord
What is the difference between a thrombus and an embolism?
Thrombus: formation of a solid mass of blood within the circulatory system
Embolism: blockage of a blood vessel by solid, liquid or gas at a site distant from its origin
How and why does infarcted tissue look different?
Can be white = occlusion of end artery in solid tissue.
Red = dual blood supply in loose tissue.
Outline ischaemia-reperfusion injury
Damage can be worse if blood flow returns to a damaged but not yet necrotic tissue = prod of oxygen radicals, increased neutrophils so increased inflam, delivery of complement proteins
When does apoptosis occur physiologically and pathologically?
Maintain a steady state, embryogenesis, cytotoxic T cells killing virus infected/neoplastic cells, damaged cells, GvsH disease
Name the 3 stages of apoptosis
Initiation: activate caspases,
execution,
degradation and phagocytosis
How is the intrinsic and extrinsic pathway resulting in apoptosis activated?
Intrinsic = p53, cytochrome C (released from mitochondria = activation of caspases).
Extrinsic = TNFα (secreted by T killer cells)
What can accumulate in a cell?
Water, electrolytes, lipids, carbs, proteins, pigments
When do lipids accumulate?
= steatosis
Alcohol, DM, obesity, toxins, when cholesterol cannot be eliminated by the liver
In what conditions do proteins accumulate in cells?
Alcoholic liver disease,
alpha1-antitrypsin def = accum in ER, not folded correctly
When do pigments accum in cells?
Exogenous = Urban air pollutant and tattooing - phagocytosed by macrophages.
Endogenous = haemosiderin, bilirubin
Name an example of an accumulation of endogenous pigments?
Hereditary haemochromatosis: genetically inherited, increased absorption = accum of iron, often associated with liver/pancreas scarring
What is accumulating in jaundice?
Bilirubin – breakdown prod of haem
Outline the mechanisms of intracellular accumulation
Abnormal met, alteration in protein folding/transport, enzyme def, inability to degrade phagocytosed particles
What are 2 the classification of calcified tissue?
Dystrophic: localised (abnormal Ca met/conc).
Metastatic: generalised (hypercalcaemia secondary to disturbances in Ca met)
What causes hypercalcaemia?
Increase PTH: primary = parathyroid hyperplasia/tumour, secondary = renal failure, ectopic = secretion of PTH-related protein by malignant tumours.
Destruction of bone tissue: tumours, paget’s diseases (increased bone turnover), immobilisation
What are the effects and lab diagnosis of excessive alcohol intake?
effects = liver cirrhosis, failure
lab = AST, ALT, CRP, GGTP
What is the presentation and lab diagnosis of Hep B?
pres = jaundice, fatigue, abdo pain, nausea/vomiting
lab = serology, AST, ALT, LDH
What is the lab diagnosis of acute pancreatitis
lipase, amylase
Outline hereditary haemochromotosis
genetically inherited, increased absorption = accum of iron, often associated with liver/pancreas scarring
pres = Fatigue, malaise, joint and bone pain, liver cirrhosis
complications = organ damage
treat = bloodletting, desferrioxamine: iron-chelating compound
What is alpha-1 antitrypsin def?
pathophysiology = liver prod incorrectly folded alpha-1 antitrypsin = accum in ER
pres = shortness of breath, wheezing, chackles
complications = proteases in lung go unchecked = emphysema
What is coal-workers pneumoconiosis?
Inhaled coal dust builds up, cannot be removed by the body = inflammation, fibrosis, necrosis
pres = cough, dyspnea, lung function impairment
complications = fibrosis, emphysema
