MS1, Block 2 Cell/Tissue Injury

  1. Atrophy
    decrease in number/size of cells
  2. Metaplasia
    change in cell type
  3. Hyperplasia
    increase in number of cells
  4. Hypertrophy
    increase in cell size (skeletal mm usually)
  5. Dysplasia
    when metaplasia or hyperplasia goes wrong
  6. Injuries to cell that are reversible
  7. 1. Cell swelling
    • 2. Bleb in cell membrane
    • 3. Dispersion of ribosomes from ER
    • 4. Clumping of chromatin
  8. Injuries that are insurmountable causing cell death
  9. 1. Cytoplasmic changes
    2. Nuclear changes (determinant of cell death)
  10. Cytoplasmic changes (3 of them)
  11. a. Homogenization of cytoplasm
    • b. Cell particles break down
    • c. mRNAs gone so no longer has blue tinge
  12. 2. Nuclear changes (determinant of cell death)
    • a. Pyknosis=small, shrunken, hyperchromatic nucleus
    • b. Karyorrhexis=nucleus that has broken apart (nuclear dust)
    • c. Karyolysis=nucleus dissolves and disappears
  13. Pyknosis
    small, shrunken, hyperchromatic nucleus
  14. Karyorrhexis
    nucleus that has broken apart (nuclear dust)
  15. Karyolysis
    nucleus dissolves and disappears
  16. Apoptosis
  17. a. Active, programmed cell suicide (physiologic event)
    • b. Usually involves a single cell
    • c. Breakdown of cell particles and packaged into membrane bodies
    • d. Membrane bodies are taken up phagocytized by macrophages
    • e. Since cell particles are never free in the environment there is no inflammation
  18. Necrosis
  19. a. Pathologic event
    • b. Usually involves many cells
    • c. Severe changes in environment cause irreversible cell injuryCell membrane torn apart and cytoplasmic content is exposed to environment leading to inflammation
  20. 1. Ischemic: poor blood supply causing hypoxia
    2. Skin may ulcerate
    3. Can still see cell boundaries
    4. Dead cells will be replaced by regenerating cells or scar tissue
    5. No nuclear contentDefined boundary between dead and alive tissues because only tissues that are supplied by the damaged blood vessels will die
    Coagulative Necrosis
  21. 1. Ischemic
    2. Wet gangrene=tissue gets infected
    3. Dry gangrene= Desiccation of dead tissue on outer skin
    a. Common in diabetics
    4. Can occur on skin our internal organs
    Gangrenous Necrosis
  22. 1. No underlying outline of tissue because it is dissolved
    2. Necrotic tissue + inflammatory cells=abscess
    a. e.g. whiteheadsCan’t heal like rest of body (no scar tissue), just leaves holes in tissue (cysts)
    Liquefactive Necrosis
  23. 1. No identity of cells
    2. Homogenous material with no underlying sense of architecture
    3. Surrounded by lymphocytes and macrophages
    4. When you see this the differential diagnosis is almost always tuberculosis
    Caseous Necrosis
  24. a. Lipases break down fat cells
    b. Lipases abnormally activated in pancreas causes pancreatitis
    c. Nondescript, chalky deposits
    Enzymatic Fat Necrosis
  25. a. Macrophages try to phagocytize fat because they see lipids as foreign
    b. When they take in too much fat they rupture leaving behind a collection of fat that forms a mass
    Traumatic Fat Necrosis
  26. 1. Doesn’t have gross appearance that shows abnormality because it has immune etiology
    2. Occurs usually in the walls of vessels of small arteries and arterials
    3. Presence within wall of pinkish stuff that looks like fibrin (hence fibrinoid)Decreases the size of the lumen of the vessel
    Fibrinoid Necrosis
  27. 1. Serum calcium levels are normal but you get concentration of calcium in tissues leading to a calcium deposit in area of necrosis
    2. Because it is solid, it can prevent organs, like the heart, from beating properly
    Dystrophic Calcification
  28. 1. High serum calcium levels
    2. May be due to hyperparathyroidism
    3. Calcium is deposited in tissues to combat the high levels in serum
    4. Can be monitored by serum calcium levelsMay prevent lungs from expanding
    Metastatic Calcification
  29. Most common type of cell injury
  30. Metabolic Cell injury includes?
    • Hypoxia/anoxia (most common cause of metabolic injury)
    • Reactive Oxygen Species
  31. Hypoxia/anoxia types
    • Cardiovascular disease
    • Pulmonary disease
    • Anemia
    • Hemoglobinopathies
    • Ischemia (most common type of hypoxia)
    • Loss of ATP production/lactic acid build-up
    • Membrane ion pumps
    • Activation of Ca dependent phospholipases
  32. hemoglobin binds too tightly or not at all to oxygen
  33. difficulty perfusing tissues; causes nutrient deficiencies and accumulation of wastes
    Ischemia (most common cause of hypoxia)
  34. Loss of ATP production due to hypoxia/anoxia
    • switch to anaerobic respiration
    • Lactic acid build up
    • Chromatin clumping
  35. membrane ion pump failure due to hypoxia/anoxia
    membrane becomes more permeable so sodium and water enters cytoplasm, causes swelling
  36. activation of calcium dependent phospholipases due to hypoxia/anoxia causes
    damage to cell membrane and autolysis
  37. A. Are byproducts of normal metabolism; however they are toxic to cells
    B. Anrioxidants break them down
    C. Capable of structural alteration of proteins through inappropriate disulfide bonding – changes 3rd degree structure
    D. Break down of cell membrane through Lipid peroxidation
    Has the ability to directly damage DNA
    Free Radicals (reactive oxygen species)
  38. Types of mechanical trauma
    • abrasion
    • contusion
    • laceration
    • incision
    • avulsion
    • puncture wound
    • penetration wound
  39. frictional injury (ex – falling off bike on to concrete). Sometimes these are patterned (ex child abuse w/ electrical cord). Usually the injury is just partial ____ of the skin.
  40. bruise. Blunt force injury in which the skin is not broken but the underlying vessels are damaged and bleed. These can be dated by its color. As Hemoglobin is broken down it produces different pigments.
  41. Caused by blunt force injury. Occurs on the body where the skin is right up against bone and so the skin splits from blunt force. Nerves & vessels stretch and can be visualized as stringy-intact material. stay in part. They can occur internally (ex. Spleen)
  42. 1. caused by sharp instruments (scalpel or razor blade)
    a. No jagged edge as in laceration; sharp instrument cuts through nerves and vessels
    b. These will heal better than laceration; and with less scaring (doctors will usually make a laceration into this)
  43. tearing away of muscle or soft tissue (ex – hand being torn off)
  44. wound from knife
    puncture wound
  45. Able to distinguish between entrance/exit wound by the shape and by the presence or absence of powder
    Penetration wound
  46. 1. Increases free radical formation through interaction with water in cytoplasm;
    2. it’s the secondary affect of free radicals that alters cellular activity (example given of PAP smear normally with round nuclei and proper nucleus/cytoplasm ratio; in abnormal cell there is irregular nuclei and not enough cytoplasm - looks similar to malignant cell)
    3. Can cause acute changes (burns)
    4. Can cause chronic changes (caused by scarring of arterial vessels; blood perfusion decreases and eventually leads to necrosis)
    Ionizing Radiation (X-rays)
  47. Hematopoietic syndrome (200-500 rads)
    Gastrointestinal syndrome (500-1000 rads)
    Cerebral syndrome (>2500 rads)
    Systemic effects of ionizing radiation (X-rays) = we use ionizing radiation to therapeutically damage bone marrow.
  48. (200-500 rads) – caused by moderate amount of exposure i. Bone marrow is very sensitive to radiation (In bone marrow transplant, radiation is used to ablate native bone marrow so transplanted bone marrow canengraft ii. In this syndrome all of the bone marrow elements are decreased (RBC, WBC, platelets)
    Hematopoietic syndrome
  49. (500-1000 rads) caused by exposure to more than moderate level of radiation Causes ulceration of --- mucosa leading to diarrhea and bleeding
    Gastrointestinal syndrome
  50. (>2500 rads) caused by over exposure to radiation (brain damage and death)
    Cerebral syndrome
  51. what sun burn is caused by
    Non-ionizing radiation
  52. (near by temperature decreases)
    1. There are different phases of frostbite (Frostnip – superficial freezing of tissue, Superficial frostbite, Deep frostbite)
    2. Digits and tip of nose are most susceptible
    Localized hypothermia
  53. can be fatal
    1. When core body temperature drops, the brain actually interprets it as being hot (Deceased will be found with out clothes, because they think they are hot)
    Systemic Hypothermia
  54. are burns
    1. Blisters caused by heat
    2. 2nd degree burn – partial thickness burn
    3. 3rd degree burns – full thickness burns; penetrates skin and goes into dermis (doesn’t hurt because you burn the nerve). Will hurt more once healing begins. There are problems with infection (leading to sepsis)
    Localized hyperthermia
  55. partial thickness burn
    2nd degree burn
  56. Blisters caused by heat
    1st degree burns
  57. full thickness burns; penetrates skin and goes into dermis (doesn’t hurt because you burn the nerve). Will hurt more once healing begins. There are problems with infection (leading to sepsis)
    3rd degree burns
  58. 1. heat cramps
    2. Heat exhaustion - still has ability to perspire; normal or subnormal temperature; moist clammy skin
    3. Heat stroke (most severe) – lost ability to perspire; very high body temperature; dry hot skin
    Systemic Hyperthermia
  59. still has ability to perspire; normal or subnormal temperature; moist clammy ski
    Heat exhaustion
  60. lost ability to perspire; very high body temperature; dry hot skin
    Heat stroke (most severe)
  61. A. interrupts electrical activity of body (ability to breath, heart) will flow through without too much change
    1. Skin has higher resistance than organs (more moist) to passage of electricity
    2. Higher resistance causes burns
  62. low pressure to high pressure; visa versa (includes blast injuries from fireworks)
    Atmospheric Pressure
  63. side effects involved with ingesting drugs/chemicals (prescription and illicit)
    Chemical/Drug injury
  64. infections with microorganisms
    Biological Injury
  65. obesity; vitamin/protein deficiency
    Nutritional Injury
  66. type of Immunological injury
    rheumatoid arthritis
  67. Father of pathology, wrote a book 19th century “Cellular Pathology”
    1. Disease previously thought to be result of “ill humors”Virchow – disease comes from malfunctioning of cells
    Rudolph Virchow
  68. These are needed for what?
    A. Production of energy
    B. Synthesis of protein
    C. Maintenance of structure
    Ability to replicate
    cell viability
  69. steady state can be changed by these? (3)
    • physiological processes
    • pathological processes
  70. A. Change in cellular activity for a prolonged period of time
    B. Basically an establishment of a new steady state in order to maintain viability. This can be physiologic or pathologic
    Cellular adaptation
  71. literally means no nutrition
    caused by hormonal changes
    Muscular dystrophy is this in muscle
  72. Hypertrophy signs
    • § Fibers are thicker
    • § Nuclei are bigger and rectangular (boxcar nuclei)
    • § b/c cells can’t divide, they are forced to instead grow bigger
  73. look of hyperplastic follicles
    • a. architecture changes as cells pile up in number
    • b. thyroid is being asked to send out more thyroid hormone which leads to enlargement of thyroid gland (goiter)
  74. A. undergrowth
    1. not an adaptation, it is a developmental failure to develop to adult size
    ------ kidney doesn’t function properly
  75. A. no growth
    1. Developmental: failure to develop
  76. Replacement of (columnar) epithelium of airways with squamous epithelium (squamous metaplasia)
  77. irreversible change in tissue
  78. i. Lined by stratified squamous epithelium, like the skin but without keratin layer
    § Basal epithelium: cells divide then migrate towards the surface
    § Then keratinize the cytoplasm, nuclei lay over, get smaller and are sloughed off the surface
    § Cells in the upper levels of the epithelium look like the cells in the basal layer (this is not good)The cells are thinking “the only way I can survive is if I don’t play by the rules”
    cervical mucosa
  79. Cells can express injury by accumulations of different kinds of material in the cytoplasm. This can result from:
    • a. Increased production of normal cell products
    • b. Inability to excrete normal cell products
    • c. Interference with normal metabolic pathways
    • d. Accumulation of abnormal metabolic products (if lacking an enzyme)
    • e. Pinocytosis or phagocytosis of exogenous material
  80. cloudy swelling (----- in the cytoplasm)
    1. ----- vacuoles pushing the nuclei to the side (hydropic change) (very reversible)
    Water accumulation
  81. --- can accumulate in the cytoplasm of hepatocytes in the liver
    a. Can be caused by alcohol use or infection
    2. Stains to distinguish whether accumulation is water vs. ----
    3. Yellow colored liver is possible indicator of lipid accumulation
    ---- infiltration (referring to the heart) ---- streaks growing into the myocardium – are not changes to the myocardium cells, is actually --- in between cells, does not really have any clinical significance
    Lipid accumulation (fatty change / steatosis)
  82. looks similar to other accumulations, differentiate using glycogen stain
    Carbohydrate accumulation
  83. 1. intracellular hyaline (little red beady things)
    a. hyaline (non specific term) means “stuff that stains pink / reddish, homogenous” and pretty much means that it is protein
    b. renal tubular epithelial cells
    2. extracellular hyaline
    a. hyaline membrane disease
    protein accumulation
  84. a. hyaline (non specific term) means “stuff that stains pink / reddish, homogenous” and pretty much means that it is protein
    b. renal tubular epithelial cells
    intracellular hyaline (little red beady things)
  85. hyaline membrane disease
    extracellular hyaline
  86. 1. inhaled carbon pigment within lymphatics on the pleural surface of the lungs (anthrocosis) is not clinically relevant, we all have some degree of anthrocosis in our lungs
    a. coal mine exposure can tear your lungs up however
    exogenous pigment accumulation
  87. 1. brownish little knot globules in the heart, usually in a perinuclear position
    2. becomes more apparent with age
    3. we don’t know exactly what it is
    4. we think it is from repeated membrane damage that has been repaired
    5. often times in the heart it is present
    a. in elderly there may be atrophy of the myofibers and the heart may take on a brownish discoloration because of accumulation of lipchromecan also be present in the liver
    lipofucsin (lipochrome) pigment accumulation
  88. a pigment (brown black pigment) that is produced by melanocytes
    You can see accumulation of ------ on the skin
  89. 1. (form of stored iron) is a byproduct of the breakdown of hemoglobin. It is a gold brown protein
    2. Are found in reticuloendothelial cells that are responsible for removing abnormal red blood cells
    Hemosiderin pigment accumulation
  90. What color does hemosiderin stain
    blue due to iron
  91. hemosiderin can accumulate where?
    in liver, pancrease, skin, and heart
  92. a metabolic disorder in which there is a defect in normal iron metabolism.
    a. Patients will have large amounts of iron in liver, pancreas, skin, and heart.
    Can see that with this disorder the pancreas is a red color and when stained the pancreas turns blue due to high presence of hemosiderin
  93. 1. a green brown color
    a. It is also a byproduct of hemoglobin breakdown but does not contain iron
    b. It can accumulate in fluid and tissue wherever there is disturbance in the uptake of ----- by hepatocytes such as a enzyme deficiency or when there is an obstruction of bile channels in the liver
    2. The liver will turn a green color when bile accumulates
    There will be increased -----in the blood and thus will see people’s eyes turn a yellowish color.
    bilirubin (bile pigment accumulation)
  94. Cytoplasmic changes
    Eosinophilia and Homogenizaton
  95. a. Will see that the cytoplasm turns pinker and is more homogenized (uniform in its composition)
    b. Happen as a result of loss of cytoplasmic RNA and denaturation of cytoplasmic proteins
  96. nucleus gets smaller
  97. nucleus gets smaller and breaks up
  98. nucleus disappears
  99. Complications of Thrombosis that leads to sudden hypoxia and subsequent necrosis
    1. Due to coagulation necrosis (except in brain-liquifactive necrosis)
  100. Things to consider about an infarction
    • 1. Cardiovascular Status
    • 2. Tissue sensitivity to hypoxia
    • 3. Rapidity of occlusion
    • 4. Vascular Anatomy
    • a. Single Blood Supply
    • b. Single Anastomosing blood vessel
    • c. Dual Blood Supply
    • d. Parallel Blood Supply( in in brain)
  101. main vessel is occluded
    results in prominent boundary line b/w necrotic and viable part of effected organ
    pale infarction
  102. A. Single vessel that branches to many vessels
    B. Found in gut mainly
    C. Protected from abrupt hypoxia due to alternate blood supply to same areaBleeding of alternate vessel into necrotic area leads to bleeding infarct (Hemmorrhagic Infarct)
    Single Anastomosing Blood Supply
  103. Two vessels that slight branch and supply blood to one areaAlso get Hemorrhagic Infarct here
    Dual Blood Supply
  104. A. Multiple vessels to get blood to same area
    B. Usually found in brainOcclusions here may be less concerning because other ways to supply blood in area if one vessel get occluded
    Parallel Blood Supply
  105. Usually hemorrhagic infarctsDue to statsis or Thrombosis in vein
    Infarcts from Venous Obstruction
  106. Can arise during obstretic emergencies, malignancies, sepsis, major trama
    Disseminated Intravascular Coagulation (DIC)
  107. Steps of the Extrinsic and Intrinsic coagulation pathways that are activated at the microvascular level unnecessarily in Disseminated Intravascular Coagulation (DIC)
    • 1. Coagulation factors and platlets are unnecessarily working
    • 2. Fibrin and platlet thrombi formed consuming the platlets, fibrinogen, and coagulation factors and also activates the fibrinolytic system
    • 3. Therefore coagulation factors are low systemically, but can’t just treat with coagulation factors bc will travel to site of microvascular occlusions.This leads to microvascular coagulation and simultaneous hemorrhaging
  108. Extrinsic and Intrinsic coagulation pathways are activated at the microvascular level unnecessarily.
    Billions of microvasculature are occluded with this problem
    Disseminated Intravascular Coagulation (DIC)
  109. Lab test results for DIC
    Increased PT, Increased PTT, Decreased Fibrinongen, Increased Fibrin Split Product (FSP), Decrased Platlets.
  110. a free floating mass that is carried through vasculatur to a point away from the point of entry
    1. Most commonly from a thromboembolis, but can also be air, water, fat…
  111. 2 types of Embolization
    • Arterial Emboli (Systemic)
    • Venous Emboli (Pulmonary)
  112. A. 80-85% of these emboli are from mural thrombi in left ventricle and atrial.
    B. Major parts these emboli infarct-brain, lower limbs, kidney, spleen.These infarcts appear wedge shaped with apex of triangle being the spot of occlusion
    Arterial Emboli
  113. A. 3rd most common reason for sudden death (after myocardial infarct and stroke)Caused by surgery, immobility, heart failure, pregnancy, obesity, muscle weakness, cancer, and stasis can all lead to
    Venous Emboli
  114. What's worse? one small venous embolus or shower of emboli
    shower! (Can lead to pulmonary hypertension due to lack of perfusable vessels)
  115. 1. Can lead to dyspnea, anginal pain, syncope, venous distention of neck.
    venous embolis
  116. can lead to the above plus sudden tachycardia and hyperventilation
    Occlusion of pulmonary artery
  117. can lead to sudden death or diaphoresis (sweating from shock), sever dyspnea, cyanosis, tachycardia, anginal pain. Therefore larger veins, like femoral/iliac vein are concerning if become thrombolized.
    Massive embolization, such as saddle-type
  118. 1. Hemorraghic coagulation necrosis ensues
    2. Pleural effusion is also possible
    characteristics of wedge shaped infarct
  119. 1. Increased D-Dimer Serum concentration can indicate fibrolysis of thrombus
    2. Chest X-Ray can show pooling of blood
    3. Pulmonary arteriography-most successful way
    4. Decreased pCO2 due to the hyperventilationUsusally located in lower right lung lobe.
    Diagnosing Emboli
  120. body is made up of how much water
  121. Body is how much water in Extracellular
  122. Body is how much water in Intravascular (blood vessels)
  123. Body is how much water in Interstitial (Outside cells in ground substance of tissues)
  124. Body is how much water in Intracellular
  125. Localized accumulation of water
  126. Body wide edema
  127. Outside of the blood vessels
    interstitial tissue
  128. Forces acting on exchange between vasculature and interstitium
    • Hydrostatic Pressure
    • Osmotic pressure
    • oncotic pressure
  129. a. Force (like water pressure in hose) that pushes water out of vasculature and into the interstial space
    b. Arteriole side: 35 mm Hg (water toward interstitial cells)
    c. Venule side: 15 mm Hg
    i. less than on arteriole side because water was pushed out into interstial cells therefore less pressure/hydrostatic when it comes out on venule side
    Hydrostatic Pressure
  130. a. Controlled predominately by Na+
    b. Think concentration gradient: Greater amount of sodium in interstitial fluid so water leaves the vessel and goes into the interstitial space to balance out the Sodium concentration
    c. Arteriole side: 5 mm Hg (water toward interstitial cells)
    d. Venule side: 2 mm Hg
    i. Less than on arteriole side because the sodium imbalance was fixed a little due to osmosis on arteriole side. (less difference in sodium concentration gradient on venule side)
    Osmotic Pressure
  131. a. Controlled by protein concentration in blood (therefore in vasculature)
    i. Major source of protein in blood is albumin
    b. Draws water back into vessels
    c. Arteriole side: 20 mm Hg (water pulled into vasculature)
    d. Venule side: 30 mm HgGreater than on arteriole side because protein can’t cross from vasculature to interstitium, and therefore it is concentrated when water left on arteriole side--due to hydrostatic (water out) + osmotic (water out) >oncotic (water in)
    Oncotic Pressure
  132. i. 35 mm Hg water out due Hydrostatic
    ii. 5 mm Hg water out due to Osmotic
    iii. 20 mm Hg water in due to Oncotic
    iv. Overall: 20 mm Hg water out
    Arteriole side
  133. 15 mm Hg water out due to Hydrostatic
    2 mm Hg water out due to osmotic
    30 mm Hg water in due to Oncotic
    Overall: 13 mm Hg water in
    Venule side
  134. Arteriole pushes 20 mm Hg water out overall
    Venule pulls in 13 mm Hg water in overall
    7 mm Hg still left over on interstitial
    What happens to this extra fluid left on interstitial side?
    Arteriole and Venule balance
  135. Carries off the extra fluid left on the interstitial side
    lymphatic system
  136. 1. More sodium in interstital fluid
    2. Draws more water out into interstitium
    3. Causes
    a. Decrease in renal function
    i. Increased sodium intake is normally not a problem for younger people, the kidneys take care of it. But as people get older, their kidneys don’t work as well.
    Increase in osmotic pressure
Card Set
MS1, Block 2 Cell/Tissue Injury
Dr. Holliman's first set of lectures