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General Pathology > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

Adaptations to cell injury

A
  • Metaplasia: convert to different cell type
  • Intracellular accumulations: engulfed material or inability to secrete
  • Atrophy: same cell number, smaller cells – was normal size previously
  • Hypotrophy: organ doesn’t grow to adult size d/t developmental problem
  • Hypertrophy: same cell number, larger cells
  • Hyperplasia: increase in cell number
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2
Q

Two options for a cell after experiencing irreversible injury

A
  1. ) Necrosis

2. ) Apoptosis

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3
Q

Types of cell injury

A
  • Reversible injury: stress to cell that is mild and transient and cell is able to return to homeostasis
  • Irreversible injury: stress to cell that is severe and progressive resulting in cell death via necrosis or apoptosis
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4
Q

What are the etiologies of cell injury?

A
  • Hypoxia
  • Physical agents, trauma
  • Chemical agents, drugs
  • Infectious agents
  • Immunologic rxns
  • Genetic defects
  • Nutritional imbalances
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5
Q

List 5 mechanisms that lead to cell injury

A
  1. ) influx of Ca/loss of Ca homeostasis
  2. ) mitochondrial damage
  3. ) depletion of ATP
  4. ) accumulation of ROS/oxidative stress
  5. ) defects in membrane permeability
    - These ultimately lead to damage to MPD: membrane, proteins/cytoskeleton and DNA
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6
Q

Describe how influx of Ca/loss of Ca homeostasis leads to cellular injury

A

1.) Influx of Ca / loss of Ca homeostasis: injury leads to Ca influx into cell = activation of cellular enzymes (phospholipases, proteases, endonucleases, ATPases) and increases mitochondrial permeability = membrane damage, nuclear damage and decreased ATP production

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7
Q

Describe how mitochondrial damage leads to cellular injury

A

2.) Mitochondrial damage: increase Ca2+, oxidative stress and phospholipase/sphingomyelin pathways lead to damage to mitochondrial membranes resulting in decreased H+ potential to drive production of ATP via ATP synthase enzymes

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8
Q

Describe how depletion of ATP leads to cellular injury

A
  1. ) Depletion of ATP: chemical injury (eg. Cyanide) and hypoxia lead to decreased oxidative phosphorylation leading to decreased ATP cellular levels =
    a. ) no energy for Na/K pump = high Na in cell = osmotic changes, h2o into cell = cellular and organelle swelling
    b. ) no energy for Ca pump = increased Ca in cell = enzyme activation
    c. ) increased anaerobic glycolysis = decreased glycogen, increased lactic acid = decreased pH and clumping of nuclear chromatin
    d. ) detachment of ribosomes = decreased protein synthesis
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9
Q

Describe how accumulation of ROS/oxidative stress leads to cellular injury

A
  1. ) Accumulation of ROS/oxidative stress: normal metabolism = formation of ROS. Inability to clear ROS = formation of bonds quickly and non-specifically = altered structure of proteins, nucleic acid and lipids
    a. ) Lipids: double bonds of unsat FAs are attacked by ROS = formation of lipid peroxides = formation of more lipid peroxides in membranes. Free radicals are normally scavenged by Vitamin E in membrane.
    b. ) Proteins: side chains are oxidized, disulfide bonds are formed = altered structure/function
    c. ) DNA: ROS interaction with thymine causes single-stranded breaks in DNA = accumulation of mutations
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10
Q

Describe how defects in membrane permeability leads to cellular injury

A
  1. ) Defects in membrane permeability = inability to maintain concentration gradients, functional compartmentalization via:
    a. ) membranes damaged from ROS via lipid peroxidation
    b. ) Ca entry into cell = phospholipase activation = phospholipid degradation in membrane. Also protease activation = cytoskeletal damage.
    c. ) Lack of ATP = no reacylation of phospholipids/diminished synthesis of phospholipids = cell membrane cannot be repaired
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11
Q

Compare and contrast morphologic appearance of cell with reversible cell injury and a cell with irreversible cell injury

A
  • Reversible:
    a. ) Swelling ER, mitochondria
    b. ) Membrane blebs
    c. ) Clumping chromatin
  • Irreversible:
    a. ) ER swelling with detachment of ribosomes
    b. ) Lysosome rupture
    c. ) Myelin figures (protein/lipid swirls)
    d. ) Nuclear condensation: pyknosis
    e. ) Swollen mitochondria with amorphous densities
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12
Q

List the types of subcellular alterations that can occur in cell injury with respect to the following organelles: lysosomes, ER, mitochondria, cytoskeleton, nucleus

A
  • Lysosomes: swelling and lysing
  • ER: swelling and ribosome detachment
  • Mitochondria: swelling, amorphous densities
  • Cytoskeleton: degradation
  • Nucleus: clumping of chromatin, condensation of nuclear material, lysing of nuclear material
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13
Q

Discuss free radical induced injury in terms of: a.) mechanism of production of free radicals, b.) protective mechanisms against free radical injury

A

a. ) Mechanism of production:
- Radiation, toxins, reperfusion = production of superoxide (o2dot-), hydrogen peroxide (h2o2) and hydroxide (OHdot)

b. ) Protective mechanisms against injury
- SOD (superoxide dismutase in mitochondria) converts o2dot- to h2o2
- Glutathione peroxidase (in mitochondria) converts OHdot to h2o2
- Catalase (in peroxisomes) converts h2o2 into h2o and o2

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14
Q

Two types of cell death. Which is pathologic and which is physiologic?

A
  • Necrosis: resulting from exogenous or endogenous damage to cellular membrane resulting in leaking cellular contents. Not controlled by the cell and doesn’t occur via signaling or activation of genes. Accompanies inflammation. Always pathologic.
  • Apoptosis: external/internal cell damage leads to programmed cell death resulting in cell fragmentation and phagocytosis. No leaking of cellular contents. Does not accompany inflammation. Is physiologic or pathologic.
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15
Q

Typical cytoplasmic and nuclear changes that accompany necrosis

A
  • Cytoplasmic: eosinophilia (reddening), glassy appearance (d/t proteins) and vacuolation
  • Nuclear: pyknosis (condensation), karyorrhexis (breaking apart) and karyolysis (dissolving)
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16
Q

Types of necrosis. Common sites/tissues and reasons for occurrence. Microscopic/gross appearance.

A
  1. ) Coagulative:
    - microscopic = outline of cell preserved, no nuclei
    - gross = firm tissue
    - Sites: tissues with CT network (most organs except for brain)
    - Reason: ischemia (eg. MI), hypoxia, reperfusion injury
  2. ) Liquefaction:
    - microscopic loss of cells and tissue lacking CT network, amorphous granular
    - gross: liquid, pus
    - Sites: tissues lacking CT network or where enzymatic digestion of tissue via neutrophils occurred
    - Reason: ischemia, pyogenic bacteria infection
  3. ) Caseous: accumulation of mononuclear cells creating granuloma
    - microscopic: accumulation of mononuclear cells surrounding amorphous, granular eosinophilic debris
    - gross: grayish, white/yellow, soft, crumbly, cheesy
    - Sites: areas where infectious organism resides and cannot be broken down by immune system leading to chronic inflammation and granuloma formation
    - Reason: TB and certain fungi (esp histoplasmosis)
  4. ) Enzymatic/Fat:
    - microscopic: material in necrotic fat cells = eosinophilic (pink), calcium/FA deposit areas are basophilic (purple)
    - gross: white and chalky
    - Sites: areas of fat
    - Reason: in areas where enzymes are activated and act on surrounding fat, fatty acids react with calcium and are saponified
  5. ) Fibrinoid: looks fibrin like
    - microscopic: intensely eosinophilic (pink) vascular walls
    - gross: ?
    - Sites: blood vessel walls
    - Reason: vasculitis/injury of blood vessels (eg. Ag/ab complex formation – Type III hypersensitivity)
  6. ) Gangrenous
    - Sites: limb or bowel
    - Reason: loss of circulation d/t various pathologies including PVD, atherosclerosis, diabetes
    - Wet: gangrene superimposed with bacterial infection
    - Dry: no bacterial infection
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17
Q

Myocardial infarction results in what type of necrosis

A
  • Coagulative
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18
Q

Abscesses are an example of what type of necrosis

A
  • Liquefaction necrosis
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19
Q

Acute appendicitis is an example of what type of necrosis

A
  • Liquefaction necrosis
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20
Q

Cerebral infarction/stroke results in what type of necrosis

A
  • Liquefaction necrosis
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21
Q

TB results in what types of necrosis

A
  • Caseous necrosis
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22
Q

Pancreatitis results in what type of necrosis

A
  • Enzymatic/Fat necrosis
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23
Q

Necrosis of lower limbs (feet and toes) is usually what type of necrosis

A
  • Gangrenous necrosis
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24
Q

Discuss the mechanisms causing reperfusion injury

A
  • Reperfusion = restoral of blood flow/oxygenation to tissue.
  • Large amount of ROS production (superoxide, hydroxide, lipid peroxide and peroxynitrite (ONOO-)). These ROS species disrupt lipids, proteins and DNA. Production exceeds degradation.
  • Expression of cytokines and CAMs = accumulation of neutrophils = induction of further injury
  • Activation of complement
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25
Q

Examples of apoptosis that is pathologic

A
  • CA/tumor-induced cell death
  • Anti-CA and other drugs
  • Radiation
  • Extreme temps
  • Transplant rejection
  • Atrophy after duct obstruction
  • Viral diseases
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26
Q

Mechanisms of apoptosis induction and pathways (and enzymes involved)

A
  • Cell injury (growth factor withdrawal, DNA damage, protein misfolding) initiates mitochondrial (intrinsic) pathway. Outside factors initiate death receptor (extrinsic) pathway.
    1. ) Intrinsic: +Bax, Bak = pro-apoptotic factors dimerization = formation of channels in mitochondrial membrane = permeability of cytochrome c = +executioner caspases
    2. ) Extrinsic: Fas (CD95)/TNF receptor interaction = +adaptor proteins = executioner caspases
  • Executioner caspases activate endonucleases and breakdown cytoskeleton directly. This leads to blebbing and formation of apoptotic bodies which are digested by phagocytes
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27
Q

P53 function

A
  • DNA damage = P53 activation = pro-apoptotic factors (Bax/Bad) = apoptosis
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28
Q

Bax/Bad function

A
  • Pro-Apoptosis factors
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29
Q

Bcl-2/Bcl-x function

A
  • Anti-apoptotic factors preventing leakage of cytochrome c and blocking pro-apoptotic factors
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30
Q

Compare and contrast necrosis and apoptosis from changes to: cell size, nucleus, plasma membrane, cellular contents, adjacent inflammation

A
  • Necrosis: enlarged/swelling, pyknosis-karyorrhexis-karyolysis, disrupted, enzymatic digestion of tissue d/t cellular contents leakage, inflammation
  • Apoptosis: reduced/shrinkage, fragmentation/round nucleosome, intact PM, no leakage of cellular contents-apoptotic bodies contain contents, no inflammation
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31
Q

Viral infection leads to what type of cell death

A
  • Necrosis (low energy, antibody against viral antigens and activation of complement)
  • Apoptosis (activation of p53, granzymes by CTL = caspase activation)
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32
Q

Describe the different mechanisms of injury d/t chemicals such as: CCl4, acetaminophen, cyanide, phalloidin, paclitaxel and alkylating agents

A
  • CCl4: metabolite CCl3dot reacts with PM and ER
  • Acetaminophen: metabolite quinone reacts with protein, DNA and causes oxygen stress = liver necrosis
  • Cyanide: target = cytochrome in mitochondria
  • Phalloidin: targets cytoskeleton
  • Paclitaxel: targets cytoskeleton preventing cell replication
  • Alkylating agents: targets DNA
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33
Q

What is hypertrophy? Physiologic or pathologic? Etiology? Mechanism of development? Examples

A
  • Increase in cell size and therefore size of organ
  • Both physiologic or pathologic
  • Etiology: increased functional demand
  • Mechanisms:
    a. ) Increase production of cellular contents – proteins, myofilaments, DNA, organelles
    b. ) 3 types of signals: mechanical triggers (stretch), vasoactive agents, growth factors/hormones = hypertrophy
  • Examples: weight lifting, pregnant uterus (with hyperplasia) = physiologic. Cardiomegaly (d/t HTN, aortic valve dz), individual fiber hypertrophy following MI = pathologic.
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34
Q

What is hyperplasia? Physiologic or pathologic? Etiologies? Mechanism of development? Examples.

A
  • Increased number of cells
  • Physiologic or pathologic
  • Etiology: constant stimulus, persistent injury, functional capacity needed
  • Mechanisms:
    a. ) result of GF-driven proliferation of mature cells
    b. ) increase in output of new cells from tissue stem cells
  • Example: female breast at puberty, lactating breast, proliferative endometrium (menses, pregnancy) liver damage/resection = physiologic. Endometrial hyperplasia d/t E and P imbalance, BPH (d/t high androgens), Graves’ disease (enlarged thyroid)
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35
Q

What is atrophy? Physiologic or pathologic? Etiologies? Mechanism of development? Examples.

A
  • Reduced cell size, therefore reduction in organ size
  • Physiologic or pathologic
  • Etiologies: disuse atrophy, denervation atrophy, decreased blood supply/senile atrophy, inadequate nutrition, loss of endocrine stimulation, pressure/tissue compression
  • Mechanisms:
    a. ) decreased protein synthesis and increased protein degradation
    b. ) degradation via ubiquitin-proteasome pathway
    c. ) autophagy (self-eating)
  • Example: pathogenic = Alzheimer’s, particularly frontal, cryptorchidism, vascular insufficiency to organ resulting from severe atherosclerosis, muscular dystrophy
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36
Q

What is metaplasia? Physiologic or pathologic? Etiologies? Mechanism of development? Examples.

A
  • Reversible change in one differentiated cell type to another cell type
  • Pathologic (step towards Cancer), function lost
  • Etiology: stress/chronic inflammation caused replacement of cell with cell better able to handle stress
  • Mechanisms: via cytokines, growth factors and ECM components
    a. ) Stem cells undergo differentiation
    b. ) Undifferentiated mesenchymal cells undergo reprogramming
  • Examples
    a. ) Bronchi in smokers: ciliated Co cells to strat squamous
    b. ) Columnar to squamous: Barrett’s esophagus
    c. ) Larynx in smokers
    d. ) CT metaplasia: formation of cartilage, bone or adipose in tissue not usually containing these component. Eg. Bone in muscle after intramuscular hemorrhage
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37
Q

What is dysplasia?

A
  • Disordered growth commonly seen in squamous epithelium following chronic injury
  • Morphology: variations in size, shape of cell, disorderly arrangement, nuclear changes
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38
Q

Primary vs secondary lysosomes

A
  • Primary = small membrane-bound vesicles budding from Golgi apparatus
  • Secondary (aka phagolysosomes) = primary lysosomes fusing with pinocytotic/phagocytotic vesicles
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39
Q

Heterophagy vs autophagy

A
  • Heterophagy: materials from EC environment taken up through endocytosis. Primary lysosome, phagolysosome and residual bodies seen.
  • Autophagy: lysosomal digestion of cell’s own components – why? Damaged/senescent organelles, cellular remodeling/differentiation, atrophy. Primary lysosome, autophagic vacuole and residual body seen.
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40
Q

What are residual bodies?

A
  • Material (lipids and other material) that remains in lysosomes undigested, eg. Lipofuscin, carbon particles
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41
Q

What induces SER hypertrophy?

A
  • Drugs (barbiturates: P450 system)
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42
Q

Three categories of intracellular accumulations

A
  1. ) Normal endogenous substance: produced at normal or increased rate, but metabolism inadequate to remove
  2. ) Normal/abnormal endogenous substance: accumulates secondary to genetic/acquired defects in metabolism, packaging, transport or secretion
  3. ) Abnormal exogenous substance deposited in cells which cannot remove it
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43
Q

Mechanisms that lead to intracellular accumulations

A
  • Abnormal metabolism
  • Alterations in protein folding/transport
  • Deficiency of enzymes
  • Inability to degrade phagocytosed particles
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44
Q

Steatosis and fatty infiltration. Causes, pathogenesis, organs involved, histologic appearance, result?

A
  • Definition = abnormal accumulations of TGLs within parenchyma of liver, heart, muscle and kidney
  • Causes: toxins, protein malnutrition, DM, obesity, anoxia, alcohol – most common = alcohol and DM
  • Pathogenesis: defect at any step in FA metabolism (FFAs to FA, FA to ketone/phospholipid/CE, apoprotein to lipoprotein)
  • Appearance = fat vesicles/vacuoles in tissue
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45
Q

In what disorders does one see cholesterol/CE accumulation

A
  • Atherosclerosis: foam cells within intimal layer of aorta and larger arteries, cholesterol clefts = crystallization of lipids in EC space
  • Xanthomas (acquired/hereditary hyperlipidemia): foam cells
  • Inflammation, necrosis: phagolysosomes accumulate from neighboring cells
  • Cholesterolosis in GB: foam cells
  • Niemann-Pick dz, type C (lysosomal storage dz)
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46
Q

In what disorder(s) are cholesterol clefts seen?

A
  • Atherosclerosis, these just represent crystallization of lipids in EC space
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47
Q

How do protein accumulations appear histologically? Causes? Where?

A
  • Hyaline: pink droplets in cytoplasm, can be extracellular; Russell bodies (excessive Igs by plasma cells); Mallory body (aka alcoholic hyaline: in alcoholic liver disease as a result of injury to cytoskeletal filaments in liver cells)
  • Causes:
    a. ) proteinuria (reabsorption of proteins in proximal renal tubules)
    b. ) synthesis of excessive protein
    c. ) defects in protein folding
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48
Q

Where are Russell bodies seen? What are they characteristic of?

A
  • Plasma cells. They represent excessive Igs (immunoglobulin) protein synthesis
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49
Q

Where are Mallory bodies found? What are they characteristic of?

A
  • aka alcoholic hyaline: in alcoholic liver disease as a result of injury to cytoskeletal filaments in liver cells
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50
Q

Describe the process of protein folding. What defects lead to abnormal folding? Response by cell to misfolded proteins?

A
  1. ) Nascent peptides associates with chaperones (heat-shock proteins), which ensures folding to mature protein
  2. ) Heat-shock protein can direct protein to correct intracellular location
    - Abnormal folding results from low energy stores, genetic mutations, viral infections, chemicals, UV, heat, free radicals etc.
    - Cellular response to misfolded
    a. ) Increase synthesis of chaperones
    b. ) Decreased translation of proteins
    c. ) Activation of ubiquitin-proteasome pathway
    d. ) Activation of caspases for cellular apoptosis
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51
Q

What is ER stress?

A
  • Protein folding demand exceeds protein folding capacity leads to apoptosis
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52
Q

Examples of defects in protein folding

A
  1. ) alpha-1-antitrypsin deficiency
  2. ) Neurodegenerative diseases
  3. ) Proteinopathies, protein-aggregation diseases (eg. Amyloidosis)
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53
Q

Describe hyaline changes in cell

A
  • Glassy, pink homogenous appearance on H&E
  • Intracellularly = protein droplets in kidney, Russell bodies, Mallory alcoholic hyaline, viral inclusions
  • Extracelluarly = collagenized scar, damaged glomeruli, hyaline arteriosclerosis, atherosclerosis, amyloid
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54
Q

What is the appearance of glycogen accumulation? Causes?

A
  • Clear cytoplasmic vacuoles

- Causes: abnormalities in metabolism of glucose or glycogen, eg. DM, glycogen storage diseases (type III, Pompe’s dz)

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55
Q

Most common exogenous pigment

A
  • Carbon
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56
Q

Examples of exogenous pigments. Location, color?

A
  • Carbon (coal dust): black, acquired via inhalation, picked up by macrophages transported to lymph nodes
  • Tattooing: various color, stored in dermal macrophages
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57
Q

What is anthracosis?

A
  • Darkened lymph nodes and lung tissue representing carbon accumulation in macrophages
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58
Q

Examples of endogenous pigment. Color, location?

A
  • Lipofuscin/lipochrome: brown-yellow wear/tear pigment representing lipids/phospholipids derived from lipid peroxidation that accumulates in heart, liver and brain and is associated with aging, atrophy. Is marker of past free radical injury. Perinuclear in EM, brown in gross specimen. This is non-injurious pigment.
  • Melanin: brown-black pigment formed in melanocytes formed by enzymatic oxidation of tyrosine in epidermis, protective against UV. Can accumulate in basal keratinocytes or dermal macrophages. Non-injurious pigment.
  • Iron/hemosiderin: golden yellow-brown pigment (with H&E, blue with Prussian blue stain) representing aggregates of ferritin micelles. Seen in macrophages, bone marrow, spleen and liver where RBC breakdown occurs. Hemosiderosis results from hemochromatosis. Can be injurious in hemochromatosis.
  • Bilirubin: yellow pigment found in bile, derived from hemoglobin breakdown without iron. Jaundice results in excess bilirubin. Underlying condition causes this.
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59
Q

What is hemosiderosis? Hemochromatosis? Causes? Result?

A
  • Hemosiderosis: systemic overload of hemosiderin/iron in many organs and tissues resulting from increase absorption of dietary iron, impaired use, hemolytic anemias, transfusions. Systemic condition = hemochromatosis. Hemosiderosis is what is seen at tissue level. Condition can lead to liver fibrosis, heart failure and DM.
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60
Q

Compare dystrophic and metastatic calcification. What are these? Etiology and pathogenesis? Morphologic appearance? Sites and associated diseases?

A
  • Calcification: abnormal deposition of calcium salts with other substances
  • Dystrophic: local process occurring in injured or dying tissue with normal serum calcium. Cause: organ dysfunction, atherosclerosis (plaques), aging, damaged heart valves, necrosis. Sites/diseases: aortic valves (atherosclerosis), atherosclerosis plaques in vasculature, breast carcinoma, stomach wall.
  • Metastatic: process occurring anywhere in body with hypercalcemia. Cause: CA destroying bone, high PTH levels (d/t parathyroid adenoma, SCCarcinoma of lung), vitamin-D disorder (sarcoid, increased intake vit D, renal failure (secondary hyperparathyroidism). Site: any, mainly in blood vessel interstitium, kidneys, lungs, gastric mucosa. Can get heterotopic bone in foci of calcification.
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61
Q

Inflammation definition

A
  • local rxn of vascularized tissue to injury
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62
Q

Time frame of inflammation: acute, subacute and chronic

A
  • Acute: 0-2 days
  • Subacute: 2-14 days
  • Chronic: >14 days
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63
Q

Typical cell types involved in acute inflammation

A
  • Neutrophils
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64
Q

Typical cell types involved in chronic inflammation

A
  • Mononuclear cells (agranulocytes) = monocytes, macrophages, lymphocytes, plasma cells
  • Granuloma cells (epithelioid and giant cells)
  • Fibroblasts
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65
Q

Predominant cell type in allergic reactions and parasitic infestations

A
  • Eosinophils
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66
Q

List the 6 cardinal signs and symptoms of inflammation and briefly describe the underlying causes

A
  • Heat: increased blood flow to site
  • Redness: increased blood flow to site
  • Swelling: accumulation of fluid and cells
  • Pain: pressure of fluid, effect of mediators
  • Loss of function: secondary to above effects
  • Systemic changes: release of humoral factors
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67
Q

Major causes of acute inflammation

A
  • Biological: infection, immunologic injury, tissue death
  • Physical: trauma/injury, thermal extremes, ionizing radiation
  • Chemical: poisons, drugs
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68
Q

Compare and contrast serous, fibrinous and suppurative acute inflammation

A

a. ) Serous: water, protein-poor fluid seen in peritoneal, pleural or pericardial cavities
b. ) Fibrinous: water, large amounts of protein including fibrin seen in severe injury and inflammation of body cavities
c. ) Suppurative: purulent/pus containing water, proteins and neutrophils with necrotic cells seen in pyogenic bacterial infections

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69
Q

What is ulceration?

A
  • local defect/excavation produced by sloughing off of inflammatory necrotic tissue only on skin or mucosa (GU/GU/mouth)
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70
Q

Outcomes of acute inflammation

A
  1. ) Resolution
  2. ) Healing by scarring
  3. ) Abscess
  4. ) Progression to chronic inflammation
71
Q

Describe classic vascular changes of the inflammatory reaction

A
  • Transient (seconds) vasoconstriciton
  • Vasodilation = increase in blood flow
  • Increased permeability as ECs contract and widen intercellular junctions = leakage of plasma proteins and leukocytes into IStitial space. Increased permeability also d/t direct injury, newly formed blood vessels being leaky
72
Q

Describe steps involved in extravasation, isolation and destruction of an infectious agent by PMNs (neutrophils). Include molecules/receptors that play a role in extravasation and intracellular factors that kill the infectious agent.

A
  1. ) Leukocyte extravasation
    a. ) margination: neutrophils line up along EC surface
    - rolling: mediated by selectins (CD62) expressed on ECs (E-selectin), platelets (P-selectin) and leukocytes (L-selectin) act to slow leukocytes down

b. ) adhesion:
- neutrophils (and macrophages) express beta-2 integrin LFA (?Mac-1 aswell?), which bind to ICAM-1 on ECs
- eosinophils, basophils, lymphocytes, monocytes express beta-1 integrin VLA-4, which binds to VCAM-1 on ECs

c. ) emigration/transmigration/diapedesis: PECAM-1 (CD31) mediates this step
d. ) chemotaxis: neutrophils move along chemical gradient to sites of injury under mediators: C5a, LTB4, bacterial products and IL-8

  1. ) Phagocytosis
    a. ) Recognition/attachment: opsonins (antibody, C3b and MBL attached to organism) are recognized by receptors on neutrophils, macrophage
    b. ) Engulfment: pseudopods surround objects forming phagosome – fusing with lysosome = phagolysosome (secondary lysosome)
  2. ) Metabolic killing
    a. ) o2-dependent (resp/oxidative burst)
    - o2 reduced to superoxide (via NADPH oxidase), superoxide converted to h2o2 (via SOD), Cl- and h2o2 react (via myeloperoxidase) to form hypochlorous acid). H2o2 and hypochlorous acid kill microbes

b.) o2-independent: granule proteins, enzymes such as hydrolases, lysozymes, lactoferrins and cationic proteins destroy microbes

73
Q

Functions of the following molecules/receptors: selectins (CD62), PECAM-1 (CD31), VCAM-1, ICAM-1, LFA, VLA-4

A
  1. ) Leukocyte extravasation
    a. ) margination: neutrophils line up along EC surface
    - rolling: mediated by selectins (CD62) expressed on ECs (E-selectin), platelets (P-selectin) and leukocytes (L-selectin) act to slow leukocytes down

b. ) adhesion:
- neutrophils (and macrophages) express beta-2 integrin LFA (?Mac-1 aswell?), which bind to ICAM-1 on ECs
- eosinophils, basophils, lymphocytes, monocytes express beta-1 integrin VLA-4, which binds to VCAM-1 on ECs

c.) emigration/transmigration/diapedesis: PECAM-1 (CD31) mediates this step

74
Q

Histamine, serotonin. Stimulus for release, origin, target, effect

A
  • Stimulus: trauma, cold, heat, platelet aggregation, anaphylatoxins (C3-5a’s), substance P, IL-1/8, IgE binding, histamine-releasing proteins
  • Origin: performed granules of mast cells (most), basophils and platelets
  • Target: H1 receptors on endothelium
  • Effect: transient arteriolar vasodilation and increased permeability to postcapillary venules, constricts large arteries
75
Q

Plasma proteins come from what 3 systems/categories

A
  • Complement
  • Kinin
  • Clotting
76
Q

Classic pathway of complement. What activates it?

A
  • Antigen:antibody complex activates C1
77
Q

Alternate pathway of complement. What activates it?

A
  • C3 activated directly by bacterial endotoxins, complex polysaccharides, aggregated globulins (IgA)
78
Q

Lectin pathway of complement. What activates it?

A
  • C1 is activated by binding of MBL to CHOs on microbes
79
Q

Convergence of complement pathways onto what molecule

A
  • C3
80
Q

Complement anaphylatoxins. What are they? Origin? Target? Functions?

A
  • C3a, C4a, C5a
  • Plasma proteins resulting from cleavage of C3, C4 and C5 respectively
  • Mast cells = target
  • Function = increase vascular permeability and vasodilation
81
Q

C5a. Origin, target, effect?

A
  • Origin: plasma protein from cleavage of C5
  • Target: monocytes and granulocytes
  • Effect: chemotaxis, increases surface expression of leukocyte CAMs and activates LOX pathway
82
Q

C3b. Origin, target, effect?

A
  • Origin: plasma protein from cleavage of C3
  • Target: opsonizes microbes and recognized by receptors on neutrophils, macrophages and eosinophils
  • Effect: opsonization for phagocytosis, degranulation of eosinophils
83
Q

C5-9. Origin, target, effect?

A
  • Origin: plasma proteins
  • Target: MAC on microbes
  • Effect: macropore formation increasing cell permeability and lysing microbe
84
Q

Hageman factor. Origin, target, effect?

A
  • aka factor XII
  • Origin: clotting system plasma protein
  • Target: contact with endotoxins, collagen or basement membrane = activation to XIIa
  • Effect:
    a. ) triggers kinin system (pre-kallikrein to kallikrein)
    b. ) triggers clotting cascade (thrombin production)
85
Q

Bradykinin. Origin, target, effect?

A
  • Origin: cleavage of HMWK (plasma protein) by kallikrein forming this kinin
  • Target: ECs, smooth muscle vasculature and non-vasculature, pain fibers
  • Effect: increase vascular permeability, dilation of blood vessels, contraction of non-vascular SM, pain
86
Q

How is bradykinin inactivated?

A
  • Short-lived, inactivated by plasma kininase
87
Q

Thrombin. Origin, target, effect?

A
  • Origin: plasma protein part of coagulation system
  • Target: binds PARs (protease-activated receptors) on platelets, endothelium, SM cells, acts on fibrinogen
  • Effect:
    a. Primarily: cleaves circulating fibrinogen into insoluble fibrin
    b. Mobilize P-selectin
    c. Produce chemokines, PAF, NO
    d. Stimulate endothelial adhesion molecule formation
    e. Induces COX-2 and production of PGs
    f. Induce shape changes of endothelium
88
Q

Plasmin. Origin, target, effect?

A
  • Origin: plasma protein part of fibrinolytic system formed by kallikrein cleavage of plasminogen OR by plasminogen activator release by endothelium and leukocytes
  • Target: fibrin, Hageman factor, C3
  • Effect:
    a. ) Primarily: degrades fibrin to FDPs (aka fibrin split products)
    b. ) Activates Hageman factor
    c. ) Cleaves C3 to C3a
89
Q

Source and action of arachidonic action

A
  • Bound to cell membrane phospholipids and released by cellular phospholipases by mechanical, chemical (C5a) and physical stimuli
  • Features in two pathways:
    a. ) COX (cyclooxygenase): creation of prostaglandin (PG) intermediates that function in inflammatory response. Products = TXA2, PGI2, PGE2, PGD2, PGF2a, PGE2
    b. ) LOX (lipoxygenase): creation of leukotrienes (LT) and lipoxins that function in the inflammatory response. Products = LT B4, LT C4/D4/E4, lipoxin A4 and B4
90
Q

Target of NSAIDs and ASA

A
  • Inhibit COX preventing formation of whole family of PG products
91
Q

Target of glucocorticoids in inflammation

A
  • Inhibit phospholipases in COX pathway
92
Q

TXA2 (thromboxane A2). Origin, effect

A
  • COX pathway product from conversion of AA

- Effect: potent platelet aggregator and vasoconstrictor

93
Q

PGI2. Origin, effect

A
  • COX pathway product from conversion of AA

- Effect: vasodilator and inhibitor of platelet aggregation

94
Q

PGE2. Origin, effect

A
  • COX pathway production from conversion of AA
  • Effect: sensitizes skin to painful stimuli and plays role in cytokine-induced fever – via IL-1 and TNF-alpha, vasodilation and potentiates edema
95
Q

PGD2. Origin, effect

A
  • COX pathway production from conversion of AA

- Effect: vasodilation and potentiates edema

96
Q

PGF2a. Origin, effect

A
  • COX pathway production from conversion of AA

- Effect: vasodilation and potentiates edema

97
Q

LT B4. Origin, effect

A
  • LOX pathway production from conversion of AA

- Effect: chemoattractant causing neutrophil aggregation and adhesion to ECs, generation of ROS, release of lysosomes

98
Q

LT C4. Origin, effect

A
  • LOX pathway production from conversion of AA

- Effect: intense vasoconstriction and bronchospasm, increases vascular permeability

99
Q

LT D4. Origin, effect

A
  • LOX pathway production from conversion of AA

- Effect: intense vasoconstriction and bronchospasm, increases vascular permeability

100
Q

LT E4. Origin, effect

A
  • LOX pathway production from conversion of AA

- Effect: intense vasoconstriction and bronchospasm, increases vascular permeability

101
Q

Lipoxin A4 and B4. Origin, effect

A
  • Origin: LOX pathway production from conversion of AA

- Effect: counter effects of leukotrienes, there inhibit neutrophil adhesion to endothelium and neutrophil chemotaxis

102
Q

PAF (platelet activating factor). Origin, effect (including in inflammation)

A
  • Origin: basophils, neutrophils, monocytes, platelets, endothelium
  • Effect:
    a. ) Platelet aggregation
    b. ) Release of platelet products: histamine, serotonin
    c. ) Vasoconstriction, bronchoconstriction. At low concentration: vasodilation and increase venular permeability
    d. ) Stimulates leukocyte oxidative burst
    e. ) Increase leukocyte adhesion to endothelium
    f. ) Leukocyte chemotaxis
    g. ) Stimulates PG and LT synthesis
103
Q

TNF-alpha, IL-1. Origin, effects

A
  • Origin: predominantly by macrophages, others = Epithelium, endothelium
  • Effect
    a. ) Acute phase rxns: fever, increase sleep, decrease appetite, increase acute-phase proteins, induce neutrophilia, shock mediators
    b. ) Endothelial: increase leukocyte adherence, stimulate PGI synthesis, increase pro-coag activity, increase production of IL-1/6/8 and PDGF
    c. ) Fibroblasts: increase proliferation, collagen synthesis, PGE synthesis, increase protease and collagenase production
    d. ) Leukocyte effects: autocrine, increase cytokine secretion – IL-1, IL-6
104
Q

Chemokine structures and what they act on

A
  1. ) CXC (alpha): on neutrophils
  2. ) CC (beta): not neutrophils, but on monocytes, eosinophils
  3. ) C (gamma): on lymphocytes
  4. ) CX3C: on monocytes and T-cells
    * C = cysteine
105
Q

NO. Origin, effect

A
  • Origin: macrophages, endothelium, some neurons in brain
  • Effect: paracrine
    a. ) Vasodilation through SM relaxation
    b. ) Reduces platelet aggregation and adhesion
    c. ) Reduces inflammatory response
    d. ) Microbicidal
106
Q

Extracellular effects of ROS released from neutrophils and macrophages

A
  • Endothelium cell damage = increased vascular permeability
  • Inactivation of antiprotease
  • Injury to other cells: tumor, RBCs, parenchymal cells
107
Q

What molecules/substances counter the effect of free radicals extracellularly?

A
  • Ceruloplasmin
  • Transferrin
  • SOD
  • Catalase
  • Glutathione peroxidase
108
Q

Substance P (and neurokinin A). Origin, function

A
  • Origin: CNS and PNS
  • Effect
    a. ) Transmission of pain signals
    b. ) Increasing vascular permeability
    c. ) Regulation of BP
109
Q

Mediators involved in vasodilation

A
  • PG, NO
110
Q

Mediators involved in vascular permeability

A
  • Histamine, serotonine, C3a, C5a, bradykinin, LT C4, D4, E4, PAF, substance P
111
Q

Mediators involved in chemotaxis and leukocyte activation

A
  • C5a, leukotriene B4, chemokines
112
Q

Mediators involved in fever

A
  • IL-1, IL-6, TNF-alpha, prostaglandins
113
Q

Mediators involved in pain

A
  • PG, bradykinin
114
Q

Mediators involved in tissue damage

A
  • Lysosomal enzymes, ROS, NO
115
Q

Why does inflammation hurt? What might make it hurt more or less?

A
  • Mediators in inflammatory cascade cause the pain. These include PG and bradykinin. NSAIDs that inhibit COX pathway will decrease pain. Potentially also anti-bradykinin drugs.
116
Q

What is the difference between an exudate and a transudate?

A
  • Exudate = result of inflammatory process = fluid with protein and anti-inflammatory cells
  • Transudate = result of disorders that increase hydrostatic pressure or decrease colloid osmotic pressure = fluid without protein
117
Q

What is the link between inflammation and fever?

A
  • Inflammation leads to synthesis and release of mediators such as IL-1, IL-6, TNF-alpha, prostaglandins, which cause fever
118
Q

Once inflammation has started, why doesn’t the whole body become inflamed?

A
  • Generation of inflammatory mediators accompanies generation of inhibitors to modulate/shut the process off preventing systemic disruption of function and also chronic inflammation.
119
Q

A person suffers from hay fever and allergic asthma breathes in a quantity of pollen. Describe the symptoms that may result. Describe the macroscopic changes in the nose and airways that cause the main symptoms. Describe the microscopic changes that cause the macroscopic appearances. Describe how pollen causes the microscopic changes. How may the symptoms be treated or prevented?

A
  • Symptoms: SOB, wheezing, runny nose, coryza (inflammation of nasal mucosa), stuffy nose
  • Macroscopic changes: nose gets red, swells and drains, perhaps is painful, becomes hot
  • Microscopic changes: vasodilation, increased blood flow, increased vascular permeability
  • How? Pollen binds to IgE bound to Fc receptors on mast cells causing degranulation of mediators including histamine and serotonin (vasoactive amines). These bind to H1 receptors and cause arteriolar vasodilation and increase permeabilities of postcapillary venules. This leads to all the microscopic and therefore macroscopic effects.
120
Q

Definition of chronic inflammation. Histological characteristics

A
  • Inflammation, tissue destruction and attempts at repair coexist
  • Histologically: mononuclear cells (macrophages, lymphocytes and plasma cells), maybe or maybe not eosinophils / mast cells, destruction (structure altered) and fibrosis/collagen/angiogenesis. If plasma cell seen, chronic inflammation is occuring
121
Q

Causes of chronic inflammation

A

1.) Persistent microbial infections: may be granulomatous rxn
2.) Immune-related inflammatory diseases
3.) Prolonged exposure to potentially toxic agents (exogenous/endogenous)
• Fueled by lifestyle factors: smoking, excessive alcohol, physical/emotional stress, obesity, lack of exercise, diet

122
Q

Cell type involved in granulomatous inflammation

A
  • Macrophage primarily
123
Q

How to determine activated vs non-activated macrophage on a tissue slide?

A
  • Activated: larger size, more lysosomes and lysosomal enzymes, appear flat and pink, are epitheliod: similar to squamous cells
124
Q

How are macrophages activated? What cytokines do these cells produce after being activated?

A
  • Cytokines: especially IFN-gamma from activated TH1 and NK cells
  • Bacterial endotoxin (LPS)
  • Other chemicals
  • Produces: TNF-alpha and IL-1
125
Q

Function of activated macrophages?

A
  1. ) Inflammation / tissue injury (under IFN-gamma): ROS/nitrogen species, proteases, cytokines (TNF-alpha, IL-1), coagulation factors (plasminogen activator), complement components, AA metabolites
  2. ) Repair (under IL-4 and others): growth factors (proliferation of SM, fibroblasts and ECM), fibrogenic cytokines, angiogenic factors, remodeling collagenase
126
Q

How are lymphocytes activated/mobilized?

A
  • Specific immune stimulus, ie. Infection

- Trauma

127
Q

Chemokine that recruits eosinophils

A
  • Eotaxin
128
Q

Contents of eosinophils and their function

A
  • MBP: major basic protein: toxic to parasites, leads to epithelial cell lysis, contributes to tissue damage in immune rxns including in allergies
129
Q

Contents of mast cells

A
  • Histamine and prostaglandins
130
Q

Histology shows mononuclear leukocytes and neutrophils. What is the diagnosis?

A
  • Chronic active inflammation aka acute and chronic inflammation
131
Q

What is granulomatous inflammation?

A
  • Distinctive pattern of chronic inflammation seen in limited number of infections and non-infections such as TB and foreign bodies. This is characterized by aggregates of activated macrophages with epithelioid appearance surrounding indigestible/insoluble substances.
  • Forms in settings of persistent T-cell responses, which leads to macrophage activation, which can cause injury to normal tissue.
132
Q

Diseases where granulomatous inflammation is seen

A
  • TB
  • Sarcoidosis
  • Cat-scratch disease
  • Lymphogranuloma inguinale
  • Leprosy
  • Brucellosis
  • Syphilis
  • Some fungal infections
  • Berylliosis
  • Rxns to irritant lipids
  • Foreign bodies: sutures, splinter, breast implant, piece of glass
133
Q

Define granuloma

A
  • Focal area of granulomatous inflammation consisting of aggregation of macrophages transformed into epithelioid cells surrounded by a collar of mononuclear leukocytes (primarily lymphocytes and plasma cells occasionally). Epithelioid cells merge together to form Langhans giant cell
134
Q

Granulation tissue

A
  • Tissue characterized by proliferation of fibroblasts, new thin-walled capillaries in a loose ECM
135
Q

Granulation tissue vs granuloma

A
  • Granulation = loose ECM with fibroblasts, thin-walled capillaries and scattered macrophages and other inflammatory cells
  • Granuloma = epithelioid cells surrounded by collar of mononuclear leukocytes typically in dense ECM
136
Q

Differentiate between granulomas that have Langhans-type or foreign body-type arrangement

A
  • Peripheral arrangement of epithelioid cells that fuse to form multinucleated giant cells = Langhans-type
  • Haphazard arrangement of epithelioid cells that fuse to form multinucleated giant cells = foreign body-type
137
Q

Lymphangitis

A
  • inflammation of lymphatic channels causing red streaks, erroneously referred to as blood poisoning
138
Q

What is reactive lymphadenitis?

A
  • Inflammation of draining lymph nodes. If overwhelming, can lead to bacteria gaining access to vascular circulation and bacteremia to sepsis
139
Q

What is acute-phase response?

A
  • Systemic inflammation aka SIRS: systemic inflammatory response system
140
Q

Clinical presentation of systemic inflammation

A
  • Fever, leukocytosis, decreased appetite, increased sleep, changes in acute phase proteins in serum
141
Q

What causes fever in acute phase response? Function?

A
  • LPS
  • IL-1 and TNF-alpha
  • These cytokines stimulate COX converting AA into PG synthesis in hypothalamic thermoregulatory center leading to resetting of body thermometer.
  • Function: improve efficiency of WBC killing and impair replication of microorganisms. Also, may induce HSPs enhancing lymphocyte response.
142
Q

Acute phase proteins seen in SIRS. Where are these synthesized, under what mediator, function?

A
  • CRP, fibrinogen, SAA (serum amyloid A protein) in hepatocytes
  • Upregulated by IL-1, TNF-alpha predominantly, but also IL-6
  • Function: bind microbial cell walls, act as opsonins and fixes complement
143
Q

Definition of leukocytosis vs leukemoid reaction

A
  • Leukocytosis = WBC count bw 15-20K, nml = 4K-10K

- Leukemoid rxn = 40K-100K count

144
Q

What is a left shit?

A
  • Increase in immature WBCs d/t accelerated production and release from bone marrow during SIRS
145
Q

When is neutrophilia typically seen?

A
  • Bacterial infections
146
Q

When is lymphocytosis typically seen?

A
  • Viral infections
147
Q

When is eosinophilia typically seen?

A
  • Asthma, hay fever, parasitic infections
148
Q

When is leukopenia seen?

A
  • Leukopenia = decrease in absolute # of WBCs seen in certain viral infections and also typhoid fever. Seen in debilitated host or overwhelming infections
149
Q

What happens to BP, pulse, sweating and behavior during SIRS?

A
  • BP, pulse increase
  • Sweating decreases d/t redirection of blood flow from cutaneous to deep vascular beds to minimize heat loss through skin
  • Behavioral: shivering, chills, anorexia, somnolence, malaise
150
Q

Definition of sepsis. Definition of septic shock

A
  • Severe bacterial infection leading to large quantities of cytokines being produced, esp. IL-1 and TNF-alpha
  • Sepsis features: cardiovascular decompensation, DIC, liver injury (hypoglycemia)
  • Septic shock: DIC, hypoglycemia, CV failure = multisystem organ dysfunction and death
151
Q

Gastritis. Associated cancers and etiologic agent

A
  • CA: gastric adenocarcinoma, maltoma

- Agent: helicobacter pylori

152
Q

Schistosomiasis. Associated cancers and etiologic agent

A
  • CA: bladder, liver, rectal carcinomas

- Agent: Schistosomas

153
Q

Cholangitis. Associated cancers and etiologic agent

A
  • CA: cholangiocarcinoma, colon carcinoma

- Agent: liver fluke, bile acid

154
Q

Chronic cholecystitis. Associated cancers and etiologic agent

A
  • CA: GB cancer

- Agent: various bacteria, gall stones

155
Q

Hepatitis. Associated cancers and etiologic agent

A
  • CA: hepatocellular carcinoma

- Agent: hep B and C

156
Q

PID. Associated cancers and etiologic agent

A
  • CA: ovarian and cervical carcinoma

- Agent: gonorrhea, chlamydia, papillomavirus

157
Q

Osteomyelitis. Associated cancers and etiologic agent

A
  • CA: skin carcinoma in draining sinuses

- Agent: various bacterial infections

158
Q

Define wound healing and wound repair

A
  • Wound healing: restoration of tissue architecture and function after an injury, ie. regeneration back to same physiology and anatomy as before injury
  • Wound repair: outcome is not anatomic restoration, but a functional compromise is achieved
159
Q

Describe model of wound healing

A
  • Damage = inflammation = removal of death tissue = healing
  • Damage = inflammation = replacement by a.) specialized tissue (regeneration) OR b.) fibrous tissue tissue (scarring) = healing
160
Q

Three groups of cells in the body. Provide examples and whether or not regeneration is possible

A
  1. ) Labile: cell population automatically enters cell cycle as part of normal turnover, chances of regeneration are excellent. Eg. Epithelium, bone marrow, epidermis
  2. ) Permanent: cell population does not change and cells don’t enter cell cycle and are not capable of proliferation, healing by scarring occurs in these tissues. Eg. neurons, cardiac muscle, smooth muscle
  3. ) Stable: cell population has little proliferation, but remains capable of rapid cell division under certain cues. Eg. liver, kidney
161
Q

Which tissue is capable of regeneration? Which is not?

A
  • Regeneration: epidermis, epithelium, bone marrow, liver, kidney
  • No regeneration: neurons, cardiac muscle, skeletal muscle
162
Q

Describe the phases of wound healing. Include the name, events and timeframes

A
  1. ) Inflammation: 1st week, depending on acute (0-2 days) vs chronic (>14 days)
    - Clot formation, chemotaxis
  2. ) Proliferation: 2nd week
    - Re-epithelialization, angiogenesis, granulation tissue, provisional matrix
  3. ) Maturation: 3rd week
    - Collagen deposition and matrix formation, wound contraction
163
Q

Angiogenesis. What is occurring, what is the regulatory molecule governing this process (where does this come from?)?

A
  • Process = endothelial cell proliferation = capillary budding
  • VEGF (from macrophages)
164
Q

Fibrogenesis. What is occurring, what is the regulatory molecule governing this process (where does this come from?)?

A
  • Process = collagen deposition as fibroblasts are activated and proliferating
  • TGF-beta (from macrophages)
165
Q

What is the name of the specialized tissue characteristic of healing? Composition?

A
  • Granulation tissue: pink, soft, granular tissue seen beneath scab of skin wound
  • Composition: fibroblasts / collagen, new delicate capillaries, loose ECM, also some macrophages
166
Q

Differentiate histologically between early and late granulation tissue

A
  • Early: numerous macrophages, myofibroblasts, blood vessels

- Late: less blood vessels, macrophages and more matrix and fibroblasts

167
Q

What is the concern when there is an overabundance of granulation tissue at a site of wound healing?

A
  • More granulation tissue = more contraction = greater risk of organ impairment via contracture
168
Q

Healing of skin wounds occurs by primary or secondary intention. What does this mean?

A
  • Primary intention: when non-infectious and non-foreign body injury occurs (such as surgical incision) causes margins to be apposed (lined up, non-gaping), healing occurs directly with minimum granulation tissue present meaning epithelial regeneration predominates over fibrosis.
  • Secondary intention: when injury causes margins to be un-apposed (not lined up, gaping) and/or infection/foreign body is present, healing occurs with more granulation tissue present and more epithelial regeneration meaning fibrosis and wound contraction predominates.
169
Q

Cell type(s) responsible for wound contraction

A
  • Myofibroblasts derived from fibroblasts. Wounds contract to prevent dehiscence, splitting of wound edges. When abnormal, ie. Too much contraction, this is called a contracture.
170
Q

What is contracture in wound healing?

A
  • Exaggerated contraction in some injured tissue resulting in severe deformity of wound and surrounding tissue. This compromises movement of joints and function of tissue.
171
Q

Factors that retard/prevent adequate healing

A
  • # 1 = Infection
  • Ischemia
  • Dry wound infection
  • Foreign bodies
  • Anti-inflammatory therapy (ie. Excess corticosteroids or pathology such as Cushing’s)
  • Nutritional deficiency
172
Q

Pathologic repair states, describe each

A
  1. ) Keloids: late stage defect of healing where there is accumulation of collagen giving rise to prominent raised scars. Hereditary component, common in AA
  2. ) Exuberant granulation tissue / proud flesh: early stage defect when there is excessive granulation tissue generated (abnormal growth and ECM production) and tissue protrudes above level of surrounding skin preventing proper wound closure and epithelialization. Bleeds easily and excessively.
  3. ) Contractures: Exaggerated contraction in some injured tissue resulting in severe deformity of wound and surrounding tissue. This compromises movement of joints and function of tissue.
173
Q

Hypotrophic vs hypertrophic scars

A
  • Hypotrophic: sunken often hyperpigemented scar appearance d/t loss of collagen and ground substance
  • Hypertrophic: similar to keloid where there is accumulation of collagen; however, does not get worse after 6 months. Excision of these does not cause regrowth, whereas excision of keloid does.
174
Q

Histological differences between keloid and hypertrophic scar

A
  • Keloid: haphazard arrangement of collagen with a few myofibroblasts
  • Hypertrophic: collagen arranged parallel to skin surface with numerous myofibroblasts

General Pathology (6 decks)

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