Download Pathology Course OSM I Study Guide [12-27

Chapter 1: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury,
and
Death
Reading assignment: 8th Edition: pp. 4-41
Learning Objectives:
1.
Define pathology and understand how it is subdivided (general and systemic).
Pathology- study of diseases
Subdivisions- structural, biochemical, and functional changes
2.
Describe the four aspects of disease processes that form the core of pathology.
Etiology- cause
Pathogenesis (mechanisms of development)
Molecular/morphologic changes- biochemical and structural alterations
Clinical manifestations- functional consequences of these changes
3.
Define hypertrophy and its mechanism.
Hypertrophy- increase in size of cells; no new cells
Due to synthesis of structural components of the cells with cellular proteins
Caused by increased functional demand, stimulation by hormones and growth factors
Can be physiologic or pathologic
Mechanism- mechanical sensors, growth factors, vaso active agents
Two main biochem pathways- phosphoinosidase 3-kinase/akt pathway or signaling
downstream of g protein coupled receptors
Selective hypertrophy possible- increase of ER, for example
4.
Define hyperplasia and its mechanism.
Increase in the number of cells in an organ or tissue; results in increased mass.
May occur with hypertrophy
Physiologic or pathologic
Mechanism by growth factor-driven proliferation of mature cells
5.
Compare and contrast physiologic and pathologic hyperplasia.
Physiologic hyperplasia- hormonal hyperplasia (increases functional capacity of a tissue
when needed) or compensatory hyperplasia (increases tissue mass after damage or partial
resection)
Pathologic hyperplasia- caused by excess of hormones or growth factors acting on target
cells
6.
Define atrophy and list and describe the common causes of atrophy.
Atrophy- reduced size of an organ/tissue; results from decrease in cell size and number
Physiologic atrophy- common during normal development
Pathologic atrophy- local or generalized; depends on underlying cause
Causes- decreased workload, loss of innervation, diminished blood supply, inadequate
nutrition, loss of endocrine stimulation, physical pressure
7.
Describe the mechanism of atrophy.
Decreased protein synthesis
Increased protein degradation
Increased autophagy (self eating done by starved cells)
8.
Define metaplasia and its mechanism.
Metaplasia- reversible change; one differentiated type of cell replaced by another type;
sensitive to stress; most common is epithelial metaplasia (barrett esophagus)
Mechanism- does not result from a change in the phenotype of an already differentiated
cell type
Result of reprogramming, precursor cells differentiate along a new pathway
9.
Describe reversible and irreversible cell injury and cell death.
Reversible can lead back to homeostasis
Irreversible can lead to either necrosis or apoptosis - continuous damage
10.
List and describe the common causes of cell injury.
Common causes- oxygen deprivation, physical agents, chemical agents, infectious agents,
immunologic reactions, genetic problems, nutritional problems
11.
Describe the basic morphologic alterations that occur in damaged cells.
Reversible injury- swelling of the cell and its organelles, blebbing of the plasma
membrane, detachment of ribosomes from the ER, clumping of nuclear chromatin, fatty
change (see lipid vacuoles from hypoxic injury)
12.
Know the features of reversible cell injury and be aware of the ultrastructural
changes.
As described above- decreased generation of atp, loss of cell membrane integrity, defects
in protein synthesis
Also- mitochondrial swelling
13.
Define necrosis and describe its general morphologic appearance.
Necrosis- continuous damage- cell injury is irreversible; lysosomal enzymes enter
cytoplasm and digest cell, cellular components leak out (causes inflammation of
surrounding tissue); always pathologic
Appearance- increased eosinophilia, glassy homogenous appearance, digestion of
organelles, dead cells
14.
Compare and contrast between the different types of necrosis.
Coagulative necrosis- architecture of dead cells is preserved for a couple of days, tissue has
firm texture, localized area is an infarct; anucleate cells can persist for weeks; caused by
ischemia
Liquefactive necrosis- characterized by digestion of dead cells- transforms the tissue into
liquid viscous mass; seen in bacterial infections; creamy yellow (pus)
Gangrenous necrosis- no specific pattern; applied to a limb, usually lost blood supply; can
complement liquefactive necrosis
Caseous necrosis- seen in tuberculous infection; looks cheese like (white appearance); see
fragmented cells and granular debris enclosed in distinctive inflammatory border; focus
known as a granuloma
Fat necrosis- no specific pattern- fat destruction- see necrotic fat cells- calcium deposites;
inflammatory reaction
Fibrinoid necrosis- immune reactions with blood vessels, see complexes of
antigens/antibodies in artery walls; see fibrinoids- deposits of immune complexes and
fibrin
15.
Discuss the major causes of ATP depletion and its effects on critical cellular
systems.
Associated with hypoxic and chemical injury
Major causes- reduced supply of oxygen/nutrients; mitochondrial damage, toxins
Major effects- sodium atp pump starts failing- sodium accumulates now in cells and
potassium accumulates outside; causes cell swelling
Metabolism is changed- oxidative phosphorylation stops- decreased cellular atp
Failure of calcium pump- leads to influx of calcium and damages organelles
Structural disruption- detachment of ribosomes from ER, not as much protein synthesis
Oxygen disruption- proteins may become misfolded
Irreversible damage to mitochondrial/lysosomal membranes- cell necrosis
16.
Describe the role of mitochondria and be aware of the two major
consequences of mitochondrial damage.
Supplies atp; players in cell injury and death
Results in formation of mitochondrial permeability transition pore- leads to loss of
membrane potential- results in failure of OP (oxidative phosphorylation)
Also results in protein accumulation between inner/outer membranes- activates apoptotic
pathways
17.
Describe how the loss of calcium homeostasis affects the cell and its organelles.
Maintained at low concentrations; usually stored in er and mitochondria
Increased calcium increases phospholipids (membrane damage) and other enzymes
Proteases- breaks down membrane and cytoskeleton proteins
end nucleases- dna/chromatin fragmentation
Atpases- atp depletion
Increase ca- induction of apoptosis
18.
Define free radical.
Chemical species with single unpaired electron in outer orbit; ROS- oxygen derived
19.
Discuss the generation and removal of free radicals and how they contribute
to cell injury.
Formed during reduction-oxidation reactions during normal metabolism
Absorption of radiant energy4
Produced by leukocytes through an inflammatory reaction
Enzymatic metabolism of drugs
Transition metals
Nitric oxide can act as a free radical
Lipid per oxidation in membranes- fatty acids in membrane lipids are attacked by o2
derived free radicals
Oxidative modification of proteins (oxidation of aa side chains) and lesions of dna
20.
Briefly describe the mechanisms and consequences of membrane damage.
Biochemical mechanisms- ROS, decreased phospholipid synthesis, increased
phospholipid breakdown, cytoskeleton abnormalities
Consequences- mitochondrial damage (open the pore), plasma membrane damage (loss of
osmotic balance, contents), injury to lysosomal membranes (leakage of enzymes)
21.
Describe ischemic and hypoxic cell injury and be familiar with the
mechanisms of ischemic cell injury.
Hypoxia- reduced oxygen availability; occurs in clinical settings
Ischemia- supply of oxygen and nutrients is decreased; because of reduced blood flow;
aerobic metabolism stops- anaerobic energy generation stopped; leads to more rapid/severe
injury than does hypoxia (with no ischemia)
Mechanism (ischemic or post-hypoxia)- oxygen tension decreases, loss of OP, decreased
production of ATP, failure of sodium pump (cell swelling), influx of calcium, loss of
glycogen, less protein production; if oxygen is restored, injury is reversible
Mechanism continued- influx of calcium into the cell, death mainly by necrosis,
mitochondria swell, lysosomes swell
22.
Describe ischemia-reperfusion injury.
Blood flow restored to cells that have been ischemic but not dead; injury is exacerbated;
may sustain injury to more cells that were ischemic in the first place- have to be careful
when restoring blood to ischemic tissues (when trying to promote recovery)
Mechanism- increased generation/accumulation of ROS, calcium may also enter cells
Associated with inflammation (production of cytokines), activation of complement system
(involved in host defense)
23.
Describe chemical (toxic) injury.
Due to drug metabolism in the liver; toxic liver injury most common for stopping drug use
Direct injury- combining of molecular components, causes increased membrane
permeability and/or inhibition of ion transport
24.
Define apoptosis and define the causes, biochemical processes, and
mechanisms of apoptosis.
Tightly regulated suicide program, no host reaction
Cause- eliminate cells that are no longer needed or beyond repair; maintains steady
population
Regression of hormone dependent tissues when the hormones are no longer administered
Elimination of self reaction lymphocytes
Responsible for death of cells in pathological states (viral infections)
Biochemical features- activation of cysteine proteases (aka capases); presence of cleaved
capases indicates apoptosis (exec 3,6, init 8,9)
Mechanism- cells get smaller and then break up into apoptotic bodies- become targets for
phagocytes
Divided- two phases- initiation- caspases become active; execution- caspases trigger
degradation
Intrinsic (mitochondrial)- major one, increased mito permeability, releases pro apoptotic
molecules into the cytoplasm
Extrinsic (death receptor)- starts by engaging plasma membrane death receptors (members
of TNF receptor family)
Both pathways lead to activation of the executioner caspases
Phosphatidylersine is present on the inner membrane of healthy cells, this membrane flips
out in apoptotic cells and is recognized by macrophages
25.
Describe autophagy.
Cell eats its own nutrients
Fuses with lysosomes to form autophagolysosome, results in intracellular accumulations
Either water/lipids/proteins/carbs accumulate or abnormal substances accumulate
26.
Be familiar with intracellular accumulations and its four types of
abnormalities.
Normal endogenous substance is produced normally, but rate of removal is deficient
Abnormal endogenous substance accumulates (misfolded/mistransport of proteins);
unable to degrade the substance normally
Normal endogenous substance accumulates because of some defect in the metabolic
enzymes
Abnormal exogenous substances accumulate because the cell is unable to transport or
doesn’t have the enzymes to degrade the substance
27.
Describe steatosis and be familiar with its mechanism and morphology.
Steatosis (fatty change)- abnormal accumulations of triglycerides within parenchyma cells,
seen in liver (due to role in fat metabolism) and heart
Causes- toxins, protein malnutrition, DM, obesity, most common- alcohol abuse in
developed countries, diabetes or obesity also
Free fatty acids usually transported into hepatocytes; if transport or metabolic errors,
triglycerides cannot be exported (may be induced by etoh)
Appears as clear vacuoles with water inside; organ appears yellow and weighs much more;
heart may have a tiger striped color effect
28.
Be familiar with the histologic manifestations of accumulated cholesterol and
its associated pathologic disease process.
Normally cells use cholesterol for cell membranes- accumulations seen by vacuoles,
atherosclerosis (lipid vacuoles filled with cholesterol), xanthomas (cholesterol in
macrophages), cholesterolosis (cholesterol in the gall bladder), niemann pick disease type
C (lysosomal storage disorder, cholesterol found in multiple organs due to general enzyme
error)
29.
Be familiar with the histologic manifestations of intracellular protein and its
diverse causes.
Rounded eosinophilic droplets, vacuoles, aggregations in cytoplasm
Could be normal proteins secreted excessively
Caused by defective intracellular transport/secretion (alpha 1 anti trypsin deficiency),
accumulation of cytoskeleton proteins, aggregation of normal proteins
30.
Describe the histologic manifestations of hyaline change and glycogen
deposition.
Alteration within cells- gives homogenous, glassy, pink appearance, does not represent
anything (and not accumulation)
Glycogen deposition- a lot intracellular, appear as clear vacuoles in cytoplasm, dissolves in
aqueous fixatives
31.
Define pigments and describe the two types of pigments produced (exogenous
and endogenous).
Endogenous- formed in the body
Lipofuscin- sign of free radical injury or lipid per oxidation; yellow brown, granular, seen
in cells going through slow, regressive changes
Melanin- non hemoglobin derived- brown black (only endogenous brown black)
Hemosiderin- golden yellow to brown- storage form of iron, seen in phagocytes of bone
marrow, spleen, liver engaged in red blood cell breakdown
Iron- coarse, golden- cause is localized breakdown of red cells
Bilirubin- major pigment found in bile, contains no iron, derived from hemoglobin
32.
Describe pathologic calcification and compare and contrast between the two
different types (dystrophic versus metastatic).
Abnormal tissue deposition of calcium salts
Dystrophic- local deposition in dying tissues, occurs with normal ca levels, seen in necrosis
Metastatic- deposition in normal tissues, probably some disturbance in ca metabolism
33.
Define cellular aging.
Progressive decline in cellular function/viability, caused by genetic abnormalities,
accumulation of damage, regulated, has definable characteristics
34.
Understand how metabolic events, genetic damage, and cellular aging are
related.
Cellular life span determined by rate of repair vs. rate of metabolic destruction
Chapter 2: Acute and Chronic Inflammation
Reading assignment: 8th Edition: pp. 44-75
Learning Objectives:
1.
Define acute and chronic inflammation.
Acute- rapid in onset, short duration, exudation of fluid/proteins, emigration of neutrophil
Chronic- may follow acute- longer duration, lymphocytes and macrophages, proliferation of
blood vessels and fibrosis, see tissue destruction
2.
Be familiar with the five cardinal signs of inflammation.
Redness, swelling, heat, pain, loss of function
3.
Describe the three major components of acute inflammation.
Alterations in vascular caliber
Structural changes of microvasculature
Emigration of leukocytes
4.
List and describe the stimuli involved in acute inflammation.
Infections- most common
Tissue necrosis- ischemia, trauma, physical injury
Foreign bodies, immune reactions
5.
Define exudate and transudate.
Exudate- inflammatory extra vascular fluid- high protein concentration (>1.020), due to
increased permeability
Transudate- fluid with low protein concentration (albumin) (sg < 1.012), permeability
usually not increased
6.
Describe the process of vasodilation.
Early sign of acute inflammation, arteriolar constriction, lasts few seconds, increased blood
flow (causes heat and redness- erythema)
Induced by histamine, nitric oxide, other mediators
7.
Be familiar with the hallmark of acute inflammation.
Increased vascular permability- hallmark #1, leads to exudate- caused by contraction of
endothelial cells
Caused by endothelial injury (results in necrosis and detachment) or transcytosis
(increased transport of fluids/proteins through the endothelial cell)
Erythema (?) - vasodilation- followed by increased vascular wall permeability - exudate
Loss of fluid and increased vessel diameter- leads to slower blood flow, increased viscosity
(due to more blood cell concentration), may result in stasis
8.
Explain the processes of leukocyte recruitment to sites of infection and injury.
During stasis- neutrophils are accumulating on vascular endothelium, they attach to the
endothelium after the endothelium has been activated via mediators; neturophils the
migrates through vascular wall into the interstitial tissue
Recruitment from blood into extra vascular tissues, recognition of microbes, removal of
offending agent
Extravasation- journey of leukocytes- vessel lumen to interstitial tissue, migration towards
tissues via chemo tactic stimulus
Margination- blood flows slowly in inflammation (stasis), since blood flow changes,
allows leukocytes to accumulate on endothelium
Transmigration/diapedesis- migration of leukocytes through endothelium via chemical
gradient
Leukocytes pierce basement membrane of endothelium, enter extra vascular tissue,
migrate still with chemicals (chemo taxis), accumulate in extra vascular site
Chemo taxis accomplished by chemoatractants (exogenous- bacteria, endogenous,
chemical mediators- cytokines, arach. Acid, AA)
Neutrophils replaced by monocytes in 1-2 days - better survival rate
Calcium activates enzymes (protein kinase C) of leukocytes to remove offending agents
(via phagocytes, intracellular killing)
Prolonged host response contributes more to pathology than initial insult
Chediak- higashi- defective fusion of phagocytes and lysosomes
Chronic granulomatous disease- defects in bacterial killing - collections of activated
macrophages that can’t kill microbes but instead wall it off (forms granulomas)
9.
Understand the general principles of the chemical mediators of inflammation.
Growth factors - produced by leukocytes- proliferation of endothelial cells and fibroblasts
for repair and remodeling
Mediators formed from cells or plasma proteins
Synthesized in response to a stimulus (prostoglandins, cytokines)
Cell derived mediators- platelets, Europhiles, macrophages, mast cells, endoth cells
Plasma derived mediators- complement proteins, kinins, produced in liver, usually inactive
Active mediators- produced in response to stimuli, complement, kinin, coagulation
systems; only activated by offending agents, so mediators are localized
Mediators are short lived, quickly decay, inactivated by enzymes, and then inhibited
10.
List and briefly discuss the source and actions of the major chemical
mediators of inflammation.
vasoactive amines- histamine (1)- from mast cells- released in response to physical injury,
antibody activity, anaphylatoxins, neuropeptides, cytokines
Causes dilation of arterioles, principal mediator of immediate increased vascular
permeability
Serotonin (2)- present in platelets- similar to histamine- stimulated when platelets
aggregate- key component in coagulation; also present in neuroendocrine cells
AA arachidonic acid metabolites- prostaglandins, leukotrienes, lipoxins
AA- released via physical, mechanical, chemical stimuli from membrane
Aa derived mediators- eicosanoids- cyclooxygenases cox1/2 (make prostaglandins),
lipoxygenases (made leukotrienes and lipoxins)
Prostoaglandins- made by mast cells, macrophages, others- involved in vascular/system
reactions of inflammation
Prostacyclin- important prostagl, vasodilator, inhibits platelet aggregation, potentiates an
increase in vascular permeability
Pgd2- made by mast cells- causes vasodilation, increased permeability of post capillary
venules, chemo attractant for neutrophils
Pgf2 alpha- contraction of uterine/bronchial smooth muscle
Pge2- makes skin hypersensitive to pain, involved in cytokine induced fever during
infections
Leukotrienes- secreted by and chemo attractants for leukocytes
5-lipoxygenase- chemo tactic for neutrophils
Ltb4- potent chemo tactic agent and activator of neutrophils, causes adhesion of cells to
endo, generates ROS, releases lysosomal enzymes
Certainly containing leukotrienes- intense vasoconstriction, bronchospasm, increased
vascular permeability
Lipoxins- inhibitors of inflammation, inhibit leukocyte recruitment, inhibit chemo taxis
and leukocyte adhesion
Platelet activating factor (paf)- causes platelet aggregation, inflammatory effects
Causes vasoconstriction, increased venular permeability, causes increased leukocyte
adhesion, chemo taxis, degranulation, and oxidative burst, boosts eicosanoid production
Reactive oxygen species (ROS) - released extracellularly from leukocytes, production
dependent on NADPH oxidase system
Seen in endothelial cell damage, increased vascular permeability, injury to other cells,
inactivation of anti proteases
Antioxidants- detoxes radicals
Cytokines- proteins- activated by lymphocytes/macrophages- involved in cellular immune
responses
TNF/IL-1- major cytokines produced by macrophages that mediate inflammation
Induce expression of endothelial adhesion molecules, promotes synthesis of other
mediators (cytokines, NO, eicosanoid, growth factors)
Induces systemic acute phase response
Regulates energy balance- promotes lipid/protein mobilization, suppresses appetite
Chemokines- primarily chemo attractants for leukocytes, stimulate leukocyte recruitment
and migration
CXC- act on neutrophils mostly, causes activation and chemo taxis
CC - attract monocytes, eosinophils, basophils, lymphocytes
C - specific for lymphocytes
CX3C11.
Understand the role of nitric oxide in the inflammatory response.
Causes vasodilation- produced by endoth cells, acts in a paracrine manner, half life is
seconds
Relaxes vascular smooth muscle and promotes vasodilation; inhibits cellular component of
inflammatory reaction
Reduces platelet aggregation, inhibits leukocyte recruitment, is a mediator of host defense
12.
Briefly describe how lysosomal constituents, free radicals, neuropeptides, and
other mediators may contribute to inflammation.
Granules can fuse with phagocytic vacuoles contained engulfed material - granule content
can be released into the extra cellular space
Neuropeptides- role in initiation and propagation of inflammation- substance P and
neurokinin A- transmit pain, regulate BP, increases vascular permeability
plasma protein mediators- described below
13.
Be familiar with the complement system.
20 proteins- function in innate and adaptive immunity, activation is dependent on cleavage
of C3
Inflammation- c3a, c5a, c4a- stimulate histamine release from mast cells, increase vascular
permeability and vasodilation- these proteins are anaphylatoxins
C5a- chemo tactic agent for neutrophils, monocytes, eosinophils; basophils, causes release
for more inflammatory mediators
Phagocytosis- c3b acts as opsonin- promotes phagocytosis
Cell lysis- deposition of MAC on cells- makes them extremely permeable- results in death
C3 and c5 are the most important- can be cleaved by enzymes in the inflammatory exudatecan initiate self perpetual cycle of neutrophils recruitment
14.
Describe coagulation and the kinin systems.
Coagulation system- Culminate with activation of thrombin, formation of fibrin
Intrinsic clotting- activated by Hageman (factor 7)
Kinins- vasoactive peptides
Bradykinin- increases vascular permeability, contracts smooth muscle, dilates blood
vessels, painful when injected into skin, short life in blood
Factor 7 also activates fibrolytic system- kallikrein- cleaves plasminogen- generates
plasmin- lyses clots, cleaves c3 to fragments- degrades fibrin to form fibrin split products
15.
Describe the three possible outcomes of acute inflammation.
Complete resolution- restoration to normal
Healing by connective tissue replacement- fibrosis after tissue destruction
Progression to chronic inflammation - persistence of offending, interference with normal
healing process
16.
List and describe the patterns of acute inflammation.
Dilation of small blood vessels, slowing blood flow, accumulation of leukocytes and fluid
Serous inflammation- outpouring of thin fluid, may accumulate into cavities (effusion),
may appear as a skin blister
Fibrinous inflammation- fibrinous exudate, large vascular leaks, procoagulant stimulus
involved, characteristic of inflammation in the lining of body cavities
Fibrinous exudate- removed by fibrinolysis and clearing via macrophages; if not removed,
ingrowth of fibroblasts occurs and leads to scarring
Suppurative inflammation- large amounts of purulent exudate- neutrophils, liquefactive
necrosis and edema fluid; bacteria can cause this
Abscesses- localized collections of purulent inflammatory tissue (can be buried in a tissue
by deep seeded bacteria); appears as a mass of neutrophils surrounded by vascular dilation
and fibroblast proliferation
17.
Describe an ulcer.
Local defect of surface of an organ or tissue
Produced by shedding of inflamed necrotic tissue
Seen usually in mucosa of mouth, stomach, intestines, genitourinary tract, skin
18.
Define chronic inflammation, describe its etiology, and describe its histologic
features.
Can take weeks/months, begin insidiously, or may follow acute inflammation
Causes- persistent infections, immune mediated inflammatory diseases, autoimmune
diseases, atherosclerosis (chronic inf process of arterial wall)
Histologic features- infiltration with mononuclear cells (macro, lympho, plasma cells),
tissue destruction, proliferation of small blood vessels, fibrosis
19.
Discuss the cell types involved and the mechanisms responsible for chronic
inflammation.
Macrophages- part of mononuclear phagocyte system (aka reticuloendothelial system),
seen in wide variety of tissues
Mononuclear phagocytes arise from bone marrow, become blood monocytes- these
monocytes migrate into tissues where they differentiate into macrophages - macros
eliminate offenders, initiate repair, responsible for tissue injury in chronic inf
Activated by increased lysosomal enzymes, ROS, production of cytos, growth factors
Lymphocytes
Plasma cells- from B lymph’s, produce antibodies
Eosinophils - popular in immune reactions (mediated by ige), parasitic reactionschemokine for eosinophil recruitment (eotaxin); granules contain toxic protein to parasites,
contributes to tissue damage in immune reactions
Mast cells- in acute/chronic inf, causes degranulation and release of mediators (histamine,
prostaglandins), responsible for allergic reactions (could result in anaphylactic shock)
20.
Describe granulomatous inflammation.
Pattern of chronic inf; cellular attempt to contain the offending, strong activation of T
lymphocytes which leads to macrophage activation; seen in TB
Granuloma- aggregation of macrophages surrounded by lymphocytes; usually pale and
pink and granular, fuses to form giant cells
Two types- foreign body granuloma- by a foreign body
Immune granulomas- caused by agents that initiate a cellular immune response (when
offending is poorly degradable or particulate)
21.
Compare and contrast between the two types of granulomas.
See above
22.
Discuss the systemic effects of inflammation.
Fever- elevation of body temp
Acute phase proteins- plasma proteins from the liver that concentrate in the plasma (CRP,
fibrinogen, SAA)
Leukocytosis- very high leukocyte count (15-20k/uL up to 40-100k/uL)
Bacterial infection (increase in blood neutrophils count)
Viral infection (increase in lymphocyte count)
Bronchial asthma, allergy, parasitic infestations - increase eosinophil count
Infections - decreased number of circulating white cells (leucopenia)
Increased pulse and BP, decreased sweating (redirected blood flow minimizes heat loss),
shivers (rigors), chills (warmth), anorexia
23.
Be familiar with the consequences of excessive inflammation.
Defective inf- Increased susceptibility to other infections
Delayed wound healing
Excessive inf- allergies, basis for many diseases
Chapter 3: Tissue Renewal and Repair: Regeneration, Healing, and Fibrosis
Reading assignment: 8th Edition: pp. 79-108
Learning Objectives:
1.
List and describe the two distinct processes of tissue repair.
Regeneration- complete restitution of lost or damaged tissue, very rare after injury
Seen often in hematopoietic system, skin, GI tract - high proliferative capacity, renew
continuously, regenerate after injury
Repair- restore some original structures, may cause structural derangements, combination of
regeneration of scarring (collagen deposition)
Occurs in chronic inf- accompanies persistent injury- stimulates scarring
Fibrosis- a lot of collagen deposition, ECM is essential for the framework, cell polarity, and
angiogenesis (formation of new blood vessels)
ECM also gets macrophages, fibroblasts which produce growth factors, cyto/chemokine
2.
Review the cell cycle and the general controlling mechanisms.
Stimulation by physiological factors- hormonal- proliferation of endometrial cells
Stimulation of pathological factors- abnormal hyperplasia
Environmental signals control cell proliferation
Cell cycle- g1(presynthetic), s (dna synthesis), g2 (premitotic), m (mitotic) (go is for the
quiescent cells)
G1/s- rate limiting restriction point to check dna integrity, after this, cells are irreversibly
committed to dna replication
Regulated by protein cyclins (enzymes CDK- cyc dependent kinases)
G2/m - checks dna after replication before mitosis
Too much damage beyond repair leads to apoptosis or enter nonreplicative state
(senescence)
3.
Be able to describe cells according to their proliferative activity as labile,
quiescent and nondividing.
Labile- continuously dividing, proliferate through life (surface epithelia, skin, oral cavity,
vagina, cervix; lining mucosa of excretory ducts; GI tracts, bone marrow cells), mature
cells derived from adult stem cells (high proliferative capacity)
Quiescent - stable tissue - low level of replication- divide under a stimuli- can reconstitute
an organ- parenchymal cells of liver, kidneys; pancreas; mesenchymal cells- fibroblasts
and smooth muscle; ability of liver to regenerate
Also fibroblasts, endoth cells, smooth muscle cells, chondrocytes, osteocytes (prolif in
response to injury)
no dividing- permanent tissues, left the cell cycle- neurons, skeletal muscle cells, cardiac
muscle cells, destruction of CNS cells replaced by supporting cells
S muscle cells- do not divide, but can regenerate through satellite cells
Cardiac cells- limited regen
4.
Fully describe the two major characteristics of stem cells.
Self renewal
Capacity to generate differentiated cell lineages - but must be maintained during the life of
the organism- obligatory asymmetric replication- each stem cell division gets one daughter
and another self renewed stem cell; stochastic differentiation- each division either results
in 2 daughters or 2 self renewing stem cells
5.
Understand the term embryonic stem cell.
Pluripotent- potential to generate all tissues of the body
Can give rise to multipotent stem cells- a little more restricted, produce differentiated cells
(3 embryonic layers)
Located within blastocyst
6.
List the three observations which have revolutionized and energized stem cell
research.
ES may be used to repopulate damaged organs
Induced pluripotent stem cells- differentiated cells of adult tissue can be reprogrammed to
become pluripotent via a nucleus transfer - reproductive cloning
Nuclear transfer to oocytes may be used in treating human diseases
7.
Discuss the pluripotent nature of embryonic stem cells and the possible nature
of this characteristic.
See above
8.
Discuss the three major impacts embryonic stem cells have on modern
biology.
9.
Define and differentiate between the adult stem cells and tissue stem cells and
know what is meant by the idea of a niche.
Niche- adult stem cells reside in special micro environments- niche cells generate stimuli
that regulate cell self renewal
Adult stem cells have restricted capacity to generate different cell types; stem cells are
present in tissues and continuously divide (bone marrow, skin, gi tract lining)
Adult stem cells - give rise to transit amplifying cells- rapidly dividing cells- eventually
lose capacity of self perpetuation- gives rise to cells with restricted developmental
potential- progenitor cells
Asc- can transdifferentiate- change in the differentiation of a cell from one type to another
(developmental plasticity)
Asc located in bone marrow, skin, gut, liver, brain, muscle, cornea
10.
Describe and compare and contrast HSC’s and bone marrow stromal cells.
Bone marrow contains HSC (hematopoietic stem cells) and stromal cells (Mesenchymal
stromal cells- MSC)
HSC- generate all blood cell lineages, and can reconstitute bone marrow after depletion
MSC- multipotent, generate chondrocytes, osteoblasts, Adipocytes, myoblasts, endoth
cells
Migrate to injured tissues and general stromal cells or other cell lineages
Don’t take part in normal homeostasis like HSC do
11.
Describe MAPCs.
12.
Briefly discuss the role of stem cells in liver, brain, muscle and renewing
epithelium.
Liver has stem cells in canals of hering- gives rise to precursor cells (oval cellsdifferentiate into hepatocytes or billiary cells)
Oval cells- reserve compartment, activated when normal hepatocytes development is
blocked (liver problems)
Brain- NSC neural stem cells- can generate neurons, astrocytes, oligodendrocytes
Skin - skin has high turnover rate of 4 weeks, stem cells located in different areas of the
epidermis (like the hair follicle bulge which creates a niche for stem cells, interfollicular
area, and the sebaceous glands)
Small intestine- stem cells located in crypts (derived from a single stem cell); villus
contains cells from multiple crypts
Skeletal muscle- myocytes don’t divide, even after injury; satellite cells have a pool of
stem cells which grow and regenerate injured skeletal muscle
Cornea- limbal stem cells lsc- maintain integrity of the outermost corneal epithelium
13.
Review the growth factors, their sources, and functions.
Function as ligants that bind to specific receptors
Epidermal growth factor (EGF) and transforming growth factor a (TGF-alpha-a) - share
common receptor EGFR
EGF- Encourages epithelial cells, hepatocytes, and fibroblasts to differentiate, distributed
in tissue secretions and fluids
TGF-a- epithelial cell proliferation (can result in cancers of lung, head, neck, breast)
HGF- hepatocytes gf- encourages hepatocytes and epithelial cells to differentiate (epit cells
of lungs, kidney, mammary glands, skin); enhances survival of hepatocytes; produced by
fibroblasts or mesenchymal cells
PDGF- platelet derived gf- produced by macrophages, endot cells, smuscle cells and tumor
cells
Migration and proliferation of fibroblasts, sm cells, monocytes in areas of inflammation
VEGF- vascular endothelial gf- inducer of blood vessel formation in early development
(vasculogenesis), as well as angiogenesis (new blood vessel formation in adults) in chronic
inflammation, wound healing, and in tumors
FGF- fibroblast gf- wound healing, re epithelialization of skin wounds; contributes to
hematopoiesis (differentiation of blood cells), angiogenesis, development (c/skeletal
muscle, lung, liver)
TGF-b- produced by platelets, endoth cells, lymphocytes, macrophages
Strong fibrogenic agent, stimulates fibroblast chemo taxis, enhances collagen production,
inhibits its degradation, responsible for fibrosis in chronic inf
Cytokines- mediators of inf and immune responses
TNF/IL-1- wound healing reactions, involved in initiation of liver regeneration
14.
List the two signals transduced at target cells by growth factors.
15.
Describe the three general modes of signaling used for cell growth.
Autocrine- molecules affecting secreting cells
Paracrine- molecules affecting neighboring cells- common in connective tissue repair and
healing wounds (and liver regen)
Endocrine signaling- hormones acting on distant cells (example is a cytokine)
16.
Review the properties of the major types of receptors and how they transduce
signals to the cell interior.
Intrinsic tyrosine kinase activity- ligands are most growth factors (egf, tgf-a, hgf, pdgf,
vegf, fgf, insulin)- has extra cellular binding domain and Tran membrane region
Cytoplasm tail has intrinsic TK activity
Binding of the ligand- tyrosine phosphorylation- activation of TK receptor, phosphorylates
downstream molecules
Lacking intrinsic tyrosine kinase activity- recruits kinases, ligands are cytokines (il2, il3,
inferons, erythropoietin, growth hormone)
Receptors transmit extra cellular signals into the nucleus, then activate janus kinase (JAK)
proteins which activate cytoplasmic transcription factors (STAT- signal transducers and
activation of transcription)- directly go into nucleus and start transcription
G Protein coupled receptors- use trimeric GTP binding proteins (g proteins), largest family
of plasma membrane receptors, has large number of ligands (chemokines, vasopressin,
serotonin, histamine, epine, norepi, glucagon, many pharma drug targets)
Steroid hormone receptors - located in nucleus- ligand dependent transcription factorsligands diffuse through cell membrane and activate receptors- ligands include thryoid
hormone, vitamin d and retinoid
Involved in adipogenesis, inflammation, and atherosclerosis
17.
Discuss the function of transcription factors.
Transfer information to the nucleus and modulate gene transcription (some also regulate
cell proliferation)
Growth promoting- cmyc, cjun, inhibiting- p53
18.
Understand the concept that regeneration of mammalian tissue is really
compensatory growth processes.
We don’t get new growth of the liver- get compensatory hyperplasia or hypertrophy (in the
case of the kidney); restitution of functional mass rather than reconstitution of the original;
there is hepatocyte replication (they are quiescent cells)
19.
List and define the components of the extracellular matrix and how they are
relevant to regeneration, healing, and fibrosis.
Ecm offers- growth regulation, remodeling, sequesters water (gives turgor), mechanical
support, control of cell growth, maintenance of cell differentiation, scaffolding for tissue
renewal, establish of microenvironment, storage of regulatory molecules
Fibrous structural proteins- collagens, elastins
Provide tensile strength and recoil
Adhesive glycoproteins- connect matrix elements together
Proteoglycans/ hyaluronan- provide resilience and lubrication
Interstitial matrix- mostly collegen, elastin, p/h - found in spaces between cells and in
connective tissue
Basement membranes- associated with cell surfaces- consists of collagen type 4,
proteoglycans
Collagen- most common protein in animal world, provides extra cellular framework for
cells
Elastin, fibrillin, elastic fibers- blood vessels, skin, uterus, lung require elasticity- elastic
fibers have a core of elastin with microfibrillar network surrounding it (serves as a scaffold
for more elastin)- deficient in Marfan’s- changes in cardiovascular system
Cell adhesion proteins- CAMs- protein transmembrane receptors allow interaction
between different or same cell types - four families exist
Integrins- provides connection between cells and ECM and adhesive proteins in other cells
for cell 2 cell contact; others in the cam family include immunoglobulin CAMs, cadherins,
selectins
Cadherins/integrins- link cell surface with cytoskeleton- for transmission of mechanical
force
Cadherins- calcium dependent- connect plasma membranes of two adjacent cells (zonal
adherans- small junctions; desmosomes- stronger, extensive junctions)
Play a major role in cell motility, prolif, differen, and inhibition of cell prolif when normal
cells contact each other (deficiencies can lead to cancer)
Fibronectin- binds to many molecules and cell surface receptors; large protein; plasma
fibronectin binds to fibrin and stabilizes blood clots
Laminin- most abundant glycoprotein in the basement membrane, team up with collagen
type 4 in the basement membrane, mediates attachment of cells to connective tissue
substrates
Sparc- tissue remodeling in response to injury, angiogenesis inhibitor
Thrombospondins- inhibit angiogenesis, like sparc
Osteopontin (OPN)- regulates calcification, mediator of leukocyte migration, vascular
remodeling
Tenascin- involved in morphogenesis and cell adhesion
Glycosaminoglycans (GAGS)- four families
Proteoglycans- ground substance, regulate CT structure and permeability; act as
modulators of inf, immune responses, cell growth and diff; activate gf and chemokines
Hyaluronan- gag- binds a lot of water- in ecm of heart valves, eye, skin, skeletal tissues
Provides resilience and lubrication (like in cartilage)
TISSUE REPAIR
3-5 days specialized type of tissue appears- granulation tissue- looks pink from fibroblast
proliferation, outcome is dense fibrosis
20.
List and describe the various types of collagen.
Types 1-4, 11 are fibrillar collagens- found in extra cellular fibrillar structures
Type 4- form sheets (not fibrils), main components of basement membrane
Type 7- forms fibrils between epith and mesenchymal structures (between epidermis and
dermis)
Vitamin c required for collagen formation
21.
Explain the process of angiogenesis.
Development of collateral circulations at sites of ischemia
Vasodilation- response to NO and VEGF (also increases vascular permeability)
Proteolytic degradation of basement membrane
Migration of endoth cells towards angiogenic stimulus
Proliferation of endoth cells
Maturation of endoth cells
Recruitment- vascular smooth muscle cells to form mature vessel
22.
Describe the processes involved in scar formation.
Inflammation- injury causes platelet adhesion/aggregation- forms a clot
Rapid activation of coagulation pathway- release of vegf- neutrophils arrive within 24 hrs
and use the fibrin scaffold to infiltrate
Proliferation- formation of granulation tissue, prolif/migrat of ct cells, re-epith of surface
Gran tissue in 24-72 hrs of repair- gran tissue is hallmark of tissue repair
See presence of new small blood vessels, prolif of fibroblasts, gran tissue looks pink, soft
and granular
Gran tissue much more prominent in healing by 2ndary union
5-7 days gran tissue fills the wound
New vessels are leaky- allows passage of plasma proteins into intravascular space, tissues
are edematous
Maturation- ecm deposition, tissue remodeling, wound contraction
Neutrophils replaced by macrophages 48-96 hours, key to tissue repair
Migration of fibroblasts to site of injury driven by chemokines (macrop stimulated)
Collagen fibers start from margins of the incision and work their way in
Do get full epithelialization of the wound surface (slower in 2ndary union)
Macrophages stim fibroblasts; cxc promotes skin re epith.
Concurrently with epithel, collagen fibrils become more abundant
Matrix containing fibrin, plasma fibronectin, and t3 collagen is formed
Tgf-b- most important fibrogenic agent- causes fibroblast migration, prolif, increase syn
and decrease degradation of collagen
Have leukocytic infiltrate, edema, increased vascularity (dissappear in 2nd week and get
blanching)
End of first month- scar made up of acellular CT, devoid of infl infiltrate, covered by intact
epidermis
23.
Compare and contrast healing by first and second intention.
First intension- healing of a clean wound- simplest type
Second intention- excisional wounds- complicated repair process- creates large defects on
skin surface - have extensive loss of cells and tissue, more intense inf reaction, more
granulation tissue, more collagen, get a substantial scar
24.
Describe the final strength of wounds.
Depends on collagen syn and decreased degradation (type 1 fibrillar collagen is major
portion of ct in repair)
Length of time for a skin wound to achieve its maximal strength
1st week- wound strength is very weak
Strength increases rapidly for next 4 weeks
Slows down at 3rd month
Plateau at 70-80% strength of unaffected skin
25.
List the major local and systemic factors which affect wound healing.
Systemic- nutrition- protein deficiency (vit c, inhibits collagen syn)
Metabolic status- diab. Mell- associated with delayed healing
Circulatory status- modulate wound healing
Hormones- glucocorticoids- anti inflam effects
-can inhibit collagen syn
Local factors:
Infection- persistent tissue injury
Mechanical factors- motion of wounds, compressing blood vessels can delay healing
Foreign bodies
Size, location, type (is it in a well vascular zed location?)
26.
Be familiar with how wound healing can be complicated.
Deficient scar formation
Wound dehiscence- rupture of a wound common after ab surgery
Ulceration- inadequate visualization during healing
Excessive formation of the repair components- get too many hypertrophy scars (raised scar
from too much collagen)- get this after thermal/traumatic injury, get keloid (individual pre
disposition) if scar doesn’t regress
Exuberant granulation- formation of a lot of gran tissue; blocks re epitheli; must be
removed by surgery, protrudes over surrounding skin
Formation of contractures- exaggeration of contraction- results in deformities of the
wound, usually on palms, soles, front of thorax; seen after burns and can compromise
movements of joints
27.
Describe fibrosis and the mechanisms involved.
Excessive deposition of collagen and other ecm components, get lots of collagen in chronic
diseases
Mechanism similar to skin wound healing- not a short lived stimulus this time, however,
leads to chronic inf
28.
Review figure 3-26.
Chapter 4: Hemodynamic Disorders, Thromboembolic Diseases and Shock
Reading assignment: 8th Edition: pp. 111-133
Learning Objectives:
1.
Describe edema including anasarca and the various causes.
Abnormal increase in interstitial fluid within tissues
Anasarca- severe/generalized edema, widespread subcutaneous tissue swelling
2.
Describe edematous fluid collections of the pericardium, pleura, and
peritoneum.
Hydrothorax
hydropericardium
Hydoperiotneum (ascites)
3.
Describe various pathologic mechanisms which lead to edema.
Increased hydrostatic pressure
Reduced plasma protein (reduced colloid pressure)
lymphedema- impaired lymphatic drainage, localized, caused by chronic inf with fibrosis,
tumors, physical disruption, radiation damage
Parasitic filariasis- lymphatic obstruction- lymphatic fibrosis- can get enlargement of
lower limbs (elephantiasis)
See ecm separation and some cell swelling, seen in subcut tissues, lungs, brain
Edema is 2ndary to renal dysfunction
Soft tissue edema- signals underlying cardiac/renal disease; impairs wound healing
Pulmonary edema- see frothy, blood-tinged fluid (air, edema, red cells), see with left
ventricular failure
Brain edema- life threatening, brain can extrude through foramen magnum; also can
compress vascular supply; can injure medullary centers
4.
Describe hyperemia and congestion and explain the mechanisms for each.
Hyperemia- leads to increased blood flow, affected tissues turn red (erythema)
Congestion- passive process, reduced outflow of blood from a tissue, can be due to cardiac
failure; get reddish-blue color (cyanosis), red cell stasis, accumulation of deoxygenated
hemoglobin
Eventually causes chronic hypoxia (get scarring), capillary rupture and catabolism of red
cells (see hemosiderin laden macrophages)
Discolored due to poorly oxygenated blood
Acute pulmonary congestion- engorged alveolar cap, alveolar edema
Chronic pulmonary congestion- septa thickened, fibrotic, alveoli contain the hemosid
laden macrophages (aka heart failure cells)
Acute hepatic congestion- central vein/sinusoids distended, hepatocytes can be ischemic
Chronic hepatic congestion- see red brown in lobar regions, nutmeg liver, see hemos-laden
macrophages, lobar hemorrhage, degeneration of hepatocytes
Get increased tendency to bleed (hemorrhagic diatheses), hemorrhage within a tissue is a
hematoma
5.
Describe acute hemorrhage including the types of hemorrhages of the
pericardium, pleura, peritoneum, and minute hemorrhages of the skin and mucous
membranes.
Petechiae- minute hemorrhages in skin, mucous membranes, or serosal surfaces (seen in
increased intravascular pressure, low platelet counts, dysfunctional platelets)
Purpura- slightly larger hemorrhages (> 3mm), associated with same disorders that cause
petechiae, 2ndary to trauma, vascular inf (vasculitis), increased vascular fragility
(amyloidosis)
Ecchymosed- 1-2 cm bruises (subcutaneous hematomas), red cells here are phagocytosed
by macrophages- get hemosiderin (golden brown color) after seeing hemoglobin (red-blue)
converting to bilirubin (blue-green)
6.
Describe normal hemostasis including anti-platelet factors, anti-coagulant
factors, fibrinolytic factors, and prothrombotic factors.
Hemostasis- maintain blood in fluid state normally, permits formation of hemostatic clot at
site of injury (complement is thrombosis- involves blood clot formation)
Endoth cells- regulate hemostasis, has anti platelet, angicoagulant, and fibrinolytic
properties (only gain procoagulation activities post injury)
Prevents platelets from binding tightly; non activated platelets can’t bind, either
Activated platelets can’t bind due to prostacyclin (pgi2) and NO produced by endoth cells
Endoth cells make adp- inhibits platelet aggregation
Anticoagulant effects mediated by endoth membrane- associated heparin like molecules
Thrombomodulin- converts thrombin into an anticoagulant (activates protein C, which
inhibits clotting- 5 and 8 are oop)
Heparin like molecules- act indirectly- enhance inactivation of thrombin- use antithrombin
3
Fibrinolytic effects- endoth cells make t-PA- plasminogen activitor- cleaves plasmino to
plasmin- cleaves fibrin to degrade thrombi
Endoth injury- allows platelets to attach to underlying membrane, interactions occur
through vWF (which is normally made by endo cells, essential for platelet attachment)
Procoagulant effects- response to cytokines (TNF/IL1) or bacteria- synthesize tissue
factor- activates extrinis cascade
Antifibrinolytic effects- endo cells secrete inhibitors of plasminogen activators- limits
fibrinolysis
Platelets- form initial hemostatic plug, provides surface that recruits other coag factors
Contains alpha-granules (adhesion and other recruitment factors), dense/gamma granulescontain adp/atp, histamine, serotonin
Upon binding to endo cells- have shape change, secretion, aggregation, mediated by vWF
(necessary to overcome shear forces in blood flow, deficiency of vWF results in bleeding
disorders- Bernard-soulier syndrome)
Agonists can bind to platelet receptors- causes release of molecules- calcium is particular
important, adp potentiates platelet aggregation
Phosphatidylserine appears on platelet surfaces to serve as sites for other coagulation
factors
Vasoconstrictor thromboxane A2- amplifies platelet aggregation and formation of
hemostatic plug (until now aggregation is reversible)
Cascade generates thrombin- stabilizes the platelet plug- thrombin binds to platelet
membrane- causes more platelet aggregation
Also causes platelet contraction- causes irreversibly fused mass of platelets- 2ndary
hemostatic plug
Thrombin converts fibrinogen to fibrin to cement platelets in place
Thrombin is the most important coagulation factor
Thrombin has proinf effects-occur through PAR- protease activated receptors
Factor 8 stabilizes the new fibrin polymers
7.
Describe each of the factors of the coagulation system including both the
intrinsic and extrinsic systems.
Extrinsic system- measured by PT assay- for 7, 10, 2, 5, fibrinogen, started by
thromboplastin (tissue factor)
Intrinsic system- measured by PTT - for 12, 11, 9, 8, 5, 2, fibrinogen, depends on activation
of factor 12 (Hageman factor)
8.
Describe the vitamin K-dependent coagulation factors and anticoagulant
factors.
Anticoagulants- prevents runaway clotting
Antithrombin (at3)- inhibits thrombin and other factors, activated by heparin like
molecules
Protein S/C- vitamin K dependent proteins, inactivate 5,8
TFPI- produced by endo cells- inactivates factor 7
9.
Describe the mechanisms of antithrombin III, Protein C, Protein S, and
plasminogen-plasmin system.
See above
10.
Describe thrombosis and the major risk factors (hypercoagulable states)
associated therewith.
Virchow’s triad- 3 abnormalities that lead to thrombus formation
Endothelial injury - impedes blood flow- normal high flow rates impedes clotting, may
occur in cardiac chambers, ulcerated plaques in atherosclerotic arteries, sites of vasculitis
Endo does not need to be disrupted- any disturbance of its balance of anticoag/coag
molecules will influence clotting events, can be perturbed by hyypertension, other obvious
factors
Stasis or turbulent flow- can cause endo injury, disrupts laminar flow and platelets may
come into contact with the endothelium
Hypercoagulability of the blood - thrombophilia, predisposes to thrombosis, most
commonly inherited- elevated levels of homocysteine- contribute to arterial/venous
thrombosis (homocysteine is prothrombotic)
May also rarely inherit deficiencies of anticoagulants- at3, pc/s
HIT- heparin induced thrombocytopenia- usually after too much heparin, start seeing
antibodies in response to platelets that are heparin bound
Get a prothrombotic state even though your platelets are being destroyed (platelets are
being activated, aggregated, and consumed due to antibodies)
Antiphospholipid antibody syndrome- lupus anticoagulant syndrome- see many
thromboses, miscarriages, low platelets, pulmonary embolism, pul hypertension, stroke,
fetal loss
Auto antibodies induce hypercoagulable state- causes endot inury
2ndary form- occurs with well defined autoimmune disease- system lupus erythematosus
Primary form- only see manifestations of hypercoagulable state- no evidence of auto
immune disease- may be caused by drugs/infections
11.
Describe the morphologies of the various thrombi.
Can be anywhere in the cardiovascular system
Arterial thrombi- see at sites of turbulence or endo injury, thrombi grow in a retrograde
manner
Usually occlusive, mostly commonly seen in coronaries, cerebral, femoral
Consists of meshwork of platelets, fibrin, rbc, leukocytes; may be on atherosclerotic plaque
Venous thrombi- see at sites of stasis, grow in direction of the blood flow
Thrombi have lines of zahn- platelets/fibrin with darker red cell layers- shows thrombus
formed in flowing blood
Invariably occlusive, thrombi forms long cast along the lumen
See more enmeshed red cells, veins in lower extremities most commonly affected
Mural thrombi- seen in heart chambers/aortic lumen- abnormal cardiac contraction
Postmortem clot- don’t confuse with antemortem venous thrombi- gelatinous with dark red
portion with yellow chicken fat upper portion
Red thrombi- firmer, locally attached (unlike post mortem clots), has lines of zahn
Vegetations- thrombi on heart valves due to bacteria, causes infective endocarditis
although can also get nonbacterial thrombotic endocarditis (sterile vegetations)
Sterile, verrucous (wart like) endocarditis- libman sacks endocarditis
12.
Describe the various clinical processes which may occur to a thrombus after
its formation.
Propagation- thrombi accumulate more platelets/fibrin
Embolization- thrombi dislodge
DVT- deep venous thrombosis- leg veins at or above the knee- thrombi can embolize to the
lungs, may be offset by collateral channels (asymptomatic in 50%)
Dissolution- result of fibrinolysis
Organization and recanalization- older thrombi become organized by ingrowth of endo
cells
13.
Compare and contrast between arterial thrombosis and venous thrombosis
and the various clinical syndromes associated with each.
See above
14.
Describe disseminated intravascular coagulation including etiologies,
morphologies, complications, and prognosis.
Disseminated intravascular coagulation- sudden/insidious onset of widespread thrombi in
microcirculation, not grossly visible, get diffuse circulatory insufficiency
Results in platelet consumption, evolves from thrombotic disorder to bleeding problem
15.
Describe pulmonary embolism including etiologies, morphologies,
complications, and prognosis.
Mostly from deep leg veins, leg/pelvic veins
Large emboli result in sudden death- can lodge in pulmonary arteries or cause acute cor
pulmonale (right ventricular failure)
Small emboli- small symptoms, except for bronchia insufficient bronchial circulation
Caused by immobilized individuals, hypercoagulable state, heart failure
Get respiratory compromise, hemodynamic compromise, may have adequate
cardiovascular function; may have infarction due to inadequate circulation
Needs cardiopulmonary resuscitation- ecg will have rhythm but with no pulses
Can be diagnosed with CT, Va-Q scan, angiography, ultrasound
Can use ambulation, stockets, anticoagulant, filter, thrombolysis to treat
Gross exam- ¾ affect lower lobes, wedge shaped, hemorrhagic in parenchyma
Get fibrinous pleural exudate, scar, and an embolus
Micro exam- ischemic necrosis, infected embolus
16.
Describe systemic (arterial) embolism including etiologies, morphologies,
complications, and prognosis.
Not described, but can guess this one pretty well
17.
Describe amniotic fluid embolism including etiology, morphology,
complications, and prognosis.
Complication of labor and immediate postpartum period- causes sudden severe dyspnea,
cyanosis, and shock - followed by neurologic impairment (seizures to coma)- if not deathget pulmonary edema, DIC
Caused by infusion of amniotic fluid into maternal circulation
See squamous cells shed from fetal skin, lanugo hair, mucin derived from fetal resp/GI
tract
18.
Describe air embolism including etiology, morphology, complications, and
prognosis.
Gas bubbles in the circulation- form frothy masses that obstruct blood flow
Decompression sickness- get from deep sea divers, un pressurized aircraft that
descent/ascend too quickly
The bends- rapid formation of gas bubbles in skeletal muscles and joints
The chokes- gas bubbles in blood cause edema, bleeding, emphysema- lead to respiratory
distress
Caisson disease- chronic form of decompression sickness- persistence of gas emboli in
skeletal system (see at femoral heads, tibia, and humeri)
19.
Describe fat embolism including etiology, morphology, complications, and
prognosis.
Microscopic fat globules - may get from fractured long bones, soft tissue injury/burns,
common to find after vigorous cardiopulmonary resuscitation, no clinical consequence
20.
Describe infarction and compare and contrast among various organs which
usually experience infarctions.
Infarction- area of ischemic necrosis caused by occlusion of arterial supply or venous
drainage, nearly all caused by thrombotic or embolic arterial occlusions
Mostly myocardial, cerebral infarction; pulmonary also common
21.
Compare and contrast between septic and bland infarction and state the
morphologies and complications for each.
Red infarct- occur with venous occlusions, loose tissues where blood can collect, in tissues
with dual circulations (lung, small intestines), tissues previously congested by sluggish
venous return, or when flow is restablished
White infarct- occur with arterial occlusion
Infarcts usually wedge shaped, start out ill defined and become more defined as time
passes; ischemic coagulative necrosis is a dominant trait
Most infarcts replaced by scar tissue
Septic infarction- occur when cardiac valve vegetations embolize; infarct converted to
abscess with inf response
Bland infarct- not described (assumed a regular infarct)
22.
Describe hypovolemic, cardiogenic, septic, and neurogenic shock and know
the pathologic mechanisms of each.
Shock characterized by systemic hypotension (reduced cardiac output or low blood
volume)
Hypovolemic (due to blood loss or fluid loss from burns) and cardiogenic shock (pumping
failure)- patient has hypotension (weak rapid pulse, fast heart rate, cool cyanotic skin)
Septic shock- skin will be warm and flushed due to vasodilation
Results from blood pooling as part of immune system reaction to infection
Neurogenic shock- result of anesthetic accident or spinal cord injury- results in loss of
vascular tone and peripheral pooling of blood