1
Q
Distribution of fluid is a carefully controlled ____ mechanism.
A
homeostatic mechanism
deviations from normal may have profound pathological effects (eg heart failure)
2
Q
Normal circulatory functions require what 2 things?
A
- intact blood
- lymph vessels
3
Q
Endothelial cells play an important role in what 4 things?
A
- fluid distribution
- hemostasis
- inflammation
- healing
4
Q
What are the 4 components of the circulatory system and their functions?
A
- Heart: pump
- Arteries: distribution system
- Microcirculation system: nutrient/waste exchange between blood and extravascular tissue
- Veins and lymphatics: collection system
5
Q
Microcirculation is called microcirculation because it is ____.
A
microscopic
6
Q
what are the 3 components of microcirculation
A
- arterioles/metarterioles
- post-capillary venules
- capillaries
7
Q
Which component of microcirculation has walls that contain innervated smooth muscle cells called myocytes that contract to control blood flow?
A
arterioles/metarterioles
8
Q
Which component of microcirculation has a similar structure to capillaries, but acquire a thin layer of muscle as they move away from the capillary bed?
A
postcapillary venules
9
Q
Capillaries are the site of:
A
nutrient and waste exchange, and a critical area in fluid balance
10
Q
Which component of microcirculation has enormous volume (1300x the cross-sectional area of the aorta) and normally contains only about 5% of the blood?
A
Capillaries
11
Q
___% of capillary beds are not open during normal conditions.
A
95%
12
Q
all components of the circulatory system are lined by what
A
a single layer of endothelium
13
Q
What are the 4 functions of endothelial cells?
A
- synthesize and secrete substances which effect homeostasis
- inflammation/immunity
- angiogenesis
- healing
14
Q
In a normal state, endothelial cells have ________ properties, but when injured they become ________
A
antithrombotic; prothrombotic
15
Q
What is the semipermeable membrane that influences movement of fluid, nutrients, and waste between blood and the interstitial space?
A
The capillary wall
16
Q
What are the 2 mechanisms for substance transport across the capillary wall?
A
- direct diffusion
- transcytosis
17
Q
Describe normal direct diffusion of substances across the capillary wall:
A
- most small molecules move by passive diffusion through the endothelial cell membrane or the interendothelial pores
- normal interendothelial pores are too small to allow escape of large proteins such as albumin or globulins
- in inflammation, the endothelial cells contract and the pores become larger
18
Q
What is transcytosis?
A
Direct movement of fluids/macromolecules through the cell from the apical to the basal surface that occurs in some endothelium via
vesicles.
19
Q
What are the 3 different types of capillary lining?
A
- continuous
- fenestrated
- discontinuous/sinusoidal
20
Q
Which type of capillaries are:
- lined by a complete simple squamous endothelium and a basal lamina
- found in muscle, brain, thymus, skin, bone, lung, and other tissues
A
Continuous capillaries
21
Q
Which type of capillaries:
- have many small openings; found in tissues with abundant fluid transport
- often have a diaphragm such as intestinal villi, kidney interstitium, choroid plexus, or ciliary process of eye
- with no diaphragm they act as a filter such as the renal glomerulus
A
Fenestrated capillaries
22
Q
Which type of capillaries have:
- larger gaps than fenestrated with discontinuous basal lamina that allows larger molecules to even cells to exit
- hepatic and splenic sinusoids where RBCs can exit
A
Discontinuous capillaries
Hepatic & splenic sinusoids are lined by this type of endothelium
23
Q
Total body water is about what % of lean body weight?
A
65%
24
Q
What are the 4 components of total body water and their relative %’s?
A
- plasma: 5%
- interstitial fluid: 15%
- intracellular fluid: 40%
- transcellular fluid: 5%
25
What is the interstitium?
The space between microcirculation and the cells.
What binds most cellular and structural elements into discrete organs and tissues
26
What is the medium through which all metabolic products must pass between microcirculation and cells?
interstitium
27
The distribution of fluids, nutrients, and wastes between blood, the interstitium, and cells is controlled by what 3 factors?
- physical structures
- hydrostatic pressures
- ion concentration (osmotic) gradients
28
what is the interstitium composed of
ECM and supporting cells such as fibroblasts
29
what are the 3 components of the ECM that give it its adhesive and absorptive properties
- structural molecules: collagen, reticulin, and elastin fibers
- adhesive glycoproteins: fibronectin and laminin
- absorptive (hydroscopic) molecules: glycosaminoglycans and proteoglycans
30
in most areas what do capillaries allow free passage of vs what they prevent passage of
- allows free passage of water and ions and opposes passage of PP's
- mechanism of edema
31
water distribution between plasma and interstitium is primarily determined by what
differences in hydrostatic and osmotic pressure between the 2 compartments
32
what are the components of Starling's Equation
- hydrostatic pressure in the vascular system: force that moves fluid out of vessels
- osmotic pressures of PP's and to a lesser extent tissue pressure around vessels: forces that contain the fluid within the vascular system
33
how does edema appear on histo
- pale amorphous eosinophilic material due to proteins being present
- tissue spaces are distended by the edema: collagen bundles separated by increased clear space
- lymphatics are dilated
34
what is edema
the abnormal accumulation of fluid in interstitial tissue spaces or in body cavities
35
true or false: edema fluid is within both the vascular fluid and cellular fluid compartments
false it is outside of both in the interstitium
36
how does edema appear grossly
- wet, gelatinous, and heavy
- organs are swollen and fluid weeps from cut surface
- in several spp such as horses and some breeds of cattle, the fluid appears slightly yellow due to proteins
37
what are the 4 mechanisms of edema production
- increased hydrostatic pressure
- decreased plasma oncotic pressure
- lymphatic obstruction
- decreased vascular permeability/endothelial damage
38
what types of impediments to venous blood flow lead to increased hydrostatic pressure that would allow for edema production
- generalized: right-sided heart failure in dogs or left-sided in cats
- localized: too tightly bandaged limb occluding venous flow
39
what situations can lead to decreased oncotic pressure as a mechanism for the production of edema
- proteins not absorbed from diet: starvation or GI malabsorption with IBD
- proteins not produced: liver dz
- proteins lost from the body glomerular dz or intestinal damage
40
how can you check that proteins are being lost from the body due to glomerular dz
check proteinuria either via dipstick or UA
41
what factors can cause obstruction of lymphatics which leads to edema production
- surgery/trauma
- neoplasia: lymphoma
- inflammation of lymph nodes/vessels: lymphangitis
42
what are the fluid characteristics of edema produced by either lymphatic obstruction, decreased oncotic pressure, or increased hydrostatic pressure
"non-inflammatory edema": protein poor
43
edema produced by either lymphatic obstruction, decreased oncotic pressure, or increased hydrostatic pressure is referred to as what
transudate
44
what are the characteristics of edema classified as transudate
- low protein content <30 g/L
- specific gravity <1.017
- total nucleated cell count <1.5x109/L
45
describe increased vascular permeability/endothelial damage as a mechanism for the production of edema
mostly due to the initial reaction of the microvasculature to inflammatory/immunologic stimuli → release of inflammatory mediators → vasodilation and increased vascular permeability
46
increased vascular permeability/endothelial damage as a mechanism for the production of edema is called what
"inflammatory edema"
47
what are the fluid characteristics of edema produced by increased vascular permeability/endothelial damage
exudate: protein rich
48
what are the characteristics of euxdate
- high concentration of protein >30 g/L
- specific gravity >1.025
- total nucleated cell count >7.0x109/L
49
fluid from an FIP cat would be what kind of edema
exudative "inflammatory edema" that is rich in proteins and feels sticky beetween fingers
50
what are the mechanisms of local edema
- local impaired venous drainage
- local lymphatic obstruction
- local inflammation
51
what are the mechanisms of generalized edema
- increased generalized hydrostatic pressure of blood: right-sided heart failure
- decreased oncotic pressure of PP's
52
what are examples of "dependent edema"
- "Bottle jaw": subcutis of the ventral mandibular/cervical region that stems from parasites in abomasum
- "Brisket edema": SQ tissues of the ventral abdomen
- "Stocking up": subcutis of the limbs
53
which generalized edema we often see a combination of what 3 things
- ascites
- hydrothorax
- SQ "dependent" edema
54
define pitting edema
when pressure is applied to an area of SQ edema and a depression or dent results as excessive interstitial fluid is forced to adjacent areas
55
define anasarca
severe and generalized edema with profound SQ tissue swelling
56
define hydrothorax
non-inflammatory fluid (transudate) in the thoracic cavity
57
define hydropericardium
non-inflammatory fluid (transudate) in the sac around the heart
58
define ascites/hydropericardium
non-inflammatory fluid (transudate) in the peritoneal cavity
59
what do we always need to remember when describing edema in cavities of birds
they have no diaphragm to separate the thorax and abdomen, so they have a coelomic cavity instead
60
the clinical significance of edema is dependent on what 3 things
- extent: mild vs moderate vs marked/severe
- location: site of accumulation i.e. skin vs lung vs brain
- duration: tissues may become more firm and distorted due to increased fibrous CT after prolonged edema
61
define pulmonary edema
accumulation of edema fluid in interstitium and alveoli of the lungs and a common cause of death in many disease processes
62
what are the mechanisms of pulmonary edema
- circulatory failure
- damage to pulmonary capillary endothelium (microvascular injury)
63
what is the most common cause of pulmonary edema
circulatory failure: increased hydrostatic psi of blood in pulmonary veins leads to transudation of non-inflammatory edema fluid into alveolar spaces
64
damage to pulmonary capillary endothelium that leads to pulmonary edema is caused by what
- peracute inflammation
- toxins
- sudden increase in vascular permeability
65
what is the result of pulmonary edema caused by damage to pulmonary capillary endothelium
- often sudden death
- if the animal doesn't die it will be followed by pneumonia
66
describe the fluid dynamics seen with pulmonary edema
- fluid accumulates in the interstitium and moves through the BM into alveoli
- fluid drains via lymphatics and results in dilated interlobular and pleural lymphatics
- may eventually lead to pleural fibrosis (chronic)
67
what is the doctor term for dilation of lymphatics as seen with pulmonary edema
lymphangiectasia
68
how does pulmonary edema appear grossly
- lungs are heavy and wet
- froth due to edema fluid and air bubbles may be present within trachea and bronchi and obvious on cut sections
- interlobar septa are prominent and thickened due to increased fluid within this space
69
pulmonary edema due to left-sided heart failure is often also accompanied by what
congestion of pulmonary parenchyma
70
what is a common finding after euthanizing a patient with pulmonary edema
froth in the trachea from gasping for air
71
how does pulmonary edema appear histopathologically
- edema fluid in interstitium/alveolar spaces what can be clear or pale acidophilic in color depending on the protein content
- eventually will see dilated interlobular/pleural lymphatics
72
chronic pulmonary edema is most commonly seen with what condition
chronic cardiac failure and accompanying pulmonary congestion
73
how does chronic cardiac failure appear histologically after a long period of time
pleura and alveolar walls become thickened with fibrous CT and alveolar macrophages are present
74
edema in the brain is referred to as what
cerebral edema
75
what are the causes of cerebral edema
- trauma (head injury)
- obstruction of venous outflow
- intercranial infections such as meningitis or encephalitis
76
how does cerebral edema appear grossly
- brain is heavier than normal
- gyri are swollen and become flattened and sulci are narrow
- lose difference between grey and white matter
77
what is the quickest CS due to cerebral edema
delerium due to the swollen brain being constricted by the bony cranium
78
what are the gross appearances seen with severe cerebral edema
- cerebellar coning: herniation of cerebellum through the foramen magnum
- cerebral herniation: herniation of the caudal cerebral cortex beneath the tentorium cerebella
79
how does edema of the brain appear histopathologically
expansion of perivascular (Virchow-Robin) spaces
80
what is the definition of dehydration
deficiency of water resulting from imbalance between the uptake and loss of water from the body
81
what are the causes of dehydration
- uncontrolled diarrhea
- vomiting
- renal failure
- diabetes
- heat stroke
- water deprivation
82
what are the mechanisms of dehydration
- decrease in total body water leads to water deficit which is shared among plasma, intracellular, and interstitial fluid compartments
- reduced renal perfusion
83
what can accompany severe dehydration as plasma water is drawn into the interstitium
hypovolemic shock
84
what are the pathological findings associated with dehydration
- Tenting: folds of skin pulled out from the body hesitate before returning to their normal position
- eyes are sunken, MM and SQ tissues are dry and sticky
85
what is hyperemia
active engorgement of vascular beds due to increased arteriolar flow
86
what is the difference between hyperemia and congestion
hyperemia is active and congestion is passive
87
how does hyperemia appear on the body
affected tissue is red (oxygenated blood) and warm, as arterioles and capillaries are filled with blood
88
what are the different types of hyperemia
- physiologic
- pathologic
89
what are examples of physiologic hyperemia
- blood flow to stomach and intestines during digestion
- blood flow in the muscles during exercise
- blood flow in skin to dissipate heat
- neurovascular hyperemia: blushing
90
what is happening in any case of physiologic hyperemia
blood is traveling to site and redness occurs due to natural increased effort
91
what will you often see accompanying pathologic hyperemia
associated edema
92
what are the characteristics of pathological hyperemia
- result of an underlying pathologic process
- arteriolar dilation is a response to an inflammatory stimulus and red coloration is one of the cardinal signs of inflammation
93
define congestion
passive engorgement of a vascular bed generally caused by a decreased outflow of blood
94
how does congestion appear grossly
- tissues are dark red to blue/black (cyanotic), depending on degree of stagnation
- deoxygenated blood due to heart failure and the heart not pumping blood properly/lack of oxygen
- cut surfaces ooze blood and are often wet due to accompanying edema
95
how does congestion appear histologically
- acute: capillaries are engorged with blood and usually some edema
- chronic: engorgement by poorly oxygenated venous blood → degree of chronic local hypoxia → atrophy, degeneration, or even necrosis of parenchymal cells
96
what 2 factors define the type of congestion
- duration
- extent
97
describe how duration can define the type of congestion
- acute: implies abrupt onset with rapid development i.e. emboli
- chronic slowly developing or present for a long time i.e. CHF
98
describe how extent can define the type of congestion
- localized: change confined to a discrete area i.e. isolated venous obstruction
- generalized: indicates a systemic change i.e. cardiac failure
99
what are the different types of congestion
- localized
- acute generalized
- congestion associated with pathology of heart or lung
100
describe localized congestion
- local obstruction to venous drainage such as intestinal volvulus/intussusception/strangulation
- blood backs up into the microvascular bed and leads to passive engorgement of the drainage area
101
when is acute generalized congestion most often seen
acute heart failure or following euthanasia with barbiturates
102
what should you keep in mind on necropsy of a dog that was euthanized with barbiturates
will often see congestion/edema secondary to the euthanasia method rather than pathological
103
what are examples of congestion associated with pathologies of the heart and lungs
- left-sided heart failure: congestion of lungs
- right-sided heart failure: systemic congestion, especially in the liver, and edema (ascites and subcutis)
104
what is cor pulmonale
with certain types of primary pulmonary disease → progressive loss of pulmonary vascular bed → pulmonary hypertension → right-sided heart failure secondary to pulmonary dz
105
pulmonary congestion is usually secondary to what
left-sided heart failure
106
what will you see with acute pulmonary congestion
diffuse red lungs which are wet and heavy from extra blood and edema/congestion
107
what will you see with chronic pulmonary congestion
lungs can be lightly tan in color due to "heart failure cells"
108
what are "heart failure cells"
macrophages in alveolar spaces that eat RBCs and present hemosiderin in the cytoplasm; called siderophages
109
what are the consequences of chronic pulmonary congestion
- alveolar capillaries become engorged with blood due to chronic left ventricular failure impeding forward flow of blood from lungs
- intra-alveolar hemorrhage
- pulmonary edema
- fibrosis of interstitium
- pulmonary hypertension
110
how does intra-alveolar hemorrhage occur as a result of chronic pulmonary congestion
small capillaries rupture and cause focal hemorrhage into alveolar spaces → red cells are phagocytized by alveolar macrophages and the iron from the RBCs is stored as hemosiderin
111
pulmonary edema as a result of chronic pulmonary congestion causes what
interference with gaseous exchange
112
how does fibrosis of the interstitium occur as a result of chronic pulmonary congestion
fibroblasts secrete excess collagen in response to increased pressure in alveolar capillaries and chronic edema in alveolar interstitium
113
how does pulmonary hypertension occur as a result of chronic pulmonary congestion
increased pressure in alveolar capillaries leads to increased pressure in pulmonary arteries
114
hepatic congestion is most commonly due to what
right-sided heart failure, which can occasionally be secondary to pulmonary hypertension
115
how does hepatic congestion appear grossly
- liver enlarged with rounded edges and is dark red-brown in color
- "nutmeg liver": reticular appearance on cut surface
- dark red areas correspond to congested zones around central veins
- yellow-brown areas correspond to the less affected/normal parenchyma around the portal/midzone areas
116
what is the difference in the gross appearance of the liver in the case of hepatic congestion
- acutely there is overall increase in liver size due to increased volume of added blood
- chronically there is low grade hypoxia which leads to atrophy and death of centrolobular hepatocytes and fibrosis
117
describe the histological appearance of acute hepatic congestion
- central vein and sinusoids in zone 3 are distended with RBCs
- central hepatocyte degeneration and/or necrosis due to hypoxia in stagnant blood
- midzonal hepatocyte (zone 2) fatty change due to partial hypoxia
- periportal hepatocytes (zone 1) are mostly normal
118
describe the histological appearance of chronic hepatic congestion
- hemosiderin-filled macrophages due to RBC phagocytosis
- central (zone 3) dilation of sinusoids which leads to atrophy and/or loss of centrilobular hepatocytes
- increase in fibrous CT due to low-grade hypoxia and increased pressure in zone 3
119
what are macrophages in the liver called
Kupffer cells
120
what is the name for the fibrous CT build up due to low-grade hypoxia seen with chronic hepatic congestion
"Cardiac Cirrhosis"
121
what is the difference between hyperemia/congestion and hemorrhage
- Hyperemia/congestion: blood inside of vessel wall (i.e. intravascular)
- Hemorrhage: blood outside vessel wall (ie: extravascular)
122
define hemorrhage
escape of blood from the CVS, called extravasation
123
hemorrhage can present as discharge of blood from the vascular compartment to the _________ of the body or __________ within a tissue
exterior; enclosed
124
capillary bleeding can occur under conditions of _______ congestion
chronic
125
what are the causes of hemorrhage and their specific result
- trauma: SQ, body cavity, IM, or tissue hemorrhage
- septicemia, viremia, or toxic conditions: widespread petechiae and ecchymoses
- abdominal neoplasia hemoperitoneum
- coagulation disorders: often large hemorrhages
- thrombocytopenia: small mucosal hemorrhages
126
what are the two critical locations of hemorrhage
CNS and heart
127
what is a subdural or epidural hematoma
blood accumulation above or beneath the dura that can compress the brain
128
what is cardiac tamponade due to hemopericardium
acute right heart failure due to massive blood accumulation within the pericardial sac causing restriction of diastolic cardiac filling and compression
129
what is the most common cause of hypovolemic shock
hemorrhagic shock with severe blood loss
130
define hemorrhage by rhexis
hemorrhage due to a substantial tear in a blood vessel or the heart that results in moderate/marked flow of blood out of the vascular system
131
define hemorrhage by diapedesis
hemorrhage due to small defect or RBCs passing through the vessel wall in inflammation or congestion
132
define hemorrhagic diathesis
increased tendency to hemorrhage from usually insignificant injuries that is seen in a wide variety of clinical disorders such as coagulation/platelet disorders
133
define hematoma
accumulation of blood in tissue (a 3D extravascular clot) that can be small or very large
134
define hemopericardium
blood in the pericardial sac
135
define hemothorax
blood in the pleural cavity
136
define hemoperitoneum
blood in the peritoneal cavity
137
define hemarthrosis
blood in a joint space
138
define hemoptysis
coughing up of blood from the lungs or airway
139
define epistaxis
bleeding from the nose: purulent exudate
140
what is the difference in the location of epistaxis depending on which nostril the blood is coming from
- unilateral: URT
- bilateral: LRT
141
define petechiae
small, up to 1-2 mm, hemorrhages especially on the skin, mucosal surfaces or serosal surfaces
142
define purpura
hemorrhages, 3 mm to 1 cm, that are often scattered on skin and MM that are often seen with diseases that cause petechiae
143
define ecchymosis
hemorrhages larger than petechiae and purpura that is often blotchy or irregular in appearance as what is seen with bruises or small hematomas
144
define agonal hemorrhages
small hemorrhages associated with the death struggle (terminal hypoxia); located on the thymus in young animals
145
define suffusive hemorrhage
affected areas of hemorrhage are larger than ecchymosis and contiguous
146
define paint brush hemorrhages
hemorrhages which look as though red paint was hastily applied with a paint brush and is most commonly found on serosal or mucosal surfaces
147
what are the possible resolutions for hemorrhage
- resorption of small amounts of hemorrhage
- organization of larger amounts of hemorrhage that requires phagocytosis and degradation by macrophages
- organizing hematoma that consists of a central mass of fibrin and RBCs surrounded by vascular CT in which macrophages phagocytose and degrade the fibrin and RBCs
148
what is the order of events in the breakdown of hemorrhage by macrophages
hemoglobin ➔ bilirubin ➔ hemosiderin (red-blue) (blue-green) (yellow-brown)
149
hemostasis refers to the _____ of bleeding
arrest
150
what kind of process is hemostasis normally
a well-regulated process that maintains blood in a fluid, clot-free state within a normal vessel
151
what occurs at the site of a vessel injury as a result of hemostasis
rapid clot formation via a hemostatic plug
152
what is the term for an inappropriate activation of the normal hemostatic processes
thrombosis
153
what are the 3 general components required for hemostasis and thrombosis
- endothelial cells (vascular wall)
- platelets
- coagulation cascade
154
what are the normal sequence of events following an endothelial injury
- transient arterial vasoconstriction
- primary hemostasis: PLATELETS
- secondary hemostasis: COAGULATION and formation of thrombin
- antithrombotic counter-regulation
155
transient arteriolar vasoconstriction in normal hemostasis is due to what
reflex neurogenic mechanism and local secretion of endothelin from the endothelium
156
damage to the endothelium exposes that
subendothelial ECM
157
damage to the endothelium and exposure of subendothelial ECM causes platelets to do what 4 things in primary hemostasis
- adhere to ECM
- shape change from round discs to flat plates
- release granules to promote hemostasis
- recruit other platelets to the site (aggregation)
158
what is the result of primary hemostasis
forms a first hemostatic plug that covers and seals the small area of vascular damage which may be adequate in the case of a minimal injury
159
what are the components of secondary hemostasis
- tissue factor
- platelets
- thrombin activation
- fibrin polymerization/stabilization
160
what role does tissue factor play in secondary hemostasis
membrane-bound procoagulant that is exposed at the site of injury which initiates the coag cascade
161
what role does platelets play in secondary hemostasis
exposed phospholipid complexes provide sites for coagulation reactions and helps localize the coagulation process
162
what role does thrombin activation play in secondary hemostasis
thrombin converts fibrinogen (soluble) to fibrin monomers what are able to precipitate
163
what role does fibrin polymerization/stabilization play in secondary hemostasis
fibrin monomers polymerize into an insoluble gel called fibrin which cements and anchors the primary platelet aggregate
164
what is antithrombotic counter-regulation
release of components which limit the size of hemostatic plug
165
what is the major initiating event for thrombosis and coagulation
injury to the endothelium
166
what are the functions of normal endothelium
- provides a surface that promotes smooth, non-turbulent flow of blood
- when necessary produces and responds to substances to form a thrombus or blood clot
- can enhance vasodilation and inhibit platelet adhesion, aggregation, and coagulation when required
167
what are the antithrombotic properties of endothelial cells
- antiplatelet
- anticoagulant
- fibrinolytic
168
what are the antiplatelet components of endothelial cells
- barrier: prevents platelets and plasma factors from being exposed to subendothelial matrix
- prostacyclin and NO: inhibit platelet adhesion/aggregation and maintains vascular relaxation
- adenosine diphosphatase: degrades ADP which promotes platelet aggregation
169
what are the anticoagulant properties of endothelial cells
- heparin-like molecules: membrane binding sites for antithrombin III which inactivates thrombin, factor Xa, and others
- thrombomodulin: binds to thrombin and converts it to anticoagulant which can activate protein C
- tissue factor pathway inhibitor: complexes on the membrane and inactivates TF-VIIa and Xa
170
active protein C from thrombomodulin plays what role in anticoagulation
inhibits clotting by cleaving factors Va and VIIIa
171
what are the fibrinolytic properties of endothelial cells
plasminogen activators: synthesize tissue PA which activates plasmin and removes fibrin from endothelial surfaces
172
how are the prothrombotic properties of endothelial cells activated
Endothelial cells may be injured directly or activated by infectious agents (eg bacterial endotoxin), hemodynamic factors, plasma mediators and cytokines
173
what are the prothrombotic properties of endothelial cells
- vWF: synthesized, stored, and released as an essential cofactor for platelet binding to collagen and other surfaces
- TF: secreted by injured endothelial cells which activate the extrinsic clotting pathway
- plasminogen activator inhibitors: suppress fibrinolysis and keeps the clot in place
174
platelet-derived growth factor
stimulates smooth muscle and fibroblast proliferation
175
fibroblast growth factor
stimulates angiogenesis and fibroblasts in wound healing
176
transforming growth factor-B
modulates vascular repair
177
platelets
plays a central role in normal hemostasis
178
megakaryocytes
platelets are derived from
179
how do platelets appear in circulation
round, smooth discs with glycoprotein receptors
180
what is the major function of platelets
forms the initial (1st hemostatic) plug that covers and seals a small damaged area
181
what is contained within platelets
granules with procoagulant (and a few anticoagulant) mediators
182
what are the 3 reactions between platelets and the ECM once it exposed following endothelial injury
- adhesion and shape change
- secretion (release reaction) of granules
- aggregation
183
describe the adhesion and shape change reaction between platelets and ECM
adhesion mediated via interactions with vWF that acts as a bridge for platelet surface receptors and ECM
184
describe the secretion of granules reaction between platelets and ECM
granule release important as Ca is required for coagulation cascade and aDP is an important mediator of platelet aggregation; leads to surface expression of phospholipid complexes which provide a binding site for Ca and coag factors
185
describe the aggregation reaction between platelets and ECM
- thromboxane A2 secreted by platelets which indices vasoconstriction and platelet aggregation
- ADP + TxA2 starts reaction which leads to enlarging platelet aggregation and formation of first degree hemostatic plug
186
thrombocytopenia
platelet numbers are low when compared to normal reference range
187
how is thrombocytopenia diagnosed
history of bleeding and low platelet counts
188
what are the mechanisms by which thrombocytopenia occurs
- deficient formation of platelets i.e. estrogen toxicity suppressing marrow production
- excessive utilization i.e. consumptive coagulopathies
- premature destruction i.e. Ab's to platelets
189
thrombocytopathy
defective platelet function
190
what are the mechanisms by which thrombocytopathy can occur
- defect in adhesion i.e. vWF dz
- defect in aggregation
- defect in release of granules = no ADP or Ca
191
coagulation cascade
the third arm in the hemostatic process, which is an amplifying series of enzymatic conversions
192
what occurs in each step of the coag cascade
An enzyme (activated coagulation factor) + a substrate (next unactivated coagulation factor) → newly activated coagulation factor
193
where is each reaction of the coag cascade taking place
assembled on a platelet phospholipid complex which is held together by Ca ions
194
what is the culmination of the coag cascade
the production of thrombin (bound to platelet surface) → thrombin converts soluble fibrinogen to fibrin which stabilizes the hemostatic plug
195
what is the most important factor in the progression and stabilization of a blood clot
generation of thrombin
196
how is thrombin generated at the site of injury
by either the intrinsic or extrinsic coagulation pathways which converge where factor X is activated
197
describe the intrinsic pathway of the coagulation cascade
all factors in the intrinsic system are present in normal plasma and the cascade is activated by contact of factor XII (Hageman factor) with subendothelial collagen of the ECM
198
describe the extrinsic pathway of the coagulation cascade
tissue factor (factor III or thromboplastin) is a cell surface protein that interacts with circulating factor VII to initiate the extrinsic pathway
199
what are the steps of the common pathway after the extrinsic and extrinsic portions of the coagulation cascade converge
- Xa produced by proteolysis of factor X along with Ca and platelet surface phospholipid
- Xa converts prothrombin to thrombin
- thrombin cleaves peptides from plasma fibrinogen to form fibrin monomers that self-polymerize into large polymers
- large polymers are cross-linked/stabilized by factor XIIIa
200
what is the result of the common coagulation pathway
contraction of fibrin-platelet thrombus allows for reduced size of the thrombus which restores blood flow and draws damaged vessel edges closer for healing
201
coagulation must be restricted to what location in order to prevent extensive clotting
the site of vascular injury
202
what is the role of the fibrinolytic cascade
limits the size and/or dissolves the thrombus
203
how does the fibrinolytic system complete its goal
primarily by the generation of plasmin which is derived from inactive circulating precursor plasminogen
204
how is plasminogen activated to plasmin
plasminogen activators especially tPA and the part of the coagulation pathway that involves XIIa-kallikrein
205
fibrin degradation products (FDPs)
have anticoagulant activity and used as a measure of thrombotic states
206
what is the difference in what is indicated by large hematomas vs petechial or ecchymotic hemorrhage
- large hematomas: coagulation disorder
- petechial or ecchymotic hemorrhage: platelet deficiency or abnormality
207
what are the characteristics of inherited deficiencies of coagulation
- numerous specific genetic disorders
- can be inherited or acquired
- can be due to decreased production or increased use
208
how can secondary diseases cause deficiencies in coagulation
- transitory depression of factor synthesis
- excessive utilization of factors
209
what are some acquired disorders that can cause deficiencies in coagulation
- severe trauma or deep burns
- snake venom and plant toxin
- vitamin K deficiency as it is required for many of the factors in the coag cascade
210
why can liver failure contribute to deficiencies in coagulation
- site of synthesis of many coag factors
- acute destruction of hepatocytes or chronic liver disease may result in coagulopathies
211
thrombosis
inappropriate activation of hemostatic process in injured or slightly injured vessels; formation or presence of a solid mass (thrombus) in the blood vessels or heart
212
thrombus
aggregate of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation
213
what is a differentiating feature between a thrombus and a simple PM blood clot
thrombus is often adherent to the vessel wall
214
where and how do thrombi develop
- thrombi grow in vessel lumen and either toward the heart or in either direction and pieces can break off and form an emboli
- may develop anywhere in CVS, valves, arteries, veins, and capillaries
215
what are the 3 primary influences of thrombosis called together
Virchow's triad
216
what are the 3 parts of Virchow's triad
- endothelial injury
- alterations in normal blood flow
- hypercoagulability
217
what is the dominant influence of thrombosis and the factor that can lead to thrombosis by itself
endothelial injury: an example would be endocarditis which is inflammation of the valves of the heart
218
describe the appearance of normal blood flow
laminar: cellular elements in the middle and surrounded by plasma
219
how does turbulence contribute to thrombosis
disrupts normal laminar flow and allows platelets to contact the endothelium promotes endothelial cell injury and activation
220
describe stasis with respect to thrombosis
prevents dilution of activated clotting factors by fresh-flowing blood and allows the build up of thrombi
221
saddle thrombus
condition often seen in cats with left-sided heart failure/hypertrophic cardiomyopathy; thrombus at the bifurcation of the iliac arteries
222
hypercoagulability
any alteration of the coagulation pathways that predisposes to thrombosis generally due to increased prothrombic factors or decreased inhibitory factors
223
where do arterial thrombi usually form
at sites of turbulence or endothelial injury
224
describe the appearance of arterial thrombi
often paler and "meatier"; composed mainly of platelets and fibrin because rapid blood flow tends to exclude RBCs
225
what are the lines of Zahn
- alternating pale and dark lamination seen with arterial thrombi that reflects continued waves of thrombosis
- pale layers are mostly fibrin and platelets and dark red layers are the entrapped RBCs
226
how are venous thrombi different from arterial thrombi
they usually form in more static environments with more entrapped RBCs and thus appear darker red usually
227
why is a venous thrombi sometimes hard to differentiate from a PM blood clot
attachment to the wall is often focal and loose
228
what is a blood clot
clotted blood within a blood vessel; can refer to a thrombus or a PM blood clot
229
what is the difference between the appearance of a thrombus and a PM blood clot
- PM clot usually not associated with a pathological condition and usually not attached to the wall
- can appear similarly since the two are clearly related
230
chicken-fat clot
- common gelatinous, yellow, PM blood clot seen at necropsy in horses and occasionally pigs
- plasma clot that develops because of rapid erythrocyte sedimentation in animals with high fibrinogen
231
what are the yellow vs red areas in a chicken-fat clot due to
- yellow represents fibrin and plasma
- dark red represents sedimented RBCs at the margins
232
what are the color differences between an arterial thrombus, venous thrombus, and PM clot
- arterial: pale to dark red
- venous: red
- PM: red to yellow (chicken fat)
233
what are the lamination differences between an arterial thrombus, venous thrombus, and PM clot
- arterial: yes
- venous: not frequent
- PM: no
234
what are the attachment differences between an arterial thrombus, venous thrombus, and PM clot
- arterial: yes
- venous: focal/loose (can be difficult to detect)
- PM: no
235
what are the size and location differences between an arterial thrombus, venous thrombus, and PM clot
- arterial: often small
- venous: often fill lumen
- PM: fill lumen
236
what are some possible outcomes of thrombi
- lysis especially when small and in early phase due to potential thrombolytic/fibrinolytic activity of blood
- propagation: increase in size which can eventually obstruct the vessel
- embolization can occur if pieces break off
- organization and recanalization
237
describe organization/recanalization as a possible outcome of thrombi
- presence of thrombi induces inflammation and fibrosis which reduces size
- new small blood vessels can penetrate/grow within the organizing thrombus
- both aid in reflow of blood
238
embolism
passage through the venous or arterial circulations of any material capable of lodging in a blood vessel and thereby obstructing the lumen
239
what is the most common type of embolism
thromboembolism, which is a result of a piece broken off from a thrombus
240
embolus
detached intravascular material that can be solid, liquid, or gaseous that is carried via the blood to a site distant from its origin
241
thromboembolism
occlusion of a blood vessel by an embolus that has broken away from a thrombus that localizes at a point where it can no longer fit through
242
thromboembolus
the piece of thrombotic material transported in the bloodstream to a different site
243
what other types exist
- parasitic
- fibrocartilaginous
- fat
- other: foreign material, tumor cell clusters, amniotic fluid, etc.
244
what can cause a parasitic embolism
- nematodes: D. immitis
- nematode larvae: ascarid or strongyle larvae
245
describe a fibrocartilaginous embolism
originates from intervertebral disc material that is traumatically implanted into spinal vessels; causes necrotizing myelopathy in the form of a spinal cord infarction
246
how does a fat embolism originate
several sources i.e. bone fractures, surgery, osteomyelitis, or hyperlipidemia
247
how do infectious agents cause thrombosis/thromboembolism
damage to endothelium
248
give some examples of infectious causes of thromboembolism
many bacteria can cause valvular endocarditis with resultant thrombosis and thromboembolism; histophilus somni in cattle can cause thrombotic meningoencephalitis; several viral agents can damage endothelium and lead to thrombosis
249
what is disseminated intravascular coagulation (DIC)
sudden or insidious onset of widespread fibrin thrombi in microcirculation; not usually visible grossly but are readily apparent microscopically
250
what can be caused by DIC
diffuse circulatory insufficiency particularly in the brain, lungs, heart, and kidneys
251
With the development of the multiple thrombi as seen with DIC, there is a rapid concurrent consumption of ______ and ______ proteins
platelets, coagulation
252
where does the term "consumption coagulopathy" some into play in reference to DIC
fibrinolytic mechanisms are activated in the event of a DIC event that can cause an initial thrombotic disorder to evolve into a serious bleeding disorder
253
true or false: DIC is a primary disease
false: DIC is not a primary disease but a complication of any condition associated with widespread activation of thrombin
254
what are some potential causes of DIC
severe burns; heatstroke; systemic viral disease; shock; widespread metastatic tumors; heartworm disease
255
what is an infarct
area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage
256
how does an infarct originate
from thrombotic or embolic events or vascular occlusion due to compression of a vessel i.e. intestinal volvulus, testicular torsion, etc.
257
what are the factors that influence the development of an infarct
nature of vascular supply i.e. end artery vs collateral blood availability; rate of development of occlusion; vulnerability to hypoxia: certain cell types have different susceptibilities; oxygen content of blood at time of infarct: underlying anemia would increase the severity of an infarct
258
how does a slow rate of development of an infarct affect it
it allows collateral blood supply to fully open
259
describe the gross appearance of an infarct
often wedge-shaped with base at the periphery and the occluded vessel at the apex; ill-defined, and often red in early stages
260
what is the color of many acute infarcts in the early stages of their development
dark red due to entrapment of blood or pale/white due to lack of blood supply to infarct
261
what are some reasons for why an acute infarct might appear dark red
acute hemorrhagic infarct: RBC leakage from damaged arteries and veins; venous occlusions: blood cannot drain from the area; organs with dual blood supply or where tissues/organs have spongy/expandable consistency (lung, liver, spleen)
262
what are some reasons for why an acute infarct might appear pale/white
arterial occlusion in solid organs with end arterial circulation (heart, kidney); hemorrhagic infarcts become pale after a few days because of RBCs in necrotic areas undergoing lysis and necrotic tissue swelling squeezing RBCs out from the area
263
why will you often see a red zone in the viable tissue immediately adjacent to an infarct
associated with the inflammatory reaction to the necrotic tissue
264
local ischemia in an organ affected with an infarct results in what
coagulation necrosis except in the brain it is liquefactive
265
Infarcts arising from septic (bacterially infected) emboli may be convert to an _______
abscess
266
how does repair of infarcts occur
fibrous CT replaces parenchyma and as it matures and condenses it forms a depression/indentation on the surface of the organ
267
what does a septic infarction usually develop from
a bacterially-infected thromboembolus or occasionally when the necrotic tissue of an infarct is seeded by bacteria and becomes a good growth medium for nearby opportunistic pathogens
268
how is a venous infarction caused
mostly due to twisting of the vessels which leads to shock and death; seen a lot with torsion and strangulation in dogs and horses; also seen with obstruction of anterior or posterior vena cava causing slowly developing stasis with engorgement of the tributary veins
269
how does acute blockage of the portal venous system occur
mostly with twists in portions of GIT/portal venous system which causes venous infarction of stomach or intestine; twisted vessels become compressed and because arterial pressure > venous pressure, blood can get in but not out
270
what is the result of acute blockage of the portal venous system
shock and death without surgery
271
use the example of gastric torsion in a dog to explain acute blockage of the portal venous system
obstruction of gastric portion of portal vein → severe venous congestion → vascular stasis → ischemic necrosis (infarction) → loss of endothelial integrity → hemorrhage → shock
272
what are possible etiologies of a blockage to the posterior vena cava
severe dirofilariasis or adrenal tumors in dogs; hepatic abscesses in ruminants
273
what are the results of blockage of the posterior vena cava
acute: complete occlusion and death; chronic: possibility of collateral circulation developing from azygous vein
274
what are possible causes of thrombosis of the pulmonary artery
pneumonia; parasite infestations (ex heartworm); hypercoagulability (eg hyperadrenocorticism, nephrotic syndrome); liver abscess rupture into vena cava, etc
275
what are the results of pulmonary artery thrombosis
if sudden and large branch of the artery it causes death; if incomplete and smaller branches it can cause variably altered circulation or possibly pulmonary infarcts
276
what is shock characterized by
systemic hypotension due either to reduced cardiac output or to reduced effective circulating blood volume
277
what is the result of shock
impaired tissue perfusion and cellular hypoxia
278
what are the organs most susceptible to ischemic damage from shock
brain and heart
279
______ is the final common pathway for many potentially lethal clinical events which include microbial sepsis, severe hemorrhage, extensive trauma or burns, myocardial infarction, severe pulmonary embolism, etc.
shock
280
what are the 3 general categories of shock
cardiogenic; hypovolemic; blood maldistribution (vasogenic)
281
what does cardiogenic shock result from
failure of the heart to adequately pump blood and cardiac output is decreased
282
when does cardiogenic shock occur
an occur with a variety of heart diseases such as myocardial infarction, ventricular tachycardia, arrhythmias, cardiomyopathy, or an obstruction of the flow of blood from the heart
283
what does hypovolemic shock result from
decreased circulating blood volume
284
what can hypovolemic shock be due to
blood loss from hemorrhage (internal or external); fluid loss (dehydration) secondary to vomiting, diarrhea or burns
285
what will you see with blood maldistribution (vasogenic) shock
decrease in peripheral vascular resistance and resultant pooling of blood in peripheral tissues
286
what are some possible causes of blood maldistribution shock
Many causes, including neural or cytokine induced vasodilation, trauma, systemic hypersensitivity to allergens (anaphylaxis) or endotoxemia
287
anaphylactic shock, neurogenic shock, and septic shock are all examples of what type of shock
blood maldistribution
288
what is anaphylactic shock
vasodilation due to release of vasoactive amines (ex histamine), etc.
289
what is neurogenic shock
vasodilation due to loss of the autonomic nervous system signals to the smooth muscle in vessel walls
290
what is septic shock
vasodilation due to release of inflammatory mediators associated with overwhelming infections
291
describe the pathogenesis of septic shock
inflammatory cells have a number of receptors that respond to a variety of substances derived from microbes; when microbial components bind to WBC surface receptors the WBC releases cytokines that cause vasodilation, DIC, complement activation, etc.
292
what is endotoxin
bacterial wall lipopoysaccharide (LPS) released when bacterial cell walls are degraded; important in pathogenesis of septic shock
293
what are the 3 stages of shock
non-progressive (compensated); progressive; irreversible
294
describe non-progressive stage of shock
reflex compensatory mechanisms are activated and perfusion of vital organs is maintained; i.e. increased heart rate and peripheral vasoconstriction
295
describe progressive stage of shock
characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances, including acidosis
296
describe irreversible stage of shock
sets in after the body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected survival is not possible
297
Shock is characterized by failure of ______ organ systems
multiple
298
what is the prominent shock organ of cattle and horses
pulmonary congestion and edema
299
what is the prominent shock organ of dogs
liver congestion
300
what are the lesions of shock associated with the kidneys
acute tubular necrosis
301
what are the lesions of shock associated with the heart
subendocardial hemorrhage and myocardial necrosis
302
what are the lesions of shock associated with the blood vessels
endothelial damage with possible thrombosis/DIC
303
what are the lesions of shock associated with the brain
neuronal cell death; looks "barbie pink" acidophilic
304
what are the lesions of shock associated with the adrenal glands
hemorrhage
305
what are the lesions of shock associated with the GIT
mucosal congestion and necrosis
306
what are the lesions of shock associated with the skeletal muscle
pallor probably due to peripheral vasoconstriction
Veterinary Pathology 1
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