Vtpa 342 Hemodynamics

Front 1

Hemodynamic disorders can be divided into four subgroups

Back 1

which often overlap in vivo, namely

disorders of blood flow
`` hyperemia
`` congestion

disorders of blood fluidity
`` thrombosis
`` lack of coagulation

disorders of blood vessel permeability
``hemorrhage
`` edema

intravascular/interstitial fluid equilibrium
``edema

Front 2

Hyperemia or congestion is usually a

Back 2

consequence of a pathological process not its cause

Front 3

Hyperemia is

Back 3

an engorgement of the vascular (capillary) bed
`` caused by
`` increased arteriolar blood flow into the area/organ

Front 4

Pathogenes is

Back 4

The
`` pathologic,
`` physiologic, or
`` biochemical
mechanism resulting in the
``development of a disease or
`` morbid process

Front 5

Physiological hyperemia is

Back 5

associated with increased workload

e.g.
`` gastrointestinal hyperemia after meals or
`` muscular and dermal hyperemia during exercise

or with neurovascular regulation

e.g.
`` blushing due to embarrassment

Front 6

Pathological hyperemia is

Back 6

almost exclusively associated with
`` acute inflammation and/or
`` tissue injury

Front 7

Hyperemia is a

Back 7

local increase in blood volume due to
`` increased blood inflow as a consequence of
`` arteriolar dilatation induced by
`` `` histamine,
`` `` bradykinin and
`` `` other vasoactive substances
`` released during acute inflammatory reaction

Front 8

Majority of capillaries in the hyperemic area are

Back 8

opened, dilated and filled with blood

Front 9

Hyperemia is an

Back 9

active process and

occurs in a localized area/organ because

if it occurred all over the body,
`` there would not be sufficient blood in the major vessels to
`` maintain systemic blood pressure and
`` shock would occur

Front 10

Hyperemia Morphologic characteristics

Macroscopic:

Back 10

bright red
`` oxygenized hemoglobin

and warm area/organ
`` in live animal

Front 11

Hyperemia Morphologic characteristics

Microscopic:

Back 11

distended capillaries
`` the same as congestion)

accompanied by acute inflammatory features
`` e.g. leucocytes

Front 12

Hpperemiea

Significance to the animal:

Back 12

Hyperemia is part of the inflammatory process and

it contributes to the host defense

It is not life-threatening by itself

Front 13

Hyeremia

Significance to the diagnostician/clinician:

Back 13

Hyperemia
`` redness and
`` warmth

are very useful indicators of
`` acute inflammation or
`` tissue injury

Front 14

Hyperemia

Outcome

Back 14

Hyperemia is a
`` transient phenomenon of
`` acute inflammation which
`` usually disappears in
`` `` subacute and chronic inflammatory processes

Front 15

Congestion is an

Back 15

engorgement of the vascular (capillary) bed caused by
`` impeded venous outflow

Front 16

Hypostatic congestion is

Back 16

congestion due to pooling of venous blood in a
`` dependent part

Front 17

Livor mortis is

Back 17

discoloration appearing on
`` dependent parts of the carcasses,

as a result of
`` cessation of circulation,
`` stagnation of blood, and
`` settling of the blood by gravity

It is a hypostatic congestion in a carcass

Front 18

Livor

Back 18

The livid discoloration of the skin
`` on the dependent parts of a carcass

Front 19

Cyanosis

Back 19

A dark blue or purple discoloration of the
`` skin and
`` mucous membrane

due to
`` deficient oxygenation of the blood

Front 20

Ischemia

Back 20

Local anemia due to
`` obstruction of the blood supply

Front 21

Hypoxia -

Back 21

Decrease below normal levels of oxygen in
`` inspired gases,
`` arterial blood, or
`` tissue

Front 22

Congestion is caused by

Pathogenesis

Back 22

obstruction of either
`` small or
`` large draining vessels e.g.
`` `` venous thrombosis,
`` `` compression,
`` `` torsion

or failure of forward blood flow
`` e.g. heart failure

Front 23

Congestion is an extremely common lesion in carcasses because

Back 23

it occurs rapidly as part of hemodynamic alterations in the course of dying

Even after death blood trapped within tissues may undergo gravitational settling
`` hypostatic congestion or
`` livor mortis
`` causing the depended site e.g.
`` `` lungs,
`` `` kidney
`` to be darker red than the opposite one

Front 24

Congeston

Morphologic characteristics

Macroscopic:

Back 24

diffusely
`` dark red,
`` cyanotic
`` hemoglobin not oxygenized

heavy
`` due to additional weight of the entrapped blood

oozing blood from cut surface.

Front 25

Congeston

Morphologic characteristics

Microscopic:

Back 25

distended capillaries
`` the same as hyperemia

often accompanied by
`` edema,
`` but usually without evidence of
`` `` inflammation

Front 26

Conjestion

Duration:

Back 26

acute vs. chronic

Front 27

Conjestion

Distribution:

Back 27

local
`` e.g. intestinal strangulation

vs.

generalized
`` e.g. right-sided heart failure

Front 28

Congestion

Significance to the animal:

Back 28

Significance of congestion depends on its
`` duration and
`` location

Front 29

Congestion

Significance to the animal:

Short term (acute) congestion

Back 29

especially when it is seen as a terminal event,
`` has no impact on tissue health/morphology
`` even though it might be associated with terminal pulmonary edema

Front 30

Congestion

Significance to the animal:

Prolonged (chronic) congestion

Back 30

will lead to ischemic necrosis
`` regardless of the paradox of an excessively blood-filled tissue.

The affected tissue is
`` nevertheless hypoxic because of
`` lack of oxygenated hemoglobin due to
`` `` decreased blood flow

Decrease blood flow also results in
`` decreased delivery of nutrients
`` `` e.g. glucose and
`` `` decreased removal of metabolites.

The affected tissue will commonly be
`` edematous due to
`` increased hydrostatic pressure in the vessels

`` as well as due to
`` `` local endothelial hypoxic injury resulting in
`` `` increased endothelial permeability.

In addition, mild hemorrhage by
`` diapedesis may occur.

Therefore, clinical significance of prolonged congestion will depend on
`` location and
`` cause
`` and in some cases could be fatal
`` `` e.g. left- and right-sided heart failure

In addition, prolonged blood stasis is a major factor in
`` development of venous thrombosis,
`` which may also be occasionally fatal

Front 31

Congestion

Significance to the diagnostician/clinician:

Back 31

Congestion is an extremely common lesion
`` and it is very difficult to determine its significance,
`` unless there are changes of
`` `` tissue necrosis or
`` `` fibrosis
`` to suggest that congestion has been chronic.

In most cases, it is considered to have
`` no pathologic significance,
`` if observed without any other pathological processes

Front 32

Congestion

4 Outcomes

Back 32

Resolution

Increased hydrostatic pressure
`` edema
`` `` Fibrosis
`` `` hemorrhage
`` `` `` Fibrosis

Ischemia
`` degeneration
`` `` necrosis
`` `` `` fibrosis

Death

Front 33

Heart failure

Most of the lesions secondary to heart failure result from

Back 33

backup of blood rather than
`` from failure of adequate forward flow of blood

Front 34

Animals that die with suspected acute heart failure will have only

Back 34

congestion and edema that are often
`` indistinguishable
from the hemodynamic events accompanying death of
`` almost all causes

Front 35

Chronic right-sided heart failure is

Back 35

Manifested as
`` chronic passive congestion of the liver,
`` ascites and
`` generalized edema
`` that might be more intense in
`` `` dependent areas

Hepatic changes depend on the
`` `` duration and
`` `` magnitude of
`` venous stasis or
`` decreased outflow

Initially, there is
``dilatation of central lobular veins and
``distention of hepatic sinusoids with blood

As the duration of the congestion increases,
`` there is ischimic injury to the
`` `` hepatocytes in the center of the lobule around central vein,
`` `` `` because they are furthest from the triads at the periphery of lobules
`` `` `` `` where arterial and portal venous blood enters

Initial ischimic injury is manifested by
`` accumulation of triglyceride vacuoles
`` `` fatty degeneration
`` `` visible macroscopically as
`` `` `` yellow centrilobular discoloration
`` `` `` `` only in large animals
`` `` `` that progresses to necrosis/apoptosis

Death of centrilobular necrotic hepatocytes is followed by
`` blood-filled centrilobular area
`` `` macroscopically visible as
`` `` `` dark red centrilobular area
`` `` `` surrounded by a zone of ischemic hepatocytes
`` `` `` `` affected by fatty degeneration
`` `` `` `` `` macroscopically visible as yellow areas surrounded by brown periportal zone
`` `` `` `` `` `` normal hepatocytes

This process is followed by
`` `` centrilobular fibrosis `` tissue repair occurs, rather than regeneration due to
`` lack of appropriate blood supply and
`` due to presence of persistent edema in space of Disse

The distinctive macroscopic zonal pattern of dark red, yellow and brown color changes resemble
`` cross section of a nutmeg,
`` hence the name of “nutmeg liver”
`` in large animals

The entire liver is
`` `` slightly enlarged,
`` `` congested and
`` `` firm
`` due to
`` `` diffuse subtle fibrosis

A typical nutmeg appearance of the liver is rarely observed
`` in dogs and cats with chronic right-sided heart failure,
`` instead, liver in these animals is
`` slightly enlarged,
`` firm, and
`` on cut section has
`` `` `` accentuated zonal pattern of dark red and brown color changes

Due to increased hydrostatic venous pressure in
`` `` portal and
`` `` systemic circulation
`` ascites is frequently present with
`` `` subcutaneous edema which is
`` `` `` more intense in dependent areas

Front 36

Chronic left-sided heart failure

Left-sided heart failure results in

Back 36

Chronic passive congestion of lungs.

Cellular degeneration and necrosis of pulmonary parenchyma due to
`` `` chronic congestion and
`` `` blood stasis
`` is not an obvious feature as in chronic passive congestion of the liver
`` `` due to right sided heart failue

Instead, initially there is
`` diffuse severe congestion of alveolar capillaries
`` followed by edema in
`` `` alveolar septa and
`` `` alveolar spaces
`` due to increased hydrostatic pressure

Congestion of alveolar capillaries and blood stasis favors
`` diapedesis of erythrocytes into
`` alveolar lumen

Part of this extravasation of erythrocytes
`` might be due to
`` `` increased pressure in capillaries,
`` while the part of intra-alveolar hemorrhage could be related to
`` `` ischemic injury to the endothelium and
`` `` increased endothelial permeability.

The persistent alveolar septal edema stimulates
`` diffuse and subtle fibrosis

Intra-alveolar erythrocytes are
`` engulfed by pulmonary macrophages which
`` process the erythrocytic iron into
`` hemosiderin (golden-brown pigment)
`` to be stored in lysosomes

This gives a blue color in tissue sections stained with Perl’s technique

Abundant hemosiderin laden macrophages
`` `` heart failure cells
`` in pulmonary parenchyma may produce a macroscopic golden discoloration of lungs,
`` `` hence name “golden lungs”

The diffuse subtle alveolar septal fibrosis with
`` persistent intra-alveolar edema interferes with
``proper oxygenation of blood resulting in
`` clinical signs of
`` `` exertional weakness,
`` `` dyspnea and
`` `` coughing

Front 37

Edema and hemorrhage are usually consequences of

Back 37

Pathological process,
`` not causes

Front 38

Interstitium is

Back 38

interstitial tissue

Front 39

Interstitial

Back 39

pertaining to or

situated between parts or

in the interspaces of a tissue

Front 40

Edema is

Back 40

excessive accumulation of fluid in
`` interstitial spaces of tissue or
`` in a body cavity

Front 41

Anasarca

Back 41

Generalized severe infiltration of
`` edema fluid into the
`` subcutaneous connective tissue

Front 42

Dependent edema -

Back 42

a clinically detectable increase in
`` extracellular fluid volume
`` localized in a dependent area
`` `` e.g. limbs
`` characterized by
`` `` swelling or
`` `` pitting

Front 43

Pitting edema –

Back 43

the term is used for edematous tissue that
`` remains indented for a few minutes after
`` firm finger-pressure is applied on it

Front 44

Dehydration

Back 44

Reduction of water content

Front 45

Hydrothorax

Back 45

A non-inflammatory accumulation of
`` fluid in the pleural cavity;

Pleural effusion

Front 46

Hydropericardium

Back 46

A non-inflammatory accumulation of fluid
`` in the pericardial sac;

Pericardial effusion

Front 47

Ascites

Back 47

Accumulation of non-inflammatory fluid in the
`` peritoneal cavity;

Hydroperitoneum,

Peritoneal effusion

Front 48

Effusion

Back 48

The escape of fluid from the
`` `` blood vessels or
`` `` lymphatics
`` into the tissues or
`` a cavity

usually non inflammatory fluid,
`` but occasionally inflammatory fluid
`` `` (serous exudate)

Front 49

Lymphedema -

Back 49

Edema as a result of
`` `` obstruction of lymphatic vessels or
`` `` lymph nodes
`` and the accumulation of large amounts of lymph in
`` `` the affected region

Front 50

Transudate

Back 50

Any fluid (solvent and solute) that
`` has passed through a presumably normal membrane,
`` `` such as the capillary wall,
`` as a result of imbalanced hydrostatic and osmotic forces;

characteristically low in
`` `` protein
`` unless there has been
`` `` secondary concentration

Transudate has
`` protein concentration
`` `` <30 g/L and
`` number of cells
`` `` <1500 cells/µL

Front 51

Exudate

Back 51

Any fluid that has
`` `` exuded out of a tissue or
`` `` its capillaries,
`` more specifically because of
`` `` injury or
`` `` inflammation
`` `` `` e.g., fibrinous peritoneal exudate in peritonitis, or
`` `` `` the exudate that forms a scab over a skin abrasion
`` `` in which case it is characteristically high in
`` `` `` protein and
`` `` `` white blood cells

Exudate has
`` protein concentration
`` `` >30 g/L and
`` number of cells
`` `` >1500 cells/µL

Front 52

Water distribution

Back 52

Approximately 60% of lean body weight is
`` water:
`` `` two thirds of this water is
`` `` `` intracellular, and
`` `` the remainder is
`` `` `` extracellular space,
`` `` `` `` mostly as interstitial fluid
`` `` `` `` (only about 5% of total body water is in blood plasma)

Normal equilibrium of intravascular and extravascular fluid compartments requires
`` intact, normally functioning
`` `` cardiovascular and
`` `` lymphatic systems and
`` a normal plasma protein composition

Front 53

Pathogenesis

Edema results from one or more of four mechanistic (pathogenetic) processes:

Back 53

Increased venous hydrostatic pressure,

decreased plasma osmotic pressure,

lymphatic obstruction, or

endothelial leakage

Front 54

Increased venous hydrostatic pressure

Back 54

Increased venous hydrostatic pressure occurs under the same circumstances as
`` for congestion, namely,
`` it is caused by obstruction of either
`` `` small or
`` `` large
`` draining vessels
`` `` e.g. venous thrombosis,
`` `` compression,
`` `` torsion
`` resulting in local increase in venous hydrostatic pressure
`` or
`` `` failure of forward blood flow
`` `` `` e.g. heart failure
`` resulting in generalized/systemic increase in venous hydrostatic pressure

Accordingly, both congestion and edema
`` will be present in these conditions at
`` `` the same time

In chronic right-sided heart failure there is
`` `` generalized congestion and
`` `` increased venous hydrostatic pressure
`` resulting in
`` `` generalized systemic low proteinaceous edema
`` `` which is most obvious in
`` `` `` the peritoneal cavity (ascites)
`` `` `` and dependent subcutaneous tissue

In chronic right-sided heart failure the kidneys are
`` hypoperfused and
`` secondary aldosteronism results in
`` retention of salt and water increasing
`` `` plasma volume

If the failing heart cannot increase cardiac output,
`` the extra fluid load increases
`` venous hydrostatic pressure even more and
`` aggravates generalized edema

Front 55

Decreased plasma osmotic pressure

Back 55

Hypoproteinemia leads to
`` edema by
`` `` reducing the plasma osmotic pressure which leads to
`` `` a net movement of fluid
`` into the interstitial tissues and a
`` decrease in total plasma volume

The cause of hypoproteinemia
`` must always be determined

It is most commonly caused by
`` one or several of the following conditions:

protein losing nephropathy
`` loss of low MW proteins –`` `` e.g. albumin,

protein-losing enteropathy

decreased protein production by the liver
`` `` e.g. album
`` due to chronic severe hepatic disease or
`` severe malnutrition

Because hypoproteinemia is present everywhere in the circulation,
`` diffuse/generalized edema affecting the entire body is anticipated

To some extent this is true, but there are
`` striking differences in the susceptibility of different tissues to
`` the development of edema `` dense tissues are more resistant to edema than
`` `` loose tissues
`` e.g. heart and kidney vs.
`` `` subcutis and lungs
`` as well as differences in capacity of
`` `` auxiliary lymphatic drainage

Accordingly, in many cases, edema due to hypoproteinemia will be most striking in
`` dependent subcutaneous tissues and
`` body cavities

There will be associated
`` renal hypoperfusion and
`` secondary aldosteronism that result in
`` `` retained salt and
`` `` water.

However, retained salt and water
`` cannot correct the plasma volume deficit because
`` the primary defect of
`` `` low serum proteins persists and
`` generalized edema is
`` `` exacerbated

Front 56

Lymphatic obstruction

Back 56

Lymphatic obstruction is
`` the least frequent cause of edema

It is seen most commonly with
`` neoplasms that
`` obliterate the lymph node with
`` consequent impairment of lymph transit

Pathological conditions that involve
`` venous obstruction due to
`` `` torsion,
`` `` strangulation or
`` `` compression
`` prevent both
`` `` venous and
`` `` lymphatic drainage,
`` nevertheless the resultant edema is
`` `` considered to be predominantly due to
`` `` `` increased venous hydrostatic pressure

Rarely, partial torsion or organ displacement seems to
`` spare the blood vessels but
`` collapse/obstruct the less pressurized
`` `` lymphatic vessels

In contrast to hypoproteinemic edema, lymphedema is almost always
`` localized;
`` and in contrast to edema due to increased venous hydrostatic pressure, lymphedema is
`` not accompanied by intense congestion

Front 57

Endothelial leakage

Back 57

The most common cause of local edema is
`` endothelial leakage associated with
`` `` acute inflammation and
`` `` trauma

Inflammatory endothelial leakage is caused by
`` activation and
`` contraction of the endothelial cells that
`` result in
`` `` increased capillary permeability for
`` `` `` plasma proteins

Accordingly, edema induced by inflammation contains a
`` higher concentration of
`` `` proteins than
`` edema induced by
`` `` the other three processes

In addition,
`` leakage could be caused also by
`` `` direct injury to endothelium by
`` `` `` certain toxins or
`` `` `` microorganisms,
`` `` which usually results in both
`` `` `` edema and
`` `` `` hemorrhage

There are only a few examples of
`` toxic endothelial damage causing edema
`` `` without hemorrhage
`` `` `` e.g. Shiga toxin 2e (of E. coli)
`` `` `` causing edema disease in pigs and
`` `` `` epsilon toxin (of C. perfringens type D)
`` `` `` causing pulmonary edema and hydropericardium without hemorrhage

Front 58

Sodium and water retention are clearly

Back 58

contributory factors in several forms of edema

They expand intravascular fluid volume contributing to
`` increased hydrostatic pressure
`` `` in failing heart
`` or to diminished vascular colloid osmotic pressure by
`` `` dilution effect

So even in conditions
`` `` e.g. acute renal failure
`` in which salt retention is
`` `` considered to be the primary cause of edema,
`` pathogenesis of edema involves
`` `` one or more of the primary mechanisms of edema

Front 59

Edema

Morphologic characteristics

Macroscopic:

Back 59

excessive clear fluid in tissue or cavity

tissue is
`` heavy,
`` wet,
`` shiny/glistening;
`` oozing fluid on cut section

slightly enlarged organs
`` liver,
`` kidney

lung –
`` increase in firmness,
`` failure to collapse,
`` stable foam within major airway
`` `` liquid +
`` `` surfactant +
`` `` agitation due to respiration
`` tf foam

brain –
`` flattened sulci,
`` herniation of
`` `` brain and
`` `` cerebellum

subcutis –
`` pitting edema in
`` `` dependent areas,
`` gelatinous clear fluid

body cavity –
`` accumulation of fluid
`` `` transparent,
`` `` not clotted if
`` `` `` transudate; and
`` `` clotted with cellular component
`` `` `` if exudate

Front 60

Edema

Morphologic characteristics

Microscopic

Back 60

low proteinaceous edema –
`` non-staining clear spaces

proteinaceous edema –
`` pale eosinophilic amorphous material
`` `` often with leucocytic inflammatory infiltrate if
`` `` `` exudate

dilated lymphatics

Front 61

Edema

Classification

Back 61

Duration:
`` acute vs.
`` chronic

Distribution:
`` local
`` e.g.
`` `` intestinal strangulation,
`` `` lymphatic obstruction
`` vs. generalized
`` e.g.
`` `` right-sided heart failure,
`` `` hypoproteinemia

Front 62

Edema

Significance to the animal:

Back 62

Significance of edema
`` depending on
`` `` extent,
`` `` location and
`` `` duration
`` may range from
`` `` complete clinical irrelevance to
`` `` very important clinical consequences including
`` `` `` fatal outcome

Mild to moderate subcutaneous edema is
`` usually not important to the overall health status of the animal
`` Nevertheless, it may prolong
`` `` wound healing and
`` `` partially impair antimicrobial defenses

Chronic diffuse edema in the interstitium of the vital organs
`` `` e.g. lung,
`` `` kidney
`` will induce diffuse fibrosis that will
`` `` lead to malfunction of the organ
`` `` in most cases due to poor blood perfusion
`` `` or due to loss of elasticity
`` and potentially to the death of the animal

Intra-alveolar edema occupies
`` `` airspace and
`` decreases
`` `` the pulmonary surface available for the gas exchange
`` If severe and diffuse,
`` `` intraalveolar edema may be fatal
`` `` `` (“drowning from within”).

Brain edema is
`` a consequence of several different pathological processes
`` `` e.g. encephalitis
`` and may be fatal due to
`` confined space
`` `` edematous brain cannot expand,
`` `` `` therefore, intracranial pressure is increased due to
`` `` `` `` swollen/injured tissue leading to
`` `` `` `` `` poor blood perfusion and
`` `` `` `` `` herniation of the brain under tentorium cerebelli and of the cerebellum into foramen magnum

Front 63

Edema

Significance to the diagnostician/clinician:

Back 63

Edema often provides a clue about
`` underlying disease process

With the possible exceptions of
`` `` brain and
`` `` pulmonary edema,
`` `` `` where direct intervention may be needed to prevent a fatality,
`` diagnostician/clinician usually approaches edema by
`` attempting to sort out the ultimate cause
`` and pathogenesis and then
`` to treat it accordingly

This is as it should be, and an understanding of the basic mechanisms underlying the development of edema
`` makes the process of therapy a good deal easier

Front 64

Edema

Outcome

Back 64

 Resolution

 Fibrosis

 Death

Front 65

Hemorrhage

Back 65

An escape of blood from
`` the intravascular space

Front 66

Anemia –

Back 66

Any condition in which
`` `` the number of red blood cells,
`` `` the amount of hemoglobin of blood,
`` `` and/or the volume of packed red blood cells
`` are less than normal

Anemia is frequently manifested by
`` pallor of the skin
`` `` and mucous membranes,
`` shortness of breath,
`` lethargy, and
`` fatigability

Front 67

Hematopoiesis

Back 67

The process of
`` `` formation and
`` `` development of
`` the various types of
`` `` blood cells and
`` `` other formed elements

Front 68

Internal Hemorrhage:

Petechiae (sing. petechia)

Back 68

Minute hemorrhagic spots, of
`` pinpoint to
`` pinhead size

Petechial hemorrhage

Front 69

Internal Hemorrhage:

Ecchymosis

Back 69

A red-purple patch caused by
`` extravasation of blood into the
`` `` skin or tissue,
`` differing from petechiae only in
`` `` size
`` `` `` (larger than 3 mm diameter)

Ecchymotic hemorrhage

Front 70

Internal Hemorrhage:

Purpura

Back 70

A systemic generalized multifocal random hemorrhages
`` (up to 1 cm diameter)
`` in many organs and tissues

Front 71

Internal Hemorrhage:

Paintbrush hemorrhage –

Back 71

linear hemorrhage found in
`` very dense tissues,
`` `` substructures of which are organized in a
`` `` `` linear manner
`` ``e.g.
`` `` `` myocardium,
`` `` `` thoracic parietal pleural underlying tissue

Front 72

Internal Hemorrhage:

Suffusion

Back 72

The act of pouring a fluid (blood) over the body, tissue

Suffusive hemorrhage –
`` large flat spreading hemorrhage

Front 73

Internal Hemorrhage:

Hematoma

Back 73

A localized mass of
`` extravasated blood that
`` is relatively or completely confined
`` within an
`` `` organ or
`` `` tissue, a space,
`` `` or a potential space;
`` the blood is usually
`` `` clotted
`` `` (or partly clotted),
`` and, depending on how long it has been there,
`` may manifest various degrees of
`` `` organization and
`` `` discoloration

Front 74

Internal Hemorrhage:

Cardiac tamponade -

Back 74

compression of the heart due to
`` critically increased volume of fluid in
`` the pericardium

Front 75

Internal Hemorrhage:

Hemothorax

Back 75

Blood in the pleural cavity

Front 76

Internal Hemorrhage:

Hemopericardium

Back 76

Blood in the pericardial sac

Front 77

Internal Hemorrhage:

Hemoperitoneum

Back 77

Blood in the peritoneal cavity

Front 78

Internal Hemorrhage:

Hemarthrosis

Back 78

Blood in a joint

Front 79

External Hemorrhage:

Melena

Back 79

Passage of
`` `` dark-colored,
`` `` tarry stools, due to
`` the presence of blood altered by the
`` `` gastrointestinal juices

Front 80

External Hemorrhage:

Hematochezia

Back 80

Passage of bloody stools
`` (undigested blood in feces),
`` in contradistinction to
```` melena, or
`` `` tarry stools

Front 81

External Hemorrhage:

Epistaxis

Back 81

Bleeding from the nose

Front 82

External Hemorrhage:

Hemoptysis

Back 82

Spitting of blood
`` derived from the
`` `` lungs or
`` `` bronchial tubes
`` as a result of
`` `` pulmonary or
`` `` bronchial
`` hemorrhage

Front 83

External Hemorrhage:

Hematuria

Back 83

Presence of
`` `` blood or
`` `` red blood cells
`` in the urine

Front 84

Hemorrhage

Pathogenesis 4

Back 84

Blood vessel damage –
`` trauma,
`` endothelial necrosis

Platelet disorders –

Coagulation factor disorders

Diapedesis –
`` with increased venous hydrostatic pressure

Front 85

Hemorrhage

Classification

Back 85

Duration:
`` acute vs.
`` chronic

Distribution:
`` `` local
`` `` `` (e.g. hematoma)
`` vs.
`` `` generalized
`` `` `` (e.g. purpura)

Front 86

Hemorrhage

Significance to the animal:

Back 86

Depends on
`` `` location,amount,
`` `` rapidity (rate)
`` of hemorrhage

Small hematomas often result from
`` `` intra-venous or
`` `` intra-arterial injections
`` and from traumatic events

Hematomas in skin or muscle may be
`` `` awkward or
`` `` painful
`` but they are not life threatening

Even a small suddenly developed subdural hematoma in the brain stem
`` may result in sudden death
`` `` as a result of the
`` `` `` pressure on vital centers of brain
`` `` `` which is in confined anatomical space
`` `` `` (surrounded by bones)

Rapid loss of
`` up to 10% of the blood volume
`` or slow losses of
`` even larger amounts
`` may have little impact
`` in healthy adult animals;
`` greater losses, however, may result in
`` hemorrhagic (hypovolemic) shock

Loss of iron and subsequent
`` iron-deficiency anemia become
`` a consideration in
`` `` chronic or
`` `` recurrent
external blood loss
`` `` gastric ulcer,
`` `` blood-sucking parasitism

In contrast, when red cells are retained,
`` `` as in hemorrhage into
`` `` `` body cavities or
`` `` `` tissues,
`` `` the iron and proteins can be
`` `` `` reused for hemoglobin synthesis

Gradual blood loss may be compensated by
`` a vigorous hematopoietic response within
`` `` bone marrow and
`` `` spleen

The regenerative response to profound blood loss will be
`` evident within less than
`` `` 7 days because it
`` `` takes only ~ 4 days to
`` `` `` produce an erythrocyte.

However, it should be noted that,
`` `` in an adult animal, it takes
`` `` 4-6 weeks of chronic or recurrent anemia to
`` awaken the “sleeping giant”,
`` `` white yellow fatty marrow of long bones,
`` to become
`` `` diffusely red hyperplastic bone marrow

Front 87

Hemorrhage

Significance to the diagnostician/clinician:

Back 87

Presence of hemorrhage usually indicates
`` damage to blood vessels,
`` except when it happens by
`` `` diapedesis, or
`` `` hemostatic disorder

Hemorrhage should be always
`` investigated as a potential cause of death
`` `` if hemorrhage is
`` `` `` abundant or
`` `` `` if affecting vital organs
`` `` or as a potential diagnostic indicator/clue of
`` `` `` pathological conditions
`` `` `` `` eg generalized petechiation due to septicemia

One noteworthy exception is the observation of
`` `` subendocardial and
`` `` subepicardial
`` `` and occasionally tracheal
`` petechial and ecchymotic hemorrhages in
`` `` dead ruminants and horses, because
`` `` `` these hemorrhages are considered to be
`` `` `` non-specific indicators of
`` `` `` so-called “agonal death”, and
`` `` `` their pathogenesis is not clear

Front 88

Hemorrhage

Outcome 3

Back 88

Resolution
`` Re-absorption
`` `` the extravasated erythrocytes are
`` `` degraded and
`` `` phagocytosed by
`` `` `` macrophages;
`` the hemoglobin
`` `` `` (red-blue color) is then
`` enzymatically converted into
`` `` bilirubin
`` `` `` (blue-green color)
`` and eventually into
`` `` hemosiderin
`` `` `` (gold-brown color),
`` accounting for the characteristic color changes in a bruise

Anemia

Death

Front 89

Coagulation

Back 89

Clotting;
`` the process of changing from a liquid to a solid,
`` said especially of blood

i.e., blood coagulation)

Front 90

Hemostasis

Back 90

The arrest of bleeding –
`` normal physiological process;

Stagnation of blood

Front 91

Thrombosis is

Back 91

coagulation within
`` cardiovascular systems associated with
`` `` pathological process

Front 92

Thrombus

Back 92

A clot in the cardiovascular systems formed
`` `` during life from
`` constituents of blood
``pathological process

Front 93

Embolus

Back 93

A plug, composed of
`` `` a detached thrombus,
`` `` mass of bacteria, or
`` `` other material, that
`` is carried by blood and
`` occludes a vessel

Front 94

Thrombo-embolus

Back 94

Embolus from a thrombus

Front 95

Infarct

Back 95

is an area of
`` ischemic necrosis in which
`` `` all components of the
`` `` `` affected tissue have
`` `` `` `` undergone necrosis

Front 96

DIC -

Back 96

Disseminated intravascular coagulation

Front 97

“Chicken fat” clot -

Back 97

clot formed
`` `` in vitro or
`` `` postmortem
`` from leukocytes and
`` plasma of
`` sedimented blood

Front 98

Thrombocytopenia

Back 98

A condition in which there is
`` an abnormally small number of platelets in
`` the circulating blood

Front 99

Normal hemostasis is

Back 99

the result of a set of well-regulated processes that
`` accomplish two important functions

maintain blood in a
`` ``fluid,
`` ``clot-free state
`` in normal vessels

induce a
`` `` rapid and
`` `` localized
`` hemostatic plug at
`` a site of vascular injury

Front 100

The pathologic opposite to hemostasis is

Back 100

thrombosis

Front 101

Both hemostasis and thrombosis are regulated by three general components

Back 101

 vascular wall
`` (endothelium)

 platelets

 coagulation cascade

Front 102

Sequence of normal hemostasis

4 Processes

Back 102

After initial injury,
`` there is a brief period of arteriolar vasoconstriction,
`` `` largely attributable to
`` `` `` reflex neurogenic mechanisms and
`` `` `` augmented by the local secretion of factors such as
`` `` `` `` endothelin (a potent endothelium-derived vasoconstrictor)
`` The effect is transient, however, and
`` `` bleeding would resume if not for
`` `` activation of the
`` `` `` platelet and
`` `` `` coagulation systems

Endothelial injury exposes
`` highly thrombogenic subendothelial extracellular matrix (ECM),
`` to which platelets adhere via
`` `` von Willebrand factor (vWF)
`` `` and are activated, undergoing
`` `` `` a shape change
`` `` `` `` (from disk to sphere) and
`` `` `` granule release.
`` Released
`` `` adenosine diphosphate (ADP) and
`` `` thromboxane A2 (TxA2)
`` lead to further platelet aggregation and
`` formation of the
`` `` primary hemostatic plug
`` `` `` (primary hemostasis)

Local activation of the coagulation cascade at the site of injury
`` `` involving tissue factor and
`` `` platelet phospholipids
`` culminates in the activation of
`` `` thrombin and
`` `` subsequent polymerization of fibrin
`` `` `` conversion of circulating soluble fibrinogen to
`` `` `` insoluble fibrin
`` Deposited fibrin together with platelets form
`` secondary hemostatic plug
`` `` `` (secondary hemostasis
`` Thrombin also induces
`` `` further platelet recruitment and
`` `` granule release

Polymerized fibrin and platelet aggregates form
`` `` a solid,
`` `` permanent
`` plug to prevent any further hemorrhage
`` At this stage,
`` `` counter-regulatory mechanisms, such as
`` `` `` release of tissue type plasminogen activator (t-PA)
`` `` `` `` t-PA necessary for conversion of
`` `` `` `` `` plasminogen into plasmin,
`` `` `` `` `` which lyses fibrin
`` `` `` `` and thrombomodulin
`` `` `` `` `` interfering with the coagulation cascade
`` `` `` limit the hemostatic process to
`` `` `` `` the site of injury

Front 103

Endothelium

Endothelial cells modulate

Back 103

several
`` `` anticoagulant and
`` `` procoagulant
`` aspects of
`` `` normal hemostasis

Front 104

Endothelium

The balance between

endothelial antithrombotic

and

prothrombotic activities

determines

Back 104

whether
`` `` thrombus formation,
`` `` propagation, or
`` `` dissolution
occurs

Front 105

Endothelium

intact endothelial cells serve primarily

Back 105

to inhibit
`` platelet adherence and
`` blood clotting

Front 106

Endothelium

injured or activated endothelial cells

Back 106

augment local clot formation

Front 107

Endothelium

the normal flow of liquid blood is maintained by

Back 107

endothelial
`` antiplatelet,
`` anticoagulant, and
`` fibrinolytic
properties

Front 108

Endothelium

Antiplatelet effects:

Back 108

An intact endothelium prevents
`` `` platelets and
`` `` plasma coagulation factors from
`` meeting the highly thrombogenic
`` `` subendothelial ECM

Non-activated platelets do not
`` adhere to the endothelium,
`` a property intrinsic to
`` `` endothelial plasma membrane

Moreover, even if platelets are activated after focal endothelial injury,
`` they are inhibited from adhering to
`` the surrounding uninjured endothelium by
`` `` endothelial prostacyclin
`` `` `` (PGI2)
`` `` and nitric oxide

Both mediators are potent
`` `` vasodilators and
`` `` inhibitors of platelet aggregation

Endothelial cells also express
`` `` adenosine diphosphatase,
`` which degrades ADP and
`` `` thereby contributes to the inhibition of
`` `` platelet aggregation

Front 109

Endothelium

Anticoagulant effects: 3

Back 109

The heparin-like molecules interact with
`` antithrombin III to
`` `` inactivate thrombin and
`` `` factor Xa

Thrombomodulin binds to
`` `` thrombin, converting it
`` `` from a procoagulant to an
`` `` anticoagulant capable of
`` `` activating protein C
`` Activated protein C, in turn,
`` `` inhibits clotting by
`` `` proteolytic cleavage of factors
`` `` Va and
`` `` VIIIa.

Endothelium synthesizes
`` tissue factor inhibitor

Front 110

Endothelium

Fibrinolytic effects:

Back 110

Endothelium synthesizes
`` tissue-type plasminogen activator
`` `` (t-PA)
`` t-PA converts
`` plasminogen into
`` plasmin, which lyses
`` `` fibrin,
`` promoting
`` `` fibrinolysis and
`` `` clearance of fibrin deposits from
`` `` endothelial surfaces

Front 111

Endothelial procoagulant properties

3

Back 111

hemodynamic factors, plasma mediators and cytokines are
`` exhibited after endothelial injury or
`` activation by infectious agents

Platelet effects:

Procoagulant effects:

Antifibrinolytic effects:

Front 112

Endothelial procoagulant properties

Platelet effects:

Back 112

Endothelial injury leads to
`` exposure of the underlying extracellular matrix to which
`` platelets attach via
`` `` von Willebrand factor (vWF)
`` `` produced by
`` `` `` normal endothelium and
`` `` `` megakaryocytes

Front 113

Endothelial procoagulant properties

Procoagulant effects:

Back 113

Activated endothelium synthesizes
`` tissue factor, which
`` activates the extrinsic clotting cascade

Front 114

Endothelial procoagulant Properties

Antifibrinolytic effects:

Back 114

Endothelial cells also secrete
`` inhibitors of plasminogen activator (PAIs),
`` which depress fibrinolysis

Front 115

Platelets

Mammals vs Lower Verts

Back 115

Mammals have platelets
`` (without nuclei),

whereas lower vertebrates have thrombocytes
`` (with nuclei)

Front 116

Platelets

After vascular injury, platelets 4

Back 116

adhere to ECM
`` `` (collagen) and
`` undergo three general reactions:

adhesion and shape change,

secretion
`` (release reaction), and

aggregation

Front 117

Platelets

Platelet adhesion to extracellular matrix is mediated

Back 117

largely via interactions with vWF,
`` which acts as a bridge between
`` `` platelet surface receptors
`` `` `` (glycoprotein Ib – GpIb)
`` `` and
`` `` exposed collagen

During this process platelets
`` change their shape from
`` `` disk-like to
`` `` sphere-like

Front 118

Platelets

Platelets secrete after adhesion

Back 118

content of α granules
`` containing
`` `` fibrinogen,
`` `` factors
`` `` `` V and
`` `` `` VIII,
`` `` TGF-β and
`` `` on membrane P-selectin

content of δ granules granules (dense bodies)
`` containing
`` `` ADP,
`` `` Ca,
`` `` histamine,
`` `` serotonin

Front 119

Platelets

The release of the δ granules contents is very important because 2

Back 119

calcium is required in the
`` coagulation cascade,

ADP is a potent mediator of
`` platelet aggregation

Front 120

Platelets

Platelet activation also leads to

Back 120

surface expression of
`` phospholipid complexes `` providing the necessary
`` binding sites for
`` calcium and
`` coagulation factors

Front 121

Platelets

Thromboxane A2 (TxA2) secreted by platelets

and

ADP released from δ granules

stimulate

Back 121

platelet aggregation
`` resulting in
`` `` the primary hemostatic plug.

This primary aggregation is reversible.

It is followed by generation of
`` `` thrombin and
`` `` deposition of fibrin
`` that binds aggregated platelets resulting in
`` irreversible secondary hemostatic plug.

Front 122

Platelets

Both erythrocytes and leukocytes are also found in

Back 122

hemostatic plugs

Front 123

Platelets

leukocytes adhere to 2

Back 123

platelets
`` via the adhesion molecule
`` `` P-selectin

endothelium
`` using a number of
`` `` adhesion receptors

Front 124

Clinical points:

Thrombin is central in the

Back 124

formation of thrombi

and, as such,

is a major target for
`` therapeutic modulation of the thrombotic process
`` `` (e.g. heparin therapy)

Front 125

Clinical points:

The endothelium-derived PGI2 is a potent

Back 125

vasodilator and
`` inhibits platelet aggregation

Front 126

Clinical points:

platelet-derived TxA2 is a potent

Back 126

vasoconstrictor and
`` activates platelet aggregation

Front 127

Clinical points:

Balanced interaction between

PGI2

and

TxA2

is necessary for 2

Back 127

prevention of intravascular platelet aggregation
`` under normal conditions

formation of hemostatic plugs after
`` endothelial injury

Front 128

Clinical points:

The clinical utility of aspirin

in patients at risk for coronary thrombosis

is largely due to

Back 128

ability of aspirin to
`` block TxA2 synthesis by
`` irreversible inactivation of
`` cyclooxygenase pathway of
`` arachidonic acid metabolism in
`` platelets

Front 129

Coagulation cascade

2 Point Answer

Back 129

The coagulation cascade constitutes
`` the third component of the hemostatic process

is a major contributor to
`` thrombosis

The coagulation cascade is a
`` series of enzymatic conversions,
`` `` turning inactive proenzymes
`` `` into activated enzymes and
`` culminating in the formation of
`` thrombin

Thrombin then converts the
`` soluble plasma fibrinogen into
`` the insoluble fibrin

Front 130

Coagulation cascade

Traditionally, the blood coagulation scheme has been divided into

Back 130

extrinsic and intrinsic pathways,

converging where
`` factor X is activated

However, there is
`` interconnection and
`` overlap between
`` these pathways
`` `` in vivo

Front 131

Coagulation cascade

The intrinsic pathway may be initiated in vitro by

Back 131

activation of Hageman factor
`` (factor XII)

PTT test –
`` activated partial thromboplastin time –
`` intrinsic coagulation time

Front 132

Coagulation cascade

extrinsic pathway is activated by

Back 132

tissue factor

PT test –
`` one-stage prothrombin time -
`` extrinsic coagulation time)

Front 133

Coagulation cascade

Once activated, the coagulation cascade must be

Back 133

restricted to the local site of vascular injury to
`` prevent clotting of the
`` `` entire vascular tree

Front 134

Coagulation cascade

Clotting is also regulated by three types of natural anticoagulants

Back 134

Antithrombin III

Proteins C and S

Tissue Factor Pathway Inhibitor

Front 135

Coagulation cascade

Antithrombin III

Back 135

inhibits the activity of thrombin

Antithrombin III is activated by
`` binding to heparin-like molecules on
`` `` endothelial cells;

hence the clinical usefulness of administering
`` `` heparin
`` to minimize thrombosis

Front 136

Coagulation cascade

Proteins C and S

Back 136

inactivate factors
`` `` Va and
`` `` VIIIa

protein C is activated by
`` thrombomodulin

Front 137

Coagulation cascade

Tissue factor pathway inhibitor

Back 137

protein secreted by endothelium

inactivates
`` `` tissue factor and
`` `` factor Xa
`` and rapidly limits
`` `` coagulation

Front 138

Coagulation cascade

fibrinolytic cascade

Back 138

is initiated to
`` limit the size of the final clot

This is primarily accomplished by
`` the generation of
`` `` plasmin
`` `` `` from enzymatic breakdown of
`` `` `` `` plasminogen induced by
`` `` `` `` `` plasminogen activators
`` `` `` `` `` `` (tissue plasminogen activator [t-PA] is most important)

Plasmin breaks down
`` `` fibrin
`` `` and interferes with its
`` `` `` polymerization (

The resulting fibrin split products
`` `` FSPs or
`` `` so-called fibrin degradation products
`` can also act as weak anticoagulants

Any free plasmin rapidly complexes to
`` α2-plasmin inhibitor and
`` is inactivated

Front 139

Coagululation Cascade

Elevated levels of FSPs determined by clinical laboratory test are helpful

Back 139

in diagnosing intravascular thrombosis
`` (e.g. DIC)

Front 140

Coagululation Cascade

Endothelial cells further modulate

the

coagulation/anticoagulation

balance by

Back 140

releasing plasminogen activator inhibitors
`` (PAIs)

these block fibrinolysis by
`` inhibiting t-PA

Front 141

Common inherited bleeding disorders

von Willebrand’s Disease

Back 141

Inherited abnormalities in vWF results in
`` variable degree of dysfunction of platelets,

therefore clinical signs may range from
`` spontaneous petechiation to
`` increased incidence and severity of hemorrhages
`` `` due to trauma
`` `` with prolonged bleeding


Diagnosis:

CBC: normal number of platelets

BMBT: prolonged; PT normal;

PTT: usually normal.

Decreased concentration of vWF
`` `` (determined by ELISA) and/or
`` `` altered multimeric structure

Front 142

Common inherited bleeding disorders

Hemophilia

Back 142

Inherited factor
`` VIII
`` `` Hemophilia A
`` `` `` more common
`` and factor IX
`` `` Hemophilia B
`` deficiency

observed usually in
`` young male animals with
```` suffusive hemorrhages,
`` `` hematomas and
`` `` bleeding in body cavities
`` after trauma

Prolonged bleeding after
`` surgery or
`` injury

Diagnosis:

`` History

`` CBC – normal number of platelets

``BMBT: normal, PT: normal;

`` PTT: prolonged

Front 143

Common acquired bleeding disorders

Thrombocytopenia

Back 143

Markedly decreased platelet number in blood can result in
`` spontaneous
`` `` petechial dermal,
`` `` mucosal and
`` `` serosal
`` hemorrhages or
`` suffusive hemorrhages,
`` hematomas and
`` bleeding in body cavities
`` following injury

Most common causes of thrombocytopenia are
`` due to decreased production
`` `` (e.g. bone marrow disorders)
`` or increased destruction of platelets
`` `` immune mediated thrombocytopenia or
`` `` infections
`` `` [Ehrlichia platys]

Diagnosis:

History

CBC – low number of platelets

BMBT: prolonged; PT normal;

PTT: normal

Front 144

Common acquired bleeding disorders

Dicumarol and moldy sweet clover toxicity

Back 144

Dicumarol is
`` vitamin K antagonist and
`` interferes with carboxylation of glutamate residues of
`` `` intrinsic (IX),
`` `` extrinsic (VII) and
`` `` common (X and II)
`` coagulation factors resulting in
`` wide spread potentially fatal hemorrhages

Diagnosis:

History

CBC – normal number of
platelets

BMBT: normal, PT: prolonged;

PTT: prolonged

Front 145

Common acquired bleeding disorders

Endothelial injury

Back 145

Septicemia/endotoxemia

Bacterial endothelial injury
`` (e.g. Haemophilus somnus)

Viral endothelial injury
`` hog cholera,
`` bluetongue and
`` epizootic hemorrhagic disease of deer

Front 146

Diagnosing bleeding disorders

Clinical history 2

Back 146

Unexplained hemorrhages in soft tissues or body cavities

Excessive or prolonged bleeding even after minor injuries

Front 147

Diagnosing bleeding disorders

Common in vitro diagnostic tests for blood coagulation

4

Back 147

PTT

PT

BMBT

TBT


















BMBT
Buccal mucosal bleeding time – measures ability of platelets to plug a minute wound. BMBT is prolonged in patients with severe acquired or inherited platelet dysfunction or severe von Willebrand disease.




Toenail bleeding time - measures ability of both platelets and coagulation factors to stop hemorrhage. It is increased in patients with acquired or inherited platelet dysfunction, coagulation factor deficiency, severe von Willebrand disease, or the hemorrhagic phase of DIC

Front 148

Common in vitro diagnostic tests for blood coagulation

PTT

Back 148

activated partial thromboplastin time –
` intrinsic coagulation time

Front 149

Common in vitro diagnostic tests for blood coagulation

PT

Back 149

one-stage prothrombin time -
`` extrinsic coagulation time

Front 150

Common in vitro diagnostic tests for blood coagulation

BMBT

Back 150

Buccal mucosal bleeding time –

measures ability of
`` platelets to
`` `` plug a minute wound

BMBT is prolonged in patients with
`` `` severe acquired or
`` `` inherited
`` platelet dysfunction
`` or severe von Willebrand disease

Front 151

Common in vitro diagnostic tests for blood coagulation

TBT

Back 151

Toenail bleeding time -

measures ability of both
`` `` platelets and
`` `` coagulation factors
`` to stop hemorrhage

It is increased in patients with
`` `` acquired or
`` `` inherited
`` platelet dysfunction,
`` coagulation factor deficiency,
`` severe von Willebrand disease, or
`` the hemorrhagic phase of DIC

Front 152

Thrombosis

The endothelium-covered vascular surface

is the

Back 152

largest and most active surface in the body

Front 153

Thrombosis

Small endothelial injuries

due to various causes

are most likely

Back 153

numerous and ongoing and in
`` great majority of cases
`` heal without any consequences
`` for the overall health of the host

This is achieved by marvelous
`` `` efficiency and
`` `` preciseness of
`` a “biological masterpiece”,
`` normal hemostasis,
`` constantly balancing the delicate equilibrium between
`` `` fluid and
`` `` solid state of
`` blood/plasma

Front 154

Thrombosis

thrombi and thromboemboli are the most common

Back 154

“mass murderers” of
`` people in the western world

Fortunately, this is
`` not the case in
`` `` veterinary medicine

Front 155

Thrombosis

In human patients, the common degenerative vascular diseases

Back 155

(e.g. atherosclerosis, hypertension)

are associated with
`` large vessel thrombosis and,
`` subsequently, often with
`` fatal thromboembolism

Front 156

Thrombosis

Degenerative vascular diseases in domestic animals

Back 156

are not very common in domestic animals;

Front 157

Thrombosis

in veterinary medicine,

thrombosis

is most commonly encountered in

Back 157

the heart
`` `` mural or
`` `` valvular vegetative endocardatis

or in small vessels
`` disseminated intravascular coagulation

Front 158

Thrombosis

Pathogenesis

The three major determinants in the pathogenesis of

thrombosis

are grouped in

Back 158

the so-called Virchow’s triad:

endothelial injury

stasis or turbulence of blood flow

blood hypercoagulability

Front 159

Thrombosis

Pathogenesis

The elements of Virchow's triad may act

Back 159

independently

or

may combine

to cause
`` thrombus formation

Front 160

Thrombosis

Pathogenesis

Endothelial injury is the single most important factor

Back 160

which, by itself,
`` can lead to thrombosis

It is particularly important for
`` thrombus formation occurring
`` `` in the heart or
`` `` in the arterial circulation,
`` where
`` `` the normally high flow rates might
`` `` otherwise hamper clotting by
`` `` `` preventing
`` `` `` `` platelet adhesion or
`` `` `` `` by diluting coagulation factors

Front 161

Thrombosis

Pathogenesis

Clearly, physical loss of endothelium will lead to 4

Back 161

exposure of subendothelial ECM,

adhesion of platelets,

release of tissue factor,

local depletion of
`` PGI2 and
`` PAs

Front 162

Thrombosis

Pathogenesis

it is important to note that endothelium

need not be

Back 162

denuded or physically disrupted to
`` contribute to the development of thrombosis;

any imbalance between
`` `` the pro- and
`` `` antithrombotic effects of endothelium
`` can influence local clotting events
`` `` turbulent flow,
`` `` LPS

Front 163

Thrombosis

Pathogenesis

Alterations in normal blood flow 4

Back 163

i.e.
`` stasis and
`` turbulence

disrupt laminar flow and
`` bring platelets into contact with the endothelium

prevent dilution of activated clotting factors by
`` fresh flowing blood

retard the inflow of
`` clotting factor inhibitors and
`` permit the build-up of thrombi

promote endothelial cell activation,
`` predisposing to
`` `` local thrombosis and
`` `` leukocyte adhesion

Front 164

Thrombosis

Pathogenesis

Hypercoagulability includes

Back 164

wide range of pathophysiologic disturbances of
`` equilibrium between
`` `` pro- and
`` `` anti-coagulant
`` resulting in increased predisposition to
`` coagulation such as
`` `` in late pregnancy in primates
`` `` `` high concentration of factor
`` `` `` `` I,
`` `` `` `` VII,
`` `` `` `` VIII
`` `` `` `` and X
`` protein-losing nephropathy in dogs
`` `` (loss of antithrombin III),
`` uremia,
`` disseminated neoplastic metastasis,
`` widespread damage
`` `` trauma,
`` `` extensive surgery,
`` `` burns
`` etc

Front 165

Thrombosis

Morphologic characteristics

Thrombi forming

in a rapidly flowing arterial bloodstream

Back 165

arterial thrombi are
`` different from
`` thrombi formed in
`` `` sluggish venous vessels

Front 166

Thrombosis

Morphologic characteristics

Arterial thrombi

Back 166

are
`` `` relatively firm,
`` `` cohesive,
`` `` grey-white
``mixtures of
`` `` platelets,
`` `` fibrin
`` `` leucocytes and
`` ``very low number of erythrocytes
`` at the early stage of thrombus formation

The arterial
`` `` rapid blood flow and
`` `` high pressure
`` sweep away all but
`` `` most firmly attached
`` components of clotted plasma

platelets attached to ECM
`` via vWF
`` `` leucocytes attached to
`` `` `` platelets,
`` `` `` fibrin and
`` `` `` activated endothelium

Progressive deposition of firmly attached components
`` `` (propagation of the thrombus)
`` with incorporation of low number of
`` `` erythrocytes
`` gives laminar appearance to arterial thrombi
`` `` (lines of Zahn)

If the arterial thrombus is to become occlusive,
`` the blood follow after the site of thrombosis
`` becomes turbulent
`` ``initially and then
`` `` slower, allowing
`` `` `` higher number of erythrocytes to be
`` `` `` `` entrapped within the fibrin,

hence the end
`` ``(tail)
`` of the thrombus becomes
`` `` red and gelatinous,
`` versus
`` the head is
`` `` firm,
`` `` friable and
`` `` grey-white
`` `` `` (pale)

The tail may be suspended in
`` flowing blood
`` `` (not attached to vascular wall)
`` or broken-off segments of this part may become
`` the source of emboli

Front 167

Thrombosis

Morphologic characteristics

Venous thrombi

Back 167

are typically
`` `` soft,
`` `` gelatinous,
`` `` red,
`` because during formation of the thrombus
`` numerous
`` `` slowly moving
`` erythrocytes are entrapped within
`` `` mixture of
`` `` `` platelets and
`` `` `` fibrin

Venous thrombi must be
`` distinguished from postmortem clots
`` forming in all vessels
`` after death

Both are
`` `` soft,
`` `` red and
`` `` gelatinous,
`` but a genuine thrombus will be
`` `` attached to the vessel wall

The site of adhesion should have
`` some evidence of
`` `` endothelial roughening
`` `` or at least microscopic evidence of endothelial injury
`` and at least a small area of
`` `` the adjacent attached thrombus should have
`` `` `` increased amount of
`` `` `` `` fibrin and
`` `` `` `` platelets
`` `` `` manifested as grey-white-pink material

Front 168

Thrombosis

Morphologic characteristics

Vegetative valvular endocarditis

Back 168

is characterized by
`` thrombosis on the cardiac valves
`` secondary to endothelial injury
`` almost always superimposed by
`` `` bacterial attachment/colonization

therefore, it appears that both
`` `` endothelial injury and
`` `` bacteremia
`` are necessary

Macroscopic appearance of the valvular thrombi is
`` similar to “vegetation”,
`` `` hence name “vegetative”

They consist predominantly of
`` `` fibrin,
`` `` neutrophils,
`` `` platelets,
`` `` small number of erythrocytes and
`` `` almost invariably bacteria

Therefore valvular thrombi are
`` `` grey-yellow,
`` `` firm and
`` `` friable,
`` similar to arterial thrombi

Front 169

Thrombosis

Morphologic characteristics

Disseminated intravascular coagulation

Back 169

is a relatively common condition in
`` domestic animals
`` characterized by widespread formation of
`` `` microvascular thrombi,
`` most commonly seen as result of
`` `` septicemia/endotoxemia,
`` `` viral or
`` `` immunologic
`` injury to endothelium,
`` protein loosing-nephropathy
`` (loss of antithrombin III in urine),
`` uremia,
`` disseminated metastatic neoplasia ect

Widespread coagulation leads also to
`` initiation of fibrinolysis

Propagation of the both processes
`` `` thrombosis and
`` `` fibrinolysis
`` results in consumption of clotting factors,
`` hence the name
`` `` “consumptive coagulopathy”

Paradoxically, this initially
`` `` thrombotic disorder
`` evolves into a
`` bleeding disorder
`` `` (generalized petechial/ecchymotic hemorrhages)
`` due to consumptive coagulopathy

Fibrinolytic disintegration of microvascular thrombi continues
`` also after death and
`` if necropsy is not performed within
`` `` 3 hours after death,
`` they might not be found

Front 170

Thrombosis

Significance to the animal:

Back 170

Thrombosis of large vessels is
`` relatively rare in animals,
`` but when present they may cause
`` infarction of tissue supplied by
`` the affected vessels
`` `` if collateral circulation is not sufficient to
`` `` `` take over the blood
`` `` `` `` supply or
`` `` `` `` drainage
``and they may also be fatal source of
`` thromboemboli

Vegetative valvular endocarditis causes
`` `` intermittent pyrexia (fever),
`` `` cardiac murmurs,
`` `` lameness
`` `` `` (left-sided vegetative endocarditis),
`` `` dyspnea
`` `` `` (right-sided vegetative endocarditis)
`` and/or heart-failure,
`` and it is commonly fatal

DIC
`` `` localized or
`` `` generalized (systemic)
`` is always
`` `` significant clinical condition
`` that may have a fatal outcome

Front 171

Thrombosis

Significance to the diagnostician:

Back 171

Macroscopic or microscopic thrombosis is always
`` a very important finding and
`` it is a very valuable clue used for
`` determination of
`` `` pathogenesis and
`` `` etiology of
`` diseases

Front 172

Fate of thrombi

4

Back 172

A small, newly formed delicate thrombus has
`` an uphill battle to survive

The majority of such thrombi formed at the minute endothelial injury will be
`` resolved and the
`` injured endothelium regenerated

However, if this healing process does not happen
`` the thrombi undergo some combination of the following four events

Propogation

Embolization

Dissolution

Organization and Recanalization

Front 173

Fate of Thrombi

Propagation

Back 173

The thrombus may
`` `` accumulate more platelets and
`` `` fibrin
`` propagate
`` eventually leading to
`` `` vessel obstruction

Front 174

Fate of Thrombi

Embolization

Back 174

Thrombi may
`` `` dislodge and
`` `` travel to other sites
`` in the vasculature

Front 175

Fate of Thrombi

Dissolution

Back 175

Recent thrombi may be
`` removed by fibrinolytic activity,

whereas
`` `` extensive fibrin polymerization
`` in older thrombi is substantially
`` `` more resistant to
`` `` `` proteolysis, and
`` `` `` `` lysis is not effective

Clinical point in human medicine:
`` therapeutic infusions of fibrinolytic agents such as
`` `` t-PA (
`` `` `` for pulmonary thromboemboli or
`` `` `` coronary thrombosis
`` are likely to be effective
`` `` for only a short time after formation of thrombi

Front 176

Fate of Thrombi

Organization and recanalization

Back 176

Older thrombi
`` tend to become organized

This refers to the ingrowth of
`` `` angioblasts
`` `` `` (primordial endothelial cells)
`` `` and fibroblasts
`` into the fibrin-rich thrombus together with
`` `` neutrophils and
`` `` “cleaner” macrophages

Fibrin is replaced by
`` vascularized fibrous tissue,
`` the capillaries of which may
`` `` anastomose to create channels that
`` `` `` pass through the
`` `` `` `` previously occlusive thrombotic mass
`` `` `` `` `` (recanalization of the occlusive thrombus)

With time,
`` the progressive contraction of the fibrous tissue
`` pulls the occlusive thrombus
`` `` closer to the vessel wall and
`` `` allows endothelial cells to slide over it

This process may result in
`` incorporation of residual thrombotic tissue in
`` subendothelial layer of the thickened vascular wall

Front 177

Embolism

3 Point Answer

Back 177

An embolus is a detached
`` intravascular
`` `` solid
`` `` `` thrombi,
`` `` `` tumor cells,
`` `` `` bacteria)
`` `` liquid
`` `` `` fat,
`` `` or gaseous
`` `` `` air
`` mass that is carried by the blood
`` to a site
`` `` distant from
`` `` its point of origin
`` and occludes the
`` `` lumen of a vessel

If emboli represent some part of a dislodged thrombus
`` they are called thromboemboli

Inevitably,
`` emboli lodge in vessels too small to permit further passage,
`` resulting in
`` `` partial or
`` `` complete
`` vascular occlusion with
`` subsequent
`` `` ischemic necrosis
`` `` `` if there is no effective collateral circulatory supply

Front 178

Embolism

Valvular vegetative endocarditis

Back 178

Thromboembolism associated with valvular vegetative endocarditis causes
`` the familiar clinical syndrome of

left-sided vegetative endocarditis
`` `` `` intermittent pyrexia (fever),
`` `` `` cardiac murmurs,
`` `` `` shifting lameness,
`` `` `` renal infarction

right-sided vegetative endocarditis
`` `` `` dyspnea,
`` `` `` pulmonary thromboembolism

`` and/or heart-failure,

and it is commonly fatal

Front 179

Embolism

“Saddle thromboembolism”

Back 179

Cats with hypertrophic cardiomyopathy usually
`` have congestive heart failure
`` and 10 to 20% have
`` `` posterior paresis due to
`` `` `` thromboembolic occlusion
`` `` `` `` (“saddle thromboembolus”)
`` of the
`` `` terminal abdominal aorta
`` `` and iliac arteries

The mural left atrial thrombus forms due to
`` turbulence caused by
`` `` cardiomyopathy

Detachment of
`` `` left atrial thrombus and
`` `` occlusion of the distal abdominal aorta results in
`` `` `` very painful
`` `` `` instant
`` `` paresis/paralysis of the
`` `` `` hind legs with
`` `` `` absent or decreased pulse

The affected limbs will become
`` cold and
`` swollen

Front 180

Embolism

Strongylus vulgaris in foals

Back 180

Ingested larvae
`` penetrate the large intestinal wall
`` and migrate on or within the tunica intima
`` `` NB histology: tunica intima consists of
`` `` `` endothelium,
`` `` `` subendothelial connective tissue
`` `` `` and internal elastic membrane
`` along intestinal
`` `` arterioles and
`` `` arteries
`` towards cranial mesenteric root

Larval migration causes
`` `` vascular damage,
`` `` inflammation and
`` `` thrombosis

Occasionally detached thromboemboli
`` occlude downstream smaller intestinal arteries
`` and cause
`` `` local ischemia
`` resulting in intermittent colic episodes,
`` even though fatal incidents are
`` rare
`` `` most likely due to extensive collateral circulation

Effective anthelmintics
`` `` e.g. ivermectin
`` markedly diminished prevalence of S. vulgaris infection in horses

Front 181

Embolism

Caudal vena caval thrombosis

Back 181

Following damage of rumenal mucosal barrier
`` caused usually by grain overload in feedlot cattle,
`` bacteria gain access to
`` `` portal circulation
`` `` and localize in liver

Majority if not all of these bacteria are
`` killed by residual macrophages within liver

However, if hepatic phagocytic defense is overwhelmed,
`` `` focal bacterial proliferation,
`` `` necrosis and
`` `` eventual abscess formation occurs

Under stressful circumstances
`` `` which have negative effect on
`` `` `` specific and
`` `` `` innate
`` `` immunity,
`` a weakening of an abscess wall
`` `` located adjacent to vena cava caudalis
`` `` may gradually erode into the
`` `` `` venous wall
`` causing local thrombosis

Progression of this process will
`` lead to leakage of abscess content into
`` venous lumen resulting in
`` `` pulmonary arteriolar embolism
`` `` `` by pus consisting of
`` `` `` `` neutrophilic debris,
`` `` `` `` bacteria,
`` `` `` `` bacterial toxins etc

Depending on
`` `` the amount of abscess material showering the lungs,
`` the affected animal may
`` `` literally
drop dead,
`` `` may develop severe suppurative pneumonia
`` `` `` terminated by massive fatal pulmonary hemorrhage,
`` `` or may develop chronic pneumonia
`` `` `` with pulmonary abscessation

These abscesses,
`` `` if not controlled effectively by immune defenses,
`` may erode into major pulmonary vessels causing
`` `` fatal pulmonary hemorrhage

Front 182

Infarction

An infarct is what how and when for 5 points

Back 182

an area of ischemic necrosis in which
`` all components of the affected tissue
`` `` have undergone necrosis

It is caused by
`` occlusion of either
`` `` the arterial supply or
`` `` the venous drainage

While in human patients the great majority of infarcts are
`` `` secondary to arterial/arteriolar occlusions
`` `` (arterial infarcts)
`` by
`` `` thrombi or
`` `` thromboemboli

in veterinary patients venous infarcts are
`` relatively common and
`` they are caused by
`` `` occlusion of venous drainage in
`` `` `` various organ displacements
`` `` `` `` torsion,
`` `` `` `` volvulus

Infarcts may be
`` `` wedge-shaped or
`` `` irregular;
`` `` tan-pale,
`` `` red, or
`` `` green;
`` `` solid or
`` `` liquid;
`` may heal rapidly by
`` `` scarring or
`` `` by sloughing,
`` or may persist for relatively long time
`` `` as sequestra

This seemingly random array of variables is
`` quite easily explained,
`` `` when pathogenesis of infarction
`` `` in various tissues is
`` `` understood

Front 183

Determinants of infarction

Consequence and 4 Factors

Back 183

The consequences of a vascular occlusion can range from
`` no or minimal effect,
`` all the way up to death of a tissue
`` or even the individual animal via

Nature of the Vascular Supply

Vulnerability to Hypoxia

Oxygen Content of Blood

Rate of Development of Occulsion

Front 184

Determinants of infarction

Nature of the vascular supply

Back 184

The availability of an alternative blood supply is
`` the most important factor in determining whether
`` `` occlusion of a vessel will
`` `` `` cause damage.

Lungs, for example,
`` have a dual
`` `` pulmonary and
`` `` bronchial
`` artery blood supply;
`` thus, obstruction of a small pulmonary arteriole
`` `` does not cause infarction
`` `` `` in an otherwise healthy animal
`` `` `` with an intact bronchial circulation

Similarly, the liver,
`` with its dual
`` `` hepatic artery and
`` `` portal vein
`` circulation is relatively
`` `` insensitive to infarction

Intestinal blood supply has
`` a lot of
`` `` anastomoses and
`` `` collateral
`` blood supply;
`` consequently, infarction by intestinal arterial occlusion
`` `` is uncommon
`` `` `` (e.g. thromboemboli secondary to Strongylus vulgaris)

In contrast, renal circulation is
`` `` end-arterial,
`` and obstruction of such vessels generally causes
`` `` infarction

Front 185

Determinants of infarction

Vulnerability to hypoxia.

Back 185

The susceptibility of a tissue to hypoxia
`` influences the likelihood of infarction

Neurons undergo
`` `` irreversible damage
`` when deprived of their blood supply for
`` `` only 3 to 4 minutes

Myocardial cells,
`` `` although hardier than neurons,
`` are also quite sensitive
`` and die after only
`` `` 20 to 30 minutes of ischemia

In contrast, fibroblasts within myocardium remain
`` viable even after
`` `` many hours of ischemia

Front 186

Determinants of infarction

Oxygen content of blood

Back 186

The partial pressure of oxygen in blood
`` also determines the outcome of vascular occlusion

Partial flow obstruction of
`` a small vessel
`` `` in an
`` `` `` anemic or
`` `` `` cyanotic
`` `` patient might lead to
`` `` tissue infarction,
`` whereas it would be without effect
`` under conditions of normal oxygen tension

In this way, congestive heart failure,
`` with compromised
`` `` flow and
`` `` ventilation,
`` could cause infarction in the setting of
`` `` an otherwise inconsequential blockage

Front 187

Determinants of infarction

Rate of development of occlusion

Back 187

Slowly developing occlusions are
`` less likely to cause infarction because
`` they provide time for the
`` development of alternative perfusion pathways

Front 188

Infarction

Morphologic characteristics

Infarcts change in

Back 188

their appearance over time
`` in a relatively predictable fashion

Accordingly, these changes are useful
`` when clinician/diagnostician attempts to
`` determine the chronological sequence of
`` `` lesions and
`` `` disease
`` progression

Front 189

Infarction

Morphologic characteristics

Color

Color of an infarct depends mostly

Back 189

on its age and,
`` to lesser degree,
`` on its origin
`` `` arterial vs.
`` `` venous

Front 190

Infarction

Morphologic characteristics

Color

White-pale (anemic) infarcts occur

Back 190

with arterial occlusions in solid organs with
`` end-arterial circulation
`` `` such as
`` `` `` heart and
`` `` `` kidney

Initially, infarcted area will be
`` `` pale and
`` `` swollen
`` due to
`` `` cellular necrosis
`` and due to
`` `` increased local pressure
`` `` `` secondary to cellular swelling in a solid tissue
`` that temporarily prevents
`` `` seepage of the blood into infarcted tissue
`` `` from the adjacent tissue

During this time, the margins of infarcts are
`` `` red
`` due to
`` `` hyperemia
`` and due to
`` `` hemorrhage from
`` `` `` necrotic vessels at the junction of the viable tissue

Inside the red margins,
`` a white line may develop
`` `` within 1-2 days,
`` which represents
`` `` neutrophils attracted by
`` `` `` dead tissue

Subsequently, infarcted tissue undergoes
`` liquefaction mediated by
`` `` lysosomal degrading enzymes
`` as well as by
`` `` infiltrated neutrophils

This process
`` decreases local pressure within infarcted tissue
`` and blood seeps in from the
`` `` vasculature of the adjacent tissue
`` `` or through the site of initial arterial occlusion,
`` `` `` if obstruction was
`` `` `` `` not complete or
`` `` `` `` not permanent

Consequently, initially pale infarct becomes
`` red

Front 191

Infarction

Morphologic characteristics

Color

Red (hemorrhagic) infarcts

5 Ways

Back 191

Initially pale infarcts that became red (see anemic ifarcts)

Venous occlusions –
`` venous infarcts
`` `` intestinal torsion,
`` `` strangulation

Infarcts in tissues with
`` dual circulations
`` `` lung and
`` `` liver
`` permitting flow of blood from the
`` `` unobstructed vessel into
`` `` `` the necrotic zone
`` provided such perfusion is
`` `` not sufficient to rescue the
`` `` `` ischemic tissues

Infarcts in loose tissues
`` ``such as lungs:
``the swelling of the dead cells usually is
`` `` insufficient to create turgidity
`` `` `` increased pressure
`` `` that prevents seepage of blood from
`` `` `` the adjacent tissue

Reperfusion of infarcts will
`` result in red discoloration of
`` `` affected tissues
`` Reperfusion injury occurs when
`` `` blood flow is re-established to
`` `` `` a site of
`` `` `` `` previous arterial occlusion
`` `` `` `` and necrosis
`` In this paradoxical situation in which
`` `` the restoration of blood flow
`` `` after a period of ischemia actually
`` `` accelerates rather than reverses
`` `` the cell injury
``It should be emphasized that restoration of blood flow
`` `` after a brief period of ischemia
`` is most likely to reverse the injury process,
`` allowing restoration of
`` `` normal cell
`` `` `` structure and
`` `` `` function
`` A prolonged period of complete ischemia will
`` `` result in irreversible cell injury and death
`` Ischemic periods of moderate duration
`` `` (poorly defined period and probably variable for different tissues)
`` followed by re-establishment of blood flow
`` may result in reperfusion injury

Front 192

Infarction

Morphologic characteristics

Shape

Back 192

In organs
`` `` kidney,
`` `` lung
`` that have dichotomous branching pattern of blood vessels,
`` infarcts tend to be
`` `` wedge-shaped,
`` `` with the occluded vessel at the
`` `` `` apex
`` `` and the periphery of the organ
`` `` `` forming the base

Cardiac vessels
`` do not have this uniform branching pattern;
`` therefore, myocardial infarcts tend
`` `` to be irregular

Front 193

Infarction

Morphologic characteristics

Histology:

Back 193

The dominant microscopic characteristic of infarction is
`` ischemic coagulative necrosis

The brain is an exception,
`` ischemic injury in the central nervous system results in
`` `` liquefactive necrosis
`` `` `` termed malacia

Front 194

Infarction

Outcome

4

Back 194

Inflammatory Response

Scarring

Sloughing

Sequesteration

Front 195

Infarction

Outcome

An inflammatory response

Back 195

begins to develop
`` along the margins of infarcts within
`` `` a few hours
`` and is usually well defined within
`` `` 1 or 2 days

Inflammation at these sites is
`` incited by the
`` `` necrotic material;
`` given sufficient time, there is
`` `` gradual degradation of the dead tissue through
`` `` `` phagocytosis of the cellular debris by
`` `` `` `` neutrophils and
`` `` `` `` macrophages

Eventually the inflammatory response is
`` followed by a reparative response beginning
`` in the preserved margins
`` characterized by ingrowth of
`` `` angioblasts and
`` `` fibroblasts

Front 196

Infarction

Outcome

Scarring is the

Back 196

normal outcome of infarction because,
`` by definition,
`` `` all constituents of the tissue are
`` `` `` dead
`` `` and thus there is no
`` `` `` scaffolding or
`` `` `` germinal cells
`` `` necessary for regeneration

Front 197

Infarction

Outcome

Sloughing of infarcted tissue is

Back 197

occasionally seen in some organs
`` `` renal medulla,
`` `` intestinal mucosa,
`` `` skin-extremities

In some of these cases,
`` scarring might be limited

Front 198

Infarction

Outcome

Sequestration of the infarcted tissue occurs

Back 198

occasionally in some organs

Sequestrum is a focus of
`` coagulation necrosis that
`` fails to undergo
`` `` liquefaction/debriment for
`` `` `` prolonged period

Front 199

Infarction

Significance to the animal:

Back 199

Depends on size and location of infarct

Front 200

Infarction

Significance to the diagnostician:

Back 200

Infarcts are
`` always important findings
`` and they provide valuable clues about
`` the nature of underlying disease process

Front 201

Infarction

Intestinal accidents

Back 201

Intestinal accidents
`` `` (most common in horses)
`` are by far the most common
`` `` fatal infarcts seen in domestic animals

Intestinal
`` `` torsion,
`` `` intussusception or
`` `` strangulation
`` obstructs
`` `` venous flow first and
`` `` then arterial flow;

consequently, the affected intestines are
`` edematous
`` `` (increased hydrostatic pressure),
`` dark red-purple
`` `` congestion –
`` ``` `` obstructed venous outflow;
`` `` followed by
`` `` `` hemorrage
`` and subsequently friable
`` `` ischemic necrosis –
`` `` `` venous infarction

Front 202

Infarction

Renal infarcts

Back 202

Renal cortical infarction due to
`` `` arcuate artery obstruction
`` is relatively common in animals

They are
`` rarely functionally significant,
`` `` because of large renal reserve

Scarred cortical areas due to infarction are
`` relatively common in
`` `` older dogs

If
`` `` acute or
`` `` subacute
`` renal infarcts are found in dead animals
`` `` they are often caused by
`` `` `` thromboembolism originating from the
`` `` `` `` left-sided vegetative valvular endocarditis

Renal medullary infarction is
`` a relatively rare event
`` except when associated with the
`` `` injudicious use of non-steroidal anti-inflammatory drugs
`` `` `` in severely dehydrated and
`` `` `` hypotensive animals
`` `` (especially horses)

Front 203

Infarction

Infarction of the distal extremities

Back 203

ear and tail tips, distal extremities
`` occurs relatively frequently under several different circumstances:

septicemia
`` `` due to DIC and/or
`` `` hypoperfusion)

toxic injure to vasculature
`` ergot
`` `` ingestion of grain/seeds
`` `` infected by Claviceps purpurea
`` `` producing ergotamin,
`` which causes
`` `` vascular damage and
`` `` infarction of
`` `` `` distal extremities and
`` `` `` tail

frostbite

Front 204

Infarction

Infarction of the distal extremities

Back 204

ear and tail tips, distal extremities
`` occurs relatively frequently under several different circumstances:

septicemia
`` `` due to DIC and/or
`` `` hypoperfusion)

toxic injure to vasculature
`` ergot
`` `` ingestion of grain/seeds
`` `` infected by Claviceps purpurea
`` `` producing ergotamin,
`` which causes
`` `` vascular damage and
`` `` infarction of
`` `` `` distal extremities and
`` `` `` tail

frostbite