DISTURBANCES OF CIRCULATION (Homodynamic Disorder)

Coagulation: Blood coagulation involves a sequence of events that converts culminating

in the formation of thrombin and its conversion of soluble fibrinogen to insoluble fibrin.
This conversion is accelerated by the presence of ca++ and heat labile accelerator.

Dissolution of clots: There are endothelial factor and some enzymes that prevent or
inhibit the coagulation mechanism. In addition to the endothelial factors that prevent
coagulation by inhibiting platelet aggregation, a system known as “fibrinolytic system”
causes dissolution of clot. This is effected by the fibrinolytic protease, plasmin. Plasmin
is formed from its precursor “plasminogen” which circulates in the plasma. This
conversion requires tissue plasminogen activator (TPA) or urokinase.

Thrombosis: It is the pathologic formation of clot called thrombus within the

cardiovascular system. Depending on their location and size, thrombi may lead to serious
impairment with the blood circulation resulting in infarct or passive congestion and may
give rise of emboli as well as may act as a favorable site for bacterial growth.

Causes of thrombosis/antemortem clot: There are three principles of thrombosis

I. Endothelial injury
II. Disruption in regular flow of blood
III. Hypercoagulability

I. Endothelial injury: Endothelial cells may be injured through trauma, toxaemias,

metabolic disorder, inflammatory disease caused by virus and bacteria or immunologic
reaction. Injury caused by the parasite Strongylus vulgaris larva causes thrombosis in
anterior mesenteric artery in horse and Dirofilaria immitis may cause thrombosis in
pulmonary artery in dog. Different causes of endocarditis (uremia and bacteremia) may
cause thrombosis in endocardium and heart valves.

II. Disruption in normal flow of blood: Such disorders may cause turbulence in the
arterial circulation or stasis in the venous circulation and disrupt the normal laminar flow
and bring platelet in contact with endothelial cells encouraging coagulation.

III. Hypercoagulability of blood: This is due to either increased level of activated

clotting factor or decreased level of inhibitor factor found in endothelium. A hereditary
deficiency of antithrombin-III is detected in human in association with
hypercoagulability of blood. In dogs, deficiency of antithrombin has been found in
association with glomerular disease and liver disease.

Gross appearance of thrombus: Thrombus within heart or arteries appears as a friable

mass with a dull, irregularly roughened or somewhat stringy surface. The color is
mixture of red and gray, usually in irregular layers or lamination (line of Zahn). The
thrombus remains attached to the vascular wall. The arterial thrombi are often referred to
on gray thrombi.

The venous thrombi are usually red often have a shiny surface, closely resembling
a postmortem clot.
 If a thrombus totally obstructs the lumen, it is termed occlusive or occluding
thrombus.
A thrombus with a free end trailing downstream is termed obturating thrombus.
The thrombus formed in the heart is called mural thrombi when on the wall and
vegetative thrombi when on the valves.
Microscopic features of thrombi: Arterial thrombi are composed of alternating zones
of homogenous platelets and fibrin mixed with varying numbers of erythrocytes and
leukocytes. These often appear as regular lamination but more often are rather
disorganized. Venous thrombi contain larger number of erythrocytes admixed with fibrin
and zone of platelets are usually not apparent.

Outcome of thrombi: Thrombi may be removed through fibrinolytic activity but more
usually are organized. Through dissolution by the action of leukocytes and their gradual
replacement by fibrovascular connective tissue blood channel may develop within the
organized thrombi, some of which may restore circulation and in this case the thrombus
in called “canalized” thrombus.

Differentiation from postmortem clot: The postmortem clots are dark red, smooth and
shiny on outside and molded to the vessel in which they formed, like jelly in a container.
They are of uniform texture and unattached to the vessel wall. Because of these
characteristics they are sometime called currant-jelly clot. Settling and separation of red
cells from the fluid phase of the blood before coagulation results in chicken fat clot. This
type of postmortem clot is often found in chambers of heart. Microscopically,
postmortem clot is composed of RBC, WBC and fine strands of fibrin in contrast to
coarse strands of fibrin of thrombi.

Emboli: Foreign bodies floating in the circulation is termed as emboli.

e.g. I. Thromboemboli / fibrin emboli (most important)

II. Fat emboli
III. Gas emboli
IV. Bacterial emboli
V. Parasitic emboli
VI. Neoplastic emboli

Short description:

Thromboemboli / fibrin emboli: The most common and important emboli are
thromboemboli i.e, pieces of thrombi that have broken loose. They are almost always
found lodged in an arterial bifurcation or in a place where the lumen of the artery
becomes too small to permit their passage. Thromboemboli arising from venous thrombi
most often lodge in the pulmonary arterial tree. They may cause pulmonary infarct or
right sided heart failure.

Fat emboli: Droplets of fat that have entered the circulation. They are not detected
grossly but are easily visible under microscope as a sharply defined clear vacuole of
various sizes lodged within the arteriole or capillaries. Fracture of bone is the most
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common cause of fat embolism. The mechanical trauma frees fat from marrow’s adipose
tissue or subcutaneous tissue and occasionally from severe metabolic disease like
diabetes mellitus. Excessive fat emboli can be fatal because of interference with
pulmonary circulation causing unexpected death rapidly after a traumatic incident.

Gas emboli: Most commonly air causes bubbles in the blood that may obstruct the flow
of blood resulting in infarct. In human, gas emboli is seen following rapid change in
atmospheric pressure i.e. in scuba and deep sea divers and in construction workers
emerging from under water compartments in which atmospheric pressure has been raised
to several times that of normal atmospheric pressure. When the atmospheric pressure
returns to normal, the gases dissolved under high pressure returns to their gaseous state
becoming gas emboli. Oxygen in the blood remains in solution or utilized but nitrogen or
helium does not. The result is termed decompression sickness, which occurs in acute
form known as bends and in a chronic form known as caisson’s disease. The bent is
characterized by acute pain originated from occlusion of vessels in the muscles and
joints, respiratory distress and coma/occlusion of pulmonary and cerebral vessel.

Bacterial emboli: Clumps of bacteria in the circulation.

Parasitic emboli: It may happen by fragments of parasite or whole parasite. e.g.

Dirofilaria immitis, Schistosoma nasalis
Neoplastic emboli: Are occasionally seen and must occur often in patients with cancer
during metastasis.
Spodogenous emboli: Arises from clumps of agglutinated red cells.
Failure to clot: A number of acquired and congenital disorders results in interference
with the normal coagulation process and are characterized by spontaneous hemorrhage or
excessive hemorrhage after injury.
Causes of failure to clot:
1. Inherited coagulation factor deficiency:

- Factor I (Fibrinogen) deficiency

- Factor II (Prothrombin) deficiency
- Factor VII (Proconvertin) deficiency
- Factor VIII deficiency (hemophilia A) – this is the classic hemophilia of historical
fame as the tragic affection of many male members of the European and Russian
royal families
- Factory IX deficiency (hemophilia B)-also known as Chrismas disease in several
breeds of dogs
- Factor X (stuartpower factor) deficiency
- Factor XI deficiency
- Factor XII (Hageman factor) deficiency

2. Disorders of thrombocytes: It could be due to defective function or decreased

number of platelets.

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A. Defective functions: May be caused by

a. Inherited: Defect in membrane glycoproteins preventing adhesion or aggregation

and defect in release of ADP and other platelet factors.
b. Acquired : Causes of thrombocyte defect
drug induced e.g.
 Aspirin
 Uremia
B. Thrombocytopenia: Decreased number of thrombocytes in the circulation due to
a. Increased destruction of platelet
b. Decreased production of platelet

a. Increased destruction

i. Autoimmune (idiopathic) thrombocytopenia (autoantibody)

ii. Isoimmune thrombocytopenia
iii. Drug induced thrombocytopenia
 Quinidine
 Thiazide diuretics
 Heparin
 Streptomycin, Penicillin, Sulphonamide

b. Decreased production of thrombocytes:

It is associated with generalized disease of bone marrow. This includes various causes of
aplastic and myelophthisic anemia as well as infectious disease and certain poisons and
drugs that have a predilection for destruction of bone marrow. In addition to this,
leukemia and lymphoma also cause decreased production by replacing bone marrow with
malignant cells. eg. Poison – Bracken fern causes severe hypoplasia of hemopoietic
tissue with thrombocytopenia.

Drug: chloramphenicol, streptomycin, estrogen, chlorothiazide, cyclophosphamide

(anticancer drug) and azothiaprine (cytotoxic and immunosuppresive).

3. Acquired coagulopathies:

The best known acquired coagulopathes is poisoning by vit-K antagonist. This is seen in
sweet clover poisoning which contain coumarin and in warfarin poisons of rodenticides.
Sulphaquinoxaline is another vit-K antagonist.

Hepatic disease may affect the production of many different coagulation factors that are
synthesized by hepatocytes. The most common factors are I, II, V, VII, IX, X, XI, XII &
XIII, protein C & S and plasminogen.

HAEMORRHAGE

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Hemorrhage is the escape of blood from a vessel, whether it be to the outside of the
body, into the body cavity or into adjacent tissues.

The ordinary rapid flow of blood through a break or cut in a vessel wall is called
"hemorrhage by rhexis". Considerable amount of blood may be lost by slow oozing of
fluid and the escape of blood cells one by one through minute or imperceptible
imperfection in the vessel wall. This is called "hemorrhage by diapedesis".

The hemorrhage that leaves dots of blood not much larger than the point of a pin is called
"petechiae". Slightly larger hemorrhages are called "purpura". Somewhat larger
hemorrhagic spots, about 1 cm in diameter, on the body surface or in the tissue is called
"ecchymoses". Haemorrhages in the tissue spread over considerable area is referred to as
"extravasation". Hemorrhage in the body cavity is referred to as hemothorax,
hemoperitoneum, hemopericardium etc.

When blood escapes into the tissues and produces a tumor like enlargement, it is called
hematoma.

Causes of hemorrhage:

All the factors that are associated with failure to clot are responsible with hemorrhage. In
addition to this, mechanical trauma, cutting or breaking of vessel, necrosis and
destruction of vessel walls as by an ulcer or spreading neoplasm, rupture of a vessel
weakened by an aneurysm or other degenerative disease of vessel wall may result in
hemorrhage. Several deficiency diseases such as vit-C deficiency or scurvy are
characterized by hemorrhage. Vit-K deficiency that is associated with synthesis of
several clotting factor is one of the most important cause of hemorrhage.

Certain infectious diseases such as anthrax, hepatitis, black leg, leptospirosis,

hemorrhagic septicemia are accompanied by moderate to severe hemorrhage.

Effect of hemorrhage:

Effect of hemorrhage depends on the amount of blood loss. The acute loss of excessive
blood may cause death. Other effects of hemorrhage are hypoxia and anoxia. Chronic
hemorrhage often leads to anemia.

Hyperemia and congestion:

Both the terms denote an excess of blood in the vessel of a given part. This occurs by one
of the following two/both ways.

I. Too much blood being brought in by the arteries with dilation of arteries and
arterioles.
II. Too little being drained by veins.

Active hyperemia: The increased volume of blood is of arterial origin. It is always

associated with inflammatory process. It may also follow exposure to heat either locally
or total body. It is mediated by vasoactive amines and neurogenic mechanism.

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Vasoactive amines- Histamine, Serotonin, Kinin

Gross appearance of active hyperemia:

The hyperemic part takes bright red color of arterial blood. The part is warmer than usual
and pulsating arteries which are not perceptible may be felt.

Microscopic appearance of hyperemia:

Microscopically, the arteries and capillaries are dilated and filled with blood. They also
appear to be more numerous.

Passive congestion:

This condition results from obstruction of venous return. Local passive congestion may
develop as a consequence of complete or partial obstruction of veins draining a part.
Force of centre of gravity is the cause of hypostatic congestion. Heart failure causes
more generalized passive congestion.

Gross appearance:

Grossly, the congested part is slightly swollen and tends to have a bluish-red tinge. The
part is usually wet than normal as a result of edema and if the congestion is chronic the
part may be firm due to fibrosis. The part is cool to touch.

Microscopic appearance:

Microscopically, the capillaries and veins are dilated and full of blood. The hypoxia
resulting from congestion leads to necrosis of parenchymal tissue, which is acute.
Cardiac failure may cause extensive centrilobular necrosis of liver. With chronic passive
congestion, loss of parenchymal tissue is evident. Fibrous connective tissue surrounds
the veins and replaces the lost parenchyma. This results in cirrhosis of liver and what is
termed "brown induration of lung" resulting from fibrosis of alveolar septa and presence
of heart failure cells.

OEDEMA

The old name of oedema in medical feature is dropsy.

Oedema is the excessive accumulation of fluid in the interstitium or into the body
cavities. Excessive fluid within the cell is called acute cellular swelling or hydropic
degeneration. Oedema may be inflammatory or non-inflammatory. Oedema of most
organs is generally termed oedema and the organ is termed oedematous. Extensive
oedema of subcutaneous tissue is termed anasarca, within body carvities, hydrothorax,
hydropericardium ascites, in the scrotum-hydrocoel and in the amniotic sac-hydrops
amnii. Certain diseases characterized by oedema have been given name such as "brisket
disease” -accumulation of fluid in the sternal region.

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Gross appearance of oedema:

Oedematous organ and tissues are swollen and wet and may ooze when cut. The fluid is
pale yellowish and may clot but usually it drips from the cut surface; if pressure is
applied, a much larger amount of fluid may be squeezed from the tissue. During life, the
oedematous part, if external, is cool. There is no redness and no sign of pain. The
affected tissues have a firm but drought consistency. “Pit on pressure" meaning that if a
finger is pressed into oedematous tissues, the fluid is dispersed into the nearby tissue
spaces. When finger is removed the pit remains for a moment or two.

Sometimes, oedema appears as a principal sign of many diseases such as the condition
called "bottle jaw" is found in sheep suffering from gastrointestinal parasitism.

Microscopic appearance of oedema

Microscopically, the spaces between adjacent cells, fibrils and other structures are
swollen. During life they were, of course, filled with fluid; in the microscopic section, a
faint, pink staining residue of precipitated albumin may or may not remain, depending on
the amount of protein in the oedema fluid. A few erythrocytes, leukocytes or fibrils of
fibrin may be present but any considerable number of the last two indicate inflammation.
Oedemas of long standing become organized by fibrous connective tissue.

Causes of oedema:

Oedema results from a disruption of the normal balance between the fluid compartment
of the blood, interstitium and lymphatics. Normally, there is a continuous flow of fluid
from the blood into the interstitium and then back to the blood stream. Fluid leaves the
blood stream at the arteriolar end of the microcirculation as a result of greater hydrostatic
pressure in the arterioles than in the interstitium. The force of hydrostatic pressure is
opposed by osmotic pressure from the plasma protein (chiefly albumin), however, the
hydrostatic pressure exceeds the osmotic force. At the venous side of the
microcirculation, the hydrostatic pressure has decreased such that most of the interstitial
fluid is drawn back into the blood stream. The fluid which does not re-enter the venules
is conveyed by lymphatics back to the blood stream.

Mechanisms of oedema

Disruption of normal fluid exchange mechanism leads of oedema. There are such four
mechanisms resulting in oedema.

i) Increased hydrostatic pressure

ii) Decreased plasma osmotic pressure
iii) Lymphatic obstruction
iv) Retention of sodium

Short description:

i) Increased hydrostatic pressure:

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This mechanism has its effects by increasing the flow of fluid from blood to the
interstitium and decreasing the flow from the interstitium back to the blood. The oedema
of passive congestion is caused by increased venular blood pressure and may be
localized or generalized. Localized oedema resulting from increased hydrostatic pressure
occurs when the flow of blood in veins is obstructed due to thrombosis, external
pressure, or disorders such as cirrhosis. Generalized oedema caused by increased
hydrostatic pressure results from impaired cardiac function leading to congestive heart
failure and cardiac oedema.

ii) Decreased plasmal osmotic pressure:

The mechanism results from hypoproteinemia, which lowers the osmotic force necessary
for movement of fluid from the interstitium into venule. Hypoproteinemia may result
from

a) Renal diseases characterized by proteinuria

b) Dietary protein deficiency (Nutritional oedema, cachectic oedema)
c) Decreased synthesis of plasma protein caused by liver disease
d) Loss of plasma protein caused by heavy infestation with intestinal parasites such a
Trichostrongyles
iii) Lymphatic obstruction:

This mechanism, which is similar to localized venous stasis, leads to lymphoedema.

Condition that place external pressure on veins also affect lymphatics. Brugia and
Wuchereria inhibit lymphatics causing obstruction and oedema in man and animal.
Congenital hereditary lymphoedema is rare disorder characterized by discontinuity or
absence of lymph vessels.

iv) Retention of sodium:

Failure to excrete sodium and its associated retention of water leads to generalized
oedema. This is seen is renal disorders in which there is increased reabsorption of
sodium as in glomerulonephritis.

Shock: It is the sudden agitation of mind or sudden over stimulation of nerves by sudden
pain.

Shock is the result of a relatively sudden generalized inability of the circulatory system
to perfuse cells and tissues with adequate oxygen and nutrients to meet metabolic
requirements. It is often defined as circulatory collapse and is characterized by marked
hypotension. If not corrected very early, the absence of oxygen and nutrients leads to
anaerobic metabolism, lactic acidosis, cellular and organic dysfunction, death of cell and
ultimately death of the patient.

Causes of shock:
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The causes of shock are any insults that dramatically reduce cardiac output or peripheral
resistance.

Classification of shock:

On the basis of cause, shock can be classified as

i) Hypovolumic shock
ii) Cardiogenic shock
iii) Septic (endotoxic) shock
iv) Neurogenic shock
v) Anaphylactic shock
(iii + iv + v) is called distributive shock

i) Hypovolumic shock: It results from large loss of fluid, eg. extensive haemorrhage,
vomiting, diarrhoea or severe burns.

ii) Cardiogenic shock: This results from inadequate cardiac systolic output caused by
primary cardiac disease.

iii) Septic (endotoxic) shock: Septic shock results from an infection, most usually with
gram negative bacteria such as strains of E. coli, Klebsiella, Pseudomonas species.

iv) Neurogenic shock: Results from severe trauma and pain.

v) Anaphylactic shock: Usually caused from antigen-antibody reaction (immediate

hypersensitivity reaction). In man, only IgE is able to produce anaphylactic reaction.
Anaphylactic phenomenon is caused by antigen-antibody reaction on the surface of the
mast cell activating a series of enzymes leading to the release of vasodilators (histamine,
serotonin, kinins, etc.) from the mast cells. The kinins cause increased permeability of
capillary and fall in blood pressure.

Lesions of shock:
Cellular degeneration and necrosis may be found in heart, kidney & liver. Congestion
may be found in lungs, heart, kidney, liver and GI tract. Similarly, haemorrhages are also
found in various locations.
NB: Brain haemorrhage is fatal and it is caused by

 hypotension
 Diabetes mellitus
 CVD - Coronary Valvular Disease
 IHD - Ischemic Heart Disease
 MI - Myocardial Infarction
 VS- Valvular Stenosis
 Milk leg: Oedema of leg during advanced pregnancy
 Eclampsia: Characterized by albuminuria and oedema due to hypostatic pressure.
 Causes of sudden death
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 Coronary heart disease (1st killer)
 Neoplasia/cancer (2nd killer)

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