General Considerations

Cardiovascular diseases are the commonest cause of death in Westernised communities. The main forms are:

The following general abnormalities of circulation are common to both.

Thrombosis

A thrombus is a mass formed from blood constituents within a vessel or the heart during life. Blood clotting is a physiological protective mechanism but thrombosis is a pathological process with serious consequences.

Mechanism of Formation

Factors Leading to Thrombosis

The 3 MAIN factors leading to thrombosis are known as Virchow’s triad:

1. Alterations of blood flow.

2. Damage to endothelium of vessel.

3. Changes in composition of the blood.

1. ALTERATIONS OF BLOOD FLOW

The main effect is to bring platelets into contact with the vessel wall. This results from: Slowing of blood flow, e.g. in cardiac failure or during bed rest. With slowing, the normal axial stream of blood cells is lost and white cells and platelets fall out of the main stream and accumulate in the peripheral plasma zone.

Turbulence, e.g. by deformation of vessel wall or around venous valves.

These changes in flow and shear stress cause altered endothelial function with increased production of agents which promote thrombosis (p.160).

3. CHANGES IN COMPOSITION of the BLOOD

(a) INCREASE in platelets, fibrinogen and prothrombin after operations and childbirth: usually after 5–10 days.

(b) INCREASE in platelet adhesiveness – again after surgery.

(c) Rare inherited abnormalities of thrombosis inhibitors – e.g. antithrombin III deficiency, protein C deficiency.

(d) Miscellaneous factors – e.g. oral contraceptives, smoking, some cancers.

Common Sites and Types of Thrombus

Arterial

Thrombi are common in arteries as a complication of atheroma. Forming in a rapid circulation, the thrombus consists mainly of platelets (white thrombus).

Common sites include:

Capillary

Thrombi, composed mainly of fused red cells, form when capillaries are damaged, usually in acute inflammatory processes.

Capillaries are occluded by fibrin thrombi in cases of disseminated intravascular coagulation (DIC – see p.414).

Cardiac

Thrombi may be seen in the atria (especially in the auricles in atrial fibrillation); in the ventricles and on the heart valves.

Sequels of Thrombosis

1. FIBRINOLYSIS

Many small thrombi are completely removed by the Fibrinolytic System which exists to limit thrombosis.

2. EMBOLISM

Part of the thrombus may be detached and carried along in the blood stream to impact in a distant vessel. This is extremely important clinically.

3. ORGANISATION

Capillaries grow into the point of thrombus attachment within a day or two. Fibroblasts and phagocytic cells accompany the capillaries, and gradually the thrombus material is dissolved and replaced by fibrovascular tissue. At the same time endothelium covers the ends of the thrombus, thus limiting the thrombotic process.

4. CALCIFICATION

In diseased vessels, organisation may not take place. The thrombus shrinks, calcium salts are deposited and convert it into a phlebolith – seen in X-rays.

5. INCORPORATION

A mural thrombus, e.g. in a large artery, may be covered by endothelium and incorporated in the vessel wall. This process may be important in the formation of atheroma.

PROPHYLAXIS and THERAPY of thrombosis aims at:

1. Reducing coagulability utilising (a) anticoagulants aimed at specific sites in the coagulation cascade, e.g. warfarin derivatives, heparin (see p.413) and (b) inhibiting specific prostaglandin synthesis, e.g. aspirin.

2. Encouraging fibrinolysis, using fibrinolysins.

Embolism

An embolus is any abnormal mass of matter carried in the blood stream and large enough to occlude some vessel.

The commonest emboli are derived from material generated within the vascular system, e.g. fragments of thrombus or material from atheromatous plaques.

1. Pulmonary thrombo-embolism

Emboli from the systemic veins (especially deep venous thrombosis, e.g. in the calf) pass through the right side of the heart to the pulmonary circulation. The consequences depend on the size of the embolus and the patient’s previous health.

(a) Massive embolus → blocks main pulmonary artery trunk → acute total circulatory block → SUDDEN DEATH.

(b) Moderate embolus

As the lungs have a double blood supply (pulmonary and bronchial arteries), and a vast anastomosis, obstruction of a pulmonary artery branch does not necessarily cause infarction. If, however, there is pre-existing cardiac failure, infarction may occur as the bronchial arterial blood flow is sluggish.

(c) Small emboli

Many are removed by the fibrinolytic system and are asymptomatic. However, repeated minor emboli may result in pulmonary hypertension and right heart failure. Repeated small emboli → blockage of peripheral pulmonary arterial branches → pulmonary hypertension.

2. Emboli of the arterial system are derived from the heart or the larger arteries which have become atheromatous. The results of arterial obstruction are very important.

EMBOLISM – Other forms

Matter entering the vascular system may be:

(a) Solid –tumour cells, bacterial clumps, fat, parasites.

(b) Gaseous – air.

(c) Liquid – amniotic fluid with fetal derived matter.

Arterial Obstruction

Arterial obstruction is usually due to thrombosis or embolism and may be (i) partial or complete, (ii) acute or slowly progressive.

The effects depend on the local anatomy, particularly on the presence of an anastomotic collateral circulation.

Infarcts

An infarct is an area of necrosis due to ischaemia. It is often found at the periphery of an organ, e.g. the kidney.

Healing

This takes place slowly. Capillaries and fibroblasts replace the necrotic tissue. Collagen is formed, the fibroblasts contract and this results in a depressed scar.

Important Sites of Infarction

The heart, the lungs and the brain are the most common sites. Less common are the small intestines and the kidney and spleen.

Important Sites of Infarction

Heart (p.175)

Infarction is almost always due to coronary arterial thrombosis complicating atheroma.

Cardiac function is immediately compromised, eddies form, the endocardium may be damaged and a thrombus forms on the inner surface of the infarcted area. The damage may extend to the external surface causing pericarditis.

If the patient survives, the infarct heals by fibrosis.

Brain (p.177)

Infarcts are commonly due to thrombosis of diseased vessels or to embolism from the left heart or carotid arteries, e.g. MIDDLE CEREBRAL, posterior cerebral and basilar arteries.

The usual changes of infarction take place, but the necrosis is colliquative – cerebral softening.

Infarction may occur without arterial occlusion in severe, prolonged hypotension (shock). Parts of the brain at the junction of arterial territories are affected (boundary zone or watershed infarcts) (see p.177).

Intestine

Infarction may follow thrombosis of or embolisation to the mesenteric arteries. The sequence of changes usually seen in solid organs is altered by the effects of anastomoses and, in the later stages, by bacterial invasion (gangrenous necrosis).

Normal Tissue Fluid Circulation

There is continuous interchange of fluid between blood and tissues. Some fluid enters the lymphatics before eventually returning to the blood stream. Two main forces operate pressure gradients controlling the fluid movement.

1. Hydrostatic pressure, i.e. capillary blood pressure (BP) encouraging the passage of fluid through the capillary wall, = 35 mm mercury.

2. Protein osmotic pressure (OP), i.e. the plasma proteins encourage the retention of fluid in the capillaries to maintain osmotic equilibrium. This pressure is equivalent to 25 mm mercury.

At the arterial end the blood pressure is greater than the osmotic pressure and fluid is forced out of the capillary. The reverse is true at the venous end and fluid is attracted into the vessel.

A small amount of fluid enters lymphatics. This is partly the result of tissue pressure and partly due to osmotic attraction of proteins in the lymphatic system.

In addition to those forces operating at capillary level, there are other mechanisms which influence the movement of fluid within the body.

1. Fluid intake

Intake via the gut or parenterally may exceed the ability of the kidneys to eliminate water.

2. Integrity of the kidneys

Damage to the kidney may diminish the elimination of fluid.

3. Hormone activity

Oedema

Oedema is an accumulation of excess fluid in the extravascular tissues. It can be local or generalised. There are a wide variety of causes.

More than one factor may apply:

Cerebral (p.532) and pulmonary (p.187) oedema are life threatening and are dealt with separately.

Shock

Shock is a condition in which there is reduced perfusion of the vital organs due to a severe and acute reduction in cardiac output and effective circulating blood volume. There is progressive cardiovascular collapse characterised by hypotension, hyperventilation and clouding of consciousness.

Changes in the Blood and Cell Metabolism

As well as these basic circulatory disturbances, important changes in the blood and cellular metabolism occur in shock.

Septic Shock (Endotoxic)

Causes

1. Bacteria – gram-negative bacteria, especially the coliform group, are the commonest cause. They release endotoxin (lipopolysaccharide) from their cell wall when it is damaged. This toxin initiates cytokine cascades with the activation of damaging effectors including nitric oxide and platelet-activating factor. Other organisms can also produce shock, e.g. staphylococci, streptococci and meningococci. These produce exotoxins.

2. Associated conditions

(a) Serious primary bacterial infection, e.g. septicaemia, peritonitis – potentiated by deficiency in immune status (p.64) and liver disease where detoxification is impaired.

(b) Bacterial shock may complicate pre-existing shock due to other causes, e.g. burns.

(c) Bacterial shock may complicate relatively trivial surgical procedures, especially in the gastrointestinal and urinary tracts in the presence of infection.

Mechanism

Shock in Burns and Scalds

Shock – Individual Organs

Heart

There are two ways in which heart failure may be associated with shock.

1. In hypovolaemic and bacteraemic shock, heart failure is a COMPLICATION.

2. In cardiogenic shock, acute heart failure is the CAUSE of shock.

Lungs

Respiratory function is disturbed in 2 ways:

Circulatory changes in the lung (especially in septic/traumatic shock). These occur when compensatory mechanisms are failing. There is congestion and oedema, with the formation of hyaline membranes. At autopsy the lungs are heavy and wet. This condition is called ‘shock lung’ or adult respiratory distress syndrome (ARDS).

Early patchy changes throughout the lungs:

Brain

During the compensated phase of shock, relatively mild cerebral ischaemia is associated with changes in the state of consciousness. When the blood pressure falls to below 50–60 mmHg, the brain suffers serious ischaemic damage with infarction in the ‘boundary zones’ of the cerebral cortex and cerebellum.

Alimentary Tract

In the stomach and duodenum there may be acute ulceration (Curling’s or ‘stress’ ulcers) with perforation.

Shock – Individual Organs: Outcome

Liver

The liver acinus is supplied by portal venous blood and hepatic arterial blood: in shock, Zone 3 of the hepatic acinus is vulnerable to anoxia.

Shock → reduced arterial blood supply → ANOXIA

May proceed to Zone 3 necrosis.

The Outcome of Shock

There are 3 possibilities, depending on several factors:

1. RECOVERY after convalescence, which may be long.

2. SURVIVAL with permanent damage to various organs.

3. DEATH

Factors favouring recovery	Factors favouring progression of shock
1. AVAILABILITY of EARLY TREATMENT of: (a) the INITIATING CAUSE (b) the HYPOVOLAEMIA 2. Youth 3. Good general health	1. DELAY in TREATMENT 2. FAILURE to REMOVE the INITIATING CAUSE 3. Old age 4. Poor general health 5. Pre-existing cardiovascular and lung disease 6. Onset of complications, esp. infection and organ damage

Cardiac Function

The main function of the heart is to provide the pumping action in a closed circulation.

Comparison with a simple mechanical system is useful and valid provided that it is appreciated that the human heart is infinitely more sophisticated with delicate built-in controls and balances which influence the inotropic (intrinsic contractility) activity of the heart.

The pump is the essential part of the system: it has to be flexible to accommodate any changes required in the distribution side of the system.

In the human circulation, reserves of ventricular muscle power are available to meet the wide range of metabolic activity required in the distribution area.

Heart Failure

Heart failure is very common and occurs when the ventricular muscle is incapable of maintaining a circulation adequate for the needs of the body, producing symptoms on exercise and at rest.

Causes of heart failure can be separated into two main groups:

Acute and Chronic

This depends on the suddenness of onset and rate of development.

The causes and effects are different.

	Acute	Chronic
Time factors
Causes	(a) ACUTE CORONARY ARTERIAL OCCLUSION with infarction or arrhythmia (b) Pulmonary embolism (c) Severe malignant hypertension (d) Acute myocarditis (e) Acute valve rupture	(a) Ischaemic heart disease (b) Hypertension (c) Chronic valvular diseases (d) Chronic lung diseases (e) Chronic severe anaemia
Effects	SUDDEN DEATH May be no time for compensatory mechanisms to be initiated. Acute pulmonary oedema is common. May be acute ischaemic effects in brain and kidneys.	Compensatory mechanisms fully developed – hypertrophy and dilatation. Chronic oedema and chronic venous congestion.

Acute and chronic failure are at opposite ends of a spectrum but may merge.

Left, Right and Combined Ventricular Failure

From a clinical point of view it is convenient to consider heart failure as affecting one or other side of the heart.

The pulmonary circulation		The systemic circulation
A low pressure system		A high pressure syste
Systolic arterial pressure = 24 mmHg		Systolic arterial pressure = 120 mmHg
Pressure gradient, artery/vein = 8 mmHg		Pressure gradient, artery/vein = 90 mmHg
Right ventricular mass and coronary blood supply	< 1:4 (approx.)	Left ventricular mass and coronary blood supply