Lecture 5

Derangements of blood flow

Derangements of blood flow or haemodynamic disturbances are considered under 2 broad headings:
I. Disturbances in the volume of the circulating blood. These include: hyperemia and congestion,
hemorrhage, and shock.
II. Circulatory disturbances of obstructive nature. These are: thrombosis, embolism, ischaemia and
infarction.
I. DISTURBANCES IN THE VOLUME OF CIRCULATING BLOOD
HYPERAEMIA AND CONGESTION
Hyperemia and congestion are the terms used for increased volume of blood within dilated vessels
of an organ or tissue; the increased volume from arterial and arteriolar dilatation being referred to-
as hyperemia or active hyperemia, whereas the impaired venous drainage is called venous conges-
tion or passive hyperemia. If the condition develops rapidly it is called acute, while more prolonged
and gradual response is known as chronic.
Active Hyperemia
The dilatation of arteries, arterioles and capillaries is effected either through sympathetic
neurogenic mechanism or via the release of vasoactive substances. The affected tissue or organ is
pink or red in appearance (erythema).
The examples of active hyperemia are seen in the following conditions:
Inflammation e.g. congested vessels in the walls of alveoli in pneumonia
Blushing i.e. flushing of the skin of face in response to emotions
Muscular exercise
High grade fever.
Passive Hyperemia (Venous Congestion)
The dilatation of veins and capillaries due to impaired venous drainage results in passive hyperemia
or venous congestion, commonly referred to as congestion. Congestion may be acute or chronic, the
latter being more common and called chronic venous congestion (CVC). The affected tissue or
organ is bluish in color due to accumulation of venous blood (cyanosis). Obstruction to the venous
outflow may be local or systemic. Accordingly, venous congestion is of 2 types:
Local venous congestion results from obstruction to the venous outflow from an organ or part of
the body e.g. portal venous obstruction in cirrhosis of the liver, outside pressure on the vessel wall
as occurs in tight bandage, plasters, tumors, pregnancy, hernia etc, or intraluminal occlusion by
thrombosis.
Systemic (General) venous congestion is engorgement of systemic veins e.g. in left-sided and
right-sided heart failure and diseases of the lungs which interfere with pulmonary blood flow like
pulmonary fibrosis, emphysema etc. Usually the fluid accumulates upstream to the specific
chamber of the heart which is initially affected. For example, in left-sided heart failure (such as due
to mechanical overload in aortic stenosis, or due to weakened left ventricular wall as in myocardial
infarction) pulmonary congestion results, whereas in right-sided heart failure (such as due to
pulmonary stenosis or pulmonary hypertension) systemic venous congestion results.
Morphology of CVC of Organs
Morphologic changes seen in CVC of the lungs, liver, spleen and kidney are discussed below.
CVC LUNGS. Chronic venous congestion of lung occurs in left heart failure, especially in rheu-
matic mitral stenosis so that there is consequent rise in pulmonary venous pressure.
Grossly, the lungs are heavy and firm in consistency. The sectioned surface is dark brown in color
referred to as brown induration of the lungs.
Histologically, the alveolar septa are widened due to the presence of interstitial edema as well as
due to dilated and congested capillaries. The septa mildly thickened due to slight increase in fibrous
connective tissue. Rupture of dilated and congested capillaries may result in minute intra-alveolar
hemorrhages. The breakdown of erythrocytes liberates haemosiderin pigment which is taken up by
alveolar macrophages, so called heart failure cells, present in the alveolar lumina. The brown

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indurations of the cut surface of the lungs is due to the pigmentation and fibrosis.
CVC LIVER. Chronic venous congestion of the liver occurs in right heart failure and sometimes
due to occlusion of inferior vena cava and hepatic vein.
Grossly the liver is enlarged and tender and the capsule is tense. Cut surface shows characteristic
nutmeg liver due to red and yellow mottled appearance, corresponding to congested centre of
lobules and fatty peripheral zone respectively.
Microscopically the changes of congestion are more marked in the centrilobular zone due to severe
hypoxia than in the peripheral zone. The central veins as well as the adjacent sinusoids are dis-
tended and filled with blood. The centrilobular hepatocytes undergo degenerative changes, and
eventually centrilobular haemorrhagic necrosis may be seen. Long-standing cases may show fine
centrilobular fibrosis and regeneration of hepatocytes, resulting in cardiac cirrhosis. The peripheral
zone of the lobule is less severely affected by chronic hypoxia and shows some fatty change in the
hepatocytes.
CVC SPLEEN. Chronic venous congestion of the spleen occurs in right heart failure and in portal
hypertension from cirrhosis of liver. Grossly, the spleen in early stage is slightly to moderately
enlarged (up to 250 g as compared to normal 150 g), while in long-standing cases there is
progressive enlargement and may weigh up to 500 g to 1000 g. The organ is deeply congested, tense
and cyanotic. Sectioned surface exudes blood freely.
Microscopically, the red pulp shows congestion and marked sinusoidal dilatation with areas of
recent and old hemorrhages. These hemorrhages may get organized and form Gamna-Gandy bodies
or siderofibrotic nodules which are deposits of haemosiderin pigment and calcium salts on fibrous
connective tissue and elastic fibers. The reticulin-network as well as fibrous trabeculae are
thickened. In the late stage, there is hyperplasia of macrophages and fibroblasts resulting in increase
in fibrous tissue of the capsule and hyperplasia of red pulps which account for firmness of the
spleen. This advanced stage seen more commonly in hepatic cirrhosis is called congestive
splenomegaly and is the commonest cause of hypersplenism.
CVC KIDNEY. Grossly, the kidneys are slightly enlarged and the medulla is congested.
Microscopically the changes are rather mild. The tubules may show degenerative changes like
cloudy swelling and fatty change. The glomeruli may show mesangial proliferation.
HEMORRHAGE
Hemorrhage is the escape of blood from a blood vessel. The bleeding may occur externally, or in-
ternally into the serous cavities (e.g. hemothorax, hemoperitoneum, hemopericardium) or into a
hollow viscus. Extravasation of blood into the tissues with resultant swelling is known as
haematoma. Large extravasations of blood into the skin and mucous membranes are called
ecchymoses. Purpuras are small areas of hemorrhages (up to 1 cm) into the skin and mucous
membrane, whereas petechiae are minute pinhead-sized hemorrhages. Microscopic escape of
erythrocytes into loose tissues may occur following marked congestion and is known as diapedesis.
CAUSES OF HAEMORRHAGE. The blood loss may be large and sudden (acute), or small re-
peated bleeds may occurs over a period of time (chronic). The various causes of hemorrhage are
listed below:
1. Trauma to the vessel wall, e.g., penetrating wound in the heart or great vessels, during labour etc.
2. Spontaneous hemorrhage e.g. rupture of an aneurysm, septicaemia, bleeding diathesis (such as
purpura), acute leukemia, pernicious anemia, scurvy.
3. Inflammatory lesions of the vessel wall, e.g., bleeding from chronic peptic ulcer, typhoid ulcers,
blood vessels traversing a tuberculosis cavity in the lung, syphilitic involvement of the aorta,
polyarteritis nodosa.
4. Neoplastic invasion e.g., hemorrhage following vascular invasion in carcinoma of the tongue.
5. Vascular diseases, e.g. atherosclerosis.
6. Elevated pressure within the vessels, e.g., cerebral and retinal hemorrhage in systemic
hypertension, severe hemorrhage from varicose veins due to high pressure in the veins of legs or
esophagus.

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EFFECTS OF HAEMORRHAGE. The effects of blood loss depend upon 3 main factors:
the amount of bloodless;
the speed of blood loss; and
the site of the hemorrhage.
The loss up to 20% of blood volume suddenly or slowly generally has little clinical effects
because of compensatory mechanisms. A sudden loss of 33% of blood volume may cause death,
while loss of up to 50% of blood volume over a period of 24 hours may not be necessarily fatal.
However, chronic blood loss generally produces an iron deficiency anemia, whereas acute
hemorrhage may lead to serious immediate consequences such as hypovolemic shock.
SHOCK DEFINITION AND TYPES
Shock is defined as a clinical state of circulatory collapse characterized by :
an acute reduction of effective circulating blood volume; and
an inadequate perfusion of cells and tissues.
Shock may be of 2 main types: primary (initial) and secondary (true) shock.
PRIMARY OR INITIAL SHOCK. It is a transient and usually a benign vasovagal attack resulting
from sudden reduction of venous return to the heart caused by neurogenic vasodilatation and con-
sequent peripheral pooling of blood. It can occur immediately following trauma, severe pain or
emotional over-reaction such as due to fear, sorrow or surprise. Clinically, the patient generally
develops unconsciousness, weakness, sinking sensation, pale and clammy limbs, weak and rapid
pulse, and low blood pressure. The attack usually lasts for a few seconds or minutes.
SECONDARY OR TRUE SHOCK. This is the form of shock which occurs due to hemodynamic
derangements with hypo perfusion of the cells. This type of shock is the true shock which is com-
monly referred to as 'shock' if not specified.
ETIOLOGY AND CLASSIFICATION
Many types of injuries and diseases can cause shock. These causes are broadly grouped under 3
major headings and accordingly shock is classified into 3 main etiologic forms: hypovolemic,
cardiogenic, and septic.
1. HYPOVOLAEMIC SHOCK. Reduction in blood volume induces hypovolemic shock. The
causes of hypovolemia include the following:
i) Severe hemorrhage (external or internal) e.g., in trauma, surgery.
ii) Fluid loss e.g., in severe burns, crush injury to a limb, persistent vomiting and severe diarrhea
causing dehydration.
2. SEPTIC SHOCK. Severe bacterial infections or septicemia induce septic shock. The predomi-
nant causes are as under:
i) Gram-negative septicemia (endotoxic shock)
e.g., infection with E. coli, Proteus, Klebsiella, Pseudomonas, bacteroides.
ii) Gram-positive septicemia (exotoxic shock)
is less common e.g., infection with streptococci, pneumococci.
3. CARDIOGENIC SHOCK. Acute circulatory failure with sudden fall in cardiac output from
acute diseases of the heart without actual reduction of blood volume (normovolemia) results in
cardiogenic shock. The causes include the following:
i) Deficient emptying e.g,,
Myocardial infarction
Rupture of the heart
Cardiac arrhythmias
ii) Deficient filling e.g.,
Cardiac tamponade from hemopericardium
iii) Obstruction to the outflow e.g.
Pulmonary embolism
Ball valve thrombus.
Besides the three major forms of shock described above, neurogenic shock (following

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anesthesia or spinal cord injury) and anaphylactic shock are two other types of shock resulting from
peripheral vasodilatation with pooling of blood.
MORPHOLOGIC COMPLICATIONS IN SHOCK
The morphologic changes in shock are due to hypoxia resulting in degeneration and necrosis in
various organs. The major organs affected are the brain, heart, lungs and kidneys. Morphologic
changes are also noted in the adrenals, gastrointestinal tract, liver and other organs.
1. HYPOXIC ENCEPHALOPATHY. Cerebral ischaemia in compensated shock may produce al-
tered state of consciousness. However, if the blood pressure falls below 50 mm Hg as occurs in sys-
temic hypotension in prolonged shock and cardiac arrest, brain suffers from serious ischemic
damage with loss of cortical functions, coma, and a vegetative state.
Grossly the area supplied by the most distal branches of the cerebral arteries suffers from severe
ischemic necrosis which is usually the border zone between the anterior and middle cerebral
arteries.
Microscopically, the changes are noticeable if ischaemia is prolonged for 12 to 24 hours. Neurons,
particularly Purkinje cells, are more prone to develop the effects of ischaemia. The cytoplasm of the
affected neurons is intensely eosinophilic and the nucleus is small pyknotic. Dead and dying nerve
cells are replaced by gliosis.
2. HEART IN SHOCK. Heart is more vulnerable to the effects of hypoxia than any other organ.
Heart is affected in cardiogenic as well as in other forms of shock. There are 2 types of morphologic
changes in heart in all types of shock:
i) Hemorrhages and necrosis. There may be small or large ischemic areas or infarcts, particularly
located in the subepicardial and subendocardial region.
ii) Zonal lesions These are opaque transverse contraction bands in a myocyte near an intercalated
disc.
3. SHOCK LUNG. Lungs due to dual blood supply are generally not affected by hypovolemic
shock but in septic shock the morphologic changes in lungs are quite prominent termed shock lung.
Grossly the lungs are heavy and wet.
Microscopically changes of adult respiratory distress syndrome (ARDS) are seen. Briefly, the
changes include congestion, interstitial and alveolar edema, interstitial lymphocyte infiltrate,
alveolar hyaline membranes, thickening and fibrosis of alveolar septa, and fibrin and platelet
thrombi in the pulmonary microvasculature.
4. SHOCK KIDNEY. One of the important complications of shock is irreversible renal injury, first
noted in persons who sustained crush injuries in building collapses in air raids in World War II. The
renal ischaemia following systemic hypo-tension is considered responsible for renal changes in
shock. The end-result is generally anuria and death.
Grossly, the kidneys are soft and swollen. Sectioned surface shows blurred architectural markings.
Microscopically, the tubular lesions are seen at all levels of nephron and are referred to as acute
tubular necrosis (ATN) which can occur following other causes besides shock. If extensive muscle
injury or intravascular haemolysis are also associated, peculiar brown tubular casts are seen.
5. ADRENALS IN SHOCK. The adrenals show stress response in shock. This includes release of
aldosterone in response to hypoxic kidney, release of glucocorticoids from adrenal cortex and
catecholamines like adrenaline from adrenal medulla. In severe shock, adrenal hemorrhages may
occur.
6. HAEMORRHAGIC GASTROENTEROPATHY. The hypoperfusion of the alimentary tract in
conditions such as shock and cardiac failure may result in mucosal and mural infarction called
haemorrhagic gastroenteropathy. This type of non-occlusive ischemic injury of bowel must be
distinguished from full pledged infarction in which case the deeper layers of gut (muscularis and
serosa) are also damaged. In shock due to burns, acute stress ulcers of the stomach or duodenum
may occur and are known as Curling's ulcers.
Grossly, the lesions are multifocal and widely distributed throughout the bowel. The lesions are
superficial ulcers, reddish purple in color. The adjoining bowel mucosa is edematous and

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haemorrhagic.
Microscopically, the involved areas show dilated and congested vessels and haemorrhagic necrosis
of the mucosa and sometimes sub mucosa. Secondary infection may supervene and condition may
progress into pseudo membranous enterocolitis.
7. LIVER IN SHOCK Due to effects to hypoxia on liver, VDM is released from the liver which
causes vasodilatation. Besides, focal necrosis may be seen, fatty change may occur and the liver
function may be impaired.
8. OTHER ORGANS. Other organs such as lymph nodes, spleen and pancreas may also show foci
of necrosis in shock.