General Pathology

Hemodynamic disorders
Dr. Moamer Kday, MSc.
Pathology department - Faculty of Pharmacy
Alasmarya Islamic University Zliten
2023©

Hemodynamic disorders, thromboembolitic disease and shock

1. OEDEMA.

2. HEMORRHAGE.

3. HYPEREMIA AND CONGESTION.

4. THROMBOSIS.

5. EMBOLISM.

6. ISCHEMIA AND INFARCTION.

7. SHOCK.

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 Introduction
The health of cells and tissues depends on an intact circulation and normal fluid
homeostasis (vessel wall integrity as well as maintenance of intravascular pressure
and osmolarity).

Water crosses the vascular wall can be a result of Increases in vascular volume
or pressure, decreases in plasma protein content, or alterations in endothelial
function.

Absence of clotting after vascular injury results in hemorrhage, which if

extensive can result in hypotension (shock) and death. Conversely, inappropriate
clotting (thrombosis) or migration of clots (embolism) can obstruct tissue blood
supplies and cause cell death (infarction).

Abnormal fluid homeostasis (i.e., hemorrhage or thrombosis) underlies three of

the most important causes of morbidity and mortality worldwide : myocardial
infarction MI, pulmonary embolism PE, and cerebrovascular accident (stroke).

Edema
Definition:- Edema is the term used for accumulation of excess fluid within body
cavities or intercellular tissue (interstitial) or intracellular (cellular swelling ).

e.g., body cavities, pleural space= hydrothorax, pericardial space=hydro- pericardium

and peritoneal space = hydroperitoneum or ( ascites ).

anasarca is severe generalized edema within subcutaneous tissue.

According the proteins content there are inflammatory edema called (exudate
protein-rich ) and specific gravity over (1,020) and edema results from hemodynamic
disorders or (non inflammatory edema) called transudate protein-poor and specific
gravity below (1,012).

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causes of edema :
1-Increasing hydrostatic pressure:- Divided into two types:

A-local : increasing hydrostatic pressure such as deep vein thrombosis (DVT) in

the lower limb leads to edema restricted to the affected leg.

B-systemic ( generalized) : increasing venous pressure leads to systemic edema

during right side heart failure.

2-Reduced plasma osmotic pressure (oncotic):-

reduced plasma proteins (albumin ) may result from excessive loss of proteins such
as nephrotic syndrome or reduced synthesis of proteins in liver during cirrhosis of
the liver or decrease intake as a consequence of protein malnutrition.

all factors lead to escape the fluid from vascular space to intercellular tissue.

3-Sodium and water retention:-

Retention of sodium, sodium as active osmolar substance leads to water retention

which resulting increasing hydrostatic pressure.
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4-increased capillary permeability

Caused by Toxins and chemicals (serotonin – histamine ) where plasma escape in to

tissue.

5- lymphatic obstruction:-

when the lymphatic drainage impaired lead to lymphedema and usually local
caused by inflammatory or neoplastic process. e.g.,

parasitic infection:( filariasis or elaphanthesis?) causes lymphatic and lymph-nodes

fibrosis in inguinal region resulting massive edema in the lower limb.

(Filariasis) Oedema of upper limp

neoplastic: (breast cancer) lymphatic and lymph- nodes will be removed during
surgery or affected by radiotherapy leads edema in upper limbs.

Morphology of edema:

A-subcutaneous edema (dependent edema): during cardiac failure, it depends on

the position of the patient, if he is standing, edema will appear at the legs, if confined
to bed will appear at the sacral region, during renal failure edema will appear in
periorbital region.

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 Pitting edema: finger pressure on edematous area results to displaces the
interstitial fluid and leaves a finger-shaped depression.

B -pulmonary edema:- seen during left ventricular failure ,renal failure and
pulmonary infection , lung will be heavier than normal lung and usually seen in lower
lobes.

microscopic picture: interstitial and intra-alveolar fluid mixed with air and
extravasation of red blood cells

C-brain edema:- divided into two types

1- Localized edema as in abscess, neoplasm,

2- Generalized edema of brain show grossly swollen, narrowed sulci , distended

gyri. generalized edema as in encephalitis, hypertensive crises, obstruction of venous
outflow.

Note: brain edema results increasing of intra-cranial pressure and leads to

herniate (extrude) brain tissue through foramen magnum and can injury medullary
vital centers (respiratory and cardiac centers or compress blood vessels).

Hemorrhage
Definition :- is extra-vasation of blood due to vessel rupture, there are two types –
external hemorrhage- bleeding out of the body, and internal hemorrhage- bleeding in
body cavity or in the tissue.

Subcutaneous hemorrhage classified according to the size :

1-minute 1- to 2 mm (petechiae)usually seen in to mucous membranes or skin

(thrombocytopenia).

2-slightly larger >3mm (purpura) seen during vasculitis.

3-larger >1 to 2 cm subcutaneous hematoma or (ecchymosis ).

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petechial hemorrhages of the colonic mucosa, a consequence of thrombocytopenia. B, Fatal
intracerebral hemorrhage.

The color changes in the location of hemorrhage, erythrocytes degraded and

phagocytosed by macrophages lead to hemoglobin (red-blue color) then by
enzymes converted into biliurbin( blue-green color)then into hemosiderin(golden-
brown color).

bleeding in body cavities such as hemothorax, hemopericardium,

hemoperitoneum, hemarthrosis (bleeding inside joint).

the bleeding can be fatal if rapid blood loss up to 20% , the patient die by
hypovolemic shock ,,if bleeding slowly the body can compensate by blood
redistribution to vital organs and renal filtration.

Causes of hemorrhage:

1- Traumatic:
2- Spontaneous:
A-vascular disease (aneurysm)
B-inflammatory BV
C- TB,Malignancy BV destruction
D- Increased intravascular tension
E- blood disease
F- Vit deficiency

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External hemorrhage : bleeding out of the body

Epistaxis : bleeding from nose

Melena: bleeding per-rectum.
Hemoptosis: coughing of blood.
Hematemesis: vomiting of blood.
Menoirrhagia & Metrorrhagia
Hematuria :

Effect of hemorrhage:

Small amount: No effect

Small repetitive : chronic haemorrhage ( microcytic , hypochromic anemia)

Moderate amount 750cc: (compensated )

- Immediate fall of BP in aortic arch and carotid sinus stimulates heart rate.
- Reflex vasoconstriction in the skin, muscles and splanchec area.
- Decreased hydrostatic pressure shifts fluid to BVs
- Protiens are added from liver and reticuloendothelial system.
- RBC and leukocytes added by bone marrow.

Severe: hemorrhagic shock,

Hyperemia and congestion

Hyperemia: is an active process resulting augmented tissue inflow.

Types:

Physiological: e.g. in arteriolar dilation occur during muscles exercise, emosion.

Pathological: e.g. in acute inflammation.

congestion: is a passive process resulting from impaired blood outflow from a tissue
it may occur as (systemic during cardiac failure left side in lung, or right side in the
liver and may acute or chronic ) or local resulting from isolated venous obstruction.

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 The congestion and edema commonly occur together In both cases there is an
increased volume and pressure of blood in a given tissue with associated capillary
dilation and a potential for fluid extravasation.

In hyperemia, increased inflow leads to engorgement with oxygenated blood,

resulting in erythema. In congestion, diminished outflow leads to a capillary bed
swollen with deoxygenated venous blood and resulting in cyanosis.

Microscopically such as acute pulmonary congestion characterized by alveolar

capillaries engorged with red blood cells and septal edema,,, in chronic congestion
the septa are thickened and fibrotic, within alveolar spaces may contain numerous
hemosiderin-laden macrophages ( heart failure cells ).

In acute hepatic congestion the central vein and sinusoids are distended with red
blood cells and may even be central hepatocyte degeneration.

In chronic passive congestion of liver- the central lobules are grossly red-brown and
slightly depressed, microscopically there are centrolobular necrosis with loss of
hepatocytes, hemosiderin and hemosiderin-laden macrophages if the process long-
standing associated with heart failure leads to hepatic fibrosis (cardiac cirrhosis).

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Contribution of Endothelial Cells to Coagulation Intact endothelial cells maintain :

1-liquid blood flow by actively inhibiting platelet adherence.

2-preventing coagulation factor activation,

3- lysing blood clots that may form.

Loss of endothelial integrity exposes underlying vWF and basement membrane

collagen, both are substrates for platelet aggregation and thrombus formation.

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A, vascular injury and transient vasoconstriction. B, Platelets adhesion by binding to von Willebrand
factor (vWF) and are activated, further platelet aggregation, to form the primary hemostatic plug. C, Local
activation of the coagulation cascade results in fibrin polymerization, "cementing" the platelets into a
definitive secondary hemostatic plug. D, limit the hemostatic process to the site of injury.

Thrombosis
Definition It is an intravascular (in vivo) coagulation , culminates with thrombus
formation.

Pathogenesis: there are three primary influence predispose to thrombus formation

(virchow -triad) :

A-endothelial injury- during myocardial infarction ulcerated plaque in

atherosclerotic artery, vasculitis lead to platelets adhesion.

B-stasis and turbulence- (stasis in veins and turbulence at the bifurcation )disrupt
axial flow and bring platelets into contact with endothelium, prevent dilution of
activated clotting factors by fresh blood flow and promote endothelial cells
activation.

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 Virchow's triad in thrombosis. Integrity of endothelium is the most important factor. Injury to
endothelial cells can also alter local blood flow and affect coagulability. Abnormal blood flow
(stasis or turbulence), in turn, can cause endothelial injury.

C - hypercoagulability:- divided into two groups:

1- primary (genetic ) mutation in factor V gene, mutation in prothrombin gene.

2-secondary (acquired) prolonged bed rest, atrial fibrillation, tissue damage and
cancer.

Types of thrombi:-

A -mural thrombi : formed in cardiac chambers or aortic lumen, they usually

adhere to the wall of underlying structure.
Mural thrombi, Thrombus in the left and right ventricular apices,

overlying white fibrous scar.

B-arterial thrombi : arise in the coronary, cerebral or femoral artery, the thrombus
usually occlusive and superimposed to atherosclerotic plaque or vasculitis or trauma.

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 C-venous thrombosis or phlebothrombosis:

invariable occlusive ,often creates a long cast of the vein lumen and usually
resulting from stasis and containing more erythrocytes therefore has reddish color
therefore known as red thrombi, 90% of cases occurring in lower limbs.

the most common sites are dural sinus, portal vein, hepatic vein.

At the autopsy postmortem clots may confused with vein thrombi.

Morphology:-

The thrombi may develop anywhere in the cardiovascular system with variable size
and shape depending on their site of origin.

A- Arterial and cardiac thrombi usually begin at the site of endothelial injury (e.g.
atherosclerotic plaque ) or turbulence (vessel bifurcation ).

B-Venous thrombi developed at the sites of stasis .

Arterial thrombi tend to growing retrograde direction from the point of

attachment whereas venous thrombi extend in the direction of blood flow and the
tail of thrombi may not well attached and fragmented forming embolus.

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 Grossly and microscopically thrombus formed into heart or aorta shows
laminations called (lines of Zahn) pale layers platelets with fibrin and darker
layers containing more erythrocytes.

Fate of the thrombus :

If the patient survives, thrombi undergo some combination of the following four
events :

1- propagation:- thrombi may accumulate more platelets and fibrin eventually lead to
vessel obstruction.

2- embolization:- the thrombi may travel to other site in the vasculature.

3- resolution:- thrombi may be removed by fibrinolytic activity.

4- organization and recanalization:-thrombi may induce inflammation and fibrosis

and may reestablish vasculature or incorporate in the wall.

Embolism
Definition-an embolus is a detached intravascular solid, liquid, or gaseous mass that
is carried by the blood to a site distant from its point of origin.

Types of embolus :-

1-thromboembolism : (pulmonary or systemic)

A-pulmonary thromboembolism : can assessed at autopsy ,60% to 80% clinically

are silent, the most common thromboembolism from deep leg vein thrombi above at
the level of the knee, carried trough the larger channels and usually pass though right
heart into pulmonary vasculature

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. Embolus derived from a lower extremity deep venous thrombosis and now impacted in a
pulmonary artery branch.

Depending on the size, the embolus may occlude

the main pulmonary artery, when the embolus impacted at bifurcation called
(saddle embolus)or pass throughout the smaller arteriole, paradoxical embolism
when there are inter-atrial or inter-ventricular septal defect in the heart.

Consequences of thromboembolism: 1-main

artery cause sudden death- right heart failure.

2-medium size artery lead to hemorrhage, because the lung has dual blood
supply.

3-embolic obstruction of small vessels lead to infarction.

4-multiple emboli over time may cause pulmonary hypertension and right heart
failure.

B- systemic thromboembolism-refers to emboli traveling within arterial circulation

80% arise from mural thrombi (myocardial infarction left ventricle), aortic aneurysm,
ulcerated atherosclerotic plaque.

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 the major site of arteriolar embolization are lower limbs, brain, intestine, kidney
and spleen.

consequences of systemic thromboembolism depend on the extent of collateral

vascular supply in the affected tissue.

2- Fat embolism:-

Occurs most commonly during fracture of long bones and they have fatty bone
marrow during fracture, fat globules pass to circulation trough ruptured blood vessel.

fat embolism syndrome-characterized by pulmonary failure ,neurologic symptoms,

anemia , and appear 1 to 3 days after injury.

fat emboli affection is mechanical by obstruction, or biochemical by release of free

fatty acids from fat globules causing toxic injury to endothelial cells, platelets
activation.

3- Air embolism:-

Gas bubbles within the circulation can obstruct vascular flow and lead to distal
ischemic injury.

air can enter in circulation during obstetric procedures or chest wall injury, there is
a special form of gas embolism called (decompression sickness) occurs after sudden
changes in atmospheric pressure.

rapid formation of gas (nitrogen) bubbles within skeletal muscles and joints is
responsible for painful condition.

chronic form of decompression sickness called (caisson disease )

4- Amniotic fluid embolism:-

uncommon complication of labor and immediate postpartum period with high rate
of maternal mortality and manifested as pulmonary embolism.

symptoms are dyspnea, cyanosis and hypotensive shock followed by seizures and
coma.

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 amniotic fluid emboli occur when placental membrane ruptured or ruptured
uterine.

Infarction
Definition:-infarct is a localized area of ischemic necrosis in an organ or tissue
resulting mostly from sudden reduction of its supply or venous drainage.

causes – the most common cause of infarction is arterial occlusion mostly by

thrombi, reduced venous drainage.

Types of infarcts-according to color:

A-white infarcts (anemic) usually seen in arterial occlusions and solid tissue.

B-red infarcts(hemorrhagic)usually seen in tissue with double circulation, loose and

congested tissue.

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Red and white infarcts. A, Hemorrhagic, roughly wedge-shaped pulmonary infarct (red infarct). B,
Sharply demarcated pale infarct in the spleen (white infarct).

Morphology- infarcts has wedge-shaped, the apex usually pointed toward the focus
of occlusion and the base at the peripherally ,, microscopic picture depends on the
type of tissue and necrosis.

Factors which influence on infarcts :

A-general status of blood and cardiovascular system such as anemia, atherosclerosis

and heart failure.

B-anatomic pattern of blood supply :

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 double blood supply (dual supply lung), parallel arterial system( brain), single rich
and few anastomosis.

C- rate of development of occlusion:

slowly development of occlusions are better tolerated than those occurring

suddenly occlusion and they have opportunity to activate collateral pathway.

D-vulnerability the tissue for ischemia:

neurons in CNS, proximal tubules in kidney and myocardial muscle, intestinal

mucosa are the most sensitive for ischemia and for few minutes will be irreversible
injury, fibrous tissue can resistant ischemia for hours.

Shock
Definition : It is a circulatory collapse that cause systemic hypoperfusion due to
either reduced cardiac output or reduced circulating blood volume.

Types of shock :

1 - cardiogenic (due to cardiac pump failure, for example, to myocardial

infarction).

2-hypovolemic (due to blood loss for example hemorrhage).

3- Septic shock results from the host innate immune response to sepsis (due to
infections) bacterial or fungal cell molecules (most commonly endotoxin).

4-Neurogenic, for example vagal stimulation.

Symptoms and signs of shock :

Low blood pressure. Rapid weak pulse.

Irregular breathing. Cold sweaty pale skin.

Dry mouth. Dilated pupils.

Reduced urine output.

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References :

 Robbins & Cotran Pathologic Basis of Disease - 8th Ed.

 Usmle lecture notes pathology 2010, Kaplan.

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