Lecture # 4

General medicine Faculty

Pathology of blood circulation.

(Edema, hyperemia, ischemia, hemorrhage,
thrombosis, embolism).
Prepared by:
Associate Professor,
Ph.D. R. Deev

M.Mavlikeev. MD
Kazan, 2018
 The pathology of the circulation (hemodynamic
disorders) includes:
Violation of the Disturbance of
Edema Violations of the
permeability of blood flow
blood volume
the vascular wall
• Edema • Arterial hyperemia • Bleeding • Stasis
• Anasarca • Venous plethora • Hemorrhage • Thrombosis
• Hydrotorax (acute / chronic) • Plasmorrhagia • Embolism
• Hydropericardium • Anemia (Ischemia)
• Ascites (acute / chronic)
(hydroperitoneum)
 1. Edema - accumulation of tissue fluid in serous
cavities, or stroma of organs.
Mechanisms of formation
In the thoracic duct and eventually
into the left subclavian vein
1 - Increased hydrostatic pressure in capillaries;
2 - Low osmotic pressure of plasma;
3 - Sodium and water retention;
4 - Lymphatic obstruction;
5 - Increased permeability of the vascular wall.

Increased interstitial Classification

Hydrostatic pressure fluid pressure
in capillaries
Depending on the pathological condition,
which is accompanied by edema, edema
may be:
• traumatic
• allergic
• inflammatory
Colloid-osmotic • toxic
plasma pressure • congestive
• lymphatic
• oncotic (including cahetical)
Postcapillary venule • dysmetabolic
Terminal arteriole Capillary
Edema
 General edema

Hydrostatic Renal blood flow

pressure in
capillaries Albumin
Activation of the renin-
angiotensin-
aldehsterone system

Retention of Kidney
, failure

Blood volume Osmotic plasma

pressure

Edema
Clinical significance of edema
Ascites due to liver cirrhosis
 Clinical significance of edema
Pulmonary edema

CAUSES
A) cardiac (AH, decreased contractility of the heart, etc.)
B) non-cardial (hypervolemia, hypoproteinemia, shock,
gas poisoning, etc.)

Hydrotorax
Clinical significance of edema
Cerebral edema
Clinical significance of edema
Elephantiasis

Bancroft's filaria
 Dehydration (Exicosis)
General Classification by Local
mechanism
Due to insufficient Due to excess
water intake water loss

total
loss of more than 22% is fatal

Drink excrement
intracellular

ml urine
intravascular

Food breathing/ skin

interstitial
 Violations of the blood volume
Arterial plethora – hyperemia –
is increased blood filling of the tissue due to increased arterial
blood flow. It can be general - with an increase in the volume of
circulating blood and local arising from local effects of various
factors.
1. angioneurotic (neuroparalytic) 2. collateral 3. postischemic
4. hyperemia caused by 5. inflammatory 6. vacant
arteriolovenous fistula

Causes of general arterial plethora

• Increased plasma volume (intensive infusion therapy)
• Erythrocytosis
- Primary (erythremia)
- Secondary (hypoxic conditions: lung
diseases, high altitude, etc.)
 Violations of the blood volume
Venous plethora –
is increased blood filling of an organ or tissue due to the
reduction (difficulty) of the outflow of blood; the blood flow is not
changed or reduced.
Stagnation of venous blood leads to widening of veins and
capillaries, slowing of blood flow in them, to the development of
, which is the main pathogenetic factor determining
changes in organs with venous plethora.

acute chronic

local general
 Violations of the blood volume
General acute venous plethora
General acute venous plethora is occurs with acute heart failure.
CAUSES: myocardial infarction, acute myocarditis, cardiac
tamponade (and other causes leading to a acute weakening of
the contractility of the heart)
Due to hypoxia and increased hydrostatic pressure, capillary permeability
rises acute, plasma steepness and edema, stasis in capillaries and multiple
diapedemic hemorrhages develops in the stroma of the organs; in the
parenchyma - dystrophic and necrotic changes.
Left ventricle Right ventricle
General acute venous plethora
• Lungs:
• Edema,
• Hemorrhage.
• Acute pulmonary edema is one of the main causes of death of patients
with acute cardiovascular insufficiency.
• Kidney:
• Dystrophy,
• Necrosis of the tubular epithelium.
• Liver:
• Centrolobular hemorrhages,
• Necrosis.
 2. Violations of the blood volume
General chronic venous plethora (congestion)
A general chronic venous plethora occurs with chronic cardiovascular failure
(coronary heart disease, chronic myocarditis, cardiomyopathy, heart
disease).
Prolonged tissue hypoxia leads not only to plasmorrhage, edema, stasis and
hemorrhages, dystrophy and necrosis, but also to atrophy and sclerosis
(proliferation of connective tissue): stagnant consolidation (induration) of
organs and tissues develops.

serous
skin cavities
spleen kidneys lungs liver

- Anasarca -Hydrotorax - Cyanotic - Cyanotic - Brown - Nutmeg

-Hydropericardium induration induration induration liver
-Ascites
 2. Violations of the blood volume
General chronic venous plethora (congestion)
spleen kidneys
 2. Violations of the blood volume
General chronic venous plethora (congestion)
lungs
 2. Violations of the blood volume
General chronic venous plethora (congestion)
Nutmeg liver
Local venous plethora
• Occurs when the outflow of venous blood from the body or part of
the body in connection with closure of the lumen of the vein
(thrombus or embolus) or squeezing it from the outside (swelling,
expanding tissue).
• In the organs, the same changes occur as with a common plethora.
• Muscat liver and nutmeg cirrhosis may occur with thrombophlebitis
of the hepatic veins (Badd-Chiari syndrome).
 2. Violations of the blood volume
Ischemia (local anemia) –
is decrease in the blood filling of the tissue, organ, part of the body as a
result of insufficient blood flow. Tissue changes that occur with anemia are
due to the duration of the hypoxia that occurs.

• With acute anemia, dystrophic and necrotic changes usually occur.

• With chronic anemia, there are atrophy of parenchymal elements and
sclerosis of the stroma.

due to
spastic obturating compression
repartition
 3. Bleeding and hemorrhage

Bleeding is the process of the discharge of blood from the lumen of

a blood vessel or cavities of the heart into the environment or into
the body cavity, as well as interstitial.
OUTER INTERNAL

PRIMARY SECONDARY

Hemorrhage (hematoma) is a kind of internal bleeding with a

accumulation of blood in tissues.

A special type of hemorrhage - apoplexy - is a rapidly developing

massive hemorrhage.
 Classification of hematomas *
* also distinguish uniform hemorrhagic impregnation of the tissue

petechiae purpura ecchymosis hematoma in

cavities
• 1-2 mm • 3 mm - 1 cm • more than 1 cm • hemothorax
• CAUSES: • CAUSES: • CAUSES: • hemopericardium
AH (1), impaired trauma, vasculitis injury • hemoperitoneum
number and • hemarthrosis
function of • hemocephalia
platelets (2)
 Mechanisms of bleeding
1 2 3
• per rhexin • per diabrosin • per diapedesis
• due to rupture • due to corroding • due to impregnation
• CAUSES: • CAUSES: • CAUSES:
• trauma • cancer • hypoxia
• inflammation • necrosis • intoxication
• necrosis • inflammation • hemorrhagic diathesis
• aneurysm • ectopic pregnancy
• developmental
vascular
malformations
• sclerosis
• hyalinosis
Bleeding due to rupture – per rhexin
Bleeding due to corroding – per diabrosin
Bleeding due to impregnation – per diapedesis
Outcome of hematoma
• The formation of a "rusty" cyst
(accumulation of hemosiderin)
• Encapsulation or fibrosis of the
hematoma
• Suppuration with infection
Plasmorrhagia
• Plasmorrhagia - the exit of plasma from the bloodstream due to
increased vascular permeability.
• It occurs as a result of neuro-vascular disorders (spasm), tissue
hypoxia, immunopathological reactions
• Diseases with plasmorrhagia: hypertensive disease, atherosclerosis,
decompensated cardiac defects, infectious, infectious-allergic and
autoimmune diseases
• Outcome – fibrinoid necrosis and hyalinosis
• Plasmorrhagia is important pathophysiological factor in burn disease
Blood stasis
• Stasis of blood - a sharp slowing and stopping the
flow of blood in the vessels of the microcirculation
• Causes of stasis:
• Infection,
• Intoxication,
• Venous plethora,
• Shock
• Of great importance is the sludge-phenomenon, for
which characteristic is the adherence of red blood
cells to each other, leukocytes and platelets and a
build-up of viscosity plasma, which leads to
difficulty in blood perfusion through the vessels of
the microcirculatory bed.
 Blood Stasis
• Stasis in the capillaries of the brain:
• Capillaries and venules are sharply expanded,
• Overfilled by columns of erythrocytes in the form of coins
• Swelling of the brain substance.
• Prolonged stasis in the brain leads to development focal necrosis;
clinically it manifests with brain coma.
 4. Thrombosis
A thrombosis is an intravital coagulation of blood in vessels or cavities
of the heart with the formation of fibrin. Internal pathway Outer pathway
kallikrein high- Tissue destruction
molecular
Blood coagulation occurs in 4 stages: weight
kininogen,
Tissue factor
prekallikrein (thromboplastin)
collagen

1. thromboplastinogen + activators
Thrombin
active thromboplastin. (IIa)
Tissue factor

2. prothrombin + Ca2 + + Thrombin

(IIa)
thromboplastin thrombin.

3. fibrinogen + thrombin fibrin Thrombin

(IIa)

monomer.
prothrombin thrombin

4. fibrin monomer + fibrin-stimulating Phospholipid surface fibrinogen fibrin

fibrin polymer
factor fibrin polymer. Active factor Common
Non-active factor pathway
 endothelium basal membrane Primary hemostasis
smooth muscle of an arteriola

platelet shape
Destruction site ADP, platelet
change
TxA2 mobilization
Platelet adhesion granule
Adhesion and
von Willebrand release formation of a
factor hemostatic plug

release of endothelin
reflex collagen endothelium basal
causes vasoconstriction collagen
vasoconstriction membrane
B

Secondary hemostasis
Thrombosis and angiotembotic events

Expression of Thrombin activation Release of

the phospholipid Captured neutrophils Captured
- t-PA (fibrinolysis)
complex Fibrin polymerization - Thrombomodulin erythrocytes
(coagulation
Tissue factor Tissue factor cascade blocking) Polymerized
fibrin

C fibrin D
 Thrombosis factors:
• General:
• Changes in the vascular wall
• Slowing and disturbing blood flow
• Local:
• Misbalance between coagulation and anticoagulation systems of blood
• Violation of rheological properties of blood (increased viscosity).
 4. Thrombosis
Classification of thrombi by morphological features (by
color, composition)
RED
WHITE
Erythrocytes +
Platelets + fibrin
fibrin + platelets
In large arteries
In the veins

COMPOSITE HYALINE
Layered Destroyed
Veins, aortic erythrocytes,
aneurysm, plasma proteins
chambers of the Microcirculatory
heart bed
 4. Thrombosis
Classification of thrombi
• In relation to the lumen of the vessel:
1. Parietal - lying at the wall of the vessel, thus there is a free part of
the lumen.

2. Obturating or occluding the lumen of the vessel.

3. Axial, freely lying in the lumen of the vessel or cavity of the heart.

• According to the shape:

1. Elongated thrombi.
2. Spherical thrombi in the cavities of the heart or in the saccular
aneurysm.
3. Small blood clots resembling beads, the so-called "warts". They
are often found on valve flaps.
 Thrombosis: structure of composite thrombus

1. head (has the

structure of a 1
white clot),
attached to the
vascular wall;

2. body (actually
mixed thrombus);

3. tail (has the

structure of a red 3
blood clot).
3
Thrombus vs post-mortem blood clot
Thrombus Criteria Postmortem clot

Dark-red Color White-red

Dry Consistency Elastic
Rough, dim Surface Smooth, glance
Attached with head In relation to vascular wall Free lying
Thrombus vs post-mortem blood clot

Zahn lines in trombus on cut

 Outcomes of thrombosis

FAVORABLE:
• Aseptic autolysis (dissolution of a blood clot)
ADVERSE:
• Organization of a thrombus, that is, the
replacement of a thrombus with a connective • Septic autolysis with the
tissue that grows from the side of the intima; development of septicopyemia
The process can be accompanied by • Disengage the thrombus with the
recanalization and vascularization. development of thromboembolic
• Calcification (in the veins, there are stones -
events
phlebolites)
• Progression

Clinical significance:
thrombosis - > ischemia - > infarction and gangrenes
thrombosis - > thromboembolism - > infarction and gangrenes
Embolism
• Embolism - circulation in the blood (or lymph) not occurring under
normal conditions particle with blockage of vessels
• Such particles are called embolus (emboli)
Embolism classification
• Depending on the direction of embolus movement:
• Orthograde embolism – with blood flow,
• Retrograde embolism - against blood flow,
• Paradoxical embolism - embolus from the veins of a large circle, bypassing the lungs,
enters the arteries of a large circle (through defects in the septa of the heart).
• Depending on the nature of the emboli:
• Thromboembolism (venous and arterial),
• Fat embolism,
• Air embolism,
• Gas embolism,
• Tissue (cellular) embolism (+Amniotic fluid embolism)
• Microbial embolism,
• Embolism with foreign bodies
Venous embolism: pulmonary embolism (PE)
• Source: thrombi of the veins of the lower limbs, veins of the pelvic
floor, arising with venous stasis, as well as thrombi of the right heart
chambers
• In the genesis of death in PE, closure of the lumen of the vessel with
the development of acute right ventricular failure, as well as
pulmonary-coronary reflex (Kitaev’s reflex): spasm of the bronchi,
branches of the pulmonary artery and coronary arteries
• Outcomes:
• Heart arrest and death
• Hemorrhagic lung infarction
2-4 cases per
1000
hospitalizations
(USA)

95% - source
of thrombus -
veins of lower
extremities
(above the
knee joint)
Arterial embolism
• Source: thrombi formed in left heart chambers (with endocarditis,
heart defects, myocardial infarction, arrhythmia, etc.) and in the aorta
(or large arteries) atherosclerosis
• Outcomes:
• Ischemic infarctions and gangrenes in organs
Thromboembolic syndrome = systemic
thrombosis
• Includes:
• Thrombosis
• Multiple arterial thromboembolism
• Infartion of gangrene (brain – 10%, lower limbs – 75%, other – 10%)
• Causes
• Cardiovascular diseases,
• Oncological diseases,
• Infectious (sepsis) diseases,
• Postoperative period.
Fat embolism
• Develops when drops of fat enter the bloodstream:
• In case of traumatic bone marrow injury (fractures of long tubular bones),
• Crushing subcutaneous fat,
• After intravenous administration of oil solutions.
• Fat drops obturate capillaries of the lungs and through arteriovenous
anastomoses enter a large circle blood circulation, obturate the
capillaries of the kidneys, brain and other organ
• Fat droplets can be revealed by sudan III staining in interalveolar
septae capillaries
• Outcomes: acute pulmonary insufficiency, brain capillaries obturation
with multiple brain hemorrhages
Fat embolism
Air embolism
• Develops air enters the bloodstream:
• After the wounds of the veins of the neck (negative pressure)
• After childbirth and abortion,
• through the sclerotized lung,
• with occasional intravenous injection air together with the drug substance.
• Air bubbles in the blood cause embolism of capillaries of a lung; when
air bubbles reach a large circle blood circulation embolism of
capillaries the brain can develop .
• Air embolism can be detected on the autopsy by release of air from
the right heart after puncturing it underwater and a foamy blood in
the cavities of the heart.
Air embolism test
Gas embolism
• Typical for caisson disease=decompression sickness: develops with
rapid decompression (transfer from increased pressure to normal
atmospheric pressure or from normal to decreased).
• Released nitrogen bubbles (located at high blood pressure in the
dissolved state) cause blockage of the brain and spinal cord, liver,
kidneys and other body’s parts capillaries , which is accompanied by
the appearance in them small foci of ischemia and necrosis.
Tissue embolism
• May occur when tissue is destroyed due to trauma or pathological
process leading to the inflow of pieces of tissue (cells) into the blood.
• Embolism of amniotic fluid in woman in labor may be accompanied
by the development of DIC syndrome and lead to death.
• Embolism of malignant tumor cells lies in the tumor metastasis: in
organs numerous tumor nodes round in shape are revealed, often
with a dip in the center (necrosis).
Tissue embolism (cancer cells)
Microbial embolism
• Bacteria, fungi, protozoa circulate in the blood and obturate the
capillaries lumen.
• Often, bacterial emboli are formed in purulent melting of thrombus -
thrombobacterial embolism.
• At the site of occlusion of the vessel with bacterial emboli formed
metastatic abscesses.
• An example of bacterial embolism may embolic purulent nephritis
(often found in septicopyemia):
• The kidney is enlarged in size,
• Cortex and medulla show multiple small yellowish foci (purulent
inflammation).
Foreign bodies embolism
• Catheters, bullets, as well as crystals of cholesterol from ulcerating
atherosclerotic plaques
Shock
• Shock - circulatory collapse, accompanied by hypoperfusion of tissues
and decrease in their oxygenation.
 Shock morphology
• Kidney:
• Necrotizing nephrosis (acute renal failure)
• Lungs:
• Adult Respiratory Distress Syndrome (ARDS).
• Foci of atelectasis,
• Serous hemorrhagic edema with accumulation of fibrin in lumen of the alveoli (hyaline
membranes),
• Stasis and thrombi in microcirculatory bed.
• Liver:
• Centrolobular necrosis.
• Brain:
• Foci of necrosis,
• Minor hemorrhages.
• Gastrointestinal tract:
• Hemorrhages.
Disseminated intravascular blood coagulation
syndrome (DIC)
• The syndrome of disseminated intravascular coagulation of blood
(coagulopathy of consumption, thrombohemorrhagic syndrome) - a
condition, characterized by the formation of multiple blood clots in
the vessels of the microvasculature due to the activation of
coagulation factors and developing deficit with subsequent activation
of fibrinolysis and development of numerous hemorrhages.
Stages of DIC
• Stage I - hypercoagulation and thrombus formation:
• It is characterized by intravascular aggregation of blood cells, disseminated blood
coagulation with the formation of multiple blood clots in microvessels of various
organs and tissues.
• As a rule, it is short-term, duration up to 8 -10 min.
• Clinically manifests as a shock.
• Stage II - increasing coagulopathy of consumption:
• Characterized by a significant decreased amountof platelets and fibrinogen, spent on
the formation of thrombi.
• There is a transition from hyper- to hypocoagulation, manifesting by hemorrhagic
syndrome.
• Removal of active coagulation factors from the blood stream is due to phagocytosis,
so the presence of fibrin in cytoplasm of macrophages and neutrophils is
confirmation of this stage.
Stages of DIC
• Stage III - pronounced hypocoagulation and activation fibinolysis:
• There is a lysis of previously formed microthrombi and often the degradation
of circulating clot factors
• Developing hyperplasminemia leads to the appearance of readily soluble and
fibrin-containing complexes, fibrin degradation products, and fibrin-monomer
looses its ability to polymerize.
• It usually develops 2 to 8 hours after the onset of DIC.
• Complete blood incoagulability, severe bleeding and hemorrhage,
microangiopathic hemolytic anemia are noted.
Stages of DIC
• Stage IV - Restorative (residual manifestations):
• Dystrophic, necrotic and hemorrhagic lesions of organs and tissues.
• In most cases, there is a reverse development of tissue changes.
• In severe cases of DIC syndrome, lethality is 50% due to acute polyorganic
insufficiency.
• In newborns, especially premature born, mortality is 75 - 90% (due to
imperfect fibrinolytic system, insufficient synthesis of liver clotting factors,
etc.)
 Morphology of DIC
• Morphology and morphogenesis of DIC syndrome are due to a number of
factors, among which an important role play:
• The main disease,
• DIC triggering mechanisms,
• Time,
• Treatment measures
• Regardless of the combination of these factors, the main morphological
manifestations of DIC syndrome are:
• Microthrombi,
• Necrosis,
• Hemorrhages.
 Morphology of DIC
• Multiple microthrombi in the vessels of microcirculatory bed:
• Fibrin clots:
• Detected most often and in the largest quantity.
• Consist of fibrin with single red blood cells.
• Hyaline thrombi,
• White (leukocytic) thrombi,
• Red (erythrocyte) blood clots.
 Morphology of DIC
• Lungs:
• Serous-hemorrhagic edema,
• Fibrin and hyaline thrombi,
• Sludge and agglutination of erythrocytes,
• Multiple hemorrhages,
• Small hemorrhagic infarctions (in some cases),
• Hyaline membranes (consisting of fibrin).
• Pancreas:
• Edema,
• Hemorrhages,
• Microthrombi,
• In severe cases, pancreatic necrosis.
 Morphology of DIC
• Kidney:
• Dystrophy of the proximal and distal convoluted tubules epithelium,
• In severe cases, necrotic nephrosis (necrosis tubular epithelium, tubulorhexis,
symmetrical focal and total corticonecrosis),
• Multiple hemorrhages, incl. subcapsular,
• Multiple microtrombi.
• Liver:
• Dystrophic and necrotic changes in hepatocytes (up to centrolobular necrosis),
• Fibrin thrombi in the central veins,
• filaments of fibrin lying freely in sinusoids.
“Shock kidney”
“Shock liver”
 Morphology of DIC
• Adrenal glands:
• Dystrophy with loss of lipids and necrosis of cells in cortex and medulla,
• Multiple microthrombi,
• Extensive hemorrhage (Waterhouse –Friderixen syndrome).
• Skin:
• Multiple petechial hemorrhages,
• Rarely - extensive hemorrhages (ecchymosis),
• Small necrotic foci (in some cases).
• Gastrointestinal tract:
• Multiple small hemorrhages,
• Erosions and acute ulcers.
 Morphology of DIC
• Spleen
• Small-scale hemorrhages in parenchyma and capsule
• Hyaline and fibrin thrombi in small arteries and veins
• Fibrin fibers in sinusoids
• Myocardium and brain (rarely affected)
• Single microtrombi
• Dystrophic changes
• Edema