Hemodynamic disorders. Arterial and venous hyperemia. Hemorrhages. Classification.

Questionary Systemic hemodynamic disorders –

generalized venous hyperemia. Arterial hyperemia and local venous

hyperemia. Hemorrhages. Normal hemostasis. Thrombosis – pathogenesis.

Morphology of thrombus. Evolution. Special features of thrombus

according to the localization. Fate of thrombus.

Normal fluid homeostasis/ Hemodynamic disorders

Normal fluid homeostasis requires

vessel wall integrity maintenance of

intravascular pressure and osmolarity within physiologic ranges

Normal hemostasis Microcirculation

Arterioles, capillaries, venules

Hemodynamic disorders

Hemodynamic disorders

Hyperemia Local inceased blood volume,

congestion Hemorrhages

Blood loss, shock Thrombosis

inappropriate clotting Embolism

migration of clots Ischemia/Infarctus

Obstruction of tissue blood supplies Oedemas

water extravasation into interstitial spaces

The most important causes of morbidity and mortality in Western society

myocardial infarction, pulmonary embolism, and cerebrovascular accident (stroke).

Hyperemia A local increased volume of

blood in a particular tissue Dilatation of small vessels

Two types Arterial (active) hyperemia-

hyperemia from augmented blood flow

due to arteriolar dilation Venous hyperemia-congestion,

cyanosis a passive process resulting

from impaired venous return out of a tissue

closely related to the development of edema

so that congestion and edema commonly occur together

Arterial hyperemia Active process

Due to arteriolar dilatation Sympathic stimulation The affected tissue is redder

than normal because of engorgement with oxygenated blood

Examples at sites of inflammation in skeletal muscle during

exercise Angioneurothic – face redness

Venous hyperemia/congestion

A passive process resulting from impaired venous return out of a tissue.

Two types Systemic, generalized - in cardiac

failure Acute/chronic

Local – in an isolated venous obstruction

The tissue has a blue-red color (cyanosis)

especially in worsening congestion, which leads to accumulation of deoxygenated hemoglobin in the affected tissues

Systemic venous hyperemia

Congestion- a common clinical term

often used interchangeably with the term edema or hyperemia

Heart failure Left-sided heart failure-LUNG

acute chronic

Right-sided heart failure- LIVER acute Chronic

Both sides

Left-sided heart failure=LUNG

The morphologic and clinical effects of left-sided CHF primarily result from the retension of blood within the pulmonary circulation

contractility of left ventricle, unable to eject the blood delivered to it during sistola

The most common causes of left-sided cardiac failure are

(1) CHD, (2) systemic hypertension, (3) mitral or aortic valve disease, and (4) primary diseases of the myocardium

Acute LHF =oedema pulmonum Myocardial infarction

Chronic LHF = induratio fusca pulmonum

Left-sided heart failure=LUNG

Morphology

Macroscopy/Microscopy The extracardiac effects of left-sided

heart failure are manifested most prominently in the lungs.

Acute pulmonary congestion and edema

The lungs are heavy and wet histologically there are perivascular and

interstitial transudate, alveolar septal edema, and intra-alveolar edema

Chronic pulmonary congestion the septa become thickened and fibrotic,

and the alveolar spaces may contain numerous hemosiderin-laden macrophages ("heart failure cells").

Perl’s staining for Fe+ – blue granules

ACUTE PULMONARY EDEMA

Chronic pulmonary congestion = Induratio fusca pulmonum

Heart failure cells -hemosiderin laden macrophages

Right-sided heart failure- LIVER

The major morphologic and clinical effects of pure right-sided heart failure result from the retention of blood within of the systemic and portal venous systems

with hepatic and splenic enlargement, peripheral edema, pleural effusion, and ascites.

The most common causes of right-sided cardiac failure are: consequence of left-sided heart failure

any pressure increase in the pulmonary circulation inevitably produces an increased burden on the right side of the heart

Less common - in chronic pulmonary hypertension (cor pulmonale)

intrinsic disease of lung parenchyma and/or pulmonary vasculature (pulmonic or tricuspid valve disease)

Acute RHF = cyanosis hepatis Embolia a.pulmonalis

Chronic RHF = hepar moshatum

Right-sided heart failure- LIVER

Morphology Macroscopy/Microscopy

Liver and Portal System The liver is usually increased in size

and weight (congestive hepatomegaly)

a cut section displays prominent passive congestion, a pattern referred to as nutmeg liver

congested red centers of the liver lobules are surrounded by paler, sometimes fatty, peripheral regions.

Acute congestion –cyanosis hepatis vv. centrales –dilated (severe

central hypoxia may produce centrilobular necrosis) and sinusoidal congestion.

Chronic congestion- hepar moshatum

With long-standing severe right-sided heart failure, the central areas can become fibrotic, creating so-called cardiac cirrhosis

Liver –acute/chronic congestion

ACUTE/CHRONIC PASSIVE HYPEREMIA LIVER

Cyanosis hepatis/Hepar Moschatum

• Necrosis in the cental part of the hepatic lobule, statosis – in the middle part and no change in periportal part• can progress to cirrohisis – cardiac cirrhosis

dilated vv. centrales and sinusoidal congestion

Right-sided heart failureMorphology

Right-sided heart failure also leads to elevated pressure in the portal vein other organs and transudate

congestive splenomegaly enlarged spleen, can achieve weights of 300 to

500 gm (normal <150 gm). Microscopically, there can be marked sinusoidal

dilation. Congestive kidneys

Enlarged, dark red surface Microscopically, there can be marked glomerular

loops dilation and protein accumulations in the lumen of the tubules (congestive proteinuria).

Accumulations of transudate in the peritoneal cavity – ascites in the pleural space (particularly right)-

effussions in the pericardial space - effusions. Peripheral edema of dependent portions of the

body, especially ankle (pedal) and pretibial edema

Generalized massive edema is called anasarca.

Local venous hyperemia In isolated venous obstruction - some

organs Varied severity, depends on:

The time of appearance of congestion gradually/suddenly

The presence of collaterals, anastomoses Examples

Peripheral venous failure of the legs –valve failure of the veins

Liver ciirhosis –portal hypertension the formation of portosystemic venous

shunts, with the rise in portal venous pressure

veins around and within the rectum (manifest as hemorrhoids),

the cardioesophageal junction (producing esophagogastric varices),

the retroperitoneum -periumbilical and abdominal wall collaterals-caput medusae

Acute venous obstruction + (-) collaterals haemorrhagic necrosis

V. mesenterica –gut V. lienalis V. renalis

Hypostasis

Type of venous hyperemia Where the blood detained in low body

portions In severe ill patients -lungs

Hypostatic pneumonia

HEMORRHAGE Extravasation of blood from vessels into the

extravascular space. 2 types

per rhexin -rupture of a large artery or vein results in severe hemorrhage

due to vascular injury, including trauma, atherosclerosis, or inflammatory or neoplastic erosion of the vessel wall.

per diapedesin (capillary bleeding) chronic congestion, hypoxia-pulmo toxic injury-brain

Hemorrhagic diatheses - clinical disorders with increased tendency to hemorrhage

HEMORRHAGE Hematoma - any accumulation of blood

can be external or can be confined within a tissue can be relatively insignificant (e.g., a bruise) or can involve so much bleeding as to

cause death (e.g., a massive retroperitoneal hematoma resulting from rupture of a dissecting aortic aneurysm

External hemorrhages - into skin, mucous membranes, or serosal surfaces petechiae (1-2mm) –platelets

associated with locally increased intravascular pressure, low platelet counts (thrombocytopenia), defective platelet function, or clotting factor deficiencies

purpura - <1cm (3- to 5-mm) can be associated with many of the same disorders that cause petechiae in addition, can occur with trauma, vascular inflammation (vasculitis), or increased vascular

fragility ecchymoses - larger, >1cm

subcutaneous hematomas (bruises) the hemoglobin (red-blue color) is enzymatically converted into bilirubin (blue-green color) and

eventually into hemosiderin (golden-brown), accounting for the characteristic color changes in a hematoma.

Large accumulations of blood in one or another of the body cavities are called hemo-:

-thorax, -pericardium, -peritoneum, hemarthrosis (in joints).

Acute/chronic

Haemorrhagiae punctatae cerebri

Punctate petechial hemorrhages of the colonic mucosa in

thrombocytopenia Fatal intracerebral hemorrhage

Subcutaneous hematomas (bruises), with characteristic color changes in a hematoma.

HEMORRHAGE The clinical significance of

hemorrhage depends on: the volume and rate of blood loss

rapid removal of as much as 20% of the blood volume or slow losses of even larger amounts may have little impact in healthy adults;

greater losses can cause hemorrhagic (hypovolemic) shock

The site of hemorrhage In subcutaneous tissues/ in the brain

Duration chronic or recurrent external blood loss

(e.g., a peptic ulcer or menstrual bleeding) causes a net loss of iron, frequently culminating in an iron deficiency anemia

HEMOSTASIS AND THROMBOSIS

Normal hemostasis is a consequence of tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels

inducing the rapid formation of a localized hemostatic plug at the site of vascular injury.

Thrombosis -the pathologic form of hemostasis it involves blood clot (thrombus) formation in uninjured

vessels or thrombotic occlusion of a vessel after relatively minor injury.

Both hemostasis and thrombosis involve three components

the endotelium the platelets, and the coagulation cascade

ENDOTHELIUM

NORMALLY ANTIPLATELET PROPERTIES ANTICOAGULANT PROPERTIES FIBRINOLYTIC PROPERTIES

IN INJURY PRO-COAGULANT PROPERTIES

It can be activated by infectious agents, hemodynamic factors, plasma

mediators, and cytokines

PLATELETS

Play a critical role in normal hemostasis. When circulating and nonactivated they are membrane-bound

smooth disks expressing several glycoprotein receptors of the integrin family and containing two types of granules:

ALPHA GRANULES Fibrinogen Fibronectin Factor-V, Factor-VIII Platelet factor 4, TGF-beta

DELTA GRANULES (DENSE BODIES) ADP/ATP, Ca+, Histamine, Serotonin, Epineph.

With endothelium, form TISSUE FACTOR

Coagulation Cascade

The third component of the hemostatic process and is a major contributor to thrombosis

An amplifying series of enzymatic conversions; each step in the process proteolytically cleaves an inactive proenzyme into an activated enzyme, eventually culminating in thrombin

The fibrinolytic system

Moderates the size of the ultimate clot plasminogen plasmin

by plasminogen activators - t-PA, Urokinase-like PA (u-PA) , streptokinase

the activity of plasmin is also tightly restricted by: circulating α2-antiplasmin, PAIs (endotelial cells)

Normal Hemostasis A, After vascular injury, local neurohumoral

factors induce a transient vasoconstriction.

B, Platelets adhere (via GpIb receptors) to exposed extracellular matrix (ECM) by binding to von Willebrand factor (vWF) and are activated, undergoing a shape change and granule release.

Released adenosine diphosphate (ADP) and thromboxane A2 (TXA2) lead to further platelet aggregation (via binding of fibrinogen to platelet GpIIb-IIIa receptors), to form the primary hemostatic plug.

C, Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, "cementing" the platelets into a definitive secondary hemostatic plug.

D, Counter-regulatory mechanisms, such as release of t-PA (tissue plasminogen activator, a fibrinolytic product) and thrombomodulin (interfering with the coagulation cascade), limit the hemostatic process to the site of injury.

COAGULATION TESTS

(a)PTT INTRINSIC (HEP Rx) PT (INR) EXTRINSIC (COUM Rx) BLEEDING TIME (PLATS) (2-9min) Platelet count

(150,000-400,000/mm3) Fibrinogen Factor assays