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HEMODYNAMICS AND RELATED DISORDERS

 Hemodynamics deals with flow and distribution of blood and fluids within the
body.
 Recall:
 The normal body in an average adult male is composed of 60% water (Total
body water).
 The total body water is distributed into two main compartments of body fluids
separated from each other by membranes freely permeable to water
o Extracellular fluid (ECF): has a high concentration of sodium and low
concentration of potassium
o Intracellular fluid (ICF): has a high concentration of potassium and low
concentration sodium
 Extracellular fluid accounts for 20% of the total body water (1/3). In a closed
vascular system, ECF is divided into 2 compartments:
o Interstitial fluid (Third space): consists of ¾ (75%) of ECF.
 The composition of interstitial fluid is the same as that of plasma
except that it has little protein (interstitial fluid is an ultra-filtrate of
plasma).
 Interstitial fluid also contains transcellular fluid e.g. CSF
(cerebrospinal fluid), humors (in the eye), synovial fluids, secretions
of the GIT (saliva, luminal fluids of the gut), thyroid, cochlea fluid,
pericardial fluid and fluid between layers e.g. pleura and peritoneum.
o Plasma: plasma and its cellular components constitute total blood volume
(about 5-8% of the body weight). On an average out of 5L of total blood
volume 3L is plasma.
 Intracellular fluid: accounts for about 40% of body water (2/3), the bulk of
which is found in muscles (which are made up of 80% water)
 Flow between the ECF and ICF is regulated.
 2 barriers separate ICF, interstitial fluid and plasma
o Plasma membrane separates ICF from ECF
o Blood vessel walls divide the interstitial fluid from plasma
 The normal distribution of total body water in the fluid compartments is kept
constant by two opposing sets of forces: Hydrostatic and osmotic pressure.
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Figure 1:Body fluid compartments

Figure 2: Body fluids

 To maintain the correct amount of intravascular and extravascular volumes

hydrostatic pressure should equal osmotic pressure.
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 Outflow of fluid from arterial ends into the interstitium nearly equals inflow from
venular end however, small residual amounts left in interstitium drain by
lymphatic vessels. This fluid ultimately returns to blood circulation through the
thoracic duct.
 Hydrostatic pressure is the force exerted on the walls of a container by the
molecules of a substances within the container. It tends to push fluid out of the
vascular space.
 In vessels, hydrostatic pressure refers to the pressure pushing fluid out into the
interstitial tissue.
 In the interstitial tissue hydrostatic pressure pushes fluid back into the vessels.
 Osmotic pressure is the pressure that would have to be applied to a pure solvent
to prevent it passing into a given solution by osmosis. It tends to pull fluid into
the vascular space.
 Osmotic pressure is imparted by the presence of dissolved solutes
 Colloid pressure (oncotic pressure) is a form of osmotic pressure exerted by
proteins, notably albumin in a blood vessel. It tends to pull water into the
circulatory system.
 An imbalance between the hydrostatic and osmotic pressure results in an
abnormal distribution of fluid in the cells or interstitial tissues, a condition
referred to as edema.

EDEMA
 This is accumulation of fluid within the cells, interstitial tissues and body cavities.
 Recall: Outflow of fluid from arterial ends into the interstitium nearly equals
inflow from venular end however, small residual amounts left in interstitium
drain by lymphatic vessels. This fluid ultimately returns to blood circulation
through the thoracic duct. Therefore, edema is due to increased capillary pressure
or decreased colloid osmotic pressure. If movement of water into tissues or body
cavities exceeds lymphatic drainage fluid accumulates.
PATHOPHYSIOLOGY AND ETIOLOGY OF EDEMA
 Edema is due to:
 Increased vascular hydrostatic pressure: usually due to impaired venous return
or arteriolar dilation.
 Decreased plasma osmotic pressure
 Lymphatic obstruction
 Inflammation
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INCREASED HYDROSTATIC PRESSURE

 Due to either impaired venous return or arteriolar dilation
 Impaired venous return may be caused by:
 Congestive cardiac failure (Right sided hear failure results in peripheral
edema, left sided heart failure results in pulmonary edema and biventricular
heart failure results in generalized edema): the heart is not pumping blood as
effectively as it should, so there is back up of blood into the veins.
 Constrictive pericarditis: inflammation of the pericardium results in impaired
venous return and congestion of blood in venous system.
 Cirrhosis (ascites): fibrous scarring of the liver impairs return of blood
through the portal vein, thereby increasing venous pressure in portal vein
tributaries and causing fluid to leak into the peritoneal cavity.
 Venous obstruction/compression:
o Thrombosis
o External pressure e.g. mass
o Lower extremity inactivity with prolonged dependency
 Arteriolar dilation can because caused by neurohumoral dysregulation.
DECREASED PLASMA OSMOTIC PRESSURE
 Decreased production of proteins notably albumin: decreased albumin levels
results in edema (decreased osmotic colloidal pressure), the decrease in
intravascular volume stimulates the production of aldosterone (Renin-
angiotensin system) which promotes sodium and water retention contributing
further to edema formation.
 Malnutrition: decreased dietary intake leading to insufficient raw materials to
synthesize adequate proteins
 Liver cirrhosis (ascites): the liver is unable to synthesize adequate albumin
 Loss of proteins:
 In the kidneys (protein losing glomerulopathy e.g. nephrotic syndrome)
 Protein losing gastroenteropathy
LYMPHATIC OBSTRUCTION
 Due to blockage of lymphatics by inflammation (parasitic infestations e.g.
elephantiasis), neoplasms, post-surgery, or post-irradiation.
 It causes lymphedema.
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INFLAMMATION
 Acute inflammation results in increased vascular permeability
 Chronic inflammation
 Angiogenesis: blood vessels during angiogenesis are leaky
TYPES OF EDEMA
 Anasarca- generalized edema with widespread subcutaneous tissue swelling. It is
most commonly associated with glomerular protein loss by the kidneys.
 Periorbital edema- seen around the eyes, occurs in renal disease
 Fluid collections in various body cavities:
 Hydrothorax: accumulation of fluid in the pleural cavity (pleural effusion)
 Chylothorax: lymph in the pleural space
 Hydropericardium: abnormal accumulation of fluid in the pericardial cavity
(pericardial effusion)
 Hydroperitoneum: abnormal accumulation of fluid in the peritoneal cavity
(ascites)
 Nature/content of edema:
 Transudate:
o This is non-inflammatory edema due to increased hydrostatic pressure or
decreased plasma proteins (decreased osmotic pressure).
o It has a low protein content, little or no cellular material
o Low specific gravity (<1.012)
o It is an ultra-filtrate of blood plasma
o It is seen in cardiac failure
 Exudate:
o This is due to increased vascular permeability due to either inflammation
or malignancy.
o It is a protein rich fluid
o It contains cellular debris (large number of inflammatory leukocytes) and
because the metabolically active leukocytes consume glucose, the glucose
content is often greatly reduced.
o Has a high specific gravity (>1.020)
o Associated with inflammation e.g. empyema thoracis
 Pitting edema: When the skin and underlying soft tissues of the leg with edema
are compressed with fingers, the impressions remain. This is commonly
associated with heart failure and is usually a transudate.
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 Non-pitting edema: edema is not easily compressed with fingers. It is due to

presence of glycosaminoglycan in the edema fluid.
 Dependent edema: occurs in the extremities and areas of the body where
accumulation of fluid is dependent upon gravity. It is commonly associated with
heart failure.
EFFECTS OF EDEMA
 Depend on the organ involved.
 Edema is commonly seen in subcutaneous tissues, lungs and brain.
 It can be:
 Pitting or non-pitting
 Localized or generalized
 In soft tissues of the extremities edema usually produces no clinically significant
damage. Over time edema can cause changes in the skin but these are usually
only cosmetic.
 In the lungs (pulmonary edema): edema fluid (frothy blood stained fluid) fills the
alveoli and pleural cavities impairing the ability of the lung to oxygenate the red
blood cells.
 In the brain: the brain is in a rigid compartment, edema causes the brain to swell,
producing increased intracranial pressure. There is narrowing of the sulci and
distention of the gyri. When the brain swells, there are only a few places into
which it can expand. These expansions of the brain through available spaces are
called herniation. Types of herniations include:
 Sub-falcine
 Uncal
 Cerebellar tonsillar

HEMORRHAGE
 The integrity of the vessel wall plays a critical role in maintaining normal
distribution of fluid in the vessels and interstitial tissues as well as keeping blood
and its components confined to the vascular space.
 Hemorrhage is the escape of blood from the vasculature into surrounding tissue,
a hollow organ or body cavity or to the outside.
 It is most often caused by trauma.
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TYPES OF HEMORRHAGE
 Petechiae (1-2mm): pinpoint
hemorrhages that occur in the skin,
mucous membranes and serosal
surfaces. Caused by platelet dysfunction
and increased vascular pressure
 Purpura (>3mm): larger than petechiae
and usually raised (palpable). They are
common associated with vasculitis.
 Echymoses: Diffuse hemorrhage
usually in the skin and subcutaeneous
Figure 3: Petechial hemorrhage in the palpebral
tissue. They are larger than purpura (>1 conjunctiva
cm). Are due to trauma
TERMINOLOGY ASSOCIATED WITH HEMORRHAGE
 Hematoma: It is a localized hemorrhage that occurs within a tissue or organ
(space-occupying hemorrhage).
 Hemothorax: hemorrhage within the pleural cavity
 Hemopericardium: hemorrhage within the pericardial sac
 Hemoperitoneum: hemorrhage within peritoneal sac
 Hemarthrosis: hemorrhage in the synovial space

HYPEREMIA AND CONGESTION

 Hyperemia is active accumulation of blood within vessels such as would occur
in vasodilation due to acute inflammation (Localized increase in volume of blood
in capillaries and small vessels)
 Acute hyperemia develops in a short space of time and is caused by localized
arteriolar dilation (e.g. blushing, inflammation)
 Congestion is passive accumulation of blood within vessels such as would occur
in the lungs due to left sided heart failure or in the liver and extremities due to
the right-sided heart failure. It is caused by obstructed venous return or increased
back pressure from congestive heart failure.
 Acute passive congestion: passive congestion that developed recently. It
occurs in shock, acute inflammation, or sudden right-sided heart failure
 Chronic passive congestion: passive congestion that has been occurring over
time and is often associated with hemosiderin-laden macrophages and organ
damage.
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o Chronic passive congestion of the

lung is most often caused by left
sided heart failure or mitral
stenosis.
 Congestion and distention of
alveolar capillaries leads to
capillary rupture and passage of
red cells into the alveoli
 Phagocytosis and degradation
of red cells results in intra-
alveolar hemosiderin-laden
macrophages called heart
Figure 4: Chronic passive congestion of the lung. Note:
failure cells. Alveolar septal fibrosis and hemosiderin-laden
 In longstanding congestion, macrophages (arrows) the so called "heart failure cells"
fibrosis of interstitium and
hemosiderin deposition results
in brown induration of the
lung.
o Chronic passive congestion of the
liver and lower extremities is
often caused by right sided heart
failure.
 Nutmeg liver, a speckled,
nutmeg-like appearance on a
cut section may occur.
 The condition is produced by
a combination of dilated,
congested central veins and Figure 5: Chronic passive congestion of the liver.
shrunken and congested centrilobular areas impart the
the surrounding brownish- characteristic "nutmeg" appearance of the liver. This
yellow, often fatty, liver cells. finding is most commonly associated with right sided
congestive heart failure
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HEMOSTASIS AND THROMBOSIS

 Normal hemostasis is the process of maintaining blood in a fluid state in normal
vessels. It is the spontaneous arrest or prevention of bleeding from the
injured/damaged vessels by physiological processes.
 Thrombosis is the formation of a thrombus (blood clot) in intact vessels.
 Both these processes involve 3 components:
 Vascular wall (endothelium)
 Platelets
 Coagulation cascade
 The process of coagulation serves to maintain the integrity of the vasculature in
the event of disruption of the vascular wall.
 Inappropriate coagulation can have deleterious consequences however for
example abnormal coagulation can result in vessel occlusion thus the process
must be closely controlled.
HEMOSTASIS
 Hemostasis occurs in 3 steps:
 Vasoconstriction
 Platelet plug formation
 Coagulation of blood
VASOCONTRICTION
 Immediately after injury the blood vessel constricts (initial constriction) and
decreases the loss of blood from the damaged portion.
 Usually arterioles and small arteries constrict.
 Vasoconstriction is purely a local phenomenon brought about by:
 Neural reflex resulting in release of vasoconstrictors
 Local smooth muscle spasms due to injury
 Release of endothelin from injured endothelium
 When blood vessels are cut the endothelium is damaged and collagen is exposed.
Platelets adhere to the exposed collagen and become activated. Activated
platelets secrete serotonin and other vasoconstrictor substances to cause
vasoconstriction.
 Adherence of platelets to collagen is accelerated by VonWille Brand factor (it
acts as a bridge between a specific glycoprotein present on the surface of platelets
and collagen fibrils).
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PLATELET PLUG FORMATION

 Following injury, platelets come in contact with damaged collagen fibers and
endothelial cells of the vessel wall and change their characteristics (they begin to
swell and assume irregular forms with large number of pseudopodia protruding
to the surface).
 Contractile proteins of platelets contract and cause granules inside the platelet
containing multiple factors including ADP and thromboxane A2.
 All the platelets aggregate to form a loose temporary platelet plug/temporary
hemostatic plug which closes the
ruptured vessels and prevents further
blood loss (primary hemostasis).
 Platelet activating factor (PAF) a
cytokine released by neutrophils,
monocytes and platelet cell
membrane lipids accelerates platelet
aggregation.
BLOOD COAGULATION
 Coagulation is the process which
converts soluble fibrinogen into
fibrin.
 Note: blood coagulation does not
necessarily need platelets, red blood
cells and white blood cells.
 In coagulation the temporary platelet Figure 7: Hemostasis
plug is converted into a definitive
hemostatic plug by the process of clot
formation (blood coagulation) which
involves a complex series of events.
 Fibrinogen is converted to fibrin
(Secondary hemostasis). Fibrin threads
get attached to the loose platelet plug,
which blocks the ruptured part of blood
vessel and prevents further blood loss.
 Note that counter-regulatory mechanisms
are set into motion e.g. tissue-plasmin
Figure 6: Fibrinolysis
activator (t-PA) to remove the blood clot.
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 The proenzume plasminogen is converted by proteolysis to plasmin (the most

important fibrinolytic protease). Plasmin splits fibrin. It is classic teaching that
factor XII to XIIa activation links the fibrinolytic system, coagulation system,
complement system and kinin system.
CLOTTING FACTORS
 There are 13 clotting factors involved in the coagulation of blood, they are given
roman numerals.
 To indicate the activated form of the factor a small letter “a” is added after the
roman numeral such as factor VIIa to indicate activated factor VII.
 Clotting factors were named after the scientist who discovered them or as per
activity except for factor IX (Christmas factor) which was named after the patient
in whom it was discovered.

Figure 8: Clotting factors

 Note: Factor II, VII, IX and X are vitamin K dependent factors.

 Vitamin K is a fat soluble vitamin along with vitamins A, D and E.
CLOTTING/COAGULATION CASCADES
 These have been described as following 2 distinct but interconnected pathways.
 Extrinsic pathway
 Intrinsic pathway
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EXTRINSIC PATHWAY
 It is initiated by tissue factor, which activates factor VII and forms a tissue factor-
Factor VIIa complex.
 The complex initiates coagulation through activation of factor X to factor Xa (and
additionally factor IX to factor IXa).
 Factor Xa converts prothrombin (Factor II) to thrombin (factor IIa). Factor Va is
a co-factor required in the conversion of prothrombin to thrombin.
 Thrombin converts fibrinogen to fibrin which is stabilized by factor XIII (fibrin
stabilizing factor)
 The extrinsic pathway is clinically evaluated by the prothrombin time (PT) which
is a measure of factors II, V, VII, X and fibrinogen.
INTRINSIC PATHWAY
 It involves activation of all clotting factors with the exception of factors VII and
XIII.
 This pathway may involve contact activation with interactions of the so called
contact factors: factor XII (Hageman factor), prekallikrein and high molecular
weight kininogen as well as factor XI.
 Contact activation is important in invitro clotting in glass containers and in
laboratory testing, but its physiologic role has been questioned because a
deficiency of the contact factors is not associated with abnormal bleeding.
 It is probably initiated by the tissue-factor-factor VIIa complex (From the
extrinsic pathway), activating factor IX to factor IXa.
 Factor IXa in turn leads to conversion of factor X to factor Xa, catalyzed by factor
VIIIa.
 Thrombin production further stimulates the pathway by the activation of factor
XI to factor Xia and by activation of co-factors factor V to factor Va and factor
VIII to factor VIIIa.
 The intrinsic pathway is evaluated by partial thromboplastin time (PTT) which is
a measure of factors II, V, VIII, IX, X, XI,XII and fibrinogen
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Figure 9: Coagulation cascade

 Clotting is regulated by 3 natural anticoagulants:

 Antithrombins e.g. antithrombin III
 Protein C and S- vitamin K dependent factors that inactivate factors V, VIII
 Tissue factor pathway inhibitor inactivates X, VIII
 Fibrinolytic cascade limits size of final clot
 Generation of plasmin from plasminogen by plasminogen activators (PAs)
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 Resulting fibrin degradation products act as weak anticoagulants

 Fibrin degradation products (D-dimers) are helpful in diagnosis of abnormal
thrombotic states e.g. deep vein thrombosis, DIC
 Disorders of hemostasis will be discussed under hematology section.
THROMBOSIS
 Thrombosis is intravascular coagulation of blood, often causing significant
interruption of blood flow.
 Recall: Endothelial cells prevent thrombosis by several mechanisms including:
 Block exposure to subendothelial collagen and underlying tissue factor
 Production of prostacyclin (PGI 2)- blocks platelet aggregation and NO-
causes vasodilation
 Secretion of heparin-like molecules- augment antithrombin III (ATIII) which
inactivates thrombin and coagulation factors
 Secretion of Tissue plasminogen activator (tPA)- converts plasminogen to
plasmin which
o Cleaves fibrin and serum fibrinogen
o Destroys coagulation factors
o Blocks platelet aggregation
 Secretion thrombomodulin- redirects thrombin to activate protein C, which
inactivates factors V and VIII
 Thrombogenesis occurs when there is injury to the endothelium which can be as
a result of infectious agents, hemodynamic factors, plasma mediators or
cytokines.
 Factors predisposing to thrombus formation (i.e. Virchow triad)
 Alteration in normal blood flow
o Turbulence causes end injury or local stasis. Recall normal blood flow is
laminar (flows in “layers”)
o Stasis and turbulence disrupts laminar flow.
o Stasis of blood: this is a common predisposing condition in patients who
develop venous thrombi. Stasis can be due to congestive heart failure,
obesity, immobilization.
 Hypercoagulability: hypercoagulable states may contribute to the
development of thrombi in any location the can either be:
o Primary: mutation or deficiency in coagulation factors
o Secondary:
 Prolonged bed rest or immobilization
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 Myocardial infarction, atrial fibrillation

 Tissue damage: surgery, fractures, burns
 Cancer, prosthetic cardiac valves, DIC
 Pregnancy, oral contraceptive use
 Endothelial damage: exposes sub-endothelial collagen and plays a major role
in arterial thrombi.
 Thrombotic disorders to be discussed under hematology.
MORPHOLOGY OF A THROMBI
ARTERIAL THROMBI
 These thrombi are formed in areas of active blood flow.
 When mature they demonstrate alternate dark gray
layers of platelets interspersed with lighter layers of
fibrin. This layering results in the lines of Zahn.
 Eventually they liquefy and disappear or are
organized with fibrous tissue formation.
Recanalization, new blood vessel formation within
a thrombus restores blood flow.
 Arterial thrombi are usually occlusive and effects
depend on the vessels involved and the presence of Figure 10: Lines of Zahn (alternating
collateral circulation. layers of platelets/fibrin and RBCs)

VENOUS THROMBI (PHLEBOTHROMBOSIS)

 These thrombi are formed in areas of less active blood flow, most often in the
veins of the lower extremities and in the periprostatic or other pelvic veins.
 They are predisposed by venous stasis with a high incidence occurring in
hospitalized patients on bed rest.
 They are dark red with higher concentration of red cells than arterial thrombi.
 Lines of Zahn are not prominent or are absent.
 They are often associated with concurrent venous inflammatory changes.
Inflammation of veins with thrombus formation is referred to as
thrombophlebitis.
 Venous thrombi are usually occlusive and effects depend on the vessels involved
and the presence of collateral circulation.
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POSTMORTEM CLOTS
 These clots appear soon after death and are not true thrombi. In contrast to true
thrombi, they are not attached to the vessel wall and lack lines of Zahn.
 Settling of red cells results in 2 layered appearance: Currant jelly appearance in
the red cell-rich lower layer and a chicken fat appearance in the cell-poor upper
layer.
FATE OF THROMBUS
 Propagation: accumulates more platelets and fibrin leading to obstruction
 Dissolution: thrombus removed by fibrinolytic activity
 Organization and recanalization: thrombus may induce inflammation and fibrosis
(organization) and may eventually become recanalized.
 Embolization: thrombus may dislodge and travel to other sites
COMPLICATIONS OF THROMBI
 Occlusion of blood vessels leads to ischemia. Ischemia causes cell injury and cell
death (necrosis). The region of necrotic cells is referred to as an infarct.
EMBOLUS
 An embolus is a substance that forms within or enters the vascular system at one
site and is carried through the blood stream to another area of the body, where it
lodges in a blood vessel and produces its effects (usually infarcts).
 If a thrombus breaks free from where it forms and goes to another part of the
body it becomes a thromboembolus. Most emboli are thromboembolic in nature
 Substances besides thrombi such as cardiac valvular vegetations, foreign bodies,
fat, amniotic fluid and air can also embolize.
TYPES OF EMBOLI
PULMONARY THROMBOEMBOLUS
 95% arise from veins of the legs (deep venous thrombi).
 Note most thrombi from deep veins get trapped in the pulmonary vasculature
because of the small size however if an individual has an atrial septal defect the
thrombi may bypass the lungs and lodge in the brain this type of an emboli is
called a paradoxical embolus.
 They may impact across bifurcation e.g. at the bifurcation of the pulmonary trunk
(saddle embolus)
 Most are clinically silent because they are small and in time undergo
organization.
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 Sudden death, cor pulmonale, cardiovascular collapse occurs when 60%

obstruction occurs.
 Obstruction of medium sized arteries may not cause pulmonary infarction due to
dual blood supply from bronchial arteries however pulmonary infarcts typically
occur when a patient has a thromboembolus in combination with a condition that
compromises the bronchial circulation e.g. congestive heart failure or in
combination with pneumonia. The classic radiologic finding is a Hampton Hump,
a wedge shaped pleural infiltrate in the lower lobe (it is rarely seen).
 Multiple emboli over time may cause pulmonary hypertension.
 Clinical features:
 Sudden onset of chest pain
 Dyspnea, tachypnea, cough with or without hemoptysis (50% of cases)
 Hypoxia (arterial pO2<80%)
 Respiratory alkalosis
 ECG findings:
o Tachycardia (common)
o Deep S wave in lead I, Q wave and Inverted T waves in lead III (S1-Q3-
T3) is uncommon
SYSTEMIC THROMBOEMBOLISM
 Emboli within arterial circulation
 Most arise from intra-cardiac mural thrombi.
 Remainder arise from aortic aneurysms
 Major sites for arterial embolization- lower extremities and brain, intestines,
kidneys, spleen, upper extremities
FAT EMBOLISM
 Source: bone marrow, adipose tissue
 May occur after fracture of long bones.
 Less than 10% are clinically significant.
 Clinical presentation (Clinical triad):
 Axillary petechiae from emboli lodging in cutaneous vasculature and causing
extravasation of blood
 Altered mental status from emboli in brain
 Dyspnea from emboli filling the pulmonary vasculature and impairing the
oxygenation of red blood cells.
 This type of emboli carries high mortality.
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AIR EMBOLISM
 Gas bubbles within circulation obstruction vascular flow
 May occur during obstetric procedures or chest wall injuries.
 A small amount of air injected into the arteries (1-2 ml) can cause complication
e.g. if air enters the coronary arteries, even a small amount can cause an infarct
of the heart.
 If air is injected into veins, a larger amount is required to cause complications
(100-200ml)
 Bubbles cause physical obstruction.
 Decompression sickness occurs when a person is exposed to sudden changes in
atmospheric pressure. Deep sea divers, under water construction workers are at
risk
 Caisson disease is a chronic form of decompression illness. Persistent gas
emboli in the skeletal system leads to multiple foci of infarcts.
AMNIOTIC FLUID EMOBLISM
 This is a complication of labor and immediate post-partum period.
 Sudden severe dyspnea, cyanosis, hypotensive shock, seizures and coma may be
present.
 Presence in pulmonary circulation of squamous cells shed from fetal skin, lanugo
hair, fat from vernix caseosa may cause diffuse alveolar damage.
INFARCTS
 This is a localized area of dead (necrotic) cells within an organ.
 An infarct is the pathologic finding; an infarction is the process.
 Mechanisms of infarct formation: Hypoxia and ischemia are the two main
mechanisms that result in infarction of organs.
 Hypoxia is lack of oxygen to an organ
 Ischemia is lack of blood flow to an organ.
 Note: Ischemia is more damaging than hypoxia, since in ischemia, decreased
blood flow results in both decreased oxygen delivery and decreased delivery of
nutrients to the tissue and, in addition, there is no way to remove the toxic
metabolites of cellular metabolism.
 Causes of infarcts
 Obstruction of vessel: Due to atherosclerosis, thrombi, emboli, damage to
vasculature (e.g., trauma, neoplasms and cytomegalovirus infection), or
external compression of an artery or vein (e.g., torsion of organ).
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 Generalized hypotension: As occurs in forms of shock.

 Types of infarcts:
 Red (“hemorrhagic”) infarct
o Organs affected: Most red infarcts occur due to obstruction of an artery
supplying an organ that has a dual blood supply or an organ that has loose
parenchyma, such as the lung, which allows for leakage of blood into
damaged tissue.
o Other mechanisms that produce a red infarct
 Venous infarcts: Although the vein is obstructed, the artery is still
delivering blood to the tissue, which gives the infarct a red appearance.
However, even though some blood is being delivered to the tissue,
oxygen delivery is impaired because of pooling of red blood cells.
 Reperfusion: In an infarct, the parenchyma and supporting structures
of the organ (e.g., vessels, nerves) are damaged. When blood flow is
returned to the organ, blood leaks out of damaged vessels, giving the
infarct a red appearance.
o Morphology of red infarct
 Gross: Soft, red area of tissue.
 Microscopic: Coagulative necrosis and numerous extravasated red
blood cells.
 White (“anemic”) infarct
o Organs affected: Organs with single blood supply and organs with solid
parenchyma (e.g., heart, liver, spleen).
o Morphology of white infarct
 Gross: Soft, pale area of tissue.
 Microscopic: Coagulative necrosis.
 Complications of an infarct are variable, depending on location and size. As with
hemorrhage, think of location of infarct. A 2.0-cm infarct of the liver might not
be noticed, but a 2.0-cm infarct of the brainstem would most likely cause death.
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SHOCK AND HYPOTENSION

 Hypotension is a state of low blood pressure with systolic blood pressure (SBP)
<90mmHg or mean arterial pressure <65.
 In relative hypotension the SBP is >30mmHg below baseline
 Shock is a state of cardiovascular failure resulting in impaired tissue perfusion
and disturbed cellular metabolism and function as a result of decreased oxygen
supply.
 Clinically shock can be defined as a 20% sudden blood loss or shift from
peripheral circulation.
 Adequate blood flow to tissues depends on:
 Blood volume
 Myocardial contractility
 Peripheral resistance
 Any disturbance in the above 3 can lead to shock.
 Pump failure leads to cardiogenic or obstructive failure
 Peripheral circulatory failure leads to hypovolemic (decreased blood volume)
or distributive shock (decreased peripheral resistance).
CLASSIFICATION OF SHOCK
 Shock can be classified into:
 Hypovolemic (Oligemic) shock: due to diminished blood volume (loss of
fluid/blood- hemorrhagic shock)
 Cardiogenic shock: due to inefficient myocardial function (decreased cardiac
contractility)
 Distributive shock: due to peripheral blood pooling. Can either be
o Septic shock: due to systemic infection
o Neurogenic shock: due to peripheral vasodilation, reduced peripheral
resistance and peripheral pooling of blood.
o Anaphylactic shock: due to antigen-antibody reaction that also leads to
peripheral pooling of blood e.g. injection of anti-tetanic serum
o Endocrinal shock: due to acute severe hormonal imbalance e.g. in adrenal
insufficiency or pituitary failure. It may present with a combination of
any of the above types.
 Obstructive shock: due to decreased blood flow to the left ventricle as in
cardiac tamponade, pulmonary embolism, and tension pneumothorax.
 Patients may have more than 1 type of shock e.g. hypovolemic and septic.
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PATHOPHYSOLOGY
 This includes cellular changes, microcirculatory changes, acid-base imbalances
and systemic changes.
 Cellular changes:
 Tissue hypo-perfusion resulting in a decrease in oxygen delivery to the tissue
and cells undergo anaerobic metabolism producing lactic acid (causing
metabolic acidosis).
 This continues until cellular glucose is depleted resulting in stoppage of cell
metabolism release of auto-digestive enzymes and rupture of plasma and
lysosomal membranes.
 Microcirculatory changes:
 Under the effect of catecholamines the precapillary sphincters constrict, less
blood enters the capillaries and the capillary circulation becomes sluggish.
 Untreated hypovolemia thus leads to hypoxia.
 Under normal conditions only one third of the capillary bed is open at a time.
 Under ischemic conditions however the body reacts by opening more
capillaries this results in:
o Further slowing of the capillary circulation, the so called slugging of
blood.
o Slugging encourages spontaneous coagulation of blood in these
capillaries.
o If extensive, it is called disseminated intravascular coagulation (DIC).
o This depletes coagulation factors and induces bleeding in the rest of the
body (consumption coagulopathy)
 A sluggish circulation and DIC compound tissue hypoxia and affect the
function of capillary endothelium. The result of the latter is leakage of large
protein molecules from the vessels into interstitial space dragging with them
huge amounts of fluid. This third space loss of fluid reduces blood volume.
 Acid-base imbalance: Shock is accompanied by metabolic acidosis which is
caused by accumulation of lactic acid as a result of anaerobic metabolism and
renal failure as a result of prolonged ischemia, aggravates acidosis.
 Systemic changes:
 Sympathetic response: release of catecholamines & stress hormones
(Cortisol, glucagon), release of ADH and activation of renin-angiotensin-
aldosterone system.
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 Cardiovascular: reduced coronary artery perfusion and direct depression of

myocardium by tumor necrosis factor
 Respiratory: metabolic acidosis results in tachypnea which causes carbon
dioxide washout and compensatory respiratory alkalosis. Leakage and
swelling can develop in the lungs, causing difficulty in breathing (respiratory
distress- ARDS)
 GIT: mucosal hypoperfusion causes mucosa death and stress ulcers. Mucosal
death may also result in bacterial translocation, septicemia and multi-organ
failure.
 Liver: ischemic hepatic dysfunction
 Renal: renal hypoperfusion decreases GFR, urine output and may lead to pre-
renal failure and acute tubular necrosis.
 Ischemic perfusion syndrome:
o It is due to systemic hypoperfusion, tissue hypoxia and local activation
of inflammatory mediators.
o Further injury occurs once normal circulation is restored to tissues:
 Myocardial depression
 Cellular and humoral elements activated by hypoxia are flushed back
into circulation causing more endothelial injury e.g. acute lung
injury, acute renal injury
o It only can be minimized by decreasing the period of hypoperfusion.
STAGES OF SHOCK
 Initial: decreased oxygen and increased lactate.
 Compensatory stage:
 Increased respiratory rate
 Sympathetic response: increased heart rate, fluid retention
 Increased renin and ADH secretion
 Progressive/decompensated stage: If compensatory mechanisms and treatment
are unsuccessful.
 Worsening hypotension due to vasodilation, blood pooling in capillaries,
and fluid leak from vessels.
 Altered mental status
 Electrolyte imbalances
 Refractory: irreversible
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GENERAL CLINICAL FEATURES OF SHOCK

 Change in mental status: a continuum from agitation, confusion/delirium,
obtundation/coma.
 Hypotension: absolute (systolic blood pressure <90mmHg) or relative (a drop in
systolic blood pressure >40mmHg), which is why a patient may be in shock with
a high or normal blood pressure.
 Increased heart rate, pulse may be thread (barely perceptible). Capillary refill >2s
 Oliguria (<30ml/hr)- from shunting of renal flow to other vital organs,
intravascular volume depletion or both.
 Cool, clammy skin- compensatory peripheral vasoconstriction redirects blood
from the peripheral to the vital organs (heart, brain, splanchnic). However, in
early distributive shock or terminal shock the skin may be flushed or hyperemic
due to failure of compensatory vasoconstriction.
 Metabolic acidosis- increased lactate production from anaerobic respiration when
shock progresses to circulatory failure and tissue hypoxia along with decreased
clearance of lactate by the liver, kidneys and skeletal muscle.
HYPOVOLEMIC SHOCK
ETIOLOGY
 This is due to diminished blood volume as a result of:
 Whole blood loss i.e. hemorrhage which can be traumatic or pathological
o Trauma
o Ruptured abdominal aortic aneurysm
o Aortic dissection
o Upper GI bleeding
o Ruptured ectopic pregnancy
 Plasma loss as in burns, heat exhaustion or peritonitis
 Water and electrolyte loss (especially Sodium) as in: severe vomiting,
diarrhea, intestinal obstruction and fluid sequestration (as in acute
pancreatitis).
STAGES
 Compensated stage: in this stage the body employs the physiological
mechanisms, in a trial to restore blood volume or at least, preserve the normal
function of the vital organs (brain, kidneys, heart and lung). With loss of >15%
of blood volume, the compensatory mechanisms usually fail.
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 Decompensated stage (40% blood loss): if the cause of shock is not treated
successfully and after failure of compensatory mechanisms there will be
progressive poor perfusion and micro-circulatory changes with deterioration of
functions of the brain, kidney, heart and lung.
 Refractory stage: The shock can no longer be reversed. Failure of vital organs
and death occurs imminently.
CLINICAL FEATURES
 Of shock
 Symptoms:
o Weakness and fainting
o The patient feels cold and thirsty
 Signs:
o Patient is cold and clammy with a narrow pulse pressure
o Decrease in blood pressure: SBP<90 or 60 below normal
o Orthostatic hypotension can be an early sign of hypovolemia.
o Capillary refill>2s
o Oliguria: <30ml/hr
o Altered mental status (may vary from anxious to drowsy but the patient
usually remains alert).
o Hypotension, tachycardia (increased heart rate, pulse may be thread-
barely perceptible) and decreased pulse pressure (thready pulse)
 Of the cause
 Sites of bleeding
 Signs of internal hemorrhage
 Burns
 Intestinal obstruction
 In hemorrhagic shock, trauma or signs of GI bleeding (melena, abdominal
pain)
 Of complications:
 Anuria
 Acute respiratory depress syndrome
CARDIOGENIC SHOCK
 This is due to inadequate blood flow to vital organs due to inadequate cardiac
output despite of normal blood volume.
 It is characterized by
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 SBP <90mmHg
 Mean arterial pressure drop >30mmHg
 Urine output <0.5ml/kg/hr
 Heart rate >60bpm
ETIOLOGY
 Primary pump failure due to:
 MI (commonest cause) or its complications e.g. ventricular septal rupture
 Severe arrhythmias
 Massive pulmonary embolism
 Cardiac tamponade
 Myocarditis
 Severe valve disease
 Trauma
 High spinal anesthesia
CLINICAL FEATURES
 Of shock:
 Clinical picture similar to hypovolemic shock.
 Comatose
 Patient is cold and clammy and pulse pressure may be narrow
 Peripheral cyanosis
 Poor urine output
 Increased JVP and decreased heart rate
 Of the cause: enlarged liver, chest pain, pulsus alternans, ‘gallop’ rhythm,
murmur, basal crackle, pulmonary edema.
DISTRIBUTIVE SHOCK
 Vasodilation leads to a relative (though not absolute) deficiency in volume.
SEPTIC SHOCK (ENDOTOXIC SHOCK)
 Septic shock is a type of distributive shock though it may also include an element
of hypovolemic shock as altered capillary permeability leads to volume loss from
the vasculature.
 It is the most serious type of shock and the most difficult to treat.
ETIOLOGY
 Gram negative bacilli (commonest cause)
 Staphylococci
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 Candida
PREDISPOSING FACTORS (IMMUNOSUPPRESION)
 Extremes of age
 Malignancy
 Malnutrition
 Diabetes mellitus
 Chemotherapy, corticosteroids or immunosuppressants
 HIV infection
PATHOPHYSIOLOGY
 Bacterial endotoxins are released when immune cells (i.e. macrophages) kill
gram negative bacteria.
 Immune cells release cytokine, TNF and IL-2 which damage capillary
endothelium leading to edema and vasodilation (rapid shifting of blood bypassing
capillary) and tissue ischemia.
 Septic shock starts as maldistribution of blood followed by myocardial
depression and hypovolemia.
CLINICAL FEATURES
 Hyper-dynamic (warm) septic shock (early phase): diagnosis is difficult and high
index of suspicion is required to detect it at early stage.
 Restless and confusion
 Skin: flushed, warm and dry
 Vitals:
o Fever >38oC + Chills
o Mild decreased in arterial blood pressure, pulse pressure may be wide
with a low DBP.
o Tachycardia
o Tachypnea
 High cardiac output
 Hypo-dynamic “cold” septic shock (Late phase): picture similar to hypovolemic
shock with reduced cardiac output
 Skin: cold and clammy
 Vitals:
o SBP<90mmHg
o Tachycardia
o Tachypnea
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 Oliguria
 Multi-organ failure starts at this stage.