Hemodynamics

Blood supply
Fluid imbalance

Pathologies

Edema
Vascular congestion
Hemorrhage
Thrombosis
Embolism
Infarction
Shock

Edema

60% BW is water
2/3 intracellular rest is extracellular
5% plasma
Edema means fluid in the interstitial space
hydrothorax
hydropericardium
hydroperitoneum (ascites)
Anasarca generalized edema with profound
subQ swelling

Causes of edema
Increased hydrostatic pressure
impaired venous return
arteriolar dilatation
Reduced plasma oncotic pressure
(hypoproteinemia)
Lymphatic obstruction
Sodium retention
Inflammation

Hydrostatic pressure

Plasma colloid
osmotic pressure

Venous end
Arterial end

Capillary bed
No net loss or gain of fluid across capillary bed

 Transudate
edema fluid occuring in hemodynamic
derangement. Protein poor , spfc. grav. of
1.012.
Exudate
inflammatory edema fluid
protein rich
spfc. grav . of 1.020

Increase hydrostatic pressure

Impaired venous outflow deep venous
thrombosis
Generalized increase in venous
pressure CHF right sided HF, dec CO ,
reduced renal perfusion, kidney tend to
retain water and Na
Tx diuretics, salt restriction,
aldosterone antagonist

Reduced plasma oncotic

pressure
Excessive loss or reduced synthesis of
albumin - nephrotic syndrome , liver
cirrhosis , protein malnutrition
Also cause decrease renal perfusion
water and Na retention cant correct the
condition
Hypoproteinemia is exacerbated by salt
and fluid retention

Lymphatic obstruction

Lymphedema is usually
localized
Filariasis elephantiasis
Cancer - Tx irradiation

Sodium and water retention

Salt retention may be a primary
contributor of edema
Post streptococcal glomerulonephritis
Acute renal failure

Clinical correlation
SubQ edema or renal failure signals
underlying dse.
Pulmonary edema can be fatal
collects fluid to alveolar septa and
impede O2 diffusion
Impair wound healing and clearance of
infection
Brain edema fatal herniation

Hyperemia and Congestion

H and C indicate a local increased volume
of blood in a particular tissue
Hyperemia is an active process resulting
from augmented tissue inflow arteriolar
dilation ( sk. mcle in exercise/ inflamm.)
tissue is redder
Congestion is a passive process resulting
from impaired outflow from the tissue
tissue is blue red (cyanosis)
cardiac failure

 Congestion of capillary beds is related to

edema or they may occur together
Chronic passive congestion long
standing congestion , stasis of poorly
oxygenated blood chronic hypoxia
Hypoxia results cell degeneration and
death
Congestion may result to hge. ,
phagocytosis of red ( hemosiderin laden
macrophage)

Hemorrhage
Extravasation of blood because to vessel
rupture
Capillary bleeding can occur under
conditions of chronic congestion
Bleeding diatheses increased tendency
to hemorrhage from usually insignificant
injury
Trauma, atherosclerosis, inflammation
and neoplastic process - HGE

 Hge maybe external or enclose within a

tissue (hematoma) maybe benign or fatal
Petechiae 1-2mm (thrombocytopenia,
clotting fx def)
Purpura - > or equal 3mm slightly larger than
petechiae ( vasculitis)
Ecchymoses - >1-2cm subQ hematomas
(trauma)
Accumulation of blood in spfc. Areas
hemarthrosis,
hemoperitoneum,hemothorax,hemopericardi
um

 Clinical significance of hge depends

on the volume rate of blood loss
20% loss is still no significant change
Greater loss hypovolemic shock
Hemorrhage site is impt. intracranial
hge. Inc intracranial pressure
Iron defeciency

Hemostasis and Thrombosis

Normal hemostasis
1. maintain blood in a fluid , clot free
state in normal vessels
2. they are poised to induced a rapid
and localized hemostatic plug at the site
of vascular injury
Thrombosis - is a pathologic form of
hemostasis , inappropriate activation of
normal hemostatic process (thrombus)

Normal
Hemostasis

Injury

Arteriolar constriction
(Reflex neurogenic mech.)
Endothelium
Transient

Platelet and coagulation

system
Platelets and fibrin
Permanent
hemostatic plug

Injury -thrombogenic
( subendothelial extracellular
matrix)
Platelets are activated
Shape change and release of
granules

Recruit other
platelets

Coagulation cascade
Recruit more platelets
activates thrombin to
convert fibrinogen
to fibrin

Forms temporary
hemostatic plug

Tissue factor
(endothelium)

 Endothelium
is both procoagulant
and anti platelet (fibrinolytic
system)
Counterregulatory mech.
t-PA

Antithrombotic properties
Intact BV 1. anti-platelets
anti-platelet
platelets are inactivated- they dont
adhere with each other
brought about by subs PGI2 and Nitric
oxide.
Also adenosine diphosphatase which
inhibits plt. Aggregation
2. anticoagulants
a. membrane asso. Heparin like molecules
anti thrombin III
b. thrombomodulin spfc. Thrombin
receptor

3. Fibrinolytic t-PA which

clears out clot

Prothrombotic properties
von Willebrand factor cofactor for
platelet binding with collagen and other
surfaces
bacterial endotoxins and cytokines
cause synthesis of tissue factor
activate extrinsic clotting
cascade inhibit plasminogen activator
and inhibits fibrinolysis

Platelets
Play impt. role in hemostasis
2 granules
-granules fibrinogen,
fibronectin, factor V, VwF, heparin
binding chemokine, PDGF
-granules ADP & ATP , ionized
Ca, histamine, serotonin, epinephrine

Platelets during contact of

extracellular matrix
1. adhesion and shape change vWF
2. secretion Ca & ADP
plt.aggregation (phospholipid complexes)
3. aggregation TXA2 primary
hemostatic plug thrombin plt.contraction2ndary hemostatic plug - fibrin

 Platelets adhere to extracellular matrix at sites of

endothelial injury and become activated
On activation they secrete granule product
(ADP) and synthesize TXA2
Platelets also expose phospholipid complexes
impt.in the intrinsic coagulation pathway
Injured or activated endothelial cells are expose
to tissue factors which triggers the extrinsic
coagulation cascade
Released ADP stimulates formation of primary
hemostatic plug, which is eventually converted
(via ADP, thrombin and TXA2) into larger
definitive secondary plug.
Fibrin deposition stabilizes and anchors the
aggregated platelets

Coagulation cascade

Thrombosis
1. endothelial injury
2. stasis or turbulence of
blood flow
3. blood hypercoagulability

virchows triad

Endothelial injury

Hypertension
Turbulent flow scarred valves
Bacterial endotoxins
Homocystinuria
Hypercholesterolemia
Radiation
Cigarrete smoking

Injury cause subendothelial collagen exposure

platelet aggregation , plt. adhesion, activation of
tissue factor

Alterations of normal blood

flow
Turbulence
Stasis(pool areas) countercurrent

Normal flow laminar flow

cells flow at the center
plasma at periphery ( clear
zone)

Laminar flow

cells flow at
the center

plasma at
periphery ( clear
zone

Stasis and turbulence

Disrupts laminar flow plts may
draw towards the endothelium
Prevents dilution factors fresh
blood
Retard inflow of clotting factors
Promote endothelial cell
activation local thrombosis and
leukocyte adhesion

 Ulcerated atherosclerotic plaque -

exposed subendothelial
extracellular matrix
Abnormal aortic and arterial
dilatations aneurysms
Myocardial infarctions
Mitral valve stenosis left atrial
dilatations
Hyperviscousity syndromes
polycythemia and sickle cell
anemia

Hypercoagulability
Primary genetic, mutation of factor V,
antithrombin III def., protein c & s def.,
fibrinolysis def., homocysteinuria,
variations in prothrombin level
Secondary
high risk bed rest and
immobilization, MI, tissue damage,
cancer, prosthetic heart valves, DIC,
heparin induced thrombocytopenia,
antiphospholipid antibody ( lupus
anticoagulant)

 Low risk atrial fibrillation,

cardiomyopathy, nephrotic
syndrome, hypercoagulable state,
oral contraceptive, sickle cell
anemia , smoking
Heparin induced
thrombocytopenia- given heparin
body produce antibodies against
heparin and complexes with
factor 4 resulting in platelet
activation or endothelial cell
injury (procoagulant)

 Antiphospholipid antibody syndromeantibodies to cardiolipin causing

hypercoagulable states
SLE
recurrence venous and aterial thrombi
formation
miscarriages
cardiac valvular vegetations
Tx anticoagulant, aspirin, heparin ,
coumadin
Prednisone miscarriages
immunosuppression

Fate thrombus
1. propagation accumulate more
platelet and fibrin leading to vessel
obstruction
2. embolization thrombi may dislodge
and travel to other sites
3. dissolution thrombi may be removed
by fibrinolytic system
4. organization and recanalization
Thrombi may induced inflammation and
fibrosis and recanalized (reestablish
blood flow or may incorporate into a
thickened vascular wall)

Older thrombi
Incorporate to
endothelium

Organized with
fibrin

Capillary channels or form

conduits

Recanalization

Venous thrombosis
Phlebothrombosis
superficial veins saphenous v.thrombi- pain and tenderness,
swelling and congestion- forming
varicose ulcers
Deep veins (popliteal,femoral,iliac
v) more tendency to embolized
50% are asymptomatic

 Tumor associated procoagulant

released increased risk thrombosis
migratory thrombophlebitis ( trousseau
syndrome )
Arterial thrombosis MI dyskinetic
contraction of myocardium mural
thrombi
rheumatic heart dse - mitral valve
stenosis left atrial dilatation- atrial
fibrillation - stasis
atherosclerosis major initiator
of thrombosis loss of endothelial
integrity embolized to tissues

Disseminated Intravascular
Coagulation
Multiple thrombi formation
consumption of platelets and
factor fibrinolytic system
- Hemorrhage
Thrombotic disorder that leads to
bleeding disorder

Clinical correlation
Obstruction
Emboli fatal
pulmonary
embolism

Embolism
Embolus detached intravascular
solid, liquid, or a gaseous mass that is
carried by the blood to a site distant
from its point of origin.
99% - dislodged thrombus
(thromboembolism)
Rare droplets of fats, bubbles of air,
atherosclerotic debris (cholesterol
emboli),
tumor fragment, bits of bone marrow,
foreign bodies ( bullets)
Potential consequence - infarction

Pulmonary
Thromboembolism
20 -25% / 100,000 hospitalized patient
Venous emboli from deep leg veins goes
to the right side of the heart pulmonary
vasculature via pulmonary artery (at
bifurcation Saddle emboli) some are
multiple , small or large
Paradoxical embolism pass through an
interatrial or interventricular defectsystemic circulation

 60-80% are clinically silent because

they are just small organized in
vascular wall forms web
Sudden death right sided heart failure
cor pulmonale (60%)
Pulmonary hemorrhage no infarction
due to dual blood flow
Embolic obstruction - does not cause
infarction
Multiple emboli pulmonary
hypertension
right sided heart failure

Systemic Thromboembolism
Emboli with an arterial circulation
80% intracardial mural thrombi
2/3 asso with left ventricular wall infarct
dilated left atrium (RHD) and remainder
due to aortic aneurysms, thrombi on
ulcerated atherosclerotic plaques,
fragmentation of valvular vegetation
Small fraction due to paradoxical embolism
75% lower extremities, 10% brain
GIT , spleen, kidneys, upper extremities are
rarely affected
Ischemia is the endpoint

Fat Embolism
Fracture fatty marrow adipose goes to the
circulation
90% skeletal trauma
Manifest 1-3days after injury
Tachypnea, dyspnea, tachycardia( lung )
Neurological signs irritability, restlessness delirium and coma
May also precipitate petechial rash,
thrombocytopenia - platelets adhering to fat
globules
Anemia erythrocyte aggregation and
hemolysis
Cause obstruction and biochemical injury to
endothelium
Fatal up to 10% cases

Air Embolism
Gas bubbles may obstruct vascular flow
causing distal ischemic injury
Air - enter circulation obstetric
procedure or chest wall injury
100cc of gas clinical effect
Bubbles as frothy mass may occlude
major vessels
Decompression syndrome scuba
diving/deep sea diving inc. gas like
nitrogen dissolved in blood and tissues
immediately goes up it expands inside
forming bubbles forming gas emboli

 Formation of painful gas bubbles within skeletal

muscles and supporting tissues like joints
Bends
May induce focal ischemia to heart and brain
In lungs - edema , focal hemorrhage,
emphysema leading to respiratory distress
known as chokes
Tx compression chamber barometric
pressures may be raised to turn gas bubbles
into solution. Allows gradual resorption and
exhalation of gas
Caissons dse chronic form persistence of
gas in the heads of the femur, tibia, humerus
causing ischemic necrosis

Amniotic fluid Embolism

1 in 50,000 deliveries
Mortality rate of >80%
Sudden onset of dyspnea, cyanosis,
hypotensive shock seizures and coma
If survives suffer pulmonary edema,
DIC, - due to thrombogenic subs. In
amniotic fluid
Infusion of amniotic fluid in maternal
circulation via tear in placental
membrane and rupture of uterine veins

 Presence of squamous epithelial

cells in the pulmonary circulation
Also seen lanugo, fat ( vernix
caseosa) and mucin fetal
respiratory and GI tract
Marked pulmonary edema
diffuse alveolar change , DIC

Infarction
Infarct area of ischemic necrosis caused
by occlusion of either arterial supply or
venous drainage in a particular tissue
More than half common cause of death
CVD
99% due to thrombotic or embolic events
Occasionally due vasospasm, hemorrhage
due to plaque, compression by a tumor

 Twisting of BV testicular
torsion, volvulus
Compression by edema
Traumatic rupture of blood vessel

Factors that Influence

Development of an Infarct
1. nature of blood supply
2. the rate of development of the
occlusion
3. the vulnerability of tissue to
hypoxia
4. blood oxygen content

Nature of Vascular Supply

Presence of alternative blood supply
lungs pulmonary and bronchial
arteries
liver has hepatic artery and portal
vein circulation
both resist infarction
kidneys and spleen are end organsprone to infarction if blood supply is
compromised

Rate of Development of
Occlusion
Presence of anastomosis will
prevent infarction
If one vessel is occluded
collateral circulation may flow
sufficiently to prevent infarction

Vulnerability to Ischemia
Susceptibility of tissue to ischemia
is likely to cause infarction
Neurons goes irreversible damage
with in 3-4min
Heart 20-30min
Fibroblast within myocardium
maybe viable for many years even
after ischemia

Oxygen content of Blood

Partial pressure of O2
partial obstruction of
small vessel of anemic
or cyanotic infarction
CHF - infarction

Shock
Shock is a cardiovascular collapse
Final common pathway for number of lethal
clinical events ( severe Hge, trauma, or
burns, MI, massive pulmonary embolism, and
microbial sepsis
Constitutes systemic hypoperfusion
reduced cardiac output
End results are hypotension, impaired tissue
perfusion reversible cell injury
irreversible cell injury

Types of shock
Cardiogenic shock results from
myocardial pump failure MI , ventricular
fibrillations, extrinsic compression (cardiac
tamponade), outflow obstruction (PE)
Hypovolemic shock loss of blood and
plasma volume cause by Hge, fluid loss,
severe burns, trauma
Septic shock systemic microbial
infection gram negative infxn ( endotxin)
but also in fungal and gram+ infxn

 Neurogenic shock anaesthetic

accident or spinal cord injury , affecting
vascular tone and peripheral pooling of
blood
Anaphylactic shock IgE mediated
hypersensitivity response , asso with
systemic vasodilation and increased
vascular permeability inc vascular bed
capacitance not adequately filled by
normal circulating blood
Hypotension , tissue hypoperfusion and
cellular anoxia are the outcome

Septic shock
Endotoxic shock gm negative bacteria
Endotoxins are Lipopolysaccarides LPS

LPS
TNF
IL-1
IL-6 / IL- 8
NO, PAF
Other mediators
Systemic effects
Local
Brain Fever
inflammation
Monocyte
liver
macrophage
activation

Endothelial
cell activation
Complement
activation

Acute
phase reactants

Septic shock
Low cardiac output
Low peripheral
resistance
Blood vessel
injury
thrombosis
DIC
Lungs- ARDS

Stages of shock

Non progressive
stage
Progressive stage
Irreversible stage

Non progressive phase

Reflex compensatory mechanism

Perfusion of vital organs is maintained
Baroreceptor reflexes
Release of cathecholamines
Renin angiotensin axis , ADH ,
symphathetic stimulation
Net effect tachycardia, peripheral
vasoconstriction and renal conservation of
fluid

Progressive stage
Hypoperfusion
Onset of worsening circulatory and metabolic
imbalance (acidosis)
Widespread tissue hypoxia
Anaerobic glycolysis lactic acid
Ph lowered and blunted vasomotor response
Arterioles dilate and blood begins to pool in
circulation
Pooling affects CO anoxia - DIC

Irreversible stage
Incurred cellular and tissue injury and
even hemodynamic defects are corrected
survival is not possible
Widespread cellular injury
Lysosomal enzyme leakage
Myocardial contractile function worsens by
NO
Ischemic bowel may allow intestinal flora
to enter circulation endotoxic shock
Renal shutdown acute tubular necrosis

Clinical course
Hypovolemic and cardiogenic shock presents
hypotension ( weak rapid pulse) tachypnea, cold
clammy cyanotic skin
Septic shock initiallly warm and flushed
due peripheral vasodilation
Catastrophe renal insufficiency
Hypovolemic shock 70-80% may survive in
young individuals
Cardiogenic and septic shock 75% mortality