You are on page 1of 77

Eugen Petcu

A cell activated by a lack of oxygen

releases angiogenic molecules that


attract inflammatory and endothelial
cells and promote their proliferation.

The endothelial cells that form the blood


vessels respond to the angiogenic call by
differentiating and by MMP, which digest
the blood-vessel walls to enable them to
escape and migrate toward the site of the
angiogenic stimuli.
Endothelial cells: form a capillary tube
by altering the arrangement of their
adherence-membrane proteins.

More than 20 endogenous positive


regulators of angiogenesis have been
described, including growth factors,
matrix metalloproteinases, cytokines,
and integrins.
Fibroblastic growth factor (FGF),
Vascular endothelial growth factor

(VEGF)
Transforming growth factors (TGF-

beta), epidermal growth factor (EGF),


angiogenin, can induce the division of
cultured endothelial cells thus indicating
a direct action on these cells.

http://www.youtube.com/watc
h?v=aKBZbxBnpGM

Stroke causes ischemic damage to the brain, activating angiogeneic mechanisms in response.
The degree of response is modulated by changes to the neural and vascular response caused by aging,
but the general response remains similar. Growth factors, tissue remodelling and inflammatory proteins
are released, leading to the building of new, well developed endothelial channels, which aid recovery.

http://www.angioworld.com/
angiogenesis.htm

Blood travels from the heart in arteries,

which branch into smaller and smaller


vessels, eventually becoming arterioles.

Arterioles connect with even smaller blood

vessels called capillaries.

From the capillaries, blood passes into

venules, then into veins to return to the


heart via venules and veins

Arteries and arterioles have relatively thick


muscular walls because blood pressure in
them is high and because they must adjust
their diameter to maintain blood pressure
and to control blood flow.

Veins and venules have much thinner, less


muscular walls than arteries and arterioles,
largely because the pressure in veins and
venules is much lower. Veins may dilate to
accommodate increased blood volume.

The tunica intima delimits the vessel wall

towards the lumen of the vessel and


comprises its endothelial lining and
associated connective tissue.
Beneath this we find the internal elastic

lamina, which delimits the tunica intima


from

The tunica media. The tunica media is

formed by a layer of circumferential


smooth muscle and variable amounts of
connective tissue.
A second layer of elastic fibers, the external

elastic lamina, is located beneath


smooth muscle.
It delimits the tunica media from:
The

the

tunica adventitia, which consist


mainly of connective tissue fibres. The
tunica
adventitia
blends
with
the
connective tissue surrounding the vessel.

Aorta, human - H&E , elastin &

van Gieson
The thin endothelial lining of the
aorta: the flattened cells are easily
damaged during preparation.
The majority of cells in the tunica

media are smooth muscle cells.


Smooth muscle cells and collagen
fibres are found between the layers
of elastic fibres

Small arteries
< 2 mm diameter
Penetrate tissues and
organs
Arterioles
20-100 m diameter
Primary point of

resistance to blood flow


into capillaries
Regulation of systemic

blood pressure

Capillaries: Endothelium, basement membrane (BM) and


pericytes; no media

CP: are formed by "continuous" endothelial


cells and basal lamina.
NO OPENINGS!
Both endothelial cells and the basal
lamina can act as selective filters in
continuous capillaries.

Muscles, heart, lung, skin,


nervous system

FC: The endothelial cell body forms small


openings called fenestrations, which allow
components of the blood and interstitial
fluid to bypass the endothelial cells on
their way to or from the tissue surrounding
the capillary.

Endocrine glands, glomeruli

Cardiac muscle is highly vascularised.


The capillaries roughly follow the course

of the muscle cells.

Only one or two red blood cells fit side

by side in the capillary.

A single endothelial cell forms the

wall around the entire circumference


of a segment of the capillary.

Endothelial cell nuclei are therefore not

always visible, and some red blood


cells are only surrounded by a fine
line representing the capillary wall.

DC are formed by fenestrated

endothelial cells, which may


not even form a complete layer of
cells.
The basal lamina is also

incomplete.
Discontinuous capillaries form

large irregularly shaped vessels,


sinusoids or sinusoid capillaries.
They are found where a free

exchange of substances or even


cells between bloodstream and
organ is advantageous

Liver, spleen, bone


marrow

Venules: They are larger than capillaries. Small venules are surrounded by
pericytes.
A few smooth muscle cells may surround larger venules.
The venules merge to form

Small to medium-sized veins which contain bands

of smooth muscle in the tunica media.


The tunica adventitia is well developed.
In some veins (e.g. the veins of the pampiniform
plexus in the spermatic cord) the tunica adventitia
contains longitudinally oriented bundles of smooth
muscle
.
Aside from most veins in the head and neck, small
to medium-sized veins are also characterised by the
presence of valves.
The valves are formed by loose, pocket-shaped folds
of the tunica intima, which extend into the lumen of
the vein.
The opening of the pocket will point into the
direction of blood flow towards the heart.
One to three (usually two) pockets form the valve.
Blood flowing towards heart will pass the pockets.
If the flow reverses, blood will fill the pockets
which will occlude the lumen of the vein and
prevent the return of blood into the part of the
vein preceding the valve.
.

Vein Valve - H&E

Valves: one or two


bands of tissue in the
lumen of the vein.
Each band is formed

by two apposing layers


of tunica intima.
The bands may share
their origin from the
inner aspect of the
wall of the vein or
they may have
separate origins.

The largest veins of the abdomen and thorax : Valves


are absent!!
The tunica intima is very narrow and

the internal elastic lamina is difficult to


identify - even in elastin stained
sections.
A few elastic fibres below the endothelium

form only a very thin and incomplete


internal elastic lamina.

Smooth muscle is present in the tunica

media, but it is organised less regular


than in the artery.
The tunica media is, again as compared to

the artery, very thin and there is no


sharp border between the tunica
media and the tunica adventitia.

The tunica adventitia of the largest

veins contains coarse collagen fibres,


elastic fibres and longitudinal bundles of
smooth muscle.

Lymph capillaries are somewhat larger than

blood capillaries and very irregularly shaped.


They begin as blind-ending tubes in
connective tissue.
The basal lamina is almost completely absent

and the endothelial cells do not form tight


junctions, which facilitates the entry of liquids
into the lymph capillary.

Lymph capillaries merge to form lymph

collecting vessels which are larger and form


valves but otherwise appear similar to lymph
capillaries.
The lymph is moved by the compression of the

lymph vessels by surrounding tissues.


The direction of lymph flow is determined by
the valves.
Lymph ducts contain one or two layers of

smooth muscle cells in their wall.

They also form valves.


Peristaltic contractions of the smooth muscle
contribute to the movement of lymph towards
the heart in addition to the compression of the
ducts by surrounding tissues.

Physiology
Vasoconstriction/vasodilation
Synthesis of collagen, elastin,

proteoglycans
Production of cytokines and GFs

Pathology
Migration to the intima,

proliferation and
phagocytosis

Activators: PDGF, endothelin-

1, IFN- , IL-1
Inhibitors: NO, TGF-, heparan
sulfate

Basal Tone

Vascular tone
Arterioles remain in a state of partial
is a term commonly used
constriction even when all external
to characterize the general
influences on them are removed.
contractile state of a
vessel or a vascular region.
The
understanding
of
the
mechanism is incomplete,
Smooth muscle cells resist being
stretched as they continually are
in pressurized arterioles.
The basal tone establishes a
baseline of partial arteriolar
constriction
from
which
the
external influences on arterioles
exert
their
dilating
or
constricting effects.
These influences can be separated
into
three
categories:
local

The "vascular tone" of a

region can be taken as an


indication of the "level of
activation"
of
the
individual
smooth
muscle cells in that
region.

Anticoagulants

Prostacyclin, thrombomodulin, heparinlike molecules, plasminogen activator

Coagulants

Von Willebrand factor, tissue factors,


plasminogen activator inhibitor

Extracellular matrix

Collagen, proteoglycans

Vasoconstrictors

Endothelin, angiotensin-converting
enzyme

Vasodilators

NO, prostacyclin

Pro-inflammatory
mediators

IL-1, IL-6, chemokines


VCAM-1, ICAM, E-selectin, P-selectin

GFs

PDGF, FGF

Growth inhibitors

Heparin, TGF-

Arteriosclerosis: hardening of the arteries

3 different types
Arteriolosclerosis
Monckebergs arteriosclerosis
Atherosclerosis
Cystic Medial Necrosis
Aneurysms
Varicose Veins
Phlebothrombosis/Thrombophlebitis

Occurs in old age, benign

hypertension
Homogeneous, pink, hyaline

thickening of arteriole walls


with narrowing, due to
deposition of
amorphous extracellular

substance (leakage of plasma


components across
endothelium) and
loss of smooth muscle cells.

Occurs in malignant

hypertension
Onionskin, concentric

laminated thickening of
arteriole wall with narrowing
+ fibrinoid necrosis.

AKA: medial calcific

sclerosis
Calcifications in media of

medium to small arteries with


no associated inflammation
May ossify
Femoral, tibial, radial, ulnar,

genital arteries

Definition: patchy intimal thickening with

deposition of lipid and fibrosis, causing


narrowing of the lumen
Affects large arteries (aorta) and medium-sized

arteries (coronary & cerebral arteries)

Acquired Risk
Factors for AS
Age: > 40 yrs
Sex: male
Familial predisposition
Familial

hypercholesterolemia:
defect in cholesterol (CH)
receptors inadequate
CH uptake by the liver
LDL-emia

Acquired
dyslipoproteinemia

High LDLs, high CH, low HDLs

Hypertension
DM
Cigarette smoking
Obesity
Lowered physical activity
Klebsiela pneumoniae
infection

Normal aorta post-mortem:


The faint reddish staining is
from hemoglobin that
leaked from RBC's following
death. The surface is quite
smooth, with only
occasional faint small
yellow lipid streaks visible

Chronic/repetitive endothelial injury


Insudation of LDLs and VLDs into the
intima and oxidative modification of
LDLs by activated macrophages
Toxic endothelial injury:
Monocyte, neutrophil, T-cell and platelet
adherence and activation
Migration of monocytes

and their conversion to

macrophages (foamy cells with oxidized LDLs )

Release of mediators

PDGF (platelets); IL-1, TNF (macrophages); IFN- (CD4+cells); VCAM-1, ICAM-1 (endothelium)

Migration of SMCs from the media to intima, their proliferation, lipid phagocytosis and formation of
foamy cells
Accumulated intracellular LDLs fatty streaks

Necrosis of the central zone and formation of pure atheroma


Production of ECM by SMCs (fibrosis)
Formation of atheromatous plaque (fibrofatty plaque) = atheroslerosis

Lumen

Stary HC. Virchows Archiv


Anat Pathol. 1992; 421:277290 Classification

Type I:
microscopic collections of
macrophages including
foamy cells in INTIMA

Type II: FATTY


STREAKS:
collections of lipidladen macrophages
forming streaks.
It may regress

Type III:
PREATHEROMA:
represents a bridge
between minimal and
advanced lesions;
minimal thickening

Type IV: ATHEROMA:

disruption and
disorganization of the intima
as lipid cores develop
esterified and crystalline

cholesterol
Vessel wall is thickened but

with minimal lumen


reduction

Type V:
FIBROATHEROMA: lipid
core and fibrous cap
containing collagen and
smooth muscle cells;
lumen reduction
Type VI: COMPLICATED:
fissures, erosions,
ulcerations, hematoma,
hemorrhage or thrombosis
Type VII: CALCIFIC
Type VIII: FIBROTIC

Fibrous cap collagen

rich connective tissue

Intra-intimal collections

of plasma derived lipid

Basal zone of necrosis-

rich in lipid

Lipid: cholesterol clefts

and foamy macrophages

This microscopic cross section of the aorta shows a large


overlying atheroma on the left. Cholesterol clefts are numerous in
this atheroma. The surface on the far left shows ulceration and
hemorrhage

Def: acute luminal alteration secondary to medial

spasm or plaque rupture, hemorrhage or thrombosis


Risk factors:
Soft plaque with necrotic core
Atheroma with a thin fibrous cap
Atherophagocytosis by giant cells
Intimal clusters of leukocytes
Adventitial bands of mononuclear leukocytes

Lesions range from minimal erosions to deep tears


Lesions result in exposure of luminal blood to

thrombogenic subendothelial materials


Junction of plaque with adjacent normal wall is the

frequent site of involvement


Outcomes: fibrous healing, atheroembolization to distal

vessels, thrombosis

Deep intimal tears lead to

hemorrhage
plaque enlargement and

luminal reduction
Final event: promotion of

SMC prolifeartion

May lead to non-occlusive or

occlusive episodes
depending on exposure to
underlying thrombogenic
factors
Outcomes:

thrombotic embolization

and/or luminal obstruction


thrombus organization and
incorporation leading to
plaque progression

Medium-sized and small

vessels
Small uncomplicated
plaque mild/moderate
narrowing of the
vascular lumen
chronic ischemia
Complicated plaque
vascular obstruction
acute ischemia and
infarction

Asymptomatic: stable non-critical


plaques
Angina pectoris:

Stable: stable plaques


Unstable: unstable plaques with
rupture and acute non-occlusive
thrombus

MI: unstable plaque with rupture


and acute thrombus
Chronic ischemia: stable plaques,
old thrombus, plaque progression
Sudden Death: unstable plaque
with rupture and acute thrombus; 23 vessel disease in 80% of patients

Unclear etiology; may be associated with

Marfans
Predisposes to dissections
Accumulation of amorphous material

in media, often forming cysts or


mucoid pools
Small clefts in the media filled with a

slightly basophilic ground substance

A localized abnormal permanent

dilatation of any vessel, most


common in the aorta.

Classification according to

site
etiology
shape(fusiform/saccular)

Atherosclerotic
aneurysm
Dissecting aneurysm
(aortic dissection)
Berry aneurysm
Microaneurysm
(Charcot-Bouchard)
Mycotic aneurysm
Syphilitic aneurysm
Traumatic(False)
pseudoaneurysm

Left, True aneurysm.


The wall bulges outward and may be attenuated but is intact.
Right, False aneurysm.
The wall is ruptured, and there is a hematoma that is bounded externally
by adherent extravascular tissues.

Predominantly affecting males

over 50.

Common in abdominal aorta

(infra-renal) or common iliac


arteries

Predisposed by advanced age,

hypertension, smoking,
familial clustering

Pathogenesis:
severe atherosclerosis causing

thinning or destruction of the


media.
Mural thrombus + embolism is
common.
Most cases are fusiform and

diameter ranges from 5 to


10cm.

This abdominal high speed CT


scan with contrast demonstrates
an abdominal aortic aneurysm
approximately 6 cm in diameter.
At this size, there is increased
risk for rupture.

AKA: dissecting

haematoma, aortic
dissection
male/female= 2-3/1
Hypertension is present in
95% of cases
Untreated 35% fatal in 15
minutes
Proximal dissections

are most lethal

Dissection of blood occurs


along the laminar planes of
the aortic media (between
middle and outer third).

Location
Hypertension
Iatrogenic: dissection is

associated with bypass


cannulation

Bicuspid aortic valve and

coarctation

Connective tissue disorders:

Marfans syndrome -inherited


defect of collagen cross-links

Genetic diseases like

Turners syndrome

Rupture bleeding
death
Disruption of the aortic valve

ring aortic insufficiency

Cardiac tamponade
MI (compression of the coronary

aa.)

Dissection and compression of

the renal, superior mesenteric,


iliac, femoral, etc aa.

Treatment
Surgical repair of the
aortic wall
Aggressive
antihypertensive therapy
Prognosis
With treatment: 25 35%
mortality rate
Without treatment: 100%
mortality rate

Confined to thoracic

aorta, usually ascending


and transverse

1.

2.
3.
4.
5.

Syphilitic aortitis:
inflammation of the vasa
vasorum (obliterative
endarteritis and mononuclear
infiltration)
Ischemic necrosis of the
media
Scarring and contraction
(tree barking)
Wall weakening
Aneurysm

Aneurysm dilates aortic root


(ring)
Aortic valve incompetence
Left ventricle hypertrophy
Cor bovinum, 1000 gm
Heart failure

A saccular aneurysm affecting

the cerebral arteries of the circle


of Willis at points of branching
Histology: fibrous scarring, deficiency in
medial muscles
Only symptomatic if rupture and cause
subarachnoid haemorrhage, which is often
fatal.
Incidence increased in patients with
coarctation of aorta or polycystic kidneys.
Hypertension is not a risk factor for rupture.
Emotional excitement may precipitate

Microaneurysms (CharcotBouchard)
Small intracerebral arteries of hypertensive

subjects, especially around the basal ganglia.


May rupture and cause intracerebral haemorrhage.
Histology:
fibrosis of vessel wall, irregular outpouching, thrombosis

formation, old hemorrhage

Red arrow bacteria


Yellow arrow wall of

aneurysm

Caused by bacterial or fungal


infection of an artery leading to
focal weakening of the wall resulting
in aneurysm formation rupture
Common site:

root of aorta, cerebral arteries

Predisposing
factor:
infective
endocarditis, drug abuse, diabetes
Histology: Necrotizing inflammation
of vessel wall; bacteria or fungi may
be identified

Traumatic extramural haematoma walledoff

by fibrous tissue
Common site:
Proximal descending aorta, limb and neck arteries

Histology:
Granulation tissue, adventitial fibrosis

Blood loss/hypovolemic
Clinical syndrome, systemic imbalance

between oxygen supply and demand


Inadequate blood flow to body organs

and tissue causing life-threatening


cellular dysfunction
Body responds by maintaining

perfusion to vital organs, heart and


brain
Results in inadequate tissue and

cellular perfusion; if not reversed, the


body develops
acidosis and if untreated, progresses to

organ hypoxia, ischemia and death

Decrease in circulating blood


volume
Cardiogenic shock

Decrease in cardiac output


Sepsis, Neurogenic,

Anaphylactic
Increase in size of vascular bed

Mean arterial pressure

drops 10 -15 mm Hg
Decrease in circulating

blood volume (25-35%)


1000ml
Sympathetic nervous

system stimulated:
release of catecholamine

To maintain blood pressure:

increase in heart rate and


contractility;
increase in peripheral

vasoconstriction
Circulation maintained,

but can only be sustained


short time without harm to
tissues

Intermediate or progressive
shock
Further drop in MAP (20%)
Increase in fluid loss (1800 2500 ml)
Vasoconstriction continues and leads

to oxygen deficiency
Body switches to anaerobic

metabolism forming lactic acid as a


waste product.
Body increases heart rate and

vasoconstriction.
Heart and brain become hypoxic
State of acidosis with hyperkalemia

develops
Needs rapid treatment

Refractory or
irreversible shock
Tissues are anoxic,

widespread cellular death


Even with restoration of blood

pressure and fluid volume there


is too much damage to
restore homeostasis of tissues
Cellular death leads to tissue

death; vital organs fail and


death occurs

Cardiovascular

Respiratory

Initially: slight tachycardia,

Initially: Increased respiratory rate, but gas

normal blood pressure


Progresses to weak, rapid

pulse with dysrhythmias


Progressive decrease in

systolic and diastolic blood


pressures with narrowing of
pulse pressure

exchange is impaired; leads to anaerobic


metabolism and development of acidosis
Acute Respiratory Distress Syndrome (ARDS):

complication of decreased lung perfusion


Gastrointestinal and Hepatic
GI organs become ischemic, with blood

circulation shunted to heart and brain

Neurologic
Develops cerebral hypoxia
Complications
Restlessness initially, then altered
Stress Ulcers: GI mucosa becomes ischemic,
level of consciousness, lethargy,
prone to rapid ulceration
coma
Paralytic Ileus: decreased gastrointestinal

Renal: Decreased kidney


perfusion leads to oliguria (urine
output < 20 ml/o)

Skin: cool, pale, hypothermic

motility with decreased blood flow


Altered liver metabolism: initially glucose made

available, then hypoglycemia, fat breakdown leads to


ketones and metabolic acidosis

Hypovolemic shock refers to a

medical
or surgical condition in which

rapid fluid
loss results in multiple organ

failure due to inadequate


perfusion.
Trauma
Hemorrhage
Vomiting / diarrhea
Burns

The human body

responds to acute
hemorrhage by

activating 4 major
physiologic systems:
the hematologic system
the cardiovascular system

the renal system


the neuroendocrine system

Activating the coagulation

cascade and
contracting the bleeding

vessels
(via local
thromboxane A2 release)

Platelets are activated which

form an
Immature clot on the

bleeding source

The damaged vessel exposes


collagen, which
subsequently causes fibrin
deposition and
stabilization of the clot.

Cardiovascular
system

Increases the heart rate, increasing

myocardial contractility, and constricting


peripheral blood vessels.
This response occurs secondary to an

increase in release of noradrenaline and a


decrease in baseline vagal tone

(regulated by the baroreceptors in the


carotid arch, aortic arch, left atrium,
and pulmonary vessels).

The cardiovascular system also responds by


redistributing blood to the brain, heart, and
kidneys and away from skin, muscle, and GI
tract.

Angiotensin II has 2 main

The kidneys respond

to hemorrhagic
shock by stimulating

an increase in
Renin secretion from

the juxtaglomerular
apparatus

effects, both of
which help reverse

hypovolemic shock,
vasoconstriction of

arteriolar smooth
muscle and
stimulation of aldosterone
secretion by the adrenal

cortex

Causes an increase in circulating antidiuretic hormone (ADH)

ADH is released from the posterior pituitary gland in response to a


decrease in blood pressure (as detected by baroreceptors) and a
decrease in sodium concentration.
ADH indirectly leads to an increase in reabsorption of water and

salt (NaCl) by the distal tubule, the collecting ducts, and the loop
of Henle

Medications
Inotropic agents: improve cardiac

contractility

Fluid Replacement
Essential for hypovolemic shock

Types of Intravenous Fluids


Crystalloid: Dextrose or electrolyte

Vasoactive agents: drugs causing

vasoconstriction or vasodilatation
according to symptoms
Other meds according to cause

solutions: Increase intravascular and interstitial

fluid volume:
Isotonic .9% NaCl, lactated Ringers Hypotonic (5%

dextrose in water, .45% NaCl)


Colloids: Do not diffuse easily through

capillary walls
Fluids stay in vascular compartment; increase

osmotic pressure : albumin, plasma protein and


dextran.
Blood and Blood Products
Treatment of hemorrhage
Restore coagulation properties

such as antibiotics, steroids

Oxygen Therapy

Patent airway and adequate

oxygenation critical
interventions
Monitor with ABG
Mechanical ventilation

assistance may be needed

Associated with
diabetes and smoking
Peripheral vascular
disease can affect both
legs but is often more
severe on one side

5% of males older than 50 years

have intermittent claudication

5% of claudicants progress to

critical ischaemia each year

75% of patients remain stable to

show clinical improvement

At 5 years of follow-up
10% claudicants and 50% of those

with critical ischaemia have had an


amputation.
20% claudicants and 50% of those
with critical ischaemia have died
usually from ischaemic heart disease

Rest pain is pain in the foot even

when not walking.

The affected foot looks purplish in

colour and feels cold to touch.

The foot pulses are not palpable.


Angioplasty and by-pass surgery are

the only available treatment.

Sometimes, amputation is required

as the last resort to relieve pain.

Management
History to assess disability

associated with symptoms


(claudication)
Exclude rest pain or tissue

loss (ulcer)

Risk factor reduction


Stop smoking - arrests disease
progression
Lipid-lowering drugs
Anti-platelet medication
Good diabetic control if appropriate
Regular exercise - as part of

Doppler studies to measure

pressures and assess wave


forms

supervised exercise program

Lose weight
Surgery

Dilated, tortuous veins which lead to valvular

incompetence

Superficial veins of the leg-posture/simple

orthostatic edema

Frequent thromboembolism- thrombosed deep

veins

Esophageal varices- portal hypertension

Macro appearance
Veins are dilated, elongated and scarred
Intraluminal thrombosis
Valvular deformities: thickening, rolling and

shortening of the cusps


Histology
Variation in thickness of the venous wall
Areas of smooth muscle cell hyperplasia and

intimal fibrosis
Degeneration of elastic tissue
Calcifications within the media

Venous congestion, persistent

edema and pain


Thrombosis is common but
thromboembolism is extremely
rare
Trophic changes

Stasis dermatitis
Ulcerations and poor wound healing

varicose ulcers

Thrombosis with

inflammation

Migratory thrombophlebitis

is associated with
deepseated visceral cancer
e.g. pancreas, lung, stomach.

Any condition which impedes


normal venous return
predispose to thrombosis:
Immobility
Malignancy
Pregnancy and childbirth
Estrogen therapy
Haematological disorders
Intravenous cannula

Usually manifestations are subtle


Edema distal to occluded vein
Dusky cyanosis
In some cases: local signs of inflammation (heat,

tenderness, redness, swelling and pain)


Homans sign: pain elicited by pressure over

affected veins, squeezing the calf muscles or


forced dorsiflexion of the foot
Complication: pulmonary thromboembolism

Small embolus can be silent


Large embolus can induce certain

reflex activity in the respiratory


center resulting in
bronchoconstriction,
vasoconstriction and sudden death

Chest pain or shortness of breath


Mortality rate is highest when there

is sudden massive occlusion of the


major pulmonary arteries

Due to portal

hypertension related
to cirrhosis
Common cause of

massive
haematemesis