OUR LADY OF FATIMA UNIVERSITY

COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER

BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.

HEMODYNAMIC DISORDERS

INVOLVES
———————————————————————
● Circulation
● Heart
● Aorta and arteries
● Microcirculation
● Vein and venules
● Interstitium
● Lymphatics
● Fluid balance

Passive Hyperemia
Hemodynamic disorders CHRONIC Venous Congestion
Hyperemia ● Increased blood flow • Liver
and ● Increased blood back-up • GROSS: enlarged, firm, with tense capsule
congestio • Cross-section: nutmeg appearance (alternating dark areas
n of congestion with pale areas of fatty changes)
• Lungs
Edema ● Increased fluid in ECF • Gross: enlarged, heavy, firm and deep red in color with
frothy blood oozing on squeezing
• Microscopic:
Hemorrha ● Extravasation • Thickened alveolar septa
ge • Alveoli containing edema fluid with intact or hemolyzed
RBCs and hemosiderin laden macrophages (heart failure
Hemostasi ● Formation of blood clot to stop cells)
s and bleeding • Consequences:
Thrombosi ● Inappropriate blood clotting • EDEMA – from increased pressure and volume
s • ISCHEMIC tissue injury and scarring or FIBROSIS – due to
lack of blood flow in passive long standing congestion
Embolism ● Downstream flow of a clot • Small HEMORRHAGIC foci – from capillary rupture
• HEMOSIDERIN LADEN MACROPHAGES (Heart Failure
Infraction ● Cell death due to lower blood Cells) – from subsequent catabolism of extravasated red
supply blood cells

Shock ● Circulatory failure/collapse Edema

• the result of the movement of fluid from the vasculature

HYPEREMIA
———————————————————————
● Characterized by increased in blood volume in a
particular tissue
● An active process of arteriolar dilation leading to
local increase in blood volume
● Occurs locally as a response to increased
functional demand: physiologic - exercise and
meals, pathologic - acute inflammation
● Hyperemic tissue are redder than normal because
of engorgement with oxygenated blood
into the interstitial space caused by:
1. Increased Hydrostatic Pressure(e.g.,heart failure)
2. Increased Vascular Permeability(e.g.,inflammation)
3. Decreasedcolloidosmoticpressureresultingfromreduced
plasma albumin
4. Lymphatic Obstruction(e.g.,inflammation or neoplasia)
5. Sodium Retention(e.g.,renal failure)
• the result of the movement of fluid from the vasculature into
the interstitial space
• Intracellular fluid (inside the cell)
• Extracellular fluid (inside the cell)
• Interstitial fluid
• Blood plasma
the result of the movement of fluid from the vasculature into
the interstitial space
• Hydrostatic pressure
• Osmotic or Oncotic
pressure

1 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.

• Pleural cavity –
• Pericardial cavity – HYDROpericardium
• Lymphatics • Peritoneal cavity – HYDROperitoneum / Ascites
• obstruction • ANASARCA
• Hydrostatic pressure • Osmotic or Oncotic • Severe generalized edema marked by profound swelling of
pressure subcutaneous tissues and accumulation of fluid in body
• Lymphatics cavities.
• obstruction
Decreased Op Hemorrhage
• Intravascular < Interstitial
• Due to...
• Decreased synthesis (e.g. liver disease, CHON • Extravasation of blood due to:
malnutrition) • Damage to blood vessels or vessel rupture • Defective clot
• Increased loss (e.g. nephrotic syndrome) formation
Decreased Op • Defects in Vessel Walls
• Intravascular < Interstitial • Infections – due to microbial damage to the
• Due to... microvasculature (vasculitis)
• Decreased synthesis (e.g. liver disease, CHON and disseminated intravascular coagulation
malnutrition) • Drug reaction
• Increased loss (e.g. nephrotic syndrome) • Collagen defects – e.g. scurvy, Ehler-Danlos syndrome,
• Increased vascular permeability Cushing syndrome
• Inflammation • Blood vessel fragility – e.g. perivascular amyloidosis,
• Excessive sodium retention hereditary hemorrhagic telangiectasia/Weber-Osler-Rendu
• Renal insufficiency, Glomerulonephritis, syndrome)
Hyperaldosteronism
Obligate water retention Defective clot formation
● the fluid may be protein poor (transudate) or protein • Defects in Primary Hemostasis • Thrombocytopenia
rich (exudate) • Defective platelet function

• Defects in Secondary Hemostasis

• Defects in clotting factors

• Depletion of coagulation factors
• Vitamin K deficiency

Hemorrhage Manifestations
Edema
• Petechiae
• Minute (1-2 mm in diameter) or pin-point superficial
Increased ● impaired venous return
hemorrhages
hydrostati
c pressure

Reduced ● nephrotic syndrome, malnutrition,

plasma cirrhosis
oncotic
pressure

Lymphatic ● inflammatory, neoplastic,

obstructio post-surgical, post-irradiation
n

Sodium ● renal insufficiency,

retention hyperaldosteronism

Inflammati ● acute, chronic, angiogenesis

on

• Common sites:
• Subcutaneous tissue, lungs, brain
• Body Cavities: HYDROthorax

2 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.

• Purpura
• Slightly larger (3-5 mm) diffuse superficial hemorrhages • AcuteChronic
Hemoglobin (purple)
Bilirubin (green)
Hemosiderin (brown)

• Clinical Features of Hemorrhagic Disorders: 1. Defects In

Primary Hemostasis
• petechiae (1-2 mm) or purpura (>3 mm) 2. Defects In
Secondary Hemostasis
• Bleeding from larger vessels or hematoma into tissues or
body cavities (hemarthrosis, hemoperitoneum, etc.), external
bleeding
3. Generalized Defects Involving Small Vessels
• “palpable purpura”, ecchymoses (1-2 cm) or hematoma
• *epistaxis, menorrhagia, hemarthrosis, hematuria,
hemorrhagic (hypovolemic) shock, iron deficiency anemia
(due to chronic or recurrent external blood loss)
• Ecchymoses (bruises)
• Larger (>1 cm) subcutaneous bleed Hemorrhage Significance

• Depends on:
1. Volume of blood loss
• >20% TBV = hemorrhagic shock 2. Rate
• Slow (weeks to months) vs. Fast (25-30% in a few hours)
3. Location
• Subcutaneous tissue vs. Brain

Hemostasis vs. Thrombosis

• HEMOSTASIS is a series of regulated processes that

maintain blood in a fluid, clot-free state in normal vessels and
causes bleeding to stop via clot formation in injured vessels.
• THROMBOSIS is the formation of blood clots (thrombus)
within the intact vascular system during life.
• Both involve three elements.
• Hematoma 1. vascular wall
• Clotted blood that accumulates in soft tissues 2. platelets
3. coagulation cascade

Hemostasis

1. Vascular Wall – Endothelial cells are central regulators of

hemostasis.
• INTACT endothelium is
• anti-platelet (PGI2, NO, ADP) • anti-coagulant (heparin-like
molecule thrombomodulin,
antithrombin III) • fibrinolytic (t-PA)
• INJURED Endothelium will display PRO-COAGULANT
properties:
• vWF, tissue factors, PAIs

2. Platelet Plug formation – hemostasis

1. Platelet adhesion (attachment):

• Binding of Platelet GpIb receptors to Von
Willebrand factor & GPVI receptor to collagen in
subendothelial cells (on damaged tissues)
• Leads to Platelet activation:
• Change in platelet shape
• Secretion of platelet granule contents
(calcium & ADP)

3 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.
• Change in membrane composition
(exteriorization of phosphatidylserine) • Activation
GpIIb/IIIa receptors
2. Release of Inflammatory Substances • ADP – platelet
recruitment
• Serotonin – vascular spasm (30 min
contraction)
• Thromboxane A2 – potent inducer of
platelet aggregation
3. Platelet AGGREGATION (stick together)
• fibrinogen binds to GPIIB/IIIA
receptors on surface of activated
platelets forms platelet plug
• closes small breaks
3. Coagulation – hemostasis Begins 30 seconds or more
after the injury
hemostasis
• Result: deposition of INSOLUBLE FIBRIN (CLOT)
• Blood usually clots within
3 to 6 minutes
4. Clot Stabilization & Resorption
Clot Retraction
• condensing of clot
• serum in plasma is squeezed out of the clot • help enhance
healing
Fibrinolysis
• Slow process of dissolving clot:
• thrombin and tissue plasminogen activator (t-PA):
• activate plasminogen to form plasmin
• Plasmin:
• digests fibrin strands
Hemostasis control
• Coagulation normally is restricted to sites of vascular injury
by:
• limiting enzymatic activation to phospholipid surfaces
provided by
activated platelets or endothelium,
• circulating inhibitors of coagulation factors, such as
antithrombin III, whose activity is augmented by heparin-like
molecules expressed on endothelial cells
• expression THROMBOMODULIN on normal endothelial
,which bind thrombin and convert it into an anticoagulant ,
• activation of fibrinogen (e.g.,by association of tissue
plasminogen activator with fibrin)
Defects in Primary Hemostasis
• Thrombocytopenia
• Decreased production of platelets
• drug-induced,infections(HIV, measles)
• nutritional deficiencies (B12, folate)
• bone marrow failure (e.g. aplastic
• bone marrow replacement (e.g. leukemia, disseminated
cancer, granulomatous disease)
• ineffective hematopoiesis (e.g. myelodysplastic syndromes)
of • Sequestration
• Hypersplenism – splenomegaly sequesters significant
amount of platelets
• Decreased platelet survival
• immunologic destruction – primary (e.g. autoimmune
thrombocytopenic purpura) and secondary autoimmune
disorders (e.g. alloimmune such as transfusion reactions, or
infections such as HIV & dengue)
• non immunologic disorders – disseminated intravascular
coagulation & thrombotic
• microangiopathies (in which systemic platelet activation
reduces platelet lifespan)
• Dilution
• in massive transfusions
• Defective Platelet Functions
• Defects in platelet adhesion
• von Willebrand disease – vWF
• Bernard-Soulier syndrome – GpIb
• Defects in platelet aggregation
• Glanzmann thrombasthenia – GpIIb-IIIa
• Disorders in platelet secretion
• storage pool disorders
Defects in Secondary Hemostasis
• Defects in clotting Factors • Hemophilia A – factor VIII
• Hemophilia B/Christmas disease – factor IX
• von Willebrand disease
• Depletion of coagulation factors
• Disseminated intravascular coagulation –
thrombohemorrhagic disorder, thrombotic diathesis →
consumption of platelets, fibrin, and coagulation factors →
hemorrhage
• Vitamin K deficiency
• impaired synthesis of factors II, VII, IX, X and protein C
Thrombosis
• refers to the formation of a thrombus within an intact
vascular lumen.
• A structured solid mass composed of coagulated blood
containing platelets and fibrin that are adherent to the
vascular endothelium.
• It should be distinguished from a simple blood clot.
• Clots often occur in the venous side of the circulation,
because this is
where most of the blood accumulates
• Clots occur...
• outside blood vessels (hematoma)
• outside the body (e.g. test tubes)
• outside life (post-mortem clot)
4 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.
•Linesof Zhan
• pale platelet and fibrin layers alternating with RBC layers
• Caused by imbalance between thrombogenic factors and
protective mechanisms.
• Primary abnormalities that lead to intravascular thrombosis
(the ''Virchow triad‘’):
endothelial injury– arterial thrombosis
stasis or turbulent blood flow venous
hypercoagulability of thrombosis the blood
Thrombosis cause
1. endothelial injury
• any disturbance in the dynamic balance of the pro- and
anti- thrombotic effects of the endothelium, not only physical
damage.
2. stasis or turbulent blood flow
3. Hypercoagulability of the blood
• an abnormally high tendency of the blood to clot, and is
typically caused by alterations in coagulation factors.
Thrombus classification
• According to the color composition of the thrombi.
• According to the presence or absence of bacteria.
• According to the site of thrombus.
• According to the presence or absence of bacteria:
1. SEPTIC thrombus
• containing pathogenic bacteria.
2. ASEPTIC thrombi
• without bacteria
• According to the site of thrombus:
1. VENOUS thrombi (the most common)
2. ARTERIAL thrombi - less common.
3. CARDIAC thrombi found in the heart chambers and valve
(MURAL).
4. CAPILLARY thrombi is rare.
• According to the site of thrombus:
Arterial thrombus
• Less common due to:
• rapid blood flow
• thick elastic arterial wall which resists injury
• SLOWLY Arises at sites of endothelial injury or turbulent
blood flow
• extend in a retrograde direction from blood flow
• Frequently occlusive
Arterial thrombosis-ischemia-infarction
• Location: Coronary arteries, Femoral arteries, Cerebral
arteries, Iliac arteries, Popliteal arteries, Mesenteric arteries
etc.
• Firmly attached to injured endothelium w/ poorly attached
tail embolus
• Site of embolism:
• lower extremities (75%) • CNS (10%)
Pale type with abundant platelets due to pro-
coagulant property of damaged endothelium
• Thrombosis in arteries are
affected by...
• Atherosclerosis
• Arteritis
• Aneurysms (Dilatational thrombi)
Venous thrombus
• most common due to: • slow blood flow
• thin non-muscular wall • superficial location
• RAPIDLY Arises from stasis of blood flow &
hypercoagulability state
• extend in the direction of blood flow
• Always occlusive Local congestion & swelling
• Location: superficial or deep veins of the leg (90%)
• Propagate some distance w/ tail poorly attached fragment
embolism
• Site of embolism: lungs
• Mixed or red type w/ more RBCs due to sluggish
blood flow
• Thrombosis in veins may be either: • Thrombophlebitis -
inflammation
• Phlebothrombosis - stasis
3. CARDIAC thrombi found in the aortic lumen or
(PARIETAL) the
heart chamber and valve (MURAL).
• Similar to arterial thrombus
• Arises at sites of endothelial injury or turbulent blood flow
• Extend in a retrograde direction from the point of
attachment
• Firmly attached to the injured endocardium
• PALE type
• NOT occlusive
5 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.
• Include:
• Auricular thrombosis in the left atrium over auricular
appendages in case of mitral valve stenosis.
• Mural thrombus in the left ventricle over an area of
myocardial infarction.
• Vegetations on the heart valves in rheumatic fever,
systemic lupus erythematosus and bacterial endocarditis.
4. CAPILLARY thrombi are rare.
• severe acute inflammation and frost bites.
Fate of thrombus
• Propagation.
• Tend to propagate towards the heart.
• Embolization.
• propagating portion of a thrombus is poorly attached, thus
prone to fragmentation and migration through the blood
• Dissolution.
• Due to activation of fibrinolytic factors
• for newly formed thrombi
• Organization and recanalization.
• ingrowth of endothelial cells, smooth muscle cells, and
fibroblast & eventual formation of capillary channels.
Clinical significance of thrombus
• Cause obstruction of arteries & veins
• Potential sources of emboli
Embolism
• Embolus – an intravascular solid, liquid, or gaseous mass
that is carried by the blood to a site distant from its point of
origin.
• Embolism – condition characterized by an embolus
occluding the lumen of a blood vessel, preventing blood flow
towards the organ it supplies.
• The vast majority of emboli derived from a dislodged
thrombus hence the term thromboembolism.
• The primary consequence of systemic embolization is
ischemic necrosis (infarction) of downstream tissues.
Embolism force
1. Thromboembolism – 99%
2. Fat emboli – consist of fat droplets
3. Air emboli – consists of bubbles of air or nitrogen
4. Atherosclerotic (Cholesterol) emboli – consist of
atheromatous debris
5. Tumor emboli – consist of tumor fragments
6. Bone marrow emboli
7. Foreign Body emboli
Pulmonary embolism
• Incidence: 2-4/1,000 hospitalized patients
• Source:
• 95% from deep leg vein thrombi above the knee.
• popliteal, femoral, and iliac veins
• Multiple emboli are common, either in sequence or as a
shower of
smaller emboli from a single large thrombus
• About 25% of people who have had DVT or PE are at risk
for another episode.
• Paradoxical embolism - passage through an interatrial or
interventricular defect to gain access to the systemic
circulation (rare).
60-80% clinically silent (small).
• Involvement of 60% or more of the pulmonary circulation
leads to sudden death, right heart failure or cardiovascular
collapse.
• Medium-sized arteries embolus: Usually causes pulmonary
hemorrhage not infarction (dual blood supply) unless in the
setting of left sided cardiac failure.
• End-arterial pulmonary embolism: infarction
Systemic thromboembolism
• Emboli in the arterial circulation.
• Source: 80% arise from intracardiac mural thrombi
• 2/3 assoc. with Left Ventricular Wall infarct,
• 1/4 with dilated left atria (e.g., secondary to mitral valve
disease);
• Remainder arise from aortic aneurysm, plaques or valve
vegetations.
• Often lodge in end arteries and cause infarction
• Site of embolism:
• 75% to lower extremities and 10% to the brain.
• Organs most severely affected: • Brain
• Lower extremity • Kidney
• Heart
Fat embolism
• Source: fractures of long bones, soft tissue trauma or
burns.
• 90% of individual with severe skeletal injuries, though
<10% have any clinical finding.
• Pathophysiology:
• Mechanical obstruction
• Occlusion of pulmonary and cerebral microvasculature
• Biochemical injury
• Free fatty acidslocal toxic injury to endothelium, platelet
activation &
granulocyte recruitment
• Clinical Manifestations: begins 1-3 days after injury with a
triad of...
Hypoxemia
Neurologic abnormality (irritability, restlessness)
Petechiae (20-50%) due to thrombocytopenia
• Other manifestations: tachycardia, anemia
• Rapid progression to delirium & coma
• Prognosis: Syndrome fatal in 10%.
6 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.

Air embolism • Appear wedge-shaped, overlying fibrinous exudate,

margins better defined
• AKA: with time
• Decompression sickness • Progression:
• "the bend" or "the chokes" • Caisson disease • Minute to hours: no demonstrable changes
• Cause: • 12-18 hrs: hemorrhage
• Surgery (bypass, neurosurgery in an upright (“sitting” • Few hours to 1-2 days: inflammatory response,
position) parenchymal regeneration
• Laparoscopic procedure
• Chest wall injury Type of infarct
• Sudden change in atmospheric pressure esp. Rapid RED (Hemorrhagic)
decompression in divers or • Occurs in:
those in rapidly ascending aircraft sudden bubbling of • venous occlusion of...
nitrogen dissolved in blood • loose tissues (lungs)
• Pathophysiology: • dual circulation (lungs, SI, liver)
• Gas bubble in artery can coalesce and obstruct vascular • Previously congested tissue • After flow is reestablished
flow cause distal
ischemic injury WHITE (Anemic)
• Focal ischemia to brain and heart. • Occurs in:
• Clinical: >100cc required for clinical effect. • arterial occlusions of....
• Skeletal muscle, soft tissues and joint pain • solid organs (heart, spleen, kidney, brain)
• Pulmonary vasculature pulmonary edema, hemorrhages, • where tissue density limits the seepage of blood from
and focal adjoining patent vascular bed
atelectasis or emphysema respiratory distress (chokes)
• CNSmental impairment and sudden onset of coma • Factors that influence development of an Infarct:
• Bone Multifocal ischemic necrosis of the heads of the 1. vascular supply
femur, tibiae, and 2. rate of development of occlusion (time for development of
humeri alternate perfusion pathway)
3. vulnerability of the tissue to hypoxia (neurons 3-4 minutes,
Amniotic fluid embolism myocardium 20-30 minute )
4. blood oxygen content (e.g. ventilation)
• Incidence: 1 in 40,000 deliveries. • 80% mortality rate.
• most common cause of maternal death in the developed Shock
world
• fifth most common cause of maternal death in the United • a condition of profound hemodynamic and metabolic
States. disturbance characterized by failure of the circulatory system
• Cause: to maintain an appropriate blood supply to the
• Tear in the placental membrane and/or microcirculation, with inadequate perfusion of the vital
• Uterine vein rupture organs.
• Pathophysiology: biochemical activation of the coagulation • the final common pathway for several potentially lethal
system and the innate immune system by substances in the events, including exsanguination, extensive trauma or burns,
amniotic fluid myocardial infarction, pulmonary embolism, and sepsis.
• Squamous cells shed from fetal skin , lanugo hair, fat from • characterized by systemic hypoperfusion of tissues
vernix, mucin from GI tract • it can be caused by diminished cardiac output or by
• Manifestations: reduced effective circulating blood volume
• Sudden severe dyspnea, cyanosis and hypotensive shock, • Consequences:
followed by seizures • impaired tissue perfusion cellular hypoxia
and coma
• Pulmonary edema & DIC
• Prognosis: 85% of survivors suffer some form of permanent type of shock
neurologic deficit
Hypovole ● intravascular volume loss
Infraction
mic ● Vasodilation, a hyperdynamic
process
• area of ischemic necrosis caused by occlusion of either
Distributiv ● Pump heart failure leading to
arterial supply or venous drainage.
e inadequate blood supply
• 99% from Arterial thrombosis or embolism.
● Physical constriction of blood
• Remainder: local vasospasm, extrinsic compression,
Cardiogen curriculum and inadeqaute blood
hemorrhage
ic supply
within a plaque, torsion, traumatic rupture.
• Infarcts caused by venous thrombosis are more common in
Obstructiv
organs with single venous outflows: e.g. testis, ovary.
e
• Histology: coagulative necrosis

7 I CASTELLON
 OUR LADY OF FATIMA UNIVERSITY
COLLEGE OF PHYSICAL THERAPY | BSPT 2-YA-2 1st SEMESTER
BASIC PATHOLOGY IN PHYSICAL THERAPY
Joanna Tan, M.D.

1. HYPOVOLEMIC
• secondary to a pronounced decrease in blood volume due
to:
• loss of fluid from the vascular compartment (eg, diarrhea,
excessive urine formation, & perspiration)
• hemorrhage

2. DISTRIBUTIVE
• Result from excessive vasodilation and pooling of blood
leading to impaired distribution of blood flow

3. CARDIOGENIC
• Occur when cardiac output is insufficient to meet the
demands of the body, resulting in inadequate tissue
perfusion
• characterized by decreased cardiac output and evidence of
tissue hypoxia in the presence of adequate intravascular
volume.
• leading cause of death in acute myocardial infarction (Ml)
• mortality rates as high as 70-90% in the absence of
aggressive, highly experienced technical care

4. OBSTRUCTIVE
• associated with physical obstruction of the great vessels of
the heart itself

Stages of shock

• An initial nonprogressive stage during which reflex

compensatory mechanisms are activated and vital organ
perfusion is maintained.
• A progressive stage characterized by tissue hypoperfusion
and onset of worsening circulatory and metabolic
derangement, including acidosis.
• An irreversible stage in which cellular and tissue injury is so
severe that even if the hemodynamic defects are corrected,
survival is not possible.

8 I CASTELLON