Chapter 4

HEMODYNAMIC DISORDERS
Sr. No. TOPIC Page No.
1 Classification of hemodynamic disorders 2

2 CVC of lung 2

3 CVC of liver 3

4 CVC of spleen 4

5 Shock 5

6 Stages of shock 8

7 Hemostasis 10

8 Thrombosis 14

9 Thromboembolism 17

10 Amniotic fluid embolism 20

11 Caissons disease 21

12 Fat embolism 22

13 Infarction 23

14 Pathophysiology of edema 26

15 Transudate and exudate 29

16 Cardiac edema 29

17 Pulmonary edema 31

18 Nephrotic and Nephritic edema 33

19 Important questions 33

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 CLASSIFICATION OF HEMODYNAMIC DISORDERS

HEMODYNAMICS

Hemodynamic encompasses maintenance of:

1. Optimal volume of blood in vessels
2. Blood in liquid form in an uninterrupted vasculature; with formation of clot on vascular injury
3. Interchange of fluid: fluid exits from the arteriolar end into interstitium & re-enters the circulation
at the venular end. A small residual amount of fluid in the interstitium is drained by the
lymphatics.

HEMODYNAMIC DISORDERS

1. Disorders of blood volume:

• Increase in volume:
- in arterial bed of an organ or tissue is called hyperemia
- in venous bed is called congestion

• Decrease in volume:
- due to extravasation into tissue is called hemorrhage
- extensive loss of blood or plasma leading to hypotension & tissue hypoperfusion, is called
shock

2. Disorders of obstructive nature

• Obstruction in vasculature:
- Clotting in an uninjured vasculature is called thrombosis
- Migration of the clot to a distant site is called embolism

• Effects of obstruction on tissue:

- Thrombus/embolus cause occlusion of vessel leading to deficient blood supply to tissue called
ischemia
- Complete ischemia incurs death to the tissue, called infarction

3. Increase in the interstitial fluid is called edema

CHRONIC VENOUS CONGESTION OF LUNG

Congestion

Increased volume of blood in the venous bed is called congestion.

Pathophysiology of CVC of lung

Left heart failure

Back pressure on pulmonary vein

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CVC lungs

Causes

Left heart failure:

- Mitral stenosis (Rheumatic)
- Myocardial infarction

Gross appearance

• Early stage:
- Heavy
- Cut surface: red

• In later stages:
- Firm due to fibrosis.
- Cut surface: rusty brown due to hemosiderin liberated from degenerated red cells.
- Together called ‘brown induration’.

Microscopic appearance

• Alveolar septa:
- Widened due to dilated and congested alveolar capillaries
- Later: fibrosis

• Alveoli:
- Intra-alveolar hemorrhage: red blood cells seen in alveoli due to rupture of congested alveolar
capillaries.
- ‘Heart failure cells’: are hemosiderin-laden alveolar macrophages in the alveolar lumina.
Hemosiderin is released from the degenerating red cells. Heart failure cells are the hallmark of
CVC of lung.

CHRONIC VENOUS CONGESTION OF LIVER

Congestion

Increased volume of blood in the venous bed is called congestion.

Pathophysiology of CVC of liver

Left heart failure

Back pressure on Pulmonary vein

CVC lungs

Back pressure on Pulmonary artery

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Back pressure on Right heart

Right heart failure

Back pressure on Inferior vena cava

CVC of Liver

Causes

1. Right heart failure:

- Cor pulmonale
- tricuspid valvular disease
- pulmonary valvular disease
- congenital heart disease : left to right shunt
2. Inferior vena cava obstruction
3. Hepatic vein obstruction

Gross appearance

• Size: Enlarged
• External surface:
- Rounded edges
- Tensed capsule
• Cut surface:
ü Nutmeg liver (Red & yellow mottled appearance):
- Red area correspond to congested centrilobular sinusoids & necrotic centrilobular hepatocytes
- Yellow area correspond to viable periportal hepatocytes with fatty change

Microscopic appearance

• Centrilobular zone: severely affected

- Central vein & centrilobular sinusoids: dilated & congested
- Centrilobular hepatocytes: necrosed
- Centrilobular fibrosis with regenerating hepatocytes due to heart failure is called cardiac sclerosis
or cardiac cirrhosis

• Peripheral zone: less severely affected. Peri-portal hepatocytes show fatty change.

CHRONIC VENOUS CONGESTION OF SPLEEN

Congestion

Increased volume of blood in the venous bed is called congestion.

Pathophysiology of CVC spleen

Left heart failure

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Back pressure on pulmonary vein

CVC lungs

Back pressure on Pulmonary artery

Back pressure on right heart

Right heart failure

Back pressure on Inferior vena cava

CVC of Liver

Back pressure on portal circulation

CVC of Spleen

Causes

Portal hypertension:

PRE-HEPATIC HEPATIC POST-HEPATIC

1. Portal vein thrombosis 1. Cirrhosis 1. Right heart failure
2. Neoplastic obstruction of 2. Metastasis 2. Constrictive pericarditis
portal vein 3. Budd-Chiari syndrome 3. Budd Chiari syndrome
(Hepatic vein thrombosis) (extension into IVC)

Gross appearance

• Weight: mildly enlarged, weighing up to 300-500 gms (normal 150 gms)

• Capsule: thickened
• Cut surface:
- Color ranges from gray-red to deep red, called meaty appearance
- White pulp: indistinct

Microscopic appearance

• Red pulp:
- Sinusoids: dilated & congested.
- Red pulp shows foci of hemorrhages, with deposition of iron & calcium and surrounded by
fibrosis & elastic tissue. These nodules are called Gamna-Gandy bodies.
• White pulp:
- White pulp: atrophied

SHOCK

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Definition

Shock is a state of systemic hypoperfusion; caused either by reduced cardiac output or reduced effective
circulating blood volume. The end result of shock is hypotension, impaired tissue perfusion and cellular
hypoxia.

Types of secondary shock

1. Cardiogenic shock
2. Hypovolemic shock
3. Neurogenic shock
4. Anaphylactic shock
5. Septic shock

1. Cardiogenic shock:

• Definition: Cardiogenic shock results from failure of cardiac pump.

• Causes:

Deficient filling Deficient emptying Obstruction to outflow

1. Hemopericardium 1. MI 1. Pulmonary embolism

2. Arrhythmias 2. Ball valve thrombus

• Clinical features:
- Chest pain
- Visibly dyspneic
- Nausea, vomiting

2. Hypovolemic or hemorrhagic shock:

• Definition: ‘Hypovolemic shock’ results from loss of blood or plasma volume.

• Causes:
Due to blood loss Due to fluid loss
1. Trauma 1. Severe burns
2. Surgery 2. Persistent vomiting
3. Bleeding 3. Severe diarrhea.

• Clinical features:
- H/o trauma, burns
- H/o GI bleeding: hematemesis, melena, use of NSAID
- H/o coagulopathies: bleeding episodes, petechaie.
- Gynaec cause: vaginal bleeding, vaginal passage (abortion, ectopic pregnancy)

3. Septic (endotoxic) shock:

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• Definition: ‘Septic shock’ results from the immune response to infectious organisms that may be
blood borne or localized to a particular site.

• Causes of increasing incidence of sepsis:

1. Improved life-support for high risk patients
2. Increased use of invasive procedures
3. Growing numbers of immunocompromised patients (post-chemotherapy/ HIV)

Septic shock ranks first in the causes of deaths in ICUs.

• Infective organisms:
1. 70% are caused by endotoxin-producing gram negative bacilli; hence called ‘endotoxic shock’:
- E. Coli
- Klebsiella pneumoniae
- Proteus
- Pseudomonas

2. Gram positive bacteria

3. Fungus

• Pathogenesis:
Bacteria are attacked by inflammatory cells

Endotoxin [lipopolysaccharide (LPS) in bacterial cell wall] are released

LPS consist of toxic fatty acid (lipid a) core & polysaccharide coat including O antigens

Combine with LPS-binding protein (LBP) in blood

LPS-LBP complex binds to CD-14 receptor on monocytes/ macrophages

LPS then binds to signal-transducing protein, mammalian Toll-like receptor protein-4 (TLR-4)

Inflammatory cells release mediators:

IFN-γ, TNF- α, IL-1, 12, 6, PG, TXA2, NO, ...... causing

1. Vasodilatation leading to hypotension

2. Diminished myocardial contractility
3. Widespread endothelial injury
4. Pulmonary alveolar capillary damage, causing acute respiratory distress syndrome
5. Activation of coagulation system leading to DIC

Multiorgan failure

• Superantigens: These are bacterial proteins that cause syndromes similar to ‘Septic shock’ by
activating T-lymphocytes. E.g. Toxic shock syndrome toxin-1 produced by Staphalococci

• Clinical presentation:
- Fever

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 - Peripheral leukocytosis > 12,000/cmm

4. Neurogenic shock:

• Definition: State of shock caused by sudden loss of sympathetic nervous system signals to
smooth muscle in vessel walls. As a result vessels relax resulting in peripheral vasodilatation &
peripheral pooling of blood.

• Causes:
1. Anaesthetic accident
2. Spinal cord injury

5. Anaphylactic shock:

• Definition: A state of shock due to production of IgE antibodies against certain allergic substance
like food or drug. IgE sticks to mast cells and basophils; which in turn release Histamine (a
powerful vasodilator and airway constrictor) & other mediators.

• Allergens:
1. Foods: nuts, fruit, vegetables, fish, spices
2. Drugs: Penicillins, Anaesthetic drugs, Aspirin
3. Latex: Rubber latex gloves, Catheters
4. Bee or wasp stings

STAGES OF SHOCK

Stages of shock

Unless the insult is massive & rapidly lethal, (e.g. a massive hemorrhage from a ruptured aortic
aneurysm), shock tends to evolve through following three, somewhat artificial phases.
1. Stage I : Non-progressive compensated stage
2. Stage II : Progressive decompensated stage
3. Stage III : Irreversible decompensated (Refractory) stage

Stage I- Non-progressive compensated stage

• Definition: Early stage of shock in which the attempt is to:

- restore blood volume
- maintain perfusion to vital organs (brain & heart)

• Pathophysiology:
1. Fluid conservation by kidney
2. Sympathetic stimulation

Fluid conservation by kidney:

In shock, there is reduced cardiac output & renal hypoperfusion

Low GFR, thus low conc. of Na+ in tubules

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 Stimulates granular cells of JGA to secrete renin

Angiotensinogen à Angiotensin-I à Angiotensin-II

Stimulates adrenal cortex to secrete aldosterone

Aldosterone increases reabsorption of Na+ by distal convoluted tubule

Stimulates release of ADH (hypothalamus), causing H2O retention

Increases blood volume, thus venous return & cardiac output

Sympathetic stimulation:
Shock

Decreased cardiac output, low BP

Stimulates baroreceptors

Sympathetic stimulation

Widespread vasoconstriction Compensatory sympathetic (vasomotor) response

of skin & abdominal viscera
Cerebral & cardiac vessels are less sensitive to sympathetic
response, thus maintaining normal caliber & perfusion

• Clinical features:
- Cool and pale skin due to cutaneous vasoconstriction
- Tachycardia

Stage II- Progressive decompensated shock

• Definition: In progressive decompensated stage, shock progresses to a point where:

- Vital organs begin to experience significant hypoxia
- Will eventuate into death unless treated

• Pathophysiology:
Acidosis:
Significant persistent vasoconstriction in stage I

Persistent O2 deficiency to tissues

Impairs aerobic respiration, leading to anaerobic glycolysis

Accumulation of lactic acid, thus low (acidic) pH: acidosis

Acidosis causes failure of the sympathetic (vasomotor) system, acting in Stage I

Vasodilatation Perfusion to vital organs is affected

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Peripheral pooling of blood
Worsens cardiac return & thus output

• Clinical effects:
ü Patient appears confused
ü Reduced urinary output

Stage III- Irreversible decompensated shock

• Introduction: All forms of therapy are inadequate to save life.

• Pathophysiology: Consequences of anoxic injury to various organs & tissues of body are primarily
responsible for progression of shock to irreversible stage.

1. Heart:
Nitric Oxide synthesis

Worsens myocardial contractile function

2. Kidneys:
Reveal acute tubular necrosis
Leading to oliguria, anuria and electrolyte imbalance

3. Adrenals:
Adrenal exhaustion

Reflected by cortical cell depletion

4. Intestines:
Prolonged vasoconstriction of intestinal vessels causes ischemic necrosis of intestine

Intestinal bacterial flora enters circulation through ischemic area

Moreover in shock, anoxic injury to RE-system (spleen & liver), impairs defense mechanism

Superimposed septic shock

5. Lungs:
In initial stages, lungs are rarely affected because they are resistant to hypoxia

When bacterial sepsis supervenes, lungs show diffuse alveolar damage, called ‘Shock lung’

HEMOSTASIS

DEFINITION

Hemostasis accomplish two important functions:

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 1. maintain blood in a fluid, clot-free state in normal vessels (anti-thrombotic mechanism)
2. rapid formation of localized clot at the site of vascular injury (pro-thrombotic mechanism)
Hemostatic balance between anti-thrombotic and pro-thrombotic mechanisms is regulated by vascular
wall, platelets and coagulation system.

ANTI-THROMBOTIC MECHANISM

Endothelial anti-platelet effect

Intact endothelium insulated platelets from highly thrombogenic subendothelial ECM constituents.

Endothelial anti-coagulant effect

1. Heparin-like molecule interact with antithrombin-III to inactivate aII (thrombin) and aX (common
pathway) and aIX (intrinsic pathway).
2. Thrombomodulin binds to thrombin (aII) converting it from a procoagulant to an anti-coagulant.
The complex activates protein C. Activated protein C in presence of protein S inactivates factors
aV (common pathway) and aVIII (intrinsic pathway).
3. Tissue Factor Pathway Inhibitor (TFPI) produced by intact endothelium inhibit activated Tissue
Factor, coagulation factors aVII (extrinsic pathway) and aX (common pathway).

PRO-THROMBOTIC MECHANISM

Steps of formation of hemostatic plug

1. Vasoconstriction : a function of vessel wall

2. Primary hemostatic plug : a function of platelets
3. Secondary hemostatic plug : a function of coagulation system
4. Fibrinolytic effect (tertiary hemostasis) : a function of endothelium
5. Counter current mechanism : restricts clot to site of injury

Step 1- Vasoconstriction

- Occurs for brief period

- Due to reflex neurogenic mechanisms augmented by secretion of endothelin, a potent
endothelium derived vasoconstrictor
- Reduces blood loss
- Bleeding will resume if platelets and coagulation system does not get activated.

Step 2- Primary hemostatic plug

Injured blood vessel expose platelets to highly thrombogenic subendothelial extracellular matrix
substances like collagen (most important), proteoglycans, fibronectin and other adhesive glycoproteins.
This leads to activation of platelets. Activated platelets undergo following changes:

1. Platelet adhesion: Platelets adhere to extracellular matrix largely via

- Von Willebrand Factor (vWF). vWF is produced by Weibel-Palade bodies of endothelium, α-
granules of platelets and subendothelial connective tissue. Genetic deficiency of vWF leads to
bleeding disorder called von Willebrand disease.

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 - Receptor for vWF on platelets: GpIb (genetic deficiency of GpIb receptor leads to bleeding
disorder called Bernard Soulier syndrome)
- The complex stabilizes adhesion against sheer forces of blood.

2. Platelet shape change:

- The shape of platelets changes from small rounded disks to flat plates with markedly increased
surface area
- The shape change helps in pavementing the endothelial gap

3. Platelet secretion (release reaction/ activation):

ü Platelets contain 3 types of granules: alpha (α), dense core (δ) and lysosomal granules

Platelets upon shape change

Release contents stored in α- & δ-granules

α granules δ (dense core) granules

Factor I, V, VIII, ADP, ATP
Platelet Factor-4 Ca2+
vWF Histamine, Serotonin
PDGF, EGF Epinephrine
TGF-β
P-selectin
Plasminogen activator inhibitor-1

ü Platelet activation leads to surface expression of phospholipid complexes, which provide binding
sites for calcium and coagulation factors of the intrinsic coagulation pathway.

4. Platelet recruitment:
- More platelets are recruited to the site of injury by ADP released from δ-granules &
Thromboxane-A2 (TxA2) synthesized and secreted by activated platelets.

5. Platelet aggregation:
- Adjacent platelets bind to each other through fibrinogen (Factor I)
- GpIIb-IIIa is the receptor for fibrinogen (genetic deficiency of GpIIb-IIIa receptor leads to
bleeding disorder called Glanzmann thrombasthenia)
- Called primary (reversible) plug

Step 3- Secondary plug (clot contraction)

Occurs as a result of activation of coagulation pathway

Surface contact of platelets to collagen Tissue factor (thromboplastin) released from

damaged subendothelial tissues

Activates intrinsic coagulation pathway Activates extrinsic coagulation pathway

XII aXII VII aVII

XI aXI
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 Ca 2+
IX aIX

VIII aVIII
Ca 2+
X aX

V aV
XIII

II aII (Thrombin) Ca2+

Ca 2+
aXIII
I aI (Fibrin)

Soluble fibrinogen is converted into insoluble fibrin gel, which encases platelets and other circulating
cells to form secondary hemostatic plug.

Step 4- Tertiary hemostasis (Fibrinolysis)

• When the clot is stable:

- tissue-plasminogen activator (t-PA) secreted by endothelial cells &
- urokinase plasminogen activator (u-PA) secreted by various tissue cells; convert

Plasminogen Plasmin

Fibrin Fibrinogen degradation products (FDP)

Step 5- Counter current mechanism

Normal endothelial cells adjoining the site of injury, restrict clot to the site, by secreting:
(i) Adenosine diphosphatase

Degrade ADP

Inhibiting platelet aggregation

Thereby limiting clot formation to the site of injury.

(ii) PGI2 & nitric oxide (NO)

Potent vasodilators & prevent platelet aggregation

Thereby restricting clot to the site of injury.

THROMBOSIS

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PATHOPHYSIOLOGY OF THROMBOSIS

Definition

Thrombus is a pathological process, whereby clotted mass of blood is formed in non-interrupted vascular
system or thrombotic occlusion of a vessel after a relatively minor injury.

Pathogenesis

Three primary influences predispose to thrombus formation, called Virchow’s triad are endothelial
injury, alteration in blood flow and hypercoagulability.

1. Endothelial injury:
Endothelial injury predisposes to thrombosis by 3 mechanisms:
i) it exposes platelets to highly thrombogenic subendothelial ECM culminating in activation of
intrinsic pathway.
ii) Injured endothelium releases tissue factor, which activates the extrinsic pathway.
iii) Endothelial injury also depletes locally anti-thrombotic substances like PGI2 and PAs.

Causes of endothelial injury are:

i) Heart: myocardial infarction, cardiac surgery / infection / immunological reaction
ii) Valvular disease: inflammation, prosthesis
iii) Ulcerated atherosclerotic plague: of aorta / arteries
iv) Plasma agents: Homocystinuria, hypercholesterolemia
v) Exogenous agent: bacterial toxin, cigarette, radiation

2. Alteration in blood flow:

• Normally blood flows in a laminar flow i.e. blood cells occupy central axial stream; while
periphery, close to endothelium, is free from blood cells
• Alteration in blood flow, turbulence (increased flow) or stasis (reduced) flow leads to :
1. Disturbance in laminar flow
2. Damage of endothelium
3. Retards inflow of inhibitors of coagulation factors
4. Retards hepatic clearance of activated coagulation factors

• Causes of turbulence:
1. Ulcerated atherosclerotic plaque
2. Aneurysms

• Causes of stasis:
1. MI causes region of non-contractile myocardium leading to stasis
2. Mitral valve stenosis (RHD) results in left atrial dilation and stasis
3. Atrial fibrillation causes stasis of blood in atria
4. Hyper viscosity syndrome e.g. polycythemia vera cause small vessel stasis
5. Sickle cell anemia causes vascular occlusion and stasis

3. Hypercoagulability:
• Not a common cause of thrombosis.
• Classified as:
i) Primary: genetic disorders associated with deficiency or defect of anti-thrombotic proteins:
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 a) Mutation of Factor V gene (Leiden mutation) rendering Factor Va resistant to cleavage by
protein-C
b) Anti-thrombin III deficiency
c) Mutation of prothrombin gene
d) Protein C deficiency
e) Protein S deficiency

ii) Secondary: acquired conditions:

1. Tissue injury: surgery, severe burns, severe trauma
2. Prolonged bed rest
3. Disseminated cancer: tumous of certain organs (pancreatic & bronchogenic carcinoma)
secrete pro-coagulatory substances causing migratory thrombosis
4. With advancing age, platelet aggregability increases.
5. Late pregnancy
6. Long term use of OCP increases concentrations of certain coagulation factors.
7. Obesity
8. Smoking
9. Heparin-induced thrombocytopenia (HIT) syndrome: It occurs in 5% population treated with
heparin. Patient develops antibodies against heparin-PF4 complex.
10. Anti-phospholipid antibody syndrome: These patients give a false positive test for syphilis.
ü Pathogenesis:
i) Normally, coagulation cascade is assembled on the phospholipid surface of platelets. This
is kept together by ionized calcium.
ii) In anti-phospholipid syndrome, patient develops antibodies against phospholipid protein
complexes, thus inhibiting coagulation.

ü Classification:
i) Primary
ii) Secondary: to autoimmune disease, e.g. SLE

ü Clinical manifestations:
i) thrombocytopenia
ii) recurrent thrombi
iii) venous thrombi in deep leg veins, hepatic & retinal veins
iv) arterial thrombi in cerebral, coronary, mesenteric & renal arteries
v) valvular vegetation's
vi) repeated miscarriages due to Ab-mediated inhibition of t-PA required for trophoblastic
invasion of uterus

TYPES OF THROMBI

Introduction

Thrombi can arise within the heart (cardiac), in arteries, veins or capillaries. When arterial thrombi arise
in heart chambers or in the aortic lumen, they usually adhere to the underlying wall and are called mural
thrombi.

Cardiac mural thrombi arise due to pathology in chambers or valves of heart:

1. Arrhythmia
2. Dilated cardiomyopathy
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 3. MI
4. Infective endocarditis
5. Nonbacterial thrombotic endocarditis
6. Verrucous (Libman-Sacks) endocarditis in patients of SLE due to deposition of immune
complexes

Aortic mural thrombi arise from ulcerated atherosclerotic plaque and aneurysmal dilation.

Capillary thrombi are minute thrombi present in the capillaries. They are caused by acute inflammation,
vasculitis, DIC.

Arterial & venous thrombi

Arterial thrombus Venous thrombus

Blood flow Formed in rapid-flowing blood of arteries Formed in slow moving blood of veins
Cause 1. Endothelial cell injury: Stasis
- Vasculitis
- Atherosclerotic plaque
- Traumatic
2. Turbulence:
- Vessel bifurcation
Site Coronary artery - Superficial: occur in saphenous
Cerebral artery system especially with varicosities
Femoral artery - Deep: femoral, popliteal, iliac veins
Gross - Usually occlusive - Invariably occlusive
appearance - Tail builds away from heart - Tail builds towards heart
- Lines of Zahn (alternate - Red-blue in colour, with indistinct
dark (RBC) & light (platelets & fibrin) lines of Zahn
bands seen
Microscopic - Red areas of lines of Zahn are Indistinct lines of Zahn with more
appearance composed of blood cells abundant red cells
- White areas composed of platelets,
fibrin.
Fate Entire thrombus embolizes Tail-end embolizes
Clinical - Ischemia - Edema
effect - Infarction - Skin ulcer
- Poor wound healing
- Thrombophlebitis

FATE OF THROMBI
1. Resolves: within 1-2 days by fibrinolysis
2. Propagation: enlarges accumulating more fibrin, platelets and RBCs
3. Organization & incorporation into wall:
If thrombus persists for few days

Healing occurs by granulation tissue, endothelial cells & smooth muscle cells proliferation.

By contraction of mesenchymal cells.

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 The thrombus gets incorporation into vessel wall.
4. Recanalization:
Endothelial cells send capillary channels into the thrombus.

These channels anastamose & maintain the continuity of original vessel.

5. Embolization: thrombus dislodges & transports to other site.

POST-MORTEM & ANTE-MORTEM CLOT

Postmortem clot Antemortem clot
Shape Takes the shape of vessel May or may not take the shape of
vessel
Attachment to wall Clot is not attached to wall Attached to wall at origin.
Consistency Soft, rubbery & gelatinous Dry, granular, friable & firm
Gross appearance ✓ ‘Current jelly’ (dependent portion of ✓ Shows lines of Zahn : alternate

clot is red due to gravitation of RBCs) dark (RBC) & light (platelets &
✓ ‘chicken fat’ ( supernatant serum is fibrin) bands.
yellow)
Microscopic ✓ Red blood cells in the dependent area. ✓ Red areas of lines of Zahn are
appearance ✓ Pink proteineceous material in the composed of blood cells;
supernatant area ✓ White areas composed of platelets,
fibrin.

THROMBOEMBOLISM
Definition

Embolism = ‘plug’ or ‘foreign body’. Embolus is a detached insoluble intravascular solid, liquid or
gaseous mass that is carried by the blood to a site distant from its origin.

Causes

99% of all emboli arise in thrombus. Unless otherwise qualified, the term embolus implies
thromboembolism. Rare forms of embolism:
1. Fat embolism
2. Gas embolism
3. Amniotic fluid embolism
4. Tumor embolism
5. Miscellaneous: Fragments of tissue
Placental fragments
Parasites
Barium emboli following enema
Foreign bodies e.g. needles, talc, sutures, bullet

Classification

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1. Source of embolus
a) Arterial or systemic emboli:
- Arise from left heart or arterial tree
- Lodge in arterial circulation
b) Pulmonary emboli:
- Arise from venous system
- Lodge in lung

2. Matter of embolus
Solid Liquid Gaseous
a) Thrombus a) Fat globules a) Air
b) Tumor clump b) Amniotic fluid
c) Tissue c) Bone marrow
d) Parasites
e) Foreign body

3. Presence or absence of infection

a) Bland embolus: sterile
b) Septic embolus: infected

4. Flow of blood
a) Paradoxical embolus (crossed embolus): Paradoxical embolus is an embolus which is carried
from the venous side of circulation to the arterial side or vice-versa, through:
- Patent foramen ovale
- Septal defect of heart
- Arteriovenous shunts in lungs
b) Retrograde embolus: Retrograde embolus is the embolus, which travels against the flow of blood.
E.g.:
- Normal course for tumor emboli from adenocarcinoma of prostate is :
Gonadal vein

Renal vein

IVC

Cause lung metastasis

- Retrograde embolus: due to increased pressure in body cavities as in coughing or straining

during defecation; prostatic tumor embolus enters:
L (lumbar)-vein

Cause spinal metastasis

Thromboembolism

• Classification:
1. Arterial (systemic) thromboembolism.
2. Venous (pulmonary) thromboembolism.

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• Arterial thromboembolism:
✓ Source:

Heart Arteries Paradoxical embolus

80-85%
1. Myocardial infarction 1. Atherosclerosis 1. From venous
(left ventricle & right atrium) circulation
2. Cardiomyopathy 2. Aneurysm
3. Valvular disease
4. Prosthetic heart valve

✓ Site of lodgment:
1. 70-75% arterial emboli lodge in arteries of lower limb.
2. 10% lodge in cerebral arteries.
3. 10% lodge in the arteries of abdominal viscera: spleen, kidney, intestines
4. Coronary arteries.

✓ Clinical consequence
1. Gangrene:
- Embolism of popliteal artery causes dry gangrene of lower limb.
- Embolism of femoral artery do not produce marked ill effect because of active dilatation of
muscular anastamotic branches.
2. Infarction: cerebral infarct, myocardial infarction, infarction of abdominal viscera
3. Arteritis
4. Aneurysm

• Venous thromboembolism:
✓ Source:
1. 95% arise from deep vein thrombi (DVT) of lower limb:
- popliteal vein
- femoral vein
- iliac vein

Causes of DVT of LL:

- CCF
- prolonged recumbency

2. 5% arise from:
- Varicosities of superficial veins of legs
- Pelvic veins:
a) Peri-ovarian, uterine & broad ligament venous thromboembolism are common in women :
✔ On long term OCPs,
✔ Late pregnancy
✔ Post-partum
b) Peri-prostatic vein
3. Right heart
4. Pulmonary artery disease

✓ Site of lodgment:
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 1. Large embolus gets impacted at bifurcation of main pulmonary artery, called saddle embolus.
2. Small emboli or a large embolus getting fragmented into multiple small emboli, lodge in the
peripheral branches, especially of the lower lobes of lung.
3. Paradoxical emboli of venous origin reach the arterial circulation.

✓ Clinical consequence:
1. Resolution: 60-80% of emboli dissolve by fibrinolytic activity.
2. Pulmonary infarct: emboli that lodge in the end-arteries, lead to pulmonary infarction.
3. Pulmonary hemorrhage: Obstruction of medium-sized arteries, which are not end arteries, lead to
pulmonary hemorrhage and not infarction because of dual blood supply.
4. Instantaneous death: results from saddle embolus or massive pulmonary embolism.
5. Acute cor-pulmonale (right heart failure secondary to obstruction of pulmonary micro-
circulation).
6. Chronic cor-pulmonale or pulmonary hypertension or pulmonary arteriosclerosis: result when
multiple small pulmonary emboli undergoing healing.

AMNIOTIC FLUID EMBOLISM

Definition

Embolism = ‘plug’ or ‘foreign body’. Embolus is a detached insoluble intravascular solid, liquid or
gaseous mass that is carried by the blood to a site distant from its origin. Amniotic fluid embolism is an
example of liquid embolism.

Epidemiology

• A grave complication of labor & post-partum

• Mortality rate: 86%
• Incidence: 1 in 50,000 deliveries

Contents of Amniotic fluid

1. Epithelial squames
2. Lanugo hair:
- are fine hairs found on the fetus body all over
- normally shed before birth
- replaced by vellus or terminal hair
3. Fat
4. Mucin from RT & GIT
5. Meconium:
- first intestinal discharge from newborns
- viscous, dark green
- composed of intestinal epithelial cells, mucus, bile, swallowed lanugo

Amniotic fluid into maternal circulation

Amniotic fluid enters maternal circulation at delivery due to:

1. Tear in placental membrane
2. Rupture of uterine / cervical veins
20
 Clinical presentation Pathophysiology
Respiratory distress Mechanical blockage of pulmonary circulation
Shock, Convulsions Anaphylactic reaction, accounts for majority of
Coma symptoms
DIC Liberation of thromboplastin, activates extrinsic
pathway
Death

Morphology

Ø Look for the presence of amniotic fluid in:

- veins of lung
- uterine veins
Ø Lumen of veins show presence of: epithelial squames, mucin & lanugo hair

DECOMPRESSION SICKNESS/ CAISSONS DISEASE

Definition

Embolism = ‘plug’ or ‘foreign body’. Embolus is a detached insoluble intravascular solid, liquid or
gaseous mass that is carried by the blood to a site distant from its origin. Decompression sickness is an
example of air embolism.

When an individual breathes under pressure, increased amount of gas dissolve in body fluids (blood,
interstitial fluid, fat). If this individual decompresses rapidly, gases come out of solution as minute
bubbles. O2 is readily soluble; N2 & helium (gases used by sea-divers & aeronauts) persist as gas emboli,
called decompression sickness.

Factors affecting decompression sickness

1. Depth or altitude reached: directly proportional to the difference in change of atmospheric

pressure.
2. Duration of exposure to altered pressure
3. Rate of ascent
4. General condition of individual
5. Obesity: Obese persons are more prone, since N2 is more soluble in fat.

Classification

Decompression sickness

Acute form Chronic form

(Bend’s & Chokes disease) (Caisson disease)

Clinical effects

• Acute form:
21
 ü Cause: emboli in blood vessels of mainly musculo-skeletal system, RS, CNS & heart
ü Clinical features:
1. Musculoskeletal system: patient doubles up due to pain in joints, ligaments & tendons, called
‘bends’
2. Lungs: ARDS, called ‘chokes’
3. CNS: vertigo, coma, death
4. Heart: MI
Thus acute form of decompression sickness is called 'Bends & Chokes' disease.

• Chronic form:
ü Cause: ischemic necrosis, activation of platelets & coagulation factors.
ü Clinical features:
1. Musculoskeletal system: avascular necrosis of head of femur, tibia, humerus
2. Lung: hemorrhage, edema, emphysema…
3. CNS: paresthesia, paraplegia

FAT EMBOLISM

Definition

Embolism = ‘plug’ or ‘foreign body’. Embolus is a detached insoluble intravascular solid, liquid or
gaseous mass that is carried by the blood to a site distant from its origin. Fat embolism is an example of
liquid embolism.

Source

1. Fatty marrow:
✔ multiple fractures of long bones, rib, sternum
✔ Osteomyelitis.
2. Injury to subcutaneous tissue:
✔ severe soft tissue trauma
✔ deep burns
✔ injury to pelvic fatty tissue during child birth
3. Injury to fatty liver
4. Phosphorus, carbon tetrachloride poisoning.
5. Lymphangiography

Traumatic fat embolism occurs in 90% individuals with severe skeletal injuries but less than 10% of
patients have any clinical findings.

Pathogenesis

Two-fold: Mechanical obstruction & biochemical injury

Fat globules have high surface tension, thus form microemboli

Lodge in pulmonary arterioles

Smaller emboli cross the pulmonary bed

22
 Reach the arterial system

Lodge in cerebral, coronary, renal & cutaneous arteries

Release of free fatty acids from fat globules causes local toxic endothelial injury

Fat embolism syndrome

Characterized by:
1. Pulmonary insufficiency
2. Neurologic symptoms
3. Anemia
4. Thrombocytopenia

Clinical features

Signs & symptoms begin 1-3 days after injury:

1. RS: Tachypnea, dyspnea
2. CVS: Tachycardia
3. CNS: irritability, restlessness, delirium coma
4. Thrombocytopenia: platelets adhere to countless fat globules & are removed from the circulation.
5. Anemia: RBCs form aggregates around the globi & are hemolysed
6. Diffuse petechial rashes in non-dependent areas: due to thrombocytopenia

Histological diagnosis

- Fat dissolves in paraffin embedded sections

- Microglobules can be demonstrated in tissue by Frozen section and fat stains

INFARCTION

Definition

An infarct is an area of ischemic necrosis within a tissue or an organ, produced by occlusion of either its
arterial supply or venous drainage. 99% of all infarcts result from thrombotic or embolic events, causing
arterial occlusion.

Causes

Obstruction Reduced Pathology Pressure

of lumen blood in from outside
in vessel vessel wall

1. Thrombo 1. Cardiac 1. Arteriosclerosis 1. Ligature

-embolism failure
2. Septicemia 2. Shock 2. Thromboangitis 2. Tourniquet
23
 obliterans
(Burger’s dz.)
3. SCD 3. Vasospasm 3. Tight plaster
(Raynaud’s dz.)
4. CML 4. Torsion
5. Strangulation
6. Intussuception
7. Volvulus

Factors that affect development of infarct

1. Type of blood supply to organ:

• Type of blood supply associated with increased vulnerability to infarction:
a) Single arterial supply without anastamosis: serve as end arteries. E.g.
- Central artery of retina
- Splenic arteries
- Interlobular arteries of kidney

• Type of blood supply that does not favor infarction:

a) Single arterial supply with rich anastamosis:
- Coronary arteries
- Gastric arteries
- Superior & inferior mesenteric arteries
b) Dual blood supply:
- Bronchial & pulmonary blood supply to lungs
- Portal & hepatic blood supply to liver
c) Parallel blood supply:
- Circle of Willis of brain
- Radial & ulnar blood supply in forearm

2. Vulnerability of tissue to hypoxia:

• Cells sensitive to hypoxic injury are:
a) Neurons
b) Myocardial cells
c) Epithelial cells of proximal convoluted tubules of kidney

• Cells least affected by hypoxic injury include fibroblast.

3. Degree of vascular occlusion: is directly proportional to development of infarction.

4. Rapidity of development of occlusion: Slow growing occlusions provide opportunity for

collaterals to develop, thus reducing the chances of infarction.

5. General & cardiovascular status:

- Poor general condition
- Associated diseases like cardiac failure, sickle cell disease, …. are on a higher risk of developing
infarction.

Types of infarct:

24
 Classified according to:
1. Color of infarct: white or red
White infarct Red infarct
Gross appearance ✔ White / pale / anemic ✔ Red or hemorrhagic
Cause ✔ Arterial occlusion ✔ Venous occlusion
✔ Infarcts of solid organs: heart, ✔ Infarcts of loose organs, lung
spleen, kidney ✔ Arterial occlusion with re-perfusion
e.g. if the embolus breaks into small
fragments & lodges into smaller
vessels, there is re-flow of blood
converting white infarct into red
✔ Organs with dual blood supply or with
anastomosis

2. According to the age of infarct: recent (fresh) or old (healed)

3. According to absence or presence of infection: bland (aseptic) or infected (septic)

Gross appearance of an infarct

ü Often multiple
ü Site: Commonly located at periphery of organs
ü Shape:
- Wedge
- Apex pointing towards occluded vessel at hilum of the organ
- External surface of the organ forms base of the wedge
ü Often depressed under surface, due to fibrosis

Microscopic appearance

- Infarcted areas show evidence of hemorrhage only for first 12-18 hours. Later coagulative
necrosis (liquefactive necrosis in brain) develops.
- While the margins of infarcted area show inflammatory (neutrophils & macrophages) response
beginning within few hours. Inflammation is well defined within 1-2 days.
- Most infarcts are ultimately replaced by scar tissue except brain.

Important types of infarct

• Myocardial infarction:
ü Cause
1. Coronary artery disease: atherosclerosis, embolism
2. Valvular heart disease
3. Shock
4. Emotion & exercise

ü Site:
Most common site:
- Left ventricle due to pathology of left anterior descending coronary artery which supplies
anterior wall of left ventricle & anterior 2/3rd IVS.
- Right atrium
25
 Right ventricle is spared because of thin wall and less metabolic requirements.
Left atrium is spared because it receives oxygenated blood.

• Splenic infarct:
ü Cause
1. Thromboembolism from the heart / aorta
2. Myeloproliferative diseases
3. Hodgkin’s disease
4. Sickle cell disease
5. Septicemia

• Kidney infarct:
ü Cause
1. Thromboembolism arising from heart / aorta
2. Renal artery atherosclerosis / arteritis
3. Sickle cell disease

PATHOPHYSIOLOGY OF EDEMA

DEFINITION
Edema means ‘swelling’ in Greek. Edema is defined as increased accumulation of fluid in the
interstitium. Fluid collections in different body cavities are called hydrothorax, hydropericardium and
hydroperitonium (ascites).

Any organ or tissue can be affected by edema. The commonly affected organ/ tissue is subcutaneous
tissue, lungs and brain. Severe generalized edema with profound subcutaneous swelling is called
anasarca.

Edema can be pitting, when the interstitial fluid is displaced upon pressing on the subcutaneous edema
with finger leaving a finger-shaped depression. On the other hand, fluid does not displace on pressure in
non-pitting edema. The rigid nature of this edema is due to high internal osmotic pressure in the fluid.
Examples of non-pitting edema are myxedema (hyperthyroidism) due to presence of hyaluronan in the
edema fluid, lymphedema (e.g. elephantiasis) and lipoedema.

INTRODUCTION

Body water content & distribution

• Body water in normal adult male: 60% of body weight.

• Body water is distributed in two compartments:

2/3rd (40%) 1/3rd (20%)

Intracellular Extracellular

Plasma (5%)
26
 Interstitial fluid
Lymph
Lumina of organs e.g. GIT
Body cavities: Pleural

Fluid exchange:

• Fluid exits from the arteriolar end of capillaries into interstitium & re-enters the circulation at the
venular end. A small residual amount of fluid in the interstitium is drained by the lymphatics,
ultimately reaching blood circulation via thoracic duct, which drains into left subclavian vein.

• Factors governing the exchange:

1. Capillary wall:
- An intact capillary endothelium is a semi-permeable membrane: allows passage of water &
crystalloids, with minimal passage of plasma proteins.

2. Hydrostatic pressure:
- Hydrostatic pressure is defined as the capillary blood pressure.
- It drives fluid out of the vessel.

3. Osmotic pressure:
- Osmotic pressure is the pressure exerted by chemical constituents of body fluid, e.g.: electrolytes
(crystalloid osmotic pressure) and proteins (colloid osmotic pressure or oncotic pressure).
- It draws fluid into the vessel.

Net force:

At arterial end At venous end

40 mmHg hydrostatic pressure 25 mmHg oncotic pressure
25 mmHg oncotic pressure 10 mmHg hydrostatic pressure
_________________________ _________________________
15 mmHg hydrostatic pressure 15 mmHg oncotic pressure

- At arterial end of capillaries, there is net hydrostatic force, thus fluid leaves the vessel to enter
interstitial space.
- At venous end of capillaries, there is net osmotic force, thus fluid enters the vessel
from the interstitium.

PATHOPHYSIOLOGY OF EDEMA
1. Increased hydrostatic pressure:
• At arterial end: Increased hydrostatic pressure (e.g. hypertension) has but little effect.
• At venular end: Increase in hydrostatic pressure, will reduce the net oncotic pressure, resulting in
decreased reabsorption of interstitial fluid.
• Associated clinical conditions:

Generalized increase Localized increase

in venous hydrostatic pressure in venous hydrostatic pressure
a) Right heart failure a) Deep vein thrombosis of lower limb
27
 b) Constrictive pericarditis b) Varicosities
c) Cirrhosis of liver leading to edema in c) Pressure by pregnant uterus
portal area d) Tumour pressing on vein

2. Reduced oncotic pressure:

• At arterial end: Reduced oncotic pressure, will further increase the net hydrostatic pressure,
allowing more fluid to leave the vessel.
• At venular end: Reduced oncotic pressure, will reduce the net oncotic pressure, retarding the
inward flow of fluid into the venules.
• Causes of hypoproteinema:
(i) Reduced intake:
- Malnutrition
(ii) Reduced production:
- Liver cirrhosis
(iii)Increased loss:
- Protein losing glomerulopathies (nephrotic syndrome)
- Protein losing enteropathies

3. Lymphatic obstruction:
• Lymphatic obstruction occurs due to inflammatory or neoplasm. E.g.:
ü Filariasis: lymphatic obstruction in inguinal region resulting in edema of external genitalia &
lower limbs, called elephantiasis.
ü Carcinoma of breast:
- Infiltration of superficial lymphatics by tumour emboli, cause edema of overlying skin giving
peau d’ orange appearance.
- Axillary nodes dissection or irradiation, produce lymphedema of the affected arm.

4. Increased capillary permeability:

• Mechanism:
Capillary endothelial injury

Widening of endothelial gap

Capillaries become permeable to plasma proteins

Interstitial oncotic pressure

Retaining fluid in the interstitium

• Associated clinical conditions:

Generalized Localized
a) Systemic infection a) Localized infection
b) Poisoning b) Insect-bite
c) Drugs c) Local irritant
d) Chemicals
e) Anaphylaxis
f) Anoxia

5. Sodium and water retention:

28
 • Is seldom a primary cause of edema; when there is acute reduction in renal function, reducing the
glomerular filtration rate (GFR) :
- Post-streptococcal glomerulonephritis
- Acute renal failure
• Commonly a contributory factor in several forms of edema:
- Edema due to congestive cardiac failure
- Cirrhosis of liver
- Edema of renal disease (nephrotic syndrome)

TRANSUDATE & EXUDATE

TRANSUDATE EXUDATE
1. More common 1. Less common
2. Cause: hemodynamic derangement (non- 2. Increased vascular permeability
inflammatory edema) (inflammatory edema)
3. Physical examination: 3. Physical examination:
ü Clear ü Turbid
ü SG: < 1.012 ü SG: >1.020
ü pH > 7.3 ü pH < 7.3
4. Chemical examination: 4. Chemical examination:
ü Protein: ü Protein:
- < 3 gm/dl, - > 3 gm/dl
- albumin with low fibrinogen, hence fluid - albumin with high levels of fibrinogen &
does not clot. coagulation factors, hence fluid readily clots.
ü Fluid glucose same as blood ü Fluid glucose: low
ü Fluid LDH: ü Fluid LDH:
- low - high
- eff. LDH : s. LDH = < 0.6 - > 0.6
5. Microscopic examination: 5. Microscopic examination:
ü few cells ü Many cells
ü mainly mesothelial cells ü mainly polymorphs and mesothelial cells
6. Example: CCF, ascites 6. Example: abscess

CARDIAC EDEMA

Causes

1. Isolated right-sided heart failure:

• occurs in diseases primarily affecting the lung:
− chronic emphysema
− chronic bronchitis
− pulmonary tuberculosis
− pulmonary emboli
− pneumoconiosis…..
• Or right heart valvular disease:
− Pulmonary valvular disease
29
 − Tricuspid valvular disease

2. Right heart failure secondary to left heart failure: is a more common cause of cardiac edema.
Initially left-sided heart failure will cause pulmonary edema, which is then followed by right heart
failure and cardiac edema. Causes of left heart failure:
− MI
− Hypertension
− Mitral valve disease
− Aortic valve disease

Pathogenesis of cardiac edema

Reduced cardiac output

Reduced arterial blood volume

Reduced renal hypoperfusion

Hypoxic injury to renal arterioles Reduced GFR

Increased permeability Low concentration of Na+ in renal tubules

Loss of proteins Stimulates granular cells

of juxta-glomerular apparatus
Reduced oncotic pressure to secrete renin (enzyme)

Angiotensinogen Angiotensin-I
(α2-globulin) (in lungs & kidney)

Angiotensin-II

Stimulates adrenal cortex to secrete aldosterone

Aldosterone increases reabsorption of Na+ by distal convoluted tubule

Stimulates release of ADH (hypothalamus), which leads to H2O retention

Thus increased blood volume, thus venous return;

But the failing heart cannot pump this extra volume

Increased hydrostatic pressure at venous end (Back pressure hypothesis)

(Forward pressure hypothesis)

Edema

Morphology of cardiac edema

• Cardiac edema is most common form of generalized edema.

30
• It is characterized by subcutaneous edema in the dependent parts of body, called dependent edema,
e.g. edema in legs when standing (pedal edema) and sacrum when recumbent (sacral edema).

PULMONARY EDEMA

Clinical presentation

• Patient presents with dyspnea (breathlessness).

• With further impairment there is orthopnea (dyspnea on lying down & relieved by sitting or
standing).
• Paroxysmal nocturnal dyspnea (PND), an extension of orthopnea, is characterized by attacks of
extreme dyspnea with suffocation & coughing, at night.

Classification

Pulmonary edema

Hemodynamic edema Alveolar/Irritant edema Undetermined origin

edema
Due to increased Due to microvascular injury High
altitude edema
hydrostatic pressure Neurogenic
edema

Hemodynamic pulmonary edema

• Pathophysiology:
- Normally the plasma hydrostatic pressure in pulmonary capillaries is much lower, average 10
mmHg. With plasma oncotic pressure of 25 mmHg,
25mmHg OP - 10mmHg HP = 15 mmHg OP
Thus, at the arterial end of pulmonary capillaries, there is net oncotic pressure of 15 mmHg, hence
fluid does not enter the interstitium, thus lung tissue is normally free from fluid.
- An increase in plasma hydrostatic pressure over plasma oncotic pressure will lead to escape of
fluid in the lung interstitium, thus causing pulmonary edema.

• Associated clinical conditions:

i) Left heart failure
ii) Mitral stenosis
iii) Pulmonary vein obstruction.

Alveolar or irritant edema

• Pathophysiology: Alveolar edema is caused by injury to the vascular endothelium of pulmonary bed,
leading to leaking out of plasma fluid & proteins into the interstitium & causing pulmonary edema.

• Associated clinical conditions:

i) Infection: pneumonia, septicemia.
31
 ii) Inhaled gases: oxygen, smoke.
iii) Liquid aspiration: gastric contents, near -drowning.
iv) Drugs & chemicals: kerosene…..

Pulmonary edema of undetermined origin

a) Acute high altitude pulmonary edema: Individuals climbing to high altitudes (>2500 meters), with
acclimatization, develop:
1. polycythemia
2. raised pulmonary arterial pressure
3. increased pulmonary ventilation
4. increased heart rate
5. increased cardiac output;
and the individual breathes safely even under low atmospheric pressure.
However if acclimatization is not allowed, he will develop cardio-pulmonary ill effects, leading to
pulmonary edema.

b) Neurogenic edema: anesthetic or spinal cord injury

Morphology

Irrespective of the underlying mechanism, the morphology of pulmonary edema is the same.
Pulmonary edema is most common form of localized edema.

• Gross appearance:
- Fluid accumulates in the basal regions of lower lobes due to gravity (dependent edema).
- Lungs are heavy and moist.
- Frothy fluid (mixture of air & fluid) extrudes out from cut surface.
- In late stages, the lungs become firm & heavy due to fibrosis and cut surface rusty brown in
colour due to hemosiderin, called ‘brown induration’.

• Microscopic appearance:
- Alveolar capillaries are congested.
- Excess fluid (granular pink precipitate) collects in the interstitium, called interstitial edema. As a
result alveolar septa are thickened.
- Later the alveolar linings break & the fluid enters the alveolar spaces, called alveolar edema. The
alveoli show micro-hemorrhages and inflammatory cells. The hemosiderin from degenerating red
cells is taken up by macrophages. These hemosiderin-laden macrophages are called ‘heart failure
cells’.
- In late stages, there is variable amount of fibrosis.

NEPHROTIC & NEPHRITIC EDEMA

Nephrotic syndrome

• Definition: Nephrotic syndrome is a clinical complex of:

1. Massive proteinuria, with daily loss of > 3.5 gm protein in urine
2. Hypoalbuminemia with plasma levels < 3 gm/dl
3. Generalized edema
32
 4. Hyperlipidemia & lipiduria (hypoalbuminemia triggers formation of lipoproteins from liver )

• Causes:
ü Primary kidney disease causing Nephrotic syndrome include:
1. Focal segmental glomerulosclerosis (Common causes
2. Membranous glomerulopathy of NS in adults)
3. Membranoproliferative glomerulonephritis.
4. Minimal change disease (commonest cause of NS in children)

ü Systemic disease affecting kidney, a cause of NS:

1. DM
2. Amyloidosis
3. SLE
4. Malaria
5. Hepatitis B
6. AIDS

• Pathophysiology of edema in NS:

Protein loss is due to leaky glomerular basement membrane secondary to the cause

• Differences between nephrotic & nephritic edema:

Nephrotic edema Nephritic edema

1. Cause: Nephrotic syndrome 1. Cause: Acute & rapidly progressive
glomerulonephritis
2. Mechanism: reduced oncotic pressure. 2. Mechanism: Sodium & water retention
3. Degree of edema: severe 3. Degree of edema: mild
4. Distribution of edema: subcutaneous tissue & 4. Distribution of edema: loose tissues [face, eyes
visceral organs (periorbital edema), ankles, genitalia]
5. Proteinuria: heavy 5. Proteinuria: moderate

IMPORTANT QUESTIONS

SHORT NOTES:
1. Pathophysiology of edema
2. What is edema? Discuss pathogenesis of cardiac edema.
3. Vascular endothelium as thrombo-resistant surface.
4. Define and classify thrombosis. Explain the etiopathogenesis of thrombosis.
5. Fate of a thrombus
6. Define embolism. Mention different types of emboli. Describe fat embolism.
7. Pulmonary embolism
8. Amniotic fluid embolism
9. Reversible shock
10. Pathogenesis of septic shock

SHORT ANSWERS:
(Note: Answers only to those questions not addressed in the text or written scattered are given here.

33
In some answers are given in detail to cover relative topics.)

1. Heart failure cells

2. Microscopy of CVC of liver

3. Gamna Gandy body

4. List 3 major types of shock with suitable examples.

5. Name two thrombotic factors secreted by endothelium.

Ans. Endothelin, von Willebrand factor, tissue factor
6. Two anti-thrombotic factors secreted by vascular endothelium.
Ans. Heparin-like molecule, Thrombomodulin, Tissue Factor Pathway Inhibitor (TFPI)
7. What is Virchow’s triad in thrombosis?
Ans. Three primary influences predispose to thrombus formation, called Virchow’s triad are
endothelial injury, alteration in blood flow and hypercoagulability.
8. Four causes of hyercoagulable state

9. Fate of thrombus

10. Paradoxical embolism

Ans. Paradoxical (crossed) embolus is an embolus which is carried from the venous side of
circulation to the arterial side or vice-versa, through:
1. Patent foramen ovale
2. Septal defect of heart
3. Arteriovenous shunts in lungs
11. Four organs in which pale infarct occur.
Ans. White infarct: spleen, heart, kidney, Raynaud’s phenomena in fingers/toes
Red infarct: lung, testes, ovaries, small intestine
12. Name two main factors causing edema of renal origin.
Ans. Nephrotic edema: minimal change disease, focal segmental glomerulosclerosis,
membranous glomerulopathy, membranoproliferative glomerulopathy
Nephritic edema: post streptococcal glomerulonephritis, IgA nephropathy, RPGN, CGN

34