Chapter 4
HEMODYNAMIC DISORDERS
Sr. No.
1
TOPIC
Classification of hemodynamic disorders
Page No.
2
2
Pathophysiology of edema
2
3
Transudate and exudate
6
4
Cardiac edema
6
5
Pulmonary edema
8
6
Nephrotic and nephritic edema
10
7
CVC of lung
10
8
CVC of liver
12
9
CVC of spleen
13
10
Shock
15
11
Stages of shock
17
12
Hemostasis
20
13
Thrombosis
25
14
Thromboembolism
30
15
Amniotic fluid embolism
33
16
Caissons disease
34
17
Fat embolism
35
18
Infarction
37
19
Important questions
40
Third Edition (2022) (CBME);
Notes: Robbins & Cotran, Pathologic Basis of Diseases, South Asia Edition, 2014.
Page 1 of 40
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
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 nonpitting edema. The rigid nature of this edema is due to high internal osmotic pressure in the fluid. Examples
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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%)
Intracellular
1/3rd (20%)
Extracellular
Plasma (5%)
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
40 mmHg hydrostatic pressure
25 mmHg oncotic pressure
_________________________
15 mmHg hydrostatic pressure
-
At venous end
25 mmHg oncotic pressure
10 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.
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-
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
in venous hydrostatic pressure
a) Right heart failure
b) Constrictive pericarditis
c) Cirrhosis of liver leading to edema in
portal area
Localized increase
in venous hydrostatic pressure
a)
b)
c)
d)
Deep vein thrombosis of lower limb
Varicosities
Pressure by pregnant uterus
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.
Page 4 of 40
•
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.:
✓ Filariasis: lymphatic obstruction in inguinal region resulting in edema of external genitalia &
lower limbs, called elephantiasis.
✓ 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:
a)
b)
c)
d)
e)
f)
Generalized
Systemic infection
Poisoning
Drugs
Chemicals
Anaphylaxis
Anoxia
Localized
a) Localized infection
b) Insect-bite
c) Local irritant
5. Sodium and water retention:
• 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)
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TRANSUDATE & EXUDATE
Fluid accumulating in body cavity is called effusion. Effusion can be transudate or exudate.
TRANSUDATE
1. More common
2. Cause: hemodynamic derangement
(non-inflammatory edema)
3. Physical examination:
✓ Clear
✓ SG: < 1.012
✓ pH > 7.3
4. Chemical examination:
✓ Protein:
- < 3 gm/dl,
- albumin with low fibrinogen, hence fluid
does not clot.
✓ Fluid glucose same as blood
✓ Fluid LDH:
- low
- eff. LDH : s. LDH = < 0.6
5. Microscopic examination:
✓ few cells
✓ mainly mesothelial cells
6. Example (ascites): heart failure, liver
disease, kidney disease, severe nutritional
disorders
1.
2.
3.
✓
✓
✓
4.
✓
✓
✓
5.
✓
✓
6.
EXUDATE
Less common
Increased vascular permeability
(inflammatory edema)
Physical examination:
Turbid
SG: >1.020
pH < 7.3
Chemical examination:
Protein:
> 3 gm/dl
albumin with high levels of fibrinogen &
coagulation factors, hence fluid readily clots.
Fluid glucose: low
Fluid LDH:
high
> 0.6
Microscopic examination:
Many cells
mainly polymorphs and mesothelial cells
Example: abscess
Short answer question
1. Enumerate TWO differences between transudate and exudate.
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
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− 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
Low concentration of Na+ in renal tubules
Increased permeability
Loss of proteins
Stimulates granular cells
of juxta-glomerular apparatus
to secrete renin (enzyme)
Reduced oncotic pressure
Angiotensinogen
(α2-globulin)
Angiotensin-I
(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.
Page 7 of 40
•
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
Due to increased
hydrostatic pressure
Alveolar/Irritant edema
Due to microvascular injury
Undetermined origin edema
High altitude edema
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.
ii) Inhaled gases: oxygen, smoke.
iii) Liquid aspiration: gastric contents, near -drowning.
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i) 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.
Alveolar edema
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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
4. Hyperlipidemia & lipiduria (hypoalbuminemia triggers formation of lipoproteins from liver)
•
Causes:
✓ 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)
✓
1.
2.
3.
4.
5.
6.
Systemic disease affecting kidney, a cause of NS:
DM
Amyloidosis
SLE
Malaria
Hepatitis B
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
1. Cause: Nephrotic syndrome
2. Mechanism: reduced oncotic pressure
3. Degree of edema: severe
4. Distribution of edema: subcutaneous tissue &
visceral organs
5. Proteinuria: heavy
Nephritic edema
1. Cause: Acute & rapidly progressive
glomerulonephritis
2. Mechanism: Sodium & water retention
3. Degree of edema: mild
4. Distribution of edema: loose tissues [face, eyes
(periorbital edema), ankles, genitalia]
5. Proteinuria: moderate
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
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Back pressure on pulmonary vein
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. Hemosiderin stains blue with Prussian blue stain.
Heart failure cells
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Short answer question
1.
What are ‘heart failure cells’? Which stain can be used to demonstrate them?
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
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:
✓ Nutmeg liver (Red & yellow mottled appearance):
- Red area corresponds to congested centrilobular sinusoids & necrotic centrilobular hepatocytes
- Yellow area corresponds to viable periportal hepatocytes with fatty change
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Nutmeg liver
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.
Short answer question
1.
Nutmeg liver
CHRONIC VENOUS CONGESTION OF SPLEEN
Congestion
Increased volume of blood in the venous bed is called congestion.
Pathophysiology of CVC spleen
Left heart failure
Back pressure on pulmonary vein
CVC lungs
Back pressure on Pulmonary artery
Back pressure on right heart
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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
1. Portal vein thrombosis
2. Neoplastic obstruction of
portal vein
HEPATIC
1. Cirrhosis
2. Metastasis
3. Budd-Chiari syndrome
(Hepatic vein thrombosis)
POST-HEPATIC
1. Right heart failure
2. Constrictive pericarditis
3. Budd Chiari syndrome
(extension into IVC)
Gross appearance
•
•
•
Weight: mildly enlarged, weighing up to 300-500 gm (normal 150 gm)
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
Short answer question
1.
Gamna-Gandy bodies
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SHOCK
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.
2.
3.
4.
5.
Cardiogenic shock
Hypovolemic shock
Neurogenic shock
Anaphylactic shock
Septic shock
1. Cardiogenic shock:
•
Definition: Cardiogenic shock results from failure of cardiac pump.
•
Causes:
Deficient filling
1. Hemopericardium
•
-
Deficient emptying
Obstruction to outflow
1. MI
2. Arrhythmias
1. Pulmonary embolism
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
1. Trauma
2. Surgery
3. Bleeding
•
Due to fluid loss
1. Severe burns
2. Persistent vomiting
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)
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3. Septic (endotoxic) shock:
•
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. 50% gram positive bacteria
2. Endotoxin-producing gram-negative bacilli, called ‘endotoxic shock’:
- E. Coli
- Klebsiella pneumoniae
- Proteus
- Pseudomonas
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.
2.
3.
4.
5.
Vasodilatation leading to hypotension
Diminished myocardial contractility
Widespread endothelial injury
Pulmonary alveolar capillary damage, causing acute respiratory distress syndrome
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 Staphylococci
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•
-
Clinical presentation:
Fever
-
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. Anesthetic 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: Penicillin, Anesthetic drugs, Aspirin
3. Latex: Rubber latex gloves, Catheters
4. Bee or wasp stings
Short answer question
1. List 3 major types of shock with suitable examples.
2. Superantigens
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)
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•
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
Stimulates granular cells of JGA to secrete
Angiotensinogen →
renin
Angiotensin-I → 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
of skin & abdominal viscera
Compensatory sympathetic (vasomotor) response
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
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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
Peripheral pooling of blood
Worsens cardiac return & thus output
•
Perfusion to vital organs is affected
Clinical effects:
✓
Patient appears confused
✓
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:
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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’
Short answer question
Enumerate the three stages of shock.
2. Shock lung
1.
HEMOSTASIS
DEFINITION
Hemostasis accomplish two important functions:
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.
PRO-THROMBOTIC MECHANISM
Steps of formation of hemostatic plug
1.
2.
3.
4.
5.
Vasoconstriction
Primary hemostatic plug
Secondary hemostatic plug
Fibrinolytic effect (tertiary hemostasis)
Counter current mechanism
: a function of vessel wall
: a function of platelets
: a function of coagulation system
: a function of endothelium
: 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 exposes 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
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-
-
Von Willebrand Factor (vWF). vWF is produced by Weibel-Palade bodies of endothelium, αgranules of platelets and subendothelial connective tissue. Genetic deficiency of vWF leads to
bleeding disorder called von Willebrand disease.
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):
✓ 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
Factor I, V, VIII,
Platelet Factor-4
vWF
δ (dense core) granules
ADP, ATP
Ca2+
Histamine, Serotonin
Page 21 of 40
PDGF, EGF
TGF-β
P-selectin
Plasminogen activator inhibitor-1
Epinephrine
✓ 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 & ThromboxaneA2 (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
Page 22 of 40
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
XI
Ca 2+
IX
aXI
VIII
Ca 2+
aVIII
VII
aVII
aIX
X
aX
V
aV
XIII
II
Ca 2+
aII (Thrombin)
Ca2+
aXIII
I
aI (Fibrin)
Soluble fibrinogen is converted into insoluble fibrin gel, which encases platelets and other circulating
cells to form secondary hemostatic plug.
Page 23 of 40
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
Fibrin
Plasmin
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.
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).
Page 24 of 40
Pro-thrombotic and anti-thrombotic substances
Anti-thrombotic substances
Endothelin
vWF
ADP & TxA2
Factor VIII, V, Fibrinogen activate
intrinsic pathway
5. Tissue factor activates extrinsic
coagulation pathway
6. PF-4
1.
2.
3.
4.
Pro-thrombotic substances
1. Intact endothelium
2. Plasminogen-plasmin system: lyse the clot
3. PGI2, NO & ADPase prevent propagation of
clot
4. Heparin-like molecule inactivates f.: aX, aIX,
& aII
5. Tissue factor pathway inhibitor inhibits f.
VIIa & Xa
6. Thrombomodulin inactivates f. VIIIa & Va
Short answer question
Enumerate four anti-thrombotic substances.
2. Enumerate four pro-thrombotic substances.
1.
THROMBOSIS
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.
Page 25 of 40
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.
i)
ii)
iii)
iv)
v)
Causes of endothelial injury are:
Heart: myocardial infarction, cardiac surgery / infection / immunological reaction
Valvular disease: inflammation, prosthesis
Ulcerated atherosclerotic plague: of aorta / arteries
Plasma agents: Homocystinuria, hypercholesterolemia
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
Page 26 of 40
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:
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.
✓ 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.
✓ Classification:
ii) Primary
iii) Secondary: to autoimmune disease, e.g. SLE
✓
i)
ii)
iii)
iv)
v)
vi)
Clinical manifestations:
thrombocytopenia
recurrent thrombi
venous thrombi in deep leg veins, hepatic & retinal veins
arterial thrombi in cerebral, coronary, mesenteric & renal arteries
valvular vegetation's
repeated miscarriages due to Ab-mediated inhibition of t-PA required for trophoblastic
invasion of uterus
Page 27 of 40
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
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
Blood flow
Cause
Site
Gross
appearance
Microscopic
appearance
Arterial thrombus
Formed in rapid-flowing blood of arteries
1. Endothelial cell injury:
- Vasculitis
- Atherosclerotic plaque
- Traumatic
2. Turbulence:
- Vessel bifurcation
Coronary artery
Cerebral artery
Femoral artery
- Usually occlusive
- Tail builds away from heart
- Lines of Zahn (alternate
dark (RBC) & light (platelets & fibrin)
bands seen
- Red areas of lines of Zahn are
composed of blood cells
- White areas composed of platelets,
fibrin.
Page 28 of 40
Venous thrombus
Formed in slow moving blood of veins
Stasis
-
Superficial: occur in saphenous
system especially with varicosities
Deep: femoral, popliteal, iliac veins
Invariably occlusive
Tail builds towards heart
Red-blue in colour, with indistinct
lines of Zahn
Indistinct lines of Zahn with more
abundant red cells
Fate
Clinical
effect
Entire thrombus embolizes
- Ischemia
- Infarction
Tail-end embolizes
- Edema
- 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.
The thrombus gets incorporation into vessel wall.
4. Recanalization:
Endothelial cells send capillary channels into the thrombus.
These channels anastomose & maintain the continuity of original vessel.
5. Embolization: thrombus dislodges & transports to another site.
Page 29 of 40
POST-MORTEM & ANTE-MORTEM CLOT
Postmortem clot
Takes the shape of vessel
Shape
Attachment to wall
Consistency
Gross appearance
Microscopic
appearance
Antemortem clot
May or may not take the shape of
vessel
Clot is not attached to wall
Attached to wall at origin.
Soft, rubbery & gelatinous
Dry, granular, friable & firm
‘Current jelly’ (dependent portion of
Shows lines of Zahn: alternate dark
clot is red due to gravitation of RBCs)
(RBC) & light (platelets & fibrin)
‘chicken fat’ (supernatant serum is
bands.
yellow)
Red blood cells in the dependent area.
Red areas of lines of Zahn are
Pink proteinaceous material in the
composed of blood cells;
supernatant area
White areas composed of platelets,
fibrin.
Short answer question
1.
2.
3.
4.
5.
6.
Virchow’s triad
Enumerate FOUR causes of hypercoagulable state.
Mural thrombus
State FOUR differences between arterial and venous thrombus.
Fate of thrombus
State FOUR differences between ante-mortem and post-mortem thrombus.
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
Page 30 of 40
Classification
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
a) Thrombus
b) Tumor clump
c) Tissue
d) Parasites
e) Foreign body
Liquid
a) Fat globules
b) Amniotic fluid
c) Bone marrow
Gaseous
a) Air
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
Page 31 of 40
Thromboembolism
•
Classification:
1. Arterial (systemic) thromboembolism
2. Venous (pulmonary) thromboembolism
•
Arterial thromboembolism:
Source:
Heart
Arteries
80-85%
1. Myocardial infarction
1. Atherosclerosis
(left ventricle & right atrium)
2. Cardiomyopathy
2. Aneurysm
3. Valvular disease
4. Prosthetic heart valve
Paradoxical embolus
1. From venous
circulation
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 anastomotic 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
Page 32 of 40
Post-partum
b) Peri-prostatic vein
3. Right heart
4. Pulmonary artery disease
Site of lodgment:
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.
1.
2.
3.
4.
5.
6.
Clinical consequence:
Resolution: 60-80% of emboli dissolve by fibrinolytic activity.
Pulmonary infarct: emboli that lodge in the end-arteries, lead to pulmonary infarction.
Pulmonary hemorrhage: Obstruction of medium-sized arteries, which are not end arteries, lead to
pulmonary hemorrhage and not infarction because of dual blood supply.
Instantaneous death: results from saddle embolus or massive pulmonary embolism.
Acute cor-pulmonale (right heart failure secondary to obstruction of pulmonary micro-circulation).
Chronic cor-pulmonale or pulmonary hypertension or pulmonary arteriosclerosis: result when
multiple small pulmonary emboli undergoing healing.
Short answer question
1.
2.
3.
4.
5.
6.
Paradoxical embolus
Retrograde embolus
Enumerate FOUR sources of arterial embolus.
Enumerate FOUR sites of lodgment of arterial embolus.
Enumerate FOUR sources of venous embolus.
Enumerate FOUR sites of lodgment of venous embolus.
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
Page 33 of 40
3.
4.
5.
-
normally shed before birth
replaced by vellus or terminal hair
Fat
Mucin from RT & GIT
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
Clinical presentation
Respiratory distress
Shock, Convulsions
Coma
DIC
Pathophysiology
Mechanical blockage of pulmonary circulation
Anaphylactic reaction, accounts for majority of
symptoms
Liberation of thromboplastin, activates extrinsic
pathway
Death
Morphology
➢
➢
Look for the presence of amniotic fluid in:
veins of lung
uterine veins
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.
2.
3.
4.
Depth or altitude reached: directly proportional to the difference in change of atmospheric pressure.
Duration of exposure to altered pressure
Rate of ascent
General condition of individual
Page 34 of 40
5. Obesity: Obese persons are more prone, since N2 is more soluble in fat.
Classification
Decompression sickness
Acute form
(Bends & Chokes disease)
Chronic form
(Caisson disease)
Clinical effects
•
Acute form:
✓ Cause: emboli in blood vessels of mainly musculo-skeletal system, RS, CNS & heart
✓ 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:
✓ Cause: ischemic necrosis, activation of platelets & coagulation factors.
✓ Clinical features:
1. Musculoskeletal system: avascular necrosis of head of femur, tibia, humerus
2. Lung: hemorrhage, edema, emphysema…
3. CNS: paresthesia, paraplegia
Short answer question
1. Bends and chokes disease
2. Caisson’s disease
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
Page 35 of 40
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
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
Page 36 of 40
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
of lumen
Reduced
blood
in vessel
Pathology
in
vessel wall
Pressure
from outside
1. Thrombo
-embolism
2. Septicemia
1. Cardiac
failure
2. Shock
1. Arteriosclerosis
1. Ligature
2. Thromboangitis
obliterans
(Burger’s dz.)
3. Vasospasm
(Raynaud’s dz.)
2. Tourniquet
3. SCD
4. CML
3. Tight plaster
4. Torsion
5. Strangulation
6. Intussusception
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 anastomosis: 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 anastomosis:
- 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
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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:
Classified according to:
1. Color of infarct: white or red
White infarct
Gross appearance
White / pale / anemic
Cause
Arterial occlusion
Infarcts of solid organs
White infarct are seen in heart,
spleen, kidney, Raynaud’s
phenomena in fingers/toes
Red infarct
Red or hemorrhagic
Venous occlusion
Infarcts of loose organs, lung
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
Red infarct are seen in lung, testes,
ovary, small intestine
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
✓
✓
✓
✓
Often multiple
Site: Commonly located at periphery of organs
Shape:
Wedge
Apex pointing towards occluded vessel at hilum of the organ
External surface of the organ forms base of the wedge
Often depressed under surface, due to fibrosis
Page 38 of 40
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:
✓ Cause
1. Coronary artery disease: atherosclerosis, embolism
2. Valvular heart disease
3. Shock
4. Emotion & exercise
✓ 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
Right ventricle is spared because of thin wall and less metabolic requirements.
Left atrium is spared because it receives oxygenated blood.
•
Splenic infarct:
✓ Cause
1. Thromboembolism from the heart / aorta
2. Myeloproliferative diseases
3. Hodgkin’s disease
4. Sickle cell disease
5. Septicemia
•
Kidney infarct:
✓ Cause
1. Thromboembolism arising from heart / aorta
2. Renal artery atherosclerosis / arteritis
3. Sickle cell disease
Short answer question
1.
2.
3.
4.
Enumerate FOUR factors that affect development of infarct.
Write TWO differences between red and white infarct.
List FOUR organs in which pale infarct occur.
List FOUR organs in which red infarct occur.
Page 39 of 40
IMPORTANT QUESTIONS
SHORT NOTES:
1.
2.
3.
4.
5.
6.
7.
8.
9.
Pathophysiology of edema
What is edema? Discuss pathogenesis of cardiac edema.
Define and classify thrombosis. Explain the etiopathogenesis of thrombosis.
Fate of a thrombus
Define embolism. Mention different types of emboli. Describe fat embolism.
Pulmonary embolism
Amniotic fluid embolism
Reversible shock
Pathogenesis of septic shock
The End
Please refer text for further reading.
Mistakes are regretted.
Dr. Neena Doshi
Professor, Pathology, GMERS Medical College, Gotri, Vadodara, Gujarat (Email: neenapdoshi@gmail.com)
Page 40 of 40