Undergraduate Pathology Series 26
3. Hemodynamic Disorders,
Thromboembolic Disease, and Shock
MCQs
1) Which of the following is not risk factor for thrombosis. (April, 2024)
a) Endothelial injury b) Stasis of blood flow
c) Increased anticoagulant factors d) Hypercoagulability of blood
2) Decompression sickness results in this type of embolism. (Jan. 2024)
a) Fat embolism b) Thromboembolism c) Foreign body embolism d) Air embolism
3) Multiple fracture long bones in an accident can lead to. (April, 2023)
a) Air embolism b) Dry gangrene c) Fat embolism d) Keloid
4) Fat embolism is more common in. (Dec. 2022)
a) Fracture femur b) Myocardial infarction c) Caisson disease d) Ruptured placenta
5) Gamna-Gandy bodies are classically seen in. (Dec. 2022)
a) Amyloidosis spleen b) Alcoholic liver disease
c) Chronic venous congestion spleen d) Fat necrosis pancreas
6) Pale infarct is seen in all except. (May, 2022)
a) Lung b) Spleen c) Kidney d) Heart
7) Lines of Zahn are found in. (May, 2022)
a) Thrombus b) Infarct tissue c) Post-mortem clot d) All
8) Transudate is. (Feb. 2022)
a) Protein-rich, cell-poor fluid b) Protein-poor, cell-rich fluid
c) Protein-poor, cell-poor fluid d) Protein-rich, cell-rich fluid
9) Leiden mutation is. (Feb. 2022)
a) Factor III mutation b) Factor VI mutation
c) Factor VII mutation d) Factor V mutation
15 Marks
1) A 40 year old male presented with fracture of femur. On fourth day, he suddenly
developed breathlessness, tachycardia and fever. (April, 2024)
a) What is the probable diagnosis.
b) Write on pathogenesis of the condition.
c) What are the special stains used for diagnosis?
Ans: Fat embolism.
Refresh Pathology, 5th Edition – Dr. Shiva M.D. 27
2) A 25 year old male was brought to the emergency room, 10 minutes post vaccination. On
examination, he was dyspneic. Pulse and blood pressure was low. (Jan. 2024)
a) What is the provisional diagnosis and why?
b) Discuss the sequential events in this condition.
Ans: Anaphylactic shock.
3) Define edema. How do you classify edema. Discuss the etiology, pathogenesis and
manifestations of cardiac edema. Mention two differences between transudate and exudate.
(April, 2023)
4) An young male met with a road traffic accident. He sustained multiple injuries, fractures of
femur and tibia. These fractures are stabilized at surgery after admission. He is in a stable
condition. After two days of admission, suddenly became dyspneic and develop tachypnea
and tachycardia, irritability, restlessness and progressed to delirium, coma and on seventh day
death occurred. (May, 2022)
a) What is the provisional diagnosis.
b) Discuss the pathogenesis of the lesion.
c) Microscopic picture of the lungs in the above disease.
d) How the frozen sections of the lung tissue help in the final diagnosis at autopsy and
mention the various stains specific for it.
Ans: Fat embolism.
5 Marks
1) Types of infarcts. (April, 2024)
2) Define thrombosis. Describe the Virchow triad. (April, 2024)
3) Differences between transudate and exudate. (April, 2024)
4) Pathogenesis of septic shock. (Jan. 2024)
5) Define infarct and enumerate the factors that determine the outcome of an infarct.
(Dec. 2022)
6) Pathogenesis of thrombus formation. (May, 2022)
10 Marks
1) A 30 year old man had multiple fractures of the bones of pelvis and lower limbs after a
road traffic accident. He developed sudden onset of tachypnea, dyspnea, tachycardia and
restlessness on the fourth day of hospitalization. There was diffuse petechial rash, anemia and
diffuse opacity of lungs. (May, 2022)
a) What is your diagnosis?
b) Describe in detail the etiology and pathogenesis of the condition.
c) Discuss the autopsy findings of the organs affected in this disorder.
d) What is the cause of petechial rash and anemia in this patient?
Ans: Fat embolism.
Undergraduate Pathology Series 28
2) A 55 year old lady was brought to the emergency room unconscious with history of road
accident. She sustained multiple injuries, fractures of femur and tibia. These fractures are
stabilized at surgery soon after admission. However, 2 days after admission, she suddenly
becomes dyspneic and developed tachypnea and tachycardia, irritability, restlessness and it
progressed to delirium, coma and death on 7th day. (March, 2021)
a) What is the provisional diagnosis?
b) Discuss the pathogenesis of the lesion.
c) Describe microscopic picture of the lungs in the above condition.
d) How frozen sections of the lung tissue help in final diagnosis at autopsy and mention
various stains specific for it.
Ans: Fat embolism.
3) A 55 year old lady was brought to the emergency room unconscious. Her blood pressure
was very low, pulse was weak and rapid. Her skin was warm and flushed. Her blood culture
revealed growth of Gram-positive bacteria. (Jan. 2015)
a) What is the possible diagnosis?
b) Describe the pathogenesis of this condition.
c) Describe the stages of this disorder.
Ans: Septic shock.
4) Young male met with an accident. Had fracture femur. C/o breathlessness and chest pain,
cough and frothy sputum. (Jan. 2013)
a) What is the provisional diagnosis?
b) What other conditions can produce similar symptoms?
Ans: Fat embolism.
4 Marks
1) Pathogenesis of septic shock. (Oct. 2022)
2) Pathogenesis of septic shock. (Aug. 2021)
3) Pathogenesis of septic shock. (Feb. 2020)
4) Etiopathogenesis of septic shock. (July, 2018)
5) Pathogenesis of septic shock. (Feb. 2018)
6) Pathogenesis of septic shock. (July, 2017)
7) Systemic thromboembolism. (July, 2016)
8) Air embolism. (July, 2015)
9) Pathogenesis of endotoxic shock. (July/Aug. 2014)
10) Etiology and pathogenesis of fat embolism. (Jan. 2014)
11) Systemic thromboembolism. (Jan. 2012)
12) Exudate and transudate. (April, 2009)
13) Thromboembolism. (April, 2009)
14) Fate of thrombus. (Feb. 2009)
15) Thromboembolism. (March/April, 2008)
16) Cardiac edema. (May, 2007)
Refresh Pathology, 5th Edition – Dr. Shiva M.D. 29
17) Septic shock. (May, 2006)
18) C.V.C. Liver. (Oct. 2005)
19) Nephrotic edema. (March/April, 2005)
20) Amniotic fluid embolism. (Sep. 2003)
2 Marks
1) Write the components and their inter relationship of Virchow triad. (Oct. 2022)
2) Enumerate four differences between transudate and exudate. (May, 2022)
3) List any four fate of thrombus. (Aug. 2021)
4) Fate of thrombus. (Feb. 2019)
5) List four examples for edema due to reduced plasma oncotic pressure. (Feb. 2018)
6) Fate of thrombus. (Feb. 2017)
7) Fate of thrombus. (July, 2013)
8) Nutmeg liver. (July, 2012)
9) Fate of a thrombus. (July, 2011)
10) Hypovolemic shock. (July, 2011)
11) Phlebothrombosis. (Jan. 2011)
12) Fate of a thrombus. (Aug. 2010)
13) What is paradoxical embolism? Give an example. (March, 2010)
14) Mural thrombus. (Aug. 2009)
15) Exudate and transudate. (April, 2009)
16) Thromboembolism. (April, 2009)
17) Exudate. (Feb. 2009)
18) Cardiac edema. (Oct. 2008)
19) Shock lung. (March/April, 2008)
20) Stages of shock. (Sept/Oct. 2007)
21) Fate of a thrombus. (May, 2006)
22) Amniotic fluid embolism. (May, 2006)
23) Fate of thrombus. (Oct. 2005)
24) Air embolism. (March/April, 2005)
25) Paradoxical embolism. (April/May, 2004)
26) Nutmeg liver. (April/May, 2004)
27) Brown induration of the lung. (Sep. 2003)
28) Decompensated shock. (March/April, 2003)
High-Yield Topics
Edema – Mechanisms, causes & types Chronic passive congestion of liver
Thrombus – Pathogenesis, types & fate Systemic thromboembolism
Fat embolism Air embolism
Infarct – Types & morphology Shock – Types, pathogenesis & stages
Undergraduate Pathology Series 30
Cardiac Edema
Causes: Congestive cardiac failure.
Pathogenesis: Increased capillary hydrostatic pressure and retention of sodium and water
with activated renin-angiotensin system causes development of edema.
Type of edema: Transudate.
C/P: Dyspnea, swelling of lower extremities, and fatigue.
Renal Edema
Causes: Nephrotic syndrome; Renal failure.
Pathogenesis:
1) Nephrotic syndrome: Decreased plasma osmotic pressure with massive proteinuria and
retention of sodium and water with activated renin-angiotensin system leads to edema.
2) Renal failure: Retention of sodium and water with activated renin-angiotensin system
causes increased hydrostatic pressure and decreased plasma osmotic pressure leading to
edema.
Type of edema: Transudate.
Transudate Vs Exudate
Feature Transudate Exudate
Cause Increased hydrostatic pressure Increased vascular permeability
or decreased oncotic pressure
Nature Non-inflammatory Inflammatory
Appearance Clear Cloudy
Protein Low (<3 gm/dl) High (>3gm/dl)
Specific gravity <1.012 >1.020
Cellularity Poor Rich
Fibrin Absent Present
Pitting Present Absent
Chronic Passive Hepatic Congestion
“Represent increased blood volumes within liver due to impaired outflow for prolonged
duration.”
Causes: Congestive heart failure.
Pathogenesis: 1) Chronic hypoxia leads to ischemic injury of tissues.
2) Capillary rupture causes hemorrhage and formation of hemosiderin-laden macrophages.
Morphology: Gross: Centrilobular regions are red-brown and slightly depressed and are
accentuated against the surrounding zones of uncongested tan liver.
Micro.: Centrilobular hemorrhage, hemosiderin-laden macrophages, and variable degrees of
hepatocyte dropout and necrosis (nutmeg liver).
Refresh Pathology, 5th Edition – Dr. Shiva M.D. 31
Chronic Passive Pulmonary Congestion
“Represent increased blood volumes within lung due to impaired outflow for prolonged
duration.”
Causes: Congestive heart failure.
Pathogenesis: 1) Chronic hypoxia leads to ischemic injury of tissues.
2) Capillary rupture causes hemorrhage and formation of hemosiderin-laden macrophages.
Morphology:
Gross: Lungs are firm and heavy. C/S: Rusty brown (brown induration of lungs).
Micro.: Septa are thickened and fibrotic. Numerous hemosiderin-laden macrophages (heart
failure cells) within the alveoli.
Thrombosis
Thrombosis: It is the process of formation of solid mass in circulation from the constituents
of flowing blood.
Thrombus: “Intravascular solid mass attached to the underlying blood vessel wall.”
Pathogenesis:
Virchow triad: Factors may promote thrombosis independently or in combination.
1) Endothelial injury: Injury to endothelial cells can alter local blood flow and affect
coagulability leading to platelet activation.
Causes:
i) Endothelial activation or dysfunction: Hypertension; Smoking; Hypercholesterolemia;
Homocystinemia.
ii) Endothelial damage: Myocardial infarction; Atherosclerosis; Vascular injury.
2) Alterations in normal blood flow: Abnormal blood flow (stasis or turbulence), in turn,
can cause endothelial injury and affect coagulability by disrupting laminar flow and
promoting endothelial activation.
Causes:
i) Stasis: Aneurysms; Hyperviscocity; Sickle cell disease.
ii) Turbulence: Atherosclerosis.
3) Hypercoagulability: Abnormally high tendency of the blood to clot, caused by alterations
in coagulation factors.
Causes: i) Primary (Genetic): Factor V mutation (Factor V Leiden); Prothrombin mutation.
ii) Secondary (Acquired): Immobilization; Myocardial infarction; Cancer; Tissue injury;
Antiphospholipid antibody syndrome.
Venous Thrombosis (Phlebothrombosis)
Synonyms: Red thrombi or stasis thrombi.
Mechanisms: Stasis or hypercoagulability in the sluggish venous circulation.
Sites: Veins of lower extremity (MC).
Morphology:
1) Firm solid masses, focally attached to the vessel wall and contain lines of Zahn.
2) Appear red with more RBCs and relatively few platelets.
3) Form a long luminal cast and extend in the direction of blood flow.
C/P: Always occlusive causing ischemia.
Fate: Propagation; Embolization; Dissolution; Organization or recanalization.
Undergraduate Pathology Series 32
Mural Thrombus
“Represent thrombi seen in the heart chambers or in the aortic lumen.”
Mechanisms: Endothelial injury or turbulence.
Causes: Myocardial infarction, dilated cardiomyopathy, myocarditis, arrhythmias,
atherosclerosis, and aneurysms.
Morphology:
1) Firm solid masses, focally attached to the vessel wall and contain lines of Zahn.
2) Consist of a friable meshwork of platelets, fibrin, red cells, and degenerating leukocytes.
C/P: May be occlusive causing ischemia.
Fate: Propagation; Embolization; Dissolution; Organization or recanalization.
Fate of Thrombus
Over a period of time, thrombi are seen undergoing any of the following changes.
1) Propagation: Thrombi accumulate additional platelets and fibrin.
2) Embolization: Thrombi dislodge and travel to other sites in the vasculature.
3) Dissolution: Thrombi may shrink and disappear with fibrinolysis.
4) Organization and Recanalization: Thrombi may organize with ingrowth of endothelial
cells, smooth muscle cells, and fibroblasts. Recanalization involves formation of capillary
lumens.
Thromboembolism
*Most common type of embolism.
“Represent emboli that are dislodged thrombi, carried by the blood from its point of origin to
a distant site.”
Types
I) Systemic thromboembolism
“Represent emboli in the arterial circulation.”
Origin: Intracardiac mural thrombi.
Causes: Left ventricular wall infarcts (MC), aortic aneurysms, atherosclerotic plaques,
vegetations or paradoxical emboli.
Sites of lodgement: Lower extremities (MC); Brain; Kidneys; Intestines.
C/P: Ischemia leads to infarction.
II) Pulmonary embolism
*MC form of thromboembolic disease.
*Mostly, pulmonary emboli are multiple and small.
Origin: Deep veins of lower limb.
Sites of lodgement: Main pulmonary artery, bifurcation of pulmonary artery, or smaller,
branching arteries.
Refresh Pathology, 5th Edition – Dr. Shiva M.D. 33
C/P: 1) Asymptomatic (MC): Seen with small emboli being organized with time.
2) Sudden death, acute right heart failure or cardiovascular collapse: Seen with emboli
obstructing 60% or more of pulmonary circulation.
3) Hemorrhage: Seen with embolic obstruction of medium-sized arteries with subsequent
vascular rupture.
4) Hemorrhage or infarction: Seen with embolic obstruction of small end-arteriolar
pulmonary branches.
5) Pulmonary hypertension and right ventricular failure: Seen with multiple emboli over
time.
Paradoxical Embolism
Def.: Emboli originating in venous circulation, but gain access to the systemic arterial
circulation with interatrial or interventricular defects.
Associations: ASD; VSD.
C/P: Paradoxical emboli lead to systemic thromboembolism.
Fat Embolism
Causes: Fractures of long bones (MC), soft tissue trauma and burns.
Pathogenesis: 1) Rupture of vascular sinusoids in the marrow or small venules will allow
marrow or adipose tissue into the vasculature.
2) Fat microemboli and associated red cell and platelet aggregates can occlude the pulmonary
and cerebral microvasculature.
3) Release of free fatty acids from fat globules cause toxic injury to endothelium.
C/P: 1) 1 to 3 days after injury, sudden onset of tachypnea, dyspnea, and tachycardia.
2) Irritability and restlessness progressing to delirium or coma.
3) A diffuse petechial rash may be seen.
4) Fat Embolism Syndrome: Anemia, thrombocytopenia, pulmonary insufficiency and
neurologic symptoms.
Morphology: Microscopy shows fat microglobules in pulmonary vasculature.
Diagnosis: i) Frozen sections where fat solvents are avoided.
ii) Special stains (Sudan IV; Sudan III; Sudan black; Oil Red-O) for fat.
Amniotic Fluid Embolism
Causes: As a complication of labor and the immediate postpartum period.
Pathogenesis: 1) Tear in the placental membranes or rupture of uterine veins allow infusion
of amniotic fluid or fetal tissue into the maternal circulation.
2) Substances in amniotic fluid activate coagulation factors causing DIC.
Morphology: Maternal lungs show edema, diffuse alveolar damage and the presence of
fibrin thrombi in many vascular beds.
C/P: Sudden onset of severe dyspnea; Cyanosis and shock; Neurologic impairment as
headache, seizures and coma.
Diagnosis: Microscopic demonstration of fetal squamous cells, lanugo hair, fat and mucins in
the maternal pulmonary circulation.
Comp.: Maternal death or permanent neurological deficit.
Undergraduate Pathology Series 34
Air Embolism
Causes: Obstetric or laparoscopic procedures, chest wall injury, or decompression sickness.
Decompression sickness
Predisposing factors: Deep sea diving or underwater construction.
Pathogenesis: 1) Exposure to sudden decreases in atmospheric pressure causes the nitrogen
comes out of solution in the tissues and the blood.
2) Rapid formation of gas bubbles within skeletal muscles and supporting tissues in and
about joints and pulmonary vasculature causes ischemic injury.
Morphology: Lungs show edema, hemorrhage, and focal atelectasis or emphysema.
C/P: 1) Bends: Painful musculoskeletal condition.
2) Chokes: A form of respiratory distress.
Caisson disease
“Chronic form of decompression sickness.”
Pathogenesis: Persistence of gas emboli in the skeletal system leads to ischemic necrosis
involving bones.
Sites affected: Head of femur, tibia and humerus.
Infarct
Def.: It is an area of ischemic necrosis caused by occlusion of either the arterial supply or the
venous drainage.
Types:
I) Based on color:
a) Red (hemorrhagic) infarcts: i) Occur with venous occlusions (e.g., testicular torsion).
ii) Associated with loose, spongy tissues (lung) and tissues with dual circulations (lung and
small intestine).
iii) Seen with sites of previous arterial occlusion and necrosis when flow is reestablished.
b) White (anemic) infarcts: i) Occur with arterial occlusions.
ii) Associated with solid organs with end-arterial circulation (heart, spleen and kidney).
II) Based on the presence or absence of infection:
a) Septic infarcts: Occur with embolization of infected cardiac valve vegetations or when
microbes seed necrotic tissue.
b) Bland infarcts
Factors that influence development of an infarct:
i) Anatomy of the vascular supply: Tissues with the availability of an alternative blood
supply are relatively resistant to infarction
ii) Rate of occlusion: Slowly developing occlusions are less likely to cause infarction.
iii) Tissue vulnerability to hypoxia: Neurons undergo irreversible damage when deprived of
their blood supply for only 3 to 4 minutes.
iv) Hypoxemia: Abnormally low blood oxygen content increases both the likelihood of
infarction.
Refresh Pathology, 5th Edition – Dr. Shiva M.D. 35
Shock
“A state of circulatory failure that impairs tissue perfusion and leads to cellular hypoxia.”
Types: 1) Cardiogenic shock 2) Hypovolemic shock 3) Septic shock 4) Neurogenic shock
5) Anaphylactic shock
Hypovolemic shock
Causes: Massive hemorrhage or fluid loss from vomiting, diarrhea or severe burns.
Pathogenesis: Low blood volume causes low cardiac output leading to tissue ischemia.
Anaphylactic shock
Causes: Administration of foreign proteins (e.g., antisera), hormones, enzymes,
polysaccharides, and drugs (e.g., the antibiotic penicillin) or following exposure to food
allergens (e.g., peanuts) or insect toxins (e.g., those in bee venom) in sensitized individuals.
Pathogenesis: IgE-mediated hypersensitivity reaction with acute vasodilation that leads to
vascular shock, widespread edema, and difficulty in breathing.
C/F: i) Itching, hives, and skin erythema appear within minutes after exposure to allergen
followed by respiratory distress with contraction of pulmonary bronchioles.
ii) Laryngeal edema results in hoarseness.
iii) Vomiting, abdominal cramps, diarrhea, and laryngeal obstruction.
iv) Fall in blood pressure caused by vascular dilation.
Septic shock
*MC cause of death in ICU.
Causes: Gram +ve bacteria (MC), gram -ve bacteria and fungi.
Pathogenesis: Microbial products mediate various events.
1) Activation of inflammatory cells (neutrophils and monocytes) with the production of
cytokines (IL-1, TNF) causes endothelial activation and systemic effects such as fever,
diminished myocardial contractility and metabolic abnormalities.
2) Activation of complement cascade causes endothelial activation.
3) Endothelial activation results in production of various mediators (IL-6, IL-8, NO, and
PAF) leading to vasodilation, increased permeability and tissue hypoperfusion.
4) Activation of coagulation cascade along with endothelial activation induces a procoagulant
state that causes DIC leading to tissue ischemia.
5) Finally, multiorgan failure is seen.
Stages of shock
I) Nonprogressive phase
1) Reflex compensatory mechanisms are activated. e.g., Baroreceptor reflexes, catecholamine
release, ADH release, renin-angiotensin activation and generalized sympathetic stimulation.
2) Cardiac output and BP are maintained causing tachycardia, peripheral vasoconstriction,
and renal conservation of fluid.