Hemodynamic Disorders Pathology Notes

 Hemodynamic Disorders

 

Hyperemia

 Write a short note on hyperemia.

Hyperemia of Definition: Hyperemia is an active process in which arteriolar dilation leads to increased blood flow to a tissue/organ. Hyperemia and congestion are characterized by locally increased blood volume.

Hyperemia Causes:

• Physiological: Response to increased functional demand (e.g. heart and skeletal muscle during exercise).
• Pathological: Seen in inflammation and is responsible for the two cardinal signs of inflammation namely heat (calor) and redness (rubor/erythema).

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Congestion

Definition of Congestion: Congestion is a passive process resulting from reduced venous output of blood from a tissue/organ.

Types and Causes of Congestion:

1. Systemic: For example, congestive heart failure, congestion involves the liver, spleen, and kidneys.
2. Local: examples
   • Congestion of leg veins due to deep venous thrombosis → edema of the lower extremity.
   • Local congestion at various sites due to compression of veins: for example, tight bandage, plasters, tumors, pregnancy, hernia, etc.

Onset  of Congestion:

• Acute congestion: It develops during shock or sudden right-sided heart failure. It may occur in the lungs and liver.
• Chronic passive congestion: It usually produces edema in the organ/tissue in which the venous outflow is reduced.

Appearance of Congestion: Congested tissues have a dusky reddish-blue color (cyanosis) due to the stasis of RBCs and the accumulation of deoxygenated hemoglobin.

 

Chronic Venous Congestion Of  Lung

Write a short note on CVC lung/brown induration of the lung

Causes of Lung:

• Mitral stenosis: For example, rheumatic mitral stenosis.
• Left-sided heart failure: It develops secondary to coronary artery disease or hypertension.

Mechanism of Lung:

Chronic left ventricle failure → reduces the flow of blood out of the lungs → leads to chronic passive pulmonary congestion → increases pressure in the alveolar capillaries and they become excessively filed with blood.

Consequences of Lung:

Write a short note on heart failure cells and the special stain used for its demonstration.

Four major consequences are:

1. Microhemorrhages: The wall of alveolar capillaries may rupture → minute hemorrhages into the alveolar space → release RBCs → hemoglobin breakdown → liberation of iron-containing hemosiderin pigment (brown color) → alveolar macrophages phagocytose hemosiderin. Hemosiderin-laden macrophages are known as heart failure cells. When stained by Perl’s stain, the hemosiderin in these cells appears blue-black in color.
2. Pulmonary edema: It is due to forced movement of fluid from congested vessels into the alveolar spaces.
3. Fibrosis: It develops due to increased fibrous tissue in the interstitium of the lung.
4. Pulmonary hypertension: It is due to the transmission of pressure from the alveolar capillaries to the pulmonary arterial system.

Morphology of Lung:

• Gross:
  • The lung is heavy.
  • Cut section (c/s) rusty brown color (due to hemosiderin pigment), firm in consistency (due to fibrosis) → known as brown induration of lung.

Microscopy of the Lung:

• Distension and congestion of capillaries in the alveolar septa of the lung.
• Thickened alveolar septa due to an increase in the fibrous connective tissue → responsible for the firm consistency of the lung.
• Heart failure cells are seen in the alveoli.

Chronic Passive Congestion of Liver

Write short note on causes, gross and microscopic features of chronic venous congestion of liver/ CVC liver/nutmeg liver.

Causes of Liver:

1. Right-sided heart failure is the most common cause.
2. Rare: Constrictive pericarditis, tricuspid stenosis and obstruction of inferior vena cava
   and hepatic vein.

Mechanism of Liver:

Dilatation of central veins → transmission of increased venous pressure to the sinusoids → dilatation of sinusoids → ischemic necrosis of hepatocytes in the centrilobular region.

Morphology of Liver:

Gross:

• The liver increases in size and weight and the capsule appears tense.
• The cut section shows alternate (combination of) dark and light areas and resembles a crosssection of nutmeg (nutmeg liver).
  • Congested centrilobular regions (with hemorrhage and necrosis) appear dark red-brown. Congestion is most prominent around terminal hepatic venule (central veins) within hepatic lobules.
  • The Periportal (better oxygenated) region of the lobules appears pale and may show fatty change

Microscopy of Liver:

• Centrilobular region: Congestion and hemorrhage in the central veins (terminal hepatic venule) and adjacent sinusoids.
  • Severe central hypoxia may produce centrilobular hepatocyte necrosis.
  • Thickening of central veins and fibrosis in prolonged venous congestion.
  • Cardiac sclerosis/ cardiac cirrhosis may occur with sustained chronic venous congestion (for example, Due to oocytes. constrictive pericarditis, or tricuspid stenosis).
• Periportal region: It shows the fatty change in hepatocytes.

Congestive Splenomegaly (CVC Spleen)

Write short note on CVC spleen/Gamna-Gandy bodies.

Congestion and enlargement of the spleen is called congestive splenomegaly.

Causes of Splenomegaly:
Chronic obstruction to the outflow of venous blood from the spleen leads to higher pressure in the splenic vein.

• Intrahepatic: Intrahepatic obstruction to blood flow: Cirrhosis of the liver is the main cause (for example, Alcoholic cirrhosis, Pigment cirrhosis).
• Extrahepatic disorders:
  • Systemic or central venous congestion: For example, tricuspid or pulmonic valvular disease, chronic cor pulmonale, right heart failure or following left-sided heart failure. Splenomegaly is only moderate and rarely exceeds 500 g in weight.
  • Obstruction of the extrahepatic portal vein or splenic vein: Due to spontaneous portal vein thrombosis, which is usually caused by intrahepatic obstructive disease, or inflammation of the portal vein (pylephlebitis).
  • Thrombosis of the splenic vein can also develop by infiltrating tumors arising in neighboring viscera, such as carcinomas of the stomach or pancreas.

Morphology of Splenomegaly:

Gross:

• The spleen is enlarged, firm, and tense. In long-standing chronic splenic congestion, the spleen is markedly enlargement (1000–5000 g). The capsule is thickened.
• The cut section oozes dark blood.
• May show Gamna-Gandy bodies, which consist of iron-containing, fibrotic, and calcified foci of old hemorrhage.
• An enlarged spleen may show excessive functional activity termed hypersplenism → leads to hematologic abnormalities (for example, Thrombocytopenia pancytopenia).

Microscopy of Splenomegaly:

• Red pulp
  • Dilatation and congestion in the early stages.
  • Hemorrhage and fibrosis in later stages.
  • Capillarization of sinusoids may occur, in which sinusoids get converted into capillaries.
• Thickened fibrous capsule and trabeculae.
• Slowing of blood flow from the cords to the sinusoids → prolongs the exposure of the blood cells to macrophages in the spleen → leads to excessive destruction of blood cells (hypersplenism).

Edema

Define edema.

Definition of Edema: An abnormal accumulation of fluid in the interstitial space within tissues is called edema.

Special forms of edema are listed in Table.

Types of Edema Fluid:

The edema fluid may be either transudate or exudate. The differences between transudate and exudate are presented.

Transudate and Exudate of Edema Fluid:

1. Transudate: It is a protein-poor fluid caused by increased hydrostatic pressure or reduced plasma protein.
   • Causes of Transudate: Transudate is observed in heart failure, renal failure, hepatic failure, and certain forms of malnutrition.
2. Exudate: It is a protein-rich fluid produced due to increased vascular permeability and is seen in inflammation.

Pathophysiologic Categories of Edema:

Define different pathophysiological categories of edema.

Edema may be localized or generalized in distribution.

Pathophysiologic categories of Edema:

Local/Localized Edema: Pathogenesis of edema.

Write short notes on different types of edema.

• It is limited to an organ or part (for example, arm, leg, epiglottis, larynx).
  • Obstruction of vein or lymphatic: for example, edema of the limb (usually the leg) develops due to venous or lymphatic obstruction caused by thrombophlebitis, chronic lymphangitis, resection of regional lymph nodes, filariasis, etc.
  • Inflammation: It is the most common cause of local edema.
  • Immune reaction: for example, urticaria (hives), or edema of the epiglottis or larynx (angioneurotic edema).

Generalized of  Edema:

It is systemic in distribution and affects visceral organs and the skin of the trunk and lower extremities.

Causes of Generalized Edema: Disorder of fluid and electrolyte metabolism.

• Heart failure
• Nephrotic syndrome (renal diseases with massive loss of serum proteins in the urine)
• Cirrhosis of the liver.

Mechanism/Pathogenesis of Edema:

• The movement of water and salts between the intravascular and interstitial spaces is controlled mainly by two opposite effects of Starling forces.
• The force that drives the fluid out of circulation is vascular hydrostatic pressure and the force which drives the fluid into circulation is plasma colloid osmotic pressure.

Normal Fluid Balance

• Normally the fluid flows out from the arteriolar end of the microcirculation into the interstitium.
• This is balanced by the flowing in of the fluid at the venular end.
• A small amount of fluid, which may be left in the interstitium, is drained by the lymphatic vessels, and it reaches the bloodstream via the thoracic duct.

Mechanism of Edema:

• Any mechanism, which interferes with the normal fluid balance, may produce edema.
• Increased capillary hydrostatic pressure or decreased colloid osmotic pressure produces an increased interstitial fluid.
• If the movement of the fluid into tissues (or body cavities) exceeds lymphatic drainage, the fluid accumulates in the interstitial tissue.
• These mechanisms may operate singly or in combinations.

Increased Hydrostatic Pressure:

Hydrostatic pressure at the capillary end of microcirculation drives the flid out of the capillary into the interstitial tissue space. Any conditions, which increase the hydrostatic pressure, can produce edema. The increased hydrostatic pressure may be regional or generalized.

1. Local increase in hydrostatic pressure: It can be due to local impairment in venous return.

Examples: 

• Deep venous thrombosis in a lower extremity may produce localized edema in the affected leg.
• Postural edema may be seen in the feet and ankles of individuals who stand in an erect position for a long duration.

2. Generalized increase in hydrostatic pressure: It produces generalized edema. The most common cause is congestive heart failure (CHF).

• Congestive heart failure may be a failure of the left ventricle, right ventricle, or both.
• Right-sided heart failure results in the pooling of blood on the venous side of the circulation → increases the hydrostatic pressure in the venous circulation → increases the movement of flid into the interstitial tissue spaces → shows characteristic peripheral pitting edema.
• Left-sided heart failure results in increased hydrostatic pressure in the pulmonary circulation → produces pulmonary edema.

Decreased Plasma Osmotic Pressure:

Write a short note on pathogenesis of renal edema

Plasma osmotic pressure normally tends to draw the fluid into the vessels. The plasma osmotic pressure is dependent on plasma proteins, mainly on albumin (a major plasma protein).

Decreased plasma osmotic pressure may be due to:

• Reduced albumin synthesis: Occurs in severe liver diseases (for example, Cirrhosis) or protein malnutrition (due to decreased intake of proteins).
• Loss of albumin: This may occur in the urine or stool. Nephrotic syndrome is an important cause of loss of albumin in urine. Malabsorption and protein-losing enteropathy are characterized by loss of protein in the stool.

Consequences of decreased plasma osmotic pressure:

• Decreased plasma osmotic pressure → increased movement of fluid from the circulation into the interstitial tissue spaces → reduced intravascular volume → decreased renal perfusion → activates increased production of renin, angiotensin, and aldosterone → results in salt and water retention.
• These mechanisms cannot correct the reduced plasma volume because of the persistence of the primary defect of decreased serum protein.

Sodium and Water Retention:

Increased retention of sodium salt is invariably associated with retention of water. Sodium and water retention may be a primary cause of edema.

Mechanism of  Sodium and Water Retention:

• Increased hydrostatic pressure due to increased plasma volume
• Decreased plasma colloid osmotic pressure due to dilution effect on albumin.

Causes Sodium and Water Retention: May be primary or secondary

1. Primary: It is associated with disorders of the kidney such as renal failure, and glomerulonephritis.
2. Secondary: It develops in disorders that decrease renal perfusion, the most important cause being congestive heart failure.

Mention the mechanism of cardiac edema:

• Mechanism of edema in congestive heart failure
  • Decreased cardiac output → causes the decreased flow of blood to the kidney → activates the renin-angiotensin system → retention of sodium and water.
  • Other adaptations also occur, which include increased vascular tone and elevated levels of antidiuretic hormone (ADH).
• Water retention by ADH mechanism:
  • ADH is released from the posterior pituitary, when there is reduced plasma volume or increased plasma osmolarity.
  • Primary retention of water can occur due to the increased release of ADH.
  • Increased secretion of ADH is seen in association with lung cancer and pituitary disorders.
  • This can lead to hyponatremia and cerebral edema.

Lymphatic Obstruction:

Definition of  Lymphatic Obstruction: Lymphatic obstruction causes impaired drainage of lymph and produces localized edema, called lymphedema.

Causes of lymphatic obstruction:

• Chronic inflammation of lymphatics associated with fibrosis: For example, lymphedema occurring at the scrotal and vulvar region due to lymphogranuloma venereum
• Invasive malignant tumors: For example, lymphedema of the breast due to blockage of subcutaneous lymphatics by malignant cells gives rise to orange skin (peaud  orange) appearance to the involved region of skin in the breast
• Pressure over lymphatic drainage from outside: For example, tumors obstructing thoracic ducts
• Damage by surgery/radiation: Patients with breast cancer may develop severe edema of the upper arm as a complication of surgical removal and/or irradiation of the breast and associated axillary lymph nodes.
• Parasitic infestations: In filariasis (caused by Wuchereria bancrofti), the parasite may cause extensive obstruction of lymphatics and lymph node fibrosis. If the block is in the inguinal region.
• Hereditary disorder: Milroy’s disease is a hereditary disorder characterized by abnormal development of lymphatics. The edema may be seen in one or both lower limbs.

Through lymph, proteins in the interstitial space are returned to the circulation. So, the edema fluid produced due to lymphatic obstruction has a high protein concentration. The increased protein content may stimulate firosis in the dermis of the skin and is responsible for the induration found in lymphedema.

Morphology  of lymphatic obstruction:

Edema can be easily detected on gross examination. It may involve any organ or tissue but is most common in subcutaneous tissues, the lungs, and the brain. Microscopically, edema appears as a clear space, which separates the extracellular matrix.

Generalized Edema:

It is seen mainly in the subcutaneous tissues.

• Subcutaneous edema: It may be diffuse or more easily noticed in regions with high hydrostatic pressures. In most cases, the distribution of edema is dependent on gravity and is termed dependent edema.
• Edema of renal origin: It can affect all parts of the body. Initially, it is observed in tissues with loose connective tissue matrices, such as the eyelids and scrotal region. Edema in the eyelids is called periorbital edema and is characteristic of severe renal disease.

Pulmonary Edema:

• Gross: The weight of the lungs is increased 2 to 3 times of normal weight. The cut section shows frothy, blood-tinged fluid (due to a mixture of air, edema, and extravasated red cells) oozing from the lung.

Microscopy Pulmonary Edema:

The edema fluid is seen in the alveolar septa around capillaries and reduces the diffusion of oxygen. Edema fluid present in the alveolar spaces favors bacterial infection.

Cerebral Edema:

It may be localized or generalized. In generalized edema, the brain is grossly swollen with distended gyri and narrowed sulci. The ventricular cavities are compressed and the brain expands, it may herniate.

Thrombosis

Define thrombus/Thrombosis

Definition of Thrombosis: Thrombosis is defined as the process of formation of a solid mass in the circulating blood from the constituents of flowing blood.

The solid mass formed is called a thrombus and it consists of an aggregate of coagulated blood containing platelets, fibrin, and entrapped cellular elements of blood.

Etiology of Thrombosis:

Describe the etiopathogenesis of thrombus.

What is Virchow’s triad?

Three primary abnormalities can lead to the formation of a thrombus and constitute Virchow’s triad.

These include:

• Injury to endothelium (Changes in the vessel wall)
• Stasis or turbulent blood flow (Changes in the blood flow)
• Hypercoagulability of the blood (Changes in the blood itself).

1.  Injury to Endothelium (Changes in the Vessel Wall):  Endothelial injury may be either physical damage or endothelial dysfunction (or activation).

Physical Endothelial Injury:

It is important for the formation of thrombus in the heart or the arterial circulation. The endothelial cell injury promotes the adhesion of platelets at the site of injury.

Causes of Endothelium:

1. Heart:

• Chambers of heart: for example, endocardial injury due to myocardial infarction with damage to the adjacent endocardium, catheter trauma.
• Valves: Small thrombi on the valves are called vegetations.
  • Infective endocarditis: Thombi on valves (for example, Mitral, Aortic valve) damaged by a bloodborne bacteria or fungi
  • Damaged valves: For example, due to rheumatic heart disease, congenital heart disease.

2. Arteries: For example, ulcerated atherosclerotic plaques, traumatic or inflammatory vascular injury (vasculitis).

3. Capillaries: Causes include acute inflammatory lesions, vasculitis, and disseminated intravascular coagulation (DIC).

Endothelial Dysfunction:

Definition of Endothelial Dysfunction: Endothelial dysfunction is defined as an altered state, which induces an endothelial surface that is thrombogenic or abnormally adhesive to inflammatory cells. Thus, a thrombus can develop without any denudation or physical disruption of the endothelium.

Causes Endothelial Dysfunction:

Hypertension, turbulent blood flow, toxins (for example, Bacterial endotoxins, toxins from cigarette smoke), radiation injury, metabolic abnormalities (for example, Homocystinemia or hypercholesterolemia).

2. Alterations in Normal Blood Flow:

Normal blood flow is laminar, in which platelets (and other blood cellular elements) flow centrally, separated from endothelium by a slower-moving layer of plasma.

Causes Normal Blood Flow:

• Turbulence (disturbed movement of blood): It can produce a thrombus in the arteries and heart.
• Stasis: It is a major cause of venous thrombosis.
• A clinical disorder associated with turbulence and stasis:

1. Heart:

• Acute myocardial infarction
• Arrhythmias/atrial fibrillation: For example, rheumatic mitral stenosis in conjugation with disordered atrial rhythm (atrial fibrillation), it predisposes to mural thrombi in atria.
• Dilated cardiomyopathy

2. Arteries:

• Ulceration of atherosclerotic plaques
• Aneurysms: They cause local stasis.

3. Veins: Thombi develops in the saphenous veins with varicosities or in deep veins.

Other causes of Normal Blood Flow:

• Hyperviscosity, for example, With polycythemia vera
• RBC disorders, for example, Sickle cell anemia can cause vascular occlusions and stasis.

3. Hypercoagulability:

Definition of Hypercoagulability: Hypercoagulability state (also known as thrombophilia) is defined as a systemic disorder associated with an increased tendency to develop thromboembolism.

Causes of Hypercoagulability:

• It is a less frequent cause of thrombosis. Causes can be divided into primary (genetic) and secondary (acquired) disorders.
• Secondary/acquired disorders: The pathogenesis of acquired thrombophilia is usually multifactorial.

Terminology:

• Mural thrombus: It is attached to the wall and projects into the lumen, without complete occlusion of the lumen. It occurs in heart chambers or in the aortic lumen.
• Occlusive thrombus: It occludes the lumen of the blood vessel and prevents the flow of blood. It usually occurs in veins or smaller or medium-sized arteries.
• Vegetation: It is a thrombus on the heart valve and appears as a polypoid mass projecting into the lumen (for example, Infective endocarditis).

Major causes of hypercoagulable state:

Types of Thrombi:

Thrombi may be arterial or venous type. Differences between arterial and venous thrombus are shown in Table.

Morphology of Thrombi:

• Layers in thrombus:
  • The first layer of the thrombus on the endothelium/endocardium is a platelet layer.
  • On top of the platelet layer, firing is precipitated to form upstanding laminae which anastomose to form an intricate structure that resembles coral (coralline thrombus).
  • In between the upstanding laminae and anastomosing fibrin meshwork, the red blood cells get trapped. Retraction of firing produces a ribbed

Write briefly on the lines of Zahn.

Lines of Zahn: Both gross and microscopy of thrombus show alternating light (pale or white) areas of platelets held together by firing, and dark retracted areas of firing meshwork with trapped RBCs. These alternating laminations of light and dark are known as lines of kloZahn.

Site and Types of Thrombi:

Thrombi can develop anywhere in the cardiovascular system.

1. Heart:

• Cardiac thrombi: Usually develops at sites of turbulence or endocardial injury.
• Valves: Thombi on heart valves are called vegetations. They are more common on mitral or aortic valves.

2. Blood vessels:

• Arteries: Arterial thrombi tend to be white.
  • Aorta or larger arteries usually develop mural thrombi.
  • Thombi developing in the medium or smaller arteries are frequently occlusive. They develop (in decreasing order of frequency) in the coronary, cerebral, and femoral arteries.
• Veins:
  • Venous thrombi (phlebothrombi) are usually occlusive, and form a long cast of the lumen. They occur usually at sites of stasis and contain more trapped RBCs (and relatively few platelets). They are therefore known as red or stasis thrombi.
  • Upper layer: It is poor in cells and is yellow-white. It is firm representing coagulated plasma without red blood cells. It is called chicken fat because of its color and consistency.

The fate of the Thrombus:

Write a short note on the fate of a thrombus.

1. Dissolution/lysis: of thrombi without any consequences.

• Recent thrombi may totally disappear due to the activation of fibrinolysis.
• Old thrombi are more resistant to lysis.

2. Propagation of thrombi:

It is the process in which thrombi grow and increase in size. The thrombus which was initially mural may become an occlusive thrombus. The propagating portion of a thrombus is poorly attached to the wall and therefore prone to fragmentation and embolization.

• Arterial thrombi grow retrograde from the point of attachment
• Venous thrombi extend in the direction of blood flow.

3. Embolization: Thombi may get detached from its site of origin and form emboli. These emboli can travel to other sites through circulation and lodge in a blood vessel away from the site of thrombus formation.

• The consequences depend on the site of lodgment.
• Large venous thrombi may get detached and travel to the pulmonary circulation to the lungs as pulmonary emboli.

4. Organization:

If thrombi are not dissolved (either spontaneously or by therapy), these older thrombi become organized by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts. Small, organized thrombi may be incorporated into the vessel wall.

5. Canalization/recanalization:

New lumen/channels lined by endothelial cells may form in an organized thrombus. The capillary channels may form thoroughfare channels and can establish the continuity of the original lumen.

Consequences of Thrombi:

It depends on the site of the thrombosis.

• Obstruction of involved vessels: Thombi can cause obstruction of involved arteries and veins.
  • Arterial thrombi: They may cause infarctions in the region supplied by the involved vessel. Occlusion at certain locations (for example, A coronary artery) can be life-threatening.
  • Venous thrombi: Small venous thrombi may cause no symptoms. Larger thrombi can cause congestion and edema in the region distal to obstruction by thrombus. Forced dorsiflexion of the foot produces tenderness in the calf associated with DVT and is known as the Homan sign.
• Embolization: Arterial, cardiac, and venous thrombi can undergo fragmentation and detach to form emboli.
• It is the major complication and these are called as thromboembolic:
  • The consequences of embolism depend on:
  • Site of lodgement of emboli
  • Tissue affected and
  • Source of thromboemboli.
• Arterial and cardiac thromboembolic: The commonest sites of lodgment of emboli are the brain, kidneys, and spleen because of their rich blood supply.
• Venous emboli: Thy may lodge in the lungs causing various consequences of pulmonary embolism.

Embolism

Define embolus/embolism.

Definition of Embolism: An embolus is a detached intravascular solid, liquid, or gaseous mass that is transported in the blood to a site distant from its point of origin. The process is called an embolism.

Types of Emboli:

Mention different types of emboli.

Classification: Depending on

1. Physical nature of the emboli:

• Solid: Thomboemboli, atheromatous material, tumor emboli, tissue fragments, bacterial clumps or parasites, foreign bodies.
• Liquid: Fat, bone marrow, and amniotic fluid.
• Gaseous: Air or other gases.

2. Whether infected or not:

• Bland: Sterile.
• Septic: Infected.

3. Source: The emboli may be endogenous (form within the body) or exogenous
(introduced from outside).

• Cardiac emboli: Usually, they arise from the left side of the heart. For example, emboli from:
  • Atrial appendage
  • Left ventricle in myocardial infarction
  • Vegetations on the valves in infective endocarditis.
• Vascular emboli:
  • Arterial emboli: For example, atheromatous plaque, aneurysms.
  • Venous emboli: For example, deep vein thrombus, tumor emboli.
  • Lymphatic emboli: For example, tumor emboli.

4. Flow of emboli:

Write a short note on paradoxical embolism.

• Paradoxical emboli: They are rare and the emboli originate in the venous circulation and bypass the lungs by traveling through a right-to-left shunt such as an atrial septal defect (incompletely closed/patent foramen ovale) or interventricular defect. Then, they enter the left side of the heart and block the blood flow to the systemic arteries.
• Retrograde emboli: Emboli, which travel against the flow of blood are known as retrograde emboli. For example, prostatic carcinoma metastasis to the spine.

Pulmonary Embolism (PE):

Write a short note on pulmonary embolism.

Definition of Pulmonary Embolism: It is defined as an embolism in which emboli occlude the pulmonary arterial tree.

Site of Origin of Emboli:

• Deep leg veins: DVTs are the source in more than 95% of cases of pulmonary emboli. Deep leg veins include popliteal, femoral, or iliac veins.
• Risk of pulmonary embolism: Major risk factor is after surgery. The risk increases with advancing age, obesity, prolonged operative procedure, postoperative infection, cancer, and pre-existing venous disease.

Mechanism of Pulmonary Embolism:

DVTs undergo fragmentation → These thromboembolism are carried through progressively larger vascular channels → into the right side of the heart → right ventricle → they enter into the pulmonary arterial vasculature.

The fate of Pulmonary Embolism:

Fate depends on the size of the embolus.

1. Resolution or organization: Small pulmonary emboli may travel into the smaller, branches of pulmonary arteries and may resolve completely. Most (60–80%) of them are clinically silent. With passage of time, they become organized and are incorporated into the wall of the pulmonary vessel.

2. Massive pulmonary embolism: When emboli obstruct 60% or more of the pulmonary circulation, it is known as a massive pulmonary embolism.

• Saddle embolus: It is a large pulmonary embolus that lodges at the bifurcation of the main pulmonary artery.
• Effects:
  • Acute right ventricular failure.
  • Shock.

3. Multiple recurrent pulmonary emboli:

• These may fuse to from a single large mass.
• Usually, the patient who has had one PE is likely to have recurrent emboli.

4. Paradoxical embolism.

Consequences of Pulmonary Embolism:

1. Pulmonary infarction: Most (about 75%) small pulmonary emboli do not produce infarcts. However, an embolus can produce infarction in patients with congestive heart failure or chronic lung disease.
   • Gross:
     • Type: Usually hemorrhagic type, because of blood supply to the infarcted (necrotic) area by the bronchial artery.
     • Shape: Pyramidal in shape with the base of the pyramid on the pleural surface.
2. Pulmonary hemorrhage: Obstruction of medium-sized pulmonary arteries by emboli and subsequent rupture of these vessels can result in pulmonary hemorrhage.
3. Pulmonary hypertension: Multiple recurrent pulmonary emboli → may cause mechanical blockage of the arterial bed → result in pulmonary hypertension → right ventricular failure.
4. Minimal effect: Obstruction of small end-arteriolar branches of the pulmonary artery by emboli usually neither produces hemorrhage nor infarction.

Systemic Thromboembolism

Definition of Systemic Thromboembolism: It is defined as an embolism in which emboli occlude systemic arterial circulation. Systemic arterial embolism usually produces infarcts in the region supplied by the involved vessel.

Sources of Systemic Emboli:

Write a short note on thromboembolism

1. Heart: A most common source of thromboembolic.

• Intracardiac mural thrombi: Most common source.
• Examples:
  • Myocardial infarct of the left ventricular wall
  • In mitral stenosis, dilatation of the left atrium and atrial fibrillation predispose to thrombus and embolization.
• Valvular source: Examples, bacterial endocarditis (valvular vegetation from aortic or mitral valves) or prosthetic valves

2. Blood vessels: Thombi on ulcerated atherosclerotic plaques or from aortic aneurysms

3. Unknown origin.

Consequences of Systemic Thromboembolism:

• The arterial emboli can travel to a wide variety of sites. Ths is in contrast to venous emboli, which lodge mainly in one vascular bed namely the lung.
• The arterial emboli tend to pass through the progressively narrow arterial lumen and lodge at points where the vessel lumen narrows abruptly (for example,At bifurcations or in the area of an atherosclerotic plaque).

The fate of thromboembolism at the site of arrest:

• Propagation and obstruction: Thomboemboli may grow (propagate) locally at the site of the arrest and produce severe obstruction leading to infarction of the affected tissues.
• Fragmentation and lysis.

Major Sites Affected by Arterial Thromboemboli:

• Lower extremity (75%): Embolism to an artery of the leg may produce gangrene.
• Brain: Arterial emboli to the brain may produce ischemic necrosis in the brain (strokes).
• Intestine: Emboli in the mesenteric vessels may produce infarction of the bowel.
• Kidney: Renal artery embolism may cause small peripheral infarcts in the kidney.
• Blood vessels: Emboli originating from bacterial vegetation may cause inflammation of arteries and produce a mycotic aneurysm.
• Other sites: Spleen and upper extremities are less commonly affected.

Fat And Marrow Embolism

Write a short note on fat embolism.

Fat and marrow embolus consists of microscopic globules of fat with or without bone marrow elements. The release of these elements into the circulation produces fat embolism.

Causes of fat embolism:

• Trauma to adipose tissue with fracture: Severe trauma to adipose tissue, particularly accompanied by fractures of bone releases fat globules or fatty marrow (with or without associated hematopoietic marrow cells) into ruptured blood vessels.
• Soft tissue trauma and burns.
• During vigorous cardiopulmonary resuscitation.

Manifestation of fat embolism:

• In most cases, it is asymptomatic, Sometimes, it may manifest as potentially fatal fat embolism syndrome.
• Fat embolism syndrome: It is the term applied when the patient develops symptoms due to embolism. It develops in only a minority of patients.

Pathogenesis of fat embolism:

Fat embolism syndrome involves both mechanical obstruction and biochemical injury.

1. Mechanical obstruction:

• Trauma to adipose tissue associated with fracture releases emboli consisting of fat globules and/or fatty marrow.
• These fat microemboli along with red cell and platelet aggregates may enter the capillaries which are ruptured at the site of the fracture.
• The trauma may also cause hemorrhage into the marrow and into the subcutaneous fat.
• This increases interstitial pressure above capillary pressure, and fat globules are forced into circulation.
• The emboli travel through the circulation and can occlude the pulmonary and cerebral microvasculature.

2. Biochemical injury:

• The chemical composition of the fat present in the lung in fat embolism is different from that in adipose tissue.
• The mechanical obstruction alone cannot explain this difference.
• So, pathogenesis probably involves mechanical obstruction associated with biochemical injury.
• Biochemical injury is produced by free fatty acids that are released from the fat globules. Free fatty acids produce local toxic injury to endothelium.
• They cause platelet activation and granulocyte recruitment along with the release of injurious free radicals, protease, and eicosanoids.
• This biochemical injury increases the severity of the vascular damage produced by mechanical obstruction.

Consequences of Fat Embolism:

It depends on the size and quantity of fat globules and whether the emboli are arrested in the pulmonary or systemic circulation.

• Sites of the arrest of fat emboli:
  • Emboli in the venous side lodge in the lungs.
  • If emboli pass into the systemic circulation, they may be arrested in the brain, kidneys, and other organs.
• Demonstration of fat embolism: Fat is dissolved during routine tissue preparations by the solvents (xylene/xylol) used in paraffin embedding. The microscopic demonstration of fatmicroglobules requires frozen sections and special stains for fat (for example, Sudan III and IV, OilRed O and osmic acid).

Clinical Presentation of fat embolism:

• The most severe form of fat embolism syndrome may be fatal.
• Time of development: It develops 1 to 3 days after the traumatic injury.
• Respiratory symptoms: These include sudden onset of tachypnea, dyspnea, and tachycardia which may lead to respiratory failure.
• Neurologic symptoms: These include irritability, restlessness, delirium, and coma.
• Hematological findings:
  • Thrombocytopenia: Rapid onset of thrombocytopenia produces diffuse petechial rash (found in 20–50% of cases) and may be a useful diagnostic feature.
  • Anemia: It is due to aggregation of red cells and/or due to hemolysis.
• Chest radiography: It shows diffuse opacity of the lungs → may progress to opacification of lungs (whiteout)-characteristic of acute respiratory distress syndrome.

Air Embolism

Write a short note on air/gas embolism/Caissons disease/decompression sickness.

Air embolism occurs when air is introduced into venous or arterial circulation.

Causes of Air embolism:

• Trauma/injury: Air may enter the venous circulation through neck wounds and chest wall injuries.
• Surgery/invasive procedures: These include invasive surgical procedures such as thoracocentesis, punctures of the great veins during obstetric or laparoscopic procedures, into the coronary artery during bypass surgery, cerebral circulation by neurosurgery in the “sitting position”, or hemodialysis.
• Criminal abortion
• Amount of air required: It is usually more than 100 cc to have a clinical effect of air embolism.

Decompression Sickness:

It is a form of gas embolism and may be acute or chronic.

Acute Decompression Sickness: Cause:

• It develops when individuals are exposed to a sudden decrease in atmospheric pressure.
• Risk factors include:
  • Individuals when exposed to high atmospheric pressure, such as scuba and deep sea divers and underwater construction workers (for examples, Tunnels, and drilling platform construction), during rapid ascent to low pressure.
  • Individuals in unpressurized aircraft during rapid ascent.
  • Sport diving.

Mechanism of Decompression Sickness:

• When air is breathed at high atmospheric pressure (for example, During a deep-sea dive), large amounts of an inert gas such as nitrogen or helium are dissolved in the blood, body fluids, and tissues.
• When the individual ascends gradually, the dissolved gas (particularly nitrogen) comes out from the solution in the blood and tissues and exhaled. It does not produce any injury.
• However, if the ascent is too rapid, gas bubbles form in the blood circulation and within tissues → obstruct the flow of blood → injuring the cells.

Effects Decompression Sickness:

The gas bubbles within small vessels obstruct the blood supply bends and choke.

• Musculoskeletal system: Small vessel obstruction → reduced blood supply to skeletal muscles and supporting tissues in and about joints → produces muscular and joint pain → patient doubles up in pain.
• Thus painful condition is called the bends.
• Respiratory system: Obstruction of blood vessels of the lungs causes edema, hemorrhage, and focal atelectasis or emphysema. This may lead to a form of respiratory distress called the chokes.
• Nervous system: It may cause coma or even death.

Chronic Decompression Sickness: Caisson Disease:

• A chronic form of decompression sickness is known as Caisson disease (named for the pressurized vessels/diving bells used in bridge construction).
• Workers in these pressurized vessels may develop both acute and chronic forms of decompression sickness.
• Characteristic features: Avascular necrosis: Gas embolus in vessel produces obstruction to blood flow → causes multiple foci of ischemic (avascular) necrosis of bone. The more commonly involved bone includes the head of the femur, tibia, and humerus.

Amniotic Fluid Embolism

Write a short note on amniotic fluid embolism.

Amniotic fluid embolism develops when amniotic fluid along with fetal cells and debris enters the maternal circulation The entry occurs through open (ruptured) uterine and cervical veins or a tear in the placental membranes.

• Time of occurrence: It is a rare maternal-threatening complication, which occurs at the end of labor and the immediate postpartum period.
• Consequences: From the venous circulation, amniotic fluid emboli enter the right side of the heart and finally rest in the pulmonary circulation. Amniotic fluid has a high thromboplastin activity and initiates a potentially fatal disseminated intravascular coagulation (DIC).

Morphology of amniotic fluid embolism:

• Amniotic fluid contents within pulmonary vasculature: Amniotic fluid emboli are composed of squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, and mucin derived from the fetal respiratory or gastrointestinal tract.
• Other findings: These include marked pulmonary edema, diffuse alveolar damage, and features of DIC.

Clinical Features of amniotic fluid embolism:

• Abrupt onset: It develops during the immediate postpartum period, and is characterized by sudden onset of severe dyspnea, cyanosis, and neurologic impairment ranging from headache to seizures. The patient develops shock, coma, and death.
• Bleeding: If the patient survives the initial acute crisis, the patient develops bleeding due to disseminated intravascular coagulation (DIC).
• Acute respiratory distress syndrome.

Infarction

Define Infarct/infarction.

Definition of Infarct: An infarct is a localized area of ischemic necrosis caused by occlusion of either the arterial blood supply or the venous drainage. The process of producing an infarct is known as infarction.

• Mostly infarct is a coagulative type of necrosis due to sudden occlusion of arterial blood supply. If the patient survives, the infarct heals with a scar.
• Common and important infarcts are shown in Table.

Common and important infarcts:

Causes of Infraction:

What are the causes/etiology and effects of infarction?

• Arterial causes: Most important
  • Occlusions of lumen: It is the most common cause and may be due
  • Thrombus
  • Embolus
  • Causes in the wall: For example, local vasospasm, hemorrhage into an atheromatous plaque or thromboangiitis obliterans
  • External compression of the vessel: Tumor.
• Venous causes:
  • Occlusions of the lumen may be due
    • Thrombus
    • Embolus
  • Extrinsic vessel compression: Tumor, torsion of a vessel (e.g. in testicular torsion or bowel volvulus), strangulated hernia.

Factors that Determine the Outcome of an Infarct:

Mention the factors that influence the development of an infarct.

The outcome of vascular occlusion may range from no or minimal effect to the death of a tissue or individual.

The major factors that determine the outcome of an infarct are:

1. Nature of the vascular supply:

• Dual/parallel blood supply: Organs or tissues with double or parallel blood supply are less likely to develop infarction, Infarct, Lung, Liver, Hand, and forearm.
• End-arterial blood supply: The kidney and spleen have a blood supply, which are end-arteries with little or no collaterals. Obstruction of vessels in these organs usually causes tissue death and infarction.

2. Rate of occlusion: Slow occlusion is less likely to produce infarction than rapid occlusion. This is because it provides time to develop alternate perfusion pathways.

3. Vulnerability of tissue to hypoxia:

• Neurons are highly sensitive to hypoxia: They undergo necrosis even if the blood supply is occluded for 3 to 4 minutes.
• In the heart, myocardial cells are also quite sensitive to hypoxia, but less sensitive than neurons. Myocardial cells die after only 20 to 30 minutes of ischemia.

4. Oxygen content of blood: In a normal individual, partial obstruction of a small vessel may not produce any effect, but in a patient with anemia or cyanosis same may produce infarction.

Classification of Infraction:

White/Pale Infarcts:

They occur:

1. With arterial occlusions
2. In solid organs
3. With end-arterial circulation without a dual blood supply (for example, Heart, spleen, and kidney)
4. Tissue with increased density prevents the diffusion of RBCs from adjoining capillary beds into the necrotic area.

Red/Hemorrhagic Infarcts:

They occur

• With venous occlusions, for example, Ovary.
• In loose textured tissues, for example, Lung: They allow red cells to diffuse through and collect in the necrotic zone.
• In tissues with dual blood supply, for example, Lung and small intestine: It allows blood flow from an unobstructed parallel blood supply into a necrotic zone.
• In tissues previously congested due to decreased venous drainage.
• When blood flow is re-established to a site of previous arterial occlusion and necrosis, for example, following coronary angioplasty of an obstructed coronary artery.

Morphology of Infraction:

Write a short note on the morphology of the infarct.
Or
White/pale Infarcts:

Organs involved include the heart, kidneys, spleen, and dry gangrene of the extremities.

White/pale Infarcts

• Gross:
  • Usually wedge-shaped.
  • The occluded blood vessel is seen at the apex and the periphery/ surface of the organ forms the wide base.
  • Acute infarcts are poorly defined and slightly hemorrhagic.
  • After 1 to 2 days, the infarct becomes soft, sharply demarcated, and light yellow in color.
  • Margins of infarct appear well-defined because of the narrow rim of congestion caused by inflammation.
  • As time passes, infarcts progressively become paler and more sharply defined.

Red/Hemorrhagic Infarcts:

• Organs with a double blood supply: for example, lung, liver
• Organs with extensive collateral circulation: for example, small intestine and brain
• Reperfusion of infarcted area: for example, red infarct may occur in heart when the infarcted area is reperfused
• Gross: Appears as a sharply circumscribed area of necrosis, firm in consistency and dark red to purple in color.

Microscopy of Infarct:

• Both pale and red infarct characteristically shows ischemic coagulative necrosis.
• Microscopic changes of frank necrosis appear after about 4 to 12 hours.
• Acute inflammation cells infiltrate the necrotic area from the viable margins all-round the infarcts within a few hours. It becomes prominent within 1 to 2 days.
• Followed by a reparative process, which begins at the preserved margins. The necrotic cells in infarcts and extravasated red cells are phagocytosed by macrophages.
• In tissues composed of stable or labile cells, parenchymal regeneration can occur at the periphery where stromal architecture is preserved.
• Granulation tissue may replace the infarcted area which matures to form scar tissue.
• If the infarct is large (for example, In the heart or kidney), the necrotic center may persist for months.

Septic infarctions: They may occur in two situations

• Infection: Infarct may get infected when it is seeded by pyogenic bacteria, for example, Infection of the pulmonary infarct.
• Septic emboli: They contain organisms and can produce septic infarct, for example, Vegetations of bacterial endocarditis may cause septic infarct of spleen.
• The organisms present in a septic infarct convert infarct into a frank abscess.

Shock

Definition of Shock: Shock is a pathological process that results from inadequate tissue perfusion, leading to cellular dysfunction and organ failure.

Introduction of Shock:

1. Shock is the most common, important, and very serious medical condition. It is the final common pathway for several clinical events, which are capable of causing death.
2. These events include severe hemorrhage, extensive trauma or burns, large myocardial infarction, massive pulmonary embolism, and severe microbial sepsis.

Characteristic features of Shock:

The extreme and widespread failure of the circulatory system (either due to decreased cardiac output or reduced effective circulating blood volume) → systemic hypotension (either due to reduced cardiac output or to reduced effective circulating blood volume) → life-threatening inadequate/impaired tissue perfusion (hypoperfusion) → tissue hypoxia a → reversible cellular injury → irreversible tissue injury and organ failure → death.

Classification of Shock:

• Classify shock.
• List the main types of shock with suitable examples.

According to etiology (cause), shock can be classified into three major general categories given in the table.

Major types of shock:

Etiology and Pathogenesis:

Describe the etiology and pathogenesis of shock Or Write short note on hypovolemic shock.

Hypovolemic Shock:

• Hypovolemic shock results from low cardiac output due to:
  • Loss of blood: For example, massive hemorrhage.
  • Loss of plasma: For example, severe burns.
  • Loss of fluid: Vomiting, diarrhea, severe gastroenteritis, for example, Cholera.

Inadequate blood or plasma volume and fluid loss → hypovolemia → low cardiac output → hypotension → inadequate perfusion of tissue.

Cardiogenic Shock:

Write a short note on cardiogenic shock.

Cardiogenic shock results from low cardiac output due to:

Intrinsic myocardial damage: For example, massive myocardial infarction, and ventricular arrhythmias.

• Obstruction to the outflow of blood from ventricles: for example, pulmonary embolism.
• The various causes of cardiogenic shock produce → severe dysfunction of the left ventricle → decreases cardiac output → decreased tissue perfusion of tissue.
• The left-sided heart failure also reduces the entry of blood from a pulmonary vein into the left atrium.
• This leads to the movement of fluid from pulmonary vasculature into the pulmonary interstitial space and into the alveoli resulting in pulmonary edema.

Septic Shock

Describe the pathogenesis of septic (endotoxic) shock.

Definition of Septic Shock: Septic shock is defined as a shock due to severe sepsis with hypotension, which cannot be corrected by infusing fluids.

Septic shock results from vasodilation and peripheral pooling of blood and is associated with dysfunction of multiple organs distant from the site of infection.

Causative Organisms of Septic Shock:

• Septic shock may be caused by gram-positive (most common) or gram-negative bacteria, fungi, and, very rarely, protozoa or Rickettsiae.
• The common gram-positive bacteria include Staphylococcus aureus, enterococci, Streptococcus pneumoniae, and gram-negative bacilli which are resistant to usual antibiotics.

Major Pathogenic Pathways in Septic Shock:

• Trigger: Most of septic shocks are triggered by bacteria or fungi that normally do not produce systemic disease in immunocompetent hosts.
• The hallmark of septic shock: It is tissue hypoperfusion due to a decrease in peripheral vascular resistance as a result of systemic vasodilation and pooling of blood in the periphery. Cardiac output may be normal or even increased in the early stages.
• Initiation of shock: Diverse microorganisms can cause septic shock indicating that a variety of microbial constituents can trigger the process of shock.

Major factors contributing to the pathogenesis of septic shock are:

1. Inflammatory and counter-inflammatory responses
2. Endothelial cell activation and injury
3. Organ dysfunction
4. Metabolic abnormalities and
5. Immune suppression.

1. Inflmmatory and counter-inflammatory responses: Microbial components can activate innate immune responses.

Innate immunity:

• Several substances derived from microorganisms recognize and activate cells (for example, Macrophages, neutrophils, dendritic cells, endothelial cells) and soluble components of the innate immune system (for example, Complement).
• Once activated, these cells and factors of the innate immune system initiate a number of inflammatory responses to produce septic shock and multiorgan dysfunction.
• Its activation leads to the production of proinflammatory mediators which produces endothelial cell activation/injury.

• Triggering of the innate immune response: Leukocytes (neutrophils and macrophages) and other cells of the innate immune system express pathogen receptors (for example, Toll-like receptor-TLR).
• Production of inflammatory mediators by activated inflammatory cells:
  • Proinflmmatory cytokines: TNF-α, IL-1, IFN-γ, IL-12, and IL-18.
  • Cytokine-like mediators: for example, high-mobility group box-1 protein (HMGB-1).
  • Other mediators: Reactive oxygen species, prostaglandins, and platelet activating factor (PAF).
• Effect of inflammatory mediators: The inflammatory mediators induce endothelial cells (and other cell types) to upregulate adhesion molecule expression and further stimulate cytokine and chemokine production.

Activation of the complement cascade:

• Microbial components can also activate the complement system and its components have proinflammatory effect
• Anaphylatoxins (C3a, C5a), chemotactic fragments (C5a), and opsonins (C3b).
• The hyperinflammatory state initiated by sepsis also activates counter-regulatory immunosuppressive mechanisms.
• This may involve both innate and adaptive immune cells.
• This, during the clinical course patients with septic shock may oscillate between hyperinflammatory and immunosuppressed states.

2. Endothelial cell activation and injury:

Endothelial cell activation/injury is caused by either microbial constituents or leukocyte-derived inflammatory mediators.

Sequelae of endothelial activation/injury:

1. Activation of coagulation system and thrombosis: Septic shock activates the coagulation system → forms firing-rich thrombi in small vessels → leading to the hypoperfusion of tissues throughout the body. It produces dangerous complication DIC in about 50% of septic patients.

Factors activating the coagulation system in sepsis:

• Increased production of tissue factor (TF) through endothelial injury by proinflammatory cytokines (for example, IL-6).
• Decreased production of anticoagulant factors: These include tissue factor pathway inhibitors, antithrombin, thrombomodulin, and protein C and S.

2. Increased vascular permeability: The pro-inflammatory state and endothelial cell activation associated with sepsis produce widespread vascular leakage and tissue edema. This decreases both the delivery of nutrients and waste removal.

3. Vasodilation: It is due to nitric oxide (NO) and vasoactive inflammatory mediators.

• NO: It is produced due to increased expression of nitric oxide synthetase.
• Vasoactive inflammatory mediators: These include C3a, C5a, and PAF.

The systemic vasodilation and pooling of blood in the periphery produce hypotension and decreased perfusion of tissue (hypoperfusion). This leads to the dysfunction of multiple organs.

3. Organ dysfunction:

• Decrease supply of oxygen and nutrients to the tissues: Due to systemic hypotension, interstitial edema, and thrombi in the small vessels.
• Decreased contractibility of the myocardium and cardiac output: It is due to increased levels of cytokines and secondary mediators. This along with increased vascular permeability and endothelial injury can lead to adult respiratory distress syndrome.
• Multiorgan failure: It affects, particularly the kidneys, liver, lungs, and heart.

4. Metabolic abnormalities: These may be observed in patients with septic shock.

• Insulin resistance: It is due to the action of proinflammatory cytokines.
• Hyperglycemia: It is due to gluconeogenesis stimulated by cytokines such as TNF and IL-1, stress-induced hormones (such as glucagon, growth hormone, and glucocorticoids), and catecholamines. Hyperglycemia suppresses the bactericidal activity of neutrophils.
• Decreased glucocorticoid production:
  • Initially, there is increased glucocorticoid production, and is later followed by decreased production due to adrenal insufficiency.
  • Adrenal necrosis may also develop due to DIC (Waterhouse-Friderichsen syndrome).

5. Immune suppression: It occurs in patients with septic shock. It is probably due to:

• Production of anti-inflammatory mediators (e.g. soluble TNF receptor, IL-1 receptor antagonist, and IL-10).
• Widespread apoptosis of lymphocytes.

Stages Of Shock

Describe 3 different stages of shock.

Shock is a progressive disorder, which if not treated, leads to death. It can be divided into three phases.

1. Nonprogressive (compensated/reversible) phase: During the initial phase, homeostatic compensatory mechanisms redistribute the blood supply in such a way that the effective blood supply to the vital organs is maintained. Ths is achieved by neurohumoral mechanisms, which try to maintain cardiac output and blood pressure.

• Compensatory changes: The neurohumoral mechanism produces the following compensatory changes:
• Widespread vasoconstriction except vital organs: Coronary and cerebral vessels usually maintain relatively normal blood flow, and oxygen delivery. Cutaneous vasoconstriction → produces the coolness and pallor of the skin.
• Fluid conservation by kidney.
• Tachycardia

2. Progressive phase:

If the underlying causes are not corrected, shock passes to the progressive phase.

Characterized by widespread tissue hypoperfusion and hypoxia → intracellular aerobic respiration replaced by anaerobic glycolysis → increased production of lactic acid → metabolic lactic acidosis → decreases the tissue pH → dilatation of arterioles → peripheral pooling of blood into the microcirculation → decreases the cardiac output → produces anoxic injury to endothelial cell → favors development of DIC → widespread tissue hypoxia and damage of vital organs.

3. Irreversible phase:

• Without intervention, the shock eventually enters an irreversible stage.
• At this phase, cellular and tissue injury is so severe that even if the hemodynamic defects are corrected, survival is not possible.
• Widespread cell injury results in leakage of lysosomal enzymes, which aggravate the shock state.
• Myocardial contractile function worsens partly due to nitric oxide synthesis.
• If ischemic intestine allows microbes from the intestinal flora to enter into the circulation it. This may lead to superimposed bacteremic shock.
• The patient develops acute tubular necrosis and results in death.

Morphology of Stages of Shock:

Describe the morphological changes in various organs in shock.
Or
Mention renal changes in shock
Or
Write a short note on lung changes in shock/diffuse alveolar damage.

Changes in Cardiogenic or Hypovolemic Shock:

These are mainly due to hypoxic injury. Morphological changes are particularly evident in adrenals, kidneys, lungs, brain, heart, and gastrointestinal tract.

• Adrenal:
  • Lipid depletion in cortical cell: It is due to the conversion of the relatively inactive vacuolated cells to metabolically active cells. The active cells utilize stored lipids for the synthesis of steroids.
  • Focal hemorrhage: It occurs in the inner cortex of the adrenal in severe shock.
  • Massive hemorrhagic necrosis of the entire adrenal gland is found in the Waterhouse-Friderichsen syndrome, which is associated with severe meningococcal septicemia.
• Kidney: Acute tubular necrosis (acute renal failure) is a major complication of shock.
  • Gross: Kidney is enlarged, swollen, and congested, and the cortex may appear pale. The cut section shows blood pooling in the outer region of the medulla.
  • Microscopy:
    • Tubules: Dilation of the proximal tubules and focal necrosis of tubular epithelial cells. Frequently, the tubular lumen may show pigmented casts formed due to leakage of hemoglobin or myoglobin.
    • Interstitium: It shows edema and mononuclear cells in the interstitium and within tubules.
• Lungs:
  • Lungs are relatively resistant to hypoxic injury and are usually not affected in pure hypovolemic shock. However, when the shock is due to bacterial sepsis or trauma, it shows diffuse alveolar damage which can lead to acute respiratory distress syndrome (ARDS) also known as shock lung.
  • Gross: The lung is firm and congested. The cut surface shows oozing out of frothy fluid.
  • Microscopy:
    • Edema: It first develops around peribronchial interstitial connective tissue and later in the alveoli.
    • Necrosis: Endothelial and alveolar epithelial cells undergo necrosis which leads to the formation of intravascular microthrombi.
    • Hyaline membrane: It is usually seen lining the alveolar surface. It may also line alveolar ducts and terminal bronchioles.
• Heart:
  • Gross: It shows petechial hemorrhages in the epicardium and endocardium.
  • Microscopy: Necrosis of the myocardium is seen which may range from minute focus to large areas of necrosis. Prominent contraction bands are seen by light microscopy.
• Liver:
  • Gross: Liver is enlarged. Cut section shows a mottled (blotched) appearance due to the marked pooling of blood in the centrilobular region.
  • Microscopy: The centrilobular region of the liver shows congestion and necrosis.
• Brain: Encephalopathy (ischemic or septic) and cortical necrosis.
• Gastrointestinal tract: Shock produces diffuse gastrointestinal hemorrhage. Erosions of the gastric mucosa and superficial ischemic necrosis in the intestine lead to gastrointestinal bleeding.

Changes in Septic Shock:

• Septic shock can lead to DIC which is characterized by the widespread formation of firinrich microthrombi, particularly in the brain, heart, lungs, kidney, adrenal glands, and gastrointestinal tract.
• The utilization of platelets and coagulation factors in DIC produces bleeding manifestations. It may show petechial hemorrhages on the serosal surface and the skin.

Summary of main morphological features of shock:

Clinical Consequences of Shock:

Write a short note on the clinical consequences (end result) of shock.

The clinical features of shock depend on the cause.

• Hypovolemic and cardiogenic shock: Usually, present with features of hypotension and hypoperfusion. The features include altered sensorium, cyanosis, oliguria, weak rapid pulse, tachypnea, and cool, clammy extremities.
• Septic shock: The skin initially may be warm and flushed because of peripheral vasodilation.

The initial underlying cause that precipitated the shock may be life-threatening (for example, Myocardial infarction, severe hemorrhage, or sepsis). Later, organ dysfunction involving cardiac, cerebral, and pulmonary function worsens the situation. Th electrolyte disturbances and metabolic acidosis may further exacerbate the situation.

Patients who survive the initial complications may develop renal insufficiency characterized by a progressive decrease in urine output and severe fluid and electrolyte imbalances.

Prognosis Consequences of Shock:

• The prognosis depends on the cause and duration of the shock.
• Patients with hypovolemic shock may survive with appropriate management.
• Septic shock, or cardiogenic shock associated with massive myocardial infarction, usually have high mortality rate.