General Pathology

Theme 10: Haemodynamic Disorders I • Congestion, Edema, Haemorrhage and Shock

1. Define the terms: Hyperaemia, Congestion, Edema, Haemorrhage and Shock.
2. Describe the effects of congestion on various organs.
3. Describe the pathophysiological categories and causes of edema and the mechanisms by which it occurs.
4. Discuss the clinicopathological forms of haemorrhage and explain the causes, effects and complications including diseminated intravascular coagulation.
5. Discuss the categories, causes and mechanisms of the different types of shock and describe the clinicopathological consequences in vital organs.

Hyperaemia is an active process with augmented blood inflow caused by arteriolar dilation (e.g., skeletal muscle during exercise or at sites of inflammation). Tissues are redder owing to engorgement with oxygenated blood.

Congestion is a passive process caused by impaired outflow from a tissue. Isolated venous obstruction may cause local congestion; systemic venous obstruction occurs in congestive heart failure (CHF).

Edema refers to increased fluid in the interstitial tissue spaces or body cavities (e.g., hydrothorax, hydropericardium and hydroperitoneum [ascites]). Edema may be localized (e.g., secondary to isolated venous or lymphatic obstruction) or systemic (as in heart failure), called anasarca when severe.

Hemorrhage refers to extravasation of blood because of vessel rupture. Rupture of a large artery or vein is usually due to vascular injury, such as from trauma, atherosclerosis or inflammatory or neoplastic erosion of the vessel. Capillary bleeding can occur with chronic congestion. A tendency to hemorrhage from insignificant injury is seen in a variety of disorders called hemorrhagic diatheses. Hemorrhage may be external or enclosed within a tissue; the later is called a hematoma. Hematomas may be trival (e.g., a bruise) or may accumulate sufficient blood to cause death (e.g., a massive retroperitoneal hematoma resulting from rupture of an aortic aneurysm).

Shock is systemic hypoperfusion resulting from reduction in either cardiac output or the effective circulating blood volume. This reduction results in hypotension, followed by impaired tissue perfusion and cellular hypoxia.

Congestion and Hyperemia

• Increase in blood volume of a localised area
• May be normal (e.g., exercise, blushing)

Congestion (passive hyperemia)

• deoxygenated blood
• impaired venous return causing damming back of blood
• occurs after cardiac failure (+ edema) / obstructive venous disease
• e.g., judicial hanging

Hyperemia (active hyperemia)

• oxygenated blood (area looks very red)
• arteriolar & arterial dilation with increased flow of blood into capillary beds
• occurs at sites of inflammation

Effects of congestion

• Haemorrhage (ruptures of small capillaries)
• edema
• Siderosis – Fe deposit due to RBC breakdown
• fibrosis

Left ventricular failure

• e.g., chronic heart disorder, hypertension
• leads to damming of blood into lungs (red, spongy, more fluid [frothy])
  In chronic left ventricular failure :
  • brown induration (stiffness & hardness) of lung develops
  • breakdown of Hb ~ accumulation of haemosiderin in macrophages (called heart failure cells/siderophages)
  • elastic and collagen fibres in alveolar walls causing fibrosis
  • lung is brown and firm because of fibrosis

Right ventricular failure

• e.g., mitral stenosis
• leads to chronic venous congestion (nutmeg liver)
• mottled appearance of dark and light areas in liver
  Dark :
  • around central vein where there is main congestion
  • high pressure and chronic hypoxia therefore hepatocytes die
  • therefore regulation of haemorrhage, firbosis & necrosis
  Light :
  • around portal tracts (arteries = blood inflow)
  • less congestion therefore viable parenchyma present
  • small amount of fatty change may be present
• Spleen
  • congested blood vessels in red pulp
  • congestive splenomegaly
  • fibrous nodules —> enlargement
• Enlargement of other organs in the body due to congestion.

Edema

Inflammatory edema (usually due to increased endothelial permeability and accumulation of protein in interstitial fluid) yields protein-rich exudate while non-inflammatory edema yields a protein-poor transudate.

Non-inflammatory Causes of Edema

• Increased hydrostatic pressure forces fluid out of the vessels. Congestive heart failure (CHF) falls in this category and is the most common cause of systemic edema. Edema in CHF is due, in part, to increased venous hydrostatic pressure, but reduced cardiac output with renal hypoperfusion and resulting sodium and water retention also contributes.
• Decreased osmotic pressure reduces movement of fluid into vessels. This occurs with loss of albumin (most important cause is proteinuria in the nephrotic syndrome) or reduced albumin synthesis (occurs with liver pathology [e.g., cirrhosis] or as a consequence of protein malnutrition). In either case, reduced plasma osmotic pressure leads to a net movement of fluid into the interstitium and plasma volume contraction. As with CHF, edema precipitated by hypoproteinemia is exacerbated by secondary salt and fluid retention.
• Primary sodium retention, with its obligatory associated water, causes both increased hydrostatic pressure and reduced osmotic pressure. This occurs with excessive salt intake and renal dysfunction, such as acute renal failure or poststreptococcal glomerulonephritis.
• Lymphatic obstruction blocks removal of interstitial fluid. Obstruction is usually localized and most often related to inflammatory or neoplastic processes.

Localised Edema

• Impaired venous drainage e.g., Thrombosis, Plaster of Paris (POP)
• Increased vascular permeabiliry e.g., inflammation
• Obstruction of lymphatics
  • Filariasis (infection by microfilaria, immune reaction causes the obstruction)
  • Congenital absence of lymphatics
  • Breast cancer which affects skin and lymphatics
• Hypersensitivity
  • Milroy's disease — congenital absence of lymphatics
  • Laryngeal edema
    • Can result from anaphylactic shock (allergic reaction)
    • Inhalation of noxious substances —> Obstruction —> Suffocation
  • Elephantiasis
    • Edema of external genitalia and lower limb
    • Due to lymphatic obstruction
    • Because of massive fibrosis of lymph nodes/vessels inguina1 region
    • Caused by filariasis (parasitic infection of the scrotum)
    • Edema is non-pitting because of fibrosis
  • Cerebral edema — following head injury
  • Post-operative edema — breast carcinoma removal/irradiation of entire breast + axillary lymph nodes; post operative edema of arm usually follows.

Systemic (Generalized) Edema

Cardiac Edema

• Mechanism: increased venous pressure and Na retention
• Classically more in legs and worse at the end of the day as it takes time to accumulate

Renal Oedema

Clinical manifestations
• Periorbital edema
  • Generalised edema in loose connective tissue matrix
  • Anasarca (severe edema causing swelling of subcutaneous tissues)
  • Pitting edema
• Moderate proteinuria (not due to increase in permeability of blood vessels)

Mechanism
1. nephritic glomerular damage
2. oliguria (decrease in urine output)
3. fluid retention
4. increased blood volume
5. systemic hypertension
6. cardiac failure
7. increased venous pressure

Nephrotic Syndrome

• Generalized — from head to toes
  1. Decreased plasma protein (hypoprotinemia) leading to decrease in plasma oncotic pressure
  2. Na retention
  3. Anti-diuretic hormone (ADH) secretion
• Severe proteinuria
• Decreased circulating volume
• Increase in cholesterol level
• Histology
  • Changes in basement membrane leading to dense deposits (membrane nephropathy)
  • Abnormal podocytes which are fused with no intercellular outline

Hepatic Edema

• In cirrhosis, hepatitis
• Processes:
  Changes in cell and organ structure
  • decrease in hepatic cell mass and decrease in cell volume
  • diffused fibrosis
  • nodule formation causing compression on hepatic vessels and portal hypertension
  • disruption of lobular architecture
  Vascular Shunts
  • Portal-hepatic anastomoses
  • Hepatic artery-portal vein anastomosis caused by portal hypertension
• Clinical Manifestations
  • hypoalbuminemia
  • portal hypertension
  • Na retention (compensatory mechanism due to decreased renal plasma volume)
  • lymphatic obstruction
  • compression on IVC (congestion)
  • portal vein thrombosis

Famine Edema

• Rare in Singapore
• usually caused by nutritional deficiencies (e.g., kwashiorkor)
• hypoproteinmia
• E.g., onset of beri-beri due to vitamin B deficiency which leads to right heart failure
• lax tissue accumulates fluid more easily

Pulmonary Edema

• accumulation of fluid in the alveolar spaces
• Causes: divided into 2 main types —
  (1) Venous pressure problem and (2) increase in vascular permeability
  • oxygen toxicity
  • aspiration pneumonia (e.g., comit and inhale own vomit)
  • drugs (e.g., busulphan, nitrofurantonin)
  • radiation
  • uraemia
• Types: divided into 2 main types —
  (1) Left ventricular failure and (2) Mitral stenosis
  • increased venous pressure —> back pressure recumbency
  • local redistribution of fluid
  • peripheral vasoconstriction due to adrenaline
• inhalation of noxious gases
• cerebral damage
• damage to cranial nerve X causing sympathetic overactivation —> peripheral asoconstriction —> pulmonary displacement of blood
• Adult Respiratory Distress Syndrome (ARDS)
• Peroximal nocturnal dyspnea

There is a constant balancce between bleeding and thrombosis; the fibrolysis and coagulation systems. Haemorrhage is the loss of blood from the cardiovascular phase (circulation) and can be external or internal. Haemorrhage is grouped roughly according to size:

• Petechiae: Minute 1- to 2-mm hemorrhages in skin, mucous membranes, or serosal surfaces. Petechiae occur with increased intravascular pressure, low platelet counts (thrombocytopenia), defective platelet function, and clotting factor deficits.
• Purpura: Larger (>3 mm) hemorrhages. Purpuric lesions are associated with similar pathologies as well as trauma, local vascular inflammation (vasculitis), and increased vascular fragility (e.g., in amyloidosis).
• Ecchymoses: Larger (> 1 to 2 cm) subcutaneous hematomas (commonly called bruises). Ecchymoses typically follow trauma but may be exacerbated by any of the aforementioned conditions.
• Large accumulations of blood in body cavities are called hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis, depending on the location.

Causes of Haemorrhage

Spontaneous

• Abnormal vessels (weakness of blood vessel walls) (e.g., atheroma, scurvy, arteriovenous malformation)
• Platelets:
  Thrombocytopenia
  • decreased production (marrow failure/injury)
  • increased loss/utilization
  Qualitative platelet defect
  • uncommon, usually congenital (biochemical defect)
  • an acquired defect is uremia due to renal failure (increased nitrogenous waste prevents platelet function
• Coagulation factor deficiency
  Inherited
  • factor VIII — haemophilia A
  • factor IX — haemophilia B
  • von Willebrand's disease
  Acquired
  • Liver disease
  • Vitamin K antagonists (eg warfarin)
  • Antibodies to coagulation factors
• Disseminated Intravascular Coagulation (DIC)
  • large scale formation of blood clots within circulation
  • 2 main mechanisms causing DIC: (1) release of tissue factors into circulation and (2)widespread endothelial injury
• Paradoxical bleeding
  • bleeding is due to excessive activation of the coagulation system which consumes clotting factors.
  • only way to stop bleeding is to give anticoagulants
• Acute DIC —> lethal haemorrhage
• Causes: (1) shock, (2)septicaemia, (3) accidental trauma, (4) burns, (5) snakebite, (6) acute intravascular haemolysis, (7)acute pancreatitis, (8) amniontic fluid embolism and (9) neonatal respiratory distress syndrome
• Chronic DIC —> bleeding tendency (due to increased consumption of platelets and coagulation factors)
• Causes: (1) disseminated malignancy, (2) carcinoma – pancreas, lung, stomach, (3) liver disease and (4) renal disease

Types of Internal Haemorrhage

1. Haematoma
   • accumulation of blood within body tissues
   • can cause compression
   • e.g., Extradural = rupture or compression of middle meningeal artery
   • e.g., Subdural = rupture of bridging veins between meninges and brain
   • e.g., Retroperitoneal = rupture of aneurysm (dilation) in arch of aorta (fatal)
   • e.g., Pericardial tamponade
   • e.g., Esophageal varices = rupture in portal hypertension
2. Petechiae
   • minute haemorrhages into skin, mucous/serosal membrane
   • do not turn white when pressed
   • characteristic of platelet deficiency
   • e.g., buccal haemorrahge = bone marrow failure (e.g., leukaemia, chemotherapy)
3. Purpura
   • slightly larger haemorrahges
   • e.g., thrombocytopenia
4. Ecchymosis
   • large bruise-like haemorrahges
   • e.g., haemophilia — ecchymoses at joints, deep muscles, skin which are often spontaneous or with minimal trauma

Shock is systemic hypoperfusion resulting from a reduction in either cardiac output or the effective circulating blood volume. This reduction results in hypotension, followed by impaired tissue perfusion and cellular hypoxia. If severe enough, to organ injury and death. Final common pathway for many lethal events (e.g., severe haemorrhage, extensive trauma, large myocardial infarction, massive pulmonary embolism and sepsis).

Mechanisms of Shock

1. Cardiogenic Shock — heart not pumping efficiently/stopped
   • Acute heart failure (e.g., massive myocardial infraction)
   • Ventricular fibrillation
   • Arrhythmia
   • Ventricular rupture
   • Cardiac tamponade
   • Pulmonary embolism
2. Hypovolemic Shock — inadequate/decreased blood or plasma volume
   • Sudden loss of large amounts of blood (>30%) in large haemorrhages
   • Burns (ooze plasma constantly) where there is a loss of plasma
   • Fluid loss (e.g., vomitting, diarrhea, trauma)
3. Blood Vessel Dilation — volume of vascular system too large for blood available for adequate circulation
   • Septic Shock (Septicemia)
     Due to:
     • Overwhelming microbial infections;
     • Endotoxic shock, gram-positive septicemia or fungal sepsis;
     • Superantigens
     Mechanism:
     • Peripheral vasodilation and pooling of blood;
     • Endothelial activation and injury;
     • Leukocyte-induced damage;
     • Disseminated intravascular coagulation (DIC);
   • Activation of cytokine cascades in response to inflammation
   • Anaphylactic Shock — release of excess histamine from mast cells (IgE mediated hypersensitivity) leading to systemic vasodilation and increased vascular permeability
   • Neurogenic Shock — anesthetic accident or spinal cord injury leading to loss of vascular tone and peripheral pooling

Summary of the Types of Shock

1. Cardiogenic — decreased cardiac output from any cause
2. Hypovolemic — massive loss of blood/fluid
3. Septic — infection causing vasodilation
4. Anaphylactic — systemic circulation collapse due to Type I response
5. Neurogenic — peripheral vasodilation with pooling of blood
6. Any condition causing DIC

3 Stages of Shock

Stage 1: Non-progressive Shock

• early 'shock'
• Compensation and maintenance of cardiac output and BP
  1. stimulation ofbaroreceptors
  2. releae of cathecholamines
  3. activation of renin-angiotensin axis
  4. release of ADH
  5. general sympathetic stimulation
• Pathogenesis:
  • compensated hypotension
  • but note underlying cause is not removed, decompenation may occur
  • reflex mechanisms activated
    • increased heart rate
    • increased peripheral vasoconstricrion
    • ADH, prostaglandins
• Clinical manifestation:
  1. tachycardia
  2. peripheral vasoconstriction —> cool pale skin
  3. fluid retcntion in kidneys
• Outcome of shock: CVS balance restored = recovery

Stage 2: Progressive Shock

• Tissue hypoperfusion
  1. tissue hypoxia (even in vital organs eg heart, liver, kidney, brain. lungs)
  2. anaerobic glycolysis
  3. lactic acidosis {metabolic)
  4. loss of precapillary vasomotor control (paralysis)
  5. peripheral pooling of blood (in microcirculation)
• anoxic injury to endothelial cell
• release of TXA₂ (potent platelet aggregator)
• DIC
• transudation of fluid
• Pathogenesis
  1. Oxygen deficit even in vital organs
  2. Lactic acidosis
• Clinical Manifestation
  1. confusion (cerebral derangements)
  2. oliguria
• Outcome of shock: Irreversible neuron injury = recovery but reduced mental capacity

Stage 3: Irreversible Shock

• cell/organelle injury causing a leakage of lytic enzymes
• Myocardial depressent factors
  1. e.g. ischemic pancreas
  2. decreased cardiac performance
  3. membrane transport system injury (damage of endothelium)
  4. acute tubular necrosis (renal damage)
• endotoxic shock superimposed due to infiltration of intestinal flora into circulation
• Pathogenesis
  • Damage of endothelium
  • Cardiac insufficiency
  • Renal damage
• Clinical Manifestation
  • coma
  • death
• Outcome of shock: Widespread cell injury = irreversible shock = death

Prognosis of Shock

Organs Affected in Shock

Brain

• hypoxic encephalopathy
• watershed infarction
  • occurs in area furthest from blood supply
  • boundary-zone infarct at zones of cerebra1 hemisphere
  • furthest from brainstem (circle of Willis)

Heart

• subendocardial infarction
• subendocardial surface is furthest from blood supply (epicardial)
• coagulation necrosis (with subendocardial haemorrhage), contraction band necrosis, or both.

Lungs

Kidney

• acute tubular necrosis (due to ischemic injury) causing oligouria, anuria and electrolyte disturbances.
• Histologically:
  • necrosis restricted to convoluted tubules
  • glomerulus and blood vessels appear normal
• Watershed infarction: infarction of areas furthers from perfusion

Gastrointestinal Tract (GIT)

Adrenals

• Lipid depletion
• increased steroid synthesis in response to stress