EDEMA, HEMORRHAGE, CONGESTION AND SHOCK

1
EDEMA, HEMORRHAGE, CONGESTION AND SHOCK

• Anjali Shinde, MD
• Department of Pathology
• Mount Sinai Hospital
• Chicago

2
Overview-focus on hemodynamics and hemostasis

• Edema (increased fluid in the extracellular
  matrix)
• Hyperemia (increased flow)
• Congestion (increased backup)
• Hemorrhage (extravasation)
• Hemostasis (keeping blood as a fluid)
• Thrombosis (clotting blood)
• Embolism (downstream travel of a clot)
• Infarction (death of tissues w/o blood)
• Shock (circulatory failure/collapse)
• Pages 111-115, 121-132 in Robbins Pathologic
  basis of disease, eight edition

3
A. Edema

• Approx. 60 of lean body weight is water
• 2/3 intracellular, 1/3 extracellular
• Abnormal increase in interstitial fluid within
  tissues is edema
• Fluid collection in different body cavities
• Hydrothorax, hydropericardium, ascities, anascara

4
Edema
Any imbalance in the above mechanisms leads to
edema
5
Pathophysiologic categories of edema 1.
Increased hydrostatic pressure

• Impaired venous return due to
• Constrictive pericarditis
• Congestive heart failure
• Ascites
• Venous obstruction or compression by thrombosis,
  external pressure or lower extremity inactivity
• Arteriolar dilatation
• Heat
• Neurohumoral dysregulation

6
Pathophysiologic categories of edema (contd) 2.
Reduced plasma oncotic pressure

• Protein losing glomerulopathies-leaky capillaries
  cause loss of albumin
• Liver cirrhosis- reduced albumin synthesis
• Malnutrition
• Protein losing gastroenteropathy

7
Reduced plasma oncotic pressure
8
Pathophysiologic categories of edema (contd) 3.
Lymphatic obstruction

• Impaired lymphatic drainage leads to lymphedema
• Inflammatory
• Neoplastic
• Postsurgical
• Postirradiation
• Lymphedema egs.
• Filiariasis causing elephantiasis
• irradiation of breast and axilla for
  treatment of breast cancer
• causing upper limb edema

9
Pathophysiologic categories of edema (contd) 4.
Sodium and water retention

• Excessive water intake with renal insufficiency
• Increased tubular reabsorption of sodium due to
  renal hypoperfusion and increased oncotic
  pressure
• Increased salt retention-with obligate
  associated water-causes both increased
  hydrostatic pressure (due to intravascular fluid
  volume expansion) and diminished vascular colloid
  osmotic pressure (due to dilution).

10
(No Transcript)
11
Edema-morphology
12
(No Transcript)
13
Clinical consequences of edema

• Subcutaneous edema signals potential cardiac or
  renal disease
• Pulmonary edema impedes oxygen diffusion mostly
  left ventricular failure, also renal failure,
  acute respiratory distress syndrome, pulmonary
  infection
• Brain edema- herniation of brain
• stem or impedes vascular
• supply to brain stem

14
B. Hyperemia and Congestion

• Hyperemia and congestion- locally increased blood
  volumes.
• Hyperemia - active process of arteriolar dilation
  -increased blood flow-erythema due to
  engorgement of vessels with oxygenated blood.
• Eg inflammation, muscle during exercise
• Congestion - passive process-reduced outflow of
  blood from a tissue.
• Eg. cardiac failure, venous obstruction-cyanosi
  s- due to red cell stasis and the accumulation of
  deoxygenated hemoglobin-edema

15
Chronic passive Congestion-lung

• chronic passive congestion (lung) causes
• lack of blood flow
• chronic hypoxia
• ischemic tissue injury and scarring
• septa are thickened and fibrotic, alveoli
  contain hemosiderin-laden macrophages called
  heart failure cells.

16
Acute and passive congestion-Liver

• Acute hepatic congestion
• -central vein and sinusoids are
  distended -centrilobular hepatocytes are
  ischemic -periportal hepatocytes (better
  oxygenated because of proximity to hepatic
  arterioles)develop fatty change.

17
Chronic passive congestion-Liver

• chronic passive hepatic congestion
• -centrilobular regions are grossly red-brown
  and slightly depressed and accentuated
  against the surrounding zones of uncongested
  tan liver (nutmeg liver)
• -Microscopically, there is centrilobular
  hemorrhage, hemosiderin-laden macrophages,
  degeneration of hepatocytes.

Centrilobular zone-area of least perfusion
Normal liver
Nutmeg liver
18
C. Hemorrhage

• Hemorrhage- extravasation of blood into the
  extravascular space
• Capillary bleeding can occur under conditions of
  chronic congestion
• Increased tendency to hemorrhage (usually with
  insignificant injury) occurs in a variety of
  clinical disorders that are collectively called
  hemorrhagic diatheses.
• Rupture of a large artery or vein results in
  severe hemorrhage and is almost always due to
  vascular injury, including trauma,
  atherosclerosis, or inflammatory or neoplastic
  erosion of the vessel wall.

19
Hemorrhage

• Hemorrhage may be external or
• contained within a tissue hematoma.
• Minute 1- to 2-mm hemorrhages
• into skin, mucous membranes,
• or serosal surfaces are called petechiae,
• most commonly associated with locally
• increased intravascular pressure,
• low platelet counts (thrombocytopenia),
• or defective platelet function (as in uremia)
• Slightly larger (3 mm) hemorrhages
• are called purpura, associated with
• many of the same disorders that cause petechiae
  or
• can be secondary to trauma, vascular
  inflammation
• (vasculitis), or increased vascular fragility
• (e.g., in amyloidosis).

20
Hemorrhage

• Larger (gt1 to 2 cm) subcutaneous hematomas (i.e.,
  bruises) are called ecchymoses. The red cells in
  these lesions are degraded and phagocytized by
  macrophages the hemoglobin (red-blue color) is
  then enzymatically converted into bilirubin
  (blue-green color) and eventually into
  hemosiderin (gold-brown color), accounting for
  the characteristic color changes in a bruise.
• Depending on the location, a large accumulation
  of
• blood in a body cavity is denoted as a
• hemothorax, hemopericardium, hemoperitoneum,
• or hemarthrosis (in joints).

21
Hemorrhage

• Clinical significance of hemorrhage- depends on
  the volume and rate of bleeding.
• -Rapid loss of up to 20 of blood volume/slow
  losses of even larger amounts- little impact in
  healthy adults
• - greater losses-can cause hemorrhagic
  (hypovolemic) shock
• Site of hemorrhage- Intracranial hemorrhage can
  result in an increase in pressure that is
  sufficient to compromise the blood supply or to
  cause the herniation of the brainstem
• Chronic or recurrent external blood loss (e.g.,
  peptic ulcer or menstrual bleeding)- iron
  deficiency anemia.

22
D. Shock

• Shock -characterized by systemic hypotension due
  either to reduced cardiac output or to reduced
  effective circulating blood volume.
• Final common pathway for several potentially
  lethal clinical events, including severe
  hemorrhage, extensive trauma or burns, large
  myocardial infarction, massive pulmonary
  embolism, and microbial sepsis.
• Consequences are impaired tissue perfusion and
  cellular hypoxia. Cellular injury is reversible
  in beginning prolonged shock eventually leads to
  irreversible tissue injury -fatal

23
Causes of Shock

• Cardiogenic shock results from low cardiac output
  due to myocardial pump failure. This can be due
  to intrinsic myocardial damage (infarction),
  ventricular arrhythmias, extrinsic compression
  (cardiac tamponade), or outflow obstruction
  (e.g., pulmonary embolism)
• Hypovolemic shock results from low cardiac output
  due to the loss of blood or plasma volume, such
  as can occur with massive hemorrhage or fluid
  loss from severe burns
• Septic shock results from vasodilation and
  peripheral pooling of blood as part of a systemic
  immune reaction to bacterial or fungal infection

24
Septic shock

• Septic shock is associated with severe
  hemodynamic and hemostatic derangements
• Can have a mortality rate near 20
• Septic shock ranks first among the causes of
  death in intensive care units
• Its incidence is rising, ironically due to
  improvements in life support for critically ill
  patients and the growing population of
  immunocompromised hosts (due to chemotherapy,
  immunosuppression, or HIV infection)
• Currently, septic shock is most frequently
  triggered by gram-positive bacterial infections,
  followed by gram-negative bacteria and fungi.

25
Septic shock

• In septic shock, systemic vasodilation and
  pooling of blood in the periphery - tissue
  hypoperfusion - widespread endothelial cell
  activation and injury, often leading to a
  hypercoagulable state that can manifest as DIC
• Septic shock is associated with changes in
  metabolism that directly suppress cellular
  function. The net effect of these abnormalities
  is hypoperfusion and dysfunction of multiple
  organs-culminating in morbidity and mortality
  associated with sepsis.

26
(No Transcript)
27
Septic shock

• Metabolic abnormalities.-
• Septic patients have insulin resistance and
  hyperglycemia. Cytokines such as TNF and IL-1,
  stress-induced hormones (such as glucagon, growth
  hormone, and glucocorticoids), and catecholamines
  all drive gluconeogenesis.
• Pro-inflammatory cytokines suppress insulin
  release while simultaneously promoting insulin
  resistance in the liver and other tissues, likely
  by impairing the surface expression of GLUT-4, a
  glucose transporter.
• Hyperglycemia decreases neutrophil
  function-thereby suppressing bactericidal
  activity-and causes increased adhesion molecule
  expression on endothelial cells.
• Initially there is an acute surge in
  glucocorticoid production, then there is adrenal
  insufficiency and a functional deficit of
  glucocorticoids. This may stem from depression of
  the synthetic capacity of intact adrenal glands
  or frank adrenal necrosis due to DIC
  (Waterhouse-Friderichsen syndrome)

28
Shock

• Immune suppression.- Sepsis can activate
  counter-regulatory immunosuppressive mechanisms,
  possibly causing a shift from pro-inflammatory
  (TH1) to anti-inflammatory (TH2) cytokines
• Organ dysfunction.- Systemic hypotension,
  interstitial edema, and small vessel thrombosis
  all decrease the delivery of oxygen and nutrients
  to the tissues. High levels of cytokines and
  secondary mediators may diminish myocardial
  contractility and cardiac output, and increased
  vascular permeability and endothelial injury can
  lead to the adult respiratory distress syndrome
• This may lead to failure of multiple organs,
  particularly the kidneys, liver, lungs, and
  heart, culminating in death.

29
Shock

• Severity and outcome of septic shock are
  dependent upon the extent and virulence of the
  infection, the immune status of the host the
  presence of other co-morbid conditions and the
  pattern and level of mediator production.
• Standard of care remains treatment with
  appropriate antibiotics, intensive insulin
  therapy for hyperglycemia, fluid resuscitation to
  maintain systemic pressures and corticosteroids
  to correct relative adrenal insufficiency
• An additional group of secreted bacterial
  proteins called superantigens also cause a
  syndrome similar to septic shock (e.g., toxic
  shock syndrome). Superantigens are polyclonal
  T-lymphocyte activators that induce the release
  of high levels of cytokines that result in a
  variety of clinical manifestations, ranging from
  a diffuse rash to vasodilation, hypotension, and
  death.

30
Stages of shock- non progressive phase

• In the early nonprogressive phase of shock,
  neurohumoral mechanisms maintain cardiac output
  and blood pressure. eg baroreceptor reflexes,
  catecholamine release, activation of the
  renin-angiotensin axis, ADH release, and
  generalized sympathetic stimulation. The net
  effect is tachycardia, peripheral
  vasoconstriction, and renal conservation of
  fluid, cool skin If the underlying causes are not
  corrected, shock passes into progessive phase

31
Shock- progressive phase

• Progressive phase- there is tissue hypoxia
• If there is persistent oxygen deficit,
  intracellular aerobic respiration is replaced by
  anaerobic glycolysis with excessive production of
  lactic acid. The resultant metabolic lactic
  acidosis lowers the tissue pH and blunts the
  vasomotor response arterioles dilate, and blood
  begins to pool in the microcirculation.
• Peripheral pooling worsens cardiac output, and
  can cause anoxic injury with subsequent DIC.
• With widespread tissue hypoxia, vital organs are
  affected and begin to fail.

32
Stages of shock

• Without intervention, the process eventually
  enters an irreversible stage.
• Widespread cell injury is reflected in lysosomal
  enzyme leakage
• Myocardial contractile function worsens in part
  because of nitric oxide synthesis.
• If ischemic bowel allows intestinal flora to
  enter the circulation, bacteremic shock may be
  superimposed
• There can be complete renal shutdown as a result
  of acute tubular necrosis
• At this stage, there can be a downward clinical
  spiral which almost inevitably culminates in
  death.

33
Shock- Morphology

• Changes of hypoxic injury brain, heart,
  lungs, kidneys, adrenals, and gastrointestinal
  tract most affected.
• Adrenal changes in shock increased synthesis of
  steroids
• Kidney- acute tubular necrosis
• lungs -are seldom affected in pure hypovolemic
  shock, because they are somewhat resistant to
  hypoxic injury. In bacterial sepsis or trauma,
  changes of diffuse alveolar damage are seen
• In septic shock, the development of DIC-
  fibrin-rich microthrombi, particularly in the
  brain, heart, lungs, kidney, adrenal glands, and
  gastrointestinal tract.- consumption of platelets
  and coagulation factors also often leads to the
  appearance of petechial hemorrhages on serosal
  surface and the skin
• Except neuronal and myocyte ischemic loss,
  virtually all of these tissues may revert to
  normal if the individual survives. Unfortunately,
  most patients with irreversible changes due to
  severe shock die before the tissues can recover

34
DIC
Tubular necrosis in kidney
35
Shock- less common types

• Shock can occur in the setting of anesthetic
  accident or a spinal cord injury (neurogenic
  shock), as a result of loss of vascular tone and
  peripheral pooling of blood.
• Anaphylactic shock- systemic vasodilation and
  increased vascular permeability caused by an
  IgE-mediated hypersensitivity reaction causing
  acute widespread vasodilation, tissue
  hypoperfusion and hypoxia.

36
Clinical consequences of shock

• Clinical manifestations of shock depend on the
  precipitating insult. In hypovolemic and
  cardiogenic shock the patient presents with
  hypotension, a weak, tachypnea and cool, clammy,
  cyanotic skin. In septic shock the skin may
  initially be warm and flushed because of
  peripheral vasodilation. The initial threat to
  life stems from the underlying catastrophe that
  precipitated the shock (e.g., myocardial infarct,
  severe hemorrhage, or sepsis).
• Rapidly, however, the cardiac, cerebral, and
  pulmonary changes secondary to shock worsen the
  problem. Eventually, electrolyte disturbances and
  metabolic acidosis also exacerbate the situation.
  
• Individuals who survive the initial complications
  may enter a second phase dominated by renal
  insufficiency and marked by a progressive fall in
  urine output as well as severe fluid and
  electrolyte imbalances.

37
Clinical consequences of shock

• Prognosis varies with the origin of shock and its
  duration.
• Greater than 90 of young, healthy patients with
  hypovolemic shock survive with appropriate
  management
• Septic shock or cardiogenic shock associated with
  extensive myocardial infarction, can have
  substantially worse mortality rates, even with
  optimal care.