The progressive stage of shock is caused by a vicious cycle of cardiovascular deterioration through various positive feedback mechanisms. If left uncorrected, the shock will progress to the irreversible stage where death is imminent. Some key positive feedback mechanisms include cardiac depression reducing cardiac output and blood pressure, vasomotor failure reducing sympathetic tone, and the release of toxins from ischemic tissues further deteriorating the circulatory system. Prompt, aggressive intervention is needed to break this vicious cycle and prevent the shock from progressing to irreversible stages with multi-organ failure and cell death.

1. PROGRESSIVE SHOCK
DEEPALI CHAUHAN
Para L2
Roll No.- 44

2. What is Shock????
• Profound hemodyamic and metabolic
disturbance characterized by failure of the
circulatory system to maintain adequate
perfusion of vital organs.
• Normal relationship between oxygen demand
and oxygen supply is impaired.

3. Stages of shock
• Non progressive stage
• Progressive stage
• Irreversible stage

4. Progressive stage of shock
• Caused by a vicious circle of cardiovascular
deterioration.
• Positive feedback mechanism evoked by
uncorrected shock results in the vicious progression.
• Requires prompt and aggressive intervention else
the shock enters the irreversible stage where death
is imminent

5. • Different types of “positive feedback” that can lead to progression of
shock. (courtesy- guyton n hall textbook of physiology 11thedition

6.  Cardiac depression.
• Blood pressure coronary blood
flow hypoxia and decrease nutrition of
myocardium leading to diminshed
contractility and reduced cardiac output.
• The consequent reduction in cardiac output
leads to a further declinein arterial
pressure.
• The reduced blood flow to the peripheral
tissues leads to an accumulation of
vasodilator metabolites which decreases
peripheral resistance and therefore
aggravates the fall in arterialpressure
• The heart has tremendous reserve
capability that normally allows itto pump
300 to 400 per cent more blood than is
required by the body for adequate
bodywide tissue nutrition.

7. Ventricular function curve for the left ventricle during the course of hemorrhagic shock.
Curve A represents the control function curve; curve B, 117 min; curve C, 247 min; curve D,
280 min; curve E, 295 min; and curve F, 310 min after the initial hemorrhage. (Redrawn from
Crowell JW, Guyton AC: Am J Physiol 203:248, 1962.)

8.  Vasomotor Failure.
• Diminished blood flow to the brain’s vasomotor center
depresses the center that it becomes progressively less
active and finally totally inactive.
• Complete circulatory arrest to the brain for 10 to 15 minutes,
depresses the vasomotor center such that no evidence of
sympathetic discharge can be demonstrated.
• The resulting loss of sympathetic tone then reduces cardiac
output and peripheral resistance which reduces mean arterial
pressure and intensifies the inadequate cerebral perfusion.
• Vasomotor center usually does not fail if the arterial
pressure remains above 30 mm Hg.

9.  Blockage of Very Small Vessels—“Sludged Blood.”
• Sluggish blood flow in the microvessels due to
decrease arterial pressure leads to their blockage.
• Acidosis and deterioration products from the ischemic
tissues, causes local blood agglutination, resulting in minute
blood clots, leading to small plugs in the small vessels.
• An increased tendency for the blood cells to stick to one
another makes it more difficult for blood to flow through the
microvasculature, giving rise to the term sludged blood.

10.  Increased Capillary Permeability.
• In prolonged shock due to capillary hypoxia and lack of
other nutrients, the permeability of the capillaries gradually
increases, and large quantities of fluid begin to transude into
the tissues.
• Further deteriorates blood volume and cardiac output.

11.  Release of Toxins by Ischemic Tissue.
• Shock causes tissues to release toxic substances, such as
histamine, serotonin and tissue enzymes that cause further
deterioration of the circulatory system.
• Endotoxin is released from the bodies of dead gram-
negative bacteria in the intestines.
• Diminished blood flow to the intestines often causes
enhanced formation and absorption of this toxin.
• The circulating toxin causes cardiac depression and further
decreases cardiac output.

12.  Generalized Cellular Deterioration.
• Active transport of sodium and potassium through the
cell membrane is greatly diminished sodium and
chloride accumulate in the cells, and potassium is lost
from the cells the cells begin to swell.
• Mitochondrial activity in the tissues becomes severely
depressed.
• Lysosomes in the cells in widespread tissue areas begin
to break open, with release of hydrolases that cause
further intracellular deterioration.
• Cellular deterioration further leads to multiorgan
failure.
• Lobular necrosis begins to occur in liver.

13. Necrosis of the central portion of a liver lobule in severe
circulatory shock.

14. • Pulmonary failure “shock lung’’ ensues.
• Initial phase: intrapulmonary blood volume
ventilation-perfusion ratio.
• Late phase: fibrin and leucocytes in interstitial
and alveolar spaces.
• Accumulation of Neutrophil in pulmonary
release of proteases
surfactant, edema and hemorrhagies
circulation
• permeability -

15.  Vasopressin deficiency.
• Posterior pituitary hormone released in response to increased
plasma osmolality or decreased intravascular volume.
• Plasma vasopressin levels subsequently decline, secondary
to depletion of the pituitary neurohypophyseal stores.
• Decrease vasopressin
renal absorption of fluid
decreased vasoconstriction and
decreased blood volume
decreased cardiac output.

16.  Activation of ATP-sensitive potassium
channels (KATP)
• KATP channel opening allows an efflux of potassium
ions and results in membrane hyperpolarization and
reduced calcium ion movement into the cell.
• Under resting conditions, the KATP channels are
closed.
• Altered tissue metabolism or hypoxia leads to
channels activation, causing vasodilatation.
• Vasodilation decreased peripheral resistance,
decreased venous return decreased cardiac output.

17.  Activation of the inducible form of nitric oxide
synthase enzyme.
• Nitric oxide is a vasodilator produced in vascular
endothelium.
• Production is controlled by a group of enzymes called nitric
oxide synthases.
• In shock, there is an increased expression of the inducible
form of nitric oxide synthase (NOS) due to circulating
cytokines
• Increase NOS increase NO increase vasodilation

18. Acidosis.
• The inadequate blood flow during shock affects the
metabolism of all cells in the body.
• Hypo-perfusion reduces ATP availability required for
maintenance of transmembrane potential. Leaky cell
membranes cause interstitial fluid uptake and massive
cell oedema.
• This oedema obstructs adjacent capillaries reducing
oxygen delivery.

19. • The decreased oxygen delivery to the cells accelerates
the production of lactic acid and other acid metabolites
by the tissues.
• Impaired kidney function prevents adequate excretion of
the excess H+, and generalized metabolic acidosis
ensues .
• The resulting depressant effect of acidosis on the heart
further reduces tissue perfusion and thus aggravates the
metabolic acidosis
• Acidosis also diminishes the reactivity of the heart and
resistance vessels to neurally released and circulating
catecholamines, and thereby intensifies the hypotension.

20.  Aberrations of blood clotting.
• The alterations of blood clotting after hemorrhage are
typically biphasic. An initial phase of hypercoagulability is
followed by a secondary phase of hypocoagulability and
fibrinolysis.
• In the initial phase, platelets and leukocytes adhere to the
vascular endothelium, and intravascular clots, or thrombi,
develop few minutes after the onset of severe
hemorrhage.
• Coagulation may be extensive throughout the small blood
vessels.
• The initial phase is further enhanced by the releaseof
thromboxane A2 from various ischemic tissues.

21. • Thromboxane A2 aggregates platelets. As more
platelets aggregate, more thromboxane A2 is
released and more platelets are trapped.
• Later tissue ischaemia activates endothelial
plasminogen activator whilst hypo-perfusion
inhibits plasminogen activator inhibitor, thus
promoting hyperfibrinolysis.
• Acidosis inhibits the activity of coagulation
factors and leads to increased degradation of
fibrinogen.
• Systemic activation of the anticoagulant protein
C pathway also occurs in later stage of shock.

22.  Depression of Reticuloendothelial system.
• During the course of circulatory shock, reticuloendothelial
system (RES) function becomes depressed.
• The phagocytic activity of the RES is modulated by an
opsonic protein and the opsonic activity in plasma
diminishes during shock.
• When the RES is depressed, normal flora endotoxins
invade the general circulation. Endotoxins produce
profound, generalized vasodilation, mainly by inducing the
abundant synthesis of an isoform of nitric oxide synthase
in the smooth muscle of blood vessels throughout the
body.
• The profound vasodilation aggravates the hemodynamic
changes.

23. Thanx for patience hearing…….