Pathology of Shock 2024 PDF

Prof Charles C. Anunobi MBBS, MPH, FMCPath College of Medicine University of Lagos/LUTH Idi-Araba, Lagos.  Define shock and its pathophysiology  Explain the different types and their underlying mechanisms  Discuss the morphological and clinical...

Prof Charles C. Anunobi MBBS, MPH, FMCPath College of Medicine University of Lagos/LUTH Idi-Araba, Lagos.  Define shock and its pathophysiology  Explain the different types and their underlying mechanisms  Discuss the morphological and clinical consequences of shock  Highlight diagnostic and management principles in relation to pathology  Shock is defined as a state of systemic tissue hypoperfusion due to reduced cardiac output and/or reduced effective circulating blood volume.  The hypoperfusion of cells and tissues leads to insufficient supply of oxygen (cellular hypoxia) and nutrient, inadequate clearance of waste products, and shift from aerobic to anaerobic metabolism  Widespread impairment of cellular metabolism/dysfunction  Persistence of shock state causes irreversible tissue injury leading to multi organ damage that may result in death of patient  Cells switch from aerobic to anaerobic metabolism leading to lactic acid production Cell function ceases & cell swells Membrane becomes more permeable electrolytes & fluids seep in & out of cell Na+/K+ pump impaired mitochondria damage cell death  Types of shock ◦ Cardiogenic shock ◦ Hypovolaemic shock ◦ Distributive shock  Subtypes  Shock associated with systemic inflammation [eg Septic shock]  Neurogenic shock  Anaphylactic shock  Acute circulatory failure with sudden fall in cardiac output without actual reduction of blood volume.  This results from myocardial pump failure.  The causes include: ◦ Deficient emptying ◦ Deficient filling ◦ Obstruction to outflow  Deficient emptying ◦ Myocardial infarction is the most obvious cause of pump failure. ◦ Papillary muscle rupture, ventricular rupture ◦ Acute myocarditis, ◦ Cardiac arrhythmias, ◦ Cardiomyopathies  Deficient filling ◦ Cardiac tamponade [extrinsic compression] from haemopericardium  Obstruction to outflow ◦ Pulmonary embolism ◦ Tension pneumothorax ◦ Dissecting aortic aneurysm  This results from loss of blood or plasma volume  Causes include ◦ Severe haemorrhage, ◦ Fluid loss :severe burns, diarrhoea, vomiting, extensive injury, uncontrolled diabetes mellitus, diabetes insipidus, diuretic over dose.  It is caused by a variety of insults, ◦ Microbial infections, burns, trauma, and or pancreatitis.  The common pathogenic feature is a massive outpouring of inflammatory mediators that produce arterial vasodilation, vascular leakage and venous blood pooling.  Less commonly, shock can occur in the setting of an anesthetic accident (accidental high spinal anesthesia) or a spinal cord injury (neurogenic shock) which leads to disruption of normal sympathetic control of vascular tone, or  an IgE–mediated hypersensitivity reaction (anaphylactic shock) leading to massive histamine release.  In both of these forms of shock, acute vasodilation leads to hypotension and tissue hypoperfusion  Sepsis is defined as a life-threatening dysregulated immune response to infection leading to organ dysfunction.  Sepsis accompanies infection either confined to a local site from which toxins are absorbed, or associated with the invasion of organisms into the blood stream (septicaemia).  Septic shock is defined as a severe form of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities substantially increase mortality.  Septic shock has a 20 to 75% mortality rate depending on centres.  It is associated with systemic vasodilation and peripheral pooling of blood leading to tissue hypoperfusion  It is caused by bacterial and fungal infection.  Commonly triggered by gram positive bacterial infections followed by gram negative organisms and systemic fungal infections.  There is widespread endothelial cell activation and injury often leading to a hypercoagulable state that can manifest as DIC (Disseminated Intravascular Coagulation).  Several microbial constituents can initiate the process of septic shock  Inflammatory and counter inflammatory responses ◦ Microbial cell constituents engage receptors on cells of innate immune system to activate pro inflammatory responses  TLRs [Toll-like receptors]+ Pathogen associated molecular patterns[PAMP]  G-protein coupled receptors that detect bacterial peptides  Activated immune cells (monocytes/macrophages) produce ◦ TNF, IL-1, IFN-γ, IL-12, and IL-18, reactive oxygen species and lipid mediators such as prostaglandins and platelet activating factor (PAF)  The effects of TNF-α and IL-1cytokines are as understated: ◦ a) By altering endothelial cell adhesiveness: This results in recruitment of more neutrophils which liberate free radicals that cause vascular injury.  ◦ b) Promoting nitric oxide synthase: This stimulates increased synthesis of nitric oxide which is responsible for vasodilatation and hypotension.  ii) Activation of other inflammatory responses. ◦ Microbial infection activates other inflammatory cascades which have profound effects in triggering septic shock. These are as under:  Activation of mast cells: Histamine is released which increases capillary permeability.  The complement cascade is also activated by microbial components, ◦ resulting in the production of anaphylatoxins (C3a, C5a), ◦ chemotactic fragments (C5a), and opsonins (C3b), all of which contribute to the pro-inflammatory state  Microbial components can activate coagulation directly through factor XII and indirectly through altered endothelial function  The hyperinflammatory state initiated by sepsis also activates counter-regulatory immunosuppressive mechanisms, which may involve both innate and adaptive immune cells. ◦ mechanisms for the immune suppression include a shift from pro-inflammatory (TH1) to anti-inflammatory (TH2) cytokines  The pro-inflammatory state and endothelial cell activation associated with sepsis leads to widespread vascular leakage and tissue edema.  One effect of inflammatory cytokines is to loosen endothelial cell tight junctions, making vessels leaky and resulting in the accumulation of protein-rich edema throughout the body.  Activated endothelium also upregulates production of nitric oxide (NO) and other vasoactive inflammatory mediators (e.g., C3a, C5a, and PAF), which may contribute to vascular smooth muscle relaxation and systemic hypotension  Sepsis alters the expression of many factors to favour coagulation.  Proinflammatory cytokines increase tissue factor production by monocytes and possibly endothelial cells as well, and decrease the production of endothelial anti-coagulant factors, such as tissue factor pathway inhibitor, thrombomodulin, and protein C  Decreases fibrinolysis by increasing plasminogen activator inhibitor-1 expression.  These effects lead to systemic activation of thrombin and the deposition of fibrin- rich thrombi in small vessels throughout the body.  In full-blown disseminated intravascular coagulation[DIC], the consumption of coagulation factors and platelets leads to concomitant bleeding.  Septic patients exhibit insulin resistance and hyperglycaemia  TNF, IL-1, stress induced hormones eg glucagon, GH, glucocorticoids and catecholamines all drive gluconeogenesis  Proinflammatory cytokines suppress insulin release and promote insulin resistance in liver and other tissues  Systemic hypotension and small vessel thrombosis will decrease delivery of oxygen and nutrients to tissues  Inflammatory cytokines and other mediators may decrease myocardial contractility and Cardiac Output, increase vascular permeability, and cause endothelial injury that may lead to Adult Respiratory Distress Syndrome in the lungs  All these may cause multiple organ failure, particularly the kidneys, liver, lungs, and heart, culminating in death.  The collective actions of bacterial constituents and chemical mediators result in the following: ◦ fever and increased synthesis of acute phase proteins ◦ Systemic vasodilatation (hypotension) ◦ Diminished myocardial contractility ◦ Activation of the coagulation system culminating in (DIC) disseminated intravascular coagulopathy ◦ Widespread endothelial injury and activation, causing systemic leucocyte adhesion and pulmonary alveolar capillary damage (ARDS) or shock lung.  Is similar to septic shock  It is caused by exotoxins produced by staph aureus.  The syndrome is associated with the use of absorbent tampons during menstruation.  It aids the growth of staph aureus organism in menstrual blood.  Occurs as a result of loss of vascular tone and peripheral pooling of blood  Spinal cord injury and anaesthesia are common causes.  Organ tissue hypoperfusion is due to disruption of normal sympathetic control of vascular tone.  This is initiated by generalised IgE mediated hypersensitivity reaction.  Mechanism- acute widespread systemic peripheral vasodilatation and increased vascular permeability resulting in tissue hypoperfusion and hypoxia.  Two basic features ◦ Reduced effective circulating blood volume ◦ Reduced supply of oxygen to cells and tissues with resultant anoxia  Initial non progressive phase  Progressive stage  Irreversible/intractable stage  In the early stage of shock an attempt is made to maintain an adequate cerebral and coronary blood supply by redistribution of blood so that the vital organs (brain, heart) are adequately perfused and oxygenated.  The system responds to hypotension and tissue anoxia by activating neural and humoral factors.  Neurohumoral mechanisms that help maintain C.O and blood pressure include:  Baroreceptor reflexes (baroreceptors are located in the aortic arch and each of the carotid sinuses),  Chemoreceptors (special nerve cells that monitor blood levels of CO2 & O2), stimulation of adrenal medulla with release of catecholamines (epinephrine, nor-epinephrine)  Activation of renin angiotensin aldosterone system, ADH release, generalised sympathetic stimulation.  Baroreceptors sense a drop in blood pressure and stimulate the medulla oblongata to increase the sympathetic outflow-release of neurotransmitters (acetylcholine, epinephrine, nor-epinephrine) increasing HR, enhancing vasoconstriction and CO.  Chemoreceptors (special nerve cells that monitor blood levels of CO2 & O2), - stimulation of adrenal medulla with release of catecholamines (epinephrine, nor-epinephrine), leading to increase in in heart rate and myocardial contractility resulting increased CO  Reduced renal perfusion-renin release by the juxtaglomerular cells of the kidney  Renin acts on angiotensinogen (produced by the liver) – angiotensin I  Angiotensin I is converted to Angiotensin II by angiotensin-converting enzyme primarily in the lungs  Angiotensin II causes vasoconstriction raising the blood pressure. It also stimulates adrenal cortex to release aldosterone- Na and water reabsorption in the kidneys- increasing blood volume and pressure  These mechanisms will have net effect of:  tachycardia,  peripheral vasoconstriction (vessels of skin and abdominal viscera),  renal conservation of fluid.  Widespread tissue hypoxia  Anaerobic glycolysis with lactic acidosis  Lowering of pH, makes the vasomotor response ineffective leading to arteriolar dilatation and pooling of blood in the microcirculation.  Decrease in CO, anoxic injury to the endothelium may progress to DIC  Organ failure, confusion and decreased urinary output.  Widespread cell injury with lysosomal enzyme leakage.  Decreased myocardial contractility  Renal shutdown as a result of acute tubular necrosis  Ischaemia of the bowel may allow the entry of intestinal bacterial flora into the blood causing septic shock.  Shock is characterised by multisystem failure  The morphologic changes are due to hypoxia resulting in degeneration and necrosis in various organs  Major organs affected are ◦ Heart ◦ Brain ◦ Kidneys ◦ Lungs ◦ GIT ◦ Adrenals  Basic pathologic changes include haemorrhages, tissue necrosis and fibrin thrombi in capillaries, venules and small veins.  Heart: Is more vulnerable than any other organ ◦ Flabby myocardium ◦ Subendocardial haemorrhages and necrosis, ◦ Opaque transverse contraction band necrosis ◦ Interstitial oedema and inflammatory cells infiltrates.  kidneys:  Grossly, the kidneys are pale, soft and swollen. Sectioned surface shows blurred architectural markings ◦ Microscopically: Acute tubular necrosis (ATN) leading to oliguria, anuria and electrolyte imbalance.  AKI with cortico-medullary Normal kidney differentiation Necrosis & sloughing of epithelial cells of PCT  The lungs: ◦ Heavy, red and wet due to oedema & congestion. ◦ Pulmonary alveolar capillary damage (ARDS): Adult Respiratory Distress Syndrome shows congestion, interstitial and alveolar oedema, interstitial lymphocytic infiltrate, alveolar hyaline membranes, thickening and fibrosis of alveolar septa, fibrin and platelet thrombi in the pulmonary microvasculature. ◦ The lungs are seldom affected in pure hypovolemic shock because of it’s dual vascular supply.  GIT: ◦ Patchy mucosal haemorrhages, acute stress ulcers of the stomach or duodenum may occur and are known as Curlings ulcer. ◦ Lesions are multifocal and widely distributed throughout. The lesions are superficial ulcers. The bowel mucosa is oedematous and haemorrhagic. ◦ Microscopically there is haemorrhagic necrosis of the mucosa and sometimes submucosa (haemorrhagic enteropathy),  Liver: ◦ Enlarged and congested liver ◦ Fatty change with centrilobular haemorrhagic necrosis necrosis. ◦ Faint nutmeg appearance is seen. ◦ Sinusoidal congestion with inflammatory cells infiltrates  Hypoxic encephalopathy: ◦ Sustained blood pressure of below 50mmHg leads to serious brain tissue ischaemic damage with loss of cortical functions, coma and vegetative state ◦ Grossly, oedema is noted ◦ Micros: The watershed areas, supplied by the most distal branches of the cerebral arteries (border zone between the anterior and middle cerebral arteries) suffer from severe neuronal ischaemic necrosis. ◦ Neurons particularly purkinje cells are more prone to ischaemia. The cytoplasm of the affected neuron is intensely eosinophilic and the nucleus is small and pyknotic.  Adrenals-  Gross changes ◦ Enlargement due to cortical cell lipid depletion or haemorrhage  Microscopy ◦ Cortical cell necrosis  Haemorrhage in Waterhouse –Friderichson syndrome (associated with septic shock)  Spleen  Grossly enlarged congested spleen  Microscopy ◦ Congestion of red pulp ◦ Lymphoid depletion in white pulp (in prolonged septic shock)  Hypotension  Decreased/increased SVR(Systemic vascular resistance) depending on the stage of shock  Weak rapid pulse  Tachypnea  Cool, clammy cyanotic skin. ◦ In septic shock the skin is warm and flushed because of peripheral vasodilatation.  Phase of oliguria due to ATN, later phase of diuresis due to regeneration of tubular epithelium. Electrolyte imbalance occurs in diuretic phase  History taking  Physical examination including Vital signs assessment  Laboratory investigations ◦ Blood culture ◦ HB, WBC->12 or