y HELLP syndrome, HIV Related neuropathy y Antiphospholipid antibody syndrome and so on
y It is also used to reduce blood viscosity in diseases such as Waldenstrom macroglobulinemia, cyoglobulinemia, etc.
As segregation process
y Here the plasma donors are drained of blood similarly as in treatment and the plasma is separated from the blood and the donor red cells are returned back to circulation. This allows nearly up to 1 liter of plasma to be donated at a time and also frequent (weekly) donation
y The plasma can then be used as direct plasma transfusion or segregation into factors, albumin, immunoglobulin or fresh frozen plasma transfusion.
Complications
y Bleeding at the catheter site, infection, hematoma y Risk of transfusion reactions
y Citrate toxicity and hypocalcemia
y Immunosuppression and increased susceptibility to infections y Transfusion transmitted infectious diseases.
y Blalock’s etiological classification of shock
Oligemic shock Hematologic causes (blood loss)
Loss of ECF volume (hypovolemic shock) Vomiting, diarrhea, fistula
Neurogenic shock Spinal shock
Cardiogenic shock Extrinsic—cardiac tamponade, pneumothorax Intrinsic—myocardial infarction
Vasogenic shock Vascular dilation as in sepsis
Differential diagnoses of shock types Important terms while diagnosing shock
y Cardiac index = cardiac output/body surface area [CI = CO/BSA]
y Cardiac output = heart rate stroke volume [CO = HR SV]
y Blood pressure = Cardiac output systemic vascular resistance [BP= CO SVR]
y Pulse pressure = systolic – diastolic pressure
y Mean arterial pressure (MAP) = (Systolic BP + 2 diastolic BP)/3
y Cerebral perfusion pressure (CPP) = MAP – ICP/CVP whichever is greater
y Heart rate > 120, SBP< 90 mm Hg or > 40 mm Hg decrease, MAP < 65 mm Hg are all markers of shock.
Q27. Discuss the pathophysiology of septic shock and MODS (multiple organ dysfunction syndrome).
What is MODS? Discuss how it develops in the patients.
Ans.
Important definitions y Infection
A response to the presence of microorganisms in body y Bacteremia
The presence of viable bacteria in circulating blood y Systemic inflammatory response syndrome (SIRS)
The systemic inflammatory response to a wide variety of severe clinical insults, manifested by two or more of the following conditions:
– Temperature > 38°C or < 36°C – Heart rate > 90 /min
– Respiratory rate > 20 /min or PaCO2 < 32 mm Hg
– WBC count > 12,000/mm3, < 4000/mm3 or > 10% band forms.
y Sepsis
SIRS + infection y Severe sepsis
Sepsis associated with organ dysfunction, hypoperfusion or hypotension.
y Refractory septic shock
Sepsis induced hypotension despite adequate fluid resuscitation y Multiple organ dysfunction syndrome (MODS)
Presence of altered organ function (2 or more organ systems) in an acutely ill patient
Pathophysiology
1. An infectious insult, e.g. pneumonia, UTI, perforated viscus, necrotizing a fasciitis, etc. or a noninfectious insult (Burns, trauma, pancreatitis, ruptured abdominal aortic aneurysm, etc.) triggers local inflammation and/or ischemia which is characterized by a cellular and a vascular response as follows:
Cellular response Vascular response
Increase in TNF leads to y Muscle catabolism
y Increase PAF, Il-1,6, prostaglandins and steroids
y Increase expression of adhesion molecules
y Increased neutrophil function and y Increased free radical production
y Increased tissue factor
y Increased TNF cause increased PAI-1 (plasminogen activator inhibitor-1) y Decrease in protein C levels because of
increased alfa-1 antitrypsin levels
y Decreased antithrombin 3 and tissue factor pathway inhibitor levels thus resulting in a Procoagulant state
2. Now, the further effects depend on the body’s response to these two events. If CARS (compensatory anti-inflammatory response system) predominates, then inflammation is controlled once the trigger is taken care of. However, if systemic inflammatory response syndrome (SIRS) predominates in an uncontrolled way, the further events continue as follows.
3. Because of increased inflammation and a procoagulant state, end organ ischemia results. This causes lactic acidoses and decreases ATP level which leads to increased intracellular calcium followed by increased and uncontrolled activation of intracellular proteases.
4. These proteases mediate the next event in cell injury
– Normally, in presence of adequate oxygen, hypoxanthine is converted to xanthine and then to uric acid in cells by xanthine dehydrogenase
– However, in presence of activated proteases, xanthine dehydrogenase gets converted to xanthine oxidase
– When reperfusion occurs in presence of oxygen, if leads to conversion of hypoxanthine to uric acid by xanthine oxidase which produces superoxide radicals as a byproduct – These superoxide radicals also further leads to production of hydroxyl radicals and
singlet oxygen
– These free radicals cause peroxidation of lipid bilayer of cell and cause cell membrane damage, therefore, causing ischemia reperfusion injury
5. This leads to increased capillary leaks, activation of inflammatory cascade and increased nitric oxide production which leads to hyperpolarization of plasma membrane and is responsible for lipopolysaccharide induced refractory hypotension and vasodilatation seen in severe sepsis
6. Again ineffective CARS and overactive SIRS leads to ongoing increased endothelial and cellular damage as well as ongoing ischemia reperfusion injury at cellular level which leads to SIRS/sepsis.
This results in a deadly vicious cycle as follows
This vicious cycle leads to MODS which can only be managed with appropriate and timely treatment measures and if patient responds to these treatment measures.
Benefit from treatment—recovery Unresponsive patient in MODS—death.
Q28. Discuss the management guidelines for sever sepsis/septic shock.
How will you investigate a patient in sepsis? Outline its management.
Ans. Definitions as mentioned in question “Pathophysiology of septic shock and MODS (multiple organ dysfunction syndrome)”
Investigations
Immediate y Arterial blood gas analysis y CVP (N. 8–12 mm Hg) y MAP (> 64 mm Hg)
y Hb (> or = 7), platelet (> 1,00,000/cu mm), TLC, DLC y C-reactive protein, procalcitoin levels
y Blood lactate levels (< 1 mmol/L)
y Mixed venous oxygen saturation < 65%, SVCO2< 70%
Within 45 minutes Blood culture
All indwelling lines cultures
Imaging studies for possible site of infection 1-3 beta-d glucan levels
Mannan and anti-mannan antibody levels.
Initial resuscitation
y Crystalloids at 30 mL/kg bolus (called fluid challange). Apart of this can be albumin y Blood if Hb < 7g/dL or hematocrit < 24%
y Vasopressors—target MAP (mean arterial pressure) > 64 mm Hg
norepinephrine (DOC). If patient does not respond to both fluid challange and nor- epinephrine, consider starting epinephrine and last resort should be dopamine.
Dopamine is not the preferred vasopressor because:
– It causes more tachycardia – Is arrhythmogenic
– Is immunosuppressive
– Causes endocrine manipulation due to HPA axis interaction.
y Platelet transfusion if – Counts < 10,000/ cu mm
– Patient going to surgery with platelet <50,000/cu mm – Bleeding patient with platelet <20,000/cu mm y Glycemic control to be established
y Steroid can be given as the last ditch support. 200 mg/day continous infusion of steroid is better than bolus infusion
y If still no response to vasopressors and inotropic support required, inotrope of choice in septic shock is dobutamine.
Other measures
y Antibiotics—start empiric broad spectrum antibiotics within 1 hour of patient treatment.
Deescalate once the cultures are available
y Nutrition—enteral nutrition is preferred and immune enhancing formulas can be used to hasten recovery
y DVT and stress ulcer prophylaxis to be considered
y Patient should receive ICU care with noninvasive or invasive ventilation and sedation, analgesia, muscle relaxants as per requirement
y Care to avoid the occurrence of bedsores.
y There is no role of hydroxyethyl starch or other volume expanders, selenium, immunoglobulins, erythropoietin, activated protein C, bicarbonate (unless when pH
< 7.15), renal dose dopamine, bolus steroid in absence of shock or specific indication.
Q29. Write a note on pathophysiology of hemorrhagic shock.
Discuss the pathophysiology of lethal triad.
Ans. The hemorrhagic shock is classified as follows:
y Class I—Up to 15% blood loss (750 mL). Manifest only as mild anxiety.
y Class II—Up to 30% blood loss (1500 mL). Manifest as tachycardia and change in pulse pressure.
y Class III—Up to 40% blood loss (2000 mL). Manifest as hypotension besides above changes.
y Class IV—More than 40% blood loss (> 2000 mL).
The components of lethal triad are:
y Hypothermia y Acidoses y Coagulopathy
It is called so because this is a vicious cycle which is difficult to contain and once the patient develops it usually culminates in death of the patient.
The pathophysiology of hemorrhagic shock is basically the result of tissue hypoperfusion and it leads to lethal triad as follows:
As shown in the cycle above, decreased tissue perfusion leads to decreased cellular metabolism, decreased ATP production and increased lactate production due to anaerobic metabolism as well as due to decreased clearance of metabolites. This produces hypothermia.
Effects of hypothermia y Increased fibrinolytic activity
y Decreased thromboxane formation and resultant platelet adhesion function y Decreased enzyme activity responsible for coagulation
y Decrease in the synthesis of Hagemen factor (XII) and thromboplastin
y It can lead to production of heparin-like substance and lead to DIC like syndrome.
All of which finally leads to coagulopathy
y Hypothermia for prolonged period also leads to slowing of the metabolism rate at cellular level and can lead to exacerbation of acidoses.
Other causes of coagulopathy
y Dilutional cause: Due to loss of blood and alongwith it the important clotting factors and replacement by fluids or stored blood
y Consumption coagulopathy.
Effects: Propagation of lethal triad due to ongoing bleeding and further coagulopathy The method to prevent or circumvent the lethal triad is by damage control resuscitation as explained in the question on damage control in surgery