Pathophysiology Flashcards
What is SIRS? What is the pathophysiology of SIRS.
Systemic inflammatory response syndrome (SIRS) is an exaggerated defense response of the body to a noxious stressor such as infection, trauma or surgery to localize and then eliminate the endogenous or exogenous source of the insult. It involves the release of acute-phase reactants, which are direct mediators of widespread autonomic, endocrine, hematological, and immunological alteration in the subject. Even though the purpose is defensive, the dysregulated cytokine storm can cause a massive inflammatory cascade leading to reversible or irreversible end-organ dysfunction and even death.
The cause is divided into either damage associated molecular pattern (DAMP) or pathogen associated molecular pattern (PAMP). These in turn lead to a pro inflammatory and anti inflammatory response, with the pro inflammatory response dominating.
The stages are divided into
1) Local reaction at the site of injury leading to release of NO and prostaglandin, resulting in vasodilation and disruption of endothelial tight junctions, with transfer of WCC into tissue space.
2) Compensatory anti inflammatory response (CARS) used as an attempt to maintain the balance. Stimulation of GF, Macrophages and platelets
3) Tips over to Pro inflammatory, with activation of the coagulation pathway. Results in end organ micro thrombosis and progressive increase in capillary permeability.
4) CARS takes over SIRS, leading to immunosppressive state and therefore suseptible to secondary infection.
5) MODS with dysrugulation of SIRS and CARS.
Actions
1) Propagation of cytokine pathway (IL-1 TNF alpha)
2) Alteration of coagulation - activation of tissue factor and impairment of fibrinolysis
3) Release of stress hormones - catecholamine, vasopressin, and RAS
4) CARS - IL 4 and 10 - inhibit release of IL 1, 6, 8. If this is prolonged, subjects the patient to immunosuppression.
It is defined by having 2 or more of temperature greater than 38 or less than 36, HR greater than 90, RR greater than 20 or WCC > 12 or less than 4.
https://www.ncbi.nlm.nih.gov/books/NBK547669/
What is sepsis?
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
Based on the sepsis III definition:
Confirmed or suspected infection AND increase in 2 points of the SOFA (sequential organ failure assessment) score
Liver
Coagulation
Cardiovascular
Respiratory
CNS
Renal
Score of 0-4 with increasing number for dysfunction
OR use qSOFA
2 or more of the following (HAT)
H (hypotension) Systolic blood pressure less than 100mmHg
A (altered mental status) GCS < 15
T (tachypnoea) RR > 22
The severity of the process is dependent on infective factors (load, virulence, PAMPs) and host factors (environment, genetics, age, other illness).
Progression is sepsis, to septic shock to multi organ dysfunction.
(Pathophyiologigy the same as SIRS, except it is a infection that is causing this process)
What is septic shock?
Underlying cellular or metabolic abnormalities that are profound enough to increase mortality
Presence of sepsis AND persistent hypotension requiring a vasopressor to maintain a MAP > 65mmHg AND lactate > or equal to 2
What is the definition of MODS?
This is a hypometabolic immunosuppressed state with clinical and biochemical evidence of the decreased function of the bodies organ systems.
Presence of SIRS and dysfunction of at least 2 organ systems.
Thought to be a continuation of the inflammatory response syndrome with complications;
1) **macrocirculation **due to systemic vasodilation from release of prostaglandins and leukotrienes
AND loss into third space from vascular permeability
2) **microcirculatory ** with formation of thrombi from a low flow state from blood viscosity and endothelial damage, impairing blood flow to organs.
Patients are also in an immunosuppressed state from CARS.
Organs affected:
Renal - AKI (oliguric and circulatory nephrotoxic compounds)
Lung injury - ARDS
Cardiomyopathy - MI, reduced after load from systemic hypotension, loss of preload, myocardial depression from acidosis and electrolyte abnormalities.
CNS - GCS - reduced
*GI dysfunction *- increased GIT permeability and translocation of bacteria, stress ulcers, calculus cholycystitis, GI ischaemia, ischaemic hepatitis
*Immunosuppression
Bone marrow suppression *
Management
Supportive with identifying the underlying cause and treat that
Address any complications as they arise.
What is Shock?
This is organ hypoperfusion with resultant cellular hypoxia, celluar death and dysfunction of the organ
**Hypovolaemic shock **- inadequete organ perfusion from loss of intravascular volume. Reduced cardiac preload and reduction in macro/microcirculation to organs. This can be haemorrhagic or non haemorrhagic (GI losses, renal loss, burns, third spacing, pancreatitis)
**Cardiogenic shock **- primary disorder of cardiac function, reducing the function of the heart to pump. Cause systolic or diastolic shock. Decreased cardiac output. Cardiomypoathy, arrythmia, valvular issues.
**Distributive shock **- peripheral vasodilation. From infection and SIRS - from redistribution of vascular volume. Septic, SIRS, anaphylactic (release of histamine from mast and basophil cells), neurogenic shock (imbalance between sympathetic and parasympathetic innervation)
**Obstructive shock **- decreased left ventricular function from extra cardiac cause. Such as PE, Pulm HTN, pericardial tamponade, pneumothorax.
Presence of both hypotension (systolic < 90mmhg or MAP < 65) and markers of tissue hypoperfusion (lactate > 2 or base deficit).
What is the pathophysiology of shock?
Hypoxia at a cellular level which leads to cellular and biochemical changes leading to acidosis and decreased regional blood flow, worsening the tissue hypoxia.
Phases of shock
1) Compensated phase - counter the poor perfusion (relex tachycardia, peripheral vasoconstriction to shunt blood back)
2) Compensatory mechnism overwhelmed - increased RR, decreased pulse pressure, evidence of end organ hypoperfusion with oliguria and CNS changes.
3) **End stage **- organ dysfunction, multi organ dysfunction, failure of organs and eventual death
What is the pathophysiology of acute respiratory distress syndrome?
Protein rich pumonary oedema that leads to severe hypoxemia and imparied carbon dioxide excretion.
This is a inflammatory injury to the lung epithelium and endothelium, leading to a marked increase in lung vasculature permeability, allowing the passage of protein rich oedema fluid into air spaces.
Results from injury from neutrophil and platelet dependent damage to epithelial and endothelial layers of lung.
From SIRS inflammation with cytokine release or from inhalational lung injury.
Impaired removal of the pulmonary fluid, delaying resolution of this condition, depriving the lung of surfactant. This can be compounded by ventilatory associated lung injury.
Associated with pneumonia, non pulmonary infections, systemic sepsis, aspiration, trauma with shock and haemorrhage, pancreatitis, TRALI, drug reactions.
Management is to prevent secondary lung injury with reduced lung volumes and repair of epithelium in the lungs.
What are the actions of alpha and beta receptors?
B1 - increased myocardial contraction
B2 - act on vascular SM - vasodilatation
A1 - act on vascular SM - vasocontriction
Dopaminergic - kidney and splanchnic- renal and mesenteric vasodilation
What are the MOI of vasopressors and ionotropes?
Vasopressors - vasoconstrict and improve cardiac output
1) NA - vasoconstrictor and improve CO
2) Vasopressin - vasoconstrictor only (v recpetors of smooth muscle)
3) Phenylephrine - vasocontriction of alpha adrenergic receptors
Ionotropes - increase CV contractility
1) Dopamine (high dose)
2) Dobutamine
3) Milrinone - also cause peripheral vasodilation and pulmonary vasodilation
What is the pathophysiology of reflux in hiatus hernia’s?
Loss of the protective mechanisms against reflux
1) Normally 1-2 cm of intra abdominal oesophagus, meaning when intra abdominal pressure is increased, compresses the oesophagus
2) LES - sling of fibres from the crus (if LES sphincter not at the crus, this is lost)
3) Angle of His - works like a flap valve mechanism
4) Crus helps with constant background tone at LES
What is the pathophysiology of Barrets oesophagus?
This is the metaplastic replacement of the squamous epithelium by columnar epithelium with goblet cells. Thought to be a consequence of GORD. A way of protecting the oeophagus from acid reflux or bile by changing it to columnar epithelium.
In tact tight junctions and mucous secretions associated with columnar epithelium helps this.
What is the pathophysiology of alkaline induced oesophageal injury?
Alkaline ingestion causes damage to the oesophagus, that is fast neutralised by the gastric acid.
Causes an acute penetrative injury -** liquifactive necrosis **
Associated with vascular necrosis and mucosal inflammation resulting in focal ulceration and sloughing over 2 weeks
Fibrosis occurs with re epithelisation within 1-3 months
What is the pathophysiology of acid induced oesophageal injury?
Injury to oesopahgus and stomach by adding to the acidic environment. Can also cause upper airway injury.
Superficial **coagulation necrosis **
Thrombosis of underlying blood vessels forming a protective eschar
What is the pathophysiology of achalasia?
Progressive degeneration of myenteric plexus of Auerbach. Can also be due to Chagas disease (infection with Tryposanosoma cruzi)
What is the pathophysiology of oesophageal varices?
These are the longitudinal dilatation of the submucosal veins at the lower oesophagus as this is a point of portovenous anastamosis between the portal and systemic system.
This is a consequence of raised portal venous pressure from mulitple factors.
There is associated release locally of vasodilators.
Evetually the submucosa become friable and can bleed
What is the pathophysiology of a Zenkers diverticulum?
Pulsion diverticulum of the mucosa and submucosa through the muscular layer of oesophagus from high pulsion forces from impaired relaxation of the upper oesphageal sphincter muscle
What is the pathophysiology of H.Pylori and how it causes ulcers?
Gram negative bacteria (LUVFACE)
1) Lipopolysaccharide
2) Urease - converts urea to ammonia, increasing the pH
3) VacA - cytotoxin leading to gastric mucosal injury and apoptosis
4) Flagella that allows it to burry through mucous layer
5) Adhesions
6) CagA - cellular integrity and inflammation (IL-8)
7) Enzymes - protease, mucinase, lipase injure the gastric mucosa
Additionally, antrum gastritis leads to reduced somatostatin secretion and increased gastrin secretion resulting in hypersecretion of acid in the duodenum
What is the pathophyiology of dumping syndrome?
Early - rapid transit of hyperosmolar food into small intestine leads to a rapid shift of extracelular fluid into the intestinal lumen causing luminal distension and symptoms
Late - Leads to hyperglycaemia leading to excessive release of insulin, leading to hypoglycaemia and catecholamine release
What is the pathogenesis of Pagets disease
Epidermatrophic - malignant cells from an underlying DCIS or malignancy travel up the ductal epithelium and onto the epidermis
Transformational - paget cells arise from Toker cells (multipotent cells on the epidermis)
How does empagliflozin work? What is the perioperative management of this medication?
This is a sodium glucose co-transporter (SGLT-2) located in the distal tubules of the kidney. Reduces renal reabsorption and increases excretion.
For elective cases, empagliflozin needs to be stopped 3 days prior to surgery given the concern for euglycaemic ketoacidosis.
Pre op:
- Measure both glucose and ketone levels (clinically well and ketones < 1.7, proceed)
- If empag taken within 3 days, weight up the urgency of operation, ketones, base excess, Hba1c (higher Hba1c, the greater the chance of DKA given insulin insufficiency).
Periop:
- Hourly BSL and ketones and 2 hourly post op
Anypoint in an unwell patient with ketones > 1 or base excess < -5, need to consider DKA
Post op:
- Restart empag once the patient is eating and drinking normally
