Pathophysiology Flashcards
Drowning
Initial breath hold
Swallowing
Loss of breath hold
Laryngospasm
Laryngeal relaxation
Massive aspiration
Hypoxia and hypercapnia cause hypoxic cardiac arrest
Control of aldosterone
- RAAS system triggered by low BP or decreased circulating volume recognised by reduced blood flow to macula densa of the kidney to secrete RENIN.
- this causes angiotensinogen to be cleaved to ANGIOTENSIN 1 then 2 causing potent vasoconstriction and ALDOSTERONE release
- ALDOSTERONE causes retention of salt and water in the distal convoluted tubule
Control of glucocorticoid activity
HPA axis
- hypothalamus releases corticotrophin releasing hormone (CRH)
-> pituitary releases adrenal corticotrophin hormone (ACTH)
-> adrenal cortex releases cortisol
-> cortisol negative feedback on pituitary and hypothalamus
Pathophysiology of anaphylaxis
Final common pathway is mast cell degranulation.
-> endogenous Nitric Oxide synthase activation and vasodilation
Triggers
- previous exposure causing allergen specific IgE
- immune trigger via T cells / IgG / IgM
- insect venoms
- exercise / cold / alcohol also cause mast cell degranulation
DIC
Powerful persistent trigger of haemostasis releases free thrombin
-> Widespread fibrin deposition and associated fibrinolytic response
-> Small vessel occlusion, consumptive coagulopathy and increased bleeding risk
Thrombotic, haemorrhagic or mixed complications in multiple organ systems.
Refeeding syndrome
Sudden switch to catabolism
- increased insulin secretion, protein, fat and glycogen synthesis
-> sudden shift of multiple mechanisms trying to utilise new caloric load
-> dysregulation and fluid & electrolyte abnormalities can be severe
- Hypokalaemia due to cellular reuptake
- Hypophosphataemia due to increased phosphorylation of glucose
- hypomagnesaemia due to cellular uptake
- thiamine depletion as co-factor in glycolysis
Alcohol poisoning
- Severe cortical and brain stem depression
- Depressed gluconeogenesis
- high anion gap metabolic acidosis
Treatment
- airway protection as part of supportive care
- IV thiamine, glucose and metabolic correction
- consider gastric lavage
- Rarely needs RRT but can be very effective.
Methanol toxicity
Lethal dose is 1-2ml/kg
Triad of
- GI symptoms (nausea and vomiting, pain & bleeding)
- eye signs (blurred vision, central scotoma or blindness)
- metabolic acidosis (HAGMA)
Treatment = ethanol
Asthma pathophysiology
Chronic airway inflammation causes smooth muscle hypertrophy and goblet cell hyperplasia
Increased airway reactivity, mucosal and submucosal oedema and excessive secretions
Eventually causes scarring due to epithelial collagen deposition
Haemolytic uraemic syndrome
Triad: anaemia, AKI and low plts
Typical:
- related to E. Coli infection producing shiga toxin. Prodromal bloody diarrhoea. Causing endothelial damage
Atypical
- can still present with bloody diarrhoea in 30%
- genetic predisposition and complement activation
- prodrome related to developing renal dysfunction
Secondary HUS due to complement activation in the context of illness
- infection (strep pneumoniae)
- HIV, influenza
- autoimmune
- drugs (calcineurin inhibs, quinine, chemo)
- malignant hypertension
Formation of Lactate (Anaerobic Glycolysis)
When the demand for ATP (energy) exceeds the capacity of oxidative phosphorylation (usually during intense exercise), the body shifts from aerobic to anaerobic metabolism. In this process:
• Glucose is broken down via glycolysis to form pyruvate. • If oxygen is limited or energy demand is very high, pyruvate is converted into lactate by the enzyme lactate dehydrogenase (LDH), regenerating NAD+ needed for glycolysis to continue.
Lactate as an Energy Source
Contrary to popular belief, lactate isn’t simply a waste product but also an important energy substrate:
• Lactate can be transported to the liver (Cori cycle), where it is converted back into glucose through gluconeogenesis, a process that helps maintain blood glucose levels during prolonged exercise.
• Lactate can also be taken up by tissues like the heart or muscles and converted back into pyruvate. In these tissues, pyruvate enters the mitochondria and participates in aerobic metabolism to produce energy (ATP).
Lactate Shuttle
The concept of the lactate shuttle suggests that lactate moves between tissues to meet energy demands. For example:
• Muscle-to-muscle: Fast-twitch fibers (which produce more lactate) can export lactate to slow-twitch fibers, which use it for energy.
• Muscle-to-heart: Lactate produced in muscles can be utilized by the heart as a fuel source during intense exercise.
Cori Cycle
The Cori cycle involves the conversion of lactate produced in muscles during anaerobic exercise back into glucose in the liver. This glucose can then be reused by muscles as an energy source. It is an important metabolic pathway for balancing blood glucose levels and maintaining energy supply during prolonged or intense physical activity.
Lactate metabolism
Lactate is produced when pyruvate cannot be fully oxidized due to oxygen limitation.
• It serves as a fuel for other tissues, particularly the liver, heart, and slow-twitch muscles.
• The Cori cycle recycles lactate into glucose in the liver.
• The lactate shuttle ensures lactate is efficiently used across tissues, acting as a valuable energy source rather than just a waste product.
Antinuclear antibodies (ANA)
• Systemic Lupus Erythematosus (SLE)
• Sjögren’s Syndrome
• Systemic Sclerosis (Scleroderma)
• Mixed Connective Tissue Disease (MCTD)
• Polymyositis/Dermatomyositis
Notes: ANA is a broad marker for autoimmune conditions, especially connective tissue diseases.
Anti-dsDNA (anti double stranded DNA antibodies)
SLE
Highly specific for SLE, often correlates with disease activity, particularly renal involvement.
Anti-Ro (SSA) and Anti-La (SSB)
Associated diseases:
• Sjögren’s Syndrome
• Systemic Lupus Erythematosus (SLE)
• Neonatal Lupus
Notes: Anti-Ro is associated with subacute cutaneous lupus and neonatal lupus (especially congenital heart block).
Anti-Scl-70 (Anti-topoisomerase I)
Associated disease:
• Diffuse Systemic Sclerosis (Scleroderma)
Notes: Predicts a more aggressive form of systemic sclerosis with pulmonary fibrosis.
Anti-centromere Antibodies
Associated disease:
• Limited Systemic Sclerosis (CREST syndrome)
Notes: Associated with limited scleroderma and a lower risk of interstitial lung disease.
Anti-phospholipid Antibodies (Lupus Anticoagulant, Anti-Cardiolipin, Anti-β2 Glycoprotein I)
Associated disease:
• Antiphospholipid Syndrome (APS)
• Systemic Lupus Erythematosus (SLE)
Notes: Associated with arterial and venous thrombosis, recurrent pregnancy loss, and livedo reticularis.
Anti-CCP (Cyclic Citrullinated Peptide)
Associated disease:
• Rheumatoid Arthritis (RA)
Notes: Highly specific for RA and can be detected early in the disease course.
Systemic sclerosis
Rare, multisystem, immune-mediated, inflammatory disease characterised by fibrosis and small vessel vasospasm and large vessel vasculopathy.
Anti centromere (CREST)
Or
Anti-Scl-70 or topoisomerase 1 antibodies
Can cause
- CREST
- pulmonary hypertension
- pumonary fibrosis/ILD
- Cardiac disease (3x increase of cardiac ischaemia)
- sclerodermic renal crisis
10 year survival of 66%
Scleroderma renal crisis
Rare and life threatening 10-20% of diffuse SS patients
Small vessel vasculopathy causes hypoperfusion of the kidneys
-> activation of RAAS and hyper-reninaemia
-> vasoconstriction, sodium retention and hypertension
-> malignant hypertension and microangiopathic haemolytic anaemia
Treatment is Captopril (short acting ACEi for dose adjustment)
- supportive may include additional antihypertensives and RRT
- avoid steroids as will worsen SRC
