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
Causes of infective endocarditis
Gram positive
- streptococci (31%) strep bovis
- staphylococci (S. aureus) (28%)
- coag negative staph (13%) staph epidermidis
- enterococci (E. faecalis)
- culture negative
Slow growing HACEK (1-2%)
- Haemophilus
- Aggregatobacter
- Cardiobacterium
- Eikenella
- Kingella
Fungal (Candida) in 1-2%
Transplant specific complications
Heart
- denervated SA node so only direct acting medications effect heart rate.
- Response to volume response, adrenergic response and conductivity preserved
- loss of response to hypovolaemia, hypotension and pain
Lung
- no bronchial artery perfusion so risk of tracheal dehiscence
- loss of cough response below anastomosis so cough must be conscious
Liver
- acute ischaemic injury or hepatic artery thrombosis may need urgent re-transplantation
Types of lactic acidosis
Type A = increased production
- anaerobic metabolism
- hypotension / reduced perfusion
- poor O2 utilisation (poisoning E.g. ethylene glycol)
Type B = reduced clearance
- reduced hepatic metabolism
- metformin
- haematological malignancy
- inherited enzyme defects
Causes of metabolic alkalosis
Loss of acid
- GIT (D&V)
- diuretics
- hypokalaemia
- low mineralocorticoid states
Additional alkali
- sodium bicarbonate infusion
- high chloride post NaCl infusion
Neuroleptic malignant syndrome
Systemic deficit of dopamine, typically longer presentation due to drugs blocking or withdrawal of agonists of dopamine. (Haloperidol, chlorpromazine)
Causes
- altered mental state
- autonomic instability
- muscle rigidity
- hyperthermia
Beta receptor stimulus
G protein coupled receptors causing Increase in intracellular cAMP
Alpha receptor stimulus
Acts via Phospholipase C
Hepatopulmonary Syndrome
= hepatic dysfunction + intrapulmonary vasodilation -> gas exchange abnormalities
- imbalance between intrapulmonary vasoconstriction and vasodilation at the pre- and post-capillary level
- ?NO mediated (increased NO synthetase activity)
- rarely due to an anatomic shunt
TCA overdose signs
Myocardial depression
Arrhythmias
Low GCS and seizures
Anticholinergic effects
Treat with bicarbonate if QRS >100ms
Lidocaine and magnesium may be helpful in arrhythmias
LP in bacteria meningitis
Raised opening pressure
Cloudy
WCC 100-50,000 (neutrophils)
Increased protein
Low glucose (<40% serum)
LP in viral meningitis
Mildly increased opening pressure
Clear CSF
WCC 5-1000 (lymphocytes)
Normal glucose
Mildly raised protein
LP in TB meningitis
Cloudy/yellow
Increased opening pressure
WCC 0-1000 (lymphocytes)
Glucose <30% serum
Protein very high
MRI T1 imaging
T1 loves protein. More protein = brighter on T1
So tissues are white
MRI T2 imaging
2 Ws => water is white
Fat embolism syndrome
Theory 1: mechanical fat emboli into pulmonary circulation
Theory 2: biochemical lipolysis of fat embolus causing free fatty acids release as inflammatory mediators and vascular occlusion of lungs and brain
Methaemoglobinaemia
Haemoglobin is oxidised from normal Fe2+ ferrous state to Fe3+ ferric state.
This means it is unable to bind oxygen effectively and cannot release it into tissues appropriately
This causes FUNCTIONAL HYPOXIA despite normal partial pressure of oxygen.
Typically presenting with CYANOSIS AND NORMAL PAO2 LEVELS
Normal levels <1% on cooximetry, levels 20/30% cause significant symptoms
Methaemoglobinaemia
Haemoglobin is oxidised from normal Fe2+ ferrous state to Fe3+ ferric state.
This means it is unable to bind oxygen effectively and cannot release it into tissues appropriately
This causes FUNCTIONAL HYPOXIA despite normal partial pressure of oxygen.
Typically presenting with CYANOSIS AND NORMAL PAO2 LEVELS
Normal levels <1% on cooximetry, levels 20/30% cause significant symptoms
Ehthylene glycol toxicity
Alcohol dehydrogenase triggers pathway which causes HAGMA and calcium oxalate production causing acute tubular necrosis and long QTc
Methanol
Alcohol dehydrogenase breaks down into Formic acid and formate which is a mitochondrial inhibitor causing relative hypoxia
Also causes optic nerve accumulation
HUS
Shigella toxin from E. coli 0157 causing plt aggregation and microangiopathic haemolytic anaemia, especially in the kidney
This is why you treat with PLEX to remove the toxin
TTP
ADAMST-13 dysfunction causing failure of regulation of vWF and plt multimeters causing plt aggregation.
MAHA
AKI
low plt
Fever
CNS symptoms
