Salts & Acid-Base Imbalances Flashcards
What is the definition of hyponatraemia?
Normal serum sodium: 135-145mmol/l
Anything below 135mmol/l is considered hyponatraemic
What are three important facts to remember about hyponatraemia?
It is the commonest electrolyte abnormality you will see ( 20-30% of hospital admissions )
It can kill – less than 110 mmol/l
It may be caused by sodium loss, but also – and commonly – by water gain (sodium dilution)
Why are sodium levels important for tissue oxygenation?
Oxygenation of tissue requires an appropriate water balance as blood is responsible for delivering oxygen to the tissues
Since water follows salt around (osmosis - water goes to areas of higher solute concentration), salt is important in maintaining fluid balance in all compartments including the vascular compartment - therefore making it important for tissue oxygenation.
In general terms, what are the main compartments in the body where water is located? How much water is located in each? Where and how does water leave our body?
Majority is intracellular – bound within cell membranes – reservoir that can be used in a state of disease
Extracellular – outside the cell - Interstitial (9L - between tissues) and vascular (5L of blood – 3L of water and 2L in blood cells)
From the vascular department – water will leave via all the highlighted organs – kidneys, guts and lungs and skin
Losses from lungs and skin – insensible losses – about 500ml water – effected by temperature and humidity
Note - Vascular water is the only reserve that is easily accessible
What are the two main ions in the intracellular and extracellular compartments?
In these compartment there are two main ions - sodium and potassium
Na+/K+ ATPases – keep potassium in the intracellular compartment and sodium outside in the extracellular compartment
How are the forces that move water in and out of cells? What role does sodium play here?
What causes water to move in/out of cells?
- Out of cell – internal hydrostatic pressure and external osmotic pressure (salt gradient)
- Into the cell – external hydrostatic pressure and internal osmotic pressure (salt gradient)
Hydrostatic pressure – pressure of fluid on the surrounding walls
Hydrostatic – push / osmotic – pull
Na+ is the principal extracellular cation/osmole – so it will govern whether fluid will move in/out depending on the osmotic gradient - e.g. high extracellular concentration draws water out
Hypothetical scenario - what would happen to the water volume in the extra/intracellular compartment if we were to add salt to the extracellular compartment?
Add neat salt to the extra-cellular compartment – raise the osmolality of the extracellular compartment (where it stays as the Na+/K+ ATPase maintains gradient)
Consequence – deplete water in the cellular reservoir into the extracellular space
Hypothetical scenario - what would happen to the water volume in the extra/intracellular compartment if we were to water to the vascular compartment?
Increase fluid volume across all compartments (evenly distribute until equilibrium is reached – osmotic and hydrostatic pressures)
Consequence – dilute the sodium down in the extracellular compartment
Water changes are an important driver for Na+ changes
Thinking about sodium and water, why is the following become confused after receiving dilute sodium containing fluids?
Cause of hyponatremia and confusion
Too much dilute sodium containing fluids – dilutes extracellular space has expanded causing dilution.
High hydrostatic pressure due to increased fluid and the osmotic pull shifts water into the cellular space which is hypertonic – causes cerebral oedema (occurs in hyponatremia)
What are the different terms we use to classify a patients water volume status?
Volume status – important to examine
Normovolaemic – normal total body water
Hypovolemic – volume deplete
Hypervolemic – volume overloaded
Volaemia implies – water and salt loss
When we use these terms we refer to relative changes rather than absolute - e.g. expansion/contraction of extracellular compartment relative to the intracellular compartment.
Can hyponatraemia be seen in normovolaemia, hypovolaemia and hypervolaemia?
Each of these volume states can be associated with hyponatraemia: so we have…
Norvolaemic hyponatraemia
Hypovolaemic hyponatraemia
Hypervolaemic hyponatraemia
When do we typically see clinical signs if changes in water and salts are taking place in a patient?
Clinical signs are generated when there is a difference in the relative size of fluid compartments from normal
Different ratios of fluid in each compartment create clinical signs
Expand and deplete people maintaining the ratio – people still look normal
What are some clinical signs associated with hypovolaemia?
- Postural hypotension – dizzy – lack of cerebral perfusion upon standing
- Tachycardia – feature of hypovolaemia – heart recognizes there is a depleted blood volume – beat faster to compensate
- JVP – absence of JVP – sign of hypovolaemia – keep moving the angle of the bed down until you can see the JVP – no JVP on a flat bed = very hypovolaemic
- Reduced skin turgor – elasticity - skin turgor become reduced - best examined on the chest or abdominal wall.
- Dry mucus membranes
- Supine hypotension – lying flat
- Oliguria – low urine output – late sign
- Multi-organ failure
What are some clinical signs associated with hypervolaemia?
Hypertension
1. Tachycardia – both a feature of hyper and hypo
2. Raised jugular venous pulse @ 45 degrees
3. Gallop rhythm – S1 and S2 – third sound between the two – feature of hypervolaemia
4. Peripheral and pulmonary oedema
5. Third space gains – peritoneal space, pleural space and joint spaces - water pools in these areas
6. Organ failure
In simple terms…
What happens if we lose salt?
What happens if we gain salt?
What happens if we lose water?
What happens if we gain water?
Salt movement:
* If we lose salt, we will lose water
hypovolaemia - pulls water into intracellular compartment
* If we gain salt, we will gain water:
hypervolaemia - pulls water into extracellular compartment
Water movement
* If we lose water, we will concentrate up our sodium: hypernatraemia
* If we gain water, we will dilute our sodium down: hyponatraemia
Oversimplificaiton - we rarely lose or gain just water or salt
What is happening in the following patient case? Use the questions below to guide you.
Water and salt status
Salt-rich diarrhea - water loss cannot compensate for Na+ loss - hyponatraemia ensues (concentration drops)
Hydrostatic forces favor movement of fluid out in the ECF but osmotic forces favor movement back into the cells (loss of sodium causes ECF dilution – water wants to enter into the salt rich intracellular compartment), resulting in the patient having difficulty refilling her ECF
Classic case of hypovolaemic hyponatraemia
Symptoms
* Vascular depletion causes hypotension
* Standing up causes postural hypotension & collapse
What is the most common cause of
hypovolaemic hyponatraemia?
Most common cause of hyponatraemia – excessive sodium loss with water losses that are insufficient to concentrate sodium back up
Depends on volume of water lost and concentration of sodium therein
What are some common clinical scenarios where we see hypovolaemic hyponatraemia?
Expansion
Burns – significant dehydration due to water loss from vascular system
Diuretic states – kidney’s losing large amounts of water – Diabetes mellitus and hypercalcemia
Sequestration – inflammation in a body compartment draws water in
Iatrogenic
- Diuretics
- Stomas and fistulae
- Gastric aspiration – removal of gastric juices
What is happening in the following patient case? Use the questions below to guide you.
Water and salt status
Lady infused with fluids - Water being evenly distributed across all compartments:
Hyponatraemia is dilutional
Cerebral oedema occurs - closed compartment being filled with fluids.
What are the most common causes of euvolaemic hyponatraemia?
Hyponatraemia is dilutional
- Hypotonic IVs – dilutes Na+
- Hypothyroidism
- SIADH
How does SIADH cause euvolaemic hyponatraemia?
The syndrome of inappropriate ADH secretion
ADH secretion is excessive
* not suppressed by reduced tonicity/osmolality
* free water reabsorption is excessive ( and inappropriate )
* sodium is diluted
* hyponatraemia results
Clinically euvolaemic
What are the causes of SIADH?
Neurological causes – damage to the pituitary
Ectopic secretion of ADH-like proteins – malignancy
Drugs – potentiation of ADH action
How does hypervolaemic hyponatraemia happen? What 3 classic conditions that can result in hypervolaemic hyponatraemia?
Water gains exceed sodium – dilutional hypernatreamia
3 classic cases – heart failure, liver failure and nephrotic syndrome
Why do we see hypervolaemic hyponatraemia in heart failure patients?
Reduced effective circulating volume – cardiac output drops – body’s baroreceptors, RAAS and ADH will be switched on (maintain BP) – sensors will in part bring in more volume into the circulation
Hypovolemia wins over hyponatremia/tonicity
Water gains are more than sodium gains
This creates a cycle that feeds on itself - high fluid retention worsens heart failure - driving more fluid uptake.
In general, how is hypovolaemia treated?
Hypovolemia
* Restore vascular volume – bloods, saline, etc.
* Cessation of diuretics
* Steroids for Addison’s
In general, how is hypervolaemia treated?
Hypervolemia
- Diuretics – loop diuretics – Loop diuretics – furosemide or bumetanide
- Fluid restriction
- Treatment of underlying cause
In general, how is euvolaemic hyponatraemia treated?
Treat underlying cause
* stop IV fluids
* thyroxine replacement
Fluid restriction - down to 500ml / day
Rarely - demeclocycline - reduces tubular sensitivity to ADH
What is hypernatraemia? When is it caused?
Normal serum sodium: 135-145mmol/l
Anything above 145mmol/l is considered hypernatraemic
Hypovolaemia is almost always the case (concentration) - volume of water in extracellular compartment drops resulting in increased sodium concentration - hypernatraemia
The list of potential aetiologies/causes is very similar to that for hypovolaemic hyponatraemia:
What has happened in the following patient case?
Patient with hypovolemic hyponatremia – treated with fluids but 24 hours later the patient is comatose and paralyzed
She has a condition called central pontine myelinolysis – almost always iatrogenic - Associated with rapid correction of hyponatraemia
Strip of myelin of neurons in the pons – nerve impulses in and out of the brain won’t work – we don’t really understand how it happens but is related to water fluxes into and out of the brain
Commoner in people with alcoholism and malnutrition
Important takeaway about hyponatremia – if you are going to treat it, treat it slowly! – important to keep monitoring/observing
What has happened in the following patient case?
Colostomy – she has her small bowel (allowing for Na+ absorption) but has reduced amount of her colon/large colon – meaning that water absorption is minimized
Water loss causes hypernatraemia
Osmotic and hydrostatic forces favour shifts from cells to ECF - but not enough to concentrate sodium back up
What are the specific causes of hypernatraemia associated with water loss, reduced water intake and high salt intake?
Anything that results in water losses that are greater than sodium losses.
What is diabetes insipidus?
- Diabetes insipidus (insipid urine)
- Diuresis continues unabated/uncontrolled
- ADH – insufficient ADH or doesn’t work at the kidney – no water intake from aquaporins
- Free water loss occurs – resulting in hypernatremia – no feedback mechanism to turn it off
Two types – cranial or nephrogenic
Cranial – non/reduced synthesis of ADH
Nephrogenic - Reduced tubular response to ADH – inherited (receptors don’t work or do not exist) or drugs (lithium carbonate – bipolar treatment – blocks ADH receptor on tubular cells)
What is the treatment for diabetes insipidus?
Simply telling people to drink more increases their urine output
Treatment for cranial DI – DDAVP – acts on kidneys (still work)
Supranormal doses of DDAVP might work for nephrogenic DI
NSAIDS might help
When taking a history and examination for a hypo/hyper-natraemic patient, what should we ask/look out for?
What non-sepcific investigations could we perform for a hypo/hyper-natraemic patient?
What are the two main regulators of calcium?
Two main regulators of Ca2+ are PTH and Vitamin D
How does PTH increase levels of calcium?
- Low Ca2+ - parathyroid releases PTH – increase bone release of Ca2+, increase Ca2+ renal absorption and stimulating the formation of calcitriol
- Rising Ca2+ (negative feedback) – suppresses PTH
How does vitamin D influence Ca2+ levels?
Essential for bone health
Taken from the diet or synthesized in the skin
Vitamin D3 – hydroxylated (liver) – 25 (OH) Vitamin D – hydroxylated (kidney) forming calcitriol
Calcitriol - increases calcium and phosphate absorption by the gut and kidneys + increases bone resorption - increasing levels of Ca2+ in the blood
What are the clinical manifestations of hypercalcaemia?
Stones, bones, abdominal moans and psychic groans – useful way to remember the features
Not all the effects will be apparent – depends on the underlying cause but more importantly the cause
- Muscle weakness – competitive effect between Ca2+ ions and Na+ ions into the cells – reducing excitability – electro-disturbances
- Central effects – not specific – anorexia, nausea, mood change and depression
- Renal effects – important – impaired water concentration (increase water loss – body tries to increase water loss) and renal stone formation (calculi)
- Bone involvement
- Abdominal pain – cramps – not fully understood
- ECG changes – most important – shortened QT interval – can be life-threatening at high Ca2+ levels – resulting in arrythmias
What is factitious hypercalcaemia?
Scenario when hypercalcemia is factitiously high – non-pathological
Most calcium is bound to protein/albumin – labs adjust for the amount of albumin to prevent any skew in the data
Three scenarios – high albumin binds to calcium – giving a high apparent calcium level
* Venous stasis - pooling of venous blood
* Dehydration
* IV Albumin
What are the two main causes of hypercalcaemia?
- Hyperparathyroidism
- Malignant Disease
What is primary hyperparathyroidism? What is the most common cause?
Hyperparathyroidism - Overactive parathyroid gland due to something happening in the parathyroid gland itself
Many people have this condition with minimal symptoms
Women > men, 3:2 ratio
Causes - 90% due to solitary adenoma, hyperplasia (diffuse growth of the glands), rare - carcinoma (growth of epithelial cells – more metastatic malignancy
Which slide is showing a normal parathyroid and a parathyroid adenoma?
Takeaway observation…
Normal tissue – heterogenous architecture
Adenoma – homegeneous composition
What does hyperparathyroidism look like in an x-ray?
- Loss of normal bone structure especially cortical bone (called osteopenia) due to resorption - Mottled effect – due to osteoclasts being activated by PTH
- Soft tissue and cartilage calcification.
- Renal stones – Renal stones shown circled in red
How does malignant disease cause hypercalcaemia?
Commonest cause of hypercalcaemia in hospitalised patients
Up to 20-30% cancer patients may develop hypercalcaemia during course of illness
Two reasons
1. Release of endocrine factors that act on bone
2. Metastatic tumours deposits in bone – stimulate bone resorption locally by activating osteoclasts
Different types of cancers exhibit varying frequencies for hypercalaemia
What is the classical textbook appearance of multiple myeloma?
Pepperpot skull
Classical/textbook appearance of multiple myeloma on the skull – well defined lytic lesions – due to local bone resorption – due to local signalling
What is sarcoidosis and how is it associated with hypercalcaemia?
Disease associated with hypercalcemia
Granulomas formed – lesions – full of immune cells – usually effect the lungs causing scarring and skin
High calcium with normal PTH
Granulomas have the ability to hydroxylate vitamin D - increasing active form resulting in hypercalcaemia
Rare condition – 1:10,000 + Autoimmune condition - thought to be caused by ‘overdrive’ of the immune system
What is the main clinical manifestation of hypocalcaemia?
Main effect of hypocalcemia –increased neuromuscular excitability – increase Na+ movement – calcium interacts with the plasma membrane thereby increasing the resting potential
Actions potentials may be spontaneously generated
Clinical signs
a) Chvostek’s sign (less sensitive) - excitability of facial nerve.
b) Trousseau’s sign - involuntary spasms of the forearm.
What are the effects of vitamin D deficiency on calcium levels?
- Low calcitriol - 1,25 Vitamin D
- Lack of Ca2+ absorption from the gut resulting in hypocalcemia
- Increase in parathyroid
- Increase in bone resorption and phosphate wasting (also required for the growth/develop of bones)
How does rickets normally present? How is it treated?
- Bony deformity
- Widening of cartilage at growth plates – thickening of wrists
- Bone pain
- Weakness
Treatment - Vitamin D replacement and oral calcium
If not identified early enough – deformities may become permanent
What are some inherited causes of osteomalacia/rickets?
Inherited causes of osteomalacia
- Deficient enzyme – 1-hydroylase (vitamin D - resistant rickets types 1) - supplement with calcitriol
- Defective receptors for calcitriol (VDRR type 2) – uncovered usually when patients don’t respond to vit-D – need calcitriol
Treatment - High dose calcitriol can be used
Other causes – phosphate metabolism also at play
* Hypophosphataemic rickets – low serum phosphate leading to impaired mineralization – excessive urine phosphate loss - X-linked mutatuons – mutation in FGF23
* Hypophosphatasia – low ALP
How does bone mineral density change with age?
Changes in BMD as we age - Bone loss is due to increased bone resorption
Bone loss is accelerated in females after the menopause due to low oestrogen.
What tool can we use to assess bone mineral density?
Assessment of BMD using DEXA scan
Compare your bone loss to the average – looking at the standard deviations – more than 2.5 standard deviations below the average
What are the differences between osteoporosis and osteomalacia?
Osteoporosis – less bone/BMD but the bone is normal + normal biochemistry
Osteomalacia – abnormal histology – large quantities of uncalcified osteoid and abnormal biochemistry (low vitamin D, low Calcium and high PTH)
Outline how respiratory acidosis and alkalosis can occur.
Respiratory acidosis – hypoventilation – build up in CO2 – acidosis
Respiratory alkalosis – hyperventilation (e.g. caused by a panic attack and asthma) – excess removal of CO2 reducing H+
Outline how metabolic acidosis and alkalosis can occur.
Metabolic acidosis
* Overproduction of acid (lactic acidosis - overproduction – most common)
* Impaired excretion (e.g. CKD)
* Unusual losses of HCO3- (bicarbonate loss from bowel due to diarrhea or surgical formulation of a fistula in the small bowel) and may also be due to loss from the kidney
**Metabolic alkalosis **
* High H+ release (vomiting – H+ rich or in hypokalemia and hyperaldosteronism – in both cases body uses H+ instead of K+ to excrete Na+)
* Unusual ingestion of HCO3- (ingestion)
In terms of pH reference ranges, what is acidaemia, homeostasis and alkaemia refer to?
What are the compensatory mechanisms for respiratory and metabolic acidaemia’s & alkalaemia’s?
Respiratory acidosis – compensation by increasing bicarbonate
Respiratory alkalosis - decrease hydrogen carbonate concentration – but affect is marginal as the respiratory alkalosis tends to be very acute
Metabolic acidosis – rapid and deep breathing (Kussmaul breathing) blow off CO2 and increase renal HCO3 levels
Metabolic alkalosis – reduction in respiratory rate and decrease in HCO3- (renal) - effect is marginal
Important to remember that there are buffers also helping.
What are the main features in the history and examination that we look for in acid-base disturbance? What is the primary investigation?
History – things to focus on – respiratory symptoms, fluid balance, intoxication and anything suggesting inadequate blood supply to tissues
Examination - HR, Temp, GCS, RR, oxyegn saturation, etc.
Investigation – main tool – arterial blood gas
How to interpret arterial blood gas results?
Focus on 4 parameters – pH or H+, PO2, PCO2 and HCO3- conc
Other things that might be provided – Standard bicarbonate, base excess and anion gap
Use these questions to focus on investigation:
1. Oxygenated – don’t forget about Hb levels - implications of oxygenation – low Hb means that patients are delivering enough oxygen around their body potentially suggesting lactic acidosis
2. pH/H+ - normal, acidaemia or alkalaemia
3. How did they get there – change in CO2 (respiratory) or HCO3- (metabolic)?
4. What is the compensation? Does it make sense
5. If nothing appears to make sense – was there an error, transport, measurement, repeat BG?
Remember…
* renal compensation for resp acidosis is slow… and therefore only usually occurs in chronic resp acidosis.
* compensation for alkalosis is usually limited
What acid-base disturbance is taking place in the following case?
Metabolic acidosis with partial respiratory compensation
Low CO2 doesn’t line up with high H+ - so much be metabolic acidosis (low bicarbonate) with respiratory compensation – partial compensation as blood is still acidic
Not respiratory alkalosis with metabolic compensation as the body would not mount such a significant response to alkalosis and drive the body into acidosis
What are the causes of metabolic acidosis?
- Increased acid formation - most common ketoacidosis and lactic acidosis
- Reduced excretion - renal failure
- Loss of HCO3- - GI - severe diarrhoea, high output small bowel fistula
What impact will metabolic acidosis have on the cardiovascular system, oxygen delivery, nervous system, potasium homeostasis and bones?
What type of acid-base disturbance is taking place in this case?
(Chronic) respiratory acidosis with full metabolic compensation - Respiratory cause evident by looking at the symptoms
Elevated CO2 – respiratory acidosis – retaining CO2 leading to H+ accumulation
High HCO3 – metabolic compensation – indicates that acidosis has been around for some time (slower to kick in)
What are the acute and chronic causes of respiratory acidosis?
Think - Unable to blow off CO2
What type of acid-base disturbance is taking place in the following case?
Acute respiratory alkalosis with no compensation
Respiratory alkalosis – blowing off too much CO2 – no metabolic change yet (takes time to kick in) – respiratory alkalosis
What are the different causes of respiratory alkalosis?
What are the effects of respiratory alkalosis on the body?
What type of acid-base disturbance is taking place in the following case?
Metabolic alkalosis with partial respiratory compensation
Metabolic alkalosis – vomiting = H+ loss
Hypercapnia is likely due to low Glasgow coma scale (low respiration) rather than an attempt at compensation
Why is the this patient hypokalaemic?
Extra notes:
Liver cirrhosis leads to fluid loss into the extra-cellular space + fluid loss from vomiting – drops vascular fluid volume – drives secondary hyperaldosteronism (Na+ in / K+ out) – low urine output + retain sodium in exchange for potassium (result in extra K+ loss)
Alkalemia – drives K+ movement into cells
What are the different causes of metabolic alkalosis?
Loop diuretics - block Na+/K+ and Cl- re-uptake - so H+ will be excreted instead of K+ in order to re-absorb sodium
How can we calculated the correct calcium value if values of albumin have changed?
e.g. When albumin is 42g/L we would substract 0.04 from total calcium
