Biochemistry 2- NB do magnesium again by looking at BB Flashcards
Distribution and composition of body fluids
Female: 45% solid, 55% fluid Male: 40% solid, 60% fluid (2/3 intracellular, 1/3 extracellular 80% interstitial 20% plasma) In kids the fluid level is higher this is why dehydration is very deadly
-We need 2.5-3 L/day
How to lose fluid
Urine Poo Sweat Lungs Burns Inflammation
What dehydration test do we do
Skin turgor test
-Pull skin, if it doesn’t spring back immediately= dehydration
What is the deffinition of electrolyte
Is an inorganic salt with a positive or negative charge
+= cation
- = anion
Distribution of electrolytes
Needs to be correct for AP
- We measure plasma electrolyte conc
- When this is imbalanced muscle tends to be effected due to not generating smooth AP (cardiac muscle) Na and K are most requested
Sodium and potassium levels
Usually obtained when request U+E
Na: 134-146 mmol/L
K: 3.4-5.2 mmol/L
Urea: 3.4-7.8 mmol/L
Creatinine= 7.5-155 micromol/L
eGFR
Urea
- Synthesised in liver and by product of deamination of amino acid
- High levels: renal failure, dehydration, GI-bleed Low levels: liver disease; high levels rise far quickier in acute renal failure than Cr
Sodium
Major extracellular electrolyte
- 70% in body is freely exchangeable
- In western diet, intake is approx 10-20 units needed
- Excess is excreted in urine
- Na+ important is established osmotic pressure between intra and extracellular fluids
Hypoatremia- low plasma Na+
Most common electrolyte abnormality amongst patients admitted to hospital
- Low plasma Na+ doesn’t mean low body Na+
- Usually due to water imbalance due hydration or fluid overload Hyponatremia,
- is dangerous mortality 25% with 120-125 mmol/L 50% with below 120 mmol/L
Symptoms of hyponatremia
Mild >125 mmol/L= no symptoms, headache, confusion, vomiting
Moderate (120-125)= lethargy, muscle cramps
Moderate 115-120= drowsiness, agitation
<115= seizures, respiratory depression, coma
- Electrolyte imbalance, this causes osmolarity imbalance -> cause cells to lyse this is esp bad in brain cells, can also cause increase of intracranial pressure
- Cannot recorrect to quickly because brain cells would shrink
Consequences of hyponatremia
If Na level drop rapidly extracellular fluid becomes hypotonic so greater osmotic pressure inside cell, water flows in causing lysis this is especially damaging in brain cells causing CNS symptoms If Na levels drop slowly so cells adapt, no lysis so no symptoms If we treat gradual hyponatremia to quick this causes cell shrinking, causing cell death
Hyponatremia management
- Treat the cause
- Correct Na+ levels- not to quickly this can cause potine myelinolysis (breakdown of myelin sheath in the Pons section of the brain) this is irreversible
- Don’t raise serum levels more than 0.5 mmol/L/hour
- Either by giving IV fluids containing Na or via fluid restriction and diuretic (removal of fluids from kidneys) (depending on patient fluid status)
Emergency treatment of hyponatremia
- If symptomatic and rapid onset
- Hypertonic saline (3%) to restore serum (Na+) to safe level (>120mmol/L)
- Then consider cause and treat
- We can medically induce this after an exam; marathons; people who take ecstasy
- Hyponatraemia is considered chronic if it develops slowly and persists for more than 48 hrs
Hypovolaemia
- Na+ deficit with relatively smaller water deficit
- May be excessive loss of one or more body fluids e.g. GI or kidneys due to disease or drugs (loop diuretics)
- K+ sparring diuretics (often cause hyponatraemia)- amiloride Addison’s disease, chrons disease Postural hypotension, decreases skin turgor, tachycardia, reduced urine, urea and creatinine increase, low JVP, increase in haematocrit, increase in urea and creatinine
- Severe vomiting and diarrhoea; sweating
- Treatment: underlying cause, isotonic saline until BP is restored
What is hypervolaemia
Na retention with relatively greater water retention
- Likely causes: CCF, liver cirrhosis, nephrotic syndrome and renal failure
- This causes vasodilation, fall inmean arterial BP picked up by baroreceptors, increased ADH release, increased water retention
- Symptoms: abdominal swelling, breathlessness, increase in JVP, rapid weight gain, peripheral oedema
- Treatment: underlying cause, restrict fluid intake and add loop diuretic, if refractory use vasopressin receptor antagonists (tolvaptan)
What is evolaemia
- Water retention alone
- Release of ADH (cerebral or Tumor related) promotes water retention in kidney without feedback loop, this is known as SIADH
- Hypothyroidism and glucocorticoids deficiency
- Acute- trauma and surgery
- Caused by drugs: amitryptyline, k sparing diuretics, NSAIDS, SSRI, anti-psychotics
Treatment of evolaemia
Fluid restriction 800ml-1.5L
- Measure serum osmolarity
- 275-295 mOsmol/kg, pseudo hyponatremia caused by hyperlipidaemia, hyperglycaemia or hypopeoteinamia- do nothing
- If >295 mOsmol/kg correct imbalanced osmotically active particles e.g. glucose
- If<275 also need urine osmolarity
- If urine osmolity >100
- If urine osmolity >100 Consider hypothyriodism and glucocorticoid deficiency then SIADH, if SIADH fluid restrict then demeclocycline to block renal tubular effect of ADH
- Then tolvaptan (Cause major fluid shift, v.effective this can cause effect on the brain)
Hypernatremia
- Usually due to water loss (or lack of intake)
- Symptoms: muscle weakness, confusion
- Normal body Na+: water loss is high and not replaced, don’t confuse with diabetes inspidous, were body doesn’t respond to ADH or doesn’t secrete ADH
- Drug induced: lithium, phenytoin, anabolic and corticosteroid, lactulose, oral contraceptive
- Must correct slowly, replacement of water deficit
- Treat the cause
- Choice fluid will depend on whether patient is hypovolaemic, hypervolaemic or Euvolaemic
Potassium
- Intracellular electrolyte
- 90% free, only 2% in ECF
- Serum K level is a poor reflection of overall k levels
- Balance controlled by the kidneys As H+ ions increase in plasma m, K is displaced in cells and goes into plasma (reverse for alkaline) K is driven into cells by insulin and catecholamine- Adrenaline and aldosterone
- Typical western diet contains 20-100 mmol/day
- Balance-fine control by kidney, GI tract has limited role
Hypokalaemia
This is low plasma K+ depletion
- K deficiency DO correlate with serum levels
- Usually due to insulin, this is also caused by B2-agonist (IV)- not normally in inhaler
- Causes: loss from kidney, Cushing syndrome, damage to nephrons, gentamicin, corticosteroid (mimic aldersterone cushings)
- Symptoms: causes hyperpolarization of excitable membranes: muscle weakness, constipation, cardiac arythmias Cause digoxin toxicity due to increased uptake
- If K+ <2.5 mmol/L, treat urgently
Hypokalaemia
- Not necessarily K+ depletion
- Usually due to movement of K+ into cells e.g. insulin
- Or Increase K+ excretion e.g. diuretics
- Often asymptomatic
- Causes hyperpolarisation of excitable membranes –> muscle weakness, constipation, confusion, cardiac arrhythmias
- If K <2.5 mmol/L treat urgently
Hypokalaemia management
Each 0.3 mmol/L reduction in serum reflects 100 mmol/L deficit in body stores
- Diet and drugs: loop diuretics (use K sparing diuretics)
- Not MR, liquid or effervescent prep- 40-120 mmol per day
- Oral (meds or diet)
- Only give IV K- KCl is normal saline- must be given slowly
- Dont exceed 10 mmol/Hr
- Refractory hypokalaemia may be due to hypomagnesaemia
Hyperkalaemia
- Kidney failure
- False induced by K sparring diuretics and ACEI, ARBs No insulin= K into intracellular space cause hyperkalaemia- severe tissue damage (RBC, chemotherapy)
- Above 6.5= medical emergency, hyperpolarised cells induce cardiac excitability= heart attack High levels could be poor sampling technique
Management of hyperkalaemia
Stop drugs that conserve potassium
Mild-moderate with no ECG changes= use a ion exchange resin which removes K from body e.g. sodium polystyrene sulfonate, High SA to trap ions with
- binds K in colon
- Either by mouth or enema
- Onsite slow take 2hours
Additional hyperkalaemia management
Severe >6.5 mmol/L or ECG changes
- 1st infuse calcium gluconate to stabilise conductive tissue membranes (to stabilise cardiac muscle) 10-20 ml 10% by slow infusion, NB no effect on K levels
- Shift K into cells with insulin and glucose over 1/2 hour, with 5-10 unit of soluble insulin in 50mls glucose; check U&E
- Nebulise salbutamol (not in cardiac disease as this can cause palpations)
- Haemodialysis
- Resistant hyperkalaemia- correct acidosis and check Mg levels
Phosphate
Calcium and phosphate inverse relationship 80% of PO4
-in the bones 0.1% in ECF Energy metabolism
Hyperphosphaemia
Cause renal impairment
What are measured in bone profile
Ca2+ PO4 Alkaline phosphatase Albumin
Ca
Most abundant mineral in body
- 1 kg in 70 kg
- 99% is in bone
- Important in the neuromuscular system in signalling and co enzymes, clotting and nerve conductance in heart
- 3 forms: bound to protein (mainly albumin), complexed with citrate and phosphate, free ion
- Only free ions are physiologically active
Hypocalcaemia
May be due to hypoalbuminaemia
- Causes: hypoparathyriodism, lack of vit D or impaired Vit D metabolism, renal impairment, hypomagneamic
- Symptoms: asymptomatic= mild, moderate-severe: neural and muscular excitability can be life threatening
Ca management (Hypocalcaemia)
-Treat underlying cause
Oral Ca(CO3)
- In severe hypocalcaemia, 2.2-4.5 mmol of calcium gluconate administered slowly followed by Ca IV infusion
- Correct any hypokal or magnesaemia
Hypercalcaemia
Often asymptomatic
Wide range of symptoms: thrust excessive urination, aches and pains m, constipation, drowsiness
Malignant hypercalcaemia, hyperparathyriodism account for 90% of cases When you get metastasis in bone cause hypercalcaemia
Management of hypercalcaemia
Rehydrate with saline to increase output of Ca (4-6 L over 24hrs)
May need dialysis in severe renal cases Severe symptoms give bisphosphate will rapidly decrease Ca levels If bone metastasis need chronic alendronic acid
-After rehydration, IV bisphosphonate to reduce bone turnover
Osteoporosis
- There is reduced bone density due to micro-architectural deterioration of bone tissue which leads to increased risk of fracture
- Carried out by bone absorbing cells caused osteoclast which creates wholes in bone
- Osteoblasts reforms bone Hip, vertebrae, wrist
- Post menopause women Corticosteroid induced
- Hip fractures
- Cannot diagnose with blood test much use DXA scab
Paget’s disease
Increased bone turnover Increased levels of oesteoblasts and clasts Results in bone enlargement and deformity
-Normally in pelvis, lumbar, skull, femur and tibia
Both Ca and PO4 are normally in reference range
-NB-Increase in alkaline phosphates
Osteomalacia- rickets
- Ca, PO4 will decrease
- Increase in alkaline phosphates
what is the Vit D metabolism
BONE PROFILE
- Ca
- Phosphate
- Alkaline phosphatase
- Albumin
Public Health England recommendations
- In spring and summer, the majority of the population get enough Vit D through sunlight on the skin and healthy, balanced diet
- In autumn and winter, sunce it is difficult for people to meet the 10 mcg recommendations from consuming foods naturally containing or fortified with Vit D, people should take a daily supplement containing 10 mcg vit D
Magnesium
Predominately intracellular cation
Ref range 0.7-1.0 mmol/L
Hypomagneamia is quite common but often a symtomatic, but associated with hypokalaemia and hypocalcaemia
Cause: loop diuretic, gentamicin, cis platin, PPIs, adrenergics Diarrhoea, alcoholism, renal tubular
- Treat if <0.4 mmol/L or >0.4 mmol/L if symptomatic
- No national guidelines on how to treat abnormalities
- Diarrhoea, lactation,
- A co-factor with ATP so effects metabolism; Acts as a Ca channel antagosnist so effects modulation of any activity that involves Ca influx e.g. muscle contraction and insulin release
Mg (Hypomagnesaemia)
- Mg is intregrally related to potassium and calcium levels- if K and Ca are to low and not responding to treatment may be Mg
- Mainly intracellular (only 1% is extracellullar- only 70% of this is free active form the rest is protien bound)
- Drugs that cause hypomagnesaemia- Loop and thiazide diuretics; nephrotoxins- gentamicin and cisplatin; tacrolimus and cyclosporin; PPI
- Diarrhoea, malnutrition, alcoholism, renal issue, diabetic ketoacidosis
SYMPTOMS: muscle weakness, tremor, seizure, ventricular arrhythmias, vertigo, increase insulin
- Affects metabolism and governs all process that use intracellular Ca including muscle contraction
- SOURCES: sea food, nuts, ceral
Hypermagnasaemia
