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What is a buffer?
- Strong base (HCO3-) and conjugate weak acid (H+)
- HB H+ + B-
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What are the 4 main buffers in our body? Start with best! And why?
- Bicarbonate: high capacity and ease of elimination (CO2)
- Phosphate
- Plasma proteins
- Intracellular buffers eg Hb
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How is the osmolar gap calculated?
- Difference between measured and calculated osmolality
- Calculated: 2(Na + K) + urea + glucose
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What is the significance of osmolar gap?
The presence of an osmolar GAP in metabolic acidosis indicates presnce of unmeasured osmoles eg methanol, ethanol, ethylene glycol
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What are cations? Give eg
- Positively charged
- Sodium Na+
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What are anions? Give eg
- Negatively charged particles
- Chlrodie Cl-
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How is anion gap calculated?
(Na + K) – (Cl + HCO3)
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What is the normal range of anion gap?
12-16mmol/l
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How will the addition of acid increase the anion gap?
It will lower the bicarbonate level (think equation)
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What does the anion gap indicate?
Amount of acid added
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Why is anion gap useful in clinical practice?
Monitor patients response to therapy
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What is high anion gap MA due to? (principle)
Acid added endogenously or exogenously lower bicarb concentration less anions greater GAP
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What is normal anion gap MA due to? (principle)
Loss of bicarbonate associated with HYPERCHLORAEMIA so anion gap remains normal! (as Cl- is an anion)
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Give the causes of high anion gap metabolic acidosis?
- Big MUDPILES
- Biguanides: metformin
- Methanol
- Uraemia
- DKA, alcoholic ketoacidosis (B-hydroxybutyrate, acetoacetate, acetone)
- Paraldehye (fixative)
- Isoniazid, iron, infection
- Lactate
- Ethylene glycol
- Salicylates
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Give the causes of normal anion gap metabolic acidosis?
- HARD UP AA
- Hyperalimentation
- Acetozolamide (carbonic anhydrase inhibitor)
- Renal tubular acidosis
- Diarrhoea
- Ureto-enteric fistula
- Pancreatico-duodenal fisutla
- Addison’s
- Ammonium chloride ingestion
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What are the 2 main categories od normal anion gap metabolic acidosis?
- GI loss of bicarbonate: small bowel secretions in diarrhoea or pancreatic drainage
- Renal tubular acidosis
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What is type of acidosis do you get with RTA?
Hypokalaemic Hyperchloraemic metaboic acidosis with normal anion gap
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What is type 1 RTA due to?
Inability to excrete H+
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Where does type 1 RTA occur?
Distal tubule
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What is the urinary pH in RTA1?
Over 5.5 (ie failure to acidify urine)
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What are the clinical features of RTA1?
- 1. Rickets/osteomalacia due to buffering of H+ with calcium in bone
- 2. nephrocalcinosis with renal calculi leading to recurrent UTI
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Why do you get renal stones in RTA1?
- Hypercalciuria from bone
- Decreased urinary citrate: as reabsorbed from urine as a buffer for H+
- Alkaline urine
- All favour calcium phosphate stone formation
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How is type 1 RTA diagnosed?
- 1. Urinary pH > 5.3 in face of systemic acidosis
- 2. failure to acidify urine following an oral acid load challenge: alluminium chloride test
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What is the treatment of type 1 RTA?
- Sodium bicarbonate or citrate
- correct the acidemia and reverse bone demineralisation.
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What is the cause of type 1 RTA?
- Idiopathic
- Autoimmune: Sjogren’s, SLE
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What is type 2 RTA due to?
Inability to reabsorb bicarbonate (bicarb leak)
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Where does type 2 RTA occur?
Proximal tubule
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What are the causes of type 2 RTA?
- Fanconi syndrome
- Tubulointerstitial disease: myeloma
- Drugs: lead
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What type of acidosis do you get with type 2 RTA?
- Hypokalaemic, hyperchloraemic metablic acidosis
- Normal anion gap
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What is the difference in the urine between type 1 and type 2 RTA?
- In type 2: tubules are able to reabsorb SOME HCO3
- So urine can acidify during systemic acidosis
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Which syndrome is type 2 RTA associated with?
Fanconi syndrome (generalised dysfunction of proximal tubule cells)
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Which is more common type 1 or type 2 RTA?
Type 1
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Why is hypokalaemia common in type 2 RTA?
Due to osmotic diuretic effect of reduced HCO3 reab increased flow rate to distal tubule increased K+ excretion
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How is type 2 RTA diagnosed?
Iv sodium bicarbonate load: if see high fractional excretion (>15%) of HCO3 = type 2 RTA
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What is the treatment of type 2 RTA?
High doses of bicarbonate (often intolerable)
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What is type 3 RTA?
- Combination of type 1 and 2 RTA
- Very rare
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What is the difference between type 4 RTA and type 1 and 2?
Hyperkalaemic
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What is type 4 RTA due to?
Hyporeninaemic, hypoaldosteronism
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Why do you get acidosis in type 4 RTA?
- Low aldosterone causes hyperkalaemia and acidosis
- As it decreases K+ and H+ secretion
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What are the functions of aldosterone?
- 1. acts on nuclear mineralocorticoid receptors (MR) in distal tubule and collecting duct in kidney to activate Na/K/ATP pump on basolateral membrane of cell. So sodium is reabsorbed into the blood and K+ is secreted into the urine
- 2. upreg EnaC on apical membrane to increase permeability of Na
- 3. Cl- reab with Na to maintain electrochemical balance
- 4. stimulates uptake of K+ into CELLS
- 5. stimulates H+ secretion in collecting duct, regulating HCO3- levels (acid-base)
- 6. acts on posterior pituitary gland to release ADH
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what are the causes of type 4 RTA?
- Hypoadrenalism: hypoaldo
- Mild renal impairment: DM or tubulointerstitial disease
- Drugs: K+ sparing diuretics, ACEi, ARB, NSAID
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What is the treatment of type 4 RTA?
- Remove cause
- Fludrocortisone
- Furosemide
- Calcium resonium to control hyperK+
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What is Fanconi syndrome?
- Disturbance of proximal tubule function
- So defective reabsorption of amino acids, K+, phosphate, glucose, bicarbonate (leading to type 2 RTA)
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What are the causes of Fanconi syndrome?
- Idiopathic
- Inherited: errors of metabolism eg fructose intolerance, GSD
- Acquired: tubule damage from heavy metal eg lead, mercury
- Light chain damage: myeloma or amyloidosis
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What is the treatment of Fanconi syndrome?
- Remove cause
- Replace losses – K+, HCO3-
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What are the clinical effects of metabolic acidosis?
- Air hunger
- Neuro symptoms coma
- Impaired cardiac function and state of shock
- Severe acidosis: cardiac dysrhythmias, cardiac arrest, sudden death
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Which values are raised in metabolic alkalosis? What is it compensated by?
- Raised: pH & bicarbonate
- Compensated by: rise in CO2
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What are the causes of metabolic alkalosis?
- Loss of H+/retain bicarb
- Vomit,
- Renal loss from hyperaldosteronism (Conn’s/Cushing’s): retention of Na+ but loss of H+ into urine
- Diuretics (thiazide and loop): K+ depletion
- Burns
- Retention of bicarbonate: administration of alkali with decreased GFR
- Posthypercapnic metabolic acidosis (compensatory)
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What are the clinical effects of metabolic alkalosis?
- Orthostatic hypotension
- Hypokalaemia leading to weakness and hyporeflexia
- Tetany
- Neuromuscular excitability: due to reduced free (active) calcium concentration as it is bound to albumin (as H+ is not bound to it)
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What are the causes of respiratory acidosis?
- Hypoventilation and subsequent rise in PCO2
- CO2 forms carbonic acid = source of H+
- CO2 + H20 H2CO3 HCO3- + H+
- Airway obstruction: laryngospasm/bronchospasm cause ACUTE RA, COPD cause CHRONIC RA
- Respiratory centre depression: sedative overdose, brain lesions
- Neuromuscular disorder: respiratory muscle diseaes, MS
- Restriction defect: respiratory muscle disease, pneumothorax, interstitial fibrosis, kyphoscoliosis
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What are the clinical effects of respiratory acidosis?
- Peripheral VASODILATION
- Increase ICP
- Confusion
- Myoclonus
- Coma
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What are the causes of respiratory alkalosis?
- (Hyperventilation reduces CO2) SHAPS
- Salicylates: give MIXED acid base too
- Hypoxia: Congestive cardiac failure, congenital heart disease
Acute asthma (NB if life threatening, may give respiratory acidosis if cant breathe out)
- Psychogenic hyperventilation: fear, anxiety, PAIN
- SAH
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What are the clinical effects of acute respiratory alkalosis?
lightheaded, parasthesiae, numbness around the mouth, tingling sensation in the hands and feet. Tetany
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Why do salicylates give a mixed acid base disorder?
- Salicylates stimulate resp centre over ventilate and cause resp ALKALOSIS
- Get excess production of lactic acid metabolic ACIDOSIS
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What is uraemia?
The illness accompanying renal failure
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What are the symptoms of uraemia
- Asterixis
- Tremor
- Hyperreflexia
- Upgoing planter response
- Pericarditis
- Bruising
- Fall in BP and body temp
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