• Renal Physiology
• numbers
• weight: 125mg
• blood flow: 25% of CO = approx 1250mL/min
• cortex: 500mL/min/100g, outer medula 100mL/min/100g, inner medulla 20mL/min/100g
• oxygen extraction ratio: 10%
• oxygen consumption: 6mL/100g/min
• filtered: 180L/day
• Bowman’s capsule slit membrane: 5nm
• nephrons per kidney: 1 million
• 20% enter the medulla
• ions
• osmolarity = mOsmoles/L
• calculated
• = 2(Na + K) + glu + urea = 298mosmoles/L
• osmolality = mOsmoles/kg
• lab measured freezing point depression
• specific gravity = measure of relative density, normally 1010 - 1035
• NERNST
• = the potential difference that an ion would produce across a membrane if it were fully permeable to it
• =63 log [ions outside cell] / [ions inside cell]
• Goldman equation takes account of multiple ions
• Gibbs-Donnan explains how charge does not always distribute evenly across membranes due to differing permeabilities
• types
• Mg
• 1/2 intracellular
• 1/2 in bone
• 1% extracellular fluid
• does lots
• essential for Na/K ATPase, DNA & RNA synthesis, calcium met., cAMP production
• Antagonises Ca
• depresses the CNS, is an anticonvulsant, reduces cerebral vasospasm, depresses neuromuscular transmission (reduced tendon reflexes), bronchodilator, reduces myocardial contractility, reduces catecholamine release, anti-arrythmic, tocolytic, reduces platelet activity
• used in pre- and eclampsia, tetanus, asthma
• intracellular
• extracellular
• K
• 148
• 5
• Na
• 10
• 142
• Ca
• <1
• 2.5 (1.5 ionised)
• 35% bound to albumin
• 10% in complexes w. acids and phosphate
• 55% ionised
• Mg
• 0.6 - 1
• Cl
• 4
• 100
• Fe
• 2 ferric ions bound per transferrin molecule
• fluid
• Volumes
• 42L
• 2/3 intracellular
• 1/3 extracellular
• 3/4 interstitial
• 1/4 plasma
• PLASMA VOLUME CAN BE MEASURED WITH RADIO-IODINATED IODINE
• TOTAL RED CELL VOLUME CAN BE MEASURED WITH CHROMIUM LABELLED RED CELLS
• then blood volume = plasma volume x (1 / 1-HCT)
• ECF CAN BE MEASURED USING INULIN (as well as GFR)
• TBW CAN BE MEASURED WITH DEUTERIUM OXIDE OR TRITIUM
• allow time to distribute, then take sample and use Vd = dose / plasma conc
• crystalloid
• 0.9% NaCl
• Na and Cl 154mmol/L
• = 308mOsm/L
• 9g of sodium
• cell membrane impermeable to Na and isotonic —> so fluid stays in the extracellular volume
• 1/4 stays in plasma
• pH 5
• Hartmann’s
• Na = 131mmol/L
• Cl = 111mmol/L
• K = 5mmol/L
• lactate = 29mmol/L
• Ca = 2mmol/L
• = 279mOsm/L
• pH 6.5
• 5% dextrose
• pH 4
• distributed evenly though body
• only 8% in plasma
• 8.4% bicarb
• pH 8
• hypertonic saline
• colloid
• natural
• albumin
• artificial
• dextrans
• 40
• 40,000 Da
• 70
• 70,000 Da
• volume expanders, improve microcirculatory flow BUT cause more severe anaphylactoid reactions, coagulation abnormalities and interfere with cross matching!
• gelatins
• starches
• BURNS
• Wallace rule of 9’s (Lund-Browder for children)
• Modified Parkland formula
• = 4 x weight x BSA burns
• 1/2 over 1st 8 hrs
• 1/2 over next 16hrs
• from time of injury
• does not include resuscitation fluid or maintenance!
• TURP syndrome
• fluid overload and dliutional hyponatraemia caused by absorption of fluid (normally glycene 1.5%) during TURPs and other surgery requiring large volume washouts
• minimised by:
• limiting infusion bag to 60cm above patient, using low pressures and volumes
• experienced surgeon
• limiting surgery to 60 mins
• not using hypotonic fluids
• spinal/epidural anaesthesia - to aid early detection
• symptoms
• SOB
• hypo/hypertension, bradycardia
• confusion/convulsions
• Acid Base
• normal
• H+ = 40nmol/l
• equations
• Ka = [H+][A⁻]/[HA]
• pH = pKa + log[A⁻]/[HA]
• pH = pKa + log [HCO3⁻]/H2CO3
• pH = pKa + log [HCO3⁻]/pCO2 (due to speed of carbonic anhydrase catalysed reaction)
• homeostasis
• buffers
• extracellular
• HCO3⁻/H2CO3
• pKa 6.1
• albumin
• intracellular
• phosphate
• haemoglobin
• pKa 6.8
• urine
• ammonia (NH3)
• most important
• phosphate (PO43−)
• respiratory
• central chemoreceptors
• CO2 diffuses across BBB, forms H+ and acts on ventral medulla to increase ventilation
• 80% of response to raised CO2
• peripheral chemoreceptors
• aortic BODY
• measures changes in pO2 and pCO2
• afferent Vagus (X) fibres to medulla
• carotid BODY
• glomus I cells
• COC PG
• measures changes in pH, pO2 and pCO2
• glossopharyngeal (IX) nerve to medulla
• glomus II cells
• supporting cells
• may produce erythropoietin
• highest blood supply per unit weight: 2000mL/100g/min
• renal
• intercalated cells in DCT
• Alpha
• secrete acid via H+/K+ ATPase exchanger
• Acidosis - Alpha work
• Beta
• reabsorb acid via basal H+/K+ ATPase exchanger
• problems
• alkalosis
• reduces free Ca2+ (because H+ is lost, leaving more free albumin for Ca2+ to bind to
• may lead to tetany
• pyloric stenosis
• loss of H+, Cl⁻, water and K+
• increased aldosterone in response to volume loss
• beta intercalated cells reabsorb H+ in exchange for K +—> hypokalaemia
• acidosis
• anion gap
• normal = 8-16mmol/L
• (Na+ + K+) - (HCO3⁻ + Cl⁻)
• raised anion gap = lactic acidosis, uraemia, ketoacidosis, ethylene glycol, methanol, salicylate, biguanide
• normal = HCO3⁻ loss
• low = hypoalbuminaemia
• CO2
• 25x more soluble than O2 in blood
• 500mL/L in venous blood
• Filtration
• Molecules
• pressure
• = (glomerular hydrostatic pressure - Bowmans capsule hydrostatic pressure) - (Bowmans capsule oncotic pressure - glomerular oncotic prssure)
• = (48 - 10) - (0-25) = 13mmHg
• Na
• 65% reabsorbed in PCT by AT
• 25% in ascending loop by AT
• Most in thick limb by AT
• Enables co-transport with K and Cl and counter-transport with H
• 8% in DCT by AT
• under influence of aldosterone
• 2% in CD
• Under influence of aldosterone
• H2O
• 70% reabsorbed in PCT
• 15% reabsorbed in descending loop
• K
• Variably secreted in DCT and CD under influence of aldosterone
• Glucose
• 100% in PCT
• co-transport with Na
• approx 160g/day
• Renal threshold: 11mmol/L (as max transport is 380mg/min or 21mmol/min)
• HCO3
• 80% reabsorbed in PCT
• NH3
• reabsorbed in thick ascending limb of LOH
• others
• amino acids
• completely reabsorbed in PCT
• uric acid
• reabsorbed AND secreted in PCT
• <7kDa - freely
• >70kDa - not at all
• (BBB is more selective - max is 30kDa
• -ve charge, so -ve molecules repelled
• RAS
• Cells
• Juxtaglomerular (JAS)
• In afferent arteriole
• Secrete renin
• in response to ‘BNP’
• Beta1 sympathetic stimulation
• reduced Na levels (detected by macular densa)
• reduced BP (detected by baroreceptors)
• Macula densa
• sense low Na/low volume —> produce NO synthetase —> creates NO —> produce prostaglandins —> bind to Gs —> increase cAMP —> increases renin release by juxtaglomerular cells
• sense high volume —> release adenosine (afferent arteriole vasoconstrictor —> lowers GFR) and inhibit renin release
• In DCT
• Aldosterone
• secreted in response to
• angiotensin II
• ACTH
• hyperkalaemia
• AAHldosterone!
• actions
• increases activity of Na/K pumps in principal cells of DCT and CD
• takes hours as it works via intracellular receptors to alter gene transcription
• increases Na reabsorption from gut, sweat and saliva
• ADH
• secreted in response to
• high osmolality detected by Hypothalamic osmoreceptors
• Angiotensin II
• Low blood pressure detected by baroreceptors
• ‘HAL avoids the beers because he’s a WUS’
• actions
• fluid and electrolytes
• inserts aquaporins into DCT and CT to increase water reabsorption
• also increases Urea reabsorption in inner medullary CT
• (keeps the osmolality of the medullary interstitium the same)
• and increases Sodium reabsorption in ascending loop
• vasculature
• vasoconstriction
• higher
• circadian rhythm, thermoregulation, social and sexual behaviour
• disease
• SIADH
• MDMA
• diabetes insipidus
• cranial
• nephrogenic
• lithium, cortisol, calcium excess —> blunted response to ADH
• ANP
• secreted in response to
• atrial stretch
• angiotensin II
• sympathetic stimulation
• Dilates afferent, constricts efferent arteriole —> increases GFR
• decreases Na reabsorption in PCT