Transcript Main function of the kidneys.

Renal anatomy,
pharmacology and
physiology
Anaesthetics in renal
dysfunction
James Hayward
SHO Anaesthetics Worthing
Anatomy
Kidneys located either
side of vertebral column:
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left kidney lies superior to
right kidney
superior surface capped
by adrenal gland
Typical kidney
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10 cm long, 5.5 cm wide,
and 3 cm thick
Weighs about 150 g
Kidney in cross section
Main function of the kidneys.
Regulation of the water and electrolyte
content of the body.
Retention of substances vital to the body
such as protein and glucose
Maintenance of acid/base balance.
Excretion of waste products, water soluble
toxic substances and drugs.
Endocrine functions
Renal blood flow
Kidneys receive
20–25% of total
cardiac output
1200 ml of
blood flows
through kidneys
each minute
99% of the
blood flow goes
to the cortex
and 1% to the
medulla
Regulation of water and electrolyte content
Two capillary beds arranged
in series, the glomerular
capillaries which are under
high pressure for filtering,
and the peritubular
capillaries which are
situated around the tubule
and are at low pressure
This permits large volumes
of fluid to be filtered and
reabsorbed.
The nephron
Each kidney is
made up of
about
1,000,000
nephrons
Consist of
renal tubule
and renal
corpuscle
Renal corpuscle
Each renal
corpuscle:
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150–250 µm
in diameter
Bowman’s
capsule and
glomerulus
The renal tubule
The tubule is made up of a number of
sections, the proximal tubule, the
medullary loop (loop of Henle), and the
distal tubule which finally empties into the
collecting duct.
Urine production
Urine is formed as a result of a three
phase process :
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Simple filtration
Selective and passive reabsorption
Excretion
Filtration
Blood pressure forces water and small
solutes across membrane into capsular
space .
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The driving pressure is controlled by the
afferent and efferent arterioles.
Filtration takes place through the
semipermeable walls of the glomerular
capillaries
Almost impermeable to proteins and large
molecules.
The filtrate is thus virtually free of protein and has
no cellular elements.
GFR and Autoregulation
About 20% of renal plasma flow is filtered each
minute (125 ml/min). This is the glomerular
filtration rate (GFR).
In order to keep the renal blood flow and GFR
relatively constant the hydrostatic pressure
needs to be maintained. When there is a change
in arterial blood pressure, there is constriction or
dilatation of the afferent and efferent arterioles.
Autoregualtion
At the loop of Henle, there is greater time for reabsorption
of sodium and chloride ions.
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A decrease in the number of sodium and chloride ions reaching the
distal tubule is detected by the macula densa. This in turn
decreases the resistance in the afferent arteriole which results in an
increase in renal blood flow.
It also increases renin release from the juxtaglomerular apparatus
which stimulates angiotensin II production causing constriction of
the efferent arteriole.
This is a negative feedback system
The juxtaglomerular complex consists of:
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Macula densa cells, which are special distal tubular epithelial cells
which detect chloride concentration
Juxtaglomerular cells, modified smooth muscle cells, in the walls of
the afferent and efferent arteriole. These cells produce renin.
Renin-angiotensin
Renin is an enzyme which converts the plasma
protein angiotensinogen to angiotensin I.
Angiotensin converting enzyme (ACE) which is
formed in small quantities in the lungs, proximal
tubule and other tissues, converts angiotensin
I to angiotensin II
Angiotensin II causes vasoconstriction and an
increase in blood pressure.
Angiotensin II also stimulates the adrenal gland
to produce aldosterone which causes water
and sodium retention which together increase
blood volume.
Selective and Passive
Reabsorption
The function of the renal tubule is to reabsorb selectively about 99% of
the glomerular filtrate.
The Proximal Tubule reabsorbs 60% of all solute
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100% of glucose and amino acids
90% of bicarbonate
80-90% of inorganic phosphate and water.
Reabsorption is by either active or passive transport.
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Active transport requires energy to move solute against an electrochemical
or a concentration gradient. It is the main determinant of oxygen
consumption by the kidney.
Passive transport is where reabsorption occurs down an electrochemical,
pressure or concentration gradient.
Most of the solute reabsorption is active, with water being freely
permeable and therefore moving by osmosis. Water moves because of
osmotic forces to the area outside the tubule where the concentration
of solutes is higher.
Loop of Henle
Urine is concentrated if necessary.
This is possible because of the high
concentration of solute in the substance or
interstitium of the medulla. This high
concentration of solutes is maintained by
the counter current mechanism.
The loop of Henle is a counter current
multiplier and the vasa recta is the counter
current exchanger.
Counter-current mechanism
Osmotic gradient is produced by a
countercurrent mechanism located
in the loop of Henle
The countercurrent mechanism is
based upon the Na pump; by
pumping large quantities of Na into
the interstitial fluid in the medulla a
very high concentration is built up
Distal Tubule and Collecting
Duct:
The final concentration of urine depends upon
the amount of antidiuretic hormone (ADH)
secreted by the posterior lobe of the pituitary.
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ADH is present the distal tubule and the collecting
duct become permeable to water, the water moves
out of the lumen of the duct and concentrated urine is
formed.
In the absence of ADH the tubule is minimally
permeable to water so large quantities of dilute urine
is formed.
Hypothalamic control of ADH
There is a close link between the hypothalamus
and the posterior pituitary.
Osmoreceptors within the hypothalamus,
sensitive to changes in osmotic pressure of the
blood. If there is low water intake, there is a rise in
osmotic pressure of the blood, and vice versa.
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Nerve impulses from the hypothalamus stimulate the
posterior pituitary to produce ADH when the osmotic
pressure of the blood rises, causing water retention and
an increase in circulating volume.
Acid-base
Normal extracellular fluid and arterial pH of
7.35-7.45 (34-46 nmol.l-1 H+
concentration).
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Carbon dioxide (CO2), when dissolved in the
blood is an acid, and is excreted by the lungs.
The kidney excretes fixed acid.
Tubular secretion of acid
Normal metabolism produces large amounts of CO2 continuously (about 14
moles/day)
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If this CO2 were not removed we would rapidly develop fatal acidosis
Almost all of the CO2 is removed, as a gas, from the lungs
If blood pH is low respiration is stimulated so that more CO2 is removed,
raising the pH to the normal level
Bicarbonate is adjusted in the kidney
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Most filtered bicarbonate is reabsorbed in the proximal tubule
The kidneys also dispose of non-volatile acids produced in metabolism
Additional processes are used by the kidney to regulate pH:
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Secretion of H ions
Occurs in the proximal tubule and distal tubules
Secretion into blood lowers the pH
Secretion into the tubule raises the pH
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Production of new bicarbonate in distal tubule:
The distal tubule has fine control over bicarbonate
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Secreted into the blood raises the pH
Secretion into tubule lowers the pH indirectly
Production of ammonia (NH3) in proximal tubule cells during acidosis
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Helps to remove excess H by forming ammonium ion (NH4+) in the tubule
Excretion of waste products
Filtration occurs as blood flows through
the glomerulus. Some substances not
required by the body, and some foreign
materials (e.g. drugs) may not be cleared
by filtration through the glomerulus. Such
substances are cleared by secretion into
the tubule and excreted from the body in
the urine.
Endocrine functions (1) - Renin
Increases the production of angiotensin II which
is released when there is a fall in intravascular
volume e.g. haemorrhage and dehydration.
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Constriction of the efferent arteriole to maintain GFR,
by increasing the filtration pressure in the glomerulus.
Release of aldosterone from the adrenal cortex
Increased release of ADH from the posterior pituitary
Thirst
Inotropic myocardial stimulation and systemic arterial
constriction
Endocrine functions (2) Aldosterone
Aldosterone promotes sodium ion and water
reabsorption in the distal tubule and collecting
duct where Na+ is exchanged for potassium (K+)
and hydrogen ions by a specific cellular pump.
Aldosterone is also released when there is a
decrease in serum sodium ion concentration. e.g.
vomiting.
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Gastric fluid contains significant concentrations of
sodium, chloride, hydrogen and potassium ions.
Therefore it is impossible to correct the resulting alkalosis and
hypokalaemia without first replacing the sodium ions using
0.9% saline solutions.
Endocrine functions (3) - ADH
Antidiuretic Hormone (ADH) increases
the water permeability of the distal tubule
and collecting duct, thus increasing the
concentration of urine.
Endocrine functions (4) – The rest
Atrial Natruretic Peptide(ANP) is released
when atrial pressure is increased e.g. in heart
failure or fluid overload. It promotes loss of
sodium and chloride ions and water chiefly by
increasing GFR
1,25 dihydroxy vitamin D (the most active form
vitamin D) which promotes calcium absorption
from the gut.
Erythropoietin which stimulates red cell
production.
Renal pharmacology
Problems in renal dysfunction (1)
Drug handling
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Protein bound drugs have increased freefractions due to acidosis and
hypoalbuminaemia
Lipid insoluble drugs are eliminated by the
kidney and the hepatic metabolites of lipsoluble drugs are excreted renally
Uraemia may cause denaturation of proteins
and change of structure or binding site
configuration and may affect drug action
Problems in renal dysfunction (2)
Fluid and electrolyte balance
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Hypervolaemic and hypertensive with
overload
Dehydrated with limited cardiovascular
reserve post dialysis
Metabolic acidosis with respiratory
compensation.
Hyperkalaemia
Hypermagnesaemia
Hypocalcaemia
Problems in renal dysfunction (3)
Conditions assosciated with uraemia
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Hypertension and arrythmias, cardiomegaly and failure
Pericardial effusions
IHD
Pulmonary oedema, atelectasis, pneumonia and ARDS
Immunosuppression
Poor wound healing
Coagulopathy
Peptic ulceration
Hiccups
Nausea and vomiting
Problems in renal dysfunction (4)
Anaemia
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Normochromic, normocytic secondary to
reduced erythropoetin secretion
Multiple transfusions and associated
infections.
Increased risk of surgical, pericaridial ad surgical
haemorrhage
Effect of anaesthesia on renal
function
Most operations on well-hydrated patients
cause little effect on renal function.
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Most patients with mild renal disease do well.
Autoregulation is preserved but function will
be imparied below MAP of 60mmHg
Patients with pre-operative renal dysfunction
are more likely to go on to develop renal
failure
Pre-operative
Surgery should be 24hrs after haemodialysis
Peritoneal dialysis can continue until surgery
Blood transfusion is best done during dialysis
Bloods
Correct clotting abnormalities
Note any fistulae
Consider gastro-protection and RSI
Peri-operative (1)
Consider regional approach
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Duration of LAs may be reduced
Caution with spinal or epidural
Avoid any av fistulae which should be
protected
Avoid lactate and potassium containing
solutions
Use drugs that are not primarily renally
excreted
Propofol
Atracurium, rocuronium or vecuronium are suitable
Iso, sevo, or des + nitrous
Sux is not absolutely contraindicated
May have prolonged action
Pre-existing neuropathy or hyperkalaemia
Peri-operative (2)
Caution with medications that accumulate
Morphine
Digoxin
Aminoglycosides
ACE inhibitors
Careful fluid balance to avoid overload
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Doppler
CVP
Urine output > 0.5mls/kg//hr
Volume expansion first over vasopressors
Consider improving renal perfusion
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Dopamine
Mannitol
?Frusemide
Post-operative
Observe for signs of fluid overload,
dehydration and residual neuromuscular
blockade
Patients who have already needed dialysis
should go to HDU/ITU or any location with
ready access to dialysis
Analgesia with cautious opiods, avoid
NSAIDs