Kidney Function Flashcards
Understand the nature of the glomerular filter and the dynamics of ultrafiltration Define clearance and its use in the study of renal physiology Explain how glomerular filtration rate and effective renal plasma flow are measured Describe the processes of tubular reabsorption of glucose, amino acids etc. Describe the processes of tubular secretion of organic acids and bases
What are the functions of kidneys?
Metabolite excretion (and ingested substances)
Processes the plasma
Control of body fluid composition
How are the functions of the kidneys achieved?
Volume Regulation (linked to Na+ conc)
Osmoregulation
pH regulation
What are some examples of endocrine hormones that act on the kidneys?
ADH Aldosterone Natriuretic Peptides Parathyroid hormone FGF23
What are some examples of endocrine hormones produced by the kidneys?
Renin Vitamin D Erythropoietin Prostaglandins alpha Klotho
Which kidney is slightly lower than the other?
The right kidney is lower than the left kidney
What is the outer region of the kidney called?
Cortex
What is the inner region of the kidney called?
Medulla
What is the basic unit of the kidney?
Nephron
What do nephrons consist of?
A renal corpuscle and a thin hollow tube
What is a renal corpuscle?
The initial filtering component of the nephron
What structures make up the renal corpuscle?
Bowman’s capsule
Glomerulus
What is the Bowman’s capsule composed of?
Fenestrated Endothelial cells
What is the Glomerulus composed of?
Compact interconnected capillary loops
What is the blood supply of the Glomerulus?
Blood supply from the afferent arteriole
Through which arteriole does the blood leave the glomerulus?
The efferent arteriole
What do the fenestrated capillary endothelium rest on?
A protein basement membrane
The basement membrane has negative charges. Why is that?
Has fixed polyanions
What is a feature of the tubular epithelium
Specialised filtration slits for fluid (at the level of the filtration interface)
What are podocytes?
Specialised epithelial cells with a central cell body and a long foot process which extends from it
What links the foot processes together?
Filtration slit proteins
What are the names of filtration slit proteins?
Nephrin
Podocin
What are the 2 types of nephrons?
Cortical
Juxtamedullary
Where is the renal corpuscle found in cortical nephrons?
Found in the outer 2/3rds of the cortex
Where is the renal corpuscle found in juxtamedullary nephrons?
Found in the inner 1/3rds of the cortex
What are the 2 types of cells that make up the juxtamedullary apparatus?
Juxtaglomerular cells
Macula Densa cells (directly opposite the juxtaglomerular cells)
What do juxtaglomerular cells do?
Secrete renin into the blood of the afferent arteriole
Where are Macula densa cells found?
In the walls of the ascending limb of the loop of Henle
What passes in between the afferent and efferent arteriole?
The ascending limb of the loop of Henle
Where are mesangial cells located?
Around the capillaries
Do the mesangial cells contribute to the filtration interface (barrier)?
No
Mesengial cells have smooth muscle. What can they do?
Contract meaning they can control the SA of the filtration interface
What are the 2 sets of arterioles in series which go to the nephrons?
Afferent
Efferent
What are the 2 capillary beds that are in series?
Glomeruli
Peritubular
Where is the glomeruli capillary bed located?
In the renal corpuscle
Where do Peritubular capillaries arise from?
The afferent arteriole
Peritubular capillaries in the region of the loop of Henle are called…
Vasa Recta
What are the 4 basic renal processes?
Glomerular Filtration
Tubular Secretion
Tubular Reabsorption
Metabolism
Where does glomerular filtration take place?
Only in the renal corpuscle
What is glomerular filtration?
The movement of fluid and solutes from the glomerular capillaries into Bowman’s space
What type of process is the glomerular filtration?
Non-selective process
What is an ultrafiltrate?
The fluid in the Bowman’s space
Beginning of the formation of urine
What is Tubular Secretion?
The secretion of solutes from the lumen of the peritubular capillaries into the lumen of the tubules
What is Tubular Reabsorption?
The movement of materials from the filtrate in the tubules into the peritubular capillaries
What does it mean by metabolism?
The kidney is able to eliminate certain types of molecules
The amount excreted in urine is…
The amount filtered + the amount secreted - the amount reabsorped
What is an example of a substance that is filtered and secreted but not reabsorbed?
PAH- para-aminohippuric acid
What is an example of a substance that is filtered and some of it is reabsorbed?
Water and most electrolytes
What is an example of a substance that is filtered and completely reabsorbed?
Glucose and Bicarbonate
What determines what gets through the glomerular filtration barrier?
Molecular size, shape and charge
What is the molecular size cut-off for the filtration interface?
7000kDa
The basement membrane is negative, what type of ion is more likely cross the membrane?
Positively charged
What can infection, damage to glomerulus or very high blood pressure result in?
Protein in the urine
Haemoglobin in urine
Red cells in urine
What is the glomerular filtration rate?
The volume of fluid filtered from the glomeruli per minute (ml/min)
What does the GFR depend on?
Starling Forces
Surface are of filtration interface
Hydraulic permeability of capillaries
What is the GFR regulated by?
Neural and hormonal input
How can hydrostatic pressure be altered?
Constricting or dilating the arterioles
What are Starling forces?
The opposing hydrostatic and oncotic (colloid osmotic) pressures
What direction does the driving force of fluid movement in filtration go in?
From capillary lumen to capiscular space
Which nervous system alters the surface area of the filtration interface?
Sympathetic nervous system
What is the definition of clearance?
The volume of plasma that is cleared of a substance per unit time
What is the equation of renal clearance?
(Concentration in urine* Volume of Urine)/Concentration in plasma
What are the units for renal clearance?
The same units for the volume of urine
Why can the clearance of inulin measure GFR?
Inulin is freely filtered, but not reabsorbed/secreted/metabolised
Used experimentally
What is used clinically for estimate GFR?
Creatinine (slightly secreted)
What is different about the equation used in the clinic to determine clearance?
Includes variables: age and weight
Units and value will differ
What is the definition of the haematocrit?
Percentage of whole blood that is made up of cells
What is the approximate renal plasma flow?
600ml/min
What is the formula for blood flow?
(Plasma Flow)/(1-haematocrit)
Where is the main region where reabsorption takes place?
Proximal Tubule: proximal convoluted tubule and the proximal straight tube
What cells make up the wall of the proximal tubule?
Single layer of columnar cells
What transporters are present for proximal reabsorption of organic nutrients?
Na+-coupled co-transporter
A tubular maximum (Tm) system
Specific Transporters
Where are Na+-coupled co-transporters expressed?
Luminal membrane of the tubule epithelial cells
Why can the Na+-coupled co-transporter undergo saturation?
Has a transfer maximum (tubular maximum)
What is a tubular maximum (transfer maximum)?
A transporter only has a limited number of binding sites for the molecule. Once they are full, they cannot transport anyway
What are some examples of organic nutrients?
Glucose
Amino acids
Why is glucose not normally present in the urine?
Filtered glucose is normally reabsorbed and does not undergo secretion
Where is the Na+-K+-ATPase pump expressed?
The basolateral membrane
What does the Na+-K+-ATPase pump do?
Maintains a low sodium concentration inside the cell compared to the outside of the cell
Where are amino acid reabsorbed?
Proximal tubule
How are filtered proteins reabsorbed?
Endocytosis in the PCT
What happens to reabsorbed filtered proteins?
Degraded to amino acids
What is passively reabsorbed by the PCT?
Urea
Chloride
Potassium
Calcium
What is secreted in the proximal tubule?
Endogenous molecules
Drugs
Diagnostic agent
What are some examples or endogenous molecules?
Bile salts Fatty acids Prostaglandins Creatinine Dopamine Choline
What are some examples of drugs?
Furosemide Penicillin Acetozolamide Cimetidine Morphine
What is an example of a diagnostic agent?
Para-aminohippuric acid (PAH)
How are organic anions secreted in Proximal Distribution?
Organic anion (OA-) enters cell in exchange for dicarboxylate (DC-) (organic anion transporters (OAT1 or OAT3)).
DC- accumulate in cells by metabolism and Na+-coupled cotransport
OA- enters tubule lumen via ATP- dependent transporters
How are organic cations secreted in Proximal Convoluted Tubule?
Enter vell via facilitated organic cation transporters (OCT2)
Enter tubule via multidrug and toxin extrusion proteins (MATEs) antiporter in exchange for H+ and/or OCTN
What is osmolality?
A measure of water concentration (mosm/kg)
The higher the solution osmolality the…
Lower the water concentration
Why do physiologists prefer osmolality over osmolarity?
Osmolality is independent of the temperature whereas the osmolarity is dependent on it.
What is the main osmotically active solute in plasma?
Sodium
What is the plasma sodium concentration?
135-145mmol/l
Sodium is free filtered at the renal corpuscle. What is the equation to find out what is filtered?
Plasma Na+ concentration (mmol/l) * GFR (l/min)
What kind of process is sodium reabsorption?
Active
Where does sodium reabsorption take place?
Proximal tubule
Thick ascending limb
Distal tubule
Collecting duct
What are the types of cells in the collecting duct?
Intercalated cell
Principal cell- sodium reabsorption takes place
Where does majority of sodium reabsorption take place?
Proximal tubule
Thick ascending limb
What parts of the Nephron are under hormonal control?
Distal tubule
Principle cells of the collecting duct
Is there sodium reabsorption in the descending limb?
No
What type of sodium reabsorption occurs in the thin ascending loop?
Passive- movement of Na+ from an area of high conc to an area of low conc with no transport mechanism or energy
Where is the filtrate?
In the lumen
What Na transport pathways are present in the proximal tubule?
Na+ nutrient symporter
Na+: H+ Exchanger- NH3
Na+:K+ ATPase pump
Na+ HCO3- transporter
Where is the sodium potassium ATPase pump expressed in the proximal tubule?
Basolateral membrane
What type of transporter is the sodium potassium ATPase in the proximal tubule?
Primary active transporter
What does the sodium potassium ATPase do?
ATP hydrolysis for sodium to move against conc gradient out of cell and potassium into the cell
What is the sodium conc inside a proximal tubule cell?
Low
What is useful about Na+ moving into the cell?
Can provide energy for the movement of another ion/molecule/nutrient against its concentration gradient
What isoform of the sodium hydrogen exchanger is present on the luminal membrane of the proximal tubule cells?
NH3
Where is the sodium hydrogen exchanger expressed in proximal tubule cells?
Luminal membrane
How does Sodium enter the proximal tubule epithelium?
Via the sodium hydrogen exchanger and the sodium nutrient symporter
What happens to the sodium that is inside the proximal tubule cell?
Moved into the interstitial by the sodium bicarbonate transporter or by the sodium potassium ATPase pump
How are chloride ions reabsorbed in the proximal tubule?
Mainly passive diffusion between cells which is dependent on Na to maintain electro-neutrality
What sodium transport pathways are present in the thick ascending limb?
Na+:K+:2Cl- cotransporter
Na+:K+ ATPase pump
What other channels are present on the cells in the thick ascending limb?
K+ channel (luminal membrane)
K+ Cl- symporter (basolateral membrane)
Cl- channel (basolateral membrane)
Where is the Na+:K+:2Cl- cotransporter located in the thick ascending limb?
Luminal membrane
What does the Na+:K+:2Cl- cotransporter do?
Moves sodium into the cell while moving potassium ions against their conc gradient into the cell
What happens to the sodium ions inside the thick ascending limb cells?
They pass into the interstitial fluid surrounding the capillaries by the Na+:K+ ATPase pump
What happens to the potassium ions inside the thick ascending limb cells
Return to the filtrate by moving down their conc gradient through potassium channels
What does the potassium ions cause the filtrate to do?
Causes the filtrate to have a positive charge
This will repel other positively charged molecules such as sodium.
This means sodium will move between the cells
What sodium transport pathways are present in the distal tubule?
Na+:Cl- cotransporter
Na+:K+ ATPase pump
Where is the Na+:K+ ATPase pump located in the distal tubule cells?
Basolateral membrane
Where is the Na+:Cl- cotransporter located in the distal tubule cells?
Luminal membrane
What direction does the sodium travel in through the Na+:Cl- cotransporter on the distal tube?
From the filtrate into the cell
What happens to the sodium ions that are in the distal tubule cells that have entered through the Na+:Cl- cotransporter?
They are moved into the interstitial fluid by the Na+:K+ ATPase pump
What sodium transport pathways are present in the principle cells of the collecting duct?
Na+ channels
Na+:K+ ATPase pump
Where is the Na+:K+ ATPase pump located in principle cells of the collecting duct?
Basolateral membrane
Where is the Na+:Cl- cotransporter located in principle cells of the collecting duct?
Luminal membrane
How does the sodium enter the principle cells of the collecting duct?
Through the luminal membrane
What does water reabsorption depend on?
Osmosis
Sodium reabsorption
Tubule Permeability
What is osmosis?
Movement of water from high concentration through a partially permeable membrane to an area of low concentration
What do all basolateral membranes of renal cells have?
Aquaporins
What are aquaporins?
Water channels
Are aquaporins always present on the luminal membrane of renal tubule epithelial cells?
No- there is variable expression of water channels, therefore varied water permeability properties
How do sodium ions move from the tubular lumen into the interstitial fluid?
Down its conc gradient into the tubular epithelial cells and then into the interstitial fluid by the sodium potassium ATPase pump
What happens to the osmolality of the tubule when the sodium leaves?
The osmolality decreases
What happens to the osmolality of the interstitial fluid when the sodium enters?
The osmolality increases
What water channels are present in the proximal tubule which allows water to move into the interstitial fluid?
AQP1 - aquaporin 1 water channels
AQP1 channels are present in the proximal tubule. Where are they found on the tubular epithelial cells?
The luminal membrane
What is isotonic reabsorption?
Water can move between the cells because the tight junctions have high water permeability
What happens to the water from the tubular lumen once it is in the interstitial fluid?
It moves by bulk flow into the peritubular capillaries
What force is key in moving the water into the peritubular capillaries by bulk flow?
Hydrostatic forces
Why is there no effect on osmolarity/osmolality even though the filtrate volume is reduced?
Filtrate osmolality (proximal tubule) =ultrafiltrate osmolality (Bowman’s capsule) = plasma osmolality
What is the osmolality of concentrated urine in relation to plasma?
Higher than plasma
Where does the production of concentrated urine take place?
Loop of Henle
How does the kidney produce concentrated urine?
It separates Na+ and water reabsorption
Generates high osmolarity medullary interstitium to drive water reabsorption
What does the loop of Henle consist of?
Descending and ascending limb
What are the limbs separated by?
Medulla with medullary interstitium
What is the flow in loop of Henle?
Countercurrent- flow in descending limb moves downwards towards the turn and flow in the ascending limb moving upwards
What happens to the sodium at the start of the descending loop?
Some sodium ions passively diffuse
Is the sodium diffusion into the descending loop classed as reabsorption?
No because it is movement into the lumen of the filtrate not the tissue
What channels are present in the luminal membrane of the descending limb?
AQP1
What is the purpose of the mirroring of vasa recta?
Supply blood without washing the gradient away
What is the permeability of the ascending and descending limb of the vasa recta?
Both limbs are equally permeable to salt and water
What is the blood flow like near the descending limb of the loop of Henle
Slow
What is the effect of having slow blood flow near the descending limb of the loop of Henle?
Any water that leaves and enters the medullary interstitium does not significantly contribute to the to the high osmolarity
What else contributes to the high osmolality of the interstitium?
Urea
What is urea the product of?
Protein catabolism
Where is the urea freely filtered?
Renal corpuscle
What is the urea concentration in the filtrate?
Same concentration as in the plasma
What happens to the urea in the proximal tubule?
Passive reabsorption- passes through the luminal and abluminal membrane and between the cells
What recycles urea?
The transporters in the loop of Henle and the inner medullary duct
On which segment of the loop of Henle are the transporters present?
Thin descending segment
Thin ascending segment
Where do the transporters of the loop of Henle secrete urea?
Into the lumen of the tubule
On which membrane are the transporters present in the loop of henle?
Present in the basolateral and luminal membrane
Where does the inner medullary collecting duct move the urea to?
From the filtrate into the medulla and interstitium
In the inner medullary collecting duct what increases urea reabsorption?
ADH increases urea reabsorption through UT-A3 and UT-A1
Each nephron is separate from its neighbouring nephron apart from….
where they merge at the level of the collecting duct
What happens to the majority of the urea that is filtered?
It is reabsorbed
What is Tonicity?
Concentration of non-penetrating solutes
What arises from the loop of Henle?
The distal tubule
Can water reabsorption occur at the distal tubule?
No
Why can the collecting duct concentrate urine?
it descends into the medullary interstitium which has a high osmolarity
What controls the water permeability of the collecting duct?
ADH
What secretes ADH?
Posterior pituitary gland
Where does the ADH go once it is secreted?
Enters the blood of the internal carotid artery and circulated in the blood to the kidney
Where does the ADH hormone act?
Acts at the level of the V2 receptor which is expressed on the basolateral membrane
What does the V2 receptor use?
G protein and Cyclic AMP
What water channels are expressed on the basolateral membrane?
AQP3
AQP4
What does forming concentrated urine depend on?
Renal medulla interstitial fluid high osmolarity
Collecting duct
What maintains constant plasma osmolality?
Urine Formation
Thirst
What is the term given to increased urine excretion?
Diuresis
What is the osmolality of concentrated urine?
more than 300 mosmol/l
How can an individual survive dehydration?
The kidneys can generate low volume concentrated urine
What is the concentration of waste products we are obliged to eliminate each day?
600 mosmol
What is the maximum urinary concentration possible?
1,400 mosmol/l (extreme is usually 1,200 mosmol/l
What is the obligatory water loss per day?
600 mosmol/day (waste products generated)/ 1400 mosmol/l (maximal urinary concentration)= 0.428L/day
What is the osmolality of dilute urine?
less than 300 mosmol/l
What is the term given to excessive urine output?
Polyuria
What is the term given to urine output lower than the obligatory water loss?
Oliguria
What is the normal urine output?
1-2 L/day
What is Osmolar clearance?
Volume of plasma cleared of osmotically active particles per unit time or the fictive urine flow that would have resulted in a urine which was isomolar to plasma
What is the equation for osmolar clearance?
Osmolar clearance= (Urine osmolarity (mosm/ml) * Urine flow rate (ml/min))/ Plasma osmolarity (mosm/ml)
What are the units of osmolar clearance?
ml/min
What is the fasting osmolar clearance?
2-3ml/min
What is free water clearance used to assess?
Renal function- ability of the kidneys to excrete dilute or concentrated urine
What is free water clearance?
The volume of blood plasma that is cleared of solute-free water per unit time
What is the equation for free water clearance?
C(H2O)= Urine flow rate (ml/min)- osmolar clearance (ml/min)
What is anti-diuresis?
Decreased urine formation
Where are the osmoreceptors for ADH?
Organum Vasculosum Lamina Terminalis
Median Preoptic nucleus
Subfornical Organ
Where do the osmoreceptors in the OVLT, MPN and SFO signal to?
The magnocellular neurosecretory cells in the paraventricular and supraoptic nuclei in the hypothalamus
What do the magnocellular neurosecretory cells do?
Produce and release ADH into blood through posterior pituitary
What is the relationship between plasma ADH concentration and plasma osmolality after 285-295mosm/kg?
Linear
Why is ADH effective?
Has a short plasma half-life (10-20 mins)
The release is rapid
What is ADH release sensitive to?
Plasma osmolality
Where are the osmoreceptors for thirst located?
Prelateral optic nuclei
When are the osmoreceptors for thirst triggered?
When plasma osmolarity is 295 mosm/kg
What other factors affect ADH secretion?
Blood pressure
Blood volume
(Angiotensin II and natriuretic peptides)
What effect does angiotensin II have on ADH secretion?
Increases
What effect does natriuretic peptides have on ADH secretion?
Decreases
What else stimulates ADH secretion?
Nicotine
Pain
Stress
Nausea
What else inhibits ADH secretion?
Alcohol
What is diabetes insipidus?
Water diabetes
A disease which results in the production of very large quantities of dilute urine (dehydrate and insatiable)
What are the characteristics of diabetes insipidus?
Polyruria (2L/day)
Thirst (polydipsia)
Nocturia
What are the types of diabetes insipidus?
Neurogenic (no ADH secreted)
Nephrogenic
What causes neurogenic diabetes insipidus?
Congenital defect
Head injury eg: trauma or brain tumour
What causes nephrogenic diabetes insipidus?
Inherited mutated V2 receptor or AQP2 channel
Acquired (infection or side effect of drug e.g. lithium)
What is osmotic diuresis?
Increased urination due to the accumulation of substances in the tubules of the kidney
What are the characteristics of osmotic diuresis?
Polyuria (increased urination)
Thirst (polydipsia)
What causes the increases urination in osmotic diuresis?
Small molecules (glycerol, mannitol and excess glucose) in the renal tubule lumen which reduce reabsorption of water which the later portions of the nephron cannot compensate
What do potassium ions do?
Maintain resting membrane potential
affects membrane potential and excitability
What potassium channels/ pumps are present on the luminal side of the proximal tubule epithelium?
Potassium channel (Weak)
What potassium channels/ pumps are present on the basolateral side of the proximal tubule epithelium?
Sodium potassium ATPase pump
Leaky potassium ion channel
Potassium Chloride symporter
Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the proximal tubule?
65%
Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the thick ascending tubule?
30%
Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the distal tubule?
5%
What cotransporter is present on the luminal side of the thick ascending limb?
Na+: K+: 2Cl¯ cotransporter (NKCC2 transporter) (allows them inside the cell)
What channel is present on the luminal side of the thick ascending limb?
Potassium ion channels- potassium ions flow out into the lumen
What transporters are present on the basolateral side of the thick ascending limb?
Sodium Potassium ATPase pump
Potassium Chloride cotransporter
What channels are present on the basolateral side of the thick ascending limb?
Chloride
Potassium
How else can potassium ions flow from the luminal side to the interstitial fluid?
Between the cells in the proximal tubule/ thick ascending limb
What happens to potassium ions in the collecting duct?
Reabsorbed by the intercalated cells (and distal cells) in exchange for H+
Secreted by Principal cells
What are the exit routes for the potassium ions in the principal cells?
K+:Cl- cotransporter
ROMK: Renal Outer Medullary K+ channel
BK: Ca2+ activated big-conductance K+ channel
What is the difference between sodium and potassium transport pathway?
Potassium is filtered, reabsorbed and is secreted. Sodium does not undergo secretion
What are the factors affecting K+ secretion by principal cells?
Factors affecting Na+ entry through ENaC
Aldosterone
Tubular flow rate
Acid base balance
How does Aldosterone affect K+ secretion by principal cells?
Stimulates K+ channels as well as sodium channel.
More K+ leaving the principal cells
How do tubular flow rates affect K+ secretion by principal cells?
High flow rates favour secretion
How does acid-base balance affect K+ secretion by principal cells?
Acidosis inhibits it
Alkalosis enhances it
What is hypokalaemia?
plasma potassium ion concentration is less than 3.5mM
What is mild hypokalaemia?
plasma [K+]- 3.0-3.5mM
What is moderate hypokalaemia?
plasma [K+]- 2.5-3.0mM
What is severe hypokalaemia?
plasma [K+] < 2.5mM
What causes hypokalaemia?
Increased external losses
Redistribution into cells
Inadequate K+ intake
What are some examples of increased external losses of K+ ions which causes hypokalaemia?
From the GI tract- vomiting, diarrhoea
From the kidney- diuretics, osmotic diuresis, hyperaldosteronism, transporter mutations
From the skin- burns, intense sweating
What are some examples of redistribution of K+ ions into cells which causes hypokalaemia?
Metabolic Alkalosis
Insulin Excess
How does insulin excess cause hypokalaemia?
Insulin is released after a meal and bind to the insulin receptor which supports the sodium potassium ATPase pump.
Potassium moves into the cell
Excess insulin –> activity of the transporter increased
What are the cardiac symptoms associated with hypokalaemia?
Dysrhythmias
Conduction defects
Increased likelihood of dysrhythmias due to digitalis
What are the skeletal muscle symptoms associated with hypokalaemia?
Weakness
Paralysis
Fasciculations and Tetany
What are the GI symptoms associated with hypokalaemia?
Ileus
Nausea
Vomiting
Abdominal distention
What are the renal symptoms associated with hypokalaemia?
Polyuria
What is the treatment for hypokalaemia?
Eat food which are rich is K+ (bananas, spinach)
KCl administration (oral/i.v.)
Alkalosis correction
Use of K+ sparing diuretics
What are some examples of K sparing diuretics?
Spironolactone- inhibits aldosterone
Amiloride- inhibits principal cells sodium channels (no potassium secretion)
What is hyperkalaemia?
plasma potassium ion concentration is more than 5.5 mM
What causes hyperkalaemia?
Decreased external losses
Redistribution out of cells
What are some examples of decreased external loss of K+ that cause hyperkalaemia?
Renal Failure
Hypoaldosteronism
Action of drugs
What are some examples of redistribution of K+ ions out of cells that cause hypokalaemia?
Acidosis (exacerbated by lack of insulin in diabetic ketoacidosis)
Tissue destruction/ cell lysis (e.g.: rhabdomyolysis)
What are the cardiac symptoms associated with hyperkalaemia?
Dysrhythmias
Conduction disturbances
What are the skeletal muscle symptoms associated with hyperkalaemia?
Weakness Paresthesias Paralysis Hyperreflexia Cramping
What are the GI symptoms associated with hyperkalaemia?
Nausea
Vomiting
Diarrhoea
What is a short term treatment of hyperkalaemia?
Calcium IV to antagonise the effect of K+ on heart muscle
What is the purpose of short term treatment of hyperkalaemia?
Stabilises the cardiac membrane
What is an immediate treatment of hyperkalaemia?
Insulin and glucose administered to shift K+ into cells
What is the purpose of immediate term treatment of hyperkalaemia?
Shifts potassium into the cells
What is a long term treatment of hyperkalaemia?
Diuretics
Treat for renal failure.
What is the purpose of long term treatment of hyperkalaemia?
Need to increase K+ excretion.
Removal of K+ from the body
How is the volume of ECF determined?
Total quantity of solute (mainly NaCl- sodium balance)
What is the average dietary salt intake?
2.3g/day (0.05-25g/day)
What is osmolality of the ECF maintained at the expense of?
Volume
Why is constant plasma osmolality important?
The cells will shrink or swell–> severe consequences in the brain
What does plasma volume determine?
Blood pressure in veins, cardiac chambers and arteries
Sodium content is largely regulated by the kidney by controlling:
GFR
Sodium reabsorption
What is the extrinsic control of GFR?
Activation of sympathetic nervous system (baroreceptor response)
How does activation of the sympathetic nervous system?
Vasocontricts afferent arteriole–> Lowers GFR
Reduced SA of filtration barrier via mesangial cells–> lowers GFR
(Increases renin release)
What is the purpose of extrinsic control of GFR?
To maintain systemic blood pressure- reduction in GFR will conserve Na+ and H2O–> increase bp/bv
What is the intrinsic control of GFR?
Autoregulation within kidneys which can control afferent arteriole constriction
What are the mechanisms of autoregulation of GFR?
Myogenic response by the renal smooth muscle cells that surround arterioles- vasoconstriction in response to stretch
Tubuloglomerular feedback by the juxtaglomerular apparatus- controls vasoconstriction
What is the purpose of intrinsic control of GFR?
Protects renal capillaries from hypertensive damage and maintains a health GFR
How do the afferent arterioles maintain constant capillary pressure and glomerular blood flow?
Afferent arterioles constrict when BP is raised and dilate when BP is lowered
What sensors are part of the regulatory pathways that control sodium reabsorption?
Tubular fluid NaCl concentration receptors within macula densa
Pressure receptors- central arterial tree
Pressure receptors- intrarenal baroreceptors
Volume Receptors- cardiac atria + intrathoracic veins
What effector pathways are part of the regulatory mechanism that control sodium reabsorption?
Renal sympathetic nerves- stimulate renin release
Direct pressure on kidney
Renin/angiotensis II/ aldosterone- stimulate Na+ reabsorption
Atrial Natriuretic Peptide- inhibits Na+ reabsorption
Dopamine- inhibits Na+ reabsorption
Where do the sympathetic nerves of granular cells receive signals from?
Baroreceptors in central arterial tree via cardiovascular centre
