Tut2: Water Balance Flashcards
Have not added in what the different drugs do at different sections of the nephron.
What are the eight functions of the kidney?
Remove waste products from body
Regulate plasma volume
Regulate plasma osmolarity
Regulate blood pressure
Regulate acid base balance and electrolytes
Produce erythropoietin
Synthesise enzymes required for vit D activation from skin/diet
Major route if elimination for a large number of water soluble drugs
How does the kidney regulate plasma volume
primarily altering excretion of sodium in the urine
How does the kidney regulate plasma osmolarity
Primarily by altering the excretion of water in the urine
How does the kidney regulate blood pressure
By regulation of plasma volume
By production of renin secreted in response to renal hypoxia
How does the kidney regulate acid base balance and electrolytes?
By altering excretion of H+ and HCO3- ions in the urine
Describe the Renin Angiotensin Aldosterone System
-Some change causes a decrease in renal perfusion pressure.
- this is detected by the juxtoglomerular apparatus in the kidney
- kidney releases renin
- renin reacts with angiotensinogen released from liver to produce angiotensin1
- angiotensin converting enzyme released from pulmonary and renal endothelium converts angiotensin1 to angiotensin2
- angiotensin 2 :
Increases SNA
Increases tubular Na+ and Cl- reabsorption and K+ excretion and H2O retention
Increases blood pressure by arteriolar vasoconstriction
Increases ADH secretion from posterior pituitary this causes water reabsorption from the collecting duct
And causes aldosterone secretion from adrenal medulla
- aldosterone also increases tubular Na+, Cl- reabsorption and K+ excretion and water retention
What turns off the RAAS?
RAAS causes Water and salt retention
Effective circulating volume will increase
This causes perfusion pressure of juxtoglomerular apparatus to increase to normal
What two components make up the kidney?
Vascular component and tubular component
Where does filtration take place?
In the glomerulus (vascular cmponent)
What is blood delivered by?
Afferent arterioles
Where does the blood go after leaving the afferents arterioles?
It goes to the glomerulus > efferent arterioles > capillaries which turn reabsorbed substances from tubular to the vascular component
How much filtrate is processed by the kidneys each day?
180L
How much of this filtrate is reabsorbed back into the vascular component?
99%
How is the movement of substances out of the tubule facilitated?
By the structure of the tubuel
Why do the kidneys need to produce a wide range of urine concentration and volumes?
Salt and water intake in the diet vary widely, so kidneys must produce a wide range of Urine concentration and volumes for the body to remain in water balance.
What is the most dilute urine
50mosmol/L
What is the most concentrated urine
1200mosmol/L
What is plasma osmolarity?
290mosmol/L
What is the osmolarity of the renal cortex?
300 mosmol and it does not change
What is the osmolarity of the outer medulla?
400-600mosmol
What is the osmolarity of the inner medulla?
800-1200mosmol
Where is the loop of henle 1200 mosmol?
At the bottom of the descending loop of henle
What happens when plasma osmolarity is reduced?
Circulating ADH decreases. This causes less water to be reabsorbed so more is excreted in the urine .
This decreases plasma volume, so plasma osmolarity will increase
What happens when the body is dehydrated?
Circulating ADH will be high .
This will cause more aqua porins to be inserted in the ascending loop of henle and the collecting duct so less water is excreted in the urine.
This will retain water, and increase plasma volume
What is urine specific gravity?
A measure of the density of urine compared with the density of water
What is the normal range of urine specific gravity?
1.002-1.040
What can urine specific gravity be used to estimate?
Urine osmolarity
In most cases, what does urine specific gravity increase linearly with?
Increasing urine osmolarity
How is urine generated?.
Via three processes:
Glomerular filtration,
Tubular reabsorption
Tubular secretion
Where do the three processes of urine formation take place?
In the nephrons
What is filtration.
The movement of fluid and solutes from the glomerular capillaries into the Bowman’s capsule
What is reabsorption ?
The movement of filtered substances out of the tubule and into the surrounding peritubular capillaries
This takes place throughout the nephron
What is secretion?
The movement of selected unfiltered substances from the peritubular capillaries into the renal tubule for excretion
What is in the urine?
Any substance that is filtered or secreted but not absorbed
What is osmolality
The measure of the attractiveness of water to a particular particle
What does serum osmolality measure?
The amount of solutes dissolved in the serum
What are the chemicals that affect osmolality.
Na+, Cl-, HCO3-, proteins and glucose
What is osmolality defined as?
The number of osmoles of solute per kg of solvent
Expressed in terms of osmol/kg or osm/kg
What is osmosis?
The diffusion of water through a semi-permeable membrane from an area of high to low solute concentration
What are the two homeostatic mechanisms that work together to control plasma osmolality and hence body water content?
Thirst and ADH system
What are these homeostatic mechanisms stimulated by?
Change in plasma osmolarity
Where is this stimulus which activates the thirst and ADH system detected?
In receptors in the supraventricular nuclei in the hypothalamus
There is no blood brain barrier here so neurons are exposed directly to changes in blood osmolarity
What does an increase in osmolarity result in?
Water leaving the cell, this decreases cell volume
This results in sensation of thirst and release of ADH
What does a decrease in osmolarity result in?
Water entering the cell which increases cell volume
This will suppress thirst and inhibit the release of adh
What happens if the body fluids are hyperosmotic?
This means body fluid has high concentration of particles. i.e. high osmolarity.
Circulation of ADH is high
Insertion of water channels into apical membranes of cells lining the collecting ducts occurs
Water is reabsorbed and retained by the body.
This increases plasma volume, decreasing plasma osmolarity
What happens when body fluids are hypoosmotic?
This means body fluids have less osmolarity .
This causes circulating ADH to be reduced or absent
This causes water channels to be removed from the collecting duct
Any excess water is excreted in the urine
How much of cardiac output do kidneys receive?
20%
What does renal blood flow auto regulation chiefly depend on?
A combination of:
Pre-glomerular arteriolar vasodilation and
Post glomerular arteriolar vasoconstriction
What is pre glomerular arteriolar vasodilation mediated by?
Prostaglandins and nitric oxide
What is post glomerular arteriolar vasoconstriction mediated by?
Angiotensin II
What are prostaglandins?
Potent vasodilators important for maintaining blood flow to the glomerulus and medulla
Especially in conditions that cause decreased perfusion of blood to the kidneys
E.g. In hypotension
What are some factors which affect blood supply to the kidneys?
Situations where CO is compromised
Drugs which affect action of prostaglandins or angiotensin II
Direct injury
Ischaemia (atherosclerosis)
Tumour causing renal artery obstruction
What does the rapidity which the thirst response can contribute to restoration of plasma osmolarity depend on?
The rate at which fluid is absorbed from the gut
What does this rate of which fluid is absorbed by the gut depend on?
The rate of gastric emptying and
The osmolarity of the fluid
What happens when you drink a more concentrated fluid than the blood? (HYPERTONIC)
Initially water will be removed from the body into the intestinal lumen
Water will then be reabsorbed secondary to solute absorption
What does rapid emptying and dilute solution allow?
Rapid absorption
How is water absorbed from a hypertonic solution?
It is delivered to the intestine
It then enters the portal, then systemic circulation
Plasma osmolarity falls, ADH release is inhibited
Existing circulating ADH disappears over 15-30mins
AQP are removed from collecting ducts
Rate of urine excretion rises and urine specific gravity falls,
The urine excreted will be dilute, and have a low urine osmolarity.
What happens once a hyperosmotic fluid reaches the intestine?
The osmotic gradient may first draw water from the extracellular compartment into the gut lumen
Glucose is rapidly absorbed. What follows?
Water follows.
It goes into the portal circulation, to the liver
Glucose is removed by the liver. What happens to the water?
Water is handled by the kidneys as a hypo-osmotic solution
Then plasma osmolarity decreases, what does this trigger?
ADH decreases,
AQP removed from apical membrane
excess water is excreted by kidney in the urine
What happens if an isoosmotic solution enters the stomach?
No absorption occurs as solution is isoosmotic with blood
The Na+ from the isoosmotic solution is absorbed from the intestine. What follows?
Water and Cl- follow passively
Absorbed fluid enters portal then systemic circulation
Extracellular volume is expanded but plasma osmolarity is unchanged
What effects does an isoosmotic solution have in ADH?
ADH is not stimulated and circulating levels of it a relatively unchanged
There are no major changes in urine output
If you were working within a community pharmacy and a friend of a patient with dehydration secondary to food poisoning was asking your advice, what oral rehydration would you recommend? Why?
Isoosmotic solution.
It does not change plasma osmolarity, but will change plasma volume, so will treat the dehydration and cause body to retain more water as ADH circulation will remain unchanged.
What does MSU test for, what is the reference data?
PH 4.5-8
Proteins <10 white cells/cmm
What is MSU ?
Mid stream urine
What is MSU used for?
A simple diagnostic test, usually for UTI/kidney infection
What can MSU tell us?
Evaluate causes of kidney failure
Screen for chronic diseases like diabetes mellitus and hypertension
When is urine infection generally diagnosed.
Based in results of urineanalysis -
Urine culture is often ordered as a follow up test to identify bacteria that may be causing infection
What is GFR?
The volume of plasma filtered across the glomerulus per unit of time
It is the sum of filtration rate from each functioning nephron
What directly correlates with GFR?
Renal function,
I.e. the processes of filtration, secretion and reabsorption, endocrine and metabolic functions of the kidney
Why is plasma creative an ideal endogenous substance for measuring the GFR?
It is freely filtered at the glomerulus but is not reabsorbed
What is the normal reference range for creatinine in adult males? In adult females?
Males = 60-150umol/L Females= 49-90umol/L
What is the ideal method for calculating CrCl levels ?
By performing a collection of urine over 24 hours and taking a plasma sample midway through this period
However it is difficult and inconvenient to undertake accurately in practice
Why is serum creatine not a good marker of renal function?
It is influenced by age, gender, ethnicity, muscle mass
It is much accurate account for these variables. How is this done?
These variables are accounted for by a formula which works out the creatine clearance as an estimation of GFR
What is the most widely used formulae for predicting GFR?
Cockcroft-Gault equation
This has been validated for dose adjustment in renal impairment.
CrCl= (Fx (140-age) x weight) / (SrCl (umol/L)) Weight = lean body weight in kg F = 1.04 in females, 1.23 for males
Male IBW= 50kg + (0.9x every cm over 150cm in height)
Female IBW= 45kg + (0.9 x every cm over 150cm in height)
What are some limitations of the Cockcroft Gault equation?
It is not validated in some populations
It is unreliable in extremes of body sizes (severe malnutrition/obesity)
It is imprecise and unreliable for rapidly changing renal function e.g. (ICU, ARF)
It tends to overestimate renal function at lower levels particularly in obese or fluid overloaded patients.
We use the ideal body weight calculations to overcome this.
What problems can arise when giving drugs to patients with reduced renal function?
Reduced renal excretion of drug or its metabolises may cause toxicity
Sensitivity to some drugs is increased even if elimination is unimpaired
Many side effects are tolerated poorly by patients with renal impairment
Some drugs are not effective when renal function is reduced
How can problems arising due to giving drugs to those with reduced renal function be avoided?
By reducing the dose of the drug
By giving an alternative drug
What kind of drugs act at the proximal convoluted tubule?
Acetazolamides
Which drugs act in the ascending loop of henle?
Bumetanide, furosemide, torsemide, ethacrynic acid
Which drugs act at the distal convoluted tubule?
Thiazides
Which drugs act in the collecting duct?
Spironolactone, amiloride, triamterene
What are Acetazolamides?
Act in the proximal convoluted tubule
- Carbonic anhydrase inhibitor which inhibits reabosprtion of HCO3-
- Weak diuretic properties
What do Bumetanide, Furosemide, Torsemide and Ethacrynic acids do?
Acts in Ascending loop of henle.
-Inhibits Na+/K+/Cl- co-transporter resulting in retention of Na+, Cl- and Water retention in the tubule
Most efficacious of the diuretics
What do Thiazides do?
Act in the distal convoluted tubule
- To inhibit reabsoprtion of Na+ and Cl- resulting in retention of water
Most commonly used diuretics
What do Spironolactone, Amiloride, Triamterenes do?
Act in the collecting duct
-Spironolactone is an aldosterone antagonist and inhibits the aldosterone mediated reabsorption of Na+ and secretion of K+
- Amiloride & trimterene block Na+ channels
- These drugs prevent hypokalemia which occurs with thiazide or loop diuretics
How does renal function affect BP and fluid balance?
Regulation of ECF important in long term regulation of BP
- Increased Plasma volume –> Increased BP
- Decreased plasma volume –> Decreased BP
Plasma volume regulated primarily by altering the EXCRETION of SODIUM in the urine
