Urinary Flashcards
What are the overall functions of the urinary system?
Control volume
Control osmolarity
Help control pH
Excrete some waste products
What substances are completely recovered by the kidneys?
Hydrogen Carbonate
Glucose
Amino acids
What is the anatomical position of the kidney?
Retroperitoneal organ
Roughly T12-13
Right kidney usually lower than left due to position of liver
What is the anatomical position of the bladder?
Sits behind pubic bone in adult
Sits above pubic bone in child
What is the anatomical position of the prostate?
Sits directly below the bladder
Describe the course of the ureters
Arise from renal pelvis on medial aspect of kidney
Descend in front of psoas major muscle
Cross pelvic brim near bifurcation of iliac arteries under uterine artery/ ductus deferens
Down pelvic sidewall
Insert in posterior surface of bladder
What are the bony landmarks for course of ureters?
Arise at L2
Descend in front of lumbar spine transverse processes
Cross pelvic brim in front of sacroiliac joint
Enter bladder at level of ischial spine
Where are kidney stones likely to cause blockage?
1) Junction of renal pelvis and ureter
2) Where ureters cross brim of pelvis (iliac bifurcation)
3) Where ureters pass into wall of urinary bladder
What is the kidney surrounded by?
Fibrous capsule
What is the renal cortex?
Outer portion of the kidney
What do you find the Glomerulus and Bowman’s capsule?
Renal cortex
Where does ultrafiltration take place?
In the renal cortex
What are the sections called that the renal medulla is divided into?
Pyramids
What is the function of the medulla?
Maintain salt and water balance of blood
What do pyramids empty into?
Minor calyxes
What is the point known as where pyramids empty into minor calyxes?
Papilla
What do the minor calyxes join together to form?
Major calyxes
Where does urine move into from the major calyxes?
Renal pelvis and then into ureters
What % of cardiac output do the kidneys receive?
20%
At what vertebral level do renal arteries arise?
L1/L2
Why is the right renal artery longer than the left?
Due to the position of the aorta and the IVC
What is the course of the Renal artery to the kidney?
Renal artery → Segmental artery → Interlobar artery → arcuate artery → interlobular artery → afferent arteriole → glomerulus → efferent arteriole
What is the course from the kidney to the renal vein?
Interlobular vein → Arcuate vein → Interlobar vein → renal vein
What are the layers of the kidney?
Fibrous capsule
Cortex
Medulla
What does the nephron contain?
Renal corpuscles - glomerulus & bowman’s capsule
Proximal convoluted tubule
Loop of Henle
Distal Convoluted Tubule
What are the two poles of the renal corpuscles?
Vascular pole - afferent/ efferent arterioles, glomerulus
Urinary pole - bowman’s capsule
Where is the renal tubule derived from?
Ureteric bud
How is the Bowman’s capsule formed?
The ureteric bud covers the growing glomerulus, resulting in a double-layered cover
What is the filtration barrier of the kidney made up of?
Capillary endothelium and podocytes (visceral layer of bowman’s capsule)
How are filtration slits made?
Capillary endothelium is fenestrated, with podocytes investing in them
What drains into the PCT at the urinary pole?
Parietal layer of Bowman’s capsule makes a ‘funnel’ to collect the ultrafiltrate and drain into PCT
What epithelium do you find in the PCT?
Simple cuboidal epithelium with a pronounced brush border membrane
is the longest, most convoluted section of the tubule
What are the 4 parts of the loop of henle?
o Pars recta
o Thin descending limb
o Thin ascending limb
o Thick ascending limb
What are the epithelia of the thin descending/ascending limb of the loop of henle?
Simple squamous epithelia
The thin limb dips down into the medulla. There is no active transport, and no brush border.
What are the epithelia of the thick ascending limb of the loop of henle?
Simple cuboidal epithelium, no brush borders
Best seen in the medulla, interspersed with thin limbs, vasa recta and collecting duct.
Active transport takes place here.
What are the epithelia of the Distal convoluted tubule?
Simple cuboidal epithelium, no brush borders, larger lumen than PCT
The DCT is Cortical (in the cortex), and makes contact with its ‘parent’ glomerulus. It contains numerous mitochondria.
What does the Juxtaglomerular Apparatus consist of?
Macula Densa - Dense staining region of the DCT
Juxtaglomerular Cells - Cells of afferent arteriole of the glomerulus
Extraglomerular Mesangial Cells (aka lacis cells)
Which other tubule is the collecting duct similar to?
It is similar in appearance to the thick limbs of Henle’s loop, but the lumen is larger, and tends to be more irregular rather than circular.
The collecting duct is a continuation of the DCT via the collecting tubule.
What are renal pyramids?
Progressively larger ducts merge together and empty at the renal papilla, forming a pyramidal shape
How many layers does the ureter have?
The ureter is a tube running from the renal pelvis to the bladder. It has two layers of muscle, with a third appearing in the lower third.
What epithelium is the ureter lined by?
Lined by a specialised epithelium, transitional epithelium
Describe the musculature of the bladder
The urinary bladder, like the lower third of the ureter, has three layers of muscle. Its internal epithelium is transitional, and it is surrounded by an outer adventitia.
“Urothelium” is a stratified epithelium, the “umbrella cells” on the surface layer making it impermeable.
Which transporter is used to create a concentration gradient in all the tubules?
3Na-2K-ATPase
What are the transporters in the proximal tubule?
- Na-H Antiporter
* Na-Glucose Symporter (SGLUT)
What are the transporters in the Loop of henle?
• Na-K 2Cl Symporter
What are the transporters in the early distal tubule?
• Na-Cl Symporter
What are the transports in the late distal tubule and collecting duct?
ENaC
Describe how the kidney handles organic substances
Na+ travels down its concentration gradient set up by 3Na-2K-ATPase from the tubule lumen into the Intersticium using a symporter sometimes, allowing reabsorption of organic substances.
These then move on through cells via diffusion and/or other transport processes.
How is glucose reabsorbed?
In the PCT using the Na-Glucose Symporter SGLUT. This moves glucose against its concentration gradient into the tubule cells. Glucose then moves out of the tubule cell on the basolateral side by facilitated diffusion.
The renal threshold for glucose is 200mg/100ml.
What is Transport Maximum (Tm)?
The maximum capacity that is able to be reabsorbed.
If the plasma concentration exceeds Tm, the rest spills over into the urine. If this happens, water follows into the urine, causing frequent urination (polyuria).
What is clearance?
The volume of plasma from which a substance (X) can be completely cleared to the urine per unit time
(Amount in urine × Urine flow rate)/(Arterial Plasma Concentration)
What is GFR?
The volume of plasma from which any substance (X) is completely removed by the kidney in a given amount of time (usually 1 minute)
(Amount in urine × Urine flow rate)/(Arterial Plasma Concentration)
Measure of the kidney’s ability to filter a substance, thus overall function. It is an indication of how well the kidney works
What does a fall in GFR mean?
Means kidney disease is progressing
What is important about the substance measured in GRF?
Substance (X) must be freely filtered across the glomerulus. This substance must not be reabsorbed, secreted or metabolised by the cells of the nephron. It must pass directly into the urine.
What are examples of substances used to work out GFR?
Creatinine and Inulin
What is renal plasma flow?
605ml/min of plasma
What is filtration fraction?
Proportion of a substance that is actually filtered
Glomerular Filtration Rate)/(Renal Plasma Flow
How are renal blood flow and GFR regulated?
Autoregulation
Myogenic Response
Tubular Glomerular Feedback (TGF)
Describe autoregulation
Keep GFR within normal limits when arterial BP is within physiological limit
Describe myogenic response
Arterial BP rises → Afferent Arteriole Constriction
Arterial BP falls → Afferent Arteriole Dilation
Describe tubular glomerular feedback
Change the amount of NaCl reaching distal tubule. Macula densa cells respond to these changes.
If NaCl increases:
- Response is GFR needs to decrease
- Adenosine released, causes vasoconstriction of afferent arteriole
If NaCl decreases:
- Response is GFR needs to increase
- Prostaglandins released causing vasodilation of afferent arteriole
What is general overflow aminoaciduria?
All AA’s present in the urine. This is normally due to inadequate deamination in the liver, or an increased GFR. It is often seen in early pregnancy.
What is Specific Overflow Aminoaciduria?
Only a specific AA is present in the urine. This is usually due to a genetic inability to break down one AA, e.g. phenylalanine in PKU
Discuss stone formation
Renal aminoaciduria is mainly confined to the dibasic acids, and it due to a genetically determined lack of the specific transport protein(s). For some reason cysteine is an abnormally insoluble amino acid, especially in acidic urine, and cystinuria may be associated with stone formation.
How is glomerular filtration achieved?
The diameter of each afferent arteriole is slightly greater than the diameter of the associated efferent arteriole. This diameter difference increases the pressure of the blood inside the glomerulus. This increased hydrostatic pressure helps to force the below components out of the blood in the glomerular capillaries.
However, only 20% of the delivered blood is actually filtered, 80% exits via the efferent arteriole.
What is filtered at the glomerulus?
o Most of the water
o Most/All of the salts
o Most/All of the glucose
o Most/All of the urea
What cannot be filtered by the glomerulus?
Proteins
RBC
Why can proteins not be filtered at the glomerulus?
Size is too big
Basement membrane and podocytes glycocalyx have negatively charged glycoproteins, so proteins are repelled
What physical 3 forces create the plasma filtration?
- Hydrostatic pressure in the capillary
- Hydrostatic pressure in Bowman’s capsule
- Osmotic pressure difference between the capillary and tubular lumen
What are the 3 filtration barriers?
- Capillary endothelium
o Water, salts, glucose
o Filtrate moves between cells - Basement Membrane
o Acellular gelatinous layer of collagen/glycoproteins
o Permeable to small proteins
o Glycoproteins (-‘ve charge) repel protein movement - Podocyte Layer
o Pseudopodia interdigitate to form filtration slits
How do charges affect filtration?
Neutral Molecule – The bigger it is, the less likely to get through
Anions – Negative charge also repels, more difficult to get through
Cations – Positive charge allows slightly bigger molecules through
What is tubular reabsorption?
Only about 1% of glomerular filtrate actually leaves the body, the rest is reabsorbed into the blood as it passes through the renal tubules via three mechanisms: osmosis, diffusion and active transport.
Is reabsorption in the PCT isosmotic, hyperosmotic or hyposmotic?
isosmotic
Describe tubular reabsorption of Na+
- Na+ is pumped out of tubular cells across the basolateral membrane by 3Na-2K-ATPase.
- Na+ moves across the apical (luminal) membrane down its concentration gradient
o This movement of Na+ utilises a membrane transported or channel on the apical membrane. - Water moves down the osmotic gradient created by the reabsorption of Na+
Explain the Model for Organic Cation (OC+) Secretion in the PCT
- Entry by passive carrier
Mediated diffusion across the basolateral membrane down favourable concentration and electrical gradients, created by the 3Na-2K-ATPase pump. - Secretion into the lumen
H+-OC+ exchanger that is driven by the H+ gradient created by the Na+-H+ Antiporter.
What is the purpose of secretion in kidneys?
For solutes to enter the tubular fluid. This is useful as only 20% of plasma is filtered each time the blood passes through the kidney. It also helps to maintain blood pH (7.38 – 7.42). The substances secreted into the tubular fluid are: o Protons (H+) o Potassium (K+) o Ammonium ions (NH¬4+) o Creatinine o Urea o Some hormones o Some drugs (e.g. penicillin)
What are the two fluid compartments?
Extracellular fluid (ECF) Intracellular fluid (ICF)
How is ECF volume regulated?
regulating the excretion of NaCl
What is sodium expansion?
If Na+ excretion is less than intake, water is drawn out of nephron.
Increase in volume
BP and arterial pressure increases
Oedema may follow
What is ECF contraction?
If Na+ excretion greater than intake, Na+ in ECF decreases.
Less water drawn out of nephron
ECF volume decreases
Blood volume and arterial pressure decreases
What % of sodium is reabsorbed in the PCT
67%
Describe ECF Expansion
If Na+ excretion is less than intake (patient is in positive balance), it is retained in the bodily – primarily in the ECF. Water is drawn out of the nephron causing a corresponding increase in volume. Blood volume and arterial pressure increases, and oedema may follow.
Describe ECF contraction
If Na+ excretion is greater than intake (patient is in negative balance), the Na+ content of the ECF decreases. Less water is drawn out of the nephron, so ECF volume decreases, as does blood volume and arterial pressure.
Describe the handling of sodium in the PCT
67% is reabsorbed in the PCT
This is a proportion of Na+ that is always reabsorbed, regardless of the actual amount that is filtered.
Na+ reabsorption is mainly active, driven by 3Na-2K-ATPase pumps on the basolateral membrane. Different segments of the tubule have different types of Na+ transporters and channels in the apical membrane.
Section 1 – Na+ Reabsorption
o Co-Transported with glucose
o Na-H exchange
Section 2/3 – Na+ and Water Reabsorption
o Na-H exchanger
Describe isosmotic reabsorption as a hallmark of the PCT
The PCT is highly water permeable.
This allows reabsorption to be isosmotic with plasma.
The reabsorption of water is driven by:
o Osmotic gradient established by solute reabsorption
o Hydrostatic force in Intersticium
o Oncotic force in the peritubular capillary due to the loss of 20% filtrate at the glomerulus, but cells and proteins remained in the blood.
What is Glomerulotubular balance?
The balance between Glomerular Filtration Rate and the rate of reabsorption of solutes. It must be kept as constant as possible, so if GFR increases, the rate of reabsorption must also increase.
What is the effect of ECF volume on Glomerulotubular balance?
If ECF volume increases, cardiac output will increase causing an increase in arterial blood pressure. This in turn will increase GFR.
How is sodium and water reabsorption divide in the loop of Henle
Descending limb reabsorbs water but not NaCl
Ascending limb reabsorbs NaCl but not water
• Known as the diluting segment (Dilutes the NaCl in the filtrate)
• Tubule fluid leaving the loop is therefore hypo-osmotic (more dilute) compared to plasma
Describe sodium reabsorption in Thin and Thick Descending Limb
The increase in intracellular concentrations of Na+ set up by the PCT allows for paracellular reuptake of water from the descending limb (No tight junctions).
This concentrates the Na+ and Cl- in the lumen of the descending limb, ready for active transport in the ascending.
Describe sodium reabsorption in Thick ascending Limb
o NaCl transported from the lumen into cells by NaKCC2 channel.
o Na+ then moves into the Intersticium due to the action of 3Na-2K-ATPase.
o K+ ions diffuse back into the lumen via ROMK
o Cl- ions move into the Intersticium
o NaKCC2 is the target of loop diuretics
• Increased loss of K+ in the urine → hypokalaemia
This region uses more energy than any other region of the nephron, and is particularly sensitive to hypoxia.
Describe sodium uptake by the early and late distal tubule
Water permeability of the early DCT is fairly low, and the active reabsorption of Na+ results in dilution of the filtrate.
o Hypo-osmotic fluid enters from the loop and ~5-8% of Na+ is actively transported by the NaCC transporter, driven by 3Na-2K-ATPase.
o The NCC transporter is sensitive to Thiazide Diuretics
o The DCT is also a major site of calcium reabsorption via PTH.
This further dilution means the fluid that leaves is more hypo-osmotic.
What are the two cell types in the collecting duct?
Principle cells
Intercalated cells
Describe the principle cells
o 70% of CD cells
o Reabsorb Na+ by Epithelial Na+ Channel (ENaC)
• Driven by 3Na-2K-ATPase
o Produces lumen charge
• Electrical gradient for paracellular Cl- reabsorption
• Potassium secretion into the lumen
o Variable water uptake through Aquaporin 2
• Dependent on ADH
o Have a more distinct membrane than Intercalated cells
Descrine the intercalated cells
o Active reabsorption of Chloride
o Secrete H+ ions or HCO3-
How is Renin reabsorption regulated?
- Renin-angiotensin-aldosterone system
- Sympathetic nervous system
• Vasoconstriction by α1-adrenoceptors
• Inc. force/rate of heart contraction β1-adrenoceptors
o Decreased Renal Blood flow
• Decreased GFR and Na+ excretion
• Activates Na/H exchanger in PCT
o Stimulates renin release from juxtaglomerular cells
• Increased Angiotensin II/Aldosterone levels - Antidiuretic hormone (ADH)
- Arial Natriuretic Peptide (ANP)
o Acts in the opposite direction to the others
o Synthesised and stored in atrial myocytes
o Promotes Na+ excretion
• Vasodilation of afferent arteriole
o High BP → Stretch Atrial Cells
• Increased release
• Increased Na+ excretion, volume decreases, BP decreases
o Low BP → Atrial Cells less stretched
• Reduced release
• Reduced Na+ excretion, volume increases, BP increases
o Inhibits Na+ reabsorption along the nephron
Describe how the renin-angiotensin system regulates sodium uptake in response to changes in blood pressure
Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole, causes the release of renin from the granular cells of the juxtaglomerular apparatus.
Decreased NaCl Concentration at the Macula Densa cells (Due to low perfusion and therefore low GFR) causes Sympathetic stimulation to the JGA. This also increases the release of renin.
(Also causes Macula Densa cells to release Prostaglandins → Afferent Vasodilation)
Renin cleaves Angiotensinogen → Angiotensin I, which is in turn cleaved by Angiotensin Converting Enzyme (ACE) to form the active hormone Angiotensin II.
Angiotensin II
There are two types of Angiotensin II receptors, AT1 and AT2. They are both G-protein coupled receptors. Angiotensin II’s main actions are via the AT1 receptor
What is the action of angiotensin II?
o Vasoconstriction
• Works on vascular smooth muscle cells, increases TPR thus BP
• Vasoconstriction of afferent and efferent arteriole
o Aldosterone
• Stimulates the adrenal cortex to synthesise and release Aldosterone
• Aldosterone stimulates Na+ and therefore water reabsorption
• Acts on principal cells of CD
• Activates ENaC and apical K+ channels
• Increases basolateral Na+ extrusion via 3Na-2K-ATPase
o Sympathetic Activity
o Increase Na+ reabsorption
• Stimulates Na-H exchanger in the apical membrane of PCT
o Thirst
• Stimulates ADH release at hypothalamus
o Breaks down Bradykinin
• Bradykinin is a vasodilator
Describe the sympathetic control of ADH (Anti-Diuretic Hormone) secretion and the role of the baroreceptor
The baroreceptor reflex works well to control acute changed in BP. It produces a rapid response, but does not control sustained increases as the threshold for baroreceptor firing resets.
A 5-10% drop in blood pressure causes low-pressure baroreceptors in the atria and pulmonary vasculature to send signals to the brainstem via the vagus nerve. This activity modulates both sympathetic nerve outflow, secretion of the hormone ADH and reduction of ANP release.
A 5-150% change in blood pressure causes high-pressure baroreceptors (carotid sinus/aortic arch) to send impulses via the vagus and glossopharyngeal nerves. A decrease in blood pressure will increase sympathetic nerve activity and the secretion of ADH.
Describe the action of ADH
o Addition of Aquaporin to Collecting Duct
• Reabsorption of water
• Forms concentrated urine
• Release stimulated by increases in plasma osmolarity or severe hypovolemia
o Thick Ascending Limb
• Stimulates apical Na/K/Cl co-transporter
• Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb
Describe prostaglandins
Prostaglandins are vasodilators. Locally acting prostaglandins (mainly PGE2) enhance glomerular filtration and reduce Na+ reabsorption.
They therefore may have an important protective function by acting as a buffer to excessive vasoconstriction by the sympathetic nervous system and the RAAS.
Describe NSAID
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) inhibit the cyclo-oxygenase (COX) pathway that is involved in the formation of prostaglandins.
As prostaglandins help to maintain renal blood flow and GFR in the presence of vasoconstrictors, if NSAIDs are administered when renal perfusion is compromised (e.g. in renal disease) GFR can be further decreased, leading to acute renal failure.
In heart failure or hypertensive patients, NSAIDs can exacerbate the condition by increasing NaCl and water retention.
What is hypertension?
Hypertension is a sustained increase in blood pressure.
What is essential hypertension?
In around 95% of cases, the cause is unknown. This is known as Essential Hypertension. Genetic and environmental factors may both be involved and the pathogenesis is unclear.
What is secondary hypertension?
Where a cause can be defined, hypertension is referred to as secondary hypertension. Here it is important to treat the primary cause. Examples include: o Renovascular disease o Chronic Renal Disease o Aldosteronism o Cushing’s syndrome
What are adrenal causes of hypertension?
Conn’s Syndrome o Aldosterone secreting adenoma o Hypertension and hypokalaemia Cushing’s Syndrome o Excess cortisol o At high concentrations acts on aldosterone receptors • Na+ and water retention Pheochromocytoma o Tumour of the adrenal medulla o Secretes noradrenaline and adrenaline
How do renovascular diseases cause hypertension?
Renovascular Disease is caused by an occlusion of the renal artery, causing a fall in perfusion pressure in that kidney. Decreased perfusion leads to that kidney releasing renin and activating RAAS. Vasoconstriction and Na+ retention will then take place at the other kidney.
What are the treatments for hypertension?
o ACE Inhibitors
• Prevent the production of Angiotensin II from Angiotensin I
• Angiotensin II receptor antagonists
o Thiazide Diuretics
• Inhibit NaCC co-transporter on apical membrane of DCT
• May cause hypokalaemia (more K+ lost in urine)
o Vasodilators
• Ca2+ channel blockers, reduce Ca2+ entry into smooth muscle cells
• α1 receptor blockers, reduce sympathetic tone
o Beta Blockers
• Block β1-receptors in the heart
• Reduces heart rate and contractility
Non-pharmacological approaches to the treatment of hypertension include diet, exercise, reduced Na+ intake, reduced alcohol intake.
Describe the regulation of body fluid osmolarity in terms of responses to water deprivation and drinking
Water Intake Excretion → Plasma osmolarity decreases
The more urine is produced, the less concentrated it is.
Body fluid osmolarity is maintained by osmoregulation at about 275-295 mOsm/kg
Disorders of water balance manifest as changes in body fluid osmolarity. In contrast, problems with Na+ balance causes changes in volume.
Describe and distinguish the factors that regulate thirst and cause secretion of ADH
When a change in plasma osmolarity is sensed, it coordinates responses via two different efferent pathways, which work to concentrate urine and increase thirst respectively. You only feel thirsty at ~10% dehydration.
ADH effects the kidneys by affecting renal water excretion
Thirst has an affect on the brain and controls water intake
Where are changes in plasma osmolarity detected?
Hypothalamic Osmoreceptors located in the organum vasculoum of laminae terminalis (OVLT)
Describe the role of ADH
If plasma osmolarity increases (1% change) due to a predominant loss of water, osmoreceptors in the hypothalamus (OVLT) initiate the release of ADH from the POSTERIOR Pituitary. Similarly, decreased osmolarity inhibits ADH secretion.
It acts on the kidney to regulate the volume and osmolarity of the urine. It achieves this by increasing the permeability of the kidneys to water and urea.
ADH causes the addition of the water channel
Aquaporin-2 to the apical membrane of the nephron’s collecting duct. This allows for the reabsorption of water to decrease plasma osmolarity.
How does ADH control aquaporin 2 expression?
In the absence of ADH, apical membranes do not contain Aquaporin 2. When ADH is released it is inserted into the membrane and when ADH is removed the channel is retrieved from the apical membrane via endocytosis.
The basolateral membrane always contains Aquaporin 3 and 4, so is constantly permeable to water. This means any water that enters across the apical membrane is able to pass into the peritubular blood.
What is Urea Recycling?
ADH also increases the permeability of the medullary part of the collecting duct to urea, causing its reabsorption. This in turn causes water to follow. The rise in urea concentration in the tissues causes it to passively move down its concentration gradient into the ascending limb, which is permeable to Urea but impermeable to H2O. Urea then passes back into the collecting duct, where it is reabsorbed in the medullary portion and more water follows. Urea is therefore recycled.
Describe SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone secretion)
In SIADH the secretion of ADH is not inhibited by the lowering of blood osmolarity (negative feedback is removed).
This means that excessive amounts of water is retained, causing blood osmolarity to drop and cause hyponatremia (Low blood Na+ concentration). Symptoms of hyponatremia include nausea and vomiting, headache, confusion, lethargy, fatigue, appetite loss, restlessness and irritability, muscle weakness, spasms, cramps, seizures and decreased consciousness or coma.
If hypernatremia comes about because of SIADH the condition may be treated with ADH Receptor Antagonists.
Describe the corticopapillary osmotic gradient
At the cortico-medullary border, there is no osmotic gradient. However the medullary Intersticium is hyperosmotic up to 100 mOsmol/Kg at the papilla. There is a gradient of increasing osmolarity as you descend.
The active transport of NaCl out of the TAL and the recycling of urea sets up the osmotic gradient. The action of the TAL is crucial, removing solute without water, diluting the filtrate and increasing Intersticium osmolarity.
If you block the NaK2Cl transporters in the TAL with a loop diuretic (E.g. Furosemide) the medullary Intersticium becomes isosmotic and large amounts of dilute urine is produced.
Explain the Counter-Current Multiplication
The Loop of Henle acts as a counter current multiplier, to set up the osmotic gradient:
Tubule filled initially with isotonic fluid
Na+ ions are pumped out of the ascending loop (Na/K/2Cl co-transporter), raising the osmotic pressure outside the tubule and lowering it inside.
(Max concentration difference is 200 mOsmol/L)
Fresh fluid enters from glomerulus, and enters the descending limb. As the descending limb is permeable to water, it leaves via osmosis to raise the osmotic pressure inside the descending tubule to 400mOsmol/L.
More fluid enters from the glomerulus, pushing the concentrated (400mOsmol/L) fluid into the ascending limb.
The Na+ pump then produces another 200 mOsmol/L gradient across the membrane.
But it started with a more concentrated solution (400mOsmol/L).
So external osmolarity rises to 500mOsmol/L.
This happens again, rising the external osmolarity to 700mOsmol/L.
The final gradient will be limited by the diffusional process.
What is the counter current exchange?
The concentration gradient that the loop of Henle sets up would not last long though without the Vasa Recta.
These are blood vessels that run alongside the loops, but with opposite flow direction. This counter-current flow allows for the maintenance of the concentration gradient.
Isosmotic blood in the descending limb of the vasa recta enters the hyperosmotic milieu of the medulla, where there is a high concentration of ions (Na+, Cl-, Urea). These ions therefore diffuse into the vasa recta and water diffuses out.
The osmolarity of the blood in the vasa recta increases as it reaches the tip of the hairpin loop, where it is isosmotic with the medullary Intersticium.
Blood ascending towards the cortex will have a higher solute content than the surrounding Intersticium, so solutes move back out. Water will also move back in from the descending limb of the loop of Henle.
Therefore, although there is a large amount of fluid and solute exchange across the vasa recta, there is little net dilution of the concentration of the interstitial fluid because of the U shape of the vasa recta allowing it to act as a counter current exchanger.
The vasa recta therefore do not create the medullary hyperosmolarity, but do prevent it from being dissipated.
Explain the significance of maintaining serum calcium levels within set limits
Calcium plays a critical role in many cellular processes:
◦Hormone secretion ◦Nerve conduction ◦Inactivation/activation of enzymes ◦Muscle contraction ◦Exocytosis
Therefore, the body very carefully regulates the plasma concentration of free ionised calcium ([Ca2+]), the physiologically active form of the metal, and maintains free plasma [Ca2+] within a narrow range (1.0 - 1.3mmol/L).
In plasma, calcium exists as:
◦Free ionised species – 45% (Active Form)
◦Protein Bound – 45%(80% to Albumin)
◦Complexed– 10% (Citrates, phosphate etc)
