What is the main cation in intracellular fluid?
What is the main cation in extracellular fluid?
What nervous system supplies the kidney?
Sympathetic nervous system.
Blood pressure within the capillaries of the glomeruli is
a. High, because:
- The capillaries arise directly from the renal artery which in turn comes straight from the dorsal aorta. The dorsal aorta carries blood under high pressure from the heart.
- The efferent arteriole can constrict and limit the outflow of blood from the glomerulus. The action has the effect of raising the blood pressure.
What controls the constriction of the efferent arterioles that carry oxygenated, waste-free blood away from the glomerulus into the rest of the renal tubules?
Renin is produced by granulosa cells in the smooth muscle of the afferent arteriole entering the glomerulus in response to low blood pressure.
What does ultra-filtration refer to?
Formation of glomerular filtrate or primitive urine. The glomerular filtrate consists of 99% water and 1% chemical solutes.
High pressure in the glomerulus forces fluid out of the blood and through the basement membrane of the glomerular capsule. The fluid is known as glomerular filtrate.
The passage of large sized particles such as blood cells or plasma proteins is restricted by the size of the pores in the basement membrane. Any molecules which are bound to protein molecules, such as hormones and calcium ions, are also held back by this selective filter.
What are the main functions of the proximal convoluted tubule?
Reabsorb glucose, water and sodium (Na+) from the filtrate back into the body's fluid compartments
Secrete toxins and certain drugs in the filtrate
Concentrate nitrogenous waste - principally urea
What percentage of all reabsorption in the kidney takes place in the PCT?
The glomerular filtrate, or ultrafiltrate, is xx with plasma.
This occurs because 65% of the total water in the filtrate is reabsorbed into the ECF by osmosis creating equal concentrations between the lumen of the proximal convoluted tubule and the blood.
Fluid in blood plasma is:
a. Intracellular fluid
b. Interstitial fluid
c. Transcellular fluid
d. Extracellular fluid
Blood plasma refers to the fluid AROUND BLOOD CELLS. Thus, it is:
d. Extracellular fluid
Interstitial fluid refers to fluid that surrounds cells OUTSIDE of the blood-vascular system.
Transcellular fluid is formed by active secretory membranes and includes cerebro-spinal fluid, gastro-intestinal secretions and synovial fluid.
Where does reabsorption of glucose from filtrate occur in the kidney nephron?
What percentage of NaCl in the glomerular filtrate is reabsorbed into the bloodstream from the PCT via the capillaries?
Where in the kidney parenchyma does the bulk of the descending Loop of Henle lie?
Concentration or Dilution?
What happens to urine in the descending Loop of Henle?
Water is drawn out of urine in the descending Loop of Henle by osmosis because the surrounding Medulla is filled with Na++ from being actively pumped out by the ascending Loop of Henle further alone in the nephron.
(This is part of the Counter-current Multiplier)
The walls of the descending Loop of Henle:
a. are impermeable to water
b. are permeable to water
c. actively pump sodium & chloride ions out the urine into the renal medulla
d. absorb water from the bloodstream by osmosis
b. The descending limb of the Loop of Henle is permeable to water, which is drawn out of the urine in the lumen into the medulla by sodium & chloride ions that were pumped out from the ascending limb further along the Loop.
As a result of the X-current multiplier in the kidney, is the urine LEAVING the descending Loop of Henle dilute or concentrated?
The descending limb is PERMEABLE to water, which is drawn out by osmosis into the renal medulla by the sodium & chloride ions that are actively pumped out of the urine from the ascending limb further along the Loop of Henle.
The urine is at its most concentrated at the bottom of the loop, before it enters the ascending limb.
Urine leaving the ascending limb of the Loop of Henle becomes:
a) more dilute
b) more concentrated
c) lower in volume
d) greater in volume
a & c
As the highly concentrated urine enters the ascending limb from the bottom of the loop, sodium & chloride ions are actively pumped out into the surrounding renal medulla, so the urine becomes more dilute (less concentrated).
However, the ascending limb is IMPERMEABLE to water, so none of the water that was drawn out from the urine in the descending limb earlier along the Loop of Henle will re-enter the lumen. Instead, that water in the medulla enters the capillary system, into the blood, and is conserved in the body. The total urine volume has been reduced.
What happens to urine as it leaves the Loop of Henle & enters the collecting ducts?
The urine becomes more concentrated in the collecting ducts, as the tubules pass through the renal medulla, where the solute content (Na++, Cl+ & K+) is higher in the interstitial fluid than it is in the urine. Water flows out into of the collecting tubules by osmosis.
Where does urine go after it leaves the ascending limb of the Loop of Henle? What happens in this portion of the renal tubule/nephron?
Urine enters the DCT after the Loop of Henle.
Under control of aldosterone secretion by the adrenal cortex (zona glomerulosa), the DCT makes final adjustments to the chemical makeup of the urine relative to the blood plasma and ECF. These adjustments are made by:
1. Reabsorption of sodium (NaK+) ions into capillaries/blood
2. Excretion of potassium (K+) ions into urine
3. Regulation of acid/base balance by the excretion of hydrogen (H+) ions into urine
Note that here, urine becomes MORE ACIDIC, as potassium and hydrogen ions are kicked out as sodium is retained. NB sodium can only be retained under control by aldosterone.
In the DCT, under control of aldosterone, Na++ and K+ are reabsorbed into the blood from the urine, while K+ & H+ are "kicked out" (secreted) back out into the urine, which is a way of moderating acid-base balance.
When the Na++ & K+ are re-absorbed into the blood, does water follow, further concentrating the urine in the DCT?
No. Water does NOT follow in this case as the DCT is impermeable to water.
Both the DCT & the preceding ascending limb of the Loop of Henle are impermeable to water, allowing for adjustments of chemical content of urine.
In the DCT, hydrogen ions are secreted from the blood plasma into the urine, in response to what?
pH. The lower the pH (more acidic), the more H+ will be secreted into urine.
If an animal's respiration rate is reduced, what would you expect to happen in the Distal Convulated Tubule?
If respiration is reduced, CO2 concentration in blood plasma would increase, so pH would decrease (the blood is more acidic).
This would induce the distal convoluted tubule to excrete more H+ into the lumen from the blood to cause an increase in plasma pH.
Where does urine go between the distal convoluted tubule and the bladder?
Collecting ducts, then the pyramids, then the pelvis, ureter and bladder.
What is the main control of water permeability in the collecting ducts?
b & c - ADH (anti-diuretic hormone) & vasopressin are the same thing. ADH is a peptide hormone secreted by the posterior pituitary gland in response to falling blood pressure in capillaries, detected by pressure sensors (baroreceptors) in the heart or osmoreceptors in the .
ADH causes the collecting ducts, which like the DCT & the ascending limb of the Loop of Henle, are normally IMPERMEABLE to water, to become PERMEABLE, with the insertion of integral-membrane proteins called aquaporins, or water channels.
Aquaporins selectively conduct water molecules in and out of the cell, while preventing the passage of ions and other solutes.
Renin, secreted by smooth-muscle cells of the afferent arterioles of the glomeruli, sets in motion the RAAS, which causes sodium- and water-retention in the DCT with the release of aldosterone from the adrenal cortex. This works in conjunction with the actions of ADH, but is not part of the same mechanism of action.
In the water-impermeable DCT, how does aldosterone cause water-reabsortion into the bloodstream from the urine, in response to dehydration/falling blood pressure?
Aldosterone upregulates ENaC (epithelial sodium channels) AND basolateral Na+/K+ pumps, which pumps three sodium ions out of the DCT cell into blood and two potassium ions into the cell.
ENaC is a constitutively active ion-channel.
Pumps are basolateral = move sodium out of cell into bloodstream (base of DCT cell flanks capillaries), move potassium from bloodstream into DCT cell
ENaCs are apical = move sodium out of urine into DCT cell (apex of DCT cell faces lumen); water follows
NB aldosterone has similar effects in the collecting tubules.
For every 100 liters of filtrate passing through the glomerulus, how much is excreted as urine?
1 liter. Ie., 1%.
Where are baroreceptors located and what to do they monitor?
Baroreceptors monitor the levels of arterial blood pressure. Baroreceptors are found in the walls of blood vessels, eg. the carotid artery.
Activity in the baroreceptors decreases if blood pressure falls and increases if blood pressure rises.
Where are osmoreceptors located and what do they monitor?
Osmoreceptors monitor the osmotic pressure of the blood plasma and influence the production of ADH from the posterior pituitary gland.
Osmoreceptors are located within the hypothalamus of the brain.
What happens to blood pressure and osmotic concentration in blood as a result of dehydration?
Blood pressure falls.
Osmotic concentration increases.
What percentage of kidney nephrons become non-functional before clinical disease can be seen?
Within the liver, ammonia combines with carbon dioxide in a series of reactions known as xx cycle, and urea is formed.
a) Oxidative Deamination
c) Ornithine aka Urea
c) Ornithine Cycle, or Urea Cycle
What are the three main compensatory mechanisms that work to maintain the acid base balance in the body?
1. The buffer system within the blood plasma
2. Respiration - controls the levels of carbon dioxide in the body
3. The kidney and the Na+/H+ interchange
What are the four main buffers in the blood plasma system that can absorb or give off H+ ions to keep the pH within normal limits?
1. bicarbonate ions
2. phosphate ions
3. haemoglobin (Hb)
4. plasma proteins
In the bladder sphincter, there are two layers of muscle, the inner and outer. What type of muscle are they and what are they under somatic or autonomous nervous control?
Inner layer is smooth muscle under autonomous control.
Outer layer is skeletal muscle under somatic control.
What are the differences between the urethra in the male cat & male dog.
Urethra penetrated by prostate gland & vas deferens.
Urethra is in two parts: pelvic part & penile part, which extends to the outside along the length of penis.
Urethra penetrated by bulbourethral glands & vas deferens.
Doesn't have penile urethra, just pelvic urethra.
What is the reflex process (non-voluntary) of micturition?
1. Bladder fills with urine from kidney ureters.
2. Transitional cells slide and expand, smooth muscle stretches/distends.
3. Stretch receptors in bladder wall stimulated, triggering reflex centers in spinal cord.
4. Parasympathetic nerves in sacral region of spinal cord stimulated, cause relaxation of bladder sphincter's inner layer of smooth muscle.
5. Urine expelled.
What would the specific gravity (concentration) of urine be in an animal suffering from Diabetes insipidus?
Specific gravity would be LOW because the animal would be unable to concentrate its urine.
Diabetes insipidus results from a lack of ADH, either due to a lack of secretion by the pituitary gland (Central Diabetes Insipidus - can be treated with synthetic ADH called Desmopressin, via nasal spray or eyedrops), or problem with collecting tubules in responding to ADH (Nephrogenic Diabetes Insipidus - not treatable).
ADH upregulates aquaporins in collecting ducts, which make the ducts permeable to water. Water would flow from urine across basolateral membrane into capillaries and ECF, enabling concentration of urine. Thus, a lack of ADH renders the collecting ducts impermeable to water, so urine would be excreted without the final concentration that occurs in the collecting ducts in the presence of ADH.
What are the factors that influence Glomerular Filtration Rate (GFR)?
1. Mesangial-cell relaxation or contraction:
Mesangial cells are smooth-muscle cells that increase and decrease surface area of the capillaries within in the glomerulus. When they relax, they allow the capillaries to expand, increasing surface area and thus increasing GFR. When they contract, they decrease glomerular S.A. and thus decrease GFR.
NB mesangial cells are also immune cells involved in phagocytosis. They phagocytize glomerular basal lamina components and immunoglobulins. They are an unusual example of phagocytic cells derived from smooth muscle and not monocytes. Mesangial cells aid neutrophils in removing other mesangial cells undergoing apoptosis and also other debris in the glomerulus.
2. Renal blood flow:
(Afferent arteriole and Efferent arteriole constriction or dilation)
Pressure in the renal artery, which is a short branch off the aorta & enters the kidney at the renal hilus, is roughly equal to systemic blood pressure. Blood flowing through the kidney encounters the most vascular resistance in the interlobar arteries, afferent arterioles & efferent arterioles.
Afferent arteriole dilation + Efferent arteriole constriction = increased GFR
Afferent arteriole constriction + Efferent arteriole dilation = decreased GFR
3. Blockage in renal tubules or in urinary tract:
decreases GFR, eg., struvite crystals, uritholiasis
What is renal autoregulation?
Built-in system to keep blood flow (basically GFR) relatively constant throughout the kidney, compensating for changes in systemic blood pressure by altering resistance. Otherwise the GFR would change everytime our BP dropped from standing up rapidly, etc.
This intrinsic moderation seems to operate when BP is between 80 mmHg - 180 mmHg. Ie., below 80 mmHg, a tiny bump up in renal BP leads to a big ↑ GFR & renal plasma flow (RPF) but between the 80-180 range, GFR says relatively stable despite large increase in renal blood pressure.
- Mechanism not very well-known, two theories proposed to explain the phenomenon:
i) myogenic - greater stretch of blood vessels via increase in arterial pressure causes bigger rebound due to elasticity of vascular smooth muscle; rebound makes vessel smaller, therefore returning flow to normal;
ii) tubuloglomerular feedback - the macula densa in the juxtaglomerula apparatus (around the distal tubule) somehow sense a change in the tubular flow or some kind of factor in the filtrate, such as NaCl reabsorption, or renin?) and sends a signal that alters GFR.
What are the three main cell layers involved in ultrafiltration between the capillaries of the glomerulus and lumen of Bowman's capsule?
1. Endothelial cells with fenestrae - line the capillaries inside the glomerulus, limiting RBCs and molecules larger than 4 nm from diffusing through.
2. Basement membrane aka filtration barrier - sandwiched between the capillaries' endothelial-cell layer and the visceral layer of the capsule ie. the external epithelial cells. Acellular, comprised mainly of collagen and glycoproteins that have negative charge and thus repel negatively charged molecules from getting through to the filtrate. This is the main filtration barrier that restricts proteins.
3. Single visceral (outer) epithelial layer lining the capsule is distinguished by podocytes, which have phagocytosis capability and restrict passage of medium-sized molecules such as plasma proteins. Podocytes stand upon branched pedicels (“foot processes”), which rest on the filtration membrane. Between adjacent pedicels are gaps called ￼filtration slits that permit free passage of fluid into Bowman’s space.
What percentage of total renal plasma flow ends up as ultrafiltrate through filtration by the glomeruli (in Bowman's Capsule)?
Ie., Only 20% of the Renal Plasma Flow (RPF) ends up in the GFR (glomerular filtration rate)
The remaining 500 ml/min remain in the blood & enter into the peritubular capillaries; the blood basically enters the glomerulus via the capillaries but nothing gets filtered out into the tubules, so it just passes through back out of the efferent arterioles and then into the peri-tubular capillaries.
In determining (calculating) glomerular filtration rate, certain markers are used.
What are FOUR of these markers?
2. PAH (Para-amino hippuric acid)
3. Glucose or Alanine
What are the properties, clearance rate and limitations of using the substance Inulin as a marker to calculate Glomerular Filtration Rate?
All filtered inulin ends up in urine
Not reabsorbed or secreted
If 625 ml plasma enters glomerulus in one minute, & 125 ml (20%) of that is filtered, then 125 ml/min = clearance rate of inulin = GFR. The inulin in the remaining 500 ml stays in the blood because it isn’t secreted.
Inulin isn't naturally found in the body
What are the properties & clearance rate of glucose or alanine in their use to calculate GFR?
No glucose or alanine are excreted as urine (ie., they are saved)
0 ml/min because no plasma has its glucose removed into urine as it passes through the kidney (unless there's a diabetes situation)
What are the properties and clearance of PAH when it's used to determine GFR? PAH is para-amino hippuric acid.
All PAH entering kidney - filtered & not filtered - ends up in urine
** unlike inulin, it is completely secreted, so whatever doesn't get filtered in the glomerulus gets added back to the urine via secretion from the paratubular capillaries.
625 ml/min = Renal Plasma Flow (RPF)
What is are the properties & clearance rate of urea when it's used as a marker to calculate GFR?
What develops from the mesonephric duct?
The mesonephric ducts are also known as the Wolffian ducts; they are paired organs found in mammals during embryogenesis.
It connects the primitive kidney, mesonephros, to the cloaca, and serves as the precursor for the epididymis, the vas deferens, and the seminal vesicle in the male mammal. An outgrowth of the mesonephric duct becomes the liver.
In both the male and the female, the Wolffian duct develops into the trigone of urinary bladder, a part of the bladder wall.
In a male, it develops into the epididymis, the vas deferens, and the seminal vesicle. It is critical that the ducts are exposed to testosterone during embryogenesis.
In the female, in the absence of testosterone support, the Wolffian duct regresses.
What two types of embryonic tissue give rise to the kidney's nephrons, collecting ducts and ureters?
1. Metanephrogenic blastema gives rise to the nephrons & part of the collecting-ducts system. The renal corpuscles and renal tubules are developed from the metanephrogenic blastema instead of from the ureteric bud. The metanephrogenic blastema is moulded over the growing end of the ureteric bud, and becomes a part of the metanephros in this way. The renal tubules of the metanephros, unlike those of the pronephros and mesonephros, do not open into the Wolffian duct. Instead, the tubules rapidly elongate to form the parts of the nephron: the proximal tubules, the loops of Henle and the distal convoluted tubules. These last join and establish communications with the collecting duct system derived from the ultimate ramifications of the ureteric bud. In the other end, the renal tubules give rise to Bowman's capsules and glomeruli.
2. Ureteric bud, also known as the metanephrogenic diverticulum, is a protrusion from the mesonephric duct (aka Wolffian duct) during the development. Each kidney originate as an ureteric bud from the caudal end of the Wolffian duct. The ureteric bud starts close to where the Wolffian duct opens into the cloaca, and grows dorsalward and rostralward along the posterior abdominal wall, where its blind extremity expands and subsequently divides into several buds, which form the rudiments of the renal pelvis and renal calyces; by continued growth and subdivision it gives rise to the collecting duct system of the kidney. The other, more superficial, portion of the diverticulum, on the other hand, becomes the ureter.
How is the bladder formed from the cloaca & mesonephric ducts?
The urinary bladder is formed partly from the cloaca and partly from the ends of the Wolffian ducts aka mesonephric ducts. In other words, the allantois takes no share in its formation.
The bladder is formed initially by the division of the cloaca into dorsal and ventral regions by the urorectal septum.
The dorsal region becomes the rectum, while the ventral region becomes the urogenital sinus, which is further divided into cranial and caudal regions.
The cranial region of the UG becomes the vesico-urethro canal, where the bladder develops from the endodermal layer of the UG, while the caudal region becomes the caudal urogenital sinus that leads to the urethra & vagina in the female animal and the urethra, prostate & bulbourethal glands & external genitalia in the male animal.
Where does most of the secretion of potassium ions take place in the nephron? How many sodium ions are pumped out of the DCT cell back into the blood and how many potassium ions are taken into the cell from the blood?
Potassium secretion mostly occurs in the distal convoluted tubule via sodium-potassium pumps aka Na-K-ATPase pumps in the basolateral membrane of DCT cells (ie., the part of the cells that flank the capillaries as opposed to those that face toward the DCT lumen).
Both sodium and potassium are reabsorbed initially from filtrate into the blood plasma, but then at the basolateral membrane, the Na-K pumps three sodium ions back across the membrane into the bloodstream while taking in two potassium ions into the DCT cell.
The K+ cell then exits at the apical side of the cell through K+ channels into the urine.
What is the mechanism of the Na2+-K+-ATPase pump? How is it regulated?
1. The pump, while binding ATP, binds 3 intracellular Na+ ions (ie., three sodium ions that have entered the DCT cell from the urine)
2. ATP is hydrolyzed, leading to phosphorylation of the pump at a highly conserved aspartate residue and subsequent release of ADP. Ie., ATP phosphorylates the pump & becomes ADP.
3. A conformational change in the pump exposes the Na+ ions to the outside of the DCT cell (at the basolateral, capillary-flanking side). The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released & go into the blood.
4. The pump binds 2 extracellular K+ ions, ie., from the blood. This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell.
5. The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released into the DCT cell, where they will exit at the apical side into the urine via K+ channels.
6. ATP binds, and the process starts again.
What affect does an increase in potassium concentration in plasma have on aldosterone secretion?
Changes in [K+] directly affects aldosterone secretion.
It is a negative feedback mechanism.
A sharp increase of potassium concentration in blood would suggest a low sodium concentration, so more aldosterone would be secreted to cause more sodium retention.
A sharp decrease in potassium concentration in blood would causes less release of aldosterone so that less K+ is secreted and excreted, and thus less Na+ and water are reabsorbed in the collecting tubules.
This differs from sodium plasma levels, which do not have a DIRECT effect on aldosterone secretion, but only an indirect effect via RAAS.
What is urea recycling in the kidney?
It's a bit like the cross-current multiplier.
In the MEDULLARY part of the collecting ducts, where water goes back out to the blood stream and ECF via aquaporins under control of ADH, some of the urea that gets left behind in the filtrate flows via filtration into the medullary space. Like other solutes, this increases the osmolarity in the space.
Further ahead in the nephron, some of the urea in the medullary space/interstitial fluid flows into the filtrate in both limbs of the Loop of Henle.
The urea stays in the filtrate all the way through the DCT & the cortical portion of the collecting ducts, because those parts of the nephron are IMPERMEABLE to urea.
When the filtrate/urine goes back down into the medullary portion of the collecting ducts, some of it leaves again into the intersitial space/medullary space, and so the cycle goes.