Renal urinary Flashcards
What are the three main functions of the kidneys?
1) excretion
2) endocrine organ
3) homeostasis
The kidney excretes products that need to be retained, and waste products to be discarted. Why take this approach and not just eliminate the waste product?
Two reasonds;
1) Speed; dumping everything out and then taking back what is needed is fast, and toxins can be eliminated in as little as 30 min
2) selectivity; it is more efficient to have a limited number of receptors to reabsorb the limited amount of things you need to retain, rather than have an near infinite nuber of receptors to excrete the near infinite number of toxins/metabolites etc that need to be waisted
What is the total energy use of the kidneys and why is it so low?
~10% of daily total body energy consumption (heart is ~7%). This is so low, because the kidneys use osmotic gradients to control water retention/excretion which do not require ATP
What occurs in the cortex and the medulla of the kidney ?
Cortex contains the glomeruli where blood filtration occurs. The medulla contains the nephrons which are responsive for re-absorbtion of products.
What is acute interstitial nephritis?
Inflammatory condition affecting the renal interstitium.
Symptoms may include an acute rise in plasma creatinine levels and
proteinuria (protein in urine), both reflecting a general renal dysfunction.
What are causes of acute interstitial nephritis? Is this reversible?
AIN usually results from drug exposure, -lactam antibiotics (e.g., penicil-
lin and methicillin) being the most common offenders. 1 Kidneys typically
recover normal function after discontinuing drug use.
What is polycystic kidney disease?
inherited disorder characterized by the presence of
innumerable fluid-filled cysts within the kidneys and, to a lesser degree,
the liver and pancreas. The cysts form within the nephron and progres-
sively enlarge and compress the surrounding tissues, preventing fl uid
flow through the tubules.
Symptoms associated with polycystic kidney disease?
many patients remain asymptomatic,
others may begin to show symptoms of impaired renal function such as
hypertension. Elevation in crea and BUN can result in innapetence, nausea and weight loss.
What is the treatment for polycystic kidney disease?
There is no treatment
What is the difference in tissue osmolarity between the different regions of the kidney and why the difference?
The cortex has an osmolality that approximates that of plasma, but the osmolality
of the inner medulla is increased severalfold. This osmotic gradient is essential to normal kidney function because it is used to recover virtually all of the water that is filtered from the vasculature each day
Which vascular networks are responsible for blod filtration and reabsorbtion
1) filtration; Glomerular capillary network
2) peritubular capillary network
Describe the glomerular capillary network of the kidney
Blood enters the glomerulus via an interlobular artery. Blood passes down at high pressue (~60mmHg) into the afferent arteriole that pases this into a tuft of specialised glomerular arteries. The glomerular arteries are porous, and anastamose to one another to maximise the filtration surface area. Spaces between the capillaris are filled with mesangial cells, an epithelial cell that can contracts and relaxes as a way of controlling glomerular capillary surface area and filtration rate. Blood leaves the glomerular capillariers through an efferent arteriole the leads back into an a peritubular capillary network that runds along the ascending limb of the tubule. These will then anaestamose into the peritubular veins that lead into the interlobular vein.
Where can the peritubular network be found and what are its roles?
This originates from the afferent arteriole and closely follows the renal tubule in the kidney eventulaly merging into the peritubular venous netwok
Roles include
1) providing O2 and nutrients to the tubule
2) carries away fluid and solutes that have been reabsorbed from the tubule lumen
3) prompt solute removal allows the concentration gradient to be maintained between the tubule and blood
What are the segments of the tubule (in order) ?
1) glomerulus
2) Proximal convoluted tubule (PCT)
3) proximal straight tubule (PST)
4) Descending thin limb
5) ascending thin limb
6) loop of henle
7) Ascending thick limb
8) distal convoluted tubule
9) cortical collecting duct
10) outer medullary collecting dusct
11) inner medulalry colelecting duct
Do juctamedullary and superficial nephrons interact ?
The connect tohether at the Cortical collecting duct of via the connecting tubule that lins the aformentioned with the distal convoluted tubule of the superficial nephron
what is the renal corpuscle and where is it located?
Glomerulus + bowmans capsule. Located in the cortex of the kidney
What is the bowmans space?
Filtrate from the glomerular capillaries filters into the bowmans space, which then enters the proximal tubule
Draw the layout of the nephron throughout the kidney layers
What are the differences between superficial and juxtaglomerular nephrons?
Superficial;
- receive 90% of renal blood supply
- reabsorb the majority of the filtrate
- glmeruli are in the cortex and they have short nephrons
- loops dip into the outer medulla but not medulla
Juxtaglomerular:
- receive 10% of blood
- glomeruli located in th einner cortex
- long nephron loops that dive into the inner medulla.
- have a specialised peritubular network
- juxtamedullary neprons plus the capillaries that follow dive deep into the medulla and form the vasa recta
- juxtamedullary nephrons are designed to concentrate urine
In the kidney what are the forces hat promote fluid filtration and retention?
1) filtration - capillary hydrostatic pressure (Pgc)
2) Colloing osmotic pressure (πgc)
what happens if capillary hydrostatic pressure increases?
increased urine production up until the point where we have hypertensive damage
What is the force that governs fluid movement accross the glomerular capillary wall and what is the formula?
Starling equation
GFR= Kf[(Pgc-Pbs)-(πgc-πbs)]
Kf= glomerular filtration coeficient
Pbs and πbs; are hydrostatic and colloid osmotic pressure of fluid in the bowmans space)
What is Kf in the starling equation ?
Filtration coeficient. Representation of the filtration ability of the filtrate barrier. It is a measure of glomerular permeability and the surface area
What is the filtrate barrier and what layers is it made of?
There are 3 layers, which create a 3 step molecular filter which produces protein and cell free plasma ultrafiltate. The three layers are;
1) Capillary endothelial membrane
2) Thick glomerular basement membrane
3) filtration slit diaphram
Describe the glomerular capillary endothelial membrane (of the filtrate barrier) structure and function?
Layer 1; Dense endothelial layer with fenestrations (pores of ~70nm) which allow free passage of water, solutes and proteins. Cells cannot pass and are trapped in the vasculature.
Describe the thick glomerular basement membrane structure and role (Filtration barrier)
Comprised of 3 layers (inner->outer)
1) lamina rara interna
2) lamina densa
3) lamina rara externa
The lamina rara externa if fused to podocytes.
The basement membrane has a net negative chare that repels proteins (also carry a negative charge) and reflects them back into the vasculature.
Draw a diagram of the 3 layers of the filtration barrier and its constituents
What is the filtration slit diaphragm?
Describe it
Layer 3 of the filtration barrier.
Glomerular capillaries are ensheathed in tentacle like processes from the podocytes. The podocyte tentacles, and “toes” that come off them form gaps in which a gelatinous filtration slit diaphragm lives. This filtration slit diaphram prevents proteins entering the bowmans space
Define the shifts in colloid oncotic pressure along the renal capillary network
πgc is ~25mmHg when it enters the glomerulus. This is the same as in the rest of the circulation. As water and solutes pass through into the bowmans space, protein is left behind. Blood looses 15-20% of its total volume to filtrate during passage through the capillary netweork increasing the colloid oncotic pressure to the point that this ~35mmHg when it enters the efferent arteriole
What is the colloid oncotic pressure of the bowmans space?
πbs In healthy individuals it should be 0 as proteins are prevented from entering the BS by the basement membrane and filtration diaphragm
What is the hydrostatic pressure of the bowmans space?
Pbs, is ~15mmHg due to the large veolume of fluid that enters this space from the higher driving hydrostatic pressure in the capillaries of the glomerulus (~60mmHg)
Is the hydrostatic pressure of the glomerular capillaries comparable to other capillary beds?
No, it is higher. Glomerullar Pgc is ~60mmHg, which is ~25mmHg higher than other capillary beds.
How may mesangial cells affect glomerular filtration?
Through
changes in glomerular capillary surface area, which
affects K f. The role of mesangial cells is minor com-
pared with that of glomerular arterioles, however
What are the main factors that regulate GFR?
Pgc, which is determined by the aortic pressure, renal arterial pressure and by changes in afferent and efferent vascular resistance
How does vasocontriction/dilation of the afferent arteriole affect GFR and ultrafiltrate pressure (Puf) ?
It reduces GFR and Puf. This is because contriction decreases glomerular blood flow. Dilation is the opposite
How does efferent arteriolar constriction/dilation affect GFR/Puf?
Constriction increaseds vascular resistance and increases pressure of the glomerular blood increasing GFR and Puf. Dilation reduces pressure and allows blood to flow out of the network faster reducing GFR and Puf.
What are the two main mechanisms that regulate renal blood flow (RBF) and GFR ?
1) Local vascular autoregulation; maintain RBF and optimise GFR
2) Central homeostatic control; Occurs through the atonomic nervous system can overide the local control and it will do so to adjust vlood volume and blood pressure.
What are the regulatory systems in the kidney and what are their roles;
1) Autoregulation;
2) Myogenic response
3) Tubuloglomerular
4) Paracrine
5) Central
what is the pathophysiology of disease behind glomerular disease?
Glomerular disease damages the filtration barrier and
increases Kf, thereby allowing cells and proteins to pass into the tubule.
What are the two main subtupes of glomerular disease and what heps distinguish these?
Glomerular disease can be divided into two broad and overlapping syndromes based on the characteristics of proteins and cellular debris contained within urine (urine sediments) and the associated symptoms: nephritic syndrome and nephrotic syndrome
What is nephric syndrome and describe the pathophysilogy?
associated with diseases that cause inflammation of the glomerular capillaries, mesangial cells, or podocytes (glomerulonephritis). Inflammation creates localized breaches in the filtration barrier and allows cells and modest amounts of protein to escape into the tubule and appear in urine (proteinuria). Red cells typically collect and aggregate in the distal convoluted tubule and then appear in urine as tubular red cell casts
How can you identify nephrotic syndrome clinically
Nephrotic syndrome refers to a set of clinical findings that include heavy proteinuria (>3.5 g/day), ipiduria, edema, and hyperlipidemia. Cell casts, which are characteristic of an inflammatory process, are
absent
What is the pathophysiology behind nephrotic syndrome?
Nephrotic syndrome reflects a general deterioration of the renal tubule (nephrosis) that includes degradation of glomerular barrier function and is a frequent cause of mortality in patients with diabetes mellitus. Loss of plasma proteins in urine causes plasma oncotic pressure to fall and accounts for the generalized edema associated with nephrotic
syndrome. Hyperlipidemia reflects increased lipid synthesis that helps compensate for loss of lipids in urine.
How is RBF and GFR regulated by the renal tubule?
The loop of Henle comes into direct contact with the afferent and efferent arterioles after returning from the medulla. The TAL wall is modified at the contact site to form a specialized sensory region called the macula densa.
The macula densa monitors Na and Cl concentrations within the tubule lumen, which, in turn, reflect RBF and GFR. Na and Cl permeate macula densa cells via a Na-K-2Cl cotransporter located in the apical membrane. Cl immediately exitsvia a basolateral Cl channel, causing a membrane depolarization whose magnitude is a direct reflection of tubule fluid NaCl
concentration.
How are mesangial cells involved in renal autoregulation ?
Mesangial cells provide a physical pathway for communication between the sensory (macula densa) and effector (arteriole) arms of the TGF system. All cells in
the JGA are interconnected via gap junctions , which
allows for direct chemical communication between the system components.
Draw the juxtaglomerular apparatus and its constituents?
How is the afferent arteriole involved in autoregulation?
The afferent arteriole is notable for its adenosine
receptor and for renin-producing granular cells within its walls.
A) Adenosine receptor; A1 receptors are bound to a downregulatory G protein–coupled receptor -> reduces cAMP pathway. cAMP normally inhibits smooth muslce contractily via PKA. Thus when the afferent arteriole binds adenosine it constricts
B) Granular cells; secrotory cells which contain renin granules. Release rening -> RAAS increase -> increase ANGII whuc is vasoactive
How are efferent arterioles autoregulated ?
These have A2 (adenosine 2 receptors) which bind adenosine -> Gprot -> increase cAMP -> efferent arteriolar dilation
What is autoregulation as a regulatory response in the kidneys ?
- Stabilises RBF and GFR during mean arterial pressure (MAP) changes.
- GFR remains stable with MAPS between ~80-180mmHg)
What is the myogenic regulatory response?
Myogenic response
- MEchanoreceptors in the smooth muscle of afferent arterioles cause a calcium release during vascular stretching causing vascular constriction
- this myogenic response stabilises GFR and RBF during chnages in posture
What is the tubuloglomerular feedback system?
- autoregulatory mechanism mediated by the juxtaglomerular apparatus (JGA)
- Complex involves the renal tubule, mesangial cells and afferent/efferent arteioled.
- Adjusts RBF and GFR flow through th etubules
What is the role of the paracrine autoregulation ?
several hormoes are involved
- Prostaglanding and NOX; dilate glomerular arterioles and increase RBF and GFR. May be released in response to ANGII vasocostriction in shock
- Endothelins; local vasocostrictions released in responde to ANGII or when glomerular flow rates are damagingly high
-ANGII; RAAS is the primary autoregulation system which regulates RPF and GFR. ANGII is the hormonal link between GFR and blood pressure
How is RPF and GFR controlled centrally?
kidney governs total body water and Na content, which, in turn, determines blood volume and MAP. The kidney also receives 10%
of cardiac output at rest, a significant blood volume that might be used to sustain more critical circulations (e.g., cerebral and coronary
circulations) in the event of circulatory shock Renal
blood flow is, thus, subject to control by the ANS, acting through neural and neuroal and/or endocrine pathways.
What are the two central regulatory pathways which affect RBF and GFR?
1) Neural
2) endocrine
What are neural central controls?
Glomerular arterioles are innervated by noradrenergic
sympathetic terminals that activate when MAP falls. Sympathetic activation raises systemic vascular resistance by restrict ing blood flow to all vascular beds, including the kidneys. Mild sympathetic stimulation preferentially constricts the efferent arteriole, which reduces RBF while simultaneously maintaining GFR at sufficiently high levels to ensure continued kidney function. Intense sympathetic stimulation severely curtails blood flow through both glomerular arterioles, and urine formation ceases.
In cases of severe hemorrhage, prolonged occlusion of arteriolar
supply vessels can cause renal ischemia, infarction, and failure
What are the centrally controlled endocrine pathways?
Hormonal regulation of RBF is mediated principally
by epinephrine and atrial natriuretic peptide (ANP). Epinephrine is released into the circulation following sympathetic activation and stimulates the same pathways as does norepinephrine released from sympathetic nerve terminals. ANP is released from cardiac atria when they are stressed by high blood volumes. The ANP receptor has intrinsic guanylyl cyclase activity that dilates the afferent arteriole and increases RBF. It also relaxes mesan gial cells to increase filtration barrier surface area. The net result is an increase in RBF and GFR and salt and water excretion
What is the %of H2O distribution between ECF and ICF
ICF 66% (2/3)
ECF 33% (1/3)
Of the ECF, how much of the water is found in interstitial fluid and how much in plasma?
Plasma 1/4th (25%)
Interstitial fluid 3/4th (75%
What are the major cations of the ICF ?
What are the major anions of the ECF?
Cations; K, Mg
Anions; protein and organic phosphates (ATP, ADP, AMP)
What are the major cations of the ECF ?
What are the major anions of the ECF?
Cations; Na
Anions; HCO3 and Cl
What is the major difference in composition between the interstitial fluid and plasma?
The interstitial fluid has the same composition just with a lot less protein. Thus ICF is an ultrafiltrate of plasma
what is the 60-40-20 rule?
Total body water; 60%
ICF; 40% of body weight
ECF: 20% of body weight
What is osmolarity?
What is plasma osmolarity and how is it calculated?
Osmolarity = concentration of solute particles
Normal between 275-297mOsm/Kg
Pos= 2xNa + (glucose/18) + (BUN/2.8)
What occurs to osmolarity, PCV, and BP when isotonic NaCl fluid is administered to a patient?
1) osmolarity does not change even if ECF goes up as the solution is isotonic (i.e solutes do not shift between ECF and ICF)
2) PCV drops, due to the addition of diluting volume. TS drops too, because protein is diluted
3) BP increases due to the addition of intravascular volume
What happens to osmolarity, PCV/TS, an BP when you have diarrhoea?
1) ECF decreases due to volume loss, but osmolarity stays the same due to osmosis between the ECF and ICF
2) haemocrit haemoconcentrates, and TS becomes more concentrate (ie PCV increases, and TS increases)
3) BP drops due to loss of ECF
What happens to osmolarity, PCV, an BP when you have excessive Na intake ?
1) ECF colume increases because osmoles (NaCl) have been added to the ECF drawig fluid from ICF
- ICF volume decreases as a result
2) PCV and TS decrease due to volume expansion of ECF
3) BP increases due to volume expansion of the ECF
Fill in the table
What kind of volume change occurs with Syndrome of innapropriate antidiuretic hormone (SIADH)?
What changes occur with ECF osmolarity, PCV/TS, ICF osmolarity, and plasma protein concentration?
hyposmotic volume expansion
1) ECF osmolarity decreases because water is retained
2) PCV does not change because water shifts into the RBC, making them swell, offsetting the dilution
3) Plasma protein concentration decreases due to increased ECF
4) ICF osmolarity decreases as osmosis is trying to equilibrate this with the ECF
What kind of volume change occurs with adrenocortical insufficiency?
What changes occur with ECF osmolarity, ECF volume, PCV/TS, ICF osmolarity, and plasma protein concentration?
Hyposmotic volume contraction
1) osmolarity of ECF decreases; lack of aldosterone results in lack of NaCl reabsorbtion and kidneys excrete more NaCl than water
2) ECF volume decreases, while ICF increases, as water is not lost as much as NaCl, so by osmosis it entercs the cells to equilibrate ICF and ECF.
3) water entering the cells causes volume expansion
4) haematocrit increases because of decrease ECF volume and because RBC swell as a result of water entry
5) arterial BP decreases due to decrease ECF
What is the urine clearance equation ?
C=UV/P
C= clearance ml/min or ml/24h
U= urine concentration (mg/ml)
V= urine volume/time (ml/min)
P= plasma concentration (mg/ml)
How much of CO is diverted as renal blood flow?
25% of CO
What is renal blood flow proportional to ?
What is it inversely proportional to?
renal blood flow is proportional to the pressure difference between the renal artery and renal vein.
It is inversely proportional to the vascular resistance in the renal vasculature
vasocostriction of renal arterioles occurs in response to what ?
What is the effect on renal blood flow?
What affect does this have on GFR
Decreases renal blood flow.
Occurs due to sympathetic activation and angiotensin II.
Costriction increases glomerular pressure increasing GFR - this is called the protective effec
what effect do ACEi have on GFR and renal blood flow?
These dilate the afferent arteriole increasing renal blood flow but decreasing glomerular pressure. Decreasing glomerular pressure decreases GFR (hyperfiltration is increased with increased glomerular pressure)
what innate substances dilate the renal arteriole and what effect do these have on renal blood flow and GFR?
They increase renal blood flow decreasing GFR.
these are Prostaglandin E2 and I2, Bradykinin, NO, dopamine,
What effect does atrial nutriuretic peptide have on the renal arteriole and how does this affect GFR?
Dilates afferent renal arteriole, and to a lesser extent constricts efferent arteriole, increasing renal blood flow, and GFR
How is renal blood flow autoregulated?
Accomplished by changing renal vascular resistance. Two mechanisms;
1) myogenic - renal afferent arteriole contracts in response to stretch. This increased rena arterial pressure stretches the arterioles, which contract to increase resistance to maintain constant flow
2) tubuloglomerular feedback; increased renal arterial pressure increases the delivery of fluid to the macula densa. Macula densa senses an increased load and causes constriction of nearby afferent arteriole, increasing resistance
How does a high protein diet affect GFR?
Increases GFR. High protein diet results in Na and Cl reabsorption (trying to bring in more water to maintain concentration). Increased Na and Cl delivery to the macula densa results in increasing GFR via the tubuloglomerular feedback
How can GFR be measured?
Clearance of inulin test;
GFR =[Uinulin]V/[Pinulin]
V= urine flow rate (ml/min)
How do you estimate GFR with BUN and CREA
Both serum BUN and CREA increase with decreased GFR. BUN increases more than serum creatinine resulting in an increase in BUN:Crea ration (>20:1)
in pre-renal azotemia, why does BUN increase more than CREA?
Hypovolemia increases UREA reabsorption in the proximal tubule.
Vasopressin is activated with hypovolemia, increasing H2O reabsorption in the collecting ducts. This concentrates BUN, resulting in increased passive reabsorption.
What is the filtration fraction ?
The fraction of renal plasma flow accross the glomerular capillaries;
Filtration fraction =GFR/RPF
What is a normal filtration fraction?
What happens to the non-filtered faction?
0.20
This means 20% of renal plasma flow is filtered. The remaining 80% leaves the glomerular capillaries by the efferent arterioles.
what is the driving force of GFR?
the net ultrafiltration pressure accross the glomerular capillaries
fill in the table
what is the filtered load of glucose equation and what is this determined by ?
Glucose=GFRx[P]glucose
It is determined by the plasma concentration of glucose
What transporter reabsorbs glucose and what is a rate limiting step of these?
The Na-glucose cotransporter in the proximal tubule.
The limiting factor is the limited number of these transporters
What are the normal ranges for blood glucose in a dog and cat?
80-120mg/dl
However, stressed cats can go up to 300
What is Tm in glucose reabsorbtion?
It is the point at which the glucose transporters are saturated.
At what concentrations can the glucose transporters in the kidney reabsorb all the glucose and at which point are they saturated?
At 250mg/dl all glucose can be re-absorbed (in the normal kidney) as there are enough Na-Glucose transporters in the proximal tubule.
Tm (full saturation) is ~350mg/dl
What is the plasma threshold at which glucose starts appearing in the urine and why ?
The threshold is 250mg/dl. at <250mg/dl, the proximal tubule has enough Na-Glucose transporters to re-absorb all the glucose.
At what level is Tm reached by glucose in the kidney and what happens after this point with additional glucose?
Tm, is the maximum saturation point of the Na-Glucose transporters and is reached at Bg 350mg/dl. All glucose after this point is excreted in the urine
what does Tm stand for in glucose absorption?
Tm = transport maxiumum. aka the maximum amount of glucose that can be reabsorbed
what is Para-aminohippiuric acid titration curve?
PAH filtration increases in direct proportion to PAH plasma concentration.
What are the substances with the lowest clearance in the kidneys?
Protein (not usually excreted), Na, Glucose, Amino acids, HCO3 and Cl
what are substances with clearane equal to GFR?
Those that are freely filtered, but not reabsorbed or secreted - e.g. Inulin
What are the relative clearances in order of the different cations and anions in the kidney ?
PAH>K (high -K diet)> unulin>urea> Na>glucose >amino acids and HCO3
what is inulin?
a polysacharide commonly found as a plant fiber
what substences do not undergo anionic diffusion?
Nonionic diffusion occurs for weak bases and weak acids
What is the HA and A- form of weak acidsand what does this determine?
HA is an uncharged and lipid soluble weak acid, which can back diffuse from urine to blood
A- is a charged lipid insoluble weak acid which cannot back diffuse from urine to blood
what two forms of weak base are there and what are their charachteristics ?
BH+ and B.
B form is uncharged and lipid soluble and can back diffuse from urine to blood
BH is a charged and lipid-insoluble substance which cannot back diffuse from urine to blood
What weak acid and base predominates in acidic urine?
In acidic urine;
The HA form predominates - there is more back diffusion and secretion of weak acid A
The BH form predominates - there is less back diffusion, and there is increased excretion of weak base (e..g morphine can be increased in acidifying urine )
What weak acid and base predominate in alkaline urine?
A- predominates; there is less back diffusion and there is increased excretion of weak acid - e.g. salicilyc acid can be increased in alakalanizing urine
B form predominates as there is more back diffusion and there is decreased excretion of a weak base
at what point along the nephron is tubular fluid urine?
along the whole nephron
What is the TF/Px ratio ?
This compares the concentration of a substance in the tubular flud at any point along the nephron with the concentration of plasma
What do the following mean for Na;
TF/P=1.0
TF/P<1
TF/P>1
TF/P=1 ; [Na] in the plasma and tubular fluid is identical
TF/P<1; [Na] reabsorbtion has been greater than the absorbtion of water
TF/<1; [Na] absorption has been less than H2O, OR the excretion of Na has occurred.
what does TF/Pna=8.0 mean?
[Na] in the tubular fluid is 80% of [Na] in the plasma
what is TF/Pinulin mean?
Inulin is used as a marker of water reabsorption along the nephron. Inulin is increased as water is reabsorbed. As inulin moves freely (not absorbed or secreted), the concentration of this in the tubule solely depends on how much water is diluted it
What is the normal TF/Pna ?
1.0
Na is freely filtered accross the glomerular capillaries, so the [Na] in the bowmans is the same as the plasma. Na is also reabsorbed along the whole nephrons and very little is excreted
What is the equation for the Fraction of Filtered H2O Reabsorbed;
Give an example
=1 - (1)/([TF/P]inulin
How much Na is re-absorbed at each point along the nephron (annotate image)
what is the site of glomerulotubular balance for Na in the kidneys ?
This is the proximal convoluted tubule, as it is the site which absorbs the most Na compared to the rest (67%)
Annotate the receptors for Na reabsorbtion in the attached image;
Is the process of Na reabsorbtion isosmotic, hyperosmotic or hyposmotic?
What is the TF/Posm of Na?
Isosmotic, as Na and H2O reabsortion in the proximal tubule are exactly proportional. Therefore, TF/Pna=1 and TF/Posm=1
What are the special features of the EARLY proximal tubule ?
1) Reabsorbs Na, H2O, HCO3, glucose, AA, phosphate and lactate
2) Na is reabsorbed by cotransport with Glucose, AA, phosphate and lactate
3) Na is reabsorbed by countertransport via Na-H exchanger, whih is linked directly to the reabsorption of filterd HCO3
4) Carbonic anyhydrase inhibitors (e.g. acetazolamide) are diuretics that act o the proximal tubule by inhibiting reabsorbtion of filtered HCO3
What is acetazolamide and what is its role?
Carbonic anyhydrase inhibitors (e.g. acetazolamide) are diuretics that act on the proximal tubule by inhibiting reabsorption of filtered HCO3
What are the special features of the LATE proximal tubule
Na is reabsorbed with Cl-
what is the glomerulotubular balance in the proximal tubule?
Give an example if GFR increases;
Maintains a constant fractional reabsorbtion (2/3rd -67%) of the filtered Na and H2O
e.g. if GFR inceases, filtered Na load also increases. However, the glomerulotubular balance functions such tha Na reabsorbtion will also be increased, otherwise, more Na would be lost
what is the mechanism of glomerotubular balance based on?
Starling forces in the peritubular capillareis, which alter reabsorbtion of Na and H2O in in proximal tubule
What effect does ECF volume contraction have on reabsorption?
Increases fluid reabsorption; volume contraction increases peritubular capillary protein concentration (πc) and decreases Pc of the peritubular capillary blood. These two result in increased proximal tubular reabsorption
what is πc stand for in regards to staring forces in the peritubular blood network of the kidney?
what does low and high πc result in
πc - protein oncotic pressure
High πc -fluid reabsorbtion
Low πc - fluid excretion
This is done to maintain homeostasis as high πc is consistent with protein concentration and hypovolemia
what is Pc in the peritubular blood network of the kidney?
what does low and high Pc result in
Capillary hydrostatic pressure
What effect does ECF volume expansion have on re-absorption?
It will decrease πc and increase Pc resulting DECREASED peritubular reabsorption
TF/P of various substances changes along the length of the proximal tubule. Annote the following image;
Na reabsorption is always proportional to H2O (i.e. TF/P =1), so it is a level line. Inulin is not absorbed, so its concentration grows steadily. Most glucose and amino acids are absorbed in the early portion of the proximal tubule so it drop off fast. In the proximal tubule, Cl is proportionally abdorbed less than H2O and mostly occurs in the late tubule so its concentration initially increases
Annotate the exchangers of the thick ascending limb cell
What are the key features of the cells of the thick ascending limb of the loop of henle?
- reabsorbs 25% of filtered Na
- contains the Na-K-2Cl cotransporter in the luminal membrane
- site of loop diuretic action -> inhibit Na-K-2Cl
- impermeable to water, thus NaCl is reabsorbed without water
- lumen has a positive potential difference. although Na-K-2Cl appears electronicaly neutral, some K diffuses back into the lumen making it electronically positive
Why is the thick ascending loop of henle known as the diluting segment?
impermeable to water thus, NaCl is reabsorbed without water. As a result, tubular osmolarity decreases to less than their concentrations in the plasma (TF/PNa and TF/Posm <1.0)
Whar ae key features of the tubule and collecting duct?
Divide the answer into early and late distal tubule +collecting duct
Reabsorb 8% of filtered Na together
Early;
- Reabsorbs NaCl by Na-Cl cotransporter
- site of action of thiazides
- impermeable to water (also diluting segment like thick ascending)
- called the corticula diluting segment
Late +collecting duct
- Principal cells;
- reabsorb Na and H2O and secrete K
- alpha intercalated;
- secrete H+ by H-ATPase (stimulated by aldosterone)
- Reabsorb K by an H,K ATPase
what hormones act on the principal cells and what do they do;
Aldosterone; increases Na reabsorbtion and K secretion
Antidiuretic hormone; Increases H2O permeability by depositing aquaporins 2 (AQP2) H2O channels in the luminal membrane
K-sparing diuretics (spironolactone) –> decrease K secretion
Only under certain conditions can the late distal tubule and collecting duct re-absorb water. What allows for re-absorbtion ?
When Antidiuretic hormone is upregulated (or vasopressin is given), we have deposition of aquaporin in two channels in the luminal side of the distal tubule and collecting duct. Without this, this region is not able to reabsorb water
Examples of K sparing diuretics;
- spironolactone
- Tramterene
- Amiloride
examples of loop diuretics
- torsemide
- furosemide
- bumetanide
- ethacrynic acid
what receptor is blocked by thiazide diuretics?
NaCl transporter in the early distal tubule
Annotate the early distal tubule transporters
Complete the following table
Annotate the nephron showing the amount of K excreted
What does a shift of K out of the cells cause?
what about a shift into the cells?
Shift out causes hyperkalaemia
Shift into causes hypokalaemia (or loss)
When is K balance achieved?
When urinary excretion of K exactly equals intake of K in the diet
Excretion of K can vary from 1% to 110%. What does this depend on?
- Diet intake (appropriate or excessive)
- Aldosterone levels
- insulin levels (hyperglycaemia sequesters this into the cell from the ECF)
- Acid: base status
How is K excreted into the lumen of the nephron?
What is the TF/Pk
Filtration occurs freely accross the bowman space
TF/Pk=1
Where is K reabsorbed and in what percentages?
What is it cotransported with in these locations?
- proximal tubule 67% (along with Na and H2O)
- Thick ascending 20% (involves the Na:K:Cl cotransporter)
- Distal tubule and collecting duct (ether absorb the rest or excrete depending on dietary intake)
- H; KATPase in alpha-intercalated cells
If excess K is eaten, how is this excreted into the lumen of the nephron
- passive filtration accross the bowmans capsule, but if TF/P>1 with this then, H:K ATPase in the late part of the distal convoluted tubule activate, and the principal cells of the early distal convoluted tubule also activate
Once upregulated, how long does aldosterone take to increase Na reabsorbtion and why?
Takes several hours.
This is a hormone which needs to synthesise new Na channels (ENaC)
How much Na reabsorbiton is done by aldosterone?
~2%
What are the mechanisms of distal K secretion ?
- basolateral membrane Na-K pump actively pump K into the principal cell of the distal tubule (this allows for high intracellular K concentrations )
- luminal membrane K passively secreted into the lumen through K channels. The magnitude of this is driven by the chemical and electrical driving force of K accross the luminal membrane
List the 6 factors that drive distal K secretion ?
1) Dietary intake
2) Aldosterone
3) Acid-base
4) loop diuretic /thiazide diuretics
5) K sparing diuretics
6) luminal anions
How does diet affect K secretion?
Diet high in K increases the driving force of K into the cells and thus secretion from the late distal tubule cells and vice versa
How does Aldosterone affect K balance in the kindey?
Increases K secretion
Increased Na entry (through ENaC) through the luminal membrane and increased pumping of Na out of the cell through Na-K pump which increases K uptake into the principal cells. this increased K in the principal cells increases the driving force for secretion of K. Aldosterone also increases the number of luminal K channles
What effect does hyperaldosteronism have on K blood levels?
Hypokalaemia
Increased aldosterone drives more Na into the principal cells whcih is then excreted into the blood through the Na:K exchanger. More K though is brought into the cell , increasing its driving force to be secreted. Aldosterone also increses the numebr of K transporters in the luminal membrane resulting in more K entering the lumen of the tubule
what does hypoaldosteronism do to K levels in the blood?
Hyperkalaemia
Decreased Na reabsorbtion into the pricincipal cells means less Na:K cotransporter activity, thus more K is keps in the blood and not absorbed intracellularly
How does acidosis and alkalosis affect K levels?
H and K exchange for each other across the basolateral cell membrane
Acidosis decreases K secretion; Blood contains excess H; therefore, H enters the cell across the basolateral membrane and K leaves the cell. Thus driving force for potassium decreases
Alkalosis increases K secretion; too little H+ in the blood, therefore H+ leaves the cell across the basolateral membrane, and K enters the cell, increasing the driving force
How do loop diuretics and thiazides increase K secretion ?
Diuretics increase flow rate trhough the late distal tubule diluting K concentrations. This increases driving force for K secretion
Diuretics also increase Na secretion and delivery to the late distal tubule and collecting ducts, leading to increased Na entry across the luminal membrane of principal cells, which results in increased Na pumping out of the cells by the Na: K pump, increasing intracellular K this increasing the secretion driving force
how do K sparing diuretics work?
spironolactone is an aldosterone receptor blocker. By blocking aldosterone, we have decreased Na entry into the cell and thus less function by the Na: K pump trying to pump the Na out. This means less K is pumped in from the blood, and thus, the driving force of K is lower, and we do not have a loss of K
How do luminal anions affect K levels?
Excess anions (e.g. HCO3) in the lumen cause an increase in K secretion by increasing the negatiity of the lumen and increasing the driving force for K excretion.
