Renal 31 to 40
How is H+ ion secreted in the proximal tubule of the kidney?
Secondary active transport (The renal tubular cells secrete H* into the tubular fluid in exchange for Na*; and for each H* secreted, one Na* and one HCO3 are added to the blood)
Linked to Na+/K+ ATPase
Outline the buffer systems that act to bind H+ ion in the tubular fluid.
3 systems — HCO3, HPO4, NH3
Major role of carbonic anhydrase/HCO3 system
Pass: 2 of 3 – must have bicarbonate
What is the importance of H+ buffering systems in the urine?
Limiting pH (-4.5) would rapidly be reached unless free H+ is buffered
Describe the counter-current mechanism in the kidney.
Prompt: What is the role of the vasta recta?
a) Countercurrent multipliers in the LOH through active transport of Na (& Cr) out of its thick ascending limb. Water moves out of the thin descending limb, with inflow of tubular fluid from the PCT. This increases the interstitial osmolarity. This results in hypotonic fluid flows into DCT, isotonic fluid flows into the asc thick LOH. The final result is a gradient conc from the top to the bottom of the LOH & a gradient hyperosmolarity in the medulla interstitium.
b)Vasta recta as countercurrent exchangers in the kidney in which NaCI & urea diffuse out of the asc limb of the vessel & into the desc limb, while water diffuses out of the desc into the ascending limb of the vascular loop. As a result the solute remains in the medulla pyramid & maintain the interstitial conc.
Where does sodium reabsorption occur in the nephron?
a) All parts of the nephron except thin part of the LoH (+Specify at least two of:)
b) 60% PCT primarily by Na+-H+ exchange but also a range of cotransport (glc, Pi, AA, lactate)
c) 30% thick ascending limb of LoH (Na’-2CI–K-cotransporter)
d) 7% DCT LoH (Na+-C1- cotransporter)
e) 3% collecting ducts through Na+ channels (ENaC)
What are the mechanisms of sodium re-absorption in the nephron?
Na/K ATPase active transport. Moves (by gradient thus generated) across apical membranes from tubular lumen into cell via cotransport & exchanger proteins. Driven by active transport by Na-K ATPase (3Na/2K) from tubular cell into interstitium (mainly into lateral interstitial spaced)
Please describe how the urinary bladder empties.
Prompt : Could you describe the relationship between pressure and volume in the bladder as it relates to bladder emptying?
- Smooth muscle of the bladder is arranged in spiral, longitudinal, and circular bundles
- Contraction of the circular muscle, (detrusor muscle), is mainly responsible for emptying the bladder during urination **
- Micturition is fundamentally a spinal reflex facilitated and inhibited by higher brain centers and, like defecation, subject to voluntary facilitation and inhibition **
- Urine enters the bladder without producing much increase in intravesical pressure until the viscus is well filled
- The bladder muscle has the property of plasticity; when it is stretched, the tension initially produced is not maintained
- The curve shows an initial slight rise in pressure when the first increments in volume are produced; a long, nearly flat segment as further increments are produced; and a sudden, sharp rise in pressure as the micturition reflex is triggered
- The first urge to void is felt at a bladder volume of about 150 mL, and a marked sense of fullness at about 400 mL.
- The flatness of segment Ib is a manifestation of the law of Laplace which states that the pressure in a spherical viscus is equal to twice the wall tension divided by the radius. In the case of the bladder, the tension increases as the organ fills, but so does the radius. Therefore, the pressure increase is slight until the organ is relatively full
- During micturition, the perineal muscles and external urethral sphincter are relaxed; the detrusor muscle contracts; and urine passes out through the urethra. **
- The mechanism by which voluntary urination is initiated remains unsettled. One of the initial events is relaxation of the muscles of the pelvic floor, and this may cause a sufficient downward tug on the detrusor muscle to initiate its contraction.
- The perineal muscles and external sphincter can be contracted voluntarily, preventing urine from passing down the urethra or interrupting the flow once urination has begun.
Pass: 2, 3, 9 and basic understanding the process in an organised fashion
Describe the reflex control associated with voiding.
- The bladder smooth muscle has some inherent contractile activity; however, when its nerve supply is intact, stretch receptors in the bladder wall initiate a reflex contraction that has a lower threshold than the inherent contractile response of the muscle.
- Fibers in the pelvic nerves are the afferent limb of the voiding reflex, and the parasympathetic fibers to the bladder that constitute the efferent limb also travel in these nerves.
- The reflex is integrated in the sacral portion of the spinal cord.
- In the adult, the volume of urine in the bladder that normally initiates a reflex contraction is about 300-400 mL.
- The sympathetic nerves to the bladder play no part in micturition,
- They do mediate the contraction of the bladder muscle that prevents semen from entering the bladder during ejaculation
Pass: Parasympathethetic reflex, Sacral portion of cord, Vol to trigger 300 —400MIS
Describe water handling in the collecting ducts of the kidneys.
Prompt : How does vasopressin affect water handling in the collecting ducts?
- The collecting ducts (CD) have two portions: a cortical portion and a medullary portion
- Changes in osmolality and volume in the CDs depend on amount of vasopressin acting on ducts
- This antidiuretic hormone from the post pituitary gland increases the permeability of CDs to H2O
- Key to action of vasopressin on the CDs is aquaporin-2. Unlike other aquaporins, this is stored in vesicles in cytoplasm of principal cells.
- Vasopressin causes rapid insertion of these vesicles into apical membrane of cells. Effect is mediated via the vasopressin V2 receptor, cyclic AMP, protein kinase A, and a molecular motor, one of the dyneins
- In presence of enough vasopressin to produce maximal antidiuresis, H2O moves out of hypotonic fluid entering cortical CDs into interstitium of cortex, and the tubular fluid becomes isotonic
- As much as 10% of the filtered H2O is removed
- When vasopressin is absent, the collecting duct epithelium is relatively impermeable to water and the fluid therefore remains hypotonic, and large amounts flow into renal pelvis.
Pass: 2, 3, 6
What is an osmotic diuresis?
Prompt: Describe how it occurs.
Prompt: Can you give me an example.
- Presence of large quantities of unreabsorbed solutes in renal tubules causes an increase in urine volume called osmotic diuresis.
- Solutes that are not reabsorbed in the proximal tubules exert an appreciable osmotic effect as volume of tubular fluid decreases, and their concentration increases
- Therefore, they “hold water in the tubules”
- Concentration gradient against which Na+ can be pumped out of proximal tubules is limited. Normally, movement of H2O out of proximal tubule prevents any appreciable gradient from developing, but Na+ concentration in fluid decreases when H2O reabsorption is decreasing, because of presence in tubular fluid of increased amounts of unreabsorbable solutes. Limiting concentration gradient is reached, and further proximal reabsorption of Na+ is prevented; more Na+ remains in tubule, and H2O stays with it
- The result is that loop of Henle is presented with a greatly increased volume of isotonic fluid.
- This fluid has a decreased Na+ concentration, but total amount of Na+ reaching the loop per unit time is increased
- In loop, reabsorption of water and Na+ is decreased, because the medullary hypertonicity is decreased. The decreasing is due primarily to decreased reabsorption of Na+, K+, and Cl in the ascending limb of loop because limiting concentration gradient for Na+ reabsorption is reached. More fluid passes through the distal tubule, and because of the decreased, in osmotic gradient along the medullary pyramids, less water is reabsorbed in collecting ducts. Result is a marked increase in urine volume and excretion of Na+ and other electrolytes.
- Osmotic diuresis is produced by administration of compounds such as mannitol and related polysaccharides that are filtered but not reabsorbed. It is also produced by naturally occurring substances when present in amounts exceeding the capacity of the tubules to reabsorb them. E.g. diabetes mellitus, glucose that remains in tubules when filtered load exceeds TmG causes polyuria. Osmotic diuresis can also be produced by infusion of large amounts of sodium chloride or urea.
Pass: 1, 2, 3
Describe a method for measuring the glomerular filtration rate.
Prompt: Describe the properties of a suitable substance and give an example.
Measure excretion of a substance which is freely filtered through the glomeruli neither secreted nor reabsorbed by the tubules.
Non toxic, not metablised
Eg Inulin, NB Endogenous Creatinine has limitations
GFR = UX x V/PX
Ux is the conc of X in the urine
P is the urine flow per unit time
Px is the arterial plasma level of X.
If X is not metabolized in the tissues then the peripheral venous plasma level can be substituted for the arterial plasma level.
Pass: 3 of 5 bold, one example, definition or description and basic formula
What is normal GFR and what are the factors which affect it?
125m1/min in normal 70 kg male, 10% less
for women, and correlates with surface area.
Factors RBF, Systemic BP, Ureteric obstruction, compression by oedema within renal capsule, Plasma proteins, Permeability changes, Filtration surface area
Pass: Value (100-150) and three factors
What are the major physiological factors affecting sodium excretion from the kidney?
Prompt: How does the kidney regulate sodium excretion?
1. Amount filtered versus amount reabsorbed, therefore
4. Na intake,
5. hormonal e.g. aldosterone, angiotensin and K and H excretion
4 to pass
What are the major physiological factors affecting potassium excretion from the kidney?
Prompt: How does the kidney regulate potassium excretion?
1. K is reabsorbed in PTs and secreted in distal tubule,
2. Amount secreted relates to tubular flow,
3. Na excretion or reabsorption,
4. K intake
2 to pass
Describe how water is reabsorbed in the different parts of the nephron.
I. 60-70% in the Proximal tubule
2. 15% in the loop of Henle
3. 5% in the distal tubule
4. Up to 10% in the collecting duct depending on the presence of antidiuretic hormone.
Pass: Need to understand that water is reabsorbed in different parts and the role of vasopressin in the collecting duct.
What hormonal factor influences water excretion?
Prompt: What does vasopressin do?
Vasopressin increases the permeability of the collecting duct to water & allow water to be reabsorbed.
What factors control glomerular filtration?
Mention average 125m1/min or 0.16-0.2 of RPF and its derivation Ui x V/ Pi= Ci= GFR for inulin; Creatinine Clearance is approximation
Control of GFR depends on
- size of capillary bed,
- permeability of capills,
- hydrostatic pressure,
- oncotic pressure.
These influenced by changes in RBF, MAP, [plasma proteins], effective surface area, changes in pressure across Bowman’s capsule – eg ureteric obstruction, renal oedema. Glomerular capills are 50x permeable as skeletal.
Need 3 of 4 to pass
Describe how respiration compensates for acid-base changes.
CO2 + H2O = H2CO3 = H + HCO3. Rapid responder.
Respiratory Centre responds to H, mainly at peripheral chemoreceptors, also transferred to CSF by CO2.
Metabolic acidosis —> inc ventilation, dec CO2 -> dec H, dec HCO3 (`base deficit’).
Metabolic alkalosis —> dec ventilation, inc CO2 -> inc H, inc HCO3 (‘base excess’). In reality often no compensation.
What clinical conditions might cause metabolic acidosis? / metabolic alkalosis?
– DKA; hypoxia -> lactic acid
– Vomiting ->loss of acid.