Question

1. What is the difference between ionoconformity and osmoconformity?

2. Mention and briefly describe two countercurrent mechanisms operating in cardiovascular and/or osmoregulatory physiology.

Answer 1

+Counter Current Mechanism:

Urine excretory

Hemodialysis

Following are the important steps of the countercurrent mechanism:

Thick ascending Loop of Henle Transport

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Equilibration of descending thin Loop of Henle

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Fluid Flow

The production of concentrated urine is achieved by osmotic equilibration of the collecting duct luminal fluid with the hypertonic medullary interstitium. Urinary concentration is achieved by countercurrent multiplication in the inner medulla. The single effect in the outer medulla is active NaCI absorption from the thick ascending limb. While the single effect in the inner medulla is not definitively established, the majority of experimental data favors passive NaCI absorption from the thin ascending limb. Continued experimental studies in inner medullary nephron segments will be needed to elucidate fully the process of urinary concentration.

+Mechanism
Step 1: Assume that the loop of Henle is filled with a concentration of 300mOsm/L the same as that leaving the proximal tubules.

Step 2: The active ion pump of the thick ascending limb on the loop of Henle reduces the concentration inside the tubule and raises the interstitial concentration.

Step 3: The tubular fluid in the descending limb and the interstitial fluid quickly reach osmotic equilibrium because of osmosis of water out of the descending limb.

Step 4: The Additional flow of the fluid into the loop of Henle from the proximal tubule, which causes the hyperosmotic fluid previously formed in the descending limb to flow into the ascending limb.

Step 5: Additional ions pumped into the interstitium with water remaining in the tubular fluid, until a 200-mOsm/L osmotic gradient is established.

Step 6: Again, the fluid in the descending limb reaches equilibrium with the hyperosmotic medullary interstitial fluid and as the hyperosmotic tubular fluid from the descending limb flows into the ascending limb, still more solute is continuously pumped out of the tubules and deposited into the medullary interstitium.

Step 7: These steps are repeated over and over, with net effect of adding more and more solute to the medulla in excess of water, with sufficient time, this process gradually traps solutes in the medulla and multiplies the concentration gradient established by the active pumping of ions out of the thick ascending limb , eventually raising the interstitial fluid osmolarity to 1200- 1400 mOsm/L .

+ Henle’s Loop
The existence of a steep osmotic gradient in the renal medullary interstitium is the most critical in the formation of concentrated urine. The architectural organization of the renal tubules and blood vessels in the medulla constitutes counterflow systems which are essential for both generating and
maintaining a high osmotic pressure of the renal medulla.

While it has been generally accepted that active NaCl transport in the thick ascending limb of Henle’s loop plays the most fundamental role in the operation of the countercurrent multiplication
system in the renal medulla, it is still a matter of considerable dispute whether the thin ascending limb (tAL) also has an active salt transport system to provide a “single effect” necessary for the operation of the countercurrent multiplication system

+ Role of Urea
The concept of urea recycling has been mentioned in various studies. Urea is absorbed from the inner medullary collecting duct and secreted into the thin ascending limb, after which it remains within the tubule lumen until it returns to the inner medullary collecting duct. Maximal concentrating ability is decreased in protein-deprived animals and restored by urea.

Thus, the passive mechanism, which critically depends on an adequate delivery of urea to the inner medulla, provides an explanation for the well-described importance of urea to concentrating ability. Several recent studies have improved our understanding of urea absorption across the inner medullary collecting duct.

Urea transport occurs by a vasopressin-stimulated facilitated transport process in terminal inner medullary collecting ducts. As the urea concentration in the lumen of terminal inner medullary collecting ducts exceeds that in vasa recta, urea is rapidly absorbed into the inner medullary interstitium, down its concentration gradient.

+ Quick points about Counter Current Mechanism:
*The counter current mechanism takes place in Juxtamedullary nephron.
*The function of the countercurrent multiplier is to produce the hyperosmotic Medullary Interstitium.
*The ADH promotes water reabsorption through the walls of the distal convoluted tubule and collecting duct.
*Urea reabsorbed from collecting duct to medullary interstitum produces the hyperosmotic Medullary interstitium.
*Reabsorption of urea will occur in the presence of ADH.
*Excretion of large volume or small volume of urine won’t affect the rate of solute excretion.
*Nephrogenic diabetes insipidus patients will have no response from the kidney to ADH.
*The function of the Countercurrent exchanger “vasa recta” is to maintain hyperosmolar medulla.The Countercurrent Mechanism partially contributes to generation of the corticopapillary osmotic gradient and is the product of juxtamedullary nephrons which possess long loops of Henle that extend far into the renal medulla.

+A Hemodialysis
Hemodialysis removes blood and passes it through an extracorporeal circuit and an artificial membrane, with dialysate running in countercurrent flow next to the blood in the membrane. After the blood is filtered through the membrane, it is returned to the body with a reduced quantity of metabolic waste products. Hemodialysis has the advantages of maintaining an efficient concentration gradient via rapid blood and dialysate flows as well as predictable transmembrane pressure between the blood and dialysate within the filter, thereby allowing for rapid solute and fluid removal .
The dialyzer is a series of hollow fibers that are composed of special membranes that facilitate solute transfer . The membranes are now made of various biocompatible materials (e.g., polysulfones). A large body of research has demonstrated that bioincompatible dialyzers (e.g., cellulosic dialyzers) activated leukocytes and contributed to complement generation during the dialysis procedure. Biocompatible membranes have significantly less complement generation. The tubes of the dialyzer membrane are surrounded by dialysate, with the countercurrent flow of dialysate and blood.
Dialysate is the fluid that is used in dialysis to adjust the extracellular fluid composition and to maintain body homeostasis. The dialysate is one of several variables that can be altered in a dialysis procedure to achieve certain patient care goals. For example, the dialysis prescription for a patient with a dangerously high level of potassium will be very different from that of a patient with edema and volume overload who has congestive heart failure but a normal serum potassium level. Dialysate includes bicarbonate and potassium. The potassium level in the dialysis is often lower than the desired final potassium level of the patient as a result of incomplete equilibration during the dialysis period. In an acute dialysis situation in which one particular electrolyte may be elevated, the dialysate concentration of that electrolyte can be lowered further or even removed completely to aid in the rapid removal of that electrolyte from the patient.
The standard buffer for dialysate includes bicarbonate, which has several important advantages. Bicarbonate induces far less hypotension than lactate, which is a buffer that had been used in the past. Moreover, there is evidence that buffering acid is beneficial for reducing bone loss.
Access for hemodialysis is established with either a dialysis catheter, which is most often used for temporary use and placed in a large vein (either the internal jugular or femoral vein); an arteriovenous shunt, such as an arteriovenous fistula; or an arteriovenous graft made of synthetic material such as polytetrafluoroethylene. Arteriovenous fistulas are preferred for long-term use in patients receiving hemodialysis (Fig. 13-7). These accesses can provide adequate blood flow with rates between 300 and 500 ml/min, and they also are less prone to complications such as infection and clotting.

The adequacy of hemodialysis for chronic dialysis patients is assessed on a monthly basis. Clinically, the patient is asked about signs and symptoms of uremia, including appetite, nausea, and neurologic symptoms such as restless legs. For solute clearance, the urea reduction ratio (URR) is one measure that can be used to estimate whether the dialysis treatments are effective. By assessing the difference between blood urea nitrogen levels before and after a dialysis session, the URR value can be calculated. An optimal URR is >70%. Adequacy can also be determined using the Kt/V formula, where K is clearance, t is the time on dialysis, and V is the volume of distribution of the patient's extracellular space. Recent studies have found that the value for Kt/V for a patient on hemodialysis should be >1.2, but there is little added benefit if this value exceeds 1.55 to 1.6.

Clinical assessment is most important for assessing volume status, although recent advances in technology have led to the inclusion of blood volume monitors as part of the dialysis machinery itself. High blood pressure or edema indicates hypervolemia. Low blood pressure may reflect hypovolemia, the effect of medications (e.g., antihypertensive agents), infection, or even poor cardiovascular function. In each instance, it is important to assess the patient to make sure that the dialysis treatment achieves its goals.