Tubular Reabsorption in Urine Formation

Urine Formation

• Urine formation involves continuous regulation and adjustment in response to hormonal signals
• Tubular reabsorption of sodium is almost always active and via the transcellular route
• Reabsorption of nutrients, water, and ions is also facilitated by the reabsorption of sodium

Transport Maximum (Tm)

• The transcellular transport systems for various solutes are specific and limited
• There is a transport maximum (Tm) for nearly every substance reabsorbed using a transport protein
• Tm reflects the number of transport proteins in the renal tubules available to ferry a particular substance
• When transporters are saturated, the excess is excreted in the urine

Reabsorptive Capabilities of the Renal Tubules and Collecting Ducts

• Proximal Convoluted Tubule (PCT) is the most active "reabsorber" and reabsorbs all glucose and amino acids, 65% of sodium and water, and most of the electrolytes
• Nephron Loop: water can leave the descending limb, but not the ascending limb, where aquaporins are scarce or absent
• Distal Convoluted Tubule (DCT) and Collecting Duct: reabsorption is fine-tuned by hormones
• Anti-Diuretic Hormone (ADH) inhibits diuresis and makes the principal cells of the collecting ducts more permeable to water
• Parathyroid Hormone (PTH) increases the reabsorption of calcium

Tubular Secretion

• Tubular secretion is essentially reabsorption in reverse
• It moves selected substances from the peritubular capillaries through the tubule cells into the filtrate
• The urine excreted contains both filtered and secreted substances
• Tubular secretion is important for disposing of substances that are tightly bound to plasma proteins, eliminating undesirable substances, and controlling blood pH

Urine Chemical Composition

• Water accounts for about 95% of urine volume; the remaining 5% consists of solutes
• The largest component of urine by weight, apart from water, is urea, derived from the normal breakdown of amino acids
• Other nitrogenous wastes in urine include uric acid and creatinine
• Normal solute constituents of urine, in order of descending concentration, are urea, sodium, potassium, phosphate, sulphate, creatinine, and uric acid

Urine Transport, Storage, and Elimination

• The kidneys form urine continuously, and the ureters transport it to the bladder
• Urine is usually stored in the bladder until its release is convenient, a process called micturition
• The ureters are slender tubes that convey urine from the kidneys to the bladder

Urethra

• The length and functions of the urethra differ in the two sexes
• In females, the urethra is about 3-4 cm long and fibrous connective tissue binds it tightly to the anterior vaginal wall
• In males, the urethra is approximately 20 cm long and has three regions: prostatic urethra, membranous urethra, and spongy urethra
• The male urethra has a double function: it carries semen as well as urine out of the body

Pathophysiology of Chronic Kidney Disease (CKD)

• Mild renal insufficiency patients often have normal or near-normal serum creatinine concentrations.
• Additional homeostatic mechanisms in the renal tubules allow the serum concentration of sodium, potassium, calcium, and phosphorous to remain within the normal range, especially in those with mild to moderate renal failure.
• Adaptive hyperfiltration, although beneficial initially, can result in long-term damage to glomeruli, leading to proteinuria and progression to renal failure.

Gradual Decline in Renal Function

• The gradual decline in renal function in patients with CKD is initially asymptomatic.
• The damaged kidney responds with higher filtration and excretion rates per nephron, which masks symptoms until only 10-15% of renal function remains.
• Progressive renal failure causes loss of excretory and regulatory functions, leading to End-Stage Renal Disease (ESRD) and uraemic syndrome.

Uraemic Syndrome

• Manifestations of the uraemic state include:
  • Anorexia
  • Nausea
  • Vomiting
  • Fatigue
  • Pericarditis
  • Peripheral neuropathy
  • Central nervous system abnormalities (ranging from loss of concentration and lethargy to seizures, coma, and death)
• No direct correlation exists between the absolute serum levels of blood urea nitrogen (BUN) or creatinine and the development of these symptoms.

Presentation of Uraemic Patients

• Uraemic patients may present with:
  • Peripheral oedema
  • Pulmonary oedema
  • Congestive heart failure
• To continue life, uraemic patients require the institution of Renal Replacement Therapy (RRT) using haemodialysis, peritoneal dialysis, or renal transplantation.

Loss of Excretory and Regulatory Functions

• The loss of excretory function results in the build-up of toxins in the blood, which can negatively affect cellular enzyme activities and inhibit systems such as the sodium-potassium pump.
• The loss of regulatory function results in the inability to regulate extracellular fluid volume and electrolyte concentrations, adversely affecting cardiovascular and cellular functions.

Consequences of Renal Failure

• Most patients with advanced CKD are volume overloaded, leading to hypertension and often congestive heart failure.
• Other malfunctions in regulation include:
  • Impaired generation of ammonia and hydrogen ion excess, resulting in metabolic acidosis
  • Decreased production of erythropoietin, leading to anaemia
• Excess production or inappropriate regulation of hormones such as parathyroid hormone can occur in response to renal failure.

Clinical Considerations

• Treatment is multi-pronged and typically involves control of blood pressure and diabetes, use of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), lowering urine protein, weight loss as needed, smoking cessation, and regular exercise.
• Dietary adjustments for protein, sodium, and fluid intake play an important role in the initial management of renal failure.
• If these treatments are not successful, RRT is required. Transplantation is the preferred method, but patients need to be free of other life-threatening illnesses to be considered for transplantation.

Renal Replacement Therapy (RRT)

• Haemodialysis is the most common therapy for renal failure, although it requires significant time throughout the week at a renal centre (dialysis unit).
• Peritoneal dialysis is the third RRT option, but it is the least used.
• Home dialysis, either as haemodialysis or peritoneal dialysis, is the modality of choice. RCTs have demonstrated a better outcome for patients treated with five-plus dialysis treatments per week.

Signs and Symptoms

• CKD patients often present with symptoms and signs resulting directly from diminished kidney function.
• Excess fluids consumed remains in the system, ultimately resulting in peripheral oedema, congestive heart failure, and pulmonary congestion.

Diagnostic Testing and Treatment

• The decision to begin dialysis is determined by many factors, including cardiovascular status, electrolyte levels, chronic fluid overload, severe and irreversible oliguria, anuria, significant uraemic symptoms, and abnormal laboratory values.
• RRT does not correct all signs and symptoms of uraemia and often results in other concerns and side effects.

Haemodialysis

• Haemodialysis is the most common form of RRT.
• Approximately 95% of all patients undergo haemodialysis in a centre (dialysis unit) or at home.
• In other countries, some patients prefer home-based methods such as peritoneal dialysis.
• Haemodialysis is a process of ultrafiltration (fluid removal) and clearance of toxic solutes from the blood. It necessitates vascular access by one of three methods: a fistula, a graft, or a central venous catheter.

Contraindications to Exercise in ESRD

• Contraindications to exercise in ESRD include:
  • Electrolyte abnormalities (especially hypo- or hyperkalaemia)
  • Recent changes to the ECG, especially symptomatic tachy- or brady-arrhythmias
  • Excess inter-dialytic weight gain (> 4kg) since last dialysis or exercise session
  • Unstable on dialysis treatment and changing (titrating) medication regime
  • Pulmonary congestion
  • Peripheral oedema

Exercise Recommendations

• Patients with CKD who are not on dialysis have been shown to benefit from exercise training programs using standard exercise prescriptions for the general population.
• With regard to patients with ESRD, the timing of exercise in relation to the dialysis treatment should be considered.
• Exercising during treatment (intra-dialytic exercise) is recommended since it has significant physiologic benefit, enhances exercise compliance, and reduces the boredom associated with dialysis treatments.
• Research in haemodialysis patients demonstrates that larger adaptations usually occur when exercise is completed on non-dialysis days, but that intra-dialytic exercise is likely to produce better adherence rates.