4:6 Micturition, Renal Disease, and Clinical Acid-Base Analysis, and Dialysis

Definition and Anatomy of the Urinary System

Micturition Definition: Micturition is defined as the reflex process by which urine is expelled from the bladder through the urethra.
General System Dynamics:
- Arterial input is characterized by Renal Plasma Flow ( $RPF_{x,a}$ ).
- Venous output is characterized by Renal Plasma Flow ( $RPF_{v,x,v}$ ).
- Urine output is defined by the excretion rate of a substance $x$ ( $U_x \times V$ ).
Ureters:
- These consist of two narrow muscular tubes containing both longitudinal and circular smooth muscle cells.
- Function: They carry urine from the kidneys to the urinary bladder.
- Mechanism: The ureter wall moves urine via rhythmic contractions known as peristalsis. These peristaltic waves originate from electrical pacemakers located in the renal pelvis.
Bladder:
- Function: Stores urine temporarily. As the bladder fills, the wall stretches.
- Structure: The bladder wall contains layers of multiunit smooth muscle cells collectively known as the "detrusor muscle."
- Physiology: When the bladder becomes sufficiently full, stretch receptors are activated, triggering the micturition reflex.
Urethra:
- Function: Carries urine from the bladder to the exterior of the body.
- Mechanism of Urination: During the process, the bladder contracts while the urinary sphincters relax to facilitate the exit of urine.
Physiological Innervation:
- Both the ureters and the bladder receive autonomic sympathetic and parasympathetic innervation.
- The external sphincter consists of voluntary skeletal muscle and receives somatic innervation.
- The internal urethral sphincter operates under autonomic control.

The Micturition Reflex

Reflex Nature: The micturition reflex is characterized as being partly automatic and partly voluntary.
Step-by-Step Mechanism:
1. Bladder Filling: As urine fills the bladder, the bladder wall stretches, which activates stretch receptors.
2. Signal Transmission: Sensory signals are sent to the sacral region of the spinal cord, specifically between segments $S2-S4$ .
3. Reflex Response: The spinal cord sends signals back to the bladder resulting in three distinct actions:
  - Detrusor Muscle Contraction: This squeezes the bladder to push urine out.
  - Internal Urethral Sphincter Relaxation: This allows urine to move into the urethra.
  - External Urethral Sphincter Relaxation: This occurs voluntarily, allowing urine to leave the body.

Acid-Base Disorders

Metabolic Acidosis:
- Causes:
  - Severe Diarrhea: Leads to a decrease in $HCO_3^-$ reabsorption within the gastrointestinal tract.
  - Diabetes Mellitus: Resulting from improper fat metabolism which produces increased organic acids, such as acetoacetic acid.
  - Chronic Renal Failure: A decrease in Glomerular Filtration Rate ( $GFR$ ) leads to a decrease in tubular buffers, thereby impairing $H^+$ secretion.
- Treatment: Administration of Sodium bicarbonate.
Metabolic Alkalosis:
- Causes:
  - Vomiting: Results in the loss of $HCl$ from the stomach.
  - Excess Ingestion of Alkaline Drugs.
  - Excess Aldosterone Secretion: Increases $H^+$ ion secretion in the distal tubule and collecting duct.
- Treatment: Oral ammonium chloride ( $NH_4Cl$ ), as its metabolism releases $HCl$ .
Respiratory Acidosis:
- Causes: Damage to respiratory centers, obstruction of respiratory passageways, or pneumonia.
- Treatment: Improve ventilation and remove $CO_2$ .
Respiratory Alkalosis:
- Causes: Rare psychoneurosis causing over-breathing (hyperventilation) and exposure to high altitudes.
- Treatment: Treat the underlying cause of hyperventilation.
Clinical Analysis: Analysis of simple acid-base disorders is based on arterial blood $pH$ , plasma $PCO_2$ , and plasma $HCO_3^-$ .

Renal Diseases and Syndromes

Acute Kidney Injury (AKI):
- Definition: A sudden decrease in kidney function occurring over hours to days.
- Result: The kidneys lose the ability to filter waste products properly.
Chronic Kidney Disease (CKD):
- Definition: Kidney damage or reduced function lasting for $3$ months or more.
- Major Risk Factors: Diabetes, high blood pressure (hypertension), heart disease, and a family history of kidney disease.
Nephrotic Disease: Defined by glomerular damage leading primarily to proteinuria.
Nephritic Disease: Defined by glomerular damage leading primarily to hematuria.
Comparison of Clinical Signs:
- Nephritic Syndrome:
  - Glomerular inflammation.
  - Blood in urine (hematuria).
  - Mild to moderate edema.
  - Elevated blood pressure (hypertension).
  - Mild proteinuria.
  - Oliguria (low urine output).
  - Azotemia (elevation of blood urea nitrogen and creatinine).
- Nephrotic Syndrome:
  - Glomerular protein leakage.
  - Massive proteinuria (>3.5\,g/day).
  - Severe edema.
  - Normal or high blood pressure.
  - Frothy urine (due to high protein content).
  - Fatty casts in the urine.
Acute Tubular Necrosis (ATN):
- Definition: A type of AKI where the tubular epithelial cells are damaged, impairing the reabsorption of water, sodium, glucose, and $HCO_3^-$ .
- Main Causes:
  1. Ischemia/Low Blood Flow: Examples include severe hypotension, shock, major blood loss, and sepsis.
  2. Nephrotoxins/Toxic Injury: Examples include aminoglycoside antibiotics, vancomycin, contrast dye, heavy metals, myoglobin (from rhabdomyolysis), and hemoglobin (from hemolysis).
Hydronephrosis:
- Defined as the swelling or dilation of the kidney collecting system when urine backs up due to blockage.
- Causes: Kidney stones or congenital structural abnormalities.

Progression to End-Stage Renal Disease (ESRD)

The progression of kidney disease is described as a vicious cycle:
1. Primary kidney disease leads to a reduction in the nephron number.
2. This causes hypertrophy and vasodilation of the remaining surviving nephrons to compensate.
3. Compensation leads to increased arterial pressure and increased glomerular pressure and/or filtration.
4. The increased pressure eventually causes glomerular sclerosis.
5. Glomerular sclerosis further reduces the nephron number, continuing the cycle.

Plasma Creatinine as a Marker of Renal Function

Creatinine Characteristics: Creatinine is only filtered and then excreted in the urine.
Steady State Coordination:
- In normal function: $\text{Creatinine excretion} = \text{Creatinine production} = GFR \times [Creatinine]_P$ .
- The filtration rate of creatinine is defined as: $GFR \times [Creatinine]_P = \text{Excretion rate of creatinine}$ .
Declining Function: If renal function declines, $GFR$ decreases and plasma creatinine concentration ( $[Creatinine]_P$ ) increases. Initially, excretion falls below production until a new steady state is reached at a higher plasma concentration.

Dialysis Principles and Types

Function: Dialysis removes extra waste (urea and creatinine), extra water/fluid, excess electrolytes (potassium), and acid loads ( $H^+$ ) to maintain acid-base balance. It can also remove certain toxins or drugs.
Hemodialysis:
- Uses an external machine and a filter (dialyzer).
- Blood leaves the body, passes through the dialyzer (containing a semipermeable membrane and flowing dialysate), and returns to the body.
- Setup involves a bubble trap, a constant temperature bath for the dialyzing solution, and flowing blood/dialysate in a counter-current or concurrent manner.
Peritoneal Dialysis:
- Uses the peritoneum (lining of the abdomen) as the natural filter.
- Dialysis fluid is placed into the abdominal cavity; wastes move from the blood into the fluid, which is then drained out.

Summary of Key Concepts

Micturition is a reflex process for expelling urine.
Acute renal failure (AKI) is abrupt and potentially reversible (pre-renal, intrarenal, or postrenal).
Chronic renal failure (CKD) is progressive and leads to the irreversible loss of nephrons.
The rate of creatinine excretion and its plasma concentration are used to measure $GFR$ .
Dialysis restores fluid volume and composition by removing toxic waste products.