Renal System PATHOPHYSIOLOGY

 Chapter -6 

RENAL SYSTEM

 

Introduction to Urinary System 

The urinary system consists of the kidneys, ureters, urinary bladder and urethra. The kidneys filter the blood to remove wastes and produce urine. The ureters, urinary bladder and urethra together form the urinary tract, which acts as a plumbing system to drain urine from the kidneys, store it, and then release it during urination. Besides filtering and eliminating wastes from the body, the urinary system also maintains the homeostasis of water, ions, pH, blood pressure, calcium and red blood cells. The kidneys have extensive blood supply via the renal arteries which leave the kidneys via the renal vein.

Kidneys: The kidneys are a pair of bean shaped organs found along the posterior wall of the abdominal cavity. The left kidney is located slightly higher than the right kidney because the right side of the liver is much larger than the left side. The kidneys, unlike the other organs of the abdominal cavity, are located posterior to the peritoneum and touch the muscles of the back. The kidneys are surrounded by a layer of adipose that holds them in place and protects them from physical damage. The kidneys filter metabolic wastes, excess ions, and chemicals from the blood to form urine.

Ureters: The ureters are a pair of tubes that carry urine from the kidneys to the urinary bladder. The ureters are about 10 to 12 inches long and run on the left and right sides of the body parallel to the vertebral column. Gravity and peristalsis of smooth muscle tissue in the walls of the ureters move urine toward the urinary bladder. The ends of the ureters extend slightly into the urinary bladder and are sealed at the point of entry to the bladder by the ureterovesical valves. These valves prevent urine from flowing back towards the kidneys. 

Urinary Bladder: The urinary bladder is a sac-like hollow organ used for the storage of urine. The urinary bladder is located along the body’s midline at the inferior end of the pelvis. Urine entering the urinary bladder from the ureters slowly fills the hollow space of the bladder and stretches its elastic walls. The walls of the bladder allow it to stretch to hold anywhere from 600 to 800 milliliters of urine.

Urethra: The urethra is the tube through which urine passes from the bladder to the exterior of the body. The female urethra is around 2 inches long and ends inferior to the clitoris and superior to the vaginal opening. In males, the urethra is around 8 to 10 inches long and ends at the tip of the penis. The urethra is also an organ of the male reproductive system as it carries sperm out of the body through the penis. The flow of urine through the urethra is controlled by the internal and external urethral sphincter muscles. The internal urethral sphincter is made of smooth muscle and opens involuntarily when the bladder reaches a certain set level of distention. 

 Acute Renal Failure 

Acute renal failure or Acute kidney failure (AKF) occurs when kidneys suddenly become unable to filter waste products from blood. When kidneys lose their filtering ability, it results in accumulation of nitrogenous wastes and fluid and electrolyte imbalance. Acute renal failure is also called acute kidney injury (AKI). It develops rapidly over a few hours or a few days.

 Epidemiology 

Acute kidney injury is common among hospitalized patients particularly in critically ill people who need intensive care. It affects some 3-7% of patients admitted to the hospital and approximately 25-30% of patients in the intensive care unit.

Causes 

Acute renal failure can occur when:

(i) Impaired Blood Flow to the Kidneys:

Diseases and conditions that may slow blood flow to the kidneys and lead to kidney failure include:

• Blood or fluid loss. 
• Blood pressure medications. 
• Heart attack. 
• Heart disease. 
• Infection. 
• Liver failure.
• Use of Aspirin, Ibuprofen and Naproxen. 
• Severe allergic reaction (anaphylaxis). 
• Severe burns. 
• Severe dehydration.  

(ii) Damage to the Kidneys:

Certain diseases, conditions and agents may damage the kidneys and lead to acute renal failure includes:

• Blood clots in the veins and arteries in and around the kidneys. 
• Cholesterol deposits that block blood flow in the kidneys. 
• Glomerulonephritis, inflammation of the tiny filters in the kidneys (glomeruli). 
• Hemolytic uremic syndrome, a condition that results from premature destruction of red blood cells. 
• Lupus, an immune system disorder causing glomerulonephritis. 
• Medications, such as certain chemotherapy drugs, antibiotics, dyes used during imaging tests and zoledronic acid, used to treat osteoporosis and high blood calcium levels (hypercalcemia). 
• Multiple myeloma, a cancer of the plasma cells. 
• Scleroderma, a group of rare diseases affecting the skin and connective tissues. 
• Thrombotic thrombocytopenic purpura (TTP), a rare blood disorder. 
• Toxins, such as alcohol, heavy metals and cocaine. 
• Vasculitis, an inflammation of blood vessels.   

(iii) Urine Blockage in the Kidneys:

Diseases and conditions that block the passage of urine out of the body (urinary obstructions) and can lead to acute renal failure include: 

• •Bladder cancer, 
•  Blood clots in the urinary tract, 
•  Cervical cancer, 
•  Colon cancer, 
•  Enlarged prostate, 
•  Kidney stones, 
•  Nerve damage involving the nerves that control the bladder, 
•  Prostate cancer. 

Etiologic Mechanisms in Acute Renal Failure 

Prerenal Failure Mechanism:  Reduced renal blood flow  Severe dehydration shock (all forms) Cardiac failure Renal artery stenosis Renal artery embolism or thrombosis Sickle cell crisis

Intrarenal Failure Mechanism:  Renal parenchymal disease Ischemic necrosis Nephrotoxicity Autoimmune or isoimmune disorders Hypertensive nephropathy Diabetic nephropathy Renal trauma Acute glomerulonephritis Vasculitis Acute interstitial nephritis, Rhabdomyolysis

Postrenal Failure Mechanism:  Prevention of Filtration Due to  High tubular pressure (obstructed outflow) Urolithiasis Renal-urinary neoplasms Congenital obstructive uropathies Detrusor areflexia Surgical trauma to ureters Obstructive lymphadenopathy

Risk Factors 

Acute renal failure almost always occurs in connection with another medical condition or events. Conditions that can increase risk of acute renal failure include:

• Being hospitalized, especially for a serious condition that requires intensive care, 
• Advanced age, 
• Blockages in the blood vessels in arms or legs (peripheral artery disease), 
• Diabetes, 
• High blood pressure, 
• Heart failure, 
• Kidney diseases, 
• Liver diseases.   

Pathophysiology 

The driving force for glomerular filtration is the pressure gradient from the glomerulus to the Bowman space. Glomerular pressure depends primarily on renal blood flow (RBF) and is controlled by the combined resistances of renal afferent and efferent arterioles. Regardless of the cause of AKI, reductions in RBF represent a common pathologic pathway for decreasing glomerular filtration rate (GFR). The etiology of AKI consists of 3 main mechanisms: prerenal, intrinsic and obstructive.

Obstruction of the urinary tract initially causes an increase in tubular pressure, which decreases the filtration driving force. This pressure gradient soon equalizes, and maintenance of a depressed GFR then depends on renal efferent vasoconstriction.  

Symptoms 

Signs and symptoms of acute renal failure may include:

• Decreased urine output, although occasionally urine output remains normal, 
• Fluid retention, causing swelling in legs, ankles or feet, 
• Drowsiness, 
• Shortness of breath, 
• Fatigue, 
• Confusion, 
• Nausea, 
• Seizures or coma in severe cases, 
• Chest pain or pressure.  

Sometimes Acute renal failure causes no signs or symptoms and is detected through lab tests done for another reason. 

Complications 

Potential complications of acute renal failure include:

• Fluid build-up: Acute renal failure may lead to a build-up of fluid in chest, which can cause shortness of breath.
• Chest pain: If the lining that covers heart becomes inflamed, it may lead to chest pain.
• Muscle weakness: When body’s fluids and electrolytes are out of balance, muscle weakness can result. Elevated levels of potassium in blood are particularly dangerous.
• Permanent kidney damage: Occasionally, Acute renal failure causes permanent loss of kidney function, or end stage renal disease.
• Death: Acute renal failure can lead to loss of kidney function and, ultimately death. The risk of death is highest in people who had kidney problems before acute kidney failure. 

Tests and Diagnosis 

• Urine output measurements: The amount of urine excrete in a day may help to determine the cause of kidney failure.
• Urine tests: Analyzing a sample of urine, may reveal abnormalities that suggest kidney failure.
• Blood tests: Blood sample may reveal rapidly rising levels of urea and creatinine. 
• Imaging tests: Imaging tests such as ultrasound and computerized tomography may be used to help any abnormalities in kidneys.
• Biopsy: In certain situations, a kidney biopsy may recommend to remove a small sample of kidney tissue for lab testing.

Treatments and Drugs 

Treatment for Acute renal failure involves identifying the illness or injury that originally damaged kidneys.

• Balance the amount of fluids in blood: If Acute renal failure is caused by a lack of fluids in blood, may recommend intravenous fluids. In other cases, acute renal failure may cause to have too much fluid, leading to swelling in arms and legs. In these cases, diuretics may use.
• Medications to control blood potassium: If potassium is not properly filtering from blood, may require calcium, glucose or sodium polystyrene sulfonate to prevent the accumulation of high levels of potassium in blood. Too much potassium in the blood can cause dangerous arrhythmias and muscle weakness.   
• Medications to restore blood calcium levels: In hypocalcemia, calcium infusion is recommended.
• Treatment for end-stage kidney disease: If kidneys cannot keep up with waste and fluid clearance on their own and develop complete kidney failure lead to end-stage kidney disease. At that point, dialysis or a kidney transplant is needed.  
• Dialysis: Dialysis artificially removes waste products and extra fluid from blood when kidneys can no longer perform normally. In hemodialysis, a machine filters waste and excess fluids from the blood. 
• Kidney transplant: A kidney transplant involves surgically placing a healthy kidney from a donor into body. Transplanted patient may need to take medications for the rest of life to keep body from rejecting the new organ. 

Prevention 

• Acute renal failure is often difficult to predict or prevent. But may reduce risk by taking care of kidneys.
• Yearly physical examination include blood tests and urinalysis to monitor kidney and urinary tract health.
• Drink enough fluids to keep the kidneys functioning properly. 
• Avoid taking substances or medications that can poison or damage kidney tissues. 
• Patients having other diseases or conditions that increase risk of acute kidney failure, such as diabetes or high blood pressure, must follow recommendations for managing these conditions.  
• Persons at risk for chronic renal failure may need more frequent testing for kidney function and other problems that occur with declining kidney function.  

Chronic Renal Failure 

Chronic Kidney disease (CKD), also called chronic renal failure, is the irreversible loss of renal function due to replacement of functional nephrons with fibrous scar tissue. Kidneys filter wastes and excess fluids from blood, which are then excreted in urine. When chronic renal failure reaches an advanced stage, dangerous levels of fluid, electrolytes and wastes can build up in body. In early stage of chronic renal failure, become clinically apparent as renal insufficiency, evidenced by azotemia and possibly polyurea and nocturia resulting from impaired tubular transport and concentration of urine.

Causes 

Chronic renal failure occurs when a disease or condition impairs kidney function, causing kidney damage to worsen over several months or years. 

Diseases and conditions that commonly cause chronic renal failure include:

• Type 1 or type 2 diabetes, 
• High blood pressure.  

One of the complications resulting from diabetes or high blood pressure is the damage to the small blood vessels in the body. The blood vessels in the kidneys also become damaged, resulting in CKD.

The most common cause of end-stage renal failure worldwide is IgA nephropathy (Inflammation in the kidney). 

 Pathophysiology

A normal kidney contains approximately 1 million nephrons, each of which contributes to the total glomerular filtration rate (GFR). In the face of renal injury (regardless of the etiology), the kidney has an innate ability to maintain GFR, despite progressive destruction of nephrons, as the remaining healthy nephrons manifest hyperfiltration and compensatory hypertrophy. This nephron adaptability allows for continued normal clearance of plasma solutes. Plasma levels of substances such as urea and creatinine start to show measurable increase only after total GFR has decreased to 50%.

The plasma creatinine value will approximately double with a 50% reduction in GFR. For example, a rise in plasma creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still within the adult reference range, actually represents a loss of 50% of functioning nephron mass.

The increased glomerular capillary pressure may damage the capillaries, leading initially to secondary focal and segmental glomerulosclerosis (FSGS) and eventually to global glomerulosclerosis.

 Symptoms 

Signs and symptoms of chronic renal failure develop over time if kidney damage progresses slowly. Signs and symptoms of chronic renal failure may include:

• Nausea, 
• Vomiting, 
• Loss of appetite, 
• Fatigue and weakness, 
• Sleep problems, 
• Changes in urine output,
• Decreased mental sharpness,   
• Muscle twitches and cramps, 
• Hiccups, 
• Swelling of feet and ankles, 
• Persistent itching, 
• Chest pain, if fluid builds up around the lining of the heart, 
• Shortness of breath, if fluid builds up in the lungs, 

Tests and Diagnosis 

Blood tests: Kidney function tests look for the level of waste products, such as creatinine and urea in blood. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products.

Urine tests: Testing of a urine sample shows that the kidney is allowing the loss of protein or red blood cells into the urine. It may reveal abnormalities that point to chronic kidney failure and help to identify the cause of chronic renal failure. 

 Treatments 

There are two treatments for kidney failure:

1. Dialysis. 

 2. Kidney transplantation 

1. Dialysis:  

Two different types of dialysis can be done.

• Hemodialysis (HD). 
• Peritoneal Dialysis (PD).   

(i) Hemodialysis Purpose:

Hemodialysis cleans and filters blood using a machine to temporarily rid of the body from harmful wastes, extra salt and extra water. Hemodialysis helps to control blood pressure and helps body to keep the proper balance of important chemicals such as potassium, sodium, calcium and bicarbonate. 

Dialysis can replace part of the function of kidneys. Diet, medications and fluid limits are often needed as well. Diet, fluids, and the number of medications need will depend on treatment.

Hemodialysis Working:  

Hemodialysis uses a special filter called a dialyzer that functions as an artificial kidney to clean blood. The dialyzer is a canister connected to the hemodialysis machine.

During treatment, blood travels through tubes into the dialyzer, which filters out wastes, extra salt and extra water. Then the cleaned blood flows through another set of tubes back into body. The hemodialysis machine monitors blood flow and removes wastes from the dialyzer. 

(ii) Peritoneal Dialysis:  

Peritoneal dialysis is another procedure that removes wastes, chemicals, and extra water from body. This type of dialysis uses the lining of abdomen, or belly, to filter blood. This lining is called the peritoneal membrane and acts as the artificial kidney.

Peritoneal Dialysis Working: 

A mixture of minerals and sugar dissolved in water, called dialysis solution, travels through a catheter into belly. The sugar (dextrose) draws wastes, chemicals and extra water from the tiny blood vessels in peritoneal membrane into the dialysis solution. After several hours, the used solution is drained from abdomen through the tube, taking the wastes from blood with it. Then abdomen is refilled with fresh dialysis solution, and the cycle is repeatesd. The process of draining and refilling is called an exchange.

2. Kidney Transplant:  

A kidney transplant involves surgically placing a healthy kidney from a donor into body. Transplanted patient may need to take medications for the rest of life to keep body from rejecting the new organ.

Treatments and Drugs: Chronic renal failure has no cure. In general, treatment consists of measures to help control signs and symptoms, reduce complications, and slow progression of the disease. If kidneys become severely damaged, may need treatment for end-stage kidney disease. 

Treating Complications:  Kidney disease complications can be controlled to make more comfortable. Treatments may include: 

High blood pressure medications: 

People with kidney disease may experience worsening high blood pressure. Recommend medications to lower blood pressure, commonly angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers and to preserve kidney function. High blood pressure medications can initially decrease kidney function and change electrolyte levels, may need frequent blood tests to monitor condition.

Medications to lower cholesterol levels: 

Medications (statins) used to lower the cholesterol. People with chronic renal failure often experience high levels of bad cholesterol, which can increase the risk of heart disease.

Medications to treat anemia: 

In certain situations, may recommend supplements of the hormone erythropoietin, sometimes with added iron. Erythropoietin supplements aid in production of more red blood cells, which may relieve fatigue and weakness associated with anemia.

Medications to relieve swelling:  

People with Chronic renal failure may retain fluids. This can lead to swelling in the legs, as well as high blood pressure. Diuretics can help maintain the balance of fluids in body.

Medications to protect bones:  

Calcium and vitamin D supplements may be useful to prevent weak bones and lower risk of fracture.