Introduction to Renal tubular acidosis

A syndrome of persistent dehydration, hyperchloremia, hypokalemia, metabolic acidosis, and nephrocalcinosis, renal tubular acidosis (RTA) results from the kidneys’ inability to conserve bicarbonate. This disorder occurs as distal RTA (type I, or classic RTA) or proximal RTA (type II). The prognosis is usually good but depends on the severity of renal damage that precedes treatment.

Causes
Metabolic acidosis usually results from renal excretion of bicarbonate. However, metabolic acidosis associated with RTA results from a defect in the kidneys’ normal tubular acidification of urine.

Distal RTA
Type I RTA results from an inability of the distal tubule to secrete hydrogen ions against established gradients across the tubular membrane. This results in decreased excretion of titratable acids and ammonium, increased loss of potassium and bicarbonate in the urine, and systemic acidosis.
Prolonged acidosis causes mobilization of calcium from bone and eventually hypercalciuria, predisposing the patient to the formation of renal calculi.
Distal RTA may be classified as primary or secondary:
Primary distal RTA may occur sporadically or through a hereditary defect and is most prevalent in females, older children, adolescents, and young adults.
Secondary distal RTA has been linked to many renal and systemic conditions, such as starvation, malnutrition, hepatic cirrhosis, and several genetically transmitted disorders.

Renal vein thrombosis

Clotting in the renal vein results in renal congestion, engorgement and, possibly, infarction. Renal vein thrombosis may affect both kidneys and may occur in an acute or a chronic form.
Chronic thrombosis usually impairs renal function, causing nephrotic syndrome. Abrupt onset of thrombosis that causes extensive damage may precipitate rapidly fatal renal infarction.
If thrombosis affects both kidneys, the prognosis is poor. However, less-severe thrombosis that affects only one kidney or gradual progression that allows development of collateral circulation may preserve partial renal function.

Causes
Renal vein thrombosis results from trauma to the abdomen or back, stricture (scar formation), or a tumor that obstructs the renal vein (usually hypernephroma).
Other causes include thrombophlebitis of the inferior vena cava (may result from abdominal trauma) or blood vessels of the legs, heart failure, and periarteritis. In infants, renal vein thrombosis usually follows diarrhea that causes severe dehydration.
Chronic renal vein thrombosis is a common complication of other glomerulopathic diseases, such as amyloidosis, systemic lupus erythematosus, diabetic nephropathy, and membranoproliferative glomerulonephritis.

Signs and symptoms
Signs and symptoms of renal vein thrombosis vary with the speed of onset.

Rapid onset of venous obstruction produces severe lumbar pain and tenderness in the epigastric region and the costovertebral angle. Other characteristic features include fever, leukocytosis, pallor, hematuria, proteinuria, peripheral edema and, when the obstruction is bilateral, oliguria and other uremic signs. The kidneys enlarge and become easily palpable. Hypertension is unusual but may develop.

Introduction to Neurogenic bladder

Introduction

Also known as neuromuscular dysfunction of the lower urinary tract, neurologic bladder dysfunction, and neuropathic bladder, neurogenic bladder refers to all types of bladder dysfunction caused by an interruption of normal bladder innervation. Subsequent complications include urinary incontinence, residual urine retention, urinary tract infection, calculi formation, and renal failure. A neurogenic bladder can be spastic (hypertonic, reflex, or automatic), flaccid (hypotonic, atonic, nonreflex, or autonomous), or uncoordinated (dyssynergic).

Causes
At one time, neurogenic bladder was thought to result primarily from spinal cord injury; now, it appears to stem from a host of underlying conditions:

• cerebral disorders, such as cerebrovascular accident, brain tumor (meningioma and glioma), Parkinson’s disease, multiple sclerosis, and dementia
• spinal cord disease or trauma, such as spinal stenosis (causing cord compression) or arachnoiditis (causing adhesions between the membranes covering the cord), cervical spondylosis, myelopathies from hereditary or nutritional deficiencies and, rarely, tabes dorsalis
• disorders of peripheral innervation, including autonomic neuropathies resulting from endocrine disturbances such as diabetes mellitus (most common)
• metabolic disturbances, such as hypothyroidism, porphyria, or uremia (infrequent)
• acute infectious diseases such as Guillain-Barré syndrome
• heavy metal toxicity
• chronic alcoholism
• collagen diseases such as systemic lupus erythematosus
• vascular diseases such as atherosclerosis
• distant effects of cancer such as primary oat cell carcinoma of the lung
• herpes zoster
• sacral agenesis.

An upper motor neuron lesion (above S2 to S4) causes spastic neurogenic bladder, with spontaneous contractions of the detrusor muscles, elevated intravesical voiding pressure, bladder wall hypertrophy with trabeculation, and urinary sphincter spasms.

A lower motor neuron lesion (below S2 to S4) causes flaccid neurogenic bladder, with decreased intravesical pressure, increased bladder capacity and large residual urine retention, and poor detrusor contraction.

Summary of Bladder cancer

Bladder tumors can develop on the surface of the bladder wall (benign or malignant papillomas) or grow within the bladder wall (generally more virulent) and quickly invade underlying muscles. Most bladder tumors (90%) are transitional cell carcinomas, arising from the transitional epithelium of mucous membranes. Less common are adenocarcinomas, epidermoid carcinomas, squamous cell carcinomas, sarcomas, tumors in bladder diverticula, and carcinoma in situ. Bladder tumors are most prevalent in men older than age 50 and are more common in densely populated industrial areas, but women are diagnosed at more advanced stages.

Causes
Certain environmental carcinogens—such as 2-naphthylamine, benzidine, tobacco, and nitrates—predispose people to transitional cell tumors. Thus, workers in certain industries (rubber workers, weavers, leather finishers, aniline dye workers, hairdressers, petroleum workers, and spray painters) are at high risk for such tumors. The period between exposure to the carcinogen and development of symptoms is about 18 years.
Squamous cell carcinoma of the bladder is most common in geographic areas where schistosomiasis is endemic. It’s also associated with chronic bladder irritation and infection (for example, from kidney stones, indwelling urinary catheters, and cystitis caused by cyclophosphamide).

Signs and symptoms
In early stages, about 25% of patients with bladder tumors have no symptoms. Commonly, the first sign is gross, painless, intermittent hematuria (often with clots in the urine). Patients with invasive lesions often have suprapubic pain after voiding. Other symptoms include bladder irritability, urinary frequency, nocturia, and dribbling.

Diagnosis
Only cystoscopy and a biopsy can confirm bladder cancer. Cystoscopy should be performed when hematuria first appears. When it’s performed under anesthesia, a bimanual examination is usually done to determine if the bladder is fixed to the pelvic wall. A thorough history and physical examination may help determine whether the tumor has invaded the prostate or the lymph nodes.

Lower Urinary tract infection

Introduction
Cystitis and urethritis, the two forms of lower urinary tract infection (UTI), are nearly 10 times more common in women than in men and affect approximately 10% to 20% of all women at least once. Lower UTI is also a prevalent bacterial disease in children, with girls also most commonly affected.
In men and children, lower UTIs are frequently related to anatomic or physiologic abnormalities and therefore require extremely close evaluation. UTIs often respond readily to treatment, but recurrence and resistant bacterial flare-up during therapy are possible.

Pathophysiology
Most lower UTIs result from ascending infection by a single gram-negative enteric bacterium, such as Escherichia coli, Klebsiella, Proteus, Enterobacter, Pseudomonas, or Serratia. However, in a patient with neurogenic bladder, an indwelling urinary catheter, or a fistula between the intestine and bladder, lower UTI may result from simultaneous infection with multiple pathogens.
Infection may result from a breakdown in local defense mechanisms in the bladder that allow bacteria to invade the bladder mucosa and multiply. These bacteria cannot be readily eliminated by normal micturition.
The risk of cystitis is higher when the bladder or urethra becomes blocked and urine flow stops. It can occur when instruments are inserted into the urinary tract during procedures such as catheterization or cystoscopy. Other risks include pregnancy, diabetes, and a history of analgesic or reflux nephropathy. The elderly are at increased risk for developing UTIs due to incomplete emptying of the bladder; this is associated with conditions such as benign prostatic hyperplasia (BPH), prostatitis, and urethral strictures. Also, lack of adequate fluids, bowel incontinence, immobility or decreased mobility, indwelling urinary catheters, and placement in a nursing home all place the person at risk for developing an infection.

Bacterial flare-up
During treatment, bacterial flare-up is generally caused by the pathogenic organism’s resistance to the prescribed antimicrobial therapy. The presence of even a small number (less than 10,000/ml) of bacteria in a midstream urine sample obtained during treatment casts doubt on the treatment’s effectiveness.

Recurrent UTI
In 99% of patients, recurrent lower UTI results from reinfection by the same organism or from some new pathogen; in the remaining 1%, recurrence reflects persistent infection, usually from renal calculi, chronic bacterial prostatitis, or a structural anomaly that may become a source of infection.

Introduction to Nephrotic Syndrome

Nephrotic syndrome (or nephrosis) is characterized by marked proteinuria, hypoalbuminemia, hyperlipemia, and edema. Although nephrotic syndrome isn’t a disease itself, it results from a specific glomerular defect and indicates renal damage. The prognosis is highly variable, depending on the underlying cause. Some forms may progress to end-stage renal failure.

Causes
About 75% of nephrotic syndrome cases result from primary (idiopathic) glomerulonephritis. 

Classifications include the following:

• With minimal change disease (lipid nephrosis or nil disease)—the main cause of nephrotic syndrome in children—the glomeruli appear normal by light microscopy. Some tubules may contain increased lipid deposits.
• Membraneous glomerulonephritis—the most common lesion in patients with adult idiopathic nephrotic syndrome—is characterized by uniform thickening of the glomerular basement membrane containing dense deposits. It can eventually progress to renal failure.
• Focal glomerulosclerosis can develop spontaneously at any age, follow kidney transplantation, or result from heroin abuse. Lesions initially affect the deeper glomeruli, causing hyaline sclerosis, with later involvement of the superficial glomeruli. These lesions generally cause slowly progressive deterioration in renal function. Remissions occur occasionally.
• With membranoproliferative glomerulonephritis, slowly progressive lesions develop in the subendothelial region of the basement membrane. These lesions may follow infection, particularly streptococcal infection. This disease occurs primarily in children and young adults.
• Other causes of nephrotic syndrome include metabolic diseases such as diabetes mellitus; collagen-vascular disorders, such as systemic lupus erythematosus and polyarteritis nodosa; circulatory diseases, such as heart failure and sickle cell anemia; nephrotoxins, such as mercury, gold, and nonsteroidal anti-inflammatories; allergic reactions; infections, such as tuberculosis or hepatitis B; preeclampsia toxemia; hereditary nephritis; multiple myeloma; and other neoplastic diseases. These diseases increase glomerular protein permeability, leading to the increased urinary excretion of protein, especially albumin, and subsequent hypoalbuminemia.

Approach To Dysuria In Children

Introduction
Dysuria is any discomfort with urination but particularly refers to pain or burning during urination. Generally stemming from irritation of the bladder or urethra, it is a commonly reported sensation that affects men, women, and children alike.

Although dysuria can be caused by any condition associated with inflammation, irritation, or obstruction of the urinary tract, in children and adolescents it most commonly accompanies urinary tract infections (UTIs), urethritis, and chemical or traumatic irritation. Identifying the underlying
cause of dysuria requires a detailed history, a careful physical examination, and a focused laboratory evaluation as needed.

Clinical History
The younger the child, the less precise is the complaint of painful urination. Other symptoms, such as pruritus or pain in the genital or perineal area, may be more noticeable while the child is voiding and not distracted. Although dysuria may be the only complaint, it is more often accompanied by associated symptoms.

Regardless of the child’s age, dividing the associated symptoms into either specific urinary symptoms or nonspecific symptoms is helpful.

Symptoms specific to the urinary tract include

• hematuria, 
• discharge, 
• malodorous urine, 
• frequency, 
• urgency, 
• refusal to void, 
• new-onset nocturnal enuresis, and 
• daytime incontinence. 

The physician should inquire about exposure to detergents, perfumed soaps, bubble baths, or ointments and about the type of underwear fabric, any of which can irritate the mucosal lining of the urethra or bladder.

A thorough history of the timing of toilet training, last occurrence of daytime accidents, nocturnal enuresis, withholding maneuvers, and constipation can help elucidate a diagnosis of dysfunctional elimination syndrome.The lack of a history of trauma may not be accurate because children often do not recall it or, in the case of masturbation or sexual abuse, may deliberately deny it.

To judge the possibility of a sexually transmitted infection, adolescents should be asked about sexual activity and safety practices.

A family history of nephrolithiasis should focus attention on hypercalciuria as a cause for dysuria, and a more detailed dietary history should be elicited, including intake of salt, dairy products, and vitamins.

Symptoms outside the urinary tract, such as conjunctival injection, oral and genital ulcers, arthralgia, or a generalized rash, could suggest a systemic inflammatory condition, such as Stevens-Johnson syndrome, Reiter syndrome, or Behçet disease.

A history of fever suggests an infectious condition such as pyelonephritis, appendicitis, or pelvic inflammatory disease.

Alzheimer’s Disease

Also known as primary degenerative dementia, Alzheimer’s disease accounts for more than half of all dementias. An estimated 5% of people over age 65 have a severe form of this disease, and 12% suffer from mild to moderate dementia. Because this is a primary progressive dementia, the prognosis is poor.

Causes
Several factors contribute to the progression of Alzheimer’s disease. They include neurochemical factors, such as deficiencies in acetylcholine (a neurotransmitter), somatostatin, substance P, and norepinephrine; environmental factors, such as aluminum and manganese; viral factors, such as slow-growing central nervous system viruses; trauma; and genetic immunologic factors.
The brain tissue of a patient with Alzheimer’s disease typically shows cortical atrophy, the hallmark features being neurofibrillary tangles, neuritic plaques, and granulovascular degeneration.

Signs and symptoms
Onset is insidious. Initially, the patient experiences almost imperceptible changes, such as forgetfulness, recent memory loss, difficulty learning and remembering new information, deterioration in personal hygiene and appearance, and an inability to concentrate. Gradually, tasks that require abstract thinking and activities that require judgment become more difficult. Progressive and severe deterioration in memory, language, and motor function results in a loss of coordination and an inability to write or speak.
Personality changes (restlessness, irritability) and nocturnal awakenings are common. Eventually, the patient becomes disoriented, and emotional lability and physical and intellectual disability progress. The patient becomes more susceptible to infection and accidents. Secondary to loss of the cough reflex, pulmonary diseases such as pneumonia may result in death.

Benign Prostatic Hyperplasia

Introduction

Although most men older than age 50 have some prostatic enlargement, with benign prostatic hyperplasia (BPH), the prostate gland enlarges sufficiently to compress the urethra and cause some overt urinary obstruction. Depending on the size of the enlarged prostate, the age and health of the patient, and the extent of obstruction, BPH is treated symptomatically or surgically.

Causes
Recent evidence suggests a link between BPH and hormonal activity. As men age, production of androgenic hormones decreases, causing an imbalance in androgen and estrogen levels and high levels of dihydrotestosterone, the main prostatic intracellular androgen. Other causes include neoplasm, arteriosclerosis, inflammation, and metabolic or nutritional disturbances.
Whatever the cause, BPH begins with changes in periurethral glandular tissue. As the prostate enlarges, it may extend into the bladder and obstruct urinary outflow by compressing or distorting the prostatic urethra. BPH may also cause a pouch to form in the bladder that retains urine when the rest of the bladder empties. This retained urine may lead to calculus formation or cystitis.

Signs and symptomsSigns and symptoms of BPH depend on the extent of prostatic enlargement and the lobes affected.

Urinary symptoms
Characteristically, the condition starts with a group of symptoms known as prostatism: reduced urinary stream caliber and force, difficulty starting micturition (straining), feeling of incomplete voiding and, occasionally, urine retention. As obstruction increases, urination becomes more frequent, with nocturia, incontinence and, possibly, hematuria.

Physical examination reveals a visible midline mass (distended bladder) that represents an incompletely emptied bladder; rectal palpation discloses an enlarged prostate. The examination may also detect secondary anemia and, possibly, renal insufficiency secondary to obstruction.

Later effects
As BPH worsens, complete urinary obstruction may follow infection. Complications include infection, renal insufficiency, hemorrhage, and shock.

Brief Summary of Acute Tubular Necrosis

Introduction

Also known as acute tubulointerstitial nephritis, acute tubular necrosis (ATN) is the most common cause of acute renal failure in critically ill patients, and it accounts for about 75% of all cases of acute renal failure. ATN injures the tubular segment of the nephron, causing renal failure and uremic syndrome. Mortality ranges from 40% to 70%, depending on complications from underlying diseases. Patients with non-oliguric forms of ATN have a better prognosis.

Causes
ATN results from ischemic or nephrotoxic injury, most commonly in debilitated patients, such as the critically ill and those who have undergone extensive surgery.
With ischemic injury, disruption of blood flow to the kidneys may result from circulatory collapse, severe hypotension, trauma, hemorrhage, dehydration, cardiogenic or septic shock, surgery, anesthetics, or reactions to transfusions. Ischemic ATN can damage the epithelial and basement membranes and can cause lesions in the renal interstitium.
With nephrotoxic injury, damage may follow ingestion of certain chemical agents or result from a hypersensitive reaction of the kidneys. Because nephrotoxic ATN doesn’t damage the basement membrane of the nephron, it’s potentially reversible.

ATN may result from:

• diseased tubular epithelium that allows leakage of glomerular filtrate across the membranes and reabsorption of filtrate into the blood
• obstruction of urine flow by the collection of damaged cells, casts, red blood cells (RBCs), and other cellular debris within the tubular walls
• ischemic injury to glomerular epithelial cells, resulting in cellular collapse and decreased glomerular capillary permeability
• ischemic injury to vascular endothelium, eventually resulting in cellular swelling and obstruction.

Signs and symptoms
ATN is usually difficult to recognize in its early stages because effects of the critically ill patient’s primary disease may mask the symptoms of ATN. The first recognizable effect may be decreased urine output. Generally, hyperkalemia and the characteristic uremic syndrome soon follow, with oliguria (or, rarely, anuria) and confusion, which may progress to uremic coma. Other complications include heart failure, uremic pericarditis, pulmonary edema, uremic lung, anemia, anorexia, intractable vomiting, and poor wound healing due to debilitation.
Fever and chills are ominous indications of infection, the leading cause of death in patients with ATN.

Introduction to Renal Biopsy

Renal biopsy is not a commonly performed procedure in medical practice but it is sometimes indicated when it has diagnostic value in certain kidney diseases. Most cases of acute renal failure are due to pre renal causes or acute tubular necrosis and recovery of renal function typically occurs over a course of few weeks. Renal biopsy should only be performed if knowing the histology will help in the management. Once chronic renal failure is established, the kidneys are small, may be hard to biopsy, and theresults are usually unhelpful.

Indications

• To determine the cause of unexplained renal failure.
• Persistent Heavy proteinuria >1gm/24hrs
• Investigating the cause of adult nephritic syndrome with persistent hematuria.
• Childhood nephritic or nephrotic syndrome that are unresponsive to treatment.
• Systemic disease with renal involvement like sarcoidosis, amyloidosis.
• Post transplant renal dysfunction.

Contraindication

• Underlying disorder of coagulation.
• Thrombocytopenia.
• Uncontrolled hypertension.
• Solitary kidney (except in transplanted kidneys).
• Small contracted kidneys i.e < 60% of expected bipolar length because it is technically difficult, histology is hard to interpret and prognosis cannot be altered.
• Uncooperative patient.

Introduction To Analgesic Nephropathy

Introduction: 

Analgesic Nephropathy is a condition that is associated with prolonged, heavy use of analgesics that leads to decline in renal function due to chronic papillary necrosis and chronic diffuse tubulointerstitial damage to renal cortex.

The incidence of analgesic nephropathy has declined significantly after the withdrawal of phenacetin use.

Clinical Features

• Patients with analgesic nephropathy are unable to produce maximally concentrated urine due to underlying medullary and papillary damage.
• They present with repeated UTI’s and or urinary abnormalities on urinalysis like hematuria, proteinuria, casts etc.
• Anemia is more severe as compared to level of renal insufficiency.
• Distal tubular acidosis associated with analgesic nephropathy contributes to the development of nephrocalcinosis.
• Kidneys become shrunken and calyces are deformed producing “ring sign” on IVP that is pathognomonic of papillary necrosis.
• Transitional cell carcinoma may develop in the urinary pelvis or ureters as a late complication of analgesic abuse.