Polycystic kidney disease

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Polycystic_kidney_disease 

 

Polycystic kidney disease
Other names	Kidney - polycystic
Severely affected polycystic kidneys removed at time of transplantation
Specialty	Nephrology
Symptoms	Abdominal pain
Types	ADPKD and ARPKD
Diagnostic method	MRI, CT scan, Ultrasound
Treatment	Antihypertensives, Life style management

Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These cysts may begin to develop in utero, in infancy, in childhood, or in adulthood. Cysts are non-functioning tubules filled with fluid pumped into them, which range in size from microscopic to enormous, crushing adjacent normal tubules and eventually rendering them non-functional as well.

PKD is caused by abnormal genes which produce a specific abnormal protein; this protein has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The abnormal gene exists in all cells in the body; as a result, cysts may occur in the liver, seminal vesicles, and pancreas. This genetic defect can also cause aortic root aneurysms, and aneurysms in the circle of Willis cerebral arteries, which if they rupture, can cause a subarachnoid hemorrhage.

Diagnosis may be suspected from one, some, or all of the following: new onset flank pain or red urine; a positive family history; palpation of enlarged kidneys on physical exam; an incidental finding on abdominal sonogram; or an incidental finding of abnormal kidney function on routine lab work (BUN, serum creatinine, or eGFR). Definitive diagnosis is made by abdominal CT exam.

Complications include hypertension due to the activation of the renin–angiotensin–aldosterone system (RAAS), frequent cyst infections, urinary bleeding, and declining renal function. Hypertension is treated with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Infections are treated with antibiotics. Declining renal function is treated with renal replacement therapy (RRT): dialysis and/or transplantation. Management from the time of the suspected or definitive diagnosis is by a board-certified nephrologist.

Signs and symptoms

Signs and symptoms include high blood pressure, headaches, abdominal pain, blood in the urine, and excessive urination. Other symptoms include pain in the back, and cyst formation (renal and other organs).

Cause

PKD is caused by abnormal genes which produce a specific abnormal protein which has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

Autosomal dominant

CT scan showing autosomal dominant polycystic kidney disease

 

Cartoon of autosomal dominant polycystic kidney disease with normal kidney inset to right of diagram

 

Cartoon of autosomal recessive polycystic kidney disease with normal kidney inset to right of diagram

Autosomal dominant polycystic kidney disease (ADPKD) is the most common of all the inherited cystic kidney diseases with an incidence of 1:500 live births. Studies show that 10% of end-stage kidney disease (ESKD) patients being treated with dialysis in Europe and the U.S. were initially diagnosed and treated for ADPKD.

Genetic mutations in any of the three genes PKD1, PKD2, and PKD3 have similar phenotypical presentations.

• Gene PKD1 is located on chromosome 16 and codes for a protein involved in regulation of cell cycle and intracellular calcium transport in epithelial cells, and is responsible for 85% of the cases of ADPKD.
• A group of voltage-linked cation channels, with inward selectivity for K>Na>>Ca and outward selectivity for Ca2+ ≈ Ba2+ > Na+ ≈ K+, are coded for by PKD2 on chromosome 4
• PKD3 recently appeared in research papers as a postulated third gene. Fewer than 10% of cases of ADPKD appear in non-ADPKD families. Cyst formation begins in utero from any point along the nephron, although fewer than 5% of nephrons are thought to be involved. As the cysts accumulate fluid, they enlarge, separate entirely from the nephron, compress the neighboring kidney parenchyma, and progressively compromise kidney function.

Autosomal recessive

Autosomal recessive polycystic kidney disease (ARPKD) (OMIM #263200) is the lesser common of the two types of PKD, with an incidence of 1:20,000 live births and is typically identified in the first few weeks after birth. Unfortunately, the kidneys are often underdeveloped resulting in a 30% death rate in newborns with ARPKD. PKHD1 is involved.

Mechanism

PKD1 and PKD2

Both autosomal dominant and autosomal recessive polycystic kidney disease cyst formation are tied to abnormal cilia-mediated signaling. The polycystin-1 and polycystin-2 proteins appear to be involved in both autosomal dominant and recessive polycystic kidney disease due to defects in both proteins. Both proteins have communication with calcium channel proteins, and causes reduction in resting (intracellular) calcium and endoplasmic reticulum storage of calcium.

The disease is characterized by a ‘second hit’ phenomenon, in which a mutated dominant allele is inherited from a parent, with cyst formation occurring only after the normal, wild-type gene sustains a subsequent second genetic ‘hit’, resulting in renal tubular cyst formation and disease progression.

PKD results from defects in the primary cilium, an immotile, hair-like cellular organelle present on the surface of most cells in the body, anchored in the cell body by the basal body. In the kidney, primary cilia have been found to be present on most cells of the nephron, projecting from the apical surface of the renal epithelium into the tubule lumen. The cilia were believed to bend in the urine flow, leading to changes in signalling, however this has since been shown to be an experimental error (the bending of cilia was an artifact of focal plane compensation, and also the actual effect on micturition by severe hypertension and cardiac arrest) and that bending of cilia does not contribute to alterations in Ca flux. While it is not known how defects in the primary cilium lead to cyst development, it is thought to possibly be related to disruption of one of the many signaling pathways regulated by the primary cilium, including intracellular calcium, Wnt/β-catenin, cyclic adenosine monophosphate (cAMP), or planar cell polarity (PCP). Function of the primary cilium is impaired, resulting in disruption of a number of intracellular signaling cascades which produce differentiation of cystic epithelium, increased cell division, increased apoptosis, and loss of resorptive capacity.

Diagnosis

Polycystic kidney disease can be ascertained via a CT scan of abdomen, as well as, an MRI and ultrasound of the same area. A physical exam/test can reveal enlarged liver, heart murmurs and elevated blood pressure

Natural history

Most cases progress to bilateral disease in adulthood.

Treatment

Chr 11 FISH-mapped BACs from CGAP

There is no FDA-approved treatment. However, recent research indicates that mild to moderate dietary restrictions slow the progression of autosomal dominant polycystic kidney disease (ADPKD) in mice.

If and when the disease progresses enough in a given case, the nephrologist or other practitioner and the patient will have to decide what form of renal replacement therapy will be used to treat end-stage kidney disease (kidney failure, typically stage 4 or 5 of chronic kidney disease).

That will either be some form of dialysis, which can be done at least two different ways at varying frequencies and durations (whether it is done at home or in the clinic depends on the method used and the patient's stability and training) and eventually, if they are eligible because of the nature and severity of their condition and if a suitable match can be found, unilateral or bilateral kidney transplantation.

A Cochrane Review study of autosomal dominant polycystic kidney disease made note of the fact that it is important at all times, while avoiding antibiotic resistance, to control infections of the cysts in the kidneys, and if affected, the liver, when needed for a certain duration to combat infection, by using, "bacteriostatic and bacteriocidal drugs".

Prognosis

ADPKD individuals might have a normal life; conversely, ARPKD can cause kidney dysfunction and can lead to kidney failure by the age of 40–60. ADPKD1 and ADPKD2 are very different, in that ADPKD2 is much milder.

Currently, there are no therapies proven effective to prevent the progression of ADPKD.

Epidemiology

PKD is one of the most common hereditary diseases in the United States, affecting more than 600,000 people. It is the cause of nearly 10% of all end-stage renal disease. It equally affects men, women, and all races.^[20] PKD occurs in some animals as well as humans.^[21][22]

Nephrology

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Nephrology

Nephrology

A human kidney (click on image for description).
System	Urinary
Significant diseases	Hypertension, Kidney cancer
Significant tests	Kidney biopsy, Urinalysis
Specialist	Nephrologist
Glossary	Glossary of medicine

Nephrology (from Greek nephros "kidney", combined with the suffix -logy, "the study of") is a specialty of medicine and pediatric medicine that concerns itself with the kidneys: the study of normal kidney function and kidney disease, the preservation of kidney health, and the treatment of kidney disease, from diet and medication to renal replacement therapy (dialysis and kidney transplantation).

Nephrology also studies systemic conditions that affect the kidneys, such as diabetes and autoimmune disease; and systemic diseases that occur as a result of kidney disease, such as renal osteodystrophy and hypertension. A physician who has undertaken additional training and become certified in nephrology is called a nephrologist.

The term "nephrology" was first used in about 1960. Before then, the specialty was usually referred to as "kidney medicine."

Scope

Nephrology concerns the diagnosis and treatment of kidney diseases, including electrolyte disturbances and hypertension, and the care of those requiring renal replacement therapy, including dialysis and renal transplant patients. The word 'dialysis' is from the mid 19th century: via Latin from the Greek word 'dialusis'; from 'dialuein' (split, separate), from 'dia' (apart) and 'luein' (set free). In other words, dialysis replaces the primary (excretory) function of the kidney, which separates (and removes) excess toxins and water from the blood, placing them in the urine.

Many diseases affecting the kidney are systemic disorders not limited to the organ itself, and may require special treatment. Examples include acquired conditions such as systemic vasculitides (e.g. ANCA vasculitis) and autoimmune diseases (e.g., lupus), as well as congenital or genetic conditions such as polycystic kidney disease. 

Patients are referred to nephrology specialists after a urinalysis, for various reasons, such as acute kidney failure, chronic kidney disease, hematuria, proteinuria, kidney stones, hypertension, and disorders of acid/base or electrolytes.

Nephrologist

A nephrologist is a physician who specializes in the care and treatment of kidney disease. Nephrology requires additional training to become an expert with advanced skills. Nephrologists may provide care to people without kidney problems and may work in general/internal medicine, transplant medicine, immunosuppression management, intensive care medicine, clinical pharmacology, perioperative medicine, or pediatric nephrology.

Nephrologists may further sub-specialise in dialysis, kidney transplantation, chronic kidney disease, cancer-related kidney diseases (Onconephrology), procedural nephrology or other non-nephrology areas as described above.

Procedures a nephrologist may perform include native kidney and transplant kidney biopsy, dialysis access insertion (temporary vascular access lines, tunnelled vascular access lines, peritoneal dialysis access lines), fistula management (angiographic or surgical fistulogram and plasty), and bone biopsy. Bone biopsies are now unusual.

Training

India

To become a nephrologist in India, one has to complete an MBBS (5 and1/2 years) degree, followed by a MD/DNB (3 years) either in medicine or paediatrics, followed by a DM/DNB (3 years) course in either nephrology or paediatric nephrology.

Australia and New Zealand

Nephrology training in Australia and New Zealand typically includes completion of a medical degree (Bachelor of Medicine, Bachelor of Surgery: 4–6 years), internship (1 year), Basic Physician Training (3 years minimum), successful completion of the Royal Australasian College of Physicians written and clinical examinations, and Advanced Physician Training in Nephrology (2–3 years). The training pathway is overseen and accredited by the Royal Australasian College of Physicians. Increasingly, nephrologists may additionally complete of a post-graduate degree (usually a PhD) in a nephrology research interest (3–4 years). Finally, all Australian and New Zealand nephrologists participate in career-long professional and personal development through the Royal Australasian College of Physicians and other bodies such as the Australian and New Zealand Society of Nephrology and the Transplant Society of Australia and New Zealand.

United Kingdom

In the United Kingdom, nephrology (often called renal medicine) is a subspecialty of general medicine. A nephrologist has completed medical school, foundation year posts (FY1 and FY2) and core medical training (CMT), specialist training (ST) and passed the Membership of the Royal College of Physicians (MRCP) exam before competing for a National Training Number (NTN) in renal medicine. The typical Specialty Training (when they are called a registrar, or a ST) is five years and leads to a Certificate of Completion of Training (CCT) in both renal medicine and general (internal) medicine. In that five years, they usually rotate yearly between hospitals on a region (known as a deanery). They are then accepted on to the Specialist Register of the General Medical Council (GMC). Specialty trainees often interrupt their clinical training to obtain research degrees (MD/PhD). After achieving CCT, the registrar (ST) may apply for a permanent post as Consultant in Renal Medicine. Subsequently, some Consultants practice nephrology alone. Others work in this area, and in Intensive Care (ICU) , or General (Internal) or Acute Medicine.

United States

Nephrology training can be accomplished through one of two routes. The first pathway is through an internal medicine pathway leading to an Internal Medicine/Nephrology specialty, and sometimes known as "adult nephrology". The second pathway is through Pediatrics leading to a speciality in Pediatric Nephrology. In the United States, after medical school adult nephrologists complete a three-year residency in internal medicine followed by a two-year (or longer) fellowship in nephrology. Complementary to an adult nephrologist, a pediatric nephrologist will complete a three-year pediatric residency after medical school or a four-year Combined Internal Medicine and Pediatrics residency. This is followed by a three-year fellowship in Pediatic Nephrology. Once training is satisfactorily completed, the physician is eligible to take the American Board of Internal Medicine (ABIM) or American Osteopathic Board of Internal Medicine (AOBIM) nephrology examination. Nephrologists must be approved by one of these boards. To be approved, the physician must fulfill the requirements for education and training in nephrology in order to qualify to take the board's examination. If a physician passes the examination, then he or she can become a nephrology specialist. Typically, nephrologists also need two to three years of training in an ACGME or AOA accredited fellowship in nephrology. Nearly all programs train nephrologists in continuous renal replacement therapy; fewer than half in the United States train in the provision of plasmapheresis. Only pediatric trained physicians are able to train in pediatric nephrology, and internal medicine (adult) trained physicians may enter general (adult) nephrology fellowships.

Diagnosis

History and physical examination are central to the diagnostic workup in nephrology. The history typically includes the present illness, family history, general medical history, diet, medication use, drug use and occupation. The physical examination typically includes an assessment of volume state, blood pressure, heart, lungs, peripheral arteries, joints, abdomen and flank. A rash may be relevant too, especially as an indicator of autoimmune disease. 

Examination of the urine (urinalysis) allows a direct assessment for possible kidney problems, which may be suggested by appearance of blood in the urine (haematuria), protein in the urine (proteinuria), pus cells in the urine (pyuria) or cancer cells in the urine. A 24-hour urine collection used to be used to quantify daily protein loss (see proteinuria), urine output, creatinine clearance or electrolyte handling by the renal tubules. It is now more common to measure protein loss from a small random sample of urine. 

Basic blood tests can be used to check the concentration of hemoglobin, white count, platelets, sodium, potassium, chloride, bicarbonate, urea, creatinine, albumin, calcium, magnesium, phosphate, alkaline phosphatase and parathyroid hormone (PTH) in the blood. All of these may be affected by kidney problems. The serum creatinine concentration is the most important blood test as it is used to estimate the function of the kidney, called the creatinine clearance or estimated glomerular filtration rate (GFR). 

It is good idea for patients with longterm kidney disease to know an up-to-date list of medications, and their latest blood tests, especially the blood creatinine level. In the United Kingdom, blood tests can monitored online by the patient, through a website called RenalPatientView. 

More specialized tests can be ordered to discover or link certain systemic diseases to kidney failure such as infections (hepatitis B, hepatitis C), autoimmune conditions (systemic lupus erythematosus, ANCA vasculitis), paraproteinemias (amyloidosis, multiple myeloma) and metabolic diseases (diabetes, cystinosis). 

Structural abnormalities of the kidneys are identified with imaging tests. These may include Medical ultrasonography/ultrasound, computed axial tomography (CT), scintigraphy (nuclear medicine), angiography or magnetic resonance imaging (MRI). 

In certain circumstances, less invasive testing may not provide a certain diagnosis. Where definitive diagnosis is required, a biopsy of the kidney (renal biopsy) may be performed. This typically involves the insertion, under local anaesthetic and ultrasound or CT guidance, of a core biopsy needle into the kidney to obtain a small sample of kidney tissue. The kidney tissue is then examined under a microscope, allowing direct visualization of the changes occurring within the kidney. Additionally, the pathology may also stage a problem affecting the kidney, allowing some degree of prognostication. In some circumstances, kidney biopsy will also be used to monitor response to treatment and identify early relapse. A transplant kidney biopsy may also be performed to look for rejection of the kidney.

Treatment

Treatments in nephrology can include medications, blood products, surgical interventions (urology, vascular or surgical procedures), renal replacement therapy (dialysis or kidney transplantation) and plasma exchange. Kidney problems can have significant impact on quality and length of life, and so psychological support, health education and advanced care planning play key roles in nephrology.

Chronic kidney disease is typically managed with treatment of causative conditions (such as diabetes), avoidance of substances toxic to the kidneys (nephrotoxins like radiologic contrast and non-steroidal anti-inflammatory drugs), antihypertensives, diet and weight modification and planning for end-stage kidney failure. Impaired kidney function has systemic effects on the body. An erythropoetin stimulating agent (ESA) may be required to ensure adequate production of red blood cells, activated vitamin D supplements and phosphate binders may be required to counteract the effects of kidney failure on bone metabolism, and blood volume and electrolyte disturbance may need correction. Diuretics (such as furosemide) may be used to correct fluid overload, and alkalis (such as sodium bicarbonate) can be used to treat metabolic acidosis. 

Auto-immune and inflammatory kidney disease, such as vasculitis or transplant rejection, may be treated with immunosuppression. Commonly used agents are prednisone, mycophenolate, cyclophosphamide, ciclosporin, tacrolimus, everolimus, thymoglobulin and sirolimus. Newer, so-called "biologic drugs" or monoclonal antibodies, are also used in these conditions and include rituximab, basiliximab and eculizumab. Blood products including intravenous immunoglobulin and a process known as plasma exchange can also be employed.

When the kidneys are no longer able to sustain the demands of the body, end-stage kidney failure is said to have occurred. Without renal replacement therapy, death from kidney failure will eventually result. Dialysis is an artificial method of replacing some kidney function to prolong life. Renal transplantation replaces kidney function by inserting into the body a healthier kidney from an organ donor and inducing immunologic tolerance of that organ with immunosuppression. At present, renal transplantation is the most effective treatment for end-stage kidney failure although its worldwide availability is limited by lack of availability of donor organs. Generally speaking, kidneys from living donors are 'better' than those from deceased donors, as they last longer. 

Most kidney conditions are chronic conditions and so long term followup with a nephrologist is usually necessary. In the United Kingdom, care may be shared with the patient's primary care physician, called a General Practitioner (GP).

Organizations

The world's first society of nephrology was the French 'Societe de Pathologie Renale'. Its first president was Jean Hamburger, and its first meeting was in Paris in February 1949. In 1959, Hamburger also founded the 'Société de Néphrologie', as a continuation of the older society. The UK's Renal Association was founded in 1950; the second society of nephrologists. Its first president was Arthur Osman. Its first meeting was on 30 March 1950 in London. The Società di Nefrologia Italiana was founded in 1957 and was the first national society to incorporate the phrase nephrologia (or nephrology) into its name.

The word 'nephrology' appeared for the first time in a conference, on 1–4 September 1960 at the "Premier Congrès International de Néphrologie" in Evian and Geneva, the first meeting of the International Society of Nephrology (ISN, International Society of Nephrology). The first day (1.9.60) was in Geneva and the next three (2–4.9.60) were in Evian, France. The early history of the ISN is described by Robinson and Richet in 2005 and the later history by Barsoum in 2011. The ISN is the largest global society representing medical professionals engaged in advancing kidney care worldwide. 

In the USA, founded in 1964, the National Kidney Foundation is a national organization representing patients and professionals who treat kidney diseases. Founded in 1966, the American Society of Nephrology (ASN) is the world’s largest professional society devoted to the study of kidney disease. The American Nephrology Nurses' Association (ANNA), founded in 1969, promotes excellence in and appreciation of nephrology nursing to make a positive difference for patients with kidney disease. The American Association of Kidney Patients (AAKP) is a non-profit, patient-centric group focused on improving the health and well-being of CKD and dialysis patients. The National Renal Administrators Association (NRAA), founded in 1977, is a national organization that represents and supports the independent and community-based dialysis providers. The American Kidney Fund directly provides financial support to patients in need, as well as participating in health education and prevention efforts. ASDIN (American Society of Diagnostic and Interventional Nephrology) is the main organization of interventional nephrologists. Other organizations include CIDA, VASA etc. which deal with dialysis vascular access. The Renal Support Network (RSN) is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by chronic kidney disease (CKD).

In the United Kingdom, UK National Kidney Federation and Kidney Care UK (previously known as British Kidney Patient Association, BKPA) represent patients, and the Renal Association represents renal physicians and works closely with the National Service Framework for kidney disease. 

There is as well an International Office in Brussels, Belgium.

Nephron

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Nephron

Nephron
Diagram (left) of a long juxtamedullary nephron and (right) of a short cortical nephron. The left nephron is labelled with six named nephron segments. Also labelled is the collecting duct, mislabelled the "collection duct"; it is not part of the nephron.
Details
Precursor	Metanephric blastema (intermediate mesoderm)
System	Urinary system
Identifiers
Latin	Nephroneum
MeSH	D009399
FMA	17640

The nephron is the microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and an encompassing Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 0.8 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged (some are added, others are removed); first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

The interior of Bowman's capsule, called Bowman's space, collects the filtrate from the filtering capillaries of the glomerular tuft, which also contains mesangial cells supporting these capillaries. These components function as the filtration unit and make up the renal corpuscle. The filtering structure (glomerular filtration barrier) has three layers composed of endothelial cells, a basement membrane, and podocytes (foot processes). The tubule has five anatomically and functionally different parts: the proximal tubule, which has a convoluted section the proximal convoluted tubule followed by a straight section (proximal straight tubule); the loop of Henle, which has two parts, the descending loop of Henle ("descending loop") and the ascending loop of Henle ("ascending loop"); the distal convoluted tubule ("distal loop"); the connecting tubule, and the collecting ducts. Nephrons have two lengths with different urine concentrating capacities: long juxtamedullary nephrons and short cortical nephrons.

The four mechanisms used to create and process the filtrate (the result of which is to convert blood to urine) are filtration, reabsorption, secretion and excretion. Filtration occurs in the glomerulus and is largely passive: it is dependent on the intracapillary blood pressure. About one-fifth of the plasma is filtered as the blood passes through the glomerular capillaries; four-fifths continues into the peritubular capillaries. Normally the only components of the blood that are not filtered into Bowman's capsule are blood proteins, red blood cells, white blood cells and platelets. Over 150 liters of fluid enter the glomeruli of an adult every day: 99% of the water in that filtrate is reabsorbed. Reabsorption occurs in the renal tubules and is either passive, due to diffusion, or active, due to pumping against a concentration gradient. Secretion also occurs in the tubules and is active. Substances reabsorbed include: water, sodium chloride, glucose, amino acids, lactate, magnesium, calcium phosphate, uric acid, and bicarbonate. Substances secreted include urea, creatinine, potassium, hydrogen, and uric acid. Some of the hormones which signal the tubules to alter the reabsorption or secretion rate, and thereby maintain homeostasis, include (along with the substance affected) antidiuretic hormone (water), aldosterone (sodium, potassium), parathyroid hormone (calcium, phosphate), atrial natriuretic peptide (sodium) and brain natriuretic peptide (sodium). A countercurrent system in the renal medulla provides the mechanism for generating a hypertonic interstitium, which allows the recovery of solute-free water from within the nephron and returning it to the venous vasculature when appropriate.

Some diseases of the nephron predominantly affect either the glomeruli or the tubules. Glomerular diseases include diabetic nephropathy, glomerulonephritis and IgA nephropathy; renal tubular diseases include acute tubular necrosis and polycystic kidney disease.

Structure

Fig.1) Schematic diagram of the nephron (yellow), relevant circulation (red/blue), and the four methods of altering the filtrate.

The nephron is the functional unit of the kidney. Each nephron is composed of a renal corpuscle, the initial filtering component; and a renal tubule that processes and carries away the filtered fluid.

Renal corpuscle

Fig.2) Schematic of the glomerular filtration barrier (GFB). A. The endothelial cells of the glomerulus; 1. endothelial pore (fenestra).

B. Glomerular basement membrane: 1. lamina rara interna 2. lamina densa 3. lamina rara externa.

C. Podocytes: 1. enzymatic and structural proteins 2. filtration slit 3. diaphragm.

The renal corpuscle is the site of the filtration of blood plasma. The renal corpuscle consists of the glomerulus, and the glomerular capsule or Bowman's capsule. The renal corpuscle has two poles – a vascular pole and a urinary pole.

The arterioles from the renal circulation enter and leave the glomerulus at the vascular pole. The glomerular filtrate leaves the Bowman's capsule at the renal tubule at the urinary pole.

Glomerulus

The glomerulus is the network known as a tuft, of filtering capillaries located at the vascular pole of the renal corpuscle in Bowman's capsule. Each glomerulus receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for water and solutes to be filtered out of the blood plasma, and into the interior of Bowman's capsule, called Bowman's space.

Only about a fifth of the plasma is filtered in the glomerulus. The rest passes into an efferent arteriole. The diameter of the efferent arteriole is smaller than that of the afferent, and this difference increases the hydrostatic pressure in the glomerulus.

Bowman's capsule

The Bowman's capsule, also called the glomerular capsule, surrounds the glomerulus. It is composed of a visceral inner layer formed by specialized cells called podocytes, and a parietal outer layer composed of simple squamous epithelium. Fluids from blood in the glomerulus are filtered through the visceral layer of podocytes, resulting in the glomerular filtrate.

The glomerular filtrate next moves to the renal tubule, where it is further processed to form urine. The different stages of this fluid are collectively known as the tubular fluid.

Renal tubule

The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system. 

The components of the renal tubule are:

• Proximal convoluted tubule (lies in cortex and lined by simple cuboidal epithelium with brush borders which help to increase the area of absorption greatly.)
• Loop of Henle (hair-pin like, i.e. U-shaped, and lies in medulla)
  • Descending limb of loop of Henle
  • Ascending limb of loop of Henle
    • The ascending limb of loop of Henle is divided into 2 segments: Lower end of ascending limb is very thin and is lined by simple squamous epithelium. The distal portion of ascending limb is thick and is lined by simple cuboidal epithelium.
    • Thin ascending limb of loop of Henle
    • Thick ascending limb of loop of Henle (enters cortex and becomes - distal convoluted tubule.)
• Distal convoluted tubule
• Connecting tubule

Blood from the efferent arteriole, containing everything that was not filtered out in the glomerulus, moves into the peritubular capillaries, tiny blood vessels that surround the loop of Henle and the proximal and distal tubules, where the tubular fluid flows. Substances then reabsorb from the latter back to the blood stream. 

The peritubular capillaries then recombine to form an efferent venule, which combines with efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

Length difference

Cortical nephrons (the majority of nephrons) start high in the cortex and have a short loop of Henle which does not penetrate deeply into the medulla. Cortical nephrons can be subdivided into superficial cortical nephrons and midcortical nephrons.

Juxtamedullary nephrons start low in the cortex near the medulla and have a long loop of Henle which penetrates deeply into the renal medulla: only they have their loop of Henle surrounded by the vasa recta. These long loops of Henle and their associated vasa recta create a hyperosmolar gradient that allows for the generation of a concentrated urine. Also the hairpin bend penetrates up to the inner zone of medulla.

Juxtamedullary nephrons are found only in birds and mammals, and have a specific location: medullary refers to the renal medulla, while juxta (Latin: near) refers to the relative position of the renal corpuscle of this nephron - near the medulla, but still in the cortex. In other words, a juxtamedullary nephron is a nephron whose renal corpuscle is near the medulla, and whose proximal convoluted tubule and its associated loop of Henle occur deeper in the medulla than the other type of nephron, the cortical nephron.

The juxtamedullary nephron comprises only 20–30% of the nephrons in the human kidney. However, it is this type of nephron which is most often depicted in illustrations of nephrons.

Functions

Fig.3) Secretion and reabsorption of various substances throughout the nephron.

 

The nephron uses four mechanisms to convert blood into urine: filtration, reabsorption, secretion, and excretion of numerous substances. The structure and function of the epithelial cells lining the lumen change during the course of the nephron, and have segments named by their location and which reflects their different functions.

Fig.4) Diagram outlining movement of ions in nephron, with the collecting ducts on the right.

 

Fig.5) Proximal tubule cell showing pumps involved in acid base balance, left is the lumen of tubule

Proximal convoluted tubule

The proximal tubule as a part of the nephron can be divided into an initial convoluted portion and a following straight (descending) portion. Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including approximately two-thirds of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids).

Loop of Henle

The loop of Henle is a U-shaped tube that extends from the proximal tubule. It consists of a descending limb and an ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla as the descending limb, and then returns to the cortex as the ascending limb to empty into the distal convoluted tubule. The primary role of the loop of Henle is to concentrate the salt in the interstitium, the tissue surrounding the loop.

Considerable differences aid in distinguishing the descending and ascending limbs of the loop of Henle. The descending limb is permeable to water and noticeably less permeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate. The hypertonicity of the medulla (and therefore concentration of urine) is determined in part by the size of the loop of Henle.

Unlike the descending limb, the thin ascending limb is impermeable to water, a critical feature of the countercurrent exchange mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its sodium content. This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex.

Distal convoluted tubule

The distal convoluted tubule has a different structure and function to that of the proximal convoluted tubule. Cells lining the tubule have numerous mitochondria to produce enough energy (ATP) for active transport to take place. Much of the ion transport taking place in the distal convoluted tubule is regulated by the endocrine system. In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more calcium and secretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium secreted. Atrial natriuretic peptide causes the distal convoluted tubule to secrete more sodium.

Connecting tubule

This is the final segment of the tubule before it enters the collecting duct system.

Collecting duct system

Fig.6) Cross-sectional histologic preparation showing (b)small connecting tubules with simple columnar epithelium and (a) large connecting tubules with simple cuboidal epithelium.

Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the connecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's countercurrent multiplier system.

Because it has a different origin during the development of the urinary and reproductive organs than the rest of the nephron, the collecting duct is sometimes not considered a part of the nephron. Instead of originating from the metanephrogenic blastema, the collecting duct originates from the ureteric bud.

Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). ADH affects the function of aquaporins, resulting in the reabsorption of water molecules as it passes through the collecting duct. Aquaporins are membrane proteins that selectively conduct water molecules while preventing the passage of ions and other solutes. As much as three-quarters of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or diluted. An increase in ADH is an indication of dehydration, while water sufficiency results in a decrease in ADH allowing for diluted urine.

Fig.7) Cross-sectional diagram of the juxtaglomerular apparatus and adjacent structures: 1) top, yellow - distal convoluted tubule; 2) top, brown -macula densa cuboidal cells surrounding arterioles; 3) small blue cells - juxtaglomerular cells; 4) large blue cells - mesangial cells; 5) tan - podocytes lining Bowman's capsule adjacent to capillaries, and parietal layer of capsule, 6)center - five glomerular capillaries, and the 6)bottom, purple - exiting tubule. Structures (2), (3), and (4) constitute the juxtaglomerular apparatus.

Lower portions of the collecting organ are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high concentration (which is very important for the nephron).

Urine leaves the medullary collecting ducts through the renal papillae, emptying into the renal calyces, the renal pelvis, and finally into the urinary bladder via the ureter.

Juxtaglomerular apparatus

The juxtaglomerular apparatus (JGA) is a specialized region associated with the nephron, but separate from it. It produces and secretes into the circulation the enzyme renin (angiotensinogenase), which cleaves angiotensinogen and results in the ten amino acid substance angiotensin-1 (A-1). A-1 is then converted to angiotensin-2, a potent vasoconstrictor, by removing two amino acids: this is accomplished by angiotensin converting enzyme (ACE). This sequence of events is referred to as the renin–angiotensin system (RAS) or renin-angiotensin-aldosterone system (RAAS). The JGA is located between the thick ascending limb and the afferent arteriole. It contains three components: the macula densa, juxtaglomerular cells, and extraglomerular mesangial cells.

Clinical significance

Diseases of the nephron predominantly affect either the glomeruli or the tubules. Glomerular diseases include diabetic nephropathy, glomerulonephritis and IgA nephropathy; renal tubular diseases include acute tubular necrosis, renal tubular acidosis, and polycystic kidney disease.

Additional images

Distribution of blood vessels in cortex of kidney. (Although the figure labels the efferent vessel as a vein, it is actually an arteriole.)

Glomerulus is red; Bowman's capsule is white.

Kidney tissue

Glomerulus

This image shows the types of cells present in the glomerulus part of a kidney nephron. Podocytes, Endothelial cells, and Glomerular mesangial cell are present.