Renal physiology

The principal functions of the kidneys

Formation and excretion of urine

Excretion of waste products, drugs, and toxins

Regulation of body water and mineral content of the body

Maintenance of the acid–base balance

Regulation of blood pressure through the secretion of renin

Regulation of hematopoiesis through the secretion of erythropoietin

Synthesis of the active form of vitamin D

Renal handling of major minerals. The net flow of water and solutes (arrows) varies from one portion of the nephron to another. Aldosterone and parathyroid hormone (PTH) act on the distal tubule, and antidiuretic hormone (ADH) acts on the collecting ducts.

Filtration

• Glomerular filtrate - the plasma filtered in the glomeruli

• Enters into the lumen of the proximal tubules. • The red blood cells (RBCs) and the white blood cells

(WBCs) cannot pass the endothelial cell barrier .• The semipermeable GBM allows only the passage

of proteins that have molecular weights lower than albumin (68,000 daltons).

• Almost all proteins reaching the proximal tubule are reabsorbed, and the final urine contains less than 150 mg of protein per 24 hours.

Glomerular Filtration

• in the glomerulus of the kidney

• there are fenestrated capillaries.

• The basic structure of the filtration membrane:

– the innermost lining of fenestrated endothelium

– a basement membrane

– the inner epithelium of Bowman’s capsule.

The cells form foot processes and are therefore

called podocytes.

Glomerular Filtration

• As blood flows into the afferent arteriole it has high hydrostatic pressure. • Plasma along with other soluble molecules such as

– glucose, – peptides, – amino acids, – ions, – drugs and – other metabolic waste substances,

• move from glomerulus into the Bowman’s capsule. • Blood cells and proteins are left behind. • The fluid that has moved into the Bowman’s capsule is known as the

ultrafiltrate.

ReabsorptionDifferent minerals and metabolites are handled by different parts of the nephrons.

The proximal tubule reabsorbs almost all

• the amino acids,

• glucose,

• bicarbonate

• 70% of the sodium, potassium, calcium, and phosphate.

Additional reabsorption occurs in the distal tubule:

• calcium is regulated by parathyroid hormone (PTH)

• sodium by aldosterone.

Reabsorption of sodium phosphate in the proximal tubule may be inhibited by PTH.

The reabsorption of water in the collecting duct occurs under the control of antidiuretic hormone (ADH- vasopressin)

Secretion

• The renal tubules can acidify urine by actively secreting hydrogen ions (H+).

• Aldosterone - stimulates active secretion of potassium (K+) in the distal tubules.

• Aldosterone stimulates secretion of H+in the distal tubules and collecting ducts.

• Several organic acids and organic bases are also secreted into the lumen or the renal tubules.

Passive diffusion

Water

• passively follows the movement

– of sodium and chloride in most parts of the nephron

– or moves toward areas of high osmolality.

• The ascending loop of Henle is impermeable to water

Urea

• the concentration of which increases progressively as the filtrate passes along the collecting duct,

• also diffuses from the distal parts of the collecting duct into the interstitial fluid of the medulla, which has a lower concentration of urea than the lumen of the collecting ducts.

Production of hyperosmotic and hypo-osmotic urine under the influence of ADH. A- Diuresis in the presence of high serum antidiuretic hormone (ADH). B- Diuresis in the presence of no ADH. The thicker, dotted line indicates impermeability to water. P− phosphate.

Antidiuretic Hormone-Related Water Loss or Conservation Syndromes

CONDITION SERUM ADHPLASMA

OSMOLALITY

URINE

OSMOLALITYURINE OUTPUT

Water deprivation ↑ ↑ or N ↑ ↓

SIADH ↑ ↓ ↑ ↓

(water

“intoxication”)

Polydipsia ↓ ↓ to N ↓ ↑

(hypo-osmotic

polyuria)

Central diabetes

insipidus↓ ↑ ↓ ↑

(hypo-osmotic

polyuria)

Nephrogenic

diabetes insipidus↑ ↑ ↓ ↑

(hypo-osmotic

polyuria)

Sodium handling by the kidneys. Most of the sodium filtered in the glomeruli is reabsorbed, and less than 1% is excreted in the urine. ANH, atrial natriuretic hormone.

Potassium handling by the kidneys.

Calcium handling by the kidneys. Most of the filtered calcium is reabsorbed in the proximal tubule. The reabsorption of calcium in the distal tubules is under the influence of parathyroid hormone (PTH). Less than 1% of filtered calcium is excreted in the urine.

Phosphorus handling by the kidneys. Most of the filtered phosphorus is reabsorbed. Reabsorption in the distal tubule is under the influence of parathyroid hormone (PTH). Approximately 10% of phosphorus is excreted in the urine.

Bicarbonate recovery by the kidneys

• Bicarbonate recovery by the kidneys. • Bicarbonate cannot be reabsorbed directly, • but it is reclaimed from the glomerular filtrate in

exchange for hydrogen ions (H+). • Carbonic anhydrase (CA) forms bicarbonate (HCO3−)

from the CO2, which has diffused into the cytoplasm of tubular cells.

• Bicarbonate then returns into the blood to serve as a buffer.

• This interchange is linked to the flux of sodium (Na+) and potassium (K+) mediated by an Na+/K+ ATPase.

Buffering of excreted hydrogen ions (H+)

• Buffering of excreted hydrogen ions (H+). Hydrogen excreted into the fluid in the lumen of the tubules must be buffered

• so that the pH of urine does not become too acidic.

• This is accomplished by formation of phosphate and

• ammonia buffers.

• CA- carbonic anhydrase.

The kidneys excrete metabolic waste products,

drugs, and toxins.• Urea - It is filtered in the glomeruli, and approximately one

half of it is reabsorbed in the proximal tubule.

– the ascending loops of Henle secrete urea into the lumen,

– the distal tubules resorb 30%

– the inner medullary collecting duct resorbs large amounts of the remaining urea.

• Hence only 15% of the filtered urea is excreted.

• In conditions that increase urine production urea excretion may increase up to 60% of the filtered urea concentration.

Creatinine

• Creatinine (Cr)- Most of Cr is thus derived from creatine phosphate in skeletal muscles;

• a small fraction is from the heart. • Ingestion of meat may increase the concentration

of creatinine. • It is filtered in the glomeruli and excreted without

further processing in the distal tubules. • A small amount of Cr is secreted in the tubules,

but this amount is negligible, and thus Cr is used for measuring the GFR.

The kidneys contain hormone-secreting cells and cells

that activate vitamins.Cells of the juxtaglomerular (JG) apparatus.

• the specialized sensor cells of the distal tubule (called the macula densa)

• granular renin-secreting JG cells in the outer wall of the afferent arteriole.

Erythropoietin-secreting cells.

• the cortical interstitial cells respond to hypoxia by secreting erythropoietin,

• erythropoietin stimulates the production and maturation of red blood cells in the bone marrow.

Vitamin D-activating cells.Vitamin D• is first hydroxylated in the liver into 25(OH)D3 and released

into the blood, • then is filtered in the glomeruli and reabsorbed by the

proximal renal tubules, • which hydroxylate it into the active form of vitamin,

1,25(OH)2D3, and release it back into the blood.

Angiotensin II-forming cells.• Circulating angiotensin I, formed from hepatic

angiotensinogen through the action of renin, is taken up by the endothelial cells in renal vessels and transformed into angiotensin II.

Angiotensin II is a vasoconstrictor and is important for the autoregulation of renal blood flow. Prostaglandins produced in the kidneys cause vasodilatation and counteract the action of angiotensin II.

The glomerular filtration rate

• GFR indicates the volume of primary urine filtered in the glomerulus per time unit.

• It is often expressed as ml/min

• and lies around 85 – 135 ml/min in healthy kidneys.

• It is quoted in standardized terms with reference to 1.73 m² of the body surface area.

• In many kidney diseases, its measurement is important as a parameter of kidney function

Renal Clearance

• The concept of renal clearance arises from the function of the kidney as an organ of detoxification.

• It describes the amount of plasma volume which is completely cleared of a particular substance per time unit.

• Other paths in addition to filtration are possible:– absorption – secretion – excretion, or passage through and out of the tubule and into the

collecting duct

• The amount of a substance in the tubular lumen increases through:– Secretion– Formation of new products of metabolism– Glomerular Filtration