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41.4C: Kidney Function and Physiology - Biology

41.4C: Kidney Function and Physiology - Biology


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Urine is a byproduct of the osmoregulatory function of kidneys, which filter blood, reabsorb water and nutrients, and secrete wastes.

Learning Objectives

  • Outline the process by which kidneys filter blood, reabsorb nutrients and water, and produce urine

Key Points

  • Glomerular filtration, tubular reabsorption, and tubular secretion are the three primary steps in which kidneys filter blood and maintain proper electrolyte balance.
  • Glomerular filtration removes solutes from the blood; it is the first step of urine formation.
  • In tubular reabsoption, the second step of urine formation, almost all nutrients are reabsorbed in the renal tubule by active or passive transport.
  • Tubular secretion is the last step of urine formation, where solutes and waste are secreted into the collecting ducts, ultimately flowing to the bladder in the form of urine.

Key Terms

  • arteriole: one of the small branches of an artery, especially one that connects with capillaries
  • countercurrent: a current that flows against the prevailing one
  • electrolyte: any of the various ions (such as sodium or chloride) that regulate the electric charge on cells and the flow of water across their membranes

Blood Filtration and Nutrient and Water Reabsorption

Kidneys filter blood in a three-step process. First, the nephrons filter blood that runs through the capillary network in the glomerulus. Almost all solutes, except for proteins, are filtered out into the glomerulus by a process called glomerular filtration. Second, the renal tubules collect the filtrate. Most of the solutes are reabsorbed in the PCT by a process called tubular reabsorption. In the loop of Henle, the filtrate continues to exchange solutes and water with the renal medulla and the peritubular capillary network.

Finally, some substances, such as electrolytes and drugs, are removed from blood through the peritubular capillary network into the distal convoluted tubule or collecting duct. Urine is a collection of substances that have not been reabsorbed during glomerular filtration or tubular reabsorbtion.

Glomerular Filtration

The formation of urine occurs through three steps: glomerular filtration, tubular reabsorption, and tubular secretion. The process of glomerular filtration filters out most of the solutes due to the high blood pressure and specialized membranes in the afferent arteriole. The blood pressure in the glomerulus is maintained independent of factors that affect systemic blood pressure. The “leaky” connections between the endothelial cells of the glomerular capillary network allow solutes to pass through easily. All solutes in the glomerular capillaries, including sodium ions and negatively and positively charged ions, pass through by passive diffusion; the only exception is macromolecules such as proteins. There is no energy requirement at this stage of the filtration process. Glomerular filtration rate (GFR) is the volume of glomerular filtrate formed per minute by the kidneys. GFR is regulated by multiple mechanisms and is an important indicator of kidney function.

Tubular Reabsorption and Secretion

Tubular reabsorption occurs in the PCT part of the renal tubule. Almost all nutrients are reabsorbed; this occurs either by passive or active transport. Reabsorption of water and key electrolytes are regulated and influenced by hormones. Sodium (Na+) is the most abundant ion; most of it is reabsorbed by active transport and then transported to the peritubular capillaries. Because Na+ is actively transported out of the tubule, water follows to even out the osmotic pressure. Water is also independently reabsorbed into the peritubular capillaries due to the presence of aquaporins, or water channels, in the PCT. This occurs due to the low blood pressure and high osmotic pressure in the peritubular capillaries. Every solute, however, has a transport maximum; the excess solute is not reabsorbed. Kidneys’ osmolarity of body fluids is maintained at 300 milliosmole (mOsm).

In the loop of Henle, the permeability of the membrane changes. The descending limb is permeable to water, not solutes; the opposite is true for the ascending limb. Additionally, the loop of Henle invades the renal medulla, which is naturally high in salt concentration. It tends to absorb water from the renal tubule and concentrate the filtrate. The osmotic gradient increases as it moves deeper into the medulla. Because two sides of the loop of Henle perform opposing functions, it acts as a countercurrent multiplier. The vasa recta around the loop of Henle acts as the countercurrent exchanger.

Additional solutes and wastes are secreted into the kidney tubules during tubular secretion, which is the opposite process to tubular reabsorption. The collecting ducts collect filtrate coming from the nephrons and fuse in the medullary papillae. From here, the papillae deliver the filtrate, now called urine, into the minor calyces that eventually connect to the ureters through the renal pelvis.


What do the kidneys do?

The kidneys are a pair of bean-shaped organs present in all vertebrates. They remove waste products from the body, maintain balanced electrolyte levels, and regulate blood pressure.

The kidneys are some of the most important organs. The Ancient Egyptians left only the brain and kidneys in position before embalming a body, inferring that the held a higher value.

In this article, we will look at the structure and function of the kidneys, diseases that affect them, and how to keep the kidneys healthy.

Share on Pinterest The kidneys play a role in maintaining the balance of body fluids and regulating blood pressure, among other functions.

The kidneys are at the back of the abdominal cavity, with one sitting on each side of the spine.

The right kidney is generally slightly smaller and lower than the left, to make space for the liver.

Each kidney weighs 125–170 grams (g) in males and 115–155 g in females.

A tough, fibrous renal capsule surrounds each kidney. Beyond that, two layers of fat serve as protection. The adrenal glands lay on top of the kidneys.

Inside the kidneys are a number of pyramid-shaped lobes. Each consists of an outer renal cortex and an inner renal medulla. Nephrons flow between these sections. These are the urine-producing structures of the kidneys.

Blood enters the kidneys through the renal arteries and leaves through the renal veins. The kidneys are relatively small organs but receive 20–25 percent of the heart’s output.

Each kidney excretes urine through a tube called the ureter that leads to the bladder.

The main role of the kidneys is maintaining homeostasis. This means they manage fluid levels, electrolyte balance, and other factors that keep the internal environment of the body consistent and comfortable.

They serve a wide range of functions.

Waste excretion

The kidneys remove a number of waste products and get rid of them in the urine. Two major compounds that the kidneys remove are:

  • urea, which results from the breakdown of proteins
  • uric acid from the breakdown of nucleic acids

Reabsorption of nutrients

The kidneys reabsorb nutrients from the blood and transport them to where they would best support health.

They also reabsorb other products to help maintain homeostasis.

Reabsorbed products include:

  • glucose
  • amino acids
  • bicarbonate
  • sodium
  • water
  • phosphate
  • chloride, sodium, magnesium, and potassium ions

Maintaining pH

In humans, the acceptable pH level is between 7.38 and 7.42. Below this boundary, the body enters a state of acidemia, and above it, alkalemia.

Outside this range, proteins and enzymes break down and can no longer function. In extreme cases, this can be fatal.

The kidneys and lungs help keep a stable pH within the human body. The lungs achieve this by moderating the concentration of carbon dioxide.

The kidneys manage the pH through two processes:

  • Reabsorbing and regenerating bicarbonate from urine: Bicarbonate helps neutralize acids. The kidneys can either retain it if the pH is tolerable or release it if acid levels rise.
  • Excreting hydrogen ions and fixed acids: Fixed or nonvolatile acids are any acids that do not occur as a result of carbon dioxide. They result from the incomplete metabolism of carbohydrates, fats, and proteins. They include lactic acid, sulfuric acid, and phosphoric acid.

Osmolality regulation

Osmolality is a measure of the body’s electrolyte-water balance, or the ratio between fluid and minerals in the body. Dehydration is a primary cause of electrolyte imbalance.

If osmolality rises in the blood plasma, the hypothalamus in the brain responds by passing a message to the pituitary gland. This, in turn, releases antidiuretic hormone (ADH).

In response to ADH, the kidney makes a number of changes, including:

  • increasing urine concentration
  • increasing water reabsorption
  • reopening portions of the collecting duct that water cannot normally enter, allowing water back into the body
  • retaining urea in the medulla of the kidney rather than excreting it, as it draws in water

Regulating blood pressure

The kidneys regulate blood pressure when necessary, but they are responsible for slower adjustments.

They adjust long-term pressure in the arteries by causing changes in the fluid outside of cells. The medical term for this fluid is extracellular fluid.

These fluid changes occur after the release of a vasoconstrictor called angiotensin II. Vasoconstrictors are hormones that cause blood vessels to narrow.

They work with other functions to increase the kidneys’ absorption of sodium chloride, or salt. This effectively increases the size of the extracellular fluid compartment and raises blood pressure.

Anything that alters blood pressure can damage the kidneys over time, including excessive alcohol consumption, smoking, and obesity.


Urinary System

The urinary system in human includes kidneys, ureter, urinary bladder and urethra that collectively constitute the urine excretion. Kidney is a major organ that assist the separation of nitrogenous wastes to the urinary bladder through a long tube called ureter. Let us look into the external structure of our urinary system.

The kidneys

There are two kidneys in a human body, whose average weight is 120-170 grams. Its structure appears bean-shaped that is encircled by a layer of fat and connective tissue. A vertical section of kidney shows a renal capsule, cortex, medulla, pelvis and hilum.

  • Renal capsule: It is a thin and tough outer covering of the kidneys that is composed of dense connective tissues.
  • Renal cortex: It is found interior to the renal capsule. Renal cortex includes cluster of blood capillaries and a glomerulus.
  • Renal medulla: It is found interior to the renal cortex. The renal medulla possess a radial appearance and comprises nephron tubule, vasa recta and collecting duct. It can be partitioned into an outer and inner medulla. An outer medulla comprises renal columns, which also refers as “column of Bertini”. Renal pyramids appear as cone shaped structures that constitute an inner medulla, as these extend out to form renal papillae.
  • Renal pelvis: It resembles a funnel-shape that comprises around 8-18 minor and 2-3 major projections or calyces. Renal pelvis is inner to the hilum.

Ureters: It appears as two long slender tubes that originates from the region of renal pelvis and goes downwards to the urinary bladder.

Urinary Bladder: It is located in the lower part of abdominal cavity, and connected with the ureters and urethra. Urinary bladder acts like a hollow and muscular organ that comprises an elastic wall, which can expand or contract accordingly.

Urethra: The urine is expelled out from the urinary bladder out of the body by urethra.

Nephron as a Excretory Unit

Nephrons are the functional units of the kidneys, which separates urine from the blood. In kidney, nephrons are generally categorized into cortical and juxtamedullary nephrons.

  1. Cortical nephrons: It constitutes about 80-85% of nephrons. The renal corpuscles lie within outer renal cortex. Here, the loop of Henle runs very little to the medulla. It maintains the ionic balance of blood.
  2. Juxtamedullary nephrons: In this the renal corpuscles lie close between the junction of renal cortex and medulla. Unlike cortical nephrons, the loop of Henle run deep into the medulla. It primarily concentrates the urine.

Malpighian or renal corpuscle and the coiled uriniferous tubules are the structural elements of nephron.

Malphigian Corpuscle

It comprises two components, namely glomerulus and Bowman’s capsule. A glomerulus is the capillary network of afferent arterioles, which is surrounded by the double layered epithelial cup called Bowman’s capsule. A glomerulus is composed of three layers:

  • Visceral layer of epithelial cells (podocytes) and basement membrane: The epithelial cells link with the basement membrane via pedicels, and that’s why also called as “podocytes”. Over the basement membrane, the pedicles are arranged in a sequence leaving a narrow space in between that are called as “filtration slits”. A basement membrane lies within the visceral and parietal layer. It is a thin, middle layer that retains the plasma proteins from being filtered out.
  • Parietal layer of squamous endothelial cells: It possesses large pores that permits the passage of solutes, plasma proteins etc.

A visceral layer participates in the urine filtration, and passes the filtrate to the capsular space of parietal layer via the capillaries.

Coiled Uriniferous Tubules

It consists of proximal, nephron and distal tubule that performs specific tasks inside the kidney. The proximal tubule is a 15 mm long convoluted tube that originates from the capsular space of parietal layer, and extends downwards to the medulla to form loop of Henle.

Henle’s loop or nephron tubule originates from the proximal tubule descends into a thin limb (2-14 mm long) and goes upward forming a thick limb (12 mm long). The ascending loop reaches glomerulus and passes close to its afferent and efferent arteriole forming macula densa (a part of juxtaglomerular apparatus).

Distal convoluted tubule originates from the macula densa cells of the juxtaglomerular apparatus that measures 5 mm length. It joins to the collecting duct. The filtrate from collecting tubule reaches renal pelvis, from where the urine discharge into the urinary bladder through a pair of ureter.


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Essay on Kidneys: Functions, Urine Formation and Hormones

In this article we will discuss about the kidneys:- 1. Introduction to Kidney 2. Functions of Kidney 3. Urine Formation 4. Mechanism of Action of Diuretics 5. Renal Function Tests 6. Congenital Tubular Function Defects 7. Uremia 8. The Artificial Kidney 9. Hormones.

  1. Essay on the Introduction to Kidney
  2. Essay on the Functions of Kidney
  3. Essay on the Urine Formation in Kidney
  4. Essay on the Mechanism of Action of Diuretics
  5. Essay on the Renal Function Tests
  6. Essay on the Congenital Tubular Function Defects in Kidney
  7. Essay on the Uremia –Clinical Kidney Condition
  8. Essay on the Artificial Kidney
  9. Essay on the Hormones of the Kidney

Essay # 1. Introduction to Kidney:

A large number of waste products are produced in the body as a result of metabolic activities. The main waste products are carbon dioxide, water, and nitrogenous compounds. The retention of these products produces a harmful effect on the normal health.

Therefore, the removal of these products from the body is a must. Carbon dioxide is removed mainly through lungs and water as well as nitrog­enous compounds are removed through urogenital system. The kidneys are the most important com­ponent of this system.

The kidneys are two in number, usually bean shaped, and exist behind the peritoneum on either side of the vertebral column extending from the 12th thoracic to the 3rd lumbar vertebra. Each kid­ney weighs about 120-170 grams and is about 11-13 cms. long, the left being larger than the right one.

Each kidney is found to consist of two main parts by section. The outer part is called cortex and the inner one is medulla. The cortex consists of a large number of glomeruli and convoluted tubules. The medulla is composed of renal tubules project­ing into a cavity towards the inner region of the kidney called the pelvis, the region where the renal artery and vein enters and leaves the kidney re­spectively.

Nephron –Basic Unit od Kidney:

It is a functional basic unit of kid­ney. Each kidney is provided with about one mil­lion nephrons containing the glomerulus and the tubule. The glomerulus is a network of afferent and efferent capillaries.

Each glomerulus is surrounded by a double-walled epithelial sac known as Bow­man ‘s Capsule which leads to the tubule which is divided into three parts—proximal convoluted tu­bule, loop of Henle, and the distal convoluted tubule.

The Proximal Convoluted Tubule (PCT) is about 45 mm long and 50 mm in diameter. This lies in the cortex along with glomerulus. Its lumen is continuous with that of the Bowman’s Capsule. It consists of cells with scalloped outline and brush border. The brush border is formed by numerous microvilli which increases the surface enormously for absorption.

The loop of Henle consists of three parts—the descending limb, a thin segment, and an ascending limb. The proximal convoluted tubule opens into the descending limb which is continued into the thin segment from where the ascending limb arises. The whole loop of Henle is lined by a single layer of flattened epithelial cells.

The ascending limb of the loop of Henle con­tinues into the distal convoluted tubule (DCT) which finally opens into a collecting tubule or duct which carries the urine to the renal pelvis from where it is carried to the bladder by the ureter.

The distal convoluted tubule commences near the pole of the glomerulus and establishes a close proxim­ity to the afferent arteriole of its parent glomerulus. The DCT contains cuboidal epithelium.

Nephrons are mainly of two types—cortical and juxtamedullary. The loop of Henle of the juxtamedullary is long and dips deep into the sub­stance of the medulla. But the loop of Henle of cortical is short and only a very small part of it dips into the medullary tissue and the greater part re­mains embedded in the cortical substances.

Moreo­ver, the glomeruli of the juxtamedullary lie very close to the medulla while those of cortical lie close to the surface of the kidney. The juxtamedullary nephrons constitute 20 per cent of nephrons, while the cortical nephrons constitute 80 per cent of the total nephrons. These two types of nephrons have the same common function.

Blood Supply of the Kidneys:

The short renal artery arising from the abdominal aorta supplies the blood to the kidney. The renal artery after en­tering the kidney divides into a number of arterioles—the afferent arterioles which further branch into capillaries and enter into each glomeru­lus.

The capillaries then join to form another arteri­ole—the efferent arteriole which opens into another set of capillaries called peritubular capillaries sur­rounding the proximal tubule, the loop of Henle, and the distal tubule. Ultimately, the capillary set opens into a venule which joins with other venules to form the renal vein. The renal vein then opens into the inferior vena cava.

Blood Flow to Kidney through the Nephron:

The blood flows through both the kidneys of an adult weigh­ing 70 kg at the rate of about 1200 ml/mt. The portion of the total cardiac output (about 560 ml/ mt.) which passes through the kidneys is called the renal fraction. This is about 560/1200 ml per minute, i.e., about 21 per cent.

There are two sets of capillaries—the glomeru­lus and the peritubular. These two capillaries are separated from each other by the efferent arteriole which contributes sufficient resistance to blood flow. The glomerular capillary bed provides a high pressure of about 70 mm Hg, while the peritubular bed provides a low pressure about 13 mm Hg.

The pressures in the artery and vein are 100 mm of Hg. and 8 mm of Hg respectively. The high pressure in the glomerulus exerts the filtering of fluids con­tinually into the Bowman’s Capsule. The low pres­sure in the peritubular capillary system, on the other hand, functions in the same way as the usual ve­nous ends of the tissue capillaries with the fluid being absorbed continually into the capillaries.

Essay # 2. Functions of Kidney:

a. Kidney eliminates excess of certain nutri­ents such as sugar and amino acids when their concentration increases in the blood.

b. It removes certain non-volatile waste prod­ucts such as urea, uric acid, creatinine, and sulphates, etc. from the body.

c. It eliminates certain foreign or toxic sub­stances such as iodides, pigments, drugs, and bacteria, etc. from the blood.

d. It regulates hydrogen ion concentration of the blood by removing excess of non­volatile acids and bases.

e. It maintains the osmotic pressure of the blood by regulating the excretion of wa­ter and inorganic salts and thus preserves the constant volume of the circulating blood.

f. It regulates the arterial blood pressure by causing the secretion of the hormone renin.

g. It maintains the erythrocyte production by excreting the secretion of the hormone erythropoietin.

Essay # 3. Urine Formation in Kidney:

The regulatory activities of kidneys form urine as a by-product. Urine formation involves three main steps—the glomerular filtration, the tubular reabsorption, and the tubular secretion.

a. Glomerular Filtration (Ultrafiltration):

Glomerulus filters out substances of low molecular weight from the blood with the retention of substances of high molecular weight, especially the proteins. Therefore, proteins are retained in the glomeruli and are not normally found in urine. If protein is detected in the urine, it indicates the kidney damage or other disease which ef­fect the glomerular membrane.

In normal adult, two million nephrons filter one li­tre of blood each minute to give about 1200 ml of glomerular filtrate (primary urine) at Bowman’s Capsule. Therefore, the Glomerular Filtration Rate (GFR) in adult is about 120 ml per minute. The hydrostatic pressure of the blood in the glomerular capillaires (Pg) is the main force for driving the fluid (Water and sol­ute) out of the glomerulus.

The pressure is opposed by two forces:

(i) The hydrostatic pressure of the Bow­man’s Capsule fluid (PBC).

(ii) The osmotic pressure of the plasma proteins (Ppp).

Therefore, the effective filtration pressure (Pef) is calculated by the following rela­tion:

. . . Pef = 74 – (30 + 20) mm of Hg

Thus, by substituting the normal values of the various forces, it has been found that the calculated effective (net) filtra­tion pressure (Pef) is 24 mm Hg.

A fall in blood pressure may reduce the Pef which results in less amount of urine. When the aortic systolic pressure is re­duced to 70 mm Hg, the hydrostatic pres­sure of the blood in glomerular capillaries is reduced to 50 mm. Hg. This reduces the Pef to Zero [50 – 50] and thus filtration will be ceased. Under such circumstances, urine will not be formed (anuria) until the blood pressure is maintained.

b. Tubular Reabsorption:

The rate of forma­tion of the primary urine is 120 ml/minute, while the rate of urine passing to the blad­der under the same condition is 1-2 ml/ minute. Therefore, it indicates that about 99 per cent of the glomerular filtrate is reabsorbed during its passage through the different segments of the renal tubule.

Al­though, the glomerular filtrate contains nearly the same concentration of glucose as in plasma, the urine contains nil or very little glucose. Hence, glucose is also prac­tically completely reabsorbed in the tu­bules when the blood sugar level is nor­mal. The capacity of reabsorption depends on the renal threshold of that substance.

The reabsorption of different solids takes place at different sites in the renal tubules. Amino acids, glucose, and small amounts of protein that pass through the glomeru­lus are reabsorbed in the first part of the proximal tubule.

Sodium, chloride, and bi­carbonate are reabsorbed uniformly along the entire length of the proximal tubule and also in the distal tubule. Potassium is reabsorbed in the proximal and secreted in the distal tubule.

The glomerular filtrate produces about 170 litres in a day whereas the tubules reabsorb about 168.5 litres of water, 170 gm of glucose, 100 gm of NaCl, 360 gm of NaHCO3, and small amounts of phosphate, sulphate, amino acids, urea, uric acid, etc. and excrete about 60 gm of NaCl, urea and other waste products in about 1.5 li­tres of urine. Most of these solids are reabsorbed by active transport mechanism, while some (e.g., urea) are reabsorbed by passive transport mechanism.

In diseases, the reabsorption mechanism is altered developing glycosuria, phosphaturia, and amino aciduria.

Although, most of the substances are reabsorbed by the tubular cells, some substances are actively trans­ported or actively excreted into the tubu­lar lumen. The secreted substance by the tubular epithelium in man are creatinine and potassium. The tubular epithelium also removes a number of foreign sub­stances that are introduced into the body for therapeutic and diagnostic purposes.

These foreign substances are penicillin, p-Aminosalicylic acid, phenosulphonphthalein (PSP), p-Aminohippuric acid, and diodrast. The hydrogen ions and ammo­nia formed in the distal tubular cells are also actively excreted into tubular lumen and thus pass to urine.

The function of kidney is regulated by three important hormones. These hormones are aldoster­one (from adrenal cortex), parathormone (from parathyroid), and vasopressin (from hypophyseal posterior lobe).

Aldosterone restricts the excretion of Na + and stimulates the excretion of K + . Parathormone stimulates excretion of phosphate. Vasopressin, the antidiuretic hormone, is held responsible mainly for the reabsorption of water. In the absence of this hormone, a large amount of very dilute urine is excreted.

Essay # 4. Mechanism of Action of Diuretics:

a. Diuretics, the drugs, enhance losses of water and salt via the urine through inter­ference with normal reabsorptive mecha­nisms.

b. Osmotic diuretics are nonreabsorbable substances which increase tubular osmolarity. The osmotic substances which limit the amount of water. Osmotic diuresis is responsible for the serious dehydration which accompanies diabetic ketoacidosis.

c. Diamox is the inhibitor of carbonic anhydrase. It blocks both HCO3 − reabsorption in the proximal tubule and regeneration in the distal tubule.

d. Thiazide diuretics, furosemide, ethacrynic acid and mercurials all inhibit chloride rea­bsorption in the ascending limb.

Essay # 5. Renal Function Tests:

Clearance is measured to assess quantitatively the rate of excretion of a given substance by the kid­ney. This is a volume of blood or plasma which contains the amount of the substance which is ex­creted in the urine in one minute.

A. Inulin Clearance:

a. Inulin is a polysaccharide which is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Therefore, it is a measure of glomerular filtration rate. Mannitol can also be used for the same purpose.

b. These clearances vary with the body size. The clearance is calculated on the basis of ml/1.73 m 2 .

c. To measure inulin clearance it is wise to maintain a constant plasma level of the test substance during the period of urine collections.

The clearance is measured ac­cording to the following formula:

where Cin = Clearance of inulin (ml/min)

U = Urinary inulin (mg/100 ml)

P = Plasma inulin (mg/100 ml)

B. Endogenous Creatinine Clearance:

a. Creatinine is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Its clearance is measured to get the GFR.

b. This method is convenient for the estima­tion of the GFR because it does not re­quire the intravenous administration of a test substance.

c. Normal values for creatinine clearance are in males: 130 ± 20 ml/mt and females: 120 ± 15 ml/mt.

C. The Phenolsulphonephthalein (PSP) Test:

a. The dye is almost completely eliminated within 2 hours.

b. If less than 25 per cent of the dye is not excreted in 15 minutes, it is an indication of impairment of renal function.

D. Other Functional Tests:

a. Dilution test (water excretion test)

b. Urine concentration test (specific gravity test)

d. Urine acidification test

e. Blood NPN, urea and creatinine

a. Dilution test:

(i) After emptying the bladder of the indi­vidual after overnight fast, he is advised to drink 1200 ml water in 30 minutes.

(ii) During four hours after drinking, the urine is collected at hourly intervals.

(iii) In normal individuals in cold climates, 1200 ml of urine is excreted in four hours.

(iv) This test is not applicable to warm climates since the greater part of the ingested water is lost in perspiration during summer.

(v) In case of impaired renal function, the amount of water eliminated in four hours will be less than 1200 ml depending on the degree of impairment and specific grav­ity of urine is often 1.010 or higher in con­ditions of oliguria.

b. Urine concentration test (specific gravity test):

(i) The bladder is emptied on the day of the test at 7 a.m. and the urine is discarded.

(ii) The urine is collected at 8 a.m. and the specific gravity is measured. If the sp. gr. is 1.022, the test may be rejected.

(iii) If the sp. gr, is below 1.022, another urine specimen should be collected at 9 a.m. and the sp. gr. is determined.

(iv) In case, the urine does not have a sp. gr. of 1.022, it is sure that the renal concentrat­ing power is impaired either due to tubu­lar defects or decreased secretion of ADH (diabetes insipidus). If the urine volume is large and the sp. gr. is below 1.022, the ADH test must be carried out. 3.

c. Vasopressin (ADH) test:

(i) The individual is not allowed any food or water after 6 p.m. on the night before the test. Vasopressin (5 units) is injected intramuscularly at 7 p.m. in the night.

(ii) The urine is collected at 7 a.m. and 8 a.m. and the sp. gr. is determined. If the sp. gr. is 1.022, it is quite confident that the indi­vidual suffers from diabetes insipidus and ADH injection is effective in controlling it.

d. Urine acidification test:

(i) This test should not be done on individu­als who have acidosis or poor liver func­tion.

(ii) No dietary or other restrictions are in­volved in carrying out this test. The blad­der is emptied at 8 a.m. Thereafter, hourly specimens of urine are collected until 6 p.m. At 10 a.m., ammonium chloride in a dose of 0.1 gram/kg body weight is given. A portion of each specimen is transferred to stoppered bottles and sent immediately to the laboratory for pH determination.

(iii) In normal individuals, all urine specimens collected after 2 hours from the time of administration of ammonium chloride should have a pH between 4.6 and 5.0 but in patients with renal tubular acidosis, the pH does not fall below 5.3.

v. Blood non-protein nitrogen:

(i) In acute nephritis, the NPN values are in­creased and range from a slight increase (NPN-45 mg, urea N-25 mg, creatinine-2 mg per 100 ml) to very high values (NPN- 200 mg, urea N-160 mg creatinine-25 mg per 100 ml).

(ii) NPN increase and retention are due to im­paired renal function and excessive pro­tein catabolism.

Essay # 6. Congenital Tubular Function Defects in Kidney:

a. Diabetes Insipidus:

(i) This disease is developed due to the non- production of ADHr. The individual passes large volume of urine (5-20 litres in 24 hours). The individual has to drink large amount of water to make up the loss.

(ii) The reabsorption of water in the distal tu­bules does not take place in the absence of ADH.

b. Vitamin D Resistant Rickets:

(i) The tubular reabsorption of phosphate does not take place under this condition.

(ii) Excessive loss of phosphate in urine leads to the development of a type of rickets which does not respond to usual doses of Vitamin D.

c. Renal Glycosuria:

In this condition, the tubular reabsorption of glu­cose is affected. Although the blood sugar is within normal level but glucose is excreted in urine due to defective reabsorption by the tubules.

d. Idiopathic Hypercalcinuria:

Calcium is not reabsorbed by the renal tubules in this condition. Hence, large amounts of calcium are excreted in the urine. Renal calculi may be de­veloped owing to the presence of large amounts of calcium in urine.

e. Salt losing Nephritis:

(i) Large amounts of sodium and chloride ions are excreted in urine in this condi­tion due to the defect in the tubular reab­sorption of these ions resulting in severe dehydration, hyponatremia and hypo-chloremia.

(ii) Blood urea is increased due to the reduced glomerular filtration rate.

(iii) This condition does not respond to aldos­terone administration but responds to parenteral administration of sodium chlo­ride solution.

f. Renal Tubular Acidosis:

(i) In this condition, the urine becomes alka­line or neutral due to the defect in the so­dium and hydrogen ion exchange mecha­nism in the distal tubules. There is a loss of sodium in the urine.

(ii) The acidosis is accompanied by excessive mobilization and urinary excretion of cal­cium and potassium.

(iii) These abnormalities led to clinical mani­festation of dehydration, hypokalemia, defective mineralisation of bones and nephrocalcinosis.

(i) A number of defects in tubular reabsorp­tion exist in this condition. The defects are renal amino acid in renal glycosuria, hyperphosphaturia, metabolic aciduria, with increased urinary excretion of Na, Ca and K.

(ii) In some individuals, cystinosis prevails due to the abnormality of cystine metabo­lism in which cystine crystals are depos­ited in macrophages in the liver, kidney, spleen, bone marrow, lymph nodes and cornea.

h. Hartnup Syndrome (Hard Syndrome):

(i) In this condition, a number of amino ac­ids are not reabsorbed owing to the defect in tubular reabsorption mechanism.

(ii) Disturbances in tryptophan metabolism is suggested by the presence of increased amounts of tryptophan, indican and in­dole acetic acid in urine.

(iii) The clinical symptoms are of niacin defi­ciency—a pellagra like skin lesions and mental deficiency.

i. Nephrogenic Diabetes Insipidus (Water-Losing Nephritis):

This condition is due to congenital defect in water reabsorption in the distal tubules and may, there­fore, resemble true diabetes insipidus.

Essay # 7. Uremia –Clinical Kidney Condition:

The renal failure develops the clinical condition uremia. This condition occurs both in the chronic renal failure and acute failure. The concentration of urea and other NPN constituents in plasma are increased depending on the severity of this condi­tion.

In chronic renal disease, excretion of acid (hy­drogen ion) and also of phosphate ion is impaired. This results in the steady development of acidosis in uremia.

In acute renal failure, the urine output is very low (300 ml or less in 24 hours). This leads to a steady increase in urea and NPN constituents and electrolytes (K + and Na + ) in plasma. There is rapid development of acidosis too.

The important findings of severe chronic uremia or acute uremia are:

a. High concentration of urea and other NPN constituents.

b. High serum potassium concentration.

c. – Water retention leading to generalised edema.

Uremic coma occurs in serious cases:

The concentration of urea and other NPN constituents of blood are very much increased (i.e., 10 times the nor­mal level) in severe renal failure.

The potassium ion level may be slightly increased in chronic uremia. But in acute uremia, the concentration in serum is very much increased. Potassium is released from the cells due to the break­down of cellular proteins. This released potassium passes into the blood and in­terstitial fluid.

When the concentration of potassium ion increases to 8 m. Eq/litre, it exerts a cardiotoxic effect resulting in the dilatation of the heart and when potassium ion concentration reaches at 12 to 15 mEq/ litre, the heart is likely to be stopped. This happens in severe uremia.

iii. Water Retention and Edema:

If the uremic patient drinks water and consumes other fluids, the water is retained in the body. If salt is not consumed, water retention in­creases in both the intracellular and extra­cellular fluid resulting in extracellular edema.

The metabolic processes in the body produce daily 50 to 100 m mol of more metabolic acid than alkali. This ex­tra metabolic acid is excreted mainly through the kidneys. Acidosis develops rapidly in acute uremia. The patient faces ‘Coma’ due to severe acidosis.

Essay # 8. The Artificial Kidney:

During recent years, the artificial kidney has been developed to such an extent that several thousand patients with permanent renal insufficiency or even total kidney removal are being maintained in health for years.

The artificial kidney passes blood through very minute channels bounded by thin membranes. There is a dialyzing fluid on the other side of the membrane into which unwanted substances present in the blood pass by diffusion. The blood is pumped continually between two thin sheets of cellophane the dialyzing fluid is on the outside of the sheets.

The cellophane is porous enough to allow all con­stituents of the plasma except the plasma proteins to diffuse freely in both directions—from plasma into the dialyzing fluid and from the dialyzing fluid into the plasma.

The rate of flow of blood through the artificial kidney is several hundred ml per minute. Heparin is infused into the blood as it enters the kidney to prevent clotting of blood. To prevent bleeding as a result of heparin, an anti-heparin substance, such as protamine, is infused into the blood as it is re­turned to the patient.

Sodium, potassium and chloride concentrations in the dialyzing fluid and in normal plasma are identical but in uremic plasma, the potassium and chloride concentrations are considerably greater. These two ions diffuse through the dialyzing membrane so rapidly that their concentrations fall to equal those in the dialyzing fluid within three to four hours, expo­sure to the dialyzing fluid.

On the other hand, there is no phosphate, urea, urate or creatinine in the dialyzing fluid.

When the uremic patient is dialyzed, these substances are lost in large quanti­ties into the dialyzing fluid, thereby removing major proportions of them from the plasma. Thus, the constituents of the dialyzing fluid are such that those substances in excess in the extracellular fluid in uremia be removed at rapid rates, while the es­sential electrolytes remain quite normal.

Utility of Artificial Kidney:

The artificial kid­neys can clear 100 to 200 ml of blood urea per minute which signifies that it can function about twice as rapidly as two normal kidneys together whose urea clearance is only 70 ml per minute. However, the artificial kidney can be used for not more than 12 hours once in three to four days be­cause of danger from excess heparin and infection to the subject.

Essay # 9. Hormones of the Kidney:

a. Not only the kidney performs excretory functions but it acts as an endocrine or­gan. It liberates many hormones which affect other organs and tissues and some hormones which locally act within the kid­ney itself. It also destroys several hor­mones which are liberated from other en­docrine organs.

b. The juxtaglomerular cells of the renal cor­tex produce the proteolytic enzyme rennin and secrete it into the blood. Rennin acts on a2-globulin which is normally present in blood plasma, although it is pro­duced in the liver.

Rennin splits off a polypeptide fragment called angiotensin I which is decapeptide containing 10 amino acids. Another enzyme of the lung acts on angiotensin I to split off 2 amino acids and thus form the octapeptide angiotensin II.

Angiotensin increases the force of the heartbeat and constricts the arterioles. It raises blood pressure and causes contrac­tion of smooth muscle. It is destroyed by the enzyme angiotensinases present in normal kidneys, plasma and other tissues. Recent studies suggest that rennin angi­otensin system is important in the mainte­nance of normal blood pressure.

c. Prostaglandins are the other hormones of the kidney. They cause relaxation of smooth muscles. They cause vasodilata­tion and a decrease in blood pressure. They also increase renal blood flow. Kininogen which is produced by the kidney has an antihypertensive effect.

d. The two hormones erythropoietin and erythrogenin have an effect on bone mar­row to stimulate production of red cells. Kidney plays an important role in the re­lease of erythropoietin and thus in con­trol of red cell production. Hypoxia stimu­lates production of erythropoietin.


25.5 Physiology of Urine Formation

Having reviewed the anatomy and microanatomy of the urinary system, now is the time to focus on the physiology. You will discover that different parts of the nephron utilize specific processes to produce urine: filtration, reabsorption, and secretion. You will learn how each of these processes works and where they occur along the nephron and collecting ducts. The physiologic goal is to modify the composition of the plasma and, in doing so, produce the waste product urine.

Failure of the renal anatomy and/or physiology can lead suddenly or gradually to renal failure. In this event, a number of symptoms, signs, or laboratory findings point to the diagnosis (Table 25.3).

Weakness
Lethargy
Shortness of breath
Widespread edema
Anemia
Metabolic acidosis
Metabolic alkalosis
Heart arrhythmias
Uremia (high urea level in the blood)
Loss of appetite
Fatigue
Excessive urination
Oliguria (too little urine output)

Glomerular Filtration Rate (GFR)

The volume of filtrate formed by both kidneys per minute is termed the glomerular filtration rate (GFR) . The heart pumps about 5 L blood per min under resting conditions. Approximately 20 percent or one liter enters the kidneys to be filtered. On average, this liter results in the production of about 125 mL/min filtrate produced in men (range of 90 to 140 mL/min) and 105 mL/min filtrate produced in women (range of 80 to 125 mL/min). This amount equates to a volume of about 180 L/day in men and 150 L/day in women. Ninety-nine percent of this filtrate is returned to the circulation by reabsorption so that only about 1–2 liters of urine are produced per day (Table 25.4).

Flow per minute (mL) Calculation
Renal blood flow 1050 Cardiac output is about 5000 mL/minute, of which 21 percent flows through the kidney.

Multiply urine/min times 60 minutes times 24 hours to get daily urine production.

GFR is influenced by the hydrostatic pressure and colloid osmotic pressure on either side of the capillary membrane of the glomerulus. Recall that filtration occurs as pressure forces fluid and solutes through a semipermeable barrier with the solute movement constrained by particle size. Hydrostatic pressure is the pressure produced by a fluid against a surface. If you have a fluid on both sides of a barrier, both fluids exert a pressure in opposing directions. Net fluid movement will be in the direction of the lower pressure. Osmosis is the movement of solvent (water) across a membrane that is impermeable to a solute in the solution. This creates a pressure, osmotic pressure, which will exist until the solute concentration is the same on both sides of a semipermeable membrane. As long as the concentration differs, water will move. Glomerular filtration occurs when glomerular hydrostatic pressure exceeds the luminal hydrostatic pressure of Bowman’s capsule. There is also an opposing force, the osmotic pressure, which is typically higher in the glomerular capillary.

To understand why this is so, look more closely at the microenvironment on either side of the filtration membrane. You will find osmotic pressure exerted by the solutes inside the lumen of the capillary as well as inside of Bowman’s capsule. Since the filtration membrane limits the size of particles crossing the membrane, the osmotic pressure inside the glomerular capillary is higher than the osmotic pressure in Bowman’s capsule. Recall that cells and the medium-to-large proteins cannot pass between the podocyte processes or through the fenestrations of the capillary endothelial cells. This means that red and white blood cells, platelets, albumins, and other proteins too large to pass through the filter remain in the capillary, creating an average colloid osmotic pressure of 30 mm Hg within the capillary. The absence of proteins in Bowman’s space (the lumen within Bowman’s capsule) results in an osmotic pressure near zero. Thus, the only pressure moving fluid across the capillary wall into the lumen of Bowman’s space is hydrostatic pressure. Hydrostatic (fluid) pressure is sufficient to push water through the membrane despite the osmotic pressure working against it. The sum of all of the influences, both osmotic and hydrostatic, results in a net filtration pressure (NFP) of about 10 mm Hg (Figure 25.16).

A proper concentration of solutes in the blood is important in maintaining osmotic pressure both in the glomerulus and systemically. There are disorders in which too much protein passes through the filtration slits into the kidney filtrate. This excess protein in the filtrate leads to a deficiency of circulating plasma proteins. In turn, the presence of protein in the urine increases its osmolarity this holds more water in the filtrate and results in an increase in urine volume. Because there is less circulating protein, principally albumin, the osmotic pressure of the blood falls. Less osmotic pressure pulling water into the capillaries tips the balance towards hydrostatic pressure, which tends to push it out of the capillaries. The net effect is that water is lost from the circulation to interstitial tissues and cells. This “plumps up” the tissues and cells, a condition termed systemic edema .

Net Filtration Pressure (NFP)

NFP determines filtration rates through the kidney. It is determined as follows:

NFP = Glomerular blood hydrostatic pressure (GBHP) – [capsular hydrostatic pressure (CHP) + blood colloid osmotic pressure (BCOP)] = 10 mm Hg

NFP = GBHP – [CHP + BCOP] = 10 mm Hg

NFP = 55 – [15 + 30] = 10 mm Hg

As you can see, there is a low net pressure across the filtration membrane. Intuitively, you should realize that minor changes in osmolarity of the blood or changes in capillary blood pressure result in major changes in the amount of filtrate formed at any given point in time. The kidney is able to cope with a wide range of blood pressures. In large part, this is due to the autoregulatory nature of smooth muscle. When you stretch it, it contracts. Thus, when blood pressure goes up, smooth muscle in the afferent capillaries contracts to limit any increase in blood flow and filtration rate. When blood pressure drops, the same capillaries relax to maintain blood flow and filtration rate. The net result is a relatively steady flow of blood into the glomerulus and a relatively steady filtration rate in spite of significant systemic blood pressure changes. Mean arterial blood pressure is calculated by adding 1/3 of the difference between the systolic and diastolic pressures to the diastolic pressure. Therefore, if the blood pressure is 110/80, the difference between systolic and diastolic pressure is 30. One third of this is 10, and when you add this to the diastolic pressure of 80, you arrive at a calculated mean arterial pressure of 90 mm Hg. Therefore, if you use mean arterial pressure for the GBHP in the formula for calculating NFP, you can determine that as long as mean arterial pressure is above approximately 60 mm Hg, the pressure will be adequate to maintain glomerular filtration. Blood pressures below this level will impair renal function and cause systemic disorders that are severe enough to threaten survival. This condition is called shock.

Determination of the GFR is one of the tools used to assess the kidney’s excretory function. This is more than just an academic exercise. Since many drugs are excreted in the urine, a decline in renal function can lead to toxic accumulations. Additionally, administration of appropriate drug dosages for those drugs primarily excreted by the kidney requires an accurate assessment of GFR. GFR can be estimated closely by intravenous administration of inulin . Inulin is a plant polysaccharide that is neither reabsorbed nor secreted by the kidney. Its appearance in the urine is directly proportional to the rate at which it is filtered by the renal corpuscle. However, since measuring inulin clearance is cumbersome in the clinical setting, most often, the GFR is estimated by measuring naturally occurring creatinine, a protein-derived molecule produced by muscle metabolism that is not reabsorbed and only slightly secreted by the nephron.


The Kidney

The kidneys are the two organs in the body responsible for cleaning blood. They process blood to sort out excess fluids, unwanted chemicals and waste, and turn these into urine. A kidney is comprised nephrons — the microscopic structural and functional unit of the kidney. A Nephron 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 the tubule are connected and are composed of epithelial cells with a lumen.

The Filtration of the blood takes place in three different regions of the Kidney — the outer cortex, medulla , and the renal pelvis — and in three different stages— filtration, reabsorption, and secretion. Filtration takes place in the glomerulus, which is the vascular beginning of the nephron. This process removes solutes from the blood it is the first step of urine formation. Reabsorption is the second step of urine formation. It takes place mainly in the proximal convoluted tubule of the nephron. Nearly all of the water, glucose, potassium, and amino acids lost during glomerular filtration reenter the blood from the renal tubules during reabsorption. Secretion, the last step of urine formation, occurs throughout the different parts of the nephron, from the proximal convoluted tubule to the collecting duct at the end of the nephron. In this step, solutes and waste are secreted into the collecting ducts, where they ultimately flow into the bladder in the form of urine.


Shared Interests and Overlaps

There are shared interests with Kidney and Urological Systems Function and Dysfunction (KUFD) for studies involving renal physiology and transport mechanisms. Studies that focus on transport mechanisms or their regulation may be reviewed in KUFD, while those that focus on the pathophysiological consequences of aberrant transport may be reviewed here.

There are also shared interests with KUFD with respect to renal hemodynamics, hypertension and salt handling. Studies focused on transport mechanisms and their regulation may be reviewed in KUFD, while those focused on hypertensive renal injury may be reviewed here.

There are shared interests with Integrative Vascular Physiology and Pathology (IVPP). Hypertension studies involving cardiovascular biology, microcirculation, lymphatic and central or peripheral nervous system may be reviewed in IVPP, while studies involving hypertension-induced kidney injury may be reviewed here.

There are shared interests with Kidney, Nutrition, Obesity and Diabetes (KNOD). Kidney disease studies with a sole focus on epidemiological studies involving the determinants, predictors and biomarkers of kidney disease may be reviewed in KNOD, whereas studies with mechanistic or physiologic pathway analyses, including those which also involve animals, may be reviewed here.

General studies of ciliary structure, function and development are more appropriately reviewed by the Cell Biology (CB) IRG while those that focus specifically in polycystic kidney disease may be reviewed here.


Controlled excretion of water and electrolytes is very important for homeostasis. Because slight changes in osmolraity can cause server problems like hyperkalamia can cause cardiac arrhythmia and even cardiac arrest.

Intake of water and these electrolytes depends on the needs and eating habits of person. But kidneys are responsible for the control of any increased or decreased amount. For example if a person takes too much sodium, various mechanisms in kidneys are activated that causes excretion of sodium and brings back normal plasma osmolarity.


Back to Basics in Physiology

This original six chapter book will briefly review and integrate the basic concepts behind water distribution and movement in the body. This fills a knowledge gap that most medical and undergraduate physiology students acquire when these topics are studied separately. As of now, there is no textbook that fully integrates renal, cardiovascular and water physiology in a clear understandable manner. The book is intended primarily for medical students and undergraduate physiology students. Chapters include: 1) Water and its Distribution 2) Water Dynamics 3) Fluid Handling by the Heart and Blood Vessels 4) Fluid Handling by the Kidneys 5) Water and Oxygen Delivery 6) Integration in the Response to Hemorrhage, Volume Depletion, and Water Redistribution.

This original six chapter book will briefly review and integrate the basic concepts behind water distribution and movement in the body. This fills a knowledge gap that most medical and undergraduate physiology students acquire when these topics are studied separately. As of now, there is no textbook that fully integrates renal, cardiovascular and water physiology in a clear understandable manner. The book is intended primarily for medical students and undergraduate physiology students. Chapters include: 1) Water and its Distribution 2) Water Dynamics 3) Fluid Handling by the Heart and Blood Vessels 4) Fluid Handling by the Kidneys 5) Water and Oxygen Delivery 6) Integration in the Response to Hemorrhage, Volume Depletion, and Water Redistribution.

Key Features

    An easy-to-read, step by step explanation of how water is distributed, how it moves, how this aides in oxygen delivery and how this is regulated in the human body.

Presents a complex and detailed topic in an original way that will allow students to understand more complex textbooks and explanations

    An easy-to-read, step by step explanation of how water is distributed, how it moves, how this aides in oxygen delivery and how this is regulated in the human body.

Presents a complex and detailed topic in an original way that will allow students to understand more complex textbooks and explanations



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