dr gihan gawish. function maintains homeostasis removing metabolic waste (except co2) – e.g....

Dr Gihan GawishDr Gihan Gawish


FunctionFunction

• Maintains homeostasis• Removing metabolic waste (except CO2)

– e.g. ammonia, urea, uric acid

• Removing foreign compounds– e.g. drugs, food additives, pesticides

• Regulating salt concentrations, fluid volume, and pH


AnatomyAnatomy• Kidneys (2)– process plasma into urine

• Ureters (2)– tubes that carry urine to bladder

• Urinary bladder– storage of urine

• Urethra– carries urine to exterior


AnatomyAnatomy

• Cortex– outer granular region

• Medulla– inner striated region– renal pyramids

• Renal Pelvis– central collecting cavity

• Renal artery and vein


AnatomyAnatomy

• Nephron– 1 million per kidney

– functional unit of the kidney

– smallest unit capable of forming urine


NephronNephron• Vascular Component– conducts blood• Renal Artery• Afferent Arteriole• Glomerulus• Efferent Arteriole• Peritubular Capillaries• Venules• Renal Vein


NephronNephron• Tubular Component

• – forms urine

• Bowman’s capsule

• Proximal Convoluted Tubule

• Loop of Henle

• Distal Convoluted Tubule

• Collecting duct


Urine FormationUrine Formation

• Urine - water and waste solutes• Nephrons conduct three processes to convert blood

plasma into urine1. filtration filter blood plasma to retain cells/proteins

2. reabsorption remove valuable materials from filtrate

3. secretion• transfer additional wastes to filtrate


FiltrationFiltration• Filtration driven by blood pressure

• Glomerular filtration is nonselective

• – Small particles pass (glucose, Na+, urea, H2O)

• – Large ones do not

• 20% of plasma enters tubule

– plasma filtered 65x/day


ReabsorptionReabsorption

• Occurs in remainder of nephron tubule

• Selective movement of substances from tubule into plasma

– Return of valuable substances to peritubular caps

• Active or passive

– Passive (no energy)

– Active transport (requires energy)


SecretionsSecretions

• Also occurs in tubules

• Additional materials transported from plasma in Peritubular capillaries into tubule

• – excess K+, Ca2+ and H+, uric acid

• – foreign compounds

• By passive diffusion or active carrier transport


Formation of Urine stepsFormation of Urine steps::1. Blood enters the glomerulus under

pressure.

2. This causes water, small molecules (but not macromolecules like proteins) and ions to filter through the capillary walls

into the Bowman's capsule. This fluid is called nephric filtrate.


Formation of Urine stepsFormation of Urine steps

3. Nephric filtrate collects within the Bowman's capsule and then flows into the proximal tubule.

4. Here all of the glucose, and amino acids, >90% of the uric acid, and ~60% of inorganic salts are reabsorbed

by active transport.

5. The active transport of Na+ out of the proximal tubule is controlled by angiotensin II.

6. The active transport of phosphate (PO43-) is regulated (suppressed by) the parathyroid hormone.



7. As these solutes are removed from the nephric filtrate, a large volume of the water follows them by osmosis (80–85% of the 180

liters deposited in the Bowman's capsules in 24 hours).

8. As the fluid flows into the descending segment of the loop of Henle, water continues to leave by osmosis because the interstitial fluid is

very hypertonic.

9. This is caused by the active transport of Na+ out of the tubular fluid as it moves up the ascending segment of the loop of Henle.

10. In the distal tubules, more sodium is reclaimed by active transport, and still more water follows by osmosis.

11.Final adjustment of the sodium and water content of the body occurs in the collecting ducts.



• Sodium Although 97% of the sodium has already

been removed, it is the last 3% that determines the final balance of sodium —

and hence water content and blood pressure — in the body.

The reabsorption of sodium in the distal tubule and the collecting ducts is closely

regulated, chiefly by the action of the hormone aldosterone.


Formation of Urine stepsFormation of Urine stepsWater

• The hypertonic interstitial fluid surrounding the collecting ducts provides a high osmotic

pressure for the removal of water.

• Transmembrane channels made of proteins called aquaporins are inserted in the

plasma membrane greatly increasing its permeability to water.

• (When open, an aquaporin channel allows 3 billion molecules of water to pass through

each second.)


WaterWater

• Insertion of aquaporin-2 channels requires signaling by vasopressin (also known as

arginine vasopressin [AVP] or the antidiuretic hormone [ADH]).

– Vasopressin binds to receptors (called V2 receptors) on the basolateral surface of the cells of the collecting ducts.

– Binding of the hormone triggers a rising level of cAMP within the cell.

– This "second messenger" initiates a chain of events culminating in the insertion of aquaporin-2 channels in the apical surface of

the cell.



• The release of vasopressin (from the posterior lobe of the pituitary gland) is regulated by the osmotic

pressure of the blood.

• Anything that dehydrates the body, such as perspiring heavily,

– increases the osmotic pressure of the blood; – turns on the vasopressin → V2 receptors → aquaporin-2

pathway.



• The result: – As little as 0.5 liter/day of urine may remain of

the original 180 liters/day of nephric filtrate.

– The concentration of salts in the urine can be as much as four times that of the blood. (But not high enough to enable humans to benefit from drinking sea water, which is saltier still.)



• If the blood should become too dilute (as would occur after drinking a large amount of water(

• Vasopressin secretion is inhibited.

• The aquaporin-2 channels are taken back into the cell by endocytosis.

• The result: a large volume of watery urine is formed (with a salt concentration as little as one-

fourth of that of the blood.


In 24 hours the kidneys reclaimIn 24 hours the kidneys reclaim

• ~1,300 g of NaCl • ~400 g NaHCO3 • ~180 g glucose • almost all of the 180 liters of water that entered

the tubules.


Diabetes insipidusDiabetes insipidus

• This disorder is characterized by: • excretion of large amounts of a watery urine (as much as

30 liters — about 8 gallons — each day!) • unremitting thirst.

• It can have several causes: • Insufficient secretion of vasopressin.

• Inheritance of two mutant genes for the vasopressin receptor (V2).

• Inheritance of two mutant genes for aquaporin-2.


The Kidney and HomeostasisThe Kidney and Homeostasis

• The kidney is one of the major homeostatic devices of the body.

• it removes normal components of the blood that are present in greater-than-normal concentrations.

• When excess water, sodium ions, calcium ions, potassium ions, and so on are present, the excess quickly passes out in

the urine.

• On the other hand, the kidneys step up their reclamation of these same substances when they are present in the blood in

less-than-normal amounts.

• Thus the kidney continuously regulates the chemical composition of the blood within narrow limits.


Hormones of the KidneysHormones of the Kidneys

• The human kidney is also an endocrine gland secreting two hormones:

• Erythropoietin (EPO) • Calcitriol (1,25[OH]2 Vitamin D3), the

active form of vitamin D ( See the Chapter of bone)

• as well as the enzyme renin.


1 .Erythropoietin Mechanism

Kidney (and liver to a smallerextent) releases erythropoietin

Enhanced Erythropoiesis increases RBC count

Homeostasis: Normal blood oxygen levels

Reduces O2 levels in blood

Increases O2-carrying ability of blood

Erythropoietin stimulates red bone

marrow


22 . .Role of CalcitriolRole of Calcitriol


33 . .Regulation of Blood Pressure Regulation of Blood Pressure by Hormonesby Hormones

• One of the functions of the kidney is to monitor blood pressure and take corrective action if it

should drop. The kidney does this by secreting the proteolytic enzyme renin.

• Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10

amino acids called angiotensin I.

• angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting

enzyme (ACE) — producing angiotensin II, which contains 8 amino acids.


Regulation of Blood Pressure by Regulation of Blood Pressure by HormonesHormones


Regulation of Blood Pressure by Regulation of Blood Pressure by HormonesHormones

angiotensin II • constricts the walls of arterioles closing down capillary beds;

• stimulates the proximal tubules in the kidney to reabsorb sodium ions;

• stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still more sodium and thus water

• increases the strength of the heartbeat; • stimulates the pituitary to release the vasopressin.

• All of these actions, which are mediated by its binding to G-protein-coupled receptors on the target cells, lead to an

increase in blood pressure.


The Artificial KidneyThe Artificial Kidney

• The artificial kidney uses the principle of dialysis to purify the blood of patients

whose own kidneys have failed.

dr gihan gawish. function maintains homeostasis removing metabolic waste (except co2) – e.g....

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