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renal physiology

In order to analyze the work and development of the wearable artificial kidney and bio-artificial kidney, it is important to understand the physiology that the organ replacement therapies intend to replace. This section describes the important aspects of the anatomy, functions, and failure of the kidney that will help you in analyzing the present and future research endeavors presented in this site.

The kidneys are a pair of fist sized organs located in the small of the back behind the peritoneum. Each kidney weighs about 115g-170g and have the following approximate dimensions: 11 cm in length, 6 cm in width, and 3 cm thick - about the size of a deodorant stick.[3] 

Source: Fox S.I., Human Physiology 6th edition, pg. 528
Each kidney is perfused at a rate of 600 ml/min by way of the renal artery [3]. Each renal artery branches into interlobar arteries, arcuate arteries, interlobular arteries, and then into 1.2 million afferent arterioles that each feed each nephron, the functional unit of the kidney. After blood has been filtered through the glomerulus and transported through the nephron's vasculature it passes through the interlobular, arcuate, and interlobar that merge into the renal vein and back in to systemic circulation. [2]
The kidney is composed of two regions, the renal cortex and medulla. The cortex is where the renal corpuscles reside, proximal tubules, and distal tubules are found. The medulla is home to the loop of Henle, vasa recta, and collecting tubules. Urine from the various collecting ducts drains into the renal pelvis, ureter, and bladder. 
Major functions
The kidneys are often thought of as the body's filters, removing toxins and metabolic waste products from the body. The kidneys certainly perform this task; however they have a few more responsibilities, without which we would not be able to survive.

Of the renal blood flow, 125 ml/min is filtered by glomerulus. In one day, the kidney filters approximately 180 liters of blood and produces 1.5 liters of urine. Thus, it is evident that the kidneys possess extraordinary mechanisms to reabsorb water while removing metabolic waste by-products and toxins. [3] Kidney function is measured by the glomerular filtration rate (ml/min) which is defined as the filtration of a solute that is not reabsorbed nor secreted. The clearance (mass removal of a solute/concentration of solute) of a solute can also be used to quantify renal function. 

Source: Fox S.I., Human Physiology, 6th edition, pg. 544.

Endocrine Function
The kidneys secrete the following hormones to initiate processes that occur in other parts of the body: 
1. Erythropoietin to stimulate erythrocyte production in bone marrow. 
2. The active form of Vitamin D, 1,25-dihydroxyvitamin D3, to aid in gut absorption of calcium for bone deposition. 
3. Renin to help regulate blood volume and potassium balance (described in Volume Regulation). 

Osmolarity Regulation
Antidiuretic hormone (ADH or vasopressin) is synthesized in the hypothalamus and released in the posterior pituitary in response to an increase in osmolarity as sensed by osmoreceptors in the anterior hypothalamus. The presence of ADH increases the water permeability of the collecting tubule permitting water reabsorption and a shift towards normal plasma osmolarity. In the process, concentrated urine is formed. In the absence of ADH, the water permeability of the collecting tubules is low, more water is excreted in diluted urine, and blood osmolarity returns to normal. 

Volume Regulation
In addition to the kidney being anatomically designed to create concentrated urine in order to conserve fluid volume, the kidney is also designed to regulate extracellular fluid volume through the Renin-Angiotensin-Aldosterone (RAA) pathway and Atrial Natriuretic Factor (ANF). 
The kidneys initiate the RAA pathway by secreting renin within the lumen of the afferent arteriole. Renin initiates the cascade of reactions that releases aldosterone from adrenal cortex; thereby stimulating the reabsorption of Na+ in the collecting tubule lumen. Since sodium is primarily an extracellular solute, a change in its concentration will lead to a change in extracellular volume (plasma and interstitial volume). 
Atrial Natriuretic Factor (ANF) is secreted by cells in the atria of the heart to inhibit Na+ reabsorption in the kidneys when there is an excess of Na+ and fluid in plasma. It also inhibits secretion of aldosterone, which also inhibits Na+ reabsorption. 

Acid-Base Regulation
Everyday metabolism of proteins and phospholipids generates sulfuric and phosphoric acids, respectively. In order to maintain a normal physiologic pH, the body maintains a buffer reserve of bicarbonate ions. The kidneys regenerate this buffer reserve and excrete the acidic metabolic waste products. 

Source: Fox S.I., Human Physiology, 6th edition, pg. 554.

Renal Failure
Kidney failure can be grouped into two categories: Acute and Chronic.

Acute Renal Failure
There are many mechanisms for this temporary condition when there is sudden loss of renal function in response to trauma, hemorrhage, adverse reactions to anesthesia, bacteria, and autoimmune diseases (glomerulonephritis). There is over a 50% mortality rate associated with acute renal failure. 

Chronic Renal Disease & End Stage Renal Disease (ESRD)
Chronic renal disease is defined as the irreversible degeneration of kidney function. People who are diagnosed with chronic renal disease (about 1 in 5,000 to 10,000) have a glomerular filtration rate (GFR) below 25 ml/min.[3] ESRD is diagnosed when GFR is less than 5 ml/min. Dialysis treatment or kidney transplantation is then necessary for survival. Diabetes and hypertension are the two major causes of chronic renal disease, which results in the slow or fast deterioration of nephron functionality. The degeneration of the nephrons is accelerated by the fact that the shrinking population of functional units must assume the filtering capacity of the whole kidney. The other important renal functions (as discussed above) are also compromised. Thus, a person with chronic renal disease or ESRD can be anemic and hypocalcemic and must receive erythropioetin and active vitamin D supplements. 

Renal Physiology References
1. Vander A. M.D., Sherman J. Ph.D, Luciano D, Ph.D. Human Physiology: The Mechanisms of Body Function. 6th edition, McGraw-Hill, Inc. 1994. 
2. Fox, S.I., Human Physiology, 6th edition, WCB McGraw-Hill, 1999. 
3. Lysaght, M.J. Ph.D, Biology 108 Lecture Notes, January 30, 2001.


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