RENAL PHYSIOLOGY
By: Prof. Elliot C.J.H Phiri

INTRODUCTION
Cells are the major functioning units in the body of the animal. Their ability to perform normally is dependent upon a variety of factors including: Delivery of nutrients
Removal of waste products
Maintenance of a stable physicochemical environment in the ECF The kidney plays a major role in the last two processes. As an organ that maintains homeostasis of the body the kidney works in concert with the nervous system and some endocrine glands, such as parathyroid gland (parathormone, PTH), adrenal cortex (aldosterone) neurohypophysis (Antidiuretic hormone, ADH).

In summary the functions or roles of the kidney are:
(a) Elimination of nitrogenous end products of protein metabolism primarily urea (in mammals), uric acid (in birds), creatinine and ammonia.

(b) Regulation of electrolytes such as Na+, Cl-, K+ Ca and numerous other ions. Excreting the excess and reabsorbing when the amount is low in the blood.

(c) It regulates the osmotic pressure of the body fluids through controlled excretion of excess water (Conservation of water).
(d) It is one of the principle organs of acid base regulation, excreting H+ as appropriate to keep the pH of the body, fluids within narrow limits.

(e) It eliminates complex organic compounds both endogenous and exogenous eg. antibiotics

(f) The kidney produce glucose (Gluconeogensis) from substances other than carbohydrate, thus helping to minimize the decline of the plasma glucose concentration during prolonged starvation

(g) It is also important in production and release of hormones that play a vital role in the Control of systemic blood pressure (Renin) and
Red blood cell production (Erythropoietin)
Regulation of Ca metabolism (Calcitriol)

To accomplish these tasks, the two kidneys receive approximately 25% of the cardiac output. The kidneys are composed of extensive variety of cell types; each with an individual set of functions and designed to respond as needed to a complex battery of direct and indirect signals.

The cells are arranged in a particular pattern to form the functional unit of the kidney the Nephron.

Specific functions of the kidney and the methods by which they are accomplished are the purpose of this topic.

Inorder to understand the topic review of the anatomy, basic mechanisms of solute and water transport, distribution and composition of fluid compartments, blood flow is essential

PHYSIOLOGIC ANATOMY OF THE KIDNEY
The Kidneys are paired, about 150 gm each and located adjacent to the upper abdominal wall, one on either side of the spine

The renal artery, the renal vein and ureters enter the kidney through the renal hilus The kidney can be divided into two units i.e urine forming unit and urine collecting and expelling unit Urine forming units:

Cortex
Medulla (lobed: renal pyramids)
Cortex and medulla composed chiefly of nephrons and blood vessels Supplied by renal arteries (branches of descending aorta) and renal veins (branches of inferior vena cava) Urine collecting and expelling units:

Calyces, renal pelvises ,ureters, bladder and urethra

Figure1: Kidney and its functional unit the nephron

A renal capsule, composed of dense connective tissue, covers the kidney. The kidney parenchyma is organized into an outer cortex and an inner medulla and it contains many cells making a functional units of cells called nephrons. Each nephron drains into a collecting duct and together they are called uriniferous tubule. Uriniferous tubules join into larger ducts and collectively form conical pyramids. Each pyramid and its overlying cortical tissue constitute a lobe e.g. in human there are 8 - 10 lobes in one kidney where in rats there is only one. Urine within the collecting ducts passes through openings at the papilla (apex of the pyramid and drains into the minor calyces, major calyces, renal pelvis (located at the hilus) and ureter (see figure provided Fig. 2a) NOTE: large mammals have a larger numbers of nephrons than small mammals e.g: Human contain 2,000,000 nephrons

Cattle 4,000,000
Pigs 1,200,000
Dogs 400,0000
Each of the nephron is capable of forming urine itself. Therefore, in most instances, it is not necessary to discuss the entire kidney but merely the function of a single nephron to explain the function of the kidney.

BASIC ANATOMY OF THE NEPHRON

The nephron is composed basically of (1) a glomerulus through which fluid is filtered from blood (2) a long tubule in which the filtered fluid is converted into urine on its way to the pelvis of the kidney (fig.2b). Blood enters the glomerulus through the afferent arteriole and then leaves through the efferent arteriole. The glomerulus is a network of up to 50 parallel branching and anastomosing capillaries covered by epithelial cells and encased in Bowman's capsule. Pressure of the blood in the glomerulus causes fluid to filter into Bowman's capsule, and from here the fluid flows into the proximal tubule that lies in the cortex of the kidney. From proximal tubule the fluid passes into the loop of Henle. Each loop is divided into the descending limb and ascending limb.

Figure 2: Nephron with its blood supply
The wall of the descending and ascending limb is very thin and therefore is called the thin segment of the loop of Henle. However after the ascending limb of Henle has returned part way back in the cortical direction its wall once becomes thick like other part of the tubular system this portion of the loop of Henle is called the thick segment of the loop of Henle. After passing through the loop of Henle the fluid then enters the distal tubule, which like the proximal tubule, lies in the renal cortex. Distal tubules coalesce to form the cortical collecting duct, the end of which turns once again away from the cortex and pass downward into the medulla where it becomes the medullary collecting duct.successive generations of collecting ducts joins to form progressively larger collecting ducts which empty into the renal pelvis.

NOTE There are two types of nephrons and they are classified or named depending on how deep the nephrons lie within the kidney mass. Nephrons of which the glomeruli lie close to the surface of the kidney are called Cortical nephrons. Nephrons which their glomeruli lie deep in the renal cortex near the medulla are called Juxtamedullary nephrons. Cortical nephrons have very short thin segments in their loop of Henle and the loop penetrates only a very short distance into the outer portion of the medulla. Juxtamedullary nephrons have very long loops of the Henle and especially long thin segments that penetrate deeply into the inner zone of the medulla.

Surrounding the entire tubular system of the kidney is an extensive network of capillaries called Peritubular capillaries network. This network is supplied with blood from the efferent arterioles. From the deeper portions of this peritubular network, long capillaries loops called Vasa recta extend downward into the medulla to lie side with the juxtaglomerular loops of Henle which empty into the cortical veins

BLOOD SUPPLY TO THE KIDNEY
Although the Kidneys are Tiny Organs They Receive 25% of the Cardiac Output The 2 kidneys are only 0.4% of the body weight but receive about 25% of the blood flow Blood flow rate per kilogram of tissue is almost 8 times higher in the kidneys than through muscles doing heavy exercise! Kidney: 4 liters/kg-min

Exercising muscle: 0.55 liters/kg-min
Extremely important function: to regulate the composition and volume of body fluids Blood flows in and out of kidney leaving behind the 1% which becomes urine Urine flows through ureters to bladder and then through urethra to outside world The bladder is under both voluntary and autonomic control

The kidneys filter approximately 180 liters of plasma/day (each of the 3 liters of plasma gets filtered about 60 times) To replace this much water you would have to drink a 7.5 l of water every one hour of the day Fortunately 99% of the filtrate gets reabsorbed, leaving 1.5-2 liters of urine per day It is remarkable that the kidney filter can be used continuously for 70 years or more without becoming clogged Number of nephrons declines with age, to about 50% at age 60; this causes the GFR to drop to 50% of value in a young person Loss of nephrons can cause drug overdose in older persons

SUMMARY OF NEPHRON SEGMENT FUNCTIONS

STRUCTURE
FUNCTIONS
1.
Glomerulus
Filtration of blood
2.
Proximal tubule
Bulk reabsorption of filtered water and solutes
3.
Thin limbs of Henle’s loop
Maintanance of medullary hypertonicity by countercurrent exchange 4.
Thick ascending limb of Henle’s loop
NaCl reabsorption
Generation of medullary hypertonicity
Dilution of the tubule fluid
Reabsorption of divalent ions
5.
Distal convoluted tubule
NaCl reabsorption
Dilution of the tubule fluid
Reabsorption of divalent ions
6.
Collecting duct system
Final control of the excretion rates of electrolyte, acid base balance and water

FILTRATION, REABSORPTION AND SECRETION
Filtration of blood:
About 25% of the blood that passes through the kidney gets filtered into the nephron Filtration is takes place in the glomerulus. The glomerulus is specifically designed to Retain cellular component and medium to high molecular weight protein within the vascular system To provide a tubular fluid that initially has an electrolyte and wat...

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