Kidney Functions and Regulation

• The kidneys perform glomerular filtration and regulate renal blood flow and control.

Kidney Functions

• Kidneys are homeostatic organs.
• Kidneys filter gallons of fluid daily from the bloodstream.
• Kidneys process filtrate, allowing wastes and excess ions to leave the body.
• Kidneys excrete metabolic waste products, foreign chemicals, drugs, and hormone metabolites.
• Kidneys regulate water and electrolyte balances.
• Kidneys regulate arterial pressure and acid-base balance.
• Kidneys secrete, metabolize, and excrete hormones and perform gluconeogenesis.

Regulatory Functions

• Renin regulates blood pressure.
• Erythropoietin stimulates red blood cell production.
• Vitamin D is converted to its active form.

Urinary System

• Kidneys excrete urine.
• The urinary tract eliminates urine using ureters, the urinary bladder, and the urethra.
• Urination, or micturition, eliminates urine.
• Contraction of the muscular urinary bladder forces urine through the urethra.

Location and Structure

• The two kidneys are located on the posterior abdominal wall, outside the peritoneal cavity.
• Adrenal glands are separate organs.
• The kidney produces urine, the ureter transports it to the bladder, the bladder stores it temporarily, and the urethra conducts it to the exterior.

Adult Kidney

• A typical adult kidney is about 12 cm long, 6 cm wide, and 3 cm thick.
• The average adult kidney weighs about 150 g.
• The hilus is the entry point for renal artery and nerves and the exit for renal veins and the ureter.

Renal Cortex and Medulla

• The renal cortex along with the renal pyramid make up the kidney.

Renal Blood Supply

• Blood flow to the two kidneys is normally about 20% of the cardiac output, or 1,100 ml/min.
• Blood enters and exits the glomerular capillaries at high pressure, causing fluid to filter into the tubule.
• The peritubular network reabsorbs filtered fluid from the tubule lumen.
• Renal circulation has glomerular and peritubular capillaries arranged in series and separated by efferent arterioles that regulate hydrostatic pressure in both capillary sets.
• High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration, and 13 mm Hg in the peritubular capillaries permits fluid reabsorption.

Nephron

• Each kidney contains about 1 million nephrons, which are capable of forming urine.
• Each nephron contains the glomerulus with its Bowman's capsule, through which large amounts of fluid are filtered, and a long tubule within which the filtered fluid is converted into urine.
• Glomerular capillaries have high hydrostatic pressure (about 60 mm Hg).
• Glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman's capsule.
• Fluid filtered from the glomerular capillaries flows into Bowman's capsule and then into the proximal tubule, which lies in the cortex.
• The renal corpuscle is 150-250 μm in diameter comprised of the Glomerulus and Bowman's capsule

Tubulus

• The nephron consist of the proximal tuble, the Loop of Henle, the Distal Tubule and a Connecting System
• The Loop of Henle consists of a descending and an ascending limb divided into thin and thick segments.
• Collecting Systems consist of a connecting tubule, the Cortical, and Medullary collecting duct

Nephron Structure

• Cortical nephrons comprises 80% of nephrons, with glomerulus located in the outer cortex, they have short loops of Henle and peritubular capillaries.
• Juxtamedullary nephrons comprises 20% of nephrons, with glomerulus located in the deep cortex, they have long loops of Henle and Vasa recta.
• Long efferent arterioles extend from the glomerulus down into the outer medulla for juxtamedullary nephrons, then divide into specialized peritubular capillaries called vasa recta.
• Vasa recta extend downward into the medulla, lying side by side with the loops of Henle.
• Like the loops of Henle, the vasa recta return toward the cortex and empty into the cortical veins.
• Capillaries in the medulla play an essential role in the formation of a concentrated urine.

Urine Formation

• Urine formation includes glomerular filtration, tubular reabsorption, and tubular secretion.
• The urinary excretion rate equals filtration minus reabsorption plus secretion.
• Urine formation begins with filtration of a large amount of virtually protein-free fluid from the glomerular capillaries into Bowman's capsule.
• Most plasma substances, except proteins, are freely filtered.
• After filtration the filtered fluid leaves Bowman's capsule and passes through the tubules, it is modified by reabsorption of water and specific solutes back into the blood or by secretion of other substances from the peritubular capillaries into the tubules.

Glomerular Filtration

• The glomerular filtrate the concentration is similar to plasma.
• Exceptions of being filtere as in: calcium and fatty acids are partially bound to plasma proteins
• GFR is about 20% of the renal plasma flow
• Glomerular Filtration Rate (GFR) balances hydrostatic and oncotic forces across the capillary membrane.
• Normally the GFR is about 125 ml/min or 180 L/day
• The glomerular capillaries are relatively impermeable to proteins, so that the liquid filtered (called glomerular filtrate) is essentially protein-free and devoid of cellular elements, including red blood cells.
• Consisting the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma.
• Some Exceptions to with includes calcium and fatty acids, that are not freely filtered because they are bound to the plasma proteins.

Capillary Membrane

• It has 3 major layers: The endothelium of the capillary, a basement membrane, and a layer of epithelial cells (podocytes).
• Together, these layers make up several hundred times as much water and solutes as the usual capillary membrane, the filtration barrier.
• Perforated by thousands of small holes, the capillary endothelium is called fenestrae, similar to the fenestrated capillaries found in the liver.
• The basement membrane prevents effective filtration of plasma proteins, due to strong negative electrical charges which are associated with the proteoglycans
• The podocytes are separated by gaps called slit pores
• These slit pores help the glomerular filtrate is moved

Solute and Abnormalities

• Filterebility of solutes is inversely related to their size
• Negatively charged molecules (such as plasma proteins) are not been as filtered
• Hemoglobin in normal is only used after blood cells are lysed.

Determinants of Renal Blood Flow

• Oxygen supply & Metabolic rate of kidneys is regulated by oxygen delivered to the kidneys that far exceeds their metabolic needs.
• Renal vascular resistance: regulated by Interlobular arteries, Afferent arterioles, and Efferent arterioles.
• Renal Blood Flow = Renal artery pressure - renal vein pressure all divided by Total renal vascular resistance
• Most of the renal vascular resistance resides interlobular arteries, afferent arterioles, and efferent arterioles regulated by the sympathetic nervous system, hormones, and local internal renal control mechanisms. Renal blood flow and increases with a decrease in vascular resistance

Physiologic Control of Glomerular Filtration and Renal Blood Flow

• Sympathetic activation can constrict renal arterioles reduces blood flow and thus decreases GFR
• Hormonal and Autocoid Control of Renal Circulation
• Noradrenaline, Adrenaline and Endothelin constrict renal vessels and decrease GFR
• Angiotensin II constricts efferent arterioles
• EDRF (Nitric Oxide) decreases renal vascular resistance and increases GFR
• Prostaglandins (PGE2 and PGI2) and bradykinin tend to increase GFR

Filtrarion, Reobsorption and Autoregulation

• The kidney's autoregulation prevents extreme changes in renal excretion and maintains the homeostasis
• Arterial pressure is buffered by autoregulatory mechanisms that maintain a relatively constant glomerular pressure and prevent from water and solute excretion.
• Autoregulation: Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure.
• The process also includes tubular reabsorption.

Autoregulatory Mechanisms

• Myogenic mechanism

  • Blood pressure, stretching the vessel wall activates the stretch-activated Ca++ channels, cause vasoconstriction -This process prevents overdistention of the vessel while raising vascular resistance.

• Tubuloglomerular Feedback Mechanism

  • The kidneys have a feedback mechanism that links changes in NaCl concentration

• The juxtaglomerular complex consists of Macula densa and and Juxtaglomerular cells.

• Constriction of efferent arterioles is balanced Vasodilation in the afferent arterioles and increases GFR.

• Flow rate in the tubules slows, and reduces the concentration of Na and Cl at the Macula densa cells while Renin secretion Activates of juxtaglomerular cells.

Measurement

• Total rates are "cleared" the plasma is quatitating the effectiveness of the kidney functions
• The renal clearance represents plasma volume by the kidneys by time $$ C_s= \frac{U_s \cdot V}{P_s} $$
• Clearance of Inulin is used to estimate Glomerular Filtration Rate GFR. It can used to measure a substance that is not produced in the body GFR is calculated by $$ GFR= \frac{U_{inulin} \cdot V }{P_{inulin}} $$
• PAH clearance can be used to estimate Renal Plasma Flow is about 90% of the flow $$ C_{PAH}= \frac{U_{PAH} \cdot V}{P_{PAH}} $$