Kidney Functions and Anatomy

Functions of the Kidneys

• Kidneys are perfect examples of homeostatic organs
• Kidneys filter gallons of fluid from the blood stream daily
• Kidneys process the filtrate, allowing wastes and excess ions to exit the body
• Kidneys excrete metabolic waste, foreign chemicals, drugs, and hormone metabolites
• Kidneys regulate water and electrolyte balances
• Kidneys regulate arterial pressure
• Kidneys regulate acid-base balance
• Kidneys secrete, metabolize, and excrete hormones
• Kidneys perform gluconeogenesis
• Regulatory functions of the kidneys include renin in the regulation of blood pressure
• Kidneys also produce erythropoietin to stimulate red blood cell production
• Kidneys convert Vitamin D to its active form, 1,25-dihydroxyvitamin D

Kidney Anatomy and Structure

• Kidneys excrete urine
• Ureters are paired tubes which eliminate urine
• The urinary bladder is a muscular sac which eliminates urine
• The urethra is an exit tube which eliminates urine
• Urination, also known as micturition, is the process of eliminating urine
• Eliminating urine is accomplished via contraction of the muscular urinary bladder, which forces urine through the urethra and out of the body
• Kidneys are located on the posterior wall of the abdomen, outside the peritoneal cavity
• Adrenal glands are positioned as separate organs from the kidneys
• The adult kidney averages 12 cm long, 6 cm wide, and 3 cm thick
• Kidneys weigh about 150 g
• Hilus acts as the entry point for the renal artery and renal nerves
• Hilus also serves as the exit for renal veins and the ureter

Renal Blood Supply

• The kidneys normally receive about 20% of the cardiac output in blood flow
• This equates to approximately 1100 ml/min
• The renal circulation is unique, having two capillary beds: the glomerular and peritubular capillaries
• These capillary beds are arranged in series, separated by the efferent arterioles
• Efferent arterioles help regulate the hydrostatic pressure in both sets of capillaries
• High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) allows rapid fluid filtration
• A much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption

The Nephron

• Kidneys contain approximately 1 million nephrons, which are capable of forming urine
• Each Nephron contains a glomerulus, through which large amounts of fluid are filtered from the blood
• Each Nephron also contains a long tubule which is where the filtered fluid is converted into urine on its way to the pelvis of the kidney
• The glomerulus contains a network of branching glomerular capillaries with high hydrostatic pressure (about 60 mm Hg)
• Glomerular capillaries are covered by epithelial cells
• The glomerulus is encased in Bowman’s capsule
• Fluid filtered from glomerular capillaries flows into Bowman’s capsule, then into the proximal tubule in the cortex of the kidney
• Renal corpuscles measure 150–250 µm in diameter
• The renal corpuscle include the glomerulus and Bowman’s capsule

Tubules and Loops

• The loop of Henle consists of a descending and an ascending limb
• Thin segments are parts of both the descending and ascending limb
• Thick segments are a part of the ascending limb
• Distal tubules are components of collecting systems
• Connecting tubules, cortical collecting ducts and medullary collecting ducts are parts of collecting systems

Cortical vs Juxtamedullary Nephrons

• Cortical nephrons account for 80% of nephrons and are located with the glomerulus in the outer cortex, have short loops of Henle and peritubular capillaries
• Juxtamedullary nephrons account for 20% of nephrons
• Juxtamedullary glomeruli located in the deep cortex, have long loops of Henle and vasa recta
• Long efferent arterioles extend from the glomerulus down into the outer medulla
• These arterioles divide into specialized peritubular capillaries called vasa recta
• The vasa recta extend downward into the medulla, alongside the loops of Henle
• The vasa recta return toward the cortex and empty into the cortical veins
• The specialized network of capillaries in the medulla plays a key role in forming concentrated urine

Urine Formation

• Urine Formation occurs via:
  • Glomerular Filtration
  • Tubular Reabsorption
  • Tubular Secretion
• The urinary excretion rate is equal to filtration minus reabsorption plus secretion
• Urine formation begins when a large amount of protein-free fluid filters from the glomerular capillaries into Bowman’s capsule
• Most substances in the plasma, except for proteins, are freely filtered
• This means their concentration in the glomerular filtrate within Bowman’s capsule is nearly identical to that in the plasma
• As the filtered fluid leaves Bowman’s capsule, it passes through the tubules where it is modified
• The modification is completed via 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 Composition

• Glomerular capillaries are relatively impermeable to proteins
• The glomerular filtrate is mainly protein-free and lacks most cellular elements, including red blood cells
• Concentrations of most salts and organic molecules are similar to plasma concentrations
• Exceptions to this are calcium and fatty acids, which are not freely filtered because they are partially bound to the plasma proteins
• Almost half of plasma calcium and most plasma fatty acids are bound to proteins, and these portions are not filtered through the glomerular capillaries

GFR Details

• GFR (glomerular filtration rate) is approximately 20% of the renal plasma flow
• GFR is determined by the balance between hydrostatic and oncotic forces acting across the capillary membrane
• The average GFR is about 125 ml/min or 180 L/day

Glomerular Barriers

• The glomerular capillary membrane has three major layers: the endothelium of the capillary, a basement membrane, and a layer of epithelial cells (podocytes)
• These create the filtration barrier, which filters several hundred times as much water and solutes than typical capillary membranes
• The capillary endothelium has thousands of small holes called fenestrae, similar to fenestrated capillaries in the liver
• The basement membrane effectively prevents filtration of plasma proteins given strong negative electrical charges relating to proteoglycans
• Podocytes have foot processes separated by gaps called slit pores to allow filtered molecules to pass through which the glomerular filtrate moves.
• Podocytes also have negative charges and apply added restriction to filtration of plasma proteins
• Glomerular capillary endothelial cells resemble a sieve.
• Pores measure 70 nm in diameter, to permit free passage of water, solutes, and proteins while stopping cells from passing through the pores
• Filtrate that enters the tubule is plasma ultrafiltrate

Filtration Determinants

• Filterability of solutes is inversely related to solute size
• Negatively charged molecules such as plasma proteins are less filtered

Renal Blood FLow Determinants

• Renal blood flow is determined by oxygen supply and the kidneys’ metabolic rate
• Oxygen delivered to the kidneys far exceeds metabolic needs
• Renal vascular resistance is located in interlobular arteries, afferent arterioles, and efferent arterioles
• The equation for renal blood flow is (renal artery pressure - renal vein pressure) / total renal vascular resistance
• Most renal vascular resistance resides in interlobular arteries, afferent arterioles, and efferent arterioles
• Resistance of these vessels is controlled by the sympathetic nervous system, hormones, and local internal renal control mechanisms
• An increase in any of a kidneys vascular segments reduces renal blood flow
• A decrease in vascular resistance increases renal blood flow if renal artery and renal vein pressures remain constant.

Blood Distribution to Organs

Glomerular Filtration Rate

• GFR's filtration fraction is equal to the glomerular filtration rate divided by the renal plasma flow
• Under normal conditions an example shows GFR having 125 and renal plasma flow with 625 creating a division that results in 0.2
• Total GFR for both kidneys is about 125 ml/min
• GFR is determined by the sum of hydrostatic and colloid osmotic forces across the glomerular membrane, plus the glomerular capillary filtration coefficient Kf
• The net filtration equation is: GFR = Kf x Net filtration pressure
• Net filtration pressure is the sum of hydrostatic and colloid osmotic forces related to either favor or oppose filtration across the glomerular capillaries
• Forces favoring filtration comes from glomerular hydrostatic pressure (~60 mmHg) and Bowman’s capsule oncotic pressure (~0 mmHg)
• Forces opposing filtration come from Bowman’s capsule hydrostatic pressure (~18 mmHg) and glomerular capillary oncotic pressure (~32 mmHg)
• GFR can be solved with = Kf x (PG – PB – πG + πB)
• K is the measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries
• Solving for K involves dividing GFR by net filtration pressure
• If total GFR for both kidneys has 125 ml/min, and the net filtration pressure is 10 mmHg, the normal K is ~12.5 ml/min/mmHg of filtration pressure
• Determinants of GFR include:
  • Kf from thickness of the filtration membrane and surface area of the filtration membrane
  • Filtration pressures, which include Bowman’s capsule hydrostatic pressure, Bowman’s capsule oncotic pressure, glomerular capillary oncotic pressure, glomerular hydrostatic pressure relating to afferent arteriolar resistance, efferent arteriolar resistance, and arterial pressure

Factors Impacting GFR

• Increased hydrostatic pressure in Bowman’s capsule reduces GFR because decreasing its pressure raises GFR
• Changes in Bowman’s capsule pressure normally do not regulate GFR
• Bowman's Capsule Pressure increases with pathological states resulting from obstruction of the urinary tract
• Obstructions result from precipitates which may lead to "stones" that lodge in the urinary tract thereby obstructing outflow of the urinary tract and raising Bowman's capsule pressure
• This reduces GFR as the body can damage or even destroy the kidney unless the obstruction is relieved
• Increased arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which then decreases GFR
• The filtration fraction is defined as GFR /renal plasma flow. Increasing GFR or reducing renal plasma flow increases the filtration fraction
• Any reduction in renal plasma flow with no initial change in GFR will increase filtration fraction
• Elevated glomerular capillary hydrostatic pressure leads to increased GFR
• Glomerular Hydrostatic Pressure is determined by arterial pressure and afferent and efferent arteriolar resistances
• Constriction of the afferent arterioles reduces glomerular hydrostatic pressure and decreases GFR
• If constricting efferent arterioles is high, then the rise in colloid osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure due such constriction, causing a lowering of the filtration

Auto Regulation

• Relative constancy of GFR and renal blood flow is called autoregulation
• A key function is to avoid extreme changes in renal excretion
• Average GFR is 180 L/day and tubular reabsorption is 178.5 L/day
• Glomerulotubular balance is an important balancing mechanism
• Changes in arterial pressure have significant effects on water and solute excretion
• An increase in arterial pressure raises glomerular hydrostatic pressure, increasing GFR
• Autoregulatory mechanisms maintain constant glomerular pressure during blood pressure fluctuations
• Constriction of the efferent arterioles raises resistance to outflow from the glomerular capillaries
• This raises glomerular hydrostatic pressure, and GFR increases slightly
• When afferent arterioles constrict, glomerular hydrostatic pressure is reduced, lowering GFR
• When efferent arterioles constrict modestly, GFR rises
• When efferent arterioles constrict severely, GFR falls
• With arterial pressure increasing, two primary mechanisms kick in to regulate pressure:
• The Myogenic mechanism has the stretching of the vessel wall occurs which activates stretch activated calcium channels that lead to vasoconstriction and prevents overdistention of the vessel
• The kidneys have a feedback mechanism that links changes in NaCl concentration at the Macula Densa which affect renal arteriolar resistance. This is called the Tubuloglomerular Feedback Mechanism.

Factors that Impact Functionality

Clearance Methods

• Clearance is the means of quantifying kidney function
• Rates at which various substances are "cleared" from the plasma help determine how effective the kidneys are at excreting those substances
• Renal clearance of a substance is the volume of plasma completely cleared of the substance by the kidneys per unit time

Substance Clearance

• Inulin clearance helps determine and estimate GFR
• If a substance can be filtered, but not reabsorbed or secreted by the renal tubules, then the rate can estimate filtration rate
• The substance MUST not already be found in the body, you must administer manually via intravenous transfusion
• Creatinine clearance offers another option for assessment of GFR
• Creatinine is by product of muscle metabolism
• PAH (p-aminohippuric acid) clearance helps evaluate renal plasma flow
• When substance clears entirely of plasma, then its clearance rate equals to total renal plasma flow
• PAH is a good option because it clears nearly 90% from plasma
• Because PAH is is not organic and naturally in the body, administered is managed by continuous infusion

Clearance Rates