Renal Physiology PDF

# Renal physiology ## Functions of the kidneys: - Formation of urine (the primary function) - Get rid of waste products (ingested or metabolized) - Clear unwanted substances and retain the needed ones - Control the volume and composition of body fluids: - Regulation of water and electrolyte ba...

# Renal physiology ## Functions of the kidneys: - Formation of urine (the primary function) - Get rid of waste products (ingested or metabolized) - Clear unwanted substances and retain the needed ones - Control the volume and composition of body fluids: - Regulation of water and electrolyte balance (ECF) - Regulation of fluid osmolality - Regulation of acid-base balance (the strongest & slowest) - Regulation of the arterial blood pressure - Metabolism, and excretion of hormones - Secretion of hormones (erythropoietin, and renin) - Gluconeogenesis and activation of the vitamin D ## Physiologic anatomy ### General organization of the kidney: - 150 grams, resembles the size of a clenched fist - Consists of capsule, outer cortex, and inner medulla - Medulla (renal pyramids) → papilla → renal pelvis → ureter → bladder → urethra - As urine is formed, it drains into the renal pelvis and is channeled into the ureter - Urine is stored in the urinary bladder & is emptied periodically through the urethra - The urethra serves the urinary and reproductive tracts in the male ### Renal blood supply: - Kidney is supplied by renal artery & renal vein - Kidney acts on the plasma flowing through it - Renal blood flow = 22% of the cardiac output - Renal blood flow = 1100 ml/min - Renal plasma flow = 625 ml/min - Renal artery → interlobar arteries → arcuate arteries → interlobar arteries → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries ## Nephron: - The basic functional unit of the kidney - 1 million nephrons per kidney (2 million in both kidneys) - After 40 years of age there is a 1% decrement each year - Each nephron is composed of: - **Vascular components:** - Afferent arteriole: to carry blood into the glomerulus - Glomerulus: capillaries network surrounded by the Bowman's capsule - Efferent arteriole: to carry blood from the glomerulus - Peritubular capillaries: supply renal tissue, reabsorption & secretion - **Tubular components:** - Bowman's capsule: to collect glomerular filtrate - Proximal convoluted tubule (PCT) - Loop of Henle (LOH): composed of descending & ascending limbs - Distal convoluted tubule (DCT) - Collecting duct (CD) [250/kidney]: each CD collects from 4000 nephrons ## Types of nephrons: | Type | Description | |---|---| | Cortical nephrons | 70-80% of nephrons; Glomeruli in the outer cortex; Short loop of Henle; Travel a short distance in the medulla; Surrounded by peritubular capillaries; Formation of diluted urine | | Juxtamedullary nephrons | 20-30% of nephrons; Glomeruli in the inner cortex; Long loop of Henle; Travel through the entire medulla; Surrounded by Vasa Recta; Formation of concentrated urine | ## The three basic processes of the nephron: ### Glomerular filtration: - A random and passive process that takes place in the glomerulus - A protein-free plasma is filtered from glomerulus into Bowman's capsule - Blood cells and proteins are not normally filtered - Filterability of the substances depends on: - The size of the substance (molecular weight) - The charge of the substance - 20% of the renal plasma flow is filtered - The remaining 80% passes into the efferent arteriole ### Glomerular filtrate: - Composition is similar to plasma but: - No proteins or red blood cells - Less calcium and fatty acids (bind partially to proteins) - Equals 20% of the renal plasma flow - Glomerular filtrate is produced at the rate of 125 ml per minute (180 liters per day) - Glomerular filtration rate (GFR) = 125 ml per minute (180 liters per day) - Filtration fraction = GFR/renal plasma flow = 125/625 = 20% - GFR is huge for the following reasons: - To remove waste products rapidly - To allow body fluids to be filtered by kidneys many times each day - To provide precise & rapid control over body fluids (volume, composition) ### Tubular reabsorption: - This process is highly selective and variable - Filtered substances move from the inside of the tubular part of the nephron into the blood of the peritubular capillaries (tubular lumen → peritubular capillary lumen) - The return of substances to the blood is needed to maintain the composition of ECF - Reabsorption rates are high: - 124 of 125 ml of filtered fluid per minute - 100% for glucose, 99.5% for salts, 99% for water, and 50% for urea ### Tubular secretion: - A very selective process to eliminate toxic substances rapidly - Substances from the peritubular capillaries enter the lumen of the nephron tubule ## Handling of substances by the nephron: | Type | Description | |---|---| | A - Filtration only | Plasma clearance = GFR; Ex: creatinine and inulin | | B - Filtration and partial reabsorption | Plasma clearance < GFR; Ex: plasma electrolytes | | C - Filtration and complete reabsorption | Plasma clearance = zero; Ex: glucose and amino acids | | D - Filtration and secretion | Plasma clearance > GFR; Ex: para-amino-hippuric acid (PAH) | ## Substances filtered from the glomerulus pass through three layers: - The pores (fenestra) in the wall (endothelium) of glomerular capillaries: 400 times more permeable than other capillaries - The basement membrane: negatively charged gelatinous layer (collagen and proteoglycans) between glomerulus & Bowman's capsule - The inner epithelial layer of Bowman's capsule: through filtration slits between podocytes that encircle the glomerulus tuft ## Glomerular filtration occurs by the interaction of forces: - The glomerular capillary hydrostatic pressure (55 mm Hg): - It is the result of the blood pressure - This pressure favors the filtration process - Pushes plasma from glomerulus into Bowman's capsule - The main parameter to control the filtration process - Can be increased by the following factors: - Increasing arterial blood pressure - Afferent vasodilation (reduced afferent resistance) - Moderate efferent vasoconstriction - Can be reduced by the following factors: - Reducing arterial blood pressure - Afferent vasoconstriction (increased afferent resistance) - Severe efferent vasoconstriction - The glomerular plasma-colloid osmotic (oncotic) pressure (30 mm Hg): - It is due to the retention of plasma proteins in the glomerular blood - This pressure opposes the filtration process - Determined by: - Arterial plasma colloid osmotic pressure (directly proportional) - Filtration fraction (directly proportional): increased by ↑ GFR or↓ RPF - The hydrostatic pressure of the Bowman's capsule (15 mm Hg): - Moves fluids from the Bowman's capsule into the glomerulus - This pressure opposes the filtration process - Increased by tubular obstruction (kidney stones) ## Conclusions: - The net filtration pressure = glomerular capillary pressure - (plasma colloid osmotic pressure + Bowman's capsule hydrostatic pressure) = 55 - (30 +15) = 10 mmHg - Glomerular filtration rate (GFR)= Filtration coefficient (Kf) x Net filtration pressure - Glomerular filtration rate (GFR)= 12.5 x 10 = 125 ml/min: - 125 ml/min = 180 L/day - Plasma volume is 3 liters - Plasma is filtered 60 times daily - Filtration coefficient depends on properties of the glomerular membrane: - The glomerular surface for penetration - The permeability of the glomerular membrane ## Factors that affect the GFR - Reduction in filtration coefficient (Kf) reduces the GFR: chronic uncontrolled HTN & DM - Increased Bowman's capsule hydrostatic pressure reduces GFR: kidney stones - Increased glomerular capillary colloid osmotic pressure reduces GFR - Increased glomerular capillary hydrostatic pressure increases GFR ## Factors that affect renal blood flow - Sympathetic nervous system (SNS): - Strong activation: reduces RBF and GFR - Moderate activation: little effect - Hormones and autocoids: - Afferent and efferent vasoconstrictors (NE, EN, endothelin): reduce RBF and GFR - Efferent vasoconstrictor (angiotensin II): increase RBF and GFR - Vasodilators (prostaglandin, bradykinin, nitric oxide): increase RBF and GFR ## Autoregulation of the GFR and RBF: - GFR remains constant as the arterial pressure ranges from 75 to 160 mmHg - Normally: filtration= 180 L/day, reabsorption = 178.5 L/day, and urine =1.5 L/day - Without autoregulation: - If pressure ↑ by 25% → GFR = 225 L/day - If reabsorption is constant → urine= 46.5 L/day - 30 folds increase in urine formation depletes the body - The processes of autoregulation are not 100% effective - ↑ BP will always lead to ↑ GFR (pressure diuresis or pressure natriuresis) - Autoregulation takes place by two main mechanisms: - **Myogenic mechanism:** - A mechanism responding to changes in the nephron's vascular component - Altering the caliber of the afferent arterioles due to stretch of smooth muscle - ↑ GFR by ↑ arterial pressure → afferent arterioles constrict to lower the GFR - ↓ GFR by↓ arterial pressure → afferent arterioles dilate to increase the GFR - **Tubuloglomerular feedback:** - Sensing changes in flow in the nephron's tubular parts - It is done by the juxtaglomerular apparatus: - Formed as the DCT passes between afferent & efferent arterioles - Composed of two components: macula densa & granular cells - Macula densa: monitors the NaCl concentration in the DCT - Juxtaglomerular (granular) cells: secrete the hormone renin - ↓ GFR due to ↓ arterial pressure → ↑ Na reabsorption & ↓ filtrate [NaCl]: - Macula densa will sense the low [NaCl] and activate granular cells - Granular cells will secrete renin: - Renin causes vasodilation of the afferent arteriole (↑ GFR) - Renin converts angiotensinogen into angiotensin I - Angiotensin I → angiotensin II by ACE enzyme in the lungs - Angiotensin II → vasoconstriction of efferent arteriole (↑ GFR) - Angiotensin II stimulates adrenal glands to secrete aldosterone - Aldosterone: ↑ Na reabsorption in the collecting ducts (↑ BP) - GFR due to ↑ arterial pressure → inhibition of juxtaglomerular apparatus - Other factors that increase GFR and RBF: - High protein intake: ↑ amino acids and Na reabsorption & ↓ filtrate [NaCI] - High blood glucose: ↑ glucose and Na reabsorption & ↓ filtrate [NaCI]