AP Renal Part 1 2022 PDF

Advanced Anatomy & Physiology Structure and Function of the Urinary System Chapter 37 (McCance-Heuther) Dr. Joseph Curione Objectives Discuss functions of the kidneys Describe gross anatomy of the kidney Describe kidney location Explain structure and function of ureters, bladder & urethra Explain th...

Advanced Anatomy & Physiology Structure and Function of the Urinary System Chapter 37 (McCance-Heuther) Dr. Joseph Curione Objectives Discuss functions of the kidneys Describe gross anatomy of the kidney Describe kidney location Explain structure and function of ureters, bladder & urethra Explain the micturation reflex/process Describe general kidney blood flow Explain type, structure & function of the Nephron Discuss Tubular Reabsorption/secretion Explain GFR filtration control Renal Corpuscle structure Filtration Membrane structure Juxtaglomerular apparatus Glomerular Blood flow & Autoregulation Urinalysis: normal characteristics Urinalysis: abnormal constituents Tests (urine/blood) Functions of the Urinary System Primary Function: Maintain a stable internal environment for optimal cell and tissue metabolism. 1. Electrolyte homeostasis § Na+, K+, Ca2+, Cl-, HPO42- 2. Regulation of blood pH § § Removes H+ from blood maintains bicarbonate ions (HCO3-) in blood 3. Regulation of Blood Volume/Blood Pressure § § Retention of water = increases BP Elimination of water = decreases BP 4. Osmoregulation § at 300 mOsm/L 5. Produces Hormones § § § Calcitriol - form of Vitamin D § calcium homeostasis Erythropoietin - RBC production Renin – Blood pressure regulation 6. Excretion of Wastes § Ammonia & Urea (protein metabolism) § Bilirubin § Creatinine (waste product of creatine phosphate) § Uric Acid (purine metabolism – A’s & G’s of DNA) § Arthritis known as Gout – excess uric acid § Drugs & toxins 7. Performs gluconeogenesis: Synthesis of glucose from lactate (lactate oxidized into pyruvate, then converted to glucose in PCT) Structures of the Kidneys Renal capsule § Tightly adhering capsule covers kidney Adipose capsule § Fat capsule surrounds each kidney Renal fascia § Fibrous tissue attaches/suspends kidney to the posterior abdominal wall. Hilum § Medial indentation where the renal blood vessels, nerves, lymphatic vessels, and ureter enter and exit the kidneys. Renal cortex § Is the outer layer of each kidney. § Contains all of the glomeruli, most of the proximal tubules, and some segments of the distal tubule. Renal columns § Extend from the cortex down between the renal pyramids. Structures of the Kidneys Renal medulla § inner part of each kidney that contains tubules and the collecting duct. § Consists of regions called the pyramids. Minor calyx § Receives urine from the collecting ducts through the renal papilla. § Apexes of the pyramids project into a cup-shaped cavity that join together to form a major calyx. Major calyx § Joins to form the renal pelvis. Renal pelvis § Joins the proximal end of the ureter. Internal anatomy of the Kidney Sonogram showing dilated renal pelvis - Hydronephrosis General Location Retroperitoneal T12 – L3 Inferior view of transverse section of abdomen Renal hilum Pancreas Liver L2 Spleen Protected by adipose Right Kidney Left Kidney Transverse CT Parasagittal section through right Kidney Superior Liver Posterior Adrenal gland Anterior Protected by 11th and 12th rib Protected by adipose Transverse colon 11 Parasagittal CT right kidney Ureters, Bladder, and Urethra Ureters: § § § § § Are 30 cm long. Are long, intertwining smooth muscle bundles. Pass obliquely into the posterior aspect of the bladder. Peristaltic activity moves urine to the bladder. Micturition compresses the lower end of the ureter to avoid urine reflux. Bladder: § Detrusor muscle (wall) § Transitional epithelium Urethra: § Internal urethral sphincter - involuntary control § Smooth muscle @ jct. of bladder & urethra § External urethral sphincter – voluntary control § Striated skeletal muscle Micturition Micturition or urination (voiding): when volume exceeds 250-300 mL Stretch receptors signal spinal cord and brain Micturition center in sacral spinal cord triggers reflex: parasympathetic fibers cause detrusor muscle to contract – squeezes out urine and Internal & external sphincter muscles to relax to allow flow Filling initiates a desire to urinate before the reflex actually occurs conscious control of external sphincter cerebral cortex can initiate micturition or delay it for a limited period of time Micturation Reflex Animation Bladder and Urethra Reflex arc is required for micturition When the bladder accumulates 250 to 300 ml of urine, the bladder contracts and the internal urethral sphincter relaxes from activation of the spinal reflex arc (micturition reflex) Is stimulated by mechanoreceptors from stretching At this time, the urge to void is felt Bladder fullness is sensed; impulses are sent to the sacral level of the spinal cord In older children and adults, reflex can be inhibited or facilitated by impulses coming from brain or voluntary control of micturition Blood flow through the Kidney 1. 2. Renal arteries - Supply blood to the kidneys. Segmental arteries – branches of the renal artery. 3. Interlobar arteries – Travel between the pyramids. 4. Arcuate arteries - Arch over the base of the pyramids 5. Interlobular arteries - extend through the cortex toward the periphery of the kidneys and supply the afferent glomerular arterioles. 6. Afferent arterioles – supply glomerular capillaries. 7. Glomerular capillaries - 8. Efferent arterioles - Convey blood to a second capillary bed. 9. Peritubular capillaries - Surround the proximal and distal convoluted tubules and site of filtration loop of Henle. 10. Vasa recta – Is a network of capillaries for the juxtamedullary nephrons. – Influences osmolar concentration of the medullary extracellular fluid, which is important for the formation of a concentrated urine. Blood supply *Kidneys are less than 0.5% of total body mass, but receive 20-25% of resting cardiac 19 output The Nephron 1.2 million per kidney – they are the functional unit of the kidney. § Superficial cortical nephrons: Make up 85% of all nephrons, which extend partially into the medulla. § Juxtamedullary nephrons: Lie close to and extend deep into the medulla and are important for the process of concentrating urine; secrete renin. Anatomy of the nephron Afferent arteriole 1 6 2 DCT 3 7 5 4 8 Collected by: (9) minor calyx (10) major calyx (11) renal pelvis (12) Ureter (13) Bladder (14) urethra Overview of renal physiology Renal corpuscle Renal tubule and collecting duct Glomerular capsule 1 Filtration from blood plasma into nephron Fluid in renal tubule 2 Tubular reabsorption from fluid into blood 3 Tubular secretion from blood into fluid Peritubular capillaries 1. Glomerular filtration: Urine (contains excreted substances) Blood (contains reabsorbed substances) Water & small solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubules (PCT –> loop of Henle –> DCT –> Collecting duct) 2. Tubular reabsorption: As “filtrate” moves along tubule water and many useful solutes reabsorbed = returned to blood 3. Tubular secretion: “filtrate” moves along tubule other molecules (wastes, drugs, & excess ions) are secreted into fluid Any solutes that remain in the fluid that drains into the renal pelvis are excreted as urine 23 PTH stim.s reabsorption of Ca++ here Regulation of pH via H+ & HCO3For reabsorption Na+ K+ Clreabsorbtion PTH blocks reabsorption of PO4 here H2O reabsorption ADH & Aldosterone PCT Paracellular Transport occurs via Claudin Proteins Nephron Loop Vasa recta runs through this area: fine tunes osmolarity of the blood by constantly reabsorbing water and salts to maintain plasma volume Urine Production Fluid intake is highly variable. Homeostasis requires maintenance of fluid volumes within specific limits. Urine concentration varies with ADH. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Urine Production High intake – Dilute urine of high volume Low intake – Concentrated urine of low volume Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Formation of Dilute Urine Glomerular filtrate and blood have the same osmolarity – 300mOsm/Liter Tubular osmolarity changes due to a concentration gradient in the medulla Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Animation – Urine Formation Production of dilute urine Production of concentrated urine Countercurrent Mechanism DCT In collecting duct 39 Glomerular Filtration Blood pressure drives filtration Approximately 20% of renal plasma flow becomes filtrate average adult male rate is 125 ml/min and female is 105 ml/min 180 Liters/day in males; 150 Liters/day in females 99% reabsorbed by nephron = 1 – 2 liters of urine produced per day Animation - GFR GFR Control The Renal Corpuscle § Glomerulus - Set of fenestrated capillaries Supplied by the afferent arteriole and drained by the efferent arteriole § Bowman’s (glomerular) capsule Circular space between visceral and parietal epithelium § Mesangial cells support the glomerular capillaries and respond to ANP to regulate glomerular capillary flow. § Glomerular endothelial cells Synthesize nitric oxide (a vasodilator). Synthesize endothelin-1 (a vasoconstrictor). Regulate glomerular blood flow. § Visceral epithelium of the Bowman capsule Is composed of cells called podocytes. o Have footlike processes. o Form an elaborate network of intercellular clefts called filtration slits; modulate filtration. Glomerular filtration membrane üWater, Ions, small molecules & small proteins move through the membrane and become “primary urine” or “filtrate”. üBlood cells, large/medium sized proteins cannot normally be filtered üNegative charge of basement membrane repels filtration of anionic proteins (prevents proteinuria) 44 Nephron JUXTAGLOMERULAR APPARATUS (JG cells): § Control of renal blood flow (RBF), glomerular filtration, and renin secretion occur at this site. Juxtaglomerular cells o These specialized cells are located around the afferent arteriole where the afferent arteriole enters the glomerulus. Mesangial cells specialized contractile cells that support glomeruls and help regulate glomerular blood flow; and remove macromolecules from filtration; have gap jcts. w/ granular cells Macula densa o Portion of the distal convoluted tubule with specialized sodium and chloridesensing cells is located between the afferent and efferent arterioles. o Detect high flitrate rate in the DCT which results in a decrease of nitric oxide and vasoconstriction in the afferent arterioles. JUXTAGLOMERULAR APPARATUS A – Renal corpuscle B – Proximal tubule C – Distal convoluted tubule D – Juxtaglomerular apparatus 1. Basement membrane (Basal lamina) 2. Bowman's capsule – parietal layer 3. Bowman's capsule – visceral layer 3a. Pedicels (podocyte foot processes) 3b. Podocyte 4. Bowman's space (urinary space) 5a. Mesangium – Intraglomerular cell 5b. Mesangium – Extraglomerular cell 6. Granular cells (Juxtaglomerular cells) 7. Macula densa 8. Myocytes (smooth muscle) 9. Afferent arteriole 10. Glomerulus Capillaries 11. Efferent arteriole Efferent arteriole Afferent arteriole Renal Blood Flow Kidneys receive 1000 to 1200 ml/min of blood (20-25% of CO). ~600 to 700 ml as plasma (renal plasma flow [RPF]) Glomerular filtration rate (GFR) 20% of the RPF is filtered into Bowman’s space – ex. 600ml *.20 = (120 to 140 ml/min) This is your FF = Filtration Fraction FF = GFR/RPF (represents the proportion of the fluid reaching the kidneys that passes into the renal tubules. It is normally about 20%) (ex. 120/600) Directly related to the perfusion pressure in the glomerular capillaries If mean arterial pressure decreases or vascular resistance increases, then the RBF decreases. GFR is the 1o function of the kidney. If shut down = loss of all blood homeostasis GFR is regulated by 3 mechanisms: – autoregulatory – neural – hormonal Regulation of Renal Blood Flow and Glomerular Filtration Rate 1. Autoregulation Myogenic mechanism (pressure/stretch) If arterial pressure increases, stretch of the afferent arterioles increases, mechanical stretch channels open à Na+ passes in, depolarizes membrane, VGCC open to allow Ca++ into cell à stim. SR to release Ca++ à smooth muscle contracts to constrict afferent arteriole and perfusion decreases. If arterial pressure drops, stretch of the afferent arterioles decreases, smooth muscle relaxes to dilate afferent arteriole and perfusion increases. Regulation of Renal Blood Flow and Glomerular Filtration Rate 1. Autoregulation Tubuloglomerular feedback (sodium chloride content) If sodium filtration increases, GFR decreases. – Macula densa cells release Adenosine: – stimulates afferent arteriol vasoconstriction (via A1AR receptors) ; & efferent arteriol vasodilation (via A2B receptors) – inhibits granular JG-cells = ¯ renin = ¯BP = ¯GFR = ¯ filtration Regulation of Renal Blood Flow and Glomerular Filtration Rate 1. Autoregulation Tubuloglomerular feedback (sodium chloride content) If sodium filtration decreases, the opposite occurs—GFR increases. – Macula densa cells release PGI2 & NO: – vasodilate afferents & vasoconstrict efferents – Stimulates JG-cells to ­renin = ­BP = ­ GFR = ­ filtration Regulation of Renal Blood Flow and Glomerular Filtration Rate 2. Neural Regulation § Sympathetic nervous system Sympathetic stimulation of afferent arterioles via alpha-1 (α-1) receptors causes vasoconstriction (decreases GFR). Inhibition of Sympathetic nerves causes vasodilation (increases GFR). § Exercise and change of body position Activate renal sympathetic neurons, causes mild vasoconstriction. § Severe hypoxia: Stimulation of chemoreceptors Decreases RBF by means of sympathetic stimulation. Regulation of Renal Blood Flow and Glomerular Filtration Rate 3. Hormonal Regulation § Renin-angiotensin-aldosterone system (RAAS) Increases systemic arterial pressure, and increases sodium reabsorption. Renin: Enzyme is formed and stored in the granular cells of the juxtaglomerular apparatus. Renin àangiotensin I (physiologically inactive). In the presence of angiotensin-converting enzyme (ACE), angiotensin I is converted to angiotensin II. Angiotensin II – Stimulates the secretion of aldosterone by the adrenal cortex. » Na+ retention à H2O retention – Is also a potent vasoconstrictor. – Stimulates antidiuretic hormone (ADH) secretion and thirst. Regulation of Renal Blood Flow and Glomerular Filtration Rate Hormones continued Natriuretic peptides § Atrial natriuretic peptide (ANP) is secreted from myocardial cells in the atria. § Brain natriuretic peptide (BNP) is secreted from myocardial cells in the ventricles (as well as in the brain where it was first identified, hence the name). § ANP and BNP Inhibit sodium and therefore water reabsorption by kidney tubules. Inhibit secretion of renin and aldosterone. Vasodilate the afferent arterioles; constrict the efferent arterioles. Increase urine output, leading to decreased blood volume and blood pressure; promote sodium and water loss. Regulatory Mechanisms of Glomerular Filtration Rate (GFR) EPO - doesn’t affect GFR but does increase O2 delivery to the kidney 57 26_table_05 58 Tests of Renal Function Renal clearance – techniques determine how much of a substance can be cleared from the blood by the kidneys during a given unit of time. – Permits an indirect measure of GFR, tubular secretion, tubular reabsorption, and RBF. Clearance and GFR – GFR is the best estimate for the functioning of renal tissue Inulin (a fructose polysaccharide) is often used – All inulin filtered is excreted in urine (requires constant infusion to maintain stable plasma level) Creatinine: Provides a good estimate of GFR since only a small amount enters urine (1.6g/Day). Clearance and RBF – Para-aminohippuric acid (PAH) clearance is used to determine renal plasma flow and blood flow. (renal extraction ratio 0.92, underestimates RPF ~10%) – Filtered/Secreted in one circulation through the kidney Tests of Renal Function Blood tests Plasma creatinine concentration Plasma cystatin C concentration Blood urea nitrogen (BUN) – By-product produced by muscles. – Normal value is 0.6 to 1.2 mg/dl. – Is most valuable for monitoring the progress of chronic rather than acute renal disease. – Measures progressive renal dysfunction. – Plasma protein is freely filtered at the glomerulus. – Normal value is 0.52 to 0.98 mg/L. In kidney failure levels rise. – Measures progressive renal dysfunction. – Varies as a result of altered protein intake and protein catabolism. – Is a poor measure of GFR. – Is a better indicator for hydration status. Increases in dehydration and kidney failure – Adult normal range is 7 to 20 mg/dl. Tests of Renal Function Reagent strips (dipsticks) – Glucose – Bilirubin – Urobilinogen – Leukocyte esterase – Nitrates – Ketones – Proteins – Hemoglobin and myoglobin