Advanced Pathophysiology Unit 7: Renal-Urologic Page 1 of 19

Transcription

1 Advanced Pathophysiology Unit 7: Renal-Urologic Page 1 of 19 Learning Objectives for this File: 1. Understand how the anatomy of the kidney is related to its functions 2. Understand what makes up a nephron (functional unit) 3. Understand the FOUR main processes that take place in the nephron and their contribution to maintenance of homeostasis 4. Review the overall functions of the kidney (way BEYOND formation of urine!) 5. Review the gross anatomy and blood supply of the kidney 6. Review the functional AREAS of the nephron (early, loop, distal, collecting) 7. Review stimulus for renin production as part of the greater physiologic homeostasis 8. Understand how homeostasis is maintained by the interaction of hormones that affect the kidney and systemic electrolyte concentrations, osmolality, and blood pressure (RAS)

2 Advanced Pathophysiology Unit 7: Renal-Urologic Page 2 of 19 OVERALL RENAL FUNCTIONS: Excretion: Excretion of waste products Blood pressure and vascular volume homeostasis control: Renin-angiotensin system (RAS) Monitoring vascular compartment for adequate perfusion Production of renin enzyme Endocrine homeostasis: RBC hematopoiesis stimulation: o Synthesizes erythropoietin (EPO) in response to hypoxia o Maintains RBC number by stimulation bone marrow hematopoiesis Calcium-Phosphate regulation: o Production of activated vitamin D Metabolic homeostasis: Maintains electrolyte balance Maintains water balance Maintains acid-base balance Able to perform gluconeogenesis and create glucose in hypoglycemic states MORE THAN JUST EXCRETING URINE!!!!! Discussed in detail below.

3 Advanced Pathophysiology Unit 7: Renal-Urologic Page 3 of 19 ANATOMICAL BASIS OF RENAL FUNCTION: STRUCTURES OF THE KIDNEY: Paired, posterior organs next to the abdominal wall outside peritoneal cavity o this area is therefore retroperitoneal (BEHIND the omentum) Level T12 - L3; right is lower (due to liver) Each 150 grams, size of the clenched fist Have renal capsule, renal fat, overlying renal fascia.

4 Advanced Pathophysiology Unit 7: Renal-Urologic Page 4 of Hilum: Medial (central) indentation entry & exit of blood vessels, nerves, lymphatics, ureter. 2. Cortex, Medulla, Calyces, Ureters, Bladder, Urethra: Cortex: outer layer containing glomeruli and tubules Medulla: o inner layer containing some special portions of the renal tubules called the loop of Henle o anatomically arranged in wedge shaped portions called renal pyramids Calyx (calyces): o the wide base of each (medullary) renal pyramid starts at the border of cortex/medulla o the tip of the pyramid is the papilla, projecting into a space called the minor calyx o then into a major calyx (confluence of minor calyces o and into the wide-mouth opening of the ureter called the renal pelvis. Ureters: o muscular tubes carrying urine to bladder o innervated by ANS. o Cholinergic activity is agonist on muscarinic receptors (Parasympathetic) Bladder: o smooth muscle storage area o similar innervation with special property of stretch-relaxation Urethra: o controls outflow. o External sphincter under voluntary control cholinergic somatic neuron to skeletal muscle nicotinic receptors 3. INTRODUCTION: WHAT CELLS MAKE WHAT SUBSTANCES?? (more on this in later files) RENIN enzyme: JGA cells ERYTHROPOIETIN (EPO) hormone: interstitial cells in the cortex (not associated with filtration) PROSTAGLANDINS: again, interstitial cells, but this time in the medulla. Clinical correlate: Renal transplant patients do NOT have their old kidney taken out when they receive a renal transplant Often even bad kidneys that can t perform filtration/urinary production are still left in the body in cases requiring renal transplant, because they usually can STILL perform other functions (such as making hormones)

5 Advanced Pathophysiology Unit 7: Renal-Urologic Page 5 of 19 NEPHRON THE FUNCTIONAL UNIT OF THE EXCRETORY KIDNEY: Each kidney has 1 million nephrons (total of 2 million nephrons if you have two kidneys) This is the FUNCTIONAL UNIT of the kidney Nephrons cannot regenerate if lost due to injury, disease. Normal decrease of 10% every 10 years from age 40 MORE ON THE LABELED PROCESSES AND ANATOMICAL AREAS BELOW.,.KEEP READING! Afferent (Incoming) Arteriole Efferent (Outgoing) Arteriole Glomerulus Processes: 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Bowman s Capsule Peri- Tubular Capillaries Renal Vein The unique shape of the kidney (what else is kidney shaped??) is important to its function this picture shows the path of a nephron from cortex to medulla.

6 Advanced Pathophysiology Unit 7: Renal-Urologic Page 6 of 19 CORTEX MEDULLA Towards Renal Pelvis and Ureters

7 Advanced Pathophysiology Unit 7: Renal-Urologic Page 7 of 19 Picture here is WITH the blood supply. Different TYPES of Nephrons: cortical juxtamedullary nephrons (close to the medulla). juxtamedullary nephrons have the Loop of Henle and the Vasa Recta (accompanying blood supply of the Loop). ALL nephrons eventually empty into the collecting ducts of the distal nephron and must pass through the medulla and be exposed to the hyperosmolar (salty) medulla so that free water can be reabsorbed under the influence of ADH. Juxtamedullary nephrons also have the JGA cells that release renin. Juxtamedullary nephrons also have the macula densa (monitoring device).

8 Advanced Pathophysiology Unit 7: Renal-Urologic Page 8 of 19 BASICS OF RENAL FUNCTIONS: (Numbered individual renal functions are highlighted in BLUE) THE KIDNEY IS MORE THAN JUST EXCRETION!! 1. Urinary excretion: Micro-anatomy of the kidney: Anatomy results in function ( form is function ) Function: o Excrete water-soluble waste products in water (urine) o Excrete free water (excess water with nothing in it) Processes: o Three processes to accomplish excretion: o Filtration, reabsorption, secretion finally excretion SEE BELOW Functional Anatomy: o The NEPHRON (functional unit of the kidney) is a long tube made up of the functional cells of the kidney, the renal tubular cells (renal parenchyma) USE THIS PICTURE WHEN YOU READ THE NEXT PAGE THESE ARE THE BASICS: Afferent Arteriole (incoming bloodflow) Efferent Arteriole (bloodflow leaving the glomerulus and proceeding to the peritubular capillaries) Glomerulus Processes: 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Bowman s Capsule Peri-Tubular Capillaries (accompany the nephron s tubules) Renal Vein (blood back to body)

9 Advanced Pathophysiology Unit 7: Renal-Urologic Page 9 of 19 PAY ATTENTION TO THIS NOW the description of the processes in the nephron (1,2,3,4) leading to excretion (refer back to the picture on the previous page): 1) Filtration: Liquid from the blood plasma is filtered (through a sieve) in the glomerulus in a part of the glomerulus called Bowman s capsule this liquid so captured is called filtrate This filtrate passes into the renal tubules, and the renal tubular cells will be able to modify the filtrate through the following processes of reabsorption and secretion 2) Reabsorption: the body reabsorbs (takes back into its blood supply) essential nutrients and fluids from the filtrate this is reabsorbed into the the peritubular capillary that accompanies that nephron eventually, the peritubular capillaries return to the body s vascular compartment by draining into the renal vein this means stuff is taken BACK from the filtrate INTO the body 3) Secretion: putting additional substances into the filtrate, from the peritubular capillary into the tubular lumen where the filtrate is now they can be carried out of the body as urine at the end of the nephron this means stuff is sent INTO the filtrate FROM the body 4) Excretion: whatever is finally left in filtrate in the renal tubule when it leaves the nephron and enters the ureter (fluids & substances) will be excreted as urine no further modification of the filtrate at this point Blood flow into the nephron & overview of nephron blood vessels: At the glomerulus, a liquid is created from blood plasma This liquid is called filtrate The glomerulus is a sieve (strainer) that collects the liquid portion of plasma (leaves behind in the bloodstream the formed elements, cells & protein) The location in the glomerulus for this filtration is Bowman s capsule The filtrate enters the renal tubule for modification by the renal tubular cells (reabsorption and secretion) Where does the blood plasma come from?? The incoming arteriole to the nephron o The nephron s incoming arteriole is called the afferent arteriole How does the rest of the kidney get blood supply?? o The afferent arteriole continues past the glomerulus, heading into the kidney parenchyma, and is called the efferent arteriole o This continues to supply blood to THAT NEPHRON so that when substances are reabsorbed back from filtrate they go right into that blood supply supplying that nephron, which is now called the peritubular capillary o Also, any other substances in the blood can be put INTO the filtrate through secretion from the peritubular capillary Eventually, this blood flow drains back into the body (renal vein) The nephron s tubule carries the filtrate into a collecting area (renal pelvis & ureters) storage area (bladder) urine leaves the body via the urethra.

10 Advanced Pathophysiology Unit 7: Renal-Urologic Page 10 of 19 Overall of urinary excretion: Urinary excretion includes all those substances (and fluid) that are NOT reabsorbed back into the body (those substances LEFT in the filtrate), PLUS those substances that are secreted into the filtrate (ADDED into the filtrate at the end of the nephron) Substances that are found in urine are said to be cleared and renal clearance is a clinical measure of renal health (more on this later) These processes allow control of fluid, electrolytes, acids & bases, and excretion of foreign substances (e.g. toxins, drugs). Complete renal failure death in days from anuria (accumulation of potassium, acids, fluid, & waste products that should have been removed in urine). 2. Electrolyte & Water Balance Regulated by the Nephron: This water and electrolyte balance is maintained even with huge variations in dietary intake. Large amounts of fluid filtered & reabsorbed allow for rapid removal of waste products & toxins. The blood supply & body water are filtered multiple times daily This is like having your blood dialyzed multiple times every day!! o Plasma volume is 3 liters & the renal plasma flow is 180 L/day (625 ml/min) o Glomerular filtration rate (GFR = creation of filtrate from plasma) is the rate of 125 ml/min This allowsprecise/rapid control of volume/composition of body fluids & toxin-free state Na, K, Cl, Ca, other ion concentrations & body water is controlled by the tubular cells, acting under influences of renally-controlled hormones renal failure results in fluid overload, acid-base disturbances, electrolyte abnormalities and buildup of waste products uremia 3. Excretion of Foreign Chemicals and waste products: urea (from amino acid metabolism) creatinine (from muscle creatine) uric acid (from nucleic acids) end products of hemoglobin breakdown (e.g. bilirubin) metabolites of hormones most toxins (pesticides, drugs, food additives), sulfuric & phosphoric acids (protein metabolism). 4. Regulation of body's systemic arterial pressure: Long term control of BP via renal endocrine system the RAS (Renin-Angiotensin- System) (also called the Renin-Angiotensin-Aldosterone-ADH-Kinin System (RAAAKS) Na/water balance determines intravascular volume (preload) and contributes to cardiac output (CO) Peripheral vasoconstriction determines peripheral resistance (TPR) Combination of CO & TPR determines BP, since BP=CO x TPR

11 Advanced Pathophysiology Unit 7: Renal-Urologic Page 11 of Regulation of acid-base balance: part of three-fold system of acid-base regulation (buffers, lung, renal) Buffer system (proteins) grabs excess H+ to quickly prevent acidosis Lung function ( blowing off the gas CO2 called volatile acid) Renal action is to put acids soluble in water, called fixed or titratable acids. Renal actions are also to reabsorb base (bicarbonate, HCO3-) In severe acidosis, can even synthesize brand-new bicarbonate from amino acid so that renal failure results in acidosis NOTE: usually, the CO2 gas being blown off written as an upgoing arrow next to it: CO2 (this signifies in chemistry notation that it is a gas) 6. Regulation of RBC production: Kidney monitors blood PO2 Hypoxia of the kidney causes secretion of the hormone erythropoietin (EPO) Made by interstitial cortical cells Stimulates RBC production in bone marrow. so that renal failure results in anemia of chronic disease 7. Calcium and phosphate regulation: Under the influence of PTH the kidney synthesizes & secretes activated vitamin D (1,25-dihydroxy vitamin D3, calcitriol) by hydroxylating (adding an "OH" hydroxy group) to inactive vitamin D2 Calcitriol is active with full vitamin D effects on gut to increase absorption of calcium from the gut (food). Thus, renal failure results in hypocalcemia (not enough calcium absorbed from the gut due to calcitriol deficiency) and hyperphosphatemia (from decreased renal excretion of phosphate) that leads to renal osteodystrophy and secondary hyperparathyroidism 8. Glucose Synthesis using Gluconeogenesis: In states of extreme and prolonged hypoglycemia, such as during fasting, two organs can actually make glucose from other substances This is called gluconeogenesis. Remember, the brain, eye, gonads ONLY use glucose as their energy source. Critical to maintain glucose levels for proper brain function

12 Advanced Pathophysiology Unit 7: Renal-Urologic Page 12 of 19 WE WILL GO OVER THIS AGAIN IN DETAIL THESE ARE THE BASICS be extremely comfortable with the names of the processes and what is happening before we get to the details: PAY ATTENTION TO THE DIRECTION OF THE ARROWS next to the numbers!! Afferent (Incoming) Arteriole Efferent (Outgoing) Arteriole Glomerulus Four Main Processes: 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Bowman s Capsule Peri-Tubular Capillaries that accompany the tubules Renal Vein BACK into the body Nephron tubules

13 Advanced Pathophysiology Unit 7: Renal-Urologic Page 13 of 19 B. RENAL BLOOD SUPPLY: a Vital Organ with 21% of cardiac output, 1.2 L/min The cortex has the most vascular supply Renal artery hilum (alongside renal vein & ureter) branches (interlobar arteries, arcuate arteries, radial interlobular arteries) afferent arterioles first capillary bed (glomerular capillaries) efferent arteriole (leaving glomerulus) second capillary bed (peritubular capillaries surrounding renal tubules, plus specialized blood vessel the vasa recta in the medulla) venous system (interlobular vein, arcuate vein, interlobar vein, renal vein) Plasma volume is 3 liters & the renal plasma flow is 180 L/day (625 ml/min each kidney which is 1.2 L/min both kidneys combined) Glomerular filtration rate (GFR = creation of filtrate from plasma) is the rate of 125 ml/min each kidney 625 ml/min of plasma goes to the glomerulus, and 125 ml/min are filtered into Bowman's Capsule forming the filtrate (this is known as the glomerular filtration rate, or GFR). This filtrate is identical in composition to plasma except for formed elements (protein & cells). The remaining 500 ml/min remain in the blood and enter into the peritubular capillaries. Of the 125 ml/min filtered, almost all of the water in this fluid is reabsorbed and put back into the blood.

14 Advanced Pathophysiology Unit 7: Renal-Urologic Page 14 of 19 An Unusual Circulation: Two capillary beds: o Incoming blood is the afferent arteriole at the glomerulus, exiting blood from the glomerulus is the efferent arteriole. o Instead of draining to a vein, the blood supply continues on throughout the nephron as the peritubular capillary, accompanying the nephron s tubule. Cortex blood supply: Cortex has most vascular supply Medullary blood supply: o the name of the peritubular capillary in this area is called the vasa recta o more on this later special function of this blood vessel

15 Advanced Pathophysiology Unit 7: Renal-Urologic Page 15 of 19 OVERVIEW OF THE NEPHRON STRUCTURES & BLOOD SUPPLY: 1. (EARLY) PROXIMAL NEPHRON: glomerulus & loop of Henle GLOMERULUS: The afferent arteriole leads to the glomerular capillary bed (which branch & anastomose) This capillary bed is enclosed by renal epithelial cells to make a separate space called Bowman's capsule & Space. These renal epithelial cells continue on to form a cylinder (renal tubular epithelial cells) or "tubule." The tubules are formed of renal tubular cells which do the work of the kidney (the functional basic renal cell). High afferent arteriole hydrostatic pressure (60 mm Hg) causes net filtration from capillary into Bowman's space creating filtrate (becomes urine later in the nephron) Glomerular filtration rate (GFR = creation of filtrate from plasma) is the rate of 125 ml/min each kidney PROXIMAL (convoluted) TUBULE (PCT) & LOOP OF HENLE: Filtrate flows down the proximal tubule in the cortex (reabsorption takes place here) If this is a juxtamedullary nephron o Then the proximal tubule continues on to become the Loop of Henle which descends (descending limb) into the RENAL MEDULLA o makes a hairpin turn (loop) o then ascends (ascending limb) back to the cortex of the kidney o When the loop of Henle ascends back into the cortex of the kidney, it passes back in-between the afferent & efferent arteriole of its nephron. o The ascending limb becomes very thick as it climbs back up into the cortex a special plaque in its wall contains special cells. This plaque is called the macula densa (dense body) and they monitor the body s vascular compartment by indirect means they monitor the filtrate They can signal to the juxtaglomerular apparatus (JGA) cells in the afferent & efferent arteriole to release renin enzyme (if needed to maintain blood volume & GFR). More on Juxtamedullary nephrons: o % of the nephrons are very close to the medulla and are juxtamedullary nephrons Thus, MOST nephrons are cortical and do NOT have a loop of Henle IMPORTANCE of the juxtamedulllary nephrons is that they have a loop of Henle that dip very deep into the medulla; o THE ACTIVITY OF THESE CELLS creates a concentration gradient of saltiness (osmolarity) as you go deeper into medulla. o This salt gradient eventually controls water reabsorption back into the body (form either a dilute or a concentrated urine)

16 Advanced Pathophysiology Unit 7: Renal-Urologic Page 16 of DISTAL NEPHRON: DCT, CT, CD: After the ascending limb of the loop of Henle, the distal convoluted tubule (DCT) o The DCT (distal to the glomerulus) proceeds on. They join together to form the cortical collecting tubules (CT) and cortical collecting duct (CD) This area is functionally different from the PCT & loop of Henle. Final reabsorption of free water occurs here. Once the filtrate can no longer be changed by reabsorption or secretion, the filtrate is now called urine. o It is drained by a series of medullary tubules & ducts. o These run down into the renal medulla and then into the papilla, where it empties into its minor calyx. There are 250 collecting ducts in each kidney, each serving 4,000 nephrons. 3. BLOOD SUPPLY: Afferent arteriole with its arteriolar sphincter glomerular capillary bed Efferent arteriole, with its own sphincter Peritubular capillary bed (second capillary bed). o This surrounds the proximal tubule, loop of Henle, & distal nephron o Normally a low pressure system (13 mm Hg), with net fluid movement from interstitium & tubular filtrate back INTO the capillary & vascular space (opposite from glomerulus) for reabsorption. Control of glomerular pressures: o Increased efferent arteriolar sphincter tone will cause resistance and increased HP in the glomerulus from back pressure. o This helps maintain glomerular filtration and formation of filtrate. o Part of the peritubular capillaries is the specialized blood vessels called the vasa recta o This is the part of the peritubular capillary which follow the loop of Henle into the medulla. o What is special about this blood vessel is that it makes a hairpin turn, just like the loop of Henle, so that it doesn t wash away the electrolyte gradient created by the loop of Henle.

17 Advanced Pathophysiology Unit 7: Renal-Urologic Page 17 of 19 OVERVIEW OF GLOMERULAR PERFUSION: GOAL maintain filtration and make filtrate. Afferent arteriole sphincter tone: o vasoconstriction here reduces glomerular flow o vasodilatation here would increase glomerular flow Efferent arteriole sphincter tone: o resistance to blood flow determines the back-pressure at the glomerulus o thus, vasoconstriction here increases the hydrostatic pressure at the glomerulus to improve glomerular filtration (GFR) and filtrate (urine) formation Peritubular capillaries: o Reabsorption of fluid back into the peritubular capillaries & vascular space o filtrate is reabsorbed back into the body s capillaries. o More reabsorption in low flow states means more time to perform reabsorption, thus conserves fluids & maintains vascular volume in low flow states such as hypotension. (automatic adaptation to hypotension) Efferent Arteriole (Outgoing blood from glomerulus to peritubular capillaries) with sphincter that can control back pressure (resistance) at the glomerulus -- increased pressure means more filtration pressure & more GFR. Afferent Arteriole (Incoming Blood), with sphincter that can regulate flow

18 Advanced Pathophysiology Unit 7: Renal-Urologic Page 18 of 19 RENAL PERFUSION & RENIN RELEASE & RAS ACTIVITY (SYSTEMIC BP CONTROL): the kidney controls BOTH systemic BP AND controls its own internal blood flow o This is called autoregulation Juxtaglomerular complex (apparatus) cells (JGA cells): juxta means next to JGA cells are secretory renal endocrine cells in the walls of the afferent & efferent arterioles that abut (are right up next to) the macula densa in the ascending loop of Henle where it runs between the afferent & efferent arteriole of its own nephron as it climbs back up into the cortex from the medulla JGA cells synthesize and store renin and release it based on input from the monitoring cells of the macula densa (monitoring cells) Macula densa monitoring: Macula densa cells monitor the filtrate in the ascending loop of Henle for NaCl concentration o the macula densa is located in a plaque in the thick, ascending loop of Henle as it climbs out of the medulla back into the cortex right in between the afferent & efferent arterioles of its own nephron Poor renal perfusion causes slow flow through the whole tubular system o increases time spent in the loop of Henle o and increases NaCl reabsorption o THUS lowers NaCl concentration in the filtrate o this is an indirect measure of low renal perfusion and the MAIN stimulus for rennin release Low NaCl concentration in the filtrate causes the macula densa to stimulate the JGA cells to release renin & start the RAS volume loading, vasoconstriction and increased BP Actions of the macula densa: if there is a LOW concentration of NaCl in the filtrate, macula densa cells save the GFR cause an decrease in the afferent sphincter arteriolar tone (allowing greater blood flow into the glomerulus more vasodilated) they send signals to the JGA cells found in the walls of the afferent and efferent arterioles of the same nephron to release the enzyme renin to activate the RAS There is also a direct monitoring of incoming renal BP: there are baroreceptors of the actual incoming pressure in the afferent arteriole but this is NOT the MAIN stimulus to renin production

19 Advanced Pathophysiology Unit 7: Renal-Urologic Page 19 of 19 OVERALL Results of activation of RAS activation increased CO & BP: increased NaCl reabsorption (salt loading) increased water reabsorption (overall volume loading) increased K secretion (excretion) & H+ secretion (excretion) peripheral vasoconstriction Autoregulation of renal vessels Efferent Arteriole Macula Densa Cells in Ascending thick Limb Loop of Henle Afferent Arteriole JGA cells in wall of afferent arteriole (make renin) Glomerulus where filtration occurs Filtrate leaves here into Bowman s Capsule and the proximal tubule