Update_Urinary System Physiology I_with QA PDF

FFFJ 1023: Anatomy, Physiology & Biochemistry THE URINARY SYSTEM DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSA...

FFFJ 1023: Anatomy, Physiology & Biochemistry THE URINARY SYSTEM DR. NUR ‘IZZATI MANSOR DEPARTMENT OF NURSING FACULTY OF MEDICINE UNIVERSITI KEBANGSAAN MALAYSIA Email: [email protected] # FPERUKM50Years www.ukm.my/fper INSPIRING FUTURES, NURTURING POSSIBILITIES  Learning Objectives 1 Explain general functions of the kidney Describe renal blood flow & plasma flow and factors that control and affect renal 2 blood flow Explain glomerular filtration rate (GFR), its measurement, factors determining and 3 affecting it 4 Define renal clearance and explain its principles and importance 5 Describe the renal reabsorption of various substances # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES The urinary system consists of 3 main components: 1) Kidneys 2) Ureters Nephron is the functional unit of kidney. 3) Urinary bladder # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  What are the Functions of Kidneys? Most people know that a major function of the kidneys is to remove waste products and excess fluid from the body in the form of urine. The more important function of kidney is to regulate the body homeostasis. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES In general, kidney functions are divided into 4 main functions: 1. Regulation of Body Fluid, Electrolytes and Acid-base balance. 2. Production of Hormones and Enzymes. 3. Elimination of Waste and Foreign substances (from metabolic reaction) 4. Reabsorption and Metabolism of Amino acids and Glucose. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Regulation of Body Fluid, Electrolytes and Acid-base balance. Regulate osmotic pressure of body fluid by excreting osmotically diluted or concentrated urine Regulate the plasma ionic composition Regulate acid-base balance by excreting H+ or HCO3- Regulate the extracellular fluid (ECF) volume by controlling Na+ and water excretion Regulate arterial blood pressure by adjusting Na+ excretion and producing various substances that can affect blood pressure # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES Production of Hormones and Enzymes Erythropoietin 1,25-dihydroxycholecalciferol Renin Kinins # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Elimination of Waste and Foreign substances (from metabolic reaction) Metabolic reaction Urea end-product of protein metabolism Uric acid end-product of purine (nucleic acid) metabolism Creatinine end-product of muscle metabolism Foreign substances Penicillin Urea Urobillinogen # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Which is NOT a function of the kidneys? A. excrete waste products B. regulate blood pressure C. balance fluid and electrolytes D. white blood cell production Answer: D. Healthy kidneys produce a hormone called erythropoietin or EPO, which stimulates the bone marrow to make red blood cells. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Structure and Function of Nephron  Nephron is the basic functional unit of the kidney. Each part of nephron carry out specific function (Will be discussed in the following slide).  Two basic types of nephrons: 1) Cortical nephrons or superficial nephrons 2) Juxtamedullary nephrons.  Each nephrons is made up of two major parts 1) Renal corpuscle – consists of glomerulus and Bowman capsule 2) Renal tubule – consists of proximal convoluted tubule, loop of Henle, distal convoluted tubule # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Structure and Function of Nephron  The primary function of the nephron is to filter the blood by removing waste, excess fluid and unwanted ions in the urine.  They do this by accomplishing three key processes — filtration, reabsorption, and secretion. Cocchiaro et al. (2017) Front. Cell Dev. Biol. 5,114. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Filtration from blood plasma into nephron Three Basic Renal Processes: Afferent Efferent arteriole arteriole GF 1. Glomerular filtration refers to the 80% of the plasma movement of fluid and solutes from that enters the the glomerular capillaries into Glomerulus glomerulus is not GF filtered and leaves Bowman’s capsule. Bowman’s through the efferent capsule arteriole TR 2. Tubular reabsorption refers to the 20% of the plasma that enters the TR movement of materials from the glomerulus is filtrate in the kidney tubules into the filtered Peritubular capillary peritubular capillaries. TS To venous Kidney tubule system TS 3. Tubular secretion refers to the (entire length, uncoiled) (conserved for secretion of solutes from the the body) peritubular capillaries into the kidney Urine Excretion (eliminated from the body) tubules. Excretion = Filtration - Reabsorption + Secretion # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES Which of the following choices correctly traces the route of glomerular filtrate on its path to the collecting duct of a nephron? A. proximal tubule, Bowman’s capsule, descending loop of Henle, ascending loop of Henle, distal tubule B. Bowman’s capsule, proximal tubule, descending loop of Henle, ascending loop of Henle, distal tubule C. Bowman’s capsule, distal tubule, descending loop of Henle, ascending loop of Henle, proximal tubule D. Bowman’s capsule, proximal tubule, ascending loop of Henle, descending loop of Henle, distal tubule Answer: B. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  How are cortical nephrons different from juxtamedullary nephrons? A. cortical nephrons lie almost entirely outside the renal medulla. B. cortical nephrons have an associated vasa recta. C. cortical nephrons have a longer tubule. D. there are fewer cortical nephrons. Answer is A: Cortical nephrons are situated almost entirely within the cortex, while the far less numerous juxtamedullary nephrons have their glomeruli adjacent to the medulla and extend their loop of Henle into the medulla. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  The Micturition Reflex (Sherwood, pg. 531)  Micturition, or urination, the process of bladder emptying, is governed by two mechanisms: the micturition reflex and voluntary control.  Micturition reflex is an autonomic spinal cord reflex, integrated in the sacral segment (S2-4).  As the bladder is filled with urine, stretch receptor on its wall is stimulated, and signals are sent to the brain and spinal cord.  Signal from the spinal cord reflexively sent back to the bladder via parasympathetic nerve causing contraction.  Signals from the brain may facilitate or inhibit micturition.  Inhibition of pudendal nerve in the spinal cord causes relaxation of the external sphincter to facilitate micturition process.  Internal sphincter relaxation is caused by contraction of the bladder INSPIRING FUTURES, NURTURING POSSIBILITIES Renal Clearance, Blood Flow & Filtration # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Renal Blood Flow (RBF) RBF is volume of blood that reaches kidneys in unit time: determined by pressure gradient (pressure in renal artery – pressure in renal vein) divided by arteriolar On Average, the resistance. heart pumps out the blood almost 5 L/min Purpose of high flow:  to supply enough plasma for high glomerular filtration necessary to regulate fluid and Aorta electrolytes Interior vena cava Renal artery 20-25% (~1.25 Renal veins L/min) of the Segmental arteries resting cardiac output (CO) to Interlobar veins the kidneys Interlobar arteries Mechanism that regulate RBF: Arcuate veins Arcuate arteries  closely linked to the Only in regulation of glomerular Interlobular arteries Interlobular veins Juxtaglomerular nephron filtration rate (GFR) and excretory functions of the Peritubular capillaries Vena recta Afferent arteriole kidneys Glomerular arteries # FPERUKM50Years Efferent arteriole INSPIRING FUTURES, NURTURING POSSIBILITIES  Substances in the blood plasma pass through glomerulus Some will be filtered into the Bowman capsule Some filtrates* will be reabsorbed into the interstitium and capillaries Some will remain in the renal tubules and excreted Renal tubular cells can secrete substances to be excreted in urine *What goes into the tubule is called the “filtrate” because it has been filtered out of the blood. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Glomerular membrane Glomerular capillary membrane is composed of 3 structural layers: Wall of glomerular capillaries (endothelial cell layer) with large fenestration (pores: 70- 100 nm in diameter) Basement membrane (collagen & glycoprotein) Inner layer of Bowman capsule (epithelial cells with podocytes) To be filtered, a substance must pass through: 1) The pores between and the fenestrations within the endothelial cells of the glomerular capillary. 2) The basal lamina, an acellular basement membrane 3) The filtration slits between the foot processes of the podocytes in the inner layer of Bowman’s capsule. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Glomerular Filtration Rate (GFR) GFR is the volume of plasma filtered through the glomerulus per unit time. Normal GFR = 125 ml/min (7.5 L/hr; 180 L/day). GFR is a crucial determinant of renal function.  Forces Involved in Glomerular Filtration: a) Glomerular blood hydrostatic pressure (GBHP) is the blood pressure in glomerular capillaries. It promotes filtration by forcing water and solutes in blood plasma through the filtration membrane. b) Capsular hydrostatic pressure (CHP) is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and renal tubule. c) Blood colloid osmotic pressure (BCOP), which is due to the presence of proteins such as albumin, globulins, and fibrinogen in blood plasma, also opposes filtration. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Glomerular Filtration Rate (GFR) – Cont’d.  Glomerular filtration is driven by the Starling forces across the wall and, with the assumption that the oncotic pressure of Bowman’s space is zero, is described by the Starling equation: GFR = Kf  [(PGC – PBC) – (πGC – πBC)] Where, Kf = Coefficient filtration = surface area  permeability of capillaries PGC = Glomerular capillaary hydrostatic pressure PBS = Bowman space Hydrostatic pressure πGC = Glomerular capillary oncotic pressure Starling forces πBS = Bowman space oncotic pressure  In words, glomerular filtration rate is the product of Kf and the net ultrafiltration pressure. The net ultrafiltration pressure (NFP) is the algebraic sum of the three Starling pressures (omitting the oncotic pressure in Bowman’s space).  The greater the net ultrafiltration pressure, the higher the rate of glomerular filtration. NFP=(PGC – PBC) – (πGC – πBC) # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Factors affecting GFR 1. Renal blood flow  During Baseline: constant blood flow (RBF) through afferent arteriole, glomerulus and efferent arteriole constant the hydrostatic capillary pressure (PGC) constant GFR  Increase renal blood flow ( RBF) through the nephron elevates the hydrostatic capillary pressure ( PGC)  GFR  And vise versa. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Factors affecting GFR 2. Diameter of glomerular blood vessels b) Changes to efferent arteriole a) Changes to afferent arteriole  Mild Constriction: Decrease renal blood flow ( RBF) increase hydrostatic capillary  Constriction: Decrease renal blood flow ( RBF) reduce the hydrostatic pressure ( PGC)  GFR capillary pressure ( PGC)  GFR  Extreme Constriction: Decrease renal blood flow ( RBF) increase the capillary  Dilation: Increase renal blood flow ( RBF) increase the hydrostatic capillary oncotic force ( πGC)  GFR pressure ( PGC)  GFR  Dilation: Increase renal blood flow ( RBF) e.g.: Adrenaline decrease the hydrostatic capillary Noradrenaline pressure ( PGC)  GFR e.g.: Angiotensin II e.g.: Angiotensin II High-protein diet blockade # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Baseline The relationship between afferent and efferent arteriole resistance and how this affects blood flow, pressure and filtration # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Factors affecting GFR 3. Coefficient filtration (Kf) - Pathophysiology caused: Renal disease, diabetes mellitus, hypertension  Surface area of the membrane  Contraction of mesangial cells reduces surface area  Agents that affects mesangial cells: i. Contraction: PGF2, angiotensin II, norepinephrine, vasopressin ii. Relaxation: cAMP, PGE2, ANP, Dopamine  Glomerular capillary permeability  Size of molecules. Neutral & small molecules ( 8 nm are not filtered  Charge of molecules. Negatively charged molecules are less easily filtered (e.g. albumin) # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Physiologic Control of GFR Two major control mechanisms regulate the GFR: 1. Autoregulation, which is; aimed at preventing spontaneous changes in GFR 2. Extrinsic sympathetic control, which is aimed at long-term regulation of arterial blood pressure. i. Nervous regulation (Sympathetic nervous system) ii. Hormonal regulation # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Autoregulation of GFR Occurs when stretching of blood vessels (in response to BP) triggers contraction of arteriolar smooth muscle in the wall Myogenic mechanism of afferent arterioles, vise versa (myo- muscle; -genic producing) This mechanism normalizes RBF and GFR within seconds after a change in BP. An adaptive mechanism that links the GFR to the concentration of salt in the Tubuloglomerular tubule fluid at the macula densa in feedback juxtaglomerular apparatus Autoregulation prevents inappropriate (from the tubule to fluctuations in the GFR in response to the glomerulus) changes in the mean arterial driving pressure Mediators released by macula densa to within the range of 80 to 180 mm Hg. regulate GFR: (1) ATP (adenosine) (2) Nitric oxide (NO), prostaglandins (PGE2) # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Myogenic Autoregulation This response helps limit blood flow into the glomerulus to normal despite the elevated arterial pressure # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  *At ascending loop of henley # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Mechanism of Tubuloglomerular Feedback  GFR  [NaCl] at macula densa  NaCl uptake via Na+-K+-2Cl- Macula densa Extraglomerular Granular & Afferent  ATP & Adenosine release Tubular fluid mesangial cells *VSM cells arteriole  Intracellular [Ca2+] in Vasoconstriction afferent arteriole smooth muscle [NaCl] Vasoconstriction of afferent arteriole  GFR to normal level *VSM cells: Vascular smooth muscle cells # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES Mechanism of Tubuloglomerular Feedback  Renin released from these cells then functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II.  Finally, the angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and helping to return GFR toward normal. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Extrinsic controls of GFR: Neural and endocrine mechanisms  The extrinsic control mechanisms have an effect on GFR, but their primary function is to maintain systemic blood pressure.  The neural and endocrine mechanisms used in extrinsic controls of GFR include the sympathetic nervous system and the renin–angiotensin–aldosterone mechanism.  At rest (normal condition):  Renal blood vessels are dilated  Renal autoregulation mechanism prevail  Under extreme stress,:  Norepinephrine (NE) is released by sympathetic nervous system; epinephrine (Epi) is released by the adrenal medulla.  NE and Epi cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin from juxtaglomerular apparatus cells leading to renin-angiotensin cascade.  Renal Clearance Definition Clearance concept Renal clearance is the volume of blood or  High renal plasma clearance = EFFICIENT plasma that is “cleaned” or cleared of a EXCRETION of a substance in the urine. substance by the kidney per minute.  Low renal plasma clearance = INEFFICIENT EXCRETION of a substance in the urine. The IMPORTANCE of Measurement of glomerular filtration rate renal clearance (GFR) and Renal Plasma Flow (RPF) Assess severity of renal damage Measurement of tubular reabsorption and secretion # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Renal Handling of Substances during urine formation  Substance W: Filtered & secreted, but not reabsorbed (e.g. H+ ions, Para AminoHippurate (PAH))  Substance X: Filtered & partially reabsorbed (e.g. Urea, Na+, phosphate.)  Substance Y: Filtered & completely reabsorbed (e.g. glucose & amino acid)  Substance Z: Filtered but neither reabsorbed nor secreted (e.g. Creatinine & inulin)  Renal Clearance (contd.) Clearance calculation Clearance rate of a substance X, UX  V Excretion rate C (ml/min) = = Plasma concentration PX  Inulin clearance can be used to estimate GFR  Creatinine clearance is used Where, clinically to estimate GFR U = concentration of substance X in urine (mg/ml) V = urine flow rate (ml/min) P = concentration of substance X in plasma (mg/ml) # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Renal Handling of Inulin INULIN (exogenous), a biologically inert polysaccharide, can be used to estimate GFR since it is filtered, but not reabsorbed or secreted. UX  V CInulin = PX Amount filtered = Amount excreted Properties of a substance used for GFR measurement GFRInulin = CInulin  Freely filtered UInulin  V  NOT secreted by the tubular cells GFR = PInulin  NOT reabsorbed by the tubular cells  1 ml/min GFR = 125 mg/ml 1.0 mg/ml  NOT toxic  NOT be metabolized GFR = 125ml/min  Easily measurable  Creatinine clearance  Creatinine (endogenous) is a by-product of skeletal muscle metabolism and almost entirely removed from the body through kidneys.  Measurement of creatinine clearance does not require intravenous infusion into the patient, this method is much more widely used than inulin clearance for estimating GFR clinically.  Creatinine is freely filtered across the glomerular capillaries but also is secreted to a small extent. Thus, the clearance of creatinine slightly overestimates the GFR.  Creatinine production is proportional to total muscle mass.  creatinine clearance can be estimated from serum creatinine concentration  Creatinine clearance is inversely proportional with extent of renal functional impairment.  serum creatinine concentration rises as the creatinine clearance decreases. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Renal Plasma Flow (RPF)  If a substance is completely cleared from the plasma, the clearance rate of that substance is equal to renal plasma flow (RPF). Renal Handling of PAH  E.g. para-aminohippuric acid (PAH). PAH have the highest clearances of all substances because they are both filtered and secreted. Amount entered kidney = Amount excreted Properties of a substance used UPAH  V RPFPAH = CPAH = for RBF measurement PPAH  Freely filtered  NOT reabsorbed  Secreted 10% # FPERUKM50Years 90% INSPIRING FUTURES, NURTURING POSSIBILITIES  Measurement of RPF using clearance of PAH  The clearance of PAH can be used as an estimation of RPF (ERPF). The percentage of PAH removed from the blood is known as the extraction ratio of PAH and averages about 90% in normal kidneys. E.g.: UPAH  V 5.85  1 ERPFPAH = CPAH = = = 585 ml/min PPAH 0.01 ERPF 585 Actual RPF = = = 650 ml/min ∗Extraction ratio 0.9 RPF Renal blood flow = 1 −#𝐻𝑎𝑒𝑚𝑎𝑡𝑜𝑐𝑟𝑖𝑡 650 = = 1182 ml/min 1 −0.45 #Hematocrit = 0.45 PPAH − Renal venousPAH *Extraction ratio = PPAH # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Glucose Clearance  In normal adult, all glucose filtered are reabsorbed at the proximal tubule so clearance of glucose = zero. Renal Handling of Glucose  Amount of glucose reabsorbed is proportionate to the amount filtered.  The transport maximum (TmG) for glucose reabsorption is 375 mg/min (man) & 300 mg/min (woman).  When TmG is exceeded, amount of glucose in the urine rises.  Filtered load = GFR  Plasma glucose up to transport maximum (TmG). E.g.: Normal plasma glucose = 80 - 100 mg/dL GFR = 1.25 dL/min. Filtered load = 1.25 dL/min  100mg/dL = 125 mg/min.  Since 125 mg/min < 375 mg /min, all the glucose is reabsorbed. # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Glucose Clearance (Contd.)  Glucose is reabsorbed with Na+ in the kidneys by secondary active transport  Glucose requires transport for reabsorption from tubular lumen into cell # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  Renal threshold for glucose  Plasma concentration at which glucose first appears in the urine  GFR  Renal Threshold = TmG  1.25 dL/min  Renal Threshold = 375 mg/min  Thus, renal threshold = 300 mg/dL  Actual renal threshold = 200 mg/dL (because some nephrons have lower absorptive capacity) # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES  THANK YOU GANGWAR ER-DR INSTITUTE # FPERUKM50Years INSPIRING FUTURES, NURTURING POSSIBILITIES