Physio Renal System PDF

# Physiology of the Renal System ## Overview of Renal Function The kidneys have several major regulatory functions, which include: 1. **Regulation of water and electrolyte balance:** - For regulation of homeostasis, excretion of water and electrolytes must be precisely matched to intake. 2. **...

# Physiology of the Renal System ## Overview of Renal Function The kidneys have several major regulatory functions, which include: 1. **Regulation of water and electrolyte balance:** - For regulation of homeostasis, excretion of water and electrolytes must be precisely matched to intake. 2. **Excretion of metabolic waste products:** - The kidneys are the primary means for eliminating waste products of metabolism as urea, uric acid, creatinine, metabolites of various hormones. 3. **Excretion of foreign chemicals,** e.g. drugs, food additives and pesticides. 4. **Endocrine functions of the kidney:** - **a) Regulation of erythrocyte production:** - The kidneys secrete erythropoietin hormone, which stimulates the production of R.B.Cs. - The kidneys account for almost all the erythropoietin secreted into the circulation. - Severe anemia develops in people with severe kidney disease as a result of decreased erythropoietin production. - **b) Regulation of 1,25-Dihydroxy vit. D3 production:** - The kidneys produce the active form of vitamin D: 1,25-dihydroxycholecalciferol by hydroxylating 25-hydroxycholecalciferol at the number "1" position. - Active vitamin D plays an important role in calcium and phosphate homeostasis. - **c) Renin secretion.** 5. **Regulation of arterial blood pressure:** - **a) Short-term regulation:** renin-angiotensin aldosterone system. - **b) Long-term regulation:** through excreting variable amounts of sodium and water. 6. **Regulation of acid-base balance by:** - **a) Elimination of acids produced from the metabolism of proteins such as sulphuric and phosphoric acid.** - **b) Regulation of the buffer stores in the body.** 7. **Gluconeogenesis:** - The kidneys synthesize glucose from amino acids during prolonged fasting and add it to the blood. - This helps to maintain blood glucose concentration. 8. **Secretion of prostaglandins (PGE2, PGI2) and bradykinins:** - These act as paracrine hormones that play important role in regulation of the renal blood flow. ## Physiologic Anatomy Of The Kidneys - The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity. - The kidney is surrounded by thin, tough capsule. ### Fig. 1: An illustration of the major structures observed in a vertically sectioned human kidney - The renal mass is divided into two major regions: - **An outer cortex** - **An inner medulla** ### Fig. 2: The main portions of the nephron ## The functional unit of the kidney is the nephron: - There are approximately 1.3 million nephrons in each human kidney. - Each nephron is capable of forming urine. - The parts of the nephron are shown in Fig 2. (refer to histology) ### Fig. 3: Types of nephrons ## Types of Nephrons According to location of renal corpuscle, nephrons are of two types (Fig 3). The following table shows the differences between the two types of nephrons: | | Cortical Nephrons | Juxtamedullary Nephrons | |---|---|---| | **% of the total number** | 85% | 15% | | **Glomeruli** | In the outer portion of the renal cortex. <br/> Short & penetrate a short distance into the medulla no further than the junction between the inner & outer medulla. | Deep in the renal cortex near the medulla. <br/> Long & dips deeply into the medullary pyramids. | | **Loop of Henle** | | | ## Vascular structures supplying tubule | | | |---|---| | **The tubule is surrounded by a network of peritubular capillaries.** | **Vasa recta which are specialized peritubular capillaries (hairpin U-shaped capillary loops) that lie side by side with loop of Henle. In addition to the peritubular capillary network** | | **Special functions** | **Plays an important role in the process of urine concentration.** | ## Juxta Glomerular Apparatus JGA is a combination of specialized tubular and vascular cells located at the vascular pole where the afferent and efferent arterioles enter and leave the glomerulus. ### Fig. 4: Juxta Glomerular Apparatus ### It consists of: 1. **Macula densa:** These are modified tubular cells in the initial portion of distal tubule that comes in contact with the afferent and efferent arterioles. These cells function as chemoreceptors that detect NaCl load in the tubular lumen at this point. 2. **Juxtaglomerular cells:** There are specialized smooth muscles located in the media of the afferent arterioles and to a lesser extent the efferent arterioles as they enter the glomeruli. - These cells synthesize, store and secrete renin. - These cells are baroreceptors which respond to changes in perfusion pressure in afferent arteriole and are stimulated by a decreased renal perfusion pressure or hypovolemia, to release rennin. - JGA plays an important role in auto-regulation of the renal blood flow and GFR during changes in arterial pressure and is important for regulation of arterial blood pressure through rennin-angiotensin aldosterone system. ## Renal blood flow - In a resting adult, the kidneys receive 1.2-1.3 liter of blood per minute, i.e. 21% of the cardiac output. - The renal arteries are direct branches of the aorta. ## Renal Vascular Arrangement: Refer to anatomy Afferent arterioles arise from the interlobular arteries → glomerular capillaries → efferent arterioles → peritubular capillaries → interlobular veins → renal veins (Fig 5) ### Fig. 5: Schematic of relations between blood Vessels & tubular structures & differences between cortical & juxtamedullary nephrons ## Therefore, there are two capillary beds associated with each nephron: (Fig 6) 1. **The glomerular capillary bed: "High pressure bed"** - It receives its blood from the afferent arteriole. - The hydrostatic pressure in the glomerular capillaries is about 60 mmHg which cause rapid filtration of fluid. - The pressure in the glomerular capillaries is higher than in other capillary beds due to: - a) The renal arteries are direct branches of the abdominal aorta. - b) The afferent arterioles are short, straight branches of the interlobular arteries. - c) The efferent arterioles have high resistance than the afferent arteriole. 2. **The peritubular capillary bed "Low pressure bed"** - The hydrostatic pressure is about 13 mmHg. - The peritubular capillaries behave like the venous ends of other capillaries. - The low pressure in these capillaries permits fluid reabsorption from the interstitium into the blood... ### Fig. 6: Glomerular capillaries and peritubular capillaries ## Regional Blood Flow: - The main function of the renal cortex is filtration of large volumes of plasma through the glomeruli, so it is no surprising that the renal cortex receives most of the renal blood flow (98%), while renal medullary blood flow accounts for 2% of the total renal blood flow. - This sluggish blood flow in the renal medulla allows the kidney to form concentrated urine. - The main function of the renal cortex is filtration of large volumes of plasma through the glomeruli, so it is no surprising that the renal cortex receives most of the renal blood flow (98%), while renal medullary blood flow accounts for 2% of the total renal blood flow. - This sluggish blood flow in the renal medulla allows the kidney to form concentrated urine. ## Autoregulation of the renal blood flow: (Fig 7). - When the kidney is perfused at a moderate pressure (90 - 200 mmHg) the renal blood flow is kept relatively constant by change of the renal vascular resistance - Renal autoregulation occurs in denervated and isolated kidney, i.e. independent of nerves or hormones. ### Fig. 7: Autoregulation of renal blood flow ## Mechanisms of autoregulation of renal blood flow: ### A-Myogenic mechanism: this is a rapid response, thus it is the first line defense against changes in blood pressure a- With rise of pressure: (Up to 220 mmHg). - Direct contractile response of the muscle of the afferent arteriole due to stretch. This contraction prevents excessive increase in renal blood flow. - Stretch of the vascular wall increases calcium influx from the extracellular fluid into the muscle fibers by opening stretch sensitive Ca++ channel causing them to contract → increase the vascular resistance of different arterioles maintain renal blood flow. b- At low pressure: relaxation of the vascular smooth muscles of afferent arterioles → decrease of vascular resistance maintains a constant blood flow. ### B-Tubuloglomerular feedback: 1. When renal arterial pressure increases both RBF and GFR increase. The increase in GFR results in increase delivery of solutes and water to the macula densa. The macula densa responds by secreting adenosine which acts on A1 receptor producing vasoconstriction of afferent arterioles → reduces RBF, HPGC and GFR back to normal. (Fig 8) ### Fig. 8: Macula densa feed back mechanism for autoregulation of the Glomerular filtration rate during increased renal arterial pressure. 2. Conversely with drop of arterial blood pressure, the HPGc tends to drop, the GFR decreases. The flow rate in the loop of Henle decreases, so that reabsorption of sodium and chloride ions in the ascending loop of Henle increases. Sodium chloride reaching the macula densa decreases. ## Macula densa sends signals to: (Fig 9). a) Afferent arteriole: producing dilatation which raises HPGC and help to return GFR towards normal. b) Efferent arteriole: producing constriction, which occurs though increase of renin release from JGC. Renin released increases the formation of angiotensin I, which is converted to angiotensin II, which constricts the efferent arteriole, thereby increasing HPGc and return GFR toward normal ## Aim of autoregulation: - The aim of autoregulation in the kidney is to maintain constant glomerular filtration rate and to allow precise control of renal excretion of water and solutes despite marked changes in arterial blood pressure. ### Fig. 9: Macula densa feedback mechanism for autoregulation of the glomerular filtration rate during decreased renal arterial pressure.