Renal Blood Flow & Control Lecture Notes PDF

Semester -3- LECTURE-1- RENAL PHYSIOLOGY Renal blood flow and its control Learning outcomes At the end of the lecture, you should be able to: 1. Describe the different functions of the kidneys. 2. Describe the different parts of the nephron....

Semester -3- LECTURE-1- RENAL PHYSIOLOGY Renal blood flow and its control Learning outcomes At the end of the lecture, you should be able to: 1. Describe the different functions of the kidneys. 2. Describe the different parts of the nephron. 3. Explain the physiological significance of the juxtaglomerular apparatus. 4. Relate renal blood flow (RBF), renal plasma flow (RPF) to filtration fraction and give normal values. 5. Explain autoregulation of RBF and describe the mechanisms underlying autoregulation. 6. Explain how sympathetic nervous system influences RBF. 7. List hormones regulate renal blood flow. FUNCTIONS OF THE KIDNEY: 1) Regulatory Functions: a. Regulation of electrolyte balance: the kidneys regulate the quantity and concentration of most extracellular fluid electrolytes (such as sodium, chloride, potassium, calcium, etc…) by excreting them in amounts adequate to achieve total-body balance of these substances and maintain their normal concentrations in the extracellular fluid. b. Regulation of water balance: the kidneys maintain water balance in the body, which is important in maintaining proper extracellular fluid (ECF) osmolarity (concentration of solutes). This role is important in maintaining the stability of cell volume by preventing cells from swelling or shrinking as a result of water osmotically moving in or out of the cells, respectively. c. Regulation of plasma volume: the kidneys help maintain proper plasma volume, which is important in the long-term regulation of arterial blood pressure by controlling the salt balance in the body. The  ECF volume, including the plasma volume, is a reflection of the total salt load in ECF, because Na + and its attendant anion Cl- are responsible for over 90% of the ECF’s osmotic (water-holding) activity. d. Regulation of acid-base balance: the kidneys contribute to maintenance of proper pH, along with the lungs and body fluid buffers, by eliminating excess H+ (acid) or HCO3- (base) in the urine. 2) Excretory functions: a. Excretion of metabolic waste products: These include urea (from protein), uric acid (from nucleic acids), creatinine (from muscle creatine), the end products of haemoglobin breakdown, and many others. b. Excretion of many foreign chemicals such as drugs, food additives, pesticides, and other exogenous nonnutritive materials that have gained entrance to the body. 3) Endocrine functions: three hormones are secreted by the kidneys: a. Erythropoietin, a hormone that stimulates red blood cell production in the bone marrow. This action contributes to homeostasis by helping to maintain the optimal O2 content of the blood. b. Renin, an enzymatic hormone that initiates the renin-angiotensin-aldosterone pathway for controlling renal tubular Na+ reabsorption, which is important in the long-term regulation of plasma volume and arterial blood pressure. c. 1,25dihydroxycholecalciferol, the active form of vitamin D, which is essential for Ca++ absorption from the gastrointestinal tract. Calcium, in turn, exerts a wide variety of homeostatic functions. 4) Metabolic functions: a. Gluconeogenesis: during prolonged fasting, the kidneys synthesize glucose from amino acids and other precursors and release it into the blood. Regional differences in nephron structure: There are two types of nephrons distinguished by the location and length of some of their structures: 1. Cortical nephrons: arise from the outer cortex and have short loops of Henle which dip slightly into the medulla. 2. Juxtamedullary nephrons: arise from deep within the cortex next to the medulla. The loops of Henle are long and plunge through the entire length of the medulla. These nephrons are responsible for concentrating urine when the body needs to conserve water. The juxtaglomerular apparatus. Near its end, the ascending limb of loop of Henle passes between the afferent and efferent arterioles supplying its glomerulus. At this point there is a patch of cells in the wall of the ascending limb called the macula densa, and the wall of the afferent arteriole contains secretory cells known as juxtaglomerular cells (or granular cells). The combination of the macula densa, juxtaglomerular cells and extraglomerularmesangialcells or lacis cells is called the juxtaglomerular apparatus (JGA). The JGA has many functions: 1. The juxtaglomerular cells secrete renin, which is involved in blood pressure regulation and sodium balance.  2. The macula densa senses the flow and composition of tubular fluid and contributes to the control of glomerular filtration rate and the control of renin secretion. 3. Lacis cells, like mesangial cells, exhibit phagocytic activity. Renal Blood Flow (RBF), renal plasma flow (RPF): In a resting adult, the combined blood flow through both kidneys is about 1200 ml/min or about 22% of the cardiac output even though their combined weight is less than 0.5 % of total body weight. As with other organs, blood flow supplies the kidneys with nutrients and removes waste products. However, the high flow to the kidneys greatly exceeds this need. The purpose of this additional flow is to supply enough plasma for the high rates of glomerular filtration that are necessary for precise regulation of body fluid volumes and solute concentrations. REGULATION OF RBF AND GFR: The kidneys, regulate their blood flow by adjusting the vascular resistance in response to changes in arterial pressure. This adjustment maintains blood flow relatively constant as arterial blood pressure changes between 90 and 200 mm Hg (autoregulatory range). GFR is also regulated over the same range of arterial pressures. The phenomenon whereby RBF and GFR are maintained relatively constant is called autoregulation. Autoregulation of RBF and GFR occur in denervated kidneys (e.g. transplanted kidney) and isolated, perfused kidneys (i.e. it is not dependent on the nerve supply or on blood-borne substances). A. Intrarenal mechanismsresponsible for autoregulation of RBF and GFR (Intrinsic mechanisms): Two mechanisms are responsible for autoregulation of RBF and GFR; both regulate the tone of the afferent arteriole. These mechanisms are: 1. The myogenic mechanism: This is related to an intrinsic property of vascular smooth muscle – the tendency to contract when it is stretched. Accordingly, when arterial pressure rises and the renal afferent arteriole is stretched, the smooth muscle contracts. 2. Tubuloglomerular feedback: when arterial blood pressure increases within the autoregulation range, it tends to raise both RBF and glomerular capillary pressure (P GC) and hence, GFR. As the rate of flow through the macula densa increases, the macula densa respond to the increased delivered  NaCl load by secreting a vasoconstrictor substance (adenosine) that constricts afferent arterioles. Local vasoconstriction of the afferent arterioles then reduces the RBF and GFR back to normal Importance of autoregulation: Autoregulation is important as it blunts the large changes in solute and water excretion that would otherwise occur because of large changes in GFR whenever blood pressure changes. If it were not for autoregulation, the GFR would increase and water and solutes would be lost needlessly as a result of the rise in blood pressure accompanying exercise for example. B. Nervous control of RBF and GFR: Sympathetic nervous system: extrinsic control of RBF and GFR, which is mediated by sympathetic nervous system input to the afferent arterioles, is aimed at the regulation of arterial blood pressure. If plasma volume is decreased, for example, because of haemorrhage, the fall in blood pressure is detected by the arterial baroreceptors, which lead to increase sympathetic activity to the heart and blood vessels. C. Hormonal and paracrine control of RBF and GFR: a. Vasoconstrictors: i. Angiotensin II: Angiotensin II constricts the afferent and efferent arterioles and decreases RBF and GFR. Increased angiotensin II formation usually occurs in circumstances associated with decreased arterial pressure or volume depletion. ii. Endothelin: secreted by endothelial cells of renal vessels, causes profound vasoconstriction of afferent and efferent arterioles and decreases GFR and RBF. Endothelin production is elevated in disease states e.g. renal disease associated with diabetes mellitus.  iii. Adenosine: produced within the kidneys, causes vasoconstriction of the afferent arteriole (in contrast to its vasodilator effect on most vascular beds), thereby reducing RBF and GFR. It plays a role in Tubuloglomerular feedback. b. Vasodilators: i. Nitric oxide: an endothelium-derived factor that causes vasodilation of the afferent and efferent arterioles and counteracts the vasoconstriction produced by angiotensin II and catecholamines. ii. Prostacyclin and prostaglandin E2 (prostaglandins): may not regulate RBF and GFR in healthy people but during pathological conditions such as hemorrhage, they are produced locally within the kidneys and dampen the vasoconstrictor effects of sympathetic nerves and angiotensin II. This effect is important because it prevents severe and harmful vasoconstriction and renal ischemia. iii. Bradykinin: produced in the kidney is a vasodilator that increases GFR and RBF. iv. Dopamine: is made in the kidney and causes renal vasodilation. REFERENCES: 1- Guyton & Hall: Text book of Medical Physiology, The body fluids and the kidneys, 13th edition,2016. 2- Ganong, William F:” Review of Medical Physiology”, Renal Physiology, 2020