Learning objectives By the end of this lecture, you should be able to; List the structures in the urinary system Describe the functional anatomy of the renal system Outline the functions of the kidneys Describe the process of urine formation
Outline Physiologic anatomy of kidney Multiple functions of the kidney Renal blood supply The nephron (functional unit)
Functional Relationships
KIDNEY paired organs in abdominal cavity held firmly by peritoneum embedded in fat solid, dark red & bean shape below stomach renal artery vs renal vein
The Kidney
Structure of the kidney Kidney
Multiple functions of the kidney Excretion of metabolic waste products and foreign chemicals Regulation of water and electrolyte balances Regulation of body fluid osmolality and electrolyte concentrations Regulation of arterial pressure Regulation of acid-base balance Regulation of erythrocyte production Secretion, metabolism, & excretion of hormones Gluconeogenesis Regulation of 1,25 dihyroxyvitamin D3 production
Renal blood flow About 22 per cent of the cardiac output, or 1100 ml/min. The renal artery enters the kidney through the hilum and then branches progressively to form the interlobar arteries, arcuate arteries, interlobular arteries and afferent arterioles, these lead to the glomerular capillaries, where large amounts of fluid and solutes (except the plasma proteins) are filtered to begin urine formation. The distal ends of the capillaries of each glomerulus coalesce to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surrounds the renal tubules. two capillary beds, the glomerular and peritubular capillaries, are arranged in series and separated by the efferent arterioles, This helps to regulate the hydrostatic pressure in both sets of capillaries.
Renal blood flow
Cont’d High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration, lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption. By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, This changes the rate of glomerular filtration, tubular reabsorption, or both in response to body homeostatic demands. The peritubular capillaries empty into the vessels of the venous system, These run parallel to the arteriolar vessels and progressively form the interlobular vein, arcuate vein, interlobar vein, and renal vein, which leaves the kidney beside the renal artery and ureter.
The nephron as functional unit Each kidney in the human contains about 1 to 1.3 million nephrons, each capable of forming urine. The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, there is a gradual decrease in nephron number. After age 40, the number of functioning nephrons usually decreases about 10 per cent every 10 years thus, at age 80, many people have 40 per cent fewer functioning nephrons than they did at age 40. This loss is not life threatening because adaptive changes in the remaining nephrons allow them to excrete the proper amounts of water, electrolytes, and waste
Basic tubular segments of the nephron
The Nephron Each nephron contains a tuft of glomerular capillaries- the glomerulus, through which large amounts of fluid are filtered from the blood, a long tubule in which the filtered fluid is converted into urine on its way to the pelvis of the kidney The glomerulus contains a network of branching and anastomosing glomerular capillaries that, compared with other capillaries, have high hydrostatic pressure (about 60 mm Hg). The glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman’s capsule. Fluid filtered from the glomerular capillaries flows into Bowman’s capsule and then into the proximal tubule, which lies in the cortex of the kidney
Cont’d From the proximal tubule, fluid flows into the loop of Henle , which dips into the renal medulla. Each loop consists of a descending and an ascending limb The walls of the descending limb and the lower end of the ascending limb are very thin and therefore are called the thin segment of the loop of Henle . After the ascending limb of the loop has returned partway back to the cortex, its wall becomes much thicker, and it is referred to as the thick segment of the ascending limb.
Cont’d At the end of the thick ascending limb is a short segment, which is actually a plaque in its wall, known as the macula densa . Beyond the macula densa , fluid enters the distal tubule, which, like the proximal tubule, lies in the renal cortex. This is followed by the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct. The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct. The collecting ducts merge to form progressively larger ducts that eventually empty into the renal pelvis through the tips of the renal papillae. In each kidney, there are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons.
Juxtamedullary Nephron Cortical Nephron
Nephron Function Filtration Tubular Secretion Selective Reabsorption
Glomerular functions Histology of the filtration barrier Factors which determine filtration Glomerular Filtration Rate (GFR) Physiological Regulation of GFR Volume and composition of the filtrate
Glomerular filtration Process by which blood is filtered while passing through the glomerular capillaries by filtration membrane. First process of urine formation The filtration membrane ahs three layers i. Glomerular capillary membrane -formed by single layer of epithelial cells -Has pores called fenestrae with a diameter of 0.1um ii. Basement membrane -formed by fusion of basement membrane of glomerular capillaries and visceral layer of Bowman capsule iii. Visceral layer of Bowman capsule -formed by single layer of flattened epithelial cells resting on basement membrane -Each cell connected by cytoplasmic extension called pedicel or feet with basement membrane -Cells called podocytes
Process of glomerular filtration When blood passes through glomerular capillaries, the plasma is filtered into the Bowman capsule All other substances are filtered except the plasma proteins (larger size than pores) Process also called ultra filtration (even minute particles are filtered) Filtered fluid is now called glomerular filtrate GF = plasma components – proteins
Glomerular filtration rate Total quantity of filtrate formed in all the nephrons of both kidneys in the given unit time Normal GFR is 125ml/minute (180L/day)
Pressures involved in glomerular filtration Glomerular capillary pressure -pressure exerted by blood in glomerular capillaries - approx 60mmHg (45 to 70mmHg) -highest capillary pressure in the body -favours glomerular filtration Colloid osmotic pressure -pressure exerted by plasma proteins in glomeruli -plasma proteins are not filtered so remain in glomerular capillaries -Approx 25mmHg -opposes glomerular filtration
Hydrostatic pressure in Bowman capsule -pressure exerted by filtrate in Bowman capsule -Also called capsular pressure -approx;15mmHg and opposes glomerular filtration Net filtration pressure -balance between pressure favouring filtration and pressure opposing filtration -NFP = GCP –(COP+HP) = 60 – 25 +15 = 20mmHg All pressures in filtration are called Starling forces; Starling hypothesis states that; The net filtration through a capillary membrane is proportional to hydrostatic pressure difference across the membrane minus oncotic pressure differences.
Determinants of GFR 2 main determinants 1. Net filtration pressure –the sum of hydrostatic and colloid osmotic forces across the glomerular membrane 4 main forces; (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), promotes filtration; (2) the hydrostatic pressure in Bowman’s capsule (PB) outside the capillaries, opposes filtration; (3) the colloid osmotic pressure of the glomerular capillary plasma proteins ( pG ), opposes filtration; and (4) the colloid osmotic pressure of the proteins in Bowman’s capsule ( pB ), promotes filtration. 2.Filtration coefficient-ratio of GFR to net filtration pressure
Factors regulating GFR Renal blood flow Tubuloglomerular feedback Glomerular capillary pressure Colloid osmotic pressure Hydrostatic pressure in Bowman capsule Constriction of afferent arteriole Constriction of efferent arteriole Systemic arterial pressure Sympathetic stimulation Surface area of capillary membrane Permeability of capillary membrane Contraction of glomerular mesangial cells
Hormonal and other factors Factors that increase GFR by vasodilation; Atria natriuretic peptide Brain natriuretic peptide Cyclic AMP Dopamine Endothelial derived nitric oxide Prostaglandin E2 Factors decreasing GFR by vasoconstriction Angiotensin II Endothelins Noradrenaline Platelet activating factor Platelet derived growth factor Prostagalnding F2
Proximal tubular functions Size and parts of the proximal tubule Histology of proximal Tubular wall Re-absorption in the proximal tubule Bidirectional transport into and out of tubular fluid Glomerulo -Tubular Balance Transport maximum (Tm) Limitations
2.Tubular reabsorption Process by which water and other substances are transported from renal tubule back to the blood Large quantity of water (over 99%) is reabsorbed by the tubular epithelia cells Reabsorbed substances move into the interstitial fluid of renal medulla to blood in peritubular capillaries Only substances necessary for the body are reabsorbed hence “selective reabsorption” Unwanted substances like metabolic wastes are excreted through urine
Sites for reabsorption Almost all segment of the tubular portion of nephron 1)PCT ; almost 88% Brush border of epithelial cells increases surface area and facilitates reabsorption Substances include; glucose, amino acids, Na, K, Ca , bicarbonate, chlorides, phosphates, urea, uric acid and water 2) Loop of Henle ; Na , Cl 3) DCT; water, Na, Ca , bicarbonate, water
Mechanism of tubular reabsorption 1) Active reabsorption Involves movement of substances against electrochemical gradient Need liberation of energy from ATP Substances include; sodium, calcium, potassium, sulphate, bicarbonate, glucose, amino acid, ascorbic acid, uric acid and ketone bodies. 2) Passive reabsorption; Involves movement of substances along electrochemical grad No energy required Substances include ; chloride, urea and water
Routes of reabsorption Substances move form tubular lumen into peritubular capillaries by two routes 1) Trancellular route From tubular lumen into tubular cell through epical surface of membrane, to interstitial fluid and finally into capillary 2) Paracellular route From tubular lumen into interstitial fluid present in lateral intercellular space through tight junctions between cells and finally into peritubular capillary
Routes of reabsorption
Regulation of tubular reabsorption 4 main factors 1) Glomerulotubular balance; ability of the tubules to increase reabsorption rate in response to increased tubular load 2) Peritubular capillary and renal interstitial physical forces 2) Hormonal factors 3) Nervous factors
Hormonal factors Aldosterone; Increases sodium reabsorption in ascending limb, DCT and collecting duct and increases K secretion Angiotensin II; Increases sodium reabsorption in PCT, thick ascending limb, DCT and collecting duct (mainly in PCT) ADH; Increases water reabsorption in DCT and collecting duct ANP; Decreases sodium reabsorption BNP; Decreases sodium reabsorption Parathormone ; Increases reabsorption of Ca , Mg and H. Decreases phosphate reabsorption Calcitonin ; Decreases calcium reabsorption
Nervous factors Activation of the sympathetic nervous system can; decrease sodium and water excretion by constrictingnthe renal arterioles, thereby reducing GFR. increase sodium reabsorption in the PCT, TALLH, and perhaps in more distal parts of the renal tubule. increases renin release and angiotensin II formation, which adds to the overall effect to increase tubular reabsorption and decrease renal excretion of sodium.
Tubular secretion Process by which the substance are transported form blood into renal tubules Also called tubular excretion Substances secreted include; i. K by Na-K pump in PCT,DCT and collecting ducts ii. ammonia in PCT iii. Hydrogen in PCT, DCT, maximum in PCT iv. Urea in the loop of Henle Secretion rate = excretion rate – filtered load
THE END Read about; Process of urine formation Reference; Guyton Textbook of medical Physiology 13 th edition chapter 26-29