URINE FORMATION 1.Ultrafiltration/Glomerular filtration 2.Selective Reabsorption 3. Hormonal secretion Process of Glomerular Filtration When blood passes through glomerular capillaries, the plasma is filtered into the Bowman capsule. All the substances of plasma are filtered except the plasma proteins. The filtered fluid is called glomerular filtrate. Ultrafiltration Glomerular filtration is called ultrafiltration because even the minute particles are filtered. But, the plasma proteins are not filtered due to their large molecular size. The protein molecules are larger than the slit pores present in the endothelium of capillaries. Thus, the glomerular filtrate contains all the substances present in plasma except the plasma proteins. GLOMERULAR FILTRATION RATE ( GFR) Glomerular filtration rate (GFR) represents the flow of plasma from the glomerulus into Bowman’s space over a specified period and is the chief measure of kidney function. It represents the flow of plasma from the glomerulus into Bowman’s space over a specified period and is the chief measure of kidney function. Normal value of GFR:it is approximately 125mL/min or about 180L/day. A low GFR may indicate A/CKD (Acute or chronic kidney diseases) N:B : there are essential five(5) stages of kidney diseases ranging from mild stage to end stage kidney disease Stage 1( mild/normal) : kidney damage with normal kidney function eGFR = 90-120ml/min Stage 2 (mild ) eGFR= 60-89ml/min Stage 3( mild -moderate) eGFR= 30-59ml/min Stage 4(moderate - severe) eGFR= 15-29ml/min Stage 5 ( end- stage ) eGRR= <15ml/min Filteration Fraction (FF) Filtration fraction is the fraction (portion) of the renal plasma, which becomes the filtrate. It is the ratio between renal plasma flow and glomerular filtration rate. It is expressed in percentage. Filteration Fraction= GFR/renal plasma flow(RPF) *100 N:B : Renal plamal flow is the volume of the blood delivered to the kidney per unit time .It is about 25% of the cardiac output Filteration Fraction=. 125ml/min÷650ml/min =19.2% So ,it ranges from 15-20% Pressures determining filtration 1. Glomerular capillary pressure - blood 2. Colloidal osmotic pressure - plasmal protein 3. hydrostatic pressure in bowman's capsule- by filterates Factors affecting GFR 1. Age : GFR tends to decline with age. This is a natural part of aging and is influenced by factors such as reduced kidney function, changes in blood vessels, and other age-related physiological changes. 2. RBF: An increase in renal blood flow often leads to an increase in GFR because more blood is being filtered by the glomeruli. Conversely, a decrease in renal blood flow can result in a lower GFR. 3. Constriction of the afferent capillaries: Constriction of afferent arteriole reduces the blood flow to the glomerular capillaries, which in turn reduces 4.Sympathetic stimulation: Strong sympathetic stimulation causes severe constriction of the blood vessels by releasing the neurotransmitter substance, noradrenaline. 5.Hormonal factors : E.g ANP(Atrial natriuretic peptide),BNP(Brain natriuretic peptide ) , prostaglandin(PGE2) ,dopamine ,cAmp(cyclic adenosine monophosphate) all leads to the vasodilation of Afferent arteriole Renin , Angiotensin ii,endothelins lead to the constriction of the afferent arteriole TUBULAR REABSORPTION It is the process by which water and other substances are transported from renal tubules back to the blood through the peritubular capillaries. It is also known as selective Reabsorption because only Wanted materials such as protein , glucose , vitamins and reabsorbed back while unwanted waste materials are excreted through urine . MECHANISM OF REABSORPTION Active reabsorption: Against the electrochemical (uphill gradient) It leads liberatiok of energy derived from ATP substances absorbed by this mechanism:ascorbic acids ,ketone bodies Na ,Ca,K, Phosphate, sulphate, amino acids . Passive Reabsorption: Along the concentration gradient. No need of energy ( ATP) Chloride ,urea and water are absorbed passively Routes of reabsorption 1. Transcellular route: movement of materials from : Tubular lumen ----->tubular cell( apical surface) ---->interstitial fluid---->peritubular capillaries 2. Paracellular route Tubular lumen ----> lateral intracellular space ----IF ---->Peritubular capillaries. SITES OF REABSORPTION 1. In the PCT : about 88% of the filterates are reabsorbed here They include : amino acids ,glucose ,Na ,K , Ca,chlorides,. Phosphate(most electrolytes), uric acid ans water 2. Loop of henle : Na and clorides 3. In the DCT : Na ,Ca, bicarbonate and water Regulation of glomerular balance 1. Glomerulotubular balance: this is the balance between the filteration and Reabsorption. An increase in filtration loads will tentatively increase the rate of Reabsorption 2. Hormonal factors : Aldosterone, Angiotensin ii , ADH , calcitonin and parathormone 3. Nervous factors :i.e activation of sympathetic stimulation can lead to the tubular Reabsorption .An example is s Stimulation of renin from JG cells which can lead to the Reabsorption of Na and H20 THRESHOLD SUBSTANCES( This is based on the degree of reabsorption) 1. Low threshold substances:These are substances that are being reabsorbed in a little quantity and they are normally present in the urine under normal conditions e.g uric acid , phosphate and some electrolytes etc 2. High threshold substances: These are substances that are completely absorbed back imto the blood and they are not present in the urine under normal condition . They can be present if their concentration is high or in case of kidney diseases . They include amino acids , glucose , vitamins, acetoacetate ions etc 3. Non - threshold substances: they are not reabsorbed and they are completely excreted in the urine e.g creatine ,mannitol ,inulin TRANSPORT MAXIMUM - Tm value Tubular transport maximum or Tmaxis the rate at which the maximum amount of a substance is reabsorbed from the renal tubules. Every reabsorbed substances have the maximum amount in which it can be reabsorbed. For example the TMG of glucose is 375mg/min in adult males and 300mg/min in adult females. Renal threshold and Tmmax Renal threshold is the plasma concentration at which a substance appears in urine. Every substances having a Tm value also has a threshold value in the plasma or blood.Below this threshold, the substances is completely reabsorbed and when the concentration of the substances reaches this threshold,the excess amountis not reabsorbed and it is pass out as urine . For example the renal threshold of glucose is 180 mg/dl . This means that sodium is completely Reabsorbed back into the blood if its plasma threshold is below 180mg/dl and it is not present in the urine .When the blood level of glucose reaches 180g/ml ,it is not completely Reabsorbed hence there is presence of glucose in urine (Glucosuria). Differences between Transport Maximum and Renal threshold 1 .Renal threshold is the plasma concentration at which substances appear in the urine Transport Maximum is the maximum rate of active transport of a substances across renal tubules per unit time . 2. Plasma threshold indicates the limit of Reabsorption for a specific substances Transport Maximum reflects the capacity of renal tubules to transport and absorb a substances. REABSORPTION OF IMPORTANT SUBSTANCES 1. Reabsorption of sodium From the glomerular filtrate, 99% of sodium is reabsorbed. Two thirds of sodium is reabsorbed in proximal convoluted tubule and remaining one third in other segments (except descending limb) and collecting duct. The transport of sodium uses the Transcellular route for its transport into the blood ( peritubular capillaries) That is; 1. Transport from lumen of renal tubules into the tubular epithelial cells: This involves antiport( countertransport)and symport(cotransport) Antiport helps in the simultaneous movement of sodium in one direction and another ion(H+) in another direction. An example is the NHE that contributes for the Reabsorption of sodium and secretes hydrgen iom into the tubular lumen Symport involves the movement of different substances in the same direction across the cell membrane. An example is the SGLT( sodium glucose cotransporter is an example of symport) 2. Transport from tubular cells into the interstitial fluid 3. Transport from interstitial fluid to the blood.