Introduction to renal physiology

• Kidneys are bilateral organs, as big as a close fist, located in the lumbar region of the body, each at a different height, and are retroperitoneal organs, meaning they are behind the peritoneal cavity.
• Kidneys are able to take 1/5 of cardiac output, indicating their high vascularity.
• The functions of kidneys include filtration of blood, active detoxification, regulation of blood pressure and blood pH, and haematopoiesis.
• Kidneys are responsible for active Vitamin D production.
• Filteration requires a pump, the heart with the RAAS, which is used to adjust the pressure by modifying the vascular resistance.
• The filter consists of three layers: endothelial cells of the blood vessels, glomerular basement membrane, and slit diaphragm.
• Endothelial cells of the blood vessels have holes in them called fenestrae which are 100nm large and RBC are not able to pass through this layer.
• Clearance of the endothelial cells is done by blood flow and phagocytes, which only work for big obstructions.
• The glomerular basement membrane acts as anticlogging through pinocytosis, a process similar to endocytosis where the membrane pinches off a vesicle filled with the clog material.
• Pinocytosis in GBM can only work up until a certain size, large aggregate proteins such as antibodies, and platelets are too large to undergo pinocytosis.
• The slit diaphragm is formed by podocyte cells which form extensions that interdigitate (interlock like fingers), coming very close and connect to each other with protein structures that have extremely fine holes
• The slit is made of integral membrane proteins called nephrins, that stick to each other in a certain pattern where they form an adhesive lattice in the middle and proteins with gaps in the ends.
• Only around 3% of the total area is the slit (the hole), which is why the slit diaphragm is a major source or resistance to fluid flow.
• Pressure regulation in the kidney is achieved by constricting the arterial and venular ends of the capillary beds, affecting the filtration pressure and rate.
• Arterial constriction leads to reduced blood flow into the capillary beds (reduced pressure) and results in decreased filtration rate.
• Venular constriction leads to reduced blood flow out of the capillary beds (increased pressure in glomerular capillary) and results in increased filtration rate.
• the GBM is renewed by mesangial cells
• Space efficiency in the kidney is achieved by having many blood vessels that contain podocytes knotted and bundled up, forming the glomerulus.
• The glomerulus is surrounded by the Bowman’s capsule which collects the filtered material.
• Mesangial cells are present in the spaces between the glomerulus and the Bowman’s capsule.
• The glomerulus and the Bowman’s capsule are collectively referred to as renal corpuscle.
• Humans have around 50,000-1,000,000 renal corpuscles per kidney, and variation can occur due to foetal programming, as per the Barker hypothesis, which suggests that the number of nephrons follows the mother’s amino acid nutrition.
• The rate of filtration in the kidney is around 130 ml/min, around 20% of plasma is removed as filtrate.
• The glomerular filtration rate (GFR) can be determined by measuring creatinine, as it is filtered through the glomerulus but it is not resorbed into the blood.
• GFR= clearance= (urine concentration x urine flow rate)/plasma concentration.
• A dialysis machine is a chamber split by a very fine filter, blood comes in on one side and a dilysate is kept on the other side of the filter.
• The dilysate in a dialysis machine has an identical concentration of the wanted thing in plasma (e.g., glucose, amino acids, Na+…), but there is no waste, thus there is passive flow, which extracts the waste materials from the blood.
• Transplantation issues include availability of donors, social (theft or selling organs), organ rejection in recipients, and anti-rejection medication increasing likelihood of infection and tumours.
• blood flow to the kidneys is around 1.2l/min, plasma flow to kidneys is 0.66l/min (assuming normal haematocrit of 0.45)
• glomerular filtration rate = 180ml/min
• renal blood flow = 1.2L/min
• renal plasma flow = 600ml/min