Irfan Idris Physiology Department, Medical Faculty, UNHAS Physiology of kidney Irfan Idris Physiology Department, Medical Faculty, UNHAS

Objectives With the end of this session you are be able to : have knowledge of physiologic anatomy of the kidneys understand how kidney creates urine understand filtration & tubular transport process have knowledge about role of tubuloglomerular feedback

Physiologic anatomy of the kidneys

Blood Supply Interlobular vein Interlobular artery Renal pelvis Renal artery Renal vein Ureter Cortex Medulla Arcuate vein Arcuate artery

Renal artery  interlobar artery  arcuate artery  interlobular artery  afferent arteriole  glomerulus  efferent arteriole  peritubular artery  vasa recta  vv. peritubular  arcuate vein  interlobar vein  renal vein

NEPHRON Nephron is a functional unit of kidney. Each kidney consists of about one million nephrons. The tubule is made up of a number of sections, the proximal tubule, the medullary loop (loop of Henle), and the distal tubule which finally empties into the collecting duct.

URINE FORMATION

Filtration and tubular transport Filtration : a fluid that resembles plasma is filtered through the glomerular capillaries into the renal tubules Molecules with a radius of r <1.8 nm (molecular mass < 10 000 Da) freely pass through the filter, While those with a radius of r > 4.4nm (molecular mass >80 000DA, e.g., globulins) normally cannot pass through. Only a portion of molecules where 1.8 nm < r < 4.4nm applies are able to pass through the filter. Negatively charged particles (e.g., albumin: r = 3.4 nm) are less permeable than neutral substances of equal radius because negative charges on the wall of the glomerular filter repel the ions.

The GFR in an average-sized normal man is approximately 125 mL/min GFR = Kf x (pG – pB – G + B)

Transport of Substances Through the Cell Membrane

Transport of Substances Through the Cell Membrane Active Transport Passive Transport

Active transport Primary active transport Secondary active transport Ion Pump Secondary active transport Co transport Counter transport

Passive Transport Simple diffusion Facilitated diffusion

SGLT-2 SGLT-1

PepT2 PepT1/2

Role of Tubuloglomerular Feedback The tubuloglomerular feedback (1) an afferent arteriolar feedback mechanism and (2) an efferent arteriolar feedback mechanism  arrangements of the juxtaglomerular complex The juxtaglomerular complex consists of macula densa cells in the initial portion of the distal tubule and juxtaglomerular cells in the walls of the afferent and efferent arterioles.

Acid base The lungs and kidneys work together to produce a normal extracellular fluid and arterial pH of 7.35-7.45. The kidney excretes fixed acid and performs three functions to achieve this 1)Tubular secretion of acid 2) Glomerular filtration of buffers which combine with H+ 3) Ammonia is produced enzymatically from glutamine and other amino acids, and is secreted in the tubules

Excretion of waste products Filtration occurs as blood flows through the glomerulus. Some substances not required by the body, and some foreign materials (e.g. drugs) may not be cleared by filtration through the glomerulus. Such substances are cleared by secretion into the tubule and excreted from the body in the urine

Hormones and the Kidney Renin (see above) increases the production of angiotensin II which is released when there is a fall in intravascular volume e.g. haemorrhage and dehydration. Aldosterone promotes sodium ion and water reabsorption in the distal tubule and collecting duct where Na+ is exchanged for potassium (K+) and hydrogen ions by a specific cellular pump.

Atrial Natruretic Peptide(ANP) is released when atrial pressure is increased e.g. in heart failure or fluid overload. It promotes loss of sodium and chloride ions and water chiefly by increasing GFR. Antidiuretic Hormone (ADH) increases the water permeability of the distal tubule and collecting duct, thus increasing the concentration of urine.

The hormones interact when blood loss or dehydration occurs to maintain intravascular volume. The flow diagram (left) illustrates this

Other Substances Produced by the kidney 1,25 dihydroxy vitamin D (the most active form vitamin D) which promotes calcium absorption from the gut. Erythropoietin which stimulates red cell production

Micturition Process by which the urinary bladder empties when it becomes filled First, the bladder fills progressively until the tension in its walls rises above a threshold level this elicits the second step, which is a nervous reflex called the micturition reflex that empties the bladder or, if this fails, at least causes a conscious desire to urinate. Although the micturition reflex is an autonomic spinal cord reflex, it can also be inhibited or facilitated by centers in the cerebral cortex or brain stem

Blood vessels and have little to do with bladder contraction. Some sensory nerve fibers also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain. The sensory fibers : degree of stretch in the bladder wall, reflexes that cause bladder emptying. The motoric fibers : innervate wall of the ballder and the detrusor muscle. Also Most important are the skeletal motor fibers transmitted through the pudendal nerve to the external bladder sphincter. These are somatic nerve fibers that innervate and control the voluntary skeletal muscle of the sphincter

As a summary  Functions of the Kidney Regulation of the water and electrolyte content of the body. Retention of substances vital to the body such as protein and glucose Maintenance of acid/base balance. Excretion of waste products, water soluble toxic substances and drugs. Endocrine functions. 

Recommended references Textbook of Medical Physiology, 11th edition, Guyton & Hall, Elsevier Saunders, 2006 Review of Medical Physiology,, 21th edition, WF. Ganong, McGraw-Hill Company, 2003

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