Function Of Kidney

kidney- urine formation

Functions of kidney • The main function of the kidneys is to regulate the volume and composition of the extracellular fluid • Excrete metabolic waste products including creatinine, urea, uric acid and some end products of haemoglobin breakdown • Excrete foreign substances and their derivatives, including drugs, and food additives • Function as endocrine organs, producing the hormones renin, erythropoietin and calcitriol, the active form of vitamin D.

Kidney Location and External Anatomy • The bean-shaped kidneys lie in a retroperitoneal position in the superior lumbar region and extend from the twelfth thoracic to the third lumbar vertebrae

• Renal capsule – fibrous capsule that prevents kidney infection • Adipose capsule – fatty mass that cushions the kidney and helps attach it to the body wall • Renal fascia – outer layer of dense fibrous connective tissue that anchors the kidney

• The lateral surface is convex and the medial surface is concave, with a vertical cleft called the renal hilus leading to the renal sinus • Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus

– Renal Hilum • Opening to Kidney – Renal Sinus • Space within hilus • Kidneys receive blood vessels and nerves.

Internal anatomy • Medulla divided in to multiple cone shaped masses called as renal pyramid. • It terminates in to renal papilla which projects in to the space of renal pelvis which continues as ureter

Major calyx and minor calyx

Blood supply

Nephron • Each kidney is made up of 1 million nephrons. • It is a functional unit of kidney • Kidney cannot regenerate nephrons • After age of 40 nephron usually decreases about 10 percent every 10 years • At the age of 80 many people have 40 percent less nephrons

The glomerulus and juxtaglomerular apparatus

Regional differences in structure

Urine formation • A. Glomerular Filtration • B. Tubular Reabsorption • C. Tubular Secretion • Expressed mathematically as: • Urinary excretion rate = Filtration rate Reabsorption rate + Secretion rate

Renal handling of 4 hypothetical substances • A- creatinin • B- many electrolytes • C- amino acid and glucose • D- toxic products

Glomerular Capillary Membrane 1. The fenestrated endothelium of the capillary which is the filtering membrane 2. The basement membrane of the Bowman’s capsule contains mesangial cells that are both phagocytic and contractile 3. The epithelial cells of the capsule. These are known as podocytes because they have numerous foot-like projections (pedicels) that clasp the tubes of capillary endothelium.

Glomerular Filtration - The first Step in Urine Formation • Composition of the Glomerular Filtrate • - protein free and devoid of cellular elements including red blood cells • - calcium and fatty acids not freely filtered because they are bound to plasma proteins

• GFR = 125 ml/min or 180 L/day Filterability of Solutes is inversely Related to their size Negatively Charged Large Molecules are Filtered Less Easily Than Positively Charged Molecules of Equal Membrane Size

• In certain condition negative charge of basement membrane is lost even before change in histology called as minimal change nephropathy • As a result low molecular weight protein is lost (albumin) and appear in urine called as proeinurea

Measurement of GFR • GFR is not measured directly, but by measurement of the excretion of a marker substance • GFR can be measured by using inulin, a polymer of fructose, which is freely filtered and neither secreted nor reabsorbed by the nephron • Inulin does not occur naturally in the body and must be given as a continuous intravenous infusion to achieve a constant plasma concentration

GFR =UX × V PX where PX = concentrations in plasma UX = concentrations in urine of the substance X, V = urine flow as a volume per unit time.

Clinically, creatinine is often used for the measurement of GFR. It is naturally occurring and is released into plasma at a fairly constant rate by skeletal muscle. Therefore there is no need to give an infusion

Determinants of the GFR • The net filtration pressure represents sum of hydrostatic and colloid osmotic forces that either favor or oppose the filtration

Renal blood flow • Combined blood flow through kidney is about 1200ml/min or about 21% of cardiac output • Purpose of high blood flow is to supply enough plasma for high rate of glomerular filtration

Measurement of renal blood flow • If a substance is completely removed from the plasma passing through the kidney, leaving none in the plasma in the renal vein, then the clearance of that substance is equal to renal plasma • Para-aminohippuric acid (PAH) is a substance that approaches this ideal.

Physiologic Control of Glomerular Filtration and Blood Flow •

Sympathetic nervous system Activation Decreases GFR by constricting the renal arterioles and decreasing the renal blood flow

Hormonal and Autocoid Control of Renal Circulation • Norepinephrine, epinephrine constrict renal blood vessels and reduce GFR • Angiotensin constricts efferent arteriole which rise glomerular hydrostatic pressure. It is secreted when arterial pressure is decreased and helps to maintain the filtration rate

Contd • Endothelial derived nitric oxide decreases the vascular resistance and increase GFR • Prostaglandin, bradykinin causes vasodilation and increase in GFR, hence NSAID like aspirin may cause reduction in GFR under stressful condition

Role of Tubuloglomerular Feedback in Autoregulation of GFR

Tubular processing of glomerular filtrate • Reabsorption Primary Active reabsorption – by hydrolysis of ATP (sodium) Secondary Active reabsorption - energy released during primary reabsorption is utilized for to drive another sub (glucose) symport and antiport. Passive water reabsorption by osmosis Reabsorption of chloride, urea by passive diffusion

Reabsorption and secretion along different part of nephron

PCT • Na+/K+ ATPase pump located in basal and lateral sides of cell membrane, creates gradient for diffusion of Na+ across the apical membrane. • Na+/K+ ATPase pump extrudes Na+. • Creates potential difference across the wall of the tubule, with lumen as –pole. • Electrical gradient causes Cl- movement towards higher [Na+]. • H20 follows by osmosis.

•

Glucose reabsorption- It is cotransported with sodium at the luminal membrane • Amino acids- reabsorbed by cotransport with sodium at the luminal membrane • Potassium-The proximal tubule reabsorbs about 80% of filtered potassium, reabsorbed passively

Bicarbonate reabsorption

Significance of PCT Reabsorption • 65% Na+, Cl-, and H20 reabsorbed across the PCT into the vascular system. • 90% K+ reabsorbed. • Reabsorption occurs constantly regardless of hydration state. • Not subject to hormonal regulation.

Descending Limb LH • Impermeable to passive diffusion of NaCl. • Permeable to H20. • Hypertonic interstitial fluid causes H20 movement out of the descending limb via osmosis, and H20 enters capillaries. • Fluid volume decreases in tubule, causing higher [Na+] in the ascending limb.

Ascending Limb LH • NaCl is actively extruded from the ascending limb into surrounding interstitial fluid. • Na+ diffuses into tubular cell with the secondary active transport of K+ and Cl-. • Occurs at a ratio of 1 Na+ and 1 K+ to 2 Cl-. • Ascending walls are impermeable to H20.

Distal tubule • First part of DCT forms the part of juxtaglomerular complex that provides the feedback control of GFR • Called as diluting segment because it is impermeable to water and actively reasorbs most of the ion including sodium, potassium and chloride

Collecting Duct - cortical • Principle cell – reabsorbs sodium and secretes potassium • Intercalated cell- secretes hydrogen and reabsorbs bicarbonates • Permeable to H20 depends upon the presence of ADH

Medullary • Medullary area impermeable to high [NaCl] that surrounds it. • Permeable to H20 depends upon the presence of ADH. – When ADH binds to its membrane receptors on CD, it acts via cAMP. • Stimulates fusion of vesicles with plasma membrane. – Incorporates water channels into plasma membrane.

Secretion • Secretion of substances from the peritubular capillaries into interstitial fluid. • Then transported into lumen of tubule, and into the urine. • Allows the kidneys to rapidly eliminate certain potential toxins.

Countercurrent mechanism

The role of urea • NaCl only accounts for about half (600 mOsm/kg H2O) of The total osmolality of the interstitial fluid. • The remaining 600 mOsm/kg H2O is due to urea.

Osmolality of Different Regions of the Kidney

Vasa Recta countercurrent exchanger • Vasa recta maintains hypertonicity by countercurrent exchange. • NaCl and urea diffuse into descending limb and diffuse back into medullary tissue fluid. • Walls are permeable to H20, NaCl and urea. • Colloid osmotic pressure in vasa recta > interstitial fluid.

Countercurrent exchanger

Summary

Glucose and Amino Acid Reabsorption • Filtered glucose and amino acids are normally reabsorbed by the nephrons. • In PCT occurs by secondary active transport with membrane carriers. • Renal transport threshold: • Renal plasma threshold for glucose = 180200 mg/dl.

Electrolyte Balance • Kidneys regulate Na+, K+, H+, Cl-, HC03-, and PO4-3. • Control of plasma Na+ is important in regulation of blood volume and pressure. • Control of plasma of K+ important in proper function of cardiac and skeletal muscles. – Match ingestion with urinary excretion.

Renal Acid-Base Regulation • Kidneys help regulate blood pH by excreting H+ and reabsorbing HC03-. • Most of the H+ secretion occurs across the walls of the PCT in exchange for Na+. • proximal tubule - H+ secretion mainly occurs via the Na+/H+ countertransporter • distal tubule and collecting duct - bicarbonate reabsorption is linked to H+ secretion • Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03- and excrete H+. • Returns blood pH back to normal range.

Renal regulation • Renin–angiotensin system Renin angiotensin I from angiotensinogen angiotensin converting enzyme (ACE)

angiotensin II

• It stimulates sodium reabsorption by the proximal tubule, and chloride and water follow passively. • It stimulates aldosterone secretion by the adrenal cortex. • It stimulates antidiuretic hormone (ADH) secretion from the posterior pituitary gland. • It stimulates thirst

Aldosterone • • 3. 4. • • •

Aldosterone released by the adrenal cortex. stimuli Increase in the concentration of angiotensin II increase in plasma K+ concentration. Aldosterone acts to stimulate Na+ absorption and K+ secretion by the principal cells of the distal tubule and collecting duct increasing the number of Na+ and K+ channels in the luminal membrane and in increasing the activity of Na+/K+ ATPase

• Atrial natriuretic peptide – secreted by cells of atria when distended by excess volume • Inhibits sodium and water reabsorption • Parathyroid – calcium regulating hamone • Increases reabsorption of calcium from DCT and loop of henle

Role of ADH

Regulation of body fluid volume

Production of calcitriol. • Vitamin D3 is present in diet and that can be synthesized in the skin in the presence of ultraviolet light. • Converted to 25-hydroxycholecalciferol in the liver • Then to the active metabolite calcitriol in the kidney (mainly in the proximal tubule). • The conversion to calcitriol is stimulated by PTH and is therefore indirectly stimulated by a reduction in Ca2+. • Calcitriol increases Ca2+ and phosphate absorption by the gut and it enhances bone resorption

Applied physiology • • • 4. 5. 6.

Acute renal failure: Ability of kidneys to excrete wastes and regulate homeostasis of blood volume, pH, and electrolytes impaired. Types Prerenal renal failure - due to a failure of renal perfusion. Renal’ renal failure - the cause of the renal failure lies within the kidneys Postrenal renal failure problem lies distal to the kidneys. Obstruction to the renal tract can occur in one ureter and lead to loss of function of the corresponding kidney

• • • • • • •

Effects (a) fluid and electrolyte balance; (b)excretion (c) endocrine functions Glomerulonephritis: Inflammation of the glomeruli. Autoimmune disease by which antibodies have been raised against the glomerulus basement membrane. • Leakage of protein into the urine.

• • • • • •

Renal insufficiency: Nephrons are destroyed. Clinical manifestations: Salt and H20 retention. Uremia. Elevated plasma [H+] and [K+].

Diuretics • Increase urine volume excreted. – Increase the proportion of glomerular filtrate that is excreted as urine.

• Loop diuretics: – Inhibit NaCl transport out of the ascending limb of the LH.

• Thiazide diuretics: – Inhibit NaCl reabsorption in the 1st segment of the DCT.

• ACE inhibitors • Osmotic diuretics: – Increase osmotic pressure of filtrate