• Renal Pelvis Physiology of the Renal system Blood supply
• Renal artery Renal vein
• Segmental arteries (hilum) NO Segmental veins • Interlobar arteries (in renal columns Interlobar veins (in renal columns in medulla) in medulla) • Arcuate arteries (cortex/medulla junction) Arcuate veins (cortex/medulla junction) • Cortical radiate arteries Cortical radiate veins
Arrows show direction of blood flow. Red denotes arterial blood; Blue venous blood Renal Function Homeostasis of Body fluid • Regulation of Water and Electrolyte balance • sodium and water • potassium • calcium and phosphate balance Regulation of • acid-base balance • ECF Osmolality Water and Electrolyte balance have an effect on regulation of • ECF Volume Extracellular fluid Osmolality and Volume --- Blood Volume and Blood pressure Clearance of Metabolic End-products Endocrine function Blood Volume Blood Pressure Renal Function Endocrine function • Renin – regulates blood pressure (see adrenal gland)
• Erythropoietin – stimulates bone
marrow RBC production
• Converts Vitamin D to its active
form (see endo – Parathyroid hormone + Ca) Total Body Water INTAKE (2300 ml/day) • 2/3 ingested as liquid (~ 1.5L) • 1/3 ingested in solids (750ml) • metabolic oxidation of food (~200 ml) OUTPUT (2300 ml/day) • Urine (60%) 1400 ml • Skin + Sweat (450ml) • Respiratory tracts (350ml) • Faeces (100ml) Extra losses
Intracellular fluid Extracellular fluid Blood (5L) = Haematocrit (2L) + Plasma (3L) Plasma Extracellular and Intracellular fluid • Body compartments are in a dynamic and steady state (not in equilibrium) • Intracellular and Extracellular components differ in electrolyte composition
Na K+ + Mg++ Cl- Proteins HCO3 Physiology of the Renal System The Nephron Dr Cynthia Sammut Physiology of the Renal System Nephron Nephrons in kidney • Cortical – most nephrons are found in the cortex of the kidney with the tubule extending into the medulla (80%) • Juxtamedullary (20% of nephrons) • Nephrons lie close to the cortical- medullary border. • Tubules extend deeper into the medulla • Can form more concentrated urine Physiology of the Renal System Nephron - Structure • Renal corpuscle (Malphigian’s) • Glomerulus • Glomerular Capsule (Bowman’s) • Proximal tubule • Loop of Henle • Thin descending limb • Ascending limb with thin and thick segments • Distal tubule • Collecting duct …..which drains into the renal pelvis Physiology of the Renal System Nephron - Function Four processes occur in the nephron • Filtration • Reabsorption • Secretion • Excretion Physiology of the Renal System Nephron – Renal corpuscle Glomerulus – Capillaries in a ‘knot’ • Glomerular Capillary bed - fed and drained by arterioles (high resistance vessels) • Afferent arteriole (entry) has a larger diameter than the Efferent arteriole (exit). • Blood pressure in glomerular capillary bed is high – promotes filtration – forces fluids and solutes (smaller than proteins) out of the blood into the glomerular capsule 99% of this filtrate is eventually reabsorbed by the renal tubule cells and returned to the body. Physiology of the Renal System Nephron – Renal Corpuscle Filtration barrier (glomerular membrane) has 3 layers • Glomerular capillary endothelium - thousands of 50- 100 nm pores – Fenestrated capillaries • Basal lamina (negatively charged glycoproteins, collagen, laminin and other proteins repel negatively charged plasma proteins ) • Bowman’s capsule (Podocytes with foot processes form slit diaphragm – 25nm filtration slits) Physiology of the Renal System Nephron – Renal Corpuscle Filtration Barrier (glomerular membrane) • Highly permeable (several hundred times that of a typical capillary membrane) • Highly selective for the size of molecules it allows to pass through. E.g. albumin (69kDa - smallest plasma protein): 0.005%; inulin (5.2kDa): 100%. Podocyte sit Diaphragm – nephrin molecules from neighbouring foot processes interact at centre of slit to form a zipper-like structure
• Anionic (negatively charged)
Almost completely impermeable to all plasma proteins, but is highly permeable to essentially all other dissolved substances in normal plasma Physiology of the Renal System Nephron – Renal Corpuscle -Function Glomerular Filtration Filtrate – blood plasma without proteins and blood cells. Presence of the latter indicates a problem with the glomerulus filtration
• Filtrate Contains • Water • NaCl, K+, HCO3- • Creatinine and Urea (waste products) • Glucose • Amino acids • Some drugs Physiology of the Renal System Nephron – Renal Corpuscle -Function Glomerular Filtration rate Definition The volume of filtrate formed each minute by both kidneys • Average GFR is 125 mL/min (180L/dy) • Primary determinant of urine volume and excretory potential of kidney • Kidney filters entire plasma volume 60times a day. • Depends on pressures, surface area available (glomerular capillaries) and permeability of barrier (capillary/BM/podocytes) Physiology of the Renal System Nephron – Renal Corpuscle -Function Measurement of Glomerular Filtration rate Can be done using clearance principle Clearance definition – the volume of (blood) plasma cleared of a given substance per unit time. • Clearance of substance X = excretion rate of X (mg>min) [X]plasma (mg>mL plasma) Applied to the kidney Clearance of substance X = [X] Urine / Urine flow rate [X] arterial plasma Creatinine Clearance (clinical measurement used) Physiology of the Renal System Nephron – Renal Corpuscle -Function Autoregulation of Glomerular Filtration Rate (GFR) Through changes in the diameter of the afferent and efferent arterioles Physiology of the Renal System Nephron – Renal Corpuscle -Function Autoregulation of Glomerular Filtration Rate GFR is regulated by • Local paracrine secretions Tubuloglomerular feedback by the Juxtaglomerular apparatus • Autonomic nervous system Sympathetic stimulation • Endocrine Hormones Physiology of the Renal System Nephron – Renal Corpuscle -Function Tubuloglomerular feedback – Juxtaglomerular apparatus - Macula densa cells in tubule (loop of Henle) - Granular cells (secrete renin) • Cells in the macula densa sense rise in NaCl levels • Send paracrine signals to neighbouring afferent arteriole which contracts • GFR is decreased due to decrease in blood flow entering glomerular capillaries • Multiple paracrine signals involved (ATP adenosine, nitric oxide). Physiology of the Renal System Nephron - Structure • Renal corpuscle (Malphigian’s) • Glomerulus • Glomerular Capsule (Bowman’s) • Proximal tubule • Loop of Henle • Thin descending limb • Ascending limb with thin and thick segments • Distal tubule • Collecting duct …..which drains into the renal pelvis Physiology of the Renal System Nephron – Proximal Convoluted Tubule Reabsorption* Secretion^ • NaCl (65%), K+ • Uric acid • HCO3- (90%) • Organic acids • H20 (65%) • Amino Acids (~ 100%) • Glucose (~ 100%)
* Reabsorption occurs from the tubules into the extracellular space
^ Secretion from the extracellular space/peritubular capillaries into the PCT Physiology of the Renal System Nephron – Proximal Convoluted Tubule Effect of reabsorption at PCT
• Isosmotic fluid • Reuptake of ions and substances that body needs • Water re-uptake • Acid/Base regulation (H+) • Elimination of harmful substances Physiology of the Renal System Nephron – Proximal Convoluted Tubule Tubular Reabsorption • Transcellular pathway • Paracellular pathway Physiology of the Renal System Nephron – Proximal Convoluted Tubule Tubular Reabsorption • Most reabsorption involves active transport. • Membrane carriers found on the tubular cell membranes • Selective carriers • Number of carriers per substance depend on how much of the substance needs to be retained (glucose and amino acid are entirely reabsorbed so their carriers are abundant) Physiology of the Renal System Nephron – Proximal Convoluted Tubule Tubular Reabsorption • Water is reabsorbed by passive movement across an osmotic gradient. Physiology of the Renal System Nephron – Loop of Henle - Function
• The Function of the Loop of Henle is creating Hyposmotic (dilute) Urine Physiology of the Renal System – Renal Medulla • Another factor important for maintaining the high Osmolarity of the Medullary Interstitium is Urea. • Membrane transporters for reuptake of urea found in loop of Henle and collecting ducts Physiology of the Renal System Nephron – Loop of Henle - Function • Descending limb – water moves out to the interstitium to reach same osmolarity as the renal medulla (1200mOsm) • The renal medulla maintains a high osmotic concentration in its cells* and interstitial fluid. • Tubule fluid at the bottom of the loop will be the same osmolarity as in the medulla (1200 mOsM) *Renal tubule cells in the medulla of the kidney are constantly exposed to high extracellular fluid osmolarity. They maintain normal cell volume. by synthesizing organic solutes as needed to make their intracellular osmolarity match that of the medullary interstitial fluid. The organic solutes used to raise intracellular osmolarity include sugar, alcohols and certain amino acids. Physiology of the Renal System Nephron – Loop of Henle - Function • Ascending limb – apical surfaces of cells are impermeable to water. They transport ions out of the tubules but water does not follow.
• Fluid in the thick part of the ascending limb decreases in concentration
as solutes move out but water remains – • Hypososmotic fluid created in loop (around 100mOsM) Physiology of the Renal System Distal convoluted tubule and Collecting duct • Distal Convoluted tubules and Collecting ducts are responsible for the fine regulation of salt and water balance • Normally distal parts of DCT and CT are Impermeable to water and urea. But made highly permeable under the effect of ADH (effect on dilution of urine) Urine osmolality regulated by ADH, and to a lesser extent Physiology of the Renal System Distal convoluted tubule and Collecting duct Distal Convoluted tubules
• Water permeability of tubular
cells is variable. ADH controls insertion of Aquaporins (Water pores in apical membrane) ‘inserted’ when water needs to be conserved. Physiology of the Renal System Ureters
• Smooth muscle in the walls contract
and propel urine into the bladder (peristalsis) • This becomes evident if there is a stone which is being passed in the ureter.
Cross-section of the ureter
Physiology of the Renal System Ureters
• Urine which enters the bladder is
prevented from going back into the ureter by valve-like folds of the bladder mucosa • Vesicoureteral reflux- urine goes back into the ureters Physiology of the Renal System Ureters Physiology of the Renal System Bladder
• Three layers of smooth muscle
– collectively called Detrusor muscle • Mucosal lining Transitional epithelium Physiology of the Renal System Urethra
Urine flow from the bladder into the
urethra to the outside is controlled by two sphincters • Internal urethral sphincter thickening of the smooth muscle of urethra; involuntary • External urethral sphincter skeletal muscle of the pelvic floor; voluntary Physiology of the Renal System Infection of the Urinary tract
• Urethritis – inflammation of the urethra
• Cystitis – inflammation of the bladder • Pyelonephritis – inflammation of the kidney, particularly the renal pelvis/calyx system • Pyelitis – inflammation and collection of pus in renal pelvis Physiology of the Renal System Infection of the Urinary tract Symptoms • Dysuria – painful micturition, burning • Urgency – urgent need to pass urine • Frequency – passing urine often usually in small amounts • Cloudy or blood-tinged urine • Back pain and Headache if kidneys are involved Physiology of the Renal System Urine Normal Composition of Urine • Volume 1.0-1.8L/24hrs • Water • Nitrogenous waste products • Other unwanted products Physiology of the Renal System Urine Substances NOT normally found in urine • Glucose • Glucosuria • Blood proteins • Proteinuria • Red blood cells • Haematuria • Haemoglobin • Haemoglobinuria • White blood cells • Pyuria (pus) • Bile • Bilirubinuria Physiology of the Renal System Micturition Sympathetic fibres Via hypogastric nerve • Micturition involves a spinal reflex • Facilitated and inhibited by higher brain centres • Subject to voluntary inhibition or facilitation Physiology of the Renal System Micturition Physiology of the Renal System Micturition
• External urethral sphincter is skeletal
muscle, under voluntary control • Relaxation of the ext. urethral sphincter will occur if convenient • Voiding may be postponed temporarily Physiology of the Renal System Micturition – Innervation of the bladder
Somatic innervation of the
external urethral sphincter • From S2-S4 nerve roots • Travel in the pudendal nerve
Voluntary contraction of the external urethral
sphincter prevents micturition Physiology of the Renal System Micturition - Incontinence
• Involuntary loss of urine
• Occurs when the person is unable to control the external urethral sphincter • Normal in children who have not yet gained control over their voluntary sphincter (usually 2 years or younger) Physiology of the RENAL SYSTEM Lecture 5 Dr Cynthia Sammut Physiology of the Renal System • Composition of Urine also depends on reabsorption and secretion in tubules • Volume and composition of urine is adjusted in the DCT and CD under the influence of hormones Renal Physiology Regulation of the Kidney function Kidney function is regulated by • Hormones • Hypothalamus – Anti-Diuretic Hormone (ADH) Vasopressin • Juxtaglomerular apparatus – RAAS /ATP • Adrenal Gland – Aldosterone (RAAS) • Heart - ANP • Others – Endothelins, PTH
• Autonomic nervous system (Lecture 2, Renal Corpuscle)
Regulation of the Kidney function Hypothalamus - ADH Antidiuretic Hormone (ADH) Vasopressin • Promotes recovery of water so Decreases urine volume • By stimulating the movement of aquaporin proteins into the apical cell membrane of principal cells of the Collecting Ducts to form water channels allowing transcellular movement of water from lumen, to collecting ducts, into the interstitial space in medulla by osmosis
Aquaporins - Nobel Prize Chemistry 2003
Regulation of the Kidney function Juxtaglomerular apparatus • Juxtaglomerular apparatus Cells in the macula densa (Loop of Henle) sense rise in NaCl levels • Send paracrine signals (ATP adenosine, nitric oxide) to neighbouring afferent arteriole which contracts
The nephron loops back so that the DCT/Loop of
Henle passes between the afferent and efferent arteries Regulation of the Kidney function Juxtaglomerular apparatus
• Decrease in blood pressure in the
afferent arteriole of the glomerulus stimulates the release of Renin by the granular cells of the JGA into the blood stream • Renin initiates a chemical reaction which converts the plasma protein angiotensin to a peptide angiotensin II Regulation of the Kidney function Renin – Angiotensin – Aldosterone system Aldosterone • Secreted by the adrenal cortex after stimulation by Angiotensin II • Induces cells of late DCT and CD to • Reabsorb Sodium (water follows) • Secrete Potassium • Aldosterone secretion mainly stimulated by • Angiotensin II (RAAS) • Increased plasma Potassium levels Regulation of the Kidney function Atrial Natriuretic Peptide Natriuretic Peptides hormones Peptides act on the kidneys to inhibit sodium and water reabsorption (effect opposite to Aldosterone) Atrial Natriuretic Factor (ANP) is one such peptide • Released by the heart when there overstretching of the atrial walls due to an increase in blood flow through the atria (heart failure or systemic hypertension) • Causes dilatation of blood vessels with a consequent decrease in blood pressure. • Decreases salt appetite and thirst Endocrine Function of the kidney • Erythropoietin • Calcitriol (1,25-dihydroxycholecalciferol; Vitamin D3) • Renin • Prostaglandins The role of the Kidney in Homeostasis and Renal Disease Dr Cynthia Sammut Renal dysfunction Symptoms depend on the part of kidney/urinary system affected
• Glomerulus/Tubules • Medulla - Interstitium • Renal Calyces/Pelvis • Ureters/Bladder/ urethra • Vascular • Hormonal Renal dysfunction – classified according to Part diseased • Localised -affecting a part of the kidney • Generalised – problem spreads to affect all the kidney • One kidney/ Both kidneys
Onset/Course of Disease • Acute • Chronic
Cause of Disease • Primary • Secondary (eg. Volume loss, Cardiac, Adrenal, hypothalamus, Diabetes) • Vascular (HT, Vasculitis) • Neurological Renal Dysfunction • Onset / Progression of the Disease • Acute • Chronic Chronic renal disease Gradual loss of kidney function • Few signs and symptoms may be present in the first stages • If only one kidney is affected, the other may compensate (late diagnosis) • Usually progressive • Aim of treatment is to slow progression of disease Acute Kidney Failure • Sudden loss of kidney function – kidneys lose their ability to excrete waste products • Toxins may accumulate • Imbalance in water and chemical composition of blood and interstitial fluids
• Develops rapidly (few hours or few days)
• More common in patients who are already hospitalised (critical condition, ITU) • May be reversible (completely or partial)
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