Physiology of Urinary tract Kidney, Ureter, Urinary bladder Urethra Kidney function Excretion Physiology of volume regulation Functions of the kidney Excretion of dangerous substances endogenous (metabolites): Urea (aminoacids),creatinine (creatine), uric acid (nucleic acids), UBG (haemoglobin), hormone metabolits exogenous (organic and anorganicus substances): toxins, drugs, food additives Maintainance of homeostasis of water compartments (mainly: extracellularly) Regulation of water and electrolyte balances (isovolemia) Regulation of body fluid osmolality and electrolyte concentrations (isosmia, isoionia) 1
Effect of increasing sodium intake on urinary sodium excretion and extracellular fluid volume. Functions of the kidney Regulation of arterial pressure Short- and long-term regulation! Regulation of acid-base balance (isohydria) H + secretion HCO 3 reabsorption/secretion H 2 SO 4, H 3 PO 4 secretion NH 3 /NH 4 2
Functions of the kidney Hormonal regulation Erythropoetin => production of red blood cells Renin => angiotensin => blood pressure regulation Hydroxilation of D3 vitamin => bone metabolism Synthesis of prostaglandines (PGE2, PGI2) => vasodilation => blood pressure regulation Gluconeogenesis during fasting Anatomy Kidney Location : On the posterior wall of the abdomen Structure: Capsule (fibrous, fat, fascicular) Layers: cortex, medulla Pyramids, papilla Pelvis, major calyces, minor calyces Ureter Bladder Urethra 3
Micturition Bladder: Receptive relaxation 50-200 ml loading Parasympathetic reflex (S1-4) Somatic nerves (S3-4) Sympathetic nerve (L1-3) 4
Urinary tract -Micturition Calyx minor, major, Renal pelvis Ureter Urinary bladder Urethra Innervation Sensory: pelvic nerve Motor: Parasympathetic: pelvic nerve (S1-4) Somatic nerve : pudendal nerve (S3-4) Sympathetic nerve: hypogastric nerve (L1-3) 5
Micturition reflex Receptive relaxation 50-200 ml loading Micturition reflex 6
Higher centers Brainstem: pons, midbrain: Hypothalamus Cerebral cortex:frontal cortex, insula Renal blood supply RBF, RPF (Renal blood flow: RBF, 1000-1100 ml/min Renal plasma flow: RPF, 600-660 ml/min) Renal artery => Interlobar arteries => Arcuate arteries => Interlobular arteries Afferent arteriole Glomerulus (high pressure: 45-60 mmhg) Efferent arteriole Peritubular capillaries (vasa recta) (low pressure: 13 mmhg) Interlobular vein => Arcuate vein => Interlobar vein => Renal vein 7
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Kidney circulation Main role: Urine production Organ kg / (%) brain 1.4 (2) heart 0.3 (0.4) splanch 4 (4) liver 1.5 (2.1) kidney0.3 (0.4) Muscle 35 (50) skin 2 (2.9) fat 9 (13) Bone etc. 18 (25.6) Resting CO 5 l/min % ml ml/min/100g 15 750 50 5 250 70 20 1000 5 250 20 1000 360 16 800 4 6 300 6 8 400 5 250 3 Resting O 2 250 ml/min % ml 18 45 12 30 22 55 7 17.5 20 50 4 10 17 42.5 exercise CO 25 l/min % ml 3 750 5 1250 3 750 3 750 85 21250 1 250 Max. vasodilation ml 1500 1250 9000 5000 1800 21250 3000 1800 2000 Organ Basal Constrictor Sympathetic activation coronary +++++ - - brain +++++ - - muscle ++ ++ +++ kidney + - +++ splanchnic ++ ++ ++++ skin- acral ++++ ++++ skin- non-acral + ++++ ++++ 9
High effective filtration pressure 10
Autoregulation (Bayliss- effect) Sympathetic innervation of blood vessels It is not involved in the depressor responses It is involved in pressor responses Regulation 11
Regulatory factors Vasoconstrictors Sympathetic akctivation (ECV ) Angiotensin II (ECV, ADH, serotonin) Endothelin (strech, angiotensin II, ECV, bradikinin) Vasodilators: Prostaglandines (strech, ECV, angiotensin II) NO (strech, Ach, histamin, bradikinin, ATP) Bradikinin (prostaglandin) ANP (ECV ), Dopamin (adrenal medulla) 12
Nephron Functional unit of the kidney; 1 million/kidney Structure: Glomerulus + Bowman s capsule (cortex) =>filtration Tubules => urine formation (reabsorption, secretion) proximal tubule (cortex) convoluted tubules descending segment loop of Henle (medulla) descending limb (thin segment) ascending limb (thin and thick segments) Macula densa Distal convoluted tubules (cortex) Connecting tubules (cortex, medulla) Collecting ducts (cortex and medulla) 13
Regional differences in nephron structure Cortical nephrons short loops of Henle (70-80%) Juxtamedullar nephrons: long loops of Henle (20-30%) vasa recta 14
Basic kidney processes that determine the composition of the urine: Glomerular function Filtration (GFR) Tubular functions Reabsorption Secretion Urinary excretion rate of a substance is equal to the rate at which the substance is filtered minus its reabsorption rate plus the rate at which it is secreted from the peritubular capillary blood into the tubules. 15
A, The substance is freely filtered but not reabsorbed (creatinine, inulin) B, The substance is freely filtered, but part of the filtered load is reabsorbed back in the blood. (electrolytes) C, The substance is freely filtered but is not excreted in the urine because all the filtered substance is reabsorbed from the tubules into the blood. (glucose, amino acids) D, The substance is freely filtered and is not reabsorbed but is secreted from the peritubular capillary blood into the renal tubules. (organic acids, bases, PAH) 16
Filtration 180 l/nap Control (rough) Control (fine) Concentration Glomerular filtration 120 ml/min 180 l/day Filtration fraction: FF = GFR/RPF FF= 120/600 = 0.2 = 20% 17
The advantage of large amounts of filtration: Rapid remove of waste products by glomerular filtration It allows all the body fluids to be processed by the kidney many times each day (60 times/day). Determinants of the GFR 1. Structure of glomerular capillary (surface, permeability) 2. Size and electrical charge of substances 3. Net filtration pressure 18
Structure of glomerular capillary membrane endothelium, basement membrane epithelial cells (podocytes) Permeability of glomerular capillary Fenestrated endothel: 50-100 nm (negative charge) Basement membrane : collagen and proteoglycan fbrillae: 3-5 nm (negative charge) Podocytes: 25 nm (negative charge) NO protein, and NO lipid filtration!!! 19
Effect of size and electrical charge of dextran on its filterability by the glomerular capillaries. 20
Net filtration pressure Starling-law: GFR= Kf*[(P G - P B ) - (π G - π B )] GFR = glomerular filtration ratio Kf = filtration coefficient (depend on permeability and surface area) Kf = 12.5 ml/min/mmhg P G = glomerular hydrostatic pressure P B = hydrostatic pressure in Bowman s capsule π G = colloid osmotic pressure in glomerular capillary π B = colloid osmotic pressure in Bowman s capsule 21
P G is affected by Afferent arterioral resistance and Efferent arterioral resistance 22
Macula densa feedback mechanism for autoregulation of glomerular hydrostatic pressure and glomerular filtration rate (GFR) during decreased renal arterial pressure. 23