The Renal System Dr Noel Sharkey
Learning Objectives Function Anatomy Physiology Pharmacology Pathophysiology
The Function of the Kidney Excretion - Urea - Metabolites - Drugs Regulation - BP control (RAAS) - Acid-base balance - Electrolyte balance Synthesis - Activated Vit D - Erythropoietin
Renal Anatomy (The Basics) 2 bean shaped organs Retroperitoneal Immediately lateral to vertebral column Extend from T7 superiorly to L3 inferiorly R lies lower than L due to liver Blood supply via renal arteries from the aorta Venous return via renal veins into IVC Urine drains via ureters to bladder Adrenal gland lies on top
Each kidney has outer cortex and inner medulla. Urine is formed within functional subunits known as nephrons. Each nephron contains a glomerulus, consisting of a tuft of capillaries with an afferent and efferent arteriole. The glomerulus is surrounded by epithelium of the Bowman s capsule. Glomerulus and Bowman s capsule form renal corpuscle.
Filtrate is modified by a variety of secretory and reabsorptive processes as it passes through: 1. Proximal convoluted tubule 2. Loop of Henle 3. Distal convoluted tubule 4. Collecting duct The glomeruli and convoluted tubules lie within outer cortex and loop of Henle and collecting duct extend into medullary region. End product, urine, is delivered via renal pelvis to ureter. Flow of Urine Medullary pyramids Renal Papilla Renal Calyxes Renal Pelvis Ureter Bladder Urethra To produce urine- 1) filtration 2) reabsorption 3) secretion
Filtration Blood plasma from the afferent arteriole is filtered through the glomerular barrier, which is made up of 3 layers: - Fenestrated capillary endothelium - Glomerular Basement membrane - Epithelium of Bowman s capsulepodoctyes The glomerulus is highly permeable with a large surface area which aids filtration. Filtration is dependent on the hydrostatic pressure, flow rate and surface area. Water, ions and low molecular weight solutes can filter through but NOT proteins (they remain in the blood) The end product is glomerular filtrate
Reabsorption (back into the body) Wherever Na+ goes H2O follows Proximal tubule- reabsorbs 65% of filtered Na+ as well as; Cl-, K+, Ca2+, PO4, HCO3. 75-90% of water, glucose, carbohydrates and amino acids Loop of Henle- reabsorbs 25% of filtered Na+ Distal tubule- reabsorbs 8% of filtered Na+ and reabsorbs HCO3- Collecting Duct- reabsorbs 2% of filtered Na+, but only if hormone aldoesterone is present. Reabsorbs water in the present of ADH
Secretion (into urine) Proximal tubule- uric acid, bile salts, metabolites, some drugs, some creatinine Distal tubule/collecting duct- most active secretion occurs here, including organic acids, K+, H+ and drugs
Renin- Angiotensin- Aldosterone System: Regulation of Salt & Water Renin is released from the juxtaglomerular apparatus in response to low blood flow or low Na+. Dehydration & hypotension Poor renal perfusion Angiotensiongen Angiotensin I -Vasodilation of afferent arteriole -Sodium excretion -Water retention Renin Juxtaglomerular apparatus & macula dense release of renin
Angiotensin I ACE Angiotensin II -Potent vasoconstrictor - thirst (acts on medulla) - ADH release Aldosterone -Released from adrenal cortex -Acts on DCT/ collecting ducts - Na+ and H20 reabsorption ADH (anti-diuretic hormone) -Secreted from posterior pituitary - Acts on DCT/ collecting ducts to stimulate water retention Increased hydration & BP
Acid Base Balance Kidneys are vital for regulation H+ removal HCO3- secretion (buffer)
Pharmacology- Diuretic
Thiazide Diuretics E.g. Bendroflumethiazide Mode of action: Inhibition of Na+ via rebsorption by acting on Na+/Cltransporter in distal tubule Indications: Hypertension, heart failure, fluid overload Cautions - Never use in pregnancy - Can exacerbate gout and SLE Side Effects - Postural hypotension - Hyperuricaemia (gout) - K+ - Na+
Loop Diuretics E.g. Furosemide Mode of action: Na+/K+/Cl- cotransporter blocker on thick ascending limb of the loop of henle Indications: Fluid overload- first line treatment in acute HF Side Effects - Postural hypotension - K+ - metabolic acidosis
Potassium Sparing Diuretics E.g. Spironolactone Mode of action: Aldosterone receptor antagonist Indications: Oedema (used in HF and ascites), primary hyperaldoesterism (Conns) Cautions Side Effects - Postural hypotension - Hyperuricaemia (gout) - K+ - Gynaecomastia
Nephrotoxic Drugs Many drugs are harmful to the kidney and should either be avoided or have their dose reduced in renal impairment e.g. NSAIDS, Ace-I, aminoglycosides, metformin, large doses of penicillin. Principles of prescribing in renal failure: Look at the patients renal function (egfr & serum creatinine) and reduce dose/ increase dose intervals according to this Use plasma drug levels to guide dose if possible e.g. Gentamicin, digoxin Avoid nephrotoxin drugs Stop the DAMN drugs
Management: -Encourage oral intake with water/ cranberry products -Analgesia- paracetamol will also help with pyrexia -Antibiotic according to trust protocol and sensitivities Organisms: - E.Coli -Staphylococcus saprophyticus -Proteus mirabilis Antibiotics: -Trimethoprim is usually 1 st line. It is a bacterial dihydrofolate reductase inhibitor which works by limiting bacterial reproduction. - Nitrofurantoin is also commonly used. It inhibits bacterial enzymes involved in carbohydrate metabolism and cell wall synthesis Investigations: -Urine Dipstick (leucocytes and nitrites) -MSSU (pre-abx) for microscopy and culture -Imaging- if recurrent to rule out reflux/renal scarring Symptoms: - urinary frequency - Urgency - Dysuria PYELONEPHRITIS: Flank pain, rigors, malaise Risk Factors: - Female - Catheter - Stasis of urine- stones, retention, reflux
Post- renal: = Urinary tract obstruction by abnormalities in lumen, wall or outside wall of urinary tract - Rx - Relieve obstruction e.g. urinary catheter, treat underlying cause, prevent/ treat infections, common in urinary tract obstruction with stasis Renal: = Renal parenchymatous disease /acute tubular necrosis often from ischaemic damage or prolonged pre-renal AKI - Compensatory mechanisms result in reduced Na + and water reabsorption, reduced tubular K + secretion, reduced tubular H + secretion, reduced GFR - Rx - Limit Na +, K +, fluid and protein intake. Dialysis as needed until renal function recovers Symptoms: Reflect build up of nitrogenous waste products. Anorexia, nausea & vomiting, pruritis confusion, reduced consciousness Definition: An abrupt and sustained decline in renal function characterised by an increase in creatinine and/or reduced urine output. Categorised into 3 types: pre-renal, renal and postrenal Pre-renal: = Acute reduction in renal perfusion - Causes: hypovolaemic shock, acute cardiac failure, obstruction of renal vasculature - Compensatory mechanisms result in increased urine osmolality, increased urine specific gravity, reduced urine [Na + ] - Rx - Fluid resuscitation to restore renal perfusion
Treatment: 1) Renoprotection- maintain normal BP and restrict proteinuria. Reduce angii activity ACE-I. Reduce BP diuretics and CCB. Manage other pathogenic conditions e.g. smoking, diabetes. 2) Treat complications- anaemia - EPO. Hyperk+ - restrict intake. Acidosis oral bicarbonate. Hyperphosphataemia phosphate binders. Ostemomalacia - activated vit D analogues. 3) Haemodialysis- Manages waste products + fluid/electrolyte overload Complications: -Reduced GFR oedema - Reduced tubular function polyuria, hyperkalaemia, reduced acid secretion resulting in metabolic acidosis -Reduced EPO production anaemia - Reduced production of activated Vit D renal bone disease (increased phosphate) -Activation of RAAS hypertension -Nitrogenous waste products pruritis Definition and Causes: Kidney damage or reduced GFR for 3+ months. Causes: 1. Congenital / inherited e.g. ADPKD 2. Glomerular disease primary glomerulonephritis, secondary to diabetes 3. Vascular disease 4. Urinary tract obstruction 70% cases caused by diabetes, hypertension and atherosclerosis