Kidney Anatomy and Physiology An Overview Noah Hoffman 2006
Functions of the Kidney: Maintaining balance• Regulation of body fluid volume and osmolality• Regulation of electrolyte balance• Regulation of acid-base balance• Excretion of waste products (urea, ammonia, drugs, toxins)• Production and secretion of hormones• Regulation of blood pressure
The Kidney and the Nephron A. Renal Vein B. Renal Artery C. Ureter D. Medulla E. Renal Pelvis F. Cortex 7. Ascending loop of Henle 8. Descending loop of Henle 9. Peritubular capillaries 10. Proximal tubule 11. Glomerulus 12. Distal tubule
The Nephron• Functional unit of the kidney (1,000,000)• Responsible for urine formation: – Filtration – Secretion – Reabsorption
Components of the nephron•Glomerulus•Afferent andEfferent arterioles•Proximal Tubule•Loop of Henle•Distal Tubule•Collecting Duct
Overview of nephron functionFrom http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html
Plasma is filtered through the glomerular barrier•Components of plasma cross the three layers of theglomerular barrier during filtration •Capillary endothelium •Basement membrane (net negative charge) •Epithelium of Bowman’s Capsule (Podocytes –filtration slits allow size <60kD)•The ability of a molecule to cross the membrane depends onsize, charge, and shape• Glomerular filtrate therefore contains all molecules notcontained by the glomerular barrier - it is NOT URINE YET!
Glomerular Filtration Rate (GFR)• Measure of functional capacity of the kidney• Dependent on difference in pressures between capillaries and Bowman’s space• Normal = 120 ml/min =7.2 L/h=180 L/day!! (99% of fluid filtered is reabs.)
Oncotic pressure Oncotic pressure is the component of total osmotic pressure due to colloid particles. Water molecules cross the membrane to equalize the concentration of colloid particles on each side.
Glomerular filtration rate (GFR)• Depends on the difference in hydrostatic and oncotic pressure on either side of the glomerular basement membrane GFR = Glomerular Bowman’s Capillary (GC) space (BS) Kf(PGC - PBS - COPGC) P = hydrostatic PGC PBS pressure COPGC COPBS COP = colloid osmotic pressure Kf determined by surface area and permeability of H2O
Reabsorption• Active Transport –requires ATP – Na+, K+ ATP pumps• Passive Transport- – Na+ symporters (glucose, a.a., etc) – Na+ antiporters (H+) – Ion channels – Osmosis
Factors influencing Reabsorption• Saturation: Transporters can get saturated by high concentrations of a substance - failure to resorb all of it results in its loss in the urine (eg, renal threshold for glucose is about 180mg/dl).• Rate of flow of the filtrate: affects the time available for the transporters to reabsorb molecules.
What is Reabsorbed Where?Proximal tubule - reabsorbs 65 % of filtered Na+ as wellas Cl-, Ca2+, PO4, HCO3-. 75-90% of H20. Glucose,carbohydrates, amino acids, and small proteins arealso reabsorbed here.Loop of Henle - reabsorbs 25% of filtered Na+.Distal tubule - reabsorbs 8% of filtered Na+. ReabsorbsHCO3-.Collecting duct - reabsorbs the remaining 2% of Na+only if the hormone aldosterone is present. H20depending on hormone ADH.
Secretion• Proximal tubule – uric acid, bile salts, metabolites, some drugs, some creatinine• Distal tubule – Most active secretion takes place here including organic acids, K+, H+, drugs, Tamm-Horsfall protein (main component of hyaline casts).
Countercurrent exchange• The structure and transport properties of the loop of Henle in the nephron create the Countercurrent multiplier effect.• A substance to be exchanged moves across a permeable barrier in the direction from greater to lesser concentration. Image from http://en.wikipedia.org/wiki/Countercurrent_exchange
Countercurrent exchange• Countercurrnet exchange is found throughout nature…• Birds reduce heat loss through their feet by heating venous (returning) blood and cooling arterial (outgoing) blood in their legs. Image from http://ecology.botany.ufl.edu/ecologyf02/homeostasis.html
Loop of Henle – Goal= make isotonic filtrate into hypertonic urine (don’t waste H20!!) – Counter-current multiplier: • Descending loop is permeable to Na+, Cl-, H20 • Ascending loop is impermeable to H20- active NaCl transport • Creates concentration gradient in interstitium • Urine actually leaves hypotonic but CD takes adv in making hypertonic
Hormones Produced by the Kidney• Renin: – Released from juxtaglomerular apparatus when low blood flow or low Na+. Renin leads to production of angiotensin II, which in turn ultimately leads to retention of salt and water.• Erythropoietin: – Stimulates red blood cell development in bone marrow. Will increase when blood oxygen low and anemia (low hemoglobin).• Vitamin D3: – Enzyme converts Vit D to active form 1,25(OH)2VitD. Involved in calcium homeostasis.
Renin, Angiotensin, Aldosterone:Regulation of Salt/Water Balance
Renin/AII and Regulation of GFR GFR = Kf(PGC - PBS - COPGC)• “flight or fright”∀⇑ sympathetic tone• afferent arteriolar constriction (divert cardiac output to otherorgans)∀⇓PGC∀⇓GFR and renal blood flow
Renin/AII and Regulation of GFR GFR = Kf(PGC - PBS - COPGC)•Low BP sensed in afferentarteriole or low Na in distal tubule•renin released•renin converts angiotensinogento Angiotensin I PGC⇑•ACE converts AI to AII•efferent > afferent arteriolarconstriction∀⇑ PGC ⇒ ⇑ GFR (this is constrictsAUTOREGULATION of GFR)
Aldosterone• Secreted by the adrenal glands in response to angiotensin II or high potassium• Acts in distal nephron to increase resorption of Na+ and Cl- and the secretion of K+ and H+• NaCl resorption causes passive retention of H2O
Anti-Diuretic Hormone (ADH)• Osmoreceptors in the brain (hypothalamus) sense Na+ concentration of blood.• High Na+ (blood is highly concentrated) stimulates posterior pituitary to secrete ADH.• ADH upregulates water channels on the collecting ducts of the nephrons in the kidneys.• This leads to increased water resorption and decrease in Na concentration by dilution
Case I• A 52 yo male is seen for a routine physical exam for the first time in a few years. His physician discovers that the patient has been feeling more tired than usual for “a while.” He also complains of increased thirst and hunger, and says that he has to get up several times at night to urinate.• The lab measured a random blood glucose of 350 mg/dl, urine dipstick positive for glucose, and urine albumin/creatinine of 40 mg/g.
Case 1 - DMII• Diabetes mellitus type II (“adult onset”)• Diabetes from Greek words meaning "siphon" or "run through”; mellitus is Latin for “sweet.”• Saturation of glucose transporters results in glucose in urine.• Glucose in urine results in osmotic diuresis.• Chronic hyperglycemia leads to microvascular damage, including damage to glomerular capillary wall, resulting in microalbuminuria.
Case 2• A 39-yr-old male with AIDS was admitted with nausea, vomiting, abdominal pain, light- headedness on standing, and weight loss. During hospitalization, the patient developed hypotonic polyuria with urine volumes of 9L/day associated with intense thirst.• serum Na - 149 mmol/L [136-145]• urine osmolality - 71 to 88 mmol/kg [100-1000]
Case 2• A water restriction test was performed, in which the patient was given about 450 ml of 3% saline IV over 2 hours. – serum osm - 306 mmol/kg [280-300] – urine osm - 102 – urinary ADH - undetectable• MR imaging showed changes in the posterior pituitary.• In response to treatment with desmopressin (10 g twice daily by nasal spray), urine volumes decreased to 2–3 liters per day. The patient later died of bowel perforation. Autopsy showed evidence of damage to the posterior pituitary caused by CMV infection.
Case 2 - Diabetes Insipidus• Inability to concentrate urine despite high serum sodium and osmolality. Results in large volume of dilute urine.• Central – damage to the posterior pituitary results in inadequate ADH production – treatment is exogenous ADH• Nephrogenic – kidney unresponsive to ADH – can be hereditary or acquired (eg, lithium therapy) – serum ADH is high
Case 3• A 61 year old male presented with confusion and seizures two days after starting a new medication (citalopram, an antidepressant). – serum Na - 124 mmol/L [136–145] – serum osmolarity - 263 mOsm/L [285–295] – urine Na - 141 mEq/L [40-220] – urine osmolarity - 400 mosm/L [100-1000] – urine output - < 1L/day• The patients serum sodium gradually normalized after the medication was discontinued.
Case 3 - SIADH• SIADH = syndrome of inappropriate antidiuretic hormone secretion• Open channels in the collecting duct lead to excessive water resorption and a dilutional hyponatremia.• can be caused by brain injury, ectopic production by tumors, various drugs, major surgery, pulmonary diseases, exogenous ADH• Treatment includes water restriction and salt administration