Final Exam Review

Final Exam Review Summer 2010 Chapters 16, 25, and 26

Kidney Functions • Removal of toxins, metabolic wastes, and excess ions from the blood • Regulation of blood volume, chemical composition, and pH

Kidney Functions • Gluconeogenesis during prolonged fasting • Endocrine functions • Renin: regulation of blood pressure and kidney function • Erythropoietin: regulation of RBC production • Activation of vitamin D

Urine Movement • glomerulus • proximal convoluted tubule • loop of Henle • distal convoluted tubule • collecting duct • minor calyx • major calyx • pelvis • ureter • bladder urethra

Figure 25.5

Nephron • Functional unit of kidney • Units of nephron • Renal corpuscle • Bowman’s (glomerular) capsule • Glomerulus • Tubules • PCT • Loop of Henle • DCT • Collecting duct

Renal hilum Renal cortex Renal medulla Major calyx Papilla of pyramid Renal pelvis Minorcalyx Ureter Renal pyramid in renal medulla Renal column Fibrous capsule (a) Photograph of right kidney, frontal section (b) Diagrammatic view Figure 25.3

Filtration Membrane • Porous membrane between the blood and the capsular space • Consists of • Fenestrated endothelium of the glomerular capillaries • Visceral membrane of the glomerular capsule (podocytes with foot processes and filtration slits) • Gel-like basement membrane (fused basal laminae of the two other layers)

Glomerular capsular space Efferent arteriole Proximal convoluted tubule Afferent arteriole Cytoplasmic extensions of podocytes Glomerular capillary covered by podocyte- containing visceral layer of glomerular capsule Parietal layer of glomerular capsule Filtration slits Podocyte cell body (a) Glomerular capillaries and the visceral layer of the glomerular capsule Fenestrations (pores) Glomerular capillary endothelium (podocyte covering and basement membrane removed) Foot processes of podocyte Figure 25.9a

Basement membrane Podocyte Fenestrated endothelium of the glomerulus Glomerular capsule: visceral layer Figure 25.5

Filtration Membrane • Allows passage of water and solutes smaller than most plasma proteins • Fenestrations prevent filtration of blood cells • Negatively charged basement membrane repels large anions such as plasma proteins • Slit diaphragms also help to repel macromolecules

Filtration membrane • Capillary endothelium • Basement membrane • Foot processes of podocyte of glomerular capsule Capillary Filtration slit Slit diaphragm Plasma Filtrate in capsular space Foot processes of podocyte Fenestration (pore) (c) Three parts of the filtration membrane Figure 25.9c

Kidney Physiology: Mechanisms of Urine Formation • Filtrate • Blood plasma minus proteins • Urine • <1% of total filtrate • Contains metabolic wastes and unneeded substances

Juxtaglomerular Apparatus (JGA) • One per nephron • Important in regulation of filtrate formation and blood pressure • Involves modified portions of the • Distal portion of the ascending limb of the loop of Henle • Afferent (sometimes efferent) arteriole

Juxtaglomerular Apparatus (JGA) • Granular cells (juxtaglomerular, or JG cells) • Enlarged, smooth muscle cells of arteriole • Secretory granules contain renin • Act as mechanoreceptors that sense blood pressure • decrease in BP stimulates renin secretion • Renin activates angiotensinogen then converted to angiotensin II • Angiotensin II stimulates aldosterone secretion and vasoconstriction

Juxtaglomerular Apparatus (JGA) • Macula densa • Tall, closely packed cells of the ascending limb • Act as chemoreceptors that sense NaCl content of filtrate

SYSTEMIC BLOOD PRESSURE (–) Blood pressure in afferent arterioles; GFR Baroreceptors in blood vessels of systemic circulation Granular cells of juxtaglomerular apparatus of kidney GFR Release (+) Stretch of smooth muscle in walls of afferent arterioles Filtrate flow and NaCl in ascending limb of Henle’s loop (+) (+) Renin Sympathetic nervous system Catalyzes cascade resulting in conversion Targets Vasodilation of afferent arterioles Angiotensinogen Angiotensin II (+) (+) (+) Macula densa cells of JG apparatus of kidney Adrenal cortex Systemic arterioles Releases Vasoconstriction; peripheral resistance Aldosterone Release of vasoactive chemical inhibited Targets Kidney tubules Vasodilation of afferent arterioles Na+ reabsorption; water follows (+) Stimulates (–) Inhibits Increase Decrease GFR Blood volume Systemic blood pressure Tubuloglomerular mechanism of autoregulation Myogenic mechanism of autoregulation Hormonal (renin-angiotensin) mechanism Neural controls Intrinsic mechanisms directly regulate GFR despite moderate changes in blood pressure (between 80 and 180 mm Hg mean arterial pressure). Extrinsic mechanisms indirectly regulate GFR by maintaining systemic blood pressure, which drives filtration in the kidneys. Figure 25.12

Mechanisms of Urine Formation • Glomerular filtration • Tubular reabsorption • Returns all glucose and amino acids, 99% of water, salt, and other components to the blood • Tubular secretion • Reverse of reabsorption: selective addition to urine

Glomerular Filtration • Passive mechanical process driven by hydrostatic pressure • The glomerulus is a very efficient filter because • Its filtration membrane is very permeable and it has a large surface area • Glomerular blood pressure is higher (55 mm Hg) than other capillaries • Molecules >5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood

Sodium Reabsorption • Na+ (most abundant cation in filtrate) • Primary active transport out of the tubule cell by • Na+-K+ ATPase

Sodium Reabsorption • Low hydrostatic pressure and high osmotic pressure in the peritubular capillaries • Promotes bulk flow of water and solutes (including Na+)

Reabsorption of Nutrients, Water, and Ions • Na+ reabsorption provides the energy and the means for reabsorbing most other substances • Organic nutrients are reabsorbed by secondary active transport

Reabsorption of Nutrients, Water, and Ions • Water is reabsorbed by osmosis (obligatory water reabsorption) • Cations and fat-soluble substances follow by diffusion

Formation of Dilute Urine • Filtrate is diluted in the ascending loop of Henle • In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine • Alcohol inhibits secretion of ADH • Na+ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm

Formation of Concentrated Urine • Depends on the medullary osmotic gradient and ADH • ADH triggers reabsorption of H2O in the collecting ducts • Facultative water reabsorption occurs in the presence of ADH so that 99% of H2O in filtrate is reabsorbed

Regulation of Water Output: Influence of ADH • Water reabsorption in collecting ducts is proportional to ADH release •  ADH  dilute urine and  volume of body fluids •  ADH  concentrated urine

Tubular Secretion • Reabsorption in reverse • K+, H+, NH4+, creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrate • Disposes of substances that are bound to plasma proteins

Tubular Secretion • Eliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid) • Rids the body of excess K+ • Controls blood pH by altering amounts of H+ or HCO3– in urine

Regulation of Water Output: Influence of ADH • Hypothalamic osmoreceptors trigger or inhibit ADH release • Other factors may trigger ADH release via large changes in blood volume or pressure, e.g., fever, sweating, vomiting, or diarrhea; blood loss; and traumatic burns

Osmolality Na+ concentration in plasma Plasma volume BP (10–15%) Stimulates Osmoreceptors in hypothalamus Inhibits Negative feedback inhibits Baroreceptors in atrium and large vessels Stimulates Stimulates Posterior pituitary Releases ADH Antidiuretic hormone (ADH) Targets Collecting ducts of kidneys Effects Water reabsorption Results in Osmolality Plasma volume Scant urine Figure 26.6

Disorders of Water Balance: Hypotonic Hydration • Cellular over hydration or water intoxication • Occurs with renal insufficiency or rapid excess water ingestion or SIADH • ECF is diluted  hyponatremia  net osmosis into tissue cells  swelling of cells  severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema)  possible death

Homeostatic Imbalances of ADH • ADHdeficiency — diabetesinsipidus; huge output of urine and intense thirst • ADH hypersecretion (after neurosurgery, trauma, or secreted by cancer cells)—syndrome of inappropriate ADH secretion (SIADH)

Disorders of Water Balance: Edema • Atypical accumulation of IF fluid  tissue swelling • Due to anything that increases flow of fluid out of the blood or hinders its return • Blood pressure •  Capillary permeability (usually due to inflammatory chemicals) • Incompetent venous valves, localized blood vessel blockage • Congestive heart failure, hypertension,  blood volume • Loss or decrease production of plasma proteins, liver disease, urine loss of proteins

Edema • Hindered fluid return occurs with an imbalance in colloid osmotic pressures, e.g., hypoproteinemia ( plasma proteins) • Fluids fail to return at the venous ends of capillary beds • Results from protein malnutrition, liver disease, or glomerulonephritis

Edema • Blocked (or surgically removed) lymph vessels • Cause leaked proteins to accumulate in IF •  Colloid osmotic pressure of IF draws fluid from the blood • Results in low blood pressure and severely impaired circulation

Composition of Body Fluids • Electrolytes • Dissociate into ions in water; e.g., inorganic salts, all acids and bases, and some proteins • The most abundant (most numerous) solutes • Have greater osmotic power than nonelectrolytes, so may contribute to fluid shifts • Determine the chemical and physical reactions of fluids

Composition of Body Fluids • Water: the universal solvent • Solutes: nonelectrolytes and electrolytes • Nonelectrolytes: most are organic • Do not dissociate in water: e.g., glucose, lipids, creatinine, and urea

Extracellular and Intracellular Fluids • Each fluid compartment has a distinctive pattern of electrolytes • ECF • All similar, except higher protein content of plasma • Major cation: Na+ • Major anion: Cl–

Extracellular and Intracellular Fluids • ICF: • Low Na+ and Cl– • Major cation: K+ • Major anion HPO42–

Central Role of Sodium • Most abundant cation in the ECF • The body’s water volume is closely tied to the level of sodium in its respective space • Sodium salts in the ECF contribute 280 mOsm of the total 300 mOsm ECF solute concentration • Na+ leaks into cells and is pumped out against its electrochemical gradient • Na+ content may change but ECF Na+ concentration remains stable due to osmosis

Fluid Movement Among Compartments • Regulated by osmotic and hydrostatic pressures • Water moves freely by osmosis; osmolalities of all body fluids are almost always equal • Two-way osmotic flow is substantial • Ion fluxes require active transport or channels • Change in solute concentration of any compartment leads to net water flow

Electrolyte Balance • Importance of salts • Controlling fluid movements • Excitability • Secretory activity • Membrane permeability

Regulation of Sodium Balance: Aldosterone • Na+ reabsorption • 65% is reabsorbed in the proximal tubules • 25% is reclaimed in the loops of Henle • Aldosterone  active reabsorption of remaining Na+ • Water follows Na+ if ADH is present

Regulation of Sodium Balance: Aldosterone • Renin-angiotensin mechanism is the main trigger for aldosterone release • Granular cells of JGA secrete renin in response to • Sympathetic nervous system stimulation •  Filtrate osmolality •  Stretch (due to  blood pressure)

Regulation of Sodium Balance: Aldosterone • Renin catalyzes the production of angiotensin II, which prompts aldosterone release from the adrenal cortex • Aldosterone release is also triggered by elevated K+ levels in the ECF • Aldosterone brings about its effects slowly (hours to days)

K+ (or Na+) concentration in blood plasma* Renin-angiotensin mechanism Stimulates Adrenal cortex Negative feedback inhibits Releases Aldosterone Targets Kidney tubules Effects Na+ reabsorption K+ secretion Restores Homeostatic plasma levels of Na+ and K+ Figure 26.8

Regulation of Potassium Balance • Influence of aldosterone • Stimulates K+ secretion (and Na+ reabsorption) by principal cells • Increased K+ in the adrenal cortex causes • Release of aldosterone • Potassium secretion

Regulation of Sodium Balance: ANP • Released by atrial cells in response to stretch ( blood pressure) • Effects • Decreases blood pressure and blood volume: •  ADH, renin and aldosterone production •  Excretion of Na+ and water • Promotes vasodilation directly and also by decreasing production of angiotensin II

Stretch of atria of heart due to BP Releases Negative feedback Atrial natriuretic peptide (ANP) Targets Hypothalamus and posterior pituitary JG apparatus of the kidney Adrenal cortex Effects Effects Renin release* Aldosterone release ADH release Inhibits Angiotensin II Inhibits Collecting ducts of kidneys Vasodilation Effects Na+ and H2O reabsorption Results in Blood volume Results in Blood pressure Figure 26.9

Acid-Base Balance • pH affects all functional proteins and biochemical reactions • Normal pH of body fluids • Arterial blood: pH 7.4 • Venous blood and IF fluid: pH 7.35 • ICF: pH 7.0 • Alkalosis or alkalemia: arterial blood pH >7.45 • Acidosis or acidemia: arterial pH < 7.35

Final Exam Review