Lecture 9 - Urinary-Renal 2 (Griffith College)

LECTURE 9 The Urinary/Renal System 2: Fluid, Electrolytes & Acid-Base Balance (pH) 1808NRS: Human Anatomy & Physiology 2 Gold Coast Campus 1 Learning activities In addition to viewing this lecture, please: Com...

LECTURE 9 The Urinary/Renal System 2: Fluid, Electrolytes & Acid-Base Balance (pH) 1808NRS: Human Anatomy & Physiology 2 Gold Coast Campus 1 Learning activities In addition to viewing this lecture, please: Complete Course Content: Topic 4.2 – Fluid, electrolytes & acid- ✔ base balance (pH) ✔ Complete workbook 5 Questions ✔ Finished labs ✔ Attend and participate in your tutorials 2 1  Lecture outcomes By the end of this lecture, you should be able to: Describe the two fluid compartments of the body and their associated divisions; Describe the hormonal mechanisms involved in fluid and electrolyte balance; Explain the physiological importance of major electrolytes; Describe a chemical buffer systems; Explain the role of both the Urinary/Renal & Respiratory Systems (physiological buffers) in acid-base balance. 3 Terminology Osmolarity Intracellular Extracellular Interstitial Intravascular Sensible vs Insensible loss Buffer Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis 4 2  Body fluid Amount of body water depends on gender, age and body composition: infants: 73% or more water (low body fat, low bone mass) adult males:  60% water adult females: 50-55% water (higher fat content, less skeletal muscle mass) obese individuals and aged:  45% Body fluids refers to all the water and dissolved solutes in the body: Non-electrolytes (organic molecules) do not dissociate in water (eg. glucose, lipids, amino acids, proteins, creatinine and urea) Electrolytes dissociate into ions in water (eg. inorganic salts, all acids and bases) 7 Fluid compartments Body fluids are present in two main “compartments” Intracellular fluid (ICF) = fluid within cells (2/3 of body fluids..25L) Extracellular fluid (ECF) = fluid outside cells (1/3 of body fluids…15L); further divided into: o Interstitial fluid in between cells (12L..also includes lymph; cerebrospinal fluid in the central nervous system; synovial fluid in joints; aqueous humor in the eyes; pleural, pericardial and peritoneal fluid in the pleural, pericardial and peritoneal cavities) o Intravascular (Plasma portion of blood..3L) 8 3  Fluid compartments (2) Only 2 places for exchange between compartments: cell membranes separate intracellular from interstitial fluid capillary walls - between plasma and interstitial fluids 1063 Pg 9 Water movement between compartments 1065 Pg Compartments not fixed..always continual Intracellular fluid movement. Digestive tract Bloodstream Tissue Lymph Bloodstream fluid * Blood plasma is a good indicator of body water! 10 4  Body water gain and loss Water is 50-75% body weight; declines with age and obesity (fat contains almost no water, why?) Water gain is from ingestion (liquids and solids) and metabolism (water formed during aerobic respiration & dehydration synthesis reactions - 2.5 L/day) Water loss occurs via: ◦ sensible, observable loss in urine, feces and sweating ◦ insensible, unnoticed loss in skin transpiration (diffusion though epidermis and evaporation) and breathing Obligatory water loss is output that is unavoidable (expired air, cutaneous transpiration, sweat, faecal moisture, and urine output) 11 Body water gain and loss (2) Input Output Requires body water balance. Balancing input & output Input ~2.5L/day ~30% insensible loss ~10% faeces/sweat ~60% renal All focused on maintaining body fluid osmolarity at ~280/300mOsmol Fig.4 1065 Pg 12 5  Osmolarity Depends on the total number of particles in solution Body fluid ~280-300mOsmol (i.e. # particles – irrespective of ‘what’ they are) Blood Na+ ~135-145mMol Blood potassium ~3.5-4.5mMol Electrolyte solutions sometimes measured in mEq/L 13 Changes to ICF & ECF * Blood loss or dehydration ? 1066 Pg 14 6 15 Hormonal regulation of urine production (retain fluid or eliminate fluid) 4 main hormones Angiotensin II Anti diuretic hormone Aldosterone Atrial Natriuretic Peptide Hormone 16 7  Four Hormones that control H2O Movement Posterior pituitary Water Reabsorption → Anti-Diuretic Hormone (ADH) ◦ Inserts Aquaporins into the D.C.T & Collecting Ducts ◦ Increases water reabsorption Adrenal Cortex Na Retention → Aldosterone ◦Stimulates Na+/K+ pumps in D.C.T & Collecting Ducts ◦Increases reabsorption of Na+ ◦Increases K+ secretion into urine Overall effect? Increase Blood Volume! Parathyroid Glands Parathyroid Hormone → Ca2+ reabsorption Increase Blood Pressure! ◦ Ca2+ reabsorption in D.C.T and C.D 17 Four Hormones that control H2O Movement Cells in Atria Atrial Natriuretic Peptide Hormone (ANP) ◦ (Natrium = latin name for sodium, uretic = losing fluid) → ↑ Na/water excretion via the kidney →↓ BP & BV INHIBITS!!!! the action of ADH/Aldosterone ◦ Chronic High BP & High BV → stretch receptors within the Atria will stretch more than usual → increase stretch causes ANP to be released into the blood Decreases Na+ reabsorption → Decreases H2O reabsorption → Decreases blood volume → Decreases blood pressure 18 8  RAAS RAAS: Renin Angiotensin Aldosterone System Is a hormonal cascade that is stimulated by a decrease in blood volume and blood pressure & is a multi-step process that has long-term effects The kidneys detect a drop in BP/Blood volume in the afferent arteriole in the kidney. Drop in BP/ blood volume activate granular cells in the afferent arteriole to release renin & releases renin into the bloodstream Renin = Enzyme that converts angiotensinogen (dormant) into its active form (angiotensin 1) Note: Angiotensinogen is freely roaming around our body, and has no effect until it is activated 19 Hormonal regulation of urine production RAAS: Renin Angiotensin Aldosterone System Angiotensinogen is produced and released from the Liver ◦ Angio = blood/lymph vessels, tensin = to create tension within the blood vessels (tension = vasoconstriction) The liver can also detect changes Renin (released from the granular cells) when low BP is detected. Renin then causes Angiotensinogen to be activated into Angiotensin I. Angiotensin I by itself cannot initiate any of the effects pertaining to blood pressure and blood volume. The lungs produce an enzyme called Angiotensin Converting Enzyme (ACE). Angiotensin 1 binds to ACE and is converted from angiotensin I to angiotensin II 20 9  Hormonal regulation of urine production RAAS: Renin Angiotensin Aldosterone System Angiotensin II has a number of target organs: 1. Potent Vasoconstrictor 2. Kidneys decrease urine output (retain water) by stimulating the posterior pituitary to release ADH → reabsorb water via aquaporins. 3. Hypothalamic thirst centre is stimulated within the subfornical organ 4. Posterior Pituitary (ADH) & Adrenal cortex (Aldosterone) hormones released → increase blood volume and increase BP Overall effect: 1. Decrease urine output = fluid retention, 2. Maintain blood volume and pressure, 3. Increase vascular resistance = vasoconstriction, 4. Increase blood volume (if fluid intake occurs). Common prescribed medication = ACE inhibitors → prescribed to patients with chronic hypertension who have an overactive RAAS system (to help reduce the effects of angiotensin II) 21 Hormonal regulation of urine production 22 10 23 Hormonal regulation of urine production Antidiuretic hormone – released from posterior pituitary it regulates water reabsorption in collecting ducts & DCT ◦ osmoreceptors in the hypothalamus respond to increased concentration of blood (as in dehydration) by initiating release of ADH ◦ ADH stimulates reabsorption of water into blood ◦ overall effect: reduction of urine volume, urine concentrated Aldosterone (“salt-retaining” hormone) secreted by the adrenal cortex in response to angiotensin II or low blood Na+ concentration ◦ Aldosterone acts on distal convoluted tubule and especially collecting ducts to stimulate reabsorption of Na+ and secretion of K+ ◦ The net effect is that the body retains NaCl and water which helps maintain blood volume and pressure ◦ The urine volume is reduced and urine has an elevated K+ concentration 24 11  Hormonal regulation of urine production Atrial natriuretic peptide – released from the heart in response to increase in blood volume ( stretching) ◦ inhibits reabsorption of Na+ and water in proximal convoluted tubule (PCT) ◦ overall effect: increased excretion of Na+ (water follows) which increases urine output and decreases blood volume THIS HORMONE WORKS IN OPPOSTION/TO INHIBIT THE OTHER 3 HORMONES! 25 Hormonal regulation of urine production Renin: causes Angiotensinogen to be activated into Angiotensin I Angiotensin I → Angiotensin II by ACE Angiotensin II → Aldosterone Aldosterone: “Na+ retaining hormone” secreted by the adrenal cortex ◦ Acts on the DCT to stimulate reabsorption of Na + and secretion of K+ ◦ Increases NaCl reabsorption → increasing blood volume and blood pressure Atrial Natruiretic Peptide (ANP): Released from the heart in response to increase blood volume ◦ Inhibits reabsorption of Na+ and water in PCT ◦ Increases urine output and decreases blood volume 26 12  Regulation of water gain Formation of metabolic water is not regulated: ◦ water is a by product mainly of ATP formation → water production depends on the need for ATP Main regulator of water gain is intake regulation via activity of thirst centre in hypothalamus Stimulators of thirst centre: ◦ dry mouth due to dehydration ◦ osmoreceptors in hypothalamus (react to increased osmolarity - concentration of blood) ◦ angiotensin II caused by decreased blood volume and drop in blood pressure Thirst centre activates drinking → body water levels return to normal 27 Thirst centre response to dehydration * If water loss persists: Severe thirst Dry & wrinkled skin ↓ Blood volume & BP Circulatory shock Fig.5 1066 Pg 28 13  Regulation of water & solute loss Elimination of excess water or solutes occurs through urination Consumption of very salty meal demonstrates function of three hormones (see diagram) that increase loss of NaCl in urine 29 Hormone effects on solutes Two hormone systems show effects on solutes in blood: 1. Aldosterone release is stimulated by angiotensin II; aldosterone promotes reabsorption of NaCl/water and thus increase in blood volume 2. Atrial natriuretic peptide (ANP) is released in response to stretching of atria (due to increase in blood volume); ANP reduces reabsorption of NaCl and promotes its excretion which decreases blood volume 30 14  Hypotension Hyponatremia Hyperkalaemia H2O Na+ K+ K+ Aldosterone and solutes Renin Angiotensin Stimulates adrenal cortex to Negative secrete aldosterone feedback loop Stimulates renal tubules Increases Na+ Increases K+ reabsorption secretion Less Na+ More K+ and H2O in urine in urine Supports existing fluid volume and Na+ concentration Fig.5 1066 Pg pending oral intake 31 Hormone regulation of water balance Antidiuretic hormone (ADH) secretion from the posterior pituitary is increased due to: ◦ increased osmolarity (concentration) of blood as in dehydration ◦ large decrease in blood volume (hypovolaemia) which can be caused by bleeding or severe dehydration (vomiting, diarrhoea, heavy sweating) ADH effects: ◦ increases permeability of cells of collecting ducts for water reabsorption → water moves from urine back into blood ◦ result: small amount of very concentrated urine is formed ◦ no ADH formed at all in diabetes insipidus – large volume of diluted urine formed inappropriately---or receptors insensitive to ADH 32 15  Movement of water into cells Intracellular and interstitial fluids normally have the same osmolarity: → no net movement of water If extracellular fluid osmolarity drops, water moves into cells which swell (hypotonic over hydration) This can occur: ◦ in replacing fluid lost from diarrhoea/ vomiting/sweating with plain water ◦ in drinking water faster than kidneys can excrete it 33 Movement of water into cells (2) 1 Excessive 2 ECF osmotic 3 H2O moves H2O enters pressure falls into cells by the ECF osmosis; cells swell Fig.7 1069 Pg Extreme form is water intoxication → may cause convulsions, coma & death (result of brain swelling); the solution is rehydration with fluid that includes electrolytes (eg. Gastrolyte) Sports drinks (Gatorade, Powerade) also contain electrolytes so hypotonic over hydration can be avoided in extreme sweating 34 16  Body electrolytes Electrolyte is a substance containing free ions, that behaves as electrically conductive medium In the body, electrolytes form when salts, acids and bases dissolve in water releasing ions (ionic solutions) Functions of electrolytes: ◦ control water movement (osmosis) between fluid compartments ◦ carry electric current (eg. in nervous system and muscles) ◦ cofactors needed for some enzymatic activity eg metabolism Concentration is typically expressed in mmol/L (in USA mEq/L – the number of electrical charges per L): ◦ mEq/L = mmol/L X number of electrical charges of electrolyte ◦ eg. 1 for sodium & potassium but 2 for calcium & magnesium 35 Composition of different fluids Fig.2 1064 Pg 36 17  Composition of different fluids (2) The main difference between the two ECF’s (plasma & interstitial fluid) is that plasma contains many proteins, but interstitial fluid does not (capillary walls are not permeable for proteins) ◦ consequence: blood has higher colloid osmotic pressure than interstitial fluid (important for regulation of water movement between blood and interstitial fluid – capillary exchange) Electrolyte content of intracellular fluid differs considerably from that of extracellular fluid: ◦ extracellular fluid contains Na+ (main extracellular cation) and Cl- (main extracellular anion) ◦ intracellular fluid contains K+ (main intracellular cation) and protein anions 37 Ion absorption vs ion secretion 38 18  Sodium Most abundant extracellular ion; found in intracellular fluid in very low concentration..(90-95% of ECF osmolarity): ◦ consequence: concentration gradient for sodium exists across cell membrane; movement of sodium inside leads to a change of resting membrane potential in excitable tissues Most important solute in determining water balance/distribution Average daily intake exceeds normal requirements Hormonal control: ◦ aldosterone causes increased reabsorption Na+ from urine ◦ reduced Na+ levels cause reduced blood concentration → ADH release is reduced - dilute urine (water) lost until Na+ levels rise ◦ ANP increases Na+ excretion if Na+ levels too high 39 Potassium Most abundant cation in intracellular fluid; concentration gradient for potassium exists across the cell membrane. Helps establish resting membrane potential & has a role in second phase of action potential (repolarisation) – movement of potassium out of the cell. Control is mainly by aldosterone which stimulates increased K+ secretion into the urine. Abnormal plasma K+ levels adversely affect cardiac and neuromuscular function: ◦ Hypokalaemia (7mmol/L) → muscle weakness, constipation, confusion ◦ Both Hypo & Hyperkalaemia are incredibly dangerous 40 19  Potassium + mV – Elevated extracellular K+ concentration Less diffusion of K+ out of cell Elevated RMP (cells + partially depolarised) RMP K+ concentrations mV Cells more excitable K+ – in equilibrium Equal diffusion into (b) Hyperkalaemia and out of cell Normal resting membrane + potential (RMP) mV – Reduced extracellular K+ concentration (a) Normokalaemia Greater diffusion of K+ out of cell Reduced RMP (cells hyperpolarised) Cells less excitable (c) Hypokalaemia 41 Chloride and calcium Chloride most abundant anions in ECF and a major contributor to ECF osmolarity..important for stomach acid, pH balance & CO2 loading/unloading generally follows sodium and is controlled in that way Calcium most abundant mineral in body, mainly found in bones and teeth; abundant extracellular cation in body fluids calcium has important roles in blood clotting, neurotransmitter release/synaptic transmission, neuromuscular excitability and muscle contraction mechanism (actin-myosin interaction) regulated by parathyroid hormone (PTH) which stimulates osteoclasts to release calcium from bone and increases reabsorption of calcium from glomerular filtrate 42 20  Electrolyte imbalance Sodium retention (hypernataemia) causes water retention and increase of blood volume (hypervolaemia) and blood pressure (hypertension) → leads to abnormal accumulation of interstitial fluid (oedema = swelling) Sodium loss (hyponatraemia) causes excessive loss of water (low blood volume & low BP – hypovolaemia & hypotension) Calcium retention (hypercalcaemia) reduces membrane sodium permeability and leads to decreased depolarisation excitability of nerve and muscle cells (constipation, weakness, lethargy) Calcium loss (hypocalcaemia) increases membrane sodium permeability and cellular excitability (tingling, muscle cramping) 43 Acid, Base & Buffer Systems 44 21  Concept of pH pH - a measure of acidity or alkalinity of a solution = negative logaritham of H+ concentration in mol/L pH scale runs from 0 to 14 (refers to concentration of H+ in moles/L) pH of 7 is neutral (distilled water - concentration of OH- and H+ are equal) pH below 7 is acidic and above 7 is alkaline pH of 1 (10 times more H+ than pH of 2) * Normal pH range of ECF is 7.35 to 7.45 45 Acid-base balance Homeostasis of H+ concentration is vital: 3-D structure of proteins sensitive to pH changes (acidity and alkalinity can denature proteins such as enzymes or structural proteins which can lose their functions) consequently normal plasma pH must be maintained between 7.35 - 7.45 this is especially important as ‘Western diet’, is generally high in proteins, which tends to acidify the blood by releasing more acids during metabolism Three major mechanisms regulate pH: buffer systems exhalation of CO2 (respiratory system) kidney excretion of acids/bases (urinary system) 46 22  Acid-base balance (2) 47 Acidosis vs Alkalosis 48 23  Buffer systems Buffer system is composed of weak base and weak acid Buffers help to resist minor changes in pH by converting between their acidic or conjugate base form In the process buffer systems prevent rapid, drastic changes in pH that would otherwise have detrimental effect Buffers work extremely quickly, in fractions of a second CHEMICAL PHYSIOLOGICAL Protein Renal system Phosphate Respiratory system Bicarbonate-Carbonic Acid 49 Carbonic acid - bicarbonate buffer system Acts as extracellular and intracellular buffer system: ◦ main reaction (reversible and incomplete – not all carbonic acid is dissociated): H2CO3 ↔ HCO3- + H+ ◦ bicarbonate ion (HCO3-) is the conjugate base & can act as a weak base by binding excess H+ pushing the reaction to the left ◦ carbonic acid (H2CO3) can act as weak acid releasing extra H+ ions (the reaction is pushed to the right) When this buffer is working, the ratio between carbonic acid and bicarbonate ion changes At normal pH of blood, bicarbonate ion concentration is about 20 times that of carbonic acid (significant capacity to buffer acids exists) 50 24  Protein buffer system Protein buffer system accounts for about three-quarters of all chemical buffering in the body fluids Proteins are the most plentiful and powerful intracellular buffers; plasma proteins are also important in extracellular compartment Proteins are composed of amino acids with some having positively charged R groups, or negatively charged R groups 51 Respiratory Buffer - Exhalation of CO2 Breathing plays important role in control of pH Blood pH is monitored by chemoreceptors in medulla oblongata, aorta and carotid artery Respiratory centres are inhibited or stimulated by changes in pH → rate & depth of breathing change: ◦ faster/deeper breathing → elimination of CO2 from carbonic acid; blood pH rises ◦ slow breathing rate → accumulation of CO2 and therefore carbonic acid; blood pH drops 52 25  Renal Buffer - excretion of acids/bases This is the slowest mechanism for control of pH but also the only one that can actually remove acids or bases formed or introduced into the body Metabolic reactions constantly produce small amount of nonvolatile acids (eg. phosphoric) in the body which need to be eliminated – normal urine is slightly acidic for this reason Kidneys have almost infinite capacity to excrete acids or bases in excess by pushing them in urine; urine pH consequently can be acidic or alkaline Renal failure typically causes acidosis due to its inability to remove metabolic acids generated during metabolism 53 Disorders of Acid/Base Balance Metabolic acidosis: ↑ production of organic acids (lactic, ketones) ie. Alcoholism, diabetes. Ingestion of acidic drugs (aspirin). Loss of base (diarrhoea, laxative overuse). Metabolic alkalosis: Overuse of bicarbonates. Loss of acid (vomiting). Respiratory acidosis: Rate of alveolar ventilation falls behind CO2 production..eg? Respiratory alkalosis: CO2 eliminated faster than it is produced…eg? 54 26  Compensation for pH imbalances Respiratory System: adjusts ventilation Fast, limited compensation Hypercapnia (↑ CO2) stimulates pulmonary ventilation Hypocapnia reduces pulmonary ventilation Renal System: adjusts blood/filtrate Slow, powerful compensation Effective for imbalances of a few days or longer Acidosis causes ↑ in H+ secretion Alkalosis causes bicarbonate secretion 55 Let’s revisit the case study…. A 68-year-old man with chronic renal failure was in the hospital in serious condition recovering from a heart attack. He received fluid through an intravenous (IV) line. Late one night, a weary nurse who was on the 11th hour of a 12-hour shift came into the patient's room to replace the man's empty IV bag with a new one. Misreading the physician's orders, he hooked up a fresh bag of IV fluid that was "twice-normal" saline rather than "half-normal" saline. This mistake was not noticed until the following morning. At that time, the man had marked pitting edema around the sacral region and had inspiratory rales ("wet- sounding crackles") at the bases of the lungs on each side. He complained that it was difficult to breathe as well. Blood was drawn, revealing the following: Na+ = 157 mEq / liter (Normal = 136-145 mEq / liter) K+ = 4.7 mEq / liter (Normal = 3.5-5.0 mEq / liter) C1- = 101 mEq / liter (Normal = 96-106 mEq / liter) 56 56 27  Questions 1. Will the nurse’s mistake increase or decrease the osmolarity (saltiness) of the patient’s interstitial fluid? 2. Will this cause the cells in their body to increase or decrease in size? Explain why 3. Why does this patient have pitting oedema and inspiratory crackles? 4. What symptoms might result from hypernatremia? 5. How would this increase in salt affect the patients blood aldosterone levels? 57 Questions 1. Will the nurse’s mistake increase or decrease the osmolarity (saltiness) of the patient’s interstitial fluid? The intravenous fluid given to this patient was too concentrated with sodium and chloride. Because these ions diffuse freely between the plasma and the interstitial fluid, increases in plasma sodium and chloride concentrations will cause increases in interstitial fluid sodium and chloride concentrations 2. Will this cause the cells in their body to increase or decrease in size? Explain why Interstitial fluid that is hypertonic to intracellular fluid will cause water to shift by osmosis from the cells to the interstitial fluid. Hence, the cells will osmotically shrink. This can be particularly detrimental to the intracellular architecture, causing deformation of the vital organelles required for cell function 58 28  Questions 3.Why does this patient have pitting oedema and inspiratory crackles? Introducing hypertonic saline into this patient made the plasma and interstitial fluid sodium concentrations rise. As the plasma sodium level rises, more water than normal is passively, osmotically drawn from the renal tubules into the peritubular capillaries of the kidneys. This raises blood volume and blood pressure, causing a shift of water from the plasma into the interstitial spaces. Thus, the patient develops edema (i.e. swelling) in tissues 4. What symptoms might result from hypernatremia? Osmotic shrinkage of cells during hypernatremia can cause shrinking of the brain and concomitant central nervous system symptoms such as lethargy, confusion, coma, convulsions, and respiratory paralysis. Muscular tremor, rigidity, and hyperreflexia may also occur. 59 Questions 5. How would this increase in salt affect the patients blood aldosterone levels? As aldosterones primary role is Na+ reabsorption, if there is an increase in Na+ levels, then aldosterone levels will decrease due to the secretion of ANP. 60 29  Additional Resources https://www.youtube.com/watch?v=FEjZS oIc3So&feature=youtu.be 61 Lecture outcomes You should now be able to: Describe the two fluid compartments of the body and their associated divisions; Describe the hormonal mechanisms involved in fluid and electrolyte balance; Explain the physiological importance of major electrolytes; Describe the chemical buffer systems; Explain the role of both the Urinary/Renal & Respiratory Systems in acid-base balance. 62 30  Remember… In addition to viewing this lecture, please: Complete Course Content: Topic 4.2 – Fluid, electrolytes & acid- ✔ base balance (pH) ✔ Week 9 workbook questions ✔ Complete required readings ✔ Attend and participate in your tutorial 63 References McKinley, M.P., O’Loughlin, V.D., & Bidle, T.S. (2016). Anatomy & physiology: An integrative approach (2e. ed.). New York, NY: McGraw-Hill Education. 64 31  End 65 32