TUTORIAL GUIDE BLOCK TITLE WEEK TITLE WEEK SCHEDULLE WEEK THEME INTRODUCTION: Welcome to tutoring in the genitourinary

block. The case of Mr Arif represents the third week of the genito-urinary block. It is designed for students to learn issues around renal failure. The primary focus of this case is normal and abnormal volume production of the urine, introduction to acute renal failure with its definition, etiology, classification, complications and clinical presentation of ARF, The associated aspects of electrolyte homeostasis (especially potassium homeostasis) and acid base imbalance disorders. : GENITO-URINARY SYSTEM : RENAL FAILURE : THIRD WEEK : ACUTE RENAL FAILURE

CASE SYNOPSIS: Mr Arif has acute renal failure prior to massive watery diarrhea and vomiting suspected of food poisoning, leading to oliguria, hypovolemic syok, metabolic acidosis and hyperkalemia. The case shall only focus on the genito-urinary aspects of renal failure rather than the infection in the intestines or food poisoning aspects of this case. CASE OBJECTIVES: After completing the Mr. Arif case, students should be able to: 1. Define the normal volume of urine production. 2. Define oliguria, polyuria and anuria and the etiology of both of them. 3. Define, classify, describe stages of ARF and each clinical manifestation 4. Recognize the physical examination, laboratory findings of ARF 5. Describe the pathogenesis of high concentration of urea and creatinine in ARF (explain the mechanism of urea excretion) 6. Describe normal, abnormal potassium homeostasis and factors that cause hyperkalemia, sign and symptoms of hyperkalemia 7. Describe the electro-cardiographic changes in hyperkalemia 8. Explain acid base and electrolyte homeostasis (describe major processes that can result metabolic acidosis) 9. Describe the treatment of ARF: rehydration with fluid, pharmacological properties of diuretics and dopamine, treatment of metabolic acidosis and hyperkalemia and renal replacement therapy : hemodialysis and acute peritoneal dialysis)

CASE : When you are at the ER (Emergency Room) at the Hasan Sadikin Hospital working as a doctor assistant, a 25 years old man Mr Arif was admitted to the hospital complains of small producing urine. Before this, his urine was normal. This complains occurred prior to massive diarrhoeas and vomiting .It all started three days before admitted to the hospital He also complained of shortness of breath, weakness, and fatigue and according to his family sometimes he looked delirious. It occurred one day before he was admitted to the hospital His physical examination revealed a male who is delirious. Blood pressure of 90/60 mmHg, a small pulse 120x/mnt, a deep and rapid respiration of 34x/mnt and a temperature of 37.5 C. he is not anaemic, no sign of pulmonary rales, no enlargement of the heart with a regular tachycardia heart rate. His belly is flat and smooth with a reduced elasticity skin together with reduced elasticity skin of both legs. Laboratory findings: Haemoglobin level: 15,6 gr./dl, Hematocrit: 50%, White blood cell: 10.000/ mm3, serum urea level of 180 mg/dl, serum creatinine level of 5,3 mg/dl, serum potassium level of 7 meq/L, serum sodium level of 145 meq/L, Blood gas analysis : ph 7.245, pO2 94 cmH2O, HCO3 -: 7 meq/L. His urine analysis has no sediments or cast and no proteinuria. Stool analysis showed no erythrocytes, parasites but viewed only a few leukocytes EKG : tall and peak T wave and widening QRS complex

After the diagnose was established as Acute Renal Failure because of volume depletion, this patient was given intravenous crystalloid fluid to restore his renal function and correction of hyperkalemia and metabolic acidosis Epilog : Good rehydration treatment with crystalloid fluid, management of metabolic acidosis, and hyperkalemia save Mr Arif renal function and he doesn't have to be dialysed

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When you are at the ER (Emergency Room) at the Hasan Sadikin Hospital working as a doctor assistant, a 25 years old man Mr Arif was admitted to the hospital complains of small producing urine. Before this, his urine was normal. This complains occurred prior to massive diarrhoeas and vomiting .It all started three days before admitted to the hospital

1. Identify Mr. Arifs problem ! The problem of Mr. Arif is : a small producing urine volume 2. What is your hypothesis list and provide your rationale 1. Oliguria 2. Anuria 3. What further information do you need?

Guiding questions for student : 1. What is the definition of normal volume of urine production ? 2. What is the definition of oliguria, polyuria and anuria and the etiology of both of them ? Answer : 1. Definition of normal volume of urine production: Daily intake of water to the body has to main sources: (1) It is ingested in the form of liquids or water in the food, which together normally add about 2100 ml/day to the body fluids, and (2) it is synthesized in the body as a result of oxidation of carbohydrates, adding about 200 ml/day. This provides a total water intake of about 2300 ml/day. Intake of water is highly variable among different people and even within the same person on different days, depending on climate, habits, and level of physical activity. Daily loss of body water could happen by insensible water loss (evaporation from the respiratory tract and diffusion through the skin), fluid loss in sweat, water loss in feces. The remaining water loss from the body occurs in the urine excreted by the kidneys. There is multiple mechanism that controls the rate of urine excretion. In fact the most important means by which the body maintains balance between water intake and output as well as a balance between intake and output of most electrolytes in the body is by controlling the rates at which the kidneys excrete this substances. For example, urine volume can be as low as 0,5 L/day in a dehydrated person or as high as 20 L/day in a person who has been drinking tremendous amounts of water.

Table 1 Daily intake and output of water (in ml/day) ________________________________________________________ Prolonged Heavy Exercise ________________________________________________________ Intake Fluid ingested 2100 ? From metabolism 200 200 Total intake 2300 ? Output Insensible-skin 350 350 Insensible-lungs 350 650 Sweat 100 5000 Feces 100 100 Urine 1400 500 Total output 2300 6600 ________________________________________________________ In health, the volume of urine passed is primarily determined by diet and fluid intake. In temperate climates it lies within the range 800-2500 mL/24 hours. The minimum amount passed to stay in fluid balance is determined by the amount of solute- mainly urea and electrolytes, being excreted and the maximum concentrating power of the kidneys. On a normal diet, some 800 mOsm of solute are passed daily. Since the maximum urine concentration is approximately 1200 mOsm/kg, the minimum volume of urine obligated by excretion of 800 mOsm of solute would thus be approximately 650 mL (table 2). Fluid intake is generally greater than this, so a larger volume of more dilute urine is passed. A diet rich of carbohydrates, fat and low in protein and salt results in a lower solute excretion and as little as 300 mL of urine per day may be required. Conversely, a high salt, high protein intake obligates a larger urine flow and via the thirst mechanism, a higher fluid intake. The appropriateness of given daily urine output must therefore be related to factors such as diet, body size and fluid intake. In disease, impairment of concentrating ability requires increased volumes of urine to be passed, given the same daily solute output. An increased solute output, such as in glycosuria or increased protein catabolism following surgery or associated with sepsis, also demands increased urine volumes. The maximum urine output depends on the ability to produce a dilute urine. Intakes of 10 or even 20 L daily can be tolerated by normal humans but, given daily solute output of 800 mOsm require the ability to dilute 80 and 40 mOsm/kg, respectively. Where diluting ability is impaired, the ability to excrete large volumes of ingested water is also impaired. Normal

Table 2 Relationship between Diet, Kidney Function and Urine Volume

________________________________________________________ Diet Approximate solute Minimum urine volume required to excrete Output (mOsm/24hr) solute load (mL/24hr) With normal urine In disease (impaired Concentration (max urine concentration 1200 mOsm/kg) (max 300 mOsm/kg) ______________________________________________________________________ _________ Normal 800 667 2667 High prot/salt 1200 1000 4000 Low prot/salt 360 300 1200 ______________________________________________________________________ _________

2. Definition and etiology of Oliguria, Polyuria and Anuria : Oliguria and Anuria: Define as the excretion of less than 300 mL of urine per day, may be `physiological` as in patient with hypotension and hypovolemia , where urine is maximally concentrated in an attempt to conserve water. More often, it is due to intrinsic renal disease or obstructive nephropathy. Anuria (no urine) suggest urinary tract obstruction until it proved otherwise; bladder outflow obstruction must always be considered first. Polyuria: Polyuria is a persistent, large increase in urine output, usually associated with nocturia. It must be distinguished from frequency of micturition with the passage of small volumes of urine. Documentation of fluid intake and output may be necessary. Polyuria is the result of an excessive (hysterical) intake of water, an increased excretion of solute (as in hyperglycemia and glycosuria), or a defective renal concentrating ability or failure of production of ADH. Bibliography Kumar P, Clark M. Renal Disease In: Clinical Medicine, 5th ed. W.B Saunders, 2001, pp: 593-4 The Body Fluid Compartments: Extracellular and Intracellular fluids;interstitial Fluid and edema pp: 264-5

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He also complained of shortness of breath, weakness, and fatigue and according to his family sometimes he looked delirious. It occurred one day before he was admitted to the hospital His physical examination revealed a male who is delirious. Blood pressure of 90/60 mmHg, a small pulse 120x/mnt, a deep and rapid respiration of 34x/mnt and a temperature of 37.5 C. he is not anaemic, no sign of pulmonary rales, no enlargement of the heart with a regular tachycardia heart rate. His belly is flat and smooth with a reduced elasticity skin together with reduced elasticity skin of both legs.

1. What are the further problems of this patient? Short of breath with rapid and deep respiration rate Weakness, fatigue, delirious Low blood pressure Rapid and weak/small pulse rate Reduced elasticity of the skin 2. Confirm your hypothesis ! Dyspnea (Kussmaul Breathing) Hypotension Rapid and weak/small arterial pulse Pathogenesis of hypovolemic shock and dehydration

3. What further information do you need? Justify your rationale

Guiding questions for student : 1. Define Short of breath (Dyspnea) and types of respiration 2. Define Hypotension 3. Define rapid and small or weak arterial pulse 4. Define Shock and describe the classification of shock based on cause 5. Describe the pathogenesis of hypovolemic shock

Answer :

1.

Define Short of breath (Dyspnea) and types of respiration:

Dyspnea: Dyspnea is the patient's subjective awareness of discomfort associated with ventilatory effort. Dyspnea refers to a non-painful but uncomfortable awareness of breathing that is inappropriate to the circumstances. Only the patient can report dyspnea. An observer may notice abnormally rapid or deep breathing, but this cannot be equated with the subjective sensation. Dyspnea commonly results from cardiac or bronchopulmonory disease but also frequently accompanies anxiety. Many lung diseases result in increased respiratory effort per unit volume air. The sensation of dyspnea is particularly likely when mechanical impairment to respiratory movements or stiffening of the lung is present (decreased compliance). Decreased oxygen supply to the body tissues is due to diffusion impairment or ventilatory-perfussion imbalance, accumulation of carbon dioxide, or acid shifts of blood pH cause minute ventilation to increase, producing dyspnea. Striking increases in rate and depth of respiration, however, may occur without the patients complaining of dyspnea, as in metabolic acidosis. The normal respiratory rate is about 14-20 per minute in normal adults and up to 44 per minute in infants. Abnormality in rate and rhythm of breathing: rapid shallow breathing Rapid deep breathing (hyperpnoe, hyperventilation): rapid and deep breathing also has a number of causes, including exercise, anxiety, and metabolic acidosis. In the comatose patient, infarction, hypoxia, or hypoglycemia affecting the midbrain or pons should be considered. Kussmaul Breathing is deep breathing associated with metabolic acidosis. It may be fast, normal in rate, or slow slow breathing Cheyne-Stokes breathing Ataxic breathing (Biot`s breathing) Sighing respiration Obstructive breathing

Bibliography: Barbara Bates, An approach of symptoms and Abnormalities in rate and rhythm of breathing In: A Guide To Physical Examination and History Taking 5th ed.J.B Lippincott Company. 1991 pp: 74, 256 Delp, Manning Examination of the chest In: Major`s Physical Diagnosis An introduction to the Clinical Process 9th ed. W.B Saunders Company Philadelphia, 1981 PP: 191.

2. Define Hypotension: Hypotension or low blood pressure results from either a decrease in cardiac output or a decrease in peripheral resistance. A decreased in cardiac output occurs in Addison`s disease, myocarditis, myocardial infarction, and pericarditis with effusion; it may also follow hemorrhage, depletion of blood volume. A sudden decrease in peripheral resistance (vasomotor collapse) may occur in pneumonia, septicemia, acute adrenal insufficiency (Waterhouse-Fredrichsen syndrome), and drug intoxication. The fall in blood pressure on standing may be sufficient magnitude to produce cerebral ischemia and syncope. This orthostatic hypotension is common in severely anemic persons and in the elderly patients with severe atherosclerosis who are unable to respond quickly to a sudden change in body position. It may be a sign of disordered autonomic regulation in the Shy-Drager syndrome

3. Define rapid and small or weak arterial pulse: The arterial pulse may be describe most clearly in terms of the following characteristics: a. Rate b. Size c. Type of wave d. Rhythm e. Tension : rapid or slow : large or small : quick or prolonged : regular or irregular : hard or soft.

The average pulse rate in normal adults is 60-90 beats per minute, in chlidren 90-140, and in aged 70-80 beats per minute. Small and Weak arterial pulse: The pulse pressure is diminished, and pulse feels weak and small. The upstoke may feel slowed, the peak prolonged. Causes include: (1) decreased stroked volume as in heart failure, hypovolemia and severe aortic stenosis, (2) increased peripheral resistance, as in exposure to cold or severe congestive heart failure. Bibliography: Barbara Bates, An approach in abnormalities of arterial pulse In: A Guide To Physical Examination and History Taking 5th ed.J.B Lippincott Company. 1991 pp: 308-9 Delp, Cardiovascular system In: Major`s Physical Diagnosis An introduction to the Clinical Process 9th ed. W.B Saunders Company Philadelphia, 1981 PP: 237-245

4. Define Shock and describe the classification of shock based on cause: Definition of shock: Shock may be define as the state in which profound and widespread reduction in the effective delivery of oxygen and other nutrients to tissue leads first to reversible and then, if prolonged, to irreversible cellular injury

Classification of shock based on cause: Oligemic or hypovolemic shock Cardiogenic shock Extracardiac obstructive shock Distributive shock (See figure 34-1 Joseph.E P Shock, The pathogenesis of shock in human. In : Harrison`s Principles of Internal Medicine, Isselbacher, Braunwald , Wilson et al editors, 13th ed. McGraw-Hill, Inc New York .1994 pp: 187-192)

5. Describe the pathogenesis of hypovolemic shock: Hemorrhage or large loss of fluid secondary to vomiting, diarrhea, burns or dehydration leads to inadequate ventricular filling i.e., to severely decreased preload, reflected in decreased left and right ventricular end-diastolic volumes and pressures. This changes leads to shock by causing an inadequate stroke volume and inadequate cardiac output. Loss of fluid from all fluid compartments of the body is called dehydration; this too can reduce blood volume and cause hypovolemic shock similar to that resulting from hemorrhage. Some of the causes of this type of shock are (1) excessive sweating, (2) fluid loss in vomiting and diarrhea, (3) excess loss of fluid by nephrotic kidneys, (4) inadequate intake of fluid and electrolytes, and (5) destruction of the adrenal cortices, with consequent failure of the kidneys to reabsorb sodium chloride, and water, which occur in the absence of the adrenocortical hormone aldosterone. Bibliography: Joseph.E P Shock, The pathogenesis of shock in human. In: Harrison`s Principles of Internal Medicine, Isselbacher, Braunwald, Wilson et al editors, 13th ed. McGraw-Hill, Inc New York .1994 pp: 187-192)

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Laboratory findings: Haemoglobin level: 15,6 gr./dl, Hematocrit: 50%, White blood cell: 10.000/ mm3, serum urea level of 180 mg/dl, serum creatinine level of 5,3 mg/dl, serum potassium level of 7 meq/L, serum sodium level of 145 meq/L, Blood gas analysis : ph 7.245, pO2 94 cmH2O, HCO3 -: 7 meq/L. His urine analysis has no sediments or cast and no proteinuria. Stool analysis showed no erythrocytes, parasites but viewed only a few leukocytes EKG : tall and peak T wave and widening QRS complex

1. What is the significance of this laboratory test according to the clinical and physical examination of this patient? High range of hematocrit High level of serum ureum and creatinine concentration High level of serum potassium Low bicarbonate level

2. What is the diagnosis of this patient? Acute Renal Failure or prerenal azotemia because of volume depletion Hyperkalemia Metabolic acidosis

3. Are there other modalities or test to diagnose the patient? Radionuclide scan : to assess abnormal renal perfusion

4. What is the management plan for this patient?

Guiding questions for student : 1. Define Acute Renal failure 2. Define the phases of ARF and each clinical manifestation 3. What are the causes of ARF 4. Describe the normal potassium homeostasis 5. Describe factors can cause hyperkalemia by shifting potassium out of cells 6. Describe electrocardiographic changes occur in patient with hyperkalemia 7. Describe some signs and symptoms of hyperkalemia 8. Desribe the physiological Aspects of Acid Base Balance 9. Define the meaning of pH and how can I translate pH to free H+ 10. How can you adapt the Henderson Hasselbach equation foe clinical practice 11. Describe three major processes that can result in a metabolic acidosis 12. Describe the guidelines for treatment of prerenal azotemia (ARF) Answer :

1. Define Acute Renal failure: Acute renal failure (ARF) means abrupt deterioration in parenchymal renal function which is usually, but not invariably, reversible over a period of days and weeks. In clinical practice, such deterioration in renal function is sufficiently severe to result in uremia. Oliguria is usually but not invariably a feature. ARF may cause sudden, life threatening biochemical disturbances and is a medical emergency. Renal failure results in reduced excretion of nitrogen waste products of which urea is the commonly measured.

2. Define the phases of ARF and each clinical manifestation Oliguria Phase: Occurs within hours or days after the circulatory failure or nephro-toxicity. The duration will maintain for 1-2 weeks, if it is prolonged for more than 4 weeks , it should always consider to diagnose acute tubular necrosis. The volume urine production is about 150 mL/day and total anuria seldom exist Biochemical changes during oliguria state: increased serum urea and creatinine, hyponatremia because of vomiting and nausea, thirsty (dilutional hyponatremia), severe hyponaterima can cause peripheral edema, brain edema, and acute pulmonary edema. Brain edema causes uremic convulsion and cardiac arrhythmia Hyperkalemia is more prominent in this phase and can caused cardiac arrest or ventricular fibrillation. Acidosis occurs because of fixed acid generation from 50-100 mEq/day and causes kussmaul breathing (rapid and deep).

Diuretic Phase: During this early diuretic phase, the renal function is still impaired, the blood urea and creatinine is increased although the urine volume production is raised 1-3 L/day. This phase maintain for 5-10 days. This phase will be follow by the late diuretic phase, with 6 L/day of urine volume production. At this stage the urine osmolarity will equals

plasma osmolarity (280-295 mOsm/L) and it is called isostenuria. The urine spesific gravity will reach 1.010. Convalescence Phase: The renal function improvement will last for about 3-12 months depend to the patient`s age. In the older patients this phase will persist for years and the ability to concentrate and acidification of the urine is still impaired because of tubular cell dysfunction.

3. What are the causes of ARF:

Prerenal Causes: Prerenal ARF is rapidly reversible if the underlying cause is corrected. In the outpatient setting, vomiting, diarrhea, poor fluid intake, fever, use of diuretics and heart failure are all common causes Postrenal Causes: ARF occurs when boyh urinary outflow tracts are obtructed or when one tract is obstructed in a patient with a single functional kidney. Obstruction is commonly due to prostatic hypertrophy, cancer of the prostat or cervix or retroperitoneal disorders. It could also be intraluminal, such as bilateral renal calculi, papillary necrosis, coagulated blood, bladder carcinoma. Intrinsic Causes: Intrinsic renal diseases that result in ARF are categorized according to the primary site of injury: tubules, interstitium, vessels or glomerulus. Injury to the tubules is most often ischemic or toxin in origin (drugs)

DIAGNOSTIC EVALUATION OF THE PATIENT WITH ARF

4. Describe the normal potassium homeostasis: Total body potassium stores range between 3000 mmol and 4000 mmol. Approximately 98% of total body potassium are intracellular. Primarily the gastrointestinal tract and the kidneys regulate potassium absorption and excretion respectively. Extracellular potassium concentration also depends critically on shifts of the cation between the intraand extracellualr pool. As a corollary, hypokalemia or hyperkalemia do not necessarily reflect total body potassium stores. 5. Describe factors can cause hyperkalemia by shifting potassium out of cells: Insulin deficiency (hyperglycemia) Beta Blockade Metabolic acidosis Hypertonicity Muscle depolarizing agents such as succinylcholine Exercise

6. Describe electrocardiographic changes occur in patient with hyperkalemia: Initially peaked narrow T waves Subsequently prolonged p wave, PR prolongation, QRS widening, and ST segment elevation or depression Eventually cardiac standstill

Electrocardiogram in severe hyperkalemia. Note the widening of the QRS complex and the high peaked T waves compared to the normal tracing. The plasma potassium in this patient was 7.6 mmol/L

7. Describe some signs and symptoms of hyperkalemia:

Paresthesias Muscle weakness Cardiac arrest

8. Physiological Aspects of Acid Base Balance Source: Guyton and Hall, Textbook of Medical Physiology, 10th Ed., 2000, pp 346-363 Precise hydrogen ion regulation is essential because the activities of almost all enzyme systems in the body are influenced by hydrogen ion concentration. Therefore, changes in hydrogen concentration alter virtually all cell and body functions. Regulation of hydrogen ion balance is similar in some ways to the regulation of other ions in the body. However, precise control of extracellular fluid hydrogen ion concentration involves much more than simple elimination of hydrogen ions by the kidneys. There are three primary systems that regulate the hydrogen ion concentration in the body fluids to prevent acidosis or alkalosis, i.e. 1) the chemical acid-base buffer systems of the body fluids, which immediately combine with acid or base to prevent excessive changes in hydrogen ion concentration; 2) the respiratory center, which regulates the removal of CO2 (and, therefore H2CO3) from the extracellular fluid; and 3) the kidneys, which can excrete either acid or alkaline urine, thereby readjusting the extracellular fluid hydrogen ion concentration toward normal during acidosis or alkalosis. When there is a change in hydrogen ion concentration, the buffer systems of the body fluids react within a fraction of a second to minimize these changes. Buffer systems do not eliminate hydrogen ions from the body or add them to the body but only keep them tied up until balance can be re-established. The second line of defense, the respiratory system, also acts within a few minutes to eliminate CO2 and, therefore, H2CO3 from the body. These first two lines of defense keep the hydrogen ion concentration from changing too much until the more slowly responding third line of defense, the kidneys, can eliminate the excess acid or base from the body. Although the kidneys are relatively slow to respond, compared with the other defenses, they are over a period of hours to several days by far the most powerful of the acid-base regulatory systems. Buffer Systems There are at least three kinds of buffer system which play a role in acid-base balance, i.e. the bicarbonate buffer system, the phosphate buffer system and protein, an important intracellular buffer. The bicarbonate buffer system The bicarbonate buffer system consists of a water solution that contains two ingredients: 1) a weak acid, H2CO3 and 2) bicarbonate salt, such as NaHCO3. For the bicarbonate system, the pK is 6.1, and it is known the Henderson-Hesselbach equation to calculate the pH of a solution if the molar concentration of bicarbonate ion and the PCO 2 are known, as follow: pH = 6.1 + log HCO30.03XPCO2 The bicarbonate buffer system can not be expected to be the most powerful for two reasons: First, the pH of the extracellular fluid is about 7.4, whereas the pK of the

bicarbonate buffer system is 6.1. This means that there is about 20 times as much of the bicarbonate buffer system in the form of HCO3- as in the form of dissolved CO2. For this reason, this system operates on the portion of the buffering curve where the slope is low and the buffering power is poor. Second, the concentrations of the two elements of the bicarbonate system, CO2 and HCO3-, are not great. Despite these characteristics, the bicarbonate buffer system is the most powerful extracellular buffer in the body. This apparent paradox is due maintly to the fact that the two elements of the buffer system, HCO3- and CO2, are regulated, respectively, by the kidneys and the lungs. As a result of this regulation, the pH of the extracellular fluid can be precisely controlled by the relative rate of removal and addition of HCO3- by the kidneys and the rates of removal of CO2 by the lungs. The phosphate buffer system Although the phosphate buffer system is not important as an extracellular fluid buffer, it plays a major role in buffering renal tubular fluid and intracellular fluids. The main elements of the phosphate buffer system are H2PO4- and HPO4--. The phosphate buffer system has a pKa of 6.8, which is not far from the normal pH of 7.4 in the body fluids; this allows the system to operate near its maximum buffering power. However, its concentration in the extracellular fluid is low, only about 8 per cent of the concentration of the bicarbonate buffer. Therefore, the total buffering power of the phosphate system in the extracellular fluid is much less than that of the bicarbonate buffering system. In contrast to its rather insignificant role as an extracellular buffer, the phosphate buffer is especially important in the tubular fluids of the kidneys for two reasons: 1) phosphate usually becomes greatly concentrated in the tubules, thereby increasing buffer power of the phosphate system, and 2) the tubular fluid usually has a considerably lower pH than extracellular fluid, bringing the operating range of the buffer closer to the pK (6.9) of the system. The phosphate buffer system is also important in buffering intracellular fluids because the concentration of phosphate in these fluids is many times that in the extracellular fluids. Also, the pH of intracellular fluid is lower than that of extracellular fluid and therefore usually closer to the pK of the phosphate buffer system, compared with the extracellular fluid. Proteins Proteins are among the most plentiful buffers in the body because of their high concentration, especially within the cells. Approximately 60-70 per cent of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins. However, except for the red blood cells, the slowness of movement of hydrogen ions and bicarbonate ions through the cell membranes often delays for several hours the maximum ability of the intracellular proteins to buffer extracellular acid-base abnormalities. Another factor besides the high concentration of protein in the cells that contributes to their buffering power is the fact that the pKs of many of these protein systems are fairly close to 7.4. Respiratory role in acid-base balance

The second line of defense against acid-base disturbances is control of extracellular fluid CO2 concentrations in the lungs. An increase in ventilation eliminates CO2 from extracellular fluid, which, by mass action, reduces the hydrogen ion concentration. Conversely, decreased ventilation increases CO2, thus also increasing hydrogen ion concentration in the extracellular fluid. In general, the overall buffering power of the respiratory system is one to two times as great as the buffering power of all other chemical buffers in the extracellular fluid combined. That is, one to two times as much acid or base can normally be buffered by this mechanism as by the chemical buffers. Renal control of acid-base balance The kidneys control acid-base balance by excreting either an acidic or a basic urine. Excreting an acidic urine reduces the amount of acid in extracellular fluid, whereas excreting a basic urine removes base from the extracellular fluids. The overall mechanism by which the kidneys excrete acidic or basic urine is as follows: Large numbers of bicarbonate ions are filtered continuously into the tubules, and if they are excreted into the urine, this removes base from the blood. Large numbers of hydrogen ions are also secreted into the tubular lumen by the tubular epithelial cells, thus removing acid from the blood. If more hydrogen ions are secreted than bicarbonate ions are filtered, there will be a net loss of acid from the extracellular fluids. Conversely, if more bicarbonate ions are filtered than hydrogen ions are secreted, there will be a net loss of base. The body produces each day about 80 milliequivalents of nonvolatile acids, mainly from the metabolism of proteins. These acids are called nonvolatile because they are not H2CO3 and, therefore, cannot be excreted by the lungs. The primary mechanism for removal of these acids from the body is by renal excretion. The kidneys must also prevent the loss of bicarbonate in the urine, a task that is quantitatively more important than the excretion of nonvolatile acids. Each day the kidneys filter about 4320 milliequivalents of bicarbonate (180 L/day x 24 mEq/L), and under normal conditions, almost all of this is reabsorbed from the tubules, thereby conserving the primary buffer system of the extracellular fluids. Both the reabsorption of bicarbonate and the excretion of hydrogen ions are accomplished through the process of hydrogen ion secretion by the tubule. Because the bicarbonate ion must react with a secreted hydrogen ion to from H2CO3 before it can be reabsorbed, 4320 mEq of hydrogen ions must be secreted each day just to reabsorbed the filtered bicarbonate. Then an additional 80 mEq of hydrogen ions must be secreted to rid the body of the nonvolatile aids produced each day, for a total of 4400 mEq of hydrogen ions secreted into the tubular fluid each day. In addition to secretion of hydrogen ions and reabsorption of filtered bicarbonate ions, the kidneys have also capability in producing new bicarbonate ions to regulate extracellular hydrogen ion concentrations.

9. Define the meaning of pH and how can you translate pH to free H+

pH is the negative logarithm of the hydrogen ion concentration of a solution, expressed in equivalents per liter. The concentration of free hydrogen ion in body fluids is approximately 40 X 10 -9 Eq/L or 40 nEq/L. This corresponds to a pH of approximately 7.40. The number of free hydrogen ions per liter of body fluid can be calculated using the following approximation: A pH of 7.00 equals 100 nEq/L. Foe every 0.10 increase in pH the corresponding H+ number is 80% of the preceding value. For example at a pH 7.10, H+ = 80 nEq/L, at pH 7.20, H+ = 64 nEq/L

10. How can you adapt the Henderson Hasselbach equation for clinical practice: H+= 24 X pCO2 / HCO3 If one knows two of the three variables in the equation, the third can be calculated, allowing quick bedside assesment of acid base disorders

11. Describe three major processes that can result in a metabolic acidosis: Acid production in excess of the kidneys ability to excrete th acid and regenerate bicarbonate Decreased ability of a diseased kidney to excrete acid and generate bicarbonate Loss of bicarbonate from extracellular fluid through either kidneys or the gastrointestinal tract. 12. Describe the guidelines for treatment of prerenal azotemia (ARF): Restore the normal circulating blood volume. In the absence of heart failure, administration of fluids (usually normal saline) at the rate of 75-100 ml/hr is adequate. The type of fluid administered and the rate at which replacement fluids are given will depend on the serum electrolytes (especially serum sodium, potassium, and the acid base status of the patient) and the clinical status of the patient Monitor the adequacy of fluid replacement by clinical examination of the patient and by serial determinations of serum creatinine concentrations, which reflect renal function. Follow daily weight, fluid intake, and urine output, as well as urine sodium excretion and serial measurements of serum creatinine, urea, serum electrolytes, and acid base parameters. Hemodynamic monitoring may be necessary if clinical assessment of cardiovascular function and fluid status is difficult. Response to proper fluid replacement in prerenal azotemia is rapid, renal function usually returns to previous baseline within 3-4 days.

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After the diagnose was established as Acute Renal Failure because of volume depletion, this patient was given intravenous crystalloid fluid to restore his renal function and correction of hyperkalemia and metabolic acidosis

1. In case of treatment failure what are the other management possibilities ? Renal replacement therapy : hemodialysis or acute peritoneal dialysis

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Epilog : Good rehydration treatment with crystalloid fluid, management of metabolic acidosis, and hyperkalemia save Mr Arif renal function and he doesn't have to be dialysed.