Renal lecture 4 Kidney & acid-base balance

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1 Renal lecture 4 Kidney & acidbase balance

2 AcidBase Balance Refers to precise regulation of free H + concentration in body fluids Acids Group of H + containing substances that dissociate in solution to release free H + and anions Bases Substance that can combine with free H + and remove it from solution ph Designation used to express the concentration of H + ph 7 neutral ph less than 7 acidic ph greater than 7 basic

3 AcidBase Balance Arterial ph less than 6.8 or greater than 8.0 is not compatible with life Acidosis Exists when blood ph falls below 7.35 Alkalosis Occurs when blood ph is above 7.45 Plasma hydrogen conc = 40 nmol/l

4 ph

5 AcidBase Balance Consequences of fluctuations in ph Changes in excitability of nerve and muscle cells Marked influence on enzyme activity Changes influence K + levels in body

7 Sources of H+ gain and loss H + Gain CO 2 in blood (combine with H 2 O via carbonic anhydrase) Nonvolatile acids from metabolism (e.g. lactic) Loss of HCO 3 in diarrhoea or nongastric GI fluids Loss of HCO 3 in urine H + Loss Loss of H + in vomit Loss of H + in urine Hyperventilation (blow off CO 2 ) Loss of H + like gaining HCO 3 Loss of HCO 3 like gaining H +

8 Lines of Defense Against ph Changes Chemical buffer systems Respiratory system Kidneys

9 Chemical Buffer Systems Minimize changes in ph by binding with or yielding free H + First line of defense Body has four buffer systems H 2 CO 3, HCO 3 buffer system Primary ECF buffer for noncarbonic acids Protein buffer system Primary ICF buffer; also buffers ECF Hemoglobin buffer system Primary buffer against carbonic acid changes Phosphate buffer system Important urinary buffer; also buffers ICF

10 Carbonic Acid Bicarbonate Buffer System Respiratory component Renal component Carbonic anhydrase CO 2 + H 2 O H 2 CO 3 H + + HCO 3 Carbonic acid bicarbonate (H 2 CO 3 is a volatile acid as CO 2 exhaled ) ph = pka + log 10 [HCO 3 ] PCO 2

11 Kidneys Third line of defense against change in hydrogen ion concentration Kidneys require hours to days to compensate for changes in bodyfluid ph Control ph of body fluids by adjusting H + excretion HCO 3 excretion Ammonium excretion

12 CO 2 HCO 3 + H + HCO 3 H + : Phosphoric acid, NH 4 +

13 HCO3 reabsorption and H + secretion in PCT ATPase Na + K + HCO 3 Cl

14 Addition of new HCO 3 to plasma by secretion of H + When you use up filtered HCO 3 in tubule and still have excess H + (acidosis), then you must combine H + with another buffer e.g. HPO 4 2. Unusual since lots of HCO 3 in tubular fluid! Gives net gain of HCO 3 to plasma.

15 Addition of new HCO 3 to plasma by excretion of ammonium (NH 4+ ) Another way of adding HCO 3 to plasma by metabolising glutamine. Takes long time, usually only occurs in chronic acidosis e.g. diabetes. glutamine Glutamine deamination ammoniagenesis

16 AcidBase Imbalances Can arise from either respiratory dysfunction or metabolic disturbances Deviations divided into four general categories Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

17 The kidneys help remove excess chemicals from the blood. It is the kidneys that ultimately remove (from the body) H+ ions and other components of the ph buffers that build up in excess. Acidosis that results from failure of the kidneys to perform this excretory function is known as metabolic acidosis. However, excretion by the kidneys is a relatively slow process, and may take too long to prevent acute acidosis resulting from a sudden decrease in ph (e.g., during exercise). The lungs provide a faster way to help control the ph of the blood. The increasedbreathing response to exercise helps to counteract the phlowering effects of exercise by removing CO 2, a component of the principal ph buffer in the blood. Acidosis that results from failure of the lungs to eliminate CO 2 as fast as it is produced is known as respiratory acidosis.

18 Metabolic Acidosis Includes all types of acidosis other than those caused by excess CO 2 in body fluids Causes Severe diarrhea Diabetes mellitus Strenuous exercise Compensations Buffers take up extra H + Lungs blow off additional H + generating CO 2 Kidneys excrete more H + and conserve more HCO 3

19 Respiratory Acidosis Result of abnormal CO 2 retention arising from hypoventilation Possible causes Lung disease Depression of respiratory center by drugs or disease Nerve or muscle disorders that reduce respiratory muscle activity Holding breath Airway obstruction Compensations Chemical buffers immediately take up additional H + Kidneys are most important in compensating for respiratory acidosis

21 Metabolic Alkalosis Reduction in plasma ph caused by relative deficiency of noncarbonic acids Causes Vomiting Ingestion of alkaline drugs Compensations Chemical buffer systems immediately liberate H + Ventilation is reduced If condition persists for several days, kidneys conserve H + and excrete excess HCO 3 in the urine

22 Respiratory Alkalosis Primarily due to excessive loss of CO 2 from body as result of hyperventilation Possible causes Fever Anxiety Aspirin poisoning Physiologic mechanisms at high altitude Compensations Chemical buffer systems liberate H + If situation continues a few days, kidneys compensate by conserving H + and excreting more HCO 3

24 Patient evaluation The presence of an acidbase disturbance may be suspected on the basis of clinical presentation or by results of laboratory data (eg, a low HCO3). Evaluation of any acidbase disorder can then be approached in a stepwise manner ACIDBASE Parameters

25 Problem? A patient is found to have an arterial ph of 7.25, a plasma [HCO 3 ] of 14mM and a pco 2 of 33 mmhg. What acidbase disturbance is present?

26 Eggs, oily fish Vit D and the kidney conversion of Vit D to calcitriol Enhances Ca2+ absorption Increases Ca2+ in plasma Renal hydroxylase rickets

27 Kidney, bone and calcium balance 99% of Ca2+ in bone PTH parathyroid hormone Calcitonin thyroid gland [Ca2+]plasma ~2mmol/L

Acid/Base Homeostasis (Part 3)

Acid/Base Homeostasis (Part 3) Graphics are used with permission of: Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com) 27. Effect of Hypoventilation Now let's look at how the