Kidney Function 5

Metabolic reactions are sensitive to what?

Free H+ concentration of solutions in which they occur (reactions are catalysed by enzymes/proteins which change shape/function depending on H+ conc.)

1 of 76

Most enzymes have an optimum pH of what?

7.35-7.45 (narrow range) - also pH of ECF

2 of 76

To maintain ECF pH what must the body ensure?

Any metabolic acid produced + H+ intake is balanced by acid excretion

3 of 76

What are the possible sources of H+ gained by the body?

Generation of H+ ions from carbon dioxide. Production of non-volatile acids from metabolism of protein/other organic molecules. Gain of H+ ions due to loss of CO3- in diarrhoea/other non-gastric GI fluids. Gain H+ due to loss of CO3- in urine

4 of 76

What are the possible sources of H+ lost by the body?

Utilisation of H+ ions in metabolism of various organic ions. Loss of H+ ions in vomitus. Loss of H+ ions in urine. Hyperventilation

5 of 76

As a result of oxidative metabolism, how much carbon dioxide is added to the blood?

20,000 mmol

6 of 76

Describe the reaction between carbon dioxide and water

Carbon dioxide and water (with carbonic acid enzyme) produce carbonic acid which dissociates to form bicarbonate ions and H+ ions (doesn't cause net gain of H+, when passing through lungs (returns to CO2)

7 of 76

What is hypoventilation?

Carbon dioxide not breathed off (gain H+ ions)

8 of 76

What is hyperventilation?

Carbon dioxide breathed off (loss H+ ion)

9 of 76

Give examples of non-respiratory acids?

Sulphuric acid, phosphoric acid and lactic acid (production balanced by H+ in organic metabolism). Eating meat causes net gain of H+ ions (high protein diet - 40-80 mmol H+/day gained)

10 of 76

How does the loss of bicarbonate (e.g. diarrhoea) affect the reaction between carbon dioxide and water?

Loss of bicarbonate. Reaction to H+ becomes irreversible (can't be breathed off, body gains H+)

11 of 76

How does the loss of acid (e.g. vomitus) affect the reaction between carbon dioxide and water?

Loss of H+. Reaction to HCO3- becomes irreversible (reaction can't move to the left to CO2/carbon dioxide cannot be breathed off)

12 of 76

What is pH?

-log [H+]

13 of 76

What is normal plasma pH?

7.35-7.45 (equivalent to 35-45 nM H+/plasma acid levels regulated at nM level but acid production in mM range). pH only measured concentration of free H+ ions in solution

14 of 76

What are respiratory acids?

Acids which can be breathed off. Carbon dioxide production (oxidative metabolism) excreted by lungs

15 of 76

What are non-respiratory acids?

Other acids (e.g. phosphoric acid) excreted by kidneys

16 of 76

Why are buffers required?

To prevent huge swings in free [H+] concentration

17 of 76

What is the general form of buffering reaction?

Buffer + H+ = HBuffer (increase H+, reaction goes to the right, decrease H+, reaction goes to left)

18 of 76

Physiologically what is the most important buffer?

The bicarbonate system (HCO3- + H+ = H2CO3). Carbonic acid can dissociate to form carbon dioxide and water

19 of 76

Give examples of buffers in the blood

Bicarbonate, Hb, plasma proteins (minor)

20 of 76

Give examples of buffers in the interstitial fluid

Bicarbonates, very little protein

21 of 76

Give examples of buffers in the ICF

Intracellular proteins, phosphates, a little bicarbonate

22 of 76

Give examples of buffers in urine

Phosphate and ammonia

23 of 76

What is the pH inside cells?

<7.35. Cytosol has pH of 7.2. Organelles have lower pH (apart from mitochondria which has a pH of 8)

24 of 76

pH of a buffer solution is determined by what? (1)

The Henderson Hasselbach equation: pH = pK + (log [HCO3-]/[H2CO3]). Carbonic acid is proportional to the partial pressure of carbon dioxide due to carbon dioxide + water = carbonic acid. Able to replace carbonic acid in equation with pCO2

25 of 76

pH of a buffer solution is determined by what? (2)

(pCO2 easier to measure than carbonic acid). Henderson Hasselbach equation allows calculation of any one of pH, pCO2 and [HCO3-] if the other two variables are known. Buffer effectiveness depends on concentration and pK

26 of 76

What is pK?

-log of dissociation constant of Hbuffer

27 of 76

Qualitatively body pH is proportional to what?

[HCO3-]/pCO2

28 of 76

What are the normal plasma values?

P arterial CO2 = 5.3 kPa (4.0-6.0 kPa). Arterial [HCO3-] = ~25 mM (19-24 mM). Venous [HCO3-] = ~25 mM (22-28 mM). Arterial pH = 7.4 (7.35 - 7.45)

29 of 76

pK of a buffer equals what?

pH when the acid is half dissociated

30 of 76

What are the pK values of the main buffers?

Protein (His residues) ~6. Ammonia 9.2. Phosphate 6.8. Bicarbonate 6.1. Urate 5.8. Citrate 5.5. Different buffers accept or donate hydrogen at different pHs

31 of 76

How is the ratio of acid:base regulated? (1)

Bicarbonate dealt with by the kidney. pCO2 dealt with by the lungs. Advantage of HCO- buffer - addition of acid causes pCO2 to rise (drives respiration to increase elimination of CO2 from the body)

32 of 76

How is the ratio of acid:base regulated? (2)

HCO3- effective but short term measure (eventually run out of HCO3-). Kidney can reabsorb bicarbonate/can rid body of excess H+. Urine pH is acid (but can range 4.4-4.8, depend on diet)

33 of 76

Describe features of renal acid-base handling (1)

HCO3- freely filtered. Reabsorbed at: proximal tubule, ascending limb of the loop of Henle, cortical collecting ducts (intercalated cells type A). All HCO3- reabsorbed before filtrate reaches distal tube usually

34 of 76

Describe features of renal acid-base handling - HCO3- (2)

80% of bicarbonate reabsorbed in proximal tubule. H2O + CO2 (carbonic anhydrase, isoform 2), form carbonic acid, dissociate to form H+ and HCO3- (in tubular epithelial cell)

35 of 76

Describe features of renal acid-base handling - HCO3- (3)

HCO3- leaves cell via transporter (HCO3-/Cl exchanger and HCO3-/Na co-transporter) into interstitial fluid and enters blood via peritubular capillaries

36 of 76

Describe features of renal acid-base handling - HCO3- (4)

H+ secreted into lumen of tubule (via Na-H counter-transporter, H-ATPase pumps, H-K ATPase pumps) into filtrate, combines with HCO3- (carbonic acid - water and CO2 which can passively diffuse into cell (cycle repeats)

37 of 76

Describe features of renal acid-base handling - HCO3- (5)

HCO3- crossing basolateral membrane is not the same as HCO3- crossing luminal membrane (still called HCO3- reabsorption). H+ secreted not excreted if HCO3- available in lumen

38 of 76

Carbonic anhydrase catalysis the reaction of what?

H2O dissociates to form OH- and H+. OH- + CO2 <-> HCO3- (step skipped in the water and carbon dioxide reaction equation)

39 of 76

Describe features of renal acid-base handling - H+ excretion (1)

Occurs in combination with non-bicarbonate buffer e.g. monohydrogen phosphate (HPO4 2-). Unbuffered H+ would lower urine pH < 5. Results in addition of new HCO3- to plasma

40 of 76

Describe features of renal acid-base handling - H+ excretion (2)

CO2 + H2O (carbonic anhydrase 2) - carbonic acid - H+ and HCO3-. H+ combined with HPO4 2- to form H2PO4- which can be excreted

41 of 76

What is an additional mechanism that adds new HCO3- to plasma? (1)

Glutamine (synthesised by liver, added to the blood, freely filtered by renal corpuscle, enters interstitial fluid surrounding peritubular capillaries). Glutamine enters both sides of tubular epithelial cell

42 of 76

What is an additional mechanism that adds new HCO3- to plasma? (2)

Filtered glutamine passed into cell via Na co-transporter. On basolateral membrane, glutamine passed onto cell in exchange for amino acid (LAT2). Glutamine is metabolised to form NH4+ and HCO3-. New HCO3- added to interstitial fluid (pass into blood)

43 of 76

What is an additional mechanism that adds new HCO3- to plasma? (3)

NH4+ counter transported out of cell in exchange for Na. NH4+ (no passive diffusion in cells) could be considered as NH3+ (passive diffusion into cells)and H+

44 of 76

How is acid-base status regulated by chemical buffers?

Works in seconds, bicarbonate in ECF, phosphate in ICF, phosphate or ammonia in urine

45 of 76

How is acid-base status regulated by the brainstem respiratory centre?

Works in minutes, responds to changes in arterial pCO2, pO2 and [H+], adjust ventilation to retain or expel CO2

46 of 76

How is acid-base status regulated by the renal mechanisms?

Works in hours-days, for each H+ secreted, HCO3- reabsorbed

47 of 76

What is acidosis?

pH < 7.35

48 of 76

What is alkalosis?

pH > 7.45

49 of 76

What is respiratory acidosis or alkalosis?

Caused by respiratory problem. Acidosis (decrease pH, increase pCO2, HCO3 normal). Alkalosis (increase pH, decrease pCO2, normal HCO3)

50 of 76

What is metabolic acidosis or alkalosis?

Caused by non-respiratory problem. Acidosis (decrease pH, pCO2 normal, decrease HCO3). Alkalosis (increase pH, pCO2 normal, increase HCO3)

51 of 76

What is the [HCO3-] altered by?

Metabolic disorders

52 of 76

What is the [pCO2] altered by?

Respiratory disorders

53 of 76

How does the body compensate for changes in pH?

When a primary acid-base disorder exists, the body attempts to return the pH to normal

54 of 76

Describe features of respiratory acidosis

Caused by insufficient CO2 excretion by the lungs (alveolar hypoventilation). Patient likely to be hypoxic (low pO2) as well. Correction cannot come from respiratory change

55 of 76

What is acute respiratory acidosis?

pCO2 > 5.3 kPa, pH < 7.35. Abrupt failure in ventilation. Drug-induced respiratory depression e.g. narcotic, barbiturates. Airway disorders e.g. asthma

56 of 76

What is chronic respiratory acidosis?

pCO2 < 5.3 kPa, pH < 7.35, HCO3 > 30 mM. Secondary to many disorders (airway obstruction e.g. COPD, lung damage e.g. fibrosis, chest wall disorders e.g. pectus carinatum, neuromuscular disorders e.g. amyotrophic lateral sclerosis)

57 of 76

What is the response from chemical buffers towards respiratory acidosis?

Chemical buffers (works in seconds). Some retained CO2 converted to HCO3- by reaction of CO2 and H2O (plasma [HCO3-] increases). Result buffer attenuates arterial pCO2 increases (>5.3 kPa)

58 of 76

What is the response from the brain respiratory centre towards respiratory acidosis?

Works in minutes. Adjusts ventilation to expel CO2. However ventilation is an issue therefore correction cannot come from a respiratory change

59 of 76

What is the response from renal mechanisms towards respiratory acidosis?

Works in hours-days. For each H+ secreted, HCO3- reabsorbed. Metabolise glutamine to excrete excess H+ (as ammonium), increase plasma HCO3-, urine is highly acidic (pH of 4.4). Renal compensation for respiratory acidosis

60 of 76

Describe features of metabolic acidosis (1)

pH < 7.35. Characterised by a fall in plasma bicarbonate concentration

61 of 76

Describe features of metabolic acidosis (2)

True HCO3- deficit (normal anion gap), kidney/GI e.g. renal tubular acidosis, diarrhoea

62 of 76

Describe features of metabolic acidosis (3)

H+ gain (increased anion gap), exogenous acid, abnormal lipid metabolism, abnormal carbohydrate metabolism, normal protein metabolism e.g. NH4Cl administration, toxins, diabetic ketoacidosis (also true HCO3), lactic acidosis, uremic acidosis

63 of 76

Describe the compensation for metabolic acidosis (1)

Chemical buffer (initial increase in blood H+ causes [HCO3-] to fall and pCO2 to rise due to reaction of H2CO3 (equation). Blood H+ increase so pH decreases and this will lead to reduction of [HCO3-]

64 of 76

Describe the compensation for metabolic acidosis (2)

Respiratory (pCO2 decreased due to CO2 being breathed off) and renal compensation for (non-renal) metabolic acidosis (metabolise glutamine to get new HCO3- in blood, not returned to normal)

65 of 76

Describe features of respiratory alkalosis

Caused by excessive central respiratory drive (e.g. aspirin overdose, fever, brainstem damage) or hypoxia stimulation (e.g. response to altitude, hysterical hyperventilation, pulmonary embolism). Excess CO2 lost/lungs, pCO2 falls (<5.3 kPa/hyocapnia)

66 of 76

What is the response from chemical buffers towards respiratory alkalosis?

[HCO3-] decreases as some of it reacts to produce CO2, both HCO3- and H+ decrease (pH rises). Equation for H2CO3 shifts to the right

67 of 76

What is the respiratory compensation for respiratory alkalosis?

If possible, reduce ventilation

68 of 76

What is the renal compensation for respiratory alkalosis? (1)

Kidney responds to fall in pCO2 with reduction in H+ secretion into tubules. Insufficient H+ to ensure reabsorption of all HCO3- in filtrate and HCO3- is excreted in urine which is alkaline (pH 7.4)

69 of 76

What is the renal compensation for respiratory alkalosis? (2)

End result is pCO2 is still low, pH high and [HCO3-] low but changes smaller than they would be otherwise

70 of 76

Describe features of metabolic acidosis

Characterised by pH > 7.45 with high plasma [HCO3-]. Caused by repeated vomiting (loss of acid acid), excess aldosterone (hyperaldosteronism stimulates tubule H+-ATPase pump), excess alkali ingestion (HCO3 or citrate/lactate metabolised to HCO3)

71 of 76

What is the response from chemical buffers towards metabolic alkalosis?

Increase plasma [HCO3-], increase pH, no direct rise in pCO2 because the H2CO3 reaction needs to change H+ by a few nM

72 of 76

What is the respiratory compensation for metabolic alkalosis?

Before rise in pH should inhibit respiration, causing CO2 to be retained in the body. But resulting hypoxia will continue to stimulate respiration

73 of 76

What is the renal compensation for metabolic alkalosis?

Kidneys should excrete excess bicarbonate. Correction mechanisms should help to reduce increase in pH

74 of 76

Describe HCO3- secretion in type B intercalated cells (renal compensation)

Type B cells function in metabolic alkalosis. Pendrin transporter used (expressed on luminal membrane). HCO3 enters filtrated in exchange for Cl. HCO3 excreted in urine

75 of 76

Glutamine synthesised in the liver is affected by what?

The pH of the blood (acidosis - liver increases glutamine production, alkalosis - liver reduces glutamine production)

76 of 76

Get Revising

Kidney Function 5

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Similar Pharmacy resources:

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Related discussions on The Student Room

Similar Pharmacy resources: