Acid-Base Physiology IV :-)

What causes Respiratory Alkalosis?

1. Anxiety/Panic 2. Hypoxemia(High Altitude) 3. Salicylates 4. Tumor 5. Pulmonary Embolism 6. Mechanical Ventilation a) So if the setting is TOO HIGH and it is breathing too fast for us --> Resp. Alkalosis

What are the clinical manifestations of Gitelman Syndrome?

1. Arm/Leg Cramping 2. Polyuria

What is Respiratory Acidosis?

1. Caused by hypoventilation (which results in retention of CO2), due to impaired pulmonary excretion of CO2

So then how do we treat Hyperaldosteronism?

1. Correction of hypokalemia may partially correct alkalosis -This make sense because then we are no longer stimulating the luminal H+ K+ ATPase 2. Surgical removal of the tumor secreting mineralocorticoid 3. Administration of aldosterone antagonist (spironolactone)

What is happening to Urine pH in Fanconi?

1. DECREASED (Below 5.5) Key Players: a) Alpha Intercalated Cells b) Aldosterone Why? 1. Remember that this is happening in the PROXIMAL Tubule.. 2. Alpha intercalated cells in the DISTAL Tubule are still in tact 3. --> Throwing in H+ --> ACIDIC PEE 4. Also, note that ALDOSTERONE is high... 5. --> Stimulation of H+ ATPase

What is the Type IV Renal Tubular Acidosis location?

1. DISTAL TUBULE

What is the pathophysiology of Type I Bartter Syndrome?

1. Defect in Na+/K+/2Cl- in Thick Ascending Limb 2. --> DECREASE of Ca, K+, Na+ Reabsorption 3. --> Macula Densa Cells Sense it 4. --> HYPERRENEMIA 5. --> Increased Prostaglandin Production --> DILATION of Afferent 5. --> Increased ALDOSTERONE 6. --> HYPOKALEMIA --> Stimulated H+/K+ ATPase 7. --> INCREASED H+ Secretion 8. --> INCREASED HCO3- Reabsorption 9. --> METABOLIC ALKALOSIS!!

What causes Type IV Distal Renal Tubular Acidosis?

1. Diabetic nephropathy, -due to low renin secretion with loss of kidney function (hyporeninism). 2. Drugs that inhibit RAAS -ACEinhibitors, angiotensin II receptor blockers (ARBs), spironolactone, and aliskiren (renin inhibitor) -Remember inhibiting RAAS DECREASES Aldosterone 3. Hypovolemia 4. SLE 5. Lithium/Amphotericin -Make cells more permeable

What is Respiratory Alkalosis?

1. Due to decrease in PCO2 via increased alveolar ventilation (hyperventilation) 2. --> Rapid shallow breathing blows off too much CO2 (CO2 lost, decreased PCO2, and increased pH) -Remember: Whenever we are talking about Acid-Base disorders and the word 'RESPIRATORY' is involved... --> Think CO2 problems

What is Bartter Syndrome similar to?

1. Effects of loop diruetics

So in the entire mechanism of Volume Contraction Alkalosis, what are the MOST critical factors?

1. Elevated Aldosterone 2. Hypokalemia

What Conditions are associated with Type II Proximal Tubular Acidosis? What do they all have in common?

1. Fanconi Syndrome 2. Multiple Myeloma NOTE: They ALL involve a general defect in the proximal tubular transport processes and carbonic anhydrase inhibitors

What is metabolic acidosis?

1. GAIN of H+ or LOSS of HCO3- 2. Remember that the point here is the CONCENTRATION of HCO3 and whether that goes up or down

What is the pathophysiology of Liddle Syndrome?

1. GAIN of function mutation in the ENAC 2. ↑ Na+ reabsorption in the late distal tubule and collecting duct 3. --> Pushing K+ OUT into lumen(LATE DISTAL TUBULE/Collecting Ducts) 4. --> HYPOkalemia 5. --> METABOLIC ALKALOSIS -From the H+ K+ ATPase inhibition on luminal side --> Increase H+ Secretion --> Increase HCO3- Reabsorption 6. --> Increased Na+ in blood 7. --> INCREASED blood pressure 8. --> DECREASED Renin/Aldosterone

What is the cause listed for Type II RTA?

1. Genetic mutation 2. --> Na+-HCO3 - exchange (no HCO3 - to counterbalance excess H+ in blood) → acidemia

What are all the listed causes of Metabolic Alkalosis?

1. H+ LOSS a) Loop Diuretics b) Vomiting c) Hyperaldosteronism (e.g., Conn's Syndrome) 2. HCO3- GAIN a) Antacids REMEMBER: The definition of Metabolic Alkalosis is that for some reason or another, the HCO3- conc. is INCREASED

What is the pathophysiology of Type IV Renal Tubular Acidosis?

1. HYPOaldosteronism 2. --> Na+ Loss 3. --> MORE POSITIVE Lumen 4. --> K+ does not want to passively flow back into tubule 5. --> HYPERKALEMIA 6. --> NH3 synthesis INHIBITION 7. --> No new NH4+ excretion --> NO NEW HCO3- Reabsorption 8. --> NON-Anion gap Metabolic Acidosis

How does Hypokalemia produce Alkalosis?

1. Hypokalemia (low [K+]plasma) produces alkalosis by enhancing H+, K+ exchange

What are the main things that can come from Fanconi Syndrome besides NON-Anion Gap Metabolic Acidosis?

1. Hypophosphatemia/Hyperphosphaturia a) Chronic ↓ phosphate reabsorption and ↑ urine phosphate 2. Osteomalacia/Rickets a) Chronic ↓ phosphate reabsorption, loss of calcium, and insufficient synthesis of vitamin D 3. Hypokalemia a) muscle weakness and arrhythmia 4. Hypouricemia a) Uric acid It is both secreted and reabsorbed, but net reabsorption usually occurs b) The PCT is the only place where uric acid transport occurs

What are we going to see in the blood in Fanconi Syndrome?

1. INCREASED RENIN and ALDOSTERONE Why? 1. Loss of so much stuff 2. --> Dragging ECF Fluid with it 3. --> Fluid loss being sensed by JGA(Granular) Cells 4. --> RENIN --> ANGIOTENSIN 5. Also, baroreceptors take action as well

What are the symptoms of Renal Tubular Acidosis?

1. Vasodilation --> Shock 2. GI Problems 3. INCREASED Urine pH in Type I -Hypercalciuria 4. Kidney Stones(Calcium Phosphate) 5. Kussmaul Breathing -Acidosis --> Rapid, Shallow, Deep breathing --> breathing off CO2 6. Growth Retardation/Bone Disease

So all in all, what is volume conctraction alkalosis?

1. Volume Contraction alkalosis is just ALKALOSIS brought on by VOLUME CHANGES 2. A big point here is that there is a cascade of events that keeps the alkalosis going

What is an overview of the cascade of events that occur with VOLUME CONTRACTION ALKALOSIS?

1. Vomiting -H+ Loss, Na+, K+ loss from ECF 2. Angiotensin II a)Released from Granular Cells because of low Na+ b) --> Stimulation of Na+-H+-exchange in proximal tubular cell --> HCO3- Reabsorption 3. Aldosterone Release -Released after Adrenal Stimulated a) Stimulation of H+ ATPase in α-intercalated cells --> H+ Secretion b) Na+/K+ ATPase in Principal Cells --> K+ inside cells --> K+ Secretion --> HYPOKALEMIA 4. Hypokalemia a) --> Stimulation of Glutamine break down --> NH3 production --> HCO3- Synthesis --> HCO3- in blood b) H+/K+ ATPase Stimulation 5. All of this --> MAINTENANCE of ALKALOSIS 5. --> Maintenance of Metabolic Alkalosis

Why will Saline NOT help with Metabolic Acidosis caused by Hyperaldosteronism?

1. Well think about it... 2. HIGH ALDOSTERONE is going to FAVOR H+ EXCRETION... 3. Which will eventually lead to HCO3- formation.. 4. Not the mention causing HYPOKALEMIA which will stimulate the H+/K+ ATPase which will cause excretion of H+ and further contribute to HCO3- being made 5. So giving Saline will not do a thing if we have a tumor that is constantly pumping out Aldosterone

What are the causes of Type 1 Renal Tubular Acidosis?

1. - Genetic mutation: H+-ATPase or H+-K+-ATPase - 2. Genetic mutation: HCO3 - -Cl- exchange 3. Medications: lithium or amphotericin B

What are the 2 types of treatment of METABOLIC ALKALOSIS?

1. - Saline-responsive metabolic alkalosis 2. - Saline-resistant metabolic alkalosis

What is Fanconi Syndrome?

1. A generalized reabsorption defect in the PCT.. 2. --> Stops reabsorption of almost all amino acids, glucose, Ca2+, HCO3 - , PO4 3- , K+, and all substances reabsorbed by the PCT. 3. --> This causes all of the above to be excreted in the urine 4. No H+ Secretion --> METABOLIC ACIDOSIS 5. No H+ Secretion --> No H+ recycling to reabsorb HCO3- --> HCO3- LOST 6. --> NON-Anion Gap Metabolic Acidosis

What is the urine pH in TYPE IV Distal RTA?

1. ACIDIC 2. Urine pH is < 5.5 (because of the distal tubule H+ functions normally)

What causes Respiratory Acidosis?

1. Airway Obstruction 2. Acute/Chronic Lung Disease -COPD, Pneumonia 3. Opioids/Sedatives a) Via Inhibition of the medullary respiratory center 4. Weak Respiratory Muscles a) MS, Polio

What type of Metabolic Alkalosis will respond to Saline?

1. Alkalosis caused by a VOLUME REDUCTION a) Vomiting b) Loop Diuretics

So what are the highlights of Distal Renal Tubular Acidosis?

1. Alpha Intercalated Cells DO NOT Secrete H+ 2. NO NEW HCO3- Generated --> METABOLIC ACIDOSIS 3. Urine pH great than 6 4. HYPOKALEMIA 5. Kidney Stones

What is the pathophysiology of Type I Tubular Acidosis?

1. Antibodies attack 2. --> α-intercalated cells in the late distal convoluted tubule (DCT) and collecting duct (CD) DO NOT secrete H+ 3. --> DECREASED EXCRETION of Titratable Acid and NH4+ 4. --> Increased H+ in CELL 5. --> K+ coming OUT of blood to decreased that high intracellular H+ 6. --> HYPOKALEMIA 7. Basic Urine --> Calcium Phosphate KIDNEY STONE formation

What causes Type IV Renal Tubular Acidosis

1. Impaired ALDOSTERONE Secretion(HYPOaldosteronism) or 2. DISTAL Tubular resistance to ALDOSTERONE

What does he say happens to urine pH DURING and AFTER the insult in Type II Proximal RTA?

1. Initially --> Urine pH > 6 2. Later On --> Urine pH < 5.5 Why? 1. So remember that type II is impaired BICARB REABsorption... 2. It it makes sense that at first, the urine pH will be HIGH/BASIC 3. HOWEVER, the insult is in the PROXIMAL TUBULE... 4. But the alpha intercalated cells in the DISTAL TUBULE an COLLECTING DUCTS work just fine... 5. And will eventually catch up and put out more H+ to get that urine pH back down

How is it that Loop/Thiazide Diuretics cause Metabolic Alkalosis?

1. Just know that they INCREASE urine volume... 2. And DECREASE ECF Volume 3. Leading to HYPOKALEMIA ---> Stimulation of Glutamine break down --> NH3 production --> HCO3- Synthesis --> HCO3- in blood 4. Leading to INCREASED ANGIOTENSIN II --> Aldosterone a) --> Stimulation of Na+-H+-exchange in proximal tubular cell --> HCO3- Reabsorption b) Stimulation of H+ ATPase in α-intercalated cells --> H+ Secretion c) Na+/K+ ATPase --> K+ inside cells --> HYPOKALEMIA

What can partially counter respiratory alkalosis besides the obvious kidney compensation?

1. LACTIC ACID Process: 1. No O2 2. Body breaks down muscles for energy 3. --> LACTIC ACID 4. --> Slightly counters alkalosis

So talking about ingesting antacids as a cause of metabolic alkalosis, he gives 2 examples of things that can cause this. What are they?

1. Lactate 2. Citrate -Remember: These things can be metabolized into HCO3- just like antacids

What is the MOA of PGE2 getting released?

1. Macula Densa senses it 2. --> Expression of COX2 3. --> Production of PGE2 from kidney 4. --> PGE2 DIRECTLY STIMULATES Renin Release from Granular Cells as well as dilates the AFFERENT Arteriole (See Week 15 Master Note Sheet)

What are the NET FINDINGS of Bartter Syndrome?

1. Metabolic ALKALOSIS 2. HYPOKalemia 3. HYPERCalciurea

What is the NET EFFECT of type II Bartter Syndrome?

1. Metabolic ALKALOSIS 2. HYPOKalemia 3. HYPERCalciurea

So overall, what are the NET effects of Liddle Syndrome?

1. Metabolic Alkalosis 2. HYPOkalemia 3. HYPERTENSION 4. DECREASED Aldosterone

What are the NET effect of Gitelman Syndrome?

1. Metabolic Alkalosis 2. HYPOmagnesia 3. HYPOkalemia 4. HYPOcalciuria

What does Liddle Syndrome Mimic?

1. Mimics hyperaldosteronism (but with suppressed aldosterone and renin levels = pseudo hyperaldosteronism) How? 1. So this is just saying that aldosterone is a Na+ Keeping and K+ Wasting thing 2. That is EXACTLY what this is doing... 3. But with an Aldosterone Secreting tumor, ALDOSTERONE levels are obviously going to stay high unlike in Liddle Syndrome

What type of Metabolic Alkalosis will Saline NOT help with?

1. Mineralocorticoid Induced Alkalosis(HYPERALDOSTERONISM)

What causes type II Bartter Syndrome?

1. Mutations in the KCNJ1 gene for ATP regulated renal outer medullary potassium (ROMK) channel. 2. --> No (+) Potential on lumen side 3. --> (-) "HOLDING" on to cations 4. --> DECREASE of Ca, K+, Na+ Reabsorption 4a. --> Macula Densa Cells Sense it 4b. --> HYPERRENEMIA 4c. --> Increased Prostaglandin Production --> DILATION of Afferent 5. --> Increased ALDOSTERONE 6. --> HYPOKALEMIA --> Stimulated H+/K+ ATPase 7. --> INCREASED H+ Secretion 8. --> INCREASED HCO3- Reabsorption 9. --> METABOLIC ALKALOSIS!!

What is Gitelman Syndrome?

1. NaCl Cotransport defect in the EARLY DISTAL TUBULE from a mutation 2. --> Impaired Na+ Reabsorption 3. --> Messed up (+) lumen 4. --> Impaired Mg+ and Ca2+ Reabsorption because (-) lumen is "holding" them 5. Decreased Na+ --> INCREASED RENIN 6. --> ALDOSTERONE 7. --> HYPOKALEMIA 8. --> METABOLIC ALKALOSIS -From the H+ K+ ATPase inhibition on luminal side --> Increase H+ Secretion --> Increase HCO3- Reabsorption

What is the pathophysiology of Type 2 Renal Tubular Acidosis?

1. PROXIMAL Tubule cells can't reabsorb HCO3- 2. --> Increased HCO3- Excretion --> Increased Urine pH 3. --> NON-Anion Gap Metabolic Acidosis 4. HCO3- lost as NaHCO3 which PULLS WATER 5. --> Diuresis --> LOSS OF K+ 6. --> mild HYPOKALEMIA 7. Bone spit out PHOSPHATE to help with the Acidosis 8. Loss of HCO3- will increase the Cl- calcium ion concentration on lab tests --> HYPERCHLOREMIA

How does Hyperaldosteronism Lead to Metabolic Alkalosis?

1. Principal Cells in LATE Distal Tubules/Collecting Ducts -Stimulation of Na+/K+ ATPase --> HYPOKalemia 2. Alpha Intercalated cells in the LATE Distal Tubules/Collecting Ducts -Stimulation of H+ ATPase --> for every 1 H+ Secreted --> 1 new HCO3-

How is it that ECF Volume Contraction, METABOLIC ALKALOSIS and HYPOKALEMIA are linked?

1. Remember, volume contraction --> LOSS of K+ and Na+ --> ALDOSTERONE RELEASE MOA: 1. Volume Contraction --> Loss of K+ and Na+ 2. --> Aldosterone 3. --> Stimulation of apical H+-K+-ATPase (α-intercalated cells) 4. --> K+ OUT and H+ IN Cells 5. Intracellular Acidosis --> Glutamate breakdown --> NH3 made --> H+ Excreted 6. 2 NEW HCO3- made for every 1 H+ excreted 7. --> Continued Metabolic Alkalosis

What is the MOA of why giving saline treats VOLUME DEPLETION metabolic alkalosis?

1. Saline having NaCl REPLENISHES NaCl 2. --> Calms down those Granular Cells 3. --> No RAAS a) No Angiotensin secretion --> No Aldosterone b) --> ↓ Na+-H+-exchange activity (PT) c) --> ↓ H+-ATPase activity (CD) 4. --> DECREASED H+ Secretion 5. --> INCREASED HCO3- Secretion 6. --> Metabolic Alkalosis correction

How does Hypokalemia cause a Metabolic Alkalosis?

1. Stimulates K+/H+ Exchanger in alpha intercalated cells at LUMINAL Surface MOA: 1. Stimulation of K+/H+ Exchanger 2. --> H+ INSIDE cell 3. Intracellular Acidosis --> Stimulation of Glutamine break down 4. --> NH3 secreted --> 2 HCO3- made 5. --> Continuation of Alkalosis REMEMBER: 1. Aldosterone contributes to Hypokalemia.. 2. And then hypokalemia by itself can keep the alkalosis going

What is Renal Tubular Acidosis?

1. This is just the body not being able to SECRETE H+ 2. There are 4 TYPES.. 3. And each type is classified based on where it is found in the nephron

What is type I renal tubular acidosis?

1. This is the inability of the alpha Intercalated cells in the LATE Distal Tubule and Collecting Duct to secrete acid

0% (M1.RL.18.4872) A 46-year-old woman presents to her primary care physician with one week of intermittent nausea and vomiting. She does not have any sick contacts, and her medical history is significant only for diabetes well-controlled on metformin. She also complains of some weakness and back/leg pain. She says that she recently returned from traveling abroad and had been administered an antibiotic during her travels for an unknown infection. On presentation, her temperature is 98.6°F (37°C), blood pressure is 119/78 mmHg, pulse is 62/min, and respirations are 25/min. An EKG is obtained showing flattening of the T wave. After further testing, the physician prescribes a thiazide for this patient. Which of the following diseases is also associated with this patient's most likely diagnosis? Review Topic | Tested Concept QID: 109955 1 Rheumatoid arthritis 2 Sickle cell disease 3 Sjogren syndrome 4 Systemic lupus erythematosus 5 Wilson disease Select Answer to see Preferred Response

1. This patient with nausea and vomiting with tachypnea that was treated with thiazides most likely has metabolic acidosis caused by type II renal tubular acidosis, which is also associated with Wilson disease. 2. Type II renal tubular acidosis is a metabolic acidosis caused by a defect in proximal tubule bicarbonate reabsorption. 3. It can be caused by a variety of syndromes including Wilson disease, multiple myeloma, Fanconi syndrome, and administration of expired tetracyclines. 4. Importantly, type II renal tubular acidosis is associated with a variety of other metabolic defects because the defective proximal tubule can waste other metabolites. Examples include hypokalemia, which may manifest as weakness with a flattened T wave, as well as hypophosphatemia, which may manifest as back/leg pain or cause hypophosphatemic rickets in children.

So in Type II Proximal RTA, can urine still be acidified?

1. YES!!! 2. It can by Alpha-intercalated Cells in the LATE DT and CD... 3. But NOT enough to overcome INCREASED HCO3- 4. --> Non Anion Gap Metabolic Acidosis -He copied this straight from First Aid

QUESTIONS 1 of 2 Previous Next 0% (M1.OMB.19.1) A 28-year-old woman presents to the emergency department after breaking her wrist in a ground level fall. She says that she has been experiencing muscle pain and fatigue for the past 5 months. She has noticed that she has been drinking a lot more water than previously. She has no past medical history, but she returned from global health work in South America 6 months ago. While abroad, she had an episode of infection that was treated with old antibiotics. Urinalysis reveals amino acids and glucose. Which of the serum findings demonstrated in Figure A would most likely be seen in this patient? Review Topic | Tested Concept

Answer: C 1. This patient with aminoaciduria, glycosuria, polydipsia, and pathologic fractures after taking old antibiotics most likely has Fanconi syndrome, 2. which is associated with decreased serum sodium, potassium, calcium, and phosphate levels. 3. Fanconi syndrome is a defect in the proximal convoluted tubule of the kidney that leads to inadequate reabsorption of glucose, bicarbonate, phosphate, potassium, and almost all amino acids. 4. It has a wide variety of etiologies including medications such as cisplatin, tenofovir, valproic acid, and expired tetracyclines. Fanconi syndrome can present with renal findings such as polydipsia and polyuria, constitutional symptoms such as myalgias, weight loss, and fatigue, and bone abnormalities such as pathologic fractures. Laboratory findings will show decreased serum sodium, potassium, calcium, and phosphate levels.

What does Gitelman Syndrome imitate?

Effects of THIAZIDE Diuretics

What causes metabolic acidosis?

Keep in mind that it is divided into different categories based on Anion Gap -INCREASED Anion Gap- 1. Ingestion of Fixed Acids(Salicylate/Methanol) 2. Increased Production of Fixed Acids(Ketoacids, Lactic Acid) -NORMAL Anion Gap- 1. HCO3 Lost via Kidneys(Renal Tubular Acidosis) 2. HCO3 Lost via Gi Tract

What is the location of Type 2 Renal Tubular Acidosis?

PROXIMAL Renal Tubule