Heart Failure/ Acid Base Balance

Question 1

What is heart failure?

Answer 1

A syndrome (not a diagnosis) where patients have typical symptoms and signs resulting from an abnormality of cardiac structure or function

Question 2

What different factors/ailments can cause heart failure?

Answer 2

Most common- MI
Dilated cardiomyopathy
Hypertension
Valvular stenosis 
Alcohol
Less common: genetics, peripartum, infiltrative, arrhythmia, endocrine, nutritional, chemotherapy, pericardial

Question 3

What are symptoms of heart failure?

Answer 3

Breathlessness, ankle swelling, fatigue

Question 4

What are the classes of heart failure?

Answer 4

Class 1- no symptoms, no limitation of physical activity
Class 2- mild symptoms, occasional swelling , somewhat limited, normal activity causes fatigue, palpitations, or dyspnoea
Class 3- Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnoea.
Class 4- bed bound, symptoms of HF at rest,

Question 5

What clinical signs are related to heart failure?

Answer 5

Sinus tachycardia,
atrial fibrillation (or other arrhythmias)
hypo/hyper/normotensive 
Raised JVP
Ankle oedema (pitting)
Crackle during auscultation

Question 6

What is typical cardiac output? Include calculation

Answer 6

5L blood /min

CO= HR X SV

Question 7

Discuss the cycle of cardiac failure.

Answer 7

Myocardial injury 
Reduced ventricular functioning 
Reduced cardiac output 
Overactivation of neurohormonal signalling pathways (RAAS, sympathetic system, reduced sensitive to natriuretic peptides)
Increased Na and water retention
Increased intravascular volume
Increased pre-load 
Myocardial injury 
Reduced ventricular functioning 
Reduced cardiac output

Question 8

Discuss the cycle of cardiac failure.

Answer 8

Myocardial injury 
Reduced ventricular functioning 
Reduced cardiac output 
Overactivation of neurohormonal signalling pathways (RAAS, sympathetic system, reduced sensitive to natriuretic peptides)
Increased Na and water retention
Increased intravascular volume
Increased pre-load 
Myocardial injury

Question 9

What does elevated NT-ProBNP indicate?

Answer 9

Marker of bad outcome for heart failure.
High pressure due to back-logging of fluids in combination with stretched cardiac wall, more BNP is released to try and reduce pressure (NT-proBNP is stable inactive version of BNP released at similar amounts)

Question 10

How does heart rate relate to heart failure outcome?

Answer 10

Faster heart rate in resting, worse the outcome

Question 11

How does heart rate relate to heart failure outcome?

Answer 11

Faster heart rate in resting, worse the outcome

High NT-ProBNP is marker of bad outcome

Question 12

What drugs can precipitate or aggravate HF?

Answer 12

NSAIDs (impact renal function-> hypervolemia and reduced GFR)
Ca antagonists (exacerbate HF symptoms)
Anti-arrhythmics (impact inotropy)
Tricyclic antidepressants
Corticosteroids (can cause cardiac inflammation (particularly mineralocorticoids))

Question 13

What is an acid?

Answer 13

Donates hydrogen ion, although hydrogen ions aren’t typically free in body.
As something gets more acidic, hydrogen ion concentration increases

Question 14

What is biological pH and hydrogen concentration meant to be?

Answer 14

7. 36-7.44

36. 4 hydrogen concentration

Question 15

Why is hydrogen concentration regulation important?

Answer 15

At physiological pH, most biosynthetic/metabolic pathways involves precursors that are ionised.
pH determines the ions physical locations in cells/organelles.
If [H] changes, the ionisation state of the ions will change, blocking normal metabolic function.
All proteins are complex molecules that are folded to maintain structure, the folds are maintained by hydrogen bonds which are influenced by pH, so if proteins are exposed to high concentration, proteins will denature

Question 16

What are consequences of acid-base disorders?

Answer 16

Cardiovascular (BP, rhythm)
Respiratory (ventilation, resp rate)
Metabolic (protein wasting, bone)
Renal (electrolytes)
GI
Neurological (confusion, seizures)

Question 17

What are the main ways to regulate pH?

Answer 17

Renal processes regulating bicarbonate and hydrogen ion excretion (hours-days)
Ventilation (minutes)
Buffering (instantaneous)

Question 18

How does ventilation regulate pH?

Answer 18

Controls arterial Co2 levels via respiration rates

Question 19

How do renal processes regulate pH?

Answer 19

Controls HCO3 concentration

Question 20

Are hydrogen ion concentration an indicator of acid-base balance disturbance?

Answer 20

Hydrogen ion concentrations can be normal in presence of acid base disturbance.
Disturbance will be at expense of other blood chemistry ([HCO3], pCO2)

Question 21

How does buffering regulate pH?

Answer 21

Works to regulate bicarbonate levels in order to maintain balance with [hydrogen ions].
Buffers are weak acids which partially dissociate in solution.
At equilibrium, [H] will relate to the ratio of the [acid] over [base]
Extremely effective for regulation

Question 22

What is the Henderon-Hasselbach equation?

Answer 22

pH= pKa + log10 { [base]/[acid]}

Question 23

What elements and structures in the body aid in buffering?

Answer 23

Bicarbonate buffering
Haemoglobin (buffers COs in blood)
Proteins (intracellular buffer)
Bone (long term buffer (osteoclast resorption releasing calcium carbonate) and short term (uptake H in exchange for Na, Ca, and K))
PO4 (intracellular and urinary buffer)

Question 24

What is the equation to describe the bicarbonate buffering system?

Answer 24

CO2 + H2O = H2CO3 (carbonic acid) = H+ + HCO3 (bicarb)

= is arrow

Question 25

If the body is in a basic state, how will our bicarb buffering system respond?

Answer 25

Need to increase hydrogen concentration in blood, therefore, reduce respiration to increase CO2 in blood, causing formation of carbonic acid to hydrogen and bicarb, increasing hydrogen concentration.

Question 26

How does respiration impact pH?

Answer 26

Fast respiration -> CO2 levels drop -> respiratory alkalosis (too basic)
Slow respiration -> CO2 levels increase -> CO2 conversion to carbonic acid -> acidic blood

Question 27

How do the kidneys regulate acid-base balance?

Answer 27

1. Reabsorb filtered bicarbonate (its filtered at glomerulus, and needs to be reabsorbed otherwise patient will be come acidotic)
2. Secrete fixed acid. Titration of phosphate, and secretion of ammonium (NH4) into urine.

Question 28

What is renal tubule acidosis? Include total filtration a day

Answer 28

Inability to actively reabsorb filtered HCO3 at the proximal tubule (and Thick Ascending Loop/distal collecting tubule)
Filter bicarb 4000 mmol/day

Question 29

Describe the mechanism for reabsorbing HCO3 in the kidney.

Answer 29

HCO3 is filtered through glomerulus -> HCO3 joins with tubular H+ to form H2O and CO2 which diffuses from tubule into cell -> carbonic anhydrase forms carbonic acid from H2O and CO2 -> carbonic acids breaks down within cell to form H and HCO3 -> H+ moves back into tubule, HCO3 moves into interstitium and is reabsorbed into blood -> H+ back in tubule will join with filtered HCO3 to form H2O and CO2, restarting process.

Question 30

What is the modified Henderson-Hasselbalch equation?

Answer 30

pH= 6.1 + log ( [HCO3]/[CO2] )

Question 31

How do metabolic and respiratory acidosis/alkalosis differ?

Answer 31

Respiratory can only be acidic OR basic as it is based solely on the ventilation rate
Metabolic is influenced by many things (kidney balance, diarrhea (acidosis), vomiting (alkalosis)) and can be balanced even though there is a shift.
The 2 forms can balance each other out, i.e. respiratory acidosis + metabolic alkalosis, and can also combine.

Question 32

How does central receptor sensitivity relate to acid-base balance?

Answer 32

Lack of sensitivity to hypercapnia would not lead to typical response, being increased respiration and breathing out of CO2 to reduce acidity

Question 33

Why does CO2 rise result in increased renal retention of HCO3?

Answer 33

CO2 is rising, diffusing into renal tubular cells.
CO2 rises intracellularly, driving reaction combining H2O and CO2 to form carbonic acid and then H ions and HCO3
HCO3 is transported back into body, H is transported into urine where it can be combined with filtered bicarb.
This allows for balancing of acidic CO2 and alkaline HCO3

Question 34

What are causes of metabolic acidosis?

Answer 34

Metabolic acidosis- addition of acid, either via metabolic (lactic acidosis, keto-acidosis), or ingestion of acid (methanol).
Failure in renal mechanisms to excrete acid (renal tubular acidosis)
Excessive loss of HCO3 (stool (diarrhoea), or urine (another form of renal tubular acidosis))

Question 35

What impact does metabolic acidosis have?

Answer 35

CVS- arrhythmias, reduced cardiac contractility, vasodilation
Respiratory- increased ventilation (Kassmaul’s breathing)
Metabolic- protein wasting, resorption of Ca from bones
Other- neutrophilia

Question 36

What is lactic acidosis?

Answer 36

Lactic acid is produced through glycolysis of pyruvate
It is buffered by HCO3 to lactate and then metabolised in the liver
Production is very high
Acidosis occurs when production is high and there is hypoperfusion (not clearing lactic acid properly). This happens during hypotension or haemodynamically unstable
Can occur due to drugs (metformin), liver failure, poisoning (cyanide, aspirin)

Question 37

How does kidney failure related to acid-base balance?

Answer 37

As function is lost, most become acidotic as kidneys work to retain bicarb and excrete hydrogen ions, which can become impaired during failure
Initially, can titrate a rise in phosphate, as it is retained in kidney failure, but eventually patients become acidotic

Question 38

What are the two forms of metabolic alkalosis, and what are some examples?

Answer 38

Volume depletion:
Gastric acid loss due to vomiting
Diuretics

Volume repleted types: 
Mineralocorticoid xs,
Hyperaldosteronism
Bartter's, Cushing's
Hypokalemia

Question 39

How does vomiting cause alkalosis?

Answer 39

Volume based problem.
Not excreting bicarb, kidneys actively try to retain it, this is due to volume depletion (particularly Na and Cl retention which makes them unable to excrete bicarb, increasing bicarb meaning no compensatory response, perpetuating the alkalosis).
They should be treated with fluid (saline- as it has Na and Cl).

Question 40

What are the fixed and un-fixed (volatile) acids present in the body, how are they produced, and what buffering system works to regulate them?

Answer 40

Volatile:
CO2 (actually carbonic acid) produced as end-product of complete oxidation of fatty acids and carbohydrates, regulated by ventilation system.
Fixed:
Phosphate and sulphate (incomplete metabolism of proteins)
Lactate (incomplete metabolism of carbohydrates)
Ketones (incomplete metabolism of fats).
All regulated by metabolic buffering system (kidneys)

Question 41

Why is the phosphate and protein buffering systems important? Briefly describe how they each work to aid in buffering.

Answer 41

Only blood buffer systems capable of buffering respiratory acid-base disturbances (bicarbonate system is ineffective in buffering changes in H+ produced by itself).
Phosphate- Good intracellular buffer and urine buffer (can accept H+ ions in renal tubules helping to reduce pH)
Haemoglobin- Good blood pH buffer (histidine residues). Oxygen is unloaded, creating deoxyhaemoglobin which can more readily accept H+

Question 42

How does bone contribute to acid-base balance?

Answer 42

Compensation for acute acidosis:
Bone can take up H+ in exchange for K+, Ca++, and Na+
Compensation for chronic acidosis:
Bone can release carbonate (requires hydroxyapatite crystal dissolution- takes longer but amounts of buffer are larger- more commonly used) or bicarbonate (more rapidly exchanged as present in the bone water that makes up hydration shell around hydroxyapatite crystals).